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I.; Kox, M. title: The endotoxin-induced pulmonary inflammatory response is enhanced during the acute phase of influenza infection date: 2018-07-05 journal: Intensive Care Med Exp DOI: 10.1186/s40635-018-0182-5 sha: doc_id: 3099 cord_uid: a0acr28o file: cache/cord-006778-qnxyhmw5.json key: cord-006778-qnxyhmw5 authors: Chen, Xuxin; Tang, Lu; Feng, Jian; Wang, Yi; Han, Zhihai; Meng, Jiguang title: Downregulation of Paralemmin-3 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating Inflammatory Response and Inhibiting Formation of TLR4/MyD88 and TLR4/TRIF Complexes date: 2017-08-12 journal: Inflammation DOI: 10.1007/s10753-017-0639-9 sha: doc_id: 6778 cord_uid: qnxyhmw5 file: cache/cord-000920-68eblcke.json key: cord-000920-68eblcke authors: Gallego, Carolina; Middleton, Andrew M.; Martínez, Nhora; Romero, Stefany; Iregui, Carlos title: Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium date: 2013-03-11 journal: Vet Med Int DOI: 10.1155/2013/347086 sha: doc_id: 920 cord_uid: 68eblcke file: cache/cord-007178-h0ordzm9.json key: cord-007178-h0ordzm9 authors: Felts, Paul A.; Woolston, Anne-Marie; Fernando, Himali B.; Asquith, Stephen; Gregson, Norman A.; Mizzi, Oliver J.; Smith, Kenneth J. title: Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide date: 2005-05-04 journal: Brain DOI: 10.1093/brain/awh516 sha: doc_id: 7178 cord_uid: h0ordzm9 file: cache/cord-012828-wsjob1p8.json key: cord-012828-wsjob1p8 authors: Wang, Yan-hang; Lv, Hai-ning; Cui, Qing-hua; Tu, Peng-fei; Jiang, Yong; Zeng, Ke-wu title: Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway date: 2019-09-10 journal: Acta Pharmacol Sin DOI: 10.1038/s41401-019-0296-7 sha: doc_id: 12828 cord_uid: wsjob1p8 file: cache/cord-001496-186k6t03.json key: cord-001496-186k6t03 authors: Yuan, Qing; Jiang, Yan-wen; Ma, Ting-ting; Fang, Qiu-hong; Pan, Lei title: Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats date: 2014-12-05 journal: J Inflamm (Lond) DOI: 10.1186/s12950-014-0040-5 sha: doc_id: 1496 cord_uid: 186k6t03 file: cache/cord-006285-kkxdmzk9.json key: cord-006285-kkxdmzk9 authors: Smirnova, S. 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V. title: Long-Term Maintenance of the Functional Changes Induced by Influenza A Virus and/or LPS in Human Endothelial ECV-304 Cell Sublines date: 2019-08-26 journal: Cell tissue biol DOI: 10.1134/s1990519x19040084 sha: doc_id: 6285 cord_uid: kkxdmzk9 file: cache/cord-002079-jne14jqf.json key: cord-002079-jne14jqf authors: MacParland, Sonya A.; Ma, Xue-Zhong; Chen, Limin; Khattar, Ramzi; Cherepanov, Vera; Selzner, Markus; Feld, Jordan J.; Selzner, Nazia; McGilvray, Ian D. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 journal: J Virol DOI: 10.1128/jvi.02557-15 sha: doc_id: 2079 cord_uid: jne14jqf file: cache/cord-006888-qfnukav4.json key: cord-006888-qfnukav4 authors: nan title: Irish Thoracic Society Annual Scientific Meeting, Ramada Hotel, Belfast: 7th–8th November 2008 date: 2008-10-21 journal: Ir J Med Sci DOI: 10.1007/s11845-008-0235-y sha: doc_id: 6888 cord_uid: qfnukav4 file: cache/cord-022136-3q24qxsr.json key: cord-022136-3q24qxsr authors: Maru, Yoshiro title: Explanation of Metastasis by Homeostatic Inflammation date: 2016-02-02 journal: Inflammation and Metastasis DOI: 10.1007/978-4-431-56024-1_15 sha: doc_id: 22136 cord_uid: 3q24qxsr file: cache/cord-006605-tsk3pakb.json key: cord-006605-tsk3pakb authors: Jesmin, Subrina; Gando, Satoshi; Zaedi, Sohel; Sakuraya, Fumika title: Differential Expression, Time Course and Distribution of Four PARs in Rats with Endotoxin-induced Acute Lung Injury date: 2006-11-30 journal: Inflammation DOI: 10.1007/s10753-006-9017-8 sha: doc_id: 6605 cord_uid: tsk3pakb file: cache/cord-029969-1fa8hk2n.json key: cord-029969-1fa8hk2n authors: Ge, Xin; Meng, Xianglin; Fei, Dongsheng; Kang, Kai; Wang, Qiubo; Zhao, Mingyan title: Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway date: 2020-08-01 journal: 3 Biotech DOI: 10.1007/s13205-020-02364-5 sha: doc_id: 29969 cord_uid: 1fa8hk2n file: cache/cord-006570-v4as5gde.json key: cord-006570-v4as5gde authors: Sukhotnik, Igor; Shehadeh, Naim; Rothem, Lilah; Lurie, Michael; Mogilner, Jorge; Shiloni, Eitan; Shamir, Raanan title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat date: 2007-10-13 journal: Dig Dis Sci DOI: 10.1007/s10620-007-9990-2 sha: doc_id: 6570 cord_uid: v4as5gde file: cache/cord-000137-idffrnac.json key: cord-000137-idffrnac authors: Xiang, Meng; Fan, Jie title: Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury date: 2009-11-02 journal: Mol Med DOI: 10.2119/molmed.2009.00097 sha: doc_id: 137 cord_uid: idffrnac file: cache/cord-103496-8tq78p2z.json key: cord-103496-8tq78p2z authors: Wang, Ting; Yegambaram, Manivannan; Gross, Christine; Sun, Xutong; Lu, Qing; Wang, Hui; Wu, Xiaomin; Kangath, Archana; Tang, Haiyang; Aggarwal, Saurabh; Black, Stephen M. title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury date: 2020-11-13 journal: nan DOI: 10.1016/j.redox.2020.101794 sha: doc_id: 103496 cord_uid: 8tq78p2z file: cache/cord-022252-9yiuuye3.json key: cord-022252-9yiuuye3 authors: Mims, Cedric A.; Dimmock, Nigel J.; Nash, Anthony; Stephen, John title: Mechanisms of Cell and Tissue Damage date: 2013-11-17 journal: Mims' Pathogenesis of Infectious Disease DOI: 10.1016/b978-0-12-498262-8.50015-1 sha: doc_id: 22252 cord_uid: 9yiuuye3 file: cache/cord-004754-5596p4ma.json key: cord-004754-5596p4ma authors: Duan, X.; Nauwynck, H. 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date: 2013-02-06 journal: Semin Immunopathol DOI: 10.1007/s00281-013-0365-9 sha: doc_id: 6318 cord_uid: 9r51n241 file: cache/cord-005832-p1joajvn.json key: cord-005832-p1joajvn authors: Liu, Zhicheng; Yang, Zhengtao; Fu, Yunhe; Li, Fenyang; Liang, Dejie; Zhou, Ershun; Song, Xiaojing; Zhang, Wen; Zhang, Xichen; Cao, Yongguo; Zhang, Naisheng title: Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice date: 2013-02-23 journal: Inflamm Res DOI: 10.1007/s00011-013-0603-6 sha: doc_id: 5832 cord_uid: p1joajvn file: cache/cord-029488-l11ufs6k.json key: cord-029488-l11ufs6k authors: Tomita, Kengo; Saito, Yuna; Suzuki, Tokiko; Imbaby, Samar; Hattori, Kohshi; Matsuda, Naoyuki; Hattori, Yuichi title: Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date: 2020-07-21 journal: Naunyn Schmiedebergs Arch Pharmacol DOI: 10.1007/s00210-020-01947-6 sha: doc_id: 29488 cord_uid: l11ufs6k file: cache/cord-255578-0ltb9dpa.json key: cord-255578-0ltb9dpa authors: Li, Xiangru; Hao, Zhenhua; Liu, Xiaorong; Li, Wei title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 journal: Front Immunol DOI: 10.3389/fimmu.2020.01123 sha: doc_id: 255578 cord_uid: 0ltb9dpa file: cache/cord-300912-w85t4zz6.json key: cord-300912-w85t4zz6 authors: Wu, Beibei; Wang, Liyin; Jiang, Lili; Dong, Lili; Xu, Fengli; Lu, Yili; Jin, Jiahui; Wang, Zhanyue; Liang, Guang; Shan, Xiaoou title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils date: 2017-10-25 journal: Mol Med Rep DOI: 10.3892/mmr.2017.7870 sha: doc_id: 300912 cord_uid: w85t4zz6 file: cache/cord-280850-lku2g69k.json key: cord-280850-lku2g69k authors: Zhang, Shidong; Wang, Dongsheng; Wang, Xurong; Li, Shihong; Li, Jingyu; Li, Hongsheng; Yan, Zuoting title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits date: 2013-08-26 journal: Journal of Ethnopharmacology DOI: 10.1016/j.jep.2013.06.041 sha: doc_id: 280850 cord_uid: lku2g69k file: cache/cord-000959-nk2thkme.json key: cord-000959-nk2thkme authors: Downer, Eric J.; Jones, Raasay S.; McDonald, Claire L.; Greco, Eleonora; Brennan, Sabina; Connor, Thomas J.; Robertson, Ian H.; Lynch, Marina A. title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date: 2013-05-06 journal: PLoS One DOI: 10.1371/journal.pone.0063194 sha: doc_id: 959 cord_uid: nk2thkme file: cache/cord-002411-iiw878w8.json key: cord-002411-iiw878w8 authors: Ding, Xibing; Jin, Shuqing; Tong, Yao; Jiang, Xi; Chen, Zhixia; Mei, Shuya; Zhang, Liming; Billiar, Timothy R.; Li, Quan title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 journal: Sci Rep DOI: 10.1038/srep34278 sha: doc_id: 2411 cord_uid: iiw878w8 file: cache/cord-282336-zvc04s39.json key: cord-282336-zvc04s39 authors: Choudhary, Ishita; Vo, Thao; Bathula, Chandra S.; Lamichhane, Richa; Lewis, Brandon W.; Looper, Jayme; Jeyaseelan, Samithamby; Blackshear, Perry J.; Saini, Yogesh; Patial, Sonika title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 journal: Front Immunol DOI: 10.3389/fimmu.2020.02164 sha: doc_id: 282336 cord_uid: zvc04s39 file: cache/cord-015082-l629n8is.json key: cord-015082-l629n8is authors: nan title: Poster Sessions 323-461 date: 2002-08-29 journal: Intensive Care Med DOI: 10.1007/s00134-002-1455-7 sha: doc_id: 15082 cord_uid: l629n8is file: cache/cord-005872-w1x1i0im.json key: cord-005872-w1x1i0im authors: Volk, T.; Kox, W.J. title: Endothelium function in sepsis date: 2000 journal: Inflamm Res DOI: 10.1007/s000110050579 sha: doc_id: 5872 cord_uid: w1x1i0im file: cache/cord-012487-s920s5wb.json key: cord-012487-s920s5wb authors: Noga, Marek J.; Büke, Ferhat; van den Broek, Niels J. 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A Literature Review date: 2020-06-30 journal: Int J Mol Sci DOI: 10.3390/ijms21134639 sha: doc_id: 348391 cord_uid: xytmq2f2 file: cache/cord-354829-god79qzw.json key: cord-354829-god79qzw authors: Mao, Kaimin; Geng, Wei; Liao, Yuhan; Luo, Ping; Zhong, Hua; Ma, Pei; Xu, Juanjuan; Zhang, Shuai; Tan, Qi; Jin, Yang title: Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets date: 2020-09-23 journal: Aging (Albany NY) DOI: 10.18632/aging.104042 sha: doc_id: 354829 cord_uid: god79qzw file: cache/cord-352219-z245sb3s.json key: cord-352219-z245sb3s authors: Tallam, Aravind; Perumal, Thaneer M.; Antony, Paul M.; Jäger, Christian; Fritz, Joëlle V.; Vallar, Laurent; Balling, Rudi; del Sol, Antonio; Michelucci, Alessandro title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date: 2016-02-12 journal: PLoS One DOI: 10.1371/journal.pone.0149050 sha: doc_id: 352219 cord_uid: z245sb3s file: cache/cord-014996-p6q0f37c.json key: cord-014996-p6q0f37c authors: nan title: Posters_Monday_12 October 2009 date: 2009-08-06 journal: Intensive Care Med DOI: 10.1007/s00134-009-1593-2 sha: doc_id: 14996 cord_uid: p6q0f37c file: cache/cord-005727-li8pwigg.json key: cord-005727-li8pwigg authors: nan title: ESICM 2010 MONDAY SESSIONS 11 October 2010 date: 2010-08-31 journal: Intensive Care Med DOI: 10.1007/s00134-010-1999-x sha: doc_id: 5727 cord_uid: li8pwigg file: cache/cord-005497-w81ysjf9.json key: cord-005497-w81ysjf9 authors: nan title: 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium. 24-27 March 2020 date: 2020-03-24 journal: Crit Care DOI: 10.1186/s13054-020-2772-3 sha: doc_id: 5497 cord_uid: w81ysjf9 file: cache/cord-006229-7yoilsho.json key: cord-006229-7yoilsho authors: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 journal: Naunyn Schmiedebergs Arch Pharmacol DOI: 10.1007/s00210-016-1213-y sha: doc_id: 6229 cord_uid: 7yoilsho file: cache/cord-006230-xta38e7j.json key: cord-006230-xta38e7j authors: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 journal: Naunyn Schmiedebergs Arch Pharmacol DOI: 10.1007/s00210-012-0736-0 sha: doc_id: 6230 cord_uid: xta38e7j file: cache/cord-023026-2r84ndzv.json key: cord-023026-2r84ndzv authors: nan title: Posters date: 2013-06-14 journal: Glia DOI: 10.1002/glia.22530 sha: doc_id: 23026 cord_uid: 2r84ndzv file: cache/cord-015021-pol2qm74.json key: cord-015021-pol2qm74 authors: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 journal: Intensive Care Med DOI: 10.1007/bf02258437 sha: doc_id: 15021 cord_uid: pol2qm74 file: cache/cord-022888-dnsdg04n.json key: cord-022888-dnsdg04n authors: nan title: Poster Sessions date: 2009-08-19 journal: Eur J Immunol DOI: 10.1002/eji.200990224 sha: doc_id: 22888 cord_uid: dnsdg04n file: cache/cord-005814-ak5pq312.json key: cord-005814-ak5pq312 authors: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 journal: Intensive Care Med DOI: 10.1007/bf02426401 sha: doc_id: 5814 cord_uid: ak5pq312 file: cache/cord-015394-uj7fe5y6.json key: cord-015394-uj7fe5y6 authors: nan title: Scientific Abstracts date: 2008-12-23 journal: Reprod Sci DOI: 10.1177/19337191080150020102 sha: doc_id: 15394 cord_uid: uj7fe5y6 Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-lps-cord === file2bib.sh === id: cord-009753-6rg47f0i author: Legband, Nathan title: The Treatment of Acute Respiratory Distress Syndrome in Rats With a Peritoneal Dosing System date: 2015-06-01 pages: extension: .txt txt: ./txt/cord-009753-6rg47f0i.txt cache: ./cache/cord-009753-6rg47f0i.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-009753-6rg47f0i.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36079 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35969 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35880 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36043 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35804 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35043 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36185 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36836 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36634 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36964 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37182 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37108 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34783 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-032564-0t5lr4z9 author: Moin, Abu Saleh Md title: Pro-fibrotic M2 macrophage markers may increase the risk for COVID19 in type 2 diabetes with obesity()() date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-032564-0t5lr4z9.txt cache: ./cache/cord-032564-0t5lr4z9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-032564-0t5lr4z9.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 35496 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34986 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36565 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37027 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37058 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 36402 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34394 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37060 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37178 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 37089 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34609 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-003099-a0acr28o author: Koch, R. M. title: The endotoxin-induced pulmonary inflammatory response is enhanced during the acute phase of influenza infection date: 2018-07-05 pages: extension: .txt txt: ./txt/cord-003099-a0acr28o.txt cache: ./cache/cord-003099-a0acr28o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-003099-a0acr28o.txt' === file2bib.sh === id: cord-006285-kkxdmzk9 author: Smirnova, S. S. title: Long-Term Maintenance of the Functional Changes Induced by Influenza A Virus and/or LPS in Human Endothelial ECV-304 Cell Sublines date: 2019-08-26 pages: extension: .txt txt: ./txt/cord-006285-kkxdmzk9.txt cache: ./cache/cord-006285-kkxdmzk9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006285-kkxdmzk9.txt' === file2bib.sh === id: cord-000460-h3owwjao author: Xiong, Jing title: Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date: 2011-09-26 pages: extension: .txt txt: ./txt/cord-000460-h3owwjao.txt cache: ./cache/cord-000460-h3owwjao.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000460-h3owwjao.txt' === file2bib.sh === id: cord-000920-68eblcke author: Gallego, Carolina title: Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium date: 2013-03-11 pages: extension: .txt txt: ./txt/cord-000920-68eblcke.txt cache: ./cache/cord-000920-68eblcke.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000920-68eblcke.txt' === file2bib.sh === id: cord-270213-ygb64yxc author: Williams, Alexander T. title: Control of systemic inflammation throughearly nitric oxide supplementation with nitric oxide releasing nanoparticles date: 2020-10-02 pages: extension: .txt txt: ./txt/cord-270213-ygb64yxc.txt cache: ./cache/cord-270213-ygb64yxc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-270213-ygb64yxc.txt' === file2bib.sh === id: cord-005832-p1joajvn author: Liu, Zhicheng title: Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice date: 2013-02-23 pages: extension: .txt txt: ./txt/cord-005832-p1joajvn.txt cache: ./cache/cord-005832-p1joajvn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005832-p1joajvn.txt' === file2bib.sh === id: cord-012828-wsjob1p8 author: Wang, Yan-hang title: Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway date: 2019-09-10 pages: extension: .txt txt: ./txt/cord-012828-wsjob1p8.txt cache: ./cache/cord-012828-wsjob1p8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012828-wsjob1p8.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 34523 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002165-blbaqbo7 author: Wu, Dongdong title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice date: 2016-08-15 pages: extension: .txt txt: ./txt/cord-002165-blbaqbo7.txt cache: ./cache/cord-002165-blbaqbo7.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002165-blbaqbo7.txt' === file2bib.sh === id: cord-005607-b1a39hhw author: Bellingan, G title: Leukocytes: friend or foe date: 2000 pages: extension: .txt txt: ./txt/cord-005607-b1a39hhw.txt cache: ./cache/cord-005607-b1a39hhw.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005607-b1a39hhw.txt' === file2bib.sh === id: cord-006570-v4as5gde author: Sukhotnik, Igor title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat date: 2007-10-13 pages: extension: .txt txt: ./txt/cord-006570-v4as5gde.txt cache: ./cache/cord-006570-v4as5gde.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006570-v4as5gde.txt' === file2bib.sh === id: cord-006605-tsk3pakb author: Jesmin, Subrina title: Differential Expression, Time Course and Distribution of Four PARs in Rats with Endotoxin-induced Acute Lung Injury date: 2006-11-30 pages: extension: .txt txt: ./txt/cord-006605-tsk3pakb.txt cache: ./cache/cord-006605-tsk3pakb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006605-tsk3pakb.txt' === file2bib.sh === id: cord-004754-5596p4ma author: Duan, X. title: Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) date: 2014-04-06 pages: extension: .txt txt: ./txt/cord-004754-5596p4ma.txt cache: ./cache/cord-004754-5596p4ma.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004754-5596p4ma.txt' === file2bib.sh === id: cord-300912-w85t4zz6 author: Wu, Beibei title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils date: 2017-10-25 pages: extension: .txt txt: ./txt/cord-300912-w85t4zz6.txt cache: ./cache/cord-300912-w85t4zz6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-300912-w85t4zz6.txt' === file2bib.sh === id: cord-003055-88q36g00 author: Imai, Kenji title: Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date: 2018-06-15 pages: extension: .txt txt: ./txt/cord-003055-88q36g00.txt cache: ./cache/cord-003055-88q36g00.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-003055-88q36g00.txt' === file2bib.sh === id: cord-000217-chd9ezba author: Anas, Adam title: Role of CD14 in lung inflammation and infection date: 2010-03-09 pages: extension: .txt txt: ./txt/cord-000217-chd9ezba.txt cache: ./cache/cord-000217-chd9ezba.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000217-chd9ezba.txt' === file2bib.sh === id: cord-283427-fef9qsik author: Kim, Gwang-Ho title: Verification with the utility of an established rapid assessment of brain safety for newly developed vaccines date: 2019-11-29 pages: extension: .txt txt: ./txt/cord-283427-fef9qsik.txt cache: ./cache/cord-283427-fef9qsik.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-283427-fef9qsik.txt' === file2bib.sh === id: cord-004140-ujzrqzv3 author: Lu, Xiaying title: Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock date: 2020-01-13 pages: extension: .txt txt: ./txt/cord-004140-ujzrqzv3.txt cache: ./cache/cord-004140-ujzrqzv3.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004140-ujzrqzv3.txt' === file2bib.sh === id: cord-264145-73e61rlq author: Belančić, Andrej title: Gut microbiome dysbiosis and endotoxemia - Additional pathophysiological explanation for increased COVID-19 severity in obesity date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-264145-73e61rlq.txt cache: ./cache/cord-264145-73e61rlq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-264145-73e61rlq.txt' === file2bib.sh === id: cord-004282-tox3tuzz author: Capellini, Francesca Maria title: Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors date: 2019-12-04 pages: extension: .txt txt: ./txt/cord-004282-tox3tuzz.txt cache: ./cache/cord-004282-tox3tuzz.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004282-tox3tuzz.txt' === file2bib.sh === id: cord-001496-186k6t03 author: Yuan, Qing title: Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats date: 2014-12-05 pages: extension: .txt txt: ./txt/cord-001496-186k6t03.txt cache: ./cache/cord-001496-186k6t03.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-001496-186k6t03.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 32290 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-002079-jne14jqf author: MacParland, Sonya A. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 pages: extension: .txt txt: ./txt/cord-002079-jne14jqf.txt cache: ./cache/cord-002079-jne14jqf.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002079-jne14jqf.txt' === file2bib.sh === id: cord-280850-lku2g69k author: Zhang, Shidong title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits date: 2013-08-26 pages: extension: .txt txt: ./txt/cord-280850-lku2g69k.txt cache: ./cache/cord-280850-lku2g69k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-280850-lku2g69k.txt' === file2bib.sh === id: cord-012791-dyk5mr1q author: Zheng, Yong title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway date: 2019-09-25 pages: extension: .txt txt: ./txt/cord-012791-dyk5mr1q.txt cache: ./cache/cord-012791-dyk5mr1q.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-012791-dyk5mr1q.txt' === file2bib.sh === id: cord-103496-8tq78p2z author: Wang, Ting title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury date: 2020-11-13 pages: extension: .txt txt: ./txt/cord-103496-8tq78p2z.txt cache: ./cache/cord-103496-8tq78p2z.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-103496-8tq78p2z.txt' === file2bib.sh === id: cord-000984-64p3wpav author: Huang, Shang-Hui title: Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin date: 2013-06-10 pages: extension: .txt txt: ./txt/cord-000984-64p3wpav.txt cache: ./cache/cord-000984-64p3wpav.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000984-64p3wpav.txt' === file2bib.sh === id: cord-013067-sic08gsg author: Turzo, Maurizio title: Inhibition of overexpressed Kv3.4 augments HPV in endotoxemic mice date: 2020-10-08 pages: extension: .txt txt: ./txt/cord-013067-sic08gsg.txt cache: ./cache/cord-013067-sic08gsg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-013067-sic08gsg.txt' === file2bib.sh === id: cord-029488-l11ufs6k author: Tomita, Kengo title: Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-029488-l11ufs6k.txt cache: ./cache/cord-029488-l11ufs6k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-029488-l11ufs6k.txt' === file2bib.sh === id: cord-029969-1fa8hk2n author: Ge, Xin title: Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway date: 2020-08-01 pages: extension: .txt txt: ./txt/cord-029969-1fa8hk2n.txt cache: ./cache/cord-029969-1fa8hk2n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-029969-1fa8hk2n.txt' === file2bib.sh === id: cord-255578-0ltb9dpa author: Li, Xiangru title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 pages: extension: .txt txt: ./txt/cord-255578-0ltb9dpa.txt cache: ./cache/cord-255578-0ltb9dpa.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-255578-0ltb9dpa.txt' === file2bib.sh === id: cord-298646-wurzy88k author: van der Merwe, René title: Challenge models to assess new therapies in chronic obstructive pulmonary disease date: 2012-09-13 pages: extension: .txt txt: ./txt/cord-298646-wurzy88k.txt cache: ./cache/cord-298646-wurzy88k.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298646-wurzy88k.txt' === file2bib.sh === id: cord-311481-2awvmpyh author: Kosukegawa, Ima title: The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial date: 2020-01-14 pages: extension: .txt txt: ./txt/cord-311481-2awvmpyh.txt cache: ./cache/cord-311481-2awvmpyh.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-311481-2awvmpyh.txt' === file2bib.sh === id: cord-000959-nk2thkme author: Downer, Eric J. title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date: 2013-05-06 pages: extension: .txt txt: ./txt/cord-000959-nk2thkme.txt cache: ./cache/cord-000959-nk2thkme.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-000959-nk2thkme.txt' === file2bib.sh === id: cord-004067-psjyjvbu author: Zhou, Yile title: The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS date: 2019-12-26 pages: extension: .txt txt: ./txt/cord-004067-psjyjvbu.txt cache: ./cache/cord-004067-psjyjvbu.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-004067-psjyjvbu.txt' === file2bib.sh === id: cord-006778-qnxyhmw5 author: Chen, Xuxin title: Downregulation of Paralemmin-3 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating Inflammatory Response and Inhibiting Formation of TLR4/MyD88 and TLR4/TRIF Complexes date: 2017-08-12 pages: extension: .txt txt: ./txt/cord-006778-qnxyhmw5.txt cache: ./cache/cord-006778-qnxyhmw5.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006778-qnxyhmw5.txt' === file2bib.sh === id: cord-103592-lkngp2u6 author: Bachmaier, Kurt title: Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date: 2020-07-02 pages: extension: .txt txt: ./txt/cord-103592-lkngp2u6.txt cache: ./cache/cord-103592-lkngp2u6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-103592-lkngp2u6.txt' === file2bib.sh === id: cord-000425-isw6jeir author: Flori, Laurence title: Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date: 2011-07-29 pages: extension: .txt txt: ./txt/cord-000425-isw6jeir.txt cache: ./cache/cord-000425-isw6jeir.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000425-isw6jeir.txt' === file2bib.sh === id: cord-331887-kagggou1 author: liu, Chang title: An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury date: 2020-09-09 pages: extension: .txt txt: ./txt/cord-331887-kagggou1.txt cache: ./cache/cord-331887-kagggou1.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-331887-kagggou1.txt' === file2bib.sh === id: cord-310535-ay2cdf2w author: Cho, Chang-Won title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages date: 2017-06-20 pages: extension: .txt txt: ./txt/cord-310535-ay2cdf2w.txt cache: ./cache/cord-310535-ay2cdf2w.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-310535-ay2cdf2w.txt' === file2bib.sh === id: cord-005980-e2s0racp author: Wu, Xiaojing title: TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury date: 2019-09-05 pages: extension: .txt txt: ./txt/cord-005980-e2s0racp.txt cache: ./cache/cord-005980-e2s0racp.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 2 resourceName b'cord-005980-e2s0racp.txt' === file2bib.sh === id: cord-005875-yp1ehpeg author: Zhang, Dong title: Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways date: 2020-01-10 pages: extension: .txt txt: ./txt/cord-005875-yp1ehpeg.txt cache: ./cache/cord-005875-yp1ehpeg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-005875-yp1ehpeg.txt' === file2bib.sh === id: cord-285684-iiqyzqsb author: Li, Jin-ze title: Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier date: 2020-10-30 pages: extension: .txt txt: ./txt/cord-285684-iiqyzqsb.txt cache: ./cache/cord-285684-iiqyzqsb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-285684-iiqyzqsb.txt' === file2bib.sh === id: cord-002411-iiw878w8 author: Ding, Xibing title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 pages: extension: .txt txt: ./txt/cord-002411-iiw878w8.txt cache: ./cache/cord-002411-iiw878w8.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-002411-iiw878w8.txt' === file2bib.sh === OMP: Error #34: System unable to allocate necessary resources for OMP thread: OMP: System error #11: Resource temporarily unavailable OMP: Hint Try decreasing the value of OMP_NUM_THREADS. /data-disk/reader-compute/reader-cord/bin/file2bib.sh: line 39: 31565 Aborted $FILE2BIB "$FILE" > "$OUTPUT" === file2bib.sh === id: cord-261367-i1n8x0uc author: Hwang, Ji Young title: Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-261367-i1n8x0uc.txt cache: ./cache/cord-261367-i1n8x0uc.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-261367-i1n8x0uc.txt' === file2bib.sh === id: cord-296258-8pc2p3az author: Hwang, Eun-Ha title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation date: 2016-01-31 pages: extension: .txt txt: ./txt/cord-296258-8pc2p3az.txt cache: ./cache/cord-296258-8pc2p3az.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-296258-8pc2p3az.txt' === file2bib.sh === id: cord-337923-1vbkttzx author: Li, Xiao-Jun title: Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi date: 2019-02-21 pages: extension: .txt txt: ./txt/cord-337923-1vbkttzx.txt cache: ./cache/cord-337923-1vbkttzx.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-337923-1vbkttzx.txt' === file2bib.sh === id: cord-252859-zir02q69 author: Chung, T. Philip title: Molecular Diagnostics in Sepsis: From Bedside to Bench date: 2006-09-11 pages: extension: .txt txt: ./txt/cord-252859-zir02q69.txt cache: ./cache/cord-252859-zir02q69.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-252859-zir02q69.txt' === file2bib.sh === id: cord-007178-h0ordzm9 author: Felts, Paul A. title: Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide date: 2005-05-04 pages: extension: .txt txt: ./txt/cord-007178-h0ordzm9.txt cache: ./cache/cord-007178-h0ordzm9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-007178-h0ordzm9.txt' === file2bib.sh === id: cord-030385-btf502ju author: Sun, Zhiheng title: 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date: 2020-07-22 pages: extension: .txt txt: ./txt/cord-030385-btf502ju.txt cache: ./cache/cord-030385-btf502ju.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-030385-btf502ju.txt' === file2bib.sh === id: cord-257092-r11cgpvs author: Wu, Fengjiao title: CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation date: 2015-05-21 pages: extension: .txt txt: ./txt/cord-257092-r11cgpvs.txt cache: ./cache/cord-257092-r11cgpvs.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-257092-r11cgpvs.txt' === file2bib.sh === id: cord-013366-sbdtpsz6 author: Ramírez-Pérez, Sergio title: Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date: 2020-09-21 pages: extension: .txt txt: ./txt/cord-013366-sbdtpsz6.txt cache: ./cache/cord-013366-sbdtpsz6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013366-sbdtpsz6.txt' === file2bib.sh === id: cord-012487-s920s5wb author: Noga, Marek J. title: Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date: 2020-08-18 pages: extension: .txt txt: ./txt/cord-012487-s920s5wb.txt cache: ./cache/cord-012487-s920s5wb.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-012487-s920s5wb.txt' === file2bib.sh === id: cord-023935-o2ffxgnn author: Lorts, Angela title: Sepsis date: 2011-12-16 pages: extension: .txt txt: ./txt/cord-023935-o2ffxgnn.txt cache: ./cache/cord-023935-o2ffxgnn.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-023935-o2ffxgnn.txt' === file2bib.sh === id: cord-282336-zvc04s39 author: Choudhary, Ishita title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 pages: extension: .txt txt: ./txt/cord-282336-zvc04s39.txt cache: ./cache/cord-282336-zvc04s39.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-282336-zvc04s39.txt' === file2bib.sh === id: cord-001569-jd028cyg author: dos Santos, Gimena title: Vimentin regulates activation of the NLRP3 inflammasome date: 2015-03-12 pages: extension: .txt txt: ./txt/cord-001569-jd028cyg.txt cache: ./cache/cord-001569-jd028cyg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-001569-jd028cyg.txt' === file2bib.sh === id: cord-022136-3q24qxsr author: Maru, Yoshiro title: Explanation of Metastasis by Homeostatic Inflammation date: 2016-02-02 pages: extension: .txt txt: ./txt/cord-022136-3q24qxsr.txt cache: ./cache/cord-022136-3q24qxsr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-022136-3q24qxsr.txt' === file2bib.sh === id: cord-306577-gq6fss5l author: Hsueh, Wei title: Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date: 2002-11-11 pages: extension: .txt txt: ./txt/cord-306577-gq6fss5l.txt cache: ./cache/cord-306577-gq6fss5l.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-306577-gq6fss5l.txt' === file2bib.sh === id: cord-006279-ib5z3elq author: Ryter, Stefan W. title: Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance date: 2002 pages: extension: .txt txt: ./txt/cord-006279-ib5z3elq.txt cache: ./cache/cord-006279-ib5z3elq.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006279-ib5z3elq.txt' === file2bib.sh === id: cord-005872-w1x1i0im author: Volk, T. title: Endothelium function in sepsis date: 2000 pages: extension: .txt txt: ./txt/cord-005872-w1x1i0im.txt cache: ./cache/cord-005872-w1x1i0im.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-005872-w1x1i0im.txt' === file2bib.sh === id: cord-298224-flyx85lr author: Hibbitts, Alan J. title: In Vitro and In Vivo Assessment of PEGylated PEI for Anti-IL-8/CxCL-1 siRNA Delivery to the Lungs date: 2020-06-27 pages: extension: .txt txt: ./txt/cord-298224-flyx85lr.txt cache: ./cache/cord-298224-flyx85lr.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-298224-flyx85lr.txt' === file2bib.sh === id: cord-013840-mi3uf4vk author: Zhang, Wei title: The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation date: 2019-08-29 pages: extension: .txt txt: ./txt/cord-013840-mi3uf4vk.txt cache: ./cache/cord-013840-mi3uf4vk.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-013840-mi3uf4vk.txt' === file2bib.sh === id: cord-000137-idffrnac author: Xiang, Meng title: Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury date: 2009-11-02 pages: extension: .txt txt: ./txt/cord-000137-idffrnac.txt cache: ./cache/cord-000137-idffrnac.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-000137-idffrnac.txt' === file2bib.sh === id: cord-006700-df8ard9o author: Müller-Redetzky, Holger C. title: Dynamics of pulmonary endothelial barrier function in acute inflammation: mechanisms and therapeutic perspectives date: 2014-03-06 pages: extension: .txt txt: ./txt/cord-006700-df8ard9o.txt cache: ./cache/cord-006700-df8ard9o.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-006700-df8ard9o.txt' === file2bib.sh === id: cord-006318-9r51n241 author: Sideras, Paschalis title: Activin, neutrophils, and inflammation: just coincidence? date: 2013-02-06 pages: extension: .txt txt: ./txt/cord-006318-9r51n241.txt cache: ./cache/cord-006318-9r51n241.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 3 resourceName b'cord-006318-9r51n241.txt' === file2bib.sh === id: cord-015082-l629n8is author: nan title: Poster Sessions 323-461 date: 2002-08-29 pages: extension: .txt txt: ./txt/cord-015082-l629n8is.txt cache: ./cache/cord-015082-l629n8is.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 4 resourceName b'cord-015082-l629n8is.txt' === file2bib.sh === id: cord-032181-gmcugd8h author: Song, Jian-Xin title: Main Complications of AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 pages: extension: .txt txt: ./txt/cord-032181-gmcugd8h.txt cache: ./cache/cord-032181-gmcugd8h.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-032181-gmcugd8h.txt' === file2bib.sh === id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 pages: extension: .txt txt: ./txt/cord-015147-h0o0yqv8.txt cache: ./cache/cord-015147-h0o0yqv8.txt Content-Encoding ISO-8859-1 Content-Type text/plain; charset=ISO-8859-1 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 6 resourceName b'cord-015147-h0o0yqv8.txt' === file2bib.sh === id: cord-014996-p6q0f37c author: nan title: Posters_Monday_12 October 2009 date: 2009-08-06 pages: extension: .txt txt: ./txt/cord-014996-p6q0f37c.txt cache: ./cache/cord-014996-p6q0f37c.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-014996-p6q0f37c.txt' === file2bib.sh === id: cord-005727-li8pwigg author: nan title: ESICM 2010 MONDAY SESSIONS 11 October 2010 date: 2010-08-31 pages: extension: .txt txt: ./txt/cord-005727-li8pwigg.txt cache: ./cache/cord-005727-li8pwigg.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 21 resourceName b'cord-005727-li8pwigg.txt' === file2bib.sh === id: cord-005497-w81ysjf9 author: nan title: 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium. 24-27 March 2020 date: 2020-03-24 pages: extension: .txt txt: ./txt/cord-005497-w81ysjf9.txt cache: ./cache/cord-005497-w81ysjf9.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 8 resourceName b'cord-005497-w81ysjf9.txt' === file2bib.sh === id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 pages: extension: .txt txt: ./txt/cord-006229-7yoilsho.txt cache: ./cache/cord-006229-7yoilsho.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 38 resourceName b'cord-006229-7yoilsho.txt' === file2bib.sh === id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 pages: extension: .txt txt: ./txt/cord-006230-xta38e7j.txt cache: ./cache/cord-006230-xta38e7j.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 26 resourceName b'cord-006230-xta38e7j.txt' === file2bib.sh === id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 pages: extension: .txt txt: ./txt/cord-023026-2r84ndzv.txt cache: ./cache/cord-023026-2r84ndzv.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 9 resourceName b'cord-023026-2r84ndzv.txt' === file2bib.sh === /data-disk/reader-compute/reader-cord/bin/file2bib.sh: fork: retry: No child processes id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 pages: extension: .txt txt: ./txt/cord-015021-pol2qm74.txt cache: ./cache/cord-015021-pol2qm74.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 16 resourceName b'cord-015021-pol2qm74.txt' === file2bib.sh === id: cord-005814-ak5pq312 author: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 pages: extension: .txt txt: ./txt/cord-005814-ak5pq312.txt cache: ./cache/cord-005814-ak5pq312.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 16 resourceName b'cord-005814-ak5pq312.txt' === file2bib.sh === id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 pages: extension: .txt txt: ./txt/cord-022888-dnsdg04n.txt cache: ./cache/cord-022888-dnsdg04n.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 12 resourceName b'cord-022888-dnsdg04n.txt' === file2bib.sh === id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 pages: extension: .txt txt: ./txt/cord-015394-uj7fe5y6.txt cache: ./cache/cord-015394-uj7fe5y6.txt Content-Encoding UTF-8 Content-Type text/plain; charset=UTF-8 X-Parsed-By ['org.apache.tika.parser.DefaultParser', 'org.apache.tika.parser.csv.TextAndCSVParser'] X-TIKA:content_handler ToTextContentHandler X-TIKA:embedded_depth 0 X-TIKA:parse_time_millis 32 resourceName b'cord-015394-uj7fe5y6.txt' Que is empty; done keyword-lps-cord === reduce.pl bib === id = cord-002165-blbaqbo7 author = Wu, Dongdong title = Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice date = 2016-08-15 pages = extension = .txt mime = text/plain words = 4744 sentences = 281 flesch = 50 summary = title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. A previous study conducted by our group observed caspase-1 activation in AMs during the development of ALI/ ARDS, and further, that treatment with a specific caspase-1 inhibitor has been shown to reduce LPS-induced lung injury in mice (8) . In the present study, we showed that the absence of IRF-1 in genetic knockout mice strongly alleviates LPS-induced lung injury and abrogates its pyroptotic effects in AMs. These findings suggest that IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation, which is, in turn, a TLR4-dependent process. cache = ./cache/cord-002165-blbaqbo7.txt txt = ./txt/cord-002165-blbaqbo7.txt === reduce.pl bib === id = cord-000460-h3owwjao author = Xiong, Jing title = Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date = 2011-09-26 pages = extension = .txt mime = text/plain words = 4313 sentences = 212 flesch = 41 summary = However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. cache = ./cache/cord-000460-h3owwjao.txt txt = ./txt/cord-000460-h3owwjao.txt === reduce.pl bib === id = cord-009753-6rg47f0i author = Legband, Nathan title = The Treatment of Acute Respiratory Distress Syndrome in Rats With a Peritoneal Dosing System date = 2015-06-01 pages = extension = .txt mime = text/plain words = 1278 sentences = 78 flesch = 52 summary = Current medical treatments for conditions involving an impaired respiratory system provide inefficient methods of delivering oxygen to the patient. Previously, we have shown that peritoneal membrane oxygenation (PMO) with OMBs is a possible treatment method in acute lung injury models [2] . Our study involves two phases: (1) development and characterization of the ARDS disease model in rats; (2) design and validation of ambulatory infusion device. Phase 2 is the development of an ambulatory delivery system that will infuse fluid to the rat's peritoneal cavity for treatment. We expect to be able to continuously dose saline, inert gas microbubbles (IMBs), and OMBs into the peritoneal cavity of four animals with the current PDS design. Based upon our previous animal experiments with lung injuries, we anticipate improved pulse oximetry, blood gases, and survivability in rats provided OMBs compared to those administered saline or IMBs. Intratracheal Aerosolization of Endotoxin (LPS) in the Rat: A Comprehensive Animal Model to Study Adult (Acute) Respiratory Distress Syndrome cache = ./cache/cord-009753-6rg47f0i.txt txt = ./txt/cord-009753-6rg47f0i.txt === reduce.pl bib === id = cord-000217-chd9ezba author = Anas, Adam title = Role of CD14 in lung inflammation and infection date = 2010-03-09 pages = extension = .txt mime = text/plain words = 5544 sentences = 263 flesch = 45 summary = Furthermore, intratracheal treatment of CD14-defi cient mice with sCD14 restored the infl ammatory response to the level present in wildtype mice, whereas treatment with wild-type alveolar macrophages restored the neutrophil infi ltration of the lung but not pulmonary TNF release [26] . Th ese fi ndings indicate that sCD14, and CD14 and TLR4 on the surface of alveolar macrophages contribute to the development of LPS-induced lung infl ammation. In line with the fi ndings that CD14 contributes to LPSinduced lung infl ammation in mice, a number of studies have shown that CD14 is essential for the host defense response in the lung against Gram-negative bacteria, such as nontypeable Haemophilus infl uenzae, a possible cause of community acquired pneumonia, and A. coli-induced pneumonia has not been investigated in mice, whereas the role of the other components of the LPS receptor complex (TLR4, MD-2, MyD88, TRIF) has been determined using gene-defi cient or mutant mice. cache = ./cache/cord-000217-chd9ezba.txt txt = ./txt/cord-000217-chd9ezba.txt === reduce.pl bib === id = cord-003055-88q36g00 author = Imai, Kenji title = Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date = 2018-06-15 pages = extension = .txt mime = text/plain words = 6212 sentences = 313 flesch = 41 summary = The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure. cache = ./cache/cord-003055-88q36g00.txt txt = ./txt/cord-003055-88q36g00.txt === reduce.pl bib === id = cord-003099-a0acr28o author = Koch, R. M. title = The endotoxin-induced pulmonary inflammatory response is enhanced during the acute phase of influenza infection date = 2018-07-05 pages = extension = .txt mime = text/plain words = 3883 sentences = 194 flesch = 39 summary = In vitro studies in which influenza-infected alveolar macrophages were subsequently stimulated with bacterial lipopolysaccharide (LPS), a bacterial compound that induces a profound innate immune response, revealed increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 [4] [5] [6] [7] [8] , indicative of a priming effect on these cells by influenza. Likewise, murine influenza infection resulted in increased levels of pro-inflammatory cytokines in both plasma and lungs, and enhanced pulmonary neutrophil influx upon pneumococcal infection 7 days later [10] . In the present study, we demonstrate that a systemic LPS challenge in the acute phase of influenza infection (4 days post-infection) results in an enhanced pulmonary, but not systemic pro-inflammatory cytokine response. Our results are in accordance with in vitro data reporting a cellular priming effect of influenza observed upon secondary stimulation with LPS [4] [5] [6] [7] [8] , as well as with other murine in vivo studies that report increased inflammation and pulmonary neutrophil influx or sequestration upon a secondary bacterial infection or LPS challenge in the acute phase of influenza infection [9, 10] . cache = ./cache/cord-003099-a0acr28o.txt txt = ./txt/cord-003099-a0acr28o.txt === reduce.pl bib === id = cord-000425-isw6jeir author = Flori, Laurence title = Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date = 2011-07-29 pages = extension = .txt mime = text/plain words = 7831 sentences = 388 flesch = 46 summary = A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M. cache = ./cache/cord-000425-isw6jeir.txt txt = ./txt/cord-000425-isw6jeir.txt === reduce.pl bib === id = cord-006778-qnxyhmw5 author = Chen, Xuxin title = Downregulation of Paralemmin-3 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating Inflammatory Response and Inhibiting Formation of TLR4/MyD88 and TLR4/TRIF Complexes date = 2017-08-12 pages = extension = .txt mime = text/plain words = 8483 sentences = 576 flesch = 56 summary = Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. Adult Wistar rats (n = 6 per group) were treated as described in the BMaterials and Methods^section BEstablishment of ALI Rat Model and Experimental Design.^At 24 h after LPS challenge, the right lungs were harvested and stored in liquid nitrogen for the analysis of NF-κB phospho-p65, phospho-IRF3, TLR4, MyD88, TRIF, suppressor of cytokine signaling 3 (SOCS3) protein levels and coimmunoprecipitation assay, and the left lungs were harvested for the analysis of lung wet/dry weight ratio. cache = ./cache/cord-006778-qnxyhmw5.txt txt = ./txt/cord-006778-qnxyhmw5.txt === reduce.pl bib === id = cord-000920-68eblcke author = Gallego, Carolina title = Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium date = 2013-03-11 pages = extension = .txt mime = text/plain words = 4557 sentences = 233 flesch = 40 summary = The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. Bordetella bronchiseptica is a Gram-negative bacterium capable of colonizing the respiratory tract of a large range of mammalian hosts, including mice, rats, guinea pigs, rabbits, cats, dogs, pigs, sheep, horses, and bears [1] . bronchiseptica or its LPS in an isolated manner by using a model that more closely reflects the in vivo conditions (i.e., reconstructing the architecture and cell relationships of the respiratory epithelium in a natural host of this microorganism) has not been documented. In this work, LPS induced a higher infiltration of PMN in the respiratory epithelium and the propria of nasal septa than did the bacterium. B. bronchiseptica and its LPS distribution on the nasal septum respiratory epithelium were evaluated by the indirect immunoperoxidase and lectin histochemistry techniques. cache = ./cache/cord-000920-68eblcke.txt txt = ./txt/cord-000920-68eblcke.txt === reduce.pl bib === id = cord-007178-h0ordzm9 author = Felts, Paul A. title = Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide date = 2005-05-04 pages = extension = .txt mime = text/plain words = 9492 sentences = 425 flesch = 47 summary = At this interval the lesion was clearly discernible using differential interference contrast optics as a region of tissue disruption in the dorsal funiculus, allowing AdPC-positive cells to be counted in both demyelinated and apparently normal areas of the dorsal funiculus of LPS-injected animals. Spinal cords injected with saline ( Fig. 1) showed damage restricted to a very small number of axons undergoing either Table 1 Populations of inflammatory cells present in the spinal cord at various times following the injection of LPS or saline into the dorsal funiculus Wallerian degeneration or demyelination. The cells were often adjacent to large blood vessels, and they formed only a small subset of the substantial population of ED1-positive Fig. 7 Light micrographs showing GFAP immunoreactivity at the interface between the dorsal funiculus (DF) and the grey matter (GM) in an animal 7 days after the injection of LPS into the spinal cord. cache = ./cache/cord-007178-h0ordzm9.txt txt = ./txt/cord-007178-h0ordzm9.txt === reduce.pl bib === id = cord-012828-wsjob1p8 author = Wang, Yan-hang title = Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway date = 2019-09-10 pages = extension = .txt mime = text/plain words = 4218 sentences = 256 flesch = 41 summary = We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Some previous research has suggested that spinal cord injury induces inflammatory cytokine production by activating the nucleotide-binding domain-like receptor protein 3 inflammasome pathway, which is significantly suppressed by DRD1 agonists [14] . Therefore, in this study, we explored the mechanism of the anti-neuroinflammatory effects of isosibiricin in a BV-2 microglial model and highlighted that isosibiricin can significantly inhibit the production of multiple inflammatory mediators induced by bacterial lipopolysaccharide stimulation via targeting the DRD1/D2-dependent inflammasome pathway, providing a potential therapeutic strategy for inflammation-related neurological disorders. Isosibiricin inhibits the NLRP3/caspase-1 inflammasome pathway in LPS-or nigericin-treated BV-2 cells and LPS-treated Balb/c mice It has been reported that the expression of the pro-inflammatory mediator IL-1β significantly increases in DRD2-null mice compared with wild-type mice [24] . cache = ./cache/cord-012828-wsjob1p8.txt txt = ./txt/cord-012828-wsjob1p8.txt === reduce.pl bib === id = cord-001496-186k6t03 author = Yuan, Qing title = Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats date = 2014-12-05 pages = extension = .txt mime = text/plain words = 5022 sentences = 262 flesch = 44 summary = Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules. The goal of the present study was to clarify the effects of Ginsenoside Rb1 on LPS-induced rat lung injury and analyzed the detailed molecular mechanisms in vivo and in vitro. cache = ./cache/cord-001496-186k6t03.txt txt = ./txt/cord-001496-186k6t03.txt === reduce.pl bib === id = cord-006285-kkxdmzk9 author = Smirnova, S. S. title = Long-Term Maintenance of the Functional Changes Induced by Influenza A Virus and/or LPS in Human Endothelial ECV-304 Cell Sublines date = 2019-08-26 pages = extension = .txt mime = text/plain words = 4686 sentences = 175 flesch = 43 summary = The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The comparative study of the human endothelial ECV-304 cell sublines carried out in the present work and in our previous work (Smirnova et al., 2018) has demonstrated that the infection of nonpermissive cells with influenza A virus (both in high and in very low doses) and exposure to LPS can change migratory, proliferation, and apoptotic activity of cells and impair cell barrier function. cache = ./cache/cord-006285-kkxdmzk9.txt txt = ./txt/cord-006285-kkxdmzk9.txt === reduce.pl bib === === reduce.pl bib === id = cord-002079-jne14jqf author = MacParland, Sonya A. title = Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date = 2016-05-27 pages = extension = .txt mime = text/plain words = 7182 sentences = 388 flesch = 48 summary = Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) . cache = ./cache/cord-002079-jne14jqf.txt txt = ./txt/cord-002079-jne14jqf.txt === reduce.pl bib === id = cord-022136-3q24qxsr author = Maru, Yoshiro title = Explanation of Metastasis by Homeostatic Inflammation date = 2016-02-02 pages = extension = .txt mime = text/plain words = 12045 sentences = 615 flesch = 45 summary = Treatment of B16 melanoma cells with lipopolysaccharide (LPS) or lipid A at 1 μg/ ml each for 48 h, which induced CCL2 expression, followed by extensive washing and subcutaneous implantation, reduced the tumor growth compared with untreated B16 cells in both wild-type and TLR4-KO mice. Expression of endogenous ligands, such as S100A8 and SAA3, in endothelial cells in sterile premetastatic lungs is induced by primary tumor-derived growth factors, such as CCL2, from the circulation side and the paracrine signaling goes in an opposite direction from the circulation to airway side to result in amplification of SAA3 in club cells. Detailed analysis of stimulation and expression pattern of S100A8, SAA3, and TNFα revealed that the triggering mechanism is primary tumor-secreted CCL2 that activates CCR2 in the hyperpermeable regions in the lungs to induce S100A8 expression in the endothelial cells. cache = ./cache/cord-022136-3q24qxsr.txt txt = ./txt/cord-022136-3q24qxsr.txt === reduce.pl bib === id = cord-006605-tsk3pakb author = Jesmin, Subrina title = Differential Expression, Time Course and Distribution of Four PARs in Rats with Endotoxin-induced Acute Lung Injury date = 2006-11-30 pages = extension = .txt mime = text/plain words = 4505 sentences = 223 flesch = 43 summary = The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. Here, we also found that LPS induces increases in the protein expression of PARs isoforms 1 to 4 in the lung of rats. While our previous study demonstrated the immunolocalization of PAR-1 in these cells and tissues in LPS-treated rabbits, the present study showed strong immunoreactivities for all isoforms of PARs in the endothelium, alveolar epithelium, and lung macrophages using a rat model of ALI [10] . cache = ./cache/cord-006605-tsk3pakb.txt txt = ./txt/cord-006605-tsk3pakb.txt === reduce.pl bib === id = cord-029969-1fa8hk2n author = Ge, Xin title = Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway date = 2020-08-01 pages = extension = .txt mime = text/plain words = 4669 sentences = 291 flesch = 54 summary = Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically. Mechanism studies showed that the activation of HMGB1/TLRs/NF-κB pathway induced by LPS increased inflammatory responses and oxidative stress, while its blockade by lycorine effectively suppressed pulmonary inflammatory response and oxidative stress, and further alleviated lung injury. cache = ./cache/cord-029969-1fa8hk2n.txt txt = ./txt/cord-029969-1fa8hk2n.txt === reduce.pl bib === id = cord-006570-v4as5gde author = Sukhotnik, Igor title = Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat date = 2007-10-13 pages = extension = .txt mime = text/plain words = 4069 sentences = 206 flesch = 44 summary = title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPSanimals. The purpose of this study was to evaluate the effects of oral insulin in preventing mucosal damage caused by LPS endotoxemia in a rat model, including its effect on enterocyte proliferation and death via apoptosis, and to determine whether alterations in Toll-like receptor 4-mediated signaling may occur during LPS endotoxemia and insulin administration. Oral insulin increases the stimulating effect of LPS on Toll-like receptor 4 expression in the proximal intestine, suggesting that TLR4 is not the mediator of injury in this model. cache = ./cache/cord-006570-v4as5gde.txt txt = ./txt/cord-006570-v4as5gde.txt === reduce.pl bib === id = cord-000137-idffrnac author = Xiang, Meng title = Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury date = 2009-11-02 pages = extension = .txt mime = text/plain words = 9097 sentences = 456 flesch = 40 summary = The study further found that the induction of the negative regulators of TLR signaling IL-1R-associated kinase-M, Toll-interacting protein and A20 by intratracheal LPS in vivo and in macrophages in vitro was significantly reduced in CD44 -/mice. Thus, the study demonstrates a novel mechanism underlying HS-augmented lung inflammation, namely that induction of increased TLR2 surface expression in lung endothelial cells, which is induced by HS/R and mediated by HMGB1 activation of TLR4 signaling, is an important mechanism responsible for EC-mediated inflammation and organ injury following HS (122) . These results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and suggest a fundamental paradigm of how tissue stress and injury are monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response (147) . cache = ./cache/cord-000137-idffrnac.txt txt = ./txt/cord-000137-idffrnac.txt === reduce.pl bib === id = cord-103496-8tq78p2z author = Wang, Ting title = RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury date = 2020-11-13 pages = extension = .txt mime = text/plain words = 5855 sentences = 302 flesch = 45 summary = title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y32, preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. We anticipate that a successful clinical efficacy of NipR2 or similar product might require: 1) precision medicine approach to identify patients in the sub-group with satisfactory responsiveness of Rac1 nitration blockade, as not all triggers of ALI (e.g., trauma) will lead to endothelial oxidative stress and peroxynitrite generation; 2) combination therapy with other effective reagents, including suppressor of the cytokine storm and/or neutrophil eliminators; 3) cache = ./cache/cord-103496-8tq78p2z.txt txt = ./txt/cord-103496-8tq78p2z.txt === reduce.pl bib === === reduce.pl bib === id = cord-004754-5596p4ma author = Duan, X. title = Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) date = 2014-04-06 pages = extension = .txt mime = text/plain words = 4875 sentences = 252 flesch = 50 summary = title: Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) To evaluate the effect of maturation of monocytes/macrophages on their susceptibility to PRRSV, freshly isolated AMf, PMf and BMo from ®ve donors were seeded in 24-well tissue culture plates at a concentration of 10 6 cells/ml/well and further incubated in RPMI medium plus 5% of foetal bovine serum at 37 C with 5% CO 2 . The virus titres and percentage of viral antigen positive cells in freshly isolated porcine AMf at 24 and 48 h after inoculation were respectively 1 to 2 log 10 TCID 50 and 5 to 10 times lower than those of one day cultivated ones, which is signi®cantly different (P'0.01). Porcine reproductive and respiratory syndrome virus infection of alveolar macrophages can be blocked by monoclonal antibodies against cell surface surface antigens cache = ./cache/cord-004754-5596p4ma.txt txt = ./txt/cord-004754-5596p4ma.txt === reduce.pl bib === id = cord-032564-0t5lr4z9 author = Moin, Abu Saleh Md title = Pro-fibrotic M2 macrophage markers may increase the risk for COVID19 in type 2 diabetes with obesity()() date = 2020-09-16 pages = extension = .txt mime = text/plain words = 1052 sentences = 62 flesch = 44 summary = 5 We report here that LPS-related markers were associated with activated lung alveolar M2 macrophages in OT2D, with a reduction in plasma LBP as a surrogate marker of circulatory LPS elevation. Elevated plasma levels of TGF-β1, PDGF-β, MMP7 and MMP9 determined early in the course of COVID19 infection in a patient with OT2D may indicate potential risk for more severe disease. Moreover, it is also possible that, apart from alveolar macrophages, other cellular sources, for example lung epithelial cells [16] , arterial smooth muscle cells [17] , epithelial cells of glandular tissues like prostate [18] or bile duct epithelia [19] , might contribute to LPS-induced elevated plasma levels of those pro-fibrotic markers. In conclusion, in OT2D the lung epithelial barrier integrity is likely destabilized in response to fibroproliferative activity of elevated TGF-β1, PDGF-β, MMP7 or MMP9 derived from lung alveolar macrophages, increasing vulnerability to inhaled pathogens. cache = ./cache/cord-032564-0t5lr4z9.txt txt = ./txt/cord-032564-0t5lr4z9.txt === reduce.pl bib === id = cord-006700-df8ard9o author = Müller-Redetzky, Holger C. title = Dynamics of pulmonary endothelial barrier function in acute inflammation: mechanisms and therapeutic perspectives date = 2014-03-06 pages = extension = .txt mime = text/plain words = 10609 sentences = 582 flesch = 32 summary = However, upon infectious or sterile inflammatory stimulation via either the alveolar (e.g., in pneumonia and mechanical ventilation) or the vascular lumen (e.g., in bacteremia and sepsis), pulmonary endothelial barrier homeostasis may be disturbed, resulting in increased permeability, protein-rich fluid extravasation, lung oedema and finally acute respiratory distress syndrome (ARDS) with mortality rates ranging from 27 to 45 % depending on severity (Ranieri, et al. Although the underlying mechanisms of leukocyte mediated barrier failure are of highest scientific interest, therapeutic interference to ameliorate acute lung injury by depletion or blocking of cell recruitment should raise concerns as neutrophils and monocytes are key players of pulmonary and systemic innate immune responses and therapeutic intervention at this level might leave the patient functionally immunosuppressed. In mice, Ang-1-induced Tie-2 receptor phosphorylation stimulated the p190RhoGTPaseactivating protein (p190RhoGAP) via PI3-kinase and Rac1 to inactivate RhoA, resulting in reduced F-actin stress fibre formation and diminished endothelial permeability (Mammoto et al. cache = ./cache/cord-006700-df8ard9o.txt txt = ./txt/cord-006700-df8ard9o.txt === reduce.pl bib === id = cord-283427-fef9qsik author = Kim, Gwang-Ho title = Verification with the utility of an established rapid assessment of brain safety for newly developed vaccines date = 2019-11-29 pages = extension = .txt mime = text/plain words = 3699 sentences = 213 flesch = 54 summary = In our previous study, we established of minimal positive control conditions to ensure brain safety using experimental mice models during development of urgent vaccines before introducing to markets. In this study, we described that this module can be useful in applying a commercially available vaccine to a rapid and effective positive-control for brain safety assessment of an urgent vaccine. In brief, evidences for the BBB damage by commercially available vaccines (killed porcine genital respiratory syndrome vaccine vaccine and live canine parvovirus vaccine) were based on Evans blue EB permeability into brain parenchyma and mRNA expression of tight junctions (ZO-1 and Occludin) in the brain. However, when 2-fold concentrations of two vaccines stock solutions were injected, occludin mRNA expression was increased compared to the PBS group, but not significantly. In the present study, we confirmed that these established conditions and modules of the positive control that destroyed the BBB could be used to assess brain safety of commercial vaccines [1] . cache = ./cache/cord-283427-fef9qsik.txt txt = ./txt/cord-283427-fef9qsik.txt === reduce.pl bib === id = cord-298224-flyx85lr author = Hibbitts, Alan J. title = In Vitro and In Vivo Assessment of PEGylated PEI for Anti-IL-8/CxCL-1 siRNA Delivery to the Lungs date = 2020-06-27 pages = extension = .txt mime = text/plain words = 11340 sentences = 633 flesch = 56 summary = Following optimization with antiglyceraldehyde 3-phosphate dehydrogenase (GAPDH) siRNA, PEI and PEI-LPEG anti-IL8 siRNA nanoparticles were assessed for efficacy using polarised Calu-3 human airway epithelial cells and a twin stage impinger (TSI) in vitro lung model. This work demonstrates the potential of nebulised PEI-PEG siRNA nanoparticles in modulating pulmonary inflammation and highlights the need to move towards more relevant in vitro and in vivo models for respiratory drug development. In contrast, the nebulised PEI-LPEG siRNA nanoparticles demonstrated significantly greater levels of GAPDH knockdown versus the PBS-treated controls at higher doses. Using the differential cell staining of BAL samples with Eosin Y and azur/methylene blue, it was In the case of the PEI-LPEG siRNA nanoparticle-treated groups, both the non-targeting (NT) and anti-CXCL-1 siRNA-treated groups demonstrated 10-fold decreases in the CXCL-1 gene expression compared to the PBS-LPS samples (4-vs. cache = ./cache/cord-298224-flyx85lr.txt txt = ./txt/cord-298224-flyx85lr.txt === reduce.pl bib === id = cord-000984-64p3wpav author = Huang, Shang-Hui title = Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin date = 2013-06-10 pages = extension = .txt mime = text/plain words = 5252 sentences = 291 flesch = 54 summary = We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. Additionally, rCRT/39-272, a prokaryotically-expressed murine CRT fragment covering amino acid residues 39-272 fused with an N-terminal His-tag, was extraordinarily potent in activating B cells and macrophages in vitro and also in eliciting specific Ab production in mice [16] . The sequence of rCRT/39-272 encompasses most of the globular N domain (aa residues , and we have previously shown that it possess lectin-like activity (selective binding with polysaccharides including carrageenan, alginic acids, and hyaluronic acids in ELISAs) [16] , implying that the prokaryotically expressed recombinant polypeptide retained the lectin activity of CRT. Purified nCRT, but not BSA or recombinant enhanced green fluorescence protein (rEGFP, 28 kDa with a His-tag), was positively recognized by CRT-Abs. As evidenced by native PAGE analysis, a substantial amount of rCRT/18-412 formed higher-molecular-weight oligomers, whilst nCRT existed mostly in monomeric form (Figs. cache = ./cache/cord-000984-64p3wpav.txt txt = ./txt/cord-000984-64p3wpav.txt === reduce.pl bib === id = cord-004282-tox3tuzz author = Capellini, Francesca Maria title = Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors date = 2019-12-04 pages = extension = .txt mime = text/plain words = 4327 sentences = 280 flesch = 57 summary = Therefore, the aims of our study were to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation, as well as to evaluate the ability of this cell line to respond to infectious or non-infectious stressors. However, little is known about basal expression of genes involved in innate immunity, DNA repair, cell cycle regulation, as well as in the secretion of cytokines, and the response to infectious and non-infectious stressors. Owing to the above, the aims of our study were: 1-to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation. Moreover, in our previous study we demonstrated the ability of this heavy metal to modulate innate immune responses in IPEC-J2 cells as a function of both time and concentration (Razzuoli et al. cache = ./cache/cord-004282-tox3tuzz.txt txt = ./txt/cord-004282-tox3tuzz.txt === reduce.pl bib === id = cord-023935-o2ffxgnn author = Lorts, Angela title = Sepsis date = 2011-12-16 pages = extension = .txt mime = text/plain words = 11110 sentences = 510 flesch = 38 summary = SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. cache = ./cache/cord-023935-o2ffxgnn.txt txt = ./txt/cord-023935-o2ffxgnn.txt === reduce.pl bib === id = cord-004067-psjyjvbu author = Zhou, Yile title = The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS date = 2019-12-26 pages = extension = .txt mime = text/plain words = 5176 sentences = 333 flesch = 48 summary = Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. In the current study, the p110α isoform in PI3K/AKT/mTOR signalling pathway was demonstrated to be involved in miR-21a-3p-mediated angiogenic factor induction in TCs. However, the alteration of other protein levels and HIF-1α in TCs treated with LPS and the miR-21a-3p inhibitor indicated that more complex signalling pathways were involved in regulating the angiogenic function of TCs. Culture medium from LPS-induced TCs promoted EOMA cells proliferation in vitro, accompanied by elevated levels of VEGF mRNA and secretion, which further demonstrated that the functional miR-21a-3p was generated by TCs. These data support the hypothesis that miR-21a-3p plays a role in angiogenesis and profoundly demonstrate the mechanisms mediated by PI3K p110α. cache = ./cache/cord-004067-psjyjvbu.txt txt = ./txt/cord-004067-psjyjvbu.txt === reduce.pl bib === id = cord-006318-9r51n241 author = Sideras, Paschalis title = Activin, neutrophils, and inflammation: just coincidence? date = 2013-02-06 pages = extension = .txt mime = text/plain words = 12965 sentences = 546 flesch = 32 summary = During the 26 years that have elapsed since its discovery, activin-A, a member of the transforming growth factor β super-family originally discovered from its capacity to stimulate follicle-stimulating hormone production by cultured pituitary gonadotropes, has been established as a key regulator of various fundamental biological processes, such as development, homeostasis, inflammation, and tissue remodeling. [92] that prophylactic and therapeutic treatment with follistatin could improve the survival rate of mice in three mouse colitis models, attenuate several pathology-associated parameters and upregulate proliferation of intestinal epithelial cells and tissue repair, improving thus the barrier function of the colonic mucosa, strongly supported the association between activin-A and colitis pathophysiology [92] . The combination of aggravated innate immunity, activation of the coagulation system, and alterations in molecular systems crucial for homeostasis, such as the surfactants in the lung, can collectively lead to acute necroptotic cell death which leads to the release of highly pro-inflammatory complexes of DAMPs and cytokines that can activate via a feed-forward like response further activation of the TLR signaling pathway and further production of activin-A. cache = ./cache/cord-006318-9r51n241.txt txt = ./txt/cord-006318-9r51n241.txt === reduce.pl bib === id = cord-005607-b1a39hhw author = Bellingan, G title = Leukocytes: friend or foe date = 2000 pages = extension = .txt mime = text/plain words = 3827 sentences = 173 flesch = 37 summary = Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation.¶The body relies on the inflammatory response for protection. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage.¶It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. Endothelial cells, mesothelial cells, fibroblasts and epithelial cells are also all involved not only with their capacity to drive the inflammatory response through mediator generation but also in innate immune defences including through the production of antimicrobial proteins. cache = ./cache/cord-005607-b1a39hhw.txt txt = ./txt/cord-005607-b1a39hhw.txt === reduce.pl bib === id = cord-255578-0ltb9dpa author = Li, Xiangru title = Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date = 2020-06-19 pages = extension = .txt mime = text/plain words = 6400 sentences = 404 flesch = 55 summary = title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. In this study, Cfhr1 was deleted on C57BL/6 mouse to study the function of FHR-E on AP and the effect of FHR-E deficiency on LPS-induced sepsis. cache = ./cache/cord-255578-0ltb9dpa.txt txt = ./txt/cord-255578-0ltb9dpa.txt === reduce.pl bib === id = cord-005832-p1joajvn author = Liu, Zhicheng title = Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice date = 2013-02-23 pages = extension = .txt mime = text/plain words = 3087 sentences = 186 flesch = 53 summary = The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. CONCLUSION: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. The results showed that pretreatment with gossypol attenuated lung damage induced by LPS and decreased the W/D ratio, proinflammatory cytokine production, inflammatory cell migration into the lung, protein leakage, the activation of NF-jB and MAPK. In conclusion, the present study demonstrated that gossypol has a protective effect against LPS-induced ALI, which may be related to its suppression of NF-jB and MAPKs activation, and subsequently leads to the reduction the inflammatory cell infiltration and proinflammatory cytokine expression in lung tissues. cache = ./cache/cord-005832-p1joajvn.txt txt = ./txt/cord-005832-p1joajvn.txt === reduce.pl bib === id = cord-029488-l11ufs6k author = Tomita, Kengo title = Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date = 2020-07-21 pages = extension = .txt mime = text/plain words = 5094 sentences = 264 flesch = 45 summary = Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. We thus examined whether expression of VEGF in human pulmonary microvascular endothelial cells is regulated by MAPKs. When HPMEC-ST1.6R cells were treated with PD98059, an inhibitor of MAPK kinase which is an ERK1/2 upstream activator, or SB203580, which is widely used as a specific inhibitor of p38 MAPK, the LPS/IFN-γinduced increase in VEGF protein levels was strongly blocked (Fig. 4b) . cache = ./cache/cord-029488-l11ufs6k.txt txt = ./txt/cord-029488-l11ufs6k.txt === reduce.pl bib === id = cord-300912-w85t4zz6 author = Wu, Beibei title = n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils date = 2017-10-25 pages = extension = .txt mime = text/plain words = 3699 sentences = 224 flesch = 50 summary = title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils Our previous study investigated the effect of n-butanol extract from Folium isatidis on lipopolysaccharide (LPS)-induced septic shock. The addition of n-butanol extract from Folium isatidis inhibited this LPS-induced downregulation of CXCR1, CXCR2 and CD62L, and decreased the expression of IL-8 on neutrophils. The isolated neutrophils were treated with either vehicle or increasing concentrations (10, 100 and 1,000 ng/ml) of LPS for 4 h, and the expression levels of CXCR1, CXCR2, TLR2, TLR4, CD11b and CD62L were measured using flow cytometry. n-butanol extract from Folium isatidis prevents the LPS-induced downregulation of CXCR1, CXCR2 and CD62L. Subsequent analysis of the cells using flow cytometry indicated that the extract inhibited the LPS-induced downregulation of CXCR1, CXCR2 and CD62L ( Fig. 2A-C) in a dose-dependent manner. Effect of n-butanol extract from Folium isatidis on the gene expression levels of CXCR1, CXCR2 and CD62L. cache = ./cache/cord-300912-w85t4zz6.txt txt = ./txt/cord-300912-w85t4zz6.txt === reduce.pl bib === id = cord-280850-lku2g69k author = Zhang, Shidong title = Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits date = 2013-08-26 pages = extension = .txt mime = text/plain words = 3849 sentences = 200 flesch = 52 summary = title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits In this study, a febrigenic dosage of LPS (15 mg/kg i.v.) was injected into rabbits to form an animal febrile model, then the model animals were gavaged with BHT at the same time, and the formula's function of liver damage prevention and immunomodulation was researched in rabbits. Therefore, BHT did not affect the activated adaptive immunity, but prevented the cell immunity inhibition and excessive cytokines in innate immunity by LPS at the same time. The gene expressions of TLR4 studied herein were not affected by BHT (Fig. 5A ), but LBP expression was increased (Fig. 5B) , which bind and transport LPS to activate cells in the immunity system (Knapp et al., 2006) , and inhibiting inflammatory response at higher concentration (Hamann et al., 2005) . cache = ./cache/cord-280850-lku2g69k.txt txt = ./txt/cord-280850-lku2g69k.txt === reduce.pl bib === id = cord-000959-nk2thkme author = Downer, Eric J. title = Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date = 2013-05-06 pages = extension = .txt mime = text/plain words = 5396 sentences = 268 flesch = 48 summary = METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation. cache = ./cache/cord-000959-nk2thkme.txt txt = ./txt/cord-000959-nk2thkme.txt === reduce.pl bib === id = cord-282336-zvc04s39 author = Choudhary, Ishita title = Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date = 2020-09-02 pages = extension = .txt mime = text/plain words = 7910 sentences = 405 flesch = 48 summary = In contrast, the lung injury in LPS-challenged TTP KO mice was characterized by severe consolidation (>90% of total area of lung section) (Figures 1F,G) that included infiltration of neutrophils, edema, fibrin, and airspace hemorrhage within the airway and alveolar lumen, multifocal loss of bronchiolar epithelium with infiltration of neutrophils and red blood cells within the bronchiolar lumen, and moderate to severe perivascular edema and inflammation (Figures 1F-H) . To determine the cell-specific role of TTP levels in ALI, we modulated TTP levels in hematopoietic progenitor cells (HPCs) and non-HPCs. In order to test whether donor HPCs repopulate the recipient mouse lungs, we first made bone marrow chimeras in which total body irradiated WT mice were transplanted with HPCs from a mouse expressing green fluorescent protein (GFP) in their somatic cells. cache = ./cache/cord-282336-zvc04s39.txt txt = ./txt/cord-282336-zvc04s39.txt === reduce.pl bib === id = cord-002411-iiw878w8 author = Ding, Xibing title = TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date = 2017-02-15 pages = extension = .txt mime = text/plain words = 6653 sentences = 431 flesch = 57 summary = The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue. cache = ./cache/cord-002411-iiw878w8.txt txt = ./txt/cord-002411-iiw878w8.txt === reduce.pl bib === id = cord-015082-l629n8is author = nan title = Poster Sessions 323-461 date = 2002-08-29 pages = extension = .txt mime = text/plain words = 26569 sentences = 1648 flesch = 52 summary = 14 patients awaiting urgent cardiac surgical re-vascularisation were studied with measurement of: spirometry; percentage increase in transfer factor from sitting to lying position (TF) as an indicator of micro-vascular lung disease; overnight oximetry on air; and 24hour holter monitoring Patients, who were reintubated on decreased indices of arterial oxygenation under MOSF progressing died in 100% cases ( NIMV is effective method in complex therapy of ARF, developing in postoperative period after cardiac surgery, that leads to significant improvement of lungs biomechanics and gases change function. In a prospective observational study we performed bedside ptO2 measurements in 8 patients with sepsis/septic shock to gain insight in ptO2 values and their dynamic changes related to the course of the illness, as well as investigating the practical applicability of tissue oxygen measurement in the ICU setting. cache = ./cache/cord-015082-l629n8is.txt txt = ./txt/cord-015082-l629n8is.txt === reduce.pl bib === id = cord-103592-lkngp2u6 author = Bachmaier, Kurt title = Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date = 2020-07-02 pages = extension = .txt mime = text/plain words = 6316 sentences = 336 flesch = 47 summary = Using cecal ligation and puncture (CLP), a reproducible and clinically relevant mouse model of polymicrobial infection that causes ALI, we found that in naïve control mice after 2 sequential i.v. injections of ANP only ~4% of lung PMN endocytosed ANP as evidenced by ANP-specific fluorescence ( Figure 1B) . Importantly, we found that CCR1 receptor cell surface expression, consistent with the mRNA data, was significantly greater on lung ANP high PMN than in ANP low PMN before and 3h, 6h, and 12h after LPS stimulation ( Figure 3B ). We observed that nitrotyrosine-specific staining in inflammatory and parenchymal cells was significantly reduced in lungs and livers of mice treated with PANP when compared to ANP-treated controls ( Figure 6D ,E). Measuring a markers of overall cell damage, lactic dehydrogenase (LDH) (34) , revealed that the polymicrobial sepsis-induced increased serum activity of LDH was significantly reduced by PANP treatment when compared to ANP treated controls ( Figure 6G ). cache = ./cache/cord-103592-lkngp2u6.txt txt = ./txt/cord-103592-lkngp2u6.txt === reduce.pl bib === id = cord-005872-w1x1i0im author = Volk, T. title = Endothelium function in sepsis date = 2000 pages = extension = .txt mime = text/plain words = 8871 sentences = 463 flesch = 29 summary = Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation cache = ./cache/cord-005872-w1x1i0im.txt txt = ./txt/cord-005872-w1x1i0im.txt === reduce.pl bib === id = cord-012487-s920s5wb author = Noga, Marek J. title = Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date = 2020-08-18 pages = extension = .txt mime = text/plain words = 7414 sentences = 391 flesch = 49 summary = By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. In order to understand how the model Gram-negative species Escherichia coli coordinates membrane synthesis with growth, we quantified substrates and enzymes of the fatty acid and PL synthesis pathways under both steady-state and dynamic conditions. The trends in substrate, enzyme, and intermediate concentrations observed in ppGpp-limited cultures are consistent with growth regulating PL flux via posttranslational control-not transcriptional control-of PlsB. To test whether regulation of PlsB activity is sufficient to control steady-state PL synthesis, we constructed a simplified differential equation model that describes fatty acid, LPS initiation, and PL biosynthesis ( Fig. 2A ; see also Text S1 and Table S1 ). cache = ./cache/cord-012487-s920s5wb.txt txt = ./txt/cord-012487-s920s5wb.txt === reduce.pl bib === id = cord-001569-jd028cyg author = dos Santos, Gimena title = Vimentin regulates activation of the NLRP3 inflammasome date = 2015-03-12 pages = extension = .txt mime = text/plain words = 8469 sentences = 459 flesch = 48 summary = We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos. Exposure to bleomycin resulted in a large increase in immune cells in the airspace of both WT and Vim À / À mice as assessed by flow cytometric analysis of whole-lung lysates ( Supplementary Fig. 3a ). All together, these results suggest that vimentin-expressing bone marrow-derived cells are important for bleomycin-induced activation of the NLRP3 inflammasome and pulmonary fibrosis. Studies with IL-1R1 À / À , MyD88 À / À , ASC À / À , Caspase-1 À / À and NLRP3 À / À mice have suggested that uric acid (induced by bleomycin), asbestos and silica are detected by the NLRP3 inflammasome in macrophages, likely leading to IL-1R1/MyD88 signalling in pulmonary epithelial cells, then to inflammation, neutrophil and lymphocyte recruitment and fibroblast activation 35 . cache = ./cache/cord-001569-jd028cyg.txt txt = ./txt/cord-001569-jd028cyg.txt === reduce.pl bib === id = cord-257092-r11cgpvs author = Wu, Fengjiao title = CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation date = 2015-05-21 pages = extension = .txt mime = text/plain words = 6725 sentences = 427 flesch = 51 summary = Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. We observed reduced neutrophil infiltration and attenuated leukocyte-endothelial cell interactions in CXCR2 −/− and CXCL1 −/− mice following the intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). To identify the source of functional CXCR2 that mediates leukocyte recruitment, we generated chimeric mice by transferring bone marrow cells between WT and (See figure on previous page.) Fig. 2 Chemokine levels and the effect of CXCR2 or CXCL1 deficiency on neutrophil recruitment to the brain parenchyma after i.c.v. LPS injection. Following stimulation with TNF-α or LPS, the cerebral endothelial cells, compared with astrocytes and microglia, also expressed much higher level of CXCR2 protein (Fig. 7D ). Our results demonstrate that CXCL1, an important factor secreted by astrocytes, also plays a critical role in leukocyte recruitment to the CNS by cooperating with CXCR2 expressed on cerebral endothelial cells. cache = ./cache/cord-257092-r11cgpvs.txt txt = ./txt/cord-257092-r11cgpvs.txt === reduce.pl bib === id = cord-006279-ib5z3elq author = Ryter, Stefan W. title = Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance date = 2002 pages = extension = .txt mime = text/plain words = 8188 sentences = 464 flesch = 41 summary = Recent studies have discovered a potent anti-inflammatory effect of CO: the inhibition of pro-inflammatory cytokine production following inducing stimuli, dependent on the modulation of mitogen activated protein kinase (MAPK)signaling cascades [6, 11] . This review will (I) describe the regulation of HO-1 as an inducible source of endogenous CO, (II) describe evidence that HO-1 acts as a mediator of cellular and tissue protection against oxidative stress, and (III) emphasize recent studies that introduce novel anti-apoptotic and anti-inflammatory properties of HO-derived CO in oxidative lung injury models. MKK3 mitogen activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury Activation of heme oxygenase and heat shock protein 70 genes by stress in human hepatoma cells Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells cache = ./cache/cord-006279-ib5z3elq.txt txt = ./txt/cord-006279-ib5z3elq.txt === reduce.pl bib === id = cord-270213-ygb64yxc author = Williams, Alexander T. title = Control of systemic inflammation throughearly nitric oxide supplementation with nitric oxide releasing nanoparticles date = 2020-10-02 pages = extension = .txt mime = text/plain words = 2300 sentences = 138 flesch = 42 summary = Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19. A well-described hallmark of sepsis is endothelial dysfunction in response to a cytokine 81 'storm', which is associated with an increase in a series of negative consequences arising from 82 overproduction of reactive oxygen species (ROS), disruption of the glycocalyx, and endothelial 83 nitric oxide synthase (eNOS) uncoupling, all contributing to increased adhesion of red blood 84 cells (RBCs), white blood cells (WBCs), and platelets to the endothelium lining, enhanced 85 platelet activation, blood stagnation, decreased tissue perfusion and increased vascular 86 permeability. Mice treated with Control-np in our study 382 experienced significantly increased vascular permeability, as shown in Figure 4 , suggesting 383 endothelial cell and glycocalyx disruption in these animals. cache = ./cache/cord-270213-ygb64yxc.txt txt = ./txt/cord-270213-ygb64yxc.txt === reduce.pl bib === id = cord-012791-dyk5mr1q author = Zheng, Yong title = Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway date = 2019-09-25 pages = extension = .txt mime = text/plain words = 4152 sentences = 217 flesch = 48 summary = title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. The present study revealed that (1) ICS II protects against LPSinduced inflammation in primary-cultured astrocytes; (2) the inhibitory effect of ICS II is due to regulation of the IKK/IκB/NF-κB signaling pathway; and (3) ICS II decreases Aβ 1-40 and Aβ 1-42 levels by downregulating APP and BACE1 expression (Fig. 7) . In conclusion, the current study revealed that ICS II exerts inhibitory effects on LPS-induced inflammation in astrocytes through the IKK/IκB/NF-κB/BACE1 signaling pathway, and thus ICS II may be a promising therapeutic agent for neuroinflammatory diseases, including AD. cache = ./cache/cord-012791-dyk5mr1q.txt txt = ./txt/cord-012791-dyk5mr1q.txt === reduce.pl bib === id = cord-013067-sic08gsg author = Turzo, Maurizio title = Inhibition of overexpressed Kv3.4 augments HPV in endotoxemic mice date = 2020-10-08 pages = extension = .txt mime = text/plain words = 4396 sentences = 267 flesch = 51 summary = Inhibition of Kv3.4 with the specific blocker BDS-I increased HPV in isolated perfused endotoxemic mouse lungs. Extracts of total lung tissue from mice with LPS i.p. showed an increase of Kv3.4 gene expression (3.9 ± 0.5fold, n = 6, mean ± SEM, p < 0.05) ( Fig. 1 ) in comparison to 0.9% NaCl solution treated controls (1.0 ± 0.2-fold, normalized on 1, n = 6, means ± SEM). In order to test the role of Kv3.4 in the pulmonary vasculature, lungs of mice with and without endotoxemia were perfused with and without 50 nM of the Kv3.4 specific inhibitor BDS-I. Since Nav1.7 expression is not described in pulmonary arteries, it reduces the possibility that the effect by 50 nM BDS-I in the isolated perfused mouse lung are provoked via inhibition of Nav1.7. An isolated, perfused mouse lung model was used to study pulmonary vasoreactivity in response to acute hypoxia in LPS exposed mice. cache = ./cache/cord-013067-sic08gsg.txt txt = ./txt/cord-013067-sic08gsg.txt === reduce.pl bib === id = cord-005980-e2s0racp author = Wu, Xiaojing title = TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury date = 2019-09-05 pages = extension = .txt mime = text/plain words = 5208 sentences = 295 flesch = 48 summary = Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression. RESULTS: We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. CONCLUSIONS: Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-κB and JNK in a murine model of ALI. Compared with those in the control group, the PMN/total cell ratio in the BALF (Fig. 4c) and lung MPO activity (Fig. 4d) in LPS-challenged mice were dramatically increased, and these levels were inhibited by AAV-TIPE2 treatment. cache = ./cache/cord-005980-e2s0racp.txt txt = ./txt/cord-005980-e2s0racp.txt === reduce.pl bib === id = cord-013840-mi3uf4vk author = Zhang, Wei title = The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation date = 2019-08-29 pages = extension = .txt mime = text/plain words = 8495 sentences = 495 flesch = 43 summary = Specifically, Lamtor5 associated with TLR4 via their LZ/TIR domains and facilitated their colocalization at autolysosomes, preventing lysosomal tethering and the activation of mTORC1 upon LPS stimulation and thereby derepressing TFEB to promote autophagic degradation of TLR4. 16, 17 Loss of the autophagic components autophagy-related 16 like 1, Beclin1, and microtubule-associated protein 1A/1B light chain 3 (LC3) enhanced the macrophage response to LPS, a prototypical agonist of TLR4, and caused sustained inflammatory signaling. [26] [27] [28] A recent study identified Lamtor5 as an indispensable component of the Ragulator complex that interacts with small GTPase Ras-related GTP binding protein (RAG), contributing to lysosomal recruitment and the activation of mechanistic target of rapamycin complex 1 (mTORC1) in response to amino acids. j Immunoblotting for TLR4 and total and phosphorylated p65 in control and Lamtor5-expressing RAW264.7 cells pretreated with DMSO or Baf1 and then stimulated with LPS for the indicated time periods. cache = ./cache/cord-013840-mi3uf4vk.txt txt = ./txt/cord-013840-mi3uf4vk.txt === reduce.pl bib === id = cord-030385-btf502ju author = Sun, Zhiheng title = 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date = 2020-07-22 pages = extension = .txt mime = text/plain words = 5855 sentences = 328 flesch = 55 summary = However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively. cache = ./cache/cord-030385-btf502ju.txt txt = ./txt/cord-030385-btf502ju.txt === reduce.pl bib === id = cord-004140-ujzrqzv3 author = Lu, Xiaying title = Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock date = 2020-01-13 pages = extension = .txt mime = text/plain words = 3474 sentences = 208 flesch = 48 summary = As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. Therefore, the serum levels of multiple pro-inflammatory cytokines Male C57BL/6 mice were injected with different doses of rolipram (1 mg/kg, 5 mg/kg, and 10 mg/kg, i.p.) 1 hr before LPS injection. We demonstrate that rolipram may protect against LPS-induced inflammation and shock in mice, likely through the inhibition of the NF-κB and MAPK signaling pathways. We have found that rolipram inhibits pro-inflammatory cytokines and chemokines released by the administration of LPS, leading to the suppression of excessive inflammatory responses, cell adhesion and migration, and the further sequelae of shock and multiple organ failure in the mouse host. Our results indicated that rolipram suppresses LPS-induced ERK, JNK, and p38 MAPK phosphorylation in lung tissue, suggesting that the MAPK signaling pathway -as well as NF-κB -may mediate the anti-inflammatory actions of rolipram. cache = ./cache/cord-004140-ujzrqzv3.txt txt = ./txt/cord-004140-ujzrqzv3.txt === reduce.pl bib === === reduce.pl bib === id = cord-306577-gq6fss5l author = Hsueh, Wei title = Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date = 2002-11-11 pages = extension = .txt mime = text/plain words = 8414 sentences = 453 flesch = 40 summary = Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether) cache = ./cache/cord-306577-gq6fss5l.txt txt = ./txt/cord-306577-gq6fss5l.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-005875-yp1ehpeg author = Zhang, Dong title = Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways date = 2020-01-10 pages = extension = .txt mime = text/plain words = 5136 sentences = 346 flesch = 47 summary = OBJECTIVE: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). RESULTS: This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. The preceding results indicated that crocin might inhibit the expression of HPA by inhibiting the upstream protein of CTL in LPS-induced ARDS mice and LPS-stimulated HUVECs. The results in vivo showed that the expression of MMP-9 by LPS stimulation was significantly increased compared with that of the control group (Fig. 4c, d) . These results suggested that crocin can inhibit the activation of MAPK pathway in LPS-induced ARDS mice and LPS-stimulated HUVECs. The HMGB1 and NF-κB signaling pathway also regulate lung injury of the inflammatory process. cache = ./cache/cord-005875-yp1ehpeg.txt txt = ./txt/cord-005875-yp1ehpeg.txt === reduce.pl bib === id = cord-264145-73e61rlq author = Belančić, Andrej title = Gut microbiome dysbiosis and endotoxemia - Additional pathophysiological explanation for increased COVID-19 severity in obesity date = 2020-09-18 pages = extension = .txt mime = text/plain words = 1328 sentences = 78 flesch = 26 summary = The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. ABSTRACT: The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything previously mentioned into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity (Figure 1 ). cache = ./cache/cord-264145-73e61rlq.txt txt = ./txt/cord-264145-73e61rlq.txt === reduce.pl bib === id = cord-013366-sbdtpsz6 author = Ramírez-Pérez, Sergio title = Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date = 2020-09-21 pages = extension = .txt mime = text/plain words = 5749 sentences = 283 flesch = 45 summary = Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC. cache = ./cache/cord-013366-sbdtpsz6.txt txt = ./txt/cord-013366-sbdtpsz6.txt === reduce.pl bib === id = cord-285684-iiqyzqsb author = Li, Jin-ze title = Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier date = 2020-10-30 pages = extension = .txt mime = text/plain words = 4623 sentences = 256 flesch = 46 summary = title: Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS. We introduced a transwell coculture system to evaluate the effects of MS-MSCs on the paracellular permeability of LPS-treated ECs. Treatment with LPS significantly increased the paracellular permeabil-ity of the pulmonary microvascular endothelium barrier (Figure 6 (a); * * p < 0:01). We demonstrated that mechanical stretch could impact MSC morphology and biological function in a time-and magnitude-dependent manner and that MS-MSCs could restored the increased permeability of endothelial cells induced by LPS. In this study, we tried to discover evidences of mechanically stretched MSCs in restoring increased permeability of endothelial barrier induced by LPS. cache = ./cache/cord-285684-iiqyzqsb.txt txt = ./txt/cord-285684-iiqyzqsb.txt === reduce.pl bib === === reduce.pl bib === id = cord-261367-i1n8x0uc author = Hwang, Ji Young title = Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date = 2020-09-25 pages = extension = .txt mime = text/plain words = 7609 sentences = 309 flesch = 47 summary = Instead, mice with iBALT had reduced Th2-associated mRNA expression, less eosinophil recruitment to the lungs and airways, attenuated goblet cell hyperplasia and reduced mucus production following pulmonary sensitization and challenge with OVA. To test the effect of iBALT on the immune response to a pulmonary allergen, we administered LPS (or PBS) to neonatal mice as described above, allowed the mice to rest until they were 7 weeks old, then intranasally sensitized the iBALT and control groups with 100 µg OVA in combination with low dose (0.1 µg) LPS on days 49, 50, and 51 and challenged them on days 63, 64, 67, and 68 with 25 µg OVA ( Figure 1E ). Together, these data suggest that the spatial distribution of effector Th2 cells and Tregs is affected by the presence of iBALT (they cluster together), which may explain how iBALT and control mice can have similar numbers of Th2 cells in their lungs, but have so profoundly different outcomes in terms of eosinophil accumulation and histopathology. cache = ./cache/cord-261367-i1n8x0uc.txt txt = ./txt/cord-261367-i1n8x0uc.txt === reduce.pl bib === id = cord-298646-wurzy88k author = van der Merwe, René title = Challenge models to assess new therapies in chronic obstructive pulmonary disease date = 2012-09-13 pages = extension = .txt mime = text/plain words = 4775 sentences = 240 flesch = 40 summary = This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD. One of the main challenges in developing new therapeutic agents for the treatment or prevention of acute exacerbations of COPD is that their potential success cannot be entirely known until the investigational therapies enter relatively large Phase II studies, assessing clinical outcome over a 3-to 6-month period or longer. 20 In the first reported study of the inflammatory effects of low-level O 3 exposure (80 ppb O 3 for 6.6 hours) in healthy volunteers, 21 there were statistically significant increases in polymorphononuclear neutrophils, prostaglandin E 2 , lactate dehydrogenase, IL-6, α1-antitrypsin, and decreased phagocytosis via the complement receptor. The O 3 -challenge model potentially provides critical decision-making data in understanding whether new compounds have the desired biological effect in healthy volunteers and patients with COPD; hence it can de-risk decisions to move forwards into large Phase II safety and efficacy trials. cache = ./cache/cord-298646-wurzy88k.txt txt = ./txt/cord-298646-wurzy88k.txt === reduce.pl bib === id = cord-296258-8pc2p3az author = Hwang, Eun-Ha title = Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation date = 2016-01-31 pages = extension = .txt mime = text/plain words = 5579 sentences = 358 flesch = 54 summary = title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs–adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). When faced with an infection, mesothelial cells express specific surface markers that enable them to promote the migration of neutrophils, to interact with extracellular matrix proteins, to present antigens to immune cells, and to produce biologically important molecules such as proinflammatory cytokines, chemokines, and nitric oxide (NO) [6, 7] Toll-like receptors (TLRs) are type I transmembrane proteins and comprise an ectodomain, which contains leucine-rich repeats that mediate the recognition of pathogen-associated molecular patterns (PAMPs); a transmembrane region; and a cytosolic Toll/ IL-1 receptor (TIR) domain that activates downstream signaling pathways [8] . cache = ./cache/cord-296258-8pc2p3az.txt txt = ./txt/cord-296258-8pc2p3az.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-310535-ay2cdf2w author = Cho, Chang-Won title = Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages date = 2017-06-20 pages = extension = .txt mime = text/plain words = 4636 sentences = 262 flesch = 45 summary = title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium(DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. The effects of HMFO on the expression of inflammatory proteins such as COX-2 and iNOS in cytosolic extracts from the colon of colitis mice were detected by Western blot analysis. cache = ./cache/cord-310535-ay2cdf2w.txt txt = ./txt/cord-310535-ay2cdf2w.txt === reduce.pl bib === id = cord-252859-zir02q69 author = Chung, T. Philip title = Molecular Diagnostics in Sepsis: From Bedside to Bench date = 2006-09-11 pages = extension = .txt mime = text/plain words = 5735 sentences = 299 flesch = 47 summary = BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. 17, 18 We hypothesized that leukocyte gene expression profiles obtained using DNA microarrays could be used to predict septic states; in particular, distinguishing between sterile and infectious sources of systemic inflammation, a common conundrum in caring for the critically ill or injured. 30 PCA analysis of these 25 probe sets revealed that the seven experimental groups were clustered into three apparent phenotypes (Fig. 4) : control animals, LPS-treated animals (sterile source of systemic inflammation), and those that had any CLP treatment (Sepsis). cache = ./cache/cord-252859-zir02q69.txt txt = ./txt/cord-252859-zir02q69.txt === reduce.pl bib === === reduce.pl bib === id = cord-331887-kagggou1 author = liu, Chang title = An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury date = 2020-09-09 pages = extension = .txt mime = text/plain words = 3197 sentences = 184 flesch = 57 summary = Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses. CONCLUSIONS: In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF. LJF significantly inhibited CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, 290 IL17F, IL17C, MMP9, and TNFAIP3 mRNA expression in lung tissue homogenates according to 291 RNA-Seq, which indicates that the IL-17 signalling pathway is critical for treatment of 292 LPS-induced ALI with LJF (Fig.S4) . Consistent with the RNA-Seq data, the expression of CXCL2, CXCL1, CXCL6, 295 NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3 in lung tissue was 296 significantly decreased compared with that in the ALI and LJF groups according to the qRT-PCR 297 analyses (P<0.05) (Fig.8) . cache = ./cache/cord-331887-kagggou1.txt txt = ./txt/cord-331887-kagggou1.txt === reduce.pl bib === id = cord-311481-2awvmpyh author = Kosukegawa, Ima title = The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial date = 2020-01-14 pages = extension = .txt mime = text/plain words = 4725 sentences = 226 flesch = 53 summary = OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. In the present study, we hypothesized that LPZ has the potential to suppress IRF7 and NF-κB, in the same manner as BAY11-7082, and so prevent corticosteroid-induced ONFH in rats. The present study showed that the co-treatment of LPZ with corticosteroids prevents the development of ONFH in experimental animals, as well as in patients with immune disease treated with corticosteroids. The results of the experimental study indicate that LPZ may also prevent the development of ONFH in patients with immune diseases needing corticosteroid treatment. The present study shows that the co-treatment of LPZ with corticosteroids prevents the development of ONFH through the suppression of IRF7 activity in rats. Nevertheless, we believe that LPZ is safe to use and could be effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment. cache = ./cache/cord-311481-2awvmpyh.txt txt = ./txt/cord-311481-2awvmpyh.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-032181-gmcugd8h author = Song, Jian-Xin title = Main Complications of AECHB and Severe Hepatitis B (Liver Failure) date = 2019-05-21 pages = extension = .txt mime = text/plain words = 51165 sentences = 2516 flesch = 37 summary = 3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. The latest report indicated that basic laboratory examinations for coagulation function testing in common use at present, such as PT, APTT, international normalized ratio (INR) etc., have little correlation with occurrence of gastrointestinal bleeding in these patients, thereby revealing the importance to search and pay close attention to those complicating disease upregulating bleeding risk, such as bacterial infection, renal failure, hemodynamic change after portal hypertension, dysfunction of endotheliocyte as well as macrophagocyte and so on [107] . cache = ./cache/cord-032181-gmcugd8h.txt txt = ./txt/cord-032181-gmcugd8h.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-337923-1vbkttzx author = Li, Xiao-Jun title = Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi date = 2019-02-21 pages = extension = .txt mime = text/plain words = 3979 sentences = 246 flesch = 51 summary = henryi have strong antioxidant and antiacetyl cholinesterase activities [6] , and the 80% methanol fraction of root bark and ciwujianoside C3, which was isolated from leaves of this plant, have significant antiinflammatory effect in lipopolysaccharide-(LPS-) induced RAW264.7 macrophage cells [5, 11] . henryi, we selected 13 compounds (compounds -, , , , , , , , and -) based on their number of publications, and these compounds were screened for anti-inflammatory effects, including the inhibition of NO and PGE 2 production, in LPS-stimulated BV2 microglial cells. The concentration required to inhibit the production of NO by 50% (IC 50 value) was calculated based on the concentrations of NO and PGE 2 released into the culture Figure 2 : The effect of compound on LPS-induced iNOS and COX-2 protein expression in BV2 microglial cells. henryi, suppressed NO and PGE 2 production in LPS-stimulated BV2 microglial cells and also inhibited the LPS-induced expression of the iNOS and COX-2 protein (Figure 2) . cache = ./cache/cord-337923-1vbkttzx.txt txt = ./txt/cord-337923-1vbkttzx.txt === reduce.pl bib === === reduce.pl bib === id = cord-015147-h0o0yqv8 author = nan title = Oral Communications and Posters date = 2014-09-12 pages = extension = .txt mime = text/plain words = 73711 sentences = 3862 flesch = 43 summary = Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. cache = ./cache/cord-015147-h0o0yqv8.txt txt = ./txt/cord-015147-h0o0yqv8.txt === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === === reduce.pl bib === id = cord-014996-p6q0f37c author = nan title = Posters_Monday_12 October 2009 date = 2009-08-06 pages = extension = .txt mime = text/plain words = 85190 sentences = 5288 flesch = 54 summary = Data recorded on admission were the patient demographics with, acute physiology and chronic health evaluation II score (APACHE II), and type of admission; during intensive care stay, sepsis-related organ failure assessment score (SOFA) and clinical concomitant factors and conditions. For each severe septic patient the following data was registered: time delay, APACHE II and SOFA scores at ICU admission, diagnosis, the rate of compliance with the resucitation and management bundles, microbiological data, evolution of levels of serum lactate, empiric antibiotic therapy, length of stay and mortality in ICU. Sepsis and septic shock remain the most important causes of acute kidney injury (AKI) in critically ill patients and account for more than 50% of cases of acute renal failure (ARF) in intensive care units (ICU). There were no significant differences between the demographic data (sex, age) or the data on admission to intensive care (APACHE II score, ratio of medical to surgical patients) and duration of mechanical ventilation between the two groups. cache = ./cache/cord-014996-p6q0f37c.txt txt = ./txt/cord-014996-p6q0f37c.txt === reduce.pl bib === id = cord-005727-li8pwigg author = nan title = ESICM 2010 MONDAY SESSIONS 11 October 2010 date = 2010-08-31 pages = extension = .txt mime = text/plain words = 102770 sentences = 6408 flesch = 53 summary = Since, continuous epidural analgesia provides the required level of analgesia to support early mobilization and significant reduction in pulmonary and cardiovascular morbidity in the early postoperative period, we postulated that the use of low dose of continuous epidural morphine might improve postoperative analgesia and reduce undesirable side effects in elderly patientsTherefore, the present study was designed to evaluate the effects of morphine administered via epidural patients controlled analgesia and intravenous tramadol + metamizol on postoperative pain control and side effects in elderly patients after major abdominal surgery. For each ventilated patient the following data was registered:Age, APACHE II, the reason of admission, risk factors, use NIV, MV duration, timing of tracheostomy, time of diagnosis of VAP, microbiological data, length of stay and mortality in ICU. 23rd ESICM ANNUAL CONGRESS -BARCELONA, SPAIN -9-13 OCTOBER 2010 S131 Evaluated factors: patient characteristics, signs, symptoms, abscess location, time between symptoms and hospital admission and surgery, lab results, microbiology, antibiotic therapy, APACHE2, SAPS2, SOFA, length of ICU stay, surgical re-intervention, duration of mechanical ventilation, infectious complications, critical illness myopathy (CIM), renal replacement therapy (RRT), re-intubation, tracheotomy, mortality. cache = ./cache/cord-005727-li8pwigg.txt txt = ./txt/cord-005727-li8pwigg.txt === reduce.pl bib === id = cord-005497-w81ysjf9 author = nan title = 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium. 24-27 March 2020 date = 2020-03-24 pages = extension = .txt mime = text/plain words = 103623 sentences = 6176 flesch = 53 summary = The positive NC group had more plasma transfusion (p-value 0.03) and a lower median hematocrit at 24 hrs (p-value 0.013), but similar hospital length of stay (p=0.17) and mortality rate (p=0.80) Conclusions: NC at ICU admission identifies subclinical AKI in TBI patients and it maight be used to predictclinical AKI. In patients with pneumonia requiring intensive care (ICU) admission, we hypothesise that abnormal right ventricular (RV) function is associated with an increased 90-day mortality. The objective of this study was to describe the incidence of each AKI stages as defined by KDIGO definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (RRT)), in a mixed medical and surgical population of patients hospitalized in ICU and PCU over a 10-year period (2008-2018). This study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(ICU) and hospital length of stay (LOS), and length of mechanical ventilation (LOMV). cache = ./cache/cord-005497-w81ysjf9.txt txt = ./txt/cord-005497-w81ysjf9.txt === reduce.pl bib === id = cord-006229-7yoilsho author = nan title = Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date = 2016-02-06 pages = extension = .txt mime = text/plain words = 133493 sentences = 6804 flesch = 42 summary = It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). cache = ./cache/cord-006229-7yoilsho.txt txt = ./txt/cord-006229-7yoilsho.txt === reduce.pl bib === id = cord-006230-xta38e7j author = nan title = Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date = 2012-02-22 pages = extension = .txt mime = text/plain words = 135419 sentences = 7042 flesch = 43 summary = Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. cache = ./cache/cord-006230-xta38e7j.txt txt = ./txt/cord-006230-xta38e7j.txt === reduce.pl bib === id = cord-023026-2r84ndzv author = nan title = Posters date = 2013-06-14 pages = extension = .txt mime = text/plain words = 138458 sentences = 6513 flesch = 40 summary = Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. cache = ./cache/cord-023026-2r84ndzv.txt txt = ./txt/cord-023026-2r84ndzv.txt === reduce.pl bib === id = cord-022888-dnsdg04n author = nan title = Poster Sessions date = 2009-08-19 pages = extension = .txt mime = text/plain words = 188640 sentences = 9313 flesch = 45 summary = Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. cache = ./cache/cord-022888-dnsdg04n.txt txt = ./txt/cord-022888-dnsdg04n.txt === reduce.pl bib === id = cord-015394-uj7fe5y6 author = nan title = Scientific Abstracts date = 2008-12-23 pages = extension = .txt mime = text/plain words = 242330 sentences = 15267 flesch = 52 summary = Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. cache = ./cache/cord-015394-uj7fe5y6.txt txt = ./txt/cord-015394-uj7fe5y6.txt === reduce.pl bib === id = cord-005814-ak5pq312 author = nan title = 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date = 1995 pages = extension = .txt mime = text/plain words = 179164 sentences = 12028 flesch = 56 summary = Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life. cache = ./cache/cord-005814-ak5pq312.txt txt = ./txt/cord-005814-ak5pq312.txt === reduce.pl bib === id = cord-015021-pol2qm74 author = nan title = Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date = 1994 pages = extension = .txt mime = text/plain words = 162327 sentences = 9379 flesch = 50 summary = It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. cache = ./cache/cord-015021-pol2qm74.txt txt = ./txt/cord-015021-pol2qm74.txt ===== Reducing email addresses cord-007178-h0ordzm9 cord-015147-h0o0yqv8 Creating transaction Updating adr table ===== Reducing keywords cord-002165-blbaqbo7 cord-000460-h3owwjao cord-009753-6rg47f0i cord-003055-88q36g00 cord-000217-chd9ezba cord-003099-a0acr28o cord-000425-isw6jeir cord-000920-68eblcke cord-007178-h0ordzm9 cord-006778-qnxyhmw5 cord-012828-wsjob1p8 cord-001496-186k6t03 cord-006888-qfnukav4 cord-006285-kkxdmzk9 cord-002079-jne14jqf cord-022136-3q24qxsr 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cord-000425-isw6jeir cord-012828-wsjob1p8 cord-032564-0t5lr4z9 cord-004282-tox3tuzz cord-298224-flyx85lr cord-255578-0ltb9dpa cord-282336-zvc04s39 cord-012487-s920s5wb cord-013840-mi3uf4vk cord-004140-ujzrqzv3 cord-292862-ezrkg0dc cord-261367-i1n8x0uc cord-298646-wurzy88k cord-322729-47c9z2gk cord-252859-zir02q69 cord-294193-xjq9j2gv cord-331887-kagggou1 cord-311481-2awvmpyh cord-336432-tu00gffr cord-341458-hkopopa6 cord-349201-d88g5toc cord-354829-god79qzw cord-352219-z245sb3s cord-006229-7yoilsho cord-022888-dnsdg04n cord-014996-p6q0f37c cord-006230-xta38e7j Creating transaction Updating url table ===== Reducing named entities cord-000460-h3owwjao cord-002165-blbaqbo7 cord-009753-6rg47f0i cord-000425-isw6jeir cord-003055-88q36g00 cord-000217-chd9ezba cord-003099-a0acr28o cord-000920-68eblcke cord-006778-qnxyhmw5 cord-007178-h0ordzm9 cord-012828-wsjob1p8 cord-006285-kkxdmzk9 cord-001496-186k6t03 cord-002079-jne14jqf cord-006605-tsk3pakb cord-029969-1fa8hk2n cord-006888-qfnukav4 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cord-003099-a0acr28o cord-000217-chd9ezba cord-003055-88q36g00 cord-000920-68eblcke cord-012828-wsjob1p8 cord-000425-isw6jeir cord-006778-qnxyhmw5 cord-001496-186k6t03 cord-006285-kkxdmzk9 cord-029969-1fa8hk2n cord-006605-tsk3pakb cord-007178-h0ordzm9 cord-002079-jne14jqf cord-006570-v4as5gde cord-103496-8tq78p2z cord-004754-5596p4ma cord-000137-idffrnac cord-032564-0t5lr4z9 cord-283427-fef9qsik cord-022136-3q24qxsr cord-000984-64p3wpav cord-004282-tox3tuzz cord-004067-psjyjvbu cord-005607-b1a39hhw cord-005832-p1joajvn cord-006700-df8ard9o cord-029488-l11ufs6k cord-255578-0ltb9dpa cord-300912-w85t4zz6 cord-298224-flyx85lr cord-280850-lku2g69k cord-023935-o2ffxgnn cord-000959-nk2thkme cord-002411-iiw878w8 cord-006318-9r51n241 cord-103592-lkngp2u6 cord-282336-zvc04s39 cord-270213-ygb64yxc cord-005872-w1x1i0im cord-012487-s920s5wb cord-012791-dyk5mr1q cord-006279-ib5z3elq cord-257092-r11cgpvs cord-001569-jd028cyg cord-013067-sic08gsg cord-006888-qfnukav4 cord-022252-9yiuuye3 cord-013840-mi3uf4vk cord-005980-e2s0racp cord-030385-btf502ju cord-004140-ujzrqzv3 cord-306577-gq6fss5l cord-005875-yp1ehpeg cord-264145-73e61rlq cord-013366-sbdtpsz6 cord-285684-iiqyzqsb cord-298646-wurzy88k cord-018969-0zrnfaad cord-261367-i1n8x0uc cord-296258-8pc2p3az cord-310535-ay2cdf2w cord-322729-47c9z2gk cord-292862-ezrkg0dc cord-252855-xtsnlu1f cord-252859-zir02q69 cord-302490-em1tiz7s cord-015082-l629n8is cord-302295-nblmshni cord-311481-2awvmpyh cord-294193-xjq9j2gv cord-331887-kagggou1 cord-273594-vmbhok1u cord-329274-ncvvmkca cord-335107-ew9uid2e cord-297128-s5c9h4lm cord-280482-o887a7q9 cord-336432-tu00gffr cord-339272-trd6rkxw cord-011286-8wxih7v6 cord-337923-1vbkttzx cord-341458-hkopopa6 cord-351310-6p42b144 cord-342001-41vjh3mq cord-351730-qmbo1dmo cord-346488-y7r7el4e cord-349201-d88g5toc cord-354765-abayh871 cord-354829-god79qzw cord-348391-xytmq2f2 cord-352219-z245sb3s cord-032181-gmcugd8h cord-015147-h0o0yqv8 cord-014996-p6q0f37c cord-005727-li8pwigg cord-005497-w81ysjf9 cord-006230-xta38e7j cord-023026-2r84ndzv cord-006229-7yoilsho cord-015021-pol2qm74 cord-005814-ak5pq312 cord-022888-dnsdg04n cord-015394-uj7fe5y6 Creating transaction Updating pos table Building ./etc/reader.txt cord-005497-w81ysjf9 cord-005727-li8pwigg cord-014996-p6q0f37c cord-006700-df8ard9o cord-339272-trd6rkxw cord-006778-qnxyhmw5 number of items: 105 sum of words: 2,002,212 average size in words: 25,669 average readability score: 46 nouns: cells; patients; cell; expression; mice; results; study; levels; protein; group; blood; treatment; response; lung; activation; data; role; effects; effect; activity; analysis; time; sepsis; control; receptor; injury; infection; model; disease; days; production; studies; inflammation; ml; methods; tissue; mortality; groups; function; system; gene; factor; increase; type; changes; proteins; level; development; day; responses verbs: used; induce; shown; increased; compared; following; associated; including; reduce; suggest; found; done; treat; determine; observed; activating; performed; expressed; measured; decreases; demonstrated; mediates; indicated; investigate; identified; lead; inhibiting; caused; involving; evaluated; regulating; signaling; assess; study; resulting; developed; based; binding; analyzed; obtained; provide; stimulated; produced; required; known; related; detect; plays; revealed; occurred adjectives: inflammatory; human; significant; different; high; acute; immune; specific; anti; clinical; pulmonary; higher; severe; non; endothelial; important; respiratory; first; normal; dependent; septic; low; present; cardiac; early; positive; vascular; mean; lower; cellular; therapeutic; similar; primary; chronic; fetal; bacterial; new; major; negative; several; total; systemic; like; multiple; functional; potential; pro; molecular; arterial; renal adverbs: also; significantly; however; well; respectively; therefore; previously; furthermore; moreover; recently; even; highly; still; directly; prior; often; critically; together; mainly; interestingly; especially; less; statistically; alone; currently; specifically; finally; strongly; thereby; now; subsequently; later; first; additionally; rather; particularly; yet; potentially; probably; rapidly; almost; clinically; markedly; already; usually; far; completely; relatively; least; approximately pronouns: we; it; our; their; its; they; i; them; he; us; itself; his; one; themselves; she; you; her; your; him; me; my; ashcs; himself; il-1β; em; peli2; s; imagej; igfbp2; esat-6; ours; interleukin-15; igmcic; e2f2-/-mice; crx-527; adrb1; ␣; ≥151; ĝ; yours; y-27632; wi~; wether; tv/; trs\3; trpm4; trl2x4; tnf~; tnfrt; thei proper nouns: LPS; ICU; TNF; T; C; IL-6; mg; II; Fig; A; TLR4; University; B; kg; ARDS; mRNA; IFN; PCR; ±; ALI; M; USA; WT; RNA; SP; L; MS; CD4; ELISA; siRNA; CD8; Germany; IL-10; Care; PBS; D; α; NF; PMN; Hospital; G; E.; I; CD14; IL-1; CNS; IL-8; S; VEGF; Group keywords: lps; cell; tnf; tlr4; study; result; ali; il-6; sepsis; ards; patient; increase; university; mouse; method; level; response; protein; inflammatory; icu; hospital; group; expression; effect; pcr; lung; dna; day; conclusion; mortality; ifn; human; high; elisa; copd; care; blood; apache; western; vap; unit; tlr2; sofa; rna; pmn; pct; paf; model; introduction; intensive one topic; one dimension: cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978602/ titles(s): Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice three topics; one dimension: cells; patients; cells file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095534/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/ titles(s): Poster Sessions | 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts | Scientific Abstracts five topics; three dimensions: cells lps mice; patients icu group; cells cell il; expression cells results; liver patients blood file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165910/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095534/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498917/ titles(s): Posters | 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts | Poster Sessions | Scientific Abstracts | Main Complications of AECHB and Severe Hepatitis B (Liver Failure) Type: cord title: keyword-lps-cord date: 2021-05-25 time: 15:30 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:lps ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-000217-chd9ezba author: Anas, Adam title: Role of CD14 in lung inflammation and infection date: 2010-03-09 words: 5544.0 sentences: 263.0 pages: flesch: 45.0 cache: ./cache/cord-000217-chd9ezba.txt txt: ./txt/cord-000217-chd9ezba.txt summary: Furthermore, intratracheal treatment of CD14-defi cient mice with sCD14 restored the infl ammatory response to the level present in wildtype mice, whereas treatment with wild-type alveolar macrophages restored the neutrophil infi ltration of the lung but not pulmonary TNF release [26] . Th ese fi ndings indicate that sCD14, and CD14 and TLR4 on the surface of alveolar macrophages contribute to the development of LPS-induced lung infl ammation. In line with the fi ndings that CD14 contributes to LPSinduced lung infl ammation in mice, a number of studies have shown that CD14 is essential for the host defense response in the lung against Gram-negative bacteria, such as nontypeable Haemophilus infl uenzae, a possible cause of community acquired pneumonia, and A. coli-induced pneumonia has not been investigated in mice, whereas the role of the other components of the LPS receptor complex (TLR4, MD-2, MyD88, TRIF) has been determined using gene-defi cient or mutant mice. abstract: This article is one of ten reviews selected from the Yearbook of Intensive Care and Emergency Medicine 2010 (Springer Verlag) and co-published as a series in Critical Care. Other articles in the series can be found online at http://ccforum.com/series/yearbook. Further information about the Yearbook of Intensive Care and Emergency Medicine is available from http://www.springer.com/series/2855. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2887102/ doi: 10.1186/cc8850 id: cord-103592-lkngp2u6 author: Bachmaier, Kurt title: Selective Nanotherapeutic Targeting of the Neutrophil Subset Mediating Inflammatory Injury date: 2020-07-02 words: 6316.0 sentences: 336.0 pages: flesch: 47.0 cache: ./cache/cord-103592-lkngp2u6.txt txt: ./txt/cord-103592-lkngp2u6.txt summary: Using cecal ligation and puncture (CLP), a reproducible and clinically relevant mouse model of polymicrobial infection that causes ALI, we found that in naïve control mice after 2 sequential i.v. injections of ANP only ~4% of lung PMN endocytosed ANP as evidenced by ANP-specific fluorescence ( Figure 1B) . Importantly, we found that CCR1 receptor cell surface expression, consistent with the mRNA data, was significantly greater on lung ANP high PMN than in ANP low PMN before and 3h, 6h, and 12h after LPS stimulation ( Figure 3B ). We observed that nitrotyrosine-specific staining in inflammatory and parenchymal cells was significantly reduced in lungs and livers of mice treated with PANP when compared to ANP-treated controls ( Figure 6D ,E). Measuring a markers of overall cell damage, lactic dehydrogenase (LDH) (34) , revealed that the polymicrobial sepsis-induced increased serum activity of LDH was significantly reduced by PANP treatment when compared to ANP treated controls ( Figure 6G ). abstract: Inflammatory tissue injury such as acute lung injury (ALI) is a disorder that leads to respiratory failure, a major cause of morbidity and mortality worldwide. Excessive neutrophil influx is a critical pathogenic factor in the development of ALI. Here, we identify the subset of neutrophils that is responsible for ALI and lethality in polymicrobial sepsis. The pro-inflammatory neutrophil subpopulation was characterized by its unique ability to endocytose albumin nanoparticles (ANP), upregulation of pro-inflammatory cytokines and chemokines as well as the excessive production of reactive oxygen species (ROS) in models of endotoxemia and septicemia. ANP delivery of the drug piceatannol, a spleen tyrosine kinase (Syk) inhibitor, to the susceptible subset of neutrophils, prevented ALI and mortality in mice subjected to polymicrobial infection. Targeted inhibition of Syk in ANP-susceptible neutrophils had no detrimental effect on neutrophil-dependent host defense because the subset of ANPlow neutrophils effectively controlled polymicrobial infection. The results show that neutrophil heterogeneity can be leveraged therapeutically to prevent ALI without compromising host defense. url: https://doi.org/10.1101/2020.06.30.180927 doi: 10.1101/2020.06.30.180927 id: cord-264145-73e61rlq author: Belančić, Andrej title: Gut microbiome dysbiosis and endotoxemia - Additional pathophysiological explanation for increased COVID-19 severity in obesity date: 2020-09-18 words: 1328.0 sentences: 78.0 pages: flesch: 26.0 cache: ./cache/cord-264145-73e61rlq.txt txt: ./txt/cord-264145-73e61rlq.txt summary: The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. ABSTRACT: The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. Taking everything previously mentioned into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity (Figure 1 ). abstract: The overall intestinal lipopolysaccharide (LPS) composition in the individuals with obesity could be shifted away from immunosilent/immunoinhibitory Bacteroidetes LPS subtypes, in favor of various proinflammatory LPS subtypes due to gut microbiome dysbiosis. What is more, high-fat diet, as well as obesity per se, enhance intestinal permeability through various mechanisms. Latter results in increased paracellular absorption and transcellular (via chylomicrons) transport of endogenous endotoxin in the circulatory system (endotoxemia). In addition, it is known that lipid A initiates a signaling cascade resulting in activation of various proinflammatory pathways and increases oxidative stress upon binding to tool-like receptor 4 (TLR4). Taking everything into consideration, it is very likely that gut microbiome dysbiosis and endotoxemia represent the additional pathophysiological explanation for increased COVID-19 severity in obesity. url: https://www.sciencedirect.com/science/article/pii/S2451847620301226?v=s5 doi: 10.1016/j.obmed.2020.100302 id: cord-005607-b1a39hhw author: Bellingan, G title: Leukocytes: friend or foe date: 2000 words: 3827.0 sentences: 173.0 pages: flesch: 37.0 cache: ./cache/cord-005607-b1a39hhw.txt txt: ./txt/cord-005607-b1a39hhw.txt summary: Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation.¶The body relies on the inflammatory response for protection. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage.¶It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. Endothelial cells, mesothelial cells, fibroblasts and epithelial cells are also all involved not only with their capacity to drive the inflammatory response through mediator generation but also in innate immune defences including through the production of antimicrobial proteins. abstract: Leukocytes have a fundamental role in innate and adaptive immunity, wound healing, tumour surveillance and in tissue remodelling. It is their function in the inflammatory response however that is of most interest to us in the intensive care setting. Over the last three decades we have gained significant insights into leukocyte activation, recruitment and mediator secretion and the contribution of these agents to both the onset and resolution of sepsis and inflammation.¶The body relies on the inflammatory response for protection. Leukocytes occupy a pivotal position in this but to maintain these cells in a state of permanent activation would be unsustainable, with widespread microvascular plugging, uncontrolled free radical release and an excessive metabolic demand. Leukocytes thus circulate in a quiescent state and are rapidly activated by invading pathogens and other stimuli. A direct consequence of this protective strategy is that the inflammatory response may be inadequate, with the risk of overwhelming sepsis, or excessive, leading to rampant systemic inflammation and consequent multiple organ damage.¶It is now becoming apparent however that in addition to leukocytes other cells have important roles both in defence against invading pathogens and in driving malignant inflammation. This review will focus on two new facets of the innate immune system, the Toll family of proteins as the signal transduction element for endotoxin, and the antimicrobial peptides. These exemplify potential damaging and protective response elements but importantly neither are restricted to leukocytes. The capacity of cells and tissues other than the leukocytes to participate and even lead in the inflammatory responses will also be explored. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094984/ doi: 10.1007/s001340051127 id: cord-351310-6p42b144 author: Bohr, Adam title: Treatment of acute lung inflammation by pulmonary delivery of anti-TNF-α siRNA with PAMAM dendrimers in a murine model date: 2020-08-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract To improve the efficacy of nucleic acid-based therapeutics, e.g., small interfering RNA (siRNA), transfection agents are needed for efficient delivery into cells. Several classes of dendrimers have been found useful as transfection agents for the delivery of siRNA because their surface can readily be functionalized, and the size of the dendriplexes they form with siRNA is within the range of conventional nanomedicine. In this study, commercially available generation 3 poly(amidoamine) (PAMAM) dendrimer was investigated for pulmonary delivery of siRNA directed against tumor necrosis factor (TNF) α for the treatment of acute lung inflammation. Delivery efficiency was assessed in vitro in the RAW264.7 macrophage cell line activated with lipopolysaccharide (LPS), and efficacy was evaluated in vivo in a murine model of LPS-induced lung inflammation upon pre-treatment with TNF-α siRNA. The PAMAM dendrimer-siRNA complexes (dendriplexes) displayed strong siRNA condensation and high cellular uptake in macrophages compared with non-complexed siRNA. Q-PCR analyses showed that the dendriplexes mediated efficient and specific TNF-α silencing in vitro, as compared to non-complexed siRNA and dendriplexes with negative control siRNA. Also in vivo, the PAMAM dendriplexes induced efficacious TNF-α siRNA inhibition, as compared to non-complexed siRNA, upon pulmonary administration to mice with LPS-induced lung inflammation. Hence, these data suggest that PAMAM dendrimers are promising for the local delivery of TNF-α siRNA in the treatment of lung inflammation via pulmonary administration. url: https://www.ncbi.nlm.nih.gov/pubmed/32798665/ doi: 10.1016/j.ejpb.2020.08.009 id: cord-004282-tox3tuzz author: Capellini, Francesca Maria title: Characterization of MDCK cells and evaluation of their ability to respond to infectious and non-infectious stressors date: 2019-12-04 words: 4327.0 sentences: 280.0 pages: flesch: 57.0 cache: ./cache/cord-004282-tox3tuzz.txt txt: ./txt/cord-004282-tox3tuzz.txt summary: Therefore, the aims of our study were to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation, as well as to evaluate the ability of this cell line to respond to infectious or non-infectious stressors. However, little is known about basal expression of genes involved in innate immunity, DNA repair, cell cycle regulation, as well as in the secretion of cytokines, and the response to infectious and non-infectious stressors. Owing to the above, the aims of our study were: 1-to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation. Moreover, in our previous study we demonstrated the ability of this heavy metal to modulate innate immune responses in IPEC-J2 cells as a function of both time and concentration (Razzuoli et al. abstract: The Madin-Darby Canine Kidney (MDCK) cell line is widely used as epithelial cell model in studies ranging from viral infection to environmental pollutants, and vaccines production. However, little is known about basal expression of genes involved in innate immunity, and the ability to respond to infectious and non-infectious stressors. Therefore, the aims of our study were to evaluate the basal level of expression of pivotal genes in the innate immune response and cell cycle regulation, as well as to evaluate the ability of this cell line to respond to infectious or non-infectious stressors. As surmised in our working hypothesis, we demonstrated the constitutive expression of genes involved in the innate immune response and cell defense alike, including TLRs, Interleukins, Myd88, p65/NF-kB and p53. Moreover, we described the ability of this cell line to respond to LPS and cadmium (Cd2+) in terms of gene expression and cytokine release. These data confirm the possibility of using this cell line as a model in studies of host/pathogen interaction and response to non-infectious stressors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002637/ doi: 10.1007/s10616-019-00360-z id: cord-302490-em1tiz7s author: Cañadas, Olga title: Lipid–Protein and Protein–Protein Interactions in the Pulmonary Surfactant System and Their Role in Lung Homeostasis date: 2020-05-25 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Pulmonary surfactant is a lipid/protein complex synthesized by the alveolar epithelium and secreted into the airspaces, where it coats and protects the large respiratory air–liquid interface. Surfactant, assembled as a complex network of membranous structures, integrates elements in charge of reducing surface tension to a minimum along the breathing cycle, thus maintaining a large surface open to gas exchange and also protecting the lung and the body from the entrance of a myriad of potentially pathogenic entities. Different molecules in the surfactant establish a multivalent crosstalk with the epithelium, the immune system and the lung microbiota, constituting a crucial platform to sustain homeostasis, under health and disease. This review summarizes some of the most important molecules and interactions within lung surfactant and how multiple lipid–protein and protein–protein interactions contribute to the proper maintenance of an operative respiratory surface. url: https://www.ncbi.nlm.nih.gov/pubmed/32466119/ doi: 10.3390/ijms21103708 id: cord-339272-trd6rkxw author: Chen, Na title: Prime-O-glucosylcimifugin attenuates lipopolysaccharide-induced acute lung injury in mice date: 2013-04-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Prime-O-glucosylcimifugin is an active chromone isolated from Saposhnikovia root which has been reported to have various activities, such as anti-convulsant, anticancer, anti-inflammatory properties. The purpose of this study was to evaluate the effect of prime-O-glucosylcimifugin on acute lung injury (ALI) induced by lipopolysaccharide in mice. BALB/c mice received intraperitoneal injection of Prime-O-glucosylcimifugin 1 h before intranasal instillation (i.n.) of lipopolysaccharide (LPS). Concentrations of tumor necrosis factor (TNF)-α, interleukin (IL)-1β and interleukin (IL)-6 in bronchoalveolar lavage fluid (BALF) were measured by enzyme-linked immunosorbent assay (ELISA). Pulmonary histological changes were evaluated by hematoxylin–eosin, myeloperoxidase (MPO) activity in the lung tissue and lung wet/dry weight ratios were observed. Furthermore, the mitogen-activated protein kinases (MAPK) signaling pathway activation and the phosphorylation of IκBα protein were determined by Western blot analysis. Prime-O-glucosylcimifugin showed promising anti-inflammatory effect by inhibiting the activation of MAPK and NF-κB signaling pathway. url: https://doi.org/10.1016/j.intimp.2013.04.014 doi: 10.1016/j.intimp.2013.04.014 id: cord-006778-qnxyhmw5 author: Chen, Xuxin title: Downregulation of Paralemmin-3 Ameliorates Lipopolysaccharide-Induced Acute Lung Injury in Rats by Regulating Inflammatory Response and Inhibiting Formation of TLR4/MyD88 and TLR4/TRIF Complexes date: 2017-08-12 words: 8483.0 sentences: 576.0 pages: flesch: 56.0 cache: ./cache/cord-006778-qnxyhmw5.txt txt: ./txt/cord-006778-qnxyhmw5.txt summary: Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. Adult Wistar rats (n = 6 per group) were treated as described in the BMaterials and Methods^section BEstablishment of ALI Rat Model and Experimental Design.^At 24 h after LPS challenge, the right lungs were harvested and stored in liquid nitrogen for the analysis of NF-κB phospho-p65, phospho-IRF3, TLR4, MyD88, TRIF, suppressor of cytokine signaling 3 (SOCS3) protein levels and coimmunoprecipitation assay, and the left lungs were harvested for the analysis of lung wet/dry weight ratio. abstract: Previous studies have demonstrated paralemmin-3 (PALM3) participates in Toll-like receptor (TLR) signaling. This study investigated the effect of PALM3 knockdown on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and its underlying mechanisms. We constructed a recombinant adenoviral vector containing short hairpin RNA for PALM3 to knockdown PALM3 expression. A transgene-free adenoviral vector was used as a negative control. The ALI rat model was established by LPS peritoneal injection at 48-h post-transfection. Results showed that downregulation of PALM3 improved the survival rate, attenuated lung pathological changes, alleviated pulmonary edema, lung vascular leakage and neutrophil infiltration, inhibited the production of proinflammatory cytokines and activation of nuclear factor κB and interferon β regulatory factor 3, and promoted the secretion of anti-inflammatory cytokine interleukin-10 and expression of suppressor of cytokine signaling-3 in the ALI rat model. However, PALM3 knockdown had no effect on TLR4, myeloid differentiation factor 88 (MyD88), and Toll-interleukin-1 receptor domain-containing adaptor inducing interferon β (TRIF) expression. Moreover, PALM3 knockdown reduced the interaction of TLR4 with MyD88 or TRIF induced by LPS in rat lungs. Therefore, the downregulation of PALM3 protected rats from LPS-induced ALI and its mechanisms were partially associated with the modulation of inflammatory responses and inhibition of TLR4/MyD88 and TLR4/TRIF complex formation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102376/ doi: 10.1007/s10753-017-0639-9 id: cord-310535-ay2cdf2w author: Cho, Chang-Won title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages date: 2017-06-20 words: 4636.0 sentences: 262.0 pages: flesch: 45.0 cache: ./cache/cord-310535-ay2cdf2w.txt txt: ./txt/cord-310535-ay2cdf2w.txt summary: title: Cynanchum wilfordii Polysaccharides Suppress Dextran Sulfate Sodium-Induced Acute Colitis in Mice and the Production of Inflammatory Mediators from Macrophages As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium(DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. The effects of HMFO on the expression of inflammatory proteins such as COX-2 and iNOS in cytosolic extracts from the colon of colitis mice were detected by Western blot analysis. abstract: We recently reported the immune-enhancing effects of a high-molecular-weight fraction (HMF) of CW in macrophages and immunosuppressed mice, and this effect was attributed to a crude polysaccharide. As polysaccharides may also have anti-inflammatory functions, we investigated the anti-inflammatory effects and related molecular mechanisms of a crude polysaccharide (HMFO) obtained from HMF of CW in mice with dextran sulfate sodium- (DSS-) induced colitis and in lipopolysaccharide-induced RAW 264.7 macrophages. HMFO ameliorated the pathological characteristics of colitis and significantly reduced production of proinflammatory cytokines in the serum. Histological analysis indicated that HMFO improved the signs of histological damage such as abnormal crypts, crypt loss, and inflammatory cell infiltration induced by DSS. In addition, HMFO inhibited iNOS and COX-2 protein expression, as well as phosphorylated NF-κB p65 levels in the colon tissue of mice with DSS-induced colitis. In macrophages, HMFO inhibited several cytokines and enzymes involved in inflammation such as prostaglandin E(2), nitric oxide, tumor necrosis factor-α, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 by attenuating nuclear factor-κB (NF-κB) and mitogen-activated protein kinases. HMFO attenuated inflammation both in vitro and in vivo, primarily by inhibiting NF-κB activation. Our findings indicate that HMFO is a promising remedy for treating inflammatory bowel diseases, such as colitis. url: https://www.ncbi.nlm.nih.gov/pubmed/28751820/ doi: 10.1155/2017/3859856 id: cord-282336-zvc04s39 author: Choudhary, Ishita title: Tristetraprolin Overexpression in Non-hematopoietic Cells Protects Against Acute Lung Injury in Mice date: 2020-09-02 words: 7910.0 sentences: 405.0 pages: flesch: 48.0 cache: ./cache/cord-282336-zvc04s39.txt txt: ./txt/cord-282336-zvc04s39.txt summary: In contrast, the lung injury in LPS-challenged TTP KO mice was characterized by severe consolidation (>90% of total area of lung section) (Figures 1F,G) that included infiltration of neutrophils, edema, fibrin, and airspace hemorrhage within the airway and alveolar lumen, multifocal loss of bronchiolar epithelium with infiltration of neutrophils and red blood cells within the bronchiolar lumen, and moderate to severe perivascular edema and inflammation (Figures 1F-H) . To determine the cell-specific role of TTP levels in ALI, we modulated TTP levels in hematopoietic progenitor cells (HPCs) and non-HPCs. In order to test whether donor HPCs repopulate the recipient mouse lungs, we first made bone marrow chimeras in which total body irradiated WT mice were transplanted with HPCs from a mouse expressing green fluorescent protein (GFP) in their somatic cells. abstract: Tristetraprolin (TTP) is a mRNA binding protein that binds to adenylate-uridylate-rich elements within the 3′ untranslated regions of certain transcripts, such as tumor necrosis factor (Tnf) mRNA, and increases their rate of decay. Modulation of TTP expression is implicated in inflammation; however, its role in acute lung inflammation remains unknown. Accordingly, we tested the role of TTP in lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. LPS-challenged TTP-knockout (TTP(KO)) mice, as well as myeloid cell-specific TTP-deficient (TTP(myeKO)) mice, exhibited significant increases in lung injury, although these responses were more robust in the TTP(KO). Mice with systemic overexpression of TTP (TTP(ΔARE)) were protected from ALI, as indicated by significantly reduced neutrophilic infiltration, reduced levels of neutrophil chemoattractants, and histological parameters of ALI. Interestingly, while irradiated wild-type (WT) mice reconstituted with TTP(KO) hematopoietic progenitor cells (HPCs) showed exaggerated ALI, their reconstitution with the TTP(ΔARE) HPCs mitigated ALI. The reconstitution of irradiated TTP(ΔARE) mice with HPCs from either WT or TTP(ΔARE) donors conferred significant protection against ALI. In contrast, irradiated TTP(ΔARE) mice reconstituted with TTP(KO) HPCs had exaggerated ALI, but the response was milder as compared to WT recipients that received TTP(KO) HPCs. Finally, the reconstitution of irradiated TTP(KO) recipient mice with TTP(ΔARE) HPCs did not confer any protection to the TTP(KO) mice. These data together suggest that non-HPCs-specific overexpression of TTP within the lungs protects against ALI via downregulation of neutrophil chemoattractants and reduction in neutrophilic infiltration. url: https://doi.org/10.3389/fimmu.2020.02164 doi: 10.3389/fimmu.2020.02164 id: cord-252859-zir02q69 author: Chung, T. Philip title: Molecular Diagnostics in Sepsis: From Bedside to Bench date: 2006-09-11 words: 5735.0 sentences: 299.0 pages: flesch: 47.0 cache: ./cache/cord-252859-zir02q69.txt txt: ./txt/cord-252859-zir02q69.txt summary: BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. 17, 18 We hypothesized that leukocyte gene expression profiles obtained using DNA microarrays could be used to predict septic states; in particular, distinguishing between sterile and infectious sources of systemic inflammation, a common conundrum in caring for the critically ill or injured. 30 PCA analysis of these 25 probe sets revealed that the seven experimental groups were clustered into three apparent phenotypes (Fig. 4) : control animals, LPS-treated animals (sterile source of systemic inflammation), and those that had any CLP treatment (Sepsis). abstract: BACKGROUND: Based on recent in vitro data, we tested the hypothesis that microarray expression profiles can be used to diagnose sepsis, distinguishing in vivo between sterile and infectious causes of systemic inflammation. STUDY DESIGN: Exploratory studies were conducted using spleens from septic patients and from mice with abdominal sepsis. Seven patients with sepsis after injury were identified retrospectively and compared with six injured patients. C57BL/6 male mice were subjected to cecal ligation and puncture, or to IP lipopolysaccharide. Control mice had sham laparotomy or injection of IP saline, respectively. A sepsis classification model was created and tested on blood samples from septic mice. RESULTS: Accuracy of sepsis prediction was obtained using cross-validation of gene expression data from 12 human spleen samples and from 16 mouse spleen samples. For blood studies, classifiers were constructed using data from a training data set of 26 microarrays. The error rate of the classifiers was estimated on seven de-identified microarrays, and then on a subsequent cross-validation for all 33 blood microarrays. Estimates of classification accuracy of sepsis in human spleen were 67.1%; in mouse spleen, 96%; and in mouse blood, 94.4% (all estimates were based on nested cross-validation). Lists of genes with substantial changes in expression between study and control groups were used to identify nine mouse common inflammatory response genes, six of which were mapped into a single pathway using contemporary pathway analysis tools. CONCLUSIONS: Sepsis induces changes in mouse leukocyte gene expression that can be used to diagnose sepsis apart from systemic inflammation. url: https://www.ncbi.nlm.nih.gov/pubmed/17084318/ doi: 10.1016/j.jamcollsurg.2006.06.028 id: cord-002411-iiw878w8 author: Ding, Xibing title: TLR4 signaling induces TLR3 up-regulation in alveolar macrophages during acute lung injury date: 2017-02-15 words: 6653.0 sentences: 431.0 pages: flesch: 57.0 cache: ./cache/cord-002411-iiw878w8.txt txt: ./txt/cord-002411-iiw878w8.txt summary: The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. To address the effect of LPS/TLR4-mediated activation of TLR3 in AMΦ on inflammatory cytokines, we assessed TNF-α and IL-6 in the serum and BALF, as well as the chemokines MIP-2 and MCP-1 in the BALF, following sequential intratracheal challenges with LPS and Poly I:C. This cross talk between TLR4 and TLR3 in AMΦ resulted in the amplification of cytokine (IL-6, TNF-α ) and chemokine (MIP-2, MCP-1) expression in response to LPS and Poly I:C, which activate TLR4 and TLR3, respectively, and subsequently led to enhanced PMN sequestration into the lung, which was found to be correlated with ALI based on the assessment of alveolar-capillary permeability and histological sections of lung tissue. abstract: Acute lung injury is a life-threatening inflammatory response caused by severe infection. Toll-like receptors in alveolar macrophages (AMΦ) recognize the molecular constituents of pathogens and activate the host’s innate immune responses. Numerous studies have documented the importance of TLR-TLR cross talk, but few studies have specifically addressed the relationship between TLR4 and TLR3. We explored a novel mechanism of TLR3 up-regulation that is induced by LPS-TLR4 signaling in a dose- and time-dependent manner in AMΦ from C57BL/6 mice, while the LPS-induced TLR3 expression was significantly reduced in TLR4(−/−) and Myd88(−/−) mice and following pretreatment with a NF-κB inhibitor. The enhanced TLR3 up-regulation in AMΦ augmented the expression of cytokines and chemokines in response to sequential challenges with LPS and Poly I:C, a TLR3 ligand, which was physiologically associated with amplified AMΦ-induced PMN migration into lung alveoli. Our study demonstrates that the synergistic effect between TLR4 and TLR3 in macrophages is an important determinant in acute lung injury and, more importantly, that TLR3 up-regulation is dependent on TLR4-MyD88-NF-κB signaling. These results raise the possibility that bacterial infections can induce sensitivity to viral infections, which may have important implications for the therapeutic manipulation of the innate immune system. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5309825/ doi: 10.1038/srep34278 id: cord-341458-hkopopa6 author: Dormont, Flavio title: Squalene-based multidrug nanoparticles for improved mitigation of uncontrolled inflammation in rodents date: 2020-06-05 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Uncontrolled inflammatory processes are at the root of numerous pathologies. Most recently, studies on confirmed COVID-19 cases have suggested that mortality might be due to virally induced hyperinflammation. Uncontrolled pro-inflammatory states are often driven by continuous positive feedback loops between pro-inflammatory signaling and oxidative stress, which cannot be resolved in a targeted manner. Here, we report on the development of multidrug nanoparticles for the mitigation of uncontrolled inflammation. The nanoparticles are made by conjugating squalene, a natural lipid, to adenosine, an endogenous immunomodulator, and then encapsulating α-tocopherol, as antioxidant. This resulted in high drug loading, biocompatible, multidrug nanoparticles. By exploiting the endothelial dysfunction at sites of acute inflammation, these multidrug nanoparticles delivered the therapeutic agents in a targeted manner, conferring survival advantage to treated animals in models of endotoxemia. Selectively delivering adenosine and antioxidants together could serve as a novel therapeutic approach for safe treatment of acute paradoxal inflammation. url: https://www.ncbi.nlm.nih.gov/pubmed/32548259/ doi: 10.1126/sciadv.aaz5466 id: cord-000959-nk2thkme author: Downer, Eric J. title: Identifying Early Inflammatory Changes in Monocyte-Derived Macrophages from a Population with IQ-Discrepant Episodic Memory date: 2013-05-06 words: 5396.0 sentences: 268.0 pages: flesch: 48.0 cache: ./cache/cord-000959-nk2thkme.txt txt: ./txt/cord-000959-nk2thkme.txt summary: METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). The purpose of the study was to compare the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and the response of these cells to LPS in samples prepared from the LP cohort and a cohort which we classified as IQ memory-consistent (high-performing, HP) individuals. P) TLR4 expression on CD11b + MDMs was increased in the LP group compared with the HP group (P,0.05) and this is also shown in the representative dot plots of TLR4 + cells ( and following LPS stimulation [6] , while pro-inflammatory cytokine [52] and chemokine [53, 54] levels are elevated in peripheral blood monocytes isolated from the elderly after LPS stimulation. abstract: BACKGROUND: Cells of the innate immune system including monocytes and macrophages are the first line of defence against infections and are critical regulators of the inflammatory response. These cells express toll-like receptors (TLRs), innate immune receptors which govern tailored inflammatory gene expression patterns. Monocytes, which produce pro-inflammatory mediators, are readily recruited to the central nervous system (CNS) in neurodegenerative diseases. METHODS: This study explored the expression of receptors (CD11b, TLR2 and TLR4) on circulating monocyte-derived macrophages (MDMs) and peripheral blood mononuclear cells (PBMCs) isolated from healthy elderly adults who we classified as either IQ memory-consistent (high-performing, HP) or IQ memory-discrepant (low-performing, LP). RESULTS: The expression of CD11b, TLR4 and TLR2 was increased in MDMs from the LP group when compared to HP cohort. MDMs from both groups responded robustly to treatment with the TLR4 activator, lipopolysaccharide (LPS), in terms of cytokine production. Significantly, MDMs from the LP group displayed hypersensitivity to LPS exposure. INTERPRETATION: Overall these findings define differential receptor expression and cytokine profiles that occur in MDMs derived from a cohort of IQ memory-discrepant individuals. These changes are indicative of inflammation and may be involved in the prodromal processes leading to the development of neurodegenerative disease. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646027/ doi: 10.1371/journal.pone.0063194 id: cord-252855-xtsnlu1f author: Drago-Serrano, Maria Elisa title: Lactoferrin: Balancing Ups and Downs of Inflammation Due to Microbial Infections date: 2017-03-01 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lactoferrin (Lf) is a glycoprotein of the primary innate immune-defense system of mammals present in milk and other mucosal secretions. This protein of the transferrin family has broad antimicrobial properties by depriving pathogens from iron, or disrupting their plasma membranes through its highly cationic charge. Noteworthy, Lf also exhibits immunomodulatory activities performing up- and down-regulation of innate and adaptive immune cells, contributing to the homeostasis in mucosal surfaces exposed to myriad of microbial agents, such as the gastrointestinal and respiratory tracts. Although the inflammatory process is essential for the control of invasive infectious agents, the development of an exacerbated or chronic inflammation results in tissue damage with life-threatening consequences. In this review, we highlight recent findings in in vitro and in vivo models of the gut, lung, oral cavity, mammary gland, and liver infections that provide experimental evidence supporting the therapeutic role of human and bovine Lf in promoting some parameters of inflammation and protecting against the deleterious effects of bacterial, viral, fungal and protozoan-associated inflammation. Thus, this new knowledge of Lf immunomodulation paves the way to more effective design of treatments that include native or synthetic Lf derivatives, which may be useful to reduce immune-mediated tissue damage in infectious diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/28257033/ doi: 10.3390/ijms18030501 id: cord-004754-5596p4ma author: Duan, X. title: Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) date: 2014-04-06 words: 4875.0 sentences: 252.0 pages: flesch: 50.0 cache: ./cache/cord-004754-5596p4ma.txt txt: ./txt/cord-004754-5596p4ma.txt summary: title: Effects of origin and state of differentiation and activation of monocytes/macrophages on their susceptibility to porcine reproductive and respiratory syndrome virus (PRRSV) To evaluate the effect of maturation of monocytes/macrophages on their susceptibility to PRRSV, freshly isolated AMf, PMf and BMo from ®ve donors were seeded in 24-well tissue culture plates at a concentration of 10 6 cells/ml/well and further incubated in RPMI medium plus 5% of foetal bovine serum at 37 C with 5% CO 2 . The virus titres and percentage of viral antigen positive cells in freshly isolated porcine AMf at 24 and 48 h after inoculation were respectively 1 to 2 log 10 TCID 50 and 5 to 10 times lower than those of one day cultivated ones, which is signi®cantly different (P''0.01). Porcine reproductive and respiratory syndrome virus infection of alveolar macrophages can be blocked by monoclonal antibodies against cell surface surface antigens abstract: In this study, the susceptibility of porcine peripheral blood monocytes (BMo), peritoneal macrophages (PMφ) and alveolar macrophages (AMφ) to PRRSV was examined. To test the effect of differentiation and activation on their susceptibility, AMφ and BMo were aged, cultivated in either adhesion or suspension and treated with bacterial lipopolysaccharide (LPS) and phorbol myristate acetate (PMA). It was found that freshly isolated PMφ and BMo were non-permissive to PRRSV. PMφ remained refractory but a few BMo became susceptible after 1 day cultivation. AMφ were permissive with a significant increase of their susceptibility after one day cultivation. In a binding assay, it was demonstrated that the attachment of biotinylated PRRSV to AMf is much more efficient than to PMφ and BMo. Two monoclonal antibodies (Mabs) 41D3 and 41D5 which block PRRSV infection of AMφ and are directed against a candidate receptor for PRRSV only reacted with the cell membrane of AMφ. PMA treatment of AMφ blocked PRRSV replication in the cells in a dose-dependent manner. The blocking effect of PMA decreased after 9 h continuous pre-treatment and diminished after 24 h continuous pre-treatment. PMA treatment did not affect the binding of PRRSV and MAb 41D3 and 41D5 to AMφ. Direct or indirect treatment of AMφ and BMo with LPS or cultivation in suspension did not significantly affect their susceptibility. These results provide clear evidence that PRRSV has a strongly restricted tropism for only some sub-populations of porcine monocytes/macrophages and that some specific states of differentiation and activation of monocytes/macrophages considerably affect their susceptibility. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7086874/ doi: 10.1007/s007050050256 id: cord-007178-h0ordzm9 author: Felts, Paul A. title: Inflammation and primary demyelination induced by the intraspinal injection of lipopolysaccharide date: 2005-05-04 words: 9492.0 sentences: 425.0 pages: flesch: 47.0 cache: ./cache/cord-007178-h0ordzm9.txt txt: ./txt/cord-007178-h0ordzm9.txt summary: At this interval the lesion was clearly discernible using differential interference contrast optics as a region of tissue disruption in the dorsal funiculus, allowing AdPC-positive cells to be counted in both demyelinated and apparently normal areas of the dorsal funiculus of LPS-injected animals. Spinal cords injected with saline ( Fig. 1) showed damage restricted to a very small number of axons undergoing either Table 1 Populations of inflammatory cells present in the spinal cord at various times following the injection of LPS or saline into the dorsal funiculus Wallerian degeneration or demyelination. The cells were often adjacent to large blood vessels, and they formed only a small subset of the substantial population of ED1-positive Fig. 7 Light micrographs showing GFAP immunoreactivity at the interface between the dorsal funiculus (DF) and the grey matter (GM) in an animal 7 days after the injection of LPS into the spinal cord. abstract: Inflammation is a prominent feature of several disorders characterized by primary demyelination, but it is not clear whether a relationship exists between inflammation and myelin damage. We have found that substantial demyelination results from the focal inflammatory lesion caused by the injection of lipopolysaccharide (LPS; 200 ng) directly into the rat dorsal funiculus. Within 24 h, such injections caused a focal inflammatory response consisting of a substantial number of polymorphonuclear cells and ED1-positive and inducible nitric oxide synthase (iNOS)-positive macrophages/microglia. The number of inflammatory cells was substantially reduced by day 7. OX-52-positive T-cells were less frequently observed but were present in the meninges at 8 h, reached a maximum in the dorsal funiculus at 7 days, and were rare at 14 days. The inflammation was followed by the appearance of a large lesion of primary demyelination that encompassed up to ∼75% of the cross-sectional area of the dorsal funiculus. Treatment with dexamethasone significantly reduced the number of cells expressing iNOS, but did not prevent the demyelination. By 28 days the lesions were largely remyelinated, usually by Schwann cells. These changes were not observed in control, saline-injected animals. We conclude that the intraspinal injection of LPS results in inflammation and subsequently in prominent demyelination. The mechanisms underlying the demyelination are not clear, but it is notable that it typically begins with disruption of the adaxonal myelin. Indeed, there is an early loss of myelin-associated glycoprotein within the lesion, despite the persistence of proteolipid protein. This combination is a feature of the pattern III lesion recently described in multiple sclerosis (Lucchinetti et al., 2000), and we therefore suggest that LPS-induced demyelination may serve as the first experimental model available for the study of this type of multiple sclerosis lesion. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109778/ doi: 10.1093/brain/awh516 id: cord-000425-isw6jeir author: Flori, Laurence title: Immunity Traits in Pigs: Substantial Genetic Variation and Limited Covariation date: 2011-07-29 words: 7831.0 sentences: 388.0 pages: flesch: 46.0 cache: ./cache/cord-000425-isw6jeir.txt txt: ./txt/cord-000425-isw6jeir.txt summary: A study on Yorkshire pigs selected for eight generations for high and low adaptive IR (HIR and LIR, respectively) on an index combining four standardized measures of specific antibodies and cellmediated IR, after stimulation with specific antigens (bacillus Calmette-Guérin and hen egg white lysozyme), has revealed that HIR and LIR animals differ in response to immunization and infection [2, 11, 12, 13, 14] . Finally, several significant QTLs for total leukocyte count ( [20, 21] ; Animal-QTLdb, http://www.animalgenome.org/cgi-bin/QTLdb/index), mitogen-induced proliferation [20] , antibody response [20, 22] , cytokine production (IL10 and IFNc) [23] , complement activity [22] , and acute phase protein serum concentration [22] have been detected and mapped to different pig chromosomes. In this report, we present the results of a global genetic study, combining principal component analysis (PCA), and genetic parameter estimation applied to a large number of innate and adaptive ITs in a pig population vaccinated against Mycoplasma hyopneumoniae (M. abstract: BACKGROUND: Increasing robustness via improvement of resistance to pathogens is a major selection objective in livestock breeding. As resistance traits are difficult or impossible to measure directly, potential indirect criteria are measures of immune traits (ITs). Our underlying hypothesis is that levels of ITs with no focus on specific pathogens define an individual's immunocompetence and thus predict response to pathogens in general. Since variation in ITs depends on genetic, environmental and probably epigenetic factors, our aim was to estimate the relative importance of genetics. In this report, we present a large genetic survey of innate and adaptive ITs in pig families bred in the same environment. METHODOLOGY/PRINCIPAL FINDINGS: Fifty four ITs were studied on 443 Large White pigs vaccinated against Mycoplasma hyopneumoniae and analyzed by combining a principal component analysis (PCA) and genetic parameter estimation. ITs include specific and non specific antibodies, seric inflammatory proteins, cell subsets by hemogram and flow cytometry, ex vivo production of cytokines (IFNα, TNFα, IL6, IL8, IL12, IFNγ, IL2, IL4, IL10), phagocytosis and lymphocyte proliferation. While six ITs had heritabilities that were weak or not significantly different from zero, 18 and 30 ITs had moderate (0.10.4) heritability values, respectively. Phenotypic and genetic correlations between ITs were weak except for a few traits that mostly include cell subsets. PCA revealed no cluster of innate or adaptive ITs. CONCLUSIONS/SIGNIFICANCE: Our results demonstrate that variation in many innate and adaptive ITs is genetically controlled in swine, as already reported for a smaller number of traits by other laboratories. A limited redundancy of the traits was also observed confirming the high degree of complementarity between innate and adaptive ITs. Our data provide a genetic framework for choosing ITs to be included as selection criteria in multitrait selection programmes that aim to improve both production and health traits. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3146468/ doi: 10.1371/journal.pone.0022717 id: cord-000920-68eblcke author: Gallego, Carolina title: Interaction of Bordetella bronchiseptica and Its Lipopolysaccharide with In Vitro Culture of Respiratory Nasal Epithelium date: 2013-03-11 words: 4557.0 sentences: 233.0 pages: flesch: 40.0 cache: ./cache/cord-000920-68eblcke.txt txt: ./txt/cord-000920-68eblcke.txt summary: The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. Bordetella bronchiseptica is a Gram-negative bacterium capable of colonizing the respiratory tract of a large range of mammalian hosts, including mice, rats, guinea pigs, rabbits, cats, dogs, pigs, sheep, horses, and bears [1] . bronchiseptica or its LPS in an isolated manner by using a model that more closely reflects the in vivo conditions (i.e., reconstructing the architecture and cell relationships of the respiratory epithelium in a natural host of this microorganism) has not been documented. In this work, LPS induced a higher infiltration of PMN in the respiratory epithelium and the propria of nasal septa than did the bacterium. B. bronchiseptica and its LPS distribution on the nasal septum respiratory epithelium were evaluated by the indirect immunoperoxidase and lectin histochemistry techniques. abstract: The nasal septa of fetal rabbits at 26 days of gestation were harvested by cesarean section of the does while under anesthesia and then exposed to Bordetella bronchiseptica or its lipopolysaccharide (LPS) for periods of 2 and 4 hours. A total of 240 explants were used. The tissues were examined using the Hematoxylin & Eosin technique. Then, semithin sections (0.5 μm) were stained with toluidine blue and examined with indirect immunoperoxidase (IPI) and lectin histochemistry. The most frequent and statistically significant findings were as follows: (1) cell death and increased goblet cell activity when exposed to bacteria and (2) cell death, cytoplasmic vacuolation and infiltration of polymorphonuclear leukocytes when exposed to LPS. The lesions induced by the bacterium were more severe than with LPS alone, except for the cytoplasmic vacuolation in epithelial cells. IPI stained the ciliated border of the epithelium with the bacterium more intensely, while LPS lectin histochemistry preferentially labeled the cytoplasm of goblet cell. These data indicate that B. bronchiseptica and its LPS may have an affinity for specific glycoproteins that would act as adhesion receptors in both locations. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608130/ doi: 10.1155/2013/347086 id: cord-294193-xjq9j2gv author: Gamazo, Carlos title: Mimicking microbial strategies for the design of mucus-permeating nanoparticles for oral immunization date: 2015-01-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dealing with mucosal delivery systems means dealing with mucus. The name mucosa comes from mucus, a dense fluid enriched in glycoproteins, such as mucin, which main function is to protect the delicate mucosal epithelium. Mucus provides a barrier against physiological chemical and physical aggressors (i.e., host secreted digestive products such as bile acids and enzymes, food particles) but also against the potentially noxious microbiota and their products. Intestinal mucosa covers 400 m(2) in the human host, and, as a consequence, is the major portal of entry of the majority of known pathogens. But, in turn, some microorganisms have evolved many different approaches to circumvent this barrier, a direct consequence of natural co-evolution. The understanding of these mechanisms (known as virulence factors) used to interact and/or disrupt mucosal barriers should instruct us to a rational design of nanoparticulate delivery systems intended for oral vaccination and immunotherapy. This review deals with this mimetic approach to obtain nanocarriers capable to reach the epithelial cells after oral delivery and, in parallel, induce strong and long-lasting immune and protective responses. url: https://www.ncbi.nlm.nih.gov/pubmed/25615880/ doi: 10.1016/j.ejpb.2015.01.010 id: cord-029969-1fa8hk2n author: Ge, Xin title: Lycorine attenuates lipopolysaccharide-induced acute lung injury through the HMGB1/TLRs/NF-κB pathway date: 2020-08-01 words: 4669.0 sentences: 291.0 pages: flesch: 54.0 cache: ./cache/cord-029969-1fa8hk2n.txt txt: ./txt/cord-029969-1fa8hk2n.txt summary: Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically. Mechanism studies showed that the activation of HMGB1/TLRs/NF-κB pathway induced by LPS increased inflammatory responses and oxidative stress, while its blockade by lycorine effectively suppressed pulmonary inflammatory response and oxidative stress, and further alleviated lung injury. abstract: Lung injury associated with systemic inflammatory response is a common problem affecting human health. Previous studies have shown that lycorine exerts a anti-inflammatory effect. However, whether lycorine alleviates lung injury remains unclear. To explore this issue, BALB/c mice and MLE-12 cells were treated with lipopolysaccharide (LPS) to establish lung injury mouse model and cell model, respectively. Glycyrrhizic acid, known as an inhibitor of ALI, was also used to study the effects of lycorine in vitro. Our results showed that after LPS treatment, the lung injury score, lung wet-to-dry weight ratio, and malondialdehyde (MDA) production in the lung tissues and the expression levels of tumor necrosis factor-α, interleukin-1β, and interleukin-6 in bronchoalveolar lavage fluid were significantly increased, whereas their levels were decreased by lycorine. Additionally, LPS injection activated the high-mobility group box 1 (HMGB1)/Toll-like receptors (TLRs)/NF-κB pathway. However, lycorine treatment attenuated the activity of the HMGB1/TLRs/NF-κB pathway in the lung tissues. In vitro studies showed that lycorine administration significantly decreased the levels of inflammatory cytokines and MDA and attenuated the activity of the HMGB1/TLRs/NF-κB pathway in LPS-treated cells. Moreover, the inhibitory effects of lycorine on the inflammatory response and oxidative stress in LPS-treated lung cells were similar with that of glycyrrhizic acid, and this inhibition was intensified by both lycorine and glycyrrhizic acid treatment. We suggest that lycorine could alleviate LPS-induced lung injury of inflammation and oxidative stress by blocking the HMGB1/TLRs/NF-κB pathway, which gives a new perspective for ALI therapy to treat lycorine as a potential treatment clinically. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395800/ doi: 10.1007/s13205-020-02364-5 id: cord-018969-0zrnfaad author: Giese, Matthias title: Types of Recombinant Vaccines date: 2015-09-24 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The original scientific strategy behind vaccinology has historically been to “isolate, inactivate, and inject,” first invoked by Louis Pasteur. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7123991/ doi: 10.1007/978-3-319-25832-4_9 id: cord-354765-abayh871 author: Graham, R. S. title: Calming the Cytokine Storm - Splenic Ultrasound for Treating Inflammatory Disorders and Potentially COVID-19 date: 2020-07-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Hyperinflammation and uncontrolled cytokine release, which can be seen in severe cases of COVID-19, require therapy to reduce the innate immune response without hindering necessary adaptive immune mechanisms. Here, we show results from the first in-human trials using non-invasive ultrasound stimulation of the spleen to reduce cytokine release in the context of both an acute response in healthy subjects and a chronic inflammatory condition in rheumatoid arthritis patients. Splenic ultrasound results in a reduction in TNF serum levels, as well as IL-1B; and IL-8 transcript levels in monocytes. There is also a down regulation of pathways involved in TNF and IL-6 production, and IFNgamma- and NFKB-regulated genes. Many of these cytokines or pathways are upregulated in COVID-19 patients. There is also a reduction in chemokine transcript levels and other components of the chemotactic response, suggesting that reduction of cellular migration may contribute to the therapeutic effects of ultrasound. There is no inhibition of the adaptive immune response with ultrasound treatment relating to antibody production. This is consistent with a pre-clinical animal model where enhanced antibody production was achieved with splenic ultrasound. Therefore, this new splenic ultrasound approach has the potential to treat acute and chronic hyper-inflammatory diseases, as it lowers cytokine levels without disrupting the normal adaptive immune response. Portable ultrasound technologies are currently being developed and translated to the clinic to treat various inflammatory disorders, with more recent efforts directed towards combatting the hyperinflammation or cytokine storm in COVID-19 patients. url: http://medrxiv.org/cgi/content/short/2020.07.14.20153528v1?rss=1 doi: 10.1101/2020.07.14.20153528 id: cord-335107-ew9uid2e author: He, Xinran title: Long-term inhibition of dipeptidyl-peptidase 4 reduces islet infiltration and downregulates IL-1β and IL-12 in NOD mice date: 2020-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Dipeptidyl-peptidase 4 (DPP-4) inhibitor (sitagliptin) is a novel anti-hyperglycemia drug in the treatment of type 2 diabetes. However, its potential in type 1 diabetes is still unclear. Recent studies show that increased infection, especially respiratory tract infection, is significantly associated with DPP-4 inhibitors. In this study, we aimed to explore the effects of long-term inhibition of DPP- 4 on innate immunity in type 1 diabetes. Forty mice were randomly divided into 4 groups (n = 10 in each group): control group, lipopolysaccharide (LPS) group, sitagliptin group and sitagliptin + LPS group. The concentrations of IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α and IFN-γ were measured with Mesco Scale Discovery multiplexed-assay kit. Immunohistochemistry staining of pancreases was performed and insulitis scores for each islet were determined. The results showed that DPP-4 inhibition has no effect on incident rate of diabetes and metabolic parameters in NOD mice. Long-term inhibition of DPP-4 reduced CD4+T cells to infiltrate into islets and ameliorated insulitis in NOD mice. DPP-4 inhibition downregulated serum interleukin IL-1β and IL-12 in NOD mice. However, it had no significant effect on LPS-induced IL-1β, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in NOD mice. In conclusion, Long-term inhibition of DPP-4 exists anti-inflammatory effect in type 1 diabetes probably by reducing CD4+T cells to infiltrate into islets and downregulating L-1β and IL-12 in serum. url: https://www.sciencedirect.com/science/article/pii/S1567576920304938 doi: 10.1016/j.intimp.2020.106945 id: cord-298224-flyx85lr author: Hibbitts, Alan J. title: In Vitro and In Vivo Assessment of PEGylated PEI for Anti-IL-8/CxCL-1 siRNA Delivery to the Lungs date: 2020-06-27 words: 11340.0 sentences: 633.0 pages: flesch: 56.0 cache: ./cache/cord-298224-flyx85lr.txt txt: ./txt/cord-298224-flyx85lr.txt summary: Following optimization with antiglyceraldehyde 3-phosphate dehydrogenase (GAPDH) siRNA, PEI and PEI-LPEG anti-IL8 siRNA nanoparticles were assessed for efficacy using polarised Calu-3 human airway epithelial cells and a twin stage impinger (TSI) in vitro lung model. This work demonstrates the potential of nebulised PEI-PEG siRNA nanoparticles in modulating pulmonary inflammation and highlights the need to move towards more relevant in vitro and in vivo models for respiratory drug development. In contrast, the nebulised PEI-LPEG siRNA nanoparticles demonstrated significantly greater levels of GAPDH knockdown versus the PBS-treated controls at higher doses. Using the differential cell staining of BAL samples with Eosin Y and azur/methylene blue, it was In the case of the PEI-LPEG siRNA nanoparticle-treated groups, both the non-targeting (NT) and anti-CXCL-1 siRNA-treated groups demonstrated 10-fold decreases in the CXCL-1 gene expression compared to the PBS-LPS samples (4-vs. abstract: Inhalation offers a means of rapid, local delivery of siRNA to treat a range of autoimmune or inflammatory respiratory conditions. This work investigated the potential of a linear 10 kDa Poly(ethylene glycol) (PEG)-modified 25 kDa branched polyethyleneimine (PEI) (PEI-LPEG) to effectively deliver siRNA to airway epithelial cells. Following optimization with anti- glyceraldehyde 3-phosphate dehydrogenase (GAPDH) siRNA, PEI and PEI-LPEG anti-IL8 siRNA nanoparticles were assessed for efficacy using polarised Calu-3 human airway epithelial cells and a twin stage impinger (TSI) in vitro lung model. Studies were then advanced to an in vivo lipopolysaccharide (LPS)-stimulated rodent model of inflammation. In parallel, the suitability of the siRNA-loaded nanoparticles for nebulization using a vibrating mesh nebuliser was assessed. The siRNA nanoparticles were nebulised using an Aerogen(®) Pro vibrating mesh nebuliser and characterised for aerosol output, droplet size and fine particle fraction. Only PEI anti-IL8 siRNA nanoparticles were capable of significant levels of IL-8 knockdown in vitro in non-nebulised samples. However, on nebulization through a TSI, only PEI-PEG siRNA nanoparticles demonstrated significant decreases in gene and protein expression in polarised Calu-3 cells. In vivo, both anti-CXCL-1 (rat IL-8 homologue) nanoparticles demonstrated a decreased CXCL-1 gene expression in lung tissue, but this was non-significant. However, PEI anti-CXCL-1 siRNA-treated rats were found to have significantly less infiltrating macrophages in their bronchoalveolar lavage (BAL) fluid. Overall, the in vivo gene and protein inhibition findings indicated a result more reminiscent of the in vitro bolus delivery rather than the in vitro nebulization data. This work demonstrates the potential of nebulised PEI-PEG siRNA nanoparticles in modulating pulmonary inflammation and highlights the need to move towards more relevant in vitro and in vivo models for respiratory drug development. url: https://www.ncbi.nlm.nih.gov/pubmed/32605011/ doi: 10.3390/nano10071248 id: cord-297128-s5c9h4lm author: Hong, Joung-Woo title: Anti-inflammatory activity of cinnamon water extract in vivo and in vitro LPS-induced models date: 2012-11-28 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: BACKGROUND: Cinnamon bark is one of the most popular herbal ingredients in traditional oriental medicine and possesses diverse pharmacological activities including anti-bacterial, anti-viral, and anti-cancer properties. The goal of this study is to investigate the in vivo and in vitro inhibitory effect of cinnamon water extract (CWE) on lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-α and its underlying intracellular mechanisms. METHODS: CWE was orally administrated to mice for 6 days prior to intraperitoneal injection of LPS. Serum levels of TNF-α and interleukin (IL)-6 were determined 1 hour after LPS stimulation. Peritoneal macrophages from thioglycollate-injected mice were isolated and assayed for viability, cytokine expression and signaling molecules upon LPS stimulation. CWE was further fractioned according to molecular size, and the levels of total polyphenols and biological activities of each fraction were measured. RESULTS: The oral administration of CWE to mice significantly decreased the serum levels of TNF-α and IL-6. CWE treatment in vitro decreased the mRNA expression of TNF-α. CWE blocked the LPS-induced degradation of IκBα as well as the activation of JNK, p38 and ERK1/2. Furthermore, size-based fractionation of CWE showed that the observed inhibitory effect of CWE in vitro occurred in the fraction containing the highest level of total polyphenols. CONCLUSIONS: Treatment with CWE decreased LPS-induced TNF-α in serum. In vitro inhibition of TNF-α gene by CWE may occur via the modulation of IκBα degradation and JNK, p38, and ERK1/2 activation. Our results also indicate that the observed anti-inflammatory action of CWE may originate from the presence of polyphenols. url: https://doi.org/10.1186/1472-6882-12-237 doi: 10.1186/1472-6882-12-237 id: cord-306577-gq6fss5l author: Hsueh, Wei title: Neonatal Necrotizing Enterocolitis: Clinical Considerations and Pathogenetic Concepts date: 2002-11-11 words: 8414.0 sentences: 453.0 pages: flesch: 40.0 cache: ./cache/cord-306577-gq6fss5l.txt txt: ./txt/cord-306577-gq6fss5l.txt summary: Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. We developed a model of bowel necrosis in adult rats and mice by injecting endotoxin (lipopolysaccharide, LPS) [32] , PAF (platelet-activating factor, paf-acether) [33, 34] , tumor necrosis factor-␣ (TNF) [35] , or a combination of these agents. Experimental evidence strongly supports the role of PAF, LPS, and TNF in acute ischemic bowel necrosis and in the neonatal rat model of NEC. Hypoxia causes ischemic bowel necrosis in rats: the role of platelet-activating factor (PAF-acether) abstract: Necrotizing enterocolitis (NEC), a disease affecting predominantly premature infants, is a leading cause of morbidity and mortality in neonatal intensive care units. Although several predisposing factors have been identified, such as prematurity, enteral feeding, and infection, its pathogenesis remains elusive. In the past 20 years, we have established several animal models of NEC in rats and found several endogenous mediators, especially platelet-activating factor (PAF), which may play a pivotal role in NEC. Injection of PAF induces intestinal necrosis, and PAF antagonists prevent the bowel injury induced by bacterial endotoxin, hypoxia, or challenge with tumor necrosis factor-a (TNF) plus endotoxin in adult rats. The same is true for lesions induced by hypoxia and enteral feeding in neonatal animals. Human patients with NEC show high levels of PAF and decreased plasma PAF-acetylhydrolase, the enzyme degrading PAF. The initial event in our experimental models of NEC is probably polymorphonuclear leukocyte (PMN) activation and adhesion to venules in the intestine, which initiates a local inflammatory reaction involving proinflammatory mediators including TNF, complement, prostaglandins, and leukotriene C4. Subsequent norepinephrine release and mesenteric vasoconstriction result in splanchnic ischemia and reperfusion. Bacterial products (e.g., endotoxin) enter the intestinal tissue during local mucosal barrier breakdown, and endotoxin synergizes with PAF to amplify the inflammation. Reactive oxygen species produced by the activated leukocytes and by intestinal epithelial xanthine oxidase may be the final pathway for tissue injury. Protective mechanisms include nitric oxide produced by the constitutive (mainly neuronal) nitric oxide synthase, and indigenous probiotics such as Bifidobacteria infantis. The former maintains intestinal perfusion and the integrity of the mucosal barrier, and the latter keep virulent bacteria in check. The development of tissue injury depends on the balance between injurious and protective mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/12424605/ doi: 10.1007/s10024-002-0602-z id: cord-000984-64p3wpav author: Huang, Shang-Hui title: Self-Oligomerization Is Essential for Enhanced Immunological Activities of Soluble Recombinant Calreticulin date: 2013-06-10 words: 5252.0 sentences: 291.0 pages: flesch: 54.0 cache: ./cache/cord-000984-64p3wpav.txt txt: ./txt/cord-000984-64p3wpav.txt summary: We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. Additionally, rCRT/39-272, a prokaryotically-expressed murine CRT fragment covering amino acid residues 39-272 fused with an N-terminal His-tag, was extraordinarily potent in activating B cells and macrophages in vitro and also in eliciting specific Ab production in mice [16] . The sequence of rCRT/39-272 encompasses most of the globular N domain (aa residues , and we have previously shown that it possess lectin-like activity (selective binding with polysaccharides including carrageenan, alginic acids, and hyaluronic acids in ELISAs) [16] , implying that the prokaryotically expressed recombinant polypeptide retained the lectin activity of CRT. Purified nCRT, but not BSA or recombinant enhanced green fluorescence protein (rEGFP, 28 kDa with a His-tag), was positively recognized by CRT-Abs. As evidenced by native PAGE analysis, a substantial amount of rCRT/18-412 formed higher-molecular-weight oligomers, whilst nCRT existed mostly in monomeric form (Figs. abstract: We have recently reported that calreticulin (CRT), a luminal resident protein, can be found in the sera of patients with rheumatoid arthritis and also that recombinant CRT (rCRT) exhibits extraordinarily strong immunological activities. We herein further demonstrate that rCRT fragments 18–412 (rCRT/18-412), rCRT/39-272, rCRT/120-308 and rCRT/120-250 can self-oligomerize in solution and are 50–100 fold more potent than native CRT (nCRT, isolated from mouse livers) in activating macrophages in vitro. We narrowed down the active site of CRT to residues 150–230, the activity of which also depends on dimerization. By contrast, rCRT/18-197 is almost completely inactive. When rCRT/18-412 is fractionated into oligomers and monomers by gel filtration, the oligomers maintain most of their immunological activities in terms of activating macrophages in vitro and inducing specific antibodies in vivo, while the monomers were much less active by comparison. Additionally, rCRT/18-412 oligomers are much better than monomers in binding to, and uptake by, macrophages. Inhibition of macrophage endocytosis partially blocks the stimulatory effect of rCRT/18-412. We conclude that the immunologically active site of CRT maps between residues 198–230 and that soluble CRT could acquire potent immuno-pathological activities in microenvironments favoring its oligomerization. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3677884/ doi: 10.1371/journal.pone.0064951 id: cord-296258-8pc2p3az author: Hwang, Eun-Ha title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation date: 2016-01-31 words: 5579.0 sentences: 358.0 pages: flesch: 54.0 cache: ./cache/cord-296258-8pc2p3az.txt txt: ./txt/cord-296258-8pc2p3az.txt summary: title: Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF) mediates innate immune responses in murine peritoneal mesothelial cells through TLR3 and TLR4 stimulation In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs–adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). When faced with an infection, mesothelial cells express specific surface markers that enable them to promote the migration of neutrophils, to interact with extracellular matrix proteins, to present antigens to immune cells, and to produce biologically important molecules such as proinflammatory cytokines, chemokines, and nitric oxide (NO) [6, 7] Toll-like receptors (TLRs) are type I transmembrane proteins and comprise an ectodomain, which contains leucine-rich repeats that mediate the recognition of pathogen-associated molecular patterns (PAMPs); a transmembrane region; and a cytosolic Toll/ IL-1 receptor (TIR) domain that activates downstream signaling pathways [8] . abstract: Abstract Mesothelial cells are composed of monolayer of the entire surface of serosal cavities including pleural, pericardial, and peritoneal cavity. Although mesothelial cells are known to express multiple Toll-like receptors (TLRs) which contribute to trigger innate immune responses against infections, the precise molecular mechanism remains still unclear. In the present study, we investigated the role of Toll/IL-1 domain-containing adaptor inducing IFN-β (TRIF), one of the two major TLRs–adaptor molecules, on innate immune response induced by TLR3 and TLR4 stimulation in murine peritoneal mesothelial cells (PMCs). TRIF was strongly expressed in PMCs and its deficiency led to impaired production of cytokines and chemokines by poly I:C and LPS in the cells. Activation of NF-κB or MAPKs through poly I:C and LPS stimulation was reduced in TRIF-deficient PMCs as compared to the WT cells. TRIF was also necessary for optimal nitric oxide synthesis and gene expression of inducible nitric oxide synthase (iNOS) and IFN-β in PMCs in response to poly I:C and LPS. Furthermore, both Escherichia coli and Pseudomonas aeruginosa induced high level of IL-6, CXCL1, and CCL2 production in PMCs, which was significantly impaired by TRIF deficiency. These results demonstrated that TRIF is required for optimal activation of innate immune responses in mesothelial cells against microbial infections. url: https://doi.org/10.1016/j.cyto.2015.11.010 doi: 10.1016/j.cyto.2015.11.010 id: cord-261367-i1n8x0uc author: Hwang, Ji Young title: Inducible Bronchus–Associated Lymphoid Tissue (iBALT) Attenuates Pulmonary Pathology in a Mouse Model of Allergic Airway Disease date: 2020-09-25 words: 7609.0 sentences: 309.0 pages: flesch: 47.0 cache: ./cache/cord-261367-i1n8x0uc.txt txt: ./txt/cord-261367-i1n8x0uc.txt summary: Instead, mice with iBALT had reduced Th2-associated mRNA expression, less eosinophil recruitment to the lungs and airways, attenuated goblet cell hyperplasia and reduced mucus production following pulmonary sensitization and challenge with OVA. To test the effect of iBALT on the immune response to a pulmonary allergen, we administered LPS (or PBS) to neonatal mice as described above, allowed the mice to rest until they were 7 weeks old, then intranasally sensitized the iBALT and control groups with 100 µg OVA in combination with low dose (0.1 µg) LPS on days 49, 50, and 51 and challenged them on days 63, 64, 67, and 68 with 25 µg OVA ( Figure 1E ). Together, these data suggest that the spatial distribution of effector Th2 cells and Tregs is affected by the presence of iBALT (they cluster together), which may explain how iBALT and control mice can have similar numbers of Th2 cells in their lungs, but have so profoundly different outcomes in terms of eosinophil accumulation and histopathology. abstract: Inducible Bronchus Associated Lymphoid Tissue (iBALT) is an ectopic lymphoid tissue associated with severe forms of chronic lung diseases, including chronic obstructive pulmonary disease, rheumatoid lung disease, hypersensitivity pneumonitis and asthma, suggesting that iBALT may exacerbate these clinical conditions. However, despite the link between pulmonary pathology and iBALT formation, the role of iBALT in pathogenesis remains unknown. Here we tested whether the presence of iBALT in the lung prior to sensitization and challenge with a pulmonary allergen altered the biological outcome of disease. We found that the presence of iBALT did not exacerbate Th2 responses to pulmonary sensitization with ovalbumin. Instead, we found that mice with iBALT exhibited delayed Th2 accumulation in the lung, reduced eosinophil recruitment, reduced goblet cell hyperplasia and reduced mucus production. The presence of iBALT did not alter Th2 priming, but instead delayed the accumulation of Th2 cells in the lung following challenge and altered the spatial distribution of T cells in the lung. These results suggest that the formation of iBALT and sequestration of effector T cells in the context of chronic pulmonary inflammation may be a mechanism by which the immune system attenuates pulmonary inflammation and prevents excessive pathology. url: https://www.ncbi.nlm.nih.gov/pubmed/33101290/ doi: 10.3389/fimmu.2020.570661 id: cord-003055-88q36g00 author: Imai, Kenji title: Administration of molecular hydrogen during pregnancy improves behavioral abnormalities of offspring in a maternal immune activation model date: 2018-06-15 words: 6212.0 sentences: 313.0 pages: flesch: 41.0 cache: ./cache/cord-003055-88q36g00.txt txt: ./txt/cord-003055-88q36g00.txt summary: The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Since MIA has been considered to be a cause of behavioral abnormalities in offspring, including ASD/ Schizophrenia-like behavior, we subsequently evaluated the effect of LPS and maternal administration of HW on short-term memory, sociability, social novelty, and sensorimotor gating. Based on those findings, we subsequently performed Nissl staining and evaluated the number of neurons in the amygdala, cerebral cortex, and hippocampus to investigate the brain regions related to the results of the behavioral deficits induced by LPS exposure. abstract: The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H(2)) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H(2) attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks. The number of neurons and oligodendrocytes was also analyzed at postnatal 5 weeks by immunohistochemical analysis. Offspring of the LPS-exposed dams showed deficits in short-term memory and social interaction, following neuronal and oligodendrocytic loss in the amygdala and cortex. Maternal H(2) administration markedly attenuated these LPS-induced abnormalities. Moreover, we evaluated the effect of H(2) on LPS-induced astrocytic activation, both in vivo and in vitro. The number of activated astrocytes with hypertrophic morphology was increased in LPS-exposed offspring, but decreased in the offspring of H(2)-administered dams. In primary cultured astrocytes, LPS-induced pro-inflammatory cytokines were attenuated by H(2) administration. Overall, these findings indicate that maternal H(2) administration exerts neuroprotective effects and ameliorates MIA-induced neurodevelopmental deficits of offspring later in life. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6003913/ doi: 10.1038/s41598-018-27626-4 id: cord-006605-tsk3pakb author: Jesmin, Subrina title: Differential Expression, Time Course and Distribution of Four PARs in Rats with Endotoxin-induced Acute Lung Injury date: 2006-11-30 words: 4505.0 sentences: 223.0 pages: flesch: 43.0 cache: ./cache/cord-006605-tsk3pakb.txt txt: ./txt/cord-006605-tsk3pakb.txt summary: The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. Here, we also found that LPS induces increases in the protein expression of PARs isoforms 1 to 4 in the lung of rats. While our previous study demonstrated the immunolocalization of PAR-1 in these cells and tissues in LPS-treated rabbits, the present study showed strong immunoreactivities for all isoforms of PARs in the endothelium, alveolar epithelium, and lung macrophages using a rat model of ALI [10] . abstract: The hypothesis that the expression of protease-activated receptors (PARs) protein is regulated at the level of transcription and that PAR isoforms, PAR-1, PAR-2, PAR-3, and PAR-4, in lung tissue show different patterns of expression in lipopolysaccharide (LPS)-induced acute lung injury (ALI) was tested. Male Wistar rats were rendered endotoxemic by intra-peritoneal injection of LPS (15 mg/kg body weight). We examined the expression of protein and mRNA and the immunohistochemical localization of PAR isoforms in lung tissues 1, 3, 6, and 10 h after LPS administration. Induction of ALI by LPS was confirmed based on histopathological changes. LPS administration induced significant increases in the expression of PAR isoforms (protein) at the level of transcription in ALI. While the time course of PAR-1 and -2 expressions were different, those of PAR-3 and -4 were almost similar. An immunohistochemical analysis showed localization of PAR isoforms in the vascular endothelium, alveolar epithelium, and alveolar macrophages. However, the cellular distribution patterns of PAR isoforms were different. We conclude that LPS induces increase in protein expression of PAR isoforms at the level of transcription in rats with ALI. The differential expression patterns (over a time course) and distribution of PAR isoforms suggests a distinct role for each isoform in the pathogenesis of LPS-induced ALI. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102102/ doi: 10.1007/s10753-006-9017-8 id: cord-351730-qmbo1dmo author: Kesherwani, Rashmi title: Euglena tuba extract provides protection against lipopolysaccharide-induced inflammatory response and oxidative stress in mice date: 2020-10-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Lipopolysaccharide (LPS), an endotoxin, is known to induce inflammatory response and oxidative stress in rodents. We evaluated the protective role of Euglena tuba extract (ETME) against LPS induced inflammatory response and oxidative stress in male Balb/c mice. Male Balb/c mice were divided into 4 groups. Group 1 (control) were intraperitoneally administered 0.5 mL PBS. Group 2, 3 and 4 were treated with a single dose of LPS (i.p. 40 mg/kg body weight). Prior 1 h, Group 3 and 4 received orally 100 mg/kg body weight and 200 mg/kg body weight ETME respectively. Biomarkers of oxidative stress including TBARS, SOD, Catalase, Liver marker enzyme (SGPT and SGOT), Nitric Oxide, and inflammatory cytokines including IL-6 and TNF-α, were estimated in serum. Oxidative stress and inflammatory markers were significantly increased in the LPS treated group, whereas ETME treated group at different concentrations protected mice from pro inflammatory cytokines and oxidative stress. Our results indicate that 70% methanolic extract of Euglena tuba can efficiently counteract free radical generation and increased level of inflammatory cytokine in an LPS induced mice model. url: https://doi.org/10.2478/s11756-020-00623-7 doi: 10.2478/s11756-020-00623-7 id: cord-283427-fef9qsik author: Kim, Gwang-Ho title: Verification with the utility of an established rapid assessment of brain safety for newly developed vaccines date: 2019-11-29 words: 3699.0 sentences: 213.0 pages: flesch: 54.0 cache: ./cache/cord-283427-fef9qsik.txt txt: ./txt/cord-283427-fef9qsik.txt summary: In our previous study, we established of minimal positive control conditions to ensure brain safety using experimental mice models during development of urgent vaccines before introducing to markets. In this study, we described that this module can be useful in applying a commercially available vaccine to a rapid and effective positive-control for brain safety assessment of an urgent vaccine. In brief, evidences for the BBB damage by commercially available vaccines (killed porcine genital respiratory syndrome vaccine vaccine and live canine parvovirus vaccine) were based on Evans blue EB permeability into brain parenchyma and mRNA expression of tight junctions (ZO-1 and Occludin) in the brain. However, when 2-fold concentrations of two vaccines stock solutions were injected, occludin mRNA expression was increased compared to the PBS group, but not significantly. In the present study, we confirmed that these established conditions and modules of the positive control that destroyed the BBB could be used to assess brain safety of commercial vaccines [1] . abstract: In the twenty-first century, high contagious infectious diseases such as SARS (Severe Acute Respiratory Syndrome), MERS (Middle East Respiratory Syndrome), FMD (Foot-and-Mouth Disease) and AI (Avian Influenza) have become very prevalent, causing treat harm to humans and animals in aspect of public health, and economical issues. The critical problem is that newly-reported infectious diseases that humans firstly experience are expected to continue to emerge, and these diseases will be spreading out rapidly. Therefore, rapid and safe supplies of effective vaccines are most pivotal to prevent the rapid prevalent of new infection, but international standards or assessing protocol the safety of urgent vaccines are not established well. In our previous study, since we established a module to assess the brain safety of urgent vaccines, therefore, it is necessary to verify that this established module for assessing brain safety could work effectively in commercially available two vaccines (one killed- and on live-vaccines). We compared the results of Evans blue (EB) assay and qPCR analysis by injection of two kinds of vaccines, PBS and Lipopolysaccharide (LPS) under the condition of the module previously reported. We confirmed that the brain safety test module for urgent vaccine we established is very reproducible. Therefore, it is believed that this vaccine safety testing method can be used to validate brain safety when prompt supply of a newly developed vaccines is needed. url: https://www.ncbi.nlm.nih.gov/pubmed/32219059/ doi: 10.1186/s42826-019-0027-8 id: cord-003099-a0acr28o author: Koch, R. M. title: The endotoxin-induced pulmonary inflammatory response is enhanced during the acute phase of influenza infection date: 2018-07-05 words: 3883.0 sentences: 194.0 pages: flesch: 39.0 cache: ./cache/cord-003099-a0acr28o.txt txt: ./txt/cord-003099-a0acr28o.txt summary: In vitro studies in which influenza-infected alveolar macrophages were subsequently stimulated with bacterial lipopolysaccharide (LPS), a bacterial compound that induces a profound innate immune response, revealed increased levels of pro-inflammatory cytokines tumor necrosis factor (TNF) α, interleukin (IL)-1β, and IL-6 [4] [5] [6] [7] [8] , indicative of a priming effect on these cells by influenza. Likewise, murine influenza infection resulted in increased levels of pro-inflammatory cytokines in both plasma and lungs, and enhanced pulmonary neutrophil influx upon pneumococcal infection 7 days later [10] . In the present study, we demonstrate that a systemic LPS challenge in the acute phase of influenza infection (4 days post-infection) results in an enhanced pulmonary, but not systemic pro-inflammatory cytokine response. Our results are in accordance with in vitro data reporting a cellular priming effect of influenza observed upon secondary stimulation with LPS [4] [5] [6] [7] [8] , as well as with other murine in vivo studies that report increased inflammation and pulmonary neutrophil influx or sequestration upon a secondary bacterial infection or LPS challenge in the acute phase of influenza infection [9, 10] . abstract: BACKGROUND: Influenza infections are often complicated by secondary infections, which are associated with high morbidity and mortality, suggesting that influenza profoundly influences the immune response towards a subsequent pathogenic challenge. However, data on the immunological interplay between influenza and secondary infections are equivocal, with some studies reporting influenza-induced augmentation of the immune response, whereas others demonstrate that influenza suppresses the immune response towards a subsequent challenge. These contrasting results may be due to the use of various types of live bacteria as secondary challenges, which impedes clear interpretation of causal relations, and to differences in timing of the secondary challenge relative to influenza infection. Herein, we investigated whether influenza infection results in an enhanced or suppressed innate immune response upon a secondary challenge with bacterial lipopolysaccharide (LPS) in either the acute or the recovery phase of infection. METHODS: Male C57BL/6J mice were intranasally inoculated with 5 × 10(3) PFU influenza virus (pH1N1, strain A/Netherlands/602/2009) or mock treated. After 4 (acute phase) or 10 (recovery phase) days, 5 mg/kg LPS or saline was administered intravenously, and mice were sacrificed 90 min later. Cytokine levels in plasma and lung tissue, and lung myeloperoxidase (MPO) content were determined. RESULTS: LPS administration 4 days after influenza infection resulted in a synergistic increase in TNF-α, IL-1β, and IL-6 concentrations in lung tissue, but not in plasma. This effect was also observed 10 days after influenza infection, albeit to a lesser extent. LPS-induced plasma levels of the anti-inflammatory cytokine IL-10 were enhanced 4 days after influenza infection, whereas a trend towards increased pulmonary IL-10 concentrations was found. LPS-induced increases in pulmonary MPO content tended to be enhanced as well, but only at 4 days post-infection. CONCLUSIONS: An LPS challenge in the acute phase of influenza infection results in an enhanced pulmonary pro-inflammatory innate immune response. These data increase our insight on influenza-bacterial interplay. Combing data of the present study with previous findings, it appears that this enhanced response is not beneficial in terms of protection against secondary infections, but rather damaging by increasing immunopathology. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033844/ doi: 10.1186/s40635-018-0182-5 id: cord-311481-2awvmpyh author: Kosukegawa, Ima title: The proton pump inhibitor, lansoprazole, prevents the development of non-traumatic osteonecrosis of the femoral head: an experimental and prospective clinical trial date: 2020-01-14 words: 4725.0 sentences: 226.0 pages: flesch: 53.0 cache: ./cache/cord-311481-2awvmpyh.txt txt: ./txt/cord-311481-2awvmpyh.txt summary: OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. In the present study, we hypothesized that LPZ has the potential to suppress IRF7 and NF-κB, in the same manner as BAY11-7082, and so prevent corticosteroid-induced ONFH in rats. The present study showed that the co-treatment of LPZ with corticosteroids prevents the development of ONFH in experimental animals, as well as in patients with immune disease treated with corticosteroids. The results of the experimental study indicate that LPZ may also prevent the development of ONFH in patients with immune diseases needing corticosteroid treatment. The present study shows that the co-treatment of LPZ with corticosteroids prevents the development of ONFH through the suppression of IRF7 activity in rats. Nevertheless, we believe that LPZ is safe to use and could be effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment. abstract: BACKGROUND: An effective prevention strategy for osteonecrosis of the femoral head (ONFH) has yet to be established. We previously reported that the innate immune system via the toll-like receptor (TLR) response induced by corticosteroids leads to the development of ONFH and that repression of IRF7 activity by an inhibitor could interfere with the development of ONFH while maintaining the therapeutic effect of the corticosteroids. OBJECTIVE: In the present study, we hypothesize that lansoprazole has the potential to suppress IRF7 activity and prevent corticosteroid-induced ONFH in rats. Furthermore, we conducted a preliminary clinical trial to prevent corticosteroid-induced ONFH in autoimmune disease patients. METHODS: Male Wistar rats were randomly divided into four groups. On Day 1, each rat was injected with TLR4 ligand (LPS) or TLR7 ligand (imiquimod), followed by methylprednisolone with or without lansoprazole on Day 2. They were killed at 1 or 14 days after the last injection.We prospectively recruited 30 patients requiring primary high-dose corticosteroid treatment for immune diseases. All patients were administered lansoprazole, starting the night before corticosteroid treatment began. MRI was performed before corticosteroid treatment, and at 4, 12 and 24 weeks afterward. RESULTS: In rats, co-treatment of lansoprazole with corticosteroids significantly repressed both IRF7 activity and the development of ONFH. Moreover, in the human patients, the incidence of ONFH was significantly decreased from 53.4 to 13.3%. CONCLUSIONS: Although the present study is preliminary, the results show that co-treatment of lansoprazole with corticosteroids prevents ONFH development. Lansoprazole may be both safe and effective in preventing osteonecrosis of the femoral head in patients needing corticosteroid treatment. url: https://www.ncbi.nlm.nih.gov/pubmed/31938894/ doi: 10.1007/s00590-020-02622-5 id: cord-329274-ncvvmkca author: Labarque, G title: Porcine reproductive–respiratory syndrome virus infection predisposes pigs for respiratory signs upon exposure to bacterial lipopolysaccharide date: 2002-08-02 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: This study examined whether an infection with porcine reproductive and respiratory syndrome virus (PRRSV) potentiates respiratory signs upon exposure to bacterial lipopolysaccharides (LPS). Five-week-old conventional pigs were inoculated intratracheally with the Lelystad strain of PRRSV and received 5 days later one or two intratracheal LPS administrations. The necessary controls were included. After LPS administration, pigs were intensively monitored for clinical signs. Additionally, some pigs were euthanatized after a second LPS administration for broncho-alveolar cell analysis and virological examinations of the lungs. Broncho-alveolar lavage (BAL) cells were counted and differentiated. Lung suspensions and BAL fluids were titrated for PRRSV. Exposure of pigs to PRRSV only resulted in a fever for time periods ranging from 1 to 5 days and slight respiratory signs. Exposure of pigs to LPS only resulted in general signs, characterized by fever and depression, but respiratory signs were slight or absent. PRRSV–LPS exposed pigs, on the other hand, developed severe respiratory signs upon LPS exposure, characterized by tachypnoea, abdominal breathing and dyspnoea. Besides respiratory signs, these pigs also showed enhanced general signs, such as fever and depression. Lung neutrophil infiltration was similar in non-infected and PRRSV-infected pigs upon LPS exposure. PRRSV quantities were similar in lungs and BAL fluids of pigs infected with PRRSV only and PRRSV–LPS exposed pigs. These data show a clear synergism between PRRSV and LPS in the induction of respiratory signs in conventional pigs. The synergism was observed in 87% of the pigs. So, it can be considered as reproducible and may be used to test the efficacy of preventive and therapeutic measures. url: https://www.sciencedirect.com/science/article/pii/S0378113502001049 doi: 10.1016/s0378-1135(02)00104-9 id: cord-009753-6rg47f0i author: Legband, Nathan title: The Treatment of Acute Respiratory Distress Syndrome in Rats With a Peritoneal Dosing System date: 2015-06-01 words: 1278.0 sentences: 78.0 pages: flesch: 52.0 cache: ./cache/cord-009753-6rg47f0i.txt txt: ./txt/cord-009753-6rg47f0i.txt summary: Current medical treatments for conditions involving an impaired respiratory system provide inefficient methods of delivering oxygen to the patient. Previously, we have shown that peritoneal membrane oxygenation (PMO) with OMBs is a possible treatment method in acute lung injury models [2] . Our study involves two phases: (1) development and characterization of the ARDS disease model in rats; (2) design and validation of ambulatory infusion device. Phase 2 is the development of an ambulatory delivery system that will infuse fluid to the rat''s peritoneal cavity for treatment. We expect to be able to continuously dose saline, inert gas microbubbles (IMBs), and OMBs into the peritoneal cavity of four animals with the current PDS design. Based upon our previous animal experiments with lung injuries, we anticipate improved pulse oximetry, blood gases, and survivability in rats provided OMBs compared to those administered saline or IMBs. Intratracheal Aerosolization of Endotoxin (LPS) in the Rat: A Comprehensive Animal Model to Study Adult (Acute) Respiratory Distress Syndrome abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164493/ doi: 10.1115/1.4030140 id: cord-285684-iiqyzqsb author: Li, Jin-ze title: Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier date: 2020-10-30 words: 4623.0 sentences: 256.0 pages: flesch: 46.0 cache: ./cache/cord-285684-iiqyzqsb.txt txt: ./txt/cord-285684-iiqyzqsb.txt summary: title: Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS. We introduced a transwell coculture system to evaluate the effects of MS-MSCs on the paracellular permeability of LPS-treated ECs. Treatment with LPS significantly increased the paracellular permeabil-ity of the pulmonary microvascular endothelium barrier (Figure 6 (a); * * p < 0:01). We demonstrated that mechanical stretch could impact MSC morphology and biological function in a time-and magnitude-dependent manner and that MS-MSCs could restored the increased permeability of endothelial cells induced by LPS. In this study, we tried to discover evidences of mechanically stretched MSCs in restoring increased permeability of endothelial barrier induced by LPS. abstract: Mesenchymal stem cells (MSCs) may improve the treatment of acute respiratory distress syndrome (ARDS). However, few studies have investigated the effects of mechanically stretched -MSCs (MS-MSCs) in in vitro models of ARDS. The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. We introduced a cocultured model of pulmonary microvascular endothelial cell (EC) and MSC medium obtained from MSCs with or without mechanical stretch. We found that Wright-Giemsa staining revealed that MSC morphology changed significantly and cell plasma shrank separately after mechanical stretch. Cell proliferation of the MS-MSC groups was much lower than the untreated MSC group; expression of cell surface markers did not change significantly. Compared to the medium from untreated MSCs, inflammatory factors elevated statistically in the medium from MS-MSCs. Moreover, the paracellular permeability of endothelial cells treated with LPS was restored with a medium from MS-MSCs, while LPS-induced EC apoptosis decreased. In addition, protective effects on the remodeling of intercellular junctions were observed when compared to LPS-treated endothelial cells. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS. url: https://doi.org/10.1155/2020/8861407 doi: 10.1155/2020/8861407 id: cord-255578-0ltb9dpa author: Li, Xiangru title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway date: 2020-06-19 words: 6400.0 sentences: 404.0 pages: flesch: 55.0 cache: ./cache/cord-255578-0ltb9dpa.txt txt: ./txt/cord-255578-0ltb9dpa.txt summary: title: Deficiency of Mouse FHR-1 Homolog, FHR-E, Accelerates Sepsis, and Acute Kidney Injury Through Enhancing the LPS-Induced Alternative Complement Pathway Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. In this study, Cfhr1 was deleted on C57BL/6 mouse to study the function of FHR-E on AP and the effect of FHR-E deficiency on LPS-induced sepsis. abstract: Alternative complement pathway (AP) plays an important role in the development of sepsis, which is life threatening. Deficiency of factor H-related protein 1 (FHR-1), which is a regulator of AP, has been considered as a susceptible factor for atypical hemolytic uremic syndrome (aHUS) and other types of nephropathy when an inducer such as infection exists. However, the underlying mechanism of the disease development is largely unknown. There is no report on CFHR1 gene knockout in any animal infection model and its function in vivo is still unclear. Here, a Cfhr1 knockout mouse was generated for investigating AP in sepsis and sepsis-induced acute kidney injury (AKI). We found that murine FHR-1 homolog (FHR-E) deficiency enhanced lipopolysaccharide (LPS)-induced AP activation both in vitro and in vivo and that Cfhr1 knockout mice exhibited more severe sepsis and AKI in response to LPS challenge. These results indicated that FHR-E deficiency promoted LPS-induced sepsis and AKI through AP over-activation, providing a mouse model for studying AP regulation and sepsis. This study revealed the function of FHR-E in vivo, which may further provide hints to the pathogenesis of FHR-1 deficiency-related diseases by enhancing LPS-induced AP activation. url: https://www.ncbi.nlm.nih.gov/pubmed/32636836/ doi: 10.3389/fimmu.2020.01123 id: cord-337923-1vbkttzx author: Li, Xiao-Jun title: Chemical Constituents and an Antineuroinflammatory Lignan, Savinin from the Roots of Acanthopanax henryi date: 2019-02-21 words: 3979.0 sentences: 246.0 pages: flesch: 51.0 cache: ./cache/cord-337923-1vbkttzx.txt txt: ./txt/cord-337923-1vbkttzx.txt summary: henryi have strong antioxidant and antiacetyl cholinesterase activities [6] , and the 80% methanol fraction of root bark and ciwujianoside C3, which was isolated from leaves of this plant, have significant antiinflammatory effect in lipopolysaccharide-(LPS-) induced RAW264.7 macrophage cells [5, 11] . henryi, we selected 13 compounds (compounds -, , , , , , , , and -) based on their number of publications, and these compounds were screened for anti-inflammatory effects, including the inhibition of NO and PGE 2 production, in LPS-stimulated BV2 microglial cells. The concentration required to inhibit the production of NO by 50% (IC 50 value) was calculated based on the concentrations of NO and PGE 2 released into the culture Figure 2 : The effect of compound on LPS-induced iNOS and COX-2 protein expression in BV2 microglial cells. henryi, suppressed NO and PGE 2 production in LPS-stimulated BV2 microglial cells and also inhibited the LPS-induced expression of the iNOS and COX-2 protein (Figure 2) . abstract: The phytochemical investigation on the roots of Acanthopanax henryi (Araliaceae) resulted in the discovery of twenty compounds whose chemical structures were elucidated by the analysis of 1D-, 2D-NMR, mass spectrometry data, other physicochemical properties, and a comparison of the spectral data with the literature. They were identified as (-)-sesamin (1), helioxanthin (2), savinin (3), taiwanin C (4), 6-methoxy-7-hydroxycoumarin (5), behenic acid (6), 3-O-caffeoyl-quinic acid (7), 5-O-caffeoyl-quinic acid (8), 1,3-di-O-caffeoyl-quinic acid (9), 1,4-di-O-caffeoyl-quinic acid (10), 1,5-di-O-caffeoyl-quinic acid (11), (+)-threo-(7R,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (12), (+)-erythro-(7S,8R)-guaiacylglycerol-β-coniferyl aldehyde ether (13), ferulic acid (14), caffeic acid (15), stigmasterol (16), β-sitosterol (17), adenosine (18), syringin (19), and trans-coniferin (20). Among these isolates, compound 3 showed inhibitory activity against lipopolysaccharide- (LPS-) induced nitric oxide (NO) and prostaglandin E2 (PGE(2)) production with IC(50) values of 2.22 ± 0.11 and 2.28 ± 0.23 μM, respectively. The effects of compound 3 were associated with the suppression of LPS-induced expression of the inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein. Furthermore, compound 3 negatively regulated the production of interleukin- (IL-) 1β and tumor-necrosis factor- (TNF-) α at the transcriptional level in LPS-stimulated BV2 microglial cells. These antineuroinflammatory effects of compound 3 were mediated by p38 mitogen-activated protein kinase (MAPK). url: https://doi.org/10.1155/2019/1856294 doi: 10.1155/2019/1856294 id: cord-005832-p1joajvn author: Liu, Zhicheng title: Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice date: 2013-02-23 words: 3087.0 sentences: 186.0 pages: flesch: 53.0 cache: ./cache/cord-005832-p1joajvn.txt txt: ./txt/cord-005832-p1joajvn.txt summary: The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. CONCLUSION: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. The results showed that pretreatment with gossypol attenuated lung damage induced by LPS and decreased the W/D ratio, proinflammatory cytokine production, inflammatory cell migration into the lung, protein leakage, the activation of NF-jB and MAPK. In conclusion, the present study demonstrated that gossypol has a protective effect against LPS-induced ALI, which may be related to its suppression of NF-jB and MAPKs activation, and subsequently leads to the reduction the inflammatory cell infiltration and proinflammatory cytokine expression in lung tissues. abstract: OBJECTIVE: Gossypol has been reported to have anti-inflammatory properties. The purpose of this study was to evaluate the effect of gossypol on acute lung injury (ALI) induced by lipopolysaccharide (LPS) in mice. METHODS: Male BALB/c mice were pretreated with gossypol 1 h before intranasal instillation of LPS. Then, 7 h after LPS administration, the myeloperoxidase in histology of lungs, lung wet/dry ratio and inflammatory cells in the bronchoalveolar lavage fluid (BALF) were determined. The levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-1β (IL-1β) in the BALF were measured by ELISA. The extent of phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 were detected by western blot. RESULTS: Gossypol markedly attenuated the LPS-induced histological alterations in the lung and inhibited the production of TNF-α, IL-1β and IL-6. Additionally, gossypol reduced the inflammatory cells in BALF, decreased the wet/dry ratio of lungs and inhibited the phosphorylation of IκB-α, p65 NF-κB, p46–p54 JNK, p42–p44 ERK, and p38 caused by LPS. CONCLUSION: The data suggest that anti-inflammatory effects of gossypol against the LPS-induced ALI may be due to its ability of inhibition of the NF-κB and MAPKs signaling pathways. Gossypol may be a promising potential therapeutic reagent for ALI treatment. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095812/ doi: 10.1007/s00011-013-0603-6 id: cord-023935-o2ffxgnn author: Lorts, Angela title: Sepsis date: 2011-12-16 words: 11110.0 sentences: 510.0 pages: flesch: 38.0 cache: ./cache/cord-023935-o2ffxgnn.txt txt: ./txt/cord-023935-o2ffxgnn.txt summary: SIRS i s a state of infl ammatory/ immune activation and is based on the presence of at least two of the four following clinical criteria: Temperature >38°C or <36°C, heart rate >90th percentile for age, respiratory rate >90th percentile for age, or hyperventilation to PaCO 2 < 32 mm Hg. The defi nition attempts to "capture" all patients at risk for the subsequent development of severe sepsis or septic shock. Among these, the nuclear factor-k B (NF-k b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. Nuclear factork B (NFk b ) and the mitogen activated protein kinase (MAPK) pathways play a prominent role in regulating the expression of a number of infl ammatory gene products key to propagating the sepsis response. abstract: The health care provider faced with the management of a child with septic shock relies on a comprehensive understanding of the numerous disciplines embodied in the practice of pediatric critical care medicine. The child with septic shock may have simultaneous derangements in the function of virtually every system of the body including: cardiovascular, respiratory, immune, renal, coagulation, hepatic, metabolic and neurologic. The degree to which physiologic alterations are manifest in a given patient is variable and influenced by multiple host and non-host factors including: the developmental stage, the presence of co-morbidities, pathogen-related factors, and genetic influences on both the host inflammatory response as well as the response to pharmacologic agents, all combining to have a profound influence on outcome. The clinician must possess a systematic and multifaceted approach to these critically ill patients. The goal of this chapter is to provide a comprehensive description of the epidemiology, biology and pathophysiology (at both the cellular and organ level) of sepsis, as well as outlining the current principles of managing septic shock. It will be apparent that optimal management requires a strong working knowledge of cardiovascular physiology, infectious diseases, multiple organ interactions, immunity, coagulation, pharmacology, and the molecular biology of inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7178851/ doi: 10.1007/978-0-85729-923-9_27 id: cord-004140-ujzrqzv3 author: Lu, Xiaying title: Rolipram Protects Mice from Gram-negative Bacterium Escherichia coli-induced Inflammation and Septic Shock date: 2020-01-13 words: 3474.0 sentences: 208.0 pages: flesch: 48.0 cache: ./cache/cord-004140-ujzrqzv3.txt txt: ./txt/cord-004140-ujzrqzv3.txt summary: As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. Therefore, the serum levels of multiple pro-inflammatory cytokines Male C57BL/6 mice were injected with different doses of rolipram (1 mg/kg, 5 mg/kg, and 10 mg/kg, i.p.) 1 hr before LPS injection. We demonstrate that rolipram may protect against LPS-induced inflammation and shock in mice, likely through the inhibition of the NF-κB and MAPK signaling pathways. We have found that rolipram inhibits pro-inflammatory cytokines and chemokines released by the administration of LPS, leading to the suppression of excessive inflammatory responses, cell adhesion and migration, and the further sequelae of shock and multiple organ failure in the mouse host. Our results indicated that rolipram suppresses LPS-induced ERK, JNK, and p38 MAPK phosphorylation in lung tissue, suggesting that the MAPK signaling pathway -as well as NF-κB -may mediate the anti-inflammatory actions of rolipram. abstract: Sepsis is typically triggered by an overwhelming systemic inflammatory response to pathogens, and may lead to severe organ dysfunction and/or death. Sepsis consequently has a high mortality rate and a high rate of complications for survivors, despite modern medical advances. Therefore, drug identification and validation for the treatment of sepsis is of the utmost importance. As a selective phosphodiesterase-4 inhibitor, rolipram also exhibits the abilities of inhibiting multiple pro-inflammatory cytokines production in macrophages and toxin-induced inflammation in mice. However, this drug has never been studied as a sepsis treatment method. We found that rolipram significantly improves survival in mice challenged with gram-negative bacterium E. coli, CLP, or E. coli derived lipopolysaccharide. We have also found that rolipram inhibits organ damage, pro-inflammatory cytokine production, and intracellular migration of early-stage inflammatory elements. Our results also show that rolipram increases anti-inflammatory cytokine production. The protective effects of rolipram on septic mice may result from inhibition of the MAP kinase and NF-κB signaling pathways. Rolipram may therefore be a potential novel sepsis treatment, one that would bypass the time-consuming and costly drug-discovery process. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6957694/ doi: 10.1038/s41598-019-56899-6 id: cord-002079-jne14jqf author: MacParland, Sonya A. title: Lipopolysaccharide and Tumor Necrosis Factor Alpha Inhibit Interferon Signaling in Hepatocytes by Increasing Ubiquitin-Like Protease 18 (USP18) Expression date: 2016-05-27 words: 7182.0 sentences: 388.0 pages: flesch: 48.0 cache: ./cache/cord-002079-jne14jqf.txt txt: ./txt/cord-002079-jne14jqf.txt summary: Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. These data demonstrate that certain inflammatory stimuli (TNF-␣ and LPS), as well as ischemic injury, but not other cytokines (IL-6 and IL-10) can lead to enhanced hepatocyte USP18 expression and thereby inhibit IFN signaling. Huh7.5 cells and primary murine hepatocytes were treated with IFN-␣ (100 U/ml), TNF-␣ (20 ng/ml), LPS (100 ng/ml), IL-6 (100 ng/ml), or IL-10 (10 ng/ ml) over a 24-h time course, and USP18 expression was determined by quantitative PCR (qPCR) as previously described (8, 9) . abstract: Inflammation may be maladaptive to the control of viral infection when it impairs interferon (IFN) responses, enhancing viral replication and spread. Dysregulated immunity as a result of inappropriate innate inflammatory responses is a hallmark of chronic viral infections such as, hepatitis B virus and hepatitis C virus (HCV). Previous studies from our laboratory have shown that expression of an IFN-stimulated gene (ISG), ubiquitin-like protease (USP)18 is upregulated in chronic HCV infection, leading to impaired hepatocyte responses to IFN-α. We examined the ability of inflammatory stimuli, including tumor necrosis factor alpha (TNF-α), lipopolysaccharide (LPS), interleukin-6 (IL-6) and IL-10 to upregulate hepatocyte USP18 expression and blunt the IFN-α response. Human hepatoma cells and primary murine hepatocytes were treated with TNF-α/LPS/IL-6/IL-10 and USP18, phosphorylated (p)-STAT1 and myxovirus (influenza virus) resistance 1 (Mx1) expression was determined. Treatment of Huh7.5 cells and primary murine hepatocytes with LPS and TNF-α, but not IL-6 or IL-10, led to upregulated USP18 expression and induced an IFN-α refractory state, which was reversed by USP18 knockdown. Liver inflammation was induced in vivo using a murine model of hepatic ischemia/reperfusion injury. Hepatic ischemia/reperfusion injury led to an induction of USP18 expression in liver tissue and promotion of lymphocytic choriomeningitis replication. These data demonstrate that certain inflammatory stimuli (TNF-α and LPS) but not others (IL-6 and IL-10) target USP18 expression and thus inhibit IFN signaling. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with USP18 representing a potential target for intervention in various inflammatory states. IMPORTANCE Inflammation may prevent the control of viral infection when it impairs the innate immune response, enhancing viral replication and spread. Blunted immunity as a result of inappropriate innate inflammatory responses is a common characteristic of chronic viral infections. Previous studies have shown that expression of certain interferon-stimulated genes is upregulated in chronic HCV infection, leading to impaired hepatocyte responses. In this study, we show that multiple inflammatory stimuli can modulate interferon stimulated gene expression and thus inhibit hepatocyte interferon signaling via USP18 induction. These findings represent a new paradigm for how inflammation alters hepatic innate immune responses, with the induction of USP18 representing a potential target for intervention in various inflammatory states. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4886784/ doi: 10.1128/jvi.02557-15 id: cord-354829-god79qzw author: Mao, Kaimin title: Identification of robust genetic signatures associated with lipopolysaccharide-induced acute lung injury onset and astaxanthin therapeutic effects by integrative analysis of RNA sequencing data and GEO datasets date: 2020-09-23 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life-threatening clinical conditions predominantly arising from uncontrolled inflammatory reactions. It has been found that the administration of astaxanthin (AST) can exert protective effects against lipopolysaccharide (LPS)-induced ALI; however, the robust genetic signatures underlying LPS induction and AST treatment remain obscure. Here we performed a statistical meta-analysis of five publicly available gene expression datasets from LPS-induced ALI mouse models, conducted RNA-sequencing (RNA-seq) to screen differentially expressed genes (DEGs) in response to LPS administration and AST treatment, and integrative analysis to determine robust genetic signatures associated with LPS-induced ALI onset and AST administration. Both the meta-analyses and our experimental data identified a total of 198 DEGs in response to LPS administration, and 11 core DEGs (Timp1, Ly6i, Cxcl13, Irf7, Cxcl5, Ccl7, Isg15, Saa3, Saa1, Tgtp1, and Gbp11) were identified to be associated with AST therapeutic effects. Further, the 11 core DEGs were verified by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC), and functional enrichment analysis revealed that these genes are primarily associated with neutrophils and chemokines. Collectively, these findings unearthed the robust genetic signatures underlying LPS administration and the molecular targets of AST for ameliorating ALI/ARDS which provide directions for further research. url: https://www.ncbi.nlm.nih.gov/pubmed/32969837/ doi: 10.18632/aging.104042 id: cord-022136-3q24qxsr author: Maru, Yoshiro title: Explanation of Metastasis by Homeostatic Inflammation date: 2016-02-02 words: 12045.0 sentences: 615.0 pages: flesch: 45.0 cache: ./cache/cord-022136-3q24qxsr.txt txt: ./txt/cord-022136-3q24qxsr.txt summary: Treatment of B16 melanoma cells with lipopolysaccharide (LPS) or lipid A at 1 μg/ ml each for 48 h, which induced CCL2 expression, followed by extensive washing and subcutaneous implantation, reduced the tumor growth compared with untreated B16 cells in both wild-type and TLR4-KO mice. Expression of endogenous ligands, such as S100A8 and SAA3, in endothelial cells in sterile premetastatic lungs is induced by primary tumor-derived growth factors, such as CCL2, from the circulation side and the paracrine signaling goes in an opposite direction from the circulation to airway side to result in amplification of SAA3 in club cells. Detailed analysis of stimulation and expression pattern of S100A8, SAA3, and TNFα revealed that the triggering mechanism is primary tumor-secreted CCL2 that activates CCR2 in the hyperpermeable regions in the lungs to induce S100A8 expression in the endothelial cells. abstract: If inflammation caused by either non-self or self molecules can disseminate throughout the body and inflammatory sites actively allow entry of circulating tumor cells and assist regrowth, then circulating tumor cells metastasize to the sites of inflammation. However, disrupted sites of homeostatic inflammation do not necessarily guarantee metastatic spread and subsequent regrowth. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153410/ doi: 10.1007/978-4-431-56024-1_15 id: cord-022252-9yiuuye3 author: Mims, Cedric A. title: Mechanisms of Cell and Tissue Damage date: 2013-11-17 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7155491/ doi: 10.1016/b978-0-12-498262-8.50015-1 id: cord-032564-0t5lr4z9 author: Moin, Abu Saleh Md title: Pro-fibrotic M2 macrophage markers may increase the risk for COVID19 in type 2 diabetes with obesity()() date: 2020-09-16 words: 1052.0 sentences: 62.0 pages: flesch: 44.0 cache: ./cache/cord-032564-0t5lr4z9.txt txt: ./txt/cord-032564-0t5lr4z9.txt summary: 5 We report here that LPS-related markers were associated with activated lung alveolar M2 macrophages in OT2D, with a reduction in plasma LBP as a surrogate marker of circulatory LPS elevation. Elevated plasma levels of TGF-β1, PDGF-β, MMP7 and MMP9 determined early in the course of COVID19 infection in a patient with OT2D may indicate potential risk for more severe disease. Moreover, it is also possible that, apart from alveolar macrophages, other cellular sources, for example lung epithelial cells [16] , arterial smooth muscle cells [17] , epithelial cells of glandular tissues like prostate [18] or bile duct epithelia [19] , might contribute to LPS-induced elevated plasma levels of those pro-fibrotic markers. In conclusion, in OT2D the lung epithelial barrier integrity is likely destabilized in response to fibroproliferative activity of elevated TGF-β1, PDGF-β, MMP7 or MMP9 derived from lung alveolar macrophages, increasing vulnerability to inhaled pathogens. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7510340/ doi: 10.1016/j.metabol.2020.154374 id: cord-292862-ezrkg0dc author: Myerson, Jacob W. title: Supramolecular Organization Predicts Protein Nanoparticle Delivery to Neutrophils for Acute Lung Inflammation Diagnosis and Treatment date: 2020-04-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Acute lung inflammation has severe morbidity, as seen in COVID-19 patients. Lung inflammation is accompanied or led by massive accumulation of neutrophils in pulmonary capillaries (“margination”). We sought to identify nanostructural properties that predispose nanoparticles to accumulate in pulmonary marginated neutrophils, and therefore to target severely inflamed lungs. We designed a library of nanoparticles and conducted an in vivo screen of biodistributions in naive mice and mice treated with lipopolysaccharides. We found that supramolecular organization of protein in nanoparticles predicts uptake in inflamed lungs. Specifically, nanoparticles with agglutinated protein (NAPs) efficiently home to pulmonary neutrophils, while protein nanoparticles with symmetric structure (e.g. viral capsids) are ignored by pulmonary neutrophils. We validated this finding by engineering protein-conjugated liposomes that recapitulate NAP targeting to neutrophils in inflamed lungs. We show that NAPs can diagnose acute lung injury in SPECT imaging and that NAP-like liposomes can mitigate neutrophil extravasation and pulmonary edema arising in lung inflammation. Finally, we demonstrate that ischemic ex vivo human lungs selectively take up NAPs, illustrating translational potential. This work demonstrates that structure-dependent interactions with neutrophils can dramatically alter the biodistribution of nanoparticles, and NAPs have significant potential in detecting and treating respiratory conditions arising from injury or infections. url: https://doi.org/10.1101/2020.04.15.037564 doi: 10.1101/2020.04.15.037564 id: cord-006700-df8ard9o author: Müller-Redetzky, Holger C. title: Dynamics of pulmonary endothelial barrier function in acute inflammation: mechanisms and therapeutic perspectives date: 2014-03-06 words: 10609.0 sentences: 582.0 pages: flesch: 32.0 cache: ./cache/cord-006700-df8ard9o.txt txt: ./txt/cord-006700-df8ard9o.txt summary: However, upon infectious or sterile inflammatory stimulation via either the alveolar (e.g., in pneumonia and mechanical ventilation) or the vascular lumen (e.g., in bacteremia and sepsis), pulmonary endothelial barrier homeostasis may be disturbed, resulting in increased permeability, protein-rich fluid extravasation, lung oedema and finally acute respiratory distress syndrome (ARDS) with mortality rates ranging from 27 to 45 % depending on severity (Ranieri, et al. Although the underlying mechanisms of leukocyte mediated barrier failure are of highest scientific interest, therapeutic interference to ameliorate acute lung injury by depletion or blocking of cell recruitment should raise concerns as neutrophils and monocytes are key players of pulmonary and systemic innate immune responses and therapeutic intervention at this level might leave the patient functionally immunosuppressed. In mice, Ang-1-induced Tie-2 receptor phosphorylation stimulated the p190RhoGTPaseactivating protein (p190RhoGAP) via PI3-kinase and Rac1 to inactivate RhoA, resulting in reduced F-actin stress fibre formation and diminished endothelial permeability (Mammoto et al. abstract: The lungs provide a large inner surface to guarantee respiration. In lung alveoli, a delicate membrane formed by endo- and epithelial cells with their fused basal lamina ensures rapid and effective gas exchange between alveolar and vascular compartments while concurrently forming a robust barrier against inhaled particles and microbes. However, upon infectious or sterile inflammatory stimulation, tightly regulated endothelial barrier leakiness is required for leukocyte transmigration. Further, endothelial barrier disruption may result in uncontrolled extravasation of protein-rich fluids. This brief review summarizes some important mechanisms of pulmonary endothelial barrier regulation and disruption, focusing on the role of specific cell populations, coagulation and complement cascades and mediators including angiopoietins, specific sphingolipids, adrenomedullin and reactive oxygen and nitrogen species for the regulation of pulmonary endothelial barrier function. Further, current therapeutic perspectives against development of lung injury are discussed. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102256/ doi: 10.1007/s00441-014-1821-0 id: cord-012487-s920s5wb author: Noga, Marek J. title: Posttranslational Control of PlsB Is Sufficient To Coordinate Membrane Synthesis with Growth in Escherichia coli date: 2020-08-18 words: 7414.0 sentences: 391.0 pages: flesch: 49.0 cache: ./cache/cord-012487-s920s5wb.txt txt: ./txt/cord-012487-s920s5wb.txt summary: By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. In order to understand how the model Gram-negative species Escherichia coli coordinates membrane synthesis with growth, we quantified substrates and enzymes of the fatty acid and PL synthesis pathways under both steady-state and dynamic conditions. The trends in substrate, enzyme, and intermediate concentrations observed in ppGpp-limited cultures are consistent with growth regulating PL flux via posttranslational control-not transcriptional control-of PlsB. To test whether regulation of PlsB activity is sufficient to control steady-state PL synthesis, we constructed a simplified differential equation model that describes fatty acid, LPS initiation, and PL biosynthesis ( Fig. 2A ; see also Text S1 and Table S1 ). abstract: Every cell must produce enough membrane to contain itself. However, the mechanisms by which the rate of membrane synthesis is coupled with the rate of cell growth remain unresolved. By comparing substrate and enzyme concentrations of the fatty acid and phospholipid synthesis pathways of Escherichia coli across a 3-fold range of carbon-limited growth rates, we show that the rate of membrane phospholipid synthesis during steady-state growth is determined principally through allosteric control of a single enzyme, PlsB. Due to feedback regulation of the fatty acid pathway, PlsB activity also indirectly controls synthesis of lipopolysaccharide, a major component of the outer membrane synthesized from a fatty acid synthesis intermediate. Surprisingly, concentrations of the enzyme that catalyzes the committed step of lipopolysaccharide synthesis (LpxC) do not differ across steady-state growth conditions, suggesting that steady-state lipopolysaccharide synthesis is modulated primarily via indirect control by PlsB. In contrast to steady-state regulation, we found that responses to environmental perturbations are triggered directly via changes in acetyl coenzyme A (acetyl-CoA) concentrations, which enable rapid adaptation. Adaptations are further modulated by ppGpp, which regulates PlsB activity during slow growth and growth arrest. The strong reliance of the membrane synthesis pathway upon posttranslational regulation ensures both the reliability and the responsiveness of membrane synthesis. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439487/ doi: 10.1128/mbio.02703-19 id: cord-346488-y7r7el4e author: Prantner, Daniel title: The θ-defensin retrocyclin 101 inhibits TLR4- and TLR2-dependent signaling and protects mice against influenza infection date: 2017-07-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Despite widespread use of annual influenza vaccines, seasonal influenza-associated deaths number in the thousands each year, in part because of exacerbating bacterial superinfections. Therefore, discovering additional therapeutic options would be a valuable aid to public health. Recently, TLR4 inhibition has emerged as a possible mechanism for protection against influenza-associated lethality and acute lung injury. Based on recent data showing that rhesus macaque θ-defensins could inhibit TLR4-dependent gene expression, we tested the hypothesis that a novel θ-defensin, retrocyclin (RC)-101, could disrupt TLR4-dependent signaling and protect against viral infection. In this study, RC-101, a variant of the humanized θ-defensin RC-1, blocked TLR4-mediated gene expression in mouse and human macrophages in response to LPS, targeting both MyD88- and TRIF-dependent pathways. In a cell-free assay, RC-101 neutralized the biologic activity of LPS at doses ranging from 0.5 to 50 EU/ml, consistent with data showing that RC-101 binds biotinylated LPS. The action of RC-101 was not limited to the TLR4 pathway because RC-101 treatment of macrophages also inhibited gene expression in response to a TLR2 agonist, Pam3CSK4, but failed to bind that biotinylated agonist. Mouse macrophages infected in vitro with mouse-adapted A/PR/8/34 influenza A virus (PR8) also produced lower levels of proinflammatory cytokine gene products in a TLR4-independent fashion when treated with RC-101. Finally, RC-101 decreased both the lethality and clinical severity associated with PR8 infection in mice. Cumulatively, our data demonstrate that RC-101 exhibits therapeutic potential for the mitigation of influenza-related morbidity and mortality, potentially acting through TLR-dependent and TLR-independent mechanisms. url: https://www.ncbi.nlm.nih.gov/pubmed/28729359/ doi: 10.1189/jlb.2a1215-567rr id: cord-013366-sbdtpsz6 author: Ramírez-Pérez, Sergio title: Downregulation of Inflammatory Cytokine Release from IL-1β and LPS-Stimulated PBMC Orchestrated by ST2825, a MyD88 Dimerisation Inhibitor date: 2020-09-21 words: 5749.0 sentences: 283.0 pages: flesch: 45.0 cache: ./cache/cord-013366-sbdtpsz6.txt txt: ./txt/cord-013366-sbdtpsz6.txt summary: Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both proand anti-inflammatory cytokines. The chemical molecule ST2825 acts as an inhibitor of MyD88 dimerisation and its activity has been demonstrated through the inhibition of TLR9-dependent CpG-regulated signalling, and inhibition of IL-12, IL-1β, IL-6 and tumor necrosis factor alpha (TNF-α) expression in LPS-stimulated RAW 264.7 cells [19] [20] [21] [22] . The present study shows that the specific inhibition of critical components in the IL-1 signalling pathway is not enough to avoid the secretion of inflammatory mediators, the above suggests that various MyD88-independent mechanisms could regulate the production of cytokines in PBMC. abstract: The inflammatory process implicates homeostasis disruption and increased production of inflammatory mediators. Myeloid differentiation primary response 88 (MyD88) is an essential protein recruited after lipopolysaccharide (LPS) and interleukin (IL)-1β stimulation, a process that converges in nuclear factor kappa B (NF-κB) activation, as well as a transcription of several genes of both pro- and anti-inflammatory cytokines. The inhibition of MyD88 has shown efficacy by decrease inflammatory response, and has demonstrated potential application as a therapeutic target in chronic diseases. In this study, we investigate the effect of MyD88 dimerisation inhibitor ST2825 on cytokine production from rhIL-1β and LPS-stimulated peripheral blood mononuclear cells (PBMC) from healthy blood donors (HBD). ST2825 significantly downregulates the production of IFN-γ, IL-6, IL-12, IL-2, IL-15, IL-7, VEGF, IL-1Ra, IL-4, IL-5, IL-13 and IL-9 (p < 0.05) in LPS-stimulated PBMC. Moreover, ST2825 had a relatively low impact on IL-1β signalling pathway inhibition, showing that only a few specific cytokines, such as IFN-γ and IL-1Ra, are inhibited in rhIL-1β-stimulated PBMC (p < 0.01). In conclusion, MyD88 dimerisation inhibitor ST2825 showed high efficacy by inhibiting pro- and anti-inflammatory cytokine production in LPS-stimulated PBMC. Moreover, although rhIL-1β induced a sustained cytokine production (p < 0.05), ST2825 did not show a significant effect in the secretion of neither pro- nor anti-inflammatory cytokines in rhIL-1β-stimulated PBMC. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7570868/ doi: 10.3390/molecules25184322 id: cord-006279-ib5z3elq author: Ryter, Stefan W. title: Heme oxygenase/carbon monoxide signaling pathways: Regulation and functional significance date: 2002 words: 8188.0 sentences: 464.0 pages: flesch: 41.0 cache: ./cache/cord-006279-ib5z3elq.txt txt: ./txt/cord-006279-ib5z3elq.txt summary: Recent studies have discovered a potent anti-inflammatory effect of CO: the inhibition of pro-inflammatory cytokine production following inducing stimuli, dependent on the modulation of mitogen activated protein kinase (MAPK)signaling cascades [6, 11] . This review will (I) describe the regulation of HO-1 as an inducible source of endogenous CO, (II) describe evidence that HO-1 acts as a mediator of cellular and tissue protection against oxidative stress, and (III) emphasize recent studies that introduce novel anti-apoptotic and anti-inflammatory properties of HO-derived CO in oxidative lung injury models. MKK3 mitogen activated protein kinase pathway mediates carbon monoxide-induced protection against oxidant-induced lung injury Activation of heme oxygenase and heat shock protein 70 genes by stress in human hepatoma cells Mitogen activated protein kinase (MAPK) pathway regulates heme oxygenase-1 gene expression by hypoxia in vascular cells abstract: Carbon monoxide (CO), a gaseous second messenger, arises in biological systems during the oxidative catabolism of heme by the heme oxygenase (HO) enzymes. HO exists as constitutive (HO-2, HO-3) and inducible isoforms (HO-1), the latter which responds to regulation by multiple stress-stimuli. HO-1 confers protection in vitro and in vivo against oxidative cellular stress. Although the redox active compounds that are generated from HO activity (i.e. iron, biliverdin-IXα, and bilirubin-IXα) potentially modulate oxidative stress resistance, increasing evidence points to cytoprotective roles for CO. Though not reactive, CO regulates vascular processes such as vessel tone, smooth muscle proliferation, and platelet aggregation, and possibly functions as a neurotransmitter. The latter effects of CO depend on the activation of guanylate cyclase activity by direct binding to the heme moiety of the enzyme, stimulating the production of cyclic 3′:5′-guanosine monophosphate. CO potentially interacts with other intracellular hemoprotein targets, though little is known about the functional significance of such interactions. Recent progress indicates that CO exerts novel anti-inflammatory and anti-apoptotic effects dependent on the modulation of the p38 mitogen activated protein kinase (MAPK)-signaling pathway. By virtue of these effects, CO confers protection in oxidative lung injury models, and likely plays a role in HO-1 mediated tissue protection. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101540/ doi: 10.1023/a:1015957026924 id: cord-302295-nblmshni author: Savva, Athina title: Targeting Toll-Like Receptors: Promising Therapeutic Strategies for the Management of Sepsis-Associated Pathology and Infectious Diseases date: 2013-11-18 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Toll-like receptors (TLRs) are pattern recognition receptors playing a fundamental role in sensing microbial invasion and initiating innate and adaptive immune responses. TLRs are also triggered by danger signals released by injured or stressed cells during sepsis. Here we focus on studies developing TLR agonists and antagonists for the treatment of infectious diseases and sepsis. Positioned at the cell surface, TLR4 is essential for sensing lipopolysaccharide of Gram-negative bacteria, TLR2 is involved in the recognition of a large panel of microbial ligands, while TLR5 recognizes flagellin. Endosomal TLR3, TLR7, TLR8, TLR9 are specialized in the sensing of nucleic acids produced notably during viral infections. TLR4 and TLR2 are favorite targets for developing anti-sepsis drugs, and antagonistic compounds have shown efficient protection from septic shock in pre-clinical models. Results from clinical trials evaluating anti-TLR4 and anti-TLR2 approaches are presented, discussing the challenges of study design in sepsis and future exploitation of these agents in infectious diseases. We also report results from studies suggesting that the TLR5 agonist flagellin may protect from infections of the gastrointestinal tract and that agonists of endosomal TLRs are very promising for treating chronic viral infections. Altogether, TLR-targeted therapies have a strong potential for prevention and intervention in infectious diseases, notably sepsis. url: https://www.ncbi.nlm.nih.gov/pubmed/24302927/ doi: 10.3389/fimmu.2013.00387 id: cord-342001-41vjh3mq author: Selwyn, David title: A prospective multicentre external validation study of the Liverpool Peritonsillar abscess Score (LPS) with a no‐examination COVID‐19 modification date: 2020-10-20 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: OBJECTIVES: Our primary aim was to validate the Liverpool Peritonsillar abscess Score (LPS) externally in a new patient cohort. Our secondary aim was to modify the LPS in the light of the COVID‐19 pandemic to produce a no‐examination variant for use in this instance. DESIGN: Prospective multicentre external validation study. SETTING: Six different secondary care institutions across the United Kingdom. PARTICIPANTS: Patients over 16 years old who were referred to ENT with any uncomplicated sore throat such a tonsillitis or peritonsillar abscess (PTA). MAIN OUTCOME MEASURES: Sensitivity, specificity, positive predictive value and negative predictive value for both the original LPS model and the modified model for COVID‐19. RESULTS: The LPS model had sensitivity and specificity calculated at 98% and 79%, respectively. The LPS has a high negative predictive value (NPV) of 99%. The positive predictive value (PPV) was slightly lower at 63%. Receiver operating characteristic (ROC) curve, including the area under the curve (AUROC), was 0.888 which indicates very good accuracy. CONCLUSIONS: External validation of the LPS against an independent geographically diverse population yields high NPV. This may support non‐specialist colleagues who may have concerns about mis‐diagnosing a PTA. The COVID‐19 modification of the LPS has a similar NPV, which may be of use where routine oral examination is to be avoided during the COVID‐19 pandemic. url: https://doi.org/10.1111/coa.13652 doi: 10.1111/coa.13652 id: cord-273594-vmbhok1u author: Sichelstiel, Anke title: Targeting IL-1β and IL-17A Driven Inflammation during Influenza-Induced Exacerbations of Chronic Lung Inflammation date: 2014-06-11 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: For patients with chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), exacerbations are life-threatening events causing acute respiratory distress that can even lead to hospitalization and death. Although a great deal of effort has been put into research of exacerbations and potential treatment options, the exact underlying mechanisms are yet to be deciphered and no therapy that effectively targets the excessive inflammation is available. In this study, we report that interleukin-1β (IL-1β) and interleukin-17A (IL-17A) are key mediators of neutrophilic inflammation in influenza-induced exacerbations of chronic lung inflammation. Using a mouse model of disease, our data shows a role for IL-1β in mediating lung dysfunction, and in driving neutrophilic inflammation during the whole phase of viral infection. We further report a role for IL-17A as a mediator of IL-1β induced neutrophilia at early time points during influenza-induced exacerbations. Blocking of IL-17A or IL-1 resulted in a significant abrogation of neutrophil recruitment to the airways in the initial phase of infection or at the peak of viral replication, respectively. Therefore, IL-17A and IL-1β are potential targets for therapeutic treatment of viral exacerbations of chronic lung inflammation url: https://doi.org/10.1371/journal.pone.0098440 doi: 10.1371/journal.pone.0098440 id: cord-006318-9r51n241 author: Sideras, Paschalis title: Activin, neutrophils, and inflammation: just coincidence? date: 2013-02-06 words: 12965.0 sentences: 546.0 pages: flesch: 32.0 cache: ./cache/cord-006318-9r51n241.txt txt: ./txt/cord-006318-9r51n241.txt summary: During the 26 years that have elapsed since its discovery, activin-A, a member of the transforming growth factor β super-family originally discovered from its capacity to stimulate follicle-stimulating hormone production by cultured pituitary gonadotropes, has been established as a key regulator of various fundamental biological processes, such as development, homeostasis, inflammation, and tissue remodeling. [92] that prophylactic and therapeutic treatment with follistatin could improve the survival rate of mice in three mouse colitis models, attenuate several pathology-associated parameters and upregulate proliferation of intestinal epithelial cells and tissue repair, improving thus the barrier function of the colonic mucosa, strongly supported the association between activin-A and colitis pathophysiology [92] . The combination of aggravated innate immunity, activation of the coagulation system, and alterations in molecular systems crucial for homeostasis, such as the surfactants in the lung, can collectively lead to acute necroptotic cell death which leads to the release of highly pro-inflammatory complexes of DAMPs and cytokines that can activate via a feed-forward like response further activation of the TLR signaling pathway and further production of activin-A. abstract: During the 26 years that have elapsed since its discovery, activin-A, a member of the transforming growth factor β super-family originally discovered from its capacity to stimulate follicle-stimulating hormone production by cultured pituitary gonadotropes, has been established as a key regulator of various fundamental biological processes, such as development, homeostasis, inflammation, and tissue remodeling. Deregulated expression of activin-A has been observed in several human diseases characterized by an immuno-inflammatory and/or tissue remodeling component in their pathophysiology. Various cell types have been recognized as sources of activin-A, and plentiful, occasionally contradicting, functions have been described mainly by in vitro studies. Not surprisingly, both harmful and protective roles have been postulated for activin-A in the context of several disorders. Recent findings have further expanded the functional repertoire of this molecule demonstrating that its ectopic overexpression in mouse airways can cause pathology that simulates faithfully human acute respiratory distress syndrome, a disorder characterized by strong involvement of neutrophils. This finding when considered together with the recent discovery that neutrophils constitute an important source of activin-A in vivo and earlier observations of upregulated activin-A expression in diseases characterized by strong activation of neutrophils may collectively imply a more intimate link between activin-A expression and neutrophil reactivity. In this review, we provide an outline of the functional repertoire of activin-A and suggest that this growth factor functions as a guardian of homeostasis, a modulator of immunity and an orchestrator of tissue repair activities. In this context, a relationship between activin-A and neutrophils may be anything but coincidental. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101603/ doi: 10.1007/s00281-013-0365-9 id: cord-006285-kkxdmzk9 author: Smirnova, S. S. title: Long-Term Maintenance of the Functional Changes Induced by Influenza A Virus and/or LPS in Human Endothelial ECV-304 Cell Sublines date: 2019-08-26 words: 4686.0 sentences: 175.0 pages: flesch: 43.0 cache: ./cache/cord-006285-kkxdmzk9.txt txt: ./txt/cord-006285-kkxdmzk9.txt summary: The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The comparative study of the human endothelial ECV-304 cell sublines carried out in the present work and in our previous work (Smirnova et al., 2018) has demonstrated that the infection of nonpermissive cells with influenza A virus (both in high and in very low doses) and exposure to LPS can change migratory, proliferation, and apoptotic activity of cells and impair cell barrier function. abstract: Influenza A virus and secondary bacterial infection may have remote effects in the form of cardiovascular complications or fibrosis in different organs. However, the mechanisms governing the development of complications remain poorly studied. The present work reports the comparative assessment of the functional changes which take place in human ECV-304 endothelial cell sublines obtained previously by the long-term culturing of cells after exposure to varying infectious doses (IDs) of influenza A virus, and/or bacterial lipopolysaccharide (LPS). It has been demonstrated that, in the course of long-term culturing (six passages) after exposure to pathogenic agents (influenza virus and/or LPS), endothelial cells maintain changes in their migratory activity, permeability, and expression of mRNA for cytokines TNFα and TGFβ (along with the changes in their proliferation activity, which has been demonstrated earlier). The pattern of changes depended on the type of the agent (agents) to which the cells were exposed. The differences in migratory activity (which was at its maximum 4 h after wounding) between the cell sublines at the sixth passage correlated with the differences in their proliferation activity at the first passage (proliferation data were obtained previously). In particular, an increase in migration and proliferation was observed in the sublines exposed to low virus doses (ECV-1ID), as well as exposed to LPS (ECV-LPS), while the suppression of migration and proliferation was observed in the subline exposed to high virus doses (ECV-1000ID). In the ECV-1ID, ECV-LPS, and most notably in ECV-1ID + LPS sublines, we detected an increase in the expression of mRNA for cytokines TNFα and TGFβ, which, however, didn’t lead to the induction of apoptosis. We have also demonstrated an increase in cell permeability in the analyzed sublines, which was indicated by a decrease in the expression of the mRNAs for the genes encoding occludin and ZO-1, the tight junctions proteins . This paper also reports an evaluation of the effects of the antiviral preparations rimantadine and alpisarin on the functional state of cell sublines. As a result, it has been demonstrated that these drugs may be able to prevent the development of the pathological changes caused by influenza A virus and/or LPS in endothelial cells. The results obtained in the present work may be of use when studying the mechanisms of development of the influenza A virus and secondary bacterial infection complications. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7101551/ doi: 10.1134/s1990519x19040084 id: cord-032181-gmcugd8h author: Song, Jian-Xin title: Main Complications of AECHB and Severe Hepatitis B (Liver Failure) date: 2019-05-21 words: 51165.0 sentences: 2516.0 pages: flesch: 37.0 cache: ./cache/cord-032181-gmcugd8h.txt txt: ./txt/cord-032181-gmcugd8h.txt summary: 3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. The latest report indicated that basic laboratory examinations for coagulation function testing in common use at present, such as PT, APTT, international normalized ratio (INR) etc., have little correlation with occurrence of gastrointestinal bleeding in these patients, thereby revealing the importance to search and pay close attention to those complicating disease upregulating bleeding risk, such as bacterial infection, renal failure, hemodynamic change after portal hypertension, dysfunction of endotheliocyte as well as macrophagocyte and so on [107] . abstract: This chapter describes the clinical features, and diagnosis of complications in AECHB including secondary bacterial infections, coagulation disorder, water electrolyte disorder, hepatorenal syndrome, hepatic encephalopathy, hepatopulmonary syndrome and endotoxemia: 1. Patients with severe hepatitis have impaired immunity and are therefore vulnerable to all kinds of infections. After infection, these patients may experience shock, DIC and multiple organ failure, all of which seriously affect their prognosis and are major causes of death. Concurrent infections consist primarily of infections of the lungs, intestines, biliary tract, and urinary tract, as well as spontaneous bacterial peritonitis and sepsis. 2. Severe hepatitis may reduce the synthesis of coagulation factors and enhance their dysfunction and increase anticoagulants and platelet abnormalities, leading to coagulopathy. Infection, hepatorenal syndrome and complications can further aggravate coagulopathy, resulting in DIC and seriously affecting patient prognosis. 3. Hepatorenal syndrome, which is characterized by renal failure, hemodynamic changes in arterial circulation and abnormalities in the endogenous vascular system, is a common clinical complication of end-stage liver disease, and one of the important indicators for the prognosis of patients with severe hepatitis. 4. Water electrolyte disorder (water retention, hyponatremia, hypokalemia, hyperkalaemia) and acid-base imbalance are common in patients with severe hepatitis. These internal environment disorders can lead to exacerbation and complication of the illness. 5. Hepatic encephalopathy is a neurological and psychiatric anomaly syndrome based on metabolic disorder, and an important prognostic indicator for patients with severe hepatitis. 6. The hepatopulmonary syndrome is an important vascular complication in lungs due to systemic hypoxemia in patients with cirrhosis and portal hypertension. The majority of patients with HPS are asymptomatic. Long-term oxygen therapy remains the most frequently recommended therapy for symptoms in patients with severe hypoxemia. 7. Endotoxemia, an important complication of severe hepatitis, is not only a second hit to the liver, but also leads to other complications including SIRS and MODS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7498917/ doi: 10.1007/978-94-024-1603-9_2 id: cord-006570-v4as5gde author: Sukhotnik, Igor title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat date: 2007-10-13 words: 4069.0 sentences: 206.0 pages: flesch: 44.0 cache: ./cache/cord-006570-v4as5gde.txt txt: ./txt/cord-006570-v4as5gde.txt summary: title: Oral Insulin Up-regulates Toll-like Receptor 4 Expression and Enhances Intestinal Recovery Following Lipopolysaccharide-induced Gut Injury in a Rat LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPSanimals. The purpose of this study was to evaluate the effects of oral insulin in preventing mucosal damage caused by LPS endotoxemia in a rat model, including its effect on enterocyte proliferation and death via apoptosis, and to determine whether alterations in Toll-like receptor 4-mediated signaling may occur during LPS endotoxemia and insulin administration. Oral insulin increases the stimulating effect of LPS on Toll-like receptor 4 expression in the proximal intestine, suggesting that TLR4 is not the mediator of injury in this model. abstract: In the present study, we evaluated the protective effect of oral insulin (OI) on intestinal mucosa following lipopolysaccharide-induced intestinal damage in a rat. Male Sprague-Dawley rats were divided into three experimental groups: Sham rats, LPS-rats that were treated with lipopolysaccharide (LPS), and LPS-INS rats that were treated with OI given in drinking water 72 h before and following injection of LPS. Intestinal structural changes, enterocyte proliferation, enterocyte apoptosis, and mucosal expression of Toll-like receptor 4 (TLR4) were determined 24 h after the last LPS injection. LPS-INS animals showed a significantly greater bowel and mucosal weight in jejunum and ileum, mucosal DNA and protein in jejunum and ileum, villus height in ileum, crypt depth in jejunum and ileum, cell proliferation rates in jejunum, and significantly lower apoptotic index in ileum compared to LPS- animals. LPS rats demonstrated 50% increase in TLR4 expression in jejunum compared to sham animals. Treatment with OI resulted in a three-fold increase in TLR4 expression in jejunum, compared to LPS animals. In conclusion, OI improves intestinal recovery after LPS endotoxemia in a rat. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102045/ doi: 10.1007/s10620-007-9990-2 id: cord-030385-btf502ju author: Sun, Zhiheng title: 17β-Estradiol Promotes Trained Immunity in Females Against Sepsis via Regulating Nucleus Translocation of RelB date: 2020-07-22 words: 5855.0 sentences: 328.0 pages: flesch: 55.0 cache: ./cache/cord-030385-btf502ju.txt txt: ./txt/cord-030385-btf502ju.txt summary: However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. Our results showed that females expressed higher IL-6 and TNFα than males in sepsis, and trained immunity exacerbated this trend (Figures 1I,J) . The in vitro trained immunity model was established with RAW264.7 and J774 ( Figure 5C ) cell lines derived from male and female mice, respectively. abstract: Sepsis is more common among males than females, and the unequal estrogen levels have been suspected to play a vital role in gender differences. Recently, trained immunity is reported to be a novel strategy for the innate immune system to fight infection. However, it has not been clarified whether β-glucan-induced trained immunity causes different responses to early sepsis between male and female mice. In this study, sepsis was induced in mice by intraperitoneal injection of Escherichia coli (E. coli). The changes of inflammatory cytokines expression, and macrophage polarization in male, female, and ovariectomized C57BL/6 mice in sepsis model were investigated. For in vitro studies, different macrophages were treated with LPS. The function of estradiol (E2) on macrophage cell lines was verified and the mechanism of E2 affecting trained immunity was explored. We demonstrated that β-glucan-induced trained immunity was more resistant to sepsis in female than male mice. Macrophage polarization toward the M1 phenotype, which exhibited enhanced trained immunity, was related to the difference in sepsis resistance between female and male mice. Moreover, ovariectomized (OVX) mice manifested serious sepsis consequences with a weaker trained immunity effect than female mice. Female bone marrow-derived macrophages (BMDMs) were also apt to be polarized to the M1 phenotype in response to trained immunity in vitro. Furthermore, E2 promoted trained immunity in macrophage cell lines J774 and RAW264.7. E2 was also verified to facilitate trained immunity in primary BMDMs from female and male mice. Mechanistically, we found that E2 inhibited the nuclear translocation of RelB, which is a member of non-canonical pathway of NFκB and contributes to macrophage polarization to change the intensity of trained immunity. This study is the first to indicate the role of E2 in the trained immunity induced by β-glucan to protect against E. coli-induced sepsis via the non-canonical NFκB pathway. These results improve our understanding of the molecular mechanisms governing trained immunity in gender differences. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7387432/ doi: 10.3389/fimmu.2020.01591 id: cord-352219-z245sb3s author: Tallam, Aravind title: Gene Regulatory Network Inference of Immunoresponsive Gene 1 (IRG1) Identifies Interferon Regulatory Factor 1 (IRF1) as Its Transcriptional Regulator in Mammalian Macrophages date: 2016-02-12 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Immunoresponsive gene 1 (IRG1) is one of the highest induced genes in macrophages under pro-inflammatory conditions. Its function has been recently described: it codes for immune-responsive gene 1 protein/cis-aconitic acid decarboxylase (IRG1/CAD), an enzyme catalysing the production of itaconic acid from cis-aconitic acid, a tricarboxylic acid (TCA) cycle intermediate. Itaconic acid possesses specific antimicrobial properties inhibiting isocitrate lyase, the first enzyme of the glyoxylate shunt, an anaplerotic pathway that bypasses the TCA cycle and enables bacteria to survive on limited carbon conditions. To elucidate the mechanisms underlying itaconic acid production through IRG1 induction in macrophages, we examined the transcriptional regulation of IRG1. To this end, we studied IRG1 expression in human immune cells under different inflammatory stimuli, such as TNFα and IFNγ, in addition to lipopolysaccharides. Under these conditions, as previously shown in mouse macrophages, IRG1/CAD accumulates in mitochondria. Furthermore, using literature information and transcription factor prediction models, we re-constructed raw gene regulatory networks (GRNs) for IRG1 in mouse and human macrophages. We further implemented a contextualization algorithm that relies on genome-wide gene expression data to infer putative cell type-specific gene regulatory interactions in mouse and human macrophages, which allowed us to predict potential transcriptional regulators of IRG1. Among the computationally identified regulators, siRNA-mediated gene silencing of interferon regulatory factor 1 (IRF1) in macrophages significantly decreased the expression of IRG1/CAD at the gene and protein level, which correlated with a reduced production of itaconic acid. Using a synergistic approach of both computational and experimental methods, we here shed more light on the transcriptional machinery of IRG1 expression and could pave the way to therapeutic approaches targeting itaconic acid levels. url: https://doi.org/10.1371/journal.pone.0149050 doi: 10.1371/journal.pone.0149050 id: cord-029488-l11ufs6k author: Tomita, Kengo title: Vascular endothelial growth factor contributes to lung vascular hyperpermeability in sepsis-associated acute lung injury date: 2020-07-21 words: 5094.0 sentences: 264.0 pages: flesch: 45.0 cache: ./cache/cord-029488-l11ufs6k.txt txt: ./txt/cord-029488-l11ufs6k.txt summary: Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. We thus examined whether expression of VEGF in human pulmonary microvascular endothelial cells is regulated by MAPKs. When HPMEC-ST1.6R cells were treated with PD98059, an inhibitor of MAPK kinase which is an ERK1/2 upstream activator, or SB203580, which is widely used as a specific inhibitor of p38 MAPK, the LPS/IFN-γinduced increase in VEGF protein levels was strongly blocked (Fig. 4b) . abstract: Vascular endothelial growth factor (VEGF) is a prime regulator of vascular permeability. Acute lung injury (ALI) is characterized by high-permeability pulmonary edema in addition to refractory hypoxemia and diffuse pulmonary infiltrates. In this study, we examined whether VEGF can be implicated as a pulmonary vascular permeability factor in sepsis-associated ALI. We found that a great increase in lung vascular leak occurred in mice instilled intranasally with lipopolysaccharide (LPS), as assessed by IgM levels in bronchoalveolar lavage fluid. Treatment with the VEGF-neutralizing monoclonal antibody bevacizumab significantly reduced this hyperpermeability response, suggesting active participation of VEGF in non-cardiogenic lung edema associated with LPS-induced ALI. However, this was not solely attributable to excessive levels of intrapulmonary VEGF. Expression levels of VEGF were significantly reduced in lung tissues from mice with both intranasal LPS administration and cecal ligation and puncture (CLP)-induced sepsis, which may stem from decreases in non-endothelial cells-dependent VEGF production in the lungs. In support of this assumption, stimulation with LPS and interferon-γ (IFN-γ) significantly increased VEGF in human pulmonary microvascular endothelial cells (HPMECs) at mRNA and protein levels. Furthermore, a significant rise in plasma VEGF levels was observed in CLP-induced septic mice. The increase in VEGF released from HPMECs after LPS/IFN-γ challenge was completely blocked by either specific inhibitor of mitogen-activated protein kinase (MAPK) subgroups. Taken together, our results indicate that VEGF can contribute to the development of non-cardiogenic lung edema in sepsis-associated ALI due to increased VEGF secretion from pulmonary vascular endothelial cells through multiple MAPK-dependent pathways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371837/ doi: 10.1007/s00210-020-01947-6 id: cord-013067-sic08gsg author: Turzo, Maurizio title: Inhibition of overexpressed Kv3.4 augments HPV in endotoxemic mice date: 2020-10-08 words: 4396.0 sentences: 267.0 pages: flesch: 51.0 cache: ./cache/cord-013067-sic08gsg.txt txt: ./txt/cord-013067-sic08gsg.txt summary: Inhibition of Kv3.4 with the specific blocker BDS-I increased HPV in isolated perfused endotoxemic mouse lungs. Extracts of total lung tissue from mice with LPS i.p. showed an increase of Kv3.4 gene expression (3.9 ± 0.5fold, n = 6, mean ± SEM, p < 0.05) ( Fig. 1 ) in comparison to 0.9% NaCl solution treated controls (1.0 ± 0.2-fold, normalized on 1, n = 6, means ± SEM). In order to test the role of Kv3.4 in the pulmonary vasculature, lungs of mice with and without endotoxemia were perfused with and without 50 nM of the Kv3.4 specific inhibitor BDS-I. Since Nav1.7 expression is not described in pulmonary arteries, it reduces the possibility that the effect by 50 nM BDS-I in the isolated perfused mouse lung are provoked via inhibition of Nav1.7. An isolated, perfused mouse lung model was used to study pulmonary vasoreactivity in response to acute hypoxia in LPS exposed mice. abstract: BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a reaction of the pulmonary vasculature upon hypoxia, diverting blood flow into ventilated areas to preserve oxygenation. It is impaired in endotoxemia or ARDS. Voltage gated potassium channels have been shown to play a key role in the regulation of HPV. The aim of the study was to identify a voltage gated potassium channel involved in dysregulated HPV during endotoxemia. METHODS: Lungs of male C57BL/6 mice with and without endotoxemia (n = 6 ea. group) were analyzed for Kv3.4 gene and protein expression. HPV was examined in isolated perfused lungs of mice with and without endotoxemia and with and without selective Kv3.4 blocker BDS-I (n = 7 ea. group). Pulmonary artery pressure (PAP) and pressure-flow curves were measured during normoxic (FiO(2) 0.21) and hypoxic (FiO(2) 0.01) ventilation. HPV was quantified as the increase in perfusion pressure in response to hypoxia in percent of baseline perfusion pressure (ΔPAP) in the presence and absence of BDS-I. RESULTS: Kv3.4 gene (3.2 ± 0.5-fold, p < 0.05) and protein (1.5 ± 0.1-fold p < 0.05) expression levels were increased in endotoxemic mouse lungs. Endotoxemia reduced HPV (∆PAP control: 121.2 ± 8.7% vs. LPS 19.5 ± 8.0%, means ± SEM) while inhibition of Kv3.4 with 50 nM BDS-I augmented HPV in endotoxemic but not in control lungs (∆PAP control BDS-I: 116.6 ± 16.0% vs. LPS BDS-I 84.4 ± 18.2%, means ± SEM). CONCLUSIONS: Kv3.4 gene and protein expressions are increased in endotoxemic mouse lungs. Selective inhibition of Kv3.4 augments HPV in lungs of endotoxemic mice, but not in lungs of control mice. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543677/ doi: 10.1186/s12890-020-01278-5 id: cord-005872-w1x1i0im author: Volk, T. title: Endothelium function in sepsis date: 2000 words: 8871.0 sentences: 463.0 pages: flesch: 29.0 cache: ./cache/cord-005872-w1x1i0im.txt txt: ./txt/cord-005872-w1x1i0im.txt summary: Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. S. aureus has been reported to directly infect human umbilical vein endothelial cells (HUVEC) thereby inducing secretion of cytokines and functional upregulation of adhesion molecules [2] . Infection and activation of endothelial cells by Listeria monocytogenes is believed to be a critical component of the pathogenesis of this disease and includes ceramide generation, transcription factor activation and increases in adhesion molecule expression on HUVEC [11] . E-selectin expression in human endothelial cells by TNF-alpha-induced oxidant generation and NF-kappaB activation abstract: Endothelial cells can be the prime target for an infection and infected endothelial cells may serve as an initiating system for a systemic response as these cells are able to secrete many mediators known to be of paramount importance. Endothelial cell functions in turn are regulated by these circulating mediators. Cellular interactions with leukocytes revealed protective and destructive functions. Single cell and animal studies indicate that endothelial permeability is increased and apart from clinical obvious edema formation in septic patients, the endothelial component remains unknown. Endothelial coagulation activation has been shown in vitro, however human data supporting an endothelial procoagulatory state are lacking. Defects in endothelium dependent vasoregulation in animal models are well known and again human studies are largely missing.¶An imbalanced production of reactive oxygen species including nitric oxide has been found to be involved in all endothelial functions and may provide a common link which at present can be supported only in animal studies. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095878/ doi: 10.1007/s000110050579 id: cord-103496-8tq78p2z author: Wang, Ting title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury date: 2020-11-13 words: 5855.0 sentences: 302.0 pages: flesch: 45.0 cache: ./cache/cord-103496-8tq78p2z.txt txt: ./txt/cord-103496-8tq78p2z.txt summary: title: RAC1 nitration at Y32 IS involved in the endothelial barrier disruption associated with lipopolysaccharide-mediated acute lung injury Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y32, preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. We anticipate that a successful clinical efficacy of NipR2 or similar product might require: 1) precision medicine approach to identify patients in the sub-group with satisfactory responsiveness of Rac1 nitration blockade, as not all triggers of ALI (e.g., trauma) will lead to endothelial oxidative stress and peroxynitrite generation; 2) combination therapy with other effective reagents, including suppressor of the cytokine storm and/or neutrophil eliminators; 3) abstract: Acute lung injury (ALI), a devastating illness induced by systemic inflammation e.g., sepsis or local lung inflammation e.g., COVID-19 mediated severe pneumonia, has an unacceptably high mortality and has no effective therapy. ALI is associated with increased pulmonary microvascular hyperpermeability and alveolar flooding. The small Rho GTPases, RhoA and Rac1 are central regulators of vascular permeability through cytoskeleton rearrangements. RhoA and Rac1 have opposing functional outcome: RhoA induces an endothelial contractile phenotype and barrier disruption, while Rac1 stabilizes endothelial junctions and increases barrier integrity. In ALI, RhoA activity is increased while Rac1 activity is reduced. We have shown that the activation of RhoA in lipopolysaccharide (LPS)-mediated ALI, is dependent, at least in part, on a single nitration event at tyrosine (Y)34. Thus, the purpose of this study was to determine if the inhibition of Rac1 is also dependent on its nitration. Our data show that Rac1 inhibition by LPS is associated with its nitration that mass spectrometry identified as Y32, within the switch I region adjacent to the nucleotide-binding site. Using a molecular modeling approach, we designed a nitration shielding peptide for Rac1, designated NipR2 (nitration inhibitor peptide for the Rho GTPases 2), which attenuated the LPS-induced nitration of Rac1 at Y32, preserves Rac1 activity and attenuates the LPS-mediated disruption of the endothelial barrier in human lung microvascular endothelial cells (HLMVEC). Using a murine model of ALI induced by intratracheal installation of LPS we found that NipR2 successfully prevented Rac1 nitration and Rac1 inhibition, and more importantly attenuated pulmonary inflammation, reduced lung injury and prevented the loss of lung function. Together, our data identify a new post-translational mechanism of Rac1 inhibition through its nitration at Y32. As NipR2 also reduces sepsis induced ALI in the mouse lung, we conclude that Rac1 nitration is a therapeutic target in ALI. url: https://api.elsevier.com/content/article/pii/S221323172030999X doi: 10.1016/j.redox.2020.101794 id: cord-012828-wsjob1p8 author: Wang, Yan-hang title: Isosibiricin inhibits microglial activation by targeting the dopamine D1/D2 receptor-dependent NLRP3/caspase-1 inflammasome pathway date: 2019-09-10 words: 4218.0 sentences: 256.0 pages: flesch: 41.0 cache: ./cache/cord-012828-wsjob1p8.txt txt: ./txt/cord-012828-wsjob1p8.txt summary: We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Some previous research has suggested that spinal cord injury induces inflammatory cytokine production by activating the nucleotide-binding domain-like receptor protein 3 inflammasome pathway, which is significantly suppressed by DRD1 agonists [14] . Therefore, in this study, we explored the mechanism of the anti-neuroinflammatory effects of isosibiricin in a BV-2 microglial model and highlighted that isosibiricin can significantly inhibit the production of multiple inflammatory mediators induced by bacterial lipopolysaccharide stimulation via targeting the DRD1/D2-dependent inflammasome pathway, providing a potential therapeutic strategy for inflammation-related neurological disorders. Isosibiricin inhibits the NLRP3/caspase-1 inflammasome pathway in LPS-or nigericin-treated BV-2 cells and LPS-treated Balb/c mice It has been reported that the expression of the pro-inflammatory mediator IL-1β significantly increases in DRD2-null mice compared with wild-type mice [24] . abstract: Microglia-mediated neuroinflammation is a crucial risk factor for neurological disorders. Recently, dopamine receptors have been found to be involved in multiple immunopathological processes and considered as valuable therapeutic targets for inflammation-associated neurologic diseases. In this study we investigated the anti-neuroinflammation effect of isosibiricin, a natural coumarin compound isolated from medicinal plant Murraya exotica. We showed that isosibiricin (10−50 μM) dose-dependently inhibited lipopolysaccharide (LPS)-induced BV-2 microglia activation, evidenced by the decreased expression of inflammatory mediators, including nitrite oxide (NO), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β) and interleukin-18 (IL-18). By using transcriptomics coupled with bioinformatics analysis, we revealed that isosibiricin treatment mainly affect dopamine receptor signalling pathway. We further demonstrated that isosibiricin upregulated the expression of dopamine D1/2 receptors in LPS-treated BV-2 cells, resulting in inhibitory effect on nucleotide binding domain-like receptor protein 3 (NLRP3)/caspase-1 inflammasome pathway. Treatment with dopamine D1/2 receptor antagonists SCH 23390 (1 μM) or sultopride (1 μM) could reverse the inhibitory effects of isosibiricin on NLRP3 expression as well as the cleavages of caspase-1 and IL-1β. Collectively, this study demonstrates a promising therapeutic strategy for neuroinflammation by targeting dopamine D1/2 receptors. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471458/ doi: 10.1038/s41401-019-0296-7 id: cord-336432-tu00gffr author: Wang, Zhiyu title: Small molecule therapeutics for COVID-19: repurposing of inhaled furosemide date: 2020-07-07 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: The novel coronavirus SARS-CoV-2 has become a global health concern. The morbidity and mortality of the potentially lethal infection caused by this virus arise from the initial viral infection and the subsequent host inflammatory response. The latter may lead to excessive release of pro-inflammatory cytokines, IL-6 and IL-8, as well as TNF-α ultimately culminating in hypercytokinemia (“cytokine storm”). To address this immuno-inflammatory pathogenesis, multiple clinical trials have been proposed to evaluate anti-inflammatory biologic therapies targeting specific cytokines. However, despite the obvious clinical utility of such biologics, their specific applicability to COVID-19 has multiple drawbacks, including they target only one of the multiple cytokines involved in COVID-19’s immunopathy. Therefore, we set out to identify a small molecule with broad-spectrum anti-inflammatory mechanism of action targeting multiple cytokines of innate immunity. In this study, a library of small molecules endogenous to the human body was assembled, subjected to in silico molecular docking simulations and a focused in vitro screen to identify anti-pro-inflammatory activity via interleukin inhibition. This has enabled us to identify the loop diuretic furosemide as a candidate molecule. To pre-clinically evaluate furosemide as a putative COVID-19 therapeutic, we studied its anti-inflammatory activity on RAW264.7, THP-1 and SIM-A9 cell lines stimulated by lipopolysaccharide (LPS). Upon treatment with furosemide, LPS-induced production of pro-inflammatory cytokines was reduced, indicating that furosemide suppresses the M1 polarization, including IL-6 and TNF-α release. In addition, we found that furosemide promotes the production of anti-inflammatory cytokine products (IL-1RA, arginase), indicating M2 polarization. Accordingly, we conclude that furosemide is a reasonably potent inhibitor of IL-6 and TNF-α that is also safe, inexpensive and well-studied. Our pre-clinical data suggest that it may be a candidate for repurposing as an inhaled therapy against COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32704455/ doi: 10.7717/peerj.9533 id: cord-270213-ygb64yxc author: Williams, Alexander T. title: Control of systemic inflammation throughearly nitric oxide supplementation with nitric oxide releasing nanoparticles date: 2020-10-02 words: 2300.0 sentences: 138.0 pages: flesch: 42.0 cache: ./cache/cord-270213-ygb64yxc.txt txt: ./txt/cord-270213-ygb64yxc.txt summary: Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19. A well-described hallmark of sepsis is endothelial dysfunction in response to a cytokine 81 ''storm'', which is associated with an increase in a series of negative consequences arising from 82 overproduction of reactive oxygen species (ROS), disruption of the glycocalyx, and endothelial 83 nitric oxide synthase (eNOS) uncoupling, all contributing to increased adhesion of red blood 84 cells (RBCs), white blood cells (WBCs), and platelets to the endothelium lining, enhanced 85 platelet activation, blood stagnation, decreased tissue perfusion and increased vascular 86 permeability. Mice treated with Control-np in our study 382 experienced significantly increased vascular permeability, as shown in Figure 4 , suggesting 383 endothelial cell and glycocalyx disruption in these animals. abstract: Amelioration of immune overactivity during sepsis is key to restoring hemodynamics, microvascular blood flow, and tissue oxygenation, and in preventing multi-organ dysfunction syndrome. The systemic inflammatory response syndrome that results from sepsis ultimately leads to degradation of the endothelial glycocalyx and subsequently increased vascular leakage. Current fluid resuscitation techniques only transiently improve outcomes in sepsis, and can cause edema. Nitric oxide (NO) treatment for sepsis has shown promise in the past, but implementation is difficult due to the challenges associated with delivery and the transient nature of NO. To address this, we tested the anti-inflammatory efficacy of sustained delivery of exogenous NO using IV infused NO releasing nanoparticles (NO-np). The impact of NO-np on microhemodynamics and immune response in a lipopolysaccharide (LPS) induced endotoxemia mouse model was evaluated. NO-np treatment significantly attenuated the pro-inflammatory response by promoting M2 macrophage repolarization, which reduced the presence of pro-inflammatory cytokines in the serum and slowed vascular extravasation. Combined, this resulted in significantly improved microvascular blood flow and 72-hour survival of animals treated with NO-np. The results from this study suggest that sustained supplementation of endogenous NO ameliorates and may prevent the morbidities of acute systemic inflammatory conditions. Given that endothelial dysfunction is a common denominator in many acute inflammatory conditions, it is likely that NO enhancement strategies may be useful for the treatment of sepsis and other acute inflammatory insults that trigger severe systemic pro-inflammatory responses and often result in a cytokine storm, as seen in COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/33011274/ doi: 10.1016/j.freeradbiomed.2020.09.025 id: cord-300912-w85t4zz6 author: Wu, Beibei title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils date: 2017-10-25 words: 3699.0 sentences: 224.0 pages: flesch: 50.0 cache: ./cache/cord-300912-w85t4zz6.txt txt: ./txt/cord-300912-w85t4zz6.txt summary: title: n-butanol extract from Folium isatidis inhibits the lipopolysaccharide-induced downregulation of CXCR1 and CXCR2 on human neutrophils Our previous study investigated the effect of n-butanol extract from Folium isatidis on lipopolysaccharide (LPS)-induced septic shock. The addition of n-butanol extract from Folium isatidis inhibited this LPS-induced downregulation of CXCR1, CXCR2 and CD62L, and decreased the expression of IL-8 on neutrophils. The isolated neutrophils were treated with either vehicle or increasing concentrations (10, 100 and 1,000 ng/ml) of LPS for 4 h, and the expression levels of CXCR1, CXCR2, TLR2, TLR4, CD11b and CD62L were measured using flow cytometry. n-butanol extract from Folium isatidis prevents the LPS-induced downregulation of CXCR1, CXCR2 and CD62L. Subsequent analysis of the cells using flow cytometry indicated that the extract inhibited the LPS-induced downregulation of CXCR1, CXCR2 and CD62L ( Fig. 2A-C) in a dose-dependent manner. Effect of n-butanol extract from Folium isatidis on the gene expression levels of CXCR1, CXCR2 and CD62L. abstract: Neutrophils, immune cells crucial for protecting against invading pathogens, are important in sepsis. Neutrophil migration is regulated by chemokine receptors and their cognate ligands. Our previous study investigated the effect of n-butanol extract from Folium isatidis on lipopolysaccharide (LPS)-induced septic shock. The present study stimulated neutrophils with LPS to explore the influence of LPS on cell. Neutrophils were then pretreated with n-butanol extract from Folium isatidis followed by LPS to examine the effect of this extract on neutrophil chemotaxis. The results showed that LPS decreased the expression levels of CXC-chemokine receptor (CXCR)1, CXCR2 and L-selectin (CD62L), and increased the expression of interleukin-8 (IL-8) by neutrophils. The addition of n-butanol extract from Folium isatidis inhibited this LPS-induced downregulation of CXCR1, CXCR2 and CD62L, and decreased the expression of IL-8 on neutrophils. In addition, n-butanol extract promoted myeloperoxidase activity in neutrophils. Taken together, LPS downregulated the expression of chemokine receptors, leading to the failure of neutrophils to migrate to sites of infection. The addition of n-butanol extract, which promoted the ability of neutrophils to migrate, is a natural product and potential therapeutic agent with which to target neutrophil chemotaxis during LPS stimulation. url: https://doi.org/10.3892/mmr.2017.7870 doi: 10.3892/mmr.2017.7870 id: cord-322729-47c9z2gk author: Wu, Chieh-Shan title: Antihelminthic niclosamide modulates dendritic cells activation and function date: 2014-04-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Abstract Dendritic cells (DCs) link the sensing of the environment by the innate immune system to the initiation of adaptive immune responses. Accordingly, DCs are considered to be a major target in the development of immunomodulating compounds. In this study, the effect of niclosamide, a Food and Drug Administration-approved antihelminthic drug, on the activation of lipopolysaccharide (LPS)-stimulated murine bone marrow-derived DCs was examined. Our experimental results show that niclosamide reduced the pro-inflammatory cytokine and chemokine expression of LPS-activated DCs. In addition, niclosamide also affected the expression of MHC and costimulatory molecules and influenced the ability of the cells to take up antigens. Therefore, in mixed cell cultures composed of syngeneic OVA-specific T cells and DCs, niclosamide-treated DCs showed a decreased ability to stimulate T cell proliferation and IFN-γ production. Furthermore, intravenous injection of niclosamide also attenuated contact hypersensitivity (CHS) in mice during sensitization with 2,4-dinitro-1-fluorobenzene. Blocking the LPS-induced activation of MAPK-ERK, JNK and NF-κB may contribute to the inhibitory effect of niclosamide on DC activation. Collectively, our findings suggest that niclosamide can manipulate the function of DCs. These results provide new insight into the immunopharmacological role of niclosamide and suggest that it may be useful for the treatment of chronic inflammatory disorders or DC-mediated autoimmune diseases. url: https://www.sciencedirect.com/science/article/pii/S0008874913002062 doi: 10.1016/j.cellimm.2013.12.006 id: cord-002165-blbaqbo7 author: Wu, Dongdong title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice date: 2016-08-15 words: 4744.0 sentences: 281.0 pages: flesch: 50.0 cache: ./cache/cord-002165-blbaqbo7.txt txt: ./txt/cord-002165-blbaqbo7.txt summary: title: Interferon Regulatory Factor-1 Mediates Alveolar Macrophage Pyroptosis During LPS-Induced Acute Lung Injury in Mice Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. A previous study conducted by our group observed caspase-1 activation in AMs during the development of ALI/ ARDS, and further, that treatment with a specific caspase-1 inhibitor has been shown to reduce LPS-induced lung injury in mice (8) . In the present study, we showed that the absence of IRF-1 in genetic knockout mice strongly alleviates LPS-induced lung injury and abrogates its pyroptotic effects in AMs. These findings suggest that IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation, which is, in turn, a TLR4-dependent process. abstract: Previously, we demonstrated that pyroptosis in alveolar macrophages (AMs) plays an essential role in lipopolysaccharide (LPS)-induced acute lung injury. However, the underlying mechanism remains largely unclear. Here, we show that the absence of interferon regulatory factor 1 (IRF-1) in genetic knock-out mice strongly abrogates pyroptosis in AMs and alleviates the LPS-induced lung injury and systemic inflammation. Our study demonstrates that IRF-1 contributes to caspase-1 activation and apoptosis-associated speck-like protein containing a caspase activation and recruitment domain pyroptosome formation in AMs and leads to downstream inflammatory cytokine release, including that of IL-1β, IL-18, and HMGB1. The nuclear translocation of IRF-1 is linked to the presence of toll-like receptor 4 (TLR4). Our findings suggest that pyroptosis and the downstream inflammatory response in AMs induced by LPS is a process that is dependent on TLR4-mediated up-regulation of IRF-1. In summary, IRF-1 plays a key role in controlling caspase-1-dependent pyroptosis and inflammation. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4978602/ doi: 10.1097/shk.0000000000000595 id: cord-257092-r11cgpvs author: Wu, Fengjiao title: CXCR2 is essential for cerebral endothelial activation and leukocyte recruitment during neuroinflammation date: 2015-05-21 words: 6725.0 sentences: 427.0 pages: flesch: 51.0 cache: ./cache/cord-257092-r11cgpvs.txt txt: ./txt/cord-257092-r11cgpvs.txt summary: Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. We observed reduced neutrophil infiltration and attenuated leukocyte-endothelial cell interactions in CXCR2 −/− and CXCL1 −/− mice following the intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). To identify the source of functional CXCR2 that mediates leukocyte recruitment, we generated chimeric mice by transferring bone marrow cells between WT and (See figure on previous page.) Fig. 2 Chemokine levels and the effect of CXCR2 or CXCL1 deficiency on neutrophil recruitment to the brain parenchyma after i.c.v. LPS injection. Following stimulation with TNF-α or LPS, the cerebral endothelial cells, compared with astrocytes and microglia, also expressed much higher level of CXCR2 protein (Fig. 7D ). Our results demonstrate that CXCL1, an important factor secreted by astrocytes, also plays a critical role in leukocyte recruitment to the CNS by cooperating with CXCR2 expressed on cerebral endothelial cells. abstract: BACKGROUND: Chemokines and chemokine receptors cooperate to promote immune cell recruitment to the central nervous system (CNS). In this study, we investigated the roles of CXCR2 and CXCL1 in leukocyte recruitment to the CNS using a murine model of neuroinflammation. METHODS: Wild-type (WT), CXCL1(−/−), and CXCR2(−/−) mice each received an intracerebroventricular (i.c.v.) injection of lipopolysaccharide (LPS). Esterase staining and intravital microscopy were performed to examine neutrophil recruitment to the brain. To assess endothelial activation in these mice, the expression of adhesion molecules was measured via quantitative real-time polymerase chain reaction (PCR) and Western blotting. To identify the cellular source of functional CXCR2, chimeric mice were generated by transferring bone marrow cells between the WT and CXCR2(−/−) mice. RESULTS: Expression levels of the chemokines CXCL1, CXCL2, and CXCL5 were significantly increased in the brain following the i.c.v. injection of LPS. CXCR2 or CXCL1 deficiency blocked neutrophil infiltration and leukocyte recruitment in the cerebral microvessels. In the CXCR2(−/−) and CXCL1(−/−) mice, the cerebral endothelial expression of adhesion molecules such as P-selectin and VCAM-1 was dramatically reduced. Furthermore, the bone marrow transfer experiments demonstrated that CXCR2 expression on CNS-residing cells is essential for cerebral endothelial activation and leukocyte recruitment. Compared with microglia, cultured astrocytes secreted a much higher level of CXCL1 in vitro. Astrocyte culture conditioned medium significantly increased the expression of VCAM-1 and ICAM-1 in cerebral endothelial cells in a CXCR2-dependent manner. Additionally, CXCR2 messenger RNA (mRNA) expression in cerebral endothelial cells but not in microglia or astrocytes was increased following tumor necrosis factor-α (TNF-α) stimulation. The intravenous injection of the CXCR2 antagonist SB225002 significantly inhibited endothelial activation and leukocyte recruitment to cerebral microvessels. CONCLUSIONS: CXCL1 secreted by astrocytes and endothelial CXCR2 play essential roles in cerebral endothelial activation and subsequent leukocyte recruitment during neuroinflammation. url: https://www.ncbi.nlm.nih.gov/pubmed/25990934/ doi: 10.1186/s12974-015-0316-6 id: cord-005980-e2s0racp author: Wu, Xiaojing title: TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury date: 2019-09-05 words: 5208.0 sentences: 295.0 pages: flesch: 48.0 cache: ./cache/cord-005980-e2s0racp.txt txt: ./txt/cord-005980-e2s0racp.txt summary: Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression. RESULTS: We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. CONCLUSIONS: Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-κB and JNK in a murine model of ALI. Compared with those in the control group, the PMN/total cell ratio in the BALF (Fig. 4c) and lung MPO activity (Fig. 4d) in LPS-challenged mice were dramatically increased, and these levels were inhibited by AAV-TIPE2 treatment. abstract: OBJECTIVE: Tumour necrosis factor-α-induced protein 8-like 2 (TIPE2) has strong anti-inflammatory properties. However, it is unknown whether increased TIPE2 is protective against lipopolysaccharide (LPS)-induced ALI. In the current study, we aimed to investigate whether increased TIPE2 can exert protective effects in a mouse model of ALI induced by LPS. METHODS: We administered TIPE2 adeno-associated virus (AAV-TIPE2) intratracheally into the lungs of mice. Three weeks later, ALI was induced by intratracheal injection of LPS into BALB/c mice. Twenty-four hours later, lung bronchoalveolar lavage fluid (BALF) was acquired to analyse cells and protein, arterial blood was collected for arterial blood gas analysis and the determination of pro-inflammatory factor levels, and lung issues were collected for histologic examination, transmission electron microscopy (TEM), TUNEL staining, wet/dry (W/D) weight ratio analysis, myeloperoxidase (MPO) activity analysis and blot analysis of protein expression. RESULTS: We found that TIPE2 overexpression markedly mitigated LPS-induced lung injury, which was evaluated by the deterioration of histopathology, histologic scores, the W/D weight ratio, and total protein expression in the BALF. Moreover, TIPE2 overexpression markedly attenuated lung inflammation, as evidenced by the downregulation of polymorphonuclear neutrophils (PMNs) in the BALF, lung MPO activity, and pro-inflammatory cytokine levels in the serum. Moreover, TIPE2 overexpression not only dramatically prevented LPS-induced pulmonary cell apoptosis in mice but also blocked LPS-activated JNK phosphorylation and NF-κB p65 nuclear translocation. CONCLUSIONS: Our study shows that the increased expression of AAV-mediated TIPE2 in the lungs of mice inhibits acute inflammation and apoptosis and suppresses the activation of NF-κB and JNK in a murine model of ALI. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096061/ doi: 10.1007/s00011-019-01280-6 id: cord-348391-xytmq2f2 author: Wyganowska-Swiatkowska, Marzena title: Influence of Herbal Medicines on HMGB1 Release, SARS-CoV-2 Viral Attachment, Acute Respiratory Failure, and Sepsis. A Literature Review date: 2020-06-30 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: By attaching to the angiotensin converting enzyme 2 (ACE2) protein on lung and intestinal cells, Sudden Acute Respiratory Syndrome (SARS-CoV-2) can cause respiratory and homeostatic difficulties leading to sepsis. The progression from acute respiratory failure to sepsis has been correlated with the release of high-mobility group box 1 protein (HMGB1). Lack of effective conventional treatment of this septic state has spiked an interest in alternative medicine. This review of herbal extracts has identified multiple candidates which can target the release of HMGB1 and potentially reduce mortality by preventing progression from respiratory distress to sepsis. Some of the identified mixtures have also been shown to interfere with viral attachment. Due to the wide variability in chemical superstructure of the components of assorted herbal extracts, common motifs have been identified. Looking at the most active compounds in each extract it becomes evident that as a group, phenolic compounds have a broad enzyme inhibiting function. They have been shown to act against the priming of SARS-CoV-2 attachment proteins by host and viral enzymes, and the release of HMGB1 by host immune cells. An argument for the value in a nonspecific inhibitory action has been drawn. Hopefully these findings can drive future drug development and clinical procedures. url: https://doi.org/10.3390/ijms21134639 doi: 10.3390/ijms21134639 id: cord-000137-idffrnac author: Xiang, Meng title: Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury date: 2009-11-02 words: 9097.0 sentences: 456.0 pages: flesch: 40.0 cache: ./cache/cord-000137-idffrnac.txt txt: ./txt/cord-000137-idffrnac.txt summary: The study further found that the induction of the negative regulators of TLR signaling IL-1R-associated kinase-M, Toll-interacting protein and A20 by intratracheal LPS in vivo and in macrophages in vitro was significantly reduced in CD44 -/mice. Thus, the study demonstrates a novel mechanism underlying HS-augmented lung inflammation, namely that induction of increased TLR2 surface expression in lung endothelial cells, which is induced by HS/R and mediated by HMGB1 activation of TLR4 signaling, is an important mechanism responsible for EC-mediated inflammation and organ injury following HS (122) . These results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and suggest a fundamental paradigm of how tissue stress and injury are monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response (147) . abstract: Acute lung injury (ALI) that clinically manifests as acute respiratory distress syndrome is caused by an uncontrolled systemic inflammatory response resulting from clinical events including sepsis, major surgery and trauma. Innate immunity activation plays a central role in the development of ALI. Innate immunity is activated through families of related pattern recognition receptors (PRRs), which recognize conserved microbial motifs or pathogen-associated molecular patterns (PAMPs). Toll-like receptors were the first major family of PRRs discovered in mammals. Recently, NACHT–leucine-rich repeat (LRR) receptors and retinoic acid–inducible gene–like receptors have been added to the list. It is now understood that in addition to recognizing infectious stimuli, both Toll-like receptors and NACHT-LRR receptors can also respond to endogenous molecules released in response to stress, trauma and cell damage. These molecules have been termed damage-associated molecular patterns (DAMPs). It has been clinically observed for a long time that infectious and noninfectious insults initiate inflammation, so confirmation of overlapping receptor-signal pathways of activation between PAMPs and DAMPs is no surprise. This review provides an overview of the PRR-dependent mechanisms of ALI and clinical implication. Modification of PRR pathways is likely to be a logical therapeutic target for ALI/acute respiratory distress syndrome. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2785474/ doi: 10.2119/molmed.2009.00097 id: cord-000460-h3owwjao author: Xiong, Jing title: Leukocyte- and Platelet-Derived Microvesicle Interactions following In Vitro and In Vivo Activation of Toll-Like Receptor 4 by Lipopolysaccharide date: 2011-09-26 words: 4313.0 sentences: 212.0 pages: flesch: 41.0 cache: ./cache/cord-000460-h3owwjao.txt txt: ./txt/cord-000460-h3owwjao.txt summary: However, with LPS stimulation numbers of platelets staining positive for both plateletand leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. Alternatively, comparable activation of leukocyte as well as platelet result in formation of cell-derived microvesicles (MV) which may contribute to increased thrombogenic propensity of the blood, pro-inflammatory immune processes and thus cardiovascular risk [15, 16, 17, 18, 19, 20, 21, 22] . Therefore, the present study was designed to test the hypothesis that acute exposure to a sentinel dose of LPS would induce MV production and exchange of specific proteins/ receptors between platelets and leukocytes via TLR4 activation. The acute effects of LPS on platelet and leukocyte activation were most likely mediated through activation of TLR4 as platelet positive leukocyte antigen was not observed in blood from dTLR4 mice. Platelet-leukocyte interactions require TLR4 signaling as the dual antigen positivity of platelets was observed in blood derived from wild type but not dTLR4 mice. abstract: BACKGROUND: Pro-coagulant membrane microvesicles (MV) derived from platelets and leukocytes are shed into the circulation following receptor-mediated activation, cell-cell interaction, and apoptosis. Platelets are sentinel markers of toll-like receptor 4 (TLR4) activation. Experiments were designed to evaluate the time course and mechanism of direct interactions between platelets and leukocytes following acute activation of TLR4 by bacterial lipopolysaccharide (LPS). METHODOLOGY/PRINCIPAL FINDINGS: Blood from age-matched male and female wild type (WT) and TLR4 gene deleted (dTLR4) mice was incubated with ultra-pure E. coli LPS (500 ng/ml) for up to one hour. At designated periods, leukocyte antigen positive platelets, platelet antigen positive leukocytes and cell-derived MV were quantified by flow cytometry. Numbers of platelet- or leukocyte-derived MV did not increase within one hour following in vitro exposure of blood to LPS. However, with LPS stimulation numbers of platelets staining positive for both platelet- and leukocyte-specific antigens increased in blood derived from WT but not dTLR4 mice. This effect was blocked by inhibition of TLR4 signaling mediated by My88 and TRIF. Seven days after a single intravenous injection of LPS (500 ng/mouse or 20 ng/gm body wt) to WT mice, none of the platelets stained for leukocyte antigen. However, granulocytes, monocytes and apoptotic bodies stained positive for platelet antigens. CONCLUSIONS/SIGNIFICANCE: Within one hour of exposure to LPS, leukocytes exchange surface antigens with platelets through TLR4 activation. In vivo, leukocyte expression of platelet antigen is retained after a single exposure to LPS following turn over of the platelet pool. Acute expression of leukocyte antigen on platelets within one hour of exposure to LPS and the sustained expression of platelet antigen on leukocytes following a single acute exposure to LPS in vivo explains, in part, associations of platelets and leukocytes in response to bacterial infection and changes in thrombotic propensity of the blood. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3180459/ doi: 10.1371/journal.pone.0025504 id: cord-280482-o887a7q9 author: Xu, Suming title: Transgenic Mice Expressing MCP-1 by the Urothelium Demonstrate Bladder Hypersensitivity, Pelvic Pain and Voiding Dysfunction: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Animal Model Study date: 2016-09-29 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: Monocyte chemoattractant protein-1 (MCP-1) is one of the key chemokines that play important roles in diverse inflammatory and chronic pain conditions. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic and debilitating inflammatory condition of the urinary bladder characterized by the hallmark symptoms of pelvic pain and voiding dysfunction. To facilitate IC/BPS research, we used transgenic technology to develop a novel urothelial MCP-1 secretion mouse model (URO-MCP-1). A transgene consisting of the uroplakin II gene promoter and the mouse MCP-1 coding sequence with a secretory element was constructed and microinjected. URO-MCP-1 mice were found to express MCP-1 mRNA in the bladder epithelium and MCP-1 protein in the urine, and developed bladder inflammation 24 hours after intravesical administration of a single sub-noxious dose of lipopolysaccharide (LPS). The inflamed bladders of URO-MCP-1 mice exhibited elevated mRNAs for interleukin (IL)-1ß, IL-6, substance P precursor, and nerve growth factor as well as increased macrophage infiltration. In parallel with these phenotypic changes, URO-MCP-1 mice manifested significant functional changes at days 1 and 3 after cystitis induction. These functional changes included pelvic pain as measured by von Frey filament stimulation and voiding dysfunction (increased urinary frequency, reduced average volume voided per micturition, and reduced maximum volume voided per micturition) as measured by micturition cages. Micturition changes remained evident at day 7 after cystitis induction, although these changes were not statistically significant. Control wild-type C57BL/6 mice manifested no clear changes in histological, biochemical and behavioral features after similar cystitis induction with LPS. Taken together, our results indicate that URO-MCP-1 mice are hypersensitive to bladder irritants such as LPS and develop pelvic pain and voiding dysfunction upon cystitis induction, providing a novel model for IC/BPS research. url: https://doi.org/10.1371/journal.pone.0163829 doi: 10.1371/journal.pone.0163829 id: cord-011286-8wxih7v6 author: You, Qinghai title: MiR-802 alleviates lipopolysaccharide-induced acute lung injury by targeting Peli2 date: 2019-11-06 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: INTRODUCTION: Acute respiratory distress syndrome (ARDS) is a life-threatening medical condition. It is characterized by serious lung inflammation or injury. Characterizing novel miRNAs implicated in ARDS pathogenesis may provide new therapeutic strategy for managing ARDS. METHODS: We employed LPS-induced lung injury model to profile miRNAs associated with ARDS. We isolated one miRNA candidate and characterized its role in lipopolysaccharide (LPS)-induced proinflammatory cytokine production in lung macrophages. We further evaluated its functional role in ARDS model by assessing histological change, neutrophil activation, tissue permeability and tumor necrosis factor alpha (TNFα) production. We also characterized its downstream target using luciferase assay, Western blotting, enzyme-linked immunosorbent assay and cell inflammation assay. RESULTS: Microarray profiling revealed miR-802 was significantly downregulated in ARDS mouse model. LPS-induced miR-802 downregulation was confirmed in lung macrophages. Overexpression of miR-802 significantly suppressed LPS-induced inflammatory cytokine production in vitro and alleviates LPS-induced acute lung injury in vivo. Peli2 was identified as a downstream target of miR-802 and found upregulated in ARDS model. Overexpressing Peli2 abolished the antagonizing effect of miR-802 on LPS-mediated inflammatory response. CONCLUSION: MiR-802 carried a protective role against LPS-induced acute lung injury by downregulating Peli2. MiR-802/Peli2 axis may act as intervening targets to manage ARDS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7223969/ doi: 10.1007/s00011-019-01295-z id: cord-349201-d88g5toc author: Yu, Feng title: Exploring the biomarkers associated with different host inflammation of acute respiratory distress syndrome (ARDS) from lung metabolomics in mice date: 2020-10-13 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: RATIONALE: The aim of this study was to analyze the metabolomics of lung with different host inflammation of acute respiratory distress syndrome (ARDS) for the identification of biomarkers for predicting severity under different inflammatory conditions. METHODS: Cecal ligation and puncture (CLP) and lipopolysaccharide (LPS)‐intratracheal injection induced acute lung injury (ALI). A mouse model was used to explore lung metabolomic biomarkers in ALI/ARDS. The splenectomy model was used as an auxiliary method to distinguish between hyper‐ and hypo‐inflammatory subtypes. Plasma, lung tissue and bronchoalveolar lavage fluid (BALF) samples were collected from mice after CLP/LPS. The severity of lung injury was evaluated. Expression of Tumor Necrosis Factor‐α (TNF‐α) in mice serum and lung was tested by ELISA and PCR. Polymorphonuclear cells in BALF were counted. The lung metabolites were detected by GC/MS, and the metabolic pathways predicted using the KEGG database. RESULTS: The LPS/CLP‐Splen group had more severe lung injury than the corresponding ALI group; that in the CLP‐Splen group was more serious than in the LPS‐Splen group. TNF‐α expression was significantly elevated in the serum and lung tissue after LPS or CLP, and higher in the LPS/CLP‐Splen group than in the corresponding ALI group. The level of TNF‐α in the CLP‐Splen group was elevated significantly over that in the LPS‐Splen group. Both these groups also showed significant neutrophil exudation within the lungs. During differential inflammation, more differential metabolites were detected in the lungs of the CLP‐group ALI mice than inthe LPS group. A total of 41 compounds were detected in the lungs of the CLP and CLP‐Splen groups. Contrastingly, 8 compounds were detected in the lungs of the LPS and LPS‐Splen groups. The LPS‐Splen and CLP‐Splen groups had significant neutrophil exudation in the lung. Random forest analysis of lung‐targeted metabolomics data indicated 4‐hydroxyphenylacetic acid,1‐aminocyclopentanecarboxylic acid (ACPC), cis‐aconitic acid, and hydroxybenzoic acid as strong predictors of hyper‐inflammatory subgroup in the CLP group. Furthermore, with splenectomy, 13 differential metabolic pathways between the CLP and LPS groups were revealed. CONCLUSIONS: Hyper‐inflammatory subgroups of ARDS have a greater inflammatory response and a more active lung metabolism. Combined with host inflammation background, biomarkers from metabolomics could help evaluate the response severity of ARDS. url: https://www.ncbi.nlm.nih.gov/pubmed/33049802/ doi: 10.1002/rcm.8971 id: cord-001496-186k6t03 author: Yuan, Qing title: Attenuating effect of Ginsenoside Rb1 on LPS-induced lung injury in rats date: 2014-12-05 words: 5022.0 sentences: 262.0 pages: flesch: 44.0 cache: ./cache/cord-001496-186k6t03.txt txt: ./txt/cord-001496-186k6t03.txt summary: Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules. The goal of the present study was to clarify the effects of Ginsenoside Rb1 on LPS-induced rat lung injury and analyzed the detailed molecular mechanisms in vivo and in vitro. abstract: BACKGROUND: Sepsis causes neutrophil sequestration in the lung which leads to acute lung injury (ALI). Radix Ginseng (RG), a traditional herb used as herbal remedy in eastern Asia for thousands of years, which has been traditionally used in China to improve blood circulation and ameliorate pathological hemostasis. This study investigated whether Ginsenoside Rb1, the main components of RG, can attenuate ALI induced by LPS. METHODS: In vivo, 30 male Wistar rats were divided into three groups (n = 10 each groups) on the basis of the reagent used, which were subjected to LPS injection with or without Ginsenoside Rb1 (5 mg/kg) treatments to induce ALI model. Lung injury was assessed by pulmonary histology, lung wet-weight to dry-weight (W/D) ratio, the number of myeloperoxidase (MPO) positive cells, immunohistochemical analysis of intercellular adhesion molecule-1 (ICAM-1), gene expression of ICAM-1, ultrastructure changes of pulmonary microvasculature, concentration of inflammatory markers and in plasma. In vitro, pulmonary microvascular endothelial cells (PMVECs) were stimulated with LPS in the presence and absence of Ginsenoside Rb1 (50 mM), nuclear factor-κB (NF-κB) p65 was measured by immunocytochemistry staining and western blotting. RESULTS: Infusion of LPS induced lung injury, in vivo, as demonstrated by pulmonary edema with infiltration of neutrophils and hemorrhage, the increase in lung W/D ratio, the number of MPO positive cells, the level of inflammatory markers such as TNF-α, MCP-1 and IL-8, enhanced expression of ICAM-1 and ICAM-1 gene. Moreover, resulted in the changes of intercellular junctions in the endothelial cells of pulmonary microvasculature. In vitro, the significant increased release of NF-κB p65 and its subsequent translocation into the nucleus in PMVECs were observed. In contrast, Ginsenoside Rb1 treatment significantly ameliorated the LPS-induced lung injury, as judged by the marked improvement in all these indices. CONCLUSIONS: These results indicate that Ginsenoside Rb1 attenuated LPS-induced lung injury through an inhibition of the inflammatory signaling pathway, besides the direct inhibitory effect on proinflammatory molecules. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4272525/ doi: 10.1186/s12950-014-0040-5 id: cord-005875-yp1ehpeg author: Zhang, Dong title: Crocin alleviates lipopolysaccharide-induced acute respiratory distress syndrome by protecting against glycocalyx damage and suppressing inflammatory signaling pathways date: 2020-01-10 words: 5136.0 sentences: 346.0 pages: flesch: 47.0 cache: ./cache/cord-005875-yp1ehpeg.txt txt: ./txt/cord-005875-yp1ehpeg.txt summary: OBJECTIVE: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). RESULTS: This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. The preceding results indicated that crocin might inhibit the expression of HPA by inhibiting the upstream protein of CTL in LPS-induced ARDS mice and LPS-stimulated HUVECs. The results in vivo showed that the expression of MMP-9 by LPS stimulation was significantly increased compared with that of the control group (Fig. 4c, d) . These results suggested that crocin can inhibit the activation of MAPK pathway in LPS-induced ARDS mice and LPS-stimulated HUVECs. The HMGB1 and NF-κB signaling pathway also regulate lung injury of the inflammatory process. abstract: OBJECTIVE: To explore the mechanisms of crocin against glycocalyx damage and inflammatory injury in lipopolysaccharide (LPS)-induced acute respiratory distress syndrome (ARDS) mice and LPS-stimulated human umbilical vein endothelial cells (HUVECs). METHODS: Mice were randomly divided into control, LPS, and crocin + LPS (15, 30, and 60 mg/kg) groups. HUVECs were separated into eight groups: control, crocin, matrix metalloproteinase 9 inhibitor (MMP-9 inhib), cathepsin L inhibitor (CTL inhib), LPS, MMP-9 inhib + LPS, CTL inhib + LPS, and crocin + LPS. The potential cytotoxic effect of crocin on HUVECs was mainly evaluated through methylthiazolyldiphenyl-tetrazolium bromide assay. Histological changes were assessed via hemotoxylin and eosin staining. Lung capillary permeability was detected on the basis of wet–dry ratio and through fluorescein isothiocyanate-albumin assay. Then, protein levels were detected through Western blot analysis, immunohistochemical staining, and immunofluorescence. RESULTS: This study showed that crocin can improve the pulmonary vascular permeability in mice with LPS-induced ARDS and inhibit the inflammatory signaling pathways of high mobility group box, nuclear factor κB, and mitogen-activated protein kinase in vivo and in vitro. Crocin also protected against the degradation of endothelial glycocalyx heparan sulfate and syndecan-4 by inhibiting the expressions of CTL, heparanase, and MMP-9 in vivo and in vitro. Overall, this study revealed the protective effects of crocin on LPS-induced ARDS and elaborated their underlying mechanism. CONCLUSION: Crocin alleviated LPS-induced ARDS by protecting against glycocalyx damage and suppressing inflammatory signaling pathways. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095881/ doi: 10.1007/s00011-019-01314-z id: cord-280850-lku2g69k author: Zhang, Shidong title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits date: 2013-08-26 words: 3849.0 sentences: 200.0 pages: flesch: 52.0 cache: ./cache/cord-280850-lku2g69k.txt txt: ./txt/cord-280850-lku2g69k.txt summary: title: Aqueous extract of Bai-Hu-Tang, a classical Chinese herb formula, prevents excessive immune response and liver injury induced by LPS in rabbits In this study, a febrigenic dosage of LPS (15 mg/kg i.v.) was injected into rabbits to form an animal febrile model, then the model animals were gavaged with BHT at the same time, and the formula''s function of liver damage prevention and immunomodulation was researched in rabbits. Therefore, BHT did not affect the activated adaptive immunity, but prevented the cell immunity inhibition and excessive cytokines in innate immunity by LPS at the same time. The gene expressions of TLR4 studied herein were not affected by BHT (Fig. 5A ), but LBP expression was increased (Fig. 5B) , which bind and transport LPS to activate cells in the immunity system (Knapp et al., 2006) , and inhibiting inflammatory response at higher concentration (Hamann et al., 2005) . abstract: Abstract Ethnopharmacological relevance Bai-Hu-Tang (BHT) was traditionally used to reduce fever heat and promote generation of body fluids. Aim of the study To investigate the effect and mechanism of BHT in the prevention of lipopolysaccharide (LPS) fever in manners of immune modulation. Materials and methods The model of fever syndrome of Chinese medicine pattern was imitated by LPS injection i.v. in rabbits, and BHT was gavaged. The serum levels of tumor necrosis factor-α (TNF-α), interleukin (IL-6, 10) and immunoglobulin (IgG, IgA, and IgM) were determined by enzyme-linked immunosorbent assay (ELISA); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested by biochemical methods. Liver tissue damage was detected by hematoxylin–eosin (H&E) stain. Subpopulation of T cells was detected by Fluorescence Activated Cell Sorter (FACS). Genes expression of Toll-like receptor 4 (TLR4) and lipopolysaccharide binding protein (LBP) in liver tissue were assayed by real-time polymerase chain reaction (RT-PCR). Result The results demonstrated that BHT prevented sudden increase of IL-10, TNF-α, ALT and AST, and liver damage induced by LPS. BHT also prevented significant decrease of the percentage of CD8+ T cells since LPS injection. At the same time, BHT did not affect the gene expression of TLR4 and serum concentration of three immunoglobulins, which were increased by LPS, but made gene expression of LBP higher. Conclusion The results of this study indicated that BHT played an important role in immunity protection and anti-injury through preventing immunoinflammatory damage by LPS. The achievement thereby scientifically provided mechanism of BHT in the prevention of febrile disease, and supported its traditional use. url: https://doi.org/10.1016/j.jep.2013.06.041 doi: 10.1016/j.jep.2013.06.041 id: cord-013840-mi3uf4vk author: Zhang, Wei title: The metabolic regulator Lamtor5 suppresses inflammatory signaling via regulating mTOR-mediated TLR4 degradation date: 2019-08-29 words: 8495.0 sentences: 495.0 pages: flesch: 43.0 cache: ./cache/cord-013840-mi3uf4vk.txt txt: ./txt/cord-013840-mi3uf4vk.txt summary: Specifically, Lamtor5 associated with TLR4 via their LZ/TIR domains and facilitated their colocalization at autolysosomes, preventing lysosomal tethering and the activation of mTORC1 upon LPS stimulation and thereby derepressing TFEB to promote autophagic degradation of TLR4. 16, 17 Loss of the autophagic components autophagy-related 16 like 1, Beclin1, and microtubule-associated protein 1A/1B light chain 3 (LC3) enhanced the macrophage response to LPS, a prototypical agonist of TLR4, and caused sustained inflammatory signaling. [26] [27] [28] A recent study identified Lamtor5 as an indispensable component of the Ragulator complex that interacts with small GTPase Ras-related GTP binding protein (RAG), contributing to lysosomal recruitment and the activation of mechanistic target of rapamycin complex 1 (mTORC1) in response to amino acids. j Immunoblotting for TLR4 and total and phosphorylated p65 in control and Lamtor5-expressing RAW264.7 cells pretreated with DMSO or Baf1 and then stimulated with LPS for the indicated time periods. abstract: Comprehensive immune responses are essential for eliminating pathogens but must be tightly controlled to avoid sustained immune activation and potential tissue damage. The engagement of TLR4, a canonical pattern recognition receptor, has been proposed to trigger inflammatory responses with different magnitudes and durations depending on TLR4 cellular compartmentalization. In the present study, we identify an unexpected role of Lamtor5, a newly identified component of the amino acid-sensing machinery, in modulating TLR4 signaling and controlling inflammation. Specifically, Lamtor5 associated with TLR4 via their LZ/TIR domains and facilitated their colocalization at autolysosomes, preventing lysosomal tethering and the activation of mTORC1 upon LPS stimulation and thereby derepressing TFEB to promote autophagic degradation of TLR4. The loss of Lamtor5 was unable to trigger the TFEB-driven autolysosomal pathway and delay degradation of TLR4, leading to sustained inflammation and hence increased mortality among Lamtor5 haploinsufficient mice during endotoxic shock. Intriguingly, nutrient deprivation, particularly leucine deprivation, blunted inflammatory signaling and conferred protection to endotoxic mice. This effect, however, was largely abrogated upon Lamtor5 deletion. We thus propose a homeostatic function of Lamtor5 that couples pathogenic insults and nutrient availability to optimize the inflammatory response; this function may have implications for TLR4-associated inflammatory and metabolic disorders. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7608472/ doi: 10.1038/s41423-019-0281-6 id: cord-012791-dyk5mr1q author: Zheng, Yong title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway date: 2019-09-25 words: 4152.0 sentences: 217.0 pages: flesch: 48.0 cache: ./cache/cord-012791-dyk5mr1q.txt txt: ./txt/cord-012791-dyk5mr1q.txt summary: title: Icariside II inhibits lipopolysaccharide-induced inflammation and amyloid production in rat astrocytes by regulating IKK/IκB/NF-κB/BACE1 signaling pathway Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. The present study revealed that (1) ICS II protects against LPSinduced inflammation in primary-cultured astrocytes; (2) the inhibitory effect of ICS II is due to regulation of the IKK/IκB/NF-κB signaling pathway; and (3) ICS II decreases Aβ 1-40 and Aβ 1-42 levels by downregulating APP and BACE1 expression (Fig. 7) . In conclusion, the current study revealed that ICS II exerts inhibitory effects on LPS-induced inflammation in astrocytes through the IKK/IκB/NF-κB/BACE1 signaling pathway, and thus ICS II may be a promising therapeutic agent for neuroinflammatory diseases, including AD. abstract: β-amyloid (Aβ) is one of the inducing factors of astrocytes activation and neuroinflammation, and it is also a crucial factor for the development of Alzheimer’s disease (AD). Icariside II (ICS II) is an active component isolated from a traditional Chinese herb Epimedium, which has shown to attnuate lipopolysaccharide (LPS)-induced neuroinflammation through regulation of NF-κB signaling pathway. In this study we investigated the effects of ICS II on LPS-induced astrocytes activation and Aβ accumulation. Primary rat astrocytes were pretreated with ICS II (5, 10, and 20 μM) or dexamethasone (DXMS, 1 μM) for 1 h, thereafter, treated with LPS for another 24 h. We found that ICS II pretreatment dose dependently mitigated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) in the astrocytes. Moreover, ICS II not only exerted the inhibitory effect on LPS-induced IκB-α degradation and NF-κB activation, but also decreased the levels of Aβ(1–40), Aβ(1–42), amyloid precursor protein (APP) and beta secretase 1 (BACE1) in the astrocytes. Interestingly, molecular docking revealed that ICS II might directly bind to BACE1. It is concluded that ICS II has potential value as a new therapeutic agent to treat neuroinflammation-related diseases, such as AD. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470889/ doi: 10.1038/s41401-019-0300-2 id: cord-004067-psjyjvbu author: Zhou, Yile title: The regulatory effect of microRNA-21a-3p on the promotion of telocyte angiogenesis mediated by PI3K (p110α)/AKT/mTOR in LPS induced mice ARDS date: 2019-12-26 words: 5176.0 sentences: 333.0 pages: flesch: 48.0 cache: ./cache/cord-004067-psjyjvbu.txt txt: ./txt/cord-004067-psjyjvbu.txt summary: Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. In the current study, the p110α isoform in PI3K/AKT/mTOR signalling pathway was demonstrated to be involved in miR-21a-3p-mediated angiogenic factor induction in TCs. However, the alteration of other protein levels and HIF-1α in TCs treated with LPS and the miR-21a-3p inhibitor indicated that more complex signalling pathways were involved in regulating the angiogenic function of TCs. Culture medium from LPS-induced TCs promoted EOMA cells proliferation in vitro, accompanied by elevated levels of VEGF mRNA and secretion, which further demonstrated that the functional miR-21a-3p was generated by TCs. These data support the hypothesis that miR-21a-3p plays a role in angiogenesis and profoundly demonstrate the mechanisms mediated by PI3K p110α. abstract: BACKGROUND: Telocytes (TCs) are newly identified interstitial cells that participate in tissue protection and repair. The present study investigated the mechanisms underlying the protective effect of TCs in a mouse model of respiratory distress. METHODS: The mouse model of acute respiratory distress syndrome (ARDS) was established by intratracheal instillation of lipopolysaccharide (LPS). After instillation of TCs culture medium, lung injury was assessed, and angiogenesis markers, including CD31 and endothelial nitric oxide synthase (eNOS), were detected by immunofluorescence. Bioinformatics analysis was used to screen significantly differentially expressed microRNAs (miRNAs) in cultured TCs stimulated with LPS, and the regulation of downstream angiogenesis genes by these miRNAs was analysed and verified. PI3K subunits and pathways were evaluated by using a PI3K p110α inhibitor to study the involved mechanisms. RESULTS: In ARDS mice, instillation of TCs culture medium ameliorated LPS-induced inflammation and lung injury and increased the protein levels of CD31 and eNOS in the injured lungs. A total of 7 miRNAs and 1899 mRNAs were differentially regulated in TCs stimulated with LPS. Functional prediction analysis showed that the differentially expressed mRNAs were enriched in angiogenesis-related processes, which were highly correlated with miR-21a-3p. Culture medium from TCs with miR-21a-3p inhibition failed to promote angiogenesis in mouse models of LPS-induced ARDS. In cultured TCs, LPS stimulation upregulated the expression of miR-21a-3p, which further targeted the transcription factor E2F8 and decreased Notch2 protein expression. TCs culture medium enhanced hemangioendothelioma endothelial cells (EOMA cells) proliferation, which was blocked by the miR-21a-3p inhibitor. The PI3K p110α inhibitor decreased vascular endothelial growth factor levels in LPS-stimulated TCs and reversed the enhancing effect of TCs culture medium on EOMA cells proliferation. CONCLUSIONS: TCs exerted protective effects under inflammatory conditions by promoting angiogenesis via miR-21a-3p. The PI3K p110α subunit and transcriptional factor E2F8 could be involved in this process. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933909/ doi: 10.1186/s12967-019-02168-z id: cord-001569-jd028cyg author: dos Santos, Gimena title: Vimentin regulates activation of the NLRP3 inflammasome date: 2015-03-12 words: 8469.0 sentences: 459.0 pages: flesch: 48.0 cache: ./cache/cord-001569-jd028cyg.txt txt: ./txt/cord-001569-jd028cyg.txt summary: We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos. Exposure to bleomycin resulted in a large increase in immune cells in the airspace of both WT and Vim À / À mice as assessed by flow cytometric analysis of whole-lung lysates ( Supplementary Fig. 3a ). All together, these results suggest that vimentin-expressing bone marrow-derived cells are important for bleomycin-induced activation of the NLRP3 inflammasome and pulmonary fibrosis. Studies with IL-1R1 À / À , MyD88 À / À , ASC À / À , Caspase-1 À / À and NLRP3 À / À mice have suggested that uric acid (induced by bleomycin), asbestos and silica are detected by the NLRP3 inflammasome in macrophages, likely leading to IL-1R1/MyD88 signalling in pulmonary epithelial cells, then to inflammation, neutrophil and lymphocyte recruitment and fibroblast activation 35 . abstract: Activation of the NLRP3 inflammasome and subsequent maturation of IL-1β have been implicated in acute lung injury (ALI), resulting in inflammation and fibrosis. We investigated the role of vimentin, a type III intermediate filament, in this process using three well-characterized murine models of ALI known to require NLRP3 inflammasome activation. We demonstrate that central pathophysiologic events in ALI (inflammation, IL-1β levels, endothelial and alveolar epithelial barrier permeability, remodelling and fibrosis) are attenuated in the lungs of Vim(−/−) mice challenged with LPS, bleomycin and asbestos. Bone marrow chimeric mice lacking vimentin have reduced IL-1β levels and attenuated lung injury and fibrosis following bleomycin exposure. Furthermore, decreased active caspase-1 and IL-1β levels are observed in vitro in Vim(−/−) and vimentin-knockdown macrophages. Importantly, we show direct protein–protein interaction between NLRP3 and vimentin. This study provides insights into lung inflammation and fibrosis and suggests that vimentin may be a key regulator of the NLRP3 inflammasome. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/ncomms7574) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4358756/ doi: 10.1038/ncomms7574 id: cord-331887-kagggou1 author: liu, Chang title: An integrated network pharmacology and RNA-Seq approach for exploring the preventive effect of Lonicerae japonicae flos on LPS-induced acute lung injury date: 2020-09-09 words: 3197.0 sentences: 184.0 pages: flesch: 57.0 cache: ./cache/cord-331887-kagggou1.txt txt: ./txt/cord-331887-kagggou1.txt summary: Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses. CONCLUSIONS: In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF. LJF significantly inhibited CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, 290 IL17F, IL17C, MMP9, and TNFAIP3 mRNA expression in lung tissue homogenates according to 291 RNA-Seq, which indicates that the IL-17 signalling pathway is critical for treatment of 292 LPS-induced ALI with LJF (Fig.S4) . Consistent with the RNA-Seq data, the expression of CXCL2, CXCL1, CXCL6, 295 NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3 in lung tissue was 296 significantly decreased compared with that in the ALI and LJF groups according to the qRT-PCR 297 analyses (P<0.05) (Fig.8) . abstract: ETHNOPHARMACOLOGICAL RELEVANCE: Lonicerae japonicae flos (LJF, the dried flower bud or newly bloomed flower of Lonicera japonica Thunb.), a typical herbal medicine, targets the lung, heart and stomach meridian with the function of clearing heat and detoxication. It ameliorated inflammatory responses and protected against acute lung inflammation in animal models. Acute lung injury (ALI) is a kind of inflammatory disease in which alveolar cells are damaged. However, a network pharmacology study to thoroughly investigate the mechanisms preventing ALI has not been performed. AIM OF THE STUDY: In this study, we examined the main active ingredients in LJF and the protective effects of LJF on LPS-induced ALI in rats. MATERIALS AND METHODS: First, the main active ingredients of LJF were screened in the TCMSP database, and the ALI-associated targets were collected from the GeneCards database. Then, we used compound-target and target-pathway networks to uncover the preventive mechanisms of LJF. Furthermore, we assessed the preventive effects of LJF in an LPS-induced rat model with the RNA-Seq technique to validate the possible molecular mechanisms of the effects of LJF in the treatment of ALI. RESULTS: The network pharmacology results identified 28 main active compounds in LJF, and eight chemical components highly related to the potential targets, which were potential active compounds in LJF. In all, 94 potential targets were recognized, including IL6, TNF, PTGS2, APP, F2, and GRM5. The pathways revealed that the possible targets of LJF involved in the regulation of the IL-17 signalling pathway. Then, in vivo experiments indicated that LJF decreased the levels of proinflammatory cytokines (TNF-, IL-1, and IL-6) in serum and bronchoalveolar lavage fluid, decreased the levels of oxidative stress factors (MDA and MPO) and increased the activities of SOD and GSH-Px in lung tissue. The RNA-Seq results revealed that 7811, 775 and 3654 differentially expressed genes (DEGs) in Ctrl (control group), ALI-LJF (Lonicerae japonicae flos group) and ALI-DXSM (dexamethasone group), respectively. KEGG pathway analysis showed that the DEGs associated with immune response and inflammation signalling pathways and the IL-17 signalling pathway were significantly enriched in LJF. Compared with those in ALI, the expression of CXCL2, CXCL1, CXCL6, NFKBIA, IFNG, IL6, IL17A, IL17F, IL17C, MMP9 and TNFAIP3, which are involved in the IL-17 signalling pathway, were significantly decreased in the LJF group according to the qRT-PCR analyses. CONCLUSIONS: In view of the network pharmacology and RNA-Seq results, the study identified the main active ingredient and potential targets of LJF involved in protecting against ALI, which suggests directions for further research on LJF. url: https://api.elsevier.com/content/article/pii/S0378874120332499 doi: 10.1016/j.jep.2020.113364 id: cord-005497-w81ysjf9 author: nan title: 40th International Symposium on Intensive Care & Emergency Medicine: Brussels, Belgium. 24-27 March 2020 date: 2020-03-24 words: 103623.0 sentences: 6176.0 pages: flesch: 53.0 cache: ./cache/cord-005497-w81ysjf9.txt txt: ./txt/cord-005497-w81ysjf9.txt summary: The positive NC group had more plasma transfusion (p-value 0.03) and a lower median hematocrit at 24 hrs (p-value 0.013), but similar hospital length of stay (p=0.17) and mortality rate (p=0.80) Conclusions: NC at ICU admission identifies subclinical AKI in TBI patients and it maight be used to predictclinical AKI. In patients with pneumonia requiring intensive care (ICU) admission, we hypothesise that abnormal right ventricular (RV) function is associated with an increased 90-day mortality. The objective of this study was to describe the incidence of each AKI stages as defined by KDIGO definition (with evaluation of urine output, serum creatinine and initiation of renal replacement therapy (RRT)), in a mixed medical and surgical population of patients hospitalized in ICU and PCU over a 10-year period (2008-2018). This study aimed at investigating the relationship of goal-directed energy and protein adequacy on clinical outcomes which includes mortality, intensive care unit(ICU) and hospital length of stay (LOS), and length of mechanical ventilation (LOMV). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092506/ doi: 10.1186/s13054-020-2772-3 id: cord-005727-li8pwigg author: nan title: ESICM 2010 MONDAY SESSIONS 11 October 2010 date: 2010-08-31 words: 102770.0 sentences: 6408.0 pages: flesch: 53.0 cache: ./cache/cord-005727-li8pwigg.txt txt: ./txt/cord-005727-li8pwigg.txt summary: Since, continuous epidural analgesia provides the required level of analgesia to support early mobilization and significant reduction in pulmonary and cardiovascular morbidity in the early postoperative period, we postulated that the use of low dose of continuous epidural morphine might improve postoperative analgesia and reduce undesirable side effects in elderly patientsTherefore, the present study was designed to evaluate the effects of morphine administered via epidural patients controlled analgesia and intravenous tramadol + metamizol on postoperative pain control and side effects in elderly patients after major abdominal surgery. For each ventilated patient the following data was registered:Age, APACHE II, the reason of admission, risk factors, use NIV, MV duration, timing of tracheostomy, time of diagnosis of VAP, microbiological data, length of stay and mortality in ICU. 23rd ESICM ANNUAL CONGRESS -BARCELONA, SPAIN -9-13 OCTOBER 2010 S131 Evaluated factors: patient characteristics, signs, symptoms, abscess location, time between symptoms and hospital admission and surgery, lab results, microbiology, antibiotic therapy, APACHE2, SAPS2, SOFA, length of ICU stay, surgical re-intervention, duration of mechanical ventilation, infectious complications, critical illness myopathy (CIM), renal replacement therapy (RRT), re-intubation, tracheotomy, mortality. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095301/ doi: 10.1007/s00134-010-1999-x id: cord-005814-ak5pq312 author: nan title: 8th European Congress of Intensive Care Medicine Athens - Greece, October 18–22, 1995 Abstracts date: 1995 words: 179164.0 sentences: 12028.0 pages: flesch: 56.0 cache: ./cache/cord-005814-ak5pq312.txt txt: ./txt/cord-005814-ak5pq312.txt summary: Results: In 5 patients with treated SS, 16 tests were performed (VL n=8; Dobu n=4; NA n=4 Method: Septic shock was defined as severe sepsis with either persistent hypotension (mean arterial pressure; MAP<70 mmHg) or the requirement for a noradrenaline (NA) infusion ~> 0.1 ~g/kg/min with a MAP _< 90mmHg. Cardiovascular support was limited to NA + dobutamine (DB), 546C88 was administered for up to 8 h at a fixed dose-rate of either i, 2.5, 5, 10 or 20 mg/kg/h iv. Methods: Fourteen cases were s~udied,their gestational age ranged from(27-32)ws.Continnous positive air way pressure was applied to six cases at Peep level from (3-6)cm H2o through nasal pronge,(group I),the other 8 cases were managed as routine,(group II).Blood gases, TcPO2,TcCo2,resp.rate,depth and pattern were monitored for assessment of tissue Oxygenation and ventilation, Results: Our rasults showed that early application of CPAP improve ventilation among (83.3%)of cases,while (16.7%)of cases need IMV.The cases of group II need IMV among (75%)of the studied cases during the second or the third day of life. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095534/ doi: 10.1007/bf02426401 id: cord-006229-7yoilsho author: nan title: Abstracts of the 82(nd) Annual Meeting of the German Society for Experimental and Clinical Pharmacology and Toxicology (DGPT) and the 18(th) Annual Meeting of the Network Clinical Pharmacology Germany (VKliPha) in cooperation with the Arbeitsgemeinschaft für Angewandte Humanpharmakologie e.V. (AGAH) date: 2016-02-06 words: 133493.0 sentences: 6804.0 pages: flesch: 42.0 cache: ./cache/cord-006229-7yoilsho.txt txt: ./txt/cord-006229-7yoilsho.txt summary: It directly activates Protein Kinase A (PKA) or the Exchange protein directly activated by cAMP (Epac) which is a guanine exchange factor (GEF) for the small monomeric GTPase Rap. As Human umbilical vein endothelial cells (HUVEC) express both cAMP effectors (Epac1 and PKA), we investigated the role of cAMP-signaling using a spheroid based sprouting assay as an in vitro model for angiogenesis. After activation, S1P receptors regulate important processes in the progression of renal diseases, such as mesangial cell migration Methods and Results: Here we demonstrate that dexamethasone treatment lowered S1P 1 mRNA and protein expression levels in rat mesangial cells measured by TaqMan® and Western blot analyses. The aim of this study was to investigate the relevance of IGFBP5 in cardiogenesis and cardiac remodeling and its role as a potential target for ameliorating stress-induced cardiac remodeling Methods and Results: We investigated the expression of Igfbp5 in murine cardiac tissue at different developmental stages by qPCR normalized to Tpt1 (Tumor Protein, Translationally-Controlled 1). abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100641/ doi: 10.1007/s00210-016-1213-y id: cord-006230-xta38e7j author: nan title: Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.V. date: 2012-02-22 words: 135419.0 sentences: 7042.0 pages: flesch: 43.0 cache: ./cache/cord-006230-xta38e7j.txt txt: ./txt/cord-006230-xta38e7j.txt summary: Here, we will present our analysis of Ca 2+ signaling following stimulation of the FcεRI receptor and application of secretagogues that are supposed to affect Ca 2+ -dependent mast cell activation such as adenosine, endothelin-1, substance P and compound 48/80 in BMMCs and PMCs derived from mouse lines with inactivation of TRPC1, TRPC3, TRPC4, TRPC5 or TRPC6 since specific antagonists are still lacking for these TRP channels. These data indicate that increased PP2A activity is associated with modified gene expression in TG hearts possibly affecting stress response and regulation of cell signalling. As demonstrated by qPCR and Western blot experiments, mesangial cells showed a marked time-and dose-dependent upregulation of CSE mRNA and protein levels after treatment with platelet-derived growth factor (PDGF-BB). The transcription factor cAMP response element (CRE)-binding protein (CREB) plays a critical role in regulating gene expression in response to activation of the cAMPdependent signaling pathway, which is implicated in the pathophysiology of heart failure. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7100643/ doi: 10.1007/s00210-012-0736-0 id: cord-006888-qfnukav4 author: nan title: Irish Thoracic Society Annual Scientific Meeting, Ramada Hotel, Belfast: 7th–8th November 2008 date: 2008-10-21 words: nan sentences: nan pages: flesch: nan cache: txt: summary: abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7103299/ doi: 10.1007/s11845-008-0235-y id: cord-014996-p6q0f37c author: nan title: Posters_Monday_12 October 2009 date: 2009-08-06 words: 85190.0 sentences: 5288.0 pages: flesch: 54.0 cache: ./cache/cord-014996-p6q0f37c.txt txt: ./txt/cord-014996-p6q0f37c.txt summary: Data recorded on admission were the patient demographics with, acute physiology and chronic health evaluation II score (APACHE II), and type of admission; during intensive care stay, sepsis-related organ failure assessment score (SOFA) and clinical concomitant factors and conditions. For each severe septic patient the following data was registered: time delay, APACHE II and SOFA scores at ICU admission, diagnosis, the rate of compliance with the resucitation and management bundles, microbiological data, evolution of levels of serum lactate, empiric antibiotic therapy, length of stay and mortality in ICU. Sepsis and septic shock remain the most important causes of acute kidney injury (AKI) in critically ill patients and account for more than 50% of cases of acute renal failure (ARF) in intensive care units (ICU). There were no significant differences between the demographic data (sex, age) or the data on admission to intensive care (APACHE II score, ratio of medical to surgical patients) and duration of mechanical ventilation between the two groups. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7094934/ doi: 10.1007/s00134-009-1593-2 id: cord-015021-pol2qm74 author: nan title: Third International Congress on the Immune Consequences of Trauma, Shock and Sepsis —Mechanisms and Therapeutic Approaches date: 1994 words: 162327.0 sentences: 9379.0 pages: flesch: 50.0 cache: ./cache/cord-015021-pol2qm74.txt txt: ./txt/cord-015021-pol2qm74.txt summary: It is our current understanding that LPS is responsible for many of the pathophysiological events observed during gramnegative infections and that one of the major mechanisms leading to shock and death is the LPS-induced activation of macrophages resulting in the production and release of lipid and peptide mediators, among which tumor necrosis factor seems to be the most important. However plasma IL-6 estimation revealed a statistically significant reduction at 6 hours in tanrine-treated animals compared to glycino and TW controls ( Objective: To evaluate the effects of allogeneic blood transfusion, thermal injury and bacterial garage on interteukin 4 (IL-4), tumor necrosis factor alpha (TNF) production and host mortality and to study if the administration of thymopentth (THY) could affect these events. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095072/ doi: 10.1007/bf02258437 id: cord-015082-l629n8is author: nan title: Poster Sessions 323-461 date: 2002-08-29 words: 26569.0 sentences: 1648.0 pages: flesch: 52.0 cache: ./cache/cord-015082-l629n8is.txt txt: ./txt/cord-015082-l629n8is.txt summary: 14 patients awaiting urgent cardiac surgical re-vascularisation were studied with measurement of: spirometry; percentage increase in transfer factor from sitting to lying position (TF) as an indicator of micro-vascular lung disease; overnight oximetry on air; and 24hour holter monitoring Patients, who were reintubated on decreased indices of arterial oxygenation under MOSF progressing died in 100% cases ( NIMV is effective method in complex therapy of ARF, developing in postoperative period after cardiac surgery, that leads to significant improvement of lungs biomechanics and gases change function. In a prospective observational study we performed bedside ptO2 measurements in 8 patients with sepsis/septic shock to gain insight in ptO2 values and their dynamic changes related to the course of the illness, as well as investigating the practical applicability of tissue oxygen measurement in the ICU setting. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095316/ doi: 10.1007/s00134-002-1455-7 id: cord-015147-h0o0yqv8 author: nan title: Oral Communications and Posters date: 2014-09-12 words: 73711.0 sentences: 3862.0 pages: flesch: 43.0 cache: ./cache/cord-015147-h0o0yqv8.txt txt: ./txt/cord-015147-h0o0yqv8.txt summary: Cyclooxygenases (COX) catalyze the first step in the synthesis of prostaglandins (PG) from arachidonic acid.COX-1 is constitutively expressed.The COX-2 gene is an immediate early-response gene that is induced by variety of mitogenic and inflammatory stimuli.Levels of COX-2 are increased in both inflamed and malignant tissues.In inflamed tissues, there is both pharmacological and genetic evidence that targeting COX-2 can either improve (e.g., osteoarthritis) or exacerbate symptoms (e.g., inflammatory bowel disease).Multiple lines of evidence suggest that COX-2 plays a significant role in carcinogenesis.The most specific data that support a cause-and effect relationship between COX-2 and tumorigenesis come from genetic studies.Overexpression of COX-2 has been observed to drive tumor formation whereas COX-2 deficiency protects against several tumor types.Selective COX-2 inhibitors protect against the formation and growth of experimental tumors.Moreover, selective COX-2 inhibitors are active in preventing colorectal adenomas in humans.Increased amounts of COX-2-derived PGE2 are found in both inflamed and neoplastic tissues.The fact that PGE2 can stimulate cell proliferation, inhibit apoptosis and induce angiogenesis fits with evidence that induction of COX-2 contributes to both wound healing and tumor growth.Taken together, it seems likely that COX-2 induction contributes to wound healing in response to injury but reduces the threshold for carcinogenesis. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095932/ doi: 10.1007/bf03353884 id: cord-015394-uj7fe5y6 author: nan title: Scientific Abstracts date: 2008-12-23 words: 242330.0 sentences: 15267.0 pages: flesch: 52.0 cache: ./cache/cord-015394-uj7fe5y6.txt txt: ./txt/cord-015394-uj7fe5y6.txt summary: Studies involving immunohistochemical analysis of normal ovaries have shown that granulosa cells express significantly higher levels of the activator protein-1 (AP-1) transcription factor, cFos compared to theca cells, where cFos expression is virtually absent. Following acute hypoxia (0.5% O2) for one to six hours, RhoA mRNA, total protein and activation (RhoA-GTP) levels were analysed, using semi-quantitative PCRs and western blot, and compared to normoxic non-pregnant human uterine smooth muscle control cells. Since there is an urgent need for non-invasive methods for determination of fetal (F) and placental (P) function, this study was designed to evaluate the genes differently and commonly expressed in P tissue and leukocytes in maternal (M) and F circulation.Material and Methods. The current study: 1) localized IL-6 mRNA levels in preeclamptic versus normal decidual sections; 2) evaluated mechanisms regulating IL-6 synthesis by targeting intracellular signaling pathways with specific inhibitors; 3) identified potential IL-6 targets by immunolocalizing the IL-6 receptor (IL-6R) to specific cell types in placental bed biopsies. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104449/ doi: 10.1177/19337191080150020102 id: cord-022888-dnsdg04n author: nan title: Poster Sessions date: 2009-08-19 words: 188640.0 sentences: 9313.0 pages: flesch: 45.0 cache: ./cache/cord-022888-dnsdg04n.txt txt: ./txt/cord-022888-dnsdg04n.txt summary: Methods: Phospho-specific Western blot analyses were performed to verify the functionality of the different IFN-g pathway components, intra-and extracellular flow cytometry experiments were employed to determine the expression of antigen processing components and HLA class I cell surface antigens, quantitative real time-PCR experiments to confirm the absence of JAK2 and presence of pathway relevant molecules as well as, genomic PCR and chromosome typing technique to prove the deletion of JAK2. In order to accomplish these objectives we induced priming or tolerance of ovalbumin (OVA 323-339 peptide)-specific T cells from DO11.10 TCR transgenic mice in vitro or, following adoptive transfer of near physiologically relevant numbers of such cells into recipients, in vivo and correlated functional outcome (via proliferation and cytokine readout assays or antibody production) with E3 ubiquitin-protein ligases expression and the ubiquitination status of the TCR signalling machinery. abstract: No Abtract url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7163517/ doi: 10.1002/eji.200990224 id: cord-023026-2r84ndzv author: nan title: Posters date: 2013-06-14 words: 138458.0 sentences: 6513.0 pages: flesch: 40.0 cache: ./cache/cord-023026-2r84ndzv.txt txt: ./txt/cord-023026-2r84ndzv.txt summary: Thus, this work provides the basis to identify molecular pathways regulated by distinct niche/environmental signals and involved in the heterogeneity of adult OPCs. Multiple sclerosis (MS) is a chronic inflammatory and neurodegenerative demyelinating disease of the central nervous system (CNS) characterized by inflammation, which leads to formation of demyelinating areas due to loss of oligodendrocytes, astrogliosis and, finally, axonal degeneration. Taken together, these results demonstrate the important role of miR-200b in modulating the MAPK pathway via c-Jun which in turn affects different aspects of the inflammatory process accompanying microglia activation including cytokine response, NO production, phagocytosis and neuronal cell death. For this purpose, coronal cryostat free-floating sections from the brain of both adult transgenic mice and their corresponding wild-type (Wt) littermates, were processed for the study of astrocytes using GFAP immunohistochemistry and microglia using antibodies against Iba1 and several markers commonly related to the activated phenotype of these microglial cells, such as CD16/32 (Fc receptor), F4/80, CD11b, CD206, CD150 and MHC-II. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165910/ doi: 10.1002/glia.22530 id: cord-298646-wurzy88k author: van der Merwe, René title: Challenge models to assess new therapies in chronic obstructive pulmonary disease date: 2012-09-13 words: 4775.0 sentences: 240.0 pages: flesch: 40.0 cache: ./cache/cord-298646-wurzy88k.txt txt: ./txt/cord-298646-wurzy88k.txt summary: This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD. One of the main challenges in developing new therapeutic agents for the treatment or prevention of acute exacerbations of COPD is that their potential success cannot be entirely known until the investigational therapies enter relatively large Phase II studies, assessing clinical outcome over a 3-to 6-month period or longer. 20 In the first reported study of the inflammatory effects of low-level O 3 exposure (80 ppb O 3 for 6.6 hours) in healthy volunteers, 21 there were statistically significant increases in polymorphononuclear neutrophils, prostaglandin E 2 , lactate dehydrogenase, IL-6, α1-antitrypsin, and decreased phagocytosis via the complement receptor. The O 3 -challenge model potentially provides critical decision-making data in understanding whether new compounds have the desired biological effect in healthy volunteers and patients with COPD; hence it can de-risk decisions to move forwards into large Phase II safety and efficacy trials. abstract: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. Current therapies confer partial benefits either by incompletely improving airflow limitation or by reducing acute exacerbations, hence new therapies are desirable. In the absence of robust early predictors of clinical efficacy, the potential success of novel therapeutic agents in COPD will not entirely be known until the drugs enter relatively large and costly clinical trials. New predictive models in humans, and new study designs are being sought to allow for confirmation of pharmacodynamic and potentially clinically meaningful effects in early development. This review focuses on human challenge models with lipopolysaccharide endotoxin, ozone, and rhinovirus, in the early clinical development phases of novel therapeutic agents for the treatment and reduction of exacerbations in COPD. url: https://doi.org/10.2147/copd.s30664 doi: 10.2147/copd.s30664 ==== make-pages.sh questions [ERIC WAS HERE] ==== make-pages.sh search /data-disk/reader-compute/reader-cord/bin/make-pages.sh: line 77: /data-disk/reader-compute/reader-cord/tmp/search.htm: No such file or directory Traceback (most recent call last): File "/data-disk/reader-compute/reader-cord/bin/tsv2htm-search.py", line 51, in with open( TEMPLATE, 'r' ) as handle : htm = handle.read() FileNotFoundError: [Errno 2] No such file or directory: '/data-disk/reader-compute/reader-cord/tmp/search.htm' ==== make-pages.sh topic modeling corpus Zipping study carrel