Summary of your 'study carrel' ============================== This is a summary of your Distant Reader 'study carrel'. The Distant Reader harvested & cached your content into a collection/corpus. It then applied sets of natural language processing and text mining against the collection. The results of this process was reduced to a database file -- a 'study carrel'. The study carrel can then be queried, thus bringing light specific characteristics for your collection. These characteristics can help you summarize the collection as well as enumerate things you might want to investigate more closely. This report is a terse narrative report, and when processing is complete you will be linked to a more complete narrative report. Eric Lease Morgan Number of items in the collection; 'How big is my corpus?' ---------------------------------------------------------- 48 Average length of all items measured in words; "More or less, how big is each item?" ------------------------------------------------------------------------------------ 8012 Average readability score of all items (0 = difficult; 100 = easy) ------------------------------------------------------------------ 45 Top 50 statistically significant keywords; "What is my collection about?" ------------------------------------------------------------------------- 47 ALI 13 ARDS 12 LPS 8 lung 7 SARS 5 cell 5 acute 4 gene 4 TLR4 4 Fig 3 study 3 patient 3 COVID-19 2 respiratory 2 mortality 2 model 2 covid-19 2 TNF 2 PBEF 2 ICU 1 vascular 1 tumor 1 stem 1 sofa 1 sepsis 1 s1p 1 result 1 regulate 1 pulmonary 1 progenitor 1 organoid 1 objectives 1 net 1 method 1 melatonin 1 introduction 1 human 1 hepcidin 1 group 1 genetic 1 figure 1 examination 1 drug 1 dna 1 curcumin 1 conclusion 1 barrier 1 at2 1 ZT5 1 ZT13 Top 50 lemmatized nouns; "What is discussed?" --------------------------------------------- 2949 lung 2699 cell 2612 patient 1645 % 1493 injury 1370 study 1079 mouse 1032 group 919 protein 916 gene 846 level 777 expression 742 model 689 mortality 676 factor 671 effect 671 disease 663 response 631 p 608 infection 593 sepsis 593 day 580 tissue 577 neutrophil 545 role 545 inflammation 535 receptor 519 analysis 508 treatment 500 result 498 syndrome 482 h 462 cytokine 453 rat 450 datum 448 time 429 blood 424 pathway 412 activation 411 therapy 382 ventilation 380 control 371 virus 360 type 352 distress 351 function 346 outcome 339 failure 332 barrier 327 stem Top 50 proper nouns; "What are the names of persons or places?" -------------------------------------------------------------- 1752 ALI 905 ARDS 842 LPS 636 al 598 ICU 472 et 433 . 424 Fig 279 SARS 244 TNF 232 TTP 225 TLR4 220 ± 203 II 165 C 164 IL-6 161 organoids 159 COVID-19 158 mg 151 T 150 RNA 143 CoV-2 128 VEGF 127 USA 111 κB 109 Rac1 107 EC 102 BALF 98 α 98 I 98 APACHE 97 CLP 96 METHODS 95 NF 95 AFC 93 PCT 91 kg 88 China 84 inflammasome 84 PBS 82 Lung 81 IFN 80 PBEF 79 INTRODUCTION 78 Table 77 Care 76 IL-10 74 HMGB1 73 WT 72 VAP Top 50 personal pronouns nouns; "To whom are things referred?" ------------------------------------------------------------- 908 we 501 it 199 they 164 i 77 she 63 them 45 he 37 you 24 us 15 itself 8 themselves 5 one 5 her 3 imagej 3 him 2 pi-3-kinase 2 mrnas 1 p-450 1 otud1 1 mir-30b-3p 1 interleukin-10 1 induceotud1 1 il-8 1 aptt Top 50 lemmatized verbs; "What do things do?" --------------------------------------------- 11823 be 1937 have 1237 induce 1207 use 661 show 651 increase 637 associate 569 include 479 compare 408 derive 407 reduce 351 follow 351 find 336 mediate 311 suggest 305 activate 302 signal 290 perform 288 demonstrate 287 treat 286 involve 282 do 275 base 264 identify 262 cause 250 regulate 239 inhibit 237 indicate 236 require 236 report 232 observe 231 decrease 230 lead 225 result 210 develop 209 determine 204 provide 202 assess 195 relate 194 express 188 improve 184 describe 181 evaluate 178 enhance 176 measure 175 contain 169 analyze 167 consider 165 study 161 attenuate Top 50 lemmatized adjectives and adverbs; "How are things described?" --------------------------------------------------------------------- 1373 acute 994 - 835 inflammatory 833 not 828 respiratory 773 high 721 pulmonary 686 also 645 human 572 clinical 477 severe 418 epithelial 416 endothelial 413 significantly 400 more 388 other 384 low 377 alveolar 370 such 370 significant 351 however 344 vascular 338 anti 327 well 286 mechanical 276 most 274 septic 269 specific 266 only 254 first 252 early 249 immune 248 genetic 247 therapeutic 246 further 241 important 239 different 228 then 223 normal 213 non 212 as 201 thus 194 like 194 critical 184 several 183 negative 181 potential 180 cardiac 177 viral 172 multiple Top 50 lemmatized superlative adjectives; "How are things described to the extreme?" ------------------------------------------------------------------------- 55 most 41 least 30 high 26 good 21 Most 10 large 8 strong 8 low 7 great 4 common 3 early 3 bad 1 wide 1 simple 1 severe 1 rich 1 long 1 late 1 intensive 1 close 1 S1P 1 LPS)-tracheal 1 1:400 1 -173C Top 50 lemmatized superlative adverbs; "How do things do to the extreme?" ------------------------------------------------------------------------ 221 most 27 least 8 well Top 50 Internet domains; "What Webbed places are alluded to in this corpus?" ---------------------------------------------------------------------------- 7 doi.org 3 www.networkanalyst.ca 3 www.jgc301.com 2 www 2 orcid.org 2 github.com 2 dx.doi.org 2 cibersortx.stanford.edu 1 www.ncbi.nlm.nih.gov 1 www.ihi.org 1 www.genome.gov 1 www.geneontology.org 1 www.frontiersin.org 1 frodo.wi.mit.edu 1 doi 1 coronavirus.jhu.edu Top 50 URLs; "What is hyperlinked from this corpus?" ---------------------------------------------------- 3 http://www.networkanalyst.ca 3 http://www.jgc301.com 2 http://www 2 http://dx.doi.org/10.1007/s00134-007-0661-8 2 http://doi.org/10.1101/2020.04.02.20050997 2 http://cibersortx.stanford.edu/runcibersortx.php 1 http://www.ncbi.nlm.nih.gov/geo 1 http://www.ihi.org 1 http://www.genome.gov/ 1 http://www.geneontology.org/ 1 http://www.frontiersin.org/articles/10.3389/fimmu 1 http://orcid.org/0000-0003-3701-0758 1 http://orcid.org/0000-0002-3483-851X 1 http://github.com/najoshi/sickle 1 http://github.com/jstjohn/SeqPrep 1 http://frodo.wi.mit.edu/primer3/ 1 http://doi.org/10.6084/ 1 http://doi.org/10.1093/nar/gks1004. 1 http://doi.org/10.1038/s41590-019-0571-2.Supplementary 1 http://doi.org/10.1038/s41590-019-0571-2 1 http://doi.org/10.1038/ 1 http://doi 1 http://coronavirus.jhu.edu/map Top 50 email addresses; "Who are you gonna call?" ------------------------------------------------- 3 jgc@mail.sciencep.com Top 50 positive assertions; "What sentences are in the shape of noun-verb-noun?" ------------------------------------------------------------------------------- 9 group were significantly 9 levels were significantly 7 ali has not 7 mice were randomly 5 cells were then 5 group was significantly 5 patients did not 4 ards is still 4 expression was significantly 4 groups increased significantly 4 mortality is still 4 mortality was significantly 4 studies have also 3 ali is complex 3 cells are not 3 cells were also 3 disease is often 3 group were more 3 groups was higher 3 infections were more 3 levels were not 3 levels were similar 3 mice were significantly 3 mice were then 3 patient has classic 3 sepsis induced aki 3 studies are necessary 3 study does not 2 % had acute 2 % had septic 2 % were female 2 % were male 2 % were positive 2 ali are not 2 ali is feasible 2 ali is still 2 ali is urgently 2 ali was more 2 ards are inflammatory 2 ards are only 2 ards include head 2 ards is also 2 ards is likely 2 ards is often 2 ards was present 2 cells are able 2 cells are important 2 cells are largely 2 cells did not 2 cells following total Top 50 negative assertions; "What sentences are in the shape of noun-verb-no|not-noun?" --------------------------------------------------------------------------------------- 2 cells are not permissive 2 mice was not significantly 1 ali are not alike 1 ali are not clear 1 ali is not fully 1 ards are not fully 1 ards do not fully 1 ards was not different 1 cells was not detectable 1 cells was not specific 1 gene have not yet 1 gene is not only 1 group had no comorbid 1 groups showed no significant 1 groups was not clinical 1 groups were not significant 1 groups were not uniform 1 icu showed no statistically 1 infection was not fully 1 injury are not fully 1 injury are not well 1 level is not necessary 1 levels were not significantly 1 lps is not sufficient 1 lungs is not surprising 1 model does not completely 1 patient does not necessarily 1 patients had no sedation 1 sepsis has no impact 1 sepsis was not independently 1 studies were not consistently 1 study showed no difference 1 study showed no significant 1 study was not sufficiently A rudimentary bibliography -------------------------- id = cord-010983-2bzllo0n author = Adrover, Jose M. title = Programmed ‘disarming’ of the neutrophil proteome reduces the magnitude of inflammation date = 2020-01-13 keywords = ALI; Data; Extended; Fig; ZT13; ZT5; net summary = MRP8 CRE Arntl fl/fl mice, which have a neutrophil-specific deletion of Arntl (which encodes Bmal1, referred hereafter as Bmal1 ΔN ) showed no circadian differences in MPO + granule content between ZT5 and ZT13 (Extended Data Fig. 4a ) and NET formation (Extended Data Fig. 4b ) in blood Ly6G + neutrophils compared to neutrophils from wild-type controls, suggesting that Bmal1 controlled the changes in the neutrophil proteome. Proteome analysis in Ly6G + neutrophils purified at ZT5 (day) or ZT13 (night) from the blood of Bmal1 ΔN mice (Extended Data Fig. 4c and Supplementary Table 5) indicated that Bmal1 ΔN neutrophils did not show circadian changes in granule proteins or in NET-associated proteins (Extended Data Fig. 4d,e) . We measured neutrophil counts in blood and performed proteomic analysis, granule content and NET-formation assays in neutrophils isolated at 8:00, 14:00 and 17:00 (Extended Data Fig. 9a ), when diurnal patterns in neutrophil number and phenotype are prominent in humans 12 , from ten healthy volunteers. doi = 10.1038/s41590-019-0571-2 id = cord-017217-zjab7o2o author = Ali, Yousaf title = Self Assessment Questions date = 2008-01-08 keywords = Ali; Assessment; DOI; Questions; Rheumatology; Self; examination; patient summary = A 47-year-old patient with Crohn''s disease presents for evaluation of new onset arthritis. Although the patient has not had prior thromboses she is at high risk for developing antiphospholipid antibody syndrome in view of these blood tests. A 19-year-old previously healthy student is evaluated for new onset fever, joint pain, and rash. Her lab work reveals leukocytosis with lymphocytic predominance, normal renal function, mild transaminitis, and low serum albumin. Yousaf Ali, Self Assessment Questions in Rheumatology, DOI: 10.1007/ 978-1-59745-497-1, Humana Press, a part of Springer Science + Business Media, LLC 2009 A 55-year-old female with chronic renal failure is seen for evaluation of lower extremity edema and ankle pain. This 41-year-old patient presents with a 4-year history of recurrent sinusitis in the setting of a positive P-ANCA, destructive nasopharyngeal mass, and ophthalmoplegia.The differential diagnosis includes infection with a refractory organism, such as mucormycosis or tuberculosis, malignancy, midline granuloma, or vasculitis. doi = 10.1007/978-1-59745-497-1_1 id = cord-306835-juitltpi author = Babaei, Fatemeh title = Curcumin (a constituent of turmeric): New treatment option against COVID‐19 date = 2020-09-06 keywords = ACE2; ALI; COVID-19; SARS; curcumin summary = The keywords used for the search were as follows: coronavirus-19, COVID-19, SARS-CoV-2, curcumin, Curcuma longa, turmeric, curcumin and antiviral, curcumin and anti-inflammatory, curcumin and antipyretic, curcumin and lung, curcumin and acute lung injury, curcumin and fatigue, curcumin and antioxidant, curcumin and ARDS, curcumin and bradykinin, curcumin and fibrosis, curcumin and Interleukin-6 (IL-6), curcumin and tumor necrosis factor-alpha (TNF-α), curcumin and NF-κB, curcumin and Toll-like receptors (TLRs), curcumin and antiapoptotic. AA: arachidonic acid, ALI: acute lung injury, AP-1: activator protein 1, BK: bradykinin, ACE2: angiotensin-converting enzyme 2, Ang II: angiotensin II, ARDS: acute respiratory distress syndrome, Cas-3: caspase 3, COX: cyclooxygenase, CXCL: chemokine (C-X-C motif) ligand, 12-HPETE: 12-hydroperoxyeicosatetraenoic acid, JNK: c-Jun N-terminal kinase, 12 LOX: 12-lipoxygenase, MMP: matrix metalloproteinase NF-κB: nuclear factor kappa-light-chain-enhancer of activated B cells, MAPK: mitogen-activated protein kinase, PAI-1: plasminogen activator inhibitor-1, PLA2: phospholipase A2, PG: prostaglandin, SMAD3: mothers against decapentaplegic homolog 3, TGF-β1: transforming growth factor-beta 1, TNF-α: tumor necrosis factor-α, TLR: Toll-like receptor, TRPA1: transient receptor potential channel subfamily vanilloid member 1, TRPV1: transient receptor potential channel subfamily A member 1 mechanisms that curcumin may be useful to prevent or treat the ARDS. doi = 10.1002/fsn3.1858 id = cord-284332-p4c1fneh author = Bosma, Karen J. title = Pharmacotherapy for Prevention and Treatment of Acute Respiratory Distress Syndrome: Current and Experimental Approaches date = 2012-09-19 keywords = ALI; ARDS; acute; lung; mortality; patient; respiratory; study summary = [47] Although both of these studies were conducted prior to the 1994 AECC definition, ARDS was strictly defined in the aforementioned studies, including a PaO 2 /FiO 2 ratio <150 or intrapulmonary shunt >20% in patients requiring mechanical ventilation and who had diffuse infiltrates on chest radiograph without clinical evidence of heart failure as pulmonary arterial occlusion pressures were <18 mmHg. Building on the results of these two studies, Sinuff and colleagues [48] developed practice guidelines for prophylactic ketoconazole use, and tested the implementation and efficacy of these guidelines in two ICUs (one control and one active comparator). [119] A phase II study enrolling 98 patients with ALI compared an antioxidant enteral feeding formula containing eicosapentaenoic acid, g-linolenic acid and antioxidant vitamins with placebo, and observed improved oxygenation, reduced pulmonary inflammation, fewer days of mechanical ventilation and fewer non-pulmonary organ failures in the treatment arm, although there was no difference in mortality between this approach and the control group. doi = 10.2165/10898570-000000000-00000 id = cord-334528-xenq90xj author = Chen, Hsing I title = Acute lung injury and acute respiratory distress syndrome: experimental and clinical investigations date = 2011-03-17 keywords = ALI; ARDS; acute; lung; pulmonary summary = This literature review includes a brief historical retrospective of ALI/ARDS, the neurogenic pulmonary edema due to head injury, the long-term experimental studies and clinical investigations from our laboratory, the detrimental role of NO, the risk factors, and the possible pathogenetic mechanisms as well as therapeutic regimen for ALI/ARDS. [33, 34] In addition to the aforementioned animal experimentations and clinical observations that NO production through the iNOS may be involved in the lung injury due to various causes, our research team demonstrated that endotoxemia produced in anesthetized rats by intravenous administration of lipopolysaccharide (LPS, endotoxin) provoked systemic hypotension, endothelial damage and ALI accompanied by increased plasma nitrate/nitrite and expression of iNOS mRNA, TNF α and IL-1 β . The detrimental role of inducible nitric oxide synthase in the pulmonary edema caused by hypercalcemia in conscious rats and isolated lungs doi = 10.3724/sp.j.1263.2011.00044 id = cord-001473-aki28lhp author = Chen, Qi Xing title = Silencing airway epithelial cell-derived hepcidin exacerbates sepsis-induced acute lung injury date = 2014-08-06 keywords = ALI; hepcidin; lung summary = The knockdown of airway epithelial cell-derived hepcidin aggravated the polymicrobial sepsis-induced lung injury and pulmonary bacterial infection and increased mortality (53.33% in Ad-shHepc1-treated mice versus 12.5% in Ad-shNeg-treated mice, P <0.05). The severe lung injury in the airway epithelial cell-derived hepcidin knockdown mice is at least partially related to the altered intracellular iron level and function of alveolar macrophages. These results demonstrated that in the current study the intratracheal administration of Ad-shHepc1 only silenced the hepcidin gene transcription in AECs, which was in accordance with previous studies that adenovirus-mediated intratracheal gene delivery specifically inhibited targeted gene expression in lung epithelial cells but not in alveolar macrophages and other organs [29, 30] . The current study explored the role of AEC-derived hepcidin in polymicrobial sepsis-induced ALI, which is at least partially related to the altered intracellular iron level and function of alveolar macrophages. doi = 10.1186/s13054-014-0470-8 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 keywords = ALI; Fig; LPS; PALM3; TLR4 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. doi = 10.1007/s10753-017-0639-9 id = cord-016142-7j5cdt1b author = Chiang, Eddie T. title = Acute Lung Injury: The Injured Lung Endothelium, Therapeutic Strategies for Barrier Protection, and Vascular Biomarkers date = 2010-06-28 keywords = ALI; ARDS; MLC; PBEF; barrier; s1p summary = In this chapter, we will (1) address the role of cytoskeletal rearrangement in mechanistic regulation of pulmonary vascular barrier function and permeability, (2) define current strategies designed to enhance the integrity of the lung vascular endothelium, and (3) identify vascular biomarkers and potential prognostic determinants of acute inflammation. Phosphorylation of the substrate myosin light chain (MLC) by nmMLCK is central to paracellular gap formation and increased permeability by many edemagenic agents, including thrombin [18] and vascular endothelial growth factor (VEGF) [19] , both in vitro and in preclinical models of inflammatory lung injury. Protein kinase C (PKC)-mediated pathways exert a prominent effect on barrier regulation in a time-and speciesspecific manner without significantly increasing MLC phosphorylation and without inducing formation of actin stress fibers, but with alterations in other components of the endothelial cytoskeleton [18, 83, 84] . doi = 10.1007/978-0-387-87429-6_12 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 keywords = ALI; LPS; TTP 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. doi = 10.3389/fimmu.2020.02164 id = cord-023890-z346hh2c author = Cotogni, Paolo title = Polyunsaturated Fatty Acids and Cytokines: Their Relationship in Acute Lung Injury date = 2015 keywords = ALI; ARDS; DHA; PUFA summary = However, at present, the issue of lipid therapy in ALI/ARDS is still controversial due, at least in part, to inconclusive or contradicting results in several recent clinical trials using n-3 PUFAs. Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are inflammatory diseases whose clinical severity depends on the grade of inflammatory response. The first RCT showed the ability of an enteral formula with a high n-3/n-6 PUFA ratio (1:1) to reduce pulmonary inflammation and improve clinical outcomes, i.e., better oxygenation, shorter requirement for mechanical ventilation, shorter ICU-LOS, and less incidence of new organ failure; however, no difference in mortality was observed in ARDS patients (Gadek et al. The first RCT analyzed the effect of an enteral n-3 PUFA-enriched diet in septic patients with ALI or ARDS showing that the administration of the study formula, compared to a control formula with less lipids than in the previous three studies, was associated to a shorter ICU-LOS but not to an improvement in gas exchange or in a lower incidence of novel organ failures (Grau-Carmona et al. doi = 10.1007/978-1-4614-7836-2_112 id = cord-000492-ec5qzurk author = Devaney, James title = Clinical Review: Gene-based therapies for ALI/ARDS: where are we now? date = 2011-06-20 keywords = ALI; ARDS; gene; lung summary = Plasmid transfer (closed Easily produced at low cost No specifi c cell targeting Electroporation-mediated gene transfer of the dsDNA circles) Very ineffi cient Na + ,K + -ATPase rescues endotoxin-induced lung injury [60] Nonviral DNA complexes Complexes protect DNA Less effi cient than viral vectors Cationic lipid-mediated transfer of the Na + ,K + -(lipoplexes or polyplexes) Modifying transgene DNA to eliminate bacterial motifs [75, 76] Development of high-effi ciency tissue-specifi c promoters [77] [78] [79] [80] Development of promoters that regulate gene expression [83] Enhanced therapeutic targeting Nebulization technologies [9] Strategies to target the pulmonary endothelium [10] Improved cellular uptake of vector Surface active agents to enhance vector spread [84] Reduce ubiquitination of viral capsid proteins [85] Better therapeutic targets Enhancement or restoration of lung epithelial and/or endothelial cell function [86] Strengthening lung defense mechanisms against injury [87] Speeding clearance of infl ammation and infection Enhancement of the repair process following ALI/ARDS [88] . doi = 10.1186/cc10216 id = cord-319936-5uze06rp author = Dixon, Barry title = A phase 1 trial of nebulised heparin in acute lung injury date = 2008-05-06 keywords = ALI; APTT summary = INTRODUCTION: Animal studies of acute lung injury (ALI) suggest nebulised heparin may limit damage from fibrin deposition in the alveolar space and microcirculation. Studies in animal models of ALI have demonstrated that nebulised heparin improved the PaO 2 /FiO 2 ratio and reduced histological ALI = acute lung injury; APTT = activated partial thromboplastin time; BAL = bronchoalveolar lavage; ELISA = enzyme-linked immunosorbent assay; PaO 2 /FiO 2 = arterial oxygen partial pressure to inspired oxygen fraction ratio; PTF = prothrombin fragments; TCT = thrombin clotting time; t-PA = tissue plasminogen activator. Analysis of variance was used to compare the effect of heparin dose on the P a O 2 /F i O 2 ratio, lung compliance, the alveolar dead space fraction, the APTT, the TCT and intrapulmonary PTF and t-PA levels. We found administration of nebulised heparin to mechanically ventilated patients with ALI was feasible, was not associated with serious adverse events, and increased APTT levels at higher doses. doi = 10.1186/cc6894 id = cord-258087-93yfs7ve author = Flores, Carlos title = A quality assessment of genetic association studies supporting susceptibility and outcome in acute lung injury date = 2008-10-25 keywords = ALI; ARDS; acute; study summary = CONCLUSIONS: Although the quality of association studies seems to have improved over the years, more and better designed studies, including the replication of previous findings, with larger sample sizes extended to population groups other than those of European descent, are needed for identifying firm genetic modifiers of ALI. This quality assessment of genetic association studies with positive findings in susceptibility or outcome of ALI and ARDS identified a total of 29 articles and 16 genes. ACE, angiotensin-converting enzyme; ALI, acute lung injury; ARDS, acute respiratory distress syndrome; CAP, community-acquired pneumonia; CXCL2, chemokine CXC motif ligand 2; F5, coagulation factor V; IL-6, interleukin-6; IL-10, interleukin-10; MBL2, mannose-binding lectin-2; MIF, macrophage migration inhibitory factor; MV, mechanical ventilation; MYLK, myosin light-chain kinase; NFKB1, nuclear factor kappa light polypeptide gene enhancer in B cells; NFKBIA, nuclear factor kappa light polypeptide gene enhancer in B cells inhibitor alpha; NRF2, nuclear factor erythroid-derived 2 factor; PBEF, pre-B cell-enhancing factor; PLAU, plasminogen activator urokinase; SARS, severe acute respiratory syndrome; SFTPB, surfactant pulmonaryassociated protein B; SIRS, systemic inflammatory response syndrome; SNP, single-nucleotide polymorphism; TNF, tumor necrosis factor; TR, tandem repeat (polymorphism); VEGF, vascular endothelial growth factor. Positive genetic association studies with acute lung injury/acute respiratory distress syndrome susceptibility and/or outcome (by year of publication) doi = 10.1186/cc7098 id = cord-308892-5gbjdr0u author = Fu, Lin title = Acute liver injury and its association with death risk of patients with COVID-19: a hospital-based prospective case-cohort study date = 2020-04-06 keywords = ALI; covid-19 summary = title: Acute liver injury and its association with death risk of patients with COVID-19: a hospital-based prospective case-cohort study The aim of this study was to analyze SARS-CoV-2-induced acute liver injury (ALI), its association with death risk and prognosis after discharge. Despite of no difference on serum TBA, alkaline phosphatase and glutamyl transferase, two markers of cholestasis, were higher in critically ill patients than those of common cases. The present study aimed to analyze SARS-CoV-2-induced ALI, its association with death risk and the prognosis after discharge. The major findings of this study include: (1) ALI is more common in the critically ill COVID-19 patients; (2) Accumulating data demonstrated that SARS-CoV-2 infection caused multiple organ injuries, including myocardial dysfunction, lymphopenia and even acute renal These results provide evidence that ALI on admission is associated with the severity of COVID-19 patients. doi = 10.1101/2020.04.02.20050997 id = cord-333520-v2sb90rc author = Gardin, Chiara title = Could Mesenchymal Stem Cell-Derived Exosomes Be a Therapeutic Option for Critically Ill COVID-19 Patients? date = 2020-08-26 keywords = ALI; ARDS; COVID-19; MSC; Mesenchymal; SARS; cell summary = Exosomes derived from mesenchymal stem cells (MSCs) are being explored for the management of a number of diseases that currently have limited or no therapeutic options, thanks to their anti-inflammatory, immunomodulatory, and pro-angiogenic properties. Next, we describe some of the most significant clinical evidence of the successful use of MSC-derived exosomes in animal models of lung and heart injuries, which might strengthen our hypothesis in terms of their utility for also treating critically ill COVID-19 patients. Recently, MSC-derived exosomes have been demonstrated to have comparable and even greater effects than cells themselves in improving inflammation and injury in a variety of pre-clinical lung disease models, including ALI/ARDS (Table 1) . From the studies discussed above, it emerged that the rationale for using MSC-derived exosomes, MVs, or EVs in ALI/ARDS is based on several processes, many of which are shared with those identified in the parent MSCs. These include immunomodulation and anti-inflammatory properties on host tissue, reduction of the permeability of alveolar epithelium and endothelium, improvement of alveolar fluid clearance, enhancement of macrophage phagocytosis, and tissue repair through direct mitochondrial transfer with host cells (Figure 2 ). doi = 10.3390/jcm9092762 id = cord-001020-2iwsx727 author = Gupta, Kushagra title = Adipose-derived stem cells weigh in as novel therapeutics for acute lung injury date = 2013-02-28 keywords = ALI summary = Herein, we discuss the advantages and potential limitations of using adipose-derived stem cells as therapeutics for human acute lung injury. A strength of the paper is its novel focus on ASCs as a therapy for ALI, and its approach to test ASCs therapeutically (rather than prophylactically) in an ALI model Abstract Acute lung injury is characterized by intense neutrophilic lung infl ammation and increased alveolar-capillary barrier permeability leading to severe hypoxemia, and is associated with high mortality despite improvements in supportive care. Zhang and colleagues tested the effi cacy of adipose-derived stem cells in acute lung injury in mice. While the LPS model studied by Zhang and coworkers induces robust neutrophilic lung infl ammation, it causes only modest alveolar-capillary barrier injury, which is a hallmark of ALI/ARDS. Comparison of the therapeutic eff ects of human and mouse adipose-derived stem cells in a murine model of lipopolysaccharide-induced acute lung injury doi = 10.1186/scrt167 id = cord-102958-q8jamg07 author = Hahka, Taija M. title = Resiniferatoxin (RTX) ameliorates acute respiratory distress syndrome (ARDS) in a rodent model of lung injury date = 2020-09-14 keywords = ALI; RTX; TRPV1; lung summary = We ablated cardiopulmonary spinal afferents through either epidural T1-T4 dorsal root ganglia (DRG) application or intra-stellate ganglia delivery of a selective afferent neurotoxin, resiniferatoxin (RTX) in rats 3 days post bleomycin-induced lung injury. Our data showed that both epidural and intra-stellate ganglia injection of RTX significantly reduced plasma extravasation and reduced the level of lung pro-inflammatory cytokines providing proof of principle that cardiopulmonary spinal afferents are involved in lung pathology post ALI. Therefore, in the current study we hypothesized that ablation of lung afferent innervation (thoracic spinal) by application of an ultrapotent, selective afferent neurotoxin, resiniferatoxin (RTX) will modify the course of the pathology including lung edema and local pulmonary inflammation associated with progressive ALI. 2 1 Our data suggest that pulmonary spinal afferent ablation by intra-stellate injection of RTX reduces plasma extravasation and local pulmonary inflammation post bleomycininduced lung injury which results in improved blood gas exchange. doi = 10.1101/2020.09.14.296731 id = cord-015384-bz7ui5a0 author = Hans-Peter, Kapfhammer title = Posttraumatic stress disorder in survivors of acute respiratory distress syndrome (ARDS) and septic shock date = 2008-11-27 keywords = ALI; ARDS; PTSD; acute summary = From a perspective of C/L psychiatry persisting cognitive dysfunctions, anxiety and mood disorders, posttraumatic stress disorders (PTSD) in their negative impact on healthIn the etiopathogenesis of PTSD associated with ALI/ ARDS, many influences have to be discussed, e.g., increases in CO 2 triggering panic affects, a mismatch of norepinephric overstimulation and cortisol insufficiency, negative effects of high doses of benzodiazepines resulting in oversedation, prolonged phases of weaning and more frequent states of delirium. Social support during intensive care unit stay might improve mental impairment and consequently health-related quality of life in survivors of severe acute respiratory distress syndrome Risk factors for post-traumatic stress disorder symptoms following critical illness requiring mechanical ventilation: A prospective cohort study Post-traumatic stress disorder and posttraumatic stress symptoms following critical illness in medical intensive care unit patients: Assessing the magnitude of the problem Health-related quality of life and posttrauamtic stress disorder in survivors of the acute respiratory distress syndrome doi = 10.1007/s11800-008-0129-x id = cord-337973-djqzgc1k author = Hao, Siyuan title = Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium date = 2020-08-28 keywords = ALI; HAE; SARS summary = title: Long Period Modeling SARS-CoV-2 Infection of in Vitro Cultured Polarized Human Airway Epithelium We also identified that SARS-CoV-2 does not infect HAE from the basolateral side, and the dominant SARS-CoV-2 permissive epithelial cells are ciliated cells and goblet cells, whereas virus replication in basal cells and club cells was not detectable. Our observation that SARS-CoV-2 was unable to infect epithelial cells from the 299 basolateral side supports that the viral entry receptor ACE2 is polarly expressed at the apical 300 side 30, 31 . We 332 determined that 1 pfu of SARS-CoV-2 in Vero-E6 cells has a particle (viral genome copy) 333 number of 820, suggesting that a load of 2.46 x 10 5 particles is required to productively infect 1 334 cm 2 of the airway epithelium, which is much higher than the small DNA virus parvovirus human 335 bocavirus 1 (HBoV1) we studied 55 . doi = 10.1101/2020.08.27.271130 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 keywords = ALI; LPS; PAR-1; lung 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] . doi = 10.1007/s10753-006-9017-8 id = cord-012045-1cqqj84n author = Li, Tiao title = The Role of Deubiquitinating Enzymes in Acute Lung Injury and Acute Respiratory Distress Syndrome date = 2020-07-08 keywords = ALI; ARDS; CYLD; SARS; regulate summary = IL-1R8/Sigirr [40] Suppresses lung inflammation [40] PTEN [41] Regulates cell apoptosis [41] MCL1 [42] Regulates transformation of fibroblasts [42] STAT1 [55] Regulates IFN Signaling [55] STING [56] Negatively regulates antiviral responses [56] USP-14 I-kB [31] Increases cytokine release [31] CBP [32] Lung inflammation [32] USP-15 IκBα [57] NF-κB activation [57] USP-17 HDAC2 [58] Reverses glucocorticoid resistance [58] TRAF2/TRAF3 [59] Lung inflammation [59] [92] Inhibits type I IFN signaling and antiviral response [92] POH1 pro-IL-1β [93] Negatively regulates the immune response [93] BRCC3 NLRP3 [94] Promotes the inflammasome activation [94] STAMBP NALP7 [95] Reduces pro-inflammatory stress [95] Alveolar residential macrophages are central to the development of the inflammatory response by recruiting neutrophils and circulating macrophages to the site of injury, their functions are modulated by deubiquitinating enzymes [96, 97] . doi = 10.3390/ijms21144842 id = cord-309301-ai84el0j author = Li, Yaqi title = Organoid based personalized medicine: from bench to bedside date = 2020-11-02 keywords = ALI; CFTR; CRISPR; Cas9; Fig; cell; human; model; organoid; tumor summary = The mini-gut culture approach has been applied to the generation of organoids derived from the epithelial compartments of a variety of murine and human tissues of ecto-, meso-and endodermal origin, and promotes the study of stem cell biology of other tissues except for intestine. For translational research, tumorderived organoids can be used for biobanking, genetic repair and drug screening studies, both for personalized medicine (to choose the most effective treatment for a specific patient) and drug development (to test a compound library on a specific set of tumor organoids), as well as immunotherapy research similar in liver, small intestine, and colon stem cells, regardless of the large variation in cancer incidence of these organs. Ductal pancreatic cancer modeling and drug screening using human pluripotent stem cell-and patient-derived tumor organoids doi = 10.1186/s13619-020-00059-z id = cord-005832-p1joajvn author = Liu, Zhicheng title = Protective effect of gossypol on lipopolysaccharide-induced acute lung injury in mice date = 2013-02-23 keywords = ALI; LPS 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. doi = 10.1007/s00011-013-0603-6 id = cord-017853-mgsuwft0 author = Machado, Roberto F. title = Genomics of Acute Lung Injury and Vascular Barrier Dysfunction date = 2010-06-28 keywords = ALI; ARDS; IL-6; MIF; PBEF; gene summary = In this chapter, we utilize a systems biology approach combining cellular signaling pathway analysis with population-based association studies to review established and suspected candidate genes that contribute to dysfunction of endothelial cell barrier integrity and ALI susceptibility. Genes encoding proinflammatory cytokines, growth factors and mediators, receptors for barrier-regulatory agonists, and mechanical-stress-sensitive genes expressed in endothelium which regulate inflammatory responses also serve as attractive ALI candidate genes and are representative of the diverse but fertile areas of exploration for candidate SNPs affecting ALI susceptibility and severity. Interrogating the prospective pathways involved in endothelial permeability and correlation with these differentially expressed genes in VALI models identified the most putative ALI genes such as myosin light chain kinase (MYLK), sphingosine 1-phosphate receptor 1, cMet, and vascular endothelial growth factor (VEGF) mechanical stress [37, 38] . Role of macrophage migration inhibitory factor (MIF) in human and animal models of acute lung injury (ALI) and sepsis: association of a promoter polymorphism and increased gene expression doi = 10.1007/978-0-387-87429-6_63 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 keywords = ALI; ARDS; AST; LPS; RNA; gene summary = 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 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. We subsequently integrated the RNA-seq and microarray meta-analysis data, and 11 core DEGs (Timp1, Ly6i, Cxcl13, Irf7, Cxcl5, Ccl7, Isg15, Saa3, Saa1, Tgtp1, and Gbp11) that were upregulated in ALI models and downregulated significantly after AST treatment were identified ( Table 2) . To further identify the robust expression signature related to LPS-induced ALI and investigate the transcriptional changes in response to the treatment of ALI by AST, we performed RNA-seq on three groups of mice and integrated the data with the results of the above mentioned meta-analysis. doi = 10.18632/aging.104042 id = cord-305173-95o5z685 author = Martin, Thomas R. title = A TRIFfic Perspective on Acute Lung Injury date = 2008-04-18 keywords = ALI; TLR4 summary = In the complex inflammatory response initiated by HCl in the lungs, one might expect that TLR4 would be activated by several different endogenous stimuli; however, mice lacking TLR4, TRIF, or TRAF6 all resisted HClas well as OxPAPC-induced inflammation, supporting a role for OxPAPC as an important stimulus of TLR4 activation in this model. As in the HCl injury model, immunohistochemical analysis identified OxPAPC in the lungs, but mice lacking TLR4 or TRIF had lung inflammation that was much less severe. Mice lacking the Ncf1 protein, which lack an active NADPH oxidase complex, were protected from viral lung inflammation and did not form OxPAPC in the airspaces, further supporting a key role for oxidation of phospholipids in the pathogenic pathway. OxPAPC activates TLR4 expressed by myeloid cells (an alveolar macrophage is shown), and the intracellular signal is transduced by the adaptor proteins TRIF and TRAF6, leading to interleukin 6 (IL-6) production, inflammation, and alveolar damage. doi = 10.1016/j.cell.2008.04.006 id = cord-005812-hx6lkuj0 author = Morty, Rory E. title = Alveolar fluid clearance in acute lung injury: what have we learned from animal models and clinical studies? date = 2007-05-25 keywords = AFC; ALI; ARDS summary = To complement that report this review focuses on how intact organ and animal models and clinical studies have facilitated our understanding of alveolar edema fluid clearance in acute lung injury and acute respiratory distress syndrome. Given the established importance of the type II cell in AFC [6] and the emerging importance of the type I cell in AFC with the recent discovery that type I cells also contain functional sodium and chloride channels [12] , this epithelial damage Fig. 1 Factors that cause impaired alveolar fluid clearance in ALI/ARDS that have been investigated in animal and organ models and in clinical studies. This idea was further supported by the observations that adenovirus-mediated transfer of β-adrenergic receptor genes to live rats improved AFC due to increased sensitivity to endogenous catecholamines and consequent upregulation of Na,K-ATPase activity and ENaC protein expression the lung [73] . doi = 10.1007/s00134-007-0662-7 id = cord-317993-012hx4kc author = Movia, Dania title = Preclinical Development of Orally Inhaled Drugs (OIDs)—Are Animal Models Predictive or Shall We Move Towards In Vitro Non-Animal Models? date = 2020-07-24 keywords = ALI; OID; cell; drug; lung; model summary = SIMPLE SUMMARY: This commentary focuses on the methods currently available to test the efficacy and safety of new orally inhaled drugs for the treatment of uncurable respiratory diseases, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis or lung cancer, prior to entering human experimentation. Inhalation is the preferred administration method for treating respiratory diseases [13] , as: (i) it delivers the drug directly at the site of action, resulting in a rapid therapeutic onset with considerably lower drug doses, (ii) it is painless and minimally invasive thus improving patients'' compliance, and (iii) it avoids first-pass metabolism, providing optimal pharmacokinetic conditions for drug absorption and reducing systemic side effects [14] [15] [16] . In the context of OID preclinical testing, lung organoids can be used for modeling respiratory diseases and, therefore, as a platform for screening the efficacy of inhalation therapies [115, 116] . doi = 10.3390/ani10081259 id = cord-313091-ksrxsdpp author = Shirato, Kazuya title = Wild-type human coronaviruses prefer cell-surface TMPRSS2 to endosomal cathepsins for cell entry date = 2017-12-06 keywords = ALI; HBTE; OC43 summary = Studies using the ATCC isolate suggest that HCoV-229E enters cells via the late endosome using cathepsin L to cleave S protein, although it can enter cells via the cell surface or early endosome in the presence of transmembrane protease serine 2 (TMPRSS2) or trypsin (Bertram et al., 2013; Kawase et al., 2009) . In the present study, we found that field isolates of HCoV-OC43 and HCoV-HKU1 could be isolated using HBTE-ALI cell culture, and we then used these clinical isolates to assess whether the mode of virus entry found in HCoV-229E was also in play in other HCoVs. For isolation of HCoVs, nasal swabs were collected from outpatients who showed respiratory infection as a cardinal symptom when assessed at a hospital in Tokyo, Japan. To evaluate the entry routes of clinical isolates of HCoVs, viruses were inoculated onto HBTE-ALI in the presence of EST or camostat (10 μM) and the amounts virus that entered were estimated by detecting subgenomic mRNAs using real-time RT-PCR (Fig. 2) . doi = 10.1016/j.virol.2017.11.012 id = cord-017107-sg8n12hs author = Suri, H. S. title = Epidemiology of Acute Respiratory Failure and Mechanical Ventilation date = 2008 keywords = ALI; acute; respiratory summary = A recently completed, retrospective, community cohort study in Olmsted County, Minnesota included patients treated with NIV and found an even higher incidence of ALI, 156 per 100,000 person-years (personal communication, Rodrigo Cartin -Ceba), Mortality from ALI varies greatly depending upon the age of the patient, underlying chronic illnesses, ALI risk factors, and non-pulmonary organ dysfunctions [15] . In an international cohort study [4] , acute exacerbation of COPD was a principal indication for initiating mechanical ventilation in 13 % of patients with acute respiratory failure. The majority of patients with interstitial lung disease and acute respiratory failure admitted to the ICU require invasive mechanical ventilation . In a retrospective review [39] of 75 patients with interstitial lung disease who were mechanically ventilated at Mayo Clinic from 2003 to 2005, acute respiratory failure was the most common cause of ICU admiss ion (77 %), followed by sepsis (11 %) and cardiopulmonary arrest (4 %). doi = 10.1007/978-0-387-77383-4_18 id = cord-023928-9a1w174h author = Thomas, Neal J. title = Genetic Predisposition to Critical Illness in the Pediatric Intensive Care Unit date = 2011-12-16 keywords = ALI; TNF; dna; gene; genetic summary = authors: Thomas, Neal J.; Dahmer, Mary K.; Quasney, Michael W. Examples of the infl uence of genetic variations in proteins involved in recognition of pathogens on the severity of infections include polymorphisms in the genes coding for mannose binding Individual variability in the susceptibility to and outcome from critical care diseases has long been observed, and advances in genomic medicine now gives an opportunity to understand these differences. doi = 10.1007/978-0-85729-923-9_11 id = cord-255440-ls1l2mlg author = Tindle, Courtney title = Adult Stem Cell-derived Complete Lung Organoid Models Emulate Lung Disease in COVID-19 date = 2020-10-18 keywords = ALI; COVID-19; Fig; SARS; at2; cell summary = Besides the approaches described so far, there are a few more approaches used for modeling COVID-19-(i) 3D organoids from bronchospheres and tracheospheres have been established before (Hild and Jaffe, 2016; Rock et al., 2009; Tadokoro et al., 2016) and are now used in apical-out cultures for infection with SARS-COV-2 (Suzuki et al., 2020); (ii) the most common model used for drug screening is the air-liquid interphase (ALI model) in which pseudo-stratified primary bronchial or small airway epithelial cells are used to recreate the multilayered mucociliary epithelium (Mou et al., 2016; Randell et al., 2011) ; (iii) several groups have also generated 3D airway models from iPSCs or tissue-resident stem cells (Dye et al., 2015; Ghaedi et al., 2013; Konishi et al., 2016; McCauley et al., 2017; Miller et al., 2019; Wong et al., 2012) ; (iv) others have generated AT2 cells from iPSCs using closely overlapping protocols of sequential differentiation starting with definitive endoderm, anterior foregut endoderm, and distal alveolar expression (Chen et al., 2017; Gotoh et al., 2014; Huang et al., 2014; Jacob et al., 2017; Jacob et al., 2019; Yamamoto et al., 2017) . doi = 10.1101/2020.10.17.344002 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 keywords = ALI; IFN; LPS; VEGF; vascular 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) . doi = 10.1007/s00210-020-01947-6 id = cord-291076-p350i54m author = Wang, Renxi title = The role of C5a in acute lung injury induced by highly pathogenic viral infections date = 2015-05-06 keywords = ALI; H5N1; SARS; TNF summary = Unregulated complement activation is likely to play a crucial role in the pathogenesis of acute lung injury (ALI) induced by highly pathogenic virus including influenza A viruses H5N1, H7N9, and severe acute respiratory syndrome (SARS) coronavirus. [1] [2] [3] In addition, the complement system has been implicated in the development of acute lung diseases induced by highly pathogenic viruses including influenza A virus H1N1, 4 H5N1, 5 H7N9, 6 severe acute respiratory syndrome coronavirus (SARS-Cov), 7 Middle East respiratory syndrome coronavirus (MERS-Cov). C5a-mediated release of reactive oxygen species C5a is a strong chemoattractant for neutrophils and monocytes; it then activates these cells to generate oxidative burst with release of 10 A study demonstrated that ROS are primary pathogenic molecules in pneumonia from mice infected with influenza virus. Inhibition of Complement Activation Alleviates Acute Lung Injury Induced by Highly Pathogenic Avian Influenza H5N1 Virus Infection doi = 10.1038/emi.2015.28 id = cord-340865-sut3nf2a author = Wang, Shuang title = Blockage of P2X7 attenuates acute lung injury in mice by inhibiting NLRP3 inflammasome date = 2015-04-29 keywords = ALI; NLRP3; P2X7 summary = LPS administration increased P2X7 expression in the lung parenchyma and P2X7 −/− mice showed decreased polymorphonuclear cell infiltration, less inflammatory cytokine production and reduced collagen deposition [8] . In this study, we demonstrated that pharmacological blockade of P2X7 by using selective antagonists effectively ameliorated ALI in mice via inhibiting NLRP3 inflammasome pathway. Enhanced protein expression of P2X7, NLRP3, and ASC was observed in the lungs from LPS-induced lung injury mice compared with control mice treated by PBS (Fig. 1) . Coincident with the cell counts, the total protein level was also elevated in the LPS-induced lung injury group, which was significantly reduced by A438079 treatment (Fig. 3d) . In this study, P2X7 expression was significantly enhanced at the protein level in the lung tissues from ALI mice, paralleled with alveolar damage and inflammatory cytokine production. We found that blockage of P2X7 inhibited the activation of NLRP3 inflammasome pathway, neutrophil accumulation and production of proinflammatory cytokines, resulting in reduction of lung damage. doi = 10.1016/j.intimp.2015.04.035 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 keywords = ALI; LPS; Rac1; figure 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) doi = 10.1016/j.redox.2020.101794 id = cord-000812-mu5u5bvj author = Wiesen, Jonathan title = Relative cost and outcomes in the intensive care unit of acute lung injury (ALI) due to pandemic influenza compared with other etiologies: a single-center study date = 2012-08-28 keywords = ALI; H1N1; ICU summary = Based on clinical bedside observations and published reports [4, 5, 8] , we hypothesize that ALI/ARDS secondary to pandemic influenza is associated with similar ICU outcomes but increased resource utilization and higher hospital charges due to the frequent need for rescue interventions and prolonged ventilatory assistance. A Research Electronic Data Capture (REDCap) database was constructed with a complete listing of the patient''s demographic and clinical information, including age, gender, height, weight, body mass index (BMI), presenting symptoms, past medical history, primary reason for admission to the ICU, vital signs, presence of vasopressors, laboratory values, ventilator settings and respiratory parameters, Acute Physiology and Chronic Health Evaluation (APACHE) III and Sequential Organ Failure Assessment (SOFA) scores on admission to the MICU, number of intubated days, duration of ICU and hospital stay, mortality, and rescue therapies (namely inhaled nitric oxide, proning, high-frequency oscillatory ventilation, and extracorporeal membrane oxygenation [ECMO]) [22] . doi = 10.1186/2110-5820-2-41 id = cord-005980-e2s0racp author = Wu, Xiaojing title = TIPE2 ameliorates lipopolysaccharide-induced apoptosis and inflammation in acute lung injury date = 2019-09-05 keywords = ALI; JNK; LPS; TIPE2 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. doi = 10.1007/s00011-019-01280-6 id = cord-000137-idffrnac author = Xiang, Meng title = Pattern Recognition Receptor–Dependent Mechanisms of Acute Lung Injury date = 2009-11-02 keywords = ALI; LPS; PMN; TLR2; TLR4; Toll 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) . doi = 10.2119/molmed.2009.00097 id = cord-007858-1ijxilpb author = Xu, G.L. title = Attenuation of acute lung injury in mice by oxymatrine is associated with inhibition of phosphorylated p38 mitogen-activated protein kinase date = 2005-04-08 keywords = ALI; MAP; TNF- summary = Furthermore, pretreatment with oxymatrine significantly alleviated oleic acid-induced lung injury accompanied by reduction of lung index and wet-to-dry weight ratio, decreases in serum TNF-α level and inhibition of phosphorylated p38 MAPK. These findings suggest that oxymatrine has a beneficial effect on acute lung injury induced by oleic acid in mice and may inhibit the production of proinflammatory cytokine, TNF-α, by means of the inhibition of p38 MAPK. Light microscopic findings in the lung at 6 h after oleic acid injection demonstrated a marked lung injury resembling those seen in lung of patients with ALI/ARDS, represented by prominent atelectasis, intraalveolar and interstitial patchy hemorrhage, edema, thickened alveolar septum, formation of hyaline membranes and the existence of inflammatory cells in alveolar spaces (Fig. 1A) , which were not observed in the control group (Fig. 1B) . Effect of oxymatrine on serum TNF-␣ level in mice with lung injury induced by oleic acid. doi = 10.1016/j.jep.2005.01.026 id = cord-001945-ueccexxc author = Yang, Ce title = Stem/progenitor cells in endogenous repairing responses: new toolbox for the treatment of acute lung injury date = 2016-02-11 keywords = ALI; cell; lung; progenitor; stem summary = All these findings indicate Fig. 1 Schematic illustration of the exogenous and endogenous stem/progenitor cells as well as the regular delivery routes in the repair and regeneration in acute lung injury that the bone marrow-derived stem/progenitor cells exhibit the mobilizing courses, and play a substantial role in the regression of excessive inflammatory responses and repair in injured lungs. Concerning the protective roles of bone marrow-and peripheral blood-derived EPCs in ALI, recent studies showed that their peripheral infusion could lead to homing in injured lung tissues [24] , relieving the inflammatory injury [25, 26] and promote the endothelial repair and recovery of immune function dissonance [26, 27] , which may be enhanced by the treatment of simvastatin [28] . doi = 10.1186/s12967-016-0804-1 id = cord-006507-amo8e81h author = Yang, Zhongwei title = TLR4 as receptor for HMGB1-mediated acute lung injury after liver ischemia/reperfusion injury date = 2013-04-29 keywords = ALI; HMGB1; TLR4 summary = This study investigated whether HMGB1 was involved as a stimulating factor, and whether its downstream Toll-like receptor 4 (TLR4), p38 mitogen-activated protein kinase (p38MAPK), and activator protein-1 (AP-1) signaling pathways act as mediators in the development of liver I/R injury-induced ALI. To study the role of TLR4 and its downstream p38MAPK and AP-1 signaling pathways in the pathogenesis of liver I/R injury-induced ALI, TLR4-small hairpin RNA (shRNA) lentivirus were used to inhibit TLR4 expression in rat lung tissue. As is shown in Figure 3b , relative levels of HMGB1 mRNA in the lung tissue from I/R, shNT þ I/R, and shTLR4 þ I/R groups increased significantly at 18 h after liver I/R injury when compared to the control group, respectively. TLR4-mediated ALI after liver I/R injury Z Yang et al Figure 3 Expression of high-mobility group box protein 1 (HMGB1) in serum and lung tissue from rats at 18 h after liver ischemia/reperfusion (I/R) injury or sham operation. doi = 10.1038/labinvest.2013.66 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 keywords = ALI; ARDS; CLP; LPS; Splen summary = title: Exploring the biomarkers associated with different host inflammation of acute respiratory distress syndrome (ARDS) from lung metabolomics in mice 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. RF analysis of lung-targeted metabolomics data defined a set of 15 metabolites that constitute the best predictors of differences in host inflammation status: in particular, increased 4hydroxyphenylacetic acid, 1-aminocyclopentanecarboxylic acid (ACPC), and cis-aconitic acid, Tridecane and hydroxybenzoic acid were strong predictors of the hyper-inflammatory subgroup in CLP-induced ALI ( Figure 3B ). Interestingly, RF analysis of lung-targeted metabolomics data showed that the metabolic biomarker group with 5 products was a strong predictor of the hyper-inflammatory subgroup in CLP-induced ALI ( Figure 3B ). doi = 10.1002/rcm.8971 id = cord-002329-7s0ytfed author = Zeng, Ling title = The cellular kinetics of lung alveolar epithelial cells and its relationship with lung tissue repair after acute lung injury date = 2016-12-07 keywords = AEC2; ALI; HGF; Met summary = CONCLUSIONS: AEC2s are damage resistant during acute lung injury and the HGF/c-Met signaling pathway is of vital importance in the proliferation of AEC2s after ALI. Using a microfluidic magnetic activated cell sorting system, our previous study has isolated mouse lung multipotent stem cells (MLSCs) which play an important role in bronchiolar and alveolar epithelial cells injury repair [8] . The rat whole lung cell suspensions were incubated with FITC conjugated to anti-proSPC antibody, the percentage of AEC2s was analyzed by flow cytometry analysis (Fig. 1e) , in sham-operated mice, there were no differences in numbers of AEC2s at various time points. It can significantly accelerate AEC2 cell cycle in vitro, indicating that the proliferation of AEC2 after acute lung injury may be induced by the elevated HGF. HGF/c-Met signaling is likely a major factor responsible for the pulmonary epithelial cell proliferation after acute lung injury. doi = 10.1186/s12931-016-0480-y id = cord-006573-mwtqxwbw author = Zhang, Leifang title = SOCS-1 Suppresses Inflammation Through Inhibition of NALP3 Inflammasome Formation in Smoke Inhalation-Induced Acute Lung Injury date = 2018-06-16 keywords = ALI; NALP3; SOCS-1 summary = title: SOCS-1 Suppresses Inflammation Through Inhibition of NALP3 Inflammasome Formation in Smoke Inhalation-Induced Acute Lung Injury Similar to oxidized ATP, high protein level of SOCS-1 dampened the formation of NALP3 inflammasome and the activation of caspase-1 and IL-1β induced by smoke exposure in mouse alveolar macrophages. In conclusion, SOCS-1 relieves smoke inhalation-induced pulmonary inflammation and injury by inhibiting NALP3 inflammasome formation. To test whether SOCS-1 exerts anti-inflammatory effect through inhibition of NALP3 inflammasome formation and consequent activation of caspase-1 and IL-1β, Ad-GFP, or Ad-SOCS-1-adminstered mice were exposed to smoke for 15 min and euthanized 1 day later to collect alveolar macrophages. Alveolar macrophages were isolated from C57BL/6 mice, treated with or without oxATP, exposed to smoke for 30 min, and then analyzed for a ATP release, b extracellular, and c intracellular K + levels, d expression of inflammasome components NALP3, ASC, and caspase-1, and e the complex formed by NALP3 and ASC. doi = 10.1007/s10753-018-0802-y id = cord-320681-b3ui95vx author = Zhang, Rui title = COVID-19: Melatonin as a potential adjuvant treatment date = 2020-06-01 keywords = ALI; SARS; covid-19; melatonin summary = Based on clinical features, pathology, the pathogenesis of acute respiratory disorder induced by either highly homogenous coronaviruses or other pathogens, the evidence suggests that excessive inflammation, oxidation, and an exaggerated immune response very likely contribute to COVID-19 pathology. Herein, we review the evidence indicating that melatonin will have supportive adjuvant utility in treating COVID-19 induced pneumonia, acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). In SARS-CoV and MERS-CoV infected animal model, marked inflammatory and immune responses may activate a "cytokine storm", and apoptosis of epithelial cells and endothelial cells; subsequently, vascular leakage, abnormal T cell and macrophages responses ensue and induce ALI/ARDS or even death [13] . The amplification of the inflammatory response would promote cellular apoptosis or We postulated that lungs infected by SARS-CoV-2, and a suppressed immune response, elevated inflammation and excessive oxidation stress proceed unabated, this results in the activation of the cytokine storm. doi = 10.1016/j.lfs.2020.117583 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 keywords = ALI; LJF; LPS 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) . doi = 10.1016/j.jep.2020.113364 id = cord-014996-p6q0f37c author = nan title = Posters_Monday_12 October 2009 date = 2009-08-06 keywords = AKI; ALI; APACHE; Care; Hospital; ICU; LPS; PCT; SAPS; VAP; conclusion; group; introduction; method; mortality; objectives; patient; result; sepsis; sofa; study 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. doi = 10.1007/s00134-009-1593-2