Carrel name: keyword-ace-cord Creating study carrel named keyword-ace-cord Initializing database file: cache/cord-005931-iggkxbbf.json key: cord-005931-iggkxbbf authors: Phillips, M. Ian; de Oliveira, Edilamar Menezes title: Brain renin angiotensin in disease date: 2008-04-02 journal: J Mol Med (Berl) DOI: 10.1007/s00109-008-0331-5 sha: doc_id: 5931 cord_uid: iggkxbbf file: cache/cord-001773-mqk0sx5n.json key: cord-001773-mqk0sx5n authors: Lo, Chao-Sheng; Shi, Yixuan; Chang, Shiao-Ying; Abdo, Shaaban; Chenier, Isabelle; Filep, Janos G.; Ingelfinger, Julie R.; Zhang, Shao-Ling; Chan, John S. D. title: Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes date: 2015-08-01 journal: Diabetologia DOI: 10.1007/s00125-015-3700-y sha: doc_id: 1773 cord_uid: mqk0sx5n file: cache/cord-269151-r426u5dz.json key: cord-269151-r426u5dz authors: Turner, Jeffrey M.; Kodali, Ravi title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? date: 2020-07-09 journal: Curr Cardiol Rep DOI: 10.1007/s11886-020-01352-8 sha: doc_id: 269151 cord_uid: r426u5dz file: cache/cord-002468-onpmkjaz.json key: cord-002468-onpmkjaz authors: Roca-Ho, Heleia; Riera, Marta; Palau, Vanesa; Pascual, Julio; Soler, Maria Jose title: Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse date: 2017-03-05 journal: Int J Mol Sci DOI: 10.3390/ijms18030563 sha: doc_id: 2468 cord_uid: onpmkjaz file: cache/cord-267519-a0bcmjkn.json key: cord-267519-a0bcmjkn authors: Bravi, Francesca; Flacco, Maria Elena; Carradori, Tiziano; Volta, Carlo Alberto; Cosenza, Giuseppe; De Togni, Aldo; Acuti Martellucci, Cecilia; Parruti, Giustino; Mantovani, Lorenzo; Manzoli, Lamberto title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date: 2020-06-24 journal: PLoS One DOI: 10.1371/journal.pone.0235248 sha: doc_id: 267519 cord_uid: a0bcmjkn file: cache/cord-005386-p37rw8dh.json key: cord-005386-p37rw8dh authors: Szolnoki, Zoltán; Maasz, Anita; Magyari, Lili; Horvatovich, Katalin; Farago, Bernadett; Somogyvari, Ferenc; Kondacs, Andras; Szabo, Mihaly; Fodor, Lajos; Bodor, Anita; Hadarits, Ferenc; Melegh, Bela title: Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke date: 2006 journal: Neuromolecular Med DOI: 10.1385/nmm:8:3:353 sha: doc_id: 5386 cord_uid: p37rw8dh file: cache/cord-016742-y7jgjera.json key: cord-016742-y7jgjera authors: Bauer, Maria title: Cardiovascular Anatomy and Pharmacology date: 2017-07-03 journal: Basic Sciences in Anesthesia DOI: 10.1007/978-3-319-62067-1_11 sha: doc_id: 16742 cord_uid: y7jgjera file: cache/cord-002307-gk84fnb9.json key: cord-002307-gk84fnb9 authors: Kehoe, Patrick Gavin; Wong, Steffenny; AL Mulhim, Noura; Palmer, Laura Elyse; Miners, J. Scott title: Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology date: 2016-11-25 journal: Alzheimers Res Ther DOI: 10.1186/s13195-016-0217-7 sha: doc_id: 2307 cord_uid: gk84fnb9 file: cache/cord-024076-q9fw7ch1.json key: cord-024076-q9fw7ch1 authors: Manga, Pravin title: Should ACE Inhibitors and Angiotensin Receptor Blockers Be Withdrawn in the Current Setting of COVID-19 Infection? date: 2020-04-17 journal: nan DOI: 10.18772/26180197.2020.v2nsia4 sha: doc_id: 24076 cord_uid: q9fw7ch1 file: cache/cord-017585-0llgr357.json key: cord-017585-0llgr357 authors: Chappell, Mark C. title: Role of ACE, ACE2 and Neprilysin in the Kidney date: 2007 journal: Frontiers in Research of the Renin-Angiotensin System on Human Disease DOI: 10.1007/978-1-4020-6372-5_1 sha: doc_id: 17585 cord_uid: 0llgr357 file: cache/cord-005927-a9sj00y8.json key: cord-005927-a9sj00y8 authors: Kondoh, Gen; Tojo, Hiromasa; Nakatani, Yuka; Komazawa, Nobuyasu; Murata, Chie; Yamagata, Kazuo; Maeda, Yusuke; Kinoshita, Taroh; Okabe, Masaru; Taguchi, Ryo; Takeda, Junji title: Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization date: 2005-01-23 journal: Nat Med DOI: 10.1038/nm1179 sha: doc_id: 5927 cord_uid: a9sj00y8 file: cache/cord-282256-lqmixm7s.json key: cord-282256-lqmixm7s authors: Tsioufis, Costas; Dimitriadis, Kyriakos; Tousoulis, Dimitrios title: The interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging data as the “Ariadne’s thread” for the “labyrinth” of COVID-19 date: 2020-05-22 journal: Hellenic J Cardiol DOI: 10.1016/j.hjc.2020.05.003 sha: doc_id: 282256 cord_uid: lqmixm7s file: cache/cord-259933-ggx4v0bz.json key: cord-259933-ggx4v0bz authors: Dalan, Rinkoo; Bornstein, Stefan R.; El-Armouche, Ali; Rodionov, Roman N; Markov, Alexander; Wielockx, Ben; Beuschlein, Felix; Boehm, Bernhard O. title: The ACE-2 in COVID-19: Foe or Friend? date: 2020-04-27 journal: Horm Metab Res DOI: 10.1055/a-1155-0501 sha: doc_id: 259933 cord_uid: ggx4v0bz file: cache/cord-264828-6w13xo2a.json key: cord-264828-6w13xo2a authors: Albini, Adriana; Di Guardo, Giovanni; Noonan, Douglas McClain; Lombardo, Michele title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies date: 2020-05-19 journal: Intern Emerg Med DOI: 10.1007/s11739-020-02364-6 sha: doc_id: 264828 cord_uid: 6w13xo2a file: cache/cord-018009-8j40876m.json key: cord-018009-8j40876m authors: Campbell, Duncan J. John title: ACE Inhibition in Heart Failure and Ischaemic Heart Disease date: 2007 journal: Frontiers in Research of the Renin-Angiotensin System on Human Disease DOI: 10.1007/978-1-4020-6372-5_2 sha: doc_id: 18009 cord_uid: 8j40876m file: cache/cord-015859-5kt59ose.json key: cord-015859-5kt59ose authors: Esch, Joep H.M. Van; Danser, A.H. Jan title: Local Angiotensin Generation and AT(2) Receptor Activation date: 2007 journal: Frontiers in Research of the Renin-Angiotensin System on Human Disease DOI: 10.1007/978-1-4020-6372-5_12 sha: doc_id: 15859 cord_uid: 5kt59ose file: cache/cord-298515-5n7hxhbg.json key: cord-298515-5n7hxhbg authors: Oarhe, Chinyere I.; Dang, Vinh; Dang, MyTrang; Nguyen, Hang; Gopallawa, Indiwari; Gewolb, Ira H.; Uhal, Bruce D. title: Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts date: 2015-02-09 journal: Pediatr Res DOI: 10.1038/pr.2015.27 sha: doc_id: 298515 cord_uid: 5n7hxhbg file: cache/cord-286638-bqxyb61p.json key: cord-286638-bqxyb61p authors: Singh, Awadhesh Kumar; Gupta, Ritesh; Ghosh, Amerta; Misra, Anoop title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations date: 2020-04-09 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2020.04.004 sha: doc_id: 286638 cord_uid: bqxyb61p file: cache/cord-006082-x1kankxd.json key: cord-006082-x1kankxd authors: Romero, Cesar A.; Orias, Marcelo; Weir, Matthew R. title: Novel RAAS agonists and antagonists: clinical applications and controversies date: 2015-02-10 journal: Nat Rev Endocrinol DOI: 10.1038/nrendo.2015.6 sha: doc_id: 6082 cord_uid: x1kankxd file: cache/cord-275837-2avxd80i.json key: cord-275837-2avxd80i authors: Ahirwar, Ashok Kumar; Asia, Priyanka; Sakarde, Apurva; Kaim, Kirti title: COVID -19 outbreak – Diabetes aspect and perspective date: 2020-05-19 journal: Curr Med Res Pract DOI: 10.1016/j.cmrp.2020.05.005 sha: doc_id: 275837 cord_uid: 2avxd80i file: cache/cord-277766-rxmpi61o.json key: cord-277766-rxmpi61o authors: Guang, Cuie; Phillips, Robert D.; Jiang, Bo; Milani, Franco title: Three key proteases – angiotensin-I-converting enzyme (ACE), ACE2 and renin – within and beyond the renin-angiotensin system date: 2012-06-15 journal: Arch Cardiovasc Dis DOI: 10.1016/j.acvd.2012.02.010 sha: doc_id: 277766 cord_uid: rxmpi61o file: cache/cord-253862-jl1zhg13.json key: cord-253862-jl1zhg13 authors: Khalaf, Khalil; Papp, Natalia; Chou, Jadzia Tin-Tsen; Hana, Doris; Mackiewicz, Andrzej; Kaczmarek, Mariusz title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 journal: Front Immunol DOI: 10.3389/fimmu.2020.570927 sha: doc_id: 253862 cord_uid: jl1zhg13 file: cache/cord-006087-hynkb0a8.json key: cord-006087-hynkb0a8 authors: Acharya, K. Ravi; Sturrock, Edward D.; Riordan, James F.; Ehlers, Mario R. W. title: Ace revisited: A new target for structure-based drug design date: 2003 journal: Nat Rev Drug Discov DOI: 10.1038/nrd1227 sha: doc_id: 6087 cord_uid: hynkb0a8 file: cache/cord-266289-dkxhbmic.json key: cord-266289-dkxhbmic authors: Harrison, Charlotte; Acharya, K. Ravi title: ACE for all – a molecular perspective date: 2014-07-16 journal: Journal of Cell Communication and Signaling DOI: 10.1007/s12079-014-0236-8 sha: doc_id: 266289 cord_uid: dkxhbmic file: cache/cord-300850-59j1m2tm.json key: cord-300850-59j1m2tm authors: Peron, Jean Pierre Schatzmann; Nakaya, Helder title: Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) date: 2020-05-11 journal: Clinics (Sao Paulo) DOI: 10.6061/clinics/2020/e1912 sha: doc_id: 300850 cord_uid: 59j1m2tm file: cache/cord-266755-y2lf7ssp.json key: cord-266755-y2lf7ssp authors: Yehualashet, Awgichew Shewasinad; Belachew, Teshome Fentik title: ACEIs and ARBs and Their Correlation with COVID-19: A Review date: 2020-09-16 journal: Infect Drug Resist DOI: 10.2147/idr.s264882 sha: doc_id: 266755 cord_uid: y2lf7ssp file: cache/cord-290148-6cxndab8.json key: cord-290148-6cxndab8 authors: Rossi, Gian Paolo; Sanga, Viola; Barton, Matthias title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients date: 2020-04-06 journal: eLife DOI: 10.7554/elife.57278 sha: doc_id: 290148 cord_uid: 6cxndab8 file: cache/cord-289144-d6fgs8qg.json key: cord-289144-d6fgs8qg authors: Sieńko, Jerzy; Kotowski, Maciej; Bogacz, Anna; Lechowicz, Kacper; Drożdżal, Sylwester; Rosik, Jakub; Sietnicki, Marek; Sieńko, Magdalena; Kotfis, Katarzyna title: COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients date: 2020-07-21 journal: Clin Interv Aging DOI: 10.2147/cia.s261516 sha: doc_id: 289144 cord_uid: d6fgs8qg file: cache/cord-286825-bu7j7kdr.json key: cord-286825-bu7j7kdr authors: Macours, Nathalie; Poels, Jeroen; Hens, Korneel; Francis, Carmen; Huybrechts, Roger title: Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes date: 2004-10-04 journal: Int Rev Cytol DOI: 10.1016/s0074-7696(04)39002-9 sha: doc_id: 286825 cord_uid: bu7j7kdr file: cache/cord-289477-cjm7qhr4.json key: cord-289477-cjm7qhr4 authors: Mueller, Sylvia; Gothe, Rita; Siems, Wolf-Dieter; Vietinghoff, Gabriele; Paegelow, Inge; Reissmann, Siegmund title: Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α) date: 2005-04-25 journal: Peptides DOI: 10.1016/j.peptides.2005.03.046 sha: doc_id: 289477 cord_uid: cjm7qhr4 file: cache/cord-304742-ytf2ilw4.json key: cord-304742-ytf2ilw4 authors: Albini, Adriana; Noonan, Douglas McClain; Pelosi, Giuseppe; Di Guardo, Giovanni; Lombardo, Michele title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based antihypertensive therapies—reply date: 2020-07-14 journal: Intern Emerg Med DOI: 10.1007/s11739-020-02436-7 sha: doc_id: 304742 cord_uid: ytf2ilw4 file: cache/cord-256020-wrui3i2l.json key: cord-256020-wrui3i2l authors: Fadaka, Adewale Oluwaseun; Sibuyi, Nicole Remaliah Samantha; Adewale, Olusola Bolaji; Bakare, Olalekan Olanrewaju; Akanbi, Musa Oyebowale; Klein, Ashwil; Madiehe, Abram Madimabe; Meyer, Mervin title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 journal: J Int Med Res DOI: 10.1177/0300060520949077 sha: doc_id: 256020 cord_uid: wrui3i2l file: cache/cord-306755-9q1mawfs.json key: cord-306755-9q1mawfs authors: Rivière, Guillaume; Michaud, Annie; Corradi, Hazel R.; Sturrock, Edward D.; Ravi Acharya, K.; Cogez, Virginie; Bohin, Jean-Pierre; Vieau, Didier; Corvol, Pierre title: Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active date: 2007-09-01 journal: Gene DOI: 10.1016/j.gene.2007.05.010 sha: doc_id: 306755 cord_uid: 9q1mawfs file: cache/cord-296683-fjn29oal.json key: cord-296683-fjn29oal authors: Sarode, Sachin C; Sarode, Gargi S; Gondivkar, Shailesh; Gadbail, Amol; Gopalkrishnan, Dharmarajan; Patil, Shankargouda title: Oral submucous fibrosis and COVID-19: Perspective on comorbidity date: 2020-05-21 journal: Oral Oncol DOI: 10.1016/j.oraloncology.2020.104811 sha: doc_id: 296683 cord_uid: fjn29oal file: cache/cord-291146-f3e5ynhu.json key: cord-291146-f3e5ynhu authors: Sarangarajan, Rangaprasad; Winn, Robert; Kiebish, Michael A.; Bountra, Chas; Granger, Elder; Narain, Niven R. title: Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers date: 2020-09-08 journal: J Racial Ethn Health Disparities DOI: 10.1007/s40615-020-00853-0 sha: doc_id: 291146 cord_uid: f3e5ynhu file: cache/cord-295041-5vpawtef.json key: cord-295041-5vpawtef authors: Jakhmola, Shweta; Indari, Omkar; Chatterjee, Sayantani; Jha, Hem Chandra title: SARS-CoV-2, an Underestimated Pathogen of the Nervous System date: 2020-09-28 journal: SN Compr Clin Med DOI: 10.1007/s42399-020-00522-7 sha: doc_id: 295041 cord_uid: 5vpawtef file: cache/cord-319022-1twsxzcd.json key: cord-319022-1twsxzcd authors: Desai, Antonio; Voza, Giuseppe; Paiardi, Silvia; Teofilo, Francesca Ilaria; Caltagirone, Giuseppe; Pons, Marta Ripoll; Aloise, Monia; Kogan, Maria; Tommasini, Tobia; Savevski, Victor; Stefanini, Giulio; Angelini, Claudio; Ciccarelli, Michele; Badalamenti, Salvatore; De Nalda, Ana Lleo; Aghemo, Alessio; Cecconi, Maurizio; Boneschi, Filippo Martinelli; Voza, Antonio title: The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy() date: 2020-09-25 journal: Int J Cardiol DOI: 10.1016/j.ijcard.2020.09.062 sha: doc_id: 319022 cord_uid: 1twsxzcd file: cache/cord-315754-dq2empne.json key: cord-315754-dq2empne authors: Hasan, Anwarul; Paray, Bilal Ahamad; Hussain, Arif; Qadir, Fikry Ali; Attar, Farnoosh; Aziz, Falah Mohammad; Sharifi, Majid; Derakhshankhah, Hossein; Rasti, Behnam; Mehrabi, Masoumeh; Shahpasand, Koorosh; Saboury, Ali Akbar; Falahati, Mojtaba title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin date: 2020-04-22 journal: J Biomol Struct Dyn DOI: 10.1080/07391102.2020.1754293 sha: doc_id: 315754 cord_uid: dq2empne file: cache/cord-327697-80msva10.json key: cord-327697-80msva10 authors: Sarı, Cenk; Şimşek, Ersin Çağrı; Özdoğan, Öner title: The outcomes of the postulated interaction between SARS-CoV-2 and the renin-angiotensin system on the clinician’s attitudes toward hypertension treatment date: 2020-11-09 journal: J Hum Hypertens DOI: 10.1038/s41371-020-00436-w sha: doc_id: 327697 cord_uid: 80msva10 file: cache/cord-317878-bqpj0ey0.json key: cord-317878-bqpj0ey0 authors: Czick, Maureen; Shapter, Christine; Shapter, Robert title: COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19 date: 2020-09-11 journal: Diabetes Metab Syndr Obes DOI: 10.2147/dmso.s265518 sha: doc_id: 317878 cord_uid: bqpj0ey0 file: cache/cord-338417-7kw9lws0.json key: cord-338417-7kw9lws0 authors: Singh, Awadhesh Kumar; Gupta, Ritesh; Misra, Anoop title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers date: 2020-04-09 journal: Diabetes Metab Syndr DOI: 10.1016/j.dsx.2020.03.016 sha: doc_id: 338417 cord_uid: 7kw9lws0 file: cache/cord-326405-3446eyi3.json key: cord-326405-3446eyi3 authors: Wysocki, Jan; González-Pacheco, Francisco R.; Batlle, Daniel title: Angiotensin-converting enzyme 2: Possible role in hypertension and kidney disease date: 2008-02-07 journal: Curr Hypertens Rep DOI: 10.1007/s11906-008-0014-1 sha: doc_id: 326405 cord_uid: 3446eyi3 file: cache/cord-306739-4lokd97u.json key: cord-306739-4lokd97u authors: Gesierich, Wolfgang title: Sind ACE-Hemmer eher negativ oder doch von Vorteil bei COVID-19? date: 2020-07-14 journal: Pneumo News DOI: 10.1007/s15033-020-1857-7 sha: doc_id: 306739 cord_uid: 4lokd97u file: cache/cord-330093-asba80bi.json key: cord-330093-asba80bi authors: Leung, Janice M.; Sin, Don D. title: Smoking, ACE-2 and COVID-19: ongoing controversies date: 2020-07-16 journal: Eur Respir J DOI: 10.1183/13993003.01759-2020 sha: doc_id: 330093 cord_uid: asba80bi file: cache/cord-334490-42gykxdx.json key: cord-334490-42gykxdx authors: Kammerlander, Andreas A.; Mascherbauer, Julia title: COVID-19: frequently asked questions to the cardiologist date: 2020-07-24 journal: Wien Klin Wochenschr DOI: 10.1007/s00508-020-01696-9 sha: doc_id: 334490 cord_uid: 42gykxdx file: cache/cord-322966-o65fo853.json key: cord-322966-o65fo853 authors: Arnold, Ruth H. title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? date: 2020-05-25 journal: Heart Lung Circ DOI: 10.1016/j.hlc.2020.05.004 sha: doc_id: 322966 cord_uid: o65fo853 file: cache/cord-318327-9sh2eksm.json key: cord-318327-9sh2eksm authors: Garg, M.; Angus, P. W.; Burrell, L. M.; Herath, C.; Gibson, P. R.; Lubel, J. S. title: Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract date: 2012-01-05 journal: Aliment Pharmacol Ther DOI: 10.1111/j.1365-2036.2011.04971.x sha: doc_id: 318327 cord_uid: 9sh2eksm file: cache/cord-301546-yck1t3pp.json key: cord-301546-yck1t3pp authors: Kozaki, Toshinori; Kimmelblatt, Brian A.; Hamm, Ronda L.; Scott, Jeffrey G. title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date: 2007-12-28 journal: Arch Insect Biochem Physiol DOI: 10.1002/arch.20229 sha: doc_id: 301546 cord_uid: yck1t3pp file: cache/cord-332680-zfn81hew.json key: cord-332680-zfn81hew authors: Chan, Chieh-Kai; Huang, Yu-Shan; Liao, Hung-Wei; Tsai, I-Jung; Sun, Chiao-Yin; Pan, Heng-Chih; Chueh, Jeff S.; Wang, Jann-Tay; Wu, Vin-Cent; Chu, Tzong-Shinn title: Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis date: 2020-09-10 journal: Hypertension DOI: 10.1161/hypertensionaha.120.15989 sha: doc_id: 332680 cord_uid: zfn81hew file: cache/cord-353707-3n2nji8l.json key: cord-353707-3n2nji8l authors: Sunden-Cullberg, Jonas title: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death date: 2020-04-28 journal: Hypertension DOI: 10.1161/hypertensionaha.120.15178 sha: doc_id: 353707 cord_uid: 3n2nji8l file: cache/cord-269776-hj1s3ipp.json key: cord-269776-hj1s3ipp authors: Agostoni, Angelo; Aygören-Pürsün, Emel; Binkley, Karen E.; Blanch, Alvaro; Bork, Konrad; Bouillet, Laurence; Bucher, Christoph; Castaldo, Anthony J; Cicardi, Marco; Davis, Alvin E; De Carolis, Caterina; Drouet, Christian; Duponchel, Christiane; Farkas, Henriette; Fáy, Kálmán; Fekete, Béla; Fischer, Bettina; Fontana, Luigi; Füst, George; Giacomelli, Roberto; Gröner, Albrecht; Erik Hack, C.; Harmat, George; Jakenfelds, John; Juers, Mathias; Kalmár, Lajos; Kaposi, Pál N.; Karádi, István; Kitzinger, Arianna; Kollár, Tímea; Kreuz, Wolfhart; Lakatos, Peter; Longhurst, Hilary J.; Lopez-Trascasa, Margarita; Martinez-Saguer, Inmaculada; Monnier, Nicole; Nagy, István; Németh, Éva; Nielsen, Erik Waage; Nuijens, Jan H.; O'Grady, Caroline; Pappalardo, Emanuela; Penna, Vincenzo; Perricone, Carlo; Perricone, Roberto; Rauch, Ursula; Roche, Olga; Rusicke, Eva; Späth, Peter J; Szendei, George; Takács, Edit; Tordai, Attila; Truedsson, Lennart; Varga, Lilian; Visy, Beáta; Williams, Kayla; Zanichelli, Andrea; Zingale, Lorenza title: Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond date: 2004-09-11 journal: J Allergy Clin Immunol DOI: 10.1016/j.jaci.2004.06.047 sha: doc_id: 269776 cord_uid: hj1s3ipp file: cache/cord-326820-11sl17ap.json key: cord-326820-11sl17ap authors: Bousquet, Jean; Anto, Josep M.; Iaccarino, Guido; Czarlewski, Wienczyslawa; Haahtela, Tari; Anto, Aram; Akdis, Cezmi A.; Blain, Hubert; Canonica, G. Walter; Cardona, Victoria; Cruz, Alvaro A.; Illario, Maddalena; Ivancevich, Juan Carlos; Jutel, Marek; Klimek, Ludger; Kuna, Piotr; Laune, Daniel; Larenas-Linnemann, Désirée; Mullol, Joaquim; Papadopoulos, Nikos G.; Pfaar, Oliver; Samolinski, Boleslaw; Valiulis, Arunas; Yorgancioglu, Arzu; Zuberbier, Torsten title: Is diet partly responsible for differences in COVID-19 death rates between and within countries? date: 2020-05-27 journal: Clin Transl Allergy DOI: 10.1186/s13601-020-00323-0 sha: doc_id: 326820 cord_uid: 11sl17ap file: cache/cord-346811-gorp9n1g.json key: cord-346811-gorp9n1g authors: Hippisley-Cox, Julia; Young, Duncan; Coupland, Carol; Channon, Keith M; Tan, Pui San; Harrison, David A; Rowan, Kathryn; Aveyard, Paul; Pavord, Ian D; Watkinson, Peter J title: Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people date: 2020-07-31 journal: Heart DOI: 10.1136/heartjnl-2020-317393 sha: doc_id: 346811 cord_uid: gorp9n1g file: cache/cord-351567-ifoe8x28.json key: cord-351567-ifoe8x28 authors: Rabi, Firas A.; Al Zoubi, Mazhar S.; Kasasbeh, Ghena A.; Salameh, Dunia M.; Al-Nasser, Amjad D. title: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far date: 2020-03-20 journal: Pathogens DOI: 10.3390/pathogens9030231 sha: doc_id: 351567 cord_uid: ifoe8x28 file: cache/cord-302316-raf5rlkq.json key: cord-302316-raf5rlkq authors: Brüssow, Harald title: COVID‐19: From pathogenesis models to the first drug trials date: 2020-06-23 journal: Microb Biotechnol DOI: 10.1111/1751-7915.13611 sha: doc_id: 302316 cord_uid: raf5rlkq file: cache/cord-311099-59pnm4fn.json key: cord-311099-59pnm4fn authors: Lubel, John S; Herath, Chandana B; Burrell, Louise M; Angus, Peter W title: Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications date: 2008-06-28 journal: J Gastroenterol Hepatol DOI: 10.1111/j.1440-1746.2008.05461.x sha: doc_id: 311099 cord_uid: 59pnm4fn file: cache/cord-355807-q3bngari.json key: cord-355807-q3bngari authors: Yepes-Pérez, Andres F.; Herrera-Calderon, Oscar; Quintero-Saumeth, Jorge title: Uncaria tomentosa (cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling date: 2020-10-29 journal: Journal of biomolecular structure & dynamics DOI: 10.1080/07391102.2020.1837676 sha: doc_id: 355807 cord_uid: q3bngari file: cache/cord-346912-o09qmp7x.json key: cord-346912-o09qmp7x authors: Bayraktar, E.; Cohen, A.; Nellis, A. title: A Macroeconomic SIR Model for COVID-19 date: 2020-06-23 journal: nan DOI: 10.1101/2020.06.22.20137711 sha: doc_id: 346912 cord_uid: o09qmp7x file: cache/cord-314868-ei2b8oqn.json key: cord-314868-ei2b8oqn authors: Leung, J. M.; Yang, C. X.; Tam, A.; Shaipanich, T.; Hackett, T. L.; Singhera, G. K.; Dorscheid, D. R.; Sin, D. D. title: ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19 date: 2020-03-23 journal: medRxiv DOI: 10.1101/2020.03.18.20038455 sha: doc_id: 314868 cord_uid: ei2b8oqn file: cache/cord-352230-8mazd3eu.json key: cord-352230-8mazd3eu authors: Beeraka, Narasimha M.; Sadhu, Surya P.; Madhunapantula, SubbaRao V.; Rao Pragada, Rajeswara; Svistunov, Andrey A.; Nikolenko, Vladimir N.; Mikhaleva, Liudmila M.; Aliev, Gjumrakch title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 journal: Front Immunol DOI: 10.3389/fimmu.2020.552925 sha: doc_id: 352230 cord_uid: 8mazd3eu file: cache/cord-342786-dl8vjwfn.json key: cord-342786-dl8vjwfn authors: Sattar, Yasar; Ullah, Waqas; Rauf, Hiba; ul Hassan Virk, Hafeez; Yadav, Sunita; Chowdhury, Medhat; Connerney, Michael; Mamtani, Sahil; Pahuja, Mohit; Patel, Raj D.; Mir, Tanveer; Almas, Talal; Moussa Pacha, Homam; Chadi Alraies, M title: COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management date: 2020-07-14 journal: Int J Cardiol Heart Vasc DOI: 10.1016/j.ijcha.2020.100589 sha: doc_id: 342786 cord_uid: dl8vjwfn file: cache/cord-349445-yh6ndtgm.json key: cord-349445-yh6ndtgm authors: Mohammed El Tabaa, Manar; Mohammed El Tabaa, Maram title: Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost date: 2020-05-27 journal: Biochem Pharmacol DOI: 10.1016/j.bcp.2020.114057 sha: doc_id: 349445 cord_uid: yh6ndtgm Reading metadata file and updating bibliogrpahics === updating bibliographic database Building study carrel named keyword-ace-cord === file2bib.sh === id: cord-024076-q9fw7ch1 author: Manga, Pravin title: Should ACE Inhibitors and Angiotensin Receptor Blockers Be Withdrawn in the Current Setting of COVID-19 Infection? date: 2020-04-17 pages: extension: .txt txt: ./txt/cord-024076-q9fw7ch1.txt cache: ./cache/cord-024076-q9fw7ch1.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-024076-q9fw7ch1.txt' === file2bib.sh === id: cord-267519-a0bcmjkn author: Bravi, Francesca title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date: 2020-06-24 pages: extension: .txt txt: ./txt/cord-267519-a0bcmjkn.txt cache: ./cache/cord-267519-a0bcmjkn.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-267519-a0bcmjkn.txt' === file2bib.sh === id: cord-275837-2avxd80i author: Ahirwar, Ashok Kumar title: COVID -19 outbreak – Diabetes aspect and perspective date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-275837-2avxd80i.txt cache: ./cache/cord-275837-2avxd80i.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-275837-2avxd80i.txt' === file2bib.sh === id: cord-304742-ytf2ilw4 author: Albini, Adriana title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based antihypertensive therapies—reply date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-304742-ytf2ilw4.txt cache: ./cache/cord-304742-ytf2ilw4.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-304742-ytf2ilw4.txt' === file2bib.sh === id: cord-005931-iggkxbbf author: Phillips, M. Ian title: Brain renin angiotensin in disease date: 2008-04-02 pages: extension: .txt txt: ./txt/cord-005931-iggkxbbf.txt cache: ./cache/cord-005931-iggkxbbf.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-005931-iggkxbbf.txt' === file2bib.sh === id: cord-002468-onpmkjaz author: Roca-Ho, Heleia title: Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse date: 2017-03-05 pages: extension: .txt txt: ./txt/cord-002468-onpmkjaz.txt cache: ./cache/cord-002468-onpmkjaz.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-002468-onpmkjaz.txt' === file2bib.sh === id: cord-306739-4lokd97u author: Gesierich, Wolfgang title: Sind ACE-Hemmer eher negativ oder doch von Vorteil bei COVID-19? date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-306739-4lokd97u.txt cache: ./cache/cord-306739-4lokd97u.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-306739-4lokd97u.txt' === file2bib.sh === id: cord-296683-fjn29oal author: Sarode, Sachin C title: Oral submucous fibrosis and COVID-19: Perspective on comorbidity date: 2020-05-21 pages: extension: .txt txt: ./txt/cord-296683-fjn29oal.txt cache: ./cache/cord-296683-fjn29oal.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 2 resourceName b'cord-296683-fjn29oal.txt' === file2bib.sh === id: cord-282256-lqmixm7s author: Tsioufis, Costas title: The interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging data as the “Ariadne’s thread” for the “labyrinth” of COVID-19 date: 2020-05-22 pages: extension: .txt txt: ./txt/cord-282256-lqmixm7s.txt cache: ./cache/cord-282256-lqmixm7s.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-282256-lqmixm7s.txt' === file2bib.sh === id: cord-269151-r426u5dz author: Turner, Jeffrey M. title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? date: 2020-07-09 pages: extension: .txt txt: ./txt/cord-269151-r426u5dz.txt cache: ./cache/cord-269151-r426u5dz.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-269151-r426u5dz.txt' === file2bib.sh === id: cord-334490-42gykxdx author: Kammerlander, Andreas A. title: COVID-19: frequently asked questions to the cardiologist date: 2020-07-24 pages: extension: .txt txt: ./txt/cord-334490-42gykxdx.txt cache: ./cache/cord-334490-42gykxdx.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-334490-42gykxdx.txt' === file2bib.sh === id: cord-298515-5n7hxhbg author: Oarhe, Chinyere I. title: Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts date: 2015-02-09 pages: extension: .txt txt: ./txt/cord-298515-5n7hxhbg.txt cache: ./cache/cord-298515-5n7hxhbg.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-298515-5n7hxhbg.txt' === file2bib.sh === id: cord-264828-6w13xo2a author: Albini, Adriana title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies date: 2020-05-19 pages: extension: .txt txt: ./txt/cord-264828-6w13xo2a.txt cache: ./cache/cord-264828-6w13xo2a.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-264828-6w13xo2a.txt' === file2bib.sh === id: cord-001773-mqk0sx5n author: Lo, Chao-Sheng title: Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes date: 2015-08-01 pages: extension: .txt txt: ./txt/cord-001773-mqk0sx5n.txt cache: ./cache/cord-001773-mqk0sx5n.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-001773-mqk0sx5n.txt' === file2bib.sh === id: cord-327697-80msva10 author: Sarı, Cenk title: The outcomes of the postulated interaction between SARS-CoV-2 and the renin-angiotensin system on the clinician’s attitudes toward hypertension treatment date: 2020-11-09 pages: extension: .txt txt: ./txt/cord-327697-80msva10.txt cache: ./cache/cord-327697-80msva10.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-327697-80msva10.txt' === file2bib.sh === id: cord-353707-3n2nji8l author: Sunden-Cullberg, Jonas title: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death date: 2020-04-28 pages: extension: .txt txt: ./txt/cord-353707-3n2nji8l.txt cache: ./cache/cord-353707-3n2nji8l.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-353707-3n2nji8l.txt' === file2bib.sh === id: cord-326820-11sl17ap author: Bousquet, Jean title: Is diet partly responsible for differences in COVID-19 death rates between and within countries? date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-326820-11sl17ap.txt cache: ./cache/cord-326820-11sl17ap.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-326820-11sl17ap.txt' === file2bib.sh === id: cord-005927-a9sj00y8 author: Kondoh, Gen title: Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization date: 2005-01-23 pages: extension: .txt txt: ./txt/cord-005927-a9sj00y8.txt cache: ./cache/cord-005927-a9sj00y8.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-005927-a9sj00y8.txt' === file2bib.sh === id: cord-291146-f3e5ynhu author: Sarangarajan, Rangaprasad title: Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers date: 2020-09-08 pages: extension: .txt txt: ./txt/cord-291146-f3e5ynhu.txt cache: ./cache/cord-291146-f3e5ynhu.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-291146-f3e5ynhu.txt' === file2bib.sh === id: cord-002307-gk84fnb9 author: Kehoe, Patrick Gavin title: Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology date: 2016-11-25 pages: extension: .txt txt: ./txt/cord-002307-gk84fnb9.txt cache: ./cache/cord-002307-gk84fnb9.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-002307-gk84fnb9.txt' === file2bib.sh === id: cord-300850-59j1m2tm author: Peron, Jean Pierre Schatzmann title: Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) date: 2020-05-11 pages: extension: .txt txt: ./txt/cord-300850-59j1m2tm.txt cache: ./cache/cord-300850-59j1m2tm.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-300850-59j1m2tm.txt' === file2bib.sh === id: cord-301546-yck1t3pp author: Kozaki, Toshinori title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date: 2007-12-28 pages: extension: .txt txt: ./txt/cord-301546-yck1t3pp.txt cache: ./cache/cord-301546-yck1t3pp.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-301546-yck1t3pp.txt' === file2bib.sh === id: cord-319022-1twsxzcd author: Desai, Antonio title: The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy() date: 2020-09-25 pages: extension: .txt txt: ./txt/cord-319022-1twsxzcd.txt cache: ./cache/cord-319022-1twsxzcd.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-319022-1twsxzcd.txt' === file2bib.sh === id: cord-286638-bqxyb61p author: Singh, Awadhesh Kumar title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-286638-bqxyb61p.txt cache: ./cache/cord-286638-bqxyb61p.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-286638-bqxyb61p.txt' === file2bib.sh === id: cord-290148-6cxndab8 author: Rossi, Gian Paolo title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients date: 2020-04-06 pages: extension: .txt txt: ./txt/cord-290148-6cxndab8.txt cache: ./cache/cord-290148-6cxndab8.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-290148-6cxndab8.txt' === file2bib.sh === id: cord-005386-p37rw8dh author: Szolnoki, Zoltán title: Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke date: 2006 pages: extension: .txt txt: ./txt/cord-005386-p37rw8dh.txt cache: ./cache/cord-005386-p37rw8dh.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-005386-p37rw8dh.txt' === file2bib.sh === id: cord-330093-asba80bi author: Leung, Janice M. title: Smoking, ACE-2 and COVID-19: ongoing controversies date: 2020-07-16 pages: extension: .txt txt: ./txt/cord-330093-asba80bi.txt cache: ./cache/cord-330093-asba80bi.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-330093-asba80bi.txt' === file2bib.sh === id: cord-302316-raf5rlkq author: Brüssow, Harald title: COVID‐19: From pathogenesis models to the first drug trials date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-302316-raf5rlkq.txt cache: ./cache/cord-302316-raf5rlkq.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-302316-raf5rlkq.txt' === file2bib.sh === id: cord-314868-ei2b8oqn author: Leung, J. M. title: ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19 date: 2020-03-23 pages: extension: .txt txt: ./txt/cord-314868-ei2b8oqn.txt cache: ./cache/cord-314868-ei2b8oqn.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-314868-ei2b8oqn.txt' === file2bib.sh === id: cord-266755-y2lf7ssp author: Yehualashet, Awgichew Shewasinad title: ACEIs and ARBs and Their Correlation with COVID-19: A Review date: 2020-09-16 pages: extension: .txt txt: ./txt/cord-266755-y2lf7ssp.txt cache: ./cache/cord-266755-y2lf7ssp.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-266755-y2lf7ssp.txt' === file2bib.sh === id: cord-311099-59pnm4fn author: Lubel, John S title: Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications date: 2008-06-28 pages: extension: .txt txt: ./txt/cord-311099-59pnm4fn.txt cache: ./cache/cord-311099-59pnm4fn.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-311099-59pnm4fn.txt' === file2bib.sh === id: cord-315754-dq2empne author: Hasan, Anwarul title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin date: 2020-04-22 pages: extension: .txt txt: ./txt/cord-315754-dq2empne.txt cache: ./cache/cord-315754-dq2empne.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-315754-dq2empne.txt' === file2bib.sh === id: cord-346811-gorp9n1g author: Hippisley-Cox, Julia title: Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people date: 2020-07-31 pages: extension: .txt txt: ./txt/cord-346811-gorp9n1g.txt cache: ./cache/cord-346811-gorp9n1g.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-346811-gorp9n1g.txt' === file2bib.sh === id: cord-332680-zfn81hew author: Chan, Chieh-Kai title: Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis date: 2020-09-10 pages: extension: .txt txt: ./txt/cord-332680-zfn81hew.txt cache: ./cache/cord-332680-zfn81hew.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-332680-zfn81hew.txt' === file2bib.sh === id: cord-306755-9q1mawfs author: Rivière, Guillaume title: Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active date: 2007-09-01 pages: extension: .txt txt: ./txt/cord-306755-9q1mawfs.txt cache: ./cache/cord-306755-9q1mawfs.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-306755-9q1mawfs.txt' === file2bib.sh === id: cord-338417-7kw9lws0 author: Singh, Awadhesh Kumar title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers date: 2020-04-09 pages: extension: .txt txt: ./txt/cord-338417-7kw9lws0.txt cache: ./cache/cord-338417-7kw9lws0.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-338417-7kw9lws0.txt' === file2bib.sh === id: cord-259933-ggx4v0bz author: Dalan, Rinkoo title: The ACE-2 in COVID-19: Foe or Friend? date: 2020-04-27 pages: extension: .txt txt: ./txt/cord-259933-ggx4v0bz.txt cache: ./cache/cord-259933-ggx4v0bz.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-259933-ggx4v0bz.txt' === file2bib.sh === id: cord-289144-d6fgs8qg author: Sieńko, Jerzy title: COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients date: 2020-07-21 pages: extension: .txt txt: ./txt/cord-289144-d6fgs8qg.txt cache: ./cache/cord-289144-d6fgs8qg.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-289144-d6fgs8qg.txt' === file2bib.sh === id: cord-346912-o09qmp7x author: Bayraktar, E. title: A Macroeconomic SIR Model for COVID-19 date: 2020-06-23 pages: extension: .txt txt: ./txt/cord-346912-o09qmp7x.txt cache: ./cache/cord-346912-o09qmp7x.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-346912-o09qmp7x.txt' === file2bib.sh === id: cord-017585-0llgr357 author: Chappell, Mark C. title: Role of ACE, ACE2 and Neprilysin in the Kidney date: 2007 pages: extension: .txt txt: ./txt/cord-017585-0llgr357.txt cache: ./cache/cord-017585-0llgr357.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-017585-0llgr357.txt' === file2bib.sh === id: cord-351567-ifoe8x28 author: Rabi, Firas A. title: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far date: 2020-03-20 pages: extension: .txt txt: ./txt/cord-351567-ifoe8x28.txt cache: ./cache/cord-351567-ifoe8x28.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-351567-ifoe8x28.txt' === file2bib.sh === id: cord-006087-hynkb0a8 author: Acharya, K. Ravi title: Ace revisited: A new target for structure-based drug design date: 2003 pages: extension: .txt txt: ./txt/cord-006087-hynkb0a8.txt cache: ./cache/cord-006087-hynkb0a8.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-006087-hynkb0a8.txt' === file2bib.sh === id: cord-295041-5vpawtef author: Jakhmola, Shweta title: SARS-CoV-2, an Underestimated Pathogen of the Nervous System date: 2020-09-28 pages: extension: .txt txt: ./txt/cord-295041-5vpawtef.txt cache: ./cache/cord-295041-5vpawtef.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-295041-5vpawtef.txt' === file2bib.sh === id: cord-322966-o65fo853 author: Arnold, Ruth H. title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? date: 2020-05-25 pages: extension: .txt txt: ./txt/cord-322966-o65fo853.txt cache: ./cache/cord-322966-o65fo853.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-322966-o65fo853.txt' === file2bib.sh === id: cord-342786-dl8vjwfn author: Sattar, Yasar title: COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management date: 2020-07-14 pages: extension: .txt txt: ./txt/cord-342786-dl8vjwfn.txt cache: ./cache/cord-342786-dl8vjwfn.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-342786-dl8vjwfn.txt' === file2bib.sh === id: cord-326405-3446eyi3 author: Wysocki, Jan title: Angiotensin-converting enzyme 2: Possible role in hypertension and kidney disease date: 2008-02-07 pages: extension: .txt txt: ./txt/cord-326405-3446eyi3.txt cache: ./cache/cord-326405-3446eyi3.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-326405-3446eyi3.txt' === file2bib.sh === id: cord-266289-dkxhbmic author: Harrison, Charlotte title: ACE for all – a molecular perspective date: 2014-07-16 pages: extension: .txt txt: ./txt/cord-266289-dkxhbmic.txt cache: ./cache/cord-266289-dkxhbmic.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-266289-dkxhbmic.txt' === file2bib.sh === id: cord-289477-cjm7qhr4 author: Mueller, Sylvia title: Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α) date: 2005-04-25 pages: extension: .txt txt: ./txt/cord-289477-cjm7qhr4.txt cache: ./cache/cord-289477-cjm7qhr4.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-289477-cjm7qhr4.txt' === file2bib.sh === id: cord-256020-wrui3i2l author: Fadaka, Adewale Oluwaseun title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 pages: extension: .txt txt: ./txt/cord-256020-wrui3i2l.txt cache: ./cache/cord-256020-wrui3i2l.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-256020-wrui3i2l.txt' === file2bib.sh === id: cord-006082-x1kankxd author: Romero, Cesar A. title: Novel RAAS agonists and antagonists: clinical applications and controversies date: 2015-02-10 pages: extension: .txt txt: ./txt/cord-006082-x1kankxd.txt cache: ./cache/cord-006082-x1kankxd.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-006082-x1kankxd.txt' === file2bib.sh === id: cord-318327-9sh2eksm author: Garg, M. title: Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract date: 2012-01-05 pages: extension: .txt txt: ./txt/cord-318327-9sh2eksm.txt cache: ./cache/cord-318327-9sh2eksm.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-318327-9sh2eksm.txt' === file2bib.sh === id: cord-277766-rxmpi61o author: Guang, Cuie title: Three key proteases – angiotensin-I-converting enzyme (ACE), ACE2 and renin – within and beyond the renin-angiotensin system date: 2012-06-15 pages: extension: .txt txt: ./txt/cord-277766-rxmpi61o.txt cache: ./cache/cord-277766-rxmpi61o.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-277766-rxmpi61o.txt' === file2bib.sh === id: cord-352230-8mazd3eu author: Beeraka, Narasimha M. title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 pages: extension: .txt txt: ./txt/cord-352230-8mazd3eu.txt cache: ./cache/cord-352230-8mazd3eu.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-352230-8mazd3eu.txt' === file2bib.sh === id: cord-355807-q3bngari author: Yepes-Pérez, Andres F. title: Uncaria tomentosa (cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling date: 2020-10-29 pages: extension: .txt txt: ./txt/cord-355807-q3bngari.txt cache: ./cache/cord-355807-q3bngari.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-355807-q3bngari.txt' === file2bib.sh === id: cord-015859-5kt59ose author: Esch, Joep H.M. Van title: Local Angiotensin Generation and AT(2) Receptor Activation date: 2007 pages: extension: .txt txt: ./txt/cord-015859-5kt59ose.txt cache: ./cache/cord-015859-5kt59ose.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-015859-5kt59ose.txt' === file2bib.sh === id: cord-317878-bqpj0ey0 author: Czick, Maureen title: COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19 date: 2020-09-11 pages: extension: .txt txt: ./txt/cord-317878-bqpj0ey0.txt cache: ./cache/cord-317878-bqpj0ey0.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-317878-bqpj0ey0.txt' === file2bib.sh === id: cord-018009-8j40876m author: Campbell, Duncan J. John title: ACE Inhibition in Heart Failure and Ischaemic Heart Disease date: 2007 pages: extension: .txt txt: ./txt/cord-018009-8j40876m.txt cache: ./cache/cord-018009-8j40876m.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-018009-8j40876m.txt' === file2bib.sh === id: cord-349445-yh6ndtgm author: Mohammed El Tabaa, Manar title: Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost date: 2020-05-27 pages: extension: .txt txt: ./txt/cord-349445-yh6ndtgm.txt cache: ./cache/cord-349445-yh6ndtgm.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-349445-yh6ndtgm.txt' === file2bib.sh === id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 pages: extension: .txt txt: ./txt/cord-253862-jl1zhg13.txt cache: ./cache/cord-253862-jl1zhg13.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-253862-jl1zhg13.txt' === file2bib.sh === id: cord-016742-y7jgjera author: Bauer, Maria title: Cardiovascular Anatomy and Pharmacology date: 2017-07-03 pages: extension: .txt txt: ./txt/cord-016742-y7jgjera.txt cache: ./cache/cord-016742-y7jgjera.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-016742-y7jgjera.txt' === file2bib.sh === id: cord-286825-bu7j7kdr author: Macours, Nathalie title: Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes date: 2004-10-04 pages: extension: .txt txt: ./txt/cord-286825-bu7j7kdr.txt cache: ./cache/cord-286825-bu7j7kdr.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-286825-bu7j7kdr.txt' === file2bib.sh === id: cord-269776-hj1s3ipp author: Agostoni, Angelo title: Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond date: 2004-09-11 pages: extension: .txt txt: ./txt/cord-269776-hj1s3ipp.txt cache: ./cache/cord-269776-hj1s3ipp.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-269776-hj1s3ipp.txt' Que is empty; done keyword-ace-cord === reduce.pl bib === id = cord-005931-iggkxbbf author = Phillips, M. Ian title = Brain renin angiotensin in disease date = 2008-04-02 pages = extension = .txt mime = text/plain words = 4345 sentences = 257 flesch = 47 summary = Transgenic mice and rats bearing renin and extra copies of angiotensinogen genes revealed the importance of brain RAS. Taking the concept a step further, it was reasoned that if ANG II, formed by brain renin, was involved in hypertension, then inhibiting brain RAS would lower blood pressure. Minute injections of ANG II into key brain nuclei showed that ANG II could differentially produce pressor effects, elicit drinking, release vasopressin, inhibit the baroreflex, and increase sympathetic nervous system activity [20, 21] . In the double transgenic mice developed by Sigmund and colleagues [35] , to overexpress both human renin and human AGT so that they constantly have high ANG II levels, antisense to AT1R mRNA dramatically reduced the blood pressure. ACE-2, ANG (1-7), and Mas receptors are all localized in brain areas related to the control of cardiovascular function. cache = ./cache/cord-005931-iggkxbbf.txt txt = ./txt/cord-005931-iggkxbbf.txt === reduce.pl bib === id = cord-001773-mqk0sx5n author = Lo, Chao-Sheng title = Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes date = 2015-08-01 pages = extension = .txt mime = text/plain words = 4946 sentences = 361 flesch = 54 summary = AIMS/HYPOTHESIS: We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. RESULTS: Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1–7 receptor [MasR]) expression, and normalised urinary Ang 1–7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. We reported that insulin inhibits high glucose stimulation of rat renal Agt gene expression via two nuclear proteins-heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K)-that interact with the insulin-responsive element (IRE) in the Agt gene promoter [25] [26] [27] [28] , and that hnRNP F overexpression in RPTCs inhibits Agt gene expression and kidney hypertrophy in Akita Hnrnpf-Tg mice [29] . cache = ./cache/cord-001773-mqk0sx5n.txt txt = ./txt/cord-001773-mqk0sx5n.txt === reduce.pl bib === id = cord-269151-r426u5dz author = Turner, Jeffrey M. title = Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? date = 2020-07-09 pages = extension = .txt mime = text/plain words = 4595 sentences = 212 flesch = 42 summary = More recently, a number of indirect comparisons with pooled analysis of several randomized placebo control trials have been done to further elucidate whether ACE inhibitors and ARBs have differing effects on the risk of myocardial infarction [16] [17] [18] [19] . Finally, in the previously mentioned Bangalore paper, a separate meta-analysis of the only head to head trials between ACE inhibitors and ARBs also showed no difference in the risk for myocardial infarction or cardiovascular death between the two classes [16] . Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have resulted in significant improvements in outcomes related to congestive heart failure, cardiovascular disease, diabetes, stroke, and kidney disease. A meta-analysis reporting effects of angiotensinconverting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis cache = ./cache/cord-269151-r426u5dz.txt txt = ./txt/cord-269151-r426u5dz.txt === reduce.pl bib === id = cord-267519-a0bcmjkn author = Bravi, Francesca title = Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date = 2020-06-24 pages = extension = .txt mime = text/plain words = 3303 sentences = 144 flesch = 44 summary = AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5] [6] [7] [8] , and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9] [10] [11] [12] [13] [14] [15] [16] , some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thus the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17] [18] [19] . cache = ./cache/cord-267519-a0bcmjkn.txt txt = ./txt/cord-267519-a0bcmjkn.txt === reduce.pl bib === id = cord-002468-onpmkjaz author = Roca-Ho, Heleia title = Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse date = 2017-03-05 pages = extension = .txt mime = text/plain words = 5850 sentences = 370 flesch = 59 summary = In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. At cardiac level, there was a In serum samples, there was a significant increase of ACE2 activity in DB mice at early and late stages of diabetes as compared to CONT (p = 0.0003 and p = 0.0003, respectively) and insulin administration significantly decreased ACE2 activity in DB mice at early and late stages (p = 0.001 and p = 0.001, respectively) ( Figure 4a ). At cardiac level, there was a significant increase of ACE2 activity in DB mice in both early and late stages of DB as compared to CONT mice (p = 0.011 and p = 0.029, respectively), however, insulin administration did not modify this pattern (p = NS) (Figure 4b) . cache = ./cache/cord-002468-onpmkjaz.txt txt = ./txt/cord-002468-onpmkjaz.txt === reduce.pl bib === id = cord-005386-p37rw8dh author = Szolnoki, Zoltán title = Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke date = 2006 pages = extension = .txt mime = text/plain words = 3058 sentences = 168 flesch = 49 summary = title: Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke Our results demonstrate that ACE D/D and AT1R 1166C polymorphism were associated with the development of small-vessel ischemic stroke through a mutually facilitatory interplay between them. As both polymorphisms are associated with an enhanced activity of the angiotensin II-AT1R axis, we postulated at a clinical level, a synergistic effect between them as regards the evolution of ischemic stroke. A synergistic effect was found between the AT1R 1166C allele and the homozygous ACE D/D genotype in the small-vessel stroke subgroup (adjusted OR, 3.54; 95% CI, 1.88-7.16; p < 0.0005), the mixed vascular type (adjusted OR, 2.41; 95% CI, 1.2-5.1; p < 0.05), and the overall ischemic stroke group (adjusted OR, 2.42; 95% CI, 1.51-3.82; p < 0.005) ( Table 3 ). cache = ./cache/cord-005386-p37rw8dh.txt txt = ./txt/cord-005386-p37rw8dh.txt === reduce.pl bib === id = cord-016742-y7jgjera author = Bauer, Maria title = Cardiovascular Anatomy and Pharmacology date = 2017-07-03 pages = extension = .txt mime = text/plain words = 23159 sentences = 1335 flesch = 40 summary = The binding of an agonist to the adrenergic receptor replaces guanosine diphosphate (GDP) by guanosine triphosphate (GTP), and causes the α-subunit of the G-protein to break free from the β-γ complex, and act as a primary messenger: in beta receptors, it stimulates adenylate cyclase and triggers cyclic adenosine monophosphate (cAMP) production, which, as a second messenger in the process of signal transduction, activates its target kinases that phosphorylate regulator proteins and ultimately increases intracellular calcium levels. Their main anti-ischemic effects are due to their ability to reduce myocardial O 2 consumption by depressing contractility, decreasing heart rate and systemic afterload, and increasing O 2 supply by coronary and collateral vasodilation. Verapamil decreases the heart rate by depressing sinoatrial and AV-nodal activity (hence its utility in the treatment of supraventricular arrhythmias), lowers systemic blood pressure due to myocardial depression and peripheral vasodilation, and produces moderate coronary artery dilation (preferred in essential hypertension and vasospastic angina). cache = ./cache/cord-016742-y7jgjera.txt txt = ./txt/cord-016742-y7jgjera.txt === reduce.pl bib === id = cord-024076-q9fw7ch1 author = Manga, Pravin title = Should ACE Inhibitors and Angiotensin Receptor Blockers Be Withdrawn in the Current Setting of COVID-19 Infection? date = 2020-04-17 pages = extension = .txt mime = text/plain words = 1862 sentences = 90 flesch = 41 summary = The reports urging caution in the use of ACE inhibitors and ARBs for hypertension, diabetes and cardiovascular disease are based on laboratory data which found that SARS-CoV and COVID-19 virus binds to ACE 2 receptor which is found in the epithelial cells of the lung, kidney, intestine and blood vessels. Thus, a clear causal relationship between those with cardiovascular disease, hypertension, heart failure with reduced ejection fraction (HFrEF), and diabetes with chronic kidney disease (DCKD) on ACE inhibitors or ARB treatment and an increased risk of COVID-19 does not exist. In South Africa, hypertension, HFrEF and diabetes are common non-communicable diseases, and a significant proportion of patients are being treated with generic versions of ACE inhibitors or ARBs. There is extremely strong scientific evidence for the benefit of RAAS inhibition in patients with cardiovascular disease. cache = ./cache/cord-024076-q9fw7ch1.txt txt = ./txt/cord-024076-q9fw7ch1.txt === reduce.pl bib === id = cord-002307-gk84fnb9 author = Kehoe, Patrick Gavin title = Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology date = 2016-11-25 pages = extension = .txt mime = text/plain words = 6466 sentences = 347 flesch = 55 summary = METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. ACE-2 enzyme activity is reduced in Alzheimer's disease in association with increasing Aβ load and tau pathology ACE-2 activity was significantly reduced by approximately 50% in the mid-frontal cortex in AD compared with age-matched controls (P < 0.0001) (Fig. 1a) . Together, these data strongly suggest that reduced ACEFig. 2 Angiotensin-converting enzyme 2 (ACE-2) activity is reduced in association with apolipoprotein E (APOE) ε4 and ACE1 (rs1799752) indel polymorphism and increased in cerebral amyloid angiopathy (CAA). cache = ./cache/cord-002307-gk84fnb9.txt txt = ./txt/cord-002307-gk84fnb9.txt === reduce.pl bib === id = cord-286638-bqxyb61p author = Singh, Awadhesh Kumar title = Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations date = 2020-04-09 pages = extension = .txt mime = text/plain words = 4824 sentences = 281 flesch = 46 summary = The disease burden of coronavirus infectious disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) has been increasing continuously with more than a million confirmed patients and more than 45 thousand deaths globally [1] . Emerging data suggests that COVID-19 is common in patients with diabetes, hypertension, and cardiovascular disease (CVD), although the prevalence rate varied in different studies as well in country-wise data. Evolving data also suggest that patients of COVID-19 with diabetes are more often associated with severe or critical disease varying from 14 to 32% in different studies [15e18, 20, 22, 24] . Though there is limited data about the association of blood glucose levels with disease course in COVID-19 at present, data from other infections like SARS and influenza H1N1 has shown that patients with poor glycemic control have increased risk of complications and death [60, 61] . cache = ./cache/cord-286638-bqxyb61p.txt txt = ./txt/cord-286638-bqxyb61p.txt === reduce.pl bib === id = cord-298515-5n7hxhbg author = Oarhe, Chinyere I. title = Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts date = 2015-02-09 pages = extension = .txt mime = text/plain words = 5010 sentences = 273 flesch = 51 summary = We report here the findings that ACE-2 protein and enzyme activity are severely decreased by hyperoxia in human fetal lung fibroblast cultures. Figure 6 shows that the treatment of hyperoxia followed by normoxic recovery significantly increased ADAM17/TACE immunoreactive protein by threefold in the IMR90 cells (P < 0.05). IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), but in the presence or absence of the ADAM17/ TACE inhibitor TAPI-2. IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), but in the presence or absence of the ADAM17/ TACE inhibitor TAPI-2. IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), then were recovered for western blotting of ADAM17/TACE as described in Materials and Methods. cache = ./cache/cord-298515-5n7hxhbg.txt txt = ./txt/cord-298515-5n7hxhbg.txt === reduce.pl bib === id = cord-017585-0llgr357 author = Chappell, Mark C. title = Role of ACE, ACE2 and Neprilysin in the Kidney date = 2007 pages = extension = .txt mime = text/plain words = 7578 sentences = 336 flesch = 43 summary = Although the emergence of receptor subtypes distinguishes the distinct signaling pathways of Ang II and Ang-(1-7), the post-renin enzymes that form and degrade these peptides must be considered in lieu of the overall regulation of the functional RAAS within the kidney. ACE, angiotensin converting enzyme; EPs, endopeptidases; NEP, neprilysin demonstration of endogenous levels of the peptide in the kidney, circulation and other tissues (Nagata et al 2006) . Thus, in addition to the proximal tubule epithelium, the glomerulus may be a second key site within the kidney where ACE2 may influence the local expression of angiotensin peptides and renal function. There are few studies on the regulation of the Ang-(1-7) receptor, although chronic ACE or AT 1 blockade reduced mas mRNA expression in the renal cortex of the Ren2 Lewis congenic rat . cache = ./cache/cord-017585-0llgr357.txt txt = ./txt/cord-017585-0llgr357.txt === reduce.pl bib === id = cord-015859-5kt59ose author = Esch, Joep H.M. Van title = Local Angiotensin Generation and AT(2) Receptor Activation date = 2007 pages = extension = .txt mime = text/plain words = 9870 sentences = 499 flesch = 45 summary = Mice lacking the ren-1 d gene are characterized by sexually dimorphic hypotension (leading to a significant reduction of blood pressure in female mice), absence of dense secretory/storage granule formation in juxta-glomerular cells, altered morphology of the kidney, and a significant increase of plasma prorenin levels (Clark et al 1997) . Importantly, binding of (pro)renin to the (pro)renin receptor in human mesangial cells also induced Ang II-independent effects, such as an increase in DNA synthesis, activation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK)1 (p44)/ERK2 (p42), and plasminogenactivator inhibitor-1 release. AT 2 receptors are involved in physiological processes like development and tissue remodeling (by inhibiting cell growth and by stimulating apoptosis), regulation of blood pressure (vasodilatation), natriuresis and neuronal activity. In vitro studies using the isolated perfused rat Langendorff heart fully confirmed the idea of renin and angiotensinogen uptake underlying tissue angiotensin production. cache = ./cache/cord-015859-5kt59ose.txt txt = ./txt/cord-015859-5kt59ose.txt === reduce.pl bib === id = cord-005927-a9sj00y8 author = Kondoh, Gen title = Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization date = 2005-01-23 pages = extension = .txt mime = text/plain words = 4984 sentences = 257 flesch = 51 summary = We also assessed the effect of ACE-specific inhibitors, such as captopril and lisinopril, which bind to the catalytic center with ligation of its thiol to the zinc ion and completely inhibit the peptidase activity, but found only a minor inhibitory effect on the GPIase assay ( Fig. 1c , 1 × 10 -3 M captopril produced 40% inhibition and data not shown). We treated cells with ACE, PI-PLC or mouse glandular kallikrein (mGK), which digests EGFP protein near the carboxy termini (data not shown) and trapped the released products from the supernatants using antibody specific for GFP. We collected epididymal sperm from both wild-type and Ace knockout mice 33 and compared the distribution of GPI-anchored proteins in water-soluble and detergent-soluble fractions. In this regard, GPI-anchored proteins were not released in sperms of Ace knockout mice (Fig. 5a) . cache = ./cache/cord-005927-a9sj00y8.txt txt = ./txt/cord-005927-a9sj00y8.txt === reduce.pl bib === id = cord-291146-f3e5ynhu author = Sarangarajan, Rangaprasad title = Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers date = 2020-09-08 pages = extension = .txt mime = text/plain words = 4321 sentences = 212 flesch = 35 summary = The specificity of hypertension and cardiovascular disease as underlying causes for severity of COVID-19 infection, the inherent role of ACE-mediated generation of Ang-II and downstream signalling to potentially exacerbate inflammation and organ damage along with genotypic impact on ACE status provide compelling support of the use of ACE-I and ARBs in the clinical management of patient with positive diagnosis of COVID-19. The significant genetic, scientific and clinical data supporting a potential role for increased ACE levels and associated Ang-II effect in target organs provides compelling argument for use of ACE-I and ARBs in the clinical management of patients with COVID-19 infections to improve outcomes. In summary, this study describes the biological relevance of genetic polymorphism of ACE deletion with higher prevalence in certain ethnic populations including African Americans in context of COVID-19 infection and rationale for the use of ACE-I/ARBs for therapeutic management of severity of morbidity and improving outcomes associated with COVID-19. cache = ./cache/cord-291146-f3e5ynhu.txt txt = ./txt/cord-291146-f3e5ynhu.txt === reduce.pl bib === id = cord-282256-lqmixm7s author = Tsioufis, Costas title = The interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging data as the “Ariadne’s thread” for the “labyrinth” of COVID-19 date = 2020-05-22 pages = extension = .txt mime = text/plain words = 1847 sentences = 113 flesch = 49 summary = 4 The only available meta-analysis from Wuhan of 46248 cases, supports that hypertension constitutes the most prevalent comorbidity in 17% of patients infected with the novel coronavirus. In Italy the most current analysis shows that of 69.1% of the deceased patients were hypertensives and 30% used angiotensin converting enzyme inhibitors (ACEIs) and 17% angiotensin receptor blockers (ARBs). 18 After adjustment for confounders there was no independent association for the use of ACEIs/ARBs with susceptibility for infection or worse clinical outcome in contrast to loop diuretics that were linked to enhanced risk. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19 Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 cache = ./cache/cord-282256-lqmixm7s.txt txt = ./txt/cord-282256-lqmixm7s.txt === reduce.pl bib === id = cord-006087-hynkb0a8 author = Acharya, K. Ravi title = Ace revisited: A new target for structure-based drug design date = 2003 pages = extension = .txt mime = text/plain words = 8130 sentences = 386 flesch = 47 summary = Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. Some differences in catalytic properties have been observed for these two sites: the N-domain site is notably 50-times more active toward the haemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) 21 , 1000-times Here, we provide an overview of ACE and the RAS, current ACE inhibitors and their clinical utility, insights from the tACE crystal structure, and the rationale and prospects for developing second-generation, domainselective inhibitors by structure-guided design. BPF was a mixture of peptides 59 , which were shown to be potent and specific inhibitors of ACE (TABLE 1), and structure-activity studies indicated that the optimal C-terminal inhibitory sequence was Phe-Ala-Pro 60 . An important caveat in considering the design and pharmacological utility of domain-selective ACE inhibitors is the potential for conformational effects that have not yet been observed in the tACE crystal structure. cache = ./cache/cord-006087-hynkb0a8.txt txt = ./txt/cord-006087-hynkb0a8.txt === reduce.pl bib === id = cord-275837-2avxd80i author = Ahirwar, Ashok Kumar title = COVID -19 outbreak – Diabetes aspect and perspective date = 2020-05-19 pages = extension = .txt mime = text/plain words = 578 sentences = 49 flesch = 53 summary = Diabetes increases the risk of pneumonia in COVID-19 infected individual and it is an important risk factor for adverse outcome. ACE inhibitor and Angiotensin II Receptor Blockers (ARBs) are the few of drugs used for the appropriate management of diabetic patients. All these may lead to increased severity of COVID-19 infection in diabetic individuals. [4] Moreover, genetic polymorphism of ACE receptor has been shown to be linked with diabetes and it might also facilitate COVID-19 infections. [4] On contrary to this, some researchers say that use of ACE inhibitor or ARBs prevents the binding of COVID-19 virus to ACE receptor and thus may prevent infection. [5] All these are the lacunae in the existing knowledge of ACE inhibitor or ARBs use in diabetic individuals. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? cache = ./cache/cord-275837-2avxd80i.txt txt = ./txt/cord-275837-2avxd80i.txt === reduce.pl bib === id = cord-277766-rxmpi61o author = Guang, Cuie title = Three key proteases – angiotensin-I-converting enzyme (ACE), ACE2 and renin – within and beyond the renin-angiotensin system date = 2012-06-15 pages = extension = .txt mime = text/plain words = 9497 sentences = 476 flesch = 43 summary = In a classical RAS, the substrate angiotensinogen (AGT), which is released into the circulation from the liver, is degraded by the enzyme renin that originates in the kidney, generating the inactive angiotensin I (Ang I). The initial drug development of clinical ACE inhibitors was based on the assumption of an active site related to that of carboxypeptidase A but organized to remove a dipeptide rather than a single amino acid from the Cterminus of its substrate. The protective role of XNT against hypertension-induced cardiac fibrosis is associated with activation of ACE2, increases in Ang-(1-7) and inhibition of extracellular signal-regulated kinases [83] . The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensinconverting enzyme The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases cache = ./cache/cord-277766-rxmpi61o.txt txt = ./txt/cord-277766-rxmpi61o.txt === reduce.pl bib === id = cord-306755-9q1mawfs author = Rivière, Guillaume title = Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active date = 2007-09-01 pages = extension = .txt mime = text/plain words = 5364 sentences = 301 flesch = 52 summary = Interestingly, in silico databank analysis revealed that bacterial DNA sequences could encode putative ACE-like proteins, strikingly similar to vertebrates' enzymes. Interestingly, and though in silico evidence suggest the presence of a two-domain ACE-related protein in mosquitoes (Burnham et al., 2005) , all the cloned genes encode soluble, single active site enzymes (Tatei et al., 1995; Taylor et al., 1996; Wijffels et al., 1996) . The protein encoded by this gene, referred to as XcACE (Xanthomonas citri angiotensin-converting enzyme), is a 672 amino-acid protein. Key active site residues such as the zinc-binding motif, His 513 and Tyr 526 (tACE numbering) are conserved in XcACE and many other ACE-like enzymes. However, in line with the assay results, the non-conserved active site residues are neither identical to the C-or N-domain of human ACE, and are the presumed cause of the different substrate selectivity and inhibition profile of XcACE. Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme cache = ./cache/cord-306755-9q1mawfs.txt txt = ./txt/cord-306755-9q1mawfs.txt === reduce.pl bib === id = cord-351567-ifoe8x28 author = Rabi, Firas A. title = SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far date = 2020-03-20 pages = extension = .txt mime = text/plain words = 5745 sentences = 315 flesch = 54 summary = However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. To assess the magnitude of the risk posed by the SARS-CoV-2, we review four parameters that we believe important: the transmission rate, the incubation period, the case fatality rate (CFR), and the determination of whether asymptomatic transmission can occur. A small study of 17 patients showed that nasal viral load peaks within days of symptom onset, suggesting that transmission of disease is more likely to occur early in the course of infection [40] . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19)-China 2020 Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia cache = ./cache/cord-351567-ifoe8x28.txt txt = ./txt/cord-351567-ifoe8x28.txt === reduce.pl bib === id = cord-319022-1twsxzcd author = Desai, Antonio title = The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy() date = 2020-09-25 pages = extension = .txt mime = text/plain words = 2874 sentences = 132 flesch = 47 summary = BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. As for today, there are discordant results regarding the use of either angiotensin converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) as for their possible impact on COVID-19 mortality. We found that ACE-I, which acts by inhibiting the conversion from angiotensin I to angiotensin II, showed a trend in protecting from mortality from COVID-19 and was significant in delaying mortality as shown by multivariate Cox regression analysis unlike ARBs, which antagonize the effects of angiotensin II on its receptors 2,3 . Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 cache = ./cache/cord-319022-1twsxzcd.txt txt = ./txt/cord-319022-1twsxzcd.txt === reduce.pl bib === id = cord-006082-x1kankxd author = Romero, Cesar A. title = Novel RAAS agonists and antagonists: clinical applications and controversies date = 2015-02-10 pages = extension = .txt mime = text/plain words = 8412 sentences = 448 flesch = 42 summary = Despite the important improvements achieved with these agents in slowing the progression of established cardiorenal disease, the ACE inhibitors and the ARBs only provide a 20% reduction in the relative risk of Key points ■ Renin-angiotensin-aldosterone system (RAAS) blockade with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker provides a 20% relative risk reduction for the progression of established cardiorenal disease compared with other non-RAAS blocking therapies ■ The RAAS is an endocrine, paracrine and autocrine system that regulates blood pressure homeostasis through effects on a variety of target organs, as well as having a role in the responses to vascular injury and repair ■ The RAAS is a complex system with a variety of sites suitable for pharmacological intervention ■ Novel molecules that alter the production of various RAAS peptides or that alter receptor density, function or responsiveness to these peptides could have an important influence on haemodynamics and vascular structure and function www.nature.com/nrendo progression of cardiovascular disease when compared with non-RAAS blocking therapy. cache = ./cache/cord-006082-x1kankxd.txt txt = ./txt/cord-006082-x1kankxd.txt === reduce.pl bib === id = cord-259933-ggx4v0bz author = Dalan, Rinkoo title = The ACE-2 in COVID-19: Foe or Friend? date = 2020-04-27 pages = extension = .txt mime = text/plain words = 4187 sentences = 225 flesch = 44 summary = The SARS-CoV-2, a positive strand RNA virus, has been seen to infect humans through the angiotensin converting enzyme -2 (ACE-2) receptor [9] . In individuals with hypertension, diabetes, and other cardiovascular disorders with vascular complications, the renin angiotensin system (RAS) is known to be activated with an increase in ACE activity and a downregulation of ACE-2. Therefore, it may be assumed that the inherent downregulation of the ACE-2-Ang-(1-7)-Mas axis (as seen in metabolic conditions) is exacerbated in the COVID-19 state because (i) the virus uses the peptidase domain of the enzyme for entry into the cells and (ii) there is a decrease in ACE-2 with an increase in ACE [9] . Individuals with underlying hypertension, type 2 diabetes, or cardiovascular disease are at higher risk for respiratory failure and mortality in COVID-19. cache = ./cache/cord-259933-ggx4v0bz.txt txt = ./txt/cord-259933-ggx4v0bz.txt === reduce.pl bib === id = cord-289477-cjm7qhr4 author = Mueller, Sylvia title = Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α) date = 2005-04-25 pages = extension = .txt mime = text/plain words = 7062 sentences = 388 flesch = 46 summary = Synthetic analogues of the bradykinin potentiating nonapeptide BPP(9α) indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). As initial experimentation on the potentiation of the bradykinin action was primarily performed on isolated smooth muscle organs, in the last decade the potentiating activity was mainly investigated on the affinity and density of the receptor [54] , the intracellular mobilization of Ca 2+ [49, 54] , the release of arachidonic acid [49, 54] , of inositol phosphates [54] , and of nitric oxide [37] . Table 1 Analogues of the bradykinin potentiating peptide BPP 9␣ (TEPROTIDE) with distinct differences between potentiation of the BK-induced contraction of the isolated guinea pig ileum (GPI) and inhibition of the isolated angiotensin I-converting enzyme (ACE) cache = ./cache/cord-289477-cjm7qhr4.txt txt = ./txt/cord-289477-cjm7qhr4.txt === reduce.pl bib === id = cord-300850-59j1m2tm author = Peron, Jean Pierre Schatzmann title = Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) date = 2020-05-11 pages = extension = .txt mime = text/plain words = 3267 sentences = 171 flesch = 44 summary = Toward this, we raise two main points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. Toward this, we raise two main points of discussion, i) the increased angiotensin-converting enzyme-2 (ACE-2) expression in pulmonary and heart tissues of hypertensive patients with chronic use of AT1R blockers and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. SARS-CoV-2 spike proteins bind to angiotensin-converting enzyme-2 (ACE-2), which is expressed in the epithelial cells of the lungs (8, 9) . We believe that i) increased expression of ACE-2 in hypertensive patients being treated with ACE inhibitors and AT1R blockers and ii) previous exposure to circulating coronaviruses with low neutralizing capacity to SARS-CoV-2 may greatly contribute to the increased susceptibility of the elderly patients to COVID-19. cache = ./cache/cord-300850-59j1m2tm.txt txt = ./txt/cord-300850-59j1m2tm.txt === reduce.pl bib === id = cord-286825-bu7j7kdr author = Macours, Nathalie title = Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes date = 2004-10-04 pages = extension = .txt mime = text/plain words = 17576 sentences = 876 flesch = 47 summary = Because this peptide has been found to be an in vivo substrate specific for the N domain of sACE, it is suggested that ACE is implicated in the process of hematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor (Azizi et al., 2001; Rousseau et al., 1995) . At present mammalian M13 family of zinc proteases consists of seven known members: neutral endopeptidase (NEP); the endothelin-converting enzymes ECE-1, ECE-2, and ECE-3; the Kell blood group antigen (Kell); the phosphate regulating gene (PEX); X-converting enzyme (XCE); and secreted endopeptidase (SEP). Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme Peptidyl dipeptidases (Ance and Acer) of Drosophila melanogaster: Major diVerences in the substrate specificity of two homologs of human angiotensin I-converting enzyme cache = ./cache/cord-286825-bu7j7kdr.txt txt = ./txt/cord-286825-bu7j7kdr.txt === reduce.pl bib === id = cord-301546-yck1t3pp author = Kozaki, Toshinori title = Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date = 2007-12-28 pages = extension = .txt mime = text/plain words = 2505 sentences = 152 flesch = 52 summary = title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. The alignment of this gene with the Drosophila Ace paralogous AChEs showed that, as expected for an insecticide-susceptible strain, beetles from the Denmark-S strain had an organophosphate and carbamate sensitive type. The Drosophila Ace orthologous gene, AdAce1, was sequenced from two susceptible Denmark-S, four Waycross (tetrachlorvinphos-resistant), and two Kennebec (tetrachlorvinphos-resistant) adults. diaperinus is not due to mutations in the Ace genes (i.e., is not an altered acetylcholinesterase).Alignments of the deduced amino acid sequences from the Drosophila Ace orthologous and paralogous genes in Coleoptera are shown in Figures 4 and 5, respectively. cache = ./cache/cord-301546-yck1t3pp.txt txt = ./txt/cord-301546-yck1t3pp.txt === reduce.pl bib === id = cord-334490-42gykxdx author = Kammerlander, Andreas A. title = COVID-19: frequently asked questions to the cardiologist date = 2020-07-24 pages = extension = .txt mime = text/plain words = 1739 sentences = 96 flesch = 36 summary = The specific causes of troponin rise in COVID-19 in patients without cardiac conditions, such as acute coronary syndrome (ACS), aortic stenosis, hypertrophic cardiomyopathy, and tachycardia A. Cardiac injury, defined as elevated troponin levels, is frequently observed in patients with COVID-19. The European Association of Percutaneous Cardiovascular Interventions (EAPCI) issued a position statement on invasive management in patients with ACS during the COVID-19 pandemic [19] . The EAPCI recommends that in cases of mild troponin elevation (<2-3 times the upper limit of normal), particularly in older patients with pre-existing cardiac conditions, a work-up for type 1 MI is not indicated, unless strongly indicated by clinical presentation and electrocardiograph (ECG) findings. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Association of Renin-Angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for Coronavirus disease 2019 (COVID-19) infection in Wuhan, China cache = ./cache/cord-334490-42gykxdx.txt txt = ./txt/cord-334490-42gykxdx.txt === reduce.pl bib === id = cord-290148-6cxndab8 author = Rossi, Gian Paolo title = Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients date = 2020-04-06 pages = extension = .txt mime = text/plain words = 3145 sentences = 156 flesch = 46 summary = The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARSCoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). However, they differ markedly: ACE-1 cleaves the dipeptide His-Leu from angiotensin I, thus generating angiotensin (Ang) II, which causes vaso-and broncho-constriction, increases vascular permeability, inflammation, and fibrosis and thereby promotes the development of ARDS and lung failure in patients infected with the SARS-CoV and SARS-CoV-2 (Yang et al., 2015) (Figure 1, panel B) . In one commentary ACE-2 was suggested to be secreted at higher amounts in patients with cardiovascular disease than in healthy individuals, and in another, it was also stated that 'ACE-2 levels can be increased by the use of ACEIs' , albeit no evidence of this occurring in the lungs Mechanisms of COVID-19 by which the SARS-COV-2 virus infects the lower airway cells and modalities to increase circulating soluble ACE-2 for therapeutic use. cache = ./cache/cord-290148-6cxndab8.txt txt = ./txt/cord-290148-6cxndab8.txt === reduce.pl bib === id = cord-327697-80msva10 author = Sarı, Cenk title = The outcomes of the postulated interaction between SARS-CoV-2 and the renin-angiotensin system on the clinician’s attitudes toward hypertension treatment date = 2020-11-09 pages = extension = .txt mime = text/plain words = 3552 sentences = 180 flesch = 46 summary = Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). In the first half of 2020, it was speculated that angiotensinconverting enzyme inhibitors (ACE-i)/angiotensin receptor blockers (ARBs) may make patients more susceptible to COVID-19 disease and lead to worse outcomes. Observational studies have reported that patients taking ACE-i/ARBs treatment are at increased risk of becoming infected with SARS-CoV2 and developing severe forms of COVID-19 disease. The strategy for repeating therapy was the same in all physicians, and the practice of starting new ACE-i/ARBs reported by the cardiologists was statistically different from that of both internal medicine and family medicine/general practitioners (8.0 ± 4 vs 8.0 ± 4 vs 9.0 ± 3, p < 0.05) ( Table 2) . The present survey is the first study to have provided a snapshot showing behaviors of Turkish physicians toward prescribing ACE-i/ARBs treatment during the COVID-19 pandemic. cache = ./cache/cord-327697-80msva10.txt txt = ./txt/cord-327697-80msva10.txt === reduce.pl bib === id = cord-311099-59pnm4fn author = Lubel, John S title = Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications date = 2008-06-28 pages = extension = .txt mime = text/plain words = 7730 sentences = 401 flesch = 44 summary = Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. 42 A great deal of evidence supporting the role of the RAS in hepatic fibrosis has come from animal studies using ACE inhibitors and angiotensin receptor blockers (ARB). A pilot study examining the effects of 6 months of losartan treatment on liver fibrosis in chronic hepatitis C demonstrated a significant decrease in fibrosis stage in the treated group compared to control patients. cache = ./cache/cord-311099-59pnm4fn.txt txt = ./txt/cord-311099-59pnm4fn.txt === reduce.pl bib === id = cord-304742-ytf2ilw4 author = Albini, Adriana title = The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based antihypertensive therapies—reply date = 2020-07-14 pages = extension = .txt mime = text/plain words = 1187 sentences = 52 flesch = 41 summary = The transmembrane protease serine 2 TMPRSS2, an androgendependent enzyme, acts in reinforcing the ACE-2 receptor activity in allowing cell entry to a number of viral pathogens as well as to SARS-CoV-2 as reported in our Point of View [2] . Yet in trisomy 21 individuals a TMPRSS2 protease overexpression has been documented, as mentioned in the comment of Dr De Cauwer [1] , with this leading to an increased viral infection's rate of susceptible host's cells and tissues. In conclusion, the interesting comment by Dr De Cauwer points out the complex interactions between ACE-2 and TMPRSS2 with reference to the clinical course of CoViD-19 as well as to SARS-CoV-2 infection's pathogenic evolution and severity degree in given population segments of infected individuals, like male individuals and Down syndromeaffected patients [1] . The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACEinhibitor-and angiotensin II receptor blocker-based cardiovascular therapies: comment The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor-and angiotensin II receptor blocker-based cardiovascular therapies cache = ./cache/cord-304742-ytf2ilw4.txt txt = ./txt/cord-304742-ytf2ilw4.txt === reduce.pl bib === id = cord-302316-raf5rlkq author = Brüssow, Harald title = COVID‐19: From pathogenesis models to the first drug trials date = 2020-06-23 pages = extension = .txt mime = text/plain words = 6944 sentences = 350 flesch = 44 summary = US researchers studied the viral and cellular transcriptional response upon infection of cell cultures and in animal models with different respiratory viruses including influenza A virus and SARS-CoV-2. A French study randomizing 181 COVID-19 patients with pneumonia on hydroxychloroquine or placebo, observed, however, no significant effect of treatment on transfer to ICU, mortality, or in the prevention of development of acute respiratory distress syndrome (Mah evas et al., 2020). A total of 86 COVID-19 cases of patients from China with mild/moderate disease were randomized on the antiviral lopinavir (an inhibitor of HIV protease combined with ritonavir, which prolongs the presence of drugs in the body) or the antiviral arbidol (an influenza virus fusion inhibitor only registered in Russia) or in a control group in a 2:2:1 ratio. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial cache = ./cache/cord-302316-raf5rlkq.txt txt = ./txt/cord-302316-raf5rlkq.txt === reduce.pl bib === id = cord-346811-gorp9n1g author = Hippisley-Cox, Julia title = Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people date = 2020-07-31 pages = extension = .txt mime = text/plain words = 5104 sentences = 275 flesch = 50 summary = We report a large, population-based study where we examined the drug histories of approximately 20% of all patients tested positive for coronavirus in England to determine if there was an independent association between ACE inhibitor and ARB drug prescription and severe COVID-19 disease susceptibility and progression. We extracted data from the GP record for explanatory and potential confounding variables including variables with some evidence of being risk factors for COVID-19 disease or severe disease as measured by ICU admission and variables likely to influence prescribing of ACE inhibitors and ARB medications. In this very large population-based study, ACE inhibitor and ARB prescriptions were associated with a reduced risk of COVID-19 RT-PCR positive disease, having adjusted for a wide range of demographic factors, potential comorbidities and other medication. 11 In our study, prior prescription of ACE inhibitor and ARB drugs did not have a significant effect on the risk of patients developing COVID-19 disease severe enough to require ICU care. cache = ./cache/cord-346811-gorp9n1g.txt txt = ./txt/cord-346811-gorp9n1g.txt === reduce.pl bib === id = cord-322966-o65fo853 author = Arnold, Ruth H. title = COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? date = 2020-05-25 pages = extension = .txt mime = text/plain words = 5415 sentences = 239 flesch = 44 summary = title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? ABSTRACT Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Debate has arisen due to the finding that underlying cardiovascular disease and hypertension are associated with significantly increased risk of hospitalisation and death in COVID-19 [1, 2] , in addition to the viral receptor being angiotensin-converting enzyme-2 (ACE-2) [3 -5] . Association of renin-angiotensin system inhibitorswith severity or risk of death in patients with hypertension hospitalised for coronavirus disease 19 (COVID-19) infection in Wuhan, China cache = ./cache/cord-322966-o65fo853.txt txt = ./txt/cord-322966-o65fo853.txt === reduce.pl bib === id = cord-346912-o09qmp7x author = Bayraktar, E. title = A Macroeconomic SIR Model for COVID-19 date = 2020-06-23 pages = extension = .txt mime = text/plain words = 6788 sentences = 410 flesch = 63 summary = We develop an SIR model of the COVID-19 pandemic which explicitly considers herd immunity, behavior-dependent transmission rates, remote workers, and indirect externalities of lockdown. Additionally, if we incorporate a behavior-dependent transmission rate which represents increased personal caution in response to increased infection levels, both output loss and total mortality are lowered. Overall, our model predicts that a lockdown which ends at the arrival of herd immunity, combined with individual actions to slow virus transmission, can reduce total mortality to one-third of the no-lockdown level, while allowing high-risk individuals to leave lockdown well before vaccine arrival. • Increasing the level of remote work reduces the impact of COVID-19 by decreasing both mortality and output loss, even though a longer lockdown is imposed. Recreation of [Ace+20] model (two groups and no herd immunity), parameters from Table 1 Output Loss: 8.9676%, Total Deaths: 1.3121% All rights reserved. cache = ./cache/cord-346912-o09qmp7x.txt txt = ./txt/cord-346912-o09qmp7x.txt === reduce.pl bib === id = cord-266289-dkxhbmic author = Harrison, Charlotte title = ACE for all – a molecular perspective date = 2014-07-16 pages = extension = .txt mime = text/plain words = 9060 sentences = 505 flesch = 58 summary = The involvement of ACE in processes outside of blood pressure regulation, and in particular the differences in substrate specificity of the two domains of sACE highlight the growing need for a new generation of ACE inhibitors. Interestingly, the two residues that differ; Arg381/Glu403 and Tyr369/Phe391 are located in the S 2 subsite (Fig. 5d ), further illustrating that interactions between the enzyme and inhibitors at this site are an important determinant of domain selectivity. The N domain of human angiotensin-I-converting enzyme: the role of Nglycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407 The structure of testis angiotensin-converting enzyme in complex with the C domain-specific inhibitor RXPA380 cache = ./cache/cord-266289-dkxhbmic.txt txt = ./txt/cord-266289-dkxhbmic.txt === reduce.pl bib === id = cord-264828-6w13xo2a author = Albini, Adriana title = The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies date = 2020-05-19 pages = extension = .txt mime = text/plain words = 3662 sentences = 172 flesch = 40 summary = Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. 4. Renin-angiotensin-aldosterone system (RAAS)-interfering drugs are likely to affect ACE-2 receptor-SARS-CoV-2 interaction dynamics within lung, heart, vascular, kidney and gut tissues [5, 19] , while it is still not completely elucidated how such interactions are relevant to the clinical course of cardiovascular comorbidities in patients with COVID-19 [29] . Consequently, the up-regulation of human ACE-2 induced by RAAS-antagonists in SARS-CoV-2-infected patients could be clinically useful, due to the cardiovascular protection elicited by the increased activity of angiotensin(1-7), thereby attenuating angiotensin II effects on vasoconstriction and sodium retention [31, 34] . cache = ./cache/cord-264828-6w13xo2a.txt txt = ./txt/cord-264828-6w13xo2a.txt === reduce.pl bib === id = cord-352230-8mazd3eu author = Beeraka, Narasimha M. title = Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date = 2020-09-18 pages = extension = .txt mime = text/plain words = 9394 sentences = 543 flesch = 40 summary = Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. COVID-19 is a devastating disease caused by a coronavirus related to the one that caused outbreaks of Severe Acute Respiratory Syndrome (SARS) in the year 2002 (1, 2) . cache = ./cache/cord-352230-8mazd3eu.txt txt = ./txt/cord-352230-8mazd3eu.txt === reduce.pl bib === id = cord-306739-4lokd97u author = Gesierich, Wolfgang title = Sind ACE-Hemmer eher negativ oder doch von Vorteil bei COVID-19? date = 2020-07-14 pages = extension = .txt mime = text/plain words = 364 sentences = 48 flesch = 58 summary = Bei COVID-19 wird neben der meist vorherrschenden akuten Lungenschädigung (ARDS) auch eine relevante Rate an myokardialen Schäden (Anstieg von Troponin) und akutem Nierenversagen beobachtet. Bereits aus der Zeit von SARS gibt es experimentelle Daten, die eine entsprechende Interaktion zwischen SARS-CoV-1 und dem RAAS belegen [2] . Ebenso gibt es experimentelle Studien, die einen krankheitsfördernden Effekt einer RAAS-Aktivierung bei ARDS nicht infektiöser Genese nahelegen [3] . Die dargestellten britischen Daten dürfen als erstes Signal gewertet werden, dass ACE-Hemmer auch bei COVID-19 einen günstigen Effekt auf den Krankheitsverlauf haben könnten. Weitere klinische Studien sind also dringend erforderlich, bevor den ACE-Hemmern ein therapeutischer Effekt bei COVID-19 zugeschrieben werden kann. Vorerst darf folgendes Fazit gezogen werden, das von nationalen und internationalen Fachgesellschaften unterstützt wird: Eine vorbestehende Therapie mit einem ACE-Hemmer, die für Patienten mit kardiovaskulären Erkrankungen und Diabetes mellitus einen relevanten organprotektiven und damit prognostischen Wert hat, sollte in der aktuellen Pandemie-Situation und insbesondere bei Diagnose einer SARS-CoV-2-Infektion nicht abgesetzt werden. cache = ./cache/cord-306739-4lokd97u.txt txt = ./txt/cord-306739-4lokd97u.txt === reduce.pl bib === id = cord-317878-bqpj0ey0 author = Czick, Maureen title = COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19 date = 2020-09-11 pages = extension = .txt mime = text/plain words = 12676 sentences = 811 flesch = 45 summary = Silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, olfactory loss, myocarditis, and increased mortality rates in the elderly, in men, in African-Americans, and in patients with obesity, diabetes, and cancer—all bear the fingerprints of the renin-angiotensin system (RAS) imbalance, suggesting that RAS is the common culprit. Subpopulations manifesting higher rates of COVID-19 mortality-including hypertensives, the elderly, the obese, diabetics, men, and African-Americans-correlate with preexisting RAS imbalance, with ACE overactivity and/or ACE2 underactivity priming these patients for more severe COVID-19 outcomes. 159 Males generally have higher levels of RAS than premenopausal females, 160 perhaps explaining why male hypertensive rats show a greater blood pressure decrease with ACEIs. 161 Estrogen downregulates the expression of the AT1 gene 162, 163 and suppresses both ROS production in vascular smooth muscle and the enzymatic activity of ACE. cache = ./cache/cord-317878-bqpj0ey0.txt txt = ./txt/cord-317878-bqpj0ey0.txt === reduce.pl bib === id = cord-269776-hj1s3ipp author = Agostoni, Angelo title = Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond date = 2004-09-11 pages = extension = .txt mime = text/plain words = 49824 sentences = 2688 flesch = 44 summary = Concerning HAE-I and HAE-II, just as variations in serum concentrations of APP appear to determine which individuals in a normal population develop angioedema with a second perturbation of kinin metabolism, such as the use of ACE inhibitors, 96 it could be speculated that variations in either kinin activation or inactivation pathways might contribute to the differences in severity of angioedema in individuals with a pre-existing perturbation in kinin metabolism, such as a mutation in C1-INH (as occurs in HAE). 13, 14, 27 This increase in plasma bradykinin was demonstrated both for patients with HAE with C1-INH deficiency and for patients with drug-associated angioedema who had an angioedematous attack in conjunction with ACE inhibitor treatment. The patient's daughter had recurrent skin angioedema and gastrointestinal pain attacks since age 12 years; therefore, with a normal C1-INH concentration and activity in both mother and daughter, a diagnosis of HAE type III was assumed. cache = ./cache/cord-269776-hj1s3ipp.txt txt = ./txt/cord-269776-hj1s3ipp.txt === reduce.pl bib === id = cord-315754-dq2empne author = Hasan, Anwarul title = A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin date = 2020-04-22 pages = extension = .txt mime = text/plain words = 4662 sentences = 272 flesch = 50 summary = Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Genomic analysis of the new CoV has shown that its SP differs from that of other viruses (Du et al., 2017; Li, 2016) , indicating that the protein has a site activated by a HC enzyme called furin (Millet & Whittaker, 2015) (Figure 1 ). The furin activation site (FAS) makes the new CoV much different in cell entry than SARS, and probably affects the stability of the virus and, consequently, the transmission process (Li et al., 2015; Millet & Whittaker, 2014; Yamada & Liu, 2009) . A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2 cache = ./cache/cord-315754-dq2empne.txt txt = ./txt/cord-315754-dq2empne.txt === reduce.pl bib === id = cord-256020-wrui3i2l author = Fadaka, Adewale Oluwaseun title = Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date = 2020-08-26 pages = extension = .txt mime = text/plain words = 7097 sentences = 465 flesch = 49 summary = The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations cache = ./cache/cord-256020-wrui3i2l.txt txt = ./txt/cord-256020-wrui3i2l.txt === reduce.pl bib === id = cord-296683-fjn29oal author = Sarode, Sachin C title = Oral submucous fibrosis and COVID-19: Perspective on comorbidity date = 2020-05-21 pages = extension = .txt mime = text/plain words = 961 sentences = 70 flesch = 54 summary = Novel Corona Virus infection (COVID-19) is a highly infective disease with rapid global spread since January 2020 and was declared as pandemic by World Health Organization. 1 Angiotensin Converting Enzyme 2 (ACE 2), present on the cell surfaces of some important organs, has been identified as target receptor for COVID-19 virus entry into the host cells. 3 In addition, ACE 2 has been reported to be present at various locations in the oral cavity and hence, oral cavity is considered as a potential site for the COVID 19 virus. 8 Thus, the less availability of ACE 2 in the oral cavity might have compromised the binding of COVID 19 virus. The other way round, if OSMF patient is affected with COVID-19, then it may cause further exhaustion of ACE 2. As ACE 2 is the binding site for COVID-19, it may compromise the infectivity of the virus. cache = ./cache/cord-296683-fjn29oal.txt txt = ./txt/cord-296683-fjn29oal.txt === reduce.pl bib === id = cord-332680-zfn81hew author = Chan, Chieh-Kai title = Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis date = 2020-09-10 pages = extension = .txt mime = text/plain words = 4301 sentences = 204 flesch = 45 summary = The following variables were extracted: author, journal, publication year, study design, geographic location, participants' details (number, study population, age, sex, and comorbidities, including hypertension, diabetes mellitus, heart failure, and chronic kidney disease), use of antihypertensive drugs, such as ACE inhibitors, ARBs, calcium-channel blockers, beta-blockers, diuretics, outcomes (including positive SARS-CoV-2 test results and disease prognosis/severity, if available). The systematic review findings of the 7 high-quality studies (with comparative data on the controls) on SARS-COV-2 infection provide the best available evidence proving that therapy with ACE inhibitors or ARBs is not associated with an increase of positive SARS-CoV-2 test result and the severity of COVID-19 disease or overall population mortality as a whole in case-population and cohort studies. ACE indicates angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; CKD, chronic kidney disease; DM, diabetes mellitus; HTN, hypertension; ICU, intensive care unit; N/A, not applicable; OHA, oral hypoglycemic agents; RAASi, renin-angiotensin-aldosterone system inhibitors; and SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. cache = ./cache/cord-332680-zfn81hew.txt txt = ./txt/cord-332680-zfn81hew.txt === reduce.pl bib === id = cord-342786-dl8vjwfn author = Sattar, Yasar title = COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management date = 2020-07-14 pages = extension = .txt mime = text/plain words = 5268 sentences = 349 flesch = 37 summary = Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. The infected patients may also present with cardiovascular disease (CVD) like acute coronary syndrome(ACS) and congestive cardiac failure(CHF) [6] . The systemic inflammation in COVID-19 may also dysregulate the post-translational modification of cardiac ion channels resulting in arrhythmia [25, 26] It is also noteworthy that viral proteins of SARS-CoV-2, ORF3 and ORF8, activate NLRP3 inflammasomes which inturn promotes atrial fibrillation [27, 28] . cache = ./cache/cord-342786-dl8vjwfn.txt txt = ./txt/cord-342786-dl8vjwfn.txt === reduce.pl bib === id = cord-289144-d6fgs8qg author = Sieńko, Jerzy title = COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients date = 2020-07-21 pages = extension = .txt mime = text/plain words = 5129 sentences = 320 flesch = 49 summary = Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. 8, 13 The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. 8, 13 The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. 63 This upregulation of the ACE2 receptor causes an increase in SARS-CoV-2 binding sites, which can lead to COVID-19 infection. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19 cache = ./cache/cord-289144-d6fgs8qg.txt txt = ./txt/cord-289144-d6fgs8qg.txt === reduce.pl bib === id = cord-318327-9sh2eksm author = Garg, M. title = Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract date = 2012-01-05 pages = extension = .txt mime = text/plain words = 7219 sentences = 425 flesch = 42 summary = Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. The contemporary view of the RAS has evolved from that of a simple linear pathway involving the conversion of angiotensinogen to angiotensin II (Ang II) via a two-step process facilitated by renin and angiotensin converting enzyme (ACE), to a much more complex system involving homologues of ACE and multiple angiotensin peptides which play supplementary and counter-regulatory roles ( Figure 1 ). Angiotensin converting enzyme inhibition or angiotensin receptor antagonism have been shown to produce a number of beneficial anti-inflammatory effects in rodent models of intestinal inflammation. cache = ./cache/cord-318327-9sh2eksm.txt txt = ./txt/cord-318327-9sh2eksm.txt === reduce.pl bib === id = cord-326405-3446eyi3 author = Wysocki, Jan title = Angiotensin-converting enzyme 2: Possible role in hypertension and kidney disease date = 2008-02-07 pages = extension = .txt mime = text/plain words = 5654 sentences = 298 flesch = 48 summary = The high catalytic efficiency of ACE2 for the generation of angiotensin (ANG)-1-7 from ANG II suggests an important role of ACE2 in preventing ANG II accumulation, while at the same time enhancing ANG-1-7 formation. [41] , primarily describing an Ace2 knockout and its associated cardiac pathology, also reported that ACE2 was reduced at the gene and protein level in kidneys from three separate rat models of spontaneous and diet-induced hypertension. Investigating the role of ACE2 in those two prevalent diseases and whether its effects are mediated by ANG II or ANG-(1-7) and other biologically active peptides, which are also substrates of ACE2, opens the way for developing new therapeutic targets in hypertension. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice Also, pharmacologic ACE2 inhibition was associated with increased albuminuria, suggesting a role of glomerular ACE2 in diabetic kidney injury cache = ./cache/cord-326405-3446eyi3.txt txt = ./txt/cord-326405-3446eyi3.txt === reduce.pl bib === id = cord-353707-3n2nji8l author = Sunden-Cullberg, Jonas title = Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death date = 2020-04-28 pages = extension = .txt mime = text/plain words = 679 sentences = 44 flesch = 54 summary = title: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death We, therefore, examined the chronic use of ACE inhibitors/ARBs and associated mortality in a historic cohort of septic patients admitted to the Intensive Care Unit. Data were collected between January 2008 and December 2015 on a nationwide Swedish cohort of 2700 patients, aged 18 years and over, with community-acquired severe sepsis and septic shock admitted to the Intensive Care Unit within 24 hours of arrival to any of 32 emergency departments throughout the country. ACE inhibitors/ ARB use was common among patients admitted to the Intensive Care Unit because of sepsis. ACE inhibitors/ARB use and associated mortality among critically ill COVID-19 patients can be compared with this data. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 cache = ./cache/cord-353707-3n2nji8l.txt txt = ./txt/cord-353707-3n2nji8l.txt === reduce.pl bib === id = cord-295041-5vpawtef author = Jakhmola, Shweta title = SARS-CoV-2, an Underestimated Pathogen of the Nervous System date = 2020-09-28 pages = extension = .txt mime = text/plain words = 5012 sentences = 310 flesch = 39 summary = Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Furthermore, the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) of COVID-19 patients is confirmed through genome sequencing [4] ; however, experimental evidence is needed to validate virusmediated neurological damage. Furthermore, the interaction of SARS-CoV-2 and ACE-2-expressing neuronal/glial cells may facilitate virus entry into the nervous system through different routes. cache = ./cache/cord-295041-5vpawtef.txt txt = ./txt/cord-295041-5vpawtef.txt === reduce.pl bib === id = cord-253862-jl1zhg13 author = Khalaf, Khalil title = SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date = 2020-10-06 pages = extension = .txt mime = text/plain words = 14595 sentences = 760 flesch = 45 summary = Although this novel virus is less severe than the first SARS-CoV outbreak, human-to-human transmission remains very high and the number of cases continues to rise exponentially in major urban areas, highlighting the urgent need to develop new containment, diagnostic, and treatment protocols. In the case of SARS-CoV-2, viral evasion of the innate immune system leads to an increase in cytokine production and late CD4+/CD8+ response, which then leads to pathogenic inflammation in patients with high viral loads. (ChiCTR2000029308), involving severe SARS-CoV-2 cases, compared lopinavir/ritonavir treatment with standard care alone, and they showed that the antivirals yielded no clinical benefits. In an open-label control study conducted by Cai et al., the antiviral activity of favipiravir + IFN-α was compared to that of lopinavir/ritonavir + IFN-α in patients with confirmed SARS-CoV-2 infection. cache = ./cache/cord-253862-jl1zhg13.txt txt = ./txt/cord-253862-jl1zhg13.txt === reduce.pl bib === id = cord-018009-8j40876m author = Campbell, Duncan J. John title = ACE Inhibition in Heart Failure and Ischaemic Heart Disease date = 2007 pages = extension = .txt mime = text/plain words = 11614 sentences = 566 flesch = 41 summary = Angiotensin converting enzyme (dipeptidyl carboxypeptidase I, kininase II, EC 3.4.15.1, ACE) plays a major role in the metabolism of many different peptides, including angiotensin (Ang) I, bradykinin, kallidin, and N-acetyl-seryl-aspartyllysyl-proline (AcSDKP). Pooled analysis of the HOPE, EUROPA, and PEACE trials showed ACE inhibition reduced all cause and cardiovascular mortality, non-fatal myocardial infarction, stroke, heart failure, and coronary artery bypass surgery, leading to the recommendation that ACE inhibitors be considered in all patients with atherosclerosis (Dagenais et al 2006) . ACE inhibitor therapy did not increase either bradykinin or kallidin peptide levels in cardiac atria of patients with ischaemic heart disease, despite the reduction in Ang II levels . Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure Interaction between neutral endopeptidase and angiotensin converting enzyme inhibition in rats with myocardial infarction: effects on cardiac hypertrophy and angiotensin and bradykinin peptide levels Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure cache = ./cache/cord-018009-8j40876m.txt txt = ./txt/cord-018009-8j40876m.txt === reduce.pl bib === id = cord-349445-yh6ndtgm author = Mohammed El Tabaa, Manar title = Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost date = 2020-05-27 pages = extension = .txt mime = text/plain words = 11840 sentences = 618 flesch = 39 summary = Therefore, researchers suggested that the use of angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs), may show a positive trend towards the severe inflammatory reactions and endothelial dysfunction caused by stimulating the function of ACE/Ang II/AT-1 axis and thereby, towards the bad pulmonary effects associated with the COVID-19 infection [29, 30] . Since IL-6 would inactivate endothelial nitric oxide synthase (eNOS), it could disrupt NO production [90] , decreasing its level and inducing a state of oxidative stress that may lead to Ang II-induced impairment in endothelial responses [91] Postulating impaired endothelium functions as a principal factor in the pathogenesis of heart failure, hypertension and diabetes, it will be expected to classify the patients of such diseases as high risk groups for COVID-19 development [92] [93] [94] . Taken into consideration the numerous harmful effects possibly induced by Ang II during COVID-19 pathogenesis, we found that most novel studies aim to use the anti-hypertensive drugs which act either by inhibiting the ACE activity or by blocking AT1 receptor, suggesting that action may mitigate the disease severity in COVID-19 patients. cache = ./cache/cord-349445-yh6ndtgm.txt txt = ./txt/cord-349445-yh6ndtgm.txt === reduce.pl bib === id = cord-338417-7kw9lws0 author = Singh, Awadhesh Kumar title = Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers date = 2020-04-09 pages = extension = .txt mime = text/plain words = 3212 sentences = 172 flesch = 48 summary = RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Emerging data suggests that older COVID-19 patients with other comorbid conditions such as diabetes, hypertension, cardiac and pulmonary disease are in particular more susceptible, compared to general populations and have higher mortality. We have systematically searched the PubMed medical database up till March 27, 2020 using MeSH key words that include Covid-19, coronavirus, hypertension, diabetes, cardiovascular disease, angiotensin receptor blockers, angiotensin converting enzyme inhibitors. Interestingly, in the pooled data from the ten Chinese studies (n ¼ 2209) that have reported the characteristics of comorbidities in patients with COVID-19; associations of hypertension, diabetes and presence of established cardiovascular disease (CVD) are larger, varying from 15 to 30% (average 21%), 5e20% (average 11%) and 2e40% (average 7%) respectively (Table 1) . cache = ./cache/cord-338417-7kw9lws0.txt txt = ./txt/cord-338417-7kw9lws0.txt === reduce.pl bib === id = cord-326820-11sl17ap author = Bousquet, Jean title = Is diet partly responsible for differences in COVID-19 death rates between and within countries? date = 2020-05-27 pages = extension = .txt mime = text/plain words = 2315 sentences = 131 flesch = 52 summary = title: Is diet partly responsible for differences in COVID-19 death rates between and within countries? The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit. Although there are large differences between countries in death rates, the age-dependent severity of COVID-19 is similar between Asian, European and American countries. Identifying whether countries with high or low ACE activity have different death rates would be of great interest in understanding the clinical importance of interventions. cache = ./cache/cord-326820-11sl17ap.txt txt = ./txt/cord-326820-11sl17ap.txt === reduce.pl bib === id = cord-266755-y2lf7ssp author = Yehualashet, Awgichew Shewasinad title = ACEIs and ARBs and Their Correlation with COVID-19: A Review date = 2020-09-16 pages = extension = .txt mime = text/plain words = 4160 sentences = 221 flesch = 46 summary = 21, 22 Both ACE-1 and ACE-2 cleave angiotensin peptides in that ACE-1 cleaves angiotensin I and generating angiotensin (Ang) II, which causes vasoconstriction, bronchoconstriction, increases vascular permeability, inflammation, and fibrosis and enhance the development of acute respiratory disease syndrome (ARDS) and lung failure in patients infected with SARS-CoV-2. 36 The probable rational proposed for the possible relation between the use of ACEIs/ARBs, and progression to ARDS in COVID-19 is the increased availability of ACE-2 attached to surface in the lung endothelium, an inherent effect of these two classes, leading to enhanced coupling of SARS-CoV2 to ACE-2 and its consequent cell entry. Based on prior animal studies, it was suggested that proposed ACEIs and ARBs can enhance ACE2 activity and thereby increase infectivity of COVID-19 virus. 48 In severe lung injury animal models, preclinical studies have showed that ACE2 is significantly downregulated and it has been shown that the inhibition of the angiotensin type 1 receptor by ARB like losartan reduces severe acute lung injury in mice administered with the spike glycoprotein of SARS-CoV. cache = ./cache/cord-266755-y2lf7ssp.txt txt = ./txt/cord-266755-y2lf7ssp.txt === reduce.pl bib === id = cord-314868-ei2b8oqn author = Leung, J. M. title = ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19 date = 2020-03-23 pages = extension = .txt mime = text/plain words = 2712 sentences = 190 flesch = 58 summary = Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID19, we determined whether ACE2 expression in the lower airways was related to COPD and cigarette smoking. Results: In the discovery cohort (n=42 participants), we found that ACE2 expression levels were increased by 48% in the airways of COPD compared with non-COPD subjects (COPD=2.52 (0.66) log2 counts per million reads (CPM) versus non-COPD= 1.70 (0.51) CPM , p=.000762). In summary, active cigarette smoking and COPD up-regulate ACE-2 expression in lower airways, which in part may explain the increased risk of severe COVID-19 in these sub-populations. The P-value was obtained from the robust linear model Abbreviations: ACE-2, angiotensin converting enzyme II; COPD, chronic obstructive pulmonary disease; CPM, counts per million reads . 18.20038455 doi: medRxiv preprint Abbreviations: ACE-2, angiotensin converting enzyme II; COPD, chronic obstructive pulmonary disease; CPM, counts per million reads ACE-2 gene expression in airway epithelia is inversely related to FEV1% predicted (p=0.0348) cache = ./cache/cord-314868-ei2b8oqn.txt txt = ./txt/cord-314868-ei2b8oqn.txt === reduce.pl bib === id = cord-330093-asba80bi author = Leung, Janice M. title = Smoking, ACE-2 and COVID-19: ongoing controversies date = 2020-07-16 pages = extension = .txt mime = text/plain words = 2777 sentences = 145 flesch = 48 summary = Both research teams are reporting increased angiotensin-converting enzyme 2 (ACE-2) expression in airways of current smokers and those with COPD, with important implications for coronavirus disease 2019 (COVID-19) patients. Since ACE-2 has been shown to be the main receptor utilised by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cells [2] , the authors conclude that nicotine is a risk factor for COVID-19. Here, we bring to the discussion whether the increased susceptibility and virulence of SARS-CoV-2 via α7-nAChR and the upregulation of small airway ACE-2 expression may also be relevant for those who vape using nicotine-based e-cigarettes. While smoking may not necessarily increase one's risk for contracting COVID-19, the biological and inflammatory cascade that occurs upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be particularly devastating for a smoker. cache = ./cache/cord-330093-asba80bi.txt txt = ./txt/cord-330093-asba80bi.txt === reduce.pl bib === id = cord-355807-q3bngari author = Yepes-Pérez, Andres F. title = Uncaria tomentosa (cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling date = 2020-10-29 pages = extension = .txt mime = text/plain words = 8807 sentences = 453 flesch = 48 summary = Molecular modeling was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (cat's claw) focusing on the binding interface of the RBD–ACE-2 and the viral spike protein. tomentosa against focusing both on the binding interface of the RBD-ACE-2 and inside SARS-CoV-2 RBD spike protein, (2) simulations of ligand pathway of the best predicted compounds from step 1 to evaluate convenient entrance mechanism of the compounds to the binding site, (3) MD simulation to assess the stability of the best protein-ligand complexes from 1, (4) calculation of pharmacokinetics parameters for the most qualified compounds resulting from the previous parts of the docking protocol. Next, we used the cryo-EM structure of SARS-CoV-2 spike protein (PDB code: 6VYB) in their open state (Lipinski et al., 2012) to explore the potential inhibition of components of the cat's claw, selecting ACE-2-binding pocket to this study. cache = ./cache/cord-355807-q3bngari.txt txt = ./txt/cord-355807-q3bngari.txt ===== Reducing email addresses cord-334490-42gykxdx Creating transaction Updating adr table ===== Reducing keywords cord-005386-p37rw8dh cord-253862-jl1zhg13 cord-002307-gk84fnb9 cord-001773-mqk0sx5n cord-269151-r426u5dz cord-005931-iggkxbbf cord-259933-ggx4v0bz cord-326405-3446eyi3 cord-298515-5n7hxhbg cord-275837-2avxd80i cord-017585-0llgr357 cord-289477-cjm7qhr4 cord-351567-ifoe8x28 cord-327697-80msva10 cord-326820-11sl17ap cord-295041-5vpawtef cord-269776-hj1s3ipp cord-024076-q9fw7ch1 cord-352230-8mazd3eu cord-342786-dl8vjwfn cord-300850-59j1m2tm cord-291146-f3e5ynhu cord-315754-dq2empne cord-346912-o09qmp7x cord-006082-x1kankxd cord-289144-d6fgs8qg cord-332680-zfn81hew cord-286638-bqxyb61p cord-353707-3n2nji8l cord-330093-asba80bi cord-282256-lqmixm7s cord-296683-fjn29oal cord-015859-5kt59ose cord-317878-bqpj0ey0 cord-302316-raf5rlkq cord-290148-6cxndab8 cord-016742-y7jgjera cord-286825-bu7j7kdr cord-266289-dkxhbmic cord-256020-wrui3i2l cord-334490-42gykxdx cord-018009-8j40876m cord-006087-hynkb0a8 cord-311099-59pnm4fn cord-267519-a0bcmjkn cord-266755-y2lf7ssp cord-322966-o65fo853 cord-277766-rxmpi61o cord-349445-yh6ndtgm cord-314868-ei2b8oqn cord-338417-7kw9lws0 cord-355807-q3bngari cord-318327-9sh2eksm cord-306739-4lokd97u cord-304742-ytf2ilw4 cord-301546-yck1t3pp cord-264828-6w13xo2a cord-002468-onpmkjaz cord-319022-1twsxzcd cord-346811-gorp9n1g cord-306755-9q1mawfs cord-005927-a9sj00y8 Creating transaction Updating wrd table ===== Reducing urls cord-001773-mqk0sx5n cord-346912-o09qmp7x cord-006087-hynkb0a8 cord-353707-3n2nji8l cord-291146-f3e5ynhu cord-264828-6w13xo2a cord-259933-ggx4v0bz cord-306755-9q1mawfs cord-330093-asba80bi cord-317878-bqpj0ey0 cord-315754-dq2empne cord-332680-zfn81hew cord-319022-1twsxzcd cord-301546-yck1t3pp cord-302316-raf5rlkq cord-352230-8mazd3eu cord-314868-ei2b8oqn cord-256020-wrui3i2l cord-355807-q3bngari cord-269776-hj1s3ipp Creating transaction Updating url table ===== Reducing named entities cord-005931-iggkxbbf cord-267519-a0bcmjkn cord-001773-mqk0sx5n cord-269151-r426u5dz cord-024076-q9fw7ch1 cord-002307-gk84fnb9 cord-002468-onpmkjaz cord-298515-5n7hxhbg cord-282256-lqmixm7s cord-353707-3n2nji8l cord-005386-p37rw8dh cord-264828-6w13xo2a cord-017585-0llgr357 cord-332680-zfn81hew cord-018009-8j40876m cord-326405-3446eyi3 cord-289477-cjm7qhr4 cord-289144-d6fgs8qg cord-346811-gorp9n1g cord-016742-y7jgjera cord-266289-dkxhbmic cord-253862-jl1zhg13 cord-317878-bqpj0ey0 cord-296683-fjn29oal cord-327697-80msva10 cord-266755-y2lf7ssp cord-006087-hynkb0a8 cord-005927-a9sj00y8 cord-306739-4lokd97u cord-319022-1twsxzcd cord-351567-ifoe8x28 cord-342786-dl8vjwfn cord-314868-ei2b8oqn cord-349445-yh6ndtgm cord-302316-raf5rlkq cord-015859-5kt59ose cord-334490-42gykxdx cord-306755-9q1mawfs cord-006082-x1kankxd cord-338417-7kw9lws0 cord-304742-ytf2ilw4 cord-318327-9sh2eksm cord-346912-o09qmp7x cord-277766-rxmpi61o cord-355807-q3bngari cord-290148-6cxndab8 cord-291146-f3e5ynhu cord-295041-5vpawtef cord-311099-59pnm4fn cord-315754-dq2empne cord-326820-11sl17ap cord-330093-asba80bi cord-322966-o65fo853 cord-275837-2avxd80i cord-301546-yck1t3pp cord-286638-bqxyb61p cord-300850-59j1m2tm cord-352230-8mazd3eu cord-286825-bu7j7kdr cord-259933-ggx4v0bz cord-256020-wrui3i2l cord-269776-hj1s3ipp Creating transaction Updating ent table ===== Reducing parts of speech cord-005931-iggkxbbf cord-267519-a0bcmjkn cord-269151-r426u5dz cord-001773-mqk0sx5n cord-005386-p37rw8dh cord-282256-lqmixm7s cord-259933-ggx4v0bz cord-024076-q9fw7ch1 cord-002468-onpmkjaz cord-286638-bqxyb61p cord-002307-gk84fnb9 cord-290148-6cxndab8 cord-005927-a9sj00y8 cord-304742-ytf2ilw4 cord-296683-fjn29oal cord-275837-2avxd80i cord-006087-hynkb0a8 cord-327697-80msva10 cord-264828-6w13xo2a cord-277766-rxmpi61o cord-330093-asba80bi cord-318327-9sh2eksm cord-334490-42gykxdx cord-306755-9q1mawfs cord-289477-cjm7qhr4 cord-017585-0llgr357 cord-346811-gorp9n1g cord-018009-8j40876m cord-322966-o65fo853 cord-295041-5vpawtef cord-300850-59j1m2tm cord-351567-ifoe8x28 cord-338417-7kw9lws0 cord-006082-x1kankxd cord-256020-wrui3i2l cord-266755-y2lf7ssp cord-326405-3446eyi3 cord-016742-y7jgjera cord-266289-dkxhbmic cord-253862-jl1zhg13 cord-015859-5kt59ose cord-314868-ei2b8oqn cord-315754-dq2empne cord-289144-d6fgs8qg cord-302316-raf5rlkq cord-353707-3n2nji8l cord-319022-1twsxzcd cord-301546-yck1t3pp cord-317878-bqpj0ey0 cord-326820-11sl17ap cord-298515-5n7hxhbg cord-332680-zfn81hew cord-306739-4lokd97u cord-286825-bu7j7kdr cord-291146-f3e5ynhu cord-342786-dl8vjwfn cord-352230-8mazd3eu cord-346912-o09qmp7x cord-349445-yh6ndtgm cord-311099-59pnm4fn cord-355807-q3bngari cord-269776-hj1s3ipp Creating transaction Updating pos table Building ./etc/reader.txt cord-018009-8j40876m cord-318327-9sh2eksm cord-286825-bu7j7kdr cord-286825-bu7j7kdr cord-018009-8j40876m cord-266289-dkxhbmic number of items: 62 sum of words: 405,813 average size in words: 6,545 average readability score: 46 nouns: patients; angiotensin; ace; receptor; enzyme; disease; inhibitors; activity; cells; effects; protein; expression; system; treatment; renin; infection; coronavirus; hypertension; inhibitor; risk; heart; levels; studies; study; blood; role; virus; gene; mice; type; lung; arbs; angioedema; effect; inhibition; cell; bradykinin; use; domain; pressure; receptors; data; activation; failure; mortality; therapy; tissue; plasma; diabetes; function verbs: converting; increase; showed; used; associated; induced; binding; includes; reduced; reported; suggested; compared; found; caused; mediate; led; inhibiting; decreased; resulted; treated; expressed; known; involved; prevent; based; activates; demonstrating; indicated; related; following; infected; observed; occurred; requires; identified; developing; described; blocked; produce; containing; provide; regulates; affected; revealed; contributes; gave; confirmed; taking; consider; act adjectives: human; clinical; severe; acute; viral; respiratory; covid-19; high; cardiovascular; renal; active; cardiac; vascular; myocardial; higher; different; novel; pulmonary; new; potential; inflammatory; important; specific; significant; functional; first; endothelial; several; non; normal; many; therapeutic; low; similar; molecular; ventricular; chronic; anti; dependent; hypertensive; coronary; diabetic; possible; hereditary; early; immune; lower; available; recent; current adverbs: also; however; well; significantly; therefore; even; respectively; highly; recently; furthermore; currently; now; less; previously; yet; moreover; indeed; still; approximately; especially; potentially; interestingly; often; together; hence; already; first; directly; thereby; particularly; additionally; much; primarily; widely; frequently; usually; mainly; relatively; possibly; likely; clinically; critically; alone; similarly; rapidly; clearly; rather; far; spontaneously; specifically pronouns: it; its; we; their; i; they; our; them; his; her; my; she; one; us; themselves; itself; you; qag-2; he; your; tace; myself; me; j527; sace-2; him; endothelin-1; adace1; thymosin-2; s; mg; il-1β; il-1-β; e377; cys412; a1-antitrypsin; ):; 's proper nouns: SARS; II; ACE2; ACE; COVID-19; Ang; ACE-2; CoV-2; C1-INH; HAE; RAS; Angiotensin; CoV; Fig; I; China; Ang-(1; C; ANG; Coronavirus; C1; S; AT; ARB; NEP; Wuhan; RNA; BK; TMPRSS2; N; RAAS; angiotensinogen; kallikrein; GPI; RBD; ARDS; MERS; ICU; III; TGF; IV; AT1; F; Mas; Disease; Alzheimer; Association; losartan; kinin; Health keywords: ace; ace-2; covid-19; sars; ang; ace2; ras; patient; angiotensin; inhibitor; effect; cov-2; rna; receptor; nep; enzyme; bradykinin; arb; ang-(1; xii; wuhan; virus; ventricular; treatment; tmprss2; tgf; tace; renin; rbd; rate; raas; proanthocyanidin; plc; nrf-2; mers; left; june; infection; increase; iii; ifn; icu; hrt; hnrnpf; hereditary; heart; hae; gpi; gene; expression one topic; one dimension: ace file(s): https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095973/ titles(s): Brain renin angiotensin in disease three topics; one dimension: covid; ace; patients file(s): https://doi.org/10.3389/fimmu.2020.570927, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122178/, https://www.sciencedirect.com/science/article/pii/S0091674904017579 titles(s): SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment | Role of ACE, ACE2 and Neprilysin in the Kidney | Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond five topics; three dimensions: sars cov covid; ang ace angiotensin; patients c1 covid; angiotensin receptor heart; ace angiotensin enzyme file(s): https://doi.org/10.3389/fimmu.2020.570927, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122178/, https://www.sciencedirect.com/science/article/pii/S0091674904017579, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121118/, http://medrxiv.org/cgi/content/short/2020.06.22.20137711v1?rss=1 titles(s): SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment | Role of ACE, ACE2 and Neprilysin in the Kidney | Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond | Cardiovascular Anatomy and Pharmacology | A Macroeconomic SIR Model for COVID-19 Type: cord title: keyword-ace-cord date: 2021-05-24 time: 19:32 username: emorgan patron: Eric Morgan email: emorgan@nd.edu input: keywords:ace ==== make-pages.sh htm files ==== make-pages.sh complex files ==== make-pages.sh named enities ==== making bibliographics id: cord-006087-hynkb0a8 author: Acharya, K. Ravi title: Ace revisited: A new target for structure-based drug design date: 2003 words: 8130 sentences: 386 pages: flesch: 47 cache: ./cache/cord-006087-hynkb0a8.txt txt: ./txt/cord-006087-hynkb0a8.txt summary: Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. Some differences in catalytic properties have been observed for these two sites: the N-domain site is notably 50-times more active toward the haemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro (AcSDKP) 21 , 1000-times Here, we provide an overview of ACE and the RAS, current ACE inhibitors and their clinical utility, insights from the tACE crystal structure, and the rationale and prospects for developing second-generation, domainselective inhibitors by structure-guided design. BPF was a mixture of peptides 59 , which were shown to be potent and specific inhibitors of ACE (TABLE 1), and structure-activity studies indicated that the optimal C-terminal inhibitory sequence was Phe-Ala-Pro 60 . An important caveat in considering the design and pharmacological utility of domain-selective ACE inhibitors is the potential for conformational effects that have not yet been observed in the tACE crystal structure. abstract: Current-generation angiotensin-converting enzyme (ACE) inhibitors are widely used for cardiovascular diseases, including high blood pressure, heart failure, heart attack and kidney failure, and have combined annual sales in excess of US $6 billion. However, the use of these ACE inhibitors, which were developed in the late 1970s and early 1980s, is hampered by common side effects. Moreover, we now know that ACE actually consists of two parts (called the N- and C-domains) that have different functions. Therefore, the design of specific domain-selective ACE inhibitors is expected to produce next-generation drugs that might be safer and more effective. Here we discuss the structural features of current inhibitors and outline how next-generation ACE inhibitors could be designed by using the three-dimensional molecular structure of human testis ACE. The ACE structure provides a unique opportunity for rational drug design, based on a combination of in silico modelling using existing inhibitors as scaffolds and iterative lead optimization to drive the synthetic chemistry. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097707/ doi: 10.1038/nrd1227 id: cord-269776-hj1s3ipp author: Agostoni, Angelo title: Hereditary and acquired angioedema: Problems and progress: Proceedings of the third C1 esterase inhibitor deficiency workshop and beyond date: 2004-09-11 words: 49824 sentences: 2688 pages: flesch: 44 cache: ./cache/cord-269776-hj1s3ipp.txt txt: ./txt/cord-269776-hj1s3ipp.txt summary: Concerning HAE-I and HAE-II, just as variations in serum concentrations of APP appear to determine which individuals in a normal population develop angioedema with a second perturbation of kinin metabolism, such as the use of ACE inhibitors, 96 it could be speculated that variations in either kinin activation or inactivation pathways might contribute to the differences in severity of angioedema in individuals with a pre-existing perturbation in kinin metabolism, such as a mutation in C1-INH (as occurs in HAE). 13, 14, 27 This increase in plasma bradykinin was demonstrated both for patients with HAE with C1-INH deficiency and for patients with drug-associated angioedema who had an angioedematous attack in conjunction with ACE inhibitor treatment. The patient''s daughter had recurrent skin angioedema and gastrointestinal pain attacks since age 12 years; therefore, with a normal C1-INH concentration and activity in both mother and daughter, a diagnosis of HAE type III was assumed. abstract: Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder. url: https://www.sciencedirect.com/science/article/pii/S0091674904017579 doi: 10.1016/j.jaci.2004.06.047 id: cord-275837-2avxd80i author: Ahirwar, Ashok Kumar title: COVID -19 outbreak – Diabetes aspect and perspective date: 2020-05-19 words: 578 sentences: 49 pages: flesch: 53 cache: ./cache/cord-275837-2avxd80i.txt txt: ./txt/cord-275837-2avxd80i.txt summary: Diabetes increases the risk of pneumonia in COVID-19 infected individual and it is an important risk factor for adverse outcome. ACE inhibitor and Angiotensin II Receptor Blockers (ARBs) are the few of drugs used for the appropriate management of diabetic patients. All these may lead to increased severity of COVID-19 infection in diabetic individuals. [4] Moreover, genetic polymorphism of ACE receptor has been shown to be linked with diabetes and it might also facilitate COVID-19 infections. [4] On contrary to this, some researchers say that use of ACE inhibitor or ARBs prevents the binding of COVID-19 virus to ACE receptor and thus may prevent infection. [5] All these are the lacunae in the existing knowledge of ACE inhibitor or ARBs use in diabetic individuals. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32551334/ doi: 10.1016/j.cmrp.2020.05.005 id: cord-264828-6w13xo2a author: Albini, Adriana title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based cardiovascular therapies date: 2020-05-19 words: 3662 sentences: 172 pages: flesch: 40 cache: ./cache/cord-264828-6w13xo2a.txt txt: ./txt/cord-264828-6w13xo2a.txt summary: Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. 4. Renin-angiotensin-aldosterone system (RAAS)-interfering drugs are likely to affect ACE-2 receptor-SARS-CoV-2 interaction dynamics within lung, heart, vascular, kidney and gut tissues [5, 19] , while it is still not completely elucidated how such interactions are relevant to the clinical course of cardiovascular comorbidities in patients with COVID-19 [29] . Consequently, the up-regulation of human ACE-2 induced by RAAS-antagonists in SARS-CoV-2-infected patients could be clinically useful, due to the cardiovascular protection elicited by the increased activity of angiotensin(1-7), thereby attenuating angiotensin II effects on vasoconstriction and sodium retention [31, 34] . abstract: SARS-CoV-2 is characterized by a spike protein allowing viral binding to the angiotensin-converting enzyme (ACE)-2, which acts as a viral receptor and is expressed on the surface of several pulmonary and extra-pulmonary cell types, including cardiac, renal, intestinal and endothelial cells. There is evidence that also endothelial cells are infected by SARS-COV-2, with subsequent occurrence of systemic vasculitis, thromboembolism and disseminated intravascular coagulation. Those effects, together with the “cytokine storm” are involved in a worse prognosis. In clinical practice, angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin II receptor blockers (ARBs) are extensively used for the treatment of hypertension and other cardiovascular diseases. In in vivo studies, ACE-Is and ARBs seem to paradoxically increase ACE-2 expression, which could favour SARS-CoV-2 infection of host’s cells and tissues. By contrast, in patients treated with ACE-Is and ARBs, ACE-2 shows a downregulation at the mRNA and protein levels in kidney and cardiac tissues. Yet, it has been claimed that both ARBs and ACE-Is could result potentially useful in the clinical course of SARS-CoV-2-infected patients. As detected in China and as the Italian epidemiological situation confirms, the most prevalent comorbidities in deceased patients with COVID-19 are hypertension, diabetes and cardiovascular diseases. Older COVID-19-affected patients with cardiovascular comorbidities exhibit a more severe clinical course and a worse prognosis, with many of them being also treated with ARBs or ACE-Is. Another confounding factor is cigarette smoking, which has been reported to increase ACE-2 expression in both experimental models and humans. Sex also plays a role, with chromosome X harbouring the gene coding for ACE-2, which is one of the possible explanations of why mortality in female patients is lower. Viral entry also depends on TMPRSS2 protease activity, an androgen dependent enzyme. Despite the relevance of experimental animal studies, to comprehensively address the question of the potential hazards or benefits of ACE-Is and ARBs on the clinical course of COVID-19-affected patients treated by these anti-hypertensive drugs, we will need randomized human studies. We claim the need of adequately powered, prospective studies aimed at answering the following questions of paramount importance for cardiovascular, internal and emergency medicine: Do ACE-Is and ARBs exert similar or different effects on infection or disease course? Are such effects dangerous, neutral or even useful in older, COVID-19-affected patients? Do they act on multiple cell types? Since ACE-Is and ARBs have different molecular targets, the clinical course of SARS-CoV-2 infection could be also different in patients treated by one or the other of these two drug classes. At present, insufficient detailed data from trials have been made available. url: https://doi.org/10.1007/s11739-020-02364-6 doi: 10.1007/s11739-020-02364-6 id: cord-304742-ytf2ilw4 author: Albini, Adriana title: The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor- and angiotensin II receptor blocker-based antihypertensive therapies—reply date: 2020-07-14 words: 1187 sentences: 52 pages: flesch: 41 cache: ./cache/cord-304742-ytf2ilw4.txt txt: ./txt/cord-304742-ytf2ilw4.txt summary: The transmembrane protease serine 2 TMPRSS2, an androgendependent enzyme, acts in reinforcing the ACE-2 receptor activity in allowing cell entry to a number of viral pathogens as well as to SARS-CoV-2 as reported in our Point of View [2] . Yet in trisomy 21 individuals a TMPRSS2 protease overexpression has been documented, as mentioned in the comment of Dr De Cauwer [1] , with this leading to an increased viral infection''s rate of susceptible host''s cells and tissues. In conclusion, the interesting comment by Dr De Cauwer points out the complex interactions between ACE-2 and TMPRSS2 with reference to the clinical course of CoViD-19 as well as to SARS-CoV-2 infection''s pathogenic evolution and severity degree in given population segments of infected individuals, like male individuals and Down syndromeaffected patients [1] . The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACEinhibitor-and angiotensin II receptor blocker-based cardiovascular therapies: comment The SARS-CoV-2 receptor, ACE-2, is expressed on many different cell types: implications for ACE-inhibitor-and angiotensin II receptor blocker-based cardiovascular therapies abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32666177/ doi: 10.1007/s11739-020-02436-7 id: cord-322966-o65fo853 author: Arnold, Ruth H. title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? date: 2020-05-25 words: 5415 sentences: 239 pages: flesch: 44 cache: ./cache/cord-322966-o65fo853.txt txt: ./txt/cord-322966-o65fo853.txt summary: title: COVID-19 – Does This Disease Kill Due to Imbalance of the Renin Angiotensin System (RAS) Caused by Genetic and Gender Differences in the Response to Viral ACE 2 Attacks? ABSTRACT Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Debate has arisen due to the finding that underlying cardiovascular disease and hypertension are associated with significantly increased risk of hospitalisation and death in COVID-19 [1, 2] , in addition to the viral receptor being angiotensin-converting enzyme-2 (ACE-2) [3 -5] . Association of renin-angiotensin system inhibitorswith severity or risk of death in patients with hypertension hospitalised for coronavirus disease 19 (COVID-19) infection in Wuhan, China abstract: ABSTRACT Debate continues in the medical literature on the role of the renin angiotensin system (RAS) in Coronavirus disease 2019 (COVID-19) pathophysiology and the implications for the use of cardiovascular drugs acting on the RAS. Could these drugs – which include angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptors blockers (ARBs) – be harmful or potential key therapeutic agents in COVID-19? url: https://api.elsevier.com/content/article/pii/S1443950620301451 doi: 10.1016/j.hlc.2020.05.004 id: cord-016742-y7jgjera author: Bauer, Maria title: Cardiovascular Anatomy and Pharmacology date: 2017-07-03 words: 23159 sentences: 1335 pages: flesch: 40 cache: ./cache/cord-016742-y7jgjera.txt txt: ./txt/cord-016742-y7jgjera.txt summary: The binding of an agonist to the adrenergic receptor replaces guanosine diphosphate (GDP) by guanosine triphosphate (GTP), and causes the α-subunit of the G-protein to break free from the β-γ complex, and act as a primary messenger: in beta receptors, it stimulates adenylate cyclase and triggers cyclic adenosine monophosphate (cAMP) production, which, as a second messenger in the process of signal transduction, activates its target kinases that phosphorylate regulator proteins and ultimately increases intracellular calcium levels. Their main anti-ischemic effects are due to their ability to reduce myocardial O 2 consumption by depressing contractility, decreasing heart rate and systemic afterload, and increasing O 2 supply by coronary and collateral vasodilation. Verapamil decreases the heart rate by depressing sinoatrial and AV-nodal activity (hence its utility in the treatment of supraventricular arrhythmias), lowers systemic blood pressure due to myocardial depression and peripheral vasodilation, and produces moderate coronary artery dilation (preferred in essential hypertension and vasospastic angina). abstract: This chapter reviews the cardiovascular anatomy, the effects of medications on the cardiovascular system, and current guidelines. Patients in the perioperative period often receive agents that affect hemodynamic variables such as heart rhythm and rate, blood pressure, or cardiac output. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7121118/ doi: 10.1007/978-3-319-62067-1_11 id: cord-346912-o09qmp7x author: Bayraktar, E. title: A Macroeconomic SIR Model for COVID-19 date: 2020-06-23 words: 6788 sentences: 410 pages: flesch: 63 cache: ./cache/cord-346912-o09qmp7x.txt txt: ./txt/cord-346912-o09qmp7x.txt summary: We develop an SIR model of the COVID-19 pandemic which explicitly considers herd immunity, behavior-dependent transmission rates, remote workers, and indirect externalities of lockdown. Additionally, if we incorporate a behavior-dependent transmission rate which represents increased personal caution in response to increased infection levels, both output loss and total mortality are lowered. Overall, our model predicts that a lockdown which ends at the arrival of herd immunity, combined with individual actions to slow virus transmission, can reduce total mortality to one-third of the no-lockdown level, while allowing high-risk individuals to leave lockdown well before vaccine arrival. • Increasing the level of remote work reduces the impact of COVID-19 by decreasing both mortality and output loss, even though a longer lockdown is imposed. Recreation of [Ace+20] model (two groups and no herd immunity), parameters from Table 1 Output Loss: 8.9676%, Total Deaths: 1.3121% All rights reserved. abstract: The current COVID-19 pandemic and subsequent lockdowns have highlighted the close and delicate relationship between a country's public health and economic health. Macroeconomic models which use preexisting epidemic models to calculate the impacts of a disease outbreak are therefore extremely useful for policymakers seeking to evaluate the best course of action in such a crisis. We develop an SIR model of the COVID-19 pandemic which explicitly considers herd immunity, behavior-dependent transmission rates, remote workers, and indirect externalities of lockdown. This model is presented as an exit time control problem where the lockdown ends when the population achieves herd immunity, either naturally or via a vaccine. A social planner prescribes separate levels of lockdown for two separate sections of the adult population - those who are low-risk (ages 20-64) and those who are high-risk (ages 65 and over). These levels are determined via optimization of an objective function which assigns a macroeconomic cost to the level of lockdown and the number of deaths. We find that, by ending lockdowns once herd immunity is reached, high-risk individuals are able to leave lockdown significantly before the arrival of a vaccine without causing large increases in mortality. Additionally, if we incorporate a behavior-dependent transmission rate which represents increased personal caution in response to increased infection levels, both output loss and total mortality are lowered. Lockdown efficacy is further increased when there is less interaction between low- and high-risk individuals, and increased remote work decreases output losses. Overall, our model predicts that a lockdown which ends at the arrival of herd immunity, combined with individual actions to slow virus transmission, can reduce total mortality to one-third of the no-lockdown level, while allowing high-risk individuals to leave lockdown well before vaccine arrival. url: http://medrxiv.org/cgi/content/short/2020.06.22.20137711v1?rss=1 doi: 10.1101/2020.06.22.20137711 id: cord-352230-8mazd3eu author: Beeraka, Narasimha M. title: Strategies for Targeting SARS CoV-2: Small Molecule Inhibitors—The Current Status date: 2020-09-18 words: 9394 sentences: 543 pages: flesch: 40 cache: ./cache/cord-352230-8mazd3eu.txt txt: ./txt/cord-352230-8mazd3eu.txt summary: Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. COVID-19 is a devastating disease caused by a coronavirus related to the one that caused outbreaks of Severe Acute Respiratory Syndrome (SARS) in the year 2002 (1, 2) . abstract: Severe Acute Respiratory Syndrome-Corona Virus-2 (SARS-CoV-2) induced Coronavirus Disease - 19 (COVID-19) cases have been increasing at an alarming rate (7.4 million positive cases as on June 11 2020), causing high mortality (4,17,956 deaths as on June 11 2020) and economic loss (a 3.2% shrink in global economy in 2020) across 212 countries globally. The clinical manifestations of this disease are pneumonia, lung injury, inflammation, and severe acute respiratory syndrome (SARS). Currently, there is no vaccine or effective pharmacological agents available for the prevention/treatment of SARS-CoV2 infections. Moreover, development of a suitable vaccine is a challenging task due to antibody-dependent enhancement (ADE) and Th-2 immunopathology, which aggravates infection with SARS-CoV-2. Furthermore, the emerging SARS-CoV-2 strain exhibits several distinct genomic and structural patterns compared to other coronavirus strains, making the development of a suitable vaccine even more difficult. Therefore, the identification of novel small molecule inhibitors (NSMIs) that can interfere with viral entry or viral propagation is of special interest and is vital in managing already infected cases. SARS-CoV-2 infection is mediated by the binding of viral Spike proteins (S-protein) to human cells through a 2-step process, which involves Angiotensin Converting Enzyme-2 (ACE2) and Transmembrane Serine Protease (TMPRSS)-2. Therefore, the development of novel inhibitors of ACE2/TMPRSS2 is likely to be beneficial in combating SARS-CoV-2 infections. However, the usage of ACE-2 inhibitors to block the SARS-CoV-2 viral entry requires additional studies as there are conflicting findings and severe health complications reported for these inhibitors in patients. Hence, the current interest is shifted toward the development of NSMIs, which includes natural antiviral phytochemicals and Nrf-2 activators to manage a SARS-CoV-2 infection. It is imperative to investigate the efficacy of existing antiviral phytochemicals and Nrf-2 activators to mitigate the SARS-CoV-2-mediated oxidative stress. Therefore, in this review, we have reviewed structural features of SARS-CoV-2 with special emphasis on key molecular targets and their known modulators that can be considered for the development of NSMIs. url: https://doi.org/10.3389/fimmu.2020.552925 doi: 10.3389/fimmu.2020.552925 id: cord-326820-11sl17ap author: Bousquet, Jean title: Is diet partly responsible for differences in COVID-19 death rates between and within countries? date: 2020-05-27 words: 2315 sentences: 131 pages: flesch: 52 cache: ./cache/cord-326820-11sl17ap.txt txt: ./txt/cord-326820-11sl17ap.txt summary: title: Is diet partly responsible for differences in COVID-19 death rates between and within countries? The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit. Although there are large differences between countries in death rates, the age-dependent severity of COVID-19 is similar between Asian, European and American countries. Identifying whether countries with high or low ACE activity have different death rates would be of great interest in understanding the clinical importance of interventions. abstract: Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit. url: https://www.ncbi.nlm.nih.gov/pubmed/32499909/ doi: 10.1186/s13601-020-00323-0 id: cord-267519-a0bcmjkn author: Bravi, Francesca title: Predictors of severe or lethal COVID-19, including Angiotensin Converting Enzyme inhibitors and Angiotensin II Receptor Blockers, in a sample of infected Italian citizens date: 2020-06-24 words: 3303 sentences: 144 pages: flesch: 44 cache: ./cache/cord-267519-a0bcmjkn.txt txt: ./txt/cord-267519-a0bcmjkn.txt summary: AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). Observing that human pathogenic coronaviruses bind their target cells through angiotensin-converting enzyme 2 (ACE2) [5] [6] [7] [8] , and that a few studies reported an increase in ACE2 expression mediated by angiotensin II type-I receptor blockers (ARBs) and ACE inhibitors (more consistently on animals than in humans) [9] [10] [11] [12] [13] [14] [15] [16] , some hypothesized that the increased expression of ACE2 would facilitate infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), thus the hypertension treatment with ACE2-stimulating drugs, as well as ACE2 polymorphisms, might increase the risk of developing severe COVID-19 [17] [18] [19] . abstract: AIMS: This retrospective case-control study was aimed at identifying potential independent predictors of severe/lethal COVID-19, including the treatment with Angiotensin-Converting Enzyme inhibitors (ACEi) and/or Angiotensin II Receptor Blockers (ARBs). METHODS AND RESULTS: All adults with SARS-CoV-2 infection in two Italian provinces were followed for a median of 24 days. ARBs and/or ACEi treatments, and hypertension, diabetes, cancer, COPD, renal and major cardiovascular diseases (CVD) were extracted from clinical charts and electronic health records, up to two years before infection. The sample consisted of 1603 subjects (mean age 58.0y; 47.3% males): 454 (28.3%) had severe symptoms, 192 (12.0%) very severe or lethal disease (154 deaths; mean age 79.3 years; 70.8% hypertensive, 42.2% with CVD). The youngest deceased person aged 44 years. Among hypertensive subjects (n = 543), the proportion of those treated with ARBs or ACEi were 88.4%, 78.7% and 80.6% among patients with mild, severe and very severe/lethal disease, respectively. At multivariate analysis, no association was observed between therapy and disease severity (Adjusted OR for very severe/lethal COVID-19: 0.87; 95% CI: 0.50–1.49). Significant predictors of severe disease were older age (with AORs largely increasing after 70 years of age), male gender (AOR: 1.76; 1.40–2.23), diabetes (AOR: 1.52; 1.05–2.18), CVD (AOR: 1.88; 1.32–2.70) and COPD (AOR: 1.88; 1.11–3.20). Only gender, age and diabetes also predicted very severe/lethal disease. CONCLUSION: No association was found between COVID-19 severity and treatment with ARBs and/or ACEi, supporting the recommendation to continue medication for all patients unless otherwise advised by their physicians. url: https://www.ncbi.nlm.nih.gov/pubmed/32579597/ doi: 10.1371/journal.pone.0235248 id: cord-302316-raf5rlkq author: Brüssow, Harald title: COVID‐19: From pathogenesis models to the first drug trials date: 2020-06-23 words: 6944 sentences: 350 pages: flesch: 44 cache: ./cache/cord-302316-raf5rlkq.txt txt: ./txt/cord-302316-raf5rlkq.txt summary: US researchers studied the viral and cellular transcriptional response upon infection of cell cultures and in animal models with different respiratory viruses including influenza A virus and SARS-CoV-2. A French study randomizing 181 COVID-19 patients with pneumonia on hydroxychloroquine or placebo, observed, however, no significant effect of treatment on transfer to ICU, mortality, or in the prevention of development of acute respiratory distress syndrome (Mah evas et al., 2020). A total of 86 COVID-19 cases of patients from China with mild/moderate disease were randomized on the antiviral lopinavir (an inhibitor of HIV protease combined with ritonavir, which prolongs the presence of drugs in the body) or the antiviral arbidol (an influenza virus fusion inhibitor only registered in Russia) or in a control group in a 2:2:1 ratio. Effect of high vs low doses of chloroquine diphosphate as adjunctive therapy for patients hospitalized with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection: a randomized clinical trial abstract: The number of people infected with SARS‐CoV‐2, and sadly dying from COVID‐19, has exploded, and so the amount of literature on the novel coronavirus and the disease it causes has increased proportionately. The case numbers in some countries are beyond the epidemic peak, but the uncertainty about a second wave keeps politicians and societies under pressure. Appropriate decision‐making and winning support from the population depends on precise scientific information rather than leaving the field to scaremongers of all proveniences. This mini‐review is an update of earlier reports (Brüssow, Microb Biotechnol 2020a;13:607; Brüssow, Microb Biotechnol 2020b; https://doi.org/10.1111/1751-7915.13592). url: https://doi.org/10.1111/1751-7915.13611 doi: 10.1111/1751-7915.13611 id: cord-018009-8j40876m author: Campbell, Duncan J. John title: ACE Inhibition in Heart Failure and Ischaemic Heart Disease date: 2007 words: 11614 sentences: 566 pages: flesch: 41 cache: ./cache/cord-018009-8j40876m.txt txt: ./txt/cord-018009-8j40876m.txt summary: Angiotensin converting enzyme (dipeptidyl carboxypeptidase I, kininase II, EC 3.4.15.1, ACE) plays a major role in the metabolism of many different peptides, including angiotensin (Ang) I, bradykinin, kallidin, and N-acetyl-seryl-aspartyllysyl-proline (AcSDKP). Pooled analysis of the HOPE, EUROPA, and PEACE trials showed ACE inhibition reduced all cause and cardiovascular mortality, non-fatal myocardial infarction, stroke, heart failure, and coronary artery bypass surgery, leading to the recommendation that ACE inhibitors be considered in all patients with atherosclerosis (Dagenais et al 2006) . ACE inhibitor therapy did not increase either bradykinin or kallidin peptide levels in cardiac atria of patients with ischaemic heart disease, despite the reduction in Ang II levels . Bradykinin contributes to the systemic hemodynamic effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure Interaction between neutral endopeptidase and angiotensin converting enzyme inhibition in rats with myocardial infarction: effects on cardiac hypertrophy and angiotensin and bradykinin peptide levels Bradykinin contributes to the vasodilator effects of chronic angiotensin-converting enzyme inhibition in patients with heart failure abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122740/ doi: 10.1007/978-1-4020-6372-5_2 id: cord-332680-zfn81hew author: Chan, Chieh-Kai title: Renin-Angiotensin-Aldosterone System Inhibitors and Risks of Severe Acute Respiratory Syndrome Coronavirus 2 Infection: A Systematic Review and Meta-Analysis date: 2020-09-10 words: 4301 sentences: 204 pages: flesch: 45 cache: ./cache/cord-332680-zfn81hew.txt txt: ./txt/cord-332680-zfn81hew.txt summary: The following variables were extracted: author, journal, publication year, study design, geographic location, participants'' details (number, study population, age, sex, and comorbidities, including hypertension, diabetes mellitus, heart failure, and chronic kidney disease), use of antihypertensive drugs, such as ACE inhibitors, ARBs, calcium-channel blockers, beta-blockers, diuretics, outcomes (including positive SARS-CoV-2 test results and disease prognosis/severity, if available). The systematic review findings of the 7 high-quality studies (with comparative data on the controls) on SARS-COV-2 infection provide the best available evidence proving that therapy with ACE inhibitors or ARBs is not associated with an increase of positive SARS-CoV-2 test result and the severity of COVID-19 disease or overall population mortality as a whole in case-population and cohort studies. ACE indicates angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; BMI, body mass index; CKD, chronic kidney disease; DM, diabetes mellitus; HTN, hypertension; ICU, intensive care unit; N/A, not applicable; OHA, oral hypoglycemic agents; RAASi, renin-angiotensin-aldosterone system inhibitors; and SARS-CoV-2, severe acute respiratory syndrome coronavirus 2. abstract: The viral spike coat protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) engages the human ACE (angiotensin-converting enzyme)2 cell surface receptor to infect the host cells. Thus, concerns arose regarding theoretically higher risk for coronavirus disease-19 (COVID-19) in patients taking ACE inhibitors/angiotensin II type 1 receptor antagonists (angiotensin receptor blockers [ARBs]). We systematically assessed case-population and cohort studies from MEDLINE (Ovid), Cochrane Database of Systematic Reviews PubMed, Embase, medRXIV, the World Health Organization database of COVID-19 publications, and ClinicalTrials.gov through June 1, 2020, with planned ongoing surveillance. We rated the certainty of evidence according to Cochrane methods and the GRADE approach. After pooling the adjusted odds ratios from the included studies, no significant increase was noted in the risk of SARS-CoV-2 infection by the use of ACEinhibitors (adjusted odds ratio, 0.95 [95% CI, 0.86–1.05]) or ARBs (adjusted odds ratio, 1.05 [95% CI, 0.97–1.14]). However, the random-effects meta-regression revealed that age may modify the SARS-CoV-2 infection risk in subjects with the use of ARBs (coefficient, −0.006 [95% CI, −0.016 to 0.004]), that is, the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects (<60 yearsold). The use of ACE inhibitors might not increase the susceptibility of SARS-CoV-2 infection, severity of disease, and mortality in case-population and cohort studies. Additionally, we discovered for the first time that the use of ARBs, as opposed to ACE inhibitors, specifically augmented the risk of SARS-CoV-2 infection in younger subjects, without obvious effects on COVID-19 outcomes. url: https://doi.org/10.1161/hypertensionaha.120.15989 doi: 10.1161/hypertensionaha.120.15989 id: cord-017585-0llgr357 author: Chappell, Mark C. title: Role of ACE, ACE2 and Neprilysin in the Kidney date: 2007 words: 7578 sentences: 336 pages: flesch: 43 cache: ./cache/cord-017585-0llgr357.txt txt: ./txt/cord-017585-0llgr357.txt summary: Although the emergence of receptor subtypes distinguishes the distinct signaling pathways of Ang II and Ang-(1-7), the post-renin enzymes that form and degrade these peptides must be considered in lieu of the overall regulation of the functional RAAS within the kidney. ACE, angiotensin converting enzyme; EPs, endopeptidases; NEP, neprilysin demonstration of endogenous levels of the peptide in the kidney, circulation and other tissues (Nagata et al 2006) . Thus, in addition to the proximal tubule epithelium, the glomerulus may be a second key site within the kidney where ACE2 may influence the local expression of angiotensin peptides and renal function. There are few studies on the regulation of the Ang-(1-7) receptor, although chronic ACE or AT 1 blockade reduced mas mRNA expression in the renal cortex of the Ren2 Lewis congenic rat . abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7122178/ doi: 10.1007/978-1-4020-6372-5_1 id: cord-317878-bqpj0ey0 author: Czick, Maureen title: COVID’s Razor: RAS Imbalance, the Common Denominator Across Disparate, Unexpected Aspects of COVID-19 date: 2020-09-11 words: 12676 sentences: 811 pages: flesch: 45 cache: ./cache/cord-317878-bqpj0ey0.txt txt: ./txt/cord-317878-bqpj0ey0.txt summary: Silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, olfactory loss, myocarditis, and increased mortality rates in the elderly, in men, in African-Americans, and in patients with obesity, diabetes, and cancer—all bear the fingerprints of the renin-angiotensin system (RAS) imbalance, suggesting that RAS is the common culprit. Subpopulations manifesting higher rates of COVID-19 mortality-including hypertensives, the elderly, the obese, diabetics, men, and African-Americans-correlate with preexisting RAS imbalance, with ACE overactivity and/or ACE2 underactivity priming these patients for more severe COVID-19 outcomes. 159 Males generally have higher levels of RAS than premenopausal females, 160 perhaps explaining why male hypertensive rats show a greater blood pressure decrease with ACEIs. 161 Estrogen downregulates the expression of the AT1 gene 162, 163 and suppresses both ROS production in vascular smooth muscle and the enzymatic activity of ACE. abstract: A modern iteration of Occam’s Razor posits that “the simplest explanation is usually correct.” Coronavirus Disease 2019 involves widespread organ damage and uneven mortality demographics, deemed unexpected from what was originally thought to be “a straightforward respiratory virus.” The simplest explanation is that both the expected and unexpected aspects of COVID-19 share a common mechanism. Silent hypoxia, atypical acute respiratory distress syndrome (ARDS), stroke, olfactory loss, myocarditis, and increased mortality rates in the elderly, in men, in African-Americans, and in patients with obesity, diabetes, and cancer—all bear the fingerprints of the renin-angiotensin system (RAS) imbalance, suggesting that RAS is the common culprit. This article examines what RAS is and how it works, then from that baseline, the article presents the evidence suggesting RAS involvement in the disparate manifestations of COVID-19. Understanding the deeper workings of RAS helps one make sense of severe COVID-19. In addition, recognizing the role of RAS imbalance suggests potential routes to mitigate COVID-19 severity. url: https://doi.org/10.2147/dmso.s265518 doi: 10.2147/dmso.s265518 id: cord-259933-ggx4v0bz author: Dalan, Rinkoo title: The ACE-2 in COVID-19: Foe or Friend? date: 2020-04-27 words: 4187 sentences: 225 pages: flesch: 44 cache: ./cache/cord-259933-ggx4v0bz.txt txt: ./txt/cord-259933-ggx4v0bz.txt summary: The SARS-CoV-2, a positive strand RNA virus, has been seen to infect humans through the angiotensin converting enzyme -2 (ACE-2) receptor [9] . In individuals with hypertension, diabetes, and other cardiovascular disorders with vascular complications, the renin angiotensin system (RAS) is known to be activated with an increase in ACE activity and a downregulation of ACE-2. Therefore, it may be assumed that the inherent downregulation of the ACE-2-Ang-(1-7)-Mas axis (as seen in metabolic conditions) is exacerbated in the COVID-19 state because (i) the virus uses the peptidase domain of the enzyme for entry into the cells and (ii) there is a decrease in ACE-2 with an increase in ACE [9] . Individuals with underlying hypertension, type 2 diabetes, or cardiovascular disease are at higher risk for respiratory failure and mortality in COVID-19. abstract: COVID-19 is a rapidly spreading outbreak globally. Emerging evidence demonstrates that older individuals and people with underlying metabolic conditions of diabetes mellitus, hypertension, and hyperlipidemia are at higher risk of morbidity and mortality. The SARS-CoV-2 infects humans through the angiotensin converting enzyme (ACE-2) receptor. The ACE-2 receptor is a part of the dual system renin-angiotensin-system (RAS) consisting of ACE-Ang-II-AT (1) R axis and ACE-2-Ang-(1–7)-Mas axis. In metabolic disorders and with increased age, it is known that there is an upregulation of ACE-Ang-II-AT (1) R axis with a downregulation of ACE-2-Ang-(1–7)-Mas axis. The activated ACE-Ang-II-AT1R axis leads to pro-inflammatory and pro-fibrotic effects in respiratory system, vascular dysfunction, myocardial fibrosis, nephropathy, and insulin secretory defects with increased insulin resistance. On the other hand, the ACE-2-Ang-(1–7)-Mas axis has anti-inflammatory and antifibrotic effects on the respiratory system and anti-inflammatory, antioxidative stress, and protective effects on vascular function, protects against myocardial fibrosis, nephropathy, pancreatitis, and insulin resistance. In effect, the balance between these two axes may determine the prognosis. The already strained ACE-2-Ang-(1–7)-Mas in metabolic disorders is further stressed due to the use of the ACE-2 by the virus for entry, which affects the prognosis in terms of respiratory compromise. Further evidence needs to be gathered on whether modulation of the renin angiotensin system would be advantageous due to upregulation of Mas activation or harmful due to the concomitant ACE-2 receptor upregulation in the acute management of COVID-19. url: https://www.ncbi.nlm.nih.gov/pubmed/32340044/ doi: 10.1055/a-1155-0501 id: cord-319022-1twsxzcd author: Desai, Antonio title: The role of anti-hypertensive treatment, comorbidities and early introduction of LMWH in the setting of COVID-19: A retrospective, observational study in Northern Italy() date: 2020-09-25 words: 2874 sentences: 132 pages: flesch: 47 cache: ./cache/cord-319022-1twsxzcd.txt txt: ./txt/cord-319022-1twsxzcd.txt summary: BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. As for today, there are discordant results regarding the use of either angiotensin converting enzyme inhibitors (ACE-I) or angiotensin II receptor blockers (ARBs) as for their possible impact on COVID-19 mortality. We found that ACE-I, which acts by inhibiting the conversion from angiotensin I to angiotensin II, showed a trend in protecting from mortality from COVID-19 and was significant in delaying mortality as shown by multivariate Cox regression analysis unlike ARBs, which antagonize the effects of angiotensin II on its receptors 2,3 . Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 abstract: BACKGROUND: There is a great deal of debate about the role of cardiovascular comorbidities and the chronic use of antihypertensive agents (such as ACE-I and ARBs) on mortality on COVID-19 patients. Of note, ACE2 is responsible for the host cell entry of the virus. METHOD: We extracted data on 575 consecutive patients with laboratory-confirmed SARS-CoV-2 infection admitted to the Emergency Department (ED) of Humanitas Center, between February 21 and April 14, 2020. The aim of the study was to evaluate the role of chronic treatment with ACE-I or ARBs and other clinical predictors on in-hospital mortality in a cohort of COVID-19 patients. RESULTS: Multivariate analysis showed that a chronic intake of ACE-I was associated with a trend in reduction of mortality (OR: 0.53; 95% CI: 0.27–1.03; p = 0.06). Increased age (ORs ranging from 3.4 to 25.2 and to 39.5 for 60–70, 70–80 and > 80 years vs < 60) and cardiovascular comorbidities (OR: 1.90; 95% CI: 1.1–3.3; p = 0.02) were confirmed as important risk factors for COVID-19 mortality. Timely treatment with low-molecular-weight heparin (LMWH) in ED was found to be protective (OR: 0.36; 95% CI: 0.21–0.62; p < 0.0001). CONCLUSIONS: This study can contribute to understand the reasons behind the high mortality rate of patients in Lombardy, a region which accounts for >50% of total Italian deaths. Based on our findings, we support that daily intake of antihypertensive medications in the setting of COVID-19 should not be discontinued and that a timely LMWH administration in ED has shown to decrease in-hospital mortality. url: https://doi.org/10.1016/j.ijcard.2020.09.062 doi: 10.1016/j.ijcard.2020.09.062 id: cord-015859-5kt59ose author: Esch, Joep H.M. Van title: Local Angiotensin Generation and AT(2) Receptor Activation date: 2007 words: 9870 sentences: 499 pages: flesch: 45 cache: ./cache/cord-015859-5kt59ose.txt txt: ./txt/cord-015859-5kt59ose.txt summary: Mice lacking the ren-1 d gene are characterized by sexually dimorphic hypotension (leading to a significant reduction of blood pressure in female mice), absence of dense secretory/storage granule formation in juxta-glomerular cells, altered morphology of the kidney, and a significant increase of plasma prorenin levels (Clark et al 1997) . Importantly, binding of (pro)renin to the (pro)renin receptor in human mesangial cells also induced Ang II-independent effects, such as an increase in DNA synthesis, activation of the mitogen-activated protein kinases (MAPKs) extracellular signal-regulated kinase (ERK)1 (p44)/ERK2 (p42), and plasminogenactivator inhibitor-1 release. AT 2 receptors are involved in physiological processes like development and tissue remodeling (by inhibiting cell growth and by stimulating apoptosis), regulation of blood pressure (vasodilatation), natriuresis and neuronal activity. In vitro studies using the isolated perfused rat Langendorff heart fully confirmed the idea of renin and angiotensinogen uptake underlying tissue angiotensin production. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7119946/ doi: 10.1007/978-1-4020-6372-5_12 id: cord-256020-wrui3i2l author: Fadaka, Adewale Oluwaseun title: Understanding the epidemiology, pathophysiology, diagnosis and management of SARS-CoV-2 date: 2020-08-26 words: 7097 sentences: 465 pages: flesch: 49 cache: ./cache/cord-256020-wrui3i2l.txt txt: ./txt/cord-256020-wrui3i2l.txt summary: The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The disease is caused by SARS-CoV-2, a zoonotic pathogen that acquired mutations as it crossed the species barrier from bat to pangolin enabling it to infect humans. 5 The clinical symptoms of COVID-19 include fever, cough, and pneumonia, which makes the disease enormously dangerous with a high case fatality rate. 11 Symptoms of human SARS-CoV-1 infections include headache, fever and respiratory complications such as cough, dyspnea, and pneumonia. 81 The main goal of SARS-CoV-2 diagnosis is to accurately detect the virus and to minimize further transmissions by timely isolation and treatment of infected patients. 112 This implies that variation in ACE-2 expression in COVID-19 patients is likely to affect susceptibility, symptoms and intervention outcomes following SARS-CoV-2 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease-2019 (COVID-19): the epidemic and the challenges Comparative genetic analysis of the novel coronavirus (2019-nCoV/SARS-CoV-2) receptor ACE2 in different populations abstract: The emergence of coronavirus disease 2019 (COVID-19) in December 2019 has resulted in over 20 million cases and 741,808 deaths globally, affecting more than 200 countries. COVID-19 was declared a pandemic on 11 March 2020 by the World Health Organization. The disease is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). There is limited information on COVID-19, and treatment has so far focused on supportive care and use of repurposed drugs. COVID-19 can be transmitted via person-to-person contact through droplet spread. Some of the recommended precautionary measures to reduce the rate of disease spread include social distancing, good hygiene practices, and avoidance of crowded areas. These measures are effective because the droplets are heavy and can only travel approximately 1 meter in the air, settling quickly on fixed surfaces. Promising strategies to combat SARS-CoV-2 include discovery of therapeutic targets/drugs and vaccines. In this review, we summarize the epidemiology, pathophysiology, and diagnosis of COVID-19. We also address the mechanisms of action of approved repurposed drugs for therapeutic management of the disease. url: https://doi.org/10.1177/0300060520949077 doi: 10.1177/0300060520949077 id: cord-318327-9sh2eksm author: Garg, M. title: Review article: the pathophysiological roles of the renin–angiotensin system in the gastrointestinal tract date: 2012-01-05 words: 7219 sentences: 425 pages: flesch: 42 cache: ./cache/cord-318327-9sh2eksm.txt txt: ./txt/cord-318327-9sh2eksm.txt summary: Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. The contemporary view of the RAS has evolved from that of a simple linear pathway involving the conversion of angiotensinogen to angiotensin II (Ang II) via a two-step process facilitated by renin and angiotensin converting enzyme (ACE), to a much more complex system involving homologues of ACE and multiple angiotensin peptides which play supplementary and counter-regulatory roles ( Figure 1 ). Angiotensin converting enzyme inhibition or angiotensin receptor antagonism have been shown to produce a number of beneficial anti-inflammatory effects in rodent models of intestinal inflammation. abstract: BACKGROUND: The renin‐angiotensin system (RAS) is a homeostatic pathway widely known to regulate cardiovascular and renal physiology; however, little is known about its influence in gastrointestinal tissues. AIM: To elicit the anatomical distribution and physiological significance of the components of the RAS in the gastrointestinal tract. METHODS: An extensive online literature review including Pubmed and Medline. RESULTS: There is evidence for RAS involvement in gastrointestinal physiology and pathophysiology, with all the components required for autonomous regulation identified throughout the gastrointestinal tract. The RAS is implicated in the regulation of glucose, amino acid, fluid and electrolyte absorption and secretion, motility, inflammation, blood flow and possibly malignant disease within the gastrointestinal tract. Animal studies investigating the effects of RAS blockade in a range of conditions including inflammatory bowel disease, functional gut disorders, gastrointestinal malignancy and even intestinal ischaemia have been encouraging to date. Given the ready availability of drugs that modify the RAS and their excellent safety profile, an opportunity exists for investigation of their possible therapeutic role in a variety of human gastrointestinal diseases. CONCLUSIONS: The gastrointestinal renin‐angiotensin system appears to be intricately involved in a number of physiological processes, and provides a possible target for novel investigative and therapeutic approaches. url: https://www.ncbi.nlm.nih.gov/pubmed/22221317/ doi: 10.1111/j.1365-2036.2011.04971.x id: cord-306739-4lokd97u author: Gesierich, Wolfgang title: Sind ACE-Hemmer eher negativ oder doch von Vorteil bei COVID-19? date: 2020-07-14 words: 364 sentences: 48 pages: flesch: 58 cache: ./cache/cord-306739-4lokd97u.txt txt: ./txt/cord-306739-4lokd97u.txt summary: Bei COVID-19 wird neben der meist vorherrschenden akuten Lungenschädigung (ARDS) auch eine relevante Rate an myokardialen Schäden (Anstieg von Troponin) und akutem Nierenversagen beobachtet. Bereits aus der Zeit von SARS gibt es experimentelle Daten, die eine entsprechende Interaktion zwischen SARS-CoV-1 und dem RAAS belegen [2] . Ebenso gibt es experimentelle Studien, die einen krankheitsfördernden Effekt einer RAAS-Aktivierung bei ARDS nicht infektiöser Genese nahelegen [3] . Die dargestellten britischen Daten dürfen als erstes Signal gewertet werden, dass ACE-Hemmer auch bei COVID-19 einen günstigen Effekt auf den Krankheitsverlauf haben könnten. Weitere klinische Studien sind also dringend erforderlich, bevor den ACE-Hemmern ein therapeutischer Effekt bei COVID-19 zugeschrieben werden kann. Vorerst darf folgendes Fazit gezogen werden, das von nationalen und internationalen Fachgesellschaften unterstützt wird: Eine vorbestehende Therapie mit einem ACE-Hemmer, die für Patienten mit kardiovaskulären Erkrankungen und Diabetes mellitus einen relevanten organprotektiven und damit prognostischen Wert hat, sollte in der aktuellen Pandemie-Situation und insbesondere bei Diagnose einer SARS-CoV-2-Infektion nicht abgesetzt werden. abstract: nan url: https://doi.org/10.1007/s15033-020-1857-7 doi: 10.1007/s15033-020-1857-7 id: cord-277766-rxmpi61o author: Guang, Cuie title: Three key proteases – angiotensin-I-converting enzyme (ACE), ACE2 and renin – within and beyond the renin-angiotensin system date: 2012-06-15 words: 9497 sentences: 476 pages: flesch: 43 cache: ./cache/cord-277766-rxmpi61o.txt txt: ./txt/cord-277766-rxmpi61o.txt summary: In a classical RAS, the substrate angiotensinogen (AGT), which is released into the circulation from the liver, is degraded by the enzyme renin that originates in the kidney, generating the inactive angiotensin I (Ang I). The initial drug development of clinical ACE inhibitors was based on the assumption of an active site related to that of carboxypeptidase A but organized to remove a dipeptide rather than a single amino acid from the Cterminus of its substrate. The protective role of XNT against hypertension-induced cardiac fibrosis is associated with activation of ACE2, increases in Ang-(1-7) and inhibition of extracellular signal-regulated kinases [83] . The hemoregulatory peptide N-acetyl-Ser-Asp-Lys-Pro is a natural and specific substrate of the N-terminal active site of human angiotensinconverting enzyme The N-terminal active centre of human angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide Angiotensin-converting enzyme 2 activation protects against hypertension-induced cardiac fibrosis involving extracellular signal-regulated kinases abstract: The discovery of angiotensin-I-converting enzyme 2 (ACE2) and a (pro)renin receptor has renewed interest in the physiology of the renin-angiotensin system (RAS). Through the ACE2/angiotensin-(1–7)/Mas counter-regulatory axis, ACE2 balances the vasoconstrictive, proliferative, fibrotic and proinflammatory effects of the ACE/angiotensin II/AT1 axis. The (pro)renin receptor system shows an angiotensin-dependent function related to increased generation of angiotensin I, and an angiotensin-independent aspect related to intracellular signalling. Activation of ACE2 and inhibition of ACE and renin have been at the core of the RAS regulation. The aim of this review is to discuss the biochemistry and biological functions of ACE, ACE2 and renin within and beyond the RAS, and thus provide a perspective for future bioactives from natural plant and/or food resources related to the three proteases. url: https://www.sciencedirect.com/science/article/pii/S1875213612000952 doi: 10.1016/j.acvd.2012.02.010 id: cord-266289-dkxhbmic author: Harrison, Charlotte title: ACE for all – a molecular perspective date: 2014-07-16 words: 9060 sentences: 505 pages: flesch: 58 cache: ./cache/cord-266289-dkxhbmic.txt txt: ./txt/cord-266289-dkxhbmic.txt summary: The involvement of ACE in processes outside of blood pressure regulation, and in particular the differences in substrate specificity of the two domains of sACE highlight the growing need for a new generation of ACE inhibitors. Interestingly, the two residues that differ; Arg381/Glu403 and Tyr369/Phe391 are located in the S 2 subsite (Fig. 5d ), further illustrating that interactions between the enzyme and inhibitors at this site are an important determinant of domain selectivity. The N domain of human angiotensin-I-converting enzyme: the role of Nglycosylation and the crystal structure in complex with an N domain-specific phosphinic inhibitor, RXP407 The structure of testis angiotensin-converting enzyme in complex with the C domain-specific inhibitor RXPA380 abstract: Angiotensin-I converting enzyme (ACE, EC 3.4.15.1) is a zinc dependent dipeptidyl carboxypeptidase with an essential role in mammalian blood pressure regulation as part of the renin-angiotensin aldosterone system (RAAS). As such, it has long been targeted in the treatment of hypertension through the use of ACE inhibitors. Although ACE has been studied since the 1950s, only recently have the full range of functions of this enzyme begun to truly be appreciated. ACE homologues have been found in a host of other organisms, and are now known to be conserved in insects. Insect ACE homologues typically share over 30 % amino acid sequence identity with human ACE. Given that insects lack a mammalian type circulatory system, they must have crucial roles in other physiological processes. The first ACE crystal structures were reported during the last decade and have enabled these enzymes to be studied from an entirely different perspective. Here we review many of these key developments and the implications that they have had on our understanding of the diverse functions of these enzymes. Specifically, we consider how structural information is being used in the design of a new generation of ACE inhibitors with increased specificity, and how the structures of ACE homologues are related to their functions. The Anopheles gambiae genome is predicted to code for ten ACE homologues, more than any genome studied so far. We have modelled the active sites of some of these as yet uncharacterised enzymes to try and infer more about their potential roles at the molecular level. url: http://europepmc.org/articles/pmc4165820?pdf=render doi: 10.1007/s12079-014-0236-8 id: cord-315754-dq2empne author: Hasan, Anwarul title: A review on the cleavage priming of the spike protein on coronavirus by angiotensin-converting enzyme-2 and furin date: 2020-04-22 words: 4662 sentences: 272 pages: flesch: 50 cache: ./cache/cord-315754-dq2empne.txt txt: ./txt/cord-315754-dq2empne.txt summary: Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Genomic analysis of the new CoV has shown that its SP differs from that of other viruses (Du et al., 2017; Li, 2016) , indicating that the protein has a site activated by a HC enzyme called furin (Millet & Whittaker, 2015) (Figure 1 ). The furin activation site (FAS) makes the new CoV much different in cell entry than SARS, and probably affects the stability of the virus and, consequently, the transmission process (Li et al., 2015; Millet & Whittaker, 2014; Yamada & Liu, 2009) . A hexapeptide of the receptor-binding domain of SARS corona virus spike protein blocks viral entry into host cells via the human receptor ACE2 abstract: The widespread antigenic changes lead to the emergence of a new type of coronavirus (CoV) called as severe acute respiratory syndrome (SARS)-CoV-2 that is immunologically different from the previous circulating species. Angiotensin-converting enzyme-2 (ACE-2) is one of the most important receptors on the cell membrane of the host cells (HCs) which its interaction with spike protein (SP) with a furin-cleavage site results in the SARS-CoV-2 invasion. Hence, in this review, we presented an overview on the interaction of ACE-2 and furin with SP. As several kinds of CoVs, from various genera, have at their S1/S2 binding site a preserved site, we further surveyed the role of furin cleavage site (FCS) on the life cycle of the CoV. Furthermore, we discussed that the small molecular inhibitors can limit the interaction of ACE-2 and furin with SP and can be used as potential therapeutic platforms to combat the spreading CoV epidemic. Finally, some ongoing challenges and future prospects for the development of potential drugs to promote targeting specific activities of the CoV were reviewed. In conclusion, this review may pave the way for providing useful information about different compounds involved in improving the effectiveness of CoV vaccine or drugs with minimum toxicity against human health. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1754293 doi: 10.1080/07391102.2020.1754293 id: cord-346811-gorp9n1g author: Hippisley-Cox, Julia title: Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people date: 2020-07-31 words: 5104 sentences: 275 pages: flesch: 50 cache: ./cache/cord-346811-gorp9n1g.txt txt: ./txt/cord-346811-gorp9n1g.txt summary: We report a large, population-based study where we examined the drug histories of approximately 20% of all patients tested positive for coronavirus in England to determine if there was an independent association between ACE inhibitor and ARB drug prescription and severe COVID-19 disease susceptibility and progression. We extracted data from the GP record for explanatory and potential confounding variables including variables with some evidence of being risk factors for COVID-19 disease or severe disease as measured by ICU admission and variables likely to influence prescribing of ACE inhibitors and ARB medications. In this very large population-based study, ACE inhibitor and ARB prescriptions were associated with a reduced risk of COVID-19 RT-PCR positive disease, having adjusted for a wide range of demographic factors, potential comorbidities and other medication. 11 In our study, prior prescription of ACE inhibitor and ARB drugs did not have a significant effect on the risk of patients developing COVID-19 disease severe enough to require ICU care. abstract: BACKGROUND: There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission. METHODS: This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20–99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care. FINDINGS: Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care. There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group. INTERPRETATION: ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study. url: https://doi.org/10.1136/heartjnl-2020-317393 doi: 10.1136/heartjnl-2020-317393 id: cord-295041-5vpawtef author: Jakhmola, Shweta title: SARS-CoV-2, an Underestimated Pathogen of the Nervous System date: 2020-09-28 words: 5012 sentences: 310 pages: flesch: 39 cache: ./cache/cord-295041-5vpawtef.txt txt: ./txt/cord-295041-5vpawtef.txt summary: Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Furthermore, the presence of SARS-CoV-2 in cerebrospinal fluid (CSF) of COVID-19 patients is confirmed through genome sequencing [4] ; however, experimental evidence is needed to validate virusmediated neurological damage. Furthermore, the interaction of SARS-CoV-2 and ACE-2-expressing neuronal/glial cells may facilitate virus entry into the nervous system through different routes. abstract: Numerous clinical studies have reported neurological symptoms in COVID-19 patients since the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), apart from the atypical signs of pneumonia. Angiotensin-converting enzyme-2 (ACE-2), a potential receptor for SARS-CoV-2 entry, is expressed on various brain cells and cerebral parts, i.e., subfornical organ, paraventricular nucleus, nucleus of the tractus solitarius, and rostral ventrolateral medulla, as well as in non-cardiovascular areas such as the motor cortex and raphe. The resident CNS cells like astrocytes and microglia also express ACE-2, thus highlighting the vulnerability of the nervous system to SARS-CoV-2 infection. Additionally, transmembrane serine protease 2 (TMPRSS2) and furin facilitate virus entry into the host. Besides, the probable routes of virus entry into the nervous system include the hematogenic pathway, through the vagus, the olfactory nerve, or the enteric nervous system. However, the trajectory of SARS-CoV-2 to the brain needs investigation. Furthermore, a Th17-mediated cytokine storm is seen in COVID-19 cases with higher levels of IL-1β/2/7/8/9/10/17, GM-CSF, IFN-γ, TNF-α, CXCL-10, MCP1, and MIP1α/β. Some cytokines can cross the blood-brain barrier and activate the brain’s immune cells to produce neural cytokines, leading to neuronal dysfunctions. Nonetheless, most of the neurological conditions developed due to viral infections may not have effective and registered treatments. Although, some antivirals may inhibit the virus-mediated pathogenesis and prove to be suitable in COVID-19 treatment. Therefore, clinicians’ and researchers’ collective expertise may unravel the potential of SARS-CoV-2 infection to prevent short-term and long-term CNS damage. url: https://doi.org/10.1007/s42399-020-00522-7 doi: 10.1007/s42399-020-00522-7 id: cord-334490-42gykxdx author: Kammerlander, Andreas A. title: COVID-19: frequently asked questions to the cardiologist date: 2020-07-24 words: 1739 sentences: 96 pages: flesch: 36 cache: ./cache/cord-334490-42gykxdx.txt txt: ./txt/cord-334490-42gykxdx.txt summary: The specific causes of troponin rise in COVID-19 in patients without cardiac conditions, such as acute coronary syndrome (ACS), aortic stenosis, hypertrophic cardiomyopathy, and tachycardia A. Cardiac injury, defined as elevated troponin levels, is frequently observed in patients with COVID-19. The European Association of Percutaneous Cardiovascular Interventions (EAPCI) issued a position statement on invasive management in patients with ACS during the COVID-19 pandemic [19] . The EAPCI recommends that in cases of mild troponin elevation (<2-3 times the upper limit of normal), particularly in older patients with pre-existing cardiac conditions, a work-up for type 1 MI is not indicated, unless strongly indicated by clinical presentation and electrocardiograph (ECG) findings. Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China Association of Renin-Angiotensin system inhibitors with severity or risk of death in patients with hypertension hospitalized for Coronavirus disease 2019 (COVID-19) infection in Wuhan, China abstract: nan url: https://doi.org/10.1007/s00508-020-01696-9 doi: 10.1007/s00508-020-01696-9 id: cord-002307-gk84fnb9 author: Kehoe, Patrick Gavin title: Angiotensin-converting enzyme 2 is reduced in Alzheimer’s disease in association with increasing amyloid-β and tau pathology date: 2016-11-25 words: 6466 sentences: 347 pages: flesch: 55 cache: ./cache/cord-002307-gk84fnb9.txt txt: ./txt/cord-002307-gk84fnb9.txt summary: METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. ACE-2 enzyme activity is reduced in Alzheimer''s disease in association with increasing Aβ load and tau pathology ACE-2 activity was significantly reduced by approximately 50% in the mid-frontal cortex in AD compared with age-matched controls (P < 0.0001) (Fig. 1a) . Together, these data strongly suggest that reduced ACEFig. 2 Angiotensin-converting enzyme 2 (ACE-2) activity is reduced in association with apolipoprotein E (APOE) ε4 and ACE1 (rs1799752) indel polymorphism and increased in cerebral amyloid angiopathy (CAA). abstract: BACKGROUND: Hyperactivity of the classical axis of the renin-angiotensin system (RAS), mediated by angiotensin II (Ang II) activation of the angiotensin II type 1 receptor (AT1R), is implicated in the pathogenesis of Alzheimer’s disease (AD). Angiotensin-converting enzyme-2 (ACE-2) degrades Ang II to angiotensin 1–7 (Ang (1-7)) and counter-regulates the classical axis of RAS. We have investigated the expression and distribution of ACE-2 in post-mortem human brain tissue in relation to AD pathology and classical RAS axis activity. METHODS: We measured ACE-2 activity by fluorogenic peptide substrate assay in mid-frontal cortex (Brodmann area 9) in a cohort of AD (n = 90) and age-matched non-demented controls (n = 59) for which we have previous data on ACE-1 activity, amyloid β (Aβ) level and tau pathology, as well as known ACE1 (rs1799752) indel polymorphism, apolipoprotein E (APOE) genotype, and cerebral amyloid angiopathy severity scores. RESULTS: ACE-2 activity was significantly reduced in AD compared with age-matched controls (P < 0.0001) and correlated inversely with levels of Aβ (r = −0.267, P < 0.001) and phosphorylated tau (p-tau) pathology (r = −0.327, P < 0.01). ACE-2 was reduced in individuals possessing an APOE ε4 allele (P < 0.05) and was associated with ACE1 indel polymorphism (P < 0.05), with lower ACE-2 activity in individuals homozygous for the ACE1 insertion AD risk allele. ACE-2 activity correlated inversely with ACE-1 activity (r = −0.453, P < 0.0001), and the ratio of ACE-1 to ACE-2 was significantly elevated in AD (P < 0.0001). Finally, we show that the ratio of Ang II to Ang (1–7) (a proxy measure of ACE-2 activity indicating conversion of Ang II to Ang (1–7)) is reduced in AD. CONCLUSIONS: Together, our findings indicate that ACE-2 activity is reduced in AD and is an important regulator of the central classical ACE-1/Ang II/AT1R axis of RAS, and also that dysregulation of this pathway likely plays a significant role in the pathogenesis of AD. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13195-016-0217-7) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5123239/ doi: 10.1186/s13195-016-0217-7 id: cord-253862-jl1zhg13 author: Khalaf, Khalil title: SARS-CoV-2: Pathogenesis, and Advancements in Diagnostics and Treatment date: 2020-10-06 words: 14595 sentences: 760 pages: flesch: 45 cache: ./cache/cord-253862-jl1zhg13.txt txt: ./txt/cord-253862-jl1zhg13.txt summary: Although this novel virus is less severe than the first SARS-CoV outbreak, human-to-human transmission remains very high and the number of cases continues to rise exponentially in major urban areas, highlighting the urgent need to develop new containment, diagnostic, and treatment protocols. In the case of SARS-CoV-2, viral evasion of the innate immune system leads to an increase in cytokine production and late CD4+/CD8+ response, which then leads to pathogenic inflammation in patients with high viral loads. (ChiCTR2000029308), involving severe SARS-CoV-2 cases, compared lopinavir/ritonavir treatment with standard care alone, and they showed that the antivirals yielded no clinical benefits. In an open-label control study conducted by Cai et al., the antiviral activity of favipiravir + IFN-α was compared to that of lopinavir/ritonavir + IFN-α in patients with confirmed SARS-CoV-2 infection. abstract: The emergence and rapid spread of SARS-CoV-2 in December 2019 has brought the world to a standstill. While less pathogenic than the 2002–2003 SARS-CoV, this novel betacoronavirus presents a global threat due to its high transmission rate, ability to invade multiple tissues, and ability to trigger immunological hyperactivation. The identification of the animal reservoir and intermediate host were important steps toward slowing the spread of disease, and its genetic similarity to SARS-CoV has helped to determine pathogenesis and direct treatment strategies. The exponential increase in cases has necessitated fast and reliable testing procedures. Although RT-PCR remains the gold standard, it is a time-consuming procedure, paving the way for newer techniques such as serologic tests and enzyme immunoassays. Various clinical trials using broad antiviral agents in addition to novel medications have produced controversial results; however, the advancement of immunotherapy, particularly monoclonal antibodies and immune modulators is showing great promise in clinical trials. Non-orthodox medications such as anti-malarials have been tested in multiple institutions but definitive conclusions are yet to be made. Adjuvant therapies have also proven to be effective in decreasing mortality in the disease course. While no formal guidelines have been established, the multitude of ongoing clinical trials as a result of unprecedented access to research data brings us closer to halting the SARS-CoV-2 pandemic. url: https://doi.org/10.3389/fimmu.2020.570927 doi: 10.3389/fimmu.2020.570927 id: cord-005927-a9sj00y8 author: Kondoh, Gen title: Angiotensin-converting enzyme is a GPI-anchored protein releasing factor crucial for fertilization date: 2005-01-23 words: 4984 sentences: 257 pages: flesch: 51 cache: ./cache/cord-005927-a9sj00y8.txt txt: ./txt/cord-005927-a9sj00y8.txt summary: We also assessed the effect of ACE-specific inhibitors, such as captopril and lisinopril, which bind to the catalytic center with ligation of its thiol to the zinc ion and completely inhibit the peptidase activity, but found only a minor inhibitory effect on the GPIase assay ( Fig. 1c , 1 × 10 -3 M captopril produced 40% inhibition and data not shown). We treated cells with ACE, PI-PLC or mouse glandular kallikrein (mGK), which digests EGFP protein near the carboxy termini (data not shown) and trapped the released products from the supernatants using antibody specific for GFP. We collected epididymal sperm from both wild-type and Ace knockout mice 33 and compared the distribution of GPI-anchored proteins in water-soluble and detergent-soluble fractions. In this regard, GPI-anchored proteins were not released in sperms of Ace knockout mice (Fig. 5a) . abstract: The angiotensin-converting enzyme (ACE) is a key regulator of blood pressure. It is known to cleave small peptides, such as angiotensin I and bradykinin and changes their biological activities, leading to upregulation of blood pressure. Here we describe a new activity for ACE: a glycosylphosphatidylinositol (GPI)-anchored protein releasing activity (GPIase activity). Unlike its peptidase activity, GPIase activity is weakly inhibited by the tightly binding ACE inhibitor and not inactivated by substitutions of core amino acid residues for the peptidase activity, suggesting that the active site elements for GPIase differ from those for peptidase activity. ACE shed various GPI-anchored proteins from the cell surface, and the process was accelerated by the lipid raft disruptor filipin. The released products carried portions of the GPI anchor, indicating cleavage within the GPI moiety. Further analysis by high-performance liquid chromatography–mass spectrometry predicted the cleavage site at the mannose-mannose linkage. GPI-anchored proteins such as TESP5 and PH-20 were released from the sperm membrane of wild-type mice but not in Ace knockout sperm in vivo. Moreover, peptidase-inactivated E414D mutant ACE and also PI-PLC rescued the egg-binding deficiency of Ace knockout sperms, implying that ACE plays a crucial role in fertilization through this activity. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nm1179) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095966/ doi: 10.1038/nm1179 id: cord-301546-yck1t3pp author: Kozaki, Toshinori title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains date: 2007-12-28 words: 2505 sentences: 152 pages: flesch: 52 cache: ./cache/cord-301546-yck1t3pp.txt txt: ./txt/cord-301546-yck1t3pp.txt summary: title: Comparison of two acetylcholinesterase gene cDNAs of the lesser mealworm, Alphitobius diaperinus, in insecticide susceptible and resistant strains Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. The alignment of this gene with the Drosophila Ace paralogous AChEs showed that, as expected for an insecticide-susceptible strain, beetles from the Denmark-S strain had an organophosphate and carbamate sensitive type. The Drosophila Ace orthologous gene, AdAce1, was sequenced from two susceptible Denmark-S, four Waycross (tetrachlorvinphos-resistant), and two Kennebec (tetrachlorvinphos-resistant) adults. diaperinus is not due to mutations in the Ace genes (i.e., is not an altered acetylcholinesterase).Alignments of the deduced amino acid sequences from the Drosophila Ace orthologous and paralogous genes in Coleoptera are shown in Figures 4 and 5, respectively. abstract: Two cDNAs encoding different acetylcholinesterase (AChE) genes (AdAce1 and AdAce2) were sequenced and analyzed from the lesser mealworm, Alphitobius diaperinus. Both AdAce1 and AdAce2 were highly similar (95 and 93% amino acid identity, respectively) with the Ace genes of Tribolium castaneum. Both AdAce1 and AdAce2 have the conserved residues characteristic of AChE (catalytic triad, intra‐disulfide bonds, and so on). Partial cDNA sequences of the Alphitobius Ace genes were compared between two tetrachlorvinphos resistant (Kennebec and Waycross) and one susceptible strain of beetles. Several single nucleotide polymorphisms (SNPs) were detected, but only one non‐synonymous mutation was found (A271S in AdAce2). No SNPs were exclusively found in the resistant strains, the A271S mutation does not correspond to any mutations previously reported to alter sensitivity of AChE to organophosphates or carbamates, and the A271S was found only as a heterozygote in one individual from one of the resistant A. diaperinus strains. This suggests that tetrachlorvinphos resistance in the Kennebec and Waycross strains of A. diaperinus is not due to mutations in either AChE gene. The sequences of AdAce1 and AdAce2 provide new information about the evolution of these important genes in insects. Arch Insect Biochem Physiol. © 2007 Wiley‐Liss, Inc. url: https://doi.org/10.1002/arch.20229 doi: 10.1002/arch.20229 id: cord-314868-ei2b8oqn author: Leung, J. M. title: ACE-2 Expression in the Small Airway Epithelia of Smokers and COPD Patients: Implications for COVID-19 date: 2020-03-23 words: 2712 sentences: 190 pages: flesch: 58 cache: ./cache/cord-314868-ei2b8oqn.txt txt: ./txt/cord-314868-ei2b8oqn.txt summary: Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID19, we determined whether ACE2 expression in the lower airways was related to COPD and cigarette smoking. Results: In the discovery cohort (n=42 participants), we found that ACE2 expression levels were increased by 48% in the airways of COPD compared with non-COPD subjects (COPD=2.52 (0.66) log2 counts per million reads (CPM) versus non-COPD= 1.70 (0.51) CPM , p=.000762). In summary, active cigarette smoking and COPD up-regulate ACE-2 expression in lower airways, which in part may explain the increased risk of severe COVID-19 in these sub-populations. The P-value was obtained from the robust linear model Abbreviations: ACE-2, angiotensin converting enzyme II; COPD, chronic obstructive pulmonary disease; CPM, counts per million reads . 18.20038455 doi: medRxiv preprint Abbreviations: ACE-2, angiotensin converting enzyme II; COPD, chronic obstructive pulmonary disease; CPM, counts per million reads ACE-2 gene expression in airway epithelia is inversely related to FEV1% predicted (p=0.0348) abstract: Introduction: Coronavirus disease 2019 (COVID-19) is a respiratory infection caused by the severe acute respiratory syndrome coronavirus2 (SARSCoV-2). This virus uses the angiotensin converting enzyme II (ACE2) as the cellular entry receptor to infect the lower respiratory tract. Because individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of severe COVID19, we determined whether ACE2 expression in the lower airways was related to COPD and cigarette smoking. Methods: Using RNAseq, we determined gene expression levels in bronchial epithelia obtained from cytologic brushings of 6th to 8th generation airways in individuals with and without COPD. We externally validated these results from two additional independent cohorts, which used microarray technologies to measure gene expression levels from 6th to 12th generation airways. Results: In the discovery cohort (n=42 participants), we found that ACE2 expression levels were increased by 48% in the airways of COPD compared with non-COPD subjects (COPD=2.52 (0.66) log2 counts per million reads (CPM) versus non-COPD= 1.70 (0.51) CPM , p=.000762). There was a significant inverse relationship between ACE2 gene expression and FEV1% of predicted (r=negative 0.24; p=0.035). Current smoking also significantly increased ACE2 expression levels compared with never smokers (never current smokers=2.77 (90.91) CPM versus smokers=1.78 (0.39) CPM, p=0.024). These findings were replicated in the two external cohorts. Conclusions: ACE2 expression in lower airways is increased in patients with COPD and with current smoking. These data suggest that these two subgroups are at increased risk of serious COVID19 infection and highlight the importance of smoking cessation in reducing the risk. url: http://medrxiv.org/cgi/content/short/2020.03.18.20038455v1?rss=1 doi: 10.1101/2020.03.18.20038455 id: cord-330093-asba80bi author: Leung, Janice M. title: Smoking, ACE-2 and COVID-19: ongoing controversies date: 2020-07-16 words: 2777 sentences: 145 pages: flesch: 48 cache: ./cache/cord-330093-asba80bi.txt txt: ./txt/cord-330093-asba80bi.txt summary: Both research teams are reporting increased angiotensin-converting enzyme 2 (ACE-2) expression in airways of current smokers and those with COPD, with important implications for coronavirus disease 2019 (COVID-19) patients. Since ACE-2 has been shown to be the main receptor utilised by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to enter the host cells [2] , the authors conclude that nicotine is a risk factor for COVID-19. Here, we bring to the discussion whether the increased susceptibility and virulence of SARS-CoV-2 via α7-nAChR and the upregulation of small airway ACE-2 expression may also be relevant for those who vape using nicotine-based e-cigarettes. While smoking may not necessarily increase one''s risk for contracting COVID-19, the biological and inflammatory cascade that occurs upon severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may be particularly devastating for a smoker. abstract: Smoking increases severity of COVID-19 https://bit.ly/2yWp3jb url: https://doi.org/10.1183/13993003.01759-2020 doi: 10.1183/13993003.01759-2020 id: cord-001773-mqk0sx5n author: Lo, Chao-Sheng title: Overexpression of heterogeneous nuclear ribonucleoprotein F stimulates renal Ace-2 gene expression and prevents TGF-β1-induced kidney injury in a mouse model of diabetes date: 2015-08-01 words: 4946 sentences: 361 pages: flesch: 54 cache: ./cache/cord-001773-mqk0sx5n.txt txt: ./txt/cord-001773-mqk0sx5n.txt summary: AIMS/HYPOTHESIS: We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. RESULTS: Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1–7 receptor [MasR]) expression, and normalised urinary Ang 1–7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. We reported that insulin inhibits high glucose stimulation of rat renal Agt gene expression via two nuclear proteins-heterogeneous nuclear ribonucleoproteins F and K (hnRNP F, hnRNP K)-that interact with the insulin-responsive element (IRE) in the Agt gene promoter [25] [26] [27] [28] , and that hnRNP F overexpression in RPTCs inhibits Agt gene expression and kidney hypertrophy in Akita Hnrnpf-Tg mice [29] . abstract: AIMS/HYPOTHESIS: We investigated whether heterogeneous nuclear ribonucleoprotein F (hnRNP F) stimulates renal ACE-2 expression and prevents TGF-β1 signalling, TGF-β1 inhibition of Ace-2 gene expression and induction of tubulo-fibrosis in an Akita mouse model of type 1 diabetes. METHODS: Adult male Akita transgenic (Tg) mice overexpressing specifically hnRNP F in their renal proximal tubular cells (RPTCs) were studied. Non-Akita littermates and Akita mice served as controls. Immortalised rat RPTCs stably transfected with plasmid containing either rat Hnrnpf cDNA or rat Ace-2 gene promoter were also studied. RESULTS: Overexpression of hnRNP F attenuated systemic hypertension, glomerular filtration rate, albumin/creatinine ratio, urinary angiotensinogen (AGT) and angiotensin (Ang) II levels, renal fibrosis and profibrotic gene (Agt, Tgf-β1, TGF-β receptor II [Tgf-βrII]) expression, stimulated anti-profibrotic gene (Ace-2 and Ang 1–7 receptor [MasR]) expression, and normalised urinary Ang 1–7 level in Akita Hnrnpf-Tg mice as compared with Akita mice. In vitro, hnRNP F overexpression stimulated Ace-2 gene promoter activity, mRNA and protein expression, and attenuated Agt, Tgf-β1 and Tgf-βrII gene expression. Furthermore, hnRNP F overexpression prevented TGF-β1 signalling and TGF-β1 inhibition of Ace-2 gene expression. CONCLUSIONS/INTERPRETATION: These data demonstrate that hnRNP F stimulates Ace-2 gene transcription, prevents TGF-β1 inhibition of Ace-2 gene transcription and induction of kidney injury in diabetes. HnRNP F may be a potential target for treating hypertension and renal fibrosis in diabetes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00125-015-3700-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572079/ doi: 10.1007/s00125-015-3700-y id: cord-311099-59pnm4fn author: Lubel, John S title: Liver disease and the renin–angiotensin system: Recent discoveries and clinical implications date: 2008-06-28 words: 7730 sentences: 401 pages: flesch: 44 cache: ./cache/cord-311099-59pnm4fn.txt txt: ./txt/cord-311099-59pnm4fn.txt summary: Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. 42 A great deal of evidence supporting the role of the RAS in hepatic fibrosis has come from animal studies using ACE inhibitors and angiotensin receptor blockers (ARB). A pilot study examining the effects of 6 months of losartan treatment on liver fibrosis in chronic hepatitis C demonstrated a significant decrease in fibrosis stage in the treated group compared to control patients. abstract: The renin–angiotensin system (RAS) is a key regulator of vascular resistance, sodium and water homeostasis and the response to tissue injury. Historically, angiotensin II (Ang II) was thought to be the primary effector peptide of this system. Ang II is produced predominantly by the effect of angiotensin converting enzyme (ACE) on angiotensin I (Ang I). Ang II acts mainly through the angiotensin II type‐1 receptor (AT(1)) and, together with ACE, these components represent the ‘classical’ axis of the RAS. Drug therapies targeting the RAS by inhibiting Ang II formation (ACE inhibitors) or binding to its receptor (angiotensin receptor blockers) are now in widespread clinical use and have been shown to reduce tissue injury and fibrosis in cardiac and renal disease independently of their effects on blood pressure. In 2000, two groups using different methodologies identified a homolog of ACE, called ACE2, which cleaves Ang II to form the biologically active heptapeptide, Ang‐(1–7). Conceptually, ACE2, Ang‐(1–7), and its putative receptor, the mas receptor represent an ‘alternative’ axis of the RAS capable of opposing the often deleterious actions of Ang II. Interestingly, ACE inhibitors and angiotensin receptor blockers increase Ang‐(1–7) production and it has been proposed that some of the beneficial effects of these drugs are mediated through upregulation of Ang‐(1–7) rather than inhibition of Ang II production or receptor binding. The present review focuses on the novel components and pathways of the RAS with particular reference to their potential contribution towards the pathophysiology of liver disease. url: https://www.ncbi.nlm.nih.gov/pubmed/18557800/ doi: 10.1111/j.1440-1746.2008.05461.x id: cord-286825-bu7j7kdr author: Macours, Nathalie title: Structure, Evolutionary Conservation, and Functions of Angiotensin- and Endothelin-Converting Enzymes date: 2004-10-04 words: 17576 sentences: 876 pages: flesch: 47 cache: ./cache/cord-286825-bu7j7kdr.txt txt: ./txt/cord-286825-bu7j7kdr.txt summary: Because this peptide has been found to be an in vivo substrate specific for the N domain of sACE, it is suggested that ACE is implicated in the process of hematopoietic stem cell regulation by permanently degrading this natural circulating inhibitor (Azizi et al., 2001; Rousseau et al., 1995) . At present mammalian M13 family of zinc proteases consists of seven known members: neutral endopeptidase (NEP); the endothelin-converting enzymes ECE-1, ECE-2, and ECE-3; the Kell blood group antigen (Kell); the phosphate regulating gene (PEX); X-converting enzyme (XCE); and secreted endopeptidase (SEP). Sequencing, expression and biochemical characterization of the Porphyromonas gingivalis pepO gene encoding a protein homologous to human endothelin-converting enzyme Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme Peptidyl dipeptidases (Ance and Acer) of Drosophila melanogaster: Major diVerences in the substrate specificity of two homologs of human angiotensin I-converting enzyme abstract: Angiotensin-converting enzyme, a member of the M2 metalloprotease family, and endothelin-converting enzyme, a member of the M13 family, are key components in the regulation of blood pressure and electrolyte balance in mammals. From this point of view, they serve as important drug targets. Recently, the involvement of these enzymes in the development of Alzheimer's disease was discovered. The existence of homologs of these enzymes in invertebrates indicates that these enzyme systems are highly conserved during evolution. Most invertebrates lack a closed circulatory system, which excludes the need for blood pressure regulators. Therefore, these organisms represent excellent targets for gaining new insights and revealing additional physiological roles of these important enzymes. This chapter reviews the structural and functional aspects of ACE and ECE and will particularly focus on these enzyme homologues in invertebrates. url: https://www.ncbi.nlm.nih.gov/pubmed/15464852/ doi: 10.1016/s0074-7696(04)39002-9 id: cord-024076-q9fw7ch1 author: Manga, Pravin title: Should ACE Inhibitors and Angiotensin Receptor Blockers Be Withdrawn in the Current Setting of COVID-19 Infection? date: 2020-04-17 words: 1862 sentences: 90 pages: flesch: 41 cache: ./cache/cord-024076-q9fw7ch1.txt txt: ./txt/cord-024076-q9fw7ch1.txt summary: The reports urging caution in the use of ACE inhibitors and ARBs for hypertension, diabetes and cardiovascular disease are based on laboratory data which found that SARS-CoV and COVID-19 virus binds to ACE 2 receptor which is found in the epithelial cells of the lung, kidney, intestine and blood vessels. Thus, a clear causal relationship between those with cardiovascular disease, hypertension, heart failure with reduced ejection fraction (HFrEF), and diabetes with chronic kidney disease (DCKD) on ACE inhibitors or ARB treatment and an increased risk of COVID-19 does not exist. In South Africa, hypertension, HFrEF and diabetes are common non-communicable diseases, and a significant proportion of patients are being treated with generic versions of ACE inhibitors or ARBs. There is extremely strong scientific evidence for the benefit of RAAS inhibition in patients with cardiovascular disease. abstract: nan url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7187740/ doi: 10.18772/26180197.2020.v2nsia4 id: cord-349445-yh6ndtgm author: Mohammed El Tabaa, Manar title: Targeting Neprilysin (NEP) pathways: A potential new hope to defeat COVID-19 ghost date: 2020-05-27 words: 11840 sentences: 618 pages: flesch: 39 cache: ./cache/cord-349445-yh6ndtgm.txt txt: ./txt/cord-349445-yh6ndtgm.txt summary: Therefore, researchers suggested that the use of angiotensin converting enzyme inhibitors (ACEIs) and/or angiotensin receptor blockers (ARBs), may show a positive trend towards the severe inflammatory reactions and endothelial dysfunction caused by stimulating the function of ACE/Ang II/AT-1 axis and thereby, towards the bad pulmonary effects associated with the COVID-19 infection [29, 30] . Since IL-6 would inactivate endothelial nitric oxide synthase (eNOS), it could disrupt NO production [90] , decreasing its level and inducing a state of oxidative stress that may lead to Ang II-induced impairment in endothelial responses [91] Postulating impaired endothelium functions as a principal factor in the pathogenesis of heart failure, hypertension and diabetes, it will be expected to classify the patients of such diseases as high risk groups for COVID-19 development [92] [93] [94] . Taken into consideration the numerous harmful effects possibly induced by Ang II during COVID-19 pathogenesis, we found that most novel studies aim to use the anti-hypertensive drugs which act either by inhibiting the ACE activity or by blocking AT1 receptor, suggesting that action may mitigate the disease severity in COVID-19 patients. abstract: COVID-19 is an ongoing viral pandemic disease that is caused by SARS-CoV2, inducing severe pneumonia in humans. However, several classes of repurposed drugs have been recommended, no specific vaccines or effective therapeutic interventions for COVID-19 are developed till now. Viral dependence on ACE-2, as entry receptors, drove the researchers into RAS impact on COVID-19 pathogenesis. Several evidences have pointed at Neprilysin (NEP) as one of pulmonary RAS components. Considering the protective effect of NEP against pulmonary inflammatory reactions and fibrosis, it is suggested to direct the future efforts towards its potential role in COVID-19 pathophysiology. Thus, the review aimed to shed light on the potential beneficial effects of NEP pathways as a novel target for COVID-19 therapy by summarizing its possible molecular mechanisms. Additional experimental and clinical studies explaining more the relationships between NEP and COVID-19 will greatly benefit in designing the future treatment approaches. url: https://api.elsevier.com/content/article/pii/S0006295220302914 doi: 10.1016/j.bcp.2020.114057 id: cord-289477-cjm7qhr4 author: Mueller, Sylvia title: Potentiation of bradykinin actions by analogues of the bradykinin potentiating nonapeptide BPP(9α) date: 2005-04-25 words: 7062 sentences: 388 pages: flesch: 46 cache: ./cache/cord-289477-cjm7qhr4.txt txt: ./txt/cord-289477-cjm7qhr4.txt summary: Synthetic analogues of the bradykinin potentiating nonapeptide BPP(9α) indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). As initial experimentation on the potentiation of the bradykinin action was primarily performed on isolated smooth muscle organs, in the last decade the potentiating activity was mainly investigated on the affinity and density of the receptor [54] , the intracellular mobilization of Ca 2+ [49, 54] , the release of arachidonic acid [49, 54] , of inositol phosphates [54] , and of nitric oxide [37] . Table 1 Analogues of the bradykinin potentiating peptide BPP 9␣ (TEPROTIDE) with distinct differences between potentiation of the BK-induced contraction of the isolated guinea pig ileum (GPI) and inhibition of the isolated angiotensin I-converting enzyme (ACE) abstract: Synthetic analogues of the bradykinin potentiating nonapeptide BPP(9α) indicate significantly different structural requirements for potentiation of the bradykinin (BK)-induced smooth muscle contraction (GPI) and the inhibition of isolated somatic angiotensin I-converting enzyme (ACE). The results disprove the ACE inhibition as the only single mechanism and also the direct interaction of potentiating peptides with the bradykinin receptors in transfected COS-7 cells as molecular mechanism of potentiation. Our results indicate a stimulation of inositol phosphates (IP(n)) formation independently from the B(2) receptor. Furthermore, the results with La(3+) support the role of extracellular Ca(2+) and its influx through corresponding channels. The missing effect of calyculin on the GPI disproves the role of phosphatases in the potentiating action. These experimental studies should not only contribute to a better understanding of the potentiating mechanisms but also incorporate a shift in the research towards the immune system, in particular towards the immunocompetent polymorphonuclear leukocytes. The chemotaxis of these cells can be potentiated most likely by exclusive inhibition of the enzymatic degradation of bradykinin. Thus the obtained results give evidence that the potentiation of the bradykinin action can occur by different mechanisms, depending on the system and on the applied potentiating factor. url: https://www.ncbi.nlm.nih.gov/pubmed/15949642/ doi: 10.1016/j.peptides.2005.03.046 id: cord-298515-5n7hxhbg author: Oarhe, Chinyere I. title: Hyperoxia downregulates angiotensin-converting enzyme-2 in human fetal lung fibroblasts date: 2015-02-09 words: 5010 sentences: 273 pages: flesch: 51 cache: ./cache/cord-298515-5n7hxhbg.txt txt: ./txt/cord-298515-5n7hxhbg.txt summary: We report here the findings that ACE-2 protein and enzyme activity are severely decreased by hyperoxia in human fetal lung fibroblast cultures. Figure 6 shows that the treatment of hyperoxia followed by normoxic recovery significantly increased ADAM17/TACE immunoreactive protein by threefold in the IMR90 cells (P < 0.05). IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), but in the presence or absence of the ADAM17/ TACE inhibitor TAPI-2. IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), but in the presence or absence of the ADAM17/ TACE inhibitor TAPI-2. IMR90 cells were exposed to hyperoxic or normoxic gas as described in Figure 1 (with recovery), then were recovered for western blotting of ADAM17/TACE as described in Materials and Methods. abstract: BACKGROUND: Angiotensin (ANG) II is involved in experimental hyperoxia-induced lung fibrosis. Angiotensin-converting enzyme-2 (ACE-2) degrades ANG II and is thus protective, but is downregulated in adult human and experimental lung fibrosis. Hyperoxia is a known cause of chronic fibrotic lung disease in neonates, but the role of ACE-2 in neonatal lung fibrosis is unknown. We hypothesized that ACE-2 in human fetal lung cells might be downregulated by hyperoxic gas. METHODS: Fetal human lung fibroblast IMR90 cells were exposed to hyperoxic (95% O(2)/5% CO(2)) or normoxic (21% O(2)/5% CO(2)) gas in vitro. Cells and culture media were recovered separately for assays of ACE-2 enzymatic activity, mRNA, and immunoreactive protein. RESULTS: Hyperoxia decreased ACE-2 immunoreactive protein and enzyme activity in IMR90 cells (both P < 0.01), but did not change ACE-2 mRNA. ACE-2 protein was increased in the cell supernatant, suggesting protease-mediated ectodomain shedding. TAPI-2, an inhibitor of TNF-α−converting enzyme (TACE/ADAM17), prevented both the decrease in cellular ACE-2 and the increase in soluble ACE-2 (both P < 0.05). CONCLUSION: These data show that ACE-2 is expressed in fetal human lung fibroblasts but is significantly decreased by hyperoxic gas. They also suggest that hyperoxia decreases ACE-2 through a shedding mechanism mediated by ADAM17/TACE. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/pr.2015.27) contains supplementary material, which is available to authorized users. url: https://doi.org/10.1038/pr.2015.27 doi: 10.1038/pr.2015.27 id: cord-300850-59j1m2tm author: Peron, Jean Pierre Schatzmann title: Susceptibility of the Elderly to SARS-CoV-2 Infection: ACE-2 Overexpression, Shedding, and Antibody-dependent Enhancement (ADE) date: 2020-05-11 words: 3267 sentences: 171 pages: flesch: 44 cache: ./cache/cord-300850-59j1m2tm.txt txt: ./txt/cord-300850-59j1m2tm.txt summary: Toward this, we raise two main points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. Toward this, we raise two main points of discussion, i) the increased angiotensin-converting enzyme-2 (ACE-2) expression in pulmonary and heart tissues of hypertensive patients with chronic use of AT1R blockers and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. SARS-CoV-2 spike proteins bind to angiotensin-converting enzyme-2 (ACE-2), which is expressed in the epithelial cells of the lungs (8, 9) . We believe that i) increased expression of ACE-2 in hypertensive patients being treated with ACE inhibitors and AT1R blockers and ii) previous exposure to circulating coronaviruses with low neutralizing capacity to SARS-CoV-2 may greatly contribute to the increased susceptibility of the elderly patients to COVID-19. abstract: The world is currently facing a serious SARS-CoV-2 infection pandemic. This virus is a new isolate of coronavirus, and the current infection crisis has surpassed the SARS and MERS epidemics that occurred in 2002 and 2013, respectively. SARS-CoV-2 has currently infected more than 142,000 people, causing 5,000 deaths and spreading across more than 130 countries worldwide. The spreading capacity of the virus clearly demonstrates the potential threat of respiratory viruses to human health, thereby reiterating to the governments around the world that preventive health policies and scientific research are pivotal to overcoming the crisis. Coronavirus disease (COVID-19) causes flu-like symptoms in most cases. However, approximately 15% of the patients need hospitalization, and 5% require assisted ventilation, depending on the cohorts studied. What is intriguing, however, is the higher susceptibility of the elderly, especially individuals who are older than 60 years of age, and have comorbidities, including hypertension, diabetes, and heart disease. In fact, the death rate in this group may be up to 10-12%. Interestingly, children are somehow less susceptible and are not considered as a risk group. Therefore, in this review, we discuss some possible molecular and cellular mechanisms by virtue of which the elderly subjects may be more susceptible to severe COVID-19. Toward this, we raise two main points, i) increased ACE-2 expression in pulmonary and heart tissues in users of chronic angiotensin 1 receptor (AT1R) blockers; and ii) antibody-dependent enhancement (ADE) after previous exposure to other circulating coronaviruses. We believe that these points are pivotal for a better understanding of the pathogenesis of severe COVID-19, and must be carefully addressed by physicians and scientists in the field. url: https://doi.org/10.6061/clinics/2020/e1912 doi: 10.6061/clinics/2020/e1912 id: cord-005931-iggkxbbf author: Phillips, M. Ian title: Brain renin angiotensin in disease date: 2008-04-02 words: 4345 sentences: 257 pages: flesch: 47 cache: ./cache/cord-005931-iggkxbbf.txt txt: ./txt/cord-005931-iggkxbbf.txt summary: Transgenic mice and rats bearing renin and extra copies of angiotensinogen genes revealed the importance of brain RAS. Taking the concept a step further, it was reasoned that if ANG II, formed by brain renin, was involved in hypertension, then inhibiting brain RAS would lower blood pressure. Minute injections of ANG II into key brain nuclei showed that ANG II could differentially produce pressor effects, elicit drinking, release vasopressin, inhibit the baroreflex, and increase sympathetic nervous system activity [20, 21] . In the double transgenic mice developed by Sigmund and colleagues [35] , to overexpress both human renin and human AGT so that they constantly have high ANG II levels, antisense to AT1R mRNA dramatically reduced the blood pressure. ACE-2, ANG (1-7), and Mas receptors are all localized in brain areas related to the control of cardiovascular function. abstract: A brain renin angiotensin system (RAS) and its role in cardiovascular control and fluid homeostasis was at first controversial. This was because a circulating kidney-derived renin angiotensin system was so similar and well established. But, the pursuit of brain RAS has proven to be correct. In the course of accepting brain RAS, high standards of proof attracted state of the art techniques in all the new developments of biolo1gy. Consequently, brain RAS is a robust concept that has enlightened neuroscience as well as cardiovascular physiology and is a model neuropeptide system. Molecular biology confirmed the components of brain RAS and their location in the brain. Transgenic mice and rats bearing renin and extra copies of angiotensinogen genes revealed the importance of brain RAS. Cre-lox delivery in vectors has enabled pinpoint gene deletion of brain RAS in discrete brain nuclei. The new concept of brain RAS includes ACE-2, Ang1–7, and prorenin and Mas receptors. Angiotensin II (ANG II) generated in the brain by brain renin has many neural effects. It activates behavioral effects by selective activation of ANG II receptor subtypes in different locations. It regulates sympathetic activity and baroreflexes and contributes to neurogenic hypertension. New findings implicate brain RAS in a much wider range of neural effects. We review brain RAS involvement in Alzheimer’s disease, stroke memory, and learning alcoholism stress depression. There is growing evidence to consider developing treatment strategies for a variety of neurological disease states based on brain RAS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7095973/ doi: 10.1007/s00109-008-0331-5 id: cord-351567-ifoe8x28 author: Rabi, Firas A. title: SARS-CoV-2 and Coronavirus Disease 2019: What We Know So Far date: 2020-03-20 words: 5745 sentences: 315 pages: flesch: 54 cache: ./cache/cord-351567-ifoe8x28.txt txt: ./txt/cord-351567-ifoe8x28.txt summary: However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. To assess the magnitude of the risk posed by the SARS-CoV-2, we review four parameters that we believe important: the transmission rate, the incubation period, the case fatality rate (CFR), and the determination of whether asymptomatic transmission can occur. A small study of 17 patients showed that nasal viral load peaks within days of symptom onset, suggesting that transmission of disease is more likely to occur early in the course of infection [40] . Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: A descriptive study The Epidemiological Characteristics of an Outbreak of 2019 Novel Coronavirus Diseases (COVID-19)-China 2020 Early Transmission Dynamics in Wuhan, China, of Novel Coronavirus-Infected Pneumonia abstract: In December 2019, a cluster of fatal pneumonia cases presented in Wuhan, China. They were caused by a previously unknown coronavirus. All patients had been associated with the Wuhan Wholefood market, where seafood and live animals are sold. The virus spread rapidly and public health authorities in China initiated a containment effort. However, by that time, travelers had carried the virus to many countries, sparking memories of the previous coronavirus epidemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), and causing widespread media attention and panic. Based on clinical criteria and available serological and molecular information, the new disease was called coronavirus disease of 2019 (COVID-19), and the novel coronavirus was called SARS Coronavirus-2 (SARS-CoV-2), emphasizing its close relationship to the 2002 SARS virus (SARS-CoV). The scientific community raced to uncover the origin of the virus, understand the pathogenesis of the disease, develop treatment options, define the risk factors, and work on vaccine development. Here we present a summary of current knowledge regarding the novel coronavirus and the disease it causes. url: https://doi.org/10.3390/pathogens9030231 doi: 10.3390/pathogens9030231 id: cord-306755-9q1mawfs author: Rivière, Guillaume title: Characterization of the first angiotensin-converting like enzyme in bacteria: Ancestor ACE is already active date: 2007-09-01 words: 5364 sentences: 301 pages: flesch: 52 cache: ./cache/cord-306755-9q1mawfs.txt txt: ./txt/cord-306755-9q1mawfs.txt summary: Interestingly, in silico databank analysis revealed that bacterial DNA sequences could encode putative ACE-like proteins, strikingly similar to vertebrates'' enzymes. Interestingly, and though in silico evidence suggest the presence of a two-domain ACE-related protein in mosquitoes (Burnham et al., 2005) , all the cloned genes encode soluble, single active site enzymes (Tatei et al., 1995; Taylor et al., 1996; Wijffels et al., 1996) . The protein encoded by this gene, referred to as XcACE (Xanthomonas citri angiotensin-converting enzyme), is a 672 amino-acid protein. Key active site residues such as the zinc-binding motif, His 513 and Tyr 526 (tACE numbering) are conserved in XcACE and many other ACE-like enzymes. However, in line with the assay results, the non-conserved active site residues are neither identical to the C-or N-domain of human ACE, and are the presumed cause of the different substrate selectivity and inhibition profile of XcACE. Functional conservation of the active sites of human and Drosophila angiotensin I-converting enzyme abstract: Angiotensin-converting enzyme (ACE) is a metallopeptidase that converts angiotensin I into angiotensin II. ACE is crucial in the control of cardiovascular and renal homeostasis and fertility in mammals. In vertebrates, both transmembrane and soluble ACE, containing one or two active sites, have been characterized. So far, only soluble, single domain ACEs from invertebrates have been cloned, and these have been implicated in reproduction in insects. Furthermore, an ACE-related carboxypeptidase was recently characterized in Leishmania, a unicellular eukaryote, suggesting the existence of ACE in more distant organisms. Interestingly, in silico databank analysis revealed that bacterial DNA sequences could encode putative ACE-like proteins, strikingly similar to vertebrates' enzymes. To gain more insight into the bacterial enzymes, we cloned the putative ACE from the phytopathogenic bacterium, Xanthomonas axonopodis pv. citri, named XcACE. The 2 kb open reading frame encodes a 672-amino-acid soluble protein containing a single active site. In vitro expression and biochemical characterization revealed that XcACE is a functional 72 kDa dipeptidyl-carboxypeptidase. As in mammals, this metalloprotease hydrolyses angiotensin I into angiotensin II. XcACE is sensitive to ACE inhibitors and chloride ions concentration. Variations in the active site residues, highlighted by structural modelling, can account for the different substrate selectivity and inhibition profile compared to human ACE. XcACE characterization demonstrates that ACE is an ancestral enzyme, provoking questions about its appearance and structure/activity specialisation during the course of evolution. url: https://api.elsevier.com/content/article/pii/S0378111907002521 doi: 10.1016/j.gene.2007.05.010 id: cord-002468-onpmkjaz author: Roca-Ho, Heleia title: Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse date: 2017-03-05 words: 5850 sentences: 370 pages: flesch: 59 cache: ./cache/cord-002468-onpmkjaz.txt txt: ./txt/cord-002468-onpmkjaz.txt summary: In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. At cardiac level, there was a In serum samples, there was a significant increase of ACE2 activity in DB mice at early and late stages of diabetes as compared to CONT (p = 0.0003 and p = 0.0003, respectively) and insulin administration significantly decreased ACE2 activity in DB mice at early and late stages (p = 0.001 and p = 0.001, respectively) ( Figure 4a ). At cardiac level, there was a significant increase of ACE2 activity in DB mice in both early and late stages of DB as compared to CONT mice (p = 0.011 and p = 0.029, respectively), however, insulin administration did not modify this pattern (p = NS) (Figure 4b) . abstract: Renin angiotensin system (RAS) is known to play a key role in several diseases such as diabetes, and renal and cardiovascular pathologies. Its blockade has been demonstrated to delay chronic kidney disease progression and cardiovascular damage in diabetic patients. In this sense, since local RAS has been described, the aim of this study is to characterize angiotensin converting enzyme (ACE) and ACE2 activities, as well as protein expression, in several tissues of the non-obese diabetic (NOD) mice model. After 21 or 40 days of diabetes onset, mouse serums and tissues were analyzed for ACE and ACE2 enzyme activities and protein expression. ACE and ACE2 enzyme activities were detected in different tissues. Their expressions vary depending on the studied tissue. Thus, whereas ACE activity was highly expressed in lungs, ACE2 activity was highly expressed in pancreas among the studied tissues. Interestingly, we also observed that diabetes up-regulates ACE mainly in serum, lung, heart, and liver, and ACE2 mainly in serum, liver, and pancreas. In conclusion, we found a marked serum and pulmonary alteration in ACE activity of diabetic mice, suggesting a common regulation. The increase of ACE2 activity within the circulation in diabetic mice may be ascribed to a compensatory mechanism of RAS. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5372579/ doi: 10.3390/ijms18030563 id: cord-006082-x1kankxd author: Romero, Cesar A. title: Novel RAAS agonists and antagonists: clinical applications and controversies date: 2015-02-10 words: 8412 sentences: 448 pages: flesch: 42 cache: ./cache/cord-006082-x1kankxd.txt txt: ./txt/cord-006082-x1kankxd.txt summary: Despite the important improvements achieved with these agents in slowing the progression of established cardiorenal disease, the ACE inhibitors and the ARBs only provide a 20% reduction in the relative risk of Key points ■ Renin-angiotensin-aldosterone system (RAAS) blockade with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker provides a 20% relative risk reduction for the progression of established cardiorenal disease compared with other non-RAAS blocking therapies ■ The RAAS is an endocrine, paracrine and autocrine system that regulates blood pressure homeostasis through effects on a variety of target organs, as well as having a role in the responses to vascular injury and repair ■ The RAAS is a complex system with a variety of sites suitable for pharmacological intervention ■ Novel molecules that alter the production of various RAAS peptides or that alter receptor density, function or responsiveness to these peptides could have an important influence on haemodynamics and vascular structure and function www.nature.com/nrendo progression of cardiovascular disease when compared with non-RAAS blocking therapy. abstract: The renin–angiotensin–aldosterone system (RAAS) regulates blood pressure homeostasis and vascular injury and repair responses. The RAAS was originally thought to be an endocrine system critically important in regulating blood pressure homeostasis. Yet, important local forms of the RAAS have been described in many tissues, which are mostly independent of the systemic RAAS. These systems have been associated with diverse physiological functions, but also with inflammation, fibrosis and target-organ damage. Pharmacological modulation of the RAAS has brought about important advances in preventing morbidity and mortality associated with cardiovascular disease. Yet, traditional RAAS blockers such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) only reduce the risk of disease progression in patients with established cardiovascular or renal disease by ∼20% compared with other therapies. As more components of the RAAS are described, other potential therapeutic targets emerge, which could provide improved cardiovascular and renal protection beyond that provided by an ACE inhibitor or ARB. This Review summarizes the present and future pharmacological manipulation of this important system. SUPPLEMENTARY INFORMATION: The online version of this article (doi:10.1038/nrendo.2015.6) contains supplementary material, which is available to authorized users. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7097622/ doi: 10.1038/nrendo.2015.6 id: cord-290148-6cxndab8 author: Rossi, Gian Paolo title: Potential harmful effects of discontinuing ACE-inhibitors and ARBs in COVID-19 patients date: 2020-04-06 words: 3145 sentences: 156 pages: flesch: 46 cache: ./cache/cord-290148-6cxndab8.txt txt: ./txt/cord-290148-6cxndab8.txt summary: The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARSCoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). However, they differ markedly: ACE-1 cleaves the dipeptide His-Leu from angiotensin I, thus generating angiotensin (Ang) II, which causes vaso-and broncho-constriction, increases vascular permeability, inflammation, and fibrosis and thereby promotes the development of ARDS and lung failure in patients infected with the SARS-CoV and SARS-CoV-2 (Yang et al., 2015) (Figure 1, panel B) . In one commentary ACE-2 was suggested to be secreted at higher amounts in patients with cardiovascular disease than in healthy individuals, and in another, it was also stated that ''ACE-2 levels can be increased by the use of ACEIs'' , albeit no evidence of this occurring in the lungs Mechanisms of COVID-19 by which the SARS-COV-2 virus infects the lower airway cells and modalities to increase circulating soluble ACE-2 for therapeutic use. abstract: The discovery of angiotensin converting enzyme-2 (ACE-2) as the receptor for SARS- CoV-2 (Severe Acute Respiratory Syndrome Coronavirus-2) has implicated the renin-angiotensin-aldosterone system in acute respiratory distress syndrome (ARDS) and respiratory failure in patients with coronavirus disease-19 (COVID-19). The angiotensin converting enzyme-1–angiotensin II–angiotensin AT(1) receptor pathway contributes to the pathophysiology of ARDS, whereas activation of the ACE-2–angiotensin(1-7)-angiotensin AT(2) receptor and the ACE-2–angiotensin(1-7)–Mas receptor pathways have been shown to be protective. Here we propose and discuss therapeutic considerations how to increase soluble ACE-2 in plasma in order for ACE-2 to capture and thereby inactivate SARS-CoV-2. This could be achieved by administering recombinant soluble ACE-2. We also discuss why and how ACEIs and ARBs provide cardiovascular, renal and also pulmonary protection in SARS-CoV-2- associated ARDS. Discontinuing these medications in COVID-19 patients may therefore potentially be harmful. url: https://www.ncbi.nlm.nih.gov/pubmed/32250244/ doi: 10.7554/elife.57278 id: cord-291146-f3e5ynhu author: Sarangarajan, Rangaprasad title: Ethnic Prevalence of Angiotensin-Converting Enzyme Deletion (D) Polymorphism and COVID-19 Risk: Rationale for Use of Angiotensin-Converting Enzyme Inhibitors/Angiotensin Receptor Blockers date: 2020-09-08 words: 4321 sentences: 212 pages: flesch: 35 cache: ./cache/cord-291146-f3e5ynhu.txt txt: ./txt/cord-291146-f3e5ynhu.txt summary: The specificity of hypertension and cardiovascular disease as underlying causes for severity of COVID-19 infection, the inherent role of ACE-mediated generation of Ang-II and downstream signalling to potentially exacerbate inflammation and organ damage along with genotypic impact on ACE status provide compelling support of the use of ACE-I and ARBs in the clinical management of patient with positive diagnosis of COVID-19. The significant genetic, scientific and clinical data supporting a potential role for increased ACE levels and associated Ang-II effect in target organs provides compelling argument for use of ACE-I and ARBs in the clinical management of patients with COVID-19 infections to improve outcomes. In summary, this study describes the biological relevance of genetic polymorphism of ACE deletion with higher prevalence in certain ethnic populations including African Americans in context of COVID-19 infection and rationale for the use of ACE-I/ARBs for therapeutic management of severity of morbidity and improving outcomes associated with COVID-19. abstract: RATIONALE: Hypertension, obesity and diabetes are major risk factors associated with morbidities underlying COVID-19 infections. Regression analysis correlated presence of ACE insertion/deletion (I/D) polymorphism to COVID-19 incidence and mortality. Furthermore, COVID-19 prevalence correlated to allele frequency of angiotensin-converting enzyme (ACE) deletion (D) polymorphism within the European population. OBJECTIVE: Homozygous ACE deletion polymorphism is associated with increase in ACE and angiotensin II (Ang-II), sustained levels can result in inflammation, fibrosis and organ damage. The ACE DD polymorphism is also associated with hypertension, acute respiratory distress and diabetic nephropathy, all considered high risk for COVID-19 infection and outcomes. The study objective was to describe a biological framework associating ethnic prevalence of ACE deletion polymorphism to COVID-19 comorbidities providing rationale for therapeutic utility of ACE-I/ARBs to improve outcomes. METHOD AND RESULTS: The Allele Frequency Database (ALFRED) was queried for frequency of rs4646994 representing ACE I/D polymorphism. In a total of 349 worldwide population samples, frequency of ACE D allele was higher in European, Asian, and Africans cohorts. In the USA, the frequency of ACE D allele was higher in non-Hispanic Black compared with non-Hispanic White and Mexican Americans. CONCLUSION: COVID-19 binding mediated reduction/inactivation of ACE-II can increase ACE/Ang-II signalling pathway and related pathologies. The presence of ACE DD polymorphism with COVID-19 infection likely augments ACE/Ang-II activities, increasing severity of COVID-19 morbidities and impacts outcomes. Thus, ethnic prevalence of ACE DD polymorphism can explain in part the severity of COVID-19 morbidity providing rationale for the use of ACE-I/ARBs to improve outcomes. url: https://www.ncbi.nlm.nih.gov/pubmed/32901433/ doi: 10.1007/s40615-020-00853-0 id: cord-296683-fjn29oal author: Sarode, Sachin C title: Oral submucous fibrosis and COVID-19: Perspective on comorbidity date: 2020-05-21 words: 961 sentences: 70 pages: flesch: 54 cache: ./cache/cord-296683-fjn29oal.txt txt: ./txt/cord-296683-fjn29oal.txt summary: Novel Corona Virus infection (COVID-19) is a highly infective disease with rapid global spread since January 2020 and was declared as pandemic by World Health Organization. 1 Angiotensin Converting Enzyme 2 (ACE 2), present on the cell surfaces of some important organs, has been identified as target receptor for COVID-19 virus entry into the host cells. 3 In addition, ACE 2 has been reported to be present at various locations in the oral cavity and hence, oral cavity is considered as a potential site for the COVID 19 virus. 8 Thus, the less availability of ACE 2 in the oral cavity might have compromised the binding of COVID 19 virus. The other way round, if OSMF patient is affected with COVID-19, then it may cause further exhaustion of ACE 2. As ACE 2 is the binding site for COVID-19, it may compromise the infectivity of the virus. abstract: nan url: https://doi.org/10.1016/j.oraloncology.2020.104811 doi: 10.1016/j.oraloncology.2020.104811 id: cord-327697-80msva10 author: Sarı, Cenk title: The outcomes of the postulated interaction between SARS-CoV-2 and the renin-angiotensin system on the clinician’s attitudes toward hypertension treatment date: 2020-11-09 words: 3552 sentences: 180 pages: flesch: 46 cache: ./cache/cord-327697-80msva10.txt txt: ./txt/cord-327697-80msva10.txt summary: Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). In the first half of 2020, it was speculated that angiotensinconverting enzyme inhibitors (ACE-i)/angiotensin receptor blockers (ARBs) may make patients more susceptible to COVID-19 disease and lead to worse outcomes. Observational studies have reported that patients taking ACE-i/ARBs treatment are at increased risk of becoming infected with SARS-CoV2 and developing severe forms of COVID-19 disease. The strategy for repeating therapy was the same in all physicians, and the practice of starting new ACE-i/ARBs reported by the cardiologists was statistically different from that of both internal medicine and family medicine/general practitioners (8.0 ± 4 vs 8.0 ± 4 vs 9.0 ± 3, p < 0.05) ( Table 2) . The present survey is the first study to have provided a snapshot showing behaviors of Turkish physicians toward prescribing ACE-i/ARBs treatment during the COVID-19 pandemic. abstract: Concern has arisen about the role played in coronavirus disease 2019 (COVID-19) infection by angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs). This study was designed to assess the practice behaviors of physicians toward hypertension treatment with ACE-i or ARBs during the COVID-19 pandemic. A self-administered survey questionnaire consisting of 26 questions about current hypertension treatment with ACE-i/ ARBs was applied to cardiologists, internists, and family physicians in central and western Turkey, between 01 and 19 May 2020. A total of 460 physicians were approached, and 220 (47.8%) participated in the study. Of the total respondents, 78.7% reported that they had not changed their antihypertensive medication prescribing pattern, 8.6% of clinicians had changed ACE-i/ ARBs medicine of patients during the COVID-19 pandemic and 12.7% of them were undecided. The median (±interquartile range) score indicating general reliance level of physicians in ACE-i/ARBs therapy was 8 ± 4 (range, 1–10). In multiple comparison analyses, the general reliance level in ACE-i/ARBs, reliance level when starting a new ACEi/ARBs and changing behavior in heart failure patients were significantly different with regard to the specialties (p:0.02, p:0.009, p:0.005 respectively). Although most of the physicians found the publications about ACE-i/ ARBs during the COVID-19 pandemic untrustworthy, there were variable levels of knowledge and reliance among different physicians and specialty groups. In general, the ACE-i/ ARBs prescribing habits were not affected by safety concerns during the COVID-19 pandemic in Turkey. url: https://www.ncbi.nlm.nih.gov/pubmed/33168943/ doi: 10.1038/s41371-020-00436-w id: cord-342786-dl8vjwfn author: Sattar, Yasar title: COVID-19 Cardiovascular Epidemiology, Cellular Pathogenesis, Clinical Manifestations and Management date: 2020-07-14 words: 5268 sentences: 349 pages: flesch: 37 cache: ./cache/cord-342786-dl8vjwfn.txt txt: ./txt/cord-342786-dl8vjwfn.txt summary: Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. The infected patients may also present with cardiovascular disease (CVD) like acute coronary syndrome(ACS) and congestive cardiac failure(CHF) [6] . The systemic inflammation in COVID-19 may also dysregulate the post-translational modification of cardiac ion channels resulting in arrhythmia [25, 26] It is also noteworthy that viral proteins of SARS-CoV-2, ORF3 and ORF8, activate NLRP3 inflammasomes which inturn promotes atrial fibrillation [27, 28] . abstract: Abstract Coronavirus Disease 2019 (COVID-19) is a rapidly progressing global pandemic that may present with a variety of cardiac manifestations including, but not limited to, myocardial injury, myocardial infarction, arrhythmias, heart failure, cardiomyopathy, shock, thromboembolism, and cardiac arrest. These cardiovascular effects are worse in patients who have pre-existing cardiac conditions such as coronary artery disease, hypertension, diabetes mellitus, and coagulation abnormalities. Other predisposing risk factors include advanced age, immunocompromised state, and underlying systemic inflammatory conditions. Here we review the cellular pathophysiology, clinical manifestations and treatment modalities of the cardiac manifestations seen in patients with COVID-19. url: https://api.elsevier.com/content/article/pii/S2352906720302876 doi: 10.1016/j.ijcha.2020.100589 id: cord-289144-d6fgs8qg author: Sieńko, Jerzy title: COVID-19: The Influence of ACE Genotype and ACE-I and ARBs on the Course of SARS-CoV-2 Infection in Elderly Patients date: 2020-07-21 words: 5129 sentences: 320 pages: flesch: 49 cache: ./cache/cord-289144-d6fgs8qg.txt txt: ./txt/cord-289144-d6fgs8qg.txt summary: Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. 8, 13 The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. 8, 13 The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. 63 This upregulation of the ACE2 receptor causes an increase in SARS-CoV-2 binding sites, which can lead to COVID-19 infection. Association of inpatient use of angiotensin converting enzyme inhibitors and angiotensin II receptor blockers with mortality among patients with hypertension hospitalized with COVID-19 abstract: Since the beginning of 2020, the whole world has been struggling with the pandemic of Coronavirus Disease 2019 (COVID-19) caused by a novel coronavirus SARS-CoV-2. The SARS-CoV-2 infection depends on ACE2, TMPRSS2, and CD147, which are expressed on host cells. Several studies suggest that some single nucleotide polymorphisms (SNPs) of ACE2 might be a risk factor of COVID-19 infection. Genotypes affect ACE2 structure, its serum concentration, and levels of circulating angiotensin (1-7). Moreover, there is evidence that ACE genotype affects the outcomes of acute respiratory distress syndrome (ARDS) treatment, the most severe consequence of SARS-CoV-2 infection. COVID-19 morbidity, infection course, and mortality might depend on ACE D allele frequency. The aim of this narrative review was to analyze and identify the mechanisms of ACE-I and ARBs with particular emphasis on angiotensin receptors and their polymorphism in the light of COVID-19 pandemic as these medications are commonly prescribed to elderly patients. There is no direct evidence yet for ACE-I or ARBs in the treatment of COVID-19. However, for those already taking these medications, both the European Society of Cardiology and the American College of Cardiology recommend continuing the treatment, because at present, there is no clear clinical or scientific evidence to justify the discontinuation of ACE-I or ARBs. Individualized treatment decisions should be based on the clinical condition and co-morbidities of each patient. url: https://www.ncbi.nlm.nih.gov/pubmed/32764907/ doi: 10.2147/cia.s261516 id: cord-286638-bqxyb61p author: Singh, Awadhesh Kumar title: Diabetes in COVID-19: Prevalence, pathophysiology, prognosis and practical considerations date: 2020-04-09 words: 4824 sentences: 281 pages: flesch: 46 cache: ./cache/cord-286638-bqxyb61p.txt txt: ./txt/cord-286638-bqxyb61p.txt summary: The disease burden of coronavirus infectious disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS CoV-2) has been increasing continuously with more than a million confirmed patients and more than 45 thousand deaths globally [1] . Emerging data suggests that COVID-19 is common in patients with diabetes, hypertension, and cardiovascular disease (CVD), although the prevalence rate varied in different studies as well in country-wise data. Evolving data also suggest that patients of COVID-19 with diabetes are more often associated with severe or critical disease varying from 14 to 32% in different studies [15e18, 20, 22, 24] . Though there is limited data about the association of blood glucose levels with disease course in COVID-19 at present, data from other infections like SARS and influenza H1N1 has shown that patients with poor glycemic control have increased risk of complications and death [60, 61] . abstract: BACKGROUND AND AIMS: High prevalence of diabetes makes it an important comorbidity in patients with COVID-19. We sought to review and analyze the data regarding the association between diabetes and COVID-19, pathophysiology of the disease in diabetes and management of patients with diabetes who develop COVID-19 infection. METHODS: PubMed database and Google Scholar were searched using the key terms ‘COVID-19’, ‘SARS-CoV-2’, ‘diabetes’, ‘antidiabetic therapy’ up to April 2, 2020. Full texts of the retrieved articles were accessed. RESULTS: There is evidence of increased incidence and severity of COVID-19 in patients with diabetes. COVID-19 could have effect on the pathophysiology of diabetes. Blood glucose control is important not only for patients who are infected with COVID-19, but also for those without the disease. Innovations like telemedicine are useful to treat patients with diabetes in today’s times. url: https://doi.org/10.1016/j.dsx.2020.04.004 doi: 10.1016/j.dsx.2020.04.004 id: cord-338417-7kw9lws0 author: Singh, Awadhesh Kumar title: Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers date: 2020-04-09 words: 3212 sentences: 172 pages: flesch: 48 cache: ./cache/cord-338417-7kw9lws0.txt txt: ./txt/cord-338417-7kw9lws0.txt summary: RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Emerging data suggests that older COVID-19 patients with other comorbid conditions such as diabetes, hypertension, cardiac and pulmonary disease are in particular more susceptible, compared to general populations and have higher mortality. We have systematically searched the PubMed medical database up till March 27, 2020 using MeSH key words that include Covid-19, coronavirus, hypertension, diabetes, cardiovascular disease, angiotensin receptor blockers, angiotensin converting enzyme inhibitors. Interestingly, in the pooled data from the ten Chinese studies (n ¼ 2209) that have reported the characteristics of comorbidities in patients with COVID-19; associations of hypertension, diabetes and presence of established cardiovascular disease (CVD) are larger, varying from 15 to 30% (average 21%), 5e20% (average 11%) and 2e40% (average 7%) respectively (Table 1) . abstract: BACKGROUND AND AIMS: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). METHODS: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. RESULTS: From the pooled data of all ten available Chinese studies (n = 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. CONCLUSION: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider. url: https://doi.org/10.1016/j.dsx.2020.03.016 doi: 10.1016/j.dsx.2020.03.016 id: cord-353707-3n2nji8l author: Sunden-Cullberg, Jonas title: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death date: 2020-04-28 words: 679 sentences: 44 pages: flesch: 54 cache: ./cache/cord-353707-3n2nji8l.txt txt: ./txt/cord-353707-3n2nji8l.txt summary: title: Chronic Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers Is High Among Intensive Care Unit Patients With Non–COVID-19 Sepsis but Carries a Moderately Increased Risk of Death We, therefore, examined the chronic use of ACE inhibitors/ARBs and associated mortality in a historic cohort of septic patients admitted to the Intensive Care Unit. Data were collected between January 2008 and December 2015 on a nationwide Swedish cohort of 2700 patients, aged 18 years and over, with community-acquired severe sepsis and septic shock admitted to the Intensive Care Unit within 24 hours of arrival to any of 32 emergency departments throughout the country. ACE inhibitors/ ARB use was common among patients admitted to the Intensive Care Unit because of sepsis. ACE inhibitors/ARB use and associated mortality among critically ill COVID-19 patients can be compared with this data. Hypothesis: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers may increase the risk of severe COVID-19 abstract: nan url: https://doi.org/10.1161/hypertensionaha.120.15178 doi: 10.1161/hypertensionaha.120.15178 id: cord-005386-p37rw8dh author: Szolnoki, Zoltán title: Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke date: 2006 words: 3058 sentences: 168 pages: flesch: 49 cache: ./cache/cord-005386-p37rw8dh.txt txt: ./txt/cord-005386-p37rw8dh.txt summary: title: Coexistence of angiotensin II type-1 receptor A1166C and angiotensin-converting enzyme D/D polymorphism suggests susceptibility for small-vessel-associated ischemic stroke Our results demonstrate that ACE D/D and AT1R 1166C polymorphism were associated with the development of small-vessel ischemic stroke through a mutually facilitatory interplay between them. As both polymorphisms are associated with an enhanced activity of the angiotensin II-AT1R axis, we postulated at a clinical level, a synergistic effect between them as regards the evolution of ischemic stroke. A synergistic effect was found between the AT1R 1166C allele and the homozygous ACE D/D genotype in the small-vessel stroke subgroup (adjusted OR, 3.54; 95% CI, 1.88-7.16; p < 0.0005), the mixed vascular type (adjusted OR, 2.41; 95% CI, 1.2-5.1; p < 0.05), and the overall ischemic stroke group (adjusted OR, 2.42; 95% CI, 1.51-3.82; p < 0.005) ( Table 3 ). abstract: The renin-angiotensin system plays an important role in the maintenance of blood pressure homeostasis. The angiotensin-converting enzyme (ACE) converts angiotensin I into angiotensin II. Angiotensin II, which binds the angiotensin II type-1 receptor (AT1R), is a potent vasoconstrictor. On a pathophysiological basis, both ACE I/D and AT1R A1166C polymorphism lead to an enhanced activity of the angiotensin II-AT1R axis, thereby possibly contributing to circulatory disturbances. A mutually facilitatory effect may be presumed between the two polymorphisms. We examined whether this synergistic effect is involved in the evolution of different types of ischemic stroke. Genetic and clinical data on 308 consecutive patients with acutely developing ischemic stroke were analyzed. A total of 272 stroke and neuroimaging alteration-free subjects served as a control group. Univariate and logistic regression statistical approaches were used. The ACE D allele combined with the AT1R 1166C allele did not yield a risk of ischemic stroke. However, the co-occurrence of the homozygous ACE D/D and at least one AT1R 1166C allele was more frequent in the ischemic stroke group than in the control group (22.4 vs 11%, p<0.005, OR, 2.33; 95% CI, 1.46–3.7). After specific subgroup analysis, this synergistic association was even stronger for small-vessel ischemic stroke (OR, 3.44; 95% CI, 1.9–6.24; p<0.0005). Multivariate logistic regression analysis of the data confirmed this association (adjusted OR, 3.54, 95% CI, 1.88–7.16; p<0.0005). Our results demonstrate that ACE D/D and AT1R 1166C polymorphism were associated with the development of small-vessel ischemic stroke through a mutually facilitatory interplay between them. Genetic interactions might contribute to the altered functional network in renin-angiotensin system in vascular disorders. url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7091324/ doi: 10.1385/nmm:8:3:353 id: cord-282256-lqmixm7s author: Tsioufis, Costas title: The interplay of Hypertension, ACE-2 and SARS-CoV-2: Emerging data as the “Ariadne’s thread” for the “labyrinth” of COVID-19 date: 2020-05-22 words: 1847 sentences: 113 pages: flesch: 49 cache: ./cache/cord-282256-lqmixm7s.txt txt: ./txt/cord-282256-lqmixm7s.txt summary: 4 The only available meta-analysis from Wuhan of 46248 cases, supports that hypertension constitutes the most prevalent comorbidity in 17% of patients infected with the novel coronavirus. In Italy the most current analysis shows that of 69.1% of the deceased patients were hypertensives and 30% used angiotensin converting enzyme inhibitors (ACEIs) and 17% angiotensin receptor blockers (ARBs). 18 After adjustment for confounders there was no independent association for the use of ACEIs/ARBs with susceptibility for infection or worse clinical outcome in contrast to loop diuretics that were linked to enhanced risk. Hypertension, the renin-angiotensin system, and the risk of lower respiratory tract infections and lung injury: implications for COVID-19 Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis Association of Inpatient Use of Angiotensin Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers with Mortality Among Patients With Hypertension Hospitalized With COVID-19 abstract: nan url: https://www.ncbi.nlm.nih.gov/pubmed/32450334/ doi: 10.1016/j.hjc.2020.05.003 id: cord-269151-r426u5dz author: Turner, Jeffrey M. title: Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension? date: 2020-07-09 words: 4595 sentences: 212 pages: flesch: 42 cache: ./cache/cord-269151-r426u5dz.txt txt: ./txt/cord-269151-r426u5dz.txt summary: More recently, a number of indirect comparisons with pooled analysis of several randomized placebo control trials have been done to further elucidate whether ACE inhibitors and ARBs have differing effects on the risk of myocardial infarction [16] [17] [18] [19] . Finally, in the previously mentioned Bangalore paper, a separate meta-analysis of the only head to head trials between ACE inhibitors and ARBs also showed no difference in the risk for myocardial infarction or cardiovascular death between the two classes [16] . Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have resulted in significant improvements in outcomes related to congestive heart failure, cardiovascular disease, diabetes, stroke, and kidney disease. A meta-analysis reporting effects of angiotensinconverting enzyme inhibitors and angiotensin receptor blockers in patients without heart failure Effect of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on all-cause mortality, cardiovascular deaths, and cardiovascular events in patients with diabetes mellitus: a meta-analysis abstract: PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. RECENT FINDINGS: In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. SUMMARY: From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension. url: https://doi.org/10.1007/s11886-020-01352-8 doi: 10.1007/s11886-020-01352-8 id: cord-326405-3446eyi3 author: Wysocki, Jan title: Angiotensin-converting enzyme 2: Possible role in hypertension and kidney disease date: 2008-02-07 words: 5654 sentences: 298 pages: flesch: 48 cache: ./cache/cord-326405-3446eyi3.txt txt: ./txt/cord-326405-3446eyi3.txt summary: The high catalytic efficiency of ACE2 for the generation of angiotensin (ANG)-1-7 from ANG II suggests an important role of ACE2 in preventing ANG II accumulation, while at the same time enhancing ANG-1-7 formation. [41] , primarily describing an Ace2 knockout and its associated cardiac pathology, also reported that ACE2 was reduced at the gene and protein level in kidneys from three separate rat models of spontaneous and diet-induced hypertension. Investigating the role of ACE2 in those two prevalent diseases and whether its effects are mediated by ANG II or ANG-(1-7) and other biologically active peptides, which are also substrates of ACE2, opens the way for developing new therapeutic targets in hypertension. ACE2 inhibition worsens glomerular injury in association with increased ACE expression in streptozotocin-induced diabetic mice Also, pharmacologic ACE2 inhibition was associated with increased albuminuria, suggesting a role of glomerular ACE2 in diabetic kidney injury abstract: The discovery of angiotensin-converting enzyme (ACE) 2 adds a new level of complexity to the understanding of the renin-angiotensin system. The high catalytic efficiency of ACE2 for the generation of angiotensin (ANG)-1-7 from ANG II suggests an important role of ACE2 in preventing ANG II accumulation, while at the same time enhancing ANG-1-7 formation. ACE and ACE2 may have counterbalancing functions and a regulatory role in fine-tuning the rate at which ANG peptides are formed and degraded. By counterregulating the actions of ACE on ANG II formation, ACE2 may play a role in maintaining a balanced status of the renninangiotensin system. This review focuses on the function of ACE2 and its possible roles in kidney disease and hypertension. Studies using models of ACE2 ablation and the pharmacologic administration of an ACE2 inhibitor suggest that decreased ACE2 activity alone or in combination with increased ACE activity may play a role in both diseases. url: https://www.ncbi.nlm.nih.gov/pubmed/18367030/ doi: 10.1007/s11906-008-0014-1 id: cord-266755-y2lf7ssp author: Yehualashet, Awgichew Shewasinad title: ACEIs and ARBs and Their Correlation with COVID-19: A Review date: 2020-09-16 words: 4160 sentences: 221 pages: flesch: 46 cache: ./cache/cord-266755-y2lf7ssp.txt txt: ./txt/cord-266755-y2lf7ssp.txt summary: 21, 22 Both ACE-1 and ACE-2 cleave angiotensin peptides in that ACE-1 cleaves angiotensin I and generating angiotensin (Ang) II, which causes vasoconstriction, bronchoconstriction, increases vascular permeability, inflammation, and fibrosis and enhance the development of acute respiratory disease syndrome (ARDS) and lung failure in patients infected with SARS-CoV-2. 36 The probable rational proposed for the possible relation between the use of ACEIs/ARBs, and progression to ARDS in COVID-19 is the increased availability of ACE-2 attached to surface in the lung endothelium, an inherent effect of these two classes, leading to enhanced coupling of SARS-CoV2 to ACE-2 and its consequent cell entry. Based on prior animal studies, it was suggested that proposed ACEIs and ARBs can enhance ACE2 activity and thereby increase infectivity of COVID-19 virus. 48 In severe lung injury animal models, preclinical studies have showed that ACE2 is significantly downregulated and it has been shown that the inhibition of the angiotensin type 1 receptor by ARB like losartan reduces severe acute lung injury in mice administered with the spike glycoprotein of SARS-CoV. abstract: Although some animal studies suggested that the use of ACEIs/ARBs could contribute for the prevention and treatment of the effects of the COVID-19 infection, there are also contradictory scenarios indicating that their use may exacerbate the deleterious conditions of the infection. As a result of the paradoxical issue of using ACEIs/ARBs during COVID-19, it is still an area requiring extended investigation to prove. Additionally, a trial evidence of their efficacy and the possible benefit risk analysis of these conventional drugs during COVID-19 in connection with other comorbidities like hypertension, heart failure, and renal disease associated with diabetes should also be addressed. url: https://doi.org/10.2147/idr.s264882 doi: 10.2147/idr.s264882 id: cord-355807-q3bngari author: Yepes-Pérez, Andres F. title: Uncaria tomentosa (cat’s claw): a promising herbal medicine against SARS-CoV-2/ACE-2 junction and SARS-CoV-2 spike protein based on molecular modeling date: 2020-10-29 words: 8807 sentences: 453 pages: flesch: 48 cache: ./cache/cord-355807-q3bngari.txt txt: ./txt/cord-355807-q3bngari.txt summary: Molecular modeling was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (cat''s claw) focusing on the binding interface of the RBD–ACE-2 and the viral spike protein. tomentosa against focusing both on the binding interface of the RBD-ACE-2 and inside SARS-CoV-2 RBD spike protein, (2) simulations of ligand pathway of the best predicted compounds from step 1 to evaluate convenient entrance mechanism of the compounds to the binding site, (3) MD simulation to assess the stability of the best protein-ligand complexes from 1, (4) calculation of pharmacokinetics parameters for the most qualified compounds resulting from the previous parts of the docking protocol. Next, we used the cryo-EM structure of SARS-CoV-2 spike protein (PDB code: 6VYB) in their open state (Lipinski et al., 2012) to explore the potential inhibition of components of the cat''s claw, selecting ACE-2-binding pocket to this study. abstract: COVID-19 is a novel severe acute respiratory syndrome coronavirus. Currently, there is no effective treatment and vaccines seem to be the solution in the future. Virtual screening of potential drugs against the S protein of severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) has provided small molecular compounds with a high binding affinity. Unfortunately, most of these drugs do not attach with the binding interface of the receptor-binding domain (RBD)–angiotensin-converting enzyme-2 (ACE-2) complex in host cells. Molecular modeling was carried out to evaluate the potential antiviral properties of the components of the medicinal herb Uncaria tomentosa (cat’s claw) focusing on the binding interface of the RBD–ACE-2 and the viral spike protein. The in silico approach starts with protein–ligand docking of 26 Cat’s claw key components followed by molecular dynamics simulations and re-docked calculations. Finally, we carried out drug-likeness calculations for the most qualified cat’s claw components. The structural bioinformatics approaches led to the identification of several bioactive compounds of U. tomentosa with potential therapeutic effect by dual strong interaction with interface of the RBD–ACE-2 and the ACE-2 binding site on SARS-CoV-2 RBD viral spike. In addition, in silico drug-likeness indices for these components were calculated and showed good predicted therapeutic profiles of these phytochemicals found in U. tomentosa (cat’s claw). Our findings suggest the potential effectiveness of cat’s claw as complementary and/or alternative medicine for COVID-19 treatment. Communicated by Ramaswamy H. Sarma url: https://doi.org/10.1080/07391102.2020.1837676 doi: 10.1080/07391102.2020.1837676 ==== 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