{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,16]],"date-time":"2026-03-16T21:55:38Z","timestamp":1773698138845,"version":"3.50.1"},"reference-count":32,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,9,1]],"date-time":"2021-09-01T00:00:00Z","timestamp":1630454400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,6,24]],"date-time":"2021-06-24T00:00:00Z","timestamp":1624492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005762","name":"National Taiwan University Hospital","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005762","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2021,9]]},"DOI":"10.1016\/j.lfs.2021.119752","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T03:55:05Z","timestamp":1624420505000},"page":"119752","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":15,"special_numbering":"C","title":["Zinc supplementation augments the suppressive effects of repurposed NF-\u03baB inhibitors on ACE2 expression in human lung cell lines"],"prefix":"10.1016","volume":"280","author":[{"given":"Ming-Cheng","family":"Lee","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yin-Kai","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jyy-Jih","family":"Tsai-Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yih-Jen","family":"Hsu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bor-Ru","family":"Lin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2021.119752_bb0005","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118075","article-title":"The dual impact of ACE2 in COVID-19 and ironical actions in geriatrics and pediatrics with possible therapeutic solutions","volume":"257","author":"Behl","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0010","doi-asserted-by":"crossref","first-page":"650","DOI":"10.1038\/labinvest.2012.2","article-title":"Loss of angiotensin-converting enzyme 2 enhances TGF-beta\/Smad-mediated renal fibrosis and NF-kappaB-driven renal inflammation in a mouse model of obstructive nephropathy","volume":"92","author":"Liu","year":"2012","journal-title":"Lab. Investig."},{"key":"10.1016\/j.lfs.2021.119752_bb0015","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1165\/rcmb.2012-0451OC","article-title":"Angiotensin-converting enzyme 2\/angiotensin-(1\u20137)\/Mas axis protects against lung fibrosis by inhibiting the MAPK\/NF-kappaB pathway","volume":"50","author":"Meng","year":"2014","journal-title":"Am. J. Respir. Cell Mol. Biol."},{"key":"10.1016\/j.lfs.2021.119752_bb0020","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1161\/CIRCULATIONAHA.110.955369","article-title":"Angiotensin-converting enzyme 2 suppresses pathological hypertrophy, myocardial fibrosis, and cardiac dysfunction","volume":"122","author":"Zhong","year":"2010","journal-title":"Circulation"},{"key":"10.1016\/j.lfs.2021.119752_bb0025","doi-asserted-by":"crossref","first-page":"1456","DOI":"10.1161\/CIRCRESAHA.120.317015","article-title":"Angiotensin-converting enzyme 2: SARS-CoV-2 receptor and regulator of the renin-angiotensin system: celebrating the 20th anniversary of the discovery of ACE2","volume":"126","author":"Gheblawi","year":"2020","journal-title":"Circ. Res."},{"key":"10.1016\/j.lfs.2021.119752_bb0030","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117905","article-title":"Protective role of ACE2 and its downregulation in SARS-CoV-2 infection leading to macrophage activation syndrome: therapeutic implications","volume":"256","author":"Banu","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0035","doi-asserted-by":"crossref","first-page":"549","DOI":"10.3906\/sag-2004-127","article-title":"Coronaviruses and SARS-COV-2","volume":"50","author":"Hasoksuz","year":"2020","journal-title":"Turk. J. Med. Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0040","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118889","article-title":"Screened antipsychotic drugs inhibit SARS-CoV-2 binding with ACE2 in vitro","volume":"266","author":"Lu","year":"2021","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0045","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117970","article-title":"Potential inhibitors of the interaction between ACE2 and SARS-CoV-2 (RBD), to develop a drug","volume":"256","author":"Benitez-Cardoza","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0050","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1016\/j.peptides.2011.08.009","article-title":"Identifying the regulatory element for human angiotensin-converting enzyme 2 (ACE2) expression in human cardiofibroblasts","volume":"32","author":"Kuan","year":"2011","journal-title":"Peptides"},{"key":"10.1016\/j.lfs.2021.119752_bb0055","article-title":"The role and therapeutic potential of NF-kappa-B pathway in severe COVID-19 patients","author":"Hariharan","year":"2020","journal-title":"Inflammopharmacology"},{"key":"10.1016\/j.lfs.2021.119752_bb0060","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.118102","article-title":"Contribution of monocytes and macrophages to the local tissue inflammation and cytokine storm in COVID-19: lessons from SARS and MERS, and potential therapeutic interventions","volume":"257","author":"Jafarzadeh","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0065","doi-asserted-by":"crossref","first-page":"1272","DOI":"10.1016\/j.bcp.2009.12.021","article-title":"Identification of known drugs that act as inhibitors of NF-kappaB signaling and their mechanism of action","volume":"79","author":"Miller","year":"2010","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.lfs.2021.119752_bb0070","doi-asserted-by":"crossref","first-page":"1712","DOI":"10.3389\/fimmu.2020.01712","article-title":"The potential impact of Zinc supplementation on COVID-19 pathogenesis","volume":"11","author":"Wessels","year":"2020","journal-title":"Front. Immunol."},{"key":"10.1016\/j.lfs.2021.119752_bb0075","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ijid.2020.09.014","article-title":"COVID-19: poor outcomes in patients with zinc deficiency","volume":"100","author":"Jothimani","year":"2020","journal-title":"Int. J. Infect. Dis."},{"key":"10.1016\/j.lfs.2021.119752_bb0080","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/S0014-5793(99)00390-7","article-title":"Zinc is required in pyrrolidine dithiocarbamate inhibition of NF-kappaB activation","volume":"449","author":"Kim","year":"1999","journal-title":"FEBS Lett."},{"key":"10.1016\/j.lfs.2021.119752_bb0085","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.bbrc.2020.03.044","article-title":"Single cell RNA sequencing of 13 human tissues identify cell types and receptors of human coronaviruses","volume":"526","author":"Qi","year":"2020","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"10.1016\/j.lfs.2021.119752_bb0090","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1038\/s41591-020-0868-6","article-title":"SARS-CoV-2 entry factors are highly expressed in nasal epithelial cells together with innate immune genes","volume":"26","author":"Sungnak","year":"2020","journal-title":"Nat. Med."},{"key":"10.1016\/j.lfs.2021.119752_bb0095","doi-asserted-by":"crossref","DOI":"10.1183\/13993003.01123-2020","article-title":"Gene expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human airway epithelial cells and lung tissue","volume":"56","author":"Aguiar","year":"2020","journal-title":"Eur. Respir. J."},{"key":"10.1016\/j.lfs.2021.119752_bb0100","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics12010079","article-title":"Comparison of various cell lines and three-dimensional mucociliary tissue model systems to estimate drug permeability using an in vitro transport study to predict nasal drug absorption in Rats","volume":"12","author":"Furubayashi","year":"2020","journal-title":"Pharmaceutics"},{"key":"10.1016\/j.lfs.2021.119752_bb0105","doi-asserted-by":"crossref","DOI":"10.15252\/embj.2020105912","article-title":"An organoid-derived bronchioalveolar model for SARS-CoV-2 infection of human alveolar type II-like cells","volume":"40","author":"Lamers","year":"2021","journal-title":"EMBO J."},{"key":"10.1016\/j.lfs.2021.119752_bb0110","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/1476-4598-8-47","article-title":"Synergistic antitumor activity of oncolytic reovirus and chemotherapeutic agents in non-small cell lung cancer cells","volume":"8","author":"Sei","year":"2009","journal-title":"Mol. Cancer"},{"key":"10.1016\/j.lfs.2021.119752_bb0115","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1089\/ars.2013.5818","article-title":"The angiotensin-converting enzyme 2\/angiotensin (1\u20137)\/Mas axis protects against lung fibroblast migration and lung fibrosis by inhibiting the NOX4-derived ROS-mediated RhoA\/Rho kinase pathway","volume":"22","author":"Meng","year":"2015","journal-title":"Antioxid. Redox Signal."},{"key":"10.1016\/j.lfs.2021.119752_bb0120","first-page":"409","article-title":"Angiotensin-converting enzyme 2-angiotensin (1\u20137)-Mas axis prevents pancreatic acinar cell inflammatory response via inhibition of the p38 mitogen-activated protein kinase\/nuclear factor-kappaB pathway","volume":"41","author":"Yu","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.lfs.2021.119752_bb0125","doi-asserted-by":"crossref","DOI":"10.1016\/j.biopha.2020.110569","article-title":"NF-kappaB inhibitors in treatment and prevention of lung cancer","volume":"130","author":"Rasmi","year":"2020","journal-title":"Biomed. Pharmacother."},{"key":"10.1016\/j.lfs.2021.119752_bb0130","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1515\/BC.2003.015","article-title":"Thiol antioxidant reversal of pyrrolidine dithiocarbamate-induced reciprocal regulation of AP-1 and NF-kappaB","volume":"384","author":"Kim","year":"2003","journal-title":"Biol. Chem."},{"key":"10.1016\/j.lfs.2021.119752_bb0135","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2020.117883","article-title":"Potential therapeutic targets for combating SARS-CoV-2: drug repurposing, clinical trials and recent advancements","volume":"256","author":"Pandey","year":"2020","journal-title":"Life Sci."},{"key":"10.1016\/j.lfs.2021.119752_bb0140","doi-asserted-by":"crossref","first-page":"2367","DOI":"10.1161\/ATVBAHA.119.313309","article-title":"Identification of emetine as a therapeutic agent for pulmonary arterial hypertension: novel effects of an old drug","volume":"39","author":"Siddique","year":"2019","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"10.1016\/j.lfs.2021.119752_bb0145","first-page":"781","article-title":"IL-1, IL-4 production and IgE levels in acute and chronic fasciolosis before and after triclabendazole treatment","volume":"30","author":"Allam","year":"2000","journal-title":"J. Egypt. Soc. Parasitol."},{"key":"10.1016\/j.lfs.2021.119752_bb0150","first-page":"17","article-title":"Zinc and respiratory tract infections: perspectives for COVID19 (Review)","volume":"46","author":"Skalny","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"10.1016\/j.lfs.2021.119752_bb0155","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1001176","article-title":"Zn(2) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture","volume":"6","author":"te Velthuis","year":"2010","journal-title":"PLoS Pathog."},{"key":"10.1016\/j.lfs.2021.119752_bb0160","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1165\/rcmb.2020-0322PS","article-title":"Targeting ACE2 for COVID-19 therapy: opportunities and challenges","volume":"64","author":"Jia","year":"2021","journal-title":"Am. J. Respir. Cell Mol. Biol."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320521007384?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320521007384?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T20:49:26Z","timestamp":1758401366000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320521007384"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":32,"alternative-id":["S0024320521007384"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2021.119752","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2021.01.27.428372","asserted-by":"object"}]},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Zinc supplementation augments the suppressive effects of repurposed NF-\u03baB inhibitors on ACE2 expression in human lung cell lines","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2021.119752","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 The Authors. Published by Elsevier Inc.","name":"copyright","label":"Copyright"}],"article-number":"119752"}}