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Ferroptosis is a form of programmed cell death that plays an important role in ALF. In this study, we aimed to identify ferroptosis-related genes in ALF, thereby predicting promising compounds to treat ALF. First, mRNA microarray data were utilized to identify the ferroptosis-related differentially expressed genes (DEGs). Hub genes were screened in the protein\u2013protein interaction network and validated. Subsequently, potential drugs to treat ALF were predicted. One of the predicted drugs was tested in an ALF model of mice. Ferroptosis examination and molecular docking were analyzed to explore the mechanism. A total of 37 DEGs were identified, ten hub genes were extracted, and their expression in ALF was validated. The predicted drug niclosamide mitigated lipopolysaccharide\/D-galactosamine-induced hepatotoxicity, and decreased mortality of mice in the ALF model. Mechanically, niclosamide may combine with signal transducer and activator of transcription 3 to inhibit ALF progression by suppressing ferroptosis. This study may help advance our understanding of the role of ferroptosis in ALF, and niclosamide may be promising for therapeutic efficacy in patients with ALF.<\/jats:p>","DOI":"10.3390\/pharmaceutics15071950","type":"journal-article","created":{"date-parts":[[2023,7,14]],"date-time":"2023-07-14T08:35:47Z","timestamp":1689323747000},"page":"1950","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Repurposing Niclosamide as a Therapeutic Drug against Acute Liver Failure by Suppressing Ferroptosis"],"prefix":"10.3390","volume":"15","author":[{"given":"Xiao","family":"Zhong","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Gong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruochan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hunan Key Laboratory of Viral Hepatitis, Xiangya Hospital, Central South University, Changsha 410008, China"},{"name":"National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha 410008, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/S0140-6736(19)31894-X","article-title":"Acute liver failure","volume":"394","author":"Stravitz","year":"2019","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1002\/ncp.10459","article-title":"Pathophysiology of Acute Liver Failure","volume":"35","author":"Dong","year":"2020","journal-title":"Nutr. 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