{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T10:28:23Z","timestamp":1785925703903,"version":"3.56.0"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,7,26]],"date-time":"2021-07-26T00:00:00Z","timestamp":1627257600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,11]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>We conducted a comprehensive serum transcriptomic analysis to explore the roles of microRNAs (miRNAs) in alcohol\u2010associated hepatitis (AH) pathogenesis and their prognostic significance.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Serum miRNA profiling was performed in 15 controls, 20 heavy drinkers without liver disease, and 65 patients with AH and compared to publicly available hepatic miRNA profiling in AH patients. Among the top 26 miRNAs, expression of miR\u201030b\u20105p, miR\u201020a\u20105p, miR\u2010146a\u20105p, and miR\u201026b\u20105p were significantly reduced in both serum and liver of AH patients. Pathway analysis of the potential targets of these miRNAs uncovered the genes related to DNA synthesis and cell\u2010cycle progression pathways, including ribonucleotide reductase regulatory subunit M2 (<jats:italic toggle=\"yes\">RRM2<\/jats:italic>), cyclin D1 (<jats:italic toggle=\"yes\">CCND1<\/jats:italic>), cyclin D2 (<jats:italic toggle=\"yes\">CCND2<\/jats:italic>), MYC proto\u2010oncogene (<jats:italic toggle=\"yes\">MYC<\/jats:italic>), and phorbol\u201012\u2010myristate\u201013\u2010acetate\u2010induced protein 1 (<jats:italic toggle=\"yes\">PMAIP1<\/jats:italic>). We found a significant increase in the protein expression of RRM2, CCND1, and CCND2, but not MYC and PMAIP1, in AH patients who underwent liver transplantation; miR\u201026b\u20105p and miR\u201030b\u20105p inhibited the 3\u2032\u2010UTR (untranslated region) luciferase activity of <jats:italic toggle=\"yes\">RRM2<\/jats:italic> and <jats:italic toggle=\"yes\">CCND2<\/jats:italic>, and miR\u201020a\u20105p reduced the 3\u2032\u2010UTR luciferase activity of <jats:italic toggle=\"yes\">CCND1<\/jats:italic> and <jats:italic toggle=\"yes\">CCND2<\/jats:italic>. During a median follow\u2010up of 346\u00a0days, 21% of AH patients died; these patients had higher body mass index (BMI), Model for End\u2010Stage Liver Disease (MELD), and serum miR\u201030b\u20105p, miR\u201020a\u20105p, miR\u2010146a\u20105p, and miR\u201026b\u20105p than those who survived. Cox regression analysis showed that BMI, MELD score, miR\u201020a\u20105p, miR\u2010146a\u20105p, and miR\u201026b\u20105p predicted mortality.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Patients with AH attempt to deal with hepatocyte injury by down\u2010regulating specific miRNAs and up\u2010regulating genes responsible for DNA synthesis and cell\u2010cycle progression. Higher expression of these miRNAs, suggestive of a diminished capacity in liver regeneration, predicts short\u2010term mortality in AH patients.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31994","type":"journal-article","created":{"date-parts":[[2021,6,7]],"date-time":"2021-06-07T05:22:01Z","timestamp":1623043321000},"page":"2436-2451","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":31,"title":["Transcriptomic Analysis Reveals the MicroRNAs Responsible for Liver Regeneration Associated With Mortality in Alcohol\u2010Associated Hepatitis"],"prefix":"10.1097","volume":"74","author":[{"given":"Zhihong","family":"Yang","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Indiana University School of 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University,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Radaeva","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism,Rockville,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon","family":"Peiffer","sequence":"additional","affiliation":[{"name":"Department of Surgery,John Hopkins University,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7620-573X","authenticated-orcid":false,"given":"Vijay H.","family":"Shah","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Kamath","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Mayo Clinic,Rochester,MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greg 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