{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T17:37:49Z","timestamp":1790098669765,"version":"4.0.1"},"reference-count":44,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,12,5]],"date-time":"2021-12-05T00:00:00Z","timestamp":1638662400000},"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":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>Aging exacerbates liver neutrophil infiltration and alcohol\u2010associated liver disease (ALD) in mice and humans, but the underlying mechanisms remain obscure. This study aimed to examine the effect of aging and alcohol consumption on neutrophilic Sirtuin 1 (SIRT1) and microRNA\u2010223 (miR\u2010223), and their contribution to ALD pathogeneses.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Young and aged myeloid\u2010specific <jats:italic toggle=\"yes\">Sirt1<\/jats:italic>\u00a0knockout mice were subjected to chronic\u2010plus\u2010binge ethanol feeding. Blood samples from healthy controls and patients with chronic alcohol drinking who presented with acute intoxication were analyzed. Neutrophilic <jats:italic toggle=\"yes\">Sirt1<\/jats:italic> and miR\u2010223 expression were down\u2010regulated in aged mice compared with young mice. Deletion of the <jats:italic toggle=\"yes\">Sirt1<\/jats:italic>\u00a0gene in myeloid cells including neutrophils exacerbated chronic\u2010plus\u2010binge ethanol\u2010induced liver injury and inflammation and down\u2010regulated neutrophilic miR\u2010223 expression. Immunoprecipitation experiments revealed that SIRT1 promoted C\/EBP\u03b1 deacetylation by directly interacting with C\/EBP\u03b1, a key transcription factor that controls miR\u2010223 biogenesis, and subsequently elevated miR\u2010223 expression in neutrophils. Importantly, down\u2010regulation of SIRT1 and miR\u2010223 expression was also observed in circulating neutrophils from middle\u2010aged and elderly subjects compared with those from young individuals. Chronic alcohol users with acute intoxication had a reduction in neutrophilic <jats:italic toggle=\"yes\">SIRT1<\/jats:italic> expression in young and middle\u2010aged patients, with a greater reduction in the latter group. The neutrophilic <jats:italic toggle=\"yes\">SIRT1<\/jats:italic> expression correlated with neutrophilic miR\u2010223 and serum alanine transaminase levels in those patients.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Aging increases the susceptibility of alcohol\u2010induced liver injury in mice and humans through the down\u2010regulation of the neutrophilic SIRT1\u2010C\/EBP\u03b1\u2010miR\u2010223 axis, which could be a therapeutic target for the prevention and\/or treatment of ALD.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32152","type":"journal-article","created":{"date-parts":[[2021,9,12]],"date-time":"2021-09-12T13:49:06Z","timestamp":1631454546000},"page":"646-660","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":81,"title":["Aging exaggerates acute\u2010on\u2010chronic alcohol\u2010induced liver injury in mice and humans by inhibiting neutrophilic sirtuin 1\u2010C\/EBP\u03b1\u2010miRNA\u2010223 axis"],"prefix":"10.1097","volume":"75","author":[{"given":"Ruixue","family":"Ren","sequence":"first","affiliation":[{"name":"Department of Oncology,the First Affiliated Hospital of Anhui Medical University,Hefei,China"},{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA"},{"name":"Inflammation and Immune Mediated Diseases Laboratory of Anhui Province,Anhui Medical University,Hefei,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"He","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Ding","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoyuan","family":"Cui","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huarui","family":"Bao","sequence":"additional","affiliation":[{"name":"Department of Emergency,the First Affiliated Hospital of Anhui Medical University,Hefei,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Ma","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Hou","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6910-5933","authenticated-orcid":false,"given":"Yu","family":"Li","sequence":"additional","affiliation":[{"name":"CAS Key Laboratory of Nutrition, Metabolism and Food Safety,Shanghai Institute of Nutrition and Health,University of Chinese Academy of Sciences,Chinese Academy of Sciences,Shanghai,China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dechun","family":"Feng","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of Health,Bethesda,Maryland,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoling","family":"Li","sequence":"additional","affiliation":[{"name":"Signal Transduction Laboratory,National Institute of Environmental Health Sciences,National Institutes of Health,Research Triangle Park,North Carolina,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suthat","family":"Liangpunsakul","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology,Department of Medicine,Department of Biochemistry and Molecular Biology,Indiana University School of Medicine,Indianapolis,Indiana,USA"},{"name":"Roudebush Veterans Administration Medical Center,Indianapolis,Indiana,USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Gao","sequence":"additional","affiliation":[{"name":"Laboratory of Liver Diseases,National Institute on Alcohol Abuse and Alcoholism,National Institutes of 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