{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T03:25:56Z","timestamp":1778642756673,"version":"3.51.4"},"reference-count":51,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T00:00:00Z","timestamp":1758844800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1R21AA027310\u201001A1"],"award-info":[{"award-number":["1R21AA027310\u201001A1"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Epigenetic modifications affect the expression of genes related to inflammation. Our previous in\u00a0vitro studies demonstrated that histone deacetylase 4 (HDAC4), a class IIa histone deacetylase, promotes alcohol\u2010induced inflammation in macrophages. Therefore, we explored the role of macrophage HDAC4 in the pathogenesis of alcohol\u2010associated liver disease (ALD).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Human liver samples from healthy individuals, ALD, and metabolic dysfunction\u2010associated steatohepatitis (MASH) were used to evaluate the expression of histone deacetylases (HDACs). Also, male and female\n                      <jats:italic>Hdac4<\/jats:italic>\n                      floxed control (\n                      <jats:italic>Hdac4<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      ) and macrophage\u2010specific\n                      <jats:italic>Hdac4<\/jats:italic>\n                      knockout (\n                      <jats:italic>Hdac4<\/jats:italic>\n                      <jats:sup>MKO<\/jats:sup>\n                      ) mice were pair\u2010fed either Lieber\u2010DeCarli (LD) control diet or LD containing 5% ethanol for 10\u2009days, and the latter received a single alcohol binge.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Human liver samples from ALD, but not MASH, showed a marked induction of HDAC4 expression. Female\n                      <jats:italic>Hdac4<\/jats:italic>\n                      <jats:sup>MKO<\/jats:sup>\n                      mice fed ethanol showed less serum alcohol, triglycerides, alanine aminotransferase, and malondialdehyde levels than female\n                      <jats:italic>Hdac4<\/jats:italic>\n                      <jats:sup>fl\/fl<\/jats:sup>\n                      controls, while males showed an opposite effect. The deletion of\n                      <jats:italic>Hdac4<\/jats:italic>\n                      in macrophages did not elicit marked changes in liver steatosis, lipogenic gene expression, and NAD\n                      <jats:sup>+<\/jats:sup>\n                      metabolism, regardless of sex. However, female\n                      <jats:italic>Hdac4<\/jats:italic>\n                      <jats:sup>MKO<\/jats:sup>\n                      mice fed ethanol displayed less inflammatory gene expression and macrophage infiltration in the liver compared with female control mice, but no significant differences were found in males.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study indicates that macrophage HDAC4 plays a sex\u2010dependent role in the pathogenesis of alcohol\u2010associated hepatitis, with its deletion attenuating alcohol\u2010induced hepatic oxidative stress and inflammation in female mice while oxidative stress was aggravated in males.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/jgh.70091","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T10:08:23Z","timestamp":1758881303000},"page":"3009-3017","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Macrophage Histone Deacetylase 4 Has Sex\u2010Dependent Dimorphic Effects on the Pathogenesis of Alcohol\u2010Associated Hepatitis"],"prefix":"10.1111","volume":"40","author":[{"given":"Hyunju","family":"Kang","sequence":"first","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"},{"name":"Department of Food and Nutrition Keimyung University  Daegu South Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi\u2010Bo","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyungryun","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yoojin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jaeeun","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olivia","family":"Corvino","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adam","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medicine University of Connecticut Health  Farmington Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Young\u2010Ki","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7945-793X","authenticated-orcid":false,"given":"Ji\u2010Young","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences University of Connecticut  Storrs Connecticut USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v38.2.01"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)00933-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature25154"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1101278"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2008.03.131"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.03.007"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0053028"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119338"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/foods12050925"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018713"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.alcohol.2019.02.005"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiolgenomics.00043.2019"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41374-021-00599-1"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2020.158838"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jnutbio.2020.108477"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2013.032"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2012.03.015"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-8278(12)60005-1"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11004-3"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5758"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/360438"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2012.08.002"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.42300"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.05.019"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v13.i37.4974"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-031210-101322"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-314241"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/9831825"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.11.008"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20102407"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2021.102149"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2015.05.023"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.4093\/dmj.2023.0174"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0225531"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.24606"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6605895"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M203368200"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.E05-08-0775"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/35001622"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2011.121"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi.13.73"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13293-023-00580-1"},{"key":"e_1_2_7_44_1","first-page":"55","article-title":"Gender Differences in Moderate Drinking Effects","volume":"23","author":"Mumenthaler M. S.","year":"1999","journal-title":"Alcohol Research & Health"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1002\/iid3.692"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpendmet0616"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01931"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/me.2005-0178"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e13-08-0444"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.35946\/arcr.v35.1.06"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0164225"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2009.2634"}],"container-title":["Journal of Gastroenterology and Hepatology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jgh.70091","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T09:25:07Z","timestamp":1764581107000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jgh.70091"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,26]]},"references-count":51,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["10.1111\/jgh.70091"],"URL":"https:\/\/doi.org\/10.1111\/jgh.70091","archive":["Portico"],"relation":{},"ISSN":["0815-9319","1440-1746"],"issn-type":[{"value":"0815-9319","type":"print"},{"value":"1440-1746","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,26]]},"assertion":[{"value":"2025-06-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-11","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-09-26","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}