{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T18:26:32Z","timestamp":1788459992885,"version":"build-2803163510"},"reference-count":49,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2022,8,25]],"date-time":"2022-08-25T00:00:00Z","timestamp":1661385600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Hepatology Research"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>This study investigated serum microRNAs (miRNAs\/miRs) in autoimmune hepatitis (AIH) and the relationship of these molecules with diagnostic and relapse markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Initially, extracellular vesicle\u2010encapsulated miRNAs (EV\u2010miRNAs) in serum with altered expression in AIH relative to healthy control (HC) samples were identified using microarray analysis. To validate the microarray results, the expression levels of selected EV\u2010miRNAs were determined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among the 2569 mature miRNAs evaluated in the microarray, EV\u2010miR\u2010557 discriminated patients with AIH from healthy controls (HCs). Validation by digital polymerase chain reaction indicated that serum EV\u2010miR\u2010557 levels were higher in patients with AIH (7.75 copies\/\u03bcl) than in patients with non\u2010alcoholic steatohepatitis (1.60 copies\/\u03bcl; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001), patients with primary biliary cholangitis (2.16 copies\/\u03bcl; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.005), and HCs (1.86 copies\/\u03bcl; <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.005). The area under the receiver operating characteristic curve values for the probability of AIH using serum EV\u2010miR\u2010557 between the AIH and non\u2010alcoholic steatohepatitis, AIH and primary biliary cholangitis, and AIH and HC groups were 0.81, 0.78, and 0.79, respectively. In addition, serum EV\u2010miR\u2010557 levels &gt;7.69 copies\/\u03bcl were associated with a significantly higher risk of relapse in patients with AIH (7\u2010year incidence rate: 11.1 vs. 35.4%, log\u2010rank test, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05). Interestingly, gene expression analysis revealed that increased miR\u2010557 expression following transient transfection of peripheral blood mononuclear cells with a miR\u2010557 mimic resulted in enhanced expression of proinflammatory cytokine\u2010related genes such as interleukin\u20106, interferon\u2010\u03b3, and tumor necrosis factor. Moreover, miR\u2010557 induced significant tumor necrosis factor\u2010\u03b1 production (mean: 313.5 vs. 10\u00a0642.3 pg\/ml, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>EV\u2010miR\u2010557 may play an important role as a potential biomarker of AIH and may be a promising therapeutic target for AIH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13829","type":"journal-article","created":{"date-parts":[[2022,8,13]],"date-time":"2022-08-13T18:58:31Z","timestamp":1660417111000},"page":"1034-1049","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Circulating extracellular vesicle\u2010encapsulated microRNA\u2010557 induces a proinflammatory immune response and serves as a diagnostic or relapse marker in autoimmune hepatitis"],"prefix":"10.1111","volume":"52","author":[{"given":"Kazumichi","family":"Abe","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rei","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masashi","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manabu","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiromasa","family":"Ohira","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology Fukushima Medical University School of Medicine  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","unstructured":"KrawittEL.Autoimmune hepatitis. N Engl J Med.1996;334(14):897\u2013903.https:\/\/doi.org\/10.1056\/nejm199604043341406","DOI":"10.1056\/NEJM199604043341406"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2018.00402"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102391"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2019.102396"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaut.2019.04.014"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23377"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2020.12178"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13538"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.13674"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29833"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0136908"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840180435"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0168\u20108278(99)80297\u20109"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22322"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072\u2010021\u201010170"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1155\/2015\/913793"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22906"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072\u2010021\u201010276\u20106"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1326"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/mpa.0000000000000722"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv403"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12864\u2010015\u20102097\u20109"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40364\u2010015\u20100037\u20100"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/0168\u20108278(91)90084\u2010o"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840190629"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1139\/bcb\u20102019\u20100239"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.3892\/ol.2012.810"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0054213"},{"key":"e_1_2_9_31_1","first-page":"2109","article-title":"Gene expression profiling of gastric cancer","volume":"18","author":"Jiang HB","year":"2014","journal-title":"Eur Rev Med Pharmacol Sci"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6464"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12885\u2010018\u20104006\u20105"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1572\u20100241.2007.01153.x"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1872\u2010034x.2011.00812.x"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1111\/hepr.12397"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.1840040409"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478\u20103231.2007.01444.x"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/0016\u20105085(87)90862\u20106"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1053\/jhep.2002.32485"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1186\/1756\u20109966\u201031\u201024"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/1010428317709467"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010\u2010018\u20102773\u20108"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2018.11.010"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02487.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.510300412"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0016\u20105085(99)70458\u20100"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201001056\u20108"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1128\/cvi.00674\u201012"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.90746.2008"}],"container-title":["Hepatology Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13829","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/hepr.13829","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/hepr.13829","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,20]],"date-time":"2023-08-20T07:34:48Z","timestamp":1692516888000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/hepr.13829"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,25]]},"references-count":49,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2022,12]]}},"alternative-id":["10.1111\/hepr.13829"],"URL":"https:\/\/doi.org\/10.1111\/hepr.13829","archive":["Portico"],"relation":{},"ISSN":["1386-6346","1872-034X"],"issn-type":[{"value":"1386-6346","type":"print"},{"value":"1872-034X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,25]]},"assertion":[{"value":"2022-01-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-11","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}