{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T07:45:03Z","timestamp":1772783103249,"version":"3.50.1"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2018,11,1]],"date-time":"2018-11-01T00:00:00Z","timestamp":1541030400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2018,9,28]],"date-time":"2018-09-28T00:00:00Z","timestamp":1538092800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003395","name":"Shanghai Municipal Education Commission","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003395","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["thelancet.com","elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["EBioMedicine"],"published-print":{"date-parts":[[2018,11]]},"DOI":"10.1016\/j.ebiom.2018.09.051","type":"journal-article","created":{"date-parts":[[2018,10,10]],"date-time":"2018-10-10T10:02:31Z","timestamp":1539165751000},"page":"307-321","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":38,"special_numbering":"C","title":["Targeting hepatic miR-221\/222 for therapeutic intervention of nonalcoholic steatohepatitis in mice"],"prefix":"10.1016","volume":"37","author":[{"given":"Xiuli","family":"Jiang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aijing","family":"Shan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yutong","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yulong","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalong","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"He","family":"Ji","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang","family":"Ning","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Weiqing","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3848-7040","authenticated-orcid":false,"given":"Yanan","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.ebiom.2018.09.051_bb0005","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1002\/hep.28431","article-title":"Global epidemiology of nonalcoholic fatty liver disease-meta-analytic assessment of prevalence, incidence, and outcomes","volume":"64","author":"Younossi","year":"2016","journal-title":"Hepatology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0010","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1053\/j.gastro.2015.04.043","article-title":"Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease","volume":"149","author":"Angulo","year":"2015","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0015","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1053\/j.gastro.2011.06.061","article-title":"Frequency and outcomes of liver transplantation for nonalcoholic steatohepatitis in the United States","volume":"141","author":"Charlton","year":"2011","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0020","doi-asserted-by":"crossref","first-page":"S65","DOI":"10.1016\/j.jhep.2015.02.041","article-title":"Current efforts and trends in the treatment of NASH","volume":"62","author":"Ratziu","year":"2015","journal-title":"J Hepatol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0025","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1136\/gutjnl-2016-312431","article-title":"Current and upcoming pharmacotherapy for non-alcoholic fatty liver disease","volume":"66","author":"Rotman","year":"2017","journal-title":"Gut"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0030","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1053\/j.gastro.2016.01.038","article-title":"Elafibranor, an agonist of the peroxisome proliferator-activated receptor-\u03b1 and -\u03b4, induces resolution of nonalcoholic steatohepatitis without fibrosis worsening","volume":"150","author":"Ratziu","year":"2016","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0035","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1016\/S0140-6736(14)61933-4","article-title":"Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic, non-alcoholic steatohepatitis (FLINT): a multicentre, randomised, placebo-controlled trial","volume":"385","author":"Neuschwander-Tetri","year":"2015","journal-title":"Lancet"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0040","article-title":"The ASK1 inhibitor selonsertib in patients with nonalcoholic steatohepatitis: a randomized, phase 2 trial","author":"Loomba","year":"2017","journal-title":"Hepatology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0045","doi-asserted-by":"crossref","first-page":"1431","DOI":"10.1053\/j.gastro.2012.04.007","article-title":"MicroRNAs in liver disease","volume":"142","author":"Wang","year":"2012","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0050","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1016\/j.jhep.2012.01.030","article-title":"MicroRNA silencing and the development of novel therapies for liver disease","volume":"57","author":"Szabo","year":"2012","journal-title":"J Hepatol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0055","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/nrd.2016.246","article-title":"MicroRNA therapeutics: towards a new era for the management of cancer and other diseases","volume":"16","author":"Rupaimoole","year":"2017","journal-title":"Nat Rev Drug Discov"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0060","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.cmet.2006.01.005","article-title":"miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting","volume":"3","author":"Esau","year":"2006","journal-title":"Cell Metab"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0065","doi-asserted-by":"crossref","first-page":"1577","DOI":"10.1126\/science.1113329","article-title":"Modulation of hepatitis C virus RNA abundance by a liver-specific MicroRNA","volume":"309","author":"Jopling","year":"2005","journal-title":"Science"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0070","doi-asserted-by":"crossref","first-page":"1685","DOI":"10.1056\/NEJMoa1209026","article-title":"Treatment of HCV infection by targeting microRNA","volume":"368","author":"Janssen","year":"2013","journal-title":"N Engl J Med"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0075","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1038\/nature10112","article-title":"MicroRNAs 103 and 107 regulate insulin sensitivity","volume":"474","author":"Trajkovski","year":"2011","journal-title":"Nature"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0080","doi-asserted-by":"crossref","first-page":"1882","DOI":"10.1136\/gutjnl-2014-308883","article-title":"Liver microRNA-21 is overexpressed in non-alcoholic steatohepatitis and contributes to the disease in experimental models by inhibiting PPAR\u03b1 expression","volume":"65","author":"Loyer","year":"2016","journal-title":"Gut"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0085","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1073\/pnas.0907904107","article-title":"miR-221 overexpression contributes to liver tumorigenesis","volume":"107","author":"Pineau","year":"2011","journal-title":"Proc Natl Acad Sci U S A"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0090","doi-asserted-by":"crossref","first-page":"7608","DOI":"10.1158\/0008-5472.CAN-11-1144","article-title":"miR-221 silencing blocks hepatocellular carcinoma and promotes survival","volume":"71","author":"Park","year":"2011","journal-title":"Cancer Res"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0095","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/hep.25747","article-title":"Liver tumorigenicity promoted by microRNA-221 in a mouse transgenic model","volume":"56","author":"Callegari","year":"2012","journal-title":"Hepatology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0100","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1136\/gutjnl-2011-300717","article-title":"MicroRNA-221\/222 upregulation indicates the activation of stellate cells and the progression of liver fibrosis","volume":"61","author":"Ogawa","year":"2012","journal-title":"Gut"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0105","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/j.bbrc.2014.02.065","article-title":"MicroRNA-222 modulates liver fibrosis in a murine model of biliary atresia","volume":"446","author":"Shen","year":"2014","journal-title":"Biochem Biophys Res Commun"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0110","doi-asserted-by":"crossref","first-page":"5477","DOI":"10.1128\/MCB.00335-09","article-title":"Nuclear-cytoplasmic shuttling of menin regulates nuclear translocation of beta-catenin","volume":"29","author":"Cao","year":"2009","journal-title":"Mol Cell Biol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0115","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1038\/nmeth.3317","article-title":"HISAT: a fast spliced aligner with low memory requirements","volume":"12","author":"Kim","year":"2015","journal-title":"Nat Methods"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0120","doi-asserted-by":"crossref","first-page":"R25","DOI":"10.1186\/gb-2009-10-3-r25","article-title":"Ultrafast and memory-efficient alignment of short DNA sequences to the human genome","volume":"10","author":"Langmead","year":"2009","journal-title":"Genome Biol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0125","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1186\/1471-2105-12-323","article-title":"RSEM: accurate transcript quantification from RNA-Seq data with or without a reference genome","volume":"12","author":"Li","year":"2011","journal-title":"BMC Bioinformatics"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0130","doi-asserted-by":"crossref","first-page":"3494","DOI":"10.1172\/JCI26052","article-title":"Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF-alpha","volume":"115","author":"Federici","year":"2005","journal-title":"J Clin Invest"},{"issue":"2004","key":"10.1016\/j.ebiom.2018.09.051_bb0135","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/ng1413","article-title":"Abnormal TNF activity in Timp3\u2212\/\u2212 mice leads to chronic hepatic inflammation and failure of liver regeneration","volume":"36","author":"Mohammed","year":"2004","journal-title":"Nat Genet"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0140","doi-asserted-by":"crossref","first-page":"6747","DOI":"10.1038\/s41598-017-06439-x","article-title":"Hepatocyte specific TIMP3 expression prevents diet dependent fatty liver disease and hepatocellular carcinoma","volume":"7","author":"Casagrande","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0145","doi-asserted-by":"crossref","first-page":"454","DOI":"10.2337\/db11-0613","article-title":"TIMP3 overexpression in macrophages protects from insulin resistance, adipose inflammation, and nonalcoholic fatty liver disease in mice","volume":"61","author":"Menghini","year":"2012","journal-title":"Diabetes"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0150","doi-asserted-by":"crossref","first-page":"5651","DOI":"10.1038\/onc.2008.178","article-title":"MiR-221 controls CDKN1C\/p57 and CDKN1B\/p27 expression in human hepatocellular carcinoma","volume":"27","author":"Fornari","year":"2008","journal-title":"Oncogene"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0155","doi-asserted-by":"crossref","first-page":"3699","DOI":"10.1038\/sj.emboj.7601790","article-title":"Regulation of the p27(Kip1) tumor suppressor by miR-221 and miR-222 promotes cancer cell proliferation","volume":"26","author":"le Sage","year":"2007","journal-title":"EMBO J"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0160","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.ccr.2009.10.014","article-title":"miR-221&222 regulate TRAIL resistance and enhance tumorigenicity through PTEN and TIMP3 downregulation","volume":"16","author":"Garofalo","year":"2009","journal-title":"Cancer Cell"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0165","doi-asserted-by":"crossref","first-page":"3356","DOI":"10.1158\/0008-5472.CAN-08-4112","article-title":"The role of microRNA-221 and microRNA-222 in androgen-independent prostate cancer cell lines","volume":"69","author":"Sun","year":"2009","journal-title":"Cancer Res"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0170","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1093\/jnci\/djq102","article-title":"MicroRNA cluster 221\u2013222 and estrogen receptor alpha interactions in breast cancer","volume":"102","author":"Di Leva","year":"2010","journal-title":"J Natl Cancer Inst"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0175","doi-asserted-by":"crossref","DOI":"10.1182\/blood-2009-11-254656","article-title":"MicroRNA and proliferation control in chronic lymphocytic leukemia: functional relationship between miR-221\/222 cluster and p27","volume":"115","author":"Frenquelli","year":"2010","journal-title":"Blood"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0180","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1186\/1476-4598-9-229","article-title":"MiR-221 and miR-222 target PUMA to induce cell survival in glioblastoma","volume":"9","author":"Zhang","year":"2010","journal-title":"Mol Cancer"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0185","doi-asserted-by":"crossref","first-page":"858","DOI":"10.1038\/onc.2011.280","article-title":"miR-221\/222 overexpession in human glioblastoma increases invasiveness by targeting the protein phosphate PTP\u03bc","volume":"31","author":"Quintavalle","year":"2012","journal-title":"Oncogene"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0190","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1053\/j.gastro.2014.06.006","article-title":"A microRNA 221- and 222-mediated feedback loop maintains constitutive activation of NF\u03baB and STAT3 in colorectal cancer cells","volume":"147","author":"Liu","year":"2014","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0195","doi-asserted-by":"crossref","first-page":"1222","DOI":"10.1158\/1078-0432.CCR-15-0489","article-title":"A 13 mer LNA-i-miR-221 inhibitor restores drug sensitivity in melphalan-refractory multiple myeloma cells","volume":"22","author":"Gull\u00e0","year":"2016","journal-title":"Clin Cancer Res"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0200","doi-asserted-by":"crossref","first-page":"e326","DOI":"10.1038\/mtna.2016.36","article-title":"Pharmacokinetics and pharmacodynamics of a 13-mer LNA-inhibitor-miR-221 in mice and non-human primates","volume":"5","author":"Gallo Cantafio","year":"2016","journal-title":"Mol Ther Nucleic Acids"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0205","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.1158\/0008-5472.CAN-10-1769","article-title":"Metformin, independent of AMPK, induces mTOR inhibition and cell-cycle arrest through REDD1","volume":"71","author":"Ben Sahra","year":"2011","journal-title":"Cancer Res"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0210","doi-asserted-by":"crossref","first-page":"R855","DOI":"10.1152\/ajpregu.00285.2015","article-title":"Aberrant REDD1-mTORC1 responses to insulin in skeletal muscle from Type 2 diabetics","volume":"309","author":"Williamson","year":"2015","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0215","doi-asserted-by":"crossref","first-page":"7023","DOI":"10.1038\/s41598-017-07182-z","article-title":"Implication of REDD1 in the activation of inflammatory pathways","volume":"7","author":"Pastor","year":"2017","journal-title":"Sci Rep"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0220","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1681\/ASN.2008050492","article-title":"Loss of TIMP3 enhances interstitial nephritis and fibrosis","volume":"20","author":"Kassiri","year":"2009","journal-title":"J Am Soc Nephrol"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0225","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1093\/cvr\/cvu072","article-title":"Differential role of TIMP2 and TIMP3 in cardiac hypertrophy, fibrosis, and diastolic dysfunction","volume":"103","author":"Fan","year":"2014","journal-title":"Cardiovasc Res"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0230","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1053\/j.gastro.2008.10.079","article-title":"Tissue inhibitor of metalloproteinase 3 deficiency causes hepatic steatosis and adipose tissue inflammation in mice","volume":"136","author":"Menghini","year":"2009","journal-title":"Gastroenterology"},{"key":"10.1016\/j.ebiom.2018.09.051_bb0235","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1002\/hep.26491","article-title":"Advanced glycation endproducts induce fibrogenic activity in nonalcoholic steatohepatitis by modulating TNF-\u03b1-converting enzyme activity in mice","volume":"58","author":"Jiang","year":"2013","journal-title":"Hepatology"}],"container-title":["EBioMedicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396418304080?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S2352396418304080?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,6]],"date-time":"2025-11-06T18:53:11Z","timestamp":1762455191000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S2352396418304080"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,11]]},"references-count":47,"alternative-id":["S2352396418304080"],"URL":"https:\/\/doi.org\/10.1016\/j.ebiom.2018.09.051","relation":{},"ISSN":["2352-3964"],"issn-type":[{"value":"2352-3964","type":"print"}],"subject":[],"published":{"date-parts":[[2018,11]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Targeting hepatic miR-221\/222 for therapeutic intervention of nonalcoholic steatohepatitis in mice","name":"articletitle","label":"Article Title"},{"value":"EBioMedicine","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ebiom.2018.09.051","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2018 Published by Elsevier B.V.","name":"copyright","label":"Copyright"}]}}