{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:23:01Z","timestamp":1760142181400,"version":"build-2065373602"},"reference-count":26,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170590, 81870609, and 82170075"],"award-info":[{"award-number":["82170590, 81870609, and 82170075"]}],"id":[{"id":"10.13039\/501100001809","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":[[2025,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Although many diet\u2010induced models for nonalcoholic steatohepatitis (NASH) have been reported, most of them hardly conform to the clinical pathogenesis, particularly for the end\u2010stage NASH with the occurrence of hepatocellular carcinoma (HCC). Here, we report a rapid mouse NASH model induced from newborn mice and characterized by progression of broad fibrosis and HCC.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In newborn C57BL\/6J mice, 100\u2009mg\/kg body weight streptozotocin (STZ) by a single intraperitoneal injection at 2\u2009days after birth served as an accelerator with a special high\u2010fat, high\u2010fructose, and high cholesterol diet, combined with 4% fructose and 2% \u03b2\u2010cyclodextrin in drinking water (FFC diet). The induction strategy was named SFD treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pre\u2010treatment of STZ exacerbated the histological features of NASH in mice, which resulted in typical symptoms of NASH at 8\u2009weeks after FFC diet, including liver dysfunction, glucose and lipid metabolism disorders, hepatic steatosis, inflammation, and fibrosis. Moreover, these pathological features worsened with longer durations of 16, 24, and 32\u2009weeks, and advanced fibrosis was evidenced by activated hepatic stellate cells and ductular reaction. In particular, HCC development was observed at 16\u2009weeks.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The sucking mice induced NASH model displayed rapid progression of grievous inflammation and fibrosis, and ultimately developed HCC, which provides new insight for the effects of adolescent metabolic disorder on NASH development. Notably, impairment of islet function in early life is a critical driving factor in this process. This NASH model would be a helpful medical tool for the study of pediatric hepatology and the drug development for NASH.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.70054","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T04:38:48Z","timestamp":1754455128000},"page":"2601-2612","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Impairing Islets in Newborn Mice Promotes Liver Fibrosis and Carcinoma Development in a Rapid NASH Model"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7856-6923","authenticated-orcid":false,"given":"Xin","family":"Zeng","sequence":"first","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"},{"name":"Institutes for Systems Genetics, Frontiers Science Center for Disease\u2010Related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"},{"name":"Department of Liver Surgery, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han","family":"Yao","sequence":"additional","affiliation":[{"name":"Animal Center, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingqiu","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"},{"name":"Institutes for Systems Genetics, Frontiers Science Center for Disease\u2010Related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Younan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Liver Transplantation Center and National Health Commission (NHC) Key Laboratory of Transplant Engineering and Immunology, West China Hospital Sichuan University  Chengdu China"},{"name":"Institutes for Systems Genetics, Frontiers Science Center for Disease\u2010Related Molecular Network, West China Hospital Sichuan University  Chengdu China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_9_2_1","DOI":"10.1002\/hep.28431"},{"doi-asserted-by":"publisher","key":"e_1_2_9_3_1","DOI":"10.1016\/j.jhep.2023.04.035"},{"doi-asserted-by":"publisher","key":"e_1_2_9_4_1","DOI":"10.1007\/s10620-015-3977-1"},{"key":"e_1_2_9_5_1","first-page":"142","article-title":"Animal Models for the Study of Non\u2010Alcoholic Fatty Liver Disease (NAFLD)","volume":"181","author":"Zhou Y.","year":"2018","journal-title":"Pharmacology & Therapeutics"},{"doi-asserted-by":"publisher","key":"e_1_2_9_6_1","DOI":"10.1016\/j.ddmod.2009.03.008"},{"doi-asserted-by":"publisher","key":"e_1_2_9_7_1","DOI":"10.1126\/science.113.2948.746"},{"doi-asserted-by":"publisher","key":"e_1_2_9_8_1","DOI":"10.1016\/j.hepres.2006.07.009"},{"doi-asserted-by":"publisher","key":"e_1_2_9_9_1","DOI":"10.1016\/j.jhep.2005.10.033"},{"issue":"1","key":"e_1_2_9_10_1","first-page":"328","article-title":"Challenges and Opportunities in Drug and Biomarker Development for Nonalcoholic Steatohepatitis: Findings and Recommendations From an Expert Panel","volume":"67","author":"Sanyal A. 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