{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T14:16:32Z","timestamp":1789654592427,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Investigation"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Importance<\/jats:title>\n \n The production of tetrahydroxylated bile acids (THBAs) is associated with better prognosis in some cholestatic patients as well as in multidrug resistance protein 2 knockout (\n \n Mdr2\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n ) mice. However, it remains unclear whether this protective effect is specific to\n \n Mdr2\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To evaluate the effects of THBA (3\u03b1,6\u03b1,7\u03b1,12\u03b1\u2010Tetrahydroxy\u201010\u03b2,13\u03b2\u2010pentanoic acid) in\n \n Zfyve19\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice, a newly developed mouse model characterized by cholestatic liver injury.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n THBA was administered to\n \n Zfyve19\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice challenged with alpha\u2010naphthyl isothiocyanate (ANIT). Serum biochemistry, liver histology and immunostaining, and quantitative PCR for hepatic expression of pro\u2010fibrotic, pro\u2010inflammatory, and bile acid metabolism\u2010related genes were performed and compared against\u00a0ANIT\u2010treated wild\u2010type and\n \n Zfyve19\n \u2212\/\u2212<\/jats:sup>\n <\/jats:italic>\n mice fed normal chow.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n THBA administration reduced serum alanine aminotransferase (\n P\u2009<\/jats:italic>\n <\u20090.001) and total bile acid levels (\n P\u2009<\/jats:italic>\n <\u20090.001), decreased necrosis (\n P<\/jats:italic>\n = 0.046), portal inflammation (\n P\u2009<\/jats:italic>\n <\u20090.001), bile duct hyperplasia (\n P<\/jats:italic>\n = 0.007), and portal fibrosis (\n P<\/jats:italic>\n = 0.002) in liver histology, along with a significant reduction in hepatic expression of pro\u2010fibrotic genes (\n Acta2<\/jats:italic>\n ,\n Col1a1<\/jats:italic>\n ,\n Tgfb1<\/jats:italic>\n ,\n Tgfb2<\/jats:italic>\n , and\n Timp1<\/jats:italic>\n ), as well as the pro\u2010inflammatory cytokines\n Tnf<\/jats:italic>\n and macrophage chemokines (\n Ccl2<\/jats:italic>\n ,\n Cxcl1<\/jats:italic>\n ,\n Cxcl9<\/jats:italic>\n ,\n Cxcl10<\/jats:italic>\n , and\n Nos2<\/jats:italic>\n ). Additionally, the mRNA expression of\n Nr1h4<\/jats:italic>\n was profoundly upregulated, while key enzymes involved in bile acid synthesis were downregulated.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n THBA effectively alleviated cholestatic liver injury and fibrosis, and may represent a potential agent for the medical management of such diseases.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/ped4.70036","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:06:18Z","timestamp":1767794778000},"page":"60-69","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Therapeutic potential of tetrahydroxylated bile acids in reducing liver injury: Insights from the\n \n Zfyve19\n \u2212\/\u2212<\/sup>\n <\/i>\n mouse model"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7683-5707","authenticated-orcid":false,"given":"Li","family":"Wang","sequence":"first","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Yu","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayan","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Pathology Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanan","family":"Zhang","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renxue","family":"Wang","sequence":"additional","affiliation":[{"name":"BC Cancer Agency Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huiyu","family":"She","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teng","family":"Liu","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Ling","sequence":"additional","affiliation":[{"name":"BC Cancer Agency Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianshe","family":"Wang","sequence":"additional","affiliation":[{"name":"The Center for Pediatric Liver Diseases Children's Hospital of Fudan University, National Children's Medical Center Shanghai China"},{"name":"Shanghai Key Laboratory of Birth Defect Shanghai 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