{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T12:57:10Z","timestamp":1793710630490,"version":"4.6.1"},"reference-count":40,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,23]],"date-time":"2023-01-23T00:00:00Z","timestamp":1674432000000},"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":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>Acute\u2010on\u2010chronic liver failure (ACLF), a disease with poor prognosis, is reportedly caused by cellular senescence due to mitochondrial dysfunction. In this study, we described and analyzed the underlying mechanism of a novel approach for ACLF using ABT263\/navitoclax (Navi) that selectively eliminates senescent cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Irradiation\u2010induced senescent hepatocytes were used for <jats:italic>in\u00a0vitro<\/jats:italic> evaluation of the effects of Navi on ACLF (<jats:italic>n<\/jats:italic>\u00a0=\u00a06 for each group). Lipopolysaccharide\u2010 and carbon tetrachloride\u2010induced ACLF mouse model was used for <jats:italic>in\u00a0vivo<\/jats:italic> evaluation of the effects of Navi administration compared with the control using one\u2010way or two\u2010way analysis of variance, followed by Student's <jats:italic>t<\/jats:italic>\u2010test or Kruskal\u2013Wallis test. The effects on the senescence\u2010associated secretory phenotype (<jats:italic>n<\/jats:italic>\u00a0=\u00a08 for each group) and mitochondrial functions, including adenosine triphosphate concentration and membrane potential (<jats:italic>n<\/jats:italic>\u00a0=\u00a08 for each group), were investigated using real\u2010time polymerase chain reaction, immunohistochemistry, and enzyme analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Navi eliminated irradiation\u2010induced senescent hepatocytes <jats:italic>in\u00a0vitro<\/jats:italic>, leading to non\u2010senescent hepatocyte proliferation. Navi eliminated senescent cells in the liver <jats:italic>in\u00a0vivo<\/jats:italic>, resulting in downregulation of mRNA expression of senescence\u2010associated secretory phenotype factors, a decrease of liver enzymes, and upregulated proliferation of non\u2010senescent cells in the liver. Regarding mitochondrial functional assessment in the liver, adenosine triphosphate concentration and membrane potential were upregulated after Navi administration <jats:italic>in\u00a0vitro<\/jats:italic> and <jats:italic>in\u00a0vivo<\/jats:italic>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Navi may ameliorate ACLF damage by eliminating senescent cells in the liver, downregulating senescence\u2010associated secretory phenotype factors, and upregulating mitochondrial functions. We believe that this novel approach using Navi will pave the way for ACLF treatment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13879","type":"journal-article","created":{"date-parts":[[2023,1,11]],"date-time":"2023-01-11T08:29:22Z","timestamp":1673425762000},"page":"460-472","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Navitoclax improves acute\u2010on\u2010chronic liver failure by eliminating senescent cells in mice"],"prefix":"10.1111","volume":"53","author":[{"given":"Yusuke","family":"Watanabe","sequence":"first","affiliation":[{"name":"Division of Preemptive Medicine for Digestive Disease and Healthy Active Life School of Medicine Niigata University  Niigata Japan"},{"name":"Division of Gastroenterology and Hepatology Graduate School of Medical and Dental Sciences Niigata University  Niigata 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