{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T13:56:11Z","timestamp":1781186171227,"version":"3.54.1"},"reference-count":38,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"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":["Liver International"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background &amp; Aims<\/jats:title>\n                    <jats:p>Hepatic fibrosis (HF) is a key pathological process in the development of chronic liver disease, and the activation of hepatic stellate cells (HSCs) is its core driving factor. Although curcumin, as a natural polyphenolic compound, has therapeutic potential, its specific mechanism in HF is still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This study used the CCl4\u2010induced mouse HF model and explored its mechanism through single\u2010cell RNA sequencing (scRNA\u2010seq) combined with in\u00a0vitro and in\u00a0vivo experimental systems.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The results showed that curcumin attenuated liver injury and fibrosis levels in mice with HF in a dose\u2010dependent way, alleviated liver pathological damage, improved liver function indicators, and inhibited the release of inflammatory factors. ScRNA\u2010seq analysis revealed a significant reduction in the number of activated HSCs after curcumin treatment, and the key gene Crispld2 was identified through perturbation model prediction and pseudo\u2010temporal analysis. Curcumin significantly downregulated the expression of Crispld2 and inhibited the activation of the PI3K\/AKT signalling pathway. In the TGF\u2014\u03b2\u2014induced LX\u20102 cell activation model, curcumin inhibited HSC proliferation, promoted apoptosis, reduced fibrosis\u2010related protein expression, and decreased inflammatory cytokine secretion by regulating Crispld2. Overexpression of Crispld2 reversed the anti\u2010fibrotic effect of curcumin, while the PI3K\/AKT pathway inhibitor LY294002 restored its therapeutic effect. Animal experiments further confirmed that curcumin improved HF by regulating the Crispld2\/PI3K\/AKT axis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study elucidates the molecular mechanism by which curcumin exerts anti\u2010HF effects by inhibiting the activation of the PI3K\/AKT pathway mediated by Crispld2, providing a new strategy for targeted therapy of Crispld2.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70696","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T06:05:43Z","timestamp":1778738743000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Curcumin Targets Crispld2 to Suppress Hepatic Stellate Cell Activation via\n                    <scp>PI3K<\/scp>\n                    \/\n                    <scp>AKT<\/scp>\n                    Pathway Inhibition in Hepatic Fibrosis"],"prefix":"10.1111","volume":"46","author":[{"given":"Ling","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery Hangzhou First People's Hospital Affiliated to Medical School of Westlake University  Zhejiang Shangcheng District, Hangzhou China"},{"name":"Department of Hepatobiliary and Pancreatic Surgery The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University  Zhejiang Binjiang District, Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintao","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Hepatobiliary and Pancreatic Surgery The Fourth School of Clinical Medicine, Zhejiang Chinese Medical University  Zhejiang Binjiang District, Hangzhou 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