{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T18:28:58Z","timestamp":1791916138358,"version":"4.3.4"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2022,7,28]],"date-time":"2022-07-28T00:00:00Z","timestamp":1658966400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2023,4,17]],"date-time":"2023-04-17T00:00:00Z","timestamp":1681689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims:<\/jats:title>\n            <jats:p>Nonalcoholic fatty liver disease and its progressive form, nonalcoholic steatohepatitis (NASH), are rapidly becoming the top causes of hepatocellular carcinoma (HCC). Currently, there are no approved therapies for the treatment of NASH. DEAD\u2010box protein 5 (DDX5) plays important roles in different cellular processes. However, the precise role of DDX5 in NASH remains unclear.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>DDX5 expression was downregulated in patients with NASH, mouse models with diet\u2010induced NASH (high\u2010fat diet [HFD], methionine\u2010 and choline\u2010deficient diet, and choline\u2010deficient HFD), mouse models with NASH\u2010HCC (diethylnitrosamine with HFD), and palmitic acid\u2013stimulated hepatocytes. Adeno\u2010associated virus\u2013mediated DDX5 overexpression ameliorates hepatic steatosis and inflammation, whereas its deletion worsens such pathology. The untargeted metabolomics analysis was carried out to investigate the mechanism of DDX5 in NASH and NASH\u2010HCC, which suggested the regulatory effect of DDX5 on lipid metabolism. DDX5 inhibits mechanistic target of rapamycin complex 1 (mTORC1) activation by recruiting the tuberous sclerosis complex (TSC)1\/2 complex to mTORC1, thus improving lipid metabolism and attenuating the NACHT\u2010, leucine\u2010rich\u2010repeat (LRR)\u2010, and pyrin domain (PYD)\u2010containing protein 3 \u00a0inflammasome activation. We further identified that the phytochemical compound hyperforcinol K directly interacted with DDX5 and prevented its ubiquitinated degradation mediated by ubiquitin ligase (E3) tripartite motif protein 5, thereby significantly reducing lipid accumulation and inflammation in a NASH mouse model.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>These findings provide mechanistic insight into the role of DDX5 in mTORC1 regulation and NASH progression, as well as suggest a number of targets and a promising lead compound for therapeutic interventions against NASH.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32651","type":"journal-article","created":{"date-parts":[[2022,7,7]],"date-time":"2022-07-07T09:22:05Z","timestamp":1657185725000},"page":"1670-1687","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":36,"title":["RNA helicase DEAD\u2010box protein 5 alleviates nonalcoholic steatohepatitis progression via tethering TSC complex and suppressing mTORC1 signaling"],"prefix":"10.1097","volume":"77","author":[{"given":"Yanqiu","family":"Zhang","sequence":"first","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shengtao","family":"Ye","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weijia","family":"Lu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiawen","family":"Zhong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingrong","family":"Leng","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Yang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Luo","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjun","family":"Xu","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9366-7151","authenticated-orcid":false,"given":"Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingyi","family":"Kong","sequence":"additional","affiliation":[{"name":"Jiangsu Key Laboratory of Bioactive Natural Product Research and State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2023,4,17]]},"reference":[{"issue":"1","key":"hep32651-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1038\/nrgastro.2017.109","article-title":"Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention","volume":"15","year":"2018","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"6","key":"hep32651-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1038\/nrgastro.2013.41","article-title":"Progression of NAFLD to diabetes mellitus, cardiovascular disease or cirrhosis","volume":"10","year":"2013","journal-title":"Nat Rev Gastroenterol Hepatol"},{"issue":"1","key":"hep32651-bib-0003-20250824","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/hep.30401","article-title":"Dietary lipids differentially shape nonalcoholic steatohepatitis progression and the transcriptome of Kupffer 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