{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T14:54:09Z","timestamp":1781535249633,"version":"3.54.5"},"reference-count":31,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,31]],"date-time":"2026-05-31T00:00:00Z","timestamp":1780185600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005046","name":"Natural Science Foundation of Heilongjiang Province","doi-asserted-by":"publisher","award":["PL2024C006"],"award-info":[{"award-number":["PL2024C006"]}],"id":[{"id":"10.13039\/501100005046","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Diabetic liver injury (DLI) is a serious inflammatory complication, with tumour necrosis factor\u2010alpha (TNF\u2010\u03b1) recognized as a key pro\u2010inflammatory cytokine. This study aimed to investigate the protective effect of TNF\u2010\u03b1 inhibition on DLI and to elucidate the underlying molecular mechanisms, focusing on the novel role of pyroptosis. An integrated experimental approach was employed, commencing with in\u00a0vitro studies in HepG2 hepatocytes to dissect the signalling pathway, followed by in\u00a0vivo validation in Sprague\u2013Dawley rats. In\u00a0vitro assessments included the expression of pyroptosis\u2010related proteins (caspase1, Gasdermin D [GSDMD]), high mobility group protein B1 (HMGB1), and components of the Toll\u2010like receptor 4 (TLR4)\/myeloid differentiation factor 88 (MyD88)\/nuclear factor\u2010\u03baB (NF\u2010\u03baB) pathway under high glucose conditions with or without TNF\u2010\u03b1 inhibition. In\u00a0vivo measurements comprised liver function tests alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglycerides (TG), liver histopathology, and analysis of the HMGB1\/TLR4\/MyD88\/NF\u2010\u03baB pyroptosis axis in liver tissues. In\u00a0vitro, TNF\u2010\u03b1 inhibition mitigated high glucose\u2010induced hepatocyte pyroptosis and suppressed HMGB1 release and TLR4\/MyD88\/NF\u2010\u03baB signalling; pharmacological blockade of HMGB1 replicated these effects. In\u00a0vivo, recombinant human TNF receptor\u2010II:Fc fusion protein (rhTNFR:Fc) significantly improved liver function and histopathology in diabetic rats without affecting blood glucose levels, while also downregulating the expression of HMGB1\/TLR4\/MyD88\/NF\u2010\u03baB pathway components and key pyroptosis markers such as NOD\u2010like receptor family pyrin domain containing 3 (NLRP3). In conclusion, TNF\u2010\u03b1 promotes DLI by driving hepatocyte pyroptosis through the HMGB1\/TLR4\/MyD88\/NF\u2010\u03baB signalling axis. Inhibition of TNF\u2010\u03b1 confers potent hepatic protection independent of glycemic control, identifying it as a promising therapeutic strategy for DLI.<\/jats:p>","DOI":"10.1111\/jcmm.71220","type":"journal-article","created":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T03:49:01Z","timestamp":1780285741000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumour Necrosis Factor\u2010\u03b1 Promotes Pyroptosis in Diabetic Liver Injury via the\n                    <scp>HMGB1<\/scp>\n                    \/\n                    <scp>TLR4<\/scp>\n                    \/\n                    <scp>MyD88<\/scp>\n                    \/\n                    <scp>NF<\/scp>\n                    \u2010\n                    <scp>\u03baB<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"30","author":[{"given":"Dayin","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Urology First Affiliated Hospital, Jiamusi University  Jiamusi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiajun","family":"Cheng","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Ni","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruixin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yihe","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhimei","family":"Jiang","sequence":"additional","affiliation":[{"name":"Rehabilitation Medicine College Jiamusi University  Jiamusi China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2532-352X","authenticated-orcid":false,"given":"Hongyu","family":"Sui","sequence":"additional","affiliation":[{"name":"Department of Physiology, Basic Medical College Jiamusi University  Jiamusi Heilongjiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,31]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diabres.2021.109119"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-009-0366-2"},{"issue":"2","key":"e_1_2_10_4_1","first-page":"101","article-title":"Fatty Liver Disease in Diabetes Mellitus","volume":"4","author":"Bhatt H. 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