{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T12:15:51Z","timestamp":1780316151876,"version":"3.54.1"},"reference-count":42,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Purpose<\/jats:title>\n                    <jats:p>Hepatic sinusoidal obstruction syndrome (HSOS) is a rare liver disorder with potentially life\u2010threatening consequences for colorectal chemotherapy and haematopoietic stem cell transplant recipients. MALT1 (mucous\u2010associated lymphoid tissue lymphoma translocation protein\u20101) is a protein that plays a key role in the production of inflammatory cytokines, ischemia, atherosclerosis, apoptosis and thromboinflammation; however, its role in HSOS is largely unknown. We aimed to investigate the effect of MALT\u20101 inhibition in in\u00a0vitro and in\u00a0vivo models of HSOS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental Approach<\/jats:title>\n                    <jats:p>Two mouse models (FOLFOX challenge in immunocompetent and immunocompromised mice) were used to investigate the therapeutic benefits of the MALT\u20101 inhibitor (MI\u20102) in\u00a0vivo. HHSEC, HLEC and RAW\u2010264.7 cells served as in\u00a0vitro models. HSOS\u2010responsible genes, marker levels and downstream signalling were examined using quantitative real\u2010time PCR, western blot, immunocytochemistry and immunohistochemistry analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Results<\/jats:title>\n                    <jats:p>In the current investigation, MI\u20102 significantly reduced FOLFOX\u2010induced HSOS in both mouse models by inhibiting the occlusion of sinusoids, RBC extravasation and bridging fibrosis in liver sections. MI\u20102 treatment also dramatically reduced specific SOS markers (vWF, VEGF, ephrin, bilirubin and PECAM) and other inflammatory markers. Mechanistic investigation in in\u00a0vitro models using macrophages, sinusoidal and endothelial cells demonstrated that MI\u20102 treatment significantly diminished the inflammatory marker levels\/expression by lowering ROS production. In addition to the pharmacological approach, siRNA\u2010mediated MALT1 suppression remarkably reduced chemokine and cytokine marker expression in sinusoidal cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and Implications<\/jats:title>\n                    <jats:p>Thus, our findings demonstrate that MALT1 suppression dramatically reduces FOLFOX\u2010induced inflammatory and fibrotic conditions by modulating the NF\u2010\u03baB activation, paving the way for innovative HSOS therapy approaches.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70050","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T00:29:02Z","timestamp":1741739342000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Inhibition of\n                    <scp>MALT1<\/scp>\n                    Protease Attenuates Hepatic Sinusoidal Obstruction Syndrome by Modulating\n                    <scp>NRF2<\/scp>\n                    \/\n                    <scp>HO1<\/scp>\n                    and\n                    <scp>NF\u2010\u03baB<\/scp>\n                    Pathway"],"prefix":"10.1111","volume":"45","author":[{"given":"Nidhi","family":"Sharma","sequence":"first","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"},{"name":"Academy of Scientific and Innovative Research (AcSIR)  Ghaziabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yogesh","family":"Chandra","sequence":"additional","affiliation":[{"name":"Department of Applied Biology CSIR\u2010Indian Institute of Chemical Technology  Hyderabad India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-737X","authenticated-orcid":false,"given":"Sai 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