{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T01:53:26Z","timestamp":1792029206010,"version":"4.4.0"},"reference-count":37,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T00:00:00Z","timestamp":1769644800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82471591"],"award-info":[{"award-number":["82471591"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82460283"],"award-info":[{"award-number":["82460283"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82560284"],"award-info":[{"award-number":["82560284"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82360107"],"award-info":[{"award-number":["82360107"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32360136"],"award-info":[{"award-number":["32360136"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004637","name":"Nanchang University","doi-asserted-by":"publisher","award":["28740105"],"award-info":[{"award-number":["28740105"]}],"id":[{"id":"10.13039\/501100004637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2026,2]]},"abstract":"ABSTRACT<\/jats:title>\n \n Background<\/jats:title>\n Cachexia, characterized by severe weight loss and muscle atrophy, frequently occurs in chronic conditions such as sepsis, cancer and chemotherapy, with limited effective treatments. Despite similar clinical manifestations, the underlying mechanisms across different disease contexts remain unclear. Identifying common pathways could lead to novel therapies. This study examines the role of Toll\u2010like receptor 4 (TLR4), which is upregulated in various cachexia models, and assesses the therapeutic potential of the TLR4\u2010inhibiting peptide OH\u2010CATH30 in mitigating muscle atrophy.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n In vivo models using 8\u2010week\u2010old mice treated with lipopolysaccharide (LPS), 4T1 tumour cells and cisplatin were used to investigate common pathways in cachexia. In\u00a0vitro models were established by treating C2C12 myotubes with TNF\u2010\u03b1, 4T1 culture supernatants and cisplatin. OH\u2010CATH30's effects on muscle atrophy were assessed by measuring myotube diameter, grip strength, muscle weight and muscle fibre cross\u2010sectional area (CSA) via H&E staining. RNA\u2010seq, qPCR, ELISA and Western blotting were performed to explore pathways in cachexia\u2010induced muscle atrophy and OH\u2010CATH30's action mechanism.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Transcriptomic analysis showed significant enrichment of inflammation and protein degradation pathways in skeletal muscle in LPS\u2010induced sepsis, 4T1 tumour\u2010induced cancer cachexia and cisplatin\u2010induced cachexia models, with upregulated expression of TLR4 pathway genes such as\n Cd14<\/jats:italic>\n ,\n Tlr4<\/jats:italic>\n and\n Irak4<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009<\u20090.05). In myotube atrophy models induced by TNF\u2010\u03b1, 4T1 and cisplatin, OH\u2010CATH30 significantly increased MyHC protein levels (\n p<\/jats:italic>\n \u2009<\u20090.05) and myotube diameter (\n p<\/jats:italic>\n \u2009<\u20090.05). In mouse cachexia models induced by LPS, 4T1 and cisplatin, OH\u2010CATH30 treatment significantly increased body weight (\n p<\/jats:italic>\n \u2009<\u20090.05), muscle weight (\n p<\/jats:italic>\n \u2009<\u20090.001), CSA (\n p<\/jats:italic>\n \u2009<\u20090.05) and improved grip strength (\n p<\/jats:italic>\n \u2009<\u20090.05). Transcriptomic analysis further revealed that OH\u2010CATH30 treatment downregulated expression of inflammation and protein degradation\u2010related genes across all cachexia models. In 4T1\u2010treated mice, qPCR confirmed OH\u2010CATH30 reduced mRNA levels of\n Il6<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009=\u20090.05),\n Mstn<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009<\u20090.0001) and protein degradation genes such as\n Trim63<\/jats:italic>\n ,\n Fbxo32<\/jats:italic>\n ,\n Bnip3<\/jats:italic>\n ,\n Gabarapl1<\/jats:italic>\n and\n Ulk1<\/jats:italic>\n (\n p<\/jats:italic>\n \u2009<\u20090.05). ELISA showed reduced serum IL\u20106 levels, and Western blot confirmed downregulation of atrogin1 (\n p<\/jats:italic>\n \u2009<\u20090.05) and autophagy marker LC3II (\n p<\/jats:italic>\n \u2009<\u20090.05) with OH\u2010CATH30 treatment. Pharmacological inhibition of TLR4 using TAK\u2010242 recapitulated the protective effects of OH\u2010CATH30, with no additive benefit observed (\n p<\/jats:italic>\n \u2009>\u20090.05).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n Our findings underscore the critical role of TLR4 signalling in cachexia\u2010associated muscle wasting across different disease contexts and demonstrate the efficacy of OH\u2010CATH30, a TLR4 inhibitor, in alleviating muscle atrophy in various cachexia models.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/jcsm.70195","type":"journal-article","created":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T06:51:33Z","timestamp":1769755893000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Peptide OH\u2010CATH30 Mitigates Cachexia\u2010Induced Muscle Atrophy via Modulation of TLR4\u2010Associated Inflammation"],"prefix":"10.1002","volume":"17","author":[{"given":"Qiquan","family":"Wang","sequence":"first","affiliation":[{"name":"Metabolic Control and Aging, Human Aging Research Institute and School of Life Science Nanchang University and Jiangxi Key Laboratory of Aging and Diseases Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine The Beijing Jishuitan Hospital Guizhou Hospital Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengqi","family":"Yang","sequence":"additional","affiliation":[{"name":"Metabolic Control and Aging, Human Aging Research Institute and School of Life Science Nanchang University and Jiangxi Key Laboratory of Aging and Diseases Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caifen","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Urology The Affiliated Hospital of Guizhou Medical University Guiyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Radiation Therapy Yunnan Cancer Hospital\/Third Affiliated Hospital of KunMing Medical University Kunming China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunping","family":"Huang","sequence":"additional","affiliation":[{"name":"Metabolic Control and Aging, Human Aging Research Institute and School of Life Science Nanchang University and Jiangxi Key Laboratory of Aging and Diseases Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Metabolic Control and Aging, Human Aging Research Institute and School of Life Science Nanchang University and Jiangxi Key Laboratory of Aging and Diseases Nanchang 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