{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:53:47Z","timestamp":1785430427844,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T00:00:00Z","timestamp":1779408000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key R&amp;D Program of China","doi-asserted-by":"publisher","award":["2021YFE0115300"],"award-info":[{"award-number":["2021YFE0115300"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["7244457"],"award-info":[{"award-number":["7244457"]}],"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":["31900887"],"award-info":[{"award-number":["31900887"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["7244457"],"award-info":[{"award-number":["7244457"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"award":["31900887"],"award-info":[{"award-number":["31900887"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Endotoxemia represents a life-threatening clinical disorder driven by an aberrant host immune response to pathogenic infection, often resulting in severe multiple organ dysfunction. Among its most devastating complications are acute lung injury (ALI) and endotoxemia-associated encephalopathy (EAE), both of which are associated with elevated mortality and currently lack effective targeted interventions. This study evaluated the therapeutic efficacy and underlying molecular mechanisms of recombinant human thymosin \u03b24 (rhT\u03b24) in a murine model of lipopolysaccharide (LPS)-induced endotoxemia. Our results showed that treatment with rhT\u03b24 markedly enhanced survival rates and diminished the systemic overproduction of diverse proinflammatory cytokines and chemokines in endotoxemic mice. These systemic protective actions were achieved through the inhibition of the TLR4\/NF-\u03baB signaling cascade, the reduction in M1 macrophage polarization, and the simultaneous alleviation of mitochondrial impairment and oxidative stress. Moreover, rhT\u03b24 treatment significantly rescued EAE-related cognitive deficits and attenuated neuronal damage, primarily through the suppression of neuroinflammation and microglial overactivation. Integrative transcriptomic profiling and functional assays identified lysophosphatidic acid receptor 3 (LPAR3) as an important contributor, suggesting that rhT\u03b24 suppresses microglial-mediated neurotoxicity at least in part through LPAR3 downregulation. In conclusion, rhT\u03b24 confers robust multi-organ protection against endotoxemic injury by orchestrating the inhibition of systemic and central neuroinflammatory cascades, positioning it as a promising candidate for the treatment of endotoxemia-induced ALI and EAE.<\/jats:p>","DOI":"10.3390\/biom16060766","type":"journal-article","created":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T13:12:08Z","timestamp":1779455528000},"page":"766","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Recombinant Human Thymosin \u03b24 Attenuates Endotoxemia-Induced ALI and EAE by Suppressing Inflammatory and Oxidative Responses"],"prefix":"10.3390","volume":"16","author":[{"given":"Yumeng","family":"Ye","sequence":"first","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuefeng","family":"Yang","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingshuo","family":"Zhao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tongtong","family":"Chen","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Xing","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4911-1575","authenticated-orcid":false,"given":"Hongyan","family":"Zuo","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"Department of Pathology, Chengde Medical University, Chengde 067000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanhui","family":"Hao","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Institute of Radiation Medicine, Beijing 100850, China"},{"name":"Department of Pathology, Chengde Medical University, Chengde 067000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"594150","DOI":"10.3389\/fimmu.2020.594150","article-title":"Role of Metabolic Endotoxemia in Systemic Inflammation and Potential Interventions","volume":"11","author":"Mohammad","year":"2021","journal-title":"Front Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Chmielarz, M., Sobieszcza\u0144ska, B., and \u015aroda-Pomianek, K. 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