{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,10]],"date-time":"2026-08-10T04:30:10Z","timestamp":1786336210720,"version":"build-2736575974"},"reference-count":37,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T00:00:00Z","timestamp":1785110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["561119201"],"award-info":[{"award-number":["561119201"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["lzujbky-2021-kb05"],"award-info":[{"award-number":["lzujbky-2021-kb05"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012899","name":"Lanzhou University","doi-asserted-by":"publisher","award":["2022J01526"],"award-info":[{"award-number":["2022J01526"]}],"id":[{"id":"10.13039\/100012899","id-type":"DOI","asserted-by":"publisher"}]},{"award":["561119201"],"award-info":[{"award-number":["561119201"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}]},{"award":["lzujbky-2021-kb05"],"award-info":[{"award-number":["lzujbky-2021-kb05"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2022J01526"],"award-info":[{"award-number":["2022J01526"]}],"id":[{"id":"https:\/\/ror.org\/01mkqqe32","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Inflammation plays a pivotal role in the pathogenesis of myocardial ischemia\/reperfusion (I\/R) injury, highlighting inflammation suppression as a critical therapeutic strategy. The inflammatory response is largely mediated through Toll-like receptor 4 (TLR4), a transmembrane signal receptor whose expression is upregulated by Heat Shock Protein Family A Member 8 (HSPA8). Here, we investigated whether SEM1, a subunit of the 26S proteasome, interacts with HSPA8 and attenuates TLR4-mediated inflammation. Our results demonstrate that SEM1 expression is downregulated following myocardial I\/R. Overexpression of SEM1 alleviated cardiac injury and dysfunction, inhibited myocardial inflammation, and downregulated HSPA8 expression in the I\/R-injured heart. Co-IP assays confirmed a strong physical interaction between SEM1 and HSPA8, while the precise molecular mechanism responsible for SEM1-induced downregulation of HSPA8 remains to be fully elucidated. Mechanistically, SEM1 suppressed the activation of the TLR4\/MyD88\/NF-\u03baB signaling pathway. Collectively, these findings identify SEM1 as a novel regulator that protects against myocardial I\/R injury via its association with HSPA8 and inhibition of the TLR4-mediated inflammatory cascade, offering a promising therapeutic target for this condition.<\/jats:p>","DOI":"10.3390\/ijms27156711","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:11:56Z","timestamp":1785168716000},"page":"6711","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["SEM1 Downregulates HSPA8 to Suppress TLR4\/MyD88\/NF-\u03baB Signaling and Alleviate Myocardial I\/R Injury"],"prefix":"10.3390","volume":"27","author":[{"given":"Jingjing","family":"Liu","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhanghui","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyan","family":"Huang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, University of South China, Hengyang 421001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7490-9036","authenticated-orcid":false,"given":"Xinping","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Lanzhou University, Lanzhou 730000, China"},{"name":"Southeast Research Institute, Lanzhou University, Putian 351152, China"},{"name":"State Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.amjcard.2023.09.087","article-title":"Exploring Heart Failure Mortality Trends and Disparities in Women: A Retrospective Cohort Analysis","volume":"209","author":"Ibrahim","year":"2023","journal-title":"Am. 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