{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T14:48:23Z","timestamp":1785509303989,"version":"3.56.0"},"reference-count":38,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T00:00:00Z","timestamp":1774656000000},"content-version":"vor","delay-in-days":86,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["82001555\/0417"],"award-info":[{"award-number":["82001555\/0417"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Aortic dissection (AD), a life\u2010threatening cardiovascular emergency, poses a significant threat to global cardiovascular health. Emerging evidence implicates programmed cell death (PCD) as a critical driver of AD pathogenesis, yet the molecular mechanisms remain poorly defined. This study systematically investigates PCD\u2010related biomarkers in AD to identify novel therapeutic targets.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Multiomics analysis integrated transcriptome sequencing data from eight AD and five control aortic tissues. Differentially expressed genes (DEmRNAs,\n                      <jats:italic>n<\/jats:italic>\n                      = 3094) were intersected with 1574 programmed cell death\u2013related genes (PCD\u2010RGs) to identify candidate biomarkers. Protein\u2013protein interaction (PPI) networks, functional enrichment, immune infiltration profiling, and drug\u2010target prediction were employed to characterize key molecular drivers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Three PCD\u2010associated biomarkers were identified: IL6 (11.8\u2010fold upregulated), IL10 (26.1\u2010fold upregulated), and TLR4 (0.38\u2010fold downregulated). These biomarkers exhibited significant enrichment in immunoregulatory pathways including \u201cMYC Targets V1\u201d (FDR &lt; 0.05), with IL10 showing strong immune microenvironment correlations (memory B cells:\n                      <jats:italic>r<\/jats:italic>\n                      = 0.62; endothelial cells:\n                      <jats:italic>r<\/jats:italic>\n                      = \u22120.58). Regulatory network analysis revealed 58 transcription factors (STAT1\/SP1\/IRF8) and six key miRNAs (e.g., miR\u2010204\u20105p) orchestrating biomarker expression. Drug\u2010target mapping identified 91 repurposable agents, including etanercept\u2010szzs (dual IL6\/IL10 inhibitor) and TLR4\u2010modulating compounds.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study establishes IL6, IL10, and TLR4 as central regulators of PCD\u2010mediated AD pathogenesis, implicating immune\u2013vascular crosstalk and immunogenic cell death as therapeutic entry points. The identified biomarker network and drug candidates provide a translational framework for developing precision therapies against AD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/cdr\/4140685","type":"journal-article","created":{"date-parts":[[2026,3,28]],"date-time":"2026-03-28T18:34:41Z","timestamp":1774722881000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["IL6\/IL10\/TLR4 Govern Immunogenic Cell Death in Aortic 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