{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:21:10Z","timestamp":1787822470592,"version":"build-2784847793"},"reference-count":60,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"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":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Ischemic stroke (IS) is a cerebrovascular disease with high mortality and disability rates, currently lacking effective therapeutic targets. The STING inhibitor SN\u2010011 shows potential in IS treatment, but its mechanism of action remains unclear. This study aims to explore the key molecular mechanisms of SN\u2010011 in treating IS through bioinformatics approaches. IS transcriptome datasets were analyzed to identify differentially expressed genes. Mendelian randomization using brain eQTL and IS\u2010GWAS data identified genes with causal relationships to IS. Single\u2010cell transcriptome, pseudo\u2010time trajectory, intercellular communication, and transcription factor regulatory network analyzes were performed. Molecular docking and DARTS\u2010WB assay validated SN\u2010011 binding to transcription factors. Transcriptomic analysis identified 77 intersecting genes. Mendelian randomization revealed ADGRE5 as a protective gene for IS (OR &lt;\u20091), significantly downregulated in venous endothelial cells (vECs) during disease progression. Cell communication analysis showed ADGRE5\u2010high vECs interact with immune, glial, and stromal cells via LAMININ (Lamb2\u2010CD44, Lamb2\u2010Itga6+Itgb1, Lamb2\u2010Dag1 pair) and JAM signaling pathways. Transcription factor analysis identified JUNB as a negative regulator of ADGRE5. Molecular docking (\u22126.8\u2009kcal\/mol) combined with an in\u00a0vitro DARTS\u2010WB assay confirmed the interaction between SN\u2010011 and JUNB. In OGD\u2010induced endothelial cell injury models, SN\u2010011 suppressed JUNB expression, restored ADGRE5 expression inhibited by JUNB overexpression, reversed the downregulation of LAMB2 and CD44, and reduced the expression of the pro\u2010inflammatory cytokines IL\u20106 and IL\u20101\u03b2. Notably, blockade of LAMB2 largely abolished these protective effects, indicating that the anti\u2010inflammatory and endothelial\u2010protective activities of SN\u2010011 are mediated, at least in part, through restoration of the LAMB2\u2010CD44 signaling axis. ADGRE5 downregulation in vECs may impair vascular repair by disrupting LAMININ\u2010mediated intercellular communication. SN\u2010011 may exert neuroprotective effects by targeting JUNB to upregulate ADGRE5 expression and restore the vEC\u2010centered cellular communication network, providing a theoretical basis for SN\u2010011 as a potential IS therapeutic.<\/jats:p>","DOI":"10.1111\/cbdd.70363","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T13:34:12Z","timestamp":1785850452000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi\u2010Omics Integration Reveals That SN\u2010011 Targets JUNB to Upregulate ADGRE5 and Restore Vascular Endothelial Cell Communication in Ischemic Stroke"],"prefix":"10.1111","volume":"108","author":[{"given":"XiangLing","family":"Ou","sequence":"first","affiliation":[{"name":"The Affiliated Xuzhou Rehabilitation Hospital of Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7000-3674","authenticated-orcid":false,"given":"ZunKe","family":"Gong","sequence":"additional","affiliation":[{"name":"The Affiliated Xuzhou Rehabilitation Hospital of Xuzhou Medical University  Xuzhou Jiangsu Province China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.RA120.012962"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.4463"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.67358"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000558"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28072906"},{"issue":"2","key":"e_1_2_12_7_1","first-page":"S140","article-title":"Acute Ischemic Stroke: Management Approach","volume":"23","author":"Chugh C.","year":"2019","journal-title":"Indian Journal of Critical Care Medicine"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2019.01.016"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-024-03101-y"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00004.2017"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0039.1997.tb02897.x"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)61953-4"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1401595"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2018.09.013"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-00573-w"},{"key":"e_1_2_12_16_1","volume-title":"Junctional Adhesion Molecule (JAM)\u2010C Recruitment of Pard3 and Drebrin to Cell Contacts Initiates Neuron\u2010Glia Recognition and Layer\u2010Specific Cell Sorting in Developing Cerebella","author":"Hallada L. 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