{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T05:00:21Z","timestamp":1785301221490,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100014717","name":"National Outstanding Youth Science Fund Project of National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22407094"],"award-info":[{"award-number":["22407094"]}],"id":[{"id":"10.13039\/100014717","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the neuroprotective potential of YJ\u20102, a novel peptidylarginine deiminase 4 (PAD4) inhibitor, against ischemia\/reperfusion brain injury by targeting neutrophil extracellular trap (NET) formation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In vitro, a NETs\u2010induced injury model was established using SH\u2010SY5Y and bEnd.3 cells. YJ\u20102's effects on viability, apoptosis, oxidative stress, and barrier permeability were assessed via CCK\u20108, flow cytometry, and FITC\u2010dextran assays. In\u00a0vivo, a rat middle cerebral artery occlusion\/reperfusion (MCAO\/R) model received YJ\u20102 (10\u2009\u03bcmol\/kg) intravenously. Outcomes included infarct volume (TTC staining), neurological score, neuronal apoptosis (TUNEL), and oxidative markers (ELISA). PAD4 activity and histone H3 citrullination (H3cit) were examined by western blot and immunofluorescence.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>YJ\u20102 reduced NET\u2010mediated neuronal death and oxidative stress in\u00a0vitro, and improved endothelial barrier integrity. In MCAO\/R rats, YJ\u20102 significantly lowered infarct volume (44.2%\u2009\u2192\u200930.6%), improved neurological function, and suppressed apoptosis. It also decreased PAD4 and H3cit expression in ischemic brain tissue, confirming target engagement.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>YJ\u20102, by preserving blood\u2013brain barrier (BBB) integrity and reducing neuronal apoptosis, highlights its therapeutic potential for ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.71032","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T13:56:08Z","timestamp":1784123768000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comprehensive Evaluation of\n                    <scp>YJ<\/scp>\n                    \u20102 as a\n                    <scp>PAD4<\/scp>\n                    Inhibitor in Alleviating Ischemic Brain Injury: From\n                    <scp>NETs<\/scp>\n                    \u2010Induced Neurotoxicity to In\u00a0Vivo Neuroprotection"],"prefix":"10.1002","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3588-5334","authenticated-orcid":false,"given":"Yijiang","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry School of Pharmaceutical Sciences of Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Drug Innovation for Neuro\u2010Oncology, Beijing Engineering Research Center of Targeted Drugs and Cell Therapy for CNS Tumors, Laboratory for Clinical Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-5542-5999","authenticated-orcid":false,"given":"Ayijiang","family":"Taledaohan","sequence":"additional","affiliation":[{"name":"Department of Emergency Medicine University of California San Diego  San Diego California 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Engineering Research Center of Targeted Drugs and Cell Therapy for CNS Tumors, Laboratory for Clinical Medicine Capital Medical University  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7378-7050","authenticated-orcid":false,"given":"Rong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital  Jinan Shandong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0985-0104","authenticated-orcid":false,"given":"Liujia","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry School of Pharmaceutical Sciences of Capital Medical University  Beijing China"},{"name":"Beijing Key Laboratory of Drug Innovation for Neuro\u2010Oncology, Beijing Engineering Research Center of Targeted Drugs and 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