{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:22:19Z","timestamp":1790108539149,"version":"4.0.1"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Neuroinflammation plays a key role in the progression of secondary brain injury after ischemic stroke, and exosomes have been increasingly recognized to eliminate inflammatory responses through various mechanisms. This study aimed to explore the effect and possible mechanism of human umbilical vein endothelial cells derived exosomes (H-EXOs) on neuroinflammation. We established a transient middle cerebral artery occlusion\/reperfusion (tMCAO\/R) in male rats and oxygen-glucose-deprivation\/reoxygenation (OGD\/R) model in cultured neurons to mimic secondary brain injury after ischemic stroke\n                    <jats:italic>in vivo<\/jats:italic>\n                    . H-EXOs were administered at the same time of reperfusion. Results showed that the production of pro-inflammatory cytokines TNF-\u03b1, IL-1\u03b2, and IL-6, and the transcription factor Kr\u00fcppel-like factor 14 (KLF14) were significantly increased both in rat brain tissue and cultured neural cells after ischemic-reperfusion (I\/R) injury. H-EXOs treatment significantly improved the cultured cell viability, reduced infarct sizes, mitigated neurobehavioral defects, and alleviated the expression of pro-inflammatory cytokines compared with the control group, indicating that H-EXOs exerted anti-inflammatory effect against I\/R injury. Further studies revealed that the anti-inflammatory effect of H-EXOs could be weakened by small-interfering RNA (siKLF4) transfection. KLF14 was a protective factor produced during cerebral ischemia-reperfusion injury. In conclusion, H-EXOs protect neurons from inflammation after I\/R injury by enhancing KLF14 expression.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2024.1365928","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:54:32Z","timestamp":1714611272000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Exosomes derived from HUVECs alleviate ischemia-reperfusion induced inflammation in neural cells by upregulating KLF14 expression"],"prefix":"10.3389","volume":"15","author":[{"given":"Jianxin","family":"Qin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lihong","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Yu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingwen","family":"Ye","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunjuan","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"2344","DOI":"10.3390\/antiox11122344","article-title":"Protective effect of beta-carotene against myeloperoxidase- mediated oxidative stress and inflammation in rat ischemic brain injury","volume":"11","author":"Althurwi","year":"2022","journal-title":"Antioxidants (Basel)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"2010","DOI":"10.1002\/iub.2340","article-title":"Time-related metabolomics study in the rat plasma after global cerebral ischemia and reperfusion: effect of ischemic preconditioning","volume":"72","author":"Baranovicova","year":"2020","journal-title":"IUBMB Life"},{"key":"B3","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1016\/j.freeradbiomed.2022.12.096","article-title":"Upregulation of KLF14 expression attenuates kidney fibrosis by inducing PPAR\u03b1-mediated fatty acid oxidation","volume":"195","author":"Chen","year":"","journal-title":"Free Radic. 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