{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T10:22:15Z","timestamp":1792059735428,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,8,17]],"date-time":"2023-08-17T00:00:00Z","timestamp":1692230400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100016806","name":"Natural Science Foundation of Nantong Municipality","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100016806","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013323","name":"Yancheng Science and Technology Bureau","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013323","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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>The current evidence demonstrates that mesenchymal stem cells (MSCs) hold therapeutic potential for ischemic stroke. However, it remains unclear how changes in the secretion of MSC cytokines following the overexpression of heme oxygenase\u20101 (HO\u20101) impact excessive inflammatory activation in a mouse ischemic stroke model. This study investigated this aspect and provided further insights.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The middle cerebral artery occlusion (MCAO) mouse model was established, and subsequent injections of MSC, MSC\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      , or PBS solutions of equal volume were administered via the mice's tail vein. Histopathological analysis was conducted on Days 3 and 28 post\u2010MCAO to observe morphological changes in brain slices. mRNA expression levels of various factors, including IL\u20101\u03b2, IL\u20106, IL\u201017, TNF\u2010\u03b1, IL\u20101Ra, IL\u20104, IL\u201010, TGF\u2010\u03b2, were quantified. The effects of MSC\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      treatment on neurons, microglia, and astrocytes were observed using immunofluorescence after transplantation. The polarization direction of macrophages\/microglia was also detected using flow cytometry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The results showed that the expression of anti\u2010inflammatory factors in the MSC\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      group increased while that of pro\u2010inflammatory factors decreased. Small animal fluorescence studies and immunofluorescence assays showed that the homing function of MSCs\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      was unaffected, leading to a substantial accumulation of MSCs\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      in the cerebral ischemic region within 24\u2009h. Neurons were less damaged, activation and proliferation of microglia were reduced, and polarization of microglia to the M2 type increased after MSC\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      transplantation. Furthermore, after transplantation of MSCs\n                      <jats:sup>HO\u20101<\/jats:sup>\n                      , the mortality of mice decreased, and motor function improved significantly.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The findings indicate that MSCs overexpressing HO\u20101 exhibited significant therapeutic effects against hyper\u2010inflammatory injury after stroke in mice, ultimately promoting recovery after ischemic stroke.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/cns.14412","type":"journal-article","created":{"date-parts":[[2023,8,21]],"date-time":"2023-08-21T19:32:23Z","timestamp":1692646343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":29,"title":["Human umbilical cord derived mesenchymal stem cells overexpressing\n                    <scp>HO<\/scp>\n                    \u20101 attenuate neural injury and enhance functional recovery by inhibiting inflammation in stroke mice"],"prefix":"10.1111","volume":"30","author":[{"given":"Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianqian","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Affiliated Hospital of Nantong University, Medical School of Nantong University  Nantong 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