{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:06:19Z","timestamp":1777435579547,"version":"3.51.4"},"reference-count":50,"publisher":"SAGE Publications","issue":"7-9","license":[{"start":{"date-parts":[[2025,9,1]],"date-time":"2025-09-01T00:00:00Z","timestamp":1756684800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Antioxidants &amp; Redox Signaling"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                    <jats:title>Background and Aims:<\/jats:title>\n                    <jats:p>\n                      Ischemic stroke (IS) remains the third leading cause of death, and the treatment of acute ischemic stroke (AIS) is still a formidable challenge to clinicians. This study tested the hypothesis that combined silencing Mnf2 gene in adipose-derived mesenchymal stem cells (ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      ) and melatonin (Mel) therapy was superior to monotherapy on attenuating the brain infarct volume (BIV) and improving neurological function in AIS rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      studies were conducted.\n                      <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                      results showed that as compared with the controls (\n                      <jats:italic toggle=\"yes\">i.e.,<\/jats:italic>\n                      ADMSCs\/N2a cells), the cellular\/protein levels of oxidative stress\/reactive oxygen species (ROS)\/mitochondrial and DNA damaged\/apoptotic\/cell stress signaling (tumor necrosis factor [TNF] receptor associated factor 6\/ apoptosis signal regulating kinase\/MKK\n                      <jats:sup>4\/7<\/jats:sup>\n                      \/JUN\/ERK\n                      <jats:sup>1\/2<\/jats:sup>\n                      \/c-Jun) biomarkers were significantly increased in these cells treated by H\n                      <jats:sub>2<\/jats:sub>\n                      O\n                      <jats:sub>2<\/jats:sub>\n                      that were significantly reversed by ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      or Mel and further significantly reversed by combined therapy (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001). Animals were categorized into groups 1 (sham-operated control)\/2 (AIS)\/3 (AIS\u2009+\u2009Mel)\/4 (AIS\u2009+\u2009ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      )\/5 (AIS\u2009+\u2009Mel-ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      ) and euthanized by day 28 after AIS. By day 28, the BIV and the brain infarct area (BIA) were lowest in group 1\/highest in group 2\/significantly lower in group 5 than in groups 3 and 4\/significantly increased in group 4 than in group 3, whereas the neurological function displayed an opposite manner of BIV (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001). The protein expressions of oxidative stress\/mitochondrial damaged\/apoptotic\/inflammatory\/cell stress signaling biomarkers displayed an identical pattern, whereas the protein expressions of mitochondrial biogenesis\/antioxidants and cellular level of neuronal cells exhibited an opposite manner of BIV among the groups (all\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      &lt; 0.0001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Innovation and Conclusion:<\/jats:title>\n                    <jats:p>\n                      ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      and Mel combined therapy offered synergic effects on attenuating the BIV\/BIA and preserving neurological function in rodents after AIS mainly through suppressing oxidative stress\/ROS\/inflammatory signalings and upregulating antioxidants. Combined ADMSCs\n                      <jats:sup>sil-Mnf2<\/jats:sup>\n                      and Mel therapy offered additional benefits on protecting the brain against AIS in rodents.\n                      <jats:italic toggle=\"yes\">Antioxid. Redox Signal.<\/jats:italic>\n                      43, 427\u2013447.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/15230864251364881","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T19:28:12Z","timestamp":1757618892000},"page":"427-447","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined Deletion of Mitofusin 2 in Adipose-Mesenchymal Derived Stem Cells and Melatonin Offers Additional Benefits on Protecting the Brain Against Acute Ischemic Stroke in Rat"],"prefix":"10.1177","volume":"43","author":[{"given":"Chien-Hui","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Sheng","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Neurology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Han-Tan","family":"Chai","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Ling","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6305-5717","authenticated-orcid":false,"given":"Hon-Kan","family":"Yip","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."},{"name":"Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan."},{"name":"Center for Shockwave Medicine and Tissue Engineering, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."},{"name":"School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan."},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan."},{"name":"Department of Nursing, Asia University, Taichung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kuan-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,10]]},"reference":[{"key":"e_1_3_8_2_1","doi-asserted-by":"publisher","DOI":"10.3109\/23744235.2015.1103897"},{"key":"e_1_3_8_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.107.181486"},{"key":"e_1_3_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1326-8-32"},{"key":"e_1_3_8_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11910-009-0074-x"},{"issue":"5","key":"e_1_3_8_6_1","first-page":"2706","article-title":"Synergistic effect of combined melatonin and adipose-derived mesenchymal stem cell (ADMSC)-derived exosomes on amelioration of dextran sulfate sodium (DSS)-induced acute colitis","volume":"11","author":"Chang CL","year":"2019","unstructured":"Chang CL, , Chen CH, , Chiang JY, et al. 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