{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T15:30:35Z","timestamp":1778599835000,"version":"3.51.4"},"reference-count":43,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007834","name":"Natural Science Foundation of Ningbo","doi-asserted-by":"publisher","award":["2018A610310"],"award-info":[{"award-number":["2018A610310"]}],"id":[{"id":"10.13039\/100007834","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":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>To investigate the protective effect of VX\u2010765 on human umbilical mesenchymal stem cells (HUMSCs) in stroke and its mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>Mouse models of ischemic stroke were established using the distal middle cerebral artery occlusion (dMCAO) method. The dMCAO mice were accordingly transplanted with HUMSCs, VX\u2010765\u2010treated HUMSCs, or VX\u2010765\u00a0+\u00a0MHY185\u2010treated HUMSCs. The HUMSCs were inserted with green fluorescent protein (GFP) for measurement of transplantation efficiency which was determined by immunofluorescence assay. Oxygen\u2010glucose deprivation (OGD) was applied to mimic ischemic environment in vitro experiments, and the HUMSCs herein were transfected with AMPK inhibitor Compound C or autophagy inhibitor 3\u2010MA. MTT assay was used to test the toxicity of VX\u2010765. TUNEL staining and ELISA were applied to measure the levels of apoptosis and inflammatory cytokines (IL\u20101\u03b2, IL\u20106, and IL\u201010), respectively. The expressions of autophagy\u2010associated proteins, AMPK, and mTOR were detected by Western blotting. TTC staining was applied to reveal the infarct lesions in the brain of dMCAO mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The pro\u2010inflammatory cytokines, TUNEL\u2010positive cells, and p\u2010mTOR were decreased while the anti\u2010inflammatory cytokine, autophagy\u2010related proteins, and p\u2010AMPK were increased in HUMSCs treated with VX\u2010765 under OGD condition. Different expression patterns were found with the above factors after transfection of 3\u2010MA or Compound C. The pro\u2010inflammatory cytokines, TUNEL\u2010positive cells, and infarct sections were decreased while the anti\u2010inflammatory cytokine and autophagy\u2010related proteins were increased in dMCAO mice transplanted with VX\u2010765\u2010treated HUMSCs compared to those transplanted with HUMSCs only. The autophagy was inhibited while p\u2010mTOR was up\u2010regulated after transfection of MHY.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>VX\u2010765 protects HUMSCs against stroke\u2010induced apoptosis and inflammatory responses by activating autophagy via the AMPK\/mTOR signaling pathway in vivo and in vitro.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.13400","type":"journal-article","created":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T11:18:33Z","timestamp":1590578313000},"page":"952-961","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["VX\u2010765 enhances autophagy of human umbilical cord mesenchymal stem cells against stroke\u2010induced apoptosis and inflammatory responses via AMPK\/mTOR signaling pathway"],"prefix":"10.1111","volume":"26","author":[{"given":"Zhezhe","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"},{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ke","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kankai","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junnan","family":"Ru","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Su","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenzhong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery Yuyao people's Hospital Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qichuan","family":"Zhuge","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lijie","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8235-6868","authenticated-orcid":false,"given":"Shengwei","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery The First Affiliated Hospital of Wenzhou Medical University Wenzhou China"},{"name":"Zhejiang Provincial Key Laboratory of Aging and Neurological Disorder Research Wenzhou Medical University Wenzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1649503"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2015.05.041"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.5853\/jos.2016.01263"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368910X532855"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3727\/096368914X678337"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2008.00671.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161212802002841"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000141680.49960.d7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/STROKEAHA.110.603621"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X17700432"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200900531"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eplepsyres.2012.10.001"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-06449-x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1722041115"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-4975(01)03216-7"},{"issue":"4","key":"e_1_2_9_17_1","first-page":"2175","article-title":"Role of lincRNAp21 in the protective effect of macrophage inhibition factor against hypoxia\/serum deprivation induced apoptosis in mesenchymal stem cells","volume":"42","author":"Xia W","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.4410"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.53"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0037613"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm4024"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058207"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2016.4847"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt116"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1089\/scd.2011.0684"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2019.05.038"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1083-y"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIR.0000000000000485"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13311-016-0483-x"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1414905"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2017.03.003"},{"key":"e_1_2_9_32_1","first-page":"66","article-title":"Post\u2010stroke inflammation and the potential efficacy of novel stem cell therapies: focus on amnion epithelial cells","volume":"6","author":"Broughton BR","year":"2012","journal-title":"Front Cell Neurosci"},{"issue":"1","key":"e_1_2_9_33_1","first-page":"111","article-title":"Effects and mechanisms of potent caspase\u20101 inhibitor VX765 treatment on collagen\u2010induced arthritis in mice","volume":"34","author":"Zhang Y","year":"2016","journal-title":"Clin Exp Rheumatol"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-018-6781-2"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1080\/15384101.2015.1038685"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-015-0450-z"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2017.08.034"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2015.02.002"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.202"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2018.01.001"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8725-6"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.00034"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/0271678X18776802"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12015-016-9690-4"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcns.13400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cns.13400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cns.13400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,4]],"date-time":"2023-09-04T05:42:15Z","timestamp":1693806135000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cns.13400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":43,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9]]}},"alternative-id":["10.1111\/cns.13400"],"URL":"https:\/\/doi.org\/10.1111\/cns.13400","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]},"assertion":[{"value":"2020-01-13","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-28","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-05-27","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}