{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,18]],"date-time":"2026-04-18T20:28:16Z","timestamp":1776544096407,"version":"3.51.2"},"reference-count":55,"publisher":"Spandidos Publications","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Exp Ther Med"],"DOI":"10.3892\/etm.2021.10910","type":"journal-article","created":{"date-parts":[[2021,10,22]],"date-time":"2021-10-22T12:21:35Z","timestamp":1634905295000},"source":"Crossref","is-referenced-by-count":5,"title":["Shikonin regulates autophagy via the AMPK\/mTOR pathway and reduces apoptosis of human umbilical cord mesenchymal stem cells to improve survival in tissues surrounding brain contusion"],"prefix":"10.3892","volume":"22","author":[{"given":"Xiaohong","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. 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, Zhejiang 325000, P.R. 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, Zhejiang 325000, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhezhe","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. 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, Zhejiang 325000, P.R. 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, Zhejiang 325000, P.R. 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, Zhejiang 325000, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Linhui","family":"Ruan","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2249","published-online":{"date-parts":[[2021,10,22]]},"reference":[{"key":"key20211117123251_b1-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","article-title":"GBD 2016 Neurology Collaborators: Global, regional, and national burden of neurological disorders, 1990-2016: A systematic analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Feigin","year":"2019","journal-title":"Lancet Neurol"},{"issue":"96","key":"key20211117123251_b2-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-019-1210-4","article-title":"Calpain inhibitor MDL28170 improves the transplantation-mediated therapeutic effect of bone marrow-derived mesenchymal stem cells following traumatic brain injury","volume":"10","author":"Hu","year":"2019","journal-title":"Stem Cell Res Ther"},{"key":"key20211117123251_b3-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1","DOI":"10.15585\/mmwr.ss6609a1","article-title":"Traumatic Brain Injury-Related Emergency Department Visits, Hospitalizations, and Deaths - United States, 2007 and 2013","volume":"66","author":"Taylor","year":"2017","journal-title":"MMWR Surveill Summ"},{"issue":"CD004609","key":"key20211117123251_b4-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004609.pub3","article-title":"Hyperbaric oxygen therapy for the adjunctive treatment of traumatic brain injury","volume":"12","author":"Bennett","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"key20211117123251_b5-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1111\/j.1749-6632.2012.06683.x","article-title":"Neuroprotective and neurorestorative effects of thymosin \u03b24 treatment following experimental traumatic brain injury","volume":"1270","author":"Xiong","year":"2012","journal-title":"Ann N Y Acad Sci"},{"key":"key20211117123251_b6-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1093\/neuros\/nyaa278","article-title":"Guidelines for the Management of Severe Traumatic Brain Injury: 2020 Update of the Decompressive Craniectomy Recommendations","volume":"87","author":"Hawryluk","year":"2020","journal-title":"Neurosurgery"},{"key":"key20211117123251_b7-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"589","DOI":"10.3171\/jns.2001.94.4.0589","article-title":"Intracranial bone marrow transplantation after traumatic brain injury improving functional outcome in adult rats","volume":"94","author":"Mahmood","year":"2001","journal-title":"J Neurosurg"},{"key":"key20211117123251_b8-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1016\/j.biocel.2004.10.010","article-title":"Olfactory ensheathing cells: Their role in central nervous system repair","volume":"37","author":"Fairless","year":"2005","journal-title":"Int J Biochem Cell Biol"},{"key":"key20211117123251_b9-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1016\/s1474-4422(02)00040-6","article-title":"Treatment of neural injury with marrow stromal cells","volume":"1","author":"Chopp","year":"2002","journal-title":"Lancet Neurol"},{"key":"key20211117123251_b10-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1227\/NEU.0b013e318207734c","article-title":"Autologous bone marrow mononuclear cell therapy for severe traumatic brain injury in children","volume":"68","author":"Cox","year":"2011","journal-title":"Neurosurgery"},{"key":"key20211117123251_b11-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1080\/14653240701883061","article-title":"A combined procedure to deliver autologous mesenchymal stromal cells to patients with traumatic brain injury","volume":"10","author":"Zhang","year":"2008","journal-title":"Cytotherapy"},{"key":"key20211117123251_b12-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1089\/neu.2010.1526","article-title":"Long-term benefit of human fetal neuronal progenitor cell transplantation in a clinically adapted model after traumatic brain injury","volume":"28","author":"Skardelly","year":"2011","journal-title":"J Neurotrauma"},{"key":"key20211117123251_b13-ETM-0-0-10910","doi-asserted-by":"crossref","first-page":"283","DOI":"10.3727\/096020198389933","article-title":"Fibronectin promotes survival and migration of primary neural stem cells transplanted into the traumatically injured mouse brain","volume":"11","author":"Tate","year":"2002","journal-title":"Cell Transplant"},{"key":"key20211117123251_b14-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"439","DOI":"10.1038\/nm1548","article-title":"Stem cells act through multiple mechanisms to benefit mice with neurodegenerative metabolic disease","volume":"13","author":"Lee","year":"2007","journal-title":"Nat Med"},{"key":"key20211117123251_b15-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"12175","DOI":"10.1073\/pnas.0704091104","article-title":"Behavioral improvement in a primate Parkinson's model is associated with multiple homeostatic effects of human neural stem cells","volume":"104","author":"Redmond","year":"2007","journal-title":"Proc Natl Acad Sci USA"},{"key":"key20211117123251_b16-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1089\/neu.2005.22.398","article-title":"Calpain inhibitors prevent neuronal cell death and ameliorate motor disturbances after compression-induced spinal cord injury in rats","volume":"22","author":"Arataki","year":"2005","journal-title":"J Neurotrauma"},{"issue":"e0120257","key":"key20211117123251_b17-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0120257","article-title":"Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival","volume":"10","author":"Fillmore","year":"2015","journal-title":"PLoS One"},{"key":"key20211117123251_b18-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"2619","DOI":"10.3892\/mmr.2016.4847","article-title":"Macrophage migration inhibitory factor induces autophagy to resist hypoxia\/serum deprivation-induced apoptosis via the AMP-activated protein kinase\/mammalian target of rapamycin signaling pathway","volume":"13","author":"Xia","year":"2016","journal-title":"Mol Med Rep"},{"issue":"e58207","key":"key20211117123251_b19-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0058207","article-title":"Stromal cell-derived factor-1\u03b2 mediates cell survival through enhancing autophagy in bone marrow-derived mesenchymal stem cells","volume":"8","author":"Herberg","year":"2013","journal-title":"PLoS One"},{"key":"key20211117123251_b20-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"2861","DOI":"10.1101\/gad.1599207","article-title":"Autophagy: Process and function","volume":"21","author":"Mizushima","year":"2007","journal-title":"Genes Dev"},{"key":"key20211117123251_b21-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ceb.2009.11.014","article-title":"Mammalian autophagy: Core molecular machinery and signaling regulation","volume":"22","author":"Yang","year":"2010","journal-title":"Curr Opin Cell Biol"},{"key":"key20211117123251_b22-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.abb.2007.02.006","article-title":"Autophagic and apoptotic response to stress signals in mammalian cells","volume":"462","author":"Ferraro","year":"2007","journal-title":"Arch Biochem Biophys"},{"key":"key20211117123251_b23-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1146\/annurev-genet-102808-114910","article-title":"Regulation mechanisms and signaling pathways of autophagy","volume":"43","author":"He","year":"2009","journal-title":"Annu Rev Genet"},{"key":"key20211117123251_b24-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"205","DOI":"10.1016\/s0092-8674(04)00046-7","article-title":"Cell death: Critical control points","volume":"116","author":"Danial","year":"2004","journal-title":"Cell"},{"key":"key20211117123251_b25-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"327","DOI":"10.1111\/j.1600-065X.2012.01095.x","article-title":"Regulation of cell death and autophagy by IKK and NF-\u03baB: Critical mechanisms in immune function and cancer","volume":"246","author":"Baldwin","year":"2012","journal-title":"Immunol Rev"},{"issue":"e1056332","key":"key20211117123251_b26-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1080\/23723556.2015.1056332","article-title":"Mitophagy: In sickness and in health","volume":"3","author":"Palikaras","year":"2015","journal-title":"Mol Cell Oncol"},{"key":"key20211117123251_b27-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"66","DOI":"10.4161\/auto.1.2.1738","article-title":"Does autophagy contribute to cell death?","volume":"1","author":"Debnath","year":"2005","journal-title":"Autophagy"},{"key":"key20211117123251_b28-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"741","DOI":"10.1038\/nrm2239","article-title":"Self-eating and self-killing: Crosstalk between autophagy and apoptosis","volume":"8","author":"Maiuri","year":"2007","journal-title":"Nat Rev Mol Cell Biol"},{"key":"key20211117123251_b29-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1159\/000480474","article-title":"Effect of Shikonin on Spinal Cord Injury in Rats Via Regulation of HMGB1\/TLR4\/NF-\u03baB Signaling Pathway","volume":"43","author":"Bi","year":"2017","journal-title":"Cell Physiol Biochem"},{"key":"key20211117123251_b30-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s11064-013-1194-x","article-title":"Protective effect of shikonin in experimental ischemic stroke: Attenuated TLR4, p-p38MAPK, NF-\u03baB, TNF-\u03b1 and MMP-9 expression, up-regulated claudin-5 expression, ameliorated BBB permeability","volume":"39","author":"Wang","year":"2014","journal-title":"Neurochem Res"},{"key":"key20211117123251_b31-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"148","DOI":"10.3967\/bes2015.019","article-title":"Protective effects of shikonin on brain injury induced by carbon ion beam irradiation in mice","volume":"28","author":"Gan","year":"2015","journal-title":"Biomed Environ Sci"},{"key":"key20211117123251_b32-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"F561","DOI":"10.1152\/ajprenal.00036.2017","article-title":"Inhibiting aerobic glycolysis suppresses renal interstitial fibroblast activation and renal fibrosis","volume":"313","author":"Ding","year":"2017","journal-title":"Am J Physiol Renal Physiol"},{"key":"key20211117123251_b33-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1007\/s12519-019-00310-x","article-title":"The neuroprotective effect of mesenchymal stem cells is mediated through inhibition of apoptosis in hypoxic ischemic injury","volume":"16","author":"Li","year":"2020","journal-title":"World J Pediatr"},{"key":"key20211117123251_b34-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"403","DOI":"10.1002\/mc.21988","article-title":"PKM2 inhibitor shikonin suppresses TPA-induced mitochondrial malfunction and proliferation of skin epidermal JB6 cells","volume":"53","author":"Li","year":"2014","journal-title":"Mol Carcinog"},{"key":"key20211117123251_b35-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1080\/21691401.2019.1575229","article-title":"Shikonin induces apoptosis and prosurvival autophagy in human melanoma A375 cells via ROS-mediated ER stress and p38 pathways","volume":"47","author":"Liu","year":"2019","journal-title":"Artif Cells Nanomed Biotechnol"},{"key":"key20211117123251_b36-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.ejphar.2010.06.027","article-title":"Shikonin protects mouse brain against cerebral ischemia\/reperfusion injury through its antioxidant activity","volume":"643","author":"Wang","year":"2010","journal-title":"Eur J Pharmacol"},{"issue":"e51781","key":"key20211117123251_b37-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.3791\/51781","article-title":"Controlled cortical impact model for traumatic brain injury","volume":"90","author":"Romine","year":"2014","journal-title":"J Vis Exp"},{"key":"key20211117123251_b38-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1682","DOI":"10.1080\/15548627.2019.1596479","article-title":"Autophagy-dependent secretion: Mechanism, factors secreted, and disease implications","volume":"15","author":"New","year":"2019","journal-title":"Autophagy"},{"key":"key20211117123251_b39-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1321","DOI":"10.1089\/scd.2011.0684","article-title":"Autophagy activation: A novel mechanism of atorvastatin to protect mesenchymal stem cells from hypoxia and serum deprivation via AMP-activated protein kinase\/mammalian target of rapamycin pathway","volume":"21","author":"Zhang","year":"2012","journal-title":"Stem Cells Dev"},{"key":"key20211117123251_b40-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/nrm3311","article-title":"AMPK: A nutrient and energy sensor that maintains energy homeostasis","volume":"13","author":"Hardie","year":"2012","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"397","key":"key20211117123251_b41-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1186\/s13287-021-02469-5","article-title":"Human umbilical cord mesenchymal stromal cells attenuate pulmonary fibrosis via regulatory T cell through interaction with macrophage","volume":"12","author":"Tang","year":"2021","journal-title":"Stem Cell Res Ther"},{"key":"key20211117123251_b42-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1016\/j.neuroscience.2008.06.046","article-title":"Microglial clearance function in health and disease","volume":"158","author":"Napoli","year":"2009","journal-title":"Neuroscience"},{"key":"key20211117123251_b43-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1369","DOI":"10.1089\/neu.2008-0870","article-title":"Temporal and spatial dynamics of peroxynitrite-induced oxidative damage after spinal cord contusion injury","volume":"26","author":"Carrico","year":"2009","journal-title":"J Neurotrauma"},{"key":"key20211117123251_b44-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1195","DOI":"10.1038\/nm912","article-title":"Mesenchymal stem cells modified with Akt prevent remodeling and restore performance of infarcted hearts","volume":"9","author":"Mangi","year":"2003","journal-title":"Nat Med"},{"issue":"113409","key":"key20211117123251_b45-ETM-0-0-10910","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2020.113409","article-title":"The closed-head impact model of engineered rotational acceleration (CHIMERA) as an application for traumatic brain injury pre-clinical research: A status report","volume":"333","author":"McNamara","year":"2020","journal-title":"Exp Neurol"},{"key":"key20211117123251_b46-ETM-0-0-10910","author":"Bolouri"},{"key":"key20211117123251_b47-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1139\/bcb-2018-0310","article-title":"Shikonin exerts antitumor activity by causing mitochondrial dysfunction in hepatocellular carcinoma through PKM2-AMPK-PGC1\u03b1 signaling pathway","volume":"97","author":"Liu","year":"2019","journal-title":"Biochem Cell Biol"},{"key":"key20211117123251_b48-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"4535","DOI":"10.7150\/thno.25674","article-title":"AMPK: Potential Therapeutic Target for Ischemic Stroke","volume":"8","author":"Jiang","year":"2018","journal-title":"Theranostics"},{"key":"key20211117123251_b49-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1074\/jbc.M112.415224","article-title":"Autophagy controls p38 activation to promote cell survival under genotoxic stress","volume":"288","author":"Qiang","year":"2013","journal-title":"J Biol Chem"},{"key":"key20211117123251_b50-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"10892","DOI":"10.1074\/jbc.M800102200","article-title":"Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia","volume":"283","author":"Zhang","year":"2008","journal-title":"J Biol Chem"},{"key":"key20211117123251_b51-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1935","DOI":"10.3390\/cells9091935","article-title":"Ischemia-Like Stress Conditions Stimulate Trophic Activities of Adipose-Derived Stromal\/Stem Cells","volume":"9","author":"Bachmann","year":"2020","journal-title":"Cells"},{"key":"key20211117123251_b52-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"146","DOI":"10.1038\/sj.cdd.4401936","article-title":"Response to myocardial ischemia\/reperfusion injury involves Bnip3 and autophagy","volume":"14","author":"Hamacher-Brady","year":"2007","journal-title":"Cell Death Differ"},{"key":"key20211117123251_b53-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.3390\/nu12041133","article-title":"Shikonin Attenuates Hepatic Steatosis by Enhancing Beta Oxidation and Energy Expenditure via AMPK Activation","volume":"12","author":"Gwon","year":"2020","journal-title":"Nutrients"},{"key":"key20211117123251_b54-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"861","DOI":"10.3389\/fphar.2020.01088","article-title":"Shikonin Inhibits Cancer Through P21 Upregulation and Apoptosis Induction","volume":"11","author":"Wang","year":"2020","journal-title":"Front Pharmacol"},{"key":"key20211117123251_b55-ETM-0-0-10910","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1016\/j.cmet.2010.05.001","article-title":"With TOR, less is more: A key role for the conserved nutrient-sensing TOR pathway in aging","volume":"11","author":"Kapahi","year":"2010","journal-title":"Cell Metab"}],"container-title":["Experimental and Therapeutic Medicine"],"original-title":[],"deposited":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T10:48:24Z","timestamp":1637146104000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.spandidos-publications.com\/10.3892\/etm.2021.10910"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,10,22]]},"references-count":55,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,10,22]]}},"URL":"https:\/\/doi.org\/10.3892\/etm.2021.10910","relation":{},"ISSN":["1792-0981","1792-1015"],"issn-type":[{"value":"1792-0981","type":"print"},{"value":"1792-1015","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,10,22]]},"article-number":"1475"}}