{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T01:12:33Z","timestamp":1791508353186,"version":"4.3.4"},"reference-count":19,"publisher":"Wiley","license":[{"start":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T00:00:00Z","timestamp":1644451200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Healthcare Engineering"],"published-print":{"date-parts":[[2022,2,10]]},"abstract":"<jats:p>Glioma is one of the most common intracranial tumors worldwide, and metastasis and chemoresistance remain a challenge in glioma treatment. This study aims to investigate the effect of sodium valproate on the invasion and metastasis of glioma cells and its mechanism. Glioma cell lines were stimulated with VPA at different concentrations and for different durations of action. U87 glioma cells were transfected with Smad4 plasmid and small interfering RNA, and the changes of EMT-related protein indexes in U87 cells after up- or downregulation of Smad4 were detected by Western blotting. Immunohistochemistry was used to detect the differences in the expression of Smad4, TIF1-\u03b3, and TGF-\u03b2 proteins in 39 glioma clinical specimens from the Department of Pathology of our hospital. Based on the regulation of EMT-related transcription factors by VPA, our study indicates that VPA inhibits the EMT process of glioma by altering the expression level of Smad4, which is induced by TGF-\u03b21 to form a Smad3\/4 complex, thus inducing the EMT process of the tumor and acting as an antitumor target to inhibit the invasive ability of glioma cells. Sodium valproate inhibits glioma invasion and metastasis through the regulation of Smad4 expression.<\/jats:p>","DOI":"10.1155\/2022\/4985781","type":"journal-article","created":{"date-parts":[[2022,2,10]],"date-time":"2022-02-10T21:20:12Z","timestamp":1644528012000},"page":"1-11","source":"Crossref","is-referenced-by-count":3,"title":["Valproic Acid Inhibits Glioma and Its Mechanisms"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9106-0724","authenticated-orcid":true,"given":"Zhao-Yu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Dongying People\u2019s Hospital, Dongying 257091, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8991-2724","authenticated-orcid":true,"given":"Xiao-Hong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Dongying People\u2019s Hospital, Dongying 257091, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","reference":[{"key":"1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060-017-2379-y"},{"key":"2","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3758"},{"key":"3","doi-asserted-by":"publisher","DOI":"10.1172\/jci39104"},{"key":"4","doi-asserted-by":"publisher","DOI":"10.1016\/j.trecan.2016.11.008"},{"key":"5","doi-asserted-by":"publisher","DOI":"10.1093\/abbs\/gmx123"},{"key":"6","doi-asserted-by":"publisher","DOI":"10.1007\/s12253-018-0433-5"},{"key":"7","doi-asserted-by":"publisher","DOI":"10.1097\/ppo.0000000000000284"},{"key":"8","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.951"},{"key":"9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-11-249474"},{"key":"10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2010.03.004"},{"key":"11","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.can-15-1962"},{"key":"12","doi-asserted-by":"publisher","DOI":"10.1016\/j.coi.2011.07.002"},{"key":"13","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00092"},{"key":"14","doi-asserted-by":"publisher","DOI":"10.1080\/13543784.2016.1250882"},{"key":"15","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-017-3509-0"},{"key":"16","doi-asserted-by":"publisher","DOI":"10.1007\/s00432-015-2020-4"},{"key":"17","doi-asserted-by":"publisher","DOI":"10.7314\/apjcp.2012.13.8.3977"},{"key":"18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008522107"},{"issue":"7","key":"19","first-page":"8291","article-title":"Induction of apoptosis and autophagy in metastatic thyroid cancer cells by valproic acid (VPA)","volume":"8","author":"Y. Xu","year":"2015","journal-title":"International Journal of Clinical and Experimental Pathology"}],"container-title":["Journal of Healthcare Engineering"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/downloads.hindawi.com\/journals\/jhe\/2022\/4985781.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jhe\/2022\/4985781.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/downloads.hindawi.com\/journals\/jhe\/2022\/4985781.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,3,4]],"date-time":"2022-03-04T07:57:18Z","timestamp":1646380638000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.hindawi.com\/journals\/jhe\/2022\/4985781\/"}},"subtitle":[],"editor":[{"given":"Kalidoss","family":"Rajakani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,2,10]]},"references-count":19,"alternative-id":["4985781","4985781"],"URL":"https:\/\/doi.org\/10.1155\/2022\/4985781","relation":{},"ISSN":["2040-2309","2040-2295"],"issn-type":[{"value":"2040-2309","type":"electronic"},{"value":"2040-2295","type":"print"}],"subject":[],"published":{"date-parts":[[2022,2,10]]}}}