{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T11:20:59Z","timestamp":1776856859241,"version":"3.51.2"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T00:00:00Z","timestamp":1558569600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81560134"],"award-info":[{"award-number":["81560134"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81860097"],"award-info":[{"award-number":["81860097"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2019,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Valproic acid (VPA) is a clinical medicine primarily prescribed to control epileptic symptoms. VPA has potential side\u2010effects, such as hepatotoxicity. Fibroblast growth factor 21 (FGF21) is a functional cytokine for metabolic regulation. In this article, we aimed to evaluate the possible clinical application of FGF21 in VPA\u2010treated livers in early undetected liver injury (EULI).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Methodologically, plasma samples of VPA\u2010treated epileptic patients were isolated for biochemical and high\u2010performance liquid chromatography tests. In addition, VPA\u2010dosed mice were subjected to determinations of serological parameters, key regulatory effectors and FGF21 expressions through biochemical analyses, enzyme\u2010linked immunosorbent assay, immunohistochemistry stain, immunofluorescence stain, and reverse transcription\u2010polymerase chain reaction (RT\u2010PCR) test, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The serological data suggested that VPA\u2010treated epileptic patients showed visibly elevated FGF21 contents in plasma samples. However, other diagnostic parameters showed inconspicuous changes. As revealed in animal study, VPA\u2010dosed mice exhibited undetected morphological alterations and hormonal changes in the liver, pancreas, and kidneys. Furthermore, serological parameters and key regulatory proteins in VPA\u2010dosed livers and controls showed inconspicuous changes. Interestingly, endogenous FGF21 expressions in VPA\u2010dosed mice were increased in sera. In further experiments, the findings showed that intracellular expressions of FGF21 mRNA and protein were upregulated in VPA\u2010dosed livers as revealed in RT\u2010PCR and immunoassay.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Taken together, these preliminary data reveal that functional FGF21 cytokine may serve as a potent predictor in VPA\u2010related EULI.<\/jats:p><\/jats:sec>","DOI":"10.1002\/biof.1519","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T17:43:31Z","timestamp":1558633411000},"page":"740-749","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Potential biomarker of fibroblast growth factor 21 in valproic acid\u2010treated livers"],"prefix":"10.1002","volume":"45","author":[{"given":"Xiaoxiao","family":"Xu","sequence":"first","affiliation":[{"name":"Key Laboratory of Tumor Immunology and Microenvironmental Regulation Guilin 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