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维生素D:与巴西南部人群生化指标及身体成分变化的相关性以及对人脂肪组织来源间充质干细胞细胞毒性的诱导作用

Vitamin D: Correlation with biochemical and body composition changes in a southern Brazilian population and induction of cytotoxicity in mesenchymal stem cells derived from human adipose tissue.

作者信息

Pesarini João Renato, Oliveira Rodrigo Juliano, Pessatto Lucas Roberto, Antoniolli-Silva Andréia Conceição Milan Brochado, Felicidade Ingrid, Nardi Nance Beyer, Camassola Melissa, Mantovani Mário Sérgio, Ribeiro Lúcia Regina

机构信息

São Paulo State University (UNESP), Graduate Programme in Cellular and Molecular Biology, Institute of Biosciences of Rio Claro (IBRC), Rio Claro, São Paulo, Brazil; Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil.

Federal University of Mato Grosso do Sul (UFMS), Graduate Programme in Health and Development in the Central-West Region, School of Medicine (FAMED), Campo Grande, Mato Grosso do Sul, Brazil; Stem Cell, Cell Therapy and Toxicological Genetics Research Centre (CeTroGen), "Maria Aparecida Pedrossian" University Hospital, Brazilian Hospital Services Company (EBSERH), Campo Grande, Mato Grosso do Sul, Brazil; State University of Londrina (UEL), Graduate Programme in Genetics and Molecular Biology, Department of General Biology, Londrina, Paraná, Brazil.

出版信息

Biomed Pharmacother. 2017 Jul;91:861-871. doi: 10.1016/j.biopha.2017.05.013. Epub 2017 May 11.

DOI:10.1016/j.biopha.2017.05.013
PMID:28501775
Abstract

Studies have shown that metabolic disorders, serum inflammatory markers and weight gain (obesity) are correlated with vitamin D deficiency. Therefore, the present study correlated the serum calcidiol (s25(OH)D) levels in a sample of individuals from southern Brazil with variables related to metabolic disorders, obesity and lifestyle habits and assessed the cytotoxic effect of calcitriol on adipose tissue-derived mesenchymal stem cells (ADSCs). The results showed a 79.23% prevalence of hypovitaminosis D in the study population and a correlation (p<0.05) between a low serum vitamin D concentration and an elevated low-density lipoprotein cholesterol (LDL-c) level. Univariate linear regression analysis using 25(OH)D as a regressor showed a negative association (p<0.05) with an indoor work environment (β=-2.305), increased body fat (β=-0.095), age (β=-0.065) and high-density lipoprotein cholesterol (HDL-c; β=-0.109). An in vitro 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay performed with ADSCs using five calcitriol concentrations (15.625, 31.25, 62.5, 125 and 250nM) indicated cytotoxic potential (p<0.05) at the 62.5nM concentration at 48 and 72h and at the 125 and 250nM concentrations at 24, 48 and 72h. The results reported herein corroborate one another and suggest a key association between vitamin D deficiency and the development of obesity because ADSCs are involved in adipose tissue hyperplasia and differentiate into adipocytes that can sequester the bioavailable vitamin D necessary for homeostasis.

摘要

研究表明,代谢紊乱、血清炎症标志物和体重增加(肥胖)与维生素D缺乏有关。因此,本研究将巴西南部个体样本中的血清骨化二醇(s25(OH)D)水平与代谢紊乱、肥胖和生活习惯相关变量进行关联,并评估了骨化三醇对脂肪组织来源的间充质干细胞(ADSCs)的细胞毒性作用。结果显示,研究人群中维生素D缺乏症的患病率为79.23%,血清维生素D浓度低与低密度脂蛋白胆固醇(LDL-c)水平升高之间存在相关性(p<0.05)。以25(OH)D作为回归变量的单变量线性回归分析显示,与室内工作环境(β=-2.305)、体脂增加(β=-0.095)、年龄(β=-0.065)和高密度脂蛋白胆固醇(HDL-c;β=-0.109)呈负相关(p<0.05)。使用五种骨化三醇浓度(15.625、31.25、62.5、125和250nM)对ADSCs进行的体外3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)试验表明,在48小时和72小时时,62.5nM浓度以及在24、48和72小时时,125和250nM浓度具有细胞毒性潜力(p<0.05)。本文报道的结果相互印证,表明维生素D缺乏与肥胖发展之间存在关键关联,因为ADSCs参与脂肪组织增生并分化为可隔离内环境稳态所需生物可利用维生素D的脂肪细胞。

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The enzymatic disaggregation by trypsin does not alter cell quality and genomic stability of adipose-derived stem cells cultivated for human cell therapy.
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