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Mol Med Rep ; 17(1): 1461-1468, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29257199


The transplantation of mesenchymal stem cells (MSCs) has been a reported method for alleviating atherosclerosis (AS). Because the availability of bone marrow­derived MSCs (BM­MSCs) is limited, the authors used this study to explore the use of a new type of MSC, human induced pluripotent stem cell­derived MSCs (iPSC­MSCs), to evaluate whether these cells could alleviate AS. iPSC­MSCs were intravenously administered to ApoE knock out mice fed on a high­fat diet (HFD) for 12 weeks. It was reported that systematically administering iPSC­MSCs clearly reduced the size of plaques. In addition, the numbers of macrophages and lipids in plaques were lower in the HFD + iPSC­MSCs group than in the HFD group. Furthermore, iPSC­MSCs attenuated AS­associated inflammation by decreasing the levels of inflammatory cytokines, such as tumor necrosis factor­α and interleukin­6, in serum. In addition, the expression of Notch1 was higher in the HFD group, and injecting iPSC­MSCs reversed this effect. In conclusion, the current study provides the first evidence indicating that iPSC­MSCs may be a new optional MSC­based strategy for treating AS.

Aterosclerose/terapia , Células-Tronco Pluripotentes Induzidas/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Animais , Aterosclerose/sangue , Aterosclerose/complicações , Aterosclerose/imunologia , Células Cultivadas , Citocinas/sangue , Citocinas/imunologia , Humanos , Células-Tronco Pluripotentes Induzidas/imunologia , Inflamação/sangue , Inflamação/complicações , Inflamação/imunologia , Inflamação/terapia , Masculino , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/imunologia , Camundongos , Camundongos Endogâmicos C57BL
Eur J Clin Pharmacol ; 72(11): 1327-1334, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27488389


PURPOSE: The aim of this study was to investigate whether any of the single-nucleotide polymorphisms (SNPs) in the POR gene were significantly associated with CYP activity and expression, and could contribute to the total variability in stable warfarin maintenance doses in Han Chinese. METHODS: A total of 408 patients treated at the First Affiliated Hospital of Sun Yat-Sen University were eligible for the study and had attained a stable warfarin maintenance dose at the start of the investigation. Demographics, warfarin maintenance doses, and concomitant medications were documented. Genomic DNA was extracted from peripheral blood samples and genotyped for ten SNPs (CYP 2C9*2 and *3, CYP4F2 rs2108622, VKORC1 -1639C>T, and potential POR genes of rs10239977, rs3815455, rs41301394, rs56256515, rs1057868, and rs2286823) using the Sequenom MassARRAY genotyping system. RESULTS: A predictive model of warfarin maintenance dose was established and indicated that age, gender, body surface area, aspirin use, CYP2C9*3, CYP4F2 rs2108622, VKORC1 -1639C>T, and POR*37 831-35C>T accounted for 42.4 % of dose variance in patients undergoing anticoagulant treatment. The contribution of POR*37 831-35C>T to warfarin dose variation was only 3.9 %. CONCLUSIONS: For the first time, the SNP POR*37 831-35C>T was confirmed as a minor but statistically significant factor associated with interindividual variation in warfarin maintenance dose in Han Chinese. The POR*37 gene polymorphism should be considered in future algorithms for faster and more reliable achievement of stable warfarin maintenance doses.

Anticoagulantes/administração & dosagem , Grupo com Ancestrais do Continente Asiático/genética , Sistema Enzimático do Citocromo P-450/genética , Modelos Biológicos , Varfarina/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Varfarina/uso terapêutico , Adulto Jovem