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Objective: Warfarin is a widely prescribed narrow therapeutic index anticoagulant. Determining proper warfarin dosage remains problematic due to its narrow therapeutic index and genetic variations from individual to individual. The administration of incorrect doses of warfarin can catastrophic adverse events. Observational studies have demonstrated single nucleotide polymorphisms in CYP2C9 and VK0RC1 significantly affect warfarin dose requirements. The present study aimed to examine the influences of various genotypes on warfarin dose requirements among Iranian patients. Methods: Blood samples were taken from 117 patients and stored in tubes containing EDTA. DNA extraction was performed on the blood samples and the different alleles and genotypes of the studied SNPs were identified and recorded by the PCR-RFLP technique. Results: Of the 117 patients, no significant differences in the mean daily warfarin dose requirement were found among the genotypes of polymorphism CYP2C9 * 3 (1075A> C). However, there were significant differences among the genotypes of CYP2C9 * 2 (430C> T). The mean daily warfarin dose requirements were significantly different among wild genotypes, heterozygotes and mutants in the two polymorphisms of VKORC1 (1173C> T) and VKORC1(1639G> A). Conclusion: The results of our study demonstrated that CYP2C9 and VKORC1 polymorphisms have significant effect on warfarin maintenance dose requirements in iranian patients which would help improve the prediction of warfarin dose requirements and minimize the chance of over-anticoagulation or under-anticoagulation. [ABSTRACT FROM AUTHOR]

Background: Cinnamic acid, a phenylpropanoid acid, has been investigated as a potential alternative therapy for diabetes and its complications in some studies. Methods: In the first stage, the viability of HepG2 cells at different concentrations of glucose and CA was assessed by MTT assay. Oxidative stress markers) CAT, GPx, GSH, and MDA) were measured spectrophotometrically. After RNA extraction, the effect of different concentrations of CA on the expression of DPP4 and inflammatory factors (IL-6, NF- κB) in HepG2 cells was assessed using realtime PCR. Results: In HepG2 cells, CA increased catalase and glutathione peroxidase activity and GSH production in a dose-dependent manner in the presence of high glucose concentrations, with the greatest effect seen at a concentration of 75 mg/ml. Also, it reduced the amount of MDA in highglucose HepG2 cells. Furthermore, CA decreased the expression of DPP4, NF- κB, and IL-6 genes in HepG2 cells in the presence of high glucose levels. Conclusions: The results of our study indicated that CA reduced hyperglycemia-induced complications in HepG2 cells by decreasing inflammatory gene expression, including IL-6 and NF- κB and inhibiting the expression of DPP4, and limiting oxidative stress. [ABSTRACT FROM AUTHOR]

Background: The available evidence has increasingly demonstrated that a combination of genetic and epigenetic factors, such as DNA methylation, could be considered as causing leukemia. Epigenetic changes and methylation of the suppressor of the cytokine signaling 1 promoter (SOCS1) CpG region silence SOCS1 expression in cancer. In the current study, we evaluated the impact of epigallocatechin gallate (EGCG) and RG108 on SOCS1 promoter methylation and expression in U937 cells. Methods: In the current study, U937 leukemic cells were treated with EGCG and RG108 for 12, 24, 48, and 72 h and SOCS1 promoter methylation and its expression were measured by methylationspecific PCR (MSP) and quantitative real-time PCR, respectively. Results: The outcomes indicated that the SOCS1 promoter is methylated in U937 cells, and treatment of these cells with either EGCG or RG108 reduced its methylation. Moreover, we observed that SOCS1 expression was significantly upregulated in a time-dependent manner by both EGCG and RG108 in U937 cells compared with control cells. In the RG108-treated group at 12, 24, 48, and 72 h, SOCS1 expression was upregulated by 1, 4.2, 16.6, and 32.6 -fold respectively, and in the EGCG-treated group, by 0.5, 3.2, 10.8, and 22.3 -fold, respectively. Conclusions: Treatment with either EGCG or RG108 reduced SOCS1 promoter methylation and increased SOCS1 expression in U937 cells in a time-dependent manner, which may play a role in leukemia therapy. [ABSTRACT FROM AUTHOR]