Abstract. Evidence has indicated that human telomerase reverse transcriptase (hTERT) was overexpressed in prostate cancer (PCa). Achillea wilhelmsii (AW) is a plant that has been traditionally used for its medicinal properties. The aim of current study was to evaluate the effects of AW extract on a PCa cell line. The cytotoxic activity of the hydroalcoholic extract of AW was studied on the PCa PC3 cell line using MTT assay. Flow cytometry was used to evaluate the effects of the extract on the apoptosis. The expression of hTERT mRNA was analyzed by the reverse transcription-quantitative polymerase chain reaction method. The ELISA method was used to measure the levels of telomerase enzyme. The hydroalcoholic AW extract demonstrated the appropriate inhibitory effect in 150 µg/ml concentration (IC 50 ) on PC3 cell line following 48 h treatment. Treatment of the PC3 cells with AW resulted in a significant increase in early and late apoptotic cells and a decrease in live cells (P<0.001), in a dose-dependent manner. Moreover, the early apoptotic cells were significantly higher than late apoptotic cells. The hTERT mRNA expression was decreased following 24 h treatment of AW extract, although it was not different between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. In addition, the hTERT concentration was significantly decreased following 24 h treatment of AW extract with the marginal P-value. There was no significant difference regarding hTERT concentration between 2, 4, 8 and 12 h treatments or 24, 48 and 72 h treatments. The hydroalcoholic extract of AW induced potent antiproliferative and apoptotic effects in PC3 cell line, which could be explainable by its high potency to inhibit expression of the prominent oncogene hTERT in PCa. Therefore, targeting telomerase represents a promising strategy for PCa therapy, and AW may have considerable potential for development as a novel natural anticancer agent.

Background: Type 2 diabetes (T2D) is an inflammatory disease that may cause inflammatory responses if it is not controlled; and may also lead to clinical manifestations such as retinopathy, nephropathy, and neuropathy. Interleukin 6 (IL6) is an important proinflammatory cytokine that controls the influence of systemic inflammation on acute phase responses. To work effectively, IL6 must bind with its IL6 receptor (IL6R). Objectives: The current study aimed to investigate the possible associations between two IL6R polymorphisms, namely, rs2229238 and rs4845625, and their susceptibility to T2D. Patients and Methods: This case-control study was done on 250 T2D patients and 250 healthy individuals. The polymorphisms were genotyped using an amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). Results: Our findings showed that either the rs2229238 or the rs4845625 variant was associated with T2D in a sample of the Iranian population. The rs2229238 C/T polymorphism showed a strong significant difference in the CT genotype (OR = 0.38, %95 CI = 0.23 -0.65, P = 0.000), as well as in the TT genotype (OR = 0.18, %95 CI = 0.05 -0.63, P = 0.007) as a protective factor against T2D in both the patient and the control group. In contrast, the rs4845625 C/T polymorphism showed a significant difference in the CT genotype (OR = 1.92, %95 CI = 1.15 -3.23, P = 0.031) and in the TT genotype (OR = 1.59, %95 CI = 1.08 -2.38, P = 0.021) as a risk factor for T2D in both the patient and the control group. An investigation of the alleles relating to these single nucleotide polymorphisms (SNPs) showed that the T allele of rs2229238 (OR = 0.34, %95 CI = 0.22 -0.52, P = 0.000) and the T allele of rs4845625 (OR = 1.43, % 95 CI = 1.11 -1.84, P = 0.006) were significantly different between the subject and control groups, and that these two polymorphisms play a protective and a risk factor role in T2D, respectively. A statistical analysis of the demographic and clinical data showed no significant association between the CC genotype and the CT + TT genotype: in the patient group, with the exception of body mass index (BMI) (P = 0.023) in the rs4845625 polymorphism and in the control group, with the exception of HDL (P = 0.025) in the rs2229238 SNP. Conclusions: We identified a strong association between the T allele of IL6R gene polymorphisms (rs2229238, rs4845625) and the risk of T2D in a protective role and as a risk factor, respectively. We also found different BMI and HDL values between the patient group and the control group, respectively in compare genotypes (CT+TT vs. CC). Further studies on various ethnicities are necessary to verify our findings.

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Abstract. Type-2 diabetes (T2D) is a multifactorial (environmental and genetic factors) and global epidemic disease with an estimated high prevalence worldwide. Studies have indicated that nitric oxide synthase 3 (NOS3) has several important roles in the pathogenesis of T2D. The present study aims to investigate the association between NOS3 rs1800779(A/G) and T2D in an Iranian sample population. A case-control study was conducted on 250 T2D patients and 250 healthy control subjects (HCs). Genotyping of the rs1800779(A/G) variant was conducted using a Tetra-Amplification Refractory Mutation System polymerase chain reaction. The frequencies of genotypes AA, AG and GG polymorphisms were 56.8, 39.2 and 4% in the T2D group, and 42.8, 56 and 1.2% in the HCs group, respectively. The frequency of the minor (G) allele was 23.6% in the T2D group and 29.2% in the HCs group. The genotype frequencies of the rs1800779(A/G) variant demonstrated statistically significant differences between T2D and controls in a codominant model (AG vs. AA, OR=0.527, 95% CI=0.368-0.756, P<0.001) and dominant model (AG+GG vs. AA, OR=0.569, P=0.002). There was no significant association between clinical and demographic characteristics and the NOS3 rs1800779(A/G) polymorphism in dominant status (P>0.05). The dominant model and AG genotype of NOS3 rs1800779(A/G) polymorphism may had a protective effect on T2D of Iranian population.

Background: Since insulin receptor substrate-1 (IRS-1) is the main substrate of the insulin receptor tyrosine kinase and has been detected to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a possible candidate for development of type2 diabetes, insulin resistance, and obesity. Preilipin (PLIN) coats intracellular lipid droplets and modulates adipocyte lipolysis. Objectives: In this study, we investigated whether insulin receptor substrate-1 (IRS-1) and Perilipin (PLIN) genes polymorphism were associated with Type 2 diabetes (T2D), obesity, and lipid profiles in a sample of the Iranian population (Southeast of Iran). Methods: In this randomized case-control study (Feb, 2016

Type 2 diabetes (T2D) is a chronic disorder with different genetics and environmental factors. It is one of growing

This study aimed to investigate the effect of hydroalcoholic Achillea wilhelmsii C. Koch extract (HAWE) on phosphodiesterase 5 (PDE5) gene expression and cyclic guanosine 3′,5′ monophosphate (cGMP) signaling in the MCF-7 and MDA-Mb-468 cell lines. The effective dose (ED50) of HAWE was examined in both cell lines using a 3-(4,5-dimethylhiazol-2-yl)-2,5-diphenyltetrazolium bromide viability test, and the type of cell death was detected by flow cytometry. The expression of PDE5 and the concentration of cGMP were measured in a time-dependent manner in the ED50 by real-time polymerase chain reaction and a colorimetric assay, respectively. Treatment with HAWE showed 25 µg/mL to be the ED50 for both cell lines, and HAWE led to a reduction in the PDE5 messenger RNA expression. The intracellular cGMP increased in a time-dependent manner. The results showed that HAWE has an antiproliferative property in MCF-7 and MDA-Mb-468 cell lines through the cGMP pathway. Therefore, HAWE is a potential source to effectively isolate inhibitory PDE5.

Objective Interleukin-6 (IL-6) is an important cytokine that plays a key role in the immune system. Changes in the immune system, particularly increased IL-6 concentrations, have been reported in schizophrenia (SCZ) patients. Although this cytokine needs its receptor (IL-6R) to function properly, few studies have examined IL-6R polymorphisms and the risk of SCZ. The aim of the present study was to evaluate the possible association between IL-6R polymorphisms (rs2229238 and rs4845625) and susceptibility to SCZ. Methods A case-control study was carried out including 92 SCZ patients and 92 healthy controls. Two single-nucleotide polymorphisms were genotyped using amplification-refractory mutation system polymerase chain reaction. Results It was found that the TC genotype of rs4845625 and CT and TT of rs2229238 increased the SCZ risk (OR 2.691, 95% CI 1.075-6.736, P = 0.034; OR 4.273, 95% CI 1.937-9.433, P < 0.001; and OR 2.123, 95% CI 1.071-4.219, P = 0.031, respectively). In dominant genetic model analysis, it was found that CT+TT of rs2229238 and TC+CC of rs4845625 were associated with the risk of SCZ (OR 2.762, 95% CI 1.426-5.376, P = 0.003 and OR 2.824, 95% CI 1.545-5.154, P < 0.001, respectively). Conclusions The findings showed that the rs2229238 and rs4845625 singlenucleotide polymorphisms were prominently associated with SCZ. Further studies are required to confirm the findings.