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Vitamin D deficiency is now a recognised problem affecting multiple physiological functions. The aim of the present study was to evaluate the effect of a single dose of vitamin D3 injection on the inflammatory, muscular damage, metabolic and cardiovascular responses to an acute bout of resistance exercise (RE) in vitamin D-deficient resistance-trained males. Blood samples from fourteen vitamin D-deficient resistance-trained males were obtained during two separate trials: lower vitamin D (LVD) and higher vitamin D (HVD, after vitamin D3 injection). Metabolic, inflammatory, muscle damage and cardiovascular markers were evaluated at baseline, immediately and 1 h after RE. There were significant trial-by-time interactions for insulin and homeostatic model assessment of insulin resistance (HOMA-IR) which significantly (P < 0·05) declined for 1 h after RE in the HVD trial compared with the LVD trial. Homeostasis model assessment of β -cell function (HOMA- β) declines at 1 h post-RE in the HVD trial. There was also a time effect for blood sugar which significantly (P < 0·05) decreased and for creatine kinase, lactate dehydrogenase and IL-6 which increased significantly 1 h post-RE in both trials. There were no significant changes in other inflammatory and cardiovascular markers following both trials. A single injection of vitamin D3 improved insulin resistance and β -cell function following RE in previously vitamin D-deficient resistance-trained males. Conversely, the injection did not change muscle damage and the inflammatory response to acute RE. Intramuscular vitamin D replacement may have key implications for the promotion of glucose metabolism and lowering the risk of diabetes in vitamin D-deficient individuals. [ABSTRACT FROM AUTHOR]

Objective G protein-coupled receptor ( GPCR) agonists through their receptors can transactivate protein tyrosine kinase receptors such as epidermal growth factor receptor and serine/threonine kinase receptors most notably transforming growth factor ( TGF)-β receptor (Tβ RI). This signalling mechanism represents a major expansion in the cellular outcomes attributable to GPCR signalling. This study addressed the role and mechanisms involved in GPCR agonist, endothelin-1 ( ET-1)-mediated transactivation of the Tβ RI in bovine aortic endothelial cells ( BAECs). Method The in-vitro model used BAECs. Signalling intermediate phospho-Smad2 in the carboxy terminal was detected and quantified by Western blotting. Key finding ET-1 treatment of BAECs resulted in a time and concentration-dependent increase in pSmad2C. Peak phosphorylation was evident with 100 n m treatment of ET-1 at 4-6 h. Tβ RI antagonist, SB431542 inhibited ET-1-mediated pSmad2C. In the presence of bosentan, a mixed ETA and ETB receptor antagonist ET-1-mediated pSmad2C levels were inhibited. The ET-mediated pSmad2C was blocked by the protein synthesis inhibitor, cycloheximide. Conclusion In BAECs, ET-1 via the ETB receptor is involved in transactivation of the Tβ RI. The transactivation-dependent response is dependent upon de novo protein synthesis. [ABSTRACT FROM AUTHOR]

Background: Metals can cause male infertility through affection of spermatogenesis and sperm quality. Strong evidences confirm that male infertility in metal-exposed humans is mediated via various mechanisms such as production of reactive oxygen species (ROS). Flavonoids have antioxidant and metal chelating properties which make them suitable candidates for neutralizing adverse effects of metals on semen quality. In the current study, we have evaluated the effects of five types of flavonoids (rutin, naringin, kaempferol, quercetin, and catechin) on recovery of sperm motility and prevention of membrane oxidative damage from aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4). Materials and Methods: In this experimental study, motility and lipid peroxidation of metal-exposed sperm was investigated in the presence of different concentrations of five kinds of flavonoids. Malondialdehyde (MDA) production was assessed as a lipid peroxidation marker. Results: Aluminum chloride (AlCl3), cadmium chloride (CdCl2), and lead chloride (PbCl4) diminished sperm motility. Treatment of metal-exposed sperm with rutin, naringin, and kaempferol attenuated the negative effects of the metals on sperm motility. Quercetin and catechin decreased the motility of metal-exposed sperm. Conclusion: Based on the MDA production results, only AlCl3 significantly induced lipid peroxidation. Treatment with rutin, naringin, and kaempferol significantly decreased MDA production. [ABSTRACT FROM AUTHOR]

Background and Objective: Vitamins C and E are the two main antioxidants involved in prevention of type 2 diabetes, by reducing oxidative stress. The aim of this study was to evaluate the effects of vitamins C and E supplementation independently, on serum levels of insulin, high sensitivity C-reactive protein (hs-CRP) and resistin in people with type 2 diabetes. Methods: In this study, 38 patients with type 2 diabetes (17 men and 21 women) received 1,000 mg/day vitamin C, and 40 patients with type 2 diabetes (21 men and 19 women) received 400 IU/day vitamin E orally. Fasting blood glucose and lipid profile were measured using enzymatic method. Hs-CRP was measured by immunoturbidimetric method, and serum insulin and resistin levels were measured by ELISA. Results: total cholesterol, triglycerides, hs-CRP, insulin and resistin significantly were reduced after vitamin C supplementation (P<0.001). Moreover, the level of total cholesterol (P =0.018), low-density lipoprotein, triglycerides and hs-CRP significantly changed after vitamin E supplementation (P=0.001). Conclusion: The daily intake of 1,000 mg of vitamin C and 400 IU of vitamin E may be useful in reducing diabetic complications by decreasing serum levels of hs-CRP and lipid profile in people with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Hyperglycemia is generally regarded as one of the major causes of vascular complications in diabetic patients. It has been shown that high-glucose concentration increases nitric oxide synthase (NOS) expression and NO generation in cultured human aortic endothelial cells. The epidemiological studies have demonstrated that there is an inverse relation between vitamin use and cardiovascular disease in diabetes patients. This study tested whether a-tocopherol and ascorbic acid can alter high glucose-induced expression of NOS in vascular endothelial cells. Human umbilical vascular endothelial cells (HUVECs) were treated with a-tocopherol and ascorbic acid, and stimulated by high glucose. Expression of endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS) was measured by real-time PCR (RT-PCR). Ascorbic acid (100 μM) and α-tocopherol (200 µM) significantly inhibited glucose (25 mM)-induced expression of eNOS mRNA and iNOS mRNA. Ascorbic acid and a- tocopherol are also able to reduce concentration of NOS in HUVECs. Additionally, there is a significant positive relation between expression of eNOS and iNOS mRNA with concentration of NOS. These results suggest that ascorbic acid and a-tocopherol can inhibit high glucose-induced production of NOS proteins by downregulation of its gene expression. Therefore, important role of ascorbic acid and a-tocopherol in the treatment of vascular dysfunction associated with diabetes disease may be via this molecular mechanism. Of course, further studies on regulation of these vitamins to signaling pathways are necessary. [ABSTRACT FROM AUTHOR]

Objective: Calpains are a family of Ca2+ dependent proteases. There is some evidence that calpains involved in fusion process that occurs between spermatozoa and the oocyte. The current study aimed to investigate the association of smoking with semen quality and μ-calpain level. Materials and methods: This case-control study was conducted on 117 normospermia males between June 2013 and march 2014 in Jahad Laboratory in ahvaz, Iran. The semen samples were collected from male smokers (n = 50) and non-smokers (n = 67). We divided these participants as light, moderate, or heavy smokers based on their cigarettes per day (CPD). ELISA assays were used to measure μ-calpain concentration. All semen samples were analyzed according to World Health Organization guidelines. Results: The analysis of semen showed the volume, concentration, motility and morphology of semen were significantly lower among the smoker men than the non-smoker men. Also this significant difference was observed based on the number (light, moderate and heavy smokers) and duration (short term and long term smoker) of smoking. Although, showed no significant difference between μ-calpain of smoker men and non-smoker men. CPD showed negatively correlation with semen volume, concentration, motility and morphology of sperm. Conclusion: Sperm quality was negatively correlated with CPD and duration of smoking. However, there is no significant correlation between smoking and μ-calpain concentration. [ABSTRACT FROM AUTHOR]

BACKGROUND: Colesteryl ester transfer protein (CETP) plays a key role in the metabolism of lipoproteins; therefore, polymorphisms of its gene can affect susceptibility to coronary artery disease (CAD) in diabetes mellitus. The aim of the present study was to investigate association between I405V polymorphism of CETP gene and risk of CAD in patients with type 2 diabetes mellitus. METHODS: The current case-control study was conducted on 143 patients with type 2 diabetes and angiographically diagnosed CAD and 150 patients with type 2 diabetes and without CAD. Genotyping was performed through polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The presence of CAD was defined as higher than 50% reduction in coronary artery diameter. RESULTS: The genotype frequencies of I405V polymorphism were II (27.3% vs. 23.2%), IV (61.5% vs. 67.5%), and VV (11.2% vs. 9.3%) in diabetic with CAD compared to diabetic without CAD (χ² = 1.164) (P = 0.55). The I and V alleles were found at frequencies of 63.6% and 61.6% in the diabetic with CAD group and 36.4% and 38.4% in the diabetic without CAD group (χ² = 0.263) (P = 0.60). No significant difference was observed between two groups in terms of genotype and allele frequency. Moreover, no significant association was observed between II, IV, and VV genotypes and lipid profiles in both groups. However, a significant difference was observed between genotype distributions of I405V polymorphism in men according to the severity of CAD. CONCLUSION: It is speculated that I405V polymorphism may be associated with the severity of coronary artery stenosis only in men with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Objective: Diabetes mellitus Type 2 is one of the most widespread chronic metabolic diseases. In most cases, this type of diabetes is associated with alterations in levels of some inflammatory cytokines and hormones. Considering antiinflammatory properties of plant extracts rich in ascorbic acid (vitamin C) and alpha-tocopherol (vitamin E), anti-diabetic properties of these two well-known antioxidant vitamins were investigated through measurement of serum levels of highsensitivity C-reactive protein (hs-CRP), insulin, leptin, tumor necrosis factor alpha (TNF-α), and serum amyloid A (SAA) in patients with diabetes mellitus type 2. Materials and Methods: Male patients (n=80) were randomly divided into two groups each consisted of 40 subjects. Test groups were supplemented with ascorbic acid (1000 mg/day) or alphatocopherol (300 mg/day) orally during four weeks. Before and after treatment, serum biochemical factors of subjects were measured and compared. Results: Our results showed that both ascorbic acid and alphatocopherol could induce significant anti-inflammatory effects by decreasing the level of inflammatory factors such as TNF-α, SAA, and hs-CRP in diabetes mellitus type 2 patients. Effects of alphatocopherol and ascorbic acid in decreasing serum leptin level were similar. Ascorbic acid in contrast to alpha-tocopherol diminished fasting insulin and HOMA index but had no effect on LDL serum level. Conclusion: Concerning the obtained results, it is concluded that consumption of supplementary vitamins C and E could decrease induced inflammatory response in patients with diabetes mellitus type 2. It is also possible that vitamin C and vitamin E supplementation can attenuate incidence of some proposed pathological effects of diabetes mellitus. [ABSTRACT FROM AUTHOR]

Background: Potential association of leptin (LEP) gene polymorphisms has been suggested in the processes leading to breast cancer initiation and progression. We investigated whether genetic variations in the LEP -2548G/A gene are associated with risk of breast cancer. Methods: This case-control study consisted of 100 breast cancer cases and 100 control subjects without breast cancer that matched for age and body mass index (BMI). Genotyping of LEP -2548G/A polymorphism was performed by polymerase chain reaction-restriction fragment length polymorphism (PCRRFLP) assay. Serum leptin level was determined by ELISA in all study subjects. Results: The genotype distributions (AA, AG, and GG) were 36, 55, and 9% in breast cancer cases and 52, 45, and 3% in control group, respectively. The frequency of LEP -2548 GG genotype was significantly elevated in breast cancer cases as compared to controls (χ²=6.90, p=0.032). Similar difference was also found in allele frequencies between two groups (χ²=5.65, p=0.017). A markedly increase risk of breast cancer was associated with the LEP -2548GG genotype when compared to the LEP -2548 AA genotype (OR=4.33, 95% CI=1.09-17.22). In addition, postmenopausal women who bear at least one LEP -2548 G allele were at a markedly increased risk of breast cancer after adjusting for age and BMI confounders (OR=12.24, 95% CI=1.13-131.73). Conclusion: The LEP -2548 G/A polymorphism is associated with markedly increased risk of breast cancer especially in postmenopausal Ahvazian women and supported the hypothesis that leptin is involved in breast cancer. [ABSTRACT FROM AUTHOR]

Thyroid carcinoma is the most common endocrine malignancy of the endocrine organs, and its incidence rate has steadily increased over the last decade. Over 95% of thyroid carcinoma is derived from follicular cells that have a spectrum of differentiation to the most invasive malignancy. The molecular pathogenesis of thyroid cancer remains to be clarified, although activating the RET, RAS and BRAF oncogenes have been well characterized. Increasing evidence from previous studies demonstrates that acquired epigenetic abnormalities participating with genetic alteration results in altered patterns of gene expression/function. Aberrant DNA methylation has been established in the CpG regions and microRNAs (miRNAs) expression profile recognized in cancer development . In the present review, a literature review was performed using MEDLINE and PubMed with the terms 'epigenetic patterns in thyroid cancer [or papillary thyroid carcinoma (PTC), follicular thyroid carcinoma (FTC), medullary thyroid cancer (MTC), anaplastic thyroid cancer (ATC)]', 'DNA methylation in thyroid cancer (or PTC, FTC, MTC, ATC)', 'miRNA expression in thyroid cancer (or PTC, FTC, MTC, ATC)', 'epigenetic patterns in cancer' and the current understanding of epigenetic patterns in thyroid cancer was discussed. [ABSTRACT FROM AUTHOR]

Objective(s): Leptin receptor (LEPR) is a member of the class I cytokine receptor super-family that is known implicated in the initiation and progression of breast cancer. We have investigated the effect of Q223R polymorphism on the breast cancer susceptibly in a sample of Iranian subjects. Materials and Methods: We utilized a polymerase chain reaction (PCR) restriction fragment length polymorphism (RFLP) method to investigate the association of LEPR Q223R polymorphism with breast cancer risk in a case control study consisting of 100 breast cancer cases and 100 controls without breast cancer. Serum levels of leptin and soluble leptin receptor (sOB-R) were measured by ELISA method. Results: The genotype (QQ, QR, and RR) distributions were 25, 56, and 19 % in breast cancer cases and 54, 40, and 6% in controls, respectively. The frequency of 223 RR genotype was significantly elevated in breast cancer cases as compared to controls (χ2= 20.072, P<0.001). Similar significance differences were also found in allele frequencies for Q and R between two groups (χ2= 19.027, P< 0.001). Additionally, there were significant association between Q223R genotypes and breast cancer risk; homozygotes for RR genotype (OR= 6.840; 95% confidence interval [CI] = 2.434- 19.218), heterozygotes for QR (OR=3.024; 95% CI = 1.620-5.644, P = 0.001), and QR+RR genotype (OR= 3.522; 95% CI = 1.934-6.414, P < 0.001), respectively. Conclusion: Our results showed that the LEPR Q223R polymorphism is associated with increased breast cancer risk as well as tumor grade in a sample of Iranian subjects. [ABSTRACT FROM AUTHOR]

Background: Leptin plays a key role in the regulation of energy expenditure and is known to circulate in both free and bound forms. Soluble leptin receptor (sOB-R) is a unique circulating form of leptin receptor that can bind to leptin. Leptin and leptin receptor have been implicated in processes leading to breast cancer initiation and progression. Our study was aimed to investigate the relationship between serum levels of sOB-R and leptin with breast cancer. Materials and Methods: Serum leptin and sOB-R levels were measured by enzyme-linked immunosorbent assay in 100 women with breast cancer cases compared with 100 age and body mass index (BMI)-matched controls without cancer. Lipid profiles were measured by enzymatic method. Results: The median serum levels of sOB-R in controls were significantly higher than that in breast cancer cases (odds ratio [OR],1.98; 95% confidence interval [CI] = 0.77-188.2) versus (OR, 0.140; 95% CI = 0.09-98.1). Conversely, the median serum level of leptin in breast cancer cases was significantly higher than that in controls (OR, 67.90; 95% CI = 2.77-129.9) vs. (OR, 28.30; 95% CI = 0.60-113.1). Breast cancer was significantly associated with higher serum level of leptin (OR = 1.027, 95% CI = 1.017-1.038). Conversely, breast cancer was correlated with lower serum level of sOB-R (OR = 0.983, 95% CI = 0.969-0.997). Moreover, free leptin index (FLI) (leptin/sOB-R ratio) was associated with breast cancer (OR = 1.028, 95% CI = 1.015-1.042). The serum sOB-R level was negatively associated with leptin, BMI, and high density lipoprotein (r = -0.238, -0.186, and -0.168, respectively). Conclusion: Our results suggested that FLI and serum leptin level rather than serum level of sOB-R was associated with the breast cancer. [ABSTRACT FROM AUTHOR]

Background: Spermatozoa are a group of cells that consume adenosine triphosphate (ATP) rapidly. Creatine kinase (CK), produced by creatine phosphate, is an energy reservoir for the rapid buffering and regeneration of ATP and can play an important role in sperm motility. Therefore, this study investigates the effects of cigarette smoking on human sperm CK activity in males who smoke. Materials and Methods: In this case - control study, we obtained semen samples from male smokers (n=64) and nonsmokers (n=83). Smokers were categorized as light, moderate, or heavy smokers according to the daily number of cigarettes smoked and the number of years they have smoked. Data were analyzed by the independent t test and Pearson's analysis. Results: This investigation showed significantly lower sperm CK activity and movement in male smokers compared to nonsmokers. In addition, it was demonstrated that cigarette smoking had a dose-dependent effect on these parameters. There was a positive relation, although not significant, between sperm CK activity and its motility in male smokers. Conclusion: Smoking, by diminishing sperm CK activity, may potentially impair sperm energy homeostasis and have an association with damage to sperm motility. This effect can be an important mechanism that may cause infertility in male smokers. However, further research is necessary to elucidate the underlying mechanism of sperm motility damage caused by cigarette smoking. [ABSTRACT FROM AUTHOR]

Background and Objectives: Type 2 diabetes is the most prevalent form of diabetes mellitus and is associated with a variety of complications. Homocysteine is an important independent risk factor for atherosclerotic diseases in both diabetic and non diabetic subjects. The association between these two is still unclear. The aim of this study was to assess the serum homocysteine levels in uncomplicated type 2 diabetic patients and control subjects. Materials and Methods: Eighty five diabetic patients and 85 healthy control subjects with the mean age of 57.65 and 57.68 years, respectively, were selected during 2010 in Ahwaz City, southwest of Iran. Serum glucose, lipids and lipoproteins were measured by standard enzymatic techniques and homocysteine levels by enzyme--linked immunosorbent assay method. Results: In patients as a whole and with respect to the gender, homocysteine levels were generally lower than controls. Compared to other studies, homocysteine levels ranging from 12.19 to 18 µmol/l were slightly higher in both population. Conclusion: Homocysteine levels, however, were compatible with normal range of adults. The patients were not nephropathic and it is most likely that this is the main reason for maintaining the normal levels. Slightly higher levels of homocysteine in the region are due to multiple genetic and environmental factors. [ABSTRACT FROM AUTHOR]