Band 41, Heft 4

Background Cardiovascular disease (CVD) is one of the major cause of mortality in diabetic patients. Evidence suggests that hyperglycemia in diabetic patients contributes to increased risk of CVD. This study is to investigate the therapeutic effects of melatonin on glucose-treated human umbilical vein endothelial cells (HUVEC) and provide insights on the underlying mechanisms. Materials and methods Cell viability was determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Reactive oxygen species (ROS) and membrane potential was detected using 2′,7′-dichlorofluorescein diacetate and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbocyanine iodide (JC-1) dye staining, respectively. While, cell apoptosis was determined by Annexin-V staining and protein expression was measured using Western blot. Results Our results suggested that melatonin inhibited glucose-induced ROS elevation, mitochondria dysfunction and apoptosis on HUVEC. Melatonin inhibited glucose-induced HUVEC apoptosis via PI3K/Akt signaling pathway. Activation of Akt further activated BcL-2 pathway through upregulation of Mcl-1 expression and downregulation Bax expression in order to inhibit glucose-induced HUVEC apoptosis. Besides that, melatonin promoted downregulation of oxLDL/LOX-1 in order to inhibit glucose-induced HUVEC apoptosis. Conclusions In conclusion, our results suggested that melatonin exerted vasculoprotective effects against glucose-induced apoptosis in HUVEC through PI3K/Akt, Bcl-2 and oxLDL/LOX-1 signaling pathways.

Objectives The main purpose of this study was to compare the effects of two regimens of metformin and insulin therapy on postpartum oral glucose tolerance test (OGTT) results in pregnant women with gestational diabetes mellitus (GDM). Methods In this single-blind randomized clinical trial (RCT), a total number of 60 pregnant women meeting the inclusion criteria were assigned to two groups with a randomized block design (RBD): insulin therapy (IT) group (30 patients) and metformin therapy (MT) group (30 patients). At baseline, the data were comprised of prenatal maternal age, gestational age, GDM diagnosis, and maternal weight/height. During the postpartum period, 5-cc blood samples were taken from the pregnant women concerned to analyze their fasting blood sugar (FBS) levels. Then, the patients were asked to come back four days and six weeks later after delivery to check the OGTT results. At six weeks postpartum, in addition to OGTT, the glycated hemoglobin (HbA 1 C) test was performed for all mothers. Finally, six weeks after delivery, these mothers were evaluated with regard to weight loss and body mass index (BMI). Results Six weeks postpartum, the maternal weight and BMI significantly decreased in the MT group compared with the IT one, while there was no significant difference between both groups at baseline. On the fourth day, the OGTT results in the MT group were significantly lower in comparison with those in the IT group (p=0.012). At sixth weeks postpartum, the OGTT results were comparably lower in the MT group than those reported for the IT one; however, such a difference was not statistically significant (p=0.087). Conclusions According to the study results, metformin could be an effective and safe treatment for pregnant women suffering from GDM instead of insulin therapy.

Background Recurrent pregnancy loss (RPL) referred to two or more consecutive abortions before 20th week of pregnancy. The imbalance of inflammatory factors such as interleukins (IL) can be a significant factor in the RPL. The aim of this study was to investigate association of interleukin-33 (IL-33) gene rs16924159 polymorphism and RPL in Iranian Azeri women. Materials and methods This case-control study consisted of 100 women with RPL as case group and 100 healthy controls with successful delivery. Genomic DNA was extracted from whole blood samples using salting out method. The fragments of the rs16924159 polymorphism were amplified by PCR and the genotyping was performed using DNA sequencing. Results The obtained results showed that frequency of GA genotype and G allele of rs16924159 polymorphism in the case group was significantly more than healthy controls (p = 0.033). Conclusions Generally, we showed that the IL-33 gene rs16924159 polymorphism may play an important role in risk of RPL in the Iranian Azeri women. However, further studies on different races and geographic areas can be useful in identification of effects of rs16924159 polymorphism on RPL.

Objectives To investigate the effects of 12-week high-intensity- (HIIT) vs. moderate-intensity-interval training (MIIT) on thyroid stimulating hormone (TSH) and thyroxine (T4) and insulin-resistance in overweight/obese adolescent girls. Methods Twenty four adolescent girls (age 16.5±1.36 yrs) were randomly allocated into three groups: (1) HIIT (2 blocks per session of 6–8 bouts of 30 s runs at 100–110% maximal aerobic speed (MAS), with 30 s active recovery between bouts at 50% MAS; n=8), (2) MIIT (2 blocks per session of 6–8 bouts of 30 s runs at 70–80% MAS, with 30 s active recovery between bouts at 50% MAS; n=8) and (3) control group (no exercise, n=8). Each training groups engaged in three sessions per week during three months. Anthropometric parameters, aerobic capacity, homeostasis model assessment index for insulin resistance (HOMA-IR) as well as plasma TSH and T4 levels were assessed in all subjects before- and after-training. Results Following both training programs, body mass, body mass index Z-score, waist circumference and body fat decreased, while aerobic capacity increased. However, TSH and T4 concentrations decreased only after the HIIT (−30.47%, p<0.05, ES=1.42 and −12.86%, p<0.05, ES=1.18; respectively). The HOMA-IR decreased in both training groups (−26.25%, p<0.05, ES=1.87 for MIIT and −21.72%, p<0.05, ES=2.14 for HIIT). Conclusion Twelve weeks of HIIT was effective in reducing circulating TSH and T4 levels, unlike MIIT, in overweight/obese adolescent girls. These findings indicated that the stimulation of pituitary-thyroid function is more sensitive to training intensity than training duration. Further studies are needed to confirm this conclusion.

Objectives The present study was conducted to examine antidiabetic effects of Artemisia absinthium ethanolic extract [ A. absinthium ] and to investigate its effects on oxidative stress markers and the expression of TLR4, S100A4, Bax and Bcl-2 genes in the kidney of STZ-induced diabetic rats. Methods Thirty six rats (weight 200–250 g) were randomly divided into diabetes and control groups. Induction of diabetes was performed using STZ (55 mg/kg.bw). Biochemical parameters and oxidative stress markers (SOD and MDA) were measured using spectrophotometry after 60 days of treatment. The expression of TLR4, S100A4, Bax and Bcl-2 were analyzed by real-time PCR. One-way analysis of variance (ANOVA) and Bonferroni post hoc test were used to compare the data. Results Diabetes significantly impairs the serum fasting blood glucose (FBG), lipid profile, urea, creatinine and albumin. At the end of treatment with A. absinthium extract, these parameters were close to the normal range. The results showed that the A. absinthium extract significantly decreased the kidney expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress markers (SOD and MDA) in the kidney tissues of treated rats. Also, all of these beneficial effects of the A. absinthium were dose-dependent. Conclusions The extract of A. absinthium possesses antidiabetic effects. A. absinthium decreased the expression of TLR4, S100A4, Bax and increased the expression of Bcl-2 and improved oxidative stress. Therefore, this herbal extract can be used as an adjuvant treatment for diabetic complications.

Objectives Endothelial dysfunction contributes to the onset and progression of cardiovascular diseases. However, direct associations of vasoactive mediators with cardiovascular risk are poorly understood. Methods We have determined associations of circulating levels of stable metabolites of nitric oxide, nitrate and nitrite (NOx), endothelin-1, and the endothelin-1/NOx ratio with blood pressure in 177 asymptomatic subjects without signs of coronary atherosclerosis; associations with blood pressure and with presence of coronary lesions were also evaluated in 457 patients suspected to have coronary heart disease with or without coronary lesions confirmed by coronary angiography. All participants were on a low nitrate diet 24 h prior to blood sampling. Results In men, NOx levels were inversely correlated with blood pressure similar to women with low (0–4%) European Systematic Coronary Risk Estimation (SCORE). However, the correlation was not significant in women with high SCORE (5–8%). High systolic blood pressure over 140 mm Hg was negatively associated with NOx levels in asymptomatic men (p=0.05) but not in women. This association is disrupted in male and female patients with coronary atherosclerosis. In male patients, NOx (p=0.05), endothelin (p=0.01), and the endothelin/NOx ratio (p=0.04) were associated with presence of coronary lesions. Conclusions Thus, elevated cardiovascular risk according to SCORE over 4% in asymptomatic women, but not in men, is associated with a shift in markers of endothelial dysfunction. Presence of coronary lesions in patients is associated with significant changes in circulating levels of markers of endothelial dysfunction in men but not in women.

Objectives Recently, oxidative stress (OS) has been described extensively as an important cause of men infertility. The nitric oxide synthase 3 ( NOS3 ) gene expression involved in normal spermatogenesis regulation in testis. Several single nucleotide polymorphisms (SNPs) on NOS3 gene are reported in association with sperm function and spermatogenesis impairment in infertile men. In present study, we investigated association of NOS3 gene rs1799983 G/T polymorphism in Iranian Azeri male with idiopathic asthenozoospermia (AZS). Methods In this case-control study, we collected 50 males with idiopathic AZS as a case group and 50 age and ethnically matched male as healthy controls from East Azerbaijan area, Iran. The case and control groups genotyping was performed using tetra-primer amplification refractory mutation system-polymerase chain reaction (Tetra-ARMS PCR) method. Results Genotype frequency in AZS patients was 40% GG, 60% GT, and 0% TT, whereas in healthy controls were 60% GG, 30% GT, and 10% TT. Statistical analysis showed that the GT heterozygous genotype frequency of NOS3 gene rs1799983 G/T polymorphism in AZS patients was significantly more than healthy controls (p>0.05). Conclusions We demonstrated that NOS3 gene rs1799983 G/T polymorphism was associated with AZS in Iranian Azeri men. However, more studies on different geographic areas, races and ethnicities are required to determine exact role of NOS3 gene rs1799983 G/T polymorphism in idiopathic AZS.

Objectives Since polycystic ovarian syndrome (PCOS) is prevalent in reproductive women with obesity and insulin resistance, adipocytokines are often accused and investigated for pathophysiology. The aim of this study was to evaluate the adiponectin and leptin levels in normal-weight women with PCOS. Methods Forty women with PCOS and 40 age and body mass index (BMI) matched controls were included in the study. Adiponectin and leptin levels in addition to other biochemical parameters were measured. Results Leptin levels were statistically significantly higher in the study group compared to the control group (6.53 ± 2.670 vs 3.37 ± 2.002 ng/mL, p < 0.001 respectively). Although Adiponectin levels were lower in the study group compared to the control group (28.89 ± 16.124 μg/mL vs 31.05 ± 20.507, p = 0.714 respectively) the difference did not reach statistical significance. Leptin levels were positively correlated with fasting glucose, fasting insulin, free testosterone levels and homeostatic model assessment of insulin resistance (HOMA-IR) values. Adiponectin levels were negatively correlated with BMI. Conclusions Adiponectin and leptin have been suggested to play a crucial role in the pathogenesis of PCOS. Different adipocytokine levels in the normal weight PCOS group compared to age and BMI matched controls support the idea that adipose tissue in this group of women has some distinctive features not only in high BMI subgroup but also in normal weight subgroup.

Background The increasing prevalence of metabolic syndrome (MS) especially in female population, has become a major problem in health care systems. In this regards, it is necessary to identify the risk factors. Vitamin D deficiency is now proposed as one of the possible risk factors for metabolic syndrome, we investigated the relationship between vitamin D status and MS in female. Methods We searched observational studies with keywords Vitamin D, metabolic syndrome, metabolic syndrome X, insulin-resistance syndrome, metabolic cardiovascular syndrome and Reaven Syndrome X and female in pubmed, scopus, science direct, cochrane, web of science, google scholar and SID databases, regardless of publication time. Two hundred ninety five studies were found, and finally only 12 articles were selected according to exclusion and inclusion criteria. Results In nine studies that reported the prevalence of MS, the prevalence of MS among women with vitamin D deficiency was higher than female with normal vitamin D (34.5 vs. 30.2%). The prevalence of abdominal obesity, high blood pressure, high TG and HDL deficiency is higher in women with vitamin D deficiency. Also, the mean waist circumference, blood pressure, fast blood sugar (FBS), TG and BMI were higher. The most incident factor was high blood pressure (61.4 vs. 56.5%) and the lowest prevalence is associated with high FBS (32.2 vs. 33.5% in the other group). Conclusion The prevalence of MS is significantly associated with vitamin D deficiency, and among related factors, HDL, TG and blood pressure are statistically associated with vitamin D status.

Vitamin D contributes to numerous physiological processes within the body but primarily calcium and bone homeostasis. Emerging evidence highlights a novel role for vitamin D in maintaining and regulating optimal sleep. Sleep is a known regulator of bone health, highlighting the interconnectedness between vitamin D concentrations, sleep duration and bone metabolism. It is possible that the relationship between sleep length and vitamin D is bidirectional, with vitamin D playing a role in sleep health and conversely, sleep affecting vitamin D levels. Nevertheless, limited information on the direction of the interaction is available, and much remains to be learned concerning the complex relationship between insufficient sleep duration and vitamin D deficiency. Given the potential to implement interventions to improve sleep and vitamin D supplementation, understanding this relationship further could represent a novel way to support and improve health.

Post-traumatic stress disorder (PTSD) is a multifaceted syndrome due to its complex pathophysiology. Signals of illness include alterations in genes, proteins, cells, tissues, and organism-level physiological modifications. Specificity of sensitivity to PTSD suggests that response to trauma depend on gender and type of adverse event being experienced. Individuals diagnosed with PTSD represent a heterogeneous group, as evidenced by differences in symptoms, course, and response to treatment. It is clear that the biochemical mechanisms involved in PTSD need to be elucidated to identify specific biomarkers. A brief review of the recent literature in Pubmed was made to explore the major biochemical mechanisms involved in PTSD and the methodologies applied in the assessment of the disease. PTSD shows pre-exposure vulnerability factors in addition to trauma-induced alterations. The disease was found to be associated with dysfunctions of the hypothalamic–pituitary–adrenal axis (HPA) and hypothalamus–pituitary–thyroid axis. Sympathetic nervous system (SNS) activity play a role in PTSD by releasing norepinephrine and epinephrine. Cortisol release from the adrenal cortex amplifies the SNS response. Cortisol levels in PTSD patients, especially women, are later reduced by a negative feedback mechanism which contributes to neuroendocrine alterations and promotes structural changes in the brain leading to PTSD. Gender differences in normal HPA responsiveness may be due to an increased vulnerability in women to PTSD. Serotonin and dopamine levels were found to be abnormal in the presence of PTSD. Mechanisms such as the induction of neuroinflammation and alterations of mitochondrial energy processing were also associated with PTSD.

Urinary incontinence is a common health problem that impacts the quality of life of women at different ages. Its physiopathology is not unequivocal, and it is necessary to consider the stress urinary incontinence (SUI), the overactive bladder syndrome and the mixed incontinence (MUI). According to the type of incontinence, its impact on the quality of life and age of the patients, therapeutic strategies are currently summarized in physiotherapy, surgery and drug treatments. We already know the benefit/risk ratio of each of these strategies. Our objective is to evaluate the potential effectiveness and safety of the VEL, an innovative vaginal laser technique (VEL – Vaginal Erbium Laser, erbium yttrium-aluminum-garnet -Er: YAG) a non-invasive laser proposed as a treatment for SUI, overactive bladder syndrome and MUI. The mechanisms of action of lasers are discussed in general and those of VEL in particular with the description of the Smooth® mode. To do this, we have collected the 21 published studies including the first randomized vs. placebo and two pilot studies of intra-urethral VEL. In conclusion: VEL procedures already have their place between the rehabilitation of the perineal floor and surgery. Further properly sized, randomized studies are needed to evaluate the laser treatments in comparison with other therapies, as well as to assess the duration of the therapeutic effects and the safety of repeated applications.

Objectives Breast cancer is known as one of the deadliest forms of cancer, and it is increasing globally. There are a variety of proven and controversial risk factors for this malignancy. Herein, we aimed to undertake a systematic review and meta-analysis focus on the epidemiology of breast cancer risk factors in Iran. Methods We performed a systematic search via PubMed, Scopus, Web of Science, and Persian databases for identifying studies published on breast cancer risk factors up to March 2019. Meta-analyses were done for risk factors reported in more than one study. We calculated odds ratios (ORs) with corresponding 95% confidence intervals (CIs) using a fixed/random-effects models. Results Thirty-nine studies entered into the meta-analysis. Pooling of ORs showed a significant harmful effect for risk factors including family history (OR: 1.80, 95%CI 1.47–2.12), hormonal replacement therapy (HRT) (OR: 5.48, 95%CI 0.84–1.74), passive smokers (OR: 1.68, 95%CI 1.34–2.03), full-term pregnancy at age 30 (OR: 3.41, 95%CI 1.19–5.63), abortion (OR: 1.84, 95%CI 1.35–2.33), sweets consumption (OR: 1.71, 95%CI 1.32–2.11) and genotype Arg/Arg (crude OR: 1.59, 95%CI 1.07–2.10), whereas a significant protective effect for late menarche (OR: 0.58, 95%CI 0.32–0.83), nulliparity (OR: 0.68, 95%CI 0.39–0.96), 13–24 months of breastfeeding (OR: 0.68, 95%CI 0.46–0.90), daily exercise (OR: 0.59, 95%CI 0.44–0.73) and vegetable consumption (crude OR: 0.28, 95%CI 0.10–0.46). Conclusions This study suggests that factors such as family history, HRT, passive smokers, late full-term pregnancy, abortion, sweets consumption and genotype Arg/Arg might increase risk of breast cancer development, whereas late menarche, nulliparity, 13–24 months breastfeeding, daily exercise and vegetable consumption had an inverse association with breast cancer development.

Objectives Previous studies showed that melatonin supplementation may suppress oxidative stress, however, the results have not been consistent. So, we conducted this meta-analysis to assess the precise relationship between melatonin supplementation and oxidative stress. Methods PubMed and Scopus were searched for randomized controlled trials that investigated the effect of melatonin supplementation on oxidative stress up to March 2020. Heterogeneity was assessed by Cochran’s Q test and I-square ( I 2 ) statistic. Data were pooled using the random effect model and standardized mean difference (SMD) was considered as the summary effect size. Also, standard methods were used for assessment of sensitivity analysis and publication bias. Results We included 15 related articles and our findings indicated that melatonin supplementation significantly increased total antioxidant capacity (TAC) level (SMD: 1.03, 95% CI: 0.24, 1.81, p=0.011) and reduced protein carbonyl (PCO) (SMD: −1.78, 95% CI: −2.97, −0.58, p=0.004) and malondialdehyde (MDA) levels (SMD: −0.94, 95% CI: −1.48, −0.40, p=0.001). Additionally, there was considerable effect on TAC level by using ≥20 mg/d melatonin and in people under 35 years old. MDA level also decreased using dosage of below 20 mg/d and in people ≥35 years old. Conclusions The present study showed a promising effect of melatonin administration for reducing MDA, PCO, and increasing TAC levels. However, further studies especially with more attention to PCO level assessment are needed to confirm the findings of the present study in larger samples on different populations.