Effect of Four Weeks of Aerobic Exercise and Berberine Supplementation on the Expression of Dopamine 5 Receptor and Poly (Adenosin Diphosphat [ADP]-Ribose) Polymerase Genes in the Heart Tissue of Methamphetamine-Exposed Rats

Physical Activity and Diabetes.

The purpose of this study was to examine the effects of conjugated linoleic acid (CLA) supplementation in conjunction with 6 weeks of aerobic exercise training on the physical working capacity at the fatigue threshold (PWCFT), timed sit-ups, and the standing long jump. Thirty-three untrained to moderately trained men (mean ± SD; age = 21.6 ± 2.8 years) participated in this double-blind, placebo-controlled study and were randomly assigned to either a CLA (Clarinol A-80; n = 17) or placebo (PLA; sunflower oil; n = 16) group. Before and after 6 weeks of aerobic training (50% VO2peak for 30 minutes, twice per week) and supplementation (8 ml CLA or PLA per day), each subject completed an incremental cycle ergometer test to exhaustion to determine the PWCFT, maximal number of sit-ups in 1 minute, and the standing long jump. There were no differences (all p ≥ 0.23) between the CLA and PLA groups for the analysis of covariance-adjusted posttest mean values for PWCFT, sit-ups, or standing long jump. The PWCFT increased from pre- to posttraining in the CLA (p = 0.003) and PLA (p = 0.003) groups. There were no differences (p > 0.05) from pre- to posttraining for sit-ups and standing long jump in either the CLA or PLA groups. There was no effect of CLA on the training-induced increases in PWCFT, nor were there any effects of CLA or aerobic training on the maximum number of sit-ups or standing long jump. Thus, CLA had no ergogenic benefits on this model of aerobic training-induced improvements in neuromuscular fatigue, or on field tests of muscle endurance and power.

Post-translational protein modifications such as phosphorylation and ubiquitinylation are common molecular targets of conflict between viruses and their hosts. However, the role of other post-translational modifications, such as ADP-ribosylation, in host-virus interactions is less well characterized. ADP-ribosylation is carried out by proteins encoded by the PARP (also called ARTD) gene family. The majority of the 17 human PARP genes are poorly characterized. However, one PARP protein, PARP13/ZAP, has broad antiviral activity and has evolved under positive (diversifying) selection in primates. Such evolution is typical of domains that are locked in antagonistic ‘arms races’ with viral factors. To identify additional PARP genes that may be involved in host-virus interactions, we performed evolutionary analyses on all primate PARP genes to search for signatures of rapid evolution. Contrary to expectations that most PARP genes are involved in ‘housekeeping’ functions, we found that nearly one-third of PARP genes are evolving under strong recurrent positive selection. We identified a >300 amino acid disordered region of PARP4, a component of cytoplasmic vault structures, to be rapidly evolving in several mammalian lineages, suggesting this region serves as an important host-pathogen specificity interface. We also found positive selection of PARP9, 14 and 15, the only three human genes that contain both PARP domains and macrodomains. Macrodomains uniquely recognize, and in some cases can reverse, protein mono-ADP-ribosylation, and we observed strong signatures of recurrent positive selection throughout the macro-PARP macrodomains. Furthermore, PARP14 and PARP15 have undergone repeated rounds of gene birth and loss during vertebrate evolution, consistent with recurrent gene innovation. Together with previous studies that implicated several PARPs in immunity, as well as those that demonstrated a role for virally encoded macrodomains in host immune evasion, our evolutionary analyses suggest that addition, recognition and removal of ADP-ribosylation is a critical, underappreciated currency in host-virus conflicts.

Background and Aim: Arsenic is an environmental pollutant that can damage tissue by producing free radicals. However, regular aerobic exercise is essential in enhancing antioxidant defense and resistance to oxidative stress. This study aimed to evaluate the effect of aerobic exercise on reduced glutathione (GSH) and oxidized glutathione (GSSG) and aortic endothelial cells of of heart tissue in rats exposed to arsenic. Materials and Methods: In this experimental study, 24 male Wistar rats with a weight ranged 220-240 g and a mean age of 6-8 weeks were divided into 3 groups of 8: healthy control, toxic control, and toxic aerobic exercise. Rats receiving arsenic were prescribed 25 ppm arsenic daily in oral water for 8 weeks. The exercise program consisted of 8 weeks of aerobic exercise, five sessions per week with an intensity of 75%-80% of maximum oxygen consumption. Eventually, 24 hours after the last exercise session, the rats were anesthetized and killed, and the target tissue was removed for examination. The Kolmogorov-Smirnov statistical test and one-way analysis of variance with Tukey post hoc test were used to analyze the findings in SPSS software, version 22 (P≥0.05). Results: Exposure to arsenic significantly reduced GSH and GSSG levels in heart tissue and aortic endothelial cells (P≥0.05). In contrast, aerobic exercise increased GSH and GSSG levels in heart tissue and aortic endothelial cells in arsenic-poisoned rats (P≥0.05). Conclusion: Aerobic exercise effectively reduces oxidative stress and increases antioxidant defense against arsenic toxicity in heart disorders.

Background and Aim: Anabolic steroids cause damage to various tissues, including the heart. This study aimed to evaluate the effect of aerobic exercise on Malondialdehyde (MDA) and superoxide dismutase (SOD) of heart tissues in rats poisoned with the anabolic steroid Dianabol. Materials and Methods: In this experimental-fundamental study, 18 rats were selected and divided into three 6-series groups, including normal saline intake (Sh), Dianabol (D), and steroid intake with aerobic exercises (D+RT). For six weeks, the steroid and aerobic exercise groups received 5 mg/kg of Dianabol per day peritoneally, and the steroid aerobic exercise group performed aerobic exercise five sessions per week. Measurement of MDA and SOD gene expression in heart tissue was measured by ELISA. Kolmogorov-Smirnov statistical tests, a 1-way analysis of variance with Tukey post hoc test were used to analyze the results (P≤0.05). Results: Steroid Dianabol had a significant effect on increasing MDA (P=0.001) and decreasing SOD (P=0.001) in heart tissue. However, aerobic exercise decreased MDA (P=0.001) and increased the SOD antioxidant index (P=0.000) in the heart tissue of rats exposed to Dianabol. Conclusion: Anabolic steroids appear to increase oxidative stress indices and decrease antioxidants in heart tissue, while aerobic exercise can improve elevated levels of oxidative stress and decreased levels of antioxidants.

BackgroundWe explored the potential synergistic effects of combining multisession anodal transcranial direct current stimulation (a-tDCS) with chronic aerobic exercise (AE) on food cravings (FC), impulsivity (IMP), risky decision-making (RDM), and cognitive flexibility (CF) in women with overweight or obesity exhibiting food craving symptoms.MethodsThirty-six women with overweight or obesity and symptoms of food craving (age: 26±6,4 years) were randomly allocated into three groups using permuted block randomization (n = 12 each): (1) a-tDCS + AE, (2) Sham + AE, and (3) Control (no intervention). During Phase 1, the a-tDCS + AE group received five consecutive sessions of a-tDCS, while the Sham + AE group received sham tDCS. In Phase 2, both the a-tDCS + AE and Sham + AE groups completed three sessions of moderate-intensity continuous aerobic exercise per week for four weeks. Outcome measures, including food cravings (FC) and cognitive flexibility (CF), were assessed at baseline, after five days of tDCS, and after four weeks of AE. Follow-up measurements for FC and CF were also conducted one month post-intervention.ResultsFC was lower in the a-tDCS + AE group compared to Sham + AE and Control groups in Phase 1 (Cohen’s d = 1.4 and 1.9, respectively). In Phase 2, a-tDCS + AE and Sham + AE groups showed lower FC than the Control group (d = 3.8 and d = 2.8, respectively), and a-tDCS + AE also showed a lower FC compared to the Sham + AE group (d = 1.5). FC remained lower in the a-tDCS + AE group compared to Sham + AE and Control groups at follow-up (d = 1.7 and d = 2.4, respectively). CF was higher in the a-tDCS + AE compared to Sham + AE and Control groups (d = 2.1 and d = 1.4, respectively) and in the sham + AE (d = 1.0) compared to control in Phase 2. At follow-up, CF was higher only in the a-tDCS + AE group compared to the Control (d = 1.2). IMP scores were higher in the a-tDCS + AE group compared to the other groups in Phases 1 (d = 1.0 and d = 1.4) and 2 (d = 5.4 and d = 1.9). RDM was higher in the a-tDCS + AE compared to the Control group in phase 2 (d = 1.3).ConclusionsMultisession a-tDCS combined with four weeks of moderate AE synergistically reduces food cravings and improves related variables to a greater extent than AE alone, with sustained effects, in women with overweight or obesity and symptoms of food craving.Trial registrationThis study was registered in the Iranian Registry of Clinical Trials (IRCT id: IRCT20210617051606N7; Registration date: 04.02.2023).

Introduction: The purpose of this study is to investigate the effect of eight weeks of regular aerobic exercise along with consumption of nettle plant on Blood Glucose and insulin resistance index in patients with type II diabetes. Methods: This study was conducted on 46 women with type II diabetes referring to diabetes association of Shahrood. After obtaining the consents and taking the primary actions, cases were allocated into Four groups: 1) aerobic exercise and nettle supplementation (13 participants), 2) aerobic exercise and use of placebo (13 participants (, 3) nettle supplementation (13 participants), and 4) control (7 participants). Aerobic exercises included activities for 8 weeks, with three sessions of 30-60 minutes per week with an intensity of 45 to 65 percent target heart rate. Daily supplementation with 6 cc Nettle extract of Gorgan essential oil company was used as a solution in water ; and daily intake of 6 ml placebo (same color water extract) was used as a placebo. Variables for this study including blood glucose and insulin resistance index in two stages (before and after 8 weeks) were measured. The analysis was performed by analysis of variance using SPSS 17 software. Results: Eight weeks of aerobic exercise and use of nettle plant have no significant effect on blood glucose and insulin resistance index of elderly women with type 2 diabetes. Conclusion: Eight weeks of aerobic exercise and use of nettle plant with applied intensity and duration had no significant effect on blood glucose and insulin resistance index of elderly women with type 2 diabetes. Aerobic exercise with longer duration and nettle supplement with higher density may be effective to these patients.

This study aims to evaluate the effectiveness of aerobic exercise training on microcirculatory function among individuals with chronic kidney disease (CKD). Microcirculatory dysfunction is a prevalent complication in CKD that progresses as CKD evolves. Endothelial dysfunction is an early manifestation of microvascular disease and contributes to increased cardiovascular‐related mortality in CKD. Evidence indicates that endothelial dysfunction might be linked to deficits in blood perfusion and oxygen delivery. Aerobic exercise has been shown to improve cardiorespiratory function and blood pressure control for adults with CKD. Previous work has validated correspondence of specific frequency intervals in resting microvascular blood flow fluctuations with physiological events. Specifically, the spectrum amplitude from three frequency intervals (0.0095 – 0.02 Hz, 0.02 – 0.06 Hz, 0.06 – 0.15 Hz) have been attributed to microvascular regulation by endothelial, neurogenic, and myogenic origins, respectively. We hypothesized that 12 weeks of aerobic exercise would improve endothelial function in CKD.Ten CKD participants (Table 1) were randomized into treatment and control groups that performed progressive aerobic cycling exercise (N = 5) for 20‐45 min up to 80% of heart rate reserve and non‐aerobic, stretching exercise (N = 5). Each group performed activities 3 days/week for 12 weeks. Resting microvascular blood flow was measured in the forearm for 5 minutes using total hemoglobin (tHb) signal from near‐infrared spectroscopy. Reactive hyperemic index (RHI) was measured using peripheral artery tonometry at the upper arm, providing an accepted, single‐value index of endothelial function. Both measures were obtained at the beginning (baseline) and end of the 12‐week intervention (EOS), respectively. The resting tHb signal was analyzed using wavelet transform to obtain time‐frequency information on microcirculation regulated by endothelial, neurogenic, and myogenic functions. Differences at baseline and EOS were assessed using pairwise Student’s t‐test (statistical significance: p < 0.05). The Pearson correlation coefficient between RHI and individual mean spectral amplitude was also obtained.Endothelial spectral amplitudes significantly decreased (p = 0.007) in the stretching group over the 12‐week intervention, suggesting decreased endothelial function (Fig.1). There was no significant change in the endothelial spectral amplitude (p = 0.16) in the cycling group. Changes in individual endothelial spectral amplitude and RHI were moderately correlated (r = 0.57 and p = 0.02).In conclusion, spectral analysis of resting microvascular blood flow in CKD suggests preserved endothelial function over 12 weeks of progressive aerobic cycling exercise, compared with a decline in those who performed a non‐aerobic stretching exercise. Ongoing work focuses on adapting and applying this wavelet methodology to MRI‐derived signals that provide temporo‐spatially resolved information on tissue oxygenation and perfusion. Resting microcirculatory properties yielded from this work may be useful for monitoring disease progression and guiding targeted therapeutic strategies to improve microvascular function in CKD.

The aim of this study was investigating the effect of 12 weeks of yoga and aerobic exercise (running on a treadmill) on the sleep quality in women with Type 2 diabetes. 39 diabetic women were selected from Semnan city with the mean age of 46.85±3.35 years, weight of 69.79±17.18 kg, height of 155.03±5.00, BMI of 29.64±5.00 kg/m2 who had a background of diabetes for 6.46±2.69 years. They were then randomly divided into yoga exercise (n=15), aerobic exercise (n=13), and control group (n=11). The exercise program was performed for 12 weeks, three sessions per each week. In order to measure the sleep quality, the Pittsburgh Sleep Quality Index (PSQI) was used. The data were analyzed by non-parametric wilcoxon and Kruskal-Wallis Test at significance level of p<0.05. Overall score of sleep quality improved after six (p=0.001) and 12 (p=0.001) weeks of yoga exercise. Also, significant effect was observed after 6 weeks of aerobic exercise (p=0.039). However, the positive effect was diminished to under significant levels after 12 weeks of aerobic exercise (p=0.154). Kruskal-Wallis Test showed significant differences between yoga and aerobic groups after 12 weeks of exercise (p=0.002). No significant differences were observed in control groups in all situation. It can be concluded that yoga exercise is more effective in improving the sleep quality in comparison with the same course of aerobic exercise in women suffering from diabetes Type 2. Thus, yoga exercise can be suggested to these patients.

Background: The most common neurological complication of hyperglycemia is neuropathy which leads to changes in the central nervous system. Therefore, this study aimed to investigate the effect of six weeks of aerobic exercise with quercetin supplementation on the expression of mitochondrial Ampk and Nrf-1 genes in the hippocampus of diabetic male rats. Materials and Methods: This experimental study was performed by the laboratory method. Thus, 35 male Wistar rats were divided into five groups (n=7): Healthy Control, Diabetes Control, Diabetes Exercise, Diabetes Exercise Quercetin Supplement, and Quercetin Supplement. During the course, the supplement and diabetic groups were injected with 15 mg/kg of quercetin per day after induction of diabetes. For the training groups, six weeks of moderate-intensity aerobic exercise was performed on a revolving bar. To evaluate the expression of mitochondrial Ampk and Nrf-1 genes, hippocampal tissue was isolated 24 h after the last training session. The SPSS statistical software (version 23), one-way analysis of variance (ANOVA), and Tukey's post hoc test onther significance level of 0.05 were used to analyze the collected data. Result: The findings of this study showed that after six weeks of aerobic exercise, the expression of mitochondrial Ampk and Nrf-1 genes in the exercise supplement diabetes group significantly increased (P&lt;0.05) compared to diabetes control, exercise diabetes, and quercetin supplementation. A significant increase was observed only for Ampk in the exercise diabetic group compared to the diabetic control and quercetin diabetic groups (P&lt;0.05). Conclusion: It seems that six weeks of aerobic exercise with quercetin supplementation can positively affect the expression of mitochondrial Ampk and Nrf-1 genes in hippocampal tissue and increase it in diabetic conditions.

TYPE 2 DIABETES MELLITUS IS A MAJOR RISK FACTOR FOR excess morbidity and mortality. The excess vascular risk in type 2 diabetes is attributable both to hyperglycemia and to other metabolic disturbances associated with abdominal obesity, insulin resistance, and compensatory hyperinsulinemia. Sedentary lifestyle is also a major cardiovascular risk factor, and regular exercise attenuates the vascular risks associated with type 2 diabetes. Aerobic exercise refers to activities such as walking or jogging with continuous, repetitive movement of large muscle groups for at least 10 minutes at a time, whereas resistance exercise refers to activities such as weight lifting that use muscular strength to move a weight or work against a resistance load. Aerobic exercise for individuals with diabetes has been recommended for many decades, but the American Diabetes Association only began recommending resistance exercise in 2006. In this issue of JAMA, Church and colleagues report the results of the Health Benefits of Aerobic and Resistance Training in Individuals with Diabetes (HART-D) trial. This study provides important evidence on the effects of aerobic and resistance training on improving hemoglobin A1c (HbA1c) levels. In this trial, 262 previously sedentary patients with type 2 diabetes were randomized to a sedentary control group or to 1 of 3 exercise groups: aerobic exercise, resistance training, or a combination of both. Patients in the combined group performed smaller amounts of aerobic and resistance exercise than those in groups performing just one type of exercise so that the total amount of time devoted to exercise each week was similar among the 3 groups. The aerobic group performed 12 kcal/kg of body weight per week of aerobic exercise, equivalent to walking briskly at 4 mph for about 50 minutes per session 3 times a week. The resistance training group performed 2 to 3 sets of 10 to 12 repetitions of 9 exercises 3 times a week. The combined group performed 10 kcal/kg of body weight per week of aerobic exercise (equivalent to 42 minutes 3 times a week of walking at 4 mph, 83% of the amount done by the aerobic group) plus 1 set each of 9 exercises 2 times a week (less than a third of the resistance training volume performed by the resistance training group). No efforts were made to minimize changes in diet or medications. Only the combined training group achieved statistically significant reduction in absolute reduction in HbA1c in the HART-D trial compared with the control group (0.34%). The aerobic group had an absolute reduction of 0.24%; the resistance group, 0.16%. All groups had modest and similar decreases in waist circumference compared with the control group. In addition to the greatest HbA1c reduction, the combined training group also had the most decreases, and the least increases, in use of hypoglycemic medication. The findings of the HART-D trial are important for several reasons. First, the study duration was 9 months, making it longer than most exercise intervention trials involving patients with diabetes. Second, the study population was relatively large in number (n=262) and ethnically diverse, with almost 44% of participants being African American, and had a relatively high proportion of female participants (63%). Third, the total time spent exercising was roughly the same in the combined training group as in the other 2 singleexercise groups. Therefore, any difference between the combined exercise group and the other exercise groups can be confidently attributed to the combination of 2 types of exercise rather than the amount of time spent exercising. The HbA1c changes achieved in the HART-D trial were modest, perhaps because there was no effort to minimize medication changes. Participants whose HbA1c level did not improve with exercise were more likely to have their hypoglycemic therapy intensified, thus attenuating the difference in HbA1c that could be achieved between groups. It is likely that intergroup HbA1c differences in HART-D may have been greater if medication changes had been discouraged. The results are encouraging in that a significant incremental improvement in glycemic control was made in the HART-D combination group over and above that achieved through ongoing efforts by physicians and patients in both groups to optimize glycemic control with medications. Another possibility is that the higher proportion of women and

Obesity is a complex disease that has become increasingly prevalent. While obesity itself is not new, its widespread occurrence is a more recent concern. Stimulating brown adipose tissue (BAT) and promoting the browning of white adipose tissue (bWAT) have shown promise as therapeutic targets to increase energy expenditure and counteract weight gain. This study aimed to investigate two main aspects. First, we examined how obesity affects the expression of the fibronectin type-III domain containing 5 (FNDC5) and uncoupling protein 1 (UCP1) genes in male Wistar rats. Second, we assessed the effects of six weeks of aerobic exercise, exposure to cold water, and the combination of both on the expression of the FNDC5 and UCP1 genes in obese male Wistar rats. In this experiment, 25 male Wistar rats were randomly assigned to five groups (5 rats per group) after inducing obesity. The groups included: A control group (C), an obesity group (O), an obesity group exposed to cold water (OC), an obesity group engaged in aerobic exercise (OE), and an obesity group exposed to both cold water and aerobic exercise (OCE). The aerobic exercise sessions lasted 30 - 60 minutes, with a speed of 15 - 25 meters per minute. The cold water exposure protocol involved shallow water (2 - 4 cm) with a temperature of 14 - 18°C. The OCE group performed both aerobic and cold water exercises in each session. The expression of the FNDC5 gene in the soleus muscle and the FNDC5 and UCP1 genes in subcutaneous fat was evaluated using Real-Time PCR. All statistical analyses were performed using SPSS software version 16, with a significance level set at P ≤ 0.05. Obesity significantly increased the expression of the FNDC5 gene (P = 0.008). After six weeks of aerobic exercise (P = 0.016) or cold water exposure (P = 0.016), there was a significant decrease in FNDC5 gene expression. Surprisingly, the combination of both interventions did not result in a significant effect (P = 0.75). On the other hand, none of the interventions-whether aerobic exercise, cold water exposure, or their combination-had a significant effect on the expression of the UCP1 gene (P > 0.05). The increase in FNDC5 gene expression caused by obesity may serve as a compensatory mechanism to cope with the condition. However, both cold water exposure and aerobic exercise appear to mitigate this increase in FNDC5 gene expression through enhanced thermogenesis.

Regular aerobic exercise has a significant impact on glucose metabolism and lipid profiles, contributing to overall health improvement. However, evidence for optimal exercise duration to achieve these effects is limited. This study aims to explore the effects of 4 and 8 weeks of moderate-intensity aerobic exercise on glucose metabolism, lipid profiles, and associated metabolic changes in young female students with insulin resistance and varying body mass, seeking to determine the optimal duration for physiological adaptations. Twenty-eight physically semi-active female students were randomly assigned to 4-week (G4, n = 13, age = 23.31 ± 5.19, BMI = 24.78 ± 5.87) and 8-week (G8, n = 15, age = 21.8 ± 2.56, BMI = 24.95 ± 4.81) training groups. The aerobic intervention maintained an intensity of 40–70% of maximum heart rate (HRmax). 6-min-walk test (6MWT), handgrip strength tests, insulin, HOMA-IR, lipid profiles, and metabolic profiles were assessed pre- and post-intervention. Following the intervention, G8, but not G4, exhibited a significant decrease in HOMA-IR (-14.59%, p = 0.047). The improvement in HOMA-IR was accompanied by notable improvements in 6-MWT (+ 38.18%, p < 0.001) and handgrip strength (+ 11.62, p = 0.027 and + 17.59%, p = 0.013), and increased levels of bilirubin degradation products, ribose, and glutarate. The elevated levels of bilirubin degradation products, known for their antioxidant properties, suggested a potential antioxidative response triggered by prolonged aerobic exercise. Additionally, an increase in ribose and glutarate indicated improved metabolic flexibility and enhanced utilization of alternative energy substrates. The 8-week aerobic exercise regimen demonstrated enhanced insulin sensitivity, upper body strength, and cardiovascular performance in young females compared to a 4-week regimen by triggering specific metabolic adaptations. These findings emphasize the complex relationship between exercise duration, metabolic adaptations, and overall well-being in young women, providing valuable insights for optimizing exercise prescriptions in promoting metabolic health.

Idiopathic pulmonary arterial hypertension (IPAH) is characterized by smooth muscle cell, endothelial cell, and fibroblast hypertrophy and an increase in extracellular matrix volume in pulmonary precapillary arterioles. These features lead to a gradual increase of pulmonary vascular resistance, right-heart failure, and premature death. Bone morphogenetic protein receptor type 2 (BMPR-2) gene mutations have been identified to cause IPAH. BMPR-2 receptor mutation results in BMP signalling pathway termination and leads to disturbed growth and differentiation of pulmonary circulation cells. Transforming growth factor (TGF)-beta1 inhibits the migration and proliferation of endothelial and smooth muscle cells, and stimulates their differentiation, thus it has antiinflammatory and immunosuppressive properties, inhibiting vascular remodeling and is responsible for extracellular matrix production. The aim of this study was to analyse the profile of TGF-beta1 and the expression of its receptor (TbetaR I, TbetaR II and TbetaR III-betaglycan) genes in IPAH and in secondary forms of pulmonary arterial hypertension [Eisenmenger's syndrome (ES) patients]. Twenty-one patients with IPAH (2 men), 12 ES patients, and 10 healthy controls were enrolled in the study. QRT-PCR analysis of the transcriptive activity of TGF-beta1 and its receptor genes was performed with each patient. There were differences in receptor gene expression among the patient groups. The highest expression was observed in Eisenmenger syndrome patients (approximately 5-to 8-fold increase). There was a negative correlation between the gene expression of TGF-beta1 and that of its receptors, and a positive correlation between TbetaR II and TbetaR III in healthy controls. In IPAH patients a positive correlation between TGF-beta1 and TbetaR I was found. There was a difference in expression of TGF-beta1/receptor gene ratios and expression of receptor gene ratios between the examined groups. The differences in expression between IPAH and ES patients might suggest the role of these cytokines in IPAH pathogenesis. A disturbed proportion of expression of TGF-beta1 and receptor genes in IPAH patients might be one of the pathogenetic factors of the disease.

Introduction: Cardiac apoptosis is one of the most important cardiovascular complications of diabetes. We aimed to investigate the changes of caspase-8, Bcl-2, and N-terminal pro B-type natriuretic peptide (NT-proBNP) in cardiac tissue after 4 weeks of aerobic exercise in male rats with diabetes. Methods: Forty adult male rats were randomly allocated to healthy control, diabetes, control + exercise and exercise + diabetes groups. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ) solution (55 mg/kg). Two weeks after injection, fasting blood glucose levels were measured. After the induction of diabetes, the exercise program was performed for 4 weeks (5 sessions per week) at a speed of 15 to 18 m/min for 25 to 44 minutes. Forty-eight hours after the last training session, the subjects were anesthetized and the heart muscle was removed. Caspase-8, Bcl-2 and NT-proBNP levels were measured by ELISA method. Results: The induction of diabetes in the control group resulted in a significant increase in caspase-8, and NT-proBNP levels while an insignificant increase was observed for Bcl-2 levels (P&lt;0.05). In non-diabetic groups, exercise caused no changes in caspase-8, NT-proBNP and Bcl-2 (P&lt;0.05). Exercise in diabetic groups significantly decreased NT-proBNP while no changes were observed in caspase-8 and Bcl-2 (P&lt;0.05). Conclusion: Our findings showed that diabetes increases the pro-apoptotic and anti-apoptotic agent. In addition, 4 weeks of regular aerobic exercises can be used as a non-pharmacological strategy to reduce the complications of apoptosis in diabetic cardiomyocytes.