مجله دانشگاه علوم پزشکی اردبیل
پیاپی 77 (پاییز 1399)

The increased incidence of metabolic diseases (e.g., diabetes and obesity) has seriously affected human health and life safety worldwide. It is of great significance to find effective drugs from natural compounds and exercise to treat metabolic diseases. The aim of this study was to evaluate the effect of berberine chloride with aerobic training on Liver Gene Expression Nrf2, HO-1 and PPARγ in Streptozotocin (STZ)-induced diabetic rats.

In this experimental study,  32 male Wistar rats were randomly divided into four groups (n=8): Diabetes (DM), Diabetes-Berberine (BDM), Diabetes-Aerobic Training (TDM), Diabetes-Aerobic Training -Berberine (TBDM). Diabetes was induced by injection of STZ in male rats. Berberine chloride (30 mg/kg/day) were administered orally, by gavage, once a day. Training groups have performed a progressive aerobic running program (at 10-18 m/min, 10-40 min/day, and 5 days/week) on a motor-driven treadmill for six weeks.

There was a significant increase in Nrf2 and HO-1 expression in BDM in BDM (p=0.027 and p=0.038, respectively), TDM (p=0.022 and p=0.028, respectively) and TBDM (p=0.000 and p=0.000, respectively). This increase was also observed in TBDM groups compared to BDM (p=0.034 and p=0.034, respectively) and TDM (p=0.043 and p=0.046, respectively). PPARγ was significantly increased in TDM (p=0.046) and TBDM (p=0.001) groups.

Berberine chloride combination with exercise may possibly inhibit STZ-induced liver damage through up-regulating the Nrf2/HO-1 pathway and PPARγ.

Physical activity is one of the several factors which stimulate the secretion of growth and nerve growth factors in patients with Multiple Sclerosis (MS). Therefore, the aim of this study was to evaluate the effect of 12 weeks of Pilates training and ginger consumption on serum level of BDNF and TNF-α in women with MS.

Forty women with MS were randomly selected from 85 women referred to the Welfare Office of Urmia city, in Iran, with the age range of 30-35 in the form of a pre-test and post-test quasi-experimental study design. Participants were divided into four groups including: exercise+ supplement, exercise+ placebo, ginger supplement and control group with 10 individuals in each group. The intervention groups performed Pilates exercises for 12 weeks, 3 sessions of 60 minutes every week, and the supplement groups took three ginger capsules of one gram daily. In order to analyze the data, analysis of covariance was done using SPSS-22 software.

The results showed that ginger consumption combined with physical exercises increases BDNF in the intervention groups compared to the control groups, but this increase is more significant in the exercise+supplement group (p<0.05) than other groups. Also, the results showed that TNF-α level has a significant decrease in the intervention group compared to the control group (p<0.05).

The results showed that ginger consumption as a non-invasive method can have a positive effect on increasing BDNF level and decreasing TNF-α level in women with MS.

Osteoarthritis as a result of the destruction of articular cartilage, leads to joint pain and stiffness. The purpose of this study was to investigate the effect of endurance and ozone therapy on the expression levels of FLS and VEGF genes in the knee tissue of rats with knee osteoarthritis.

Subjects were male Wistar rats that were randomly divided into 5 groups after two weeks of adaptation, including: control-healthy, control-patient, patient-ozone, patient-exercise and patient-sport. For adapting the rats to exercise and treadmill, walking program was performed before exercise program. The training program consisted of 30 minutes of running on a treadmill with no slope at a speed of 16 m/min for the first week and one m/min added weekly until it reached 22 m/min in the eighth week. Ozone was injected into the knee through the tibiofemoral articular line at a concentration of 20 μg/ml once a week for 3 weeks at 9 ochr('39')clock in the morning. Expression levels of FLS and VEGF genes were measured by Real Time PCR. One way ANOVA and Tukeychr('39')s method were used to determine the difference between groups.

The results showed that the expression levels of FLS and VEGF genes were significantly increased in rats with osteoarthritis. It was also shown that physical training and ozone therapy led to a decrease in FLS and VEGF gene expression levels in osteoarthritic rats. VEGF and its receptors are expressed in OA cartilage and indicating the possibility that VEGF is involved in the elimination of OA articular cartilage by increasing MMP production.

The results of this study are promising for the role of VEGF as a diagnostic marker. VEGF can participate in early OA changes and a treatment modality by modulating VEGF production, which can be considered in future.

Foxo1 is a transcription factor in insulin signaling in the liver. The function of Foxo1 is important in the ability of insulin to regulate hepatic glucose production and glucose homeostasis. The aim of this study was to determine the effect of resistance training program on Foxo1 expression in liver cells as well as glucose and insulin serum levels in male Wistar rats with type 2 diabetes.

The statistical population of this experimental study was 10-weeks old, male Wistar rats weighing 220±20 g (n=14). The studied rats were subjected to 6 weeks of high-fat diet and STZ injection for type 2 diabetes induction and then rats were randomly divided into two groups (control and resistance). The training group participated in a resistance training course for 6 weeks, 5 sessions per week, in the form of 4 sets and 5 repetitions per set, climbing a 26-step ladder to a height of one meter with a vertical slope of 80%. Finally, 48 hours after the last training session, fasting blood  glucose and insulin levels as well as Foxo1 expression level  in liver cells of both groups were measured and compared by independent t-test (a=%5).

The resistance training improved fasting blood glucose compared to control subjects (p>0.001). the serum insulin levels were significantly increased (p=0.042) and Foxo1 expression significantly decreased in resistance group when compared with control subjects (p=0.023).

Based on these data, the decrease in glucose concentration in the exercise group can probably be attributed to the decreased expression of Foxo1 in hepatocyte cells in response to resistance training.

Mitochondrial dysfunction is one of the main risk factors for neurological diseases which are associated with aging. On the other hand, aerobic exercise has beneficial effects on the brain health and cognitive function, and also improves mitochondrial dynamics. Therefore, the aim of the present study was to investigate the effect of 4 weeks of aerobic exercise on spatial learning, memory performance and mitochondrial dynamics in the hippocampal tissue of old rats.

For this purpose, 14 male Wistar rats at 20 months of age were randomly divided into 2 groups: aerobic exercise (n=7) and control group (n=7). The exercise group performed 4 weeks of treadmill training (5 days per week at a speed of 10 to 15 m/min). Forty-eight hours after the last training session, the animals underwent behavioral tests. Twenty-four hours after the behavioral test, all rats were killed and hippocampal tissue was extracted. The mRNA expression of OPA1, Mfn2 and Drp1 genes were assayed using Real Time-PCR. The Independent t test was used for statistical analysis.

Aerobic exercise in old animals improved spatial learning and memory performance, increased hippocampal OPA1 gene expression, and decreased Drp1 gene expression compared to the control group (p≤0.01).

It seems that aerobic exercise can improve the function of brain mitochondria by modulating fusion and fission processes and it can be considered as an effective non-pharmacological method to deal with aging-related learning and memory perturbations.

The liver is one of the most important organs in the body and plays an essential role in the metabolism of drugs and toxins. Therefore, any damage to the liver can disrupt its function and cause various diseases. On the other hand, due to the increasing use of the medicinal herbs, in this study, the effects of hepatic protection of aqueous extracts of Humulus lupulus on liver damage induced by carbon tetrachloride in rats were investigated.

In this experimental study, 36 male Wistar rats were divided into 6 groups (n=6). Group 1 (normal control) and Group 2 (control CCl4): administered with distilled water orally for 14 days. Groups 3, 4, and 5 received 50, 100, and 200 mg/kg of Humulus lupulus extract for 14 days respectively. Group 6: administered with silymarin (as standard drug) 100 mg/kg orally for 14 days. All of the groups except group 1 received 1 ml CCl4 (1:1 v/v dissolved in olive oil) on 14th day. All animals were sacrificed and blood samples were collected to determine the biochemical parameters.

Pretreatment with a Humulus lupulus extract significantly reduced the serum levels of ALT, AST, ALP, TG, and increased the serum HDL levels, but did not have a significant effect on GGT and LDL levels.

The results of this study showed that the Humulus lupulus extract can protect the liver from damage caused by carbon tetrachloride and have beneficial effects on lipid profile.

Background & Objectives

Based on the probably positive role of exercise on total oxidative status (TOS) and total antioxidant system (TAS) and their effect on the process of angiogenesis, the aim of the current study was to evaluate the effect of one course of moderate-intensity endurance training on the gene expression level of vascular endothelial growth factor-B (VEGF-B) and angiopoietin-1(ANGPT-1) and TAS and TOS status in cardiac tissue of male rats.

In this study, 20 male Wistar rats were divided into two equal groups as follows:   1-training group and 2- control group: no sports activities were performed on them. Rats in the training group performed moderate endurance training for 6 weeks and 5 sessions per week from the twelfth week of life. Twenty-four hours after the last training session, heart tissue samples were extracted to measure gene expression levels of VEGF-B and ANGPT-1 and the TAS and TOS status in heart tissues. T-test with the statistical level of (p˂0.05) was used for between groups comparison.

Findings showed that after six weeks of endurance training, the expression level of ANGPT-1 and VEGF-B and the amount of TAS in the exercise group significantly increased (p=0.001) and the amount of TOS significantly decreased compared to the control group (p=0.008).

According to the results of the present study, it seems that moderate-intensity endurance training can be effective in preventing cardiovascular disease by increasing factors involving in angiogenesis, improving TAS and reducing TOS in heart tissue of rats.

 Drug-repurposing is the study on application of existing drugs for treatment or control of other diseases. Major advantage of the technique relies on a nominated drug molecule that is applied for pharmacodynamics optimization due to lack of serious pharmacokinetics challenges. According to the importance of the subject, a present contribution has been dedicated to the in-silico analysis of a few drug classes with the aim of achieving potential anti-leishmanial pharmacophores.   

 3D structure of protein targets within leishmania parasite were retrieved from Brookhaven Protein Data Bank (PDB) on the basis of literature reports to evaluate the related complexes with drugs via molecular docking. Qualitative and quantitative analysis of drug-target interaction patterns in docked complexes offered drugs with higher binding affinities toward targets and finally structural patterns or hypothetical anti-leishmanial pharmacophores were proposed with regard to the top-ranked pharmaceutical compounds.

 Highest free binding energy could be estimated for Nateglinide in binding to farnesyl diphosphate synthase (ΔGb -13.30 kcal/mol). Among steroids, Norgestrel synthase (ΔGb -9.48 kcal/mol) and Testosterone synthase (ΔGb -8.05 kcal/mol) exhibited higher enzyme binding affinities and Arg82 was a key residue in making hydrogen bonds. Within fused tricyclic structural patterns, mirtazapine exhibited highest binding affinity to deoxy uridine triphosphate (ΔGb -8.64 kcal/mol). In Carbamazepine, amide substituent of the central ring facilitated the formation of two effective hydrogen bonds with Gln21 and Asn25 in deoxy uridine triphosphate. 

 On the basis of obtained results for steroids and fused tricyclic scaffolds, it will be possible to design molecules that can inhibit several pathogenic targets simultaneously.

ABCA1 plays an important role in HDL biosynthesis and cellular cholesterol homeostasis and is effective in preventing the formation of atherosclerotic plaques. This study aimed to investigate the effect of combined and rehabilitation training on ABCA1 gene expression in blood lymphocytes and lipid profile in middle-aged men with coronary bypass graft.

In this quasi-experimental study, 45 middle-aged men (mean age: 55.58±4.7 years) were selected by convenience sampling method and randomly divided into three groups of combined training (15 people), rehabilitation (n=15), and control (n=15). The combined training group included resistance and aerobic exercises and rehabilitation training group included aerobic exercises for 8 weeks (3 sessions per week). Blood samples were taken from all subjects at weeks 0 and 8 to measure the expression levels of ABCA1, HDL, and LDL genes. Kruskal-Wallis, one-way ANOVA, and Tukey post hoc tests were used for statistical analysis using SPSS software, and significance level was p≤0.05 .

The results showed that eight weeks of combined training and rehabilitation training increased the expression level of the ABCA1 (p=0.001 and p=0.001, respectively) gene and plasma HDL (p=0.001 and p=0.012, respectively) level and decreased plasma LDL (p=0.001 and p=0.01, respectively) level. There was also a significant difference between the three groups in ABCA1 and HDL values in favor of the combined training group.

It seems that combined training can be more effective than rehabilitation training to further increase ABCA1 gene expression and plasma HDL levels and decrease LDL level in middle-aged men with coronary bypass graft.

Breast cancer is one of the most common diseases and the leading cause of death among women worldwide. The aim of the present study was to determine the effects of five weeks of endurance training in combination with curcumin on the cancer progression, intratumoral gene expression of angiomiR-126 and Angiopoietin-1 in breast cancer bearing female BALB/c mice.

The present study was an experimental study. 4T1 breast cancer was transplanted into forty female BALB/c mice. Afterward, they were randomly divided into four groups including, a control group (C), an endurance training group (E), an endurance training along with curcumin (EC) and curcumin group (CC). E and EC groups performed 40 min at a constant running intensity corresponding to 60-65% vVo2peak at 0% inclination, 5 weeks (five days a week). CC and EC groups were treated by oral gavage with curcumin for five weeks (six days a week). Then, tumor tissue of all mice was extracted 24 hour after the last training session. Gene expression levels of miR-126 and angiopoietin-1 were determined by qReal-time PCR. Statistical data values were also measured by One-way ANOVA.

The results showed a significant inhibition of cancer growth, increased gene expression of miR-126 (p<0.001) and decreased angiopoietin-1 gene expression (p<0.001) in E, CC, and especially E-C compared to control group. All of these changes were significantly greater in the EC group than in the other intervention groups (p<0.001).

It seems that five weeks of endurance training with curcumin supplementation possibly have a further effect on decreasing breast cancer mass growth by inhibiting miR-126 /angiopoietin-1 axis compared to other interventions alone.

Over the last couple of decades, research has focused on attempting to understand the genetic influence on sports performance. Whole exome sequencing (WES) has great potential to explore all possible genetic variants associated with physical performance. However, this new technique has not been used in sports genetics research. Therefore the aim of this case study was to report new variants in genes involved in skeletal muscles strength (ACE, NOS3, IGF1R, IL-6) in an elite weightlifter using WES.

After obtaining a written testimony from a 32-year-old man, who is a member of the Iranian national weightlifting team, 5 cc of blood was taken and then DNA was extracted. DNA samples were analyzed using the whole exome sequencing method.

Whole exome sequencing analysis revealed a missense variant (99454613G>A) in IGF1R, 22771156C>T polymorphism in IL-6, 150695726T>C and 150704250C>G polymorphisms in NOS3 and 61573761T>C and 61564052A>G in ACE genes.

Results of whole exome sequencing analysis revealed a missense variant and polymorphism in muscle strength and hypertrophy related genes in this elite weightlifter. However, other studies with larger sample sizes are needed to investigate the relationship between these variants and power athlete status.