Razi Journal of Medical Sciences

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Background & Aims: Diabetes Mellitus (DM) is an incurable disorder with various complications that causes damage to various organs. According to reports, 463 million adults worldwide suffer from DM, which is expected to increase to 578 million by 2030 (1).
Hyperglycemia is the most common symptom of diabetes, which is caused by an autoimmune disease of pancreatic cells, ultimately leading to a decrease in insulin secretion in type 1 diabetes (T1DM) or insulin resistance in type 2 diabetes (T2DM). The creation of oxidative stress in diabetic patients and subsequent disruption of vascular endothelial function directly and indirectly affects the function of the human reproductive system (1,2). It has been shown that half of the men with diabetes have poor semen quality and dysfunctional reproductive system. These factors are influenced by various mechanisms such as neuropathy, endocrine disorders and oxidative stress. According to various reports, erectile dysfunction (ED) occurs in 59% of men with diabetes. ED is caused by hyperglycemia because it increases the amount of ROS (reactive oxygen species) and advanced glycation end products (AGEs) and by disrupting the metabolism of eNOS (endothelial nitric oxide synthase), it decreases the synthesis of nitric oxide (NO)(3,4). Nitric oxide is an unstable messenger molecule that plays a role in the regulation of gonadotropin hormones, sperm capacitation, erection and ejaculation (5). Oxytocin, which induces mating behavior in both sexes, induces the release of gonadotropin-releasing hormone (GnRH) through the production of NO. Also, NO controls the mating behavior in men through neural mediators related to ejaculation, so that the inhibition of nitric oxide synthesis reduces the frequency of ejaculation and the duration of ejaculation by reducing the activity of the sympathetic nervous system. Many researches show that testosterone levels decrease in diabetic men (5). A decrease in vascular endothelial growth factor (VEGF) may disrupt the function of vascular endothelial cells, which leads to blockage of small arteries (microcirculation) in the testis, which in turn causes morphological and structural changes (6,7). It is believed that in immature rats, DM can cause gonadal growth retardation, decreased sexual behavior and testosterone synthesis while promoting gonadal atrophy (6,7). In both type 1 and type 2 diabetes animal models, studies have shown a significant decrease in antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) and a significant increase in malondialdehyde (MDA) levels (15,16). Also, studies in type 2 diabetic mice have reported upregulation of pro-apoptotic protein BAX and downregulation of anti-apoptotic protein Bcl-2. Apoptosis is a physiological process that occurs in order to remove damaged cells in testicular tissue and other tissues and plays an important role in tissue compatibility. The process of apoptosis occurs in two internal (mitochondria-dependent) and external (ligand-dependent) pathways. In the internal pathway of apoptosis, the Bcl-2 family includes BAX and Bcl-2 proteins as the upstream regulators of apoptosis. Bcl-2 is one of the apoptosis-inhibiting proteins that prevents the oxidative destruction of the cell and by maintaining the integrity of the mitochondrial membrane by removing H⁺ ions, it binds to the apoptotic protease activation factor and activates caspase 9 (17,18).This decrease in antioxidant capacity and the predominance of oxidant conditions in diabetes cause structural changes in the testicles, decrease in sperm production, decrease in sperm motility and decrease in the number of Leydig cells (testosterone secreting cells) and Sertoli cells (13,19).
 Sedentary lifestyle is one of the causes of type 2 diabetes. Physical activity is the most powerful factor in preventing diseases such as obesity and diabetes. Exercise reduces oxidative stress, increases antioxidant capacity and reduces insulin resistance (27). Physical activity increases the uptake of glucose by muscle tissues and reduces blood glucose (28). It has also been reported that physical exercises protect cells from apoptosis and improve spermatogenesis and increase sex hormones (29). However, according to our knowledge, these new evidences that investigate the effect of physical activity on blood sugar levels, sex hormones, antioxidant enzymes, oxidative stress and apoptosis indicators of testicular tissue of diabetic patients, have not been critically evaluated. Therefore, in this article, we review the published evidence to determine whether physical activity can be used as a therapeutic tool for the sexual health of patients with type 2 diabetes. It is hoped that the information presented will be valuable to physicians, exercise physiologists, and those interested in personal or public health..
Methods: This study was conducted in April and May 2024, focusing on investigating the effects of physical activity on some health and fertility indicators of the reproductive system of diabetic patients. Pub Med, Science Direct, Med Line, SID and Google Scholar databases were used in this study. Also, the keywords "diabetes", "diabetes and sexual diseases", "physical activity and diabetes", "physical activity and sexual health" were used to search for articles. The criteria for selecting articles for this study included the following: 1- Original and scientific-research articles. 2- The studied samples should not have any other disease apart from diabetes. 3- The exercise protocols used in the articles should not be short-term or acute. 4- The articles have only examined the response to sports activity (without the use of various medical drugs). The exclusion criteria for articles from this study included the following: 1- Review articles. 2- In the articles, drugs and blood sugar lowering supplements have been used. The articles used in this study were in the time range between 2015 and 2024. 25 articles were collected from scientific databases, and after reading the articles, 11 articles were included in the present study. Results: The results of the present study showed that regular physical activity reduces blood sugar levels, increases sex hormone levels, antioxidant enzymes and oxidative stress, and apoptotic indices of testicular tissue of diabetic patients. The proposed mechanism for reducing blood sugar, improving antioxidant defense and increasing the levels of sex hormones and reducing apoptotic proteins due to regular exercise can be pointed to the fact that physical activity increases the muscle response to insulin through the expression and increases the activity of proteins involved in carbohydrate metabolism. So that physical activity increases the activity of glycogen synthetase and the expression of glucose transporter 4 (GLUT4) proteins. Also, research results have shown that exercise increases insulin sensitivity in diabetic patients and facilitates the entry of blood sugar into muscle cells, which ultimately leads to a decrease in blood sugar levels.
Conclusion: The results of this study show that regular physical activity can reduce blood sugar, increase the levels of sex hormones, increase the activity of antioxidant enzymes, reduce oxidative stress, increase anti-apoptotic factors and decrease pro-apoptotic factors.

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Background: Alzheimer's disease (AD) is the most common form of dementia and amyloid peptides playing a central role in its pathogenesis. Recently, regular exercise has been considered as one of the most important non-pharmacological mechanisms to contrast with AD. Therefore, the aim of the present study was to investigate the effect of 4 weeks of exercise preconditioning on the level of soluble amyloid and memory impairment in rats with AD induced by Aβ1-42 injection.
Methods: Eighty four male rats with mean±SD weight of 195±20 g were randomly divided into two groups of aerobic training or resting for 4 weeks. Then, each group was subdivided into 3 subgroups of AD, sham and non-injected. Forty eight hours after the last training session, injection of Aβ1-42 or DMSO into the hippocampus was performed. Seven days after surgery, rats of each groups were either sacrificed (7 rats) or subjected to behavioral testing (7 rats), randomly. Following the collection of blood samples in the victim's rats, the hippocampal tissue was extracted and the levels of Aβ1-42 in plasma and hippocampus, as well as the plasma level of the soluble Low-Density Lipoprotein Receptor-Related Protein-1 (sLRP-1) evaluated.
Results: The results showed that in the exercise + AD group, hippocampal level of Aβ1-42 were lower, and plasma level of Aβ1-42 were higher than the AD group (p<0.001). Plasma sLRP-1 level in the exercise + AD group was also greater than the AD group (p<0.001). Moreover, spatial learning and memory were significantly better in the exercise + AD than AD group (p<0.01).
Conclusion: It seems that 4 weeks of exercise preconditioning could reduce the loss of spatial learning and memory through increasing soluble amyloid beta clearance from the brain.
 

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Background: Studies showed thyroid hormones influence proliferation of cancer cells. The main aim of this study was to investigate the effects of cytotoxic thyroid hormone T4 on proliferation of brain glioblastoma cells (A172) in cell culture.
Methods: In this laboratory experimental study, A172 cells were randomly divided into control group and groups exposed to doses 0.1, 0.5, 1, 5, 10, 20, 40, 50 Lambda (λ) of thyroid hormone T4. The toxic effect of hormones was measured using MTT assay method. The data were statistically analyzed between groups using ANOVA.
Results: The result demonstrated that highest toxicity of thyroid hormone T4 on glioblastoma cancer cells A172 was in 1 lambda (λ) dosage and low toxicity in 0.1 and 40 lambdas (λ) dosages.
Conclusion: Toxicity of Glioblastoma cancer cells is either hormone dependent or hormone independent.

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Background: Human growth hormone (hGH) use is increasing due to its important biological functions and therapeutic applications, the use of growth hormone for the treatment of obesity, short stature, burns and the importance of this hormone for athletes. Nowadays, the short half-life of hGH is a major challenge associated with the usage of this drug in the world. PEGylation is an effective approach to increase half-life and stability of biopharmaceutical proteins. Polyethylene glycol (PEG) due to high aqueous solubility is considered as a versatile candidate for pharmaceutical protein conjugation. Accordingly, in this study the PEGylation of human growth hormone and its plasma half-life and stability were carried out.
Methods: hGH was PEGylated by using Methoxy PEG Succinimidyl Carbonate (mPEG-SC) at 8 °C for overnight.  In this study, SDS-PAGE, Dynamic Light Scattering (DLS), and ELISA techniques were used to prove PEGylation reaction.
Results: The SDS-PAGE results showed high yield PEGylation of hGH under aqueous conditions. The zeta-potential, as an indicator of the Surface charge of PEGylated hGH, was analyzed by DLS technique. The ELISA results shown the increase half-life of pegylated hGH to 12 times.
Conclusion: In the present study, we demonstrated that the PEGylation of lysine and/or histidine residues significantly increased the half-life of the human growth hormone.