دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of 12- weeks of HIIT and L-carnitine supplementation on gene expression of some factors associated with browning of white adipose tissue and uncoupling protein-1changes in obese male rats تأثیر 12هفته HIIT و مکمل‌‌دهی ال‌‌کارنیتین بر بیان ژن برخی عوامل مرتبط با تغییر بافت چربی سفید به قهوه‌‌ای و پروتئین جفت نشده نوع-1 در رت‌‌های نر چاق 8 23 3405 10.22077/jpsbs.2025.8489.1930 FA وحید ساری صرّاف استاد گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز. ایران. مصطفی خانی استادیار گروه فیزیولوژی ورزشی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران. مهدی ساقی دانشجوی دکتری گروه فیزیولوژی، دانشکده تربیت بدنی و علوم ورزشی، دانشگاه تبریز، تبریز، ایران. Journal Article 2024 11 26 Extended abstract Background and Aim: Obesity is a risk factor for metabolic and cardiovascular diseases. White adipose tissue (WAT) stores excess fat, preventing its accumulation in vital organs; however, excessive WAT accumulation can contribute to obesity and a reduced in brown adipose tissue (BAT) activity. MicroRNAs, particularly miR-455, play a critical role in regulating the differentiation of brown adipocytes, a process that counteracts obesity. MiR-455 enhances the differentiation of brown fat cells by targeting key regulators of lipogenesis and inhibiting hypoxia-inducible factor 1 alpha (HIF-1α). Inhibition of HIF-1α activates Adenosine monophosphate-activated protein kinase-1 alpha (AMPK-1α), leading to increased expression of Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and Peroxisome proliferator-activated receptor-gamma (PPAR-γ), ultimately boosting mitochondrial biogenesis and thermogenesis in WAT. High-intensity interval training (HIIT) and L-carnitine supplementation are known as stimulants for converting WAT phenotype to beige and activating BAT; however, their impact on the UCP1/HIF-1α/miR-455 axis remains unclear. The present study aims to investigate the effects of 12 weeks of HIIT and L-carnitine supplementation on the expression of this axis in obese male rats, paving the way for innovative treatments for obesity and metabolic disorders. Materials and Methods: Thirty-six male rats were used in this experimental study. Obesity was induced by eight-week of a high-fat diet (60% fat, 20% carbohydrate, 20% protein), leading to an approximate weight of 450 g. After induction, the rats were fed a standard diet ad libitum. The rats were then randomly assigned to one of four groups: control (C), Training (T), supplementation (S), and supplementation+Training (ST). Following the induction period, all rats were fed standard chow. To determine maximal running speed, groups T and ST underwent a Bedford treadmill test. This test consisted of ten 3-min stages, beginning at 5 meters per min on a 25-degree incline, with speed increments of 5 meters per stage until exhaustion. A 12-week HIIT protocol (5 days/week) comprised: 5-min warm-up and cool-down (<60% max speed), followed by ten 4-min intervals at 85-90% max speed, with 2-min active recovery (50-60% max speed) between intervals. To account for potential changes in maximal speed and prevent uniform training intensity, a retest of maximal speed was performed every two weeks on a non-training day for groups T and ST. Groups S and ST received daily oral L-carnitine (30 mg/kg body weight) by gavage one hour after training; groups C and T received an equivalent volume of distilled water. Forty-eight hours post-training and following an overnight fast, rats were euthanized. Subcutaneous inguinal adipose tissue samples were collected and processed for analysis. The expression levels of miR-455, HIF-1α, and UCP1 were determined using RT-qPCR, Western blotting, and immunofluorescence, respectively. After confirming data normality (Shapiro-Wilk test) and homogeneity of variances (Levene test), within-group comparisons were performed using paired t-tests. Between-group comparisons were performed using one-way ANOVA, with post hoc analysis using the Bonferroni correction. Statistical analyses were performed using SPSS version 26 at p<0.05 level. Graphs were generated using Excel 2007. Findings: The results of the Shapiro-Wilk test showed that the weight distribution of all rats was normal at the beginning of the study (p=0.13). A dependent t-test confirmed the weight gain of all rats at the end of the eight-week high-fat diet (p=0.001). After dividing the rats into four groups and implementing the respective interventions, a significant difference was observed between the weights of the groups (p=0.001), such that groups T and ST had a significant decrease compared to group C (p=0.003 and p=0.001 respectively) and compared to group S (p=0.02 and p=0.001 respectively), but no significant changes were observed between groups ST and T, as well as groups S and C (p=0.001). Finally, group S had lower weight compared to group C and group ST had lower weight compared to T. Regarding the expression of miR-455, a significant difference was observed between the groups (p=0.001). Group T had a significant decrease (p=0.001) and group S had a significant increase (p=0.001) compared to group C. Group ST did not have a significant increase compared to group C (p=0.07). The difference between other pair of groups was significant (p=0.001)(Figure 1). The results for HIF-1α expression indicated a significant difference between the groups (p=0.001), such that groups T, S and ST had a significant increase compared to group C (p=0.001). There was no significant difference between groups T and S (p=1.00)( Figure 1). A significant difference was also observed in the expression of UCP1 protein (p=0.001), and all groups had a significant increase compared to group C (p=0.001), but there was no significant difference between groups T and ST (p=0.08)( Figure 1). The study of adipose tissue images showed that group C had large white fat cells with fewer mitochondria and lower capillary density, indicating low metabolic activity and inflammation. Group T had a higher number of small brown/beige multilocular fat cells and higher capillary and mitochondrial density, indicating higher metabolic activity. Group S showed slight improvement compared to group C, while group ST showed significant improvement in metabolic parameters, although not to the same extent as group T . These findings were consistent with the observed weight changes in each group. Figure 1. Comparison of mir-455 (μg/mL), HIF-1α (μg/mL) and UCP1 (μm) between groups. *significant difference between groups at p<0.05. Conclusion: This research examined the effects of L-carnitine and HIIT on factors influencing WAT browning. L-carnitine supplementation alone elevated levels of miR-455, HIF-1α, and UCP1, yet exerted no discernible impact on body weight. In contrast, HIIT paradoxically increased UCP1 activity while reducing miR-455 expression and stimulating alternative pathways associated with WAT-to-BAT conversion; this, coupled with the caloric expenditure inherent in training, resulted in weight loss. The combined administration of L-carnitine and HIIT synergistically activated UCP1 and augmented caloric consumption. These findings offer potential avenues for combating obesity and provide promising evidence for promoting WAT browning. As a novel study, this research suggests that the concurrent administration of HIIT and L-carnitine may effectively modulate BAT activity, however, further research is needed to confirm these observations. Ethical Considerations: This study received ethical approval from the Biomedical Ethics Committee of Tabriz University (IR.TABRIZU.REC.1401.042). The research was conducted using the minimum number of rats necessary and adhered to optimal laboratory animal conditions (12:12 light-dark cycle, 50% ± 3% relative humidity, and 22±2°C temperature). Non-invasive and low-pain methods, minimizing distress, were employed for stimulating the rats. All researchers completed mandatory training courses on animal handling and ethical principles. Compliance with ethical guideline: Alternative methods to animal experimentation were considered whenever feasible, and laboratory procedures were designed to minimize pain and suffering. Funding: All costs associated with this research, including analyses, materials, and publication fees, were covered by the authors. No external funding was received from any institution or organization. Conflict of interest: The authors declare no conflicts of interest pertaining to this research. زمینه و هدف: افزایش فعالیت پروتئین جفت نشده نوع یک (UCP1) باعث کاهش عوارض چاقی می‌‌شود. لذا هدف از پژوهش حاضر بررسی تأثیر دوازده هفته تمرین تناوبی با شدت بالا (HIIT) و تجویز مکمل ال‌‌کارنیتین بر بیان 455-miR، HIF-1α و تغییرات UCP1 در بافت چربی زیر پوستی رت‌‌های نر چاق بود. روش تحقیق: 36 سر رت نر ویستار پس از هشت هفته مصرف غذای پرچرب به‌‌طور تصادفی به چهار گروه: کنترل (C)، تمرین (T)، مکمل (S) و مکمل+تمرین (ST) تقسیم شدند. HIIT با شدت 90-85 درصد سرعت بیشینه روی نوارگردان، پنج روز در هفته به مدت 12 هفته برای رت‌‌های گروه T و ST اجرا شد. رت‌‌های گروه S و ST به مدت سه ماه 30 میلی‌‌گرم بر کیلوگرم وزن بدن در روز با ال‌‌کارنیتین گاواژ شدند. بیان 455-miR، HIF-1α و UCP1 به ترتیب با استفاده از روش‌‌های RT-qPCR، وسترن بلات و ایمنوفلورانس ارزیابی شدند. از آزمون‌‌های t وابسته و آنالیز واریانس یک‌‌راهه برای تجزیه و تحلیل داده‌‌ها و برای تعیین جایگاه معنی‌‌داری، از آزمون تعقیبی بونفرونی در سطح معنی‌‌داری 05/0>p استفاده شد. یافته‌‌ها: وزن رت‌‌ها در دوره چاقی افزایش داشت (001/0=p) که با تمرین (003/0=p) و مکمل+ تمرین (001/0=p) کاهش یافت. بیان‌‌ژن 455- miR گروه‌‌های T کاهش معنی‌‌دار (001/0=p)، S افزایش معنی‌‌دار (001/0=p) و ST افزایش غیرمعنی‌‌داری (07/0=p) در مقایسه با گروه C داشت. بیان پروتئین HIF-1α در همه گروه‌‌ها نسبت به گروه C افزایش معنی‌‌دار (001/0=p) داشت. بیان پروتئین UCP1 در همه گروه‌‌ها نسبت به گروه C افزایش معنی‌‌داری داشت (001/0=p). نتیجه‌‌گیری: به‌‌نظر می‌‌رسد HIIT و همزمانی HIIT با ال‌‌کارنیتین استراتژی مفیدی برای مقابله با چاقی بوده و شواهد امیدوارکننده‌‌ای برای بهبود قهوه‌‌ای شدن بافت چربی سفید ارائه می‌‌دهد. در حالی که تحقیقات بیشتری برای تعمیم این یافته‌‌ها از مدل‌‌های حیوانی به کاربردهای انسانی مورد نیاز است.

https://jpsbs.birjand.ac.ir/article_3405_d71cbd61e4fc25a58eef11a517bd6fd6.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of 12 weeks of aerobic training on expression of miR-223 and miR-92 associated with bone density in elderly women تاثیر 12هفته تمرین هوازی بر بیان miR-223 و miR-92 مرتبط با تراکم استخوان در زنان سالمند 24 37 3905 10.22077/jpsbs.2025.8226.1917 FA محسن اکبرپور بنی دانشیار گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه قم، قم، ایران. فاطمه سادات رضوی کارشناسی ارشد فیزیولوژی ورزشی، گروه علوم ورزشی، دانشکده ادبیات و علوم انسانی، دانشگاه قم، قم، ایران. ابراهیم شعبانی ازدینی دانشجوی دکتری فیزیولوژی ورزشی، گروه علوم ورزشی دانشکده علوم اجتماعی، دانشگاه بین المللی امام خمینی (ره)، قزوین، ایران. Journal Article 2024 10 11 Extended Abstract Background and Aim: The global population is rapidly aging, a major health challenge projected to affect 1.5 billion people by 2050, intensifying healthcare demands for age-related conditions like falls. A key consequence of aging is the decline in bone density and the rise of skeletal issues like osteoporosis. This is especially prevalent in elderly postmenopausal women, who face accelerated bone mass loss from hormonal changes. The underlying mechanism involves a disrupted bone-remodeling process, in which osteoblast activity declines while osteoclast activity remains unchanged, leading to a net reduction in bone density. Recent studies have highlight the role of micro ribonucleic acids (microRNAs), such as miR-223 and miR-92, in regulating bone metabolism, and show that their expression is altered with age. Recognizing that physical activity, especially aerobic exercise, is a known countermeasure against bone loss, our study investigated how 12 weeks of aerobic exercise impacts the expression of these specific microRNAs in elderly women. Materials and Methods: This semi-experimental study, with a control group, involved 30 elderly women (ages 65-70 y) selected from retired education personnel in Qom’s first district. From an initial pool of 60 volunteers, 30 were selected based on inclusion criteria: physical and mental health, at least five years post-menopause, and no history of specific diseases (cardiovascular-respiratory), regular physical activity, smoking, or special diets/therapeutic interventions within the previous six months. Exclusion criteria were irregular attendance, injury, the development of illness during the study. Before beginning, participants completed medical history, 24-hour dietary recall, PAR-Q (questionaire), and personal information forms, and then signed informed consent. They were then randomly assigned to either an experimental or control group (n=15 each). The study was ethically approved by Qom University (ID: IR.QOMREC.1399.018). The experimental group participated in a 12-week aerobic exercise program, three sessions per week. Each session, lasted 25-45 minutes, consisted of running at 50-75% maximum heart rate, a 10-minute warm-up, and a 5-minute cool-down. Intensity increased by 5% every two weeks and duration by 2 minutes weekly. Heart rate was monitored with polar series toolkit monitors. All sessions were held from 9-11 AM in the university’s indoor sports hall. The control group maintained their normal routines, avoiding intense activity. Blood samples (5 cc) were collected from the antecubital vein after a 12-hour fast, 48 hours before the first session and 48 hours after the last. Samples were centrifuged at 3000 RPM for 10 minutes and stored at −80 ∘C. MicroRNA was extracted using an Irizol RNA extraction kit (Zist Fanavarane RNA, code RB1001). Real-Time PCR, using SYBR Green Master Mix on a Rotor-Gene Q (Qiagen) system, was performed. Data were analyzed with the Livak (2−ΔΔCT) method. Statistical analysis included the Shapiro–Wilk test to verify normality and ANCOVA for between-group comparisons, using SPSS version 26. The significance level was set at p<0.05. Findings: Table 1 presents the results of descriptive and inferential statistical analyses. Pre-test measurements of microRNA expression revealed comparable levels of miR-223 between groups. Indeed, post-test analysis demonstrated highly significant and distinct changes in the exercise group. Covariance analysis (ANCOVA) indicated that the 12-week aerobic exercise program exerted a highly significant effect on the expression of both microRNAs compared to the control group. Specifically, a highly significant difference was observed for miR-223 expression (F(1,27)=21.64, p<0.0001), with the exercise intervention resulting in a 29.6% reduction. Similarly, miR-92 expression showed a significant difference (F(1,27)=13.14, p<0.0001), with aerobic exercise leading to a 71.2% increase. miR-223 expression in the exercise group decreased significantly to 3.52±0.60, whereas the control group showed minimal changes. This substantial reduction highlights a profound molecular response to the exercise intervention. Regarding miR-92, the exercise group demonstrated a significant increase to 3.97±0.98, while the control group remained relatively stable at 2.23±0.51. This upregulation of miR-92 further underscores the molecular impact of the exercise program. Conclusion: The results demonstrate that 12 weeks of aerobic exercise performed at 50-75% maximum heart rate intensity significantly modulates bone-related microRNA expression in elderly women. The observed 29.6% decrease in miR-223 expression may contribute to reduced inflammatory processes, decreased osteoclast activity, and enhanced osteoblast differentiation, while the 71.2% increase in miR-92 expression may support cartilage formation and bone morphogenetic protein signaling pathways. These molecular changes along with previous research showing that aerobic exercise influences bone metabolism through increased bone blood flow, improved nutrient delivery, and reduced inflammatory markers. The modulation of miR-223 may involve interactions with FOXO3, potentially enhancing bone formation, while increased miR-92 expression may promote osteogenesis through related signaling pathways. Based on the results, it appears that 12 weeks of aerobic exercise at an intensity of 50-75% improves miR-223 and miR-92, ultimately helping to prevent bone density loss in elderly women. These novel findings provide compelling molecular evidence for exercise-induced improvements in bone metabolism, however, further research is required to fully elucidate the underlying mechanisms and to optimize exercise prescriptions for preventing age-related bone loss. Ethical Considerations: This study was approved by the Ethics Committee of Qom University (ID: IR.QOMREC.1399.018). Compliance with Ethical Guidelines: All participants provided informed consent after receiving complete information about the study procedures. Funding: This research was extracted from a master’s thesis in exercise physiology in university of Qom. زمینه و هدف: میکرو RNAها نقش مهمی در تنظیم متابولیسم استخوان و فرآیندهای بیولوژیکی مرتبط با سلامت استخوان ایفا می‌کنند، از طرفی ورزش نیز در پیشگیری از اختلالات مربوط به استخوان نقش موثری دارد. بنابراین هدف از پژوهش حاضر بررسی تاثیر ۱۲ هفته تمرین هوازی بر بیان miR-223 و miR-92 مربوط به تراکم استخوان بود. روش‌‌ تحقیق: پژوهش حاضر از نوع نیمه‌‌تجربی با گروه کنترل بود که ۳۰ نفر از زنان سالمند با دامنه سنی 70-65 سال در دو گروه مساوی تجربی و کنترل به‌طور تصادفی تقسیم شدند. برنامه تمرین هوازی شامل دویدن با شدت حدود 57-05 درصد حداکثر ضربان قلب و مدت 45-25 دقیقه برای ۱۲ هفته (هفته ای سه جلسه) انجام شد. پیش و پس از مداخله، نمونه‌گیری خون برای سنجش شاخص‌های تحقیق انجام شد. بیان miR-223 و miR-92 از طریق روش Real Time-Pcr سنجش شد. از آزمون تحلیل کوواریانس در سطح معنی‌داری 0/05>p استفاده گردید. یافته‌‌ها: پس از 12 هفته تمرین هوازی بیان MiR-233 کاهش معنی‌دار (0/001=p، 29/60 درصد) و بیان miR-92 (0/001=p، 12/71 درصد) افزایش معنی‌دار نسبت به گروه کنترل نشان داد. نتیجه‌‌گیری: به نظر می‌‌رسد تمرین هوازی با شدت متوسط از طریق بهبود بیان miR-233 و miR-92 از کاهش تراکم استخوان در زنان سالمند جلوگیری می‌‌کند.

https://jpsbs.birjand.ac.ir/article_3905_2eb1c193684a7e0918b002217e014a09.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of resistance and continuous aerobic training on the collagen type I content and extracellular matrix proteins in the myocardial tissue of Dexamethasone‑induced female rats model تأثیر تمرین مقاومتی و تداومی هوازی بر محتوای کلاژن نوع 1 و پروتئین‌‌های ماتریکس خارج سلولی در بافت میوکارد مدل رت ماده القا شده با دگزامتازون 38 55 3241 10.22077/jpsbs.2025.8212.1912 FA نسیم عباسی فردهفشجانی د‌انشجوی د‌کتری فیزیولوژی ورزشی، د‌انشکد‌ه علوم ورزشی، د‌انشگاه شهید چمران اهواز، اهواز، ایران. عبدالحمید حبیبی استاد‌ گروه فیزیولوژی ورزشی، د‌انشکد‌ه علوم ورزشی، د‌انشگاه شهید چمران اهواز، اهواز، ایران. سعید شاکریان استاد‌ گروه فیزیولوژی ورزشی، د‌انشکد‌ه علوم ورزشی، د‌انشگاه شهید چمران اهواز، اهواز، ایران. علی اکبر علیزاده استادیار گروه فیزیولوژی ورزشی، دانشکده علوم ورزشی ، دانشگاه شهید چمران اهواز، اهواز، ایران. Journal Article 2024 09 30 Extended Abstract Background and Aim: Glucocorticoids are among the most commonly prescribed classes of drugs worldwide, so that the using of these drugs has steadily increased in recent years. Dexamethasone-induced hypertension is a well-recognized side effect that occurs following chronic administration in both animals and humans. Hypertension leads to cardiac remodeling characterized by pathological hypertrophy, reduced capillary density, and increased fibrosis. Cardiac fibrosis is a pathological extracellular matrix (ECM) remodeling process that results in abnormalities in the composition and quality of the matrix, as well as impaired myocardial function. However, excessive and persistent ECM deposition, particularly increased type I collagen secretion, could leads to tissue dysfunction. These drugs can affect cardiac tissue remodeling by disrupting the balance between matrix metalloproteinases and tissue inhibitors of metalloproteinases, resulting in ECM remodeling, cellular hypertrophy, collagen fiber accumulation, and ultimately restriction of normal organ function. Moreover, transforming growth factor-β1 (TGF-β1) is well established as one of the principal cytokines involved in the initiation and progression of the fibrotic process. Although antihypertensive treatments may lead to adverse effects and alter the clinical course of the disease, identifying safe and natural alternative therapies remains a primary objective. Exercise training, due to its compensatory and regulatory effects on biological systems, is widely used for the prevention and treatment of various diseases. Most researchers believe that regular physical activity may exert a negative regulatory or inhibitory effect on the TGF-β1 signaling cascade by influencing its activating factors. Consequently, regular exercise training is considered an effective non-pharmacological intervention for the control of hypertension and can attenuate pathological cardiac remodeling while improving arterial stiffness. Therefore, the present study aimed to investigate the effects of six weeks of resistance and continuous aerobic training on type I collagen content and ECM proteins in the myocardial tissue of female rats with Dexamethasone (DEX)-induced hypertension Materials and Methods: This experimental–laboratory study was conducted on 12 adult female Wistar rats with a mean age of four weeks and an average body weight of 200–250 g. The animals were housed under standard laboratory conditions with controlled temperature, humidity, and light–dark cycles, and had ad libitum access to food and water. The rats were randomly assigned into four equal groups including healthy control, DEX-induced control, DEX plus resistance training, and DEX plus continuous aerobic training. Hypertension was induced by subcutaneous injection of DEX at a dose of 0.1 mg per 100 g of body weight for 10 consecutive days. The resistance training protocol consisted of ladder climbing on an 80° incline with a length of 110 cm, during which a load equivalent to 60% of the animal’s body weight was attached to the tail, that follow with three sessions per week for six weeks. In contrast, the continuous aerobic training protocol involved treadmill running at moderate intensity, progressively increasing from 60% to 70% of the animals’ maximal running speed over the same training period. At the end of the training intervention, the animals were anesthetized using appropriate anesthetic agents and subsequently sacrificed. In this way, the left ventricle was excised from the heart tissue for analysis. Following tissue extraction, the protein levels of type I collagen, matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-1 (TIMP-1), and TGF-β1 were quantified using Western blotting and enzyme-linked immunosorbent assay (ELISA) techniques. For statistical analysis, the Shapiro–Wilk test was applied to assess data normality, and Levene’s test was used to evaluate the homogeneity of variances. In addition, one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test was employed to determine significant differences among groups. The level of statistical significance was set at p<0.05. Findings: The DEX induced lead to significant reduction in body weight (p=0.001) and a decrease in MMP-2 protein levels (p=0.001), whereas the protein levels of type I collagen (p=0.001), TIMP-1 (p=0.001), and TGF-β1 (p=0.001) were significantly increased. Moreover, MMP-2 protein levels increased in both exercise-trained groups compared with the Dex-induced control group (p=0.001); however, continuous aerobic training showed a significantly greater increase in this marker (p=0.03). Moreover, TIMP-1 levels decreased in both exercise-trained groups compared to Dex-induced control group (p=0.001); while in the aerobic continuous training and resistance training groups indicated significantly reduction as compare to control group (p=0.02). On the other hand, type I collagen was reduced in both exercise groups (p=0.001), with no significant difference between the training modalities (p=0.95). In addition, TGF-β1 levels decreased in both exercise groups compared to Dex-induced control group (p=0.001); however, no significant difference was observed between the two exercise interventions (p=0.43). Conclusion. It is believed that exercise could inhibit TGF-β/Smad3 signaling pathway by up-regulating the expression of cardiac endotelial proginator cells-derived exosomal miR-126, thereby weakening the trans differentiation of cardiac fibroblasts into myofibroblasts and reduce the production of collagen fibers. Also, the mechanism of the action of MMP- 2 was different according to the type of training and its adaptation in muscle and cardiomyocytes. In this way, two possibilities can be considered in regarding to the aerobic training, first that the response of MMPs is transitory, because the peak of changes occurred during or during the first few hours after training, and secondly, the induction mechanism may be related to exercise (strength training) and intensity of exercises that indicates the effect of different types of exercise (with diverse methods) on mechanisms of angiogenesis and regeneration of ECM factors in different tissues. Researchers believe that regular exercise can create negative or blocking regulation in the TGF-β signaling cascade by affecting its activating factors. Reducing the expression of TGF-β and inhibiting its signaling pathway also can reduce the expression of genes involved in the production of ECM collagen. Moreover, performing long-term resistance training could increases the antioxidant capacity of the muscle. The occurrence of this training adaptation can lead to a decrease in the expression of this factor after a period of training. Since the molecular and genetic adaptation mechanisms induced by resistance and aerobic training are different, therefore based on the each type of exercise, a set of cellular signaling pathways and specific genes are activated. Therefore, regular exercise training is an effective non-pharmacological treatment for controlling high blood pressure and can reduce pathological cardiac remodeling and improve arterial stiffness. The results of this study also emphasize the importance of targeted exercise training as a safe, low-cost, non-pharmacological alternative for the prevention, control, and management of blood pressure. Ethical Considerations: All ethical principles in this research were meticulously adhered to by the researchers and approved by the ethics commitee of the Shahid Chamran university of Ahvaz (IR.SCU.REC.1402.037). Funding: The authors of this article declare that they have not received any financial support from any organization. Conflicts of interest: The authors report no conflicts of interest in relation to this manuscript. زمینه و هدف: استفاده از گلوکوکورتیکوئیدها با انواع اثرات نامطلوب قلبی-عروقی از جمله احتباس مایعات، فشار خون بالا، بیماری آترواسکلروتیک زودرس و آریتمی همراه است. هدف از این مطالعه بررسی اثر شش هفته تمرین مقاومتی و تداومی هوازی بر محتوای کلاژن نوع 1 و پروتئین‌های ماتریکس خارج سلولی در بافت میوکارد رت‌‌های ماده مدل القا شده با دگزامتازون بود. روش تحقیق: تعــداد 12 ســر رت ماده بـا سـن چهار هفتـه‌‌ای بـه‌‌طـور تصادفـی در چهار گروه کنترل سالم، کنترل القا شده با دگزامتازون، تمرین مقاومتی+دگزامتازون و گروه تمرین تداومی+دگزامتازون قرار گرفتند. برنامـه تمریـن مقاومتـی شـش هفتـه بـا سـه نوبـت و هـر نوبـت 20-14 بـار بـالا رفتـن از نردبـان یـک متـری (بـا 26 پلـه) بـا حمـل وزنـه بـود. پروتکل تمرین تداومی شامل دویدن روی نوارگردان با شدت متوسط و به‌صورت افزایشی از ۶۰ تا ۷۰ درصد حداکثر ظرفیت سرعت حیوان، در مدت مشابه انجام شد. محتوی کلاژن نوع 1، ماتریکس متالوپروتئیناز-2 (MMP-2) و مهارکننده بافتی متالوپروتئیناز-1 (TIMP-1) در بطن چپ بافت میوکارد پس از تمرین، با روش وسترن بلات؛ و عامل رشد تغییر شکل دهنده بتا-1 (TGF-β1) با روش الایزا اندازه‌‌گیری شدند. برای تجزیه و تحلیل داده‌‌ها از روش تحلیل واریانس یک‌‌راهه و آزمون تعقیبی توکی در سطح معنی‌‌داری 05/0≥p استفاده شد. یافته ها: تزریق دگزامتازون در سه گروه موجب کاهش معنی‌‌دار پروتئین MMP2 و افزایش معنی‌‌دار محتوای کلاژن نوع 1، TIMP1 و TGF-β1 نسبت به گروه کنترل سالم شد؛ اما هر دو نوع تمرین، موجب افزایش معنی‌‌دار MMP-2 و کاهش معنی‌‌دار کلاژن نوع 1، TIMP1 و TGF-β1 گردید. نتیجه گیری: به‌‌نظر می‌‌رسد که تمرینات تداومی هوازی و مقاومتی می‌‌تواند همزمان با افزایش فعالیت MMP2 و کاهش محتوای پروتئین کلاژن 1، TGF-β1 و TIMP-1 در بطن چپ رت‌‌ها، یک اثر محافظتی بر ساختار و عملکرد بطن قلبی داشته باشد.

https://jpsbs.birjand.ac.ir/article_3241_4474b6330d10bf3c8db60fea75032a9f.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of combined training (aerobic and resistance) on the expression of Bax and VEGF indices in the cardiac of male rats following chronic methamphetamine administration تأثیر تمرین ترکیبی (هوازی و مقاومتی) بر بیان شاخص‌‌های Bax و VEGF در قلب رت‌‌های نر متعاقب مصرف مزمن مت‌‌آمفتامین 56 71 2702 10.22077/jpsbs.2023.6516.1805 FA حمید رضا سلیمی دانشجوی دکتری فیزیولوژی ورزش، دانشکده علوم ورزشی، دانشگاه حکیم سبزواری، سبزوار، ایران. 0000-0003-4747-8784 امیر حسین حقیقی استاد گروه فیزیولوژی ورزش، دانشکده علوم ورزشی، دانشگاه حکیم سبزواری، سبزوار، ایران. شیما آب آب زاده دانشیار گروه مهندسی بافت و علوم سلولی کاربردی، مرکز تحقیقات سلولی و مولکولی، دانشکده پزشکی، دانشگاه علوم پزشکی قم، قم، ایران. حمید معرفتی دانشیار گروه فیزیولوژی ورزش، دانشکده علوم ورزشی، دانشگاه حکیم سبزواری، سبزوار، ایران. Journal Article 2023 06 22 Extended Abstract Background and Aim: Methamphetamine abuse is associated with severe cardiovascular complications, including myocardial infarction, stroke, and increased risk of mortality. One of the fundamental mechanisms contributing to such pathological conditions is stress-induced cell death, which occurs primarily through necrosis and apoptosis. Apoptosis, or programmed cell death, is an active and regulated biological process that plays a crucial role in maintaining the balance between cell survival and death in various tissues, particularly in somatic tissues such as the brain, skeletal muscle, and myocardium. Among the agents capable of inducing apoptotic cell death are opioids and psychostimulants, including methamphetamine. Methamphetamine exerts detrimental and potentially fatal effects on the cardiovascular system, such as hypertension, acute vasospasm, and accelerated atherosclerosis. Despite these known outcomes, the molecular mechanisms underlying methamphetamine-induced cardiovascular injury and associated pathological responses remain poorly understood. Therefore, the present study aimed to investigate the effects of combined exercise training on the expression of Bax (Bcl-2-associated X protein) and vascular endothelial growth factor (VEGF) in the cardiac tissue of male rats following chronic methamphetamine administration. Materials and Methods: This experimental-applied study was conducted on 30 male Wistar rats (8 weeks old; 200–210 g) to examine the effects of two factors on apoptosis-related markers in cardiac tissue. Animals were housed under standard laboratory conditions with free access to food and water, a 12:12-h light–dark cycle, and a controlled temperature of 23±2 °C. Rats were randomly assigned to groups based on body weight homogeneity. Ten rats were allocated to the control group and received intraperitoneal injections of normal saline for 23 consecutive days. The remaining 20 rats received intraperitoneal injections of methamphetamine for 23 days. Methamphetamine administration followed a previously established protocol, with gradually increasing doses ranging from 2.5 to 10 mg/kg. After the addiction period, methamphetamine-treated rats were randomly divided into two groups (n=10 each): a sham (addicted) group and an addicted+combined training group. The combined training protocol was performed for 6 weeks, 6 days per week, and consisted of alternating aerobic and resistance exercise sessions. Aerobic training was conducted on a motorized treadmill for laboratory animals at an intensity of 50–60% of maximal running speed. Resistance training was performed using a specialized ladder-climbing apparatus designed for rodents, with an intensity corresponding to 50–60% of one-repetition maximum (1RM). To determine training intensities, rats underwent a 24-hour familiarization period with the equipment, followed by an incremental treadmill exhaustion test to assess maximal aerobic capacity and a maximum strength test to establish baseline resistance loads. At the end of the intervention period, cardiac tissue samples were collected. Bax protein expression was assessed using immunohistochemistry, a technique that enables the detection of specific cellular antigens through antigen–antibody binding. Vascular endothelial growth factor (VEGF) gene expression was evaluated using reverse transcription polymerase chain reaction (RT-PCR). Following cardiac tissue excision, total RNA was extracted, and VEGF expression levels were analyzed using a gene expression analysis system to determine the effects of methamphetamine exposure and combined exercise training. Data were analyzed using one-way ANOVA followed by Bonferroni post hoc test in SPSS version 26 at a significance level of p<0.01. Findings: Immunohistochemical analysis revealed that intraperitoneal administration of methamphetamine significantly increased Bax protein expression in cardiac tissue in the sham (addicted) group compared with the control group. In contrast, Bax expression was markedly reduced in the combined training group relative to the sham group. Analysis of VEGF gene expression demonstrated significant differences among groups (p<0.01). Methamphetamine administration in the sham group resulted in a significant decrease in VEGF expression compared with both the control and combined training groups. Conversely, the combined exercise group exhibited a significant increase in VEGF expression compared with the control (p<0.001) and the sham (p<0.0001) group (Figure 1). Conclusion: Immunohistochemical findings demonstrated that Bax expression was significantly elevated in the sham (methamphetamine-dependent) group compared with both the control and combined training groups, whereas combined aerobic–resistance training markedly attenuated Bax expression. Apoptosis mediated by Bax occurs when cellular stress induces Bax translocation from the outer to the inner mitochondrial membrane, triggering cytochrome C release. This process promotes apoptosome formation through interaction with caspase-9 and apoptotic protease-activating factor-1 (Apaf-1), leading to downstream caspase activation and programmed cell death. In contrast, VEGF expression was significantly reduced following methamphetamine administration, while combined training effectively restored and enhanced VEGF expression. Cardiomyocytes represent a major source of VEGF, a key cytokine involved in regulating vascular permeability, angiogenesis, and cell survival through anti-apoptotic mechanisms, including the upregulation of Bcl-2. The observed reduction in Bax expression following exercise training may therefore be attributed to increased Bcl-2 expression, as previously reported with regular exercise, and/or to improvements in antioxidant capacity. Indeed, moderate-intensity exercise has been shown to enhance total antioxidant status and suppress apoptotic signaling pathways in methamphetamine-dependent models. Overall, the present findings indicate that chronic methamphetamine exposure impairs cardiomyocyte function by promoting apoptotic signaling. However, combined exercise training emerges as an effective, non-invasive intervention capable of mitigating methamphetamine-induced cardiac apoptosis. Despite these therapeutic benefits, primary prevention of exposure to toxic stimulants remains a critical priority for public health. Compliance with ethical guideline: This study was conducted in compliance with all ethical principles of animal care and laboratory procedures, and was approved by the Ethics Committee of Qom University of Medical Sciences under the ethical code IR.MUQ.AEC.1400.007 at the Animal Care Center and the Cellular and Molecular Research Center of Qom University of Medical Sciences. Funding: This article was produced without financial support. Conflict of Interest: The authors declare that they have no conflict of interest in this study. زمینه و هدف: سوء مصرف مت‌‌آمفتامین سبب انفارکتوس میوکارد، سکته‌‌ مغزی و حتی مرگ مصرف‌‌کنندگان می‌‌شود. هدف از این پژوهش بررسی اثر تمرین ترکیبی بر بیان شاخص‌‌های Bax (پروتئین چهار شبه لنفوم دو لنفوسیت‌های بی) و VEGF (عامل رشد اندوتلیال عروقی) در قلب رت‌‌های نر متعاقب مصرف مزمن مت‌‌آمفتامین بود. روش تحقیق : در این مطالعه تجربی،30 رت با وزن 210-200 گرم به‌طور تصادفی به سه گروه مساوی شامل کنترل، شم (معتاد) و معتاد+تمرین ترکیبی تقسیم شدند. جهت ایجاد وابستگی، مت‌‌آمفتامین به گروه‌‌های شم و ترکیبی، به شکل درون صفاقی تزریق شد. تمرین ترکیبی شامل سه روز دویدن روی نوارگردان (با شدت 50 تا 60 درصد حداکثر سرعت) و سه روز تمرین مقاومتی روی نردبان (با شدت50 تا 60 درصد یک تکرار بیشینه‌‌) بود که به مدت شش هفته اجرا شد. پس از 24 ساعت از آخرین جلسه‌‌ی تمرین، حیوانات قربانی شدند و در بافت قلب، بیان Bax با روش ایمونوهیستوشیمی و بیان VEGF با روش Real-Time PCR سنجش شد. داده‌‌های تحقیق با آزمون تحلیل واریانس یک‌‌راهه و تعقیبی بونفرونی و نرم افزار SPSS نسخه‌‌ی 26 در سطح معنی‌داری 01/0>p تجزیه و تحلیل شدند. یافته‌‌ها: در گروه شم، بیان Bax افزایش معنی‌دار و بیان VEGF کاهش معنی‌‌داری (001/0>p) نسبت به گروه کنترل داشت. در گروه تمرین ترکیبی بیان Bax نسبت به گروه شم کاهش معنی‌‌دار، و بیان VEGF نسبت به دو گروه شم (0001/0>p) و کنترل (001/0>p) افزایش معنی‌‌داری نشان داد. نتیجه‌‌گیری: مصرف مزمن مت‌آمفتامین با افزایش بیان Bax و کاهش بیان VEGF سبب تشدید آپوپتوزیس در بافت قلب شد، در حالی‌که تمرین ترکیبی با تنظیم کاهشی Bax و تنظیم افزایشی VEGF، اثرات آپوپتوتیک ناشی از مت‌آمفتامین را به‌طور معنی‌داری مهار کرد.

https://jpsbs.birjand.ac.ir/article_2702_039579099eb2c0e4624cee4ba12d4d68.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of eight weeks of resistance training on serum levels of B-type natriuretic peptide and cardiac creatine kinase in elderly men with type 2 diabetes تأثیر هشت هفته تمرین مقاومتی بر مقادیر سرمی پپتید ناتریورتیک نوع B و کراتین کیناز قلبی در مردان سالمند مبتلا به دیابت نوع دو 72 85 3786 10.22077/jpsbs.2025.8722.1940 FA ابراهیم رنگرز استادیار گروه علوم ورزشی، دانشگاه آزاد اسلامی واحد بوئین زهرا، بوئین زهرا، ایران. 0000-0002-3729-4546 ملیحه اردکانی زاده استادیار گروه علوم ورزشی، دانشکده علوم انسانی، دانشگاه دامغان، دامغان، ایران. Journal Article 2025 01 08 Extended Abstract Background and Aim: Cardiovascular diseases are the leading cause of mortality among patients with type 2 diabetes mellitus (T2DM). Chronic hyperglycemia in these patients contributes to myocardial damage, often through the development of atherosclerosis and increased arterial stiffness. Creatine kinase–myocardial band (CK-MB or CK2), an enzyme that catalyzes the transfer of phosphate from phosphocreatine to ADP to regenerate ATP, has been shown to increase approximately six hours after cardiac injury. Additionally, N-terminal pro–B-type natriuretic peptide (NT-proBNP) is recognized as a cardiac neurohormone whose plasma levels rise in patients with ventricular systolic and diastolic dysfunction. This hormone is synthesized in the ventricles and released as proBNP, which is subsequently cleaved enzymatically into NT-proBNP and BNP in response to ventricular myocyte stretch. Rangarz et al. (2019) reported a reduction in BNP levels following eight weeks of resistance training in elderly men, whereas Bordbar et al. (2012) observed a significant increase in BNP after a similar training period. Conversely, other studies have reported no significant changes in BNP levels after 12 weeks of resistance training. Similarly, Saremi et al. (2016) reported elevated CK-MB levels in young women following strength training, and Ghanbari Niaki et al. (2019) demonstrated a significant increase in serum CK-MB after eight weeks of circuit resistance training in sedentary young men. In contrast, Bang et al. (2017) observed no changes in CK-MB levels following eight weeks of resistance training in trained men. The American Diabetes Association recommends regular physical activity as an effective strategy for managing diabetes-related complications. Researchers believe that regular exercise improves heart muscle function, resulting in adaptation and increased myocardial tolerance to cardiac damage. Resistance training has beneficial effects on the cardiovascular system and may serve as a potential therapeutic approach for patients with cardiac conditions. However, given the possibility of elevated cardiac CK levels following resistance exercise, this training modality has been less extensively investigated. Therefore, the aim of the present study was to investigate the effects of an eight-week resistance training program on serum levels of NT-proBNP and CK-MB in elderly patients with type 2 diabetes by comparing post-intervention values with baseline measurements and with a non-training control group. This investigation may help clarify the safety and cardiovascular implications of resistance training as a lifestyle intervention in this population. Materials and Methods: This semi-experimental study was conducted on elderly men with T2DM attending the Kahrizak elderly care center in Alborz province (mean age: 71.7±6.6 years; weight: 74.1±13.5 kg; body mass index: 26.7±4.4 kg/m²). Twenty-four participants were randomly assigned to either a control group (no exercise training; n=12) or a training group (resistance training; n=12). Baseline blood samples were collected one week prior to the intervention after 12 hours of overnight fasting. Post-test samples were obtained at the end of the eight-week intervention, 24 hours after the last training session, and again after 12 hours of fasting. The training group performed resistance exercises for eight weeks, three sessions per week. Each session included 10 minutes of warm-up (jogging or cycling), a main exercise segment consisting of eight movements performed in three sets of 10 repetitions at 70% of one-repetition maximum (1RM), and five minutes of cool-down stretching. Serum CK-MB levels were measured using a Pars Azmoun kit via the colorimetric method (sensitivity: 5 U/L) with a Hitachi 917 analyzer (Japan). Serum NT-proBNP levels were assessed using the sandwich ELISA method with a Zelbio (Germany) kit (sensitivity: 2.5 ng/L). Statistical analyses were performed using SPSS software (version 24). Analysis of covariance (ANCOVA) was applied to assess between-group differences, with statistical significance set at p≤0.05. Findings: Serum NT-proBNP levels in the training group decreased significantly following the intervention compared with baseline (F=91.55, p=0.001). In addition, post-intervention NT-proBNP concentrations were significantly lower in the resistance training group than in the control group (F=2.12, p=0.04) (Figure 1A). Serum CK-MB levels also showed a significant reduction in the training group compared with pre-training values (F=20.21, p=0.001). Although CK-MB levels decreased compared with the control group, this change was not statistically significant (F=1.87, p=0.06) (Fig. 1B). Conclusion: The observed reduction in serum NT-proBNP levels in the resistance training group suggests that exercise-induced increases in myocardial muscle mass may reduce ventricular wall stress, thereby decreasing NT-proBNP secretion. Because BNP production is stimulated by ventricular pressure overload and impaired systolic function, lower circulating levels may reflect improved cardiac performance following resistance training. Although aging and diabetes negatively affect cardiac performance, resistance training may also cause localized muscle damage, potentially involving the sarcolemma, basement membrane, contractile elements, and cytoplasm. Elevated CK-MB, along with CK and cardiac troponins, has been reported as a possible marker of myocardial injury. Factors such as exercise intensity, duration, and prior physical inactivity may influence CK-MB responses. Increases in cardiac workload during exercise, particularly in individuals with compromised health, may lead to ventricular hypertrophy and altered cardiac structure. Some studies have reported significant elevations in CK-MB following resistance training in previously untrained middle-aged men. Although the NT-proBNP improved by resistance training, but it seems that the CK-MB elevation attenuate the prospects for prevention of myocardial infraction. Therefore, it is suggested that with the application of healthy diet and exercise training the greater emphasis should be placed on prevention of diseases such as diabetes. Compliance with ethical guidelines: The study was approved by the Ethics Committee of Islamic Azad University, Buin Zahra Branch (Ethics code: IRCT20180819040831N1). Funding: This research received no specific grant from public, commercial, or not-for-profit funding agencies. Authors contributions: The first author was responsible for study conception, design, data collection, analysis, and manuscript editing. The second author contributed to study conception, design, and manuscript writing. Conflicts of interest: The authors declare no conflicts of interest. Acknowledgements: The authors sincerely thank all individuals who contributed to the conduct of this study. زمینه و هدف: آسیب و نارسایی قلبی یکی از جنبه‌‌های بیماری دیابت نوع دو است، که ممکن است با اجرای تمرینات مقاومتی کاهش پیدا کند، بنابراین هدف از پژوهش حاضر بررسی تأثیر تمرینات مقاومتی بر مقادیر پپتید ناتریورتیک نوع B و کراتین کیناز قلبی در مردان سالمند دیابتی بود. روش تحقیق: تعداد 24 مرد سالمند (78-65 ساله) مبتلا به دیابت نوع دو (شاخص توده بدن: 4/4 ± 7/26 کیلوگرم/متر مربع) به‌‌طور تصادفی به دو گروه (12 نفری) کنترل و تمرین مقاومتی تقسیم شدند. تمرین مقاومتی به مدت هشت هفته و سه جلسه در هر هفته با 50 تا 70 درصد یک تکرار بیشینه اجرا گردید. خونگیری در دو مرحله پیش و پس از مداخله تمرین انجام شد، مقادیر پپتید ناتریورتیک نوع B به روش کمی لومینسانس و الایزای ساندویچی و کراتین کیناز قلبی به روش رنگ سنجی اندازه‌‌گیری گردید، و تجزیه و تحلیل داده‌‌ها به روش تحلیل کوواریانس توسط SPSS نسخه 24 انجام گردید، و سطح معنی‌‌داری 05/p≤0 در نظر گرفته شد. یافته‌‌ها: پس از اجرای هشت هفته تمرین مقاومتی سطوح پپتید ناتریورتیک نوع B‌‌ در مقایسه با گروه کنترل کاهش معنی‌‌داری یافت (001/p=0)؛ اما مداخله هشت هفته‌‌ای تمرین مقاومتی در مردان سالمند دیابتی موجب افزایش مقادیر کراتین کیناز قلبی سرم آن‌‌ها در مقایسه با پیش از تمرین گردید (001/p=0)، اما در مقایسه با گروه کنترل تفاوت معنی‌‌داری مشاهده نشد (06/p=0). نتیجه‌‌گیری: به‌‌نظر می‌‌رسد که هرچند اجرای هشت هفته تمرین مقاومتی تأثیر معنی‌‌داری بر کاهش سطوح پپتید ناتریورتیک نوعB مردان سالمند دیابتی دارد، اما منجر به افزایش معنی‌‌دار سطوح کراتین کیناز قلبی آن‌‌ها می‌‌گردد، که ممکن است اثر سودمندی بر وضعیت قلبی این بیماران نداشته باشد.

https://jpsbs.birjand.ac.ir/article_3786_726f5a054deec7e2222bafc33b9c223d.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of moderate-intensity interval training combined with nanoemulsified betaine supplementation on the expression of the inflammatory gene CD28 in hepatocyte cells, serum urea, creatinine levels, and lipid profile of obese mice تاثیر تمرین تناوبی با شدت متوسط به ‌همراه مکمل بتائین نانوامولسیفیه بر بیان ژن التهابی CD28 در سلول‌های هپاتوسیتی، سطوح سرمی اوره، کراتینین و نیمرخ چربی موش‌های چاق 86 103 3420 10.22077/jpsbs.2025.8814.1945 FA مهدیه پورسلطانی زرندی دانشجوی دکتری فیزیولوژی ورزش، دانشکده فرهنگ و ارتباطات، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران. امیر سرشین استادیار گروه فیزیولوژی ورزش، دانشکده فرهنگ و ارتباطات، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران. علیرضا رحیمی دانشیار گروه فیزیولوژی ورزش، دانشکده فرهنگ و ارتباطات، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران. فواد فیض الهی استادیار گروه فیزیولوژی ورزش، دانشکده فرهنگ و ارتباطات، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران. Journal Article 2025 01 23 Extended Abstract Background and Aim: Obesity, resulting from a chronic imbalance between energy intake and energy expenditure, is widely increasing and is considered a major risk factor for numerous pathological conditions. Excessive energy intake—particularly from high fat diets—leads to abnormal accumulation of triglycerides (TG) within hepatocytes, promoting hepatic steatosis and the development of non-alcoholic fatty liver disease (NAFLD). Obesity often leads to chronic low-grade inflammation, increased insulin resistance, and metabolic disorders in adipose tissue and liver. The CD28 protein acts as a co-stimulatory receptor essential for the full activation of T lymphocytes and plays an important role in the induction of low-grade inflammation in obesity. Exercise is considered a major regulator of liver metabolism by stimulating beta-oxidation and reducing lipogenesis. Studies have shown that choline and betaine supplementation can reduce hepatic steatosis by reducing hepatic and blood TG levels and stimulating lipolysis. Given the established benefits of aerobic exercise in improving hepatic lipid metabolism and inflammatory status, along with emerging evidence supporting the fat-reducing and anti-inflammatory effects of betaine, a combined intervention may exert synergistic benefits. These effects may be mediated, at least in part, through modulation of inflammation-related pathways, particularly CD28 signaling. However, the interactive effects of aerobic exercise and betaine supplementation on these parameters in obesity remain largely unexplored, and existing findings regarding their independent effects are inconsistent. Therefore, the present study aimed to investigate the combined effects of moderate-intensity interval training and nanoemulsified betaine supplementation on hepatic CD28 gene expression, serum urea and creatinine levels, and lipid profile in obese mice. Materials and Methods: In this experimental study, 25 male Wistar rats (8 weeks old; body weight 270±20 g) were housed in special cages in an environment with an average temperature of 22±1.4 °C, humidity of 55±4%, and a light-dark cycle of 12:12 h. All animals had free access to water and special rat food. They were then randomly divided into 5 groups (5 rats in each group) including healthy, obese, obese+supplement, obese+exercise, and obese+supplement+exercise. Obesity was induced by feeding the designated groups a high-fat, high-cholesterol diet for 12 weeks. To confirm obesity induction, blood samples were collected from the tail vein at the end of the dietary intervention and prior to the commencement of exercise and supplementation protocols. Following obesity induction, rats in the exercise groups performed moderate-intensity interval aerobic training on a motorized treadmill for 8 weeks, 5 days per week, with progressive overload. During the first week, the protocol consisted of 10 intervals of 1-min running at 10 m/min, interspersed with 2-min active recovery at 5 m/min. Running speed during the work intervals was gradually increased, reaching 16 m/min by weeks 4–8. Nanoemulsified betaine was prepared using high-amplitude ultrasonication to enhance serum stability and bioavailability. The supplement was administered via oral gavage at a dose of 50 mg/kg body weight prior to each exercise session. Rats in the obese+supplement+exercise group received both interventions. At the end of the intervention period, hepatic tissue samples were collected for analysis of CD28 gene expression using quantitative real-time PCR (qRT-PCR). Serum lipid profile, including total cholesterol (TC), TG, low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), was measured using standard enzymatic assays. Serum urea and creatinine levels were also assessed as indicators of renal function. Data were analyzed using independent t, two-way ANOVA, and Bonferroni post hoc tests at a significance level of p≤0.05. Results: Independent t-test analysis demonstrated that obesity significantly increased hepatic CD28 gene expression, TG, TC, LDL-C, and creatinine (p=0.0001) serum, as well as urea levels (p=0.02), while significantly decreasing HDL-C levels (p=0.0001). Two-way ANOVA results (Table 1), followed by Bonferroni post hoc tests, revealed that 8 weeks of moderate-intensity interval training significantly reduced CD28 gene expression in obese rats (p=0.0001). This training intervention also resulted in significant reductions in TG, TC, LDL-C, and creatinine (p=0.0001), as well as urea (p=0.002) levels, accompanied by a significant increase in HDL-C (p=0.01). Similarly, supplementation with nanoemulsified betaine led to a significant decrease in CD28 gene expression (p=0.0001), TG, TC, LDL-C, and creatinine levels (p=0.0001), along with a significant increase in HDL-C (p=0.01). However, nanoemulsified betaine supplementation did not significantly affect serum urea levels in obese rats. Furthermore, two-way ANOVA and Bonferroni post hoc analyses indicated a significant interaction effect between moderate-intensity interval training and nanoemulsified betaine supplementation on CD28 expression (p=0.04), LDL-C (p=0.0001), TC (p=0.0001), and creatinine (p=0.005) levels. No significant interaction effect was observed for serum urea levels. Conclusion: The findings of the present study demonstrate that interval aerobic training and nanoemulsified betaine supplementation, each alone, reduced TG, TC, LDL-C levels and increased HDL-C. Aerobic training (especially moderate intensity) increases muscle TG utilization and leads to improved fat oxidation. In addition, nanoemulsified betaine supplementation effectively reduced hepatic and circulating TG levels, likely through the stimulation of lipolysis and hepatic β-oxidation, which may attenuate fat accumulation in the liver of obese subjects. The results further indicate that both interval aerobic training and nanoemulsified betaine supplementation, individually and synergistically, significantly reduced CD28 gene expression, a key marker associated with obesity-related inflammation. The underlying mechanisms through which the combined intervention exerts its beneficial effects on fat mass and inflammatory status may involve improved regulation of lipid metabolism, reduced insulin resistance, and enhanced mitochondrial function. Notably, the combined application of moderate-intensity interval training and nanoemulsified betaine supplementation was particularly effective in modulating CD28 gene expression, highlighting its potential role in attenuating inflammatory signaling pathways associated with obesity. Furthermore, the significant improvements in lipid profiles and the reduction in serum creatinine levels support the modulatory effects of this combined intervention on obesity-induced metabolic disturbances and renal dysfunction. Overall, the observed interactive effects between exercise training and nanoemulsified betaine supplementation suggest that this combined approach may serve as a safe, practical, and non-pharmacological strategy for the prevention and management of metabolic complications associated with obesity through the modulation of metabolic pathways and inflammation-related cellular signaling. Ethical Considerations: Ethical approval was obtained from the Ethics Committee of Islamic Azad University, Karaj Branch (Code: IR.IAU.K.REC.1403.65). Funding: This research received no external funding. All study-related costs were covered by the researcher. Conflict of Interest: The authors declare no conflicts of interest چکیده زمینه و هدف: افزایش شیوع چاقی و بیماری‌های همراه آن، ازجمله دیابت و کبد چرب، بیانگر اهمیت تمرین منظم به‌ عنوان یک راهبرد درمانی در کنترل چاقی است. افزون بر این، شواهد موجود حاکی از آن است که بتائین از طریق تعدیل متابولیسم چربی و گلوکز کبدی می‌تواند در بهبود چاقی مؤثر باشد. هدف این پژوهش بررسی تأثیر همزمان تمرین تناوبی با شدت متوسط به‌ همراه مکمل بتائین نانوامولسیفیه بر بیان ژن التهابی CD28 در سلول‌های هپاتوسیتی، سطوح سرمی اوره، کراتینین و نیمرخ چربی موش‌های چاق بود. روش تحقیق: در این مطالعه تجربی، ۲۵ سر موش صحرایی نر نژاد ویستار به پنج گروه مساوی سالم، چاق، چاق+مکمل، چاق+تمرین، چاق+مکمل+تمرین تقسیم شدند. موش‌های چاق به مدت شش هفته با رژیم پرچرب تغذیه شدند. تمرین تناوبی شامل دویدن روی نوارگردان به مدت ۳۰ دقیقه و پنج روز در هفته، همراه با افزایش تدریجی شدت، به مدت هشت هفته انجام شد. گاواژ مکمل بتائین نانوامولسیفیه (۵۰ میلی‌گرم/کیلوگرم وزن بدن) قبل از تمرین انجام گرفت. در پایان، بیان ژن CD28 با روش Real-Time PCR و سطوح سرمی کراتینین، اوره، تری‌گلیسرید، کلسترول تام (TC)، لیپوپروتئین کلسترول با چگالی کم (LDL-C) و لیپوپروتئین کلسترول با چگالی بالا (HDL-C) با بهره‌گیری از روش‌های استاندارد آزمایشگاهی اندازه‌گیری شد. داده‌ها با استفاده از آزمون‌های آماری t مستقل و تحلیل واریانس دو‌عاملی در سطح معنی‌داری 0/05 ≥p تجزیه و تحلیل شدند. یافته‌ها: چاقی موجب افزایش معنی‌دار میزان تری‌گلیسرید، TC، LDL-C، بیان ژن CD28، سطوح کراتینین (0/0001=p) و اوره (0/02=p) و موجب کاهش معنی‌دار HDL-C شد (0/0001=p). تمرین و مکمل هر کدام به‌طور مستقل منجر به کاهش معنی‌دار بیان CD28 (0/0001=p)، TG، TC، LDL-C و سطوح کراتینین (0/0001=p) و افزایش معنی‌دار میزان HDL-C (0/01=p) شدند. در تعامل تمرین و مکمل، نیز اثر آماری معنی‌داری بر CD28 (0/04=p)، LDL-C (0/0001=p)، TC (0/0001=p) و سطوح کراتینین (0/005=p) مشاهده شد. نتیجه‌‌گیری: تمرین هوازی با شدت متوسط و مکمل بتائین نانوامولسیفیه، به‌ صورت مستقل و ترکیبی، از طریق تأثیر بر شاخص‌های لیپیدی، التهابی و عملکرد کلیوی؛ می‌تواند در کاهش اثرات سوء چاقی در موش‌ها مؤثر باشد.

https://jpsbs.birjand.ac.ir/article_3420_9dcdd2488b088ad5f74e203a00720d85.pdf

دانشگاه بیرجند مطالعات کاربردی علوم زیستی در ورزش 2383-0182 14 37 2026 03 21 The effect of resistance and high intensity interval training on the expression of Semaphorin 3C and Lipocalin 2 in the subcutaneous fat tissue of obese elderly rats تأثیر تمرینات مقاومتی و تناوبی شدید بر بیان سمافورین C3 و لیپوکالین 2 در بافت چربی زیرجلدی رت‌های سالمند چاق 104 119 3036 10.22077/jpsbs.2024.7690.1877 FA مینا تفضلی کارشناس ارشد فیزیولوژی ورزشی، گروه تربیت بدنی و علوم ورزشی، واحد بجنورد، دانشگاه آزاد اسلامی، بجنورد، ایران. صادق چراغ بیرجندی استادیار گروه تربیت بدنی و علوم ورزشی، واحد بجنورد، دانشگاه آزاد اسلامی، بجنورد، ایران. Journal Article 2024 05 28 Extended Abstract Background and Aim: Aging is a complex and gradual process that leads to a decline in physiological function and an increased the chronic diseases. Obesity, as a chronic inflammatory condition, is an accelerator of aging and could affects metabolism, appetite, insulin sensitivity, and fat distribution through the secretion of adipokines. Among adipokines, Semaphorin C3 (Sema3C) and Lipocalin 2 (LCN2) play an important roles in the pathophysiology of obesity and metabolic disorders. Studies have reported increased expression of these two proteins in conditions of obesity and aging. Despite nutritional and pharmacological treatments, exercise—particularly resistance training (RT), endurance training, and high-intensity interval training (HIIT)—has been identified as the most effective strategy for reducing the negative effects of obesity in old age. These exercises play a key role in improving metabolism and preventing premature aging by enhancing body composition, reducing inflammation, and regulating adipokines, including Sema3C and LCN2. The present study aims to to investigate the effects of RT and HIIT on the expression of these adipokines in the adipose tissue of obese aged mice. Materials and Methods: This experimental study was conducted on 30 elderly male Wistar rats (aged 20–22 months) at the Islamic Azad University, Bojnourd branch. The animals were maintained under controlled conditions: temperature of 25±3 C, humidity of 55–60%, and a 12:12 hour light-dark cycle for one week of acclimation. Following acclimation, to induce obesity, the rats were fed a high-fat diet (HFD) consisting of 40% fat, 13% protein, and 47% carbohydrate for eight weeks. Rats with a Lee index greater than 310 were designated as obese and randomly divided into three groups of 10: obese control (OC), RT, and HIIT. The RT protocol involved ladder climbing with a tail attachment, starting at 30% of body weight and progressively increasing up to 200% of body weight. The HIIT protocol consisted of short-duration sprints at 85–90% of maximal velocity interspersed with active recovery periods. Moreover, the control group underwent no exercise but was exposed to the sound of the treadmill motor only. Forty-eight hours after the final training session, and after an eight-hour of fasting, the rats were anesthetized, and subcutaneous fat samples were collected for RNA extraction and cDNA synthesis. The gene expression of Sema3C and LCN2 was quantified using Real-time-PCR, with β-Actin serving as the reference gene for normalization. The data were entered into SPSS version 25 and analyzed using descriptive statistics, Shapiro‑Wilk test (for normality), Levene’s test (for homogeneity of variances), one‑way analysis of variance (ANOVA), and Tukey’s post‑hoc test, with the significance level set at p≤0.05. Findings: The ANOVA test showed the expression of Sema3C (p=0.001), LCN2 (p=0.01), and the Lee index (p=0.001) were significant differences between the RT, HIIT, and OC groups. Moreover, the results of Tukey’s post hoc test indicated a significant difference between the RT and HIIT groups compared to the OC group in the dependent variables. Specifically, the expression of Sema3C (p=0.001), LCN2 (p=0.003), and the Lee index (p=0.001) were significantly decreased in the training groups compared to the OC group. However, no significant differences were observed between the RT and HIIT groups in the expression of Sema3C (p=0.12), LCN2 (p=0.08), and the Lee index (p=0.10). Conclusion: The results of this study demonstrated that eight weeks of both RT and HIIT led to a significant down regulation in the gene expression of Sema3C and LCN2, alongside a meaningful reduction in the Lee index in obese aged male rats. The Sema3C gene, a member of the Class 3 semaphorin family, is recognized as a novel adipokine that is implicated in body weight alterations, insulin resistance, and adipose tissue structure. Limited research has previously explored the direct effect of exercise on Sema3C. The current findings align with reports from Supriya et al. (2023) and Saeedi et al. (2023), who documented a significant decrease in Sema3C expression following twelve weeks of CrossFit or high-intensity functional training in obese human subjects. Furthermore, other existing literature indicates that endurance and HIIT exercise protocols are associated with reduced levels of related Semaphorins, such as Sema3A, Sema3B, and Sema3G, in laboratory animals, contributing to improved metabolic parameters (Liu et al., 2020; Ghadiri Haramati et al., 2017). Therefore, it is hypothesized that the reduction observed in Sema3C and other semaphorins primarily results from the decrease in overall fat mass, given that adipose tissue serves as the main secretory source for these adipokines. Conversely, the LCN2 gene is recognized as a key inflammatory marker and an oxidative stress response factor whose levels typically escalate in conditions of obesity, aging, and metabolic diseases. The observation in this research of a decrease in LCN2 expression is consistent with reports by Esmaeili et al. (2018) and Fattahpour Marandi et al. (2023), also noted a significant reduction following aerobic and RT protocols. A potential mechanism for this downregulation involves the suppression of the inflammatory nuclear factor-kappa B (NF-kB ) pathway, which is activated under oxidative conditions and drives LCN2 expression; conversely, physical activity suppresses this pathway, consequently reducing inflammation and enhancing insulin sensitivity. In line with these molecular changes, the significant decrease in the Lee index observed in this study indicates reduced body fat mass and improved metabolic status in elderly obese rats. In conclusion, consistent, structured regular exercise, whether RT or HIIT, can substantially improve the metabolic function of adipose tissue during senescence by downregulating genes associated with inflammation and insulin resistance, thereby potentially preventing the onset of obesity-related metabolic disorders. Compliance with Ethical Guidelines: All experimental procedures were conducted in accordance with ethical guidelines for animal research and were approved by the Ethics Committee of Bojnourd Azad University (Approval Code: IR.IAU.BOJNOURD.REC.1402.004). All procedures were performed minimizing pain and distress to the animals. Funding: This research is based on a master’s thesis from a student at the Islamic Azad University, Bojnourd Branch, and was conducted without any financial support. Conflicts of interest: There are no conflicts of interest regarding this article. زمینه و هدف: سمافورین C3 و لیپوکالین 2 نوعی آدیپوکاین نسبتاً جدید هستند که از بافت چربی ترشح می‌شوند و با التهاب خفیف، چاقی و سندرم متابولیک ارتباط نزدیکی دارند. هدف از پژوهش حاضر بررسی تأثیر هشت هفته تمرینات مقاومتی و تناوبی شدید بر بیان سمافورین C3، لیپوکاین 2 و شاخص لی در رت‌های سالمند چاق است. روش تحقیق: در این مطالعه تجربی، 30 سر رت نر سالمند نژاد ویستار با میانگین سنی 20-22 ماه و میانگین وزن اولیه 20 ± 250 گرم، پس از رسیدن به حد وزنی مطلوب به سه گروه کنترل، تمرین تناوبی شدید و تمرین مقاومتی (هر گروه 10 سر) تقسیم شدند. پروتکل تمرینات مقاومتی شامل هشت هفته و هفته‌ای پنج جلسه صعود از یک نردبان یک متری با 26 پله و پروتکل تمرینات تناوبی شدید شامل سه قسمت گرم کردن، بدنه اصلی متشکل از تکرارهای تناوبی و سرد کردن بود. برای اندازه‌گیری بیان ژن‌های سمافورین C3 و لیپوکالین 2 بافت چربی از روش Real Time-PCR استفاده شد. از روش آماری تحلیل واریانس یک‌طرفه و آزمون تعقیبی توکی جهت تعیین اختلاف بین‌گروها در سطح معنی‌‌داری 0/05>p استفاده شد. یافته‌ها: نتایج پژوهش حاضر نشان داد هر دو مدل تمرین مقاومتی و تناوبی شدید سبب کاهش معنی‌‌دار بیان ژن سمافورین C3، لیپوکالین 2 و شاخص لی نسبت به گروه کنترل شد، اما تفاوتی بین گروه‌های تجربی مشاهده نشد. نتیجه‌گیری: با توجه به نتایج مطالعه حاضر، به‌‌نظر می‌رسد که تمرینات ورزشی مقاومتی و تناوبی شدید با تأثیر مثبت بر بیان ژن سمافورین C3، لیپوکالین 2 و شاخص لی می‌توانند به‌عنوان راهکار موثر در زمینه افزایش لیپولیز و کاهش اختلالات مرتبط با اضافه وزن و چاقی؛ در نظر گرفته شوند.

https://jpsbs.birjand.ac.ir/article_3036_07825b7232ee8e3663c48fdf3988b7ed.pdf