Journal of Exercise & Organ Cross Talk

Abstract Background: Sedentary obesity is associated with chronic inflammation, oxidative stress, and impaired angiogenesis, leading to endothelial dysfunction. Interval training and CoQ10 each improve redox balance and vascular health, possibly via inter-organ crosstalk, but their combined effects in sedentary obese men are unclear.

Methods: Sixty sedentary obese men (30–45 years) were randomized into four groups (n=15): control, CoQ10 (100 mg/day), moderate-intensity intermittent training (3×/week, 8 weeks), and training + CoQ10. Serum VEGF, TAC, and H₂O₂ were measured pre/post-intervention via ELISA and colorimetric assays. Data were analyzed with repeated-measures ANOVA (α=0.05). Effect sizes (partial η²) were reported.

Results: Training significantly raised VEGF (p < 0.001, η² = 0.363) and TAC (p < 0.001, η² = 0.290) , while strongly reducing H₂O₂ (p < 0.001, η² = 0.520) . CoQ10 showed no significant main or interactive effects on TAC or H₂O₂; however, a significant three-way interaction (time × exercise × supplement) was observed for VEGF (p = 0.001, η² = 0.187). Post-hoc analysis revealed that the exercise-only group showed a greater increase in VEGF compared to the combined group, though the direct comparison between TR and TR+SUP at post-intervention did not reach statistical significance (p > 0.05).

Conclusion: Eight weeks of interval training robustly improves VEGF and redox homeostasis in sedentary obese men, possibly through myokines/exerkines enhancing muscle–adipose–endothelial crosstalk and HIF-1α/VEGF signaling. CoQ10 provides no added benefit for most outcomes and may be associated with a modest attenuation of the exercise-induced VEGF response.

Abstract Background and Aim: Obesity is associated with chronic low-grade inflammation and elevated oxidative stress. This study investigated the independent and combined effects of an 8-week aerobic interval-style continuous training program and CoQ10 supplementation on serum TGF-β and MDA concentrations in inactive obese men.

Methods: Sixty inactive obese men (aged 30–45 years) were randomly assigned to four groups (n=15 each): control (CONT), CoQ10 supplementation (SUP; 100 mg/day), training (TR), and combined training + supplementation (TR+SUP). The supervised training protocol was performed three sessions per week for 8 weeks with progressive intensity. Fasting venous blood samples were collected before and after the intervention. Serum MDA was measured using colorimetric assay, and TGF-β was quantified via ELISA. Data was analyzed using two-way repeated-measures ANOVA.

Results: Significant time × exercise interactions were observed for both MDA (F(1,56) = 28.793, p < 0.001) and TGF-β (F(1,56) = 30.617, p < 0.001), with reductions in the exercise groups (MDA: exercise groups from 210 nmol/L to 156 nmol/L; TGF-β: from 35 nmol/L to 30 pg/mL). Time × supplementation interactions were also significant but smaller (MDA: η_p² = 0.082; TGF-β: η_p² = 0.068). No significant three-way interaction was detected for either marker.

Conclusion: These findings highlight aerobic interval-style continuous training as a cornerstone intervention for mitigating obesity-related oxidative stress and fibrotic signaling. CoQ10 supplementation produced a small independent reduction in both markers, but no synergistic or additive interaction with exercise was observed.

Abstract Multiple sclerosis (MS) is a chronic neurological disease associated with neurodegeneration and impaired neurotrophic support. Neuromuscular training, through integrated activation of the nervous and muscular systems, may positively influence these neurotrophic factors. Therefore, this study investigated the effect of combined training on serum BDNF and GDNF levels in individuals with multiple sclerosis. Thirty women with multiple sclerosis (mean age: 36.2±5.8 years; BMI: 22.1±4.2 kg/m²) were purposively selected and randomly assigned to an experimental group (n=15) or a control group (n=15). The experimental group completed an eight-week combined training program (three sessions per week), consisting of core stability, resistance, balance, and agility exercises with progressive overload, while exercise intensity was controlled using the Borg perceived exertion scale., while the control group continued their usual daily activities. Blood samples were collected 24 hours before and 48 hours after the final training session, and the obtained serum was used to measure BDNF and GDNF levels. Data were analyzed using repeated-measures analysis of variance with a significance level of 0.05, employing SPSS software (version 27). The results demonstrated that neuromuscular training induced significant increases in serum BDNF (p=0.001, η²=0.80) and GDNF (p=0.001, η²=0.79) levels in the experimental group compared with the control group. Overall, the results of this study demonstrate that eight weeks of neuromuscular training elicit significant increases in serum BDNF and GDNF levels in women with multiple sclerosis. These findings indicate an enhanced neurotrophic environment that may support neural plasticity and neuroprotective mechanisms. Accordingly, neuromuscular training appears to be a safe and effective non-pharmacological strategy for improving neural health and potentially attenuating neurological dysfunctions associated with multiple sclerosis.

Abstract Dear Editor-in-Chief
The global epidemic of childhood obesity continues to challenge healthcare systems, with recent epidemiological data confirming a tenfold increase in prevalence over four decades. While the complications of pediatric obesity are well documented, the field of predictive medicine urgently requires reliable biomarkers that identify at-risk children before irreversible metabolic dysfunction develops. The Journal of Exercise & Organ Cross Talk has consistently highlighted the importance of inter-organ communication in metabolic health. Herein, we propose that the brain-muscle-adipose tissue triad represents a pivotal axis for developing predictive strategies in childhood obesity.
Recent evidence has substantially advanced our understanding of adipose tissue signaling in pediatric populations. A study of 104 children aged 7-18 years demonstrated that circulating spexin and adiponectin are significantly associated with insulin resistance in pediatric obesity. Notably, spexin exhibited a biphasic pattern characterized by an initial compensatory increase followed by a decompensated decrease, suggesting its potential as an early warning signal for metabolic deterioration. Adiponectin emerged as an independent determinant of HOMA-IR (β = −0.577, p = 0.005), reinforcing the central role of adipose-derived signals in systemic insulin sensitivity (Lian et al., 2026). These findings position adipokines as accessible biomarkers for stratifying risk in children with obesity.
Expanding beyond adipose tissue, large-scale proteomic analyses have revealed multi-organ signatures of cardiometabolic risk. In a cross-sectional study of 4,024 children and adolescents, Stinson and colleagues identified protein signatures linking obesity to dyslipidemia, insulin resistance, and hypertension. Using machine learning approaches, a three-protein panel (CDCP1, FGF21, HAOX1) combined with liver enzymes improved prediction of steatotic liver disease compared to enzymes alone (ROC-AUC = 0.83 vs. 0.77, p < 0.05). Importantly, reductions in adiposity during a one-year intervention were associated with decreased inflammatory cytokines, demonstrating the modifiable nature of these biomarkers (Stinson et al., 2026). This work underscores that circulating proteomic signatures reflect integrated signals from multiple organs, including liver, adipose tissue, and potentially skeletal muscle.
The central nervous system's role in this crosstalk cannot be overlooked. A comprehensive Mendelian randomization study investigating the fat-brain axis revealed bidirectional causal relationships between body fat measures and brain phenotypes. Body fat composition showed negative genetic correlations with intelligence and cognitive performance, while positive correlations emerged with attention-deficit/hyperactivity disorder, stroke, and depression. These genetic insights suggest that the brain is not merely a passive recipient of peripheral metabolic signals but actively participates in a bidirectional dialogue with adipose tissue. For predictive medicine, this implies that neurobehavioral assessments could complement biochemical markers in identifying children at greatest metabolic risk (Baranova et al., 2025).
The convergence of these findings carries translational implications. First, the identification of early biomarkers such as spexin and adiponectin enables risk stratification before frank insulin resistance develops. Second, proteomic signatures incorporating multiple organ-derived proteins offer enhanced predictive accuracy for specific outcomes like steatotic liver disease. Third, genetic evidence linking brain phenotypes to body fat measures suggests that predictive models should incorporate both biochemical and neurobehavioral parameters.
For JEOCT readers, these advances highlight opportunities for exercise-based interventions targeting inter-organ communication Physical activity potently modulates the secretome of skeletal muscle, adipose tissue, and potentially the brain. Understanding how exercise-induced signals influence the brain-muscle-adipose triad could inform personalized exercise prescriptions for children with obesity. Future research should prioritize longitudinal studies mapping the temporal dynamics of these biomarkers during childhood development and in response to lifestyle interventions.
In conclusion, the brain-muscle-adipose tissue triad represents a conceptual framework for predictive medicine in childhood obesity. By integrating adipose-derived signals, multi-organ proteomic signatures, and brain-body genetic links, we can move toward early identification of at-risk children and targeted preventive strategies. The Journal of Exercise & Organ Cross Talk is ideally positioned to advance this research agenda.
 

Abstract The purpose of this research is to investigate the effect of High-intensity interval training and spirulina supplementation on the levels of Pannexin-1 and NLRP-1 proteins in hippocampal tissue in male rats with type 1 diabetes. In this experimental study, 30 Wistar rats, aged 10 weeks and weighing 180-260 grams, were randomly divided into 5 groups of 6 each: exercise group, supplement group, exercise + supplement group, control group, 5 healthy group. After inducing diabetes and implementing the protocol, hippocampal tissue from the rats was extracted, and the levels of PANNXIN-1 and NLRP-1 proteins were measured using the western blot method. Statistical analyses and data processing were conducted using SPSS version 26 software, with significance set at P≤0.05. The results showed a significant increase in Pannexin-1 and NLRP-1 proteins in diabetic rats (P<0.05). There was a noticeable decrease in protein expression after 6 weeks of rigorous intermittent exercise and spirulina supplements in the exercise, supplement, and exercise + supplement groups compared to the diabetic group. This reduction was mostly due to the combined effects of exercise and supplementation rather than either alone. Our research has verified the hypoglycemic effects of intense interval training and spirulina supplementation, along with their impact on reducing PANX-1 and NLRP-1 protein expression. Consequently, it appears that this form of physical activity and herbal supplement could significantly enhance the management of neurodegenerative disorders in individuals with type 1 diabetes.

Abstract Movement disorders such as Parkinson’s disease frequently present with comorbid sleep disturbances, which exacerbate motor symptoms and reduce patients’ quality of life. The striatum, a critical basal ganglia structure, is implicated in both motor control and sleep regulation and represents the key anatomical locus affected in these disorders. While nutritional and exercise interventions have shown promise independently, a significant gap remains in understanding the synergistic molecular crosstalk between these lifestyle modifications and how they collectively target the striatal mechanisms disrupted by sleep deprivation. This review synthesizes evidence to elucidate the integrated, neurobiological effects of combined nutritional and exercise interventions on sleep deprivation-associated movement disorders, emphasizing the striatum’s pivotal role. We establish that exercise, through the induction of neurotrophic factors (like BDNF/GDNF) and enhanced dopaminergic signaling (DAT), provides a critical foundation for synaptic repair. This foundation is synergistically amplified by targeted nutritional strategies, such as polyphenols and omega-3s, which augment antioxidant capacity, dampen neuroinflammation (NRF2/NFκB axis), and modulate key receptors (like A2AR) within the striatum. These combined, non-pharmacological approaches more effectively restore striatal homeostasis and redox balance than either intervention alone, resulting in superior improvement in both motor function and sleep quality. Further longitudinal and mechanistic studies (e.g., RCTs with multimodal endpoints) are warranted to refine optimal intervention protocols and personalize therapeutic strategies. Incorporating these findings into clinical guidelines could promote holistic, synergistic management strategies that improve patient outcomes and reduce healthcare costs.

Abstract This study investigated the effects of 4-week Zingiber officinale (ginger) supplementation (1 g/day) on serum lactate dehydrogenase (LDH) dynamics and fatigue perception in obese women (BMI >30 kg/m²; n=50) following acute eccentric and concentric exercise. Participants were stratified by VO₂max and allocated to: ginger+eccentric (G+E), ginger+concentric (G+C), placebo+eccentric (P+E), placebo+concentric (P+C), or control (no intervention). Following supplementation, participants completed treadmill-based eccentric (-10% to -15% incline) or concentric (+10% to +15% incline) protocols to volitional exhaustion. Fasted venous blood samples quantified serum LDH; fatigue was assessed via Fatigue Severity Scale (FSS). ANCOVA with baseline adjustment revealed: Significant LDH elevation post-exercise (η²=0.62, P<0.001), with eccentric > concentric (Δ28.3±6.2 vs. Δ18.5±5.9 U/L; P=0.008). Ginger attenuated LDH vs. placebo (mean reduction: -21.8 U/L, 95% CI: -30.1 to -13.5; P<0.001, η²=0.42), particularly after eccentric exercise (G+E vs. P+E: -24.7 U/L, P=0.002). Non-significant FSS increase overall (η²=0.09, P=0.12), though ginger reduced FSS elevation by 41% vs. placebo (Δ8.7±3.9 vs. Δ14.8±5.2; P=0.07), with strongest attenuation in G+E (-9.3 units; P=0.052). Four-week ginger supplementation significantly mitigates exercise-induced LDH release in obese women, indicating cytoprotective effects against muscular stress. While fatigue modulation was statistically non-significant, clinically relevant attenuation trends suggest potential ergogenic benefits requiring further investigation.

Abstract This study investigates the effect of home-based combined exercise on the transforming growth factor-β/Interleukin-17 ratio (TGF-β/IL-17) in maternal serum during the first, second, and third trimesters of pregnancy, as well as in umbilical cord blood. Thirty overweight pregnant women were randomly allocated to control and training groups. Blood samples were collected during each trimester of pregnancy and from the umbilical cord at birth. Fitness-related indicators were assessed in the mother throughout pregnancy. Newborn health indicators were measured at birth. The levels of IL-17 and TGF-β were determined using enzyme-linked immunosorbent assay (ELISA) and specialized kits. The exercise training significantly reduced TGF-β levels (p=0.011, effect size=1.22) and the TGF-β/IL-17 ratio (p=0.045, effect size=0.79) in the third trimester in mothers. Similarly, this ratio decreased in the fetus, accompanied by an increase in IL-17 levels (p = 0.038, effect size = 0.93). These immune changes were associated with improved maternal cardiovascular fitness and higher Apgar scores at 5 minutes for newborns (p<0.05). Obesity and excessive weight gain during pregnancy are linked to inflammatory responses and elevated cytokine levels, which may increase the risk of complications for the mother. This study highlights the long-term benefits of maternal exercise, evidenced by reduced inflammatory responses and improved neonatal health outcomes, as reflected in Apgar scores.

Abstract Non-alcoholic fatty liver disease (NAFLD) is a prevalent chronic liver disorder associated with fat accumulation, sedentary lifestyle, and poor diet. This study examined the effects of aerobic exercise and mealworm protein supplementation on oxidative balance and the expression of FGF21 and mTOR genes in the soleus muscle of rats with NAFLD. Fifteen male Wistar rats (250 ± 50 g, aged 10–12 weeks) were randomly assigned to five groups: healthy control, fatty liver, fatty liver + supplement, fatty liver + exercise, and fatty liver + supplement + exercise. A high-fat diet was used to induce NAFLD. The exercise group performed moderate-intensity treadmill running (12–16 m/min) for eight weeks, five days per week. Mealworm protein (20 mg/kg) was administered via oral gavage. Liver and muscle tissues were analyzed using Real-Time PCR (FGF21, mTOR) and ELISA (TOS, TAC). Combined treatment significantly increased FGF21 expression (~130%; p = 0.022), reduced total oxidant status (~40%; p = 0.001), increased total antioxidant capacity (~45%; p = 0.009), and lowered SGPT and ALP levels (~32% and ~38%, respectively; p < 0.05). mTOR expression showed no significant change (p = 0.113), and the 18% SGOT reduction was not significant (p = 0.169). The combination had greater effects than either treatment alone. Aerobic exercise combined with mealworm protein supplementation improves oxidative balance and FGF21 expression in NAFLD. This integrative strategy may offer a novel therapeutic approach targeting liver-muscle metabolic interactions. Further human studies are recommended.

Abstract Unmanaged Type 2 Diabetes (DM2) is a known risk factor for cognitive decline, dementia, and Alzheimer's disease (DM3). This study explores the combined effects of high-intensity interval training (HIIT) and thyme honey on the expression of genes involved in memory-related signaling pathways (BDNF-TrkB-CREB), which are compromised in both DM2 and DM3. This experimental study involved 36 young male Wistar rats, divided into four groups: control (C), HIIT (T), thyme honey (H), and HIIT-thyme honey (TH). The T and TH groups underwent 40 training sessions over two months, with progressively increasing intervals (from 2 to 8) and intensity (from 80% to 95% of maximum running speed). Concurrently, the H and TH groups were administered 3 g/kg of thyme honey 5 days a week. Changes in BDNF, TrkB, and CREB gene expression were assessed using RT-PCR. The data were analyzed through one-way ANOVA, Bonferroni post hoc test, and Univariate analysis using SPSS-22 software. A significant increase in BDNF and CREB expression in the interactive intervention group and the expression of the TrkB gene in honey intervention groups were observed compared to diabetic control (P≥0.001). The interactive intervention with HIIT exercises and thyme honey has a synergistic effect on increasing gene expression in memory-related pathways. The highest effect size was observed for HIIT training on BDNF (EF=0.667) and CREB (EF=0.540), while the honey intervention showed a significant effect size on TrkB (EF=0.666).

Abstract This article explores the impact of exercise training on brain health in older adults, focusing on the concept of muscle-brain crosstalk. As the global population ages, understanding how lifestyle interventions like exercise can support cognitive function is increasingly important. The article reviews evidence suggesting that physical activity, particularly aerobic and resistance training, plays a crucial role in maintaining and enhancing brain health. It discusses the mechanisms underlying the beneficial effects of exercise, including improved blood flow, neurogenesis, and the release of myokines proteins produced by muscle contractions that influence brain function. Additionally, the article highlights how these myokines facilitate communication between muscles and the brain, contributing to neuroplasticity, reduced inflammation, and enhanced cognitive abilities. The concept of muscle-brain crosstalk is emphasized as a key factor in understanding how exercise promotes brain health, with potential implications for designing targeted interventions to preserve cognitive function in older adults. The article concludes by suggesting that regular exercise should be a cornerstone of public health strategies aimed at improving the quality of life and cognitive health in aging populations. Further research is encouraged to deepen our understanding of the molecular pathways involved and to develop personalized exercise programs that maximize brain health benefits for older adults.

Abstract Primary objective of this study was to examine the interplay between grip strength, a functional marker of hypertrophy, and its connection to the Firmicutes to Bacteroidetes ratio in the gut microbiome. Twenty-five male Wistar rats were divided into five groups using a computerized randomizer: old and young control groups (OC, YC), old resistance training group (OR), old supplement group (OS), and old resistance training combined with supplement group (ORS). Rats in the OR and ORS cohorts underwent eight weeks of ladder-climbing resistance training three times a week, while those in the OS group were given supplements 5 times per week after the intervention. Muscle samples were collected from all rats two days’ post-intervention. FOXO1, BAX, and cytochrome C, were assessed using PCR-real time. Analysis of the data was carried out using one-way ANOVA and post-hoc Tukey testing. The results revealed a decrease in FOXO1 and apoptotic gene expression post-intervention, with a more pronounced reduction observed in the ORS group compared to the other groups (p<0.05). Notably, supplementation alone did not impact FOXO1 expression, akin to the effect of exercise on cytochrome C. A moderate negative correlation was documented between the F/B ratio and grip strength (p= 0.003; r= -0.54). Additionally, positive and moderate correlations were observed between FOXO1, BAX, cytochrome C, and the F/B ratio (p<0.05). These findings emphasize a functional association between the gut microbiome and muscle through their metabolites, indicating mutual regulation. Furthermore, it is suggested that exercise and supplements may further enhance these interconnected mechanisms.

Abstract The presence of tetracycline in animal products has toxic and destructive effects on body tissues. In this study we investigate the potential protective mechanism of high-intensity interval training (HIIT) against tetracycline-induced hepatic steatosis (HS) and testicular apoptosis in male Wistar rat. In this study, forty-eight male Wistar rats (8-week, 220±10 gram) were randomly divaded into six groups of primary control (pre week one), primary HS (tetracycline-induced HS), secondary control (after week five), secondary HS, (5) HIIT, and HS+HIIT (after week five). Tetracycline was administered to rats 140 mg / kg for 7 days by gavage. HIIT was performed on rodent treadmill 5 days/week for 5 weeks.  Oral exposure of tetracycline for 7 days caused severe testis damage as indicated by significant alterations in histomorphological, apoptosis, increase Bax, P53 and decease Bcl2 (gene and protein, p=0.001) compared to primary control. But the changes of PARP1 were not significant (p>0.05). However, HIIT and HS+HIIT groups significantly increased spermatogonium counts, spermatocyte cell counts & spermatid cell counts (p=0.001 for all) in line with Bcl-2 and PARP1 (gene and protein, p=0.001) and decreasing apoptotic cells, Bax and p53 compared with secondary HS group (p=0.001). This research provides the first evidence that the beneficial anti-apoptosis effects of HIIT on testis of rats poisoned with tetracycline. This beneficial effect of HIIT on hepatic steatosis and testicular damage and toxicity due to tetracycline might be mediated by inhibiting P53-induced BAX upregulation and preventing apoptosis-mediated degradation of PARP-1.

Abstract Aim of this study was to determine the relations among the tight junction (TJs) genes, muscle strength and cross-sectional area (CSA) influenced by resistance training with or without specific supplement (a combination of lactobacillus and bifidobacterium probiotics, leucine amino acid and Vitamin-D). For this purpose, 25 male wistar rats in two age groups (3 months in young control and 16-24 months in four other groups) randomly divided in 5 equal groups (old and young control, resistance training, supplement and resistance training plus supplement). After 8 weeks of resistance training trice a week and oral gavage of supplement 5 times per week there were no any relation between grip strength and muscle CSA with zonula occludens-1 (ZO-1) and occludin (Occ) genes. But result of one-way ANOVA revealed that there were significantly differences among study groups in TJs genes, muscle strength and CSA (P≤0.05). Our finding showed that resistance training along with supplement can increase the level of ZO-1 (P=0.011), and Occ genes (P=0.023) expression. Indeed, resistance training plus supplement had synergistic effect on muscle CSA and grip strength (P=0.001) that can be comparable with young group. In addition, supplement alone appears that doesn’t have beneficial impact on physical function but surprisingly our finding shows strong inverse correlation between Occ and grip strength (p=0.015, r= -1.0) in supplement group which implies that although supplement alone can’t improve physical function but can maintain intestinal barrier function.

Abstract The aim of this study was to considering the correlation between the muscle fibronectin type III domain-containing protein 5 (FNDC5), blood and heart level of Irisin in exercise-trained rats with Nano selenium supplementation after intraperitoneal injection of cigarette smoke extract induced chronic obstructive pulmonary disease (COPD). To this end, 49 male Wistar rats (8 weeks old) were divided into seven groups: control, SeNPs (2.5 mg/kg b.w by oral gavage, 3 days/week, 6 weeks), AIT (49 min/day, 5 days/week for 6 weeks, interval), SeNPs+AIT, CSE (150 µL by IP injection, 1 day/week for 6 weeks), CSE+AIT, and CSE+SeNPs+AIT. The results of the present study showed that CSE injection caused inflammation and damage to lung tissue, especially alveoli, compared to the healthy group. In other words, based on the histological examination of cigarette smoke extract, it was able to cause lung tissue damage similar to COPD, and doing exercise and taking nanoselenium antioxidant supplement could control these lung tissue damage. Pearson's correlation method was used to investigate the relationship between muscle FNDC5, serum and heart Irisin, and the results of this correlation were not significant in different groups (p>0.05). It seems that exercising and taking nanoselenium supplements can increase Irisin levels in serum and heart tissue by expanding muscle contraction and increasing muscle FNDC5. However, the relationship of this factor in muscle and heart crosstalk should be investigated more closely.

Abstract It is becoming more important to understand the physiological processes that contribute to the emergence of risk factors associated with menopause, and to discover strategies for preventing and reversing them. The current research aimed to determine the impact of functional and concurrent training on miR-126/miR-1 gene expression, and cardiovascular function in middle-aged postmenopausal women. In this study, 24 women between the ages of 50 and 60 years old with a sedentary life style participated. The subjects were randomly divided into the control group, concurrent training group, and functional training group. The Control received no intervention, and the experimental groups performed selected training protocols for 12 weeks. Doppler ultrasound graphs were utilized after the interventions to evaluate the cardiovascular function. Also, 48 hours after experiment, the blood collection was taken to assess miR-126/miR-1 gene expression. To compare the variables, one-way ANOVA test followed by Tukey's post hoc test was used. The significance level was set at p < 0.05. The results showed that the training programs led to significant enhancements in FLOW-mediated dilation, and PSV (peak systolic velocity). Moreover, there was a significant decrease in the vascular stiffness in the participants after undergoing the training. Additionally, miR-1 and miR-126 gene expression were found to be increased in response to both training interventions. These findings suggest that concurrent and functional training may be an effective approach for reducing the risk of age-related diseases in menopausal women through promoting cardiovascular functions and miR-126/miR-1 gene expression elevation.

Abstract Glioblastoma multiforme (GBM) is a highly aggressive malignant brain tumor with limited treatment options and a poor prognosis. In this study, we aimed to explore the potential effects of resistance training (RT) on the expression relationship between interleukin-6 (IL-6) from skeletal muscle and its interaction with Cathepsin B and Fibronectin type III domain-containing protein 5 (FNDC5) in the hippocampus of rats with GBM. To investigate the role of RT in GBM, we conducted a study using a rat model. By conducting a 4-week RT intervention (three days/week, 30 to 100% of body weight, 3 sets with 4 repetitions/session) and analyzing the expression levels of gastrocnemius muscle IL-6, hippocampal Cathepsin B, and FNDC5, we aimed to shed light on the potential impact of this RT modality on GBM progression. The results showed that GBM induced a significant decrease in gastrocnemius muscle IL-6, hippocampal FNDC5, and Cathepsin B gene expressions that were adjusted by RT. It means that there are significant increases in the GBM+RT group when compared to GBM. There were significant and positive correlations between variables (gastrocnemius muscle IL-6, hippocampal FNDC5, and hippocampal Cathepsin B gene expressions) which led to tissue crosstalk. In conclusion, this study contributes to our understanding of the molecular mechanisms associated with GBM, revealing potential avenues for future therapeutic interventions. RT may serve as a promising approach to modulate the expression relationship between IL-6, Cathepsin B, and FNDC5, offering a potential strategy for improving outcomes in GBM.

Abstract This research paper delves into the intricate interplay between the heart and liver within the realm of metabolic regulation, focusing on the impact of exercise as a pivotal modulator of this dynamic relationship. Through a comprehensive review of pertinent literature, encompassing peer-reviewed articles, reviews, and meta-analyses sourced from databases such as PubMed, Scopus, and Google Scholar, this paper analyzes the existing understanding of how exercise influences the metabolic crosstalk between the heart and liver. The findings underscore the positive influence of regular physical activity on the metabolic interplay between these vital organs, ultimately contributing to enhanced overall metabolic health. Emphasizing both physiological and molecular aspects, the review provides a succinct overview of its content, highlighting the significance of exercise in modulating metabolic processes. In exploring human studies, animal models, and molecular techniques, this review aims to not only consolidate current knowledge but also to identify research gaps, fostering a foundation for future investigations. The potential therapeutic implications of exercise in mitigating metabolic disorders through the modulation of heart-liver crosstalk are discussed. By addressing inclusion criteria such as studies published within the last decade, written in English, and focusing on human or animal models, this paper contributes to the evolving understanding of the intricate relationship between exercise, heart health, and liver function.

Abstract Dear Editor-in-Chief
The topic of the interaction between gut microbiota and skeletal muscle and its influence on the regulation of muscle mass is new. There is evidence that the composition and diversity of gut microbiota plays a role in skeletal muscle metabolism and function, especially in catabolic (sarcopenia and cachexia) or anabolic (exercise or in athletes) situations. Signals generated by gut-microbiota interactions, such as microbial metabolites, gut peptides, lipopolysaccharides, and interleukins, modulate systemic inflammation and insulin sensitivity, which in turn regulate muscle function.
Potential mechanisms by which the gut microbiota can affect muscle mass suggest that it can regulate the sensitivity of skeletal muscle to anabolic stimuli and contribute to the reduction or increase of muscle mass depending on the physiological state.
In addition, the use of probiotic strategies to prevent muscle mass loss or promote muscle mass gain in catabolic or anabolic states may be helpful. Probiotics, particularly lactic acid bacteria and bifidobacteria, have shown potential in limiting sarcopenia, cachexia, or promoting muscle health and function in rodent studies. However, more research is needed to identify specific strains that can optimize muscle mass and performance in humans (Chew et al., 2023).
Overall, this line of research suggests that a combination of strategies, including probiotics, personalized nutrition, and traditional supplementation, may be the best approach to maintaining muscle function in people of all ages. However, further studies are needed to better understand the role of gut microbiota in muscle metabolism and to identify optimal probiotic strategies for muscle health.
Researchers in this field also discuss challenges in studying the effects of probiotics on muscle mass and function, including variations in study design, participant characteristics, and measurement methods. They suggest future research directions, such as investigating the use of strict anaerobic bacteria and a mixture of probiotics or fecal microbiota transplantation (FMT) to more efficiently colonize the host's microbial ecosystem. In addition, they suggest the combination of probiotic strains with other nutritional agents to optimize their effects on the microbiota and muscles (Gizard et al., 2020).
Consequently, while probiotics have shown promising effects on muscle mass and performance in animal studies, their efficacy in humans remains unclear. Further research is needed to determine specific strains and protocols that can effectively modulate gut microbiota and improve muscle health in different populations.

Abstract The purpose of this research is to survey the effect of eight weeks of sub-maximal training on the C-Reactive Protein (CRP) in elderly males. The subjects of the research consisted of 21 elderly males between 50-80 years old, divided into two groups (one experimental group and one control group), with VO_2Peak values of 51.14±2.7, 51.92±3.17, and 43.61±1.85 (based on the 1-mile (1609 meters) Track Jog test). The experimental group carried out Balke-Ware sub-maximal aerobic exercise 5 sessions a week for 8 weeks, while the control group did not participate in the training program. The results of the research showed that the average CRP levels decreased in the experimental group, while they increased in the control group. However, these differences were not statistically significant according to the paired sample T-Test results. On the other hand, a significant difference in Vo2 Peak was observed between the two groups (p<0.039 and p<0.001), with the experimental group showing higher values compared to the control group. Additionally, there was no statistically significant difference in HS-CRP levels between the subjects (experimental group 1, experimental group 2, and control group) before and after the training period. In general, it seems that a longer duration is required to observe better markers of inflammatory and cardiovascular effects of these variables. The pre-study hypothesis of cardiorespiratory fitness on CRP response confirms that assessing control and inflammatory markers of cardiorespiratory fitness in the elderly requires more time.

Abstract This study aimed to investigate the combined effect of prolonged whey protein supplementation and resistance training on the expression of insulin-like growth factor-1 (IGF-1) gene, the weight of the Gastrocnemius muscle and One-repetition maximum in young male Wistar rats. In this study, twenty-one young male Wistar rats, aged eight weeks and weighing between 200 to 250 grams, were randomly assigned to four groups: training (T), supplementary training (ST), Sham (Sh), and control (C). The resistance training program was conducted for six weeks, five days a week, with the training intensity increasing from 50 to 100% of the rats' body weight. The rats receiving the whey supplement via the gavage method based on their body weight, using whey production by ON company. Forty-eight hours after the final training session, the quadriceps muscles of the rats were extracted and the expression level of the IGF-1 gene was evaluated using the Real-Time PCR method. Statistical analysis was conducted using one-way variance test and Scheffe's test. The results showed that the training -supplement group exhibited a significant increase in IGF-1 expression compared to the Sham group (P˂0.05). Moreover, the weight of the Gastrocnemius muscle of rats and also One-repetition maximum in the training-supplement group significantly increased compared to the training, sham, and control groups (P˂0.05). The findings suggest that the concomitant use of resistance training and whey protein supplementation has a synergistic effect on IGF-1 gene expression in skeletal muscle, which may contribute to enhanced muscle hypertrophy and One-repetition maximum.

Abstract Eccentric contractions predispose muscles to damage. Type II muscle fibers are more susceptible than type I, so it seems that contraction velocity interferes in mechanical stress and thus muscle damage. The purpose of this study was to investigate the effect of contraction velocity of acute dominant knee extensor eccentric exercise-induced muscle damage (EIMD) on running economy and metabolic responses in trained young females. Twenty-one trained young females were randomly assigned into two groups: high-velocity contraction eccentric exercise (240°s-1) and low-velocity (60°s-1). To induce muscle damage subjects, in high and low-velocity groups performed 20 and 5 sets of 15 repetitions, respectively, with a load equal to 150٪ of the maximal voluntary isometric contraction (MVIC) torque of knee extensors with a dominant limb. Then; MVIC of knee extensors was recorded before, one and 48 h after EIMD, and running economy (submaximal Steady-state vo2), and metabolic responses were recorded at 60, 70, and 80% of pre-determined vVO2max, 24 h before and 48 h after EIMD. Both exercise bouts resulted in significant changes in MVIC of knee extensor (p<0.05) with no significant difference between the two groups. No significant difference was found in running economy and metabolic responses in three different intensities following both exercise conditions between the two groups. Results of the analysis showed that a four-fold difference in contraction velocity of eccentric exercise-induced muscle damage was not sufficient to induce a difference in muscle damage, running economy, and metabolic responses when the knee extensor muscle tension duration was equalized.

Abstract High-intensity exercise training is one of the effective strategies to improve the performance of athletes to achieve excellent physical fitness. In the meantime, a look at the history of sports immunology reveals the idea of window theory, which has been of great concern. According to the history of exercise immunology, high-intensity exercise training can suppress the immune system leading to respiratory infections. It has recently been shown that high-intensity exercise training has no effect on suppressing the immune system. In this review, a new perspective on the immune system and high-intensity exercise training was presented to readers. Moreover, a new look at the history of high-intensity exercise training and the immune system and recent review studies was provided and some suggestions are offered.

Abstract Dear Editor-in-Chief
 
Based on recent studies, it is now clear that there is a muscle–brain endocrine loop that can be partly mediated by myokine signaling. There are also other metabolites as mediators which can affect circulating compounds (Rai & Demontis, 2016) and these include noncoding RNAs (Makarova et al., 2014), hormone-associated responses, as well as, muscular enzymes (Pedersen, 2019). Brain-Derived Neurotrophic Factor (BDNF) is considered to be a key role in helping to mediate the impacts of exercise on the hippocampus (Loprinzi & Frith, 2019). Studies conducted on laboratory rats showed an increase in BDNF mRNA and BDNF protein in the hippocampus of these animals when wheel running exercise was performed for 1 to 8 weeks (Adlard, Perreau, & Cotman, 2005; Farmer et al., 2004; Liu & Nusslock, 2018; Neeper, Góauctemez-Pinilla, Choi, & Cotman, 1995; Oliff, Berchtold, Isackson, & Cotman, 1998; Van Hoomissen, Chambliss, Holmes, & Dishman, 2003). In terms of cognitive functions, i.e. memory and learning, BDNF has also been demonstrated to be effective in the improvement of such functions (Vaynman, Ying, & Gomez‐Pinilla, 2004; Vaynman, Ying, & Gómez‐Pinilla, 2004).
Research on humans indicates that their brains can release BDNF while cycling (Rasmussen et al., 2009; Seifert et al., 2010), also in another study in healthy people as well as people with schizophrenia who had been training in aerobic exercise for three months, the level of BDNF increased in their hippocampus by 12% and 16%, respectively (Pajonk et al., 2010). As a growth factor for the hippocampus, BDNF plays a significant role in learning and improving cell survival (Wrann et al., 2013). Interestingly enough, research findings show that BDNF can also be expressed in skeletal muscle tissues during exercise in humans; nonetheless, it is not clear whether muscle-derived BDNF can get into the bloodstream from the muscle to create a direct interaction between muscle and brain (Matthews et al., 2009).
Some fascinating studies indicate that irisin and myokines cathepsin-B might cross the (BBB) blood-brain barrier, and consequently, BDNF levels may increase. In recent a study conducted by Moon et al. (Moon et al., 2016) a novel myokine, cathepsin B (CTSB) was identified. Other work also demonstrated that exercise can increase CTSB systemic level, therefore, BDNF expression will be promoted in the hippocampus and lead to the formation of nerve tissue as well. Running on a treadmill for four months increased CTSB plasma levels, as well as CTSB gene expression in humans, mice, and rhesus monkeys. In addition, it was indicated that CTSB could cross BBB in mice. In studies by Moon et al. (2016) on CTSB knockout mice, it was made clear that mice without CTSB refused to do voluntary exercise regarding hippocampal growth and cognitive development. It is not clear whether myokine CTSB can lead to cognitive function development in humans regarding exercise training or not (Moon et al., 2016; Suzuki, 2016).
The PGC-1α-dependent myokine irisin, which is famous for its browning impacts (Boström et al., 2012), can play a role in the intervention of the brain’s physical activity (Wrann et al., 2013). An excessive expression of irisin in the primary cortical neurons can cause a higher BDNF expression, while FNDC5 knockdown mediated by RNAi can cause a lower BDNF expression. Furthermore, irisin delivery to the mice’s liver by adenoviral vectors will raise the systemic irisin level, consequently resulting in a higher level of BDNF in the hippocampus. Whether doing exercise can increase irisin plasma concentration in humans (Albrecht et al., 2015; Wrann, 2015), and whether irisin is affected by a muscle–brain endocrine loop is a disputable issue.

Abstract Dear Editor-in-Chief
The brain weighs about 1.36 kg and is mainly composed of blood. Although the brain includes only 2% of the body's weight, it receives 25% of the whole body oxygen consumption, 15% of the cardiac output volume and 2000 L of blood flow per day (Hartmann et al., 1994; Ohta et al., 1992; Xing et al., 2017). The brain has largest and most complex structure of the central nervous system. This organ regulates the functions of human body and stands for the basis of higher neural activities such as consciousness, alertness, learning, memory, intelligence, spirit and language learning. Cognitive function in a person means the brain ability to process, store, and extract information. In addition, this ability is a kind of advanced psychological function such as thinking, memory, and attention. Cognitive function plays an irreplaceable role in our daily life and study. Based on Cognitive psychology, the brain can modify its structure and function according to environmental changes and the experience of different types of exercising, especially exercise training, plays a crucial role in the evolution of the brain (Barnes. 2015; Raichlen et al., 2017). For example, exercise can positively affect synaptic plasticity and synaptic function to promote cerebral cortex, neural network and hippocampus function (an important structure in the memory information processing) (Ding et al., 2006; Li et al., 2019; Loprinzi et al., 2017). Exercise also has a significant effect on brain metabolism. Exercise not only promotes physical health of people, but also prevents mental illness and delays cognitive aging (Robinson et al., 2018).
Brain function depends on nerve fibers, number of neurons and synapses.  The cognitive performance is also closely related to the number of nerve fibers and synaptic connections, which can be reduced by diseases and aging process. The neurotrophics factors, such as neurotrophic factor (NGF) and brain-derived neurotrophic factor (BDNF) are required to provide nutrients to maintain the structure and function of nerve fibers and synaptic connections (Ivanov, 2014). However, with aging, sharp decrease of dendritic branches, degeneration of glial cells, the reduction of neuron number and contraction of nerves may impede the transmission of electrical signals in the nervous system, leading to the shrinkage of gray matter in the brain and cognitive impairment (Reisberg et al., 2008; Thorin-Trescases et al., 2018).
Several studies have shown that an active lifestyle could delay the aging of cognitive-control areas in the brain, and exercise can significantly improve brain health in patients with Alzheimer's disease and schizophrenia (Falkai et al., 2017; Frederiksen et al., 2018). Colcombe et al. (2003; 2006) used high-resolution magnetic resonance imaging (MRI) to scan the brain of 55 healthy people aged from 55 to 79 years old and observed a decrease in tissue density in the frontal and temporal lobes with age. The important point is that brain structure atrophy was related to aerobic fitness. In another study, 59 healthy people aged from 60-79 years old were divided into exercise training groups and control group. In the exercise training group, aerobic exercise intervention was conducted for 6 months. The results showed that the volume of gray matter and white matter was significantly increased in the exercise training group, and the researchers concluded that aerobic training could effectively delay brain aging process and lead to promote brain health (Colcombe et al., 2003; Colcombe et al., 2006; Colcombe & Kramer, 2003).
In terms of the mechanism based on which exercise training may enhance cognitive ability and  delay brain aging, it has been proved that exercise training can induce fibronectin type III domain-containing protein 5 (FNDC5) expression in skeletal muscle which will be released into the circulation with Irisin variant (Wrann et al., 2013). Spiegelman found that exercise training for 30 days in mice increased the activity of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), which is a metabolic regulatory molecule in skeletal muscle. PGC-1α could stimulate the upregulation of FNDC5 expression, and when FNDC5 enters the hippocampus through the blood-brain barrier, it enhanced the expression of BDNF in the dentate nucleus of the hippocampus (responsible for learning and memory). Interestingly, the study on sedentary mice injected with FNDC5 produced by exercise showed it activated gene for the brain health and improved the growth of new neurons involved in learning and memory. This new discovery links FNDC5, PGC-1α and BDNF in the cross talk between the brain and skeletal muscle upon exercise (Wrann et al., 2013). In addition to PGC-1 α/FNDC5 signaling on other molecules have also been found to affect BDNF expression in cognitive impairment.
In a cell model simulating the effect of exercise by adding AMPK agonist to L6 myoblasts rat, proteomics and mass spectrometry were performed to screen the factors secreted by myoblasts. Data showed that Cathepsin B (CTSB) increased after treatment while other cytokines did not changed. Meanwhile, CTSB levels also increased in gastrocnemius muscle and plasma of rats after voluntary wheel running exercise, anti-fatigue ability; spatial memory ability and coordinated movement improved in the exercised rats compared to the sedentary control group. However, these beneficial effects were absent in CTSB knockout rat. In addition, intravenous injected CSTB is able to enter the brain through blood-brain barrier and upregulate DCX and BDNF expression and thus enhancing hippocampal nerve growth (Moon et al., 2016).
Aerobic Training not only promotes physical health of people, but also prevents mental illness and effectively delays brain aging process, prevents brain structure atrophy, promotes volume gray and white matter and  promotes cognitive ability in patients with Age-induced cognitive impairment. Therefore, it is very important to conduct original and cross-sectional research in order to discover relevant and new mechanisms.