Journal of Exercise & Organ Cross Talk

Abstract Skeletal muscle functions as an endocrine organ by releasing myokines—cytokines and peptides that mediate systemic physiological adaptations. This review synthesizes evidence establishing mechanical stretching (active/passive) as a potent mechanotransductive stimulus for myokine secretion. Key pathways include integrin-mediated signaling, stretch-activated ion channels (Piezo/TRP), and mechanosensitive transcriptional regulators (YAP/TAZ), which activate MAPK, calcium-dependent kinases, and other cascades to modulate myokine gene expression. We highlight stretch-responsive myokines (IL-6, irisin, myostatin, BDNF, SPARC) and their roles in metabolism, tissue repair, and inflammation. Clinical implications for aging, metabolic disease, and rehabilitation are discussed, emphasizing how targeted stretching protocols may harness myokine-mediated benefits in mobility-limited populations. Future research directions include optimizing stretch "dosing" and elucidating tissue-specific myokine actions.

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 Performing aerobic exercise in different disease conditions can regulate cardiac homeostasis and reduce cardiac apoptosis caused by the disease. In brain cancer, other tissues, including cardiac tissue, can also be affected. Since exercise training causes organ crosstalk, in this study, the effects of aerobic exercise training (AET) on cardiac apoptosis in Glioblastoma multiforme (GBM) rats are evaluated. Twenty-four male Wistar rats were divided into 3 groups (n=8 in each) of healthy control, GBM, and GBM+AET. Glioblastoma was injected into the frontal cortex of rats. The training group (AET) performed aerobic exercises on the treadmill for 4 weeks, 3 days a week at a speed of 18 meters per minute, for 25-40 minutes. In the end, the rats were sacrificed and caspase-3 and caspase-7 were analyzed from the myocardium by Real-time PCR method. Considering H&E image, the GBM group showed necrosis and apoptosis in cardiac tissue compared to the healthy group. Compared to the healthy control group, GBM significantly increased caspase-3 and caspase-7 mRNA in the myocardium (p<0.05). However, in contrast to the GBM group, the GBM+AET showed a significant decrease in caspase-3 and caspase-7 mRNA at the myocardium (p<0.05). Since tumor formation in the body can affect other distant tissues in an endocrine manner, it is suggested to prioritize aerobic exercise to control the damage caused by GBM on heart tissue. However, more studies are needed, especially on human samples.

Abstract Dear Editor-in-Chief
Exosomes contain regulatory signals such as growth factors, miRNAs, lipids, proteins, and nucleic acids that can be transported to adjacent or distant cells to affect the target tissue under both physiological and pathological conditions (Isaac et al., 2021). Exosomes are involved in various stages of disease control including apoptosis, immune regulation, angiogenesis, cell migration and cell proliferation. Exosomes are a ubiquitous, evolutionarily conserved mechanism of cellular communication. They play important roles in healthy physiological functions. Proteins, metabolites, and nucleic acids delivered by exosomes to recipient cells effectively modulate their biological response. Such exosome-mediated responses can promote or inhibit disease. The intrinsic properties of exosomes in regulating complex intracellular pathways have increased their potential application in the therapeutic control of many diseases, including neurological conditions and cancer.
Many agents are involved in modulating exosomes and other extracellular vesicles gene expression and release. One of these agents is the mechanical stress caused by exercise training. Exercise with its mechanical and oxidative stress can disrupt cell homeostasis and create adaptations at the molecular and cellular level to improve physiological health, which is effective in prevention of different diseases. Exercise by activation of all organs of the body, especially skeletal muscle, promotes the release of exosomes, through which it can develop organ crosstalk and have beneficial effects at the cellular level. It has been show that exercise promotes the release of exosomes without modification of its vesicle size (Estebanez et al., 2021). Little current data suggests that exosomes are released into the circulation in an intensity-dependent manner in response to acute endurance exercise. Many of the currently reported myokines/exerkines are also produced from exosomes. Finally, exosomes within skeletal muscle are depleted in response to an acute bout of endurance exercise (Safdar & Tarnopolsky, 2018).

Abstract Dear Editor-in-Chief
In recent years, exercise has been called an ‘amazing’ medicine and a ‘miracle’ cure. Scientific research shows that regular exercise is effective in preventing and treating many common diseases, including type 2 diabetes, dementia, depression, heart disease, some cancers, and other common diseases (Fang et al., 2022). In fact, exercise in a specific dose and formula is prescribed for each patient who is diagnosed with the disease. The prescription should be very clear in terms of modality, intensity, frequency, and duration.
In this regard, the American College of Sports Medicine (ACSM) has launched the "Exercise is Medicine" project to recognize the myriad health benefits of exercise. These include reducing the incidence of a number of different cancers, lowering the risk of excessive weight gain (along with related health problems as well as diabetes), and improving cardiovascular health (as well as reducing the risk of high blood pressure in addition to heart stroke) (Ghardashi-Afousi et al., 2018).
The acute effect of exercise has been shown to lead to a transient decrease in triglyceride levels, an increase in HDL cholesterol levels, a decrease in blood pressure, a decrease in insulin resistance, and an improvement in glucose control. Regular exercise increases blood flow and oxygen to the brain which improves memory and mental function. It also increases the production of a number of hormones that stimulate the growth of brain cells (Ueno-Pardi et al., 2022).
In addition, some literature describes exercise even better than medicine. For example, a review of more than 300 randomized controlled trials found that exercise was as effective as drugs at risk for heart disease and diabetes, and more effective than post-stroke rehabilitation drugs (Naci & Ioannidis, 2013).
It has previously been suggested that vaccinating children with exercise can control the obesity epidemic in them. Recently, in the coronavirus outbreak, exercise has been referred to as a vaccine or vaccine adjuvant (Naci & Ioannidis, 2013). A recent study in the British Journal of Sports Medicine (BJSM) suggests that routine activities may protect people with COVID-19 from serious illness.
Evidence suggests that exercise and obesity are involved in the pathogenesis of COVID-19 disease and vaccine efficacy. Regular exercise has been shown to exert immune regulatory effects, control viral gateway, modulate inflammation, stimulate NO production pathways, and control oxidative stress. Adaptation to ordinary exercise seems to affect immune function, particularly innate and adaptive immunity, and ameliorate humoral immunity with enhanced vaccination responses. Exercise may at least partially reduce the detrimental effect of SARS-CoV-2 binding to the ECA2 receptor. Exercise training can activate anti-inflammatory signaling pathways (Shirvani & Rostamkhani, 2020). Today, COVID-19 vaccination has shown that individuals who exercise continuously and regularly may develop higher antibody titers to the SARS-CoV-2 strain contained in the vaccine compared to individuals who do not exercise (Hallam et al., 2022).
On the other hand, understanding how obesity and adiposity affect immunity and more specifically the production and function of antibodies is of great importance (Malavazos et al., 2020). Numerous studies have shown the effect of obesity on antibody properties. For example, adaptive immune responses to influenza virus are impaired during obesity, innate and adaptive immune responses to influenza are delayed in obese patients, and obesity was suggested to decline influenza antibody titers following influenza vaccination and reduce vaccine efficacy with poor vaccine immunization. In the same manner, lower COVID-19 mRNA vaccine-induced antibody titers have been related to central obesity and severe acute respiratory syndrome (Ghanemi et al., 2021).     
In general, recent research on the Covid-19 epidemic has shown that exercise is not only a wonderful medicine in the prevention and treatment of many diseases, but also regular exercise can act as an adjunct vaccine. Therefore, prescribing exercise will always help promote community health and is completely in line with the P4 medicine approach (predictive, preventative, personalized, and participatory).

Abstract COPD is an inflammatory disorder caused by prolonged inhalation of harmful substances such as cigarette smoke that leads to an irreversible respiratory disorder. Airway obstruction usually has a progressive period characterized by chronic cough, sputum production, and dyspnea, resulting in decreased physical activity. Two hypotheses have been proposed for the pathogenesis of lung diseases, especially COPD, including the oxidant-antioxidant imbalance hypothesis and the protease-antioxidant imbalance hypothesis. Oxidants can cause irreversible damage to lung cells. Oxidants activate inflammatory gene expression primarily through NFκB signaling. Increase inflammation promotes apoptosis in the epithelial cells, endothelial cells, and airways, that resulting Emphysema. This pathological period causes progress the disease. Recently, has been shown that decreased physical activity is associated with COPD injuries, and the level of physical activity is most associated with COPD mortality. Therefore, the tendency to maintain and improve the physical activity of pulmonary patients, especially COPD was increased. In lung diseases, muscle mass usually decreases and severe atrophy occurs. Most studies suggest increased mobility and exercise to enhance cardiorespiratory endurance and decrease atrophy. However, the exact biological mechanism for the recovery of patients with COPD after a physical activity has not been explained. Exercise can produce Irisin and Semaphorin-3A by stimulating muscle and nerve cell, which have positive effects on other tissues, including the lungs. Limited studies have examined the role of these factors in lung tissue. Therefore, in this mini-review, the lung muscle cross-talk is examined by evaluating the role of Irisin and Semaphorin-3A.

Abstract PH stress can be caused by menopause, poor nutrition, high protein intake, old age, prolonged strenuous and anaerobic exercise, anemia, diabetes, AIDS, and respiratory diseases. High calcium enters the bloodstream from the bones during the proton buffering due to metabolic acidosis, which the renal system excretes a significant amount of this calcium to eliminate the acidosis condition and regulate body pH. At the bone surface, this increase in hydrogen ions due to metabolic acidosis can destroy osteoblastic and strengthen osteoclast activity, which negative bone turnover and increases the amount of excreted calcium, thus accelerating the progress of osteoporosis. Due to the widespread prevalence of osteoporosis in postmenopausal women and the provision of various therapies such as medication, estrogen therapy, and proper diet, in recent studies, special attention has been paid to the role of endurance and resistance exercise to decrease osteoporosis or prevent the development of this disease. Also exercise training increases irisin secretion from muscle tissue, which this myokine has beneficial effects on other tissues especially on bone. Irisin increases osteocytic survival and production of sclerostin in bone tissue, which is associated with bone remodeling. However, exercise training in some intensity through metabolic mechanisms can increase pH stress and acidosis and may contribute to the development of osteoporosis in postmenopausal women.  As a result, the hypothesis of different intensities of exercise and their induced acidosis stimuli in postmenopausal women should be considered.