Journal of Exercise & Organ Cross Talk

Abstract Osteosarcopenic adiposity (OSA) syndrome significantly impacts hepatic disorders more than each of the tissues alone. The purpose of this study is to evaluate the effects of elastic resistance training modality on hepatic health markers, including fatty liver index (FLI), lipid accumulation product (LAP), hepatic steatosis index (HSI), and Framingham steatosis index (FSI)), in the elderly with OSA. Sixty-three eligible patients aged 60-80 years meet the inclusion criteria, including a) body fat percentage (BFP) ≥32%; b) body mass index (BMI) ≥30 kg/m²; c) T-score of L1-L4, and/or total femur or femoral neck -2.5≤T-score ≤-1.0; d) gait speed (10-meter walk test (10MWT) ≤1 (m/s²); and e) skeletal muscle index (SMI) ≤28% or ≤7.76 kg/m². The participants were randomly assigned to experimental (n=32) or control (n=31) groups. The experimental group completed a 12-week elastic-band resistance training program [3x/week; 60 min/session]. The results showed a statistically significant benefit from the elastic-band resistance training on LAP (P=0.033), FLI (P=0.001), HSI (P=0.008), and FSI (P=0.001). Our findings show that an elastic-band resistance exercise training program can improve hepatic function. This relatively low-cost, highly accessible form of exercise can be easily implemented to enhance the health of this population across a wide range of settings.

Abstract Most of the intracellular and extracellular factors that play a vital role in regulating energy metabolism and determining cell fate converge in the mitochondria. To promote or hinder cell survival through regulating the function and maintaining the mitochondrial structure. The decline of mitochondrial function and homeostasis with aging is the basis of the pathogenesis of aging-related diseases, especially in skeletal muscles. One of the important components of mitochondrial quality control that helps maintain the homeostasis of myocytes is autophagy, which is an important biological and evolutionary process, and its vital function is the removal of defective organelles. Although it has been proven that regular sports activities act as autophagy stimulators and play a role in maintaining the cellular homeostasis of skeletal muscle fibers and regulating intracellular metabolism. However, cellular autophagic responses to exercise in skeletal muscle appear to be different in different exercise protocols and disease models. How exercise activity modulates autophagy in skeletal muscle and how the effect of exercise is regulated by the autophagy signaling pathway are still poorly understood. The importance of understanding the obscure angles of this process can be an important goal in preventing the pathology of age-related diseases in skeletal muscle.

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 We investigate the effect of 6 weeks of aerobic training and probiotic supplementation on glycemic index and the correlation between glutathione peroxidase (GPX) and interleukin 15 (IL-15) in rats fed a high-fat diet. 40 male Wistar rats were divided into 5 groups (8 each): healthy control, high-fat diet (HFD), HFD+ aerobic exercise (Tr), HFD+ probiotic supplement (Sup) and HFD+Tr+Sup. Rats in the HFD group received a special high-fat diet for 2 months before the main protocol. The rats in the training groups ran on a rodent treadmill for 6 weeks, 5 days a week. Lactobacillus bifidus supplement was gavage to the rats of the supplemented groups in the amount of 10⁹ CFU/ml after each round of training. The results of the statistical test showed that the HFD groups had a significant decrease in GPX compared to the healthy control group (p<0.05). However, only the HFD+Tr+Sup group showed a significant increase in GPX compared to the HFD and HFD+Tr groups (p<0.05). In contrast, HFD+Sup showed a significant increase in IL-15 gene expression compared to the healthy control group. Compared to the HFD group, the HFD+Tr and HFD+Tr+Sup groups showed a decrease and the HFD+Sup group showed a significant increase in IL-15 gene expression (p<0.05). The correlation between GPX and IL-15 was not confirmed (p<0.05). It seems that exercise training and lactobacillus supplementation are effective in regulating glucose, GPX and IL-15 indices after HFD. However, more studies should be done for the relationship and cross talk between antioxidant indices and IL-15.

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 We investigate the effect of exercise training in different stages of growth on protein synthesis (4E-BP1) and proliferation of heart cells (S6K1) in male rats. 30 male Wistar rats were prepared in three age groups of 2 weeks, 8 weeks, and 90 weeks (10 in each group), and each age group was divided into two control and training groups (5 in each group). In the exercise training group, the animals performed the resistance and aerobic training program every day (interval). The amount of overload for the resistance-training program was determined based on the body weight of the animals. For the aerobic training group, the training intensity increased from 50% of maximum speed in the first week to 80% in the last week. The results showed that there is no significant difference between the control and training groups in each age, as well as between the training groups in the three age (p>0.05). In contrast, the 2-week exercise groups (p=0.022) showed a significant increase and the 90 weeks control group (p=0.002) showed a significant decrease in S6K1 protein in cardiac tissue compared to the 2-week control groups. In the analysis of gene expression, it was also found that the 2-week training group showed a significant increase in S6K1 gene expression compared to the 2-week control group (p=0.018). It seems that doing combined exercise at different ages, especially childhood, has a greater effect on the proliferation index of heart cells (S6K1). However, studies with longer training durations should also be considered.

Abstract Physical activity performance of patients during and after breast cancer treatment is common and is associated with increased toxicity from treatment, shorter time to tumor progression, and decreased survival. Exercise is a potential intervention to maintain or increase physical performance. We conducted a meta-analysis review of the 1-year tailored exercise training, according to cytokine levels and immune function with emphasis on IL-6 in breast cancer patients. A comprehensive search was performed in September 2022 for randomized controlled trials reporting the effects of structured exercise training on breast cancer effect with cytokine levels and immune function with an emphasis on IL-6 during or after cancer treatment. A random-effects meta-analysis was completed using the absolute net difference in the change between intervention and control groups as the outcome measure. Sensitivity and subgroup analyses were also performed. Data from 18 studies involving 1833 breast cancer survivors were included in the meta-analysis. Overall, there was a significant benefit of exercise training compared with the control (I2 = 71.3%, 95% CI = 38.4% to 77.6%, P < 0.001). Subgroup analysis showed positive effects for resistance training and aerobic training and for exercise training conducted during or after cancer treatment. Compared with usual care, exercise training has a beneficial effect on in women with breast cancer, both during and after cancer treatment. Given the physiological and functional importance of women with breast cancer, oncologists should encourage their patients to engage in regular exercise training, with particular emphasis on resistance training.

Abstract Dear Editor-in-Chief
Lactate can be a key factor in cancer tumor progression
One of the clear indicators of cancerous tumors is an uneven distribution of oxygen, resulting in the presence of both hypoxic and normoxic areas within the tumor (Goodwin et al., 2015). Consequently, these conditions can contribute to the acidity of the tumor environment (Goodwin et al., 2015). The significant increase in lactate levels observed in cancerous tumors is primarily attributed to the heightened activity of the glycolysis cycle (Goodwin et al., 2015), a phenomenon identified by Otto Warburg in 1927, known as the Warburg effect (Pérez-Tomás & Pérez-Guillén, 2020). Despite the common misconception that lactate is a waste molecule, emerging evidence suggests that lactate may actually play a role in promoting cancer progression, particularly in support of cancer cells (Lavín-Pérez et al., 2023; Pérez-Tomás & Pérez-Guillén, 2020). Therefore, there is strong evidence to support the notion that lactate serves as the primary fuel to fulfill the anabolic requirements of cancer cells, potentially serving as a key factor in cancer growth (Lavín-Pérez et al., 2023; Pérez-Tomás & Pérez-Guillén, 2020). Given the complex physiological conditions associated with cancer, it raises the question of whether exercise is appropriate for cancer patients or not.
Lactate, exercise, and cancer
Considering these complex physiological conditions, whether exercise in cancer patients can be appropriate (Lavín-Pérez et al., 2023).  Several studies have investigated the effect of exercise during cancer with different mechanisms that have reported the positive effect of exercise to improve psychological or immunological effects (Lavín-Pérez et al., 2023). However, the special concentration of exercise, lactate, and its relationship with tumor growth has yet to be specifically  investigated. Physiologically, exercise with any intensity can increase lactate (Stallknecht et al., 1998). One of the factors that can have a significant effect on increasing lactate is the intensity of training (Stallknecht et al., 1998). According to Brooks et al., lactate is the largest myokine in concentration and dynamic range and the most diverse in metabolic and physiological regulation (Stallknecht et al., 1998). In the past, lactate was believed to be produced in anaerobic conditions. However, in recent years, the theory has been proposed that lactate is also produced in completely aerobic conditions (Stallknecht et al., 1998). Therefore, aerobic and anaerobic training will increase lactate (Stallknecht et al., 1998). As the intensity of training increases, the ratio of NAD+ to NADH increases. As a result, fat oxidation decreases, focuses on the glycolysis cycle, and increases lactate (A factor that can be harmful to cancer (Stallknecht et al., 1998). Also, common research supports the hypothesis that lactate increase during exercise can lead to angiogenesis and is one of the key factors of this process (Ahmadi Hekmatikar et al., 2019; Hubbard, 1973; Khoramipour et al., 2020). It seems that lactate can 1) through its effect on factors such as vascular endothelial growth factor and 2) as an important cardiac fuel and metaboreflex regulation leading to greater cardiac output for angiogenesis. On the other hand, considering that there is hyperlactatemia in cancer and the long history of cancerous tumors absorbing lactate, researchers are looking to prevent lactate transport in tumors by blocking MCTs. Accordingly, the development of therapies that limit lactate exchange and signaling within and between cancer cells should be a priority in cancer research, contrary to the physiological effects of exercise.
Finally, the hypothesis that lactate could be suitable for cancer patients during cancer seems false, given the strong results. Both directly, as an energy source, and indirectly, as a gluconeogenic precursor, lactate plays a major role in the bioenergetics and self-sufficiency of cancer cells. Acutely and chronically, exercise has positive physiological effects that cannot be suitable for cancer patients. On the other hand, the tumor environment is such that lactate is one of its key fuels for aggressiveness and growth. On the other hand, lactate itself induces angiogenesis. Physiological changes that occur due to exercise can increase lactate, angiogenesis, and lactate transporters, which can benefit the tumor. Physiological changes that occur due to exercise can increase lactate, angiogenesis, and lactate transporters, which can benefit the tumor. However, this study suggests that researchers should focus on exercise and the effects of lactate on cancerous tumors in future studies.

Abstract Dear Editor-in-Chief
 
Performing intense exercise on the body's organs is associated with various risks. At the same time, it is necessary for athletes to be aware of the dangers of intense exercise, for this purpose, studies have shown that the health of the oral cavity helps improve the performance of athletes (Gallagher et al., 2020). On the other hand, the disorder in the oral cavity with intense exercise significantly impacts the quality of life of athletes.
One of the most common diseases of oral cavity diseases caused by exercise is dental caries (D’Ercole et al., 2016). Dental caries is a chronic disease among humans and is one of the most common oral diseases worldwide. It is an important oral and dental disease that prevents achieving and maintaining oral health in all age groups. Dental caries refers to the local destruction of sensitive dental hard tissues by acidic by-products resulting from the bacterial fermentation of carbohydrates food. This disease is caused by an ecological imbalance between dental minerals and oral biofilms (plaque) (Selwitz et al., 2007; Thean et al., 2007; Yadav et al., 2017).
According to statistics announced by international organizations related to dentistry, approximately 2.43 billion people (about 36% of the population) around the world have dental caries in their permanent teeth and it affects about 620 million people or 9% of the population in milk teeth (Yadav et al., 2017). The statistics of athletes suffering from dental caries show that oral and dental cavity disorders among athletes were first recognized during the 1958 World Cup in Sweden. So that one dentist performed 118 tooth extraction surgeries on 33 athletes from different countries (Soares et al., 2014). Dental caries has also been reported among athletes in Olympic competitions. However, in the 2004 Athens Olympics, the visit of athletes by dentists took the second place among the visits of athletes to different departments of the clinic. In the 2008 Beijing Olympics, 1.600 people visited the dental department of the clinic at the venue of the competition. Similarly, in the 2012 London Olympics, 55% of the athletes were suffering from tooth decay (Needleman et al., 2013; Vougiouklakis et al., 2008; Yang et al., 2011). Azeredo et al. (2020), in a review article, investigated the prevalence of dental caries in athletes. The findings showed that the prevalence of dental caries among athletes is 46.25% (Azeredo et al., 2020). Larson et al. (2015), in a study, evaluated the intervention of exercise and energy drink consumption with health risk behaviors among adults. Findings suggest that health care providers should differentiate energy drink consumption and exercise from other unhealthy behaviors when designing programs for adults (Larson et al., 2015).
Research conducted in the field of exercise shows that exercise plays a role in reducing PH and increasing blood CO2. On the other hand, the decrease in the PH of saliva is related to the level of Co2 in the blood and the level of Co2 in the blood increases after exercise, and as a result, a high concentration of Co2 in the blood is transferred to the oral saliva, which is effective in reducing the PHof the saliva. In the same context, when the PH of saliva drops below the value of 5.5 that is assumed as the “Critical PH”, hydroxyapatite crystals in enamel begin to dissolve and decalcified areas occur (Ceyhan et al., 2020; Farsi, 2008; Milosevic et al., 1997; Okada et al., 2012). Borchers et al. (2022), analyzed saliva in their study to monitor intense exercise among male ultra-marathon runners. In this study, 9 healthy men who finished the distance of 160 km were selected as the statistical population of the research. The salivary markers were compared with blood markers following acute exercise stress in ultra-marathon runners at three baselines, shortly after the ultramarathon competition and after recovery. The findings showed that different blood markers and salivary cortisol had significant changes after the ultra-marathon running (Borchers et al., 2022).
Thus, it is recommended that athletes should be aware of the biochemical variables and other factors leading to dental caries and observe the oral and dental hygiene requirements. Moreover, due to the fact that athletes of various sports are affected by oral cavity diseases, it is necessary that athletes of competitive sports such as football, swimming, track and field, etc., pay more attention to the health of their oral cavity.
 

Abstract Air pollution is one of the most important problems of recent decades, which has serious toxic effects on human health and the environment. Sources of pollution vary from small units of cigarettes and natural sources such as volcanic activity to large volumes of emissions from car engines and industrial activities or even radioactive ones. Today, there are various pollutants around the world that negatively affect human health. Walking and being in a polluted environment can increase the penetration of pollutants such as lead in the body. Increasing physical activity such as long-term running, which is widely used in some jobs such as military jobs, can increase the activity of muscle tissue, and as a result, the cardiovascular system becomes more active and helps absorb more pollutants. Lead acetate is a possible carcinogen in humans, which is absorbed into the human body by pollutants. There is evidence that lead compounds can cause lung, brain, stomach, and kidney cancer in humans. However, pollution does not include air pollution only, and noise pollution can endanger human health as well. Since some occupations such as those of military experience various types of noise, as well as chemical and radioactive pollution and the point that having high physical fitness is essential for these people, this study examined the impact of various pollutants on the military personnel and also sought to see whether exercising and having high physical fitness of military personnel can reduce the stress caused by the pollution.

Abstract Dear Editor-in-Chief
Lifestyle-related diseases are usually caused by mistakes in daily life, such as smoking, unhealthy diet, and inactivity. Some of these diseases are including heart diseases, stroke, diabetes, obesity, metabolic syndrome, lung diseases and some types of cancer. These diseases are usually more prevalent in industrialized countries where sedentary lifestyles have spread. At the international level, these diseases are known as non-communicable and chronic diseases or degenerative diseases. Chronic diseases can lead to loss of independence, years of disability, or death, and impose a significant economic burden.
Regular physical activity helps improve your overall health, fitness and quality of life. Also, regular exercise helps reduce the risk of chronic diseases such as type 2 diabetes, heart disease, many types of cancer, depression, anxiety and dementia. Aerobic exercise can help improve your heart health and endurance. Also, these types of exercise help to lose weight. High-intensity interval training is generally safe and effective for most people. In high-intensity interval training, physical activity is performed alternately with high intensity and with low intensity, and these intensity changes have various effects on the health of the body. Strength training can improve muscle strength and endurance, make daily activities easier, reduce disease-related muscle weakness, and provide joint stability. In all these types of exercises, the skeletal muscle tissue has the most activity, and most of the positive effects of exercise are attributed to this tissue. Recently, it has been stated that muscle tissue as a secretome can secrete substances from itself and affect distant tissues. These substances secreted from muscle tissue are known as myokines.
During exercise muscles can produce and release cytokines, signaling peptides or myokines. These molecules can exert paracrine and endocrine actions. Not all of them are produced exclusively by skeletal muscle, as they can also be released by other cells such as adipose tissue (adipomyokines). Nevertheless, skeletal muscle is probably the major source of most myokines, as it constitutes more than 30% of human body mass (Piccirillo, 2019). Myokine irisin produced from muscle tissue can control many damages caused by fatty tissue and reduce the inflammatory damage of this tissue in metabolic diseases such as diabetes, fatty liver or even cardiovascular diseases. β-aminoisobutyric acid (BAIBA) is a myokine involved in browning of fat and it can reduce insulin resistance (Gonzalez-Gil & Elizondo-Montemayor, 2020). Myostatin also controls insulin resistance and prevents fat accumulation in the liver (Mikolasevic et al., 2020). Follistatin is also effective in regulating the growth of muscle tissue and reducing fat tissue (Song et al., 2019). FGF21 also promotes insulin sensitivity. Apelin and METRNL also have anti-inflammatory properties (Gholamrezayi et al., 2020). All these myokines can be effective in reducing lifestyle-related diseases with their role. Therefore, exercise should be included in your daily life.

Abstract The purpose of this research was to conduct a systematic review and meta-analysis on the effect of exercise training on neurotrophin levels in obese and overweight individuals. The research evaluated the effect of exercise training on neurotrophins in the databases of PubMed, Science Direct, Scopus, and Google Scholar with identified keywords among papers published from 2000 onwards. After preliminary screening, full-text studies as well as critical evaluation of the papers meeting the inclusion criteria were analyzed. Finally, 12 studies entered systematic research, and 6 studies entered meta-analysis research. The results show that exercise training has an addictive effect on neurotrophin levels in obese individuals, but this addictive effect is not significant. The present meta-analyze shows that the brain -Derived Neurotrophic Factor (BDNF) response to exercise in obese individuals is increasing, but the increase is not significant (Difference in means = -0.42 pg/ml, P = 0.460). On the other hand, the Nerve Growth Factor (NGF) response to exercise is also increasing which is significant (Z = 2.12, P = 0.034).  Thus, it can be concluded that exercise cannot increase neurotrophins in obese and overweight individuals; although, further studies are needed in this area.

Abstract Regular physical activity is the best defense against many diseases, illnesses, and abnormalities. Aerobic exercise and the consumption of herbal supplements strengthen the body's immune and defense systems. This study aimed to investigate the effect of a period of swimming endurance training with trachyspermum copticum (Ajwain) consumption on serum levels of some inflammatory factors in young men in a randomized clinical trial. The statistical population included all male students less than 25 years of age at the Islamic Azad University of Varamin Phishva, Iran. Among them, sample sizes of 60 people were selected by simple random sampling and were divided into four groups of 15 people each: trachyspermum copticum + training, trachyspermum copticum, training, and control. The training program included endurance swimming for 10 weeks either with or without the addition of trachyspermum copticum. Serum concentrations of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and heat shock protein 70 (HSP70) were measured in two-time stages before and after the study period. The level of CRP inflammatory index, TNF-α cytokine, and HSP70 were lower among the training + trachyspermum copticum than in the control group and other experimental groups. Endurance swimming training and trachyspermum copticum with anti-inflammatory properties strengthened the immune system, increased antioxidant defense, and decreased inflammatory markers. Also, the level of physical activity has improved this condition by improving endothelial function.

Abstract Dear Editor-in-Chief
The chemokines are a superfamily of small, secreted proteins that regulate leukocyte migration. Several of these chemokines have been associated with various diseases. Some chemokines have been reported to be expressed in the lung, including interleukin (IL)-8/CXCL8, eotaxin/CCL11, macrophage-inflammatory protein (MIP)-3α/CCL20, and DC-CK1/pulmonary- and activation-related chemokine (PARC)/alternative macrophage activation-associated CC-chemokine (AMAC)-1/CCL18 (Homey et al., 2000). It is interesting that there is even one reported chemokine that is specifically expressed in the lung, lungkine/CXCL15 (Rossi et al., 1999). Lungkine is an important mediator of neutrophil migration from the lung parenchyma into the airspace.
Chemokine CXCL15, which absorbs neutrophils during pulmonary inflammation, is also known as lungkine because of its reported exclusive expression in the lung. CXCL15, previously reported as the only lung-specific chemokine, is also highly expressed in other mucosal organs and endocrine glands of mice. The functional role of CXCL15 is unclear with precise exercise training, and little research has addressed this issue. Files et al. (2015) evaluated the effects of therapeutic exercise on lung disease and also measured CXCL15 levels (Files et al., 2015). In this study, although CXCL15 was down regulated in response to exercise therapy, they stated that exercise therapy improved both alveolar neutrophil lung damage and skeletal muscle atrophy in the animal model of ARDS. They stated that more studies are needed to identified mechanisms underlying exercise and its benefits in the lungs, which may indicate new molecular targets for the treatment of ARDS.
Clinical and experimental studies have shown that regular aerobic exercise can prevent or even eliminate a number of diseases, especially in patients in the intensive care unit. This beneficial effect of exercise is associated with anti-inflammatory and antioxidant protection. Despite the apparent benefits, the dose of exercise intensity is still unknown. Balducci et al. (Balducci et al., 2010), showed that people with type 2 diabetes who performed intense exercise had a significant improvement in their inflammatory status. High-intensity exercise reduced pneumonia and improved oxidative status in experimental models of allergic pneumonia and exposure to contaminants (Ávila et al., 2015). Due to the mechanism involved in changes in epithelial pathogenesis, strenuous exercise with hyperventilation can affect the airway epithelium by altering the viscosity, elastic force, or amount of airway fluid. In an animal model trained with an intense exercise protocol, an increase in the infiltration of leukocytes into the bronchial wall was observed (Chimenti et al., 2007). Therefore, it is believed that performing intense exercise may cause inflammatory cells to invade the airways, epithelial changes, and defective remodeling. However, studies in this area are also contradictory. In a study high-intensity swimming showed a protective effect on ALI, decreasing inflammatory processes and preventing disturbances in antioxidant defenses into the lungs (Cardoso et al., 2018). However, little is known about the possible protective effects of HIIT on lungkine CXCL15 and its mechanisms of action.

Abstract Dear Editor-in-Chief
Osteoarthritis (OA) is a progressive disease and up to now, no effective cure has been found for these diseases. OA was characterized by destruction of articular cartilage (extracellular matrix). As we age, chondrocytes show less response to growth factors, also, there is an increase abnormal accumulation of advanced glycation products (AGEs), mitochondrial dysfunction, and oxidative stress. As a result, cartilage homeostasis is impaired and ECM becomes more vulnerable to injury, leading to the onset of OA (Abramoff & Caldera, 2020). Chondrocytes are the only cell type present in articular cartilage that are solely responsible for circulating and maintaining the matrix. Exercise training with increased mechanical stress can affect the extracellular matrix in the joints. However, exercise apart from mechanical stress can also indirectly affect cartilage metabolism by increasing muscle contraction and the expansion of some myokines, which is a potential therapeutic target for osteoarthritis.
A variety of growth factors and cytokines are actively secreted by muscle tissue. Thus, muscle can act as an endocrine and paracrine organ. Secretoms are secreted not only through muscle tissue but also from other tissues and affect other organs of the body. Adipokines include adiponectin, leptin, resistin, chemerin, IL-6, and TNF-α playing an important role not only during inflammation but also in the metabolic regulation of joint cells including cartilage, osteoblasts, osteoclasts, and mesenchymal stem cells (Xie & Chen, 2019). Muscle tissue also affects cartilage metabolism with its myokines.
    FNDC5 is an important exercise myokine for slowing down age-related diseases, such as sarcopenia, osteoporosis, obesity, and neurodegeneration. Loss of FDNC5 has been shown to be associated with chondrocyte aging in the development of OA in humans and mice. 
Myokine maintains chondrocyte activity by preserving the metabolism and biology of the mitochondrial TCA cycle to protect against inflammation-induced aging. Myokine maintains chondrocyte survival and ECM synthesis by suppressing the cartilaginous inhibitory factor Wnt3a to control autophagy programs and apoptosis (Chen et al., 2020). Recently, it has been discovered that Sox9 was expressed in MTJ, tendon, and bone progenitor cells at E13 and in bone at E16. The expression of Sox9 in muscle precursor cells is also being studied. It is hypothesized that an increase in this factor of muscle tissue after exercise can also affect cartilage metabolism because it is stated that decreased Sox9 expression in connective tissues, tendons and bones is associated with cartilage hypoplasia (Nagakura et al., 2020). These hypotheses elucidated that the role of Sox9 secreted by muscle tissue can also play an important role in the development and healing of joint and cartilage, requiring animal and human studies.

Abstract Dear Editor-in-Chief
Active lymphocytes under a burst during proliferation, biosynthesis, and secretory activity increase their metabolism. In order to achieve this dramatic increase in metabolism, they must obtain a metabolic substrate. Their insignificant nutrient stores force lymphocytes to have a significant increase in the consumption of the metabolic substrate around them. Although lymphocytes are able to utilize glucose, glutamine, ketones, and fatty acids, it has been confirmed that glucose and glutamine are the most important quantitative fuels for activated lymphocytes (Curi et al., 1999). The function of T cells is closely related to the metabolic program, meaning that a T cell fights antigens, invasive agents, and inhibits infection until the main fuels of this cell, glucose and glutamine, are consumed and metabolized in sufficient quantities. There are significant and growing techniques that target the metabolism of T cells for immunotherapy.
Degradation of lymphocyte metabolism and function has been observed in various inflammatory, metabolic and autoimmune diseases. Maximum activity and levels of HK, G6PDH, CS, GLUTase enzymes of lymphocytes are always reduced for patients with Graves (Werner et al., 1996). In vitro, it has been shown that thyroid hormone increases glucose and glutamine lymphocyte metabolism in these patients. Also, it has been reported to coexist with acute and chronic infection in several diseases such as cancer or asthma, and gradation of T1 and T2 metabolism (Zhao et al., 2012).
It has been suggested that a part of the safety effects of exercise is due to the ability of exercise to modulate lymphocyte cell metabolism, especially glucose and glutamine. It has also been observed that changes in lymphocyte function are associated with different effects of moderate exercise on T and B lymphocyte metabolism. In addition, T lymphocytes increase glutamine intake by altering the metabolism of this amino acid to the aerobic pathway. At the same time, these cells reduce glucose intake and lactate production levels. In contrast, B lymphocytes were shown to increase intake of both glucose and glutamine, while aerobic metabolism of glutamine increased (Navarro et al., 2013). All of these changes in lymphocytes are possible because key enzymes in glucose and glutamine metabolism are affected by chronic exercise. Thus, as the aerobic metabolism of glutamine increases, the maximum activity of GLUTase and CS in T lymphocytes increases in response to exercise. In addition to these two enzymes, maximal activity of HK and G6PDH increased in B lymphocytes in response to chronic exercise (Navarro et al., 2013). Most of these studies have examined the immune system and T lymphocyte response to exercise with moderate intensity. High intensity interval training (HIIT) usually consists of intermittent sets of exercise (Vo2max usually equal to or greater than 90%) accompanied by few minutes of active rest. Little is known about inflammatory and metabolic immune responses after HIIT.
Moderate-intensity exercise stimulates the immune system and increases resistance to infectious diseases. However, during prolonged and intense exercise or strenuous exercise and competition, an immune suppression often occurs during the recovery period. Immune responses after exercise are almost similar to those seen in infection and inflammation (e.g., neutrophilia and lymphocytopenia) (Tauler et al., 2006). Researchers have suggested that intense exercise induces these changes with oxidative stress, changes in neuroendocrine factors such as catecholamines, growth hormone, and cortisol (Fisher et al., 2011). Therefore, it is suggested that low-intensity, high-frequency, long-term exercise be effective in improving the lymphocyte metabolic crossover.

Abstract This study aimed to investigate the interactive effect of aloe vera intake and eight weeks’ aerobic exercise on serum BDNF, glucose, and insulin levels in women with type 2 diabetes. In this experimental study, 32 women with type 2 diabetes were selected and randomly divided into four groups of control, supplement, exercise, exercise + supplement. The exercise program was performed 3 sessions per week for 8 weeks (40 min of exercise with 50-60% of heart rate reserve in the first four weeks and 60 min of exercise with 60-80% of heart rate reserve in the second four weeks). The supplement taking groups received 400 mg/kg of oral aloe Vera 3 days per week for 8 weeks. The data were analyzed using analysis of covariance (ANCOVA). A significant increase was observed in BDNF levels, insulin sensitivity of patients in the supplement, exercise, and exercise + supplement groups (p=0.001). The glucose and insulin levels, insulin resistance, BMI, and body fat percentage significantly decreased in the supplement, exercise, and exercise + supplement groups (p=0.001). It seems aloe Vera intake and aerobic exercise to have protective effects against development of type 2 diabetes complications in women.

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 Dear Editor-in-Chief
Coronaviruses are a very large family of viruses that are phenotypically and genetically diverse and are common in humans and animals. The Prevalence of Coronavirus disease 2019 (COVID-19) began in Wuhan, China. As of 17 March 2020, extensive human-to-human transmission mainly occurs via the respiratory particles of the infected person.  Among COVID-19 cases, it seems that new pandemic complications are already well-defined in obese and overweight people with body mass indexes (BMI) over 25 kg/m2 or even higher that contribute to increased risk of SARS-CoV-2 infection. The higher BMI in COVID-19 patients, the higher risk of medical complications, hospitalization in the intensive care unit (ICU), and invasive mechanical ventilation (IMV) (Földi et al., 2020). However, BMI does not show the distribution of body fat, and therefore research results cannot show the effect of excess fat in different parts of the body on the severity of COVID-19. In confirmation of this finding, it can be said that although the ratio of total body fat in women is higher than men on average, the incidence of COVID-19 is higher in men (Simonnet et al., 2020).
The possible critical mechanism by which adipose tissue accumulation increases the risk of COVID-19 in patients is unknown. However, fatty tissue may serve as a reservoir for viral production that might contribute to the increased risk from COVID-19 for patients with obesity. It is suggested that fatty tissue is targeted by SARS-CoV-2. The mechanism by which SARS-CoV-2 enters cells is not fully elucidated. But apart from a direct fusion of the virus with the plasma membrane, it appears that various types of endocytosis might be involved in this process. These lipid membrane trafficking events include clathrin-mediated endocytosis, caveolin- mediated involved in muscle hypertrophy and strength. In this regard, OCN-deficient mice have been shown to have lower muscle mass; inversely, improved muscle mass was found in older mice with ucOCN administrations. Recent data has figured out a novel mechanism of bone-muscle crosstalk in relation to OCN and IL6 signaling (Kirk et al., 2020).
Endocytosis, macropinocytosis, and phagocytosis. Caveolin-mediated endocytosis is especially interesting to study as caveolae are abundant in fat cells, caveolins participate in fatty tissue function because caveolin was shown to interact with various viral proteins. In addition, the increased number of fat cells would increase the pool of infection susceptible cells. Fatty tissue contains not only fat cells but cells of stromal vascular fraction among which adipocyte precursors and macrophages. These cells also express ACE2 and display a potential target of SARS-Cov-2 infection and thus may contribute to increased inflammatory status (Dugail, Amri, & Vitale, 2020). Another possibility is that fatty tissue droplets could provide a platform for virus replication and production. Concerning the hypothesis that fatty tissue is an infection place for the SARS-CoV-2 virus, it has not yet been established if viral loads are proportional to fatty tissue mass in patients. The ACE2 activity leading to increased levels of angiotensin II and so increased inflammation and lung damage. It seems that fat cells play a substantial role in viral infection and the viral life cycle. Adipose tissue is directly involved in contact with the viral membrane of the host cell. For example, fats are critical to the formation and function of the viral replication complex and can provide some of the energy required for viral replication. In addition, specific fats are needed for the formation of double-membrane vesicles for viral genome amplification and the production of viral particles. Viral internalization can occur with endocytosis and viral release from cells. It is possible that fat availability and fats metabolism modifications occurring in an obese patient also contribute to improving several stages of the virus's life cycle and severity of the disease (Dugail et al., 2020).
In this regard, any approach should consider reducing the costs of intensive care units to reduce the mortality of patients. Especially with concerning increase their number and people at higher risk in obese people. Moderate-intensity exercise can directly boost the immune system, antioxidant defenses, and anti-inflammatory responses Adipose tissue molecular adaptation always was considered as one of the mechanisms for the anti-inflammatory effects of physical exercise. Aerobic exercise is a physical activity that is moderate-intensity and does not put much pressure on the body. Regular exercise has been shown to improve infection, antibacterial and antiviral immunity, reduce inflammation, and delay immune aging (Campbell & Turner, 2018). Following the moderate-intensity physical activity, an increase in the number of neutrophils and natural killer (NK) cells is detected, and salivary IgA concentrations increase (Brolinson & Elliott, 2007). During physical exercise, rapid and general mobilization of NK cells into the bloodstream is induced by adrenergic B signaling and catecholamines. It is suggested that mobilized NK cells are affected by muscle-derived myokines, exercise-related hyperthermia, and coronary arteries, which are affected by regulation, redistribution, and activation of mobilized NK cells (Brolinson & Elliott, 2007). Moreover, adipocytes play a critical role in NK cell activations. Adipose tissue may respond to the activation of NK cells during exercise in a cross-talk with the immune system.
Moderate exercise was exercise is one of the mechanisms in NK cell activation following physical exercise.  The results show a 20 to 30 percent reduction in upper respiratory tract infections in people who do moderate-intensity of physical activity in their daily lives (Brolinson & Elliott, 2007). Therefore, it can be said that moderate-intensity training can be an effective way to boosting the immune system. Possible cross-talk between fat and immune tissues was approved in some other studies. It is suggested that some exercise factors such as IL-6 and Hsp70 can be effective in the possible cross-talk between the immune system and fat tissue. Molecular and structural changes in adipose tissue following physical exercise can be effective in improving immune responses.
Fatty tissue is probably targeted by the SARS-CoV-2 virus, which causes adipose tissue dysfunction. Accumulation of fat tissue also serves as a platform for replication and production of virus. Based on the evidence, it seems that exercise activities, especially combined exercise training, reduce fat mass in obese or overweight people, reduce the risk of COVID-19, as well as the risk of severity and side effects in patients. Possible cross-talks between the immune system and adipose tissue could be one of the possible mechanisms in boosting immune responses against the virus.