Journal of Exercise & Organ Cross Talk

Abstract The aim of the present study was to investigate the effect of sprint interval training on markers of bone metabolism and bone density in Male Wistar Rats under unhealthy high fat, sugar, salt Diet. The study design was an 8-week protocol consisting of three groups: Control (CO), Western diet (WD) and Western diet+Sprint interval training (SIT) (WD/SIT). WD rats received a high-fat, sugar, and salt diet, while WD/SIT rats followed the same diet combined with sprint interval training. The one-way ANOVA revealed significant differences between groups for all variables (p<0.05). Effect sizes (η²) ranged from 0.47 to 0.99, indicating large effects for bone density (η²=0.99), ALP(η²=0.77), phosphorus (η²=0.74), and calcium (η²=0.47). Post-hoc analysis by LSD test showed that the WD group exhibited a significantly lower femur bone density percentage (24.09±2.32) compared to both the control (58.40±1.64) and WD/SIT (47.67±1.60) groups (p<0.001). Regarding bone metabolism markers, the WD/SIT group demonstrated significantly reduced serum ALP levels (195.67±20.83IU/L) compared to the control (248.33±29.30IU/L) and WD (253.17±38.46IU/L) groups (p<0.001). For serum phosphorus, the WD/SIT group (5.68±0.58 mg/dL) was significantly lower than the control (7.68±0.63 mg/dL) and WD (8.58±0.78mg/dL) groups (p<0.001). Furthermore, serum calcium levels in the control group (10.27±0.80 mg/dL) were significantly higher than in the WD/SIT (8.92±0.61 mg/dL) and WD (9.18±0.28 mg/dL) groups (p<0.01). These results indicate that a high-calorie, high-salt diet had a negative effect on bone metabolism. However, sprint interval training partially attenuated these adverse effects.

Abstract This study investigated the effects of high intensity interval training (HIIT), Nano-selenium supplementation, and their combination on the expression of LDHA, LDHB, and the LDHA/LDHB ratio in mice breast tumor tissue. Female mice (n=32) were inoculated with mammary adenocarcinoma cells (4T1) and randomly assigned to four groups (n=8 each): tumor control (Tu), tumor+HIIT (Tu+Ex), tumor + Nano-selenium (Tu+Nsel, 2 mg/kg/day orally), and tumor+HIIT+Nano-selenium (Tu+Ex+Nsel). HIIT was performed on a treadmill (30 min/day, 5 days/week) for four weeks. One-way ANOVA revealed significant differences among groups for LDHA expression (F=38.66, p<0.0001). Compared to the Tu group, all intervention groups (Tu+Ex,Tu+Nsel, and Tu+Ex+Nsel) showed a significant increase in LDHA expression (p<0.05). The greatest increase was observed in the combined treatment group (Tu+Ex+Nsel), which was significantly higher than both Tu+Ex and Tu+Nsel (p<0.001). For the LDHA/LDHB ratio, a significant overall effect was found (F=163.87, p<0.0001). The Tu+Nsel group exhibited a significant increase in the ratio compared to the Tu group (p<0.05), whereas both Tu+Ex and Tu+Ex+Nsel showed a significant decrease in the ratio (p<0.05). The ratio in the Tu+Nsel group was also significantly higher than in the two exercise containing groups (p<0.05). HIIT and Nano-selenium independently upregulate LDHA expression in breast tumor tissue, with an additive effect when combined. However, only Nano-selenium alone increased the LDHA/LDHB ratio, while exercise-based interventions (with or without Nano-selenium) decreased this ratio. These findings suggest that exercise and Nano-selenium differentially shift the balance between LDHA and LDHB, potentially influencing tumor lactate metabolism and the tumor microenvironment.

Abstract To investigate the individual and combined effects of six weeks of aerobic exercise and hydroalcoholic extract of Urtica dioica (nettle) on tumor volume, body weight, and interleukin-10 (IL-10) levels in both serum and tumor tissue in male C57BL/6 mice bearing B16F10 melanoma tumors. Thirty-two male C57BL/6 mice (6–8 weeks old, 12–14 g) were randomly assigned to four equal groups (n=8): Control, Aerobic Exercise (AE), Nettle Extract (NE), and Combined (AE+NE). Melanoma was induced via surgical implantation of B16F10 tumor fragments. The AE protocol consisted of treadmill running for 6 weeks (5 days/week, progressing from 20 to 30 minutes/session at 6–16 m/min). The NE group received intraperitoneal injections of hydroalcoholic nettle extract (200 mg/kg body weight). The combined group received both interventions. The combined AE+NE group showing a significant reduction in tumor volume compared to the control group (p=0.0186). One-way ANOVA revealed significant differences in serum IL-10 across groups (F=9.811, p=0.0001), with significant increases observed in the AE (p=0.0003) and AE+NE (p = 0.0005) groups compared to controls. For tumor IL-10, a significant difference was also found across groups (F=3.047, p= 0.0451), with the combined AE+NE group showing a significant decrease (p =0.0435) compared to the control group. No significant correlation was found between serum and tumor IL-10 levels in any group (p>0.05). The combined intervention significantly suppressed tumor growth compared to controls and was associated with increased serum IL-10 levels but decreased IL-10 levels within the tumor microenvironment, suggesting a complex, compartment-specific immunomodulatory effect.

Abstract Crosstalk between muscle and adipose tissue via myokines and adipokines has critical implications for the metabolic regulation of type 2 diabetes. Irisin and adipolin are key secretory proteins involved in glucose homeostasis and anti-inflammatory pathways, yet the combined impact of pharmacological and physical interventions on their metabolism remains insufficiently characterized. This experimental study investigated the effects of metformin therapy and structured exercise on serum levels of irisin and adipolin, as well as related metabolic parameters, in male diabetic rats. Type 2 diabetes was induced in male Wistar rats (fasting glucose >250 mg/dl), while the healthy control group maintained normal glucose levels (~95 mg/dl). Animals were randomly assigned to control, metformin, or exercise (combined aerobic and resistance training) groups. Over eight weeks, interventions were administered and serum irisin, adipolin, and fasting blood glucose were measured pre- and post-intervention. Data were analyzed using the Shapiro–Wilk test, ANOVA, and Tukey post hoc tests. Results showed that both metformin and exercise significantly increased adipolin levels (p<0.01). As expected, irisin levels were higher in the non-diabetic control group compared to diabetic groups (p<0.05), consistent with the known reduction of irisin in diabetes. Fasting glucose improved most notably in the exercise group. These findings indicate that metformin and exercise exert distinct yet complementary effects on key metabolic regulators—adipolin and irisin—highlighting the benefits of integrating pharmacological and lifestyle approaches in type 2 diabetes management. Future research should explore underlying molecular mechanisms and translational potential in human populations.

Abstract Skeletal muscle is a highly plastic organ that undergoes significant metabolic and structural stress during exercise, necessitating precise nutritional support for adaptation and recovery. While the roles of macronutrients are well-established, the complex interplay, or "crosstalk," between essential micronutrients is a critical yet dynamic facet of exercise physiology. This review synthesizes current evidence on the synergistic relationships between key vitamins and minerals—specifically vitamin D, calcium, magnesium, the B-vitamins, antioxidants, and iron—in supporting skeletal muscle function during and after exercise. We explore how these micronutrients co-operate in energy production, calcium handling, contraction coupling, antioxidant defense, and anabolic signaling. Recent research continues to elucidate the molecular mechanisms behind this crosstalk, highlighting the role of the gut-muscle axis and the impact of deficiencies on adaptive outcomes. Understanding this intricate network is paramount for developing targeted nutritional strategies that optimize athletic performance, enhance recovery, and support long-term musculoskeletal health.

Abstract Dear Editor-in-Chief
While the critical role of macronutrients and established myokines (e.g., BDNF, Irisin) in muscle-brain communication during exercise is increasingly recognized, a significant and underexplored frontier lies in the specific, active modulation of this bidirectional crosstalk by essential micronutrients. This letter proposes a novel conceptual framework: that certain micronutrients act not merely as metabolic co-factors, but as dynamic orchestrators or gatekeepers of the signaling pathways fundamental to muscle-brain communication in response to acute and chronic exercise.
Beyond their classical roles in energy metabolism or antioxidant defense within each organ, compelling emerging evidence suggests specific micronutrients directly influence the production, release, stability, and reception of key signaling molecules traversing the muscle-brain axis: Vitamin D receptors (VDR) are expressed in both skeletal muscle and brain regions crucial for motor control and cognition. Recent work indicates vitamin D sufficiency potentiates exercise-induced BDNF release from muscle and brain, enhances sensitivity to neuroprotective myokines like Irisin, and may regulate muscle-derived kynurenine metabolism, shifting it away from neurotoxic metabolites (e.g., quinolinic acid) towards neuroprotective pathways (Pan et al., 2022). Deficiency may thus disrupt this protective signaling axis.
Certain polyphenols (e.g., flavonoids, curcumin) cross the BBB and exhibit potent anti-inflammatory and antioxidant effects. Novel evidence suggests they may protect neuronal receptors involved in sensing muscle-derived signals (e.g., AMPK activation) from exercise-induced oxidative stress, enhancing signal fidelity. Furthermore, they may modulate microglial activation states triggered by muscle-derived inflammatory signals during intense exercise, preventing excessive neuroinflammation (Gao et al., 2024; Gomez-Pinilla & Nguyen, 2012; Wang et al., 2024).
B-vitamins (particularly B6, B9, B12) are essential co-factors in one-carbon metabolism, critically influencing the synthesis of neurotransmitters (serotonin, dopamine) known to modulate central fatigue, motivation, and motor output. Exercise alters neurotransmitter turnover. Crucially, B-vitamin status impacts the brain's response to peripherally derived signals like IL-6, which has dual pro-inflammatory and anti-inflammatory/neuroprotective roles depending on context and magnitude (Gomez-Pinilla & Nguyen, 2012; Kato et al., 2024). Optimal B-vitamin levels may be key for interpreting muscle-derived IL-6 as an anti-fatigue signal within the CNS.
Therefore, we propose that specific micronutrients (e.g., Vitamin D, B-vitamins, polyphenols) act as dynamic modulators of the muscle-brain signaling axis during exercise, moving beyond their classical metabolic roles. Understanding this "Micronutrient Crosstalk Matrix" offers novel avenues to optimize exercise benefits for brain health and performance through targeted nutrition.

Abstract Dear Editor-in-Chief
With the alarming rise in cancer cases, which is now recognized as the leading cause of death, the importance of exercise in cancer management is gaining significant recognition (Ahmadi Hekmatikar et al., 2023). In a study titled "Exerkines in health, resilience, and disease," Chow et al. (2022) shed light on the crucial role of exerkines in relation to various diseases, highlighting the positive impact of exercise, particularly in cancer (Chow et al., 2022). However, Brooks et al. (2022), in a letter to the editor addressing the aforementioned study by Chow et al., noted that lactate, a notable myokine and exerkine, was not mentioned. They emphasized the pivotal role of lactate as an important secretory product of exercise (Brooks et al., 2022). In this regard, our recent study, which was published in the journal Support Care Cancer (Ahmadi Hekmatikar, 2023), presented a critique of the article by Depenbusch et al. 2023. We highlighted that lactate, an important myokine secreted during exercise, can potentially pose a risk to tumors (Depenbusch et al., 2023). Our study emphasized that lactate may contribute to tumor angiogenesis and immunosuppression. Therefore, caution should be exercised when designing exercise programs for cancer patients (Ahmadi Hekmatikar, 2023) In a previous study published in support Care Cancer (Lavín-Pérez et al., 2023), we found that moderate-intensity physical activity does not negatively impact the immunological changes in breast cancer patients. However, upon further examination of the role of lactate, it became evident that more research is needed. Our study aims to provide researchers with a detailed exploration of the role of lactate in cancer, offering a valuable perspective for future investigations.
  Lactate and immune checkpoint: lactate leads to immune 
system suppression (How)
One of the most crucial treatment strategies currently pursued by oncology researchers is immune checkpoint blockade (Sharma et al., 2023). Within the tumor microenvironment, PD-1 and its ligand PD-L1 play a crucial role in tumor progression and survival by evading immune surveillance aimed at neutralizing the tumor (Keir et al., 2008). In the cancer immune cycle, the immune checkpoint PD-1 and its ligand PD-L1 collaborate to facilitate immune escape and promote tumor progression (Keir et al., 2008). In this context, a study revealed that lactate can enhance the expression of PD-L1 on tumor cells, suggesting that lactate may have a protective effect against tumors by increasing PD-L1 expression (Feng et al., 2017). Furthermore, another study strongly emphasized that the lactate-induced activation of the PD-1/PD-L1 pathway can induce immunosuppression by promoting lymphocyte apoptosis in AKI (Xu et al., 2021). Additionally, it has been discovered that lactate metabolism is essential for the function of anti-tumor immune cells (Ahmadi Hekmatikar et al., 2023; Heuser et al., 2023). There are two main perspectives regarding the role of lactate in immune evasion. The first perspective suggests that lactate, by increasing PD-L1 expression, contributes to immune evasion and facilitates tumor growth. The second perspective proposes that lactate derived from the tumor inhibits the proliferation of human T lymphocytes (Ahmadi Hekmatikar et al., 2019; Heuser et al., 2023; Rami et al., 2023; Tayebi et al., 2020).
Lactate and tumor angiogenesis
One characteristic of cancerous tumors is their ability to induce angiogenesis in their surrounding environment, facilitating their growth and metastasis to other parts of the body (Bokhari & Hamar, 2023). This angiogenesis is triggered by an upregulation in the expression of the vascular endothelial growth factor (VEGF) gene (Bokhari & Hamar, 2023). While it is known that tumors promote angiogenesis through the establishment of signaling cascades in their vicinity, a more comprehensive examination of this topic reveals the involvement of lactate in tumor angiogenesis (Pérez-Tomás & Pérez-Guillén, 2020). Lactate appears to play a role in enhancing the expression of VEGF, potentially explaining the association between lactate and tumor angiogenesis (Ahmadi Hekmatikar, 2024; Ahmadi Hekmatikar & Moqhadasi, 2024; Pérez-Tomás & Pérez-Guillén, 2020).
Why exercise?
The first perspective
One of the fundamental characteristics of exercise is the elevation of blood lactate levels during physical exercise (Ahmadi Hekmatikar et al., 2024; Brooks, 2018). It was previously believed that lactate production occurred as a consequence of oxygen deprivation in skeletal muscle contractions. However, it is now understood that lactate is continually generated and utilized in various cells even under fully aerobic conditions. In fact, lactate, as a metabolic byproduct of glycolysis and a substrate for downstream pathways like mitochondrial respiration, can be considered an interface between glycolytic and aerobic pathways (Brooks, 2018). In a study titled "Physiological Significance of Elevated Levels of Lactate by Exercise Training in the Brain and Body," it was discovered that exercise can increase lactate levels in the bloodstream. Moreover, this rise in lactate was found to have implications for angiogenesis. Physical exercise stimulates the production of vascular endothelial growth factor (VEGF) and promotes angiogenesis through the lactate receptor known as HCAR1 (Lee et al., 2023). 
The second perspective
Drawing from previous research, oncology and exercise physiology researchers are striving to establish appropriate physical exercise strategies for individuals with cancer, recognizing that physical exercise is a cost-free intervention that can play a significant role in disease management (Ahmadi Hekmatikar et al., 2023; Chow et al., 2022; Depenbusch et al., 2023; Lavín-Pérez et al., 2023). The importance of physical exercise during cancer is underscored by its potential to mitigate fatigue, alleviate side effects of treatment and medication, and address general physiological mechanisms. However, the tumor microenvironment operates in a sophisticated and intricate manner, necessitating a deep exploration of its underlying mechanisms to develop tailored exercise regimens. Oncology researchers are placing their focus on immunotherapy, as enhancing the performance of tumor-specific immune cells holds promise for researchers. In a meta-analysis study, we asserted that physical exercise does not suppress tumor-specific immune cells, yet it does not significantly increase their levels either (Lavín-Pérez et al., 2023). Furthermore, we reported in another study that low-intensity physical exercise during cancers, viewed  
through the lens of "exerkines and cancer management," can be beneficial. However, caution must be exercised with moderate to high-intensity exercise, as it may contribute to disease progression. One aspect we emphasized was the significance of lactate (Ahmadi Hekmatikar et al., 2023). Lastly, in our study titled "Correspondence: Work Smart or Work Hard in Patients with Metastatic Breast Cancer: Emphasizing the Importance of Immunological and Lactate Changes," we highlighted that physical exercise induces lactate secretion, and the detrimental impact of lactate on tumors has been identified. Consequently, physical exercise recommendations should be approached with caution (Ahmadi Hekmatikar, 2023).
Low-intensity, moderate and high-intensity exercise
The American College of Sports Medicine recommends low-intensity exercise (20-40% VO₂max, 35-45% HRmax) for beginners. Studies show lactate levels typically increase by 1-2 mmol after such activity. However, responses vary based on fitness level, glycogen stores, and oxygen availability. Moderate exercise (40-60% VO₂max, 55-70% HRmax) can elevate lactate by 2-6.5 mmol (Zinman et al., 2003). Some studies also report lactate reduction after prolonged training. Lactate monitoring during moderate-intensity exercise provides insights into physiological adaptation (Andersen et al., 2023; Andersson et al., 2021; Falz et al., 2019; Wiecek et al., 2017; Yuxin et al., 2021). High-intensity exercise (≥64% VO₂max) leads to greater lactate accumulation (4.5-13.2 mmol). Trained individuals may experience lower increases compared to untrained counterparts. Long-term high-intensity training may reduce resting lactate levels. Resting lactate levels in cancer patients can be significantly elevated, but post-exercise lactate increases are generally lower than in healthy individuals. Exercise interventions may help regulate lactate metabolism and reduce fatigue in cancer patients. However, responses vary based on training intensity and individual health conditions. Overall, lactate dynamics depend on exercise intensity, fitness level, and metabolic factors. Further research is needed to optimize exercise prescriptions for different populations, including cancer patients (Andersen et al., 2023; Andersson et al., 2021; Falz et al., 2019; Wiecek et al., 2017; Yuxin et al., 2021).
Conclusion and research gap
In our study, we have demonstrated the detrimental effects of lactate on tumors. Additionally, we have taken a more specialized approach by examining the relationship between lactate and exercise. It is evident that physical exercise leads to increased lactate levels and angiogenesis. Therefore, we strongly recommend that in order to develop appropriate physical exercise strategies for cancer patients, it is crucial to delve into the deeper and more fundamental mechanisms underlying the interaction between exercise and cancer, rather than solely focusing on surface level mechanisms. Considering that immunotherapy is a key focus of cancer treatment for oncology researchers, the role of lactate secreted during exercise becomes particularly significant. It has been established that lactate can negatively impact the immune system's performance in two ways: 1) by increasing the expression of anti-PD-L1, allowing tumors to evade immune surveillance, and 2) by directly suppressing T cells. Furthermore, lactate can also contribute to angiogenesis and facilitate tumor growth (See figure 1). Therefore, our study has opened a specialized and important avenue in the field of sports oncology, presenting these significant hypotheses that can guide future research and aid in developing more effective training strategies:

Can physical exercise -induced elevation of lactate contribute to tumor growth?
Can physical exercise -induced elevation of lactate impact the expression of PD-L1 in tumors?
Can physical exercise-induced elevation of lactate affect tumor specific immune cells?

Can physical exercise -induced elevation of lactate lead to tumor angiogenesis?

What intensity of physical exercise can be effective for cancer patients, considering lactate and its relationship with tumors?

 By addressing these questions, we can gain valuable insights and uncover numerous aspects through this newly opened window.


 
 

Abstract The present study will investigate the changes and correlation between the antioxidant enzyme superoxide dismutase (SOD) and the expression of interleukin 10 (IL-10) in rats fed a high-fat diet (HFD) after 6 weeks of aerobic exercise supplemented with the probiotic Lactobacillus bifidus. 40 male Wistar rats were divided into 5 groups (8 each): healthy control, high-fat diet (HFD), HFD+aerobic exercise (Tr), HFD+probiotic supplementation (Sup), and HFD+Tr+Sup. The rats in the HFD group received a special high-fat diet for 2 months prior to the main protocol. The rats in the exercise groups ran on a rodent treadmill for 6 weeks, 5 days a week. Lactobacillus bifidus supplementation was gavaged at a dose of 1 cc to the rats in the supplementation groups after each exercise session. Finally, the rats were sacrificed, and the IL-10 variable was measured using the Real-Time PCR method. The results of the present study indicated that the high-fat diet increased cholesterol and triglyceride levels (p<0.05). The HFD and HFD+Sup groups showed a significant decrease in SOD compared to the healthy control group (p<0.05). All treatment groups demonstrated a significant increase in SOD compared to the HFD group (p<0.05). The HFD+Tr and HFD+Tr+Sup groups showed a significant increase in IL-10 compared to the HFD group (p<0.05). However, the correlation between SOD and IL-10 was not confirmed (p>0.05). There was no correlation between the antioxidant enzyme and IL-10. Nevertheless, exercise and Lactobacillus bifidus were able to regulate the lipid profile, SOD, and IL-10 after a high-fat diet.

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 The covid-19 disease has spread all over the world since 2019 and many people have been affected by this disease. One of the main characteristics of this disease was lung tissue damage, which subsequently affected the immune system as well. In other words, since there are no registered drugs or vaccines against COVID-19, the immune system is the best defense because it supports the body's natural ability to defend against pathogens and resist infections. As long as the immune system is working normally, infections like COVID-19 cannot cause serious damage to the body. The three types of immunity are: innate immunity (fast response), adaptive immunity (slow response), and passive immunity. Strengthening the immune system can guarantee a better fight against pathogens. Exercising can help strengthen the immune system. In other words, exercise is one of the non-pharmacological factors for controlling diseases related to the immune system. Recently, it has been identified that exercise training with muscle contraction, the secretion of myokines in an endocrine form can affect all body tissues. One of the target tissues of myokines is the immune system. Therefore, this study deals with the strengthening role of the immune system due to exercise and muscle contraction in the conditions of the Covid-19 epidemic.

Abstract Dear Editor-in-Chief
Meteorin-like protein (METRNL) has drawn a lot of interest in the field of exercise because of its potential contribution to muscle health (Das et al., 2020). When exercising, skeletal muscle, designed for movement, goes through a variety of adaptations (Hamilton & Booth, 2000). This letter sheds light on the complex interplay between METRNL and muscle health by providing an outline of METRNL interaction with muscle tissue and the impact of exercise on this relationship.
A newly discovered adipokine called METRNL has a variety of effects on the physiology of muscles. It seems to be involved in myogenesis, muscle growth, and muscular function. According to animal research, METRNL may promote myoblast differentiation and proliferation, promoting muscle growth and repair (Lee et al., 2022). The anti-inflammatory qualities of METRNL may also lessen muscle inflammation and injury brought on by exercise.
A strong trigger for METRNL secretion is exercise. Exercise sessions, whether short-term or long-term, have been demonstrated to boost METRNL expression in circulation and muscle tissue. Numerous signaling pathways, such as those involved in metabolic adaption, muscular contraction, and inflammation, are thought to mediate this response (Alizadeh, 2021). Research is currently being done to determine the precise processes by which exercise causes the production of METRNL.
Exercise-induced METRNL release highlights its possible importance in maintaining muscular health. Exercise-related advantages like increased muscle regeneration, less inflammation, and improved energy metabolism may be aided by METRNL (Alizadeh, 2022). Exercise-induced muscular contractions and metabolic demands may trigger METRNL release, which in turn may promote additional muscle adaptation. This suggests that there may be a bidirectional relationship between exercise and METRNL.
There could be numerous clinical implications regarding fully grasping the effect of exercise on METRNL's effect on muscle health. To improve muscle regeneration, reduce muscle-related diseases, and reverse age-related muscle degeneration, strategies focused at modifying METRNL levels through exercise treatments could be investigated. To guide focused therapeutic methods, future research should concentrate on illuminating the precise connections between exercise, METRNL, and muscle health.
The connection between METRNL and muscle health is a fascinating topic of research, especially in response to exercise. Its potential as a modulator of exercise-induced muscle adaptations becomes more intriguing as our knowledge of METRNL's impact on muscle physiology expands. Exploring how exercise affects METRNL secretion and how METRNL affects muscle growth, regeneration, and function could offer fresh perspectives on how to construct exercise regimens that are most effective for different people and circumstances.

Abstract Omicron, a new type of SARS-CoV-2 was first reported by South Africa to the World Health Organization (WHO) on November 24, 2021. Two days after Africa was reported to the World Health Organization, the Omicron was identified as a global threat. Omicron has many genetic mutations, the potential effects of which are more dangerous than other SARS-CoV-2 genetic mutations. With the increase in vaccination in the world, the amount of physical activity to improve the functioning of the immune system decreased. Relying on vaccines alone cannot guarantee an improvement in the functioning of the immune system and the people of the world, given the lack of knowledge about the prevalence of omicron and its potential dangers, should look for ways to boost the immune system. In this study, we highlight the importance of increasing physical activity at the time of omicron outbreaks, along with the proposed protocols.

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 Brain-derived neurotrophic factor (BDNF) plays a vital role in the brain. On the other hand, researchers showed that exercise may cause more release of BDNF and thus have a positive effect on the brain. Studies have reported controversial findings in multiple sclerosis, and there are no broad conclusions on this topic. This study aims to systematically investigate the effect of exercise training on BDNF concentration in multiple sclerosis animal models. Searches were conducted in the electronic databases of PubMed, Scopus, Medline, Cochrane Library and Google Scholar search engine to obtain the related articles about the role of exercise training on BDNF levels just in animal models of multiple sclerosis. All of the database searches were limited to the period from inception to February 2021. Two reviewers extracted study details and data. The methodological quality of the studies that used animal models was assessed using the PEDro Scale. Fourteen articles were included in this review with scores from 7/10 to 8/10 according to the PEDro scale. Five articles reported elevation, one article reported a reduction; and eight articles reported no changes in BDNF level following or preconditioning exercise training in model of multiple sclerosis. The findings of this study showed that aerobic exercise increases changes in central BDNF concentration in multiple sclerosis in animal model.

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.
 

Abstract NAFLD, a general term that describes several diseases caused by hepatic fat deposition such as hepatic steatosis (HS) and nonalcoholic steatohepatitis (NASH), includes the many conditions that are related to fat accumulation in the liver. Indeed, NAFLD is treated with a treatment plan consisting of weight loss, nutritional supplementation, and physical activity. Despite the lack of scientific research on diet and physical exercise, there is a paucity of evidence on NAFLD. The DASH and Mediterranean diets have been frequently used for treating cardiovascular metabolic risk factors, such as insulin resistance and type 2 diabetes mellitus (T2DM). In this study, an in-depth assessment of existing dietary and physical activity methods, involving Brazilian and other country-specific recommendations was conducted to determine their effect on the risk of nonalcoholic fatty liver disease (NAFLD).

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 The prevalence of obesity among children and adolescents is one of the most serious public health challenges of the 21st century. Implementing social distancing policy measures, such as the stay-at-home order, to control the spread of coronavirus disease 2019 (COVID-19) not only has affected lifestyles and weights in children but has also created an obesity-inducing environment, leading to modifications in the patterns of interactions between this age group and their surrounding environment. Therefore, the COVID-19 pandemic has been effective in childhood obesity and its prevalence rate may continue increasing. This narrative review aimed to synthesize evidence from global studies on physical inactivity, and obesity among children and adolescents during COVID-19, and then prescribe an evidence-based home exercise guideline for this age group. The study findings revealed that the COVID-19 restrictions have drastically multiplied physical inactivity and obesity in children. It has been further established that childhood obesity leads to numerous chronic diseases, including diabetes mellitus, cardiovascular diseases (CVDs), psychosomatic disorders, lung diseases, and other metabolic problems in childhood and even as children grow up. Physical activity/exercise at home during and after COVID-19 has been correspondingly demonstrated to mitigate the problems associated with obesity. A wide range of resistance, aerobic, balance, flexibility and other types of exercises have been accordingly shown to protect against the negative effects of the pandemic on child health. Hence, efforts to facilitate such exercises are suggested to continue and be scaled up to prevent childhood obesity and relevant diseases during and after this unusual period.

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 There is no treatment for Alzheimer's disease. However, some treatments can have a slowing and controlling effect on the disease process. The aim of this study was to investigate the effect of aerobic training with saffron extract on plasma levels of apo E4 and presenilin gene in Alzheimer's rats by trimethyltin chloride. In this experimental study, 32 male Sprague-Dawley rats with the weight of 180±20 g were selected and after Alzheimer's induction (by intraperitoneal injection of 80 mg/kg trimethyltin chloride) were randomly divided into 4 groups; control, aerobic training, saffron extract, saffron extract- aerobic training. Saffron extract was injected intraperitoneally at the dose of 25 mg/kg daily for eight weeks. The aerobic training program consisted of incremental running on the treadmill at a speed of 15 to 20 m/min and 15 to 30 min per session and 3 sessions per week for 8 weeks. Data were analyzed using two-way ANOVA at the P<0.05. The results showed that aerobic training (P=0.13), saffron extract (P=0.14) and the interaction of aerobic training and saffron extract (P=0.13) had no significant effect on apo E4in rats. Also, aerobic training (P=0.68), saffron consumption (P=0.67) and interaction of aerobic training and saffron extract (P=0.32) had no significant effect on persniline gene in rats. According to the results, it seems that aerobic training and saffron extract do not significantly alter the levels of apo E4 and the presenilin of Alzheimer's rats.

Abstract Dear Editor-in-Chief
Overweight and obesity are considered as the most important lifestyle-related diseases today such that they are known as the fifth leading causes of death worldwide according to the published statistics. Moreover, as previous studies have shown, low-grade chronic inflammation is among the symptoms of these diseases and plays a key role in the pathogenesis of various physical problems and chronic diseases, such as cancer, diabetes, metabolic syndrome, cardiovascular, and neurodegenerative diseases (Safaei et al., 2021).
Meanwhile, new evidence suggests that leucine-rich α 2-glycoprotein 1 (LRG1) proinflammatory factor, an important upstream signaling pathway of transforming growth factor_⁃β (TGF_⁃β), will cause several pathological processes (Zou et al., 2022). In other words, it can be stated that LRG1, alone or in combination with other known factors, is considered as a potential biomarker for inflammation and obesity. There is a positive relationship between high levels of LRG1 and obesity, while low levels of plasma LRG1 predict weight loss in surgery for obesity and metabolic diseases (Pek et al., 2018). Investigation of the importance and the relationship of this issue in a broad study on 2,058 patients with type 2 diabetes showed that higher plasma LRG1 levels in women than men have a significant relationship with several risk factors for cardiovascular disease, namely arterial stiffness, endothelial dysfunction, systolic blood pressure, obesity, kidney disease, and high-sensitivity C-reactive protein (Pek et al., 2018; Zou et al., 2022). A recent 8-year longitudinal study also found that pigment epithelial-derived factor and plasma LRG1 mediated the inverse relationship between skeletal muscle mass and chronic kidney disease progression in patients with type 2 diabetes (Low et al., 2021). In other words, there is a positive correlation between high LRG1 levels in blood serum and adipose stores and high levels of body-mass-index (BMI), visceral adipose tissue, and waist circumference of obese people. According to these results and laboratory observations, LRG1 has been assumed to increase fat accumulation via suppression of fatty acids catabolism and inducing lipid biosynthesis through sterol regulatory element-binding transcription factor 1 activation or may enable hyperglycemia by decreasing expression of insulin receptor substrates (IRS1 and IRS2) (He et al., 2021).
On the other hand, consistent with the findings of studies showing the high serum levels of LRG1, it is possible that LRG1 binds preferentially to liver cells. With this assumption, LRG1 is considered a new adipokine that can play a role in obesity conditions by regulating an almost unique cross-talk between adipose tissue and the liver. More broad research is required to know whether LRG1 also exerts metabolic functions in physiological circumstances or not. However, the results of a study on LRG1 knockout mice with a high-fat diet revealed weight loss, smaller fat cell size, and preservation of brown adipose tissue in this type of mice. In other words, an increase in LRG1 gene expression during the process of fat lipogenesis can play an important role in regulating energy homeostasis (He et al., 2021; MacCannell et al., 2021). However, changing lifestyle by performing regular physical activity and a balanced diet have been introduced as a useful solution to prevent obesity. In this regard, a recent study on the elderly with an average BMI of 34 ± 1 kg / m2 showed that exercise combined with diet resulted in an 8-10 % weight loss in these individuals, indicating the possibility that molecular changes in peroxisome proliferator-activated receptor γ (PPARγ) coactivator 1α (PGC-1α) pathway can help transport fat and oxidize it in the skeletal muscles of older and obese people and in some ways regulate insulin resistance (Mulya et al., 2017).
Previous research studies have referred to the key role of PGC-1α in regulating mitochondrial function and helping regulate cellular energy status by enabling cellular energy in conditions 
when the body needs energy, such as fasting, performing exercise activities, or inhibiting it when the body has enough energy available. However, the evidence obtained regarding the role of PGC-1α and its relationship with LRG1 gene expression in obesity therapy showed that LRG1 expression in white adipose tissue reduced in mice model of insulin - resistant type II diabetes and obesity following treatment with PPARγ agonists (Muise et al., 2008). Moreover, evidence regarding the positive effects of exercise activity and the role of PGC-1α showed that probably five proteins, including interleukin 15 (IL-15), fibronectin type III domain- containing protein 5 (FNDC5), vascular endothelial growth factor B (VEGF-B), LRG1, and tissue inhibitor of metalloproteinase 4 (TIMP4), secreted in skeletal muscles, increase following endurance exercise activity and contribute to longevity as well (Boström et al., 2012).
Considering the evidence presented, LRG1 seems to play a key role in the pathogenesis of obesity. However, more broad research is required to better understand its relationship with other transcription factors, vital signaling pathways in this process, as well as the important effect of type, intensity, and duration of exercise activity, and type of diet in regulating its expression and its regulatory role in cross-talk with other organs to prevent obesity (Yang et al., 2021). 

Abstract One of the harmful factors that affect athletic performance is exercise-induced fatigue, which results from excessive stress and leads to reduced physical and mental function. Physical fatigue resulting from physical activities, especially sports activities, affect the human immune system. Because the immune system responds to physiological and psychological stress, and like other physiological systems in our body, it causes temporary disorders in response to a session of exercise. The immune system is also affected by the intensity, duration, and type of exercise. As a result of exercise that leads to extreme fatigue, It also may affect immune function by causing stress responses, including inflammation, and cause immune system defects. Leukocyte blood flow and functional capacity may decrease over a long time with repeated strenuous exercise, possibly due to increased levels of stress hormones during exercise. Decreased blood glutamine levels have also been suggested as a possible cause of deficiency in one or more of the immune systems associated with strenuous exercise, although the evidence is less convincing. Also, during exercise, the production of reactive oxygen species increases and some functions of immune cells can be disrupted by excess free radicals. During exercise, exposure to airborne pathogens is higher due to the speed and depth of respiration. Therefore, the increased prevalence of infection in athletes is probably due to several factors: a variety of stressors (physical, psychological, or environmental, nutritional) can suppress immune function, and these effect, along with increased exposure to pathogens.

Abstract Dear Editor-in-Chief
 
Recently, telocytes (TCs) have been identified in various organs of the body, which are unique stromal cells (Manetti et al., 2019). Telopodes (very long and thin cytoplasmic projections) in TCs connect directly with other TCs and adjacent structures (including blood vessels, nerve endings, smooth muscles, glandular elements) through direct homo- and heterocellular junctions, or extracellular vesicles. Studies also show that TC damage and dysfunction is involved in the pathogenesis of inflammatory and fibrotic diseases, especially aging, and may be considered as therapeutic agents in the future (Chaitow, 2017). On the other hand, the evidence suggests that sarcopenia and fertility-related aging syndromes, due to their complex etiology, make pharmacological or nutritional prescriptions ineffective in their prevention and treatment (Kwak & Kwon, 2019). Therefore, the use of multidimensional strategies such as exercise programs with nutritional interventions may be more effective in preventing these age-related diseases (Nascimento et al., 2019; Pascual-Fernández et al., 2020). Research suggests that TCs may play a critical role in such matters as cross-talk preservation, regenerative mechanisms, and support for localized stem cell differentiation. In 2021, Ravalli et al. examined the presence of TCs in the anterior tibialis muscle of healthy rats under the endurance training protocol compared with sedentary rats. TCs in this study included CD34/CD117 and CD34/vimentin, which were identified by double-positive immunofluorescence staining technique. They showed that TCs in sedentary rats decreased significantly after 16 weeks. In contrast, trained rats showed a constant number of TCs after 16 weeks. In short, it can be stated that the protective relationship between TCs and regular sports activity may present new opportunities in the field of regenerative medicine and supports the hypothesis that a possible adaptative stimulus for TCs in sarcopenia and other musculoskeletal disorders is the promotion of physical activity (Ravalli et al., 2021; Rocha et al., 2021).
In order to support the repair and reconstruction of skeletal muscle, studies performed by transmission electron microscopy also show that there is a close spatial relationship between TCs and satellite cells in adult skeletal muscle. This association is probably due to the intracellular signaling mechanism of endocrine and paracrine, and although their exact function in skeletal muscle regeneration has not yet been fully understood, TCs containing vascular endothelial growth factor and platelet-derived growth factor receptor beta has been discovered in the interstitial part of skeletal muscle. In this way, TCs play an important role in promoting satellite cell self-renewal, vascular stability, facilitating angiogenesis, and preventing fibrosis (Cretoiu & Popescu, 2014; Manetti et al., 2019; Yin et al., 2013).
It is important to note that as age increases, skeletal muscle mass and potential for post-injury regeneration decrease. However, the role of intrinsic changes in satellite cells in these reductions has been controversial because studies have documented a decrease in the number of satellite cells with increasing age in mice. On the other hand, some results indicate that there is not significant reduction in this case. Moreover, evidence suggests that the potential for innate regeneration of satellite cell pools is impaired with age. Although the number of satellite cells in old muscle decreases, the inherent myogenic potential and self-renewal capacity of satellite cells remain unchanged. Factors that can play a role in the activation and differentiation of satellite cells are: paired/homeodomain box transcription factors PAX3 and PAX7 and basic helix-loop-helix myogenic regulatory factors (MRFs) such as MYF5, MRF4, MYOD (Myogenic determination gene number 1) and myogenin (Arpke et al., 2021; Mierzejewski et al., 2020).
Unlike satellite cells and fibroblasts, skeletal muscle TCs express the c-kit cell surface marker. TC-specific antigenic markers are not yet fully understood; however, CD34 is currently used as the most reliable marker to detect TCs at the site of light microscopy, also known as TCs/CD34 + stromal cells (Manetti et al., 2019; Yin et al., 2013). The positive effects of regular physical activity on the number of satellite cells have been expressed, at the same time, skeletal muscle that contracts and relaxes is likely to be affected by the mechanical support of TCs during exercise (Ceccarelli et al., 2017; Kondo & Kaestner, 2019). Studies have shown evidence and conclusions about TCs, although, little research has been done on TCs in mammalian skeletal muscle tissue. At present, there is no direct experimental evidence and results that conclusively support a TCs-satellite cells morpho-functional interaction following skeletal muscle injury (Manetti et al., 2019). However, due to the beneficial role of exercise on satellite cells and TCs in the prevention of age-related muscle disorders, there are still many issues that need to be addressed, including identifying TC-specific biomarkers and their role in sarcopenia. Therefore, the role of regular physical activity on new interstitial cells such as TCs will be a new treatment for age-related diseases such as sarcopenia, which requires further investigations (Ravalli et al., 2021; Wang et al., 2016).

Abstract The main purpose of this study was to investigate the effect of primary swimming on the hormonal anabolic-catabolic balance and serum leptin in obese children and adolescents. Sixty obese subjects (children and adolescents) were randomly assigned to one of four groups: 1) Primary swimming training (children); 2) control (children); 3) Primary swimming training (adolescents); and 4) control (adolescents) groups. Our experimental subjects performed a primary swimming training for 8 weeks, 3 sessions per week and 60 minutes per session. Before and after training period, blood samples, anthropometric and body composition measurements were taken in fasting state from all subjects. The findings showed that the primary swimming training prevents significant increase of serum leptin and insulin hormone in adolescents. Furthermore, primary swimming training caused a significant decrease in body fat percent, body fat mass and body mass index, a significant increase of VO_2max in children and adolescents, a significant decrease in cortisol hormone as well as a significant increase in fat free mass in adolescents (p<0.05). There was a positive and significant correlation between levels of leptin changes and body fat percent and fat mass after primary swimming training (p<0.05). In addition, there was a negative and significant correlation between levels of leptin hormone changes and fat free mass after primary swimming training (p<0.05). Therefore, it can be concluded that eight weeks of primary swimming training improves serum leptin and some of the anthropometric, hormonal and metabolic parameters.

Abstract The COVID-19 epidemic has caused lifestyle changes in people from all walks of life and has become a global threat to the health and well-being of all countries of the world. Considering changes caused by the prevalence of the disease and quarantine conditions, the increased likelihood of the prevalence of overweight and obesity in people is among these threats. On the other hand, patients with overweight and obesity, and consequently, non-alcoholic fatty liver disease (NAFLD) have a weaker immune system than other people with ideal weight, and as a result, are more likely to develop COVID-19. As there is currently no definitive treatment for COVID-19 and NAFLD, and because people with NAFLD are more likely to develop COVID-19 based on the research in this area, paying attention to this important issue is thus necessary. Considering a regular physical activity program and having a balanced diet are among the essential strategies and may help prevent NAFLD, and consequently, COVID-19. However, given the novelty of COVID-19 pathogen and the ambiguity of the exact cause of why people get NAFLD, further research is needed to be done on the type of effective diet, as well as the type, intensity, and volume of exercise for these people. This study aimed to summarize the available evidence on the pathology and epidemiology of NAFLDs and COVID-19, as well as the effect of NAFLD on COVID-19 in people. Given the existing risks, the nutrition and exercise strategies were investigated in this regard.