Journal of Exercise & Organ Cross Talk

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
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 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 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.