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Objectives To assess the ability of dual-energy X-ray absorptiometry (DXA) and hand-grip dynamometer to measure damage in inflammatory myopathies (IM). Methods Forty adult IM patients with a disease duration ≥12 months, low or no disease activity for ≥6 months, were prospectively enrolled. Thirty healthy age and sex-matched volunteers were enrolled as controls. Whole-body DXA and hand-grip dynamometer were used to measure muscle mass, grip strength and diagnose sarcopenia (EWGSOP2 criteria). Relationships between the results of strength in 12 muscles, functional tests, patient-reported disability, IMACS damage score, and history of the disease were assessed. The serum levels of potential molecular actors in the damage were measured. Results DXA and grip strength measurements took ≤20 min. Both muscle mass and grip strength were decreased in IM patients vs volunteers (−10% and −30%, respectively) with a dispersion that varied widely (interquartile range −24.3% to +7.8% and −51.3% to −18.9%, respectively). Muscle mass and grip strength were non-redundantly correlated (r up to 0.6, P  = 0.0001) with strength in 14 muscles (manual muscle test and hand-held dynamometer), functions (of limbs, respiratory and deglutition muscles), patient-reported disability, damage (extension and severity in muscular and extra-muscular domains) and blood levels of several myokines. Seven IM patients (17.5%) were sarcopenic. They had the worst damage, impaired functions, disability and history of severe myopathy. Decreased irisin and osteonectin levels were associated with sarcopenia (area under the curve 0.71 and 0.80, respectively). Conclusion DXA and hand-grip dynamometer are useful tools to assess damage in IM. Irisin and osteonectin may play a role in IM damage pathogenesis. [ABSTRACT FROM AUTHOR]

The first systematic reviews of the effects of exercise on appetite‐regulation and energy intake demonstrated changes in appetite‐regulating hormones consistent with appetite suppression and decreases in subsequent relative energy intake over a decade ago. More recently, an intensity‐dependent effect and several potential mechanisms were proposed, and this review aims to highlight advances in this field. While exercise‐induced appetite suppression clearly involves acylated ghrelin, glucagon‐like peptide‐1 may also be involved, though recent evidence suggests peptide tyrosine tyrosine may not be relevant. Changes in subjective appetite perceptions and energy intake continue to be equivocal, though these results are likely due to small sample sizes and methodological inconsistencies. Of the proposed mechanisms responsible for exercise‐induced appetite suppression, lactate has garnered the most support through in vitro and in vivo rodent studies as well as a growing amount of work in humans. Other potential modulators of exercise‐induced appetite suppression may include sex hormones, growth‐differentiation factor 15, Lac‐Phe, brain‐derived neurotrophic factor, and asprosin. Research should focus on the mechanisms responsible for the changes and consider these other modulators (i.e., myokines/exerkines) of appetite to improve our understanding of the role of exercise on appetite regulation. [ABSTRACT FROM AUTHOR]

Summary Background and Aims Methods Results Conclusion Myokines are the muscle‐derived hormones orchestrating muscle and systemic health. Their role in the progression of alcohol‐associated liver disease (ALD) remains elusive.Three‐hundred‐one patients across the spectrum of ALD including fatty liver (FL, N = 13), compensated cirrhosis (CC, N = 17), non‐acute decompensation (NAD, N = 95), acute decompensation (AD, N = 51) and acute‐on‐chronic liver failure (ACLF, N = 125) were recruited between 2021 and 2023. Plasma myostatin, decorin levels, nutritional status, handgrip strength (HGS), systemic inflammation, infection, ammonia, disease course and 30‐day mortality were recorded.Patients aged 48 years (IQR: 38–52) and 97.7% of males were enrolled. Myostatin was elevated while decorin was reduced in cirrhosis compared to without cirrhosis, and further in DC compared to CC (p < 0.001). A step‐wise increase in myostatin and reduction in decorin was observed transitioning from NAD to AD to ACLF (p < 0.001). Myostatin was further increased and decorin was reduced along with the grades and organ failures in AD and ACLF (p < 0.001, each). Baseline decorin (AUC: 0.797) and its combination with MELD (AUC: 0.814) predicted disease resolution in AD and ACLF. Although, both myostatin (aOR: 18.96) and decorin (aOR: 0.02) could predict mortality, decorin was independent (aOR: 0.04) and additive to MELD (AUC of MELD+logDecorin + logTLC + HE‐grade:0.815); p < 0.05 each. Myostatin increased and decorin reduced with inflammation, hyperammonaemia, malnutrition and HGS in AD and ACLF (p < 0.05, each).Myokines are linked with malnutrition, fibrosis, systemic inflammation, organ failures, disease course and mortality in ALD. Decorin enhances the risk estimation of mortality of MELD in AD and ACLF. Therapeutic modulation of myokines is a potentially disease‐modifying target in ALD. [ABSTRACT FROM AUTHOR]

Background: The lack of physical activity is a common issue in modern society and is considered a major risk factor for various chronic non-communicable diseases. Bioactive factors secreted by skeletal muscle during exercise play a crucial role in inter-organ interactions. Since the concept of "myokines" was proposed in 2004, hundreds of regulatory myokines have been identified. Visual analysis of research on exercise-regulated myokines is significant to explore research hotspots and frontiers in this field. Methods: Research literature on exercise-regulated myokines from 2003 to 2023 in the "Web of Science" database was used as the data source. Knowledge maps were drawn using "VOS Viewer, CiteSpace, and R-bibliometrix" software. Results: A total of 1,405 papers were included, showing a fluctuating yet slow growth in annual publications. The United States and China led in the number of publications and collaboration networks. Harvard University ranked first with 120 publications. CIBER (centrality 0.16) and the University of California System (centrality 0.16) were pivotal in advancing this field. PEDERSEN BK led author rankings with 41 publications and 1,952 citations. FRONTIERS IN PHYSIOLOGY ranked first among journals with 64 publications and the highest g-index (39), while PLoS One had the highest h-index (25) and most citations (2,599). Key cocited reference clusters included #1 skeletal muscle dysfunction, #2 obesity, #6 ASCs, and #7 adaptive immunocytes. Pontus Boström's paper had a notable citation burst intensity of 77.37. High-frequency keywords were "exercise" (509), "skeletal muscle" (452), and "expression" (293), with long-term keywords such as #0 irisin, #2 insulin resistance, #3 transcription, and #6 physical activity. Recently, keywords like "physical exercise," "resistance exercise," "aerobic exercise," "insulin," and "oxidative stress" have emerged. Conclusion: Research in the field of exercise-regulated myokines shows an overall upward trend. The focus areas include myokines mediated by different types of exercise, the interaction of irisin-mediated muscle with other organs, and the important role of myokine-mediated oxidative stress in exercise simulation. [ABSTRACT FROM AUTHOR]

Sarcopenia is a multifactorial age-related disorder that causes a decrease in muscle mass, strength, and function, leading to alteration of movement, risk of falls, and hospitalization. This article aims to review recent findings on the factors underlying sarcopenia and the strategies required to delay and counteract its symptoms. We focus on molecular factors linked to ageing, on the role of low-grade chronic and acute inflammatory conditions such as cancer, which contributes to the onset of sarcopenia, and on the clinical criteria for its diagnosis. The use of drugs against sarcopenia is still subject to debate, and the suggested approaches to restore muscle health are based on adequate dietary protein intake and physical exercise. We also highlight the difference in the amount and quality of amino acids within animal- and plant-based diets, as studies have often shown varying results regarding their effect on sarcopenia in elderly people. In addition, many studies have reported that non-pharmacological approaches, such as an optimization of dietary protein intake and training programs based on resistance exercise, can be effective in preventing and delaying sarcopenia. These approaches not only improve the maintenance of skeletal muscle function, but also reduce health care costs and improve life expectancy and quality in elderly people. [ABSTRACT FROM AUTHOR]

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT. [ABSTRACT FROM AUTHOR]

Postmenopausal osteoporosis is a prevalent metabolic bone disorder characterized by a decrease in bone mineral density and deterioration of bone microstructure. Despite the high prevalence of this disease, no effective treatment for osteoporosis has been developed. Exercise has long been considered a potent anabolic factor that promotes bone mass via upregulation of myokines secreted by skeletal muscle, exerting long‐term osteoprotective effects and few side effects. Irisin was recently identified as a novel myokine that is significantly upregulated by exercise and could increase bone mass. However, the mechanisms underlying exercise‐induced muscle‐bone crosstalk remain unclear. Here, we identified that polyunsaturated fatty acids (arachidonic acid and docosahexaenoic acid) are increased in skeletal muscles following a 10‐week treadmill exercise programme, which then promotes the expression and release of FNDC5/irisin. In osteoblasts, irisin binds directly to Cav1, which recruits and interacts with AMP‐activated protein kinase α (AMPKα) to activate the AMPK pathway. Nrf2 is the downstream target of the AMPK pathway and increases the transcription of HMOX1 and Fpn. HMOX1 is involved in regulating the cell cycle and promotes the proliferation of osteoblasts. Moreover, upregulation of Fpn in osteoblasts enhanced iron removal, thereby suppressing ferroptosis in osteoblasts. Additionally, we confirmed that myotube‐derived exosomes are involved in the transportation of irisin and enter osteoblasts through caveolae‐mediated endocytosis. In conclusion, our findings highlight the crucial role of irisin, present in myotube‐derived exosomes, as a crucial regulator of exercise‐induced protective effects on bone, which provides novel insights into the mechanisms underlying exercise‐dependent treatment of osteoporosis. [ABSTRACT FROM AUTHOR]

Electrical muscle stimulation (EMS) has been shown to stimulate the production of myokines (i.e., brain-derived neurotrophic factor (BDNF)), but the most effective EMS parameters for myokine production have not been fully elucidated. The purpose of this study was to quantify the optimal EMS frequency for stimulating myokine production. This study included sixteen young adults (male, n = 13, age = 27.3 ± 5.5 years). Participants underwent four EMS interventions (20 min each) with the following conditions: (1) 4 Hz, (2) 20 Hz, (3) 80 Hz, and (4) control (no intervention). Blood samples were obtained before and immediately after EMS. For the control condition, blood samples were taken before and after 20 min of quiet sitting. BDNF and cathepsin-B levels were analyzed in serum. Compared to preintervention levels, stimulation at 20 Hz resulted in significantly greater postintervention cathepsin-B and BDNF levels (p < 0.01). On the other hand, the control condition did not result in a significant change between pre- and posttreatment. Furthermore, stimulation at 20 Hz caused significantly larger increases in cathepsin-B and BDNF levels than stimulation at 4–80 Hz or the control condition (p < 0.05). In conclusion, stimulation at 20 Hz effectively causes a robust cathepsin-B and BDNF response. Based on these results, we suggest a new strategy for rehabilitation of people with neurological disorders. [ABSTRACT FROM AUTHOR]

Transient receptor potential (TRP) channels are broadly implicated in the developmental programs of most tissues. Amongst these tissues, skeletal muscle and adipose are noteworthy for being essential in establishing systemic metabolic balance. TRP channels respond to environmental stimuli by supplying intracellular calcium that instigates enzymatic cascades of developmental consequence and often impinge on mitochondrial function and biogenesis. Critically, aminoglycoside antibiotics (AGAs) have been shown to block the capacity of TRP channels to conduct calcium entry into the cell in response to a wide range of developmental stimuli of a biophysical nature, including mechanical, electromagnetic, thermal, and chemical. Paradoxically, in vitro paradigms commonly used to understand organismal muscle and adipose development may have been led astray by the conventional use of streptomycin, an AGA, to help prevent bacterial contamination. Accordingly, streptomycin has been shown to disrupt both in vitro and in vivo myogenesis, as well as the phenotypic switch of white adipose into beige thermogenic status. In vivo, streptomycin has been shown to disrupt TRP-mediated calcium-dependent exercise adaptations of importance to systemic metabolism. Alternatively, streptomycin has also been used to curb detrimental levels of calcium leakage into dystrophic skeletal muscle through aberrantly gated TRPC1 channels that have been shown to be involved in the etiology of X-linked muscular dystrophies. TRP channels susceptible to AGA antagonism are critically involved in modulating the development of muscle and adipose tissues that, if administered to behaving animals, may translate to systemwide metabolic disruption. Regenerative medicine and clinical communities need to be made aware of this caveat of AGA usage and seek viable alternatives, to prevent contamination or infection in in vitro and in vivo paradigms, respectively. [ABSTRACT FROM AUTHOR]

Aerobic exercise promotes uncoupling protein-1 (UCP-1) induced white adipose tissue browning by increasing serum nitric oxide (NO), irisin and interleukin-6 (IL-6). However, oxidative stress (OS) occurring during anaerobic exercise downregulates UCP-1. Moreover, UCP-1-3826 A/G polymorphism (UCP1P) is associated with weight gain due to impaired thermogenesis which may be due to UCP1P induced modification in OS. Therefore, our purpose was to investigate the role of UCP1P on the effects of acute maximal exercise (AME) and chronic anaerobic exercise (CAT) on serum OS, UCP-1, NO, irisin and IL-6 levels. Sport group (SG, n = 43) was formed of anaerobic athletes, while control group (CG, n = 43) comprised physically inactive men. Postprandial blood was taken from SG and CG before and after AME to determine serum UCP-1, irisin, IL-6, NO, and oxidative stress index (OSI = total oxidant/antioxidant status [TOS/TAS] ratio). To investigate the effects of CAT on serum parameters, SG and CG's results were compared. UCP1P was determined by restriction fragment length polymorphism analysis. AME significantly increased all parameters in SG and CG (P < 0.05). However, CAT increased only OSI and IL-6 (P < 0.05), decreased UCP-1 and TAS and did not affect TOS, NO and irisin. OSI of GG homozygous athletes were significantly higher than other genotype groups (P < 0.05). Although significant negative correlations were found between UCP-1 and OS markers in GG and AA genotype groups before AME, significant positive correlations were found between UCP-1 and TAS in AA genotype group after AME. GG homozygous athletes may be more prone to higher OS. Decrease in UCP-1 due to CAT may be affected by GG genotype group's genetic disposition for OS. [ABSTRACT FROM AUTHOR]

Hair loss affects men and women of all ages. Myokines, which are mainly secreted by skeletal muscles during exercise, have numerous health benefits. VEGF, IGF‐1, FGF and irisin are reprehensive myokines. Although VEGF, IGF‐1 and FGF are positively associated with hair growth, few studies have researched the effects of irisin on hair growth. Here, we investigated whether irisin promotes hair growth using in vitro, ex vivo and in vivo patch assays, as well as mouse models. We show that irisin increases proliferation, alkaline phosphatase (ALP) activity and mitochondrial membrane potential in human dermal papilla cells (hDPCs). Irisin activated the Wnt/β‐catenin signalling pathway, thereby upregulating Wnt5a, Wnt10b and LEF‐1, which play an important role in hair growth. Moreover, irisin enhanced human hair shaft elongation. In vivo, patch assays revealed that irisin promotes the generation of new hair follicles, accelerates entry into the anagen phase, and significantly increases hair growth in C57BL/6 mice. However, XAV939, a Wnt/β‐catenin signalling inhibitor, suppressed the irisin‐mediated increase in hair shaft and hair growth. These results indicate that irisin increases hair growth via the Wnt/β‐catenin pathway and highlight its therapeutic potential in hair loss treatment. [ABSTRACT FROM AUTHOR]

Chronic kidney disease (CKD) is linked to an elevated risk of malnutrition and sarcopenia, contributing to the intricate network of CKD-related metabolic disorders. Adipokines and myokines are markers and effectors of sarcopenia and nutritional status. The aim of this study was to assess whether the adipokine–myokine signature in patients on kidney replacement therapy could help identify malnutrition and sarcopenia. The study involved three groups: 84 hemodialysis (HD) patients, 44 peritoneal dialysis (PD) patients, and 52 kidney transplant recipients (KTR). Mean age was 56.1 ± 16.3 years. Malnutrition was defined using the 7-Point Subjective Global Assessment (SGA) and the Malnutrition-Inflammation Score (MIS). Sarcopenia was diagnosed based on reduced handgrip strength (HGS) and diminished muscle mass. Concentrations of adipokines and myokines were determined using the enzyme-linked immunosorbent assay (ELISA). 32.8% of all study participants were identified as malnourished and 20.6% had sarcopenia. For malnutrition, assessed using the 7-Point SGA, in ROC analysis albumin (area under the curve (AUC) 0.67 was the best single biomarker identified. In dialysis patients, myostatin (AUC 0.79) and IL-6 (AUC 0.67) had a high discrimination value for sarcopenia, and we were able to develop a prediction model for sarcopenia, including age, albumin, adiponectin, and myostatin levels, with an AUC of 0.806 (95% CI: 0.721–0.891). Adipokines and myokines appear to be useful laboratory markers for assessing malnutrition and sarcopenia. The formula we propose could contribute to a better understanding of sarcopenia and potentially lead to more effective interventions and management strategies for dialysis patients. [ABSTRACT FROM AUTHOR]

Anatomically connected bones and muscles determine movement of the body. Forces exerted on muscles are then turned to bones to promote osteogenesis. The crosstalk between muscle and bone has been identified as mechanotransduction previously. In addition to the mechanical features, bones and muscles are also secretory organs which interact closely with one another through producing myokines and osteokines. Moreover, besides the mechanical features, other factors, such as nutrition metabolism, physiological rhythm, age, etc., also affect bone-muscle crosstalk. What's more, osteogenesis and myogenesis within motor system occur almost in parallel. Pathologically, defective muscles are always detected in bone associated diseases and induce the osteopenia, inflammation and abnormal bone metabolism, etc., through biomechanical or biochemical coupling. Hence, we summarize the study findings of bone-muscle crosstalk and propose potential strategies to improve the skeletal or muscular symptoms of certain diseases. Altogether, functional improvement of bones or muscles is beneficial to each other within motor system. Key points: • Bone-muscle crosstalk is established by various osteokines and myokines. • Bone-muscle crosstalk is subjected to diseases not only defined in motor system. • MSCs secret exosomes rich in noncoding RNAs to function on muscles. • Bone metastasis of breast cancer is also harmful to muscles. [ABSTRACT FROM AUTHOR]

• Cortical excitability does not change following acute HIIT. • Acute HIIT enhances working memory and mental rotation in healthy young adults. • Acute HIIT boosts serum BDNF and CTSB levels, implying potential neuroprotection. High-intensity interval training (HIIT) is a time-efficient, safe, and feasible exercise type that can be utilized across different ages and health status. This randomized cross-over study aimed to investigate the effect of acute HIIT on cortical excitability, M1-related cognitive functions, cognition-related myokines, brain-derived neurotrophic factor (BDNF), and Cathepsin B (CTSB). Twenty-three sedentary young adults (mean age: 22.78 years ± 2.87; 14 female) participated in a cross-over design involving two sessions: either 23 min of HIIT or seated rest. Before and after the sessions, cortical excitability was measured using transcranial magnetic stimulation, and M1-related cognitive functions were assessed by the n-back test and mental rotation test. Serum levels of BDNF and CTSB were assessed using the ELISA method before and after the HIIT intervention. We demonstrated that HIIT improved mental rotation and working memory, and increased serum levels of BDNF and CTSB, whereas cortical excitability did not change. Our findings provide evidence that one session of HIIT is effective on M1-related cognitive functions and cognition-related myokines. Future research is warranted to determine whether such findings are transferable to different populations, such as cognitively at-risk children, adults, and older adults, and to prescribe effective exercise programs. [ABSTRACT FROM AUTHOR]

Oestradiol withdrawal at menopause predisposes women to metabolic syndrome, a cluster of interrelated conditions including obesity, insulin resistance, dyslipidaemia and hypertension that together confer an increased risk of developing type 2 diabetes mellitus and cardiovascular disease. Hormone replacement therapies are commonly used to treat acute symptoms of the perimenopausal period, and whilst they have been associated with metabolic improvements in many studies, long-term use is considered unviable. Novel approaches are required to mitigate the risk of postmenopausal metabolic syndrome. In 2012, the exercise-inducible myokine irisin was isolated from the skeletal muscle of mice and identified to have anti-obesity and antidiabetic effects in vivo. Irisin is now recognised to exert pleiotropic action on cognitive, bone and metabolic health. There is accumulating evidence from in vitro and in vivo rodent studies that irisin can mitigate each component condition of metabolic syndrome. In postmenopausal women, independent associations have been observed between (a) exercise and plasma irisin concentration and (b) plasma irisin concentration and reduced incidence of metabolic syndrome. To date, however, no study has considered the mechanistic basis by which irisin, whether exercise-induced or exogenously administered, could reduce the incidence or severity of metabolic syndrome in postmenopausal women. This review aims to analyse the literature concerning the metabolic actions of irisin, with a focus on its therapeutic potential for metabolic syndrome driven by a state of oestradiol depletion. It evaluates the practicality of exercise as a therapy and discusses other irisin-based therapeutic strategies that may alleviate postmenopausal metabolic syndrome. Finally, it highlights areas where future research is required to advance knowledge of irisin’s biological action such that it could be considered a viable candidate for clinical application. [ABSTRACT FROM AUTHOR]

Introduction: Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. Methods: A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. Discussion: If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. Trial registration: The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213. [ABSTRACT FROM AUTHOR]

Skeletal muscle growth is an economically important trait in the cattle industry. Secreted muscle-derived proteins, referred to as myokines, have important roles in regulating the growth, metabolism, and health of skeletal muscle in human and biomedical research models. Accumulating evidence supports the importance of myokines in skeletal muscle and whole-body health, though little is known about the potential presence and functional significance of these proteins in cattle. This study evaluates and confirms that secreted proteins acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), myostatin (MSTN), and decorin (DCN) are expressed and SPARC, FGF-21, and DCN are secreted by primary bovine satellite cells from 3- (BSC3; n = 3) and 11- (BSC11; n = 3) month -old commercial angus steers. Cells were cultured and collected at zero, 12, 24, and 48 hours to characterize temporal expression and secretion from undifferentiated and differentiated cells. The expression of SPARC was higher in the undifferentiated (p = 0.04) and differentiated (p = 0.07) BSC11 than BSC3. The same was observed with protein secretion from undifferentiated (p <0.0001) BSC11 compared to BSC3. Protein secretion of FGF-21 was higher in undifferentiated BSC11 (p < 0.0001) vs. BSC3. DCN expression was higher in differentiated BSC11 (p = 0.006) vs. BSC3. Comparing undifferentiated vs. differentiated BSC, MSTN expression was higher in differentiated BSC3 (p ≤ 0.001) for 0, 12, and 24 hours and in BSC11 (p ≤ 0.03) for 0, 12, 24, and 48 hours. There is also a change over time for SPARC expression (p ≤ 0.03) in undifferentiated and differentiated BSC and protein secretion (p < 0.0001) in undifferentiated BSC, as well as FGF-21 expression (p = 0.007) in differentiated BSC. This study confirms SPARC, FGF-21, and DCN are secreted, and SPARC, FGF-21, MSTN, and DCN are expressed in primary bovine muscle cells with age and temporal differences. [ABSTRACT FROM AUTHOR]

• Exercise-conditioned serum has inhibitory effects on cancer cell growth and promotes apoptosis in different cancer cell lines. • A single bout of moderate to vigorous intensity aerobic training may have suppressive effects on cancer cells and elicit substantial increases in circulating factors. • Training volume may play a role in inhibiting cancer cells and altering circulating factors, regardless of the training mode used, when examining short-term and chronic training interventions. • Future research should be directed to targeted investigations into the effects of exercise-conditioned serum on cancer cells, based on specific training modes, volume, and intensity stratifying by treatments or disease stage. Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells. [Display omitted] [ABSTRACT FROM AUTHOR]

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The role of bone and muscle as endocrine organs may be important contributing factors for children’s growth and development. Myokines, secreted by muscle cells, play a role in regulating bone metabolism, either directly or indirectly. Conversely, markers of bone metabolism, reflecting the balance between bone formation and bone resorption, can also influence myokine secretion. This study investigated a panel of serum myokines and their relationships with bone metabolism markers in children following vegetarian and omnivorous diets. A cohort of sixty-eight healthy prepubertal children, comprising 44 vegetarians and 24 omnivores, participated in this study. Anthropometric measurements, dietary assessments, and biochemical analyses were conducted. To evaluate the serum concentrations of bone markers and myokines, an enzyme-linked immunosorbent assay (ELISA) was used. The studied children did not differ regarding their serum myokine levels, except for a higher concentration of decorin in the vegetarian group (p = 0.020). The vegetarians demonstrated distinct pattern of bone metabolism markers compared to the omnivores, with lower levels of N-terminal propeptide of type I procollagen (P1NP) (p = 0.001) and elevated levels of C-terminal telopeptide of type I collagen (CTX-I) (p = 0.018). Consequently, the P1NP/CTX-I ratio was significantly decreased in the vegetarians. The children following a vegetarian diet showed impaired bone metabolism with reduced bone formation and increased bone resorption. Higher levels of decorin, a myokine involved in collagen fibrillogenesis and essential for tissue structure and function, may suggest a potential compensatory mechanism contributing to maintaining bone homeostasis in vegetarians. The observed significant positive correlations between myostatin and bone metabolism markers, including P1NP and soluble receptor activator of nuclear factor kappa-B ligand (sRANKL), suggest an interplay between muscle and bone metabolism, potentially through the RANK/RANKL/OPG signaling pathway. [ABSTRACT FROM AUTHOR]

Sarcopenia is a multifactorial age-related disorder that causes a decrease in muscle mass, strength, and function, leading to alteration of movement, risk of falls, and hospitalization. This article aims to review recent findings on the factors underlying sarcopenia and the strategies required to delay and counteract its symptoms. We focus on molecular factors linked to ageing, on the role of low-grade chronic and acute inflammatory conditions such as cancer, which contributes to the onset of sarcopenia, and on the clinical criteria for its diagnosis. The use of drugs against sarcopenia is still subject to debate, and the suggested approaches to restore muscle health are based on adequate dietary protein intake and physical exercise. We also highlight the difference in the amount and quality of amino acids within animal- and plant-based diets, as studies have often shown varying results regarding their effect on sarcopenia in elderly people. In addition, many studies have reported that non-pharmacological approaches, such as an optimization of dietary protein intake and training programs based on resistance exercise, can be effective in preventing and delaying sarcopenia. These approaches not only improve the maintenance of skeletal muscle function, but also reduce health care costs and improve life expectancy and quality in elderly people.

Abstract Introduction Physical activity is associated with improved disease progression and cancer-specific survival in patients with prostate cancer (PCa). However, the mechanisms underlying these associations remain unclear, while the relative impact of exercise modes is unknown. This study aims to examine the differential impact of exercise mode on tumour-suppressive skeletal muscle-associated systemic molecules as well as their delivery mechanism. This study will compare the effects of the two main exercise modes, aerobic and resistance, on (1) circulatory myokine levels, (2) skeletal muscle-induced extracellular vesicle abundance and cargo contents, and (3) uptake of extracellular vesicles (EVs) in PCa cells in patients with localised or advanced PCa. Methods A single-group cross-over design will be used for patients at opposite ends of the disease spectrum. A total of 32 patients (localised PCa, n = 16; metastatic castrate-resistant PCa, n = 16) will be recruited while capitalising on two ongoing studies. Ethics amendment has been approved for two ongoing trials to share data, implement the acute exercise sessions, and collect additional blood samples from patients. The patients will undertake two exercise sessions (aerobic only and resistance only) in random order one week apart. Blood will be collected before, after, and 30 min post-exercise. Circulating/EV-contained myokine levels (irisin, IL-6, IL-15, FGF-21, and SPARC) and plasma skeletal muscle-induced EVs will be measured using ELISA and flow cytometry. PCa cell line growth with or without collected plasma will be examined using PCa cell lines (LNCaP, DU-145, and PC-3), while evaluating cellular uptake of EVs. Ethics amendments have been approved for two capitalising studies to share data, implement acute exercise sessions and collect additional samples from the patients. Discussion If findings show a differential impact of exercise mode on the establishment of an anti-cancer systemic environment, this will provide fundamental knowledge for developing targeted exercise prescriptions for patients with PCa across different disease stages. Findings will be reported in peer-reviewed publications and scientific conferences, in addition to working with national support groups to translate findings for the broader community. Trial registration The registration for the two capitalising studies are NCT02730338 and ACTRN12618000225213.

Cancer is a major cause of morbidity and mortality worldwide, and the incidence is increasing, highlighting the need for effective strategies to treat this disease. Exercise has emerged as fundamental therapeutic medicine in the management of cancer, associated with a lower risk of recurrence and increased survival. Several avenues of research demonstrate reduction in growth, proliferation, and increased apoptosis of cancer cells, including breast, prostate, colorectal, and lung cancer, when cultured by serum collected after exercise in vitro (i.e., the cultivation of cancer cell lines in an experimental setting, which simplifies the biological system and provides mechanistic insight into cell responses). The underlying mechanisms of exercise-induced cancer suppressive effects may be attributed to the alteration in circulating factors, such as skeletal muscle-induced cytokines (i.e., myokines) and hormones. However, exercise-induced tumor suppressive effects and detailed information about training interventions are not well investigated, constraining more precise application of exercise medicine within clinical oncology. To date, it remains unclear what role different training modes (i.e., resistance and aerobic training) as well as volume and intensity have on exercise-conditioned serum and its effects on cancer cells. Nevertheless, the available evidence is that a single bout of aerobic training at moderate to vigorous intensity has cancer suppressive effects, while for chronic training interventions, exercise volume appears to be an influential candidate driving cancer inhibitory effects regardless of training mode. Insights for future research investigating training modes, volume and intensity are provided to further our understanding of the effects of exercise-conditioned serum on cancer cells.

• A single bout of exercise is likely to induce small to large increases in myokine expression immediately after and up to 60 min post-exercise, while myokine responses typically revert to baseline levels from 180 min to 24 h post-exercise. • Both aerobic exercise and resistance exercise lead to notable changes in the expression of myokines; however, the magnitude of these changes varies according to the specific myokine type. • This meta-analysis expands our knowledge of the overall effects of myokine expression in relation to exercise modes; however, substantial variation is evident, indicating that the response to exercise mode is myokine-specific. • Some exercise modes and time points have not been investigated for certain myokines and, thus, should be considered for future research. The benefits of exercise are well known; however, many of the underlying molecular mechanisms are not fully understood. Skeletal muscle secretes myokines, which mediate muscle–organ crosstalk. Myokines regulate satellite-cell proliferation and migration, inflammatory cascade, insulin secretion, angiogenesis, fatty oxidation, and cancer suppression. To date, the effects of different exercise modes (namely, aerobic and resistance exercise) on myokine response remain to be elucidated. This is crucial considering the clinical implementation of exercise to enhance general health and wellbeing and as a medical treatment. A systematic search was undertaken in PubMed, MEDLINE, CINAHL, Embase, SPORTDiscus, and Web of Science in April 2023. Eligible studies examining the effects of a single bout of exercise on interleukin15 (IL-15), irisin, secreted protein acidic and rich in cysteine (SPARC), oncostatin M (OSM), and decorin were included. A random-effects meta-analysis was also undertaken to quantify the magnitude of change. Sixty-two studies were included (n = 1193). Overall, exercise appeared to induce small to large increases in myokine expression, with effects observed immediately after to 60 min post-exercise, although these were mostly not statistically significant. Both aerobic and resistance exercise resulted in changes in myokine levels, without any significant difference between training modes, and with the magnitude of change differing across myokines. Myokine levels returned to baseline levels within 180 min to 24 h post-exercise. However, owing to potential sources of heterogeneity, most changes were not statistically significant, indicating that precise conclusions cannot be drawn. Knowledge is limited but expanding with respect to the impact of overall and specific effects of exercise on myokine expression at different time points in the systemic circulation. Further research is required to investigate the effects of different exercise modes at multiple time points on myokine response. [Display omitted] [ABSTRACT FROM AUTHOR]

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Sarcopenia is associated with progressive generalized skeletal muscle weakness, persistent decline in muscle strength, function, and quality of life in the elderly population. The presence of sarcopenia worsens the prognosis of older patients. In this regard, the study of the etiology and pathogenesis of sarcopenia, the identification of early markers for the diagnosis of this disease are relevant areas today. Myokines are secreted by skeletal muscle and play a important role in the regulation of muscle mass and function, metabolic homeostasis. Myokine synthesis disruption may contribute to the development of sarcopenia. In addition, we can see the polymorphism association of various genes with the development of the disease. This review brings together current knowledge about myokines and genetic factors as potential biomarkers for the early diagnosis of sarcopenia.

Purpose of the study: the aim of that study was an investigation of the level of adipokines, myokines and growth factors in the blood of athletes involved in acyclic sports — martial arts.Materials and methods: we have investigated 15 male athletes aged 15–19 years. The control group included 15 healthy men of the same age who did not engage in sports. In the blood serum of the all subjects, leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrin and oncostatin were determined using a multiplex analysis.Results: studies have shown that long-term regular martial arts training is accompanied by a decrease in the level of leptin, resistin and oncostatin M in the blood of athletes and a change in correlations between the content of the studied myokines, adipokines and growth factors compared with their values in the control group.Conclusions: regular long-term martial arts training is accompanied by a decrease in the level of leptin, resistin and oncostatin M in the blood of athletes. Their occurrence is associated with changes in the state of regulatory systems that control the production and secretion of myokines, adipokines and growth factors in adipose, muscle, nervous and bone tissue. The resulting shifts ensure adaptation of the athletes’ bodies to physical activity.

BACKGROUND: A special role in the development of obesity is given to the genetic polymorphism of lipid metabolism enzymes, which include triacylglycerol lipase. However, there is still no information about the relationship between the single nucleotide polymorphism (snp) of the triacylglycerol lipase (LIPC) gene and the state of the endocrine function of mesenchymal tissues in childhood and adolescence obesity.AIM: The aim of the work was to study the relationship between snp LIPC for rs2070895 and changes in the content of adipokines, myokines, and the values of blood lipid metabolism in obese children and adolescents with different sexes.MATERIALS AND METHODS: In 96 healthy children and adolescents of different sexes and 98 obese peers, a study was conducted to assess the snp of the LIPC by rs2070895. In the blood serum of the examined, the content of total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triacylglycerols, glucose, activity of alanine aminotransferase and aspartate aminotransferase, as well as the level of leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrine, oncostatin M , insulin and asprosin.RESULTS AND DISCUSSION: It has been established that obesity in boys is accompanied by hyperleptinemia, the occurrence of insulin resistance and disorders of blood lipid metabolism. In carriers of the heterozygous allele -250G/A, dyslipidemia and atherogenesis decrease in obesity, but alteration of internal organs increases. In girls with different LIPC genotypes for rs2070895, with obesity, there is an increase in the level of leptin and apelin, as well as irisin and insulin in the blood. In girls with the homozygous allele -250G/G, in addition to that, the content of resistin, asprosin and prolactin decreases in the blood, which is not are typical for girls with the heterozygous allele -250G/A. In obese girls with the heterozygous allele, the levels of adipsin, FGF-21, oncostatin M, and osteocrine increase, which are not typical for obese girls with the homozygous allele. Against the background of changes in the content of adipokines and myokines in girls homozygous for LIPC, obesity occurs dyslipemia, which is not typical for girls with the heterozygous allele -250G/A.CONCLUSION: The snp of LIPC at rs2070895 has sex-dependent effects on the levels of adipokines, myokines, and parameters lipid metabolism in the blood.

Background/Objectives: Myokines have been demonstrated to be associated with cardiovascular diseases; however, they have not been studied as biomarkers for peripheral artery disease (PAD). We identified interleukin-7 (IL-7) as a prognostic biomarker for PAD from a panel of myokines and developed predictive models for 2-year major adverse limb events (MALEs) using clinical features and plasma IL-7 levels. Methods: A prognostic study was conducted with a cohort of 476 patients (312 with PAD and 164 without PAD) that were recruited prospectively. Their plasma concentrations of five circulating myokines were measured at recruitment, and the patients were followed for two years. The outcome of interest was two-year MALEs (composite of major amputation, vascular intervention, or acute limb ischemia). Cox proportional hazards analysis was performed to identify IL-7 as the only myokine that was associated with 2-year MALEs. The data were randomly divided into training (70%) and test sets (30%). A random forest model was trained using clinical characteristics (demographics, comorbidities, and medications) and plasma IL-7 levels with 10-fold cross-validation. The primary model evaluation metric was the F1 score. The prognostic model was used to classify patients into low vs. high risk of developing adverse limb events based on the Youden Index. Freedom from MALEs over 2 years was compared between the risk-stratified groups using Cox proportional hazards analysis. Results: Two-year MALEs occurred in 28 (9%) of patients with PAD. IL-7 was the only myokine that was statistically significantly correlated with two-year MALE (HR 1.56 [95% CI 1.12–1.88], p = 0.007). For the prognosis of 2-year MALEs, our model achieved an F1 score of 0.829 using plasma IL-7 levels in combination with clinical features. Patients classified as high-risk by the predictive model were significantly more likely to develop MALEs over a 2-year period (HR 1.66 [95% CI 1.22–1.98], p = 0.006). Conclusions: From a panel of myokines, IL-7 was identified as a prognostic biomarker for PAD. Using a combination of clinical characteristics and plasma IL-7 levels, we propose an accurate predictive model for 2-year MALEs in patients with PAD. Our model may support PAD risk stratification, guiding clinical decisions on additional vascular evaluation, specialist referrals, and medical/surgical management, thereby improving outcomes. [ABSTRACT FROM AUTHOR]

Skeletal muscle (SKM), despite comprising ~40% of body mass, rarely manifests cancer. This review explores the mechanisms that help to explain this rarity, including unique SKM architecture and function, which prohibits the development of new cancer as well as negates potential metastasis to SKM. SKM also presents a unique immune environment that may magnify the anti-tumorigenic effect. Moreover, the SKM microenvironment manifests characteristics such as decreased extracellular matrix stiffness and altered lactic acid, pH, and oxygen levels that may interfere with tumor development. SKM also secretes anti-tumorigenic myokines and other molecules. Collectively, these mechanisms help account for the rarity of SKM cancer. [ABSTRACT FROM AUTHOR]

Objective: Diabetes retinopathy (DR) is one of the top listed world health issues. Screening is usually advised for diabetic cases on a routine basis. However, there is only partial access to ophthalmologists in all parts of the world. Irisin is a myokine that is being investigated for this reason. Our study aims to assess the role of irisin in detecting DR. Methods and materials: In a cross-sectional study, 140 diabetes cases, including 70 patients with diabetic retinopathy and 70 patients free from diabetic retinopathy, were enrolled. Demographic and anthropometric data were gathered, and the patients underwent physical examination. Also, microalbuminuria and serum irisin levels were assessed in both groups. The results were compared between the two study groups. Results: Among the enrolled cases, 55 (39.28%) were men, and 85 (60.72%) were women. The disease duration (p = 0.016) and the serum level of HBA1c (p = 0.014) were significantly higher in the diabetic retinopathy group compared to the group free from diabetic retinopathy. Moreover, irisin was significantly higher in the patients free from diabetic retinopathy (p = 0.007). Conclusion: Irisin may have value in screening diabetic retinopathy; however, further studies are needed for this proposal. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic inflammatory disease that affects synovial joints and that frequently involves extra-articular organs. A multiplicity of interleukins (IL) participates in the pathogenesis of RA, including IL-6, IL-1β, transforming growth factor-beta (TGF-β), and tumor necrosis factor (TNF)-α; immune cells such as monocytes, T and B lymphocytes, and macrophages; and auto-antibodies, mainly rheumatoid factor and anti-citrullinated protein antibodies (ACPAs). Skeletal muscle is also involved in RA, with many patients developing muscle wasting and sarcopenia. Several mechanisms are involved in the myopenia observed in RA, and one of them includes the effects of some interleukins and myokines on myocytes. Myostatin is a myokine member of the TGF-β superfamily; the overproduction of myostatin acts as a negative regulator of growth and differentiates the muscle fibers, limiting their number and size. Recent studies have identified abnormalities in the serum myostatin levels of RA patients, and these have been found to be associated with muscle wasting and other manifestations of severe RA. This review analyzes recent information regarding the relationship between myostatin levels and clinical manifestations of RA and the relevance of myostatin as a therapeutic target for future research. [ABSTRACT FROM AUTHOR]

Background: Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation. Methods: Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment. Results: Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA. Conclusions: RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary: Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines – molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation. Key Messages: The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic. [ABSTRACT FROM AUTHOR]

Myokines and exosomes, originating from skeletal muscle, are shown to play a significant role in maintaining brain homeostasis. While exercise has been reported to promote muscle secretion, little is known about the effects of neuronal innervation and activity on the yield and molecular composition of biologically active molecules from muscle. As neuromuscular diseases and disabilities associated with denervation impact muscle metabolism, we hypothesize that neuronal innervation and firing may play a pivotal role in regulating secretion activities of skeletal muscles. We examined this hypothesis using an engineered neuromuscular tissue model consisting of skeletal muscles innervated by motor neurons. The innervated muscles displayed elevated expression of mRNAs encoding neurotrophic myokines, such as interleukin-6, brain-derived neurotrophic factor, and FDNC5, as well as the mRNA of peroxisome-proliferator-activated receptor γ coactivator 1α, a key regulator of muscle metabolism. Upon glutamate stimulation, the innervated muscles secreted higher levels of irisin and exosomes containing more diverse neurotrophic microRNAs than neuron-free muscles. Consequently, biological factors secreted by innervated muscles enhanced branching, axonal transport, and, ultimately, spontaneous network activities of primary hippocampal neurons in vitro. Overall, these results reveal the importance of neuronal innervation in modulating muscle-derived factors that promote neuronal function and suggest that the engineered neuromuscular tissue model holds significant promise as a platform for producing neurotrophic molecules. [ABSTRACT FROM AUTHOR]

The health benefits of exercise training in a cancer setting are increasingly acknowledged; however, the underlying molecular mechanisms remain poorly understood. It has been suggested that extracellular vesicles (EVs) released from contracting skeletal muscles play a key role in mediating the systemic benefits of exercise by transporting bioactive molecules, including myokines. Nevertheless, skeletal muscle-derived vesicles account for only about 5% of plasma EVs, with the immune cells making the largest contribution. Moreover, it remains unclear whether the contribution of skeletal muscle-derived EVs increases after physical exercise or how muscle contraction modulates the secretory activity of other tissues and thus influences the content and profile of circulating EVs. Furthermore, the destination of EVs after exercise is unknown, and it depends on their molecular composition, particularly adhesion proteins. The cargo of EVs is influenced by the training program, with acute training sessions having a greater impact than chronic adaptations. Indeed, there are numerous questions regarding the role of EVs in mediating the effects of exercise, the clarification of which is critical for tailoring exercise training prescriptions and designing exercise mimetics for patients unable to engage in exercise programs. This review critically analyzes the current knowledge on the effects of exercise on the content and molecular composition of circulating EVs and their impact on cancer progression. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) is characterized by muscle metabolic dysfunction that exercise can minimize, but some patients do not respond to an exercise intervention. Myokine secretion is intrinsically altered in patients with T2D, but the role of myokines in exercise resistance in this patient population has never been studied. We sought to determine if changes in myokine secretion were linked to the response to an exercise intervention in patients with T2D. The participants followed a 10-week aerobic exercise training intervention, and patients with T2D were grouped based on muscle mitochondrial function improvement (responders versus non-responders). We measured myokines in serum and cell-culture medium of myotubes derived from participants pre- and post-intervention and in response to an in vitro model of muscle contraction. We also quantified the expression of genes related to inflammation in the myotubes pre- and post-intervention. No significant differences were detected depending on T2D status or response to exercise in the biological markers measured, with the exception of modest differences in expression patterns for certain myokines (IL-1β, IL-8, IL-10, and IL-15). Further investigation into the molecular mechanisms involving myokines may explain exercise resistance with T2D; however, the role in metabolic adaptations to exercise in T2D requires further investigation. [ABSTRACT FROM AUTHOR]

Myokines, released from the muscle, enable communication between the working muscles and other tissues. Their release during physical exercise is assumed to depend on immune–hormonal–metabolic interactions concerning mode (endurance or resistance exercise), duration, and intensity. This meta‐analysis aims to examine the acute changes of circulating myokines inducing immunoregulatory effects caused by a bout of resistance exercise and to consider potential moderators of the results. Based on this selection strategy, a systematic literature search was conducted for resistance exercise intervention studies measuring interleukin (IL‐) 6, IL‐10, IL‐1ra, tumor necrosis factor (TNF‐) α, IL‐15, IL‐7, transforming growth factor (TGF‐) β1, and fractalkines (FKN) before and immediately after resistance exercise in healthy individuals. Random‐effects meta‐analysis was performed for each myokine. We identified a moderate positive effect of resistance exercise for IL‐6 and IL‐1ra. Regarding IL‐15 and TNF‐α, small to moderate effects were found. For IL‐10, no significant effect was observed. Due to no data, meta‐analyses for IL‐7, TGF‐β1, and FKN could not be performed. No moderators (training status, type of exercise, risk of bias, age, sex, time of day, exercise volume, exercise intensity, exercise dose) of the results were detected for all tested myokines. Taken together, this systematic review and meta‐analysis showed immediate positive effects of an acute resistance exercise session on IL‐6, IL‐1ra, TNF‐α, and IL‐15 levels. [ABSTRACT FROM AUTHOR]

Interaction with the environment appears necessary for the maturation of sensorimotor and cognitive functions in early life. In rats, a model of sensorimotor restriction (SMR) from postnatal day 1 (P1) to P28 has shown that low and atypical sensorimotor activities induced the perturbation of motor behavior due to muscle weakness and the functional disorganization of the primary somatosensory and motor cortices. In the present study, our objective was to understand how SMR affects the muscle–brain dialogue. We focused on irisin, a myokine secreted by skeletal muscles in response to exercise. FNDC5/irisin expression was determined in hindlimb muscles and brain structures by Western blotting, and irisin expression in blood and cerebrospinal fluid was determined using an ELISA assay at P8, P15, P21 and P28. Since irisin is known to regulate its expression, Brain-Derived Neurotrophic Factor (BDNF) levels were also measured in the same brain structures. We demonstrated that SMR increases FNDC5/irisin levels specifically in the soleus muscle (from P21) and also affects this protein expression in several brain structures (as early as P15). The BDNF level was increased in the hippocampus at P8. To conclude, SMR affects FNDC5/irisin levels in a postural muscle and in several brain regions and has limited effects on BDNF expression in the brain. [ABSTRACT FROM AUTHOR]

Metabolic-associated fatty liver disease (MAFLD) includes several metabolic dysfunctions caused by dysregulation in the brain–gut–liver axis and, consequently, increases cardiovascular risks and fatty liver dysfunction. In MAFLD, type 2 diabetes mellitus, obesity, and metabolic syndrome are frequently present; these conditions are related to liver lipogenesis and systemic inflammation. This study aimed to review the connection between the brain–gut–liver axis and MAFLD. The inflammatory process, cellular alterations in hepatocytes and stellate cells, hypercaloric diet, and sedentarism aggravate the prognosis of patients with MAFLD. Thus, to understand the modulation of the physiopathology of MAFLD, it is necessary to include the organokines involved in this process (adipokines, myokines, osteokines, and hepatokines) and their clinical relevance to project future perspectives of this condition and bring to light new possibilities in therapeutic approaches. Adipokines are responsible for the activation of distinct cellular signaling in different tissues, such as insulin and pro-inflammatory cytokines, which is important for balancing substances to avoid MAFLD and its progression. Myokines improve the quantity and quality of adipose tissues, contributing to avoiding the development of MAFLD. Finally, hepatokines are decisive in improving or not improving the progression of this disease through the regulation of pro-inflammatory and anti-inflammatory organokines. [ABSTRACT FROM AUTHOR]

We considered in this study the possibility of developing an indirect procedure for detecting myostatin inhibition/suppression, a practice that is prohibited as doping in sport. We have specifically considered the potential diagnostic utility of human serum myokines as indirect markers of myostatin inhibition. Myostatin, its main antagonist follistatin, and other myokines (follistatin-like 1, musclin, oncostatin, osteonectin, irisin, brain derived neurotrophic factor, and insulin-like growth factor-1) were selected as a panel of potential biomarkers whose levels may be altered following myostatine suppression. The serum levels of myostatin and of the nine myokines were measured in elite athletes of different age, sex, and sport discipline, and their cross correlation assessed by multivariate analysis. All myokines resulted to be measurable in human serum, except for musclin and irisine, whose levels were below the limits of quantitation in a reduced number of samples. Serum concentrations varied of different orders in magnitude (musclin and osteonectin < 1 ng/mL; follistatin, myostatine and irisine 1-5 ng/mL; brainderived neurotrophic factor, follistatin-like 1 and iinsulin-like growth factor-1 > 10 ng/mL), while no significant differences were found between female and male subjects, with the exceptions of follistatin-like 1 and musclin, showing a higher concentrations in females (p < 0.05). Levels of insulin-like growth factor 1 and brain derived neurotrophic factor were significantly higher in power athletes than in endurance ones. Multivariate statistics showed that musclin, follistatin-like 1 and oncostatin are more clustered and correlated to myostatin than other myokines, suggesting they could be considered as potential biomarkers of doping by myostatin inhibitors. [ABSTRACT FROM AUTHOR]

Regular and planned physical activity can diminish the risk of numerous illnesses. However, school children and teenagers often exercise intermittently and for brief periods, restricting potential benefits. Furthermore, previous studies mainly focused on body composition, without providing molecular mechanisms elucidating the role of physical activity in muscle tissue and inflammatory signalling. The objective of this study was to determine the effect of a vigorous physical activity intervention on endocrine muscle function and cytokine output in children. 103 boys were divided into two groups: control (n = 51, did not perform additional physical activity) and exercise (n = 52, performed vigorous physical activity). Body composition measurements, endocrine muscle function and inflammatory signalling biomarkers were assessed at enrolment and after 6 months of intervention. No statistical significance was found for fractalkine, oncostatin, EGF, TNF-α and eotaxin. However, LIF, FBAP3, IL-6, FGF21 and IL-15 increased in the exercise group at the end of the protocol, though myostatin got decreased. In contrast, IFN-γ was increased in the exercise group at the beginning and end of the exercise protocol, IL-10 was also increased in this group, IL-1α decreased in the exercise group before and after the exercise protocol, and IP-10 and MCP-1 also decreased in the exercise group. It can be affirmed that a physical activity programme for boys was shown to produce changes in body composition (decreased fat mass, increased lean mass) and in markers of endocrine muscle function and cytokine release. It is possible that these changes, if sustained, could reduce the risk of chronic disease. [ABSTRACT FROM AUTHOR]

Recently discovered irisin, a member of the myokines family, is a potential mediator of exercise-induced energy metabolism and a factor promoting browning of the white adipose tissue. Recent evidence indicates that this myokine, released from contracting muscles, can mediate the beneficial effects of exercise on health. Irisin may be a potential therapeutic agent against obesity and has been shown to play an important role in the protection of various cells, tissues, and organs due to its anti-inflammatory, antioxidative, and anti-cancer properties. Our aim was to review the recent experimental and clinical studies on irisin and its expression, release into the bloodstream, tissue targets, and potential contribution to the protective effects of exercise in the gastrointestinal tract. Particular emphasis was placed on inflammatory bowel disease, intestinal ischemia/reperfusion injury, periodontitis, and other digestive tract disorders, including carcinogenesis. Overall, irisin holds significant potential as a novel target molecule, offering a safe and therapeutic approach to treating various gastrointestinal diseases. [ABSTRACT FROM AUTHOR]

Menopause, an extremely delicate phase in a woman's life, is characterized by a drop in estrogen levels. This decrease has been associated with the onset of several diseases, including postmenopausal osteoporosis and sarcopenia, which often coexist in the same person, leading to an increased risk of fractures, morbidity, and mortality. To date, there are no approved pharmacological treatments for sarcopenia, while not all of those approved for postmenopausal osteoporosis are beneficial to muscles. In recent years, research has focused on the field of myokines, cytokines, or peptides secreted by skeletal muscle fibers following exercise. Among these, irisin has attracted great interest as it possesses myogenic properties but at the same time exerts anabolic effects on bone and could therefore represent the link between muscle and bone. Therefore, irisin could represent a new therapeutic strategy for the treatment of osteoporosis and also serve as a new biomarker of sarcopenia, thus facilitating diagnosis and pharmacological intervention. The purpose of this review is to provide an updated summary of what we know about the role of irisin in postmenopausal osteoporosis and sarcopenia. [ABSTRACT FROM AUTHOR]

In the context of the global COVID-19 pandemic, understanding the intricate mechanisms of the body's response to infection and inflammation has become a priority for the medical and research communities. It has been proven that during COVID-19 infection, molecules are secreted—namely organokines, which may directly or indirectly play a role in the pathophysiology of COVID-19. The objective of this study was to scrutinize the potential correlation between the levels of selected myokines (myostatin, agrin, irisin, and myonectin) and the duration of rehabilitation in post-COVID-19 patients. Additionally, the study aimed to investigate whether there is a correlation between the levels of these myokines and the length of hospitalization during COVID-19 treatment. The study was conducted at the Rehabilitation Hospital in Szczecin (Poland). Patients in the study participated in a comprehensive rehabilitation program following COVID-19 treatment. In order to assess the effectiveness of rehabilitation, the following tests were performed: a 6 min walk test with an assessment of exercise tolerance (Borg scale), an assessment of dyspnea severity (mMRC scale), a spirometric assessment of respiratory function, a measurement of arm strength, and an assessment of fatigue using the Fatigue Assessment Scale (FAS). Myokine levels were measured using commercially available enzyme-linked immunosorbent assays (ELISA) according to the manufacturer's instructions. Statistical analysis was performed using Statistica 13.1 software. Lower concentrations of irisin and myonectin and higher concentrations of myostatin correlated with longer rehabilitation time. Baseline levels of specific myokines in post-COVID-19 patients could play a crucial role in anticipating the duration of rehabilitation. The duration of hospitalization for the infection may influence myokine levels in patients recovering from COVID-19. [ABSTRACT FROM AUTHOR]

ObjectivesThis review aims to summarize the common physiological mechanisms associated with both mild cognitive impairment (MCI) and musculoskeletal aging while also examining the relevant literature on how exercise regulation influences the levels of shared myokines in these conditions.MethodsThe literature search was conducted via databases such as PubMed (including MEDLINE), EMBASE, and the Cochrane Library of Systematic Reviews. The searches were limited to full-text articles published in English, with the most recent search conducted on 16 July 2024. The inclusion criteria for this review focused on the role of exercise and myokines in delaying musculoskeletal aging and enhancing cognitive health. The Newcastle‒Ottawa Scale (NOS) was utilized to assess the quality of nonrandomized studies, and only those studies with moderate to high quality scores, as per these criteria, were included in the final analysis. Data analysis was performed through narrative synthesis.ResultsThe primary outcome of this study was the evaluation of myokine expression, which included IL-6, IGF-1, BDNF, CTSB, irisin, and LIF. A total of 16 studies involving 633 older adults met the inclusion criteria. The current exercise modalities utilized in these studies primarily consisted of resistance training and moderate-to high-intensity cardiovascular exercise. The types of interventions included treadmill training, elastic band training, aquatic training, and Nordic walking training. The results indicated that both cardiovascular exercise and resistance exercise could delay musculoskeletal aging and enhance the cognitive functions of the brain. Additionally, different types and intensities of exercise exhibited varying effects on myokine expression.ConclusionCurrent evidence suggests that exercise mediates the secretion of specific myokines, including IL-6, IGF-1, BDNF, CTSB, irisin, and LIF, which establish self-regulatory circuits between the brain and muscle. This interaction enhances cognitive function in the brain and improves skeletal muscle function. Future research should focus on elucidating the exact mechanisms that govern the release of myokines, the correlation between the intensity of exercise and the secretion of these myokines, and the distinct processes by which myokines influence the interaction between muscle and the brain.

Skeletal muscle has been recognized as an endocrine organ which communicates with different systems, including the brain. In conditions involving systemic low-grade chronic inflammation, the skeletal muscle can be negatively impacted, culminating in its quantity (mass) and quality (function) losses, referred to here as muscle wasting. The inflammatory milieu, as well known, also impairs the brain function, however there are some particularities involving skeletal muscle-brain crosstalk, including cognitive function and mental health impairments. Psychoneuroimmunology (PNI) is an important field of neuroendocrine-immune-behavior science and an approach between PNI, and the movement science, or kinesiology, field can enrich future research about the relationship between skeletal muscle wasting and brain health. Thus, in this short review, we present an overview about the interplay between skeletal muscle, inflammatory mediator markers, and brain function with the purpose to strengthen the ties between kinesiology and PNI research to enhance futures discoveries and advances in health sciences.

Type 2 Diabetes (T2D) is associated with impaired vascularization of adipose tissue (AT) . IL8, GROα and IL15 are pro-angiogenic myokines, secreted at elevated levels by T2D myotubes. We explored the direct impact of these myokines on AT vascularization. AT explants from subjects with T2D and without diabetes (non-diabetic, ND) were treated with rIL8, rGROα and rIL15 in concentrations equal to those in conditioned media (CM) from T2D and ND myotubes, and sprout formation evaluated. Endothelial cells (EC) were isolated from T2D and ND-AT, treated with rGROα and tube formation evaluated. Finally, we investigated the involvement of MMP-2 and -9 in vascularization. ND and T2D concentrations of IL8 or IL15   caused similar stimulation of sprout formation in ND- and T2D-AT. GROα exerted a similar effect in ND-AT. When T2D-AT explants were exposed to GROα, sprout formation in response to T2D concentrations was reduced compared to ND. Exposure of EC from T2D-AT to GROα at T2D concentrations resulted in reduced tube formation. Reduced responses to GROα in T2D-AT and EC were also seen for secretion of MMP-2 and -9. The data indicate that skeletal muscle can potentially regulate AT vascularization, with T2D-AT having impairments in sensitivity to GROα, while responding normally to IL8 and IL15.