Current Pharmaceutical Design - Volume 22, Issue 24, 2016

Background: The concept of the muscle as a secretory organ, developed during the last decades, partially answers to the issue of how the crosstalk between skeletal muscle and distant tissues happens. The beneficial effects of exercise transcend the simple improved skeletal muscle functionality: systemic responses to exercise have been observed in distal organs like heart, kidney, brain and liver. Increasing data have accumulated regarding the synthesis, the kinetics of release and the biological roles of muscular cytokines, now called myokines. The most recent techniques have meaningfully improved the identification of the muscle cell secretome, but several issues regarding the extent of secretion from the muscle as well as the actions of the myokines remain unexplained. Methods: The goal of this review is to provide an update about the secretory properties of skeletal muscle during and after an acute bout of exercise and after exercise training, showing the main experimental evidences, but also speculate about the possible therapeutic use of the physical training-induced circulating factors, especially in some categories of patients in which the baseline conditions are heavily damaged by one or more pathological conditions. Results: studies on myokines are relatively recent, and to date most of the evidence available in humans has focused on the biological role of Il-6 during muscle contraction. Regarding to the myokines more recently identified, for example myostatin, fibroblast growth factor 21 (FGF21), secreted protein acidic and rich in cysteine (SPARC) or follistatin-like 1 some of these seem to be promising therapeutic agents, but our awareness about their potential benefits towards human health is only at the beginning. Conclusion: for many of the myokines identified to date, the information available is limited and not enough to characterize precise functions and activities carried out by those in man. Several issues need to be addressed by future studies, tailored to ascertain accurately and surely the biological role and the therapeutic potential of some myokines.

Background: Oxidative stress is involved in different pathophysiological states, such as aging, inflammatory, cardiovascular and neurodegenerative diseases, by damaging several cellular and tissue components including proteins, DNA and lipids. On the other hand, free radicals generated during physical activity are important modulators of muscle contraction, antioxidant protection, and oxidative damage repair. Indeed, ROS, generated during physical activity, are likely main mediators of antioxidant molecules upregulation, as reflected by increased glutathione reductase levels after exercise training. Methods: The aim of this review is to summarize the main mechanisms responsible for ROS-dependent adaptations to exercise training. Results: Regular moderate exercise seems to counteract oxidative stress-related detrimental changes and to promote a healthy lifestyle. Conversely, acute and strenuous exercise can generate an excess of free radicals production. Moreover, regular habitual physical activity is related to reduced risk of coronary heart disease and death, whereas vigorous exercise has been shown to favour sudden cardiac death in sedentary individuals with preexisting vascular disease. New specific markers of mitochondrial or ER dysfunction may be better clues of oxidative stress, and their application to clinical practice may help set up the optimal dose, intensity and modality of exercise training for every single subject. Conclusion: The relationship between exercise and oxidative stress is extremely complex, depending on the mode, intensity, and duration of exercise. These conflicting effects and outcomes may be explained by the hormesis theory, in which low doses of an agent that is detrimental at high doses, induces an adaptive beneficial effect on the cells or organism.

Background: The 20^th and 21^st centuries are marked by an increase in life expectancy on one hand and on the other hand by the increase of so called civilization diseases. Their share one common trait: the energy metabolism imbalance, with low energy expenditure and high energy uptake. Our age can be viewed as the age of inactivity and wealth. Methods: The aim of the present review is to highlight the influence of habitual physical activity on energy metabolism and balance. Results: Energy balance is the difference between energy intake and energy expenditure, where energy expenditure further divides into resting metabolic rate, thermic effect of feeding and energy used by physical activity. In general population, resting metabolic rate remains constant and proportional to muscle body mass. Muscle mass increases with exercise, especially resistance exercise, concomitantly with increasing energy expenditure. The effect of exercise on appetite is very strong, proportional to exercise intensity. An acute bout of aerobic exercise suppresses appetite by decreasing ghrelin plasma levels, and increasing gut hormones. Different subgroups of patients respond differently to the same exercise or habitual activity and have thus distinct effects on energy balance. Different myokines plasma levels after exercise could explain these different reactions although most of their effect is still unclear. Conclusion: Physical activity plays an important role in the prevention and treatment of many disorders, like obesity, type 1 and type 2 diabetes, dyslipidaemia, hypertension, coronary heart disease, osteoporosis, psychiatric and neurologic disorders. It is evident, that physical activity has an effect not only on energy balance but also has a direct effect on other body organ via its own molecules – myokines. The pharmacological effect of myokines gives hope that one day we could have a “myokine drug” that could be used in patients who are unable to exercise. Until then we should use our "muscle-pharmacy" and try to convince also our patients to use theirs. Physical activity makes a huge impact on human health.

Background: Chronic Kidney Disease (CKD) is considered a silent epidemic with a continuously growing prevalence around the world. Due to uremia many functional and morphological abnormalities occur in almost all systems. Mostly affected, the cardiovascular system, leads to diminished cardiac function that affects patients’ functional capacity and physical activity levels, reducing survival and increasing all-cause mortality. Systematic exercise training ameliorates uremia induced body deficits and significantly improves the survival of CKD patients. Intradialytic exercise training has been recommended as a complementary therapeutic modality equally important to hemodialysis. Methods: The aim of this systematic review is to provide an update on recent advances in our understanding of how exercise training improves functionality of the cardiovascular system through the hemodynamic changes induced by habitual or intradialytic and/or home-based exercise training programs. Results: Systematic exercise training induces beneficial adaptive responses and influences many sensitive physiological biomarkers, such as oxidative stress biomarkers that are implicated in the development of atherosclerosis. Additionally, exercise training decreases the cardiovascular risk by improving the autonomic nervous system activity and the left ventricular function and by reducing nontraditional risk factors such as epicardial adipose tissue. It seems that all these central and peripheral adaptations to exercise training significantly contribute to improvements in functional capacity and exercise tolerance among CKD patients and result in the risk reduction of CKD-associated disorders. Conclusion: Exercise training could serve as a complimentary therapeutic strategy in CKD patients while health care providers should motivate patients to engage in any type of exercise training programs.

Background: Aging and low physical activity are associated with the development of diseases (hypertension, type 2 diabetes, dyslipidemia, obesity) marked by chronic low-grade inflammation. Cardiovascular disease is the most common cause of death worldwide, while exercising muscle tissue can increase the secretion of myokines that can reestablish a possible inflammatory process in virtue of the anti-inflammatory effect. Methods: The objective of this review is to focus on molecular mechanisms involved between different kinds of exercise and cellular oxidative stress, and the emerging therapeutic strategies which have the potential to promote benefits in vascular health. Results: Regular exercise increases shear stress, mitochondrial biogenesis, and upregulates mitochondrial antioxidant system, inducing anti-inflammatory actions, such as suppression of TNF-α which may offer protection against TNF-α-induced vascular impairment. Conclusion: Exercise training of various durations and intensities appears to prevent and restore the age-related impairment of endothelial function, likely through the restoration of NO availability, reduction in oxidative stress, and turnover of the apoptotic process in the endothelium, thus minimizing vascular inflammation and decreasing the formation of atherosclerotic plaques.

Background: An individual's level of physical activity is one of a set of lifestyle and behavioral factors that can affect immune function and health. Methods: The purpose of this review is to summarize the current knowledge in this research field and to review the recent developments in exercise immunology. Results: Most studies show that regular exercise training increases immune competence and reduces the risk of infection compared to a sedentary lifestyle. In contrast, acute prolonged bouts of exercise and periods of intensified training are followed by a temporary increase in the risk of infection. These observations have been attributed to differential exercise-induced changes of a series of humoral and cellular immune system parameters. Furthermore, regular exercise training is a countermeasure against a persistent systemic inflammatory state which is a typical feature of cardiovascular and metabolic diseases is by lowering levels of pro-inflammatory cytokines. It is supposed that these effects are mediated by a modification of metabolic signals and innate immune regulation, the release of anti-inflammatory cytokines from muscle, the release of stress hormones, and a process known as browning of adipose tissue. Conclusion: The effects of physical activity on the immune system strongly depend on the mode and intensity of exercise or training. Thereby, considerable knowledge has accumulated concerning the significance of exercise as an important lifestyle factor for prevention and therapy of major chronic diseases.

Background: Physical activity has been shown to be associated with reduced risk of coronary heart disease but the same effect seems to be produced in neurological diseases. Objective: In this review, we focused on the interplay between physical activity and some neurological conditions (Stroke, dementia, epilepsy, headache, Parkinson’ s disease, amyotrophic lateral sclerosis, multiple sclerosis, insomnia, depression and anxiety) with the aim of describing the potential role of physical activity in the prevention of such diseases and the physiological mechanisms involved in these processes. Results: Despite a growing body of evidence which reveals that physical activity is able to reduce the frequency of neurological diseases, directly or indirectly by enhancing cardiovascular conditions, further studies are necessary to better characterize which type of exercise is useful for each condition. Conclusion: Physical activity could represent an additional approach to fight against such diseases.

Depression is a major medical and social problem. Here we review current body of knowledge on the benefits of exercise as an effective strategy for both the prevention and treatment of this condition. We also analyze the biological pathways involved in such potential benefits, which include changes in neurotrophic factors, oxidative stress and inflammation, telomere length, brain volume and microvessels, neurotransmitters or hormones. We also identify major caveats in this field of research: further studies are needed to identify which are the most appropriate types of exercise interventions (intensity, duration, or frequency) to treat and prevent depression.