MicroRNAs regulating signaling pathways in cardiac fibrosis: potential role of the exercise training.

Cardiovascular and metabolic diseases such as hypertension, type 2 diabetes, and obesity develop long-term fibrotic processes in the heart, promoting pathological cardiac remodeling, including after myocardial infarction, reparative fibrotic processes also occur. These processes are regulated by many intracellular signaling pathways that have not yet been completely elucidated, including those associated with microRNA (miRNA) expression. miRNAs are small RNA transcripts (18-25 nucleotides in length) that act as posttranscriptionally regulators of gene expression, inhibiting or degrading one or more target messenger RNAs (mRNAs), and proven to be involved in many biological processes such as cell cycle, differentiation, proliferation, migration, and apoptosis, directly affecting the pathophysiology of several diseases, including cardiac fibrosis. Exercise training can modulate the expression of miRNAs and it is known to be beneficial in various cardiovascular diseases, attenuating cardiac fibrosis processes. However, the signaling pathways modulated by the exercise associated with miRNAs in cardiac fibrosis were not fully understood. Thus, this review aims to analyze the expression of miRNAs that modulate signaling pathways in cardiac fibrosis processes that can be regulated by exercise training.

Long-term consequences of COVID-19 on mental health and the impact of a physically active lifestyle: a narrative review.

BACKGROUND: Coronavirus-19 disease (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Respiratory viruses damage not only the upper respiratory tract in humans, but also several different organs such as the brain. Some of the neurological consequences of COVID-19 reported are anosmia, headache, stroke, declined cognitive function, and impaired mental health, among others. People who had COVID-19 have a higher risk of sequelae in the central nervous system (CNS). However, it is not known which are all possible sequelae and how long will last the long-term effects of the COVID-19 pandemic on behavioral patterns and quality of life. AIM: We intend to address the long-term impacts of COVID-19 on mental health and the relevance of physical exercise during the pandemic. METHODS: We conducted a literature search using PubMed to find the articles that were related to these themes. RESULTS: We found 23,489 papers initially, and then we applied the inclusion/exclusion criteria to narrow down our search to 3617 articles and selected 1380 eligible articles after a thorough reading of titles and abstracts. The findings indicated that COVID-19 impacted general mental health and led many not only hospitalized patients to develop cognitive decline, memory impairment, anxiety, sleep alterations, and depressive-like behavior. Furthermore, the fear of vaccines and their effects had negatively affected mental health and directly impacted mortality rates in unvaccinated COVID-19 patients. CONCLUSIONS: Preventive measures must be undertaken, such as the vaccination of the entire population, vaccination hesitancy discouragement by creating awareness among individuals, and people's engagement in a physically active lifestyle, since being physically active is a low-cost and effective measure to restore or inhibit the negative outcomes from COVID-19 on mental health.

MicroRNAs in type 2 diabetes mellitus: potential role of physical exercise.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disease, and its prevalence has grown worldwide. Several pathophysiological processes contribute to the development, progression and aggravating of the disease, for example, decreased insulin synthesis and secretion, insulin resistance, inflammation, and apoptosis, all these processes are regulated by various epigenetic factors, including microRNAs (miRNAs). MiRNAs are small non-coding RNAs, which are around 20 nucleotides in length and are regulators of gene expression at the post-transcriptional level, have a specific function of inhibiting or degrading a messenger RNA target. Thus, miRNAs modulate the expression of many associated genes with the pathophysiological processes in T2DM. On the other hand, miRNAs are also modulated through physical exercise (PE), which induces a change in their expression pattern during and after exercise. Some scientific evidence shows that PE modulates miRNAs beneficially and improves the signaling pathway of insulin resistance, however, little is known about the function of PE modulating miRNAs associated with the processes of insulin secretion, inflammation, and apoptosis. Thus, the objective of this review is to identify the miRNAs expression pattern in T2DM and compare it with the exercise-induced miRNAs expression pattern, identifying the signaling pathways that these miRNAs are regulating in the processes of insulin secretion, insulin resistance, inflammation, and apoptosis in T2DM, and how PE may have a potential role in modulating these signal transduction pathways, promoting benefits for patients with T2DM.

Regulation of microRNAs in Alzheimer´s disease, type 2 diabetes, and aerobic exercise training.

Alzheimer's disease (AD) is the most common type of dementia. The evolution and aggregation of amyloid beta (ß) oligomers is linked to insulin resistance in AD, which is also the major characteristic of type 2 diabetes (T2D). Being physically inactive can contribute to the development of AD and/or T2D. Aerobic exercise training (AET), a type of physical exercise, can be useful in preventing or treating the negative outcomes of AD and T2D. AD, T2D and AET can regulate the expression of microRNAs (miRNAs). Here, we review some of the changes in miRNAs expression regulated by AET, AD and T2D. MiRNAs play an important role in the gene regulation of key signaling pathways in both pathologies, AD and T2D. MiRNA dysregulation is evident in AD and has been associated with several neuropathological alterations, such as the development of a reactive gliosis. Expression of miRNAs are associated with many pathophysiological mechanisms involved in T2D like insulin synthesis, insulin resistance, glucose intolerance, hyperglycemia, intracellular signaling, and lipid profile. AET regulates miRNAs levels. We identified 5 miRNAs (miR-21, miR-29a/b, miR-103, miR-107, and miR-195) that regulate gene expression and are modulated by AET on AD and T2D. The identified miRNAs are potential targets to treat the symptoms of AD and T2D. Thus, AET is a non-pharmacological tool that can be used to prevent and fight the negative outcomes in AD and T2D.

Molecular mechanisms of physical exercise on depression in the elderly: a systematic review.

Depressive disorders are common among the elderly. Major depressive disorder will be one of the highest healthcare costs in middle and higher income countries by 2030. It is known that physical inactivity leads to negative effects on mental health in the elderly.The purpose of this review was to explore investigate the consequences of physical exercise (aerobic and resistance exercise) on major depressive disorder among elderly, and presenting its potential biological mechanisms. This study was designed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical trials or randomized clinical trials or cohort studies participated of the study design. Ten studies were evaluated and the main outcomes of each were reported. Aerobic and resistance training revealed to be effective in fighting the symptoms of depression. The most common physical exercise protocol adopted to reduce the consequences of major depressive disorder in humans was the prescription of aerobic exercise at moderate-intensity lasting 60 min per session, 3 times per week, for 24 weeks. Physical exercise enhances IGF-I and activates PGC-1α/FNDC5/Irisin pathway. Physical exercise also increases expression of BDNF and its receptor, TrkB, in the hippocampus and prefrontal cortex leading to upstream of ERK and inhibiting depressive-like behavior. Physical exercise brings mental health benefits and plays a crucial role in avoiding the development of major depressive disorder.

Exercise-linked consequences on epilepsy.

OBJECTIVE: Epilepsy is a brain disorder that leads to seizures and neurobiological, cognitive, psychological, and social consequences. Physical inactivity can contribute to worse epilepsy pathophysiology. Here, we review how physical exercise affects epilepsy physiopathology. METHODS: An extensive literature search was performed and the mechanisms of physical exercise on epilepsy were discussed. The search was conducted in Scopus and PubMed. Articles with relevant information were included. Only studies written in English were considered. RESULTS: The regular practice of physical exercise can be beneficial for individuals with neurodegenerative diseases, such as epilepsy by decreasing the production of pro-inflammatory and stress biomarkers, increasing socialization, and reducing the incidence of epileptic seizures. Physical exercise is also capable of reducing the symptoms of depression and anxiety in epilepsy. Physical exercise can also improve cognitive function in epilepsy. The regular practice of physical exercise enhances the levels of brain-derived neuro factor (BDNF) in the hippocampi, induces neurogenesis, inhibits oxidative stress and reactive gliosis, avoids cognitive impairment, and stimulates the production of dopamine in the epileptic brain. CONCLUSION: Physical exercise is an excellent non-pharmacological tool that can be used in the treatment of epilepsy.

Physical exercise effects on the brain during COVID-19 pandemic: links between mental and cardiovascular health.

The current pandemic was caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The quarantine period during corona virus disease 19 (COVID-19) outbreak might affect the quality of life leading thousands of individuals to diminish the daily caloric expenditure and mobility, leading to a sedentary behavior and increase the number of health disorders. Exercising is used as a non-pharmacological treatment in many chronic diseases. Here, we review the molecular mechanisms of physical exercise in COVID-19 pandemic on mental health. We also point links between exercise, mental, and cardiovascular health. The infection caused by SARS-CoV-2 affects host cells binding to angiotensin-converting enzyme-2 (ACE2), which is the receptor for SARS-CoV-2. If there is not enough oxygen supply the lungs and other tissues, such as the heart or brain, are affected. SARS-CoV-2 enhances ACE2 leading to inflammation and neuronal death with possible development of mood disorders, such as depression and anxiety. Physical exercise also enhances the ACE2 expression. Conversely, the activation of ACE2/Ang 1-7/Mas axis by physical exercise induces an antiinflammatory and antifibrotic effect. Physical exercise has beneficial effects on mental health enhancing IGF-1, PI3K, BDNF, ERK, and reducing GSK3ß levels. In addition, physical exercise enhances the activity of PGC-1α/ FNDC5/Irisin pathway leading to neuronal survival and the maintenance of a good mental health. Thus, SARS-CoV-2 infection leads to elevation of ACE2 levels through pathological mechanisms that lead to neurological and cardiovascular complications, while the physiological response of ACE2 to physical exercise improves cardiovascular and mental health.

Effects of physical exercise on memory in type 2 diabetes: a brief review.

Type 2 diabetes (T2D) is a metabolic disorder that can lead to memory impairment. T2D main features are insulin resistance and hyperglycemia. Physical exercise is a non-pharmacological intervention that can regulate glycemic levels and fight insulin resistance in T2D, but whether it influences memory has been discussed. There are 2 main types of physical exercise: aerobic exercise and resistance exercise. Here, we review about the consequences of different physical exercise protocols on memory in diabetic subjects and animal models of T2D. Physical exercise, aerobic or resistance training, most of the times, is a capable agent to prevent and treat memory loss on diabetic subjects and animal models of T2D. However, whether aerobic and resistance training combined improve memory in subjects with T2D remains controversial. Regarding animal models of T2D, aerobic and resistance training have been showed to be capable to prevent and treat memory loss. Acute and chronic protocols of exercise, generally, induce positive physiological responses and adaptations in T2D, such as a better glucose control. The ideal physical exercise protocol that will produce the best benefits to diabetic subjects and to animal models of T2D has not been described yet. A variety of combination between intensity, volume, frequency, and duration of the physical exercise protocol on future studies is necessary to both diabetic subjects and animal models of T2D to determine the best protocol that will induce more benefits on memory in T2D.

Physical exercise protocols in animal models of Alzheimer's disease: a systematic review.

Several animal studies have showed the beneficial effects of physical exercise (PE) on brain function and health. Alzheimer's Disease (AD) is the most common type of dementia, characterized by the presence of aggregated extracellular amyloid-beta (Aß) and neurofibrillary tangles, with progressive cognitive decline. Therapeutic approaches such as PE showed to be effective in halting AD progression. Here, we present a systematic review about PE and AD. The search was carried out using the PubMed and LILACS databases. The following keywords were used: Alzheimer; PE; animal model. All found studies adopted aerobic exercise training as the PE protocol (100%). We identified running on treadmill as the most commonly used PE routine (62.5%). The duration of each session, intensity, frequency, and period of training most used were 60 min/day (62.5%), moderate intensity (87.5%), 5 days/week (62.5%), and 4 (37.5%) or 12 (37.5%) weeks, respectively. The AD animal models most used were the Tg APP/PS1ΔE9 (25%), models based on i.c.v. infusion of AßOs (25%) and streptozotocin (25%). All protocols used rodents to their experiments (100%), but mice were the most common (62.5%). Finally, the main results presented in all studies were capable to reduce significantly AD consequences, such as reducing Aß or pro-inflammatory proteins levels (100%). The lack of resistance training protocols in animal models of AD indicates a huge gap that should be investigated in future studies. We suggest that PE protocols must be adapted according to the specie, lineage and life span of the animal.

Exercise-Linked Irisin: Consequences on Mental and Cardiovascular Health in Type 2 Diabetes.

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and hyperglycemia. Chronic exposure to a T2DM microenvironment with hyperglycemia, hyperinsulinemia, oxidative stress and increased levels of proinflammatory mediators, has negative consequences to the cardiovascular system and mental health. Therefore, atherosclerotic cardiovascular diseases (CVD) and mental health issues have been strongly associated with T2DM. Lifestyle modifications, including physical exercise training, are necessary to prevent T2DM development and its associated complications. It is widely known that the regular practice of exercise provides several physiological benefits to subjects with T2DM, such as managing glycemic and blood pressure levels. Different types of exercise, from aerobic to resistance training, are effective to improve mental health and cognitive function in T2DM. Irisin is a myokine produced in response to exercise, which has been pointed as a relevant mechanism of action to explain the benefits of exercise on cardiovascular and mental health in T2DM patients. Here, we review emerging clinical and experimental evidence about exercise-linked irisin consequences to cardiovascular and mental health in T2DM.

Modulation of MicroRNAs as a Potential Molecular Mechanism Involved in the Beneficial Actions of Physical Exercise in Alzheimer Disease.

Alzheimer disease (AD) is one of the most common neurodegenerative diseases, affecting middle-aged and elderly individuals worldwide. AD pathophysiology involves the accumulation of beta-amyloid plaques and neurofibrillary tangles in the brain, along with chronic neuroinflammation and neurodegeneration. Physical exercise (PE) is a beneficial non-pharmacological strategy and has been described as an ally to combat cognitive decline in individuals with AD. However, the molecular mechanisms that govern the beneficial adaptations induced by PE in AD are not fully elucidated. MicroRNAs are small non-coding RNAs involved in the post-transcriptional regulation of gene expression, inhibiting or degrading their target mRNAs. MicroRNAs are involved in physiological processes that govern normal brain function and deregulated microRNA profiles are associated with the development and progression of AD. It is also known that PE changes microRNA expression profile in the circulation and in target tissues and organs. Thus, this review aimed to identify the role of deregulated microRNAs in the pathophysiology of AD and explore the possible role of the modulation of microRNAs as a molecular mechanism involved in the beneficial actions of PE in AD.

Exercise Training-Induced Changes in MicroRNAs: Beneficial Regulatory Effects in Hypertension, Type 2 Diabetes, and Obesity.

MicroRNAs are small non-coding RNAs that regulate gene expression post-transcriptionally. They are involved in the regulation of physiological processes, such as adaptation to physical exercise, and also in disease settings, such as systemic arterial hypertension (SAH), type 2 diabetes mellitus (T2D), and obesity. In SAH, microRNAs play a significant role in the regulation of key signaling pathways that lead to the hyperactivation of the renin-angiotensin-aldosterone system, endothelial dysfunction, inflammation, proliferation, and phenotypic change in smooth muscle cells, and the hyperactivation of the sympathetic nervous system. MicroRNAs are also involved in the regulation of insulin signaling and blood glucose levels in T2D, and participate in lipid metabolism, adipogenesis, and adipocyte differentiation in obesity, with specific microRNA signatures involved in the pathogenesis of each disease. Many studies report the benefits promoted by exercise training in cardiovascular diseases by reducing blood pressure, glucose levels, and improving insulin signaling and lipid metabolism. The molecular mechanisms involved, however, remain poorly understood, especially regarding the participation of microRNAs in these processes. This review aimed to highlight microRNAs already known to be associated with SAH, T2D, and obesity, as well as their possible regulation by exercise training.

Resistance Training Reduces Blood Pressure: Putative Molecular Mechanisms.

Arterial hypertension is a multifactorial clinical condition characterized by higher blood pressure levels. The main treatment for controlling high blood pressure consists of drug therapy, but the scientific literature has been pointing to the efficiency of aerobic and resistance exercises acting in a therapeutic and/or preventive way to reduce and control the blood pressure levels. Resistance training is characterized by sets and repetitions on a given muscle segment that uses overload, such as machine weights, bars, and dumbbells. As it successfully affects a number of variables associated to practitioners' functional and physiological features as well as emotional and social variables, resistance training has been a crucial part of physical exercise programs. Several reports highlight the various adaptive responses it provides, with a focus on the improvement in strength, balance, and muscular endurance that enables a more active and healthy lifestyle. Resistance training programs that are acute, sub-chronic, or chronic can help people with varying ages, conditions, and pathologies reduce their arterial hypertension. However, molecular mechanisms associated with resistance training to reduce blood pressure still need to be better understood. Thus, we aimed to understand the main effects of resistance training on blood pressure as well as the associated molecular mechanisms.

Morbimortality and determinants of reperfusion in ischemic stroke.

BACKGROUND: Cerebrovascular accident (or stroke) and ischemic heart disease are the the major causes of death in the world. It is estimated that about 85% of strokes are ischemic in origin. Reperfusion therapy in the acute phase of ischemic stroke with a recombinant human tissue plasminogen activator is effective, but some factors influence the success of this treatment. OBJECTIVE: The aim of this study was to evaluate clinical aspects and possible determinants for reperfusion after venous thrombolysis. METHODS: This is a retrospective, cross-sectional, observational study based on a review of hospital records of inpatients diagnosed with ischemic stroke treated with intravenous thrombolysis, the main outcome being reperfusion or not. RESULTS: Data from this study revealed a predominance of females in the group of reperfused patients and males in the non-reperfused group, both maintaining moderate severity on the National Institutes of Health Stroke Scale and admission without statistical significance (p>0.18). In addition, the mean admission severity score was 13.2 for the group of reperfused patients and 14.2 for those not reperfused, and the mean ejection fraction of both groups was within normal functionality, with a mean of 0.50 for reperfused patients and 0.62 for non-reperfused patients. CONCLUSION: We found an association between successful venous chemical thrombolysis reperfusion and lower mortality in patients with acute stroke.

Mortality in hospitalized HIV-infected patients in a referral center in Bahia, Brazil.

The number of people living with HIV / AIDS in the world has increased and, in Salvador, Brazil, the mortality rate is above the state and national rates. This study sought to describe the characteristics of HIV patients who died in a referral hospital. This is a retrospective cohort study between 2012 and 2017 conducted at the, Federal University of Bahia´s Hospital, involving patients who died during hospitalization. There were 62 deaths among the 461 hospitalized patients with a predominance of males, blacks, and residents of Salvador. Mean age was 41.4 years. Most patients had at least one associated infection and 13% had a malignant neoplasm. The main reported cause of death was septic shock / HIV-associated infections. About 6.4% had an undetectable viral load and in-hospital survival was longer in this group. The lowest in-hospital survival was seen in patients presenting with pneumonia. Although the HIV / AIDS mortality rate at this center reflects the complexity of the country's epidemiological scenario poor adherence and therapeutic failure play a key role in the risk of death.

The Epigenetic Role of MiRNAs in Endocrine Crosstalk Between the Cardiovascular System and Adipose Tissue: A Bidirectional View.

Overweight and obesity (OBT) is a serious health condition worldwide, and one of the major risk factors for cardiovascular disease (CVD), the main reason for morbidity and mortality worldwide. OBT is the proportional increase of Adipose Tissue (AT) compared with other tissue and fluids, associated with pathological changes in metabolism, hemodynamic overload, cytokine secretion, systemic inflammatory profile, and cardiac metabolism. In turn, AT is heterogeneous in location, and displays secretory capacity, lipolytic activation, insulin sensitivity, and metabolic status, performing anatomic, metabolic, and endocrine functions. Evidence has emerged on the bidirectional crosstalk exerted by miRNAs as regulators between the heart and AT on metabolism and health conditions. Here, we discuss the bidirectional endocrine role of miRNAs between heart and AT, rescuing extracellular vesicles' (EVs) role in cell-to-cell communication, and the most recent results that show the potential of common therapeutic targets through the elucidation of parallel and /or common epigenetic mechanisms.

Physical Exercise Training and Chagas Disease: Potential Role of MicroRNAs. / Treinamento com Exercício Físico e Doença de Chagas: Função Potencial dos MicroRNAs.

Chagas disease (CD) is caused by Trypanosoma Cruzi. This parasite can infect several organs of the human body, mainly the heart, causing inflammation, fibrosis, arrhythmias, and cardiac remodeling, promoting long-term Chronic Chagas Cardiomyopathy (CCC). However, little scientific evidence has elucidated the molecular mechanisms that govern the pathophysiological processes in this disease. MicroRNAs (miRNAs) are regulators of post-transcriptional gene expression that modulate signaling pathways, participating in pathophysiological mechanisms in CD, but the understanding of miRNAs in this disease is limited. On the other hand, a wide range of scientific evidence shows that physical exercise training (PET) modulates the expression of miRNAs by modifying different signaling pathways in healthy individuals. Some studies also show that PET is beneficial for individuals with CD; however, these did not evaluate the miRNA expressions. Thus, there is no evidence showing the role of PET in the expression of miRNAs in CD. Therefore, this review aimed to identify miRNAs expressed in CD that could potentially be modified by PET.

A doença de Chagas (DC) é causada pelo Trypanosoma Cruzi. Esse parasita pode infectar vários órgãos do corpo humano, especialmente o coração, causando inflamação, fibrose, arritmias e remodelação cardíaca, e promovendo a cardiomiopatia chagásica crônica (CCC) no longo prazo. Entretanto, poucas evidências científicas elucidaram os mecanismos moleculares que regulam os processos fisiopatológicos nessa doença. Os microRNAs (miRNAs) são reguladores de expressão gênica pós-transcricional que modulam a sinalização celular, participando de mecanismos fisiopatológicos da DC, mas o entendimento dos miRNAs nessa doença é limitado. Por outro lado, há muitas evidências científicas demonstrando que o treinamento com exercício físico (TEF) modula a expressão de miRNAs, modificando a sinalização celular em indivíduos saudáveis. Alguns estudos também demonstram que o TEF traz benefícios para indivíduos com DC, porém esses não avaliaram as expressões de miRNA. Dessa forma, não há evidências demonstrando o papel do TEF na expressão dos miRNAs na DC. Portanto, essa revisão teve o objetivo de identificar os miRNAs expressos na DC que poderiam ser modificados pelo TEF.

Physical exercise consequences on memory in obesity: A systematic review.

Obesity is associated with changes in memory. Thus, the aim of this systematic review was to investigate the physical exercise consequences on memory in obesity. A search was carried out in the PubMed, Lilacs, and Scielo databases with the following descriptors: "physical exercise," "memory," and "obesity." A total of 16 studies were analyzed in this review. Low, moderate, and high intensity exercise training showed positive effects on memory in patients with obesity (100%). The animal models of obesity used in their physical exercise protocols: treadmill (72.7%) or wheel running (27.3%). Most of the animal studies (81.8%) revealed positive effects of the physical exercise protocol on memory in obesity. Mouse was the most commonly used animal (54.5%), and a 60% high-fat diet (HFD) was the most commonly method used to induce obesity (82%). We did not identify any knockout model of obesity that was used to evaluate memory and used physical exercise as the main intervention. Thus, exercise training, independently if it is resistance or endurance training, seems to be an excellent intervention to prevent and inhibit cognitive impairment and memory loss on obese patients and animal models of obesity.

MicroRNAs Regulating Renin-Angiotensin-Aldosterone System, Sympathetic Nervous System and Left Ventricular Hypertrophy in Systemic Arterial Hypertension.

MicroRNAs are small non-coding RNAs that regulate gene and protein expression. MicroRNAs also regulate several cellular processes such as proliferation, differentiation, cell cycle, apoptosis, among others. In this context, they play important roles in the human body and in the pathogenesis of diseases such as cancer, diabetes, obesity and hypertension. In hypertension, microRNAs act on the renin-angiotensin-aldosterone system, sympathetic nervous system and left ventricular hypertrophy, however the signaling pathways that interact in these processes and are regulated by microRNAs inducing hypertension and the worsening of the disease still need to be elucidated. Thus, the aim of this review is to analyze the pattern of expression of microRNAs in these processes and the possible associated signaling pathways.