Combined physical exercise re-synchronizes expression of Bmal1 and REV-ERBα and up-regulates apoptosis and metabolism in the prostate during aging.

BACKGROUND: Aging increases the prevalence of prostate cancer. The circadian clock coordinates metabolism, cell cycle, and tumor suppressor p53. Although physical exercise has several effects on preventing prostate diseases, its effect on regulating genes and proteins of the circadian rhythm of the prostate needs to be better evaluated. The present study verified expression of REV-ERBα (Nr1d1), Bmal1, apoptosis, tumor suppressors, energetic metabolism markers, and androgen receptors in the prostatic microenvironment in 18-month-old mice submitted to combined physical training. METHODS: C57BL/6 J mice were divided into 2 groups: 6 months-old (n = 10) and 18 months-old, (n = 20). The 18-month-old animals were divided into 2 subgroups: sedentary (n = 10, 18 m Sed) and submitted to combined physical training (n = 10, 18 m TR). Combined physical training protocol was performed by running on the treadmill (40-60 % of incremental load test) and climbing strength training (40-50 % of maximum repetition test), consisting of 5×/week (3 days aerobic and 2 days strength) for 3 weeks. The prostate was prepared for Western blot and RT-qPCR analysis, and the plasm was prepared for the biochemistry analysis. RESULTS: Combined physical exercise during aging led to increased levels of Bmal1 and decreased levels of REV-ERBα in the prostate. These results were accompanied by a reduction in the AMPK/SIRT1/PGC-1α proteins and an increase in the PI3K/AKT and p53/PTEN/caspase 3 pathways, promoting apoptotic potential. CONCLUSION: These findings suggest that strength and aerobic physical exercise may be preventive in the development of preneoplastic molecular alterations and age-related features by re-synchronizes Bmal1 and REV-ERBα in prostatic tissues.

Integrated aerobic exercise with LDE-docetaxel treatment: a novel approach to combat prostate cancer progression.

The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.

Aerobic physical exercise modifies the prostate tumoral environment.

Exercise is recognized for its potential role in reducing the risk of certain cancers. However, the molecular mechanisms behind this risk reduction are not fully understood. Here, we hypothesized that aerobic physical exercise induces cancer attenuating effects through the modulation of oxidative stress and inflammation. To test this hypothesis, twenty male Sprague Dawley rats with chemically induced prostate tumors were divided into two groups: Prostate cancer (PC) in the absence and presence of exercise (PC + Ex). Rats in the PC + Ex group performed exercises on a treadmill for 8 weeks, 5 sessions per week, at an intensity of 60 % of maximum capacity. Weight and feed efficiency, Ki-67, apoptosis, prostatic inflammation, and markers of oxidative stress were analyzed. We found that aerobic physical exercise significantly decreased prostate cell proliferation (p < 0.05) across modulation, tumor size, and prostate weight. The PC + Ex group also significantly reduced anti-apoptosis protein expression (p < 0.05) and increased pro-apoptotic protein expression. Furthermore, physical exercise increased enzymatic antioxidant defenses in the prostate, plasma, and whole blood. Moreover, PC + Ex reduced lipid peroxidation and protein carbonyl levels (p < 0.05). In the prostate, there was an increase in anti-inflammatory cytokines (IL-10), and a reduction in pro-inflammatory cytokines (IL-6, TNF-α, and NF-κB) after 8 weeks of physical exercise. In conclusion, we found that aerobic physical exercise is a functional, beneficial, and applicable approach to control PC progression, because it modifies the systemic environment, including the regulation of glucose and circulating lipids. This modification of the cancer cells environment has anti-inflammatory and antioxidant effects that attenuate tumor growth.

High-Intensity Interval Training Minimizes the Deleterious Effects of Arterial Hypertension on the Urinary Bladder of Spontaneously Hypertensive Rats.

Arterial hypertension promotes urological complications by modifying the functional capacity of the urinary bladder. On the other hand, physical exercise has been suggested as a nonpharmacological tool to improve blood pressure regulation. High-intensity interval training (HIIT) can effectively increase peak oxygen consumption, body composition, physical fitness, and health-related characteristics of adults; however, its action on the urinary bladder is little discussed. In the present study, we verified the effect of HIIT on the modulation of the redox state, morphology, and inflammatory and apoptotic processes of the urinary bladder of hypertensive rats. Spontaneously hypertensive rats (SHR) were divided into two groups: SHR sedentary and SHR submitted to HIIT. Arterial hypertension promoted an increase in the plasma redox state, modified the volume of the urinary bladder, and increased collagen deposition in detrusor muscle. It was also possible to identify, in the sedentary SHR group, an increase in inflammatory markers such as IL-6 and TNF-α in the urinary bladder, as well as a reduction in BAX expression. However, in the HIIT group, reduced blood pressure levels were observed, together with an improvement in morphology, such as a decrease in collagen deposition. HIIT also regulated the proinflammatory response, promoting increases in IL-10 and BAX expressions and in the number of plasma antioxidant enzymes. The present work highlights the intracellular pathways involved with the oxidative and inflammatory capacity of the urinary bladder and the potential effect of HIIT on the regulation of the urothelium and detrusor muscle of hypertensive rats.

Strength training for arterial hypertension treatment: a systematic review and meta-analysis of randomized clinical trials.

Cardiovascular diseases are the leading cause of death in the world and arterial hypertension (AH) accounts for 13.8% of deaths caused by cardiovascular diseases. Strength training interventions could be an important alternative tool for blood pressure control, however, consistent evidence and the most effective training protocol for this purpose are yet to be established. The current study used the Cochrane methodology to systematically review randomized controlled trials (RCTs) that investigated the effect of strength training on blood pressure in hypertensive patients. A systematic search was conducted in the PubMed, EMBASE, Scopus, Cochrane Library, and World Health Organization databases. This review included controlled trials that evaluated the effect of strength training for 8 weeks or more in adults with arterial hypertension, published up to December 2020. Data are described and reported as the weighted mean difference of systolic and diastolic pressure and a 95% confidence interval. Protocol registration: PROSPERO registration number CRD42020151269. A total of 14 studies were identified, including a combined total of 253 participants with hypertension. The meta-analysis showed that mean values of systolic blood pressure (SBP) and diastolic blood pressure (DBP) decreased significantly after strength training interventions. The strongest effect of strength training on decreasing blood pressure was observed in protocols with a moderate to vigorous load intensity (> 60% of one-repetition maximum-1RM), a frequency of at least 2 times per week, and a minimum duration of 8 weeks. We concluded that strength training interventions can be used as a non-drug treatment for arterial hypertension, as they promote significant decreases in blood pressure.

Effect of resistance training on bioelectrical phase angle in older adults: a systematic review with Meta-analysis of randomized controlled trials.

Resistance training has been proposed as a valid practice to counteract the aging effect on body mass and its components, which can be easily evaluated though the bioelectrical impedance analysis. This study aimed to achieve a systematic review with meta-analysis on the impact of resistance training on bioelectrical proprieties in older adults.A literature review was done in four electronic databases up to 1 January 2022. The inclusion criteria were: (i) participants aged ≥ 60 years; (ii) resistance training lasted ≥ 8 weeks; (iii) measurement of raw bioelectrical parameters in randomized controlled study designs.The outcomes of the trial had to be bioelectrical phase angle (PhA), resistance (R), and reactance (Xc). The methodological quality was assessed using the Rosendal scale.Overall, seven studies with a total of 344 participants were eligible for the analysis. The quality assessment yielded a score of 71.3%. Bioelectrical PhA (0.52 degree [95%CI 0.32, 0.71], p < 0.001) and Xc (3.58 ohms [95%CI 1.97, 5.19], p < 0.001) increased, whereas R decreased (-28.50 ohms [95%CI -41.39, -15.60], p < 0.001) after the resistance training programs.In this meta-analysis, resistance training promoted increases of PhA, which result from an increase in Xc concomitant with a reduction in R. According to the bioimpedance vector analysis, resistance-trained people experienced a beneficial leftward vector displacement, whilst inactivity induced a rightward vector displacement within the R-Xc graph. In future, more sophisticated and rigorous studies that address specific criteria, methods and targeted designs are required to identify which equipment and protocols allow for an optimization of the resistance training effects.Registration code in PROSPERO: CRD42020168057.

Physical exercise and the functions of microRNAs.

MicroRNAs (miRNAs) control RNA translation and are a class of small, tissue-specific, non-protein-coding RNAs that maintain cellular homeostasis through negative gene regulation. Maintenance of the physiological environment depends on the proper control of miRNA expression, as these molecules influence almost all genetic pathways, from the cell cycle checkpoint to cell proliferation and apoptosis, with a wide range of target genes. Dysregulation of the expression of miRNAs is correlated with several types of diseases, acting as regulators of cardiovascular functions, myogenesis, adipogenesis, osteogenesis, hepatic lipogenesis, and important brain functions. miRNAs can be modulated by environmental factors or external stimuli, such as physical exercise, and can eventually induce specific and adjusted changes in the transcriptional response. Physical exercise is used as a preventive and non-pharmacological treatment for many diseases. It is well established that physical exercise promotes various benefits in the human body such as muscle hypertrophy, mental health improvement, cellular apoptosis, weight loss, and inhibition of cell proliferation. This review highlights the current knowledge on the main miRNAs altered by exercise in the skeletal muscle, cardiac muscle, bone, adipose tissue, liver, brain, and body fluids. In addition, knowing the modifications induced by miRNAs and relating them to the results of prescribed physical exercise with different protocols and intensities can serve as markers of physical adaptation to training and responses to the effects of physical exercise for some types of chronic diseases. This narrative review consists of randomized exercise training experiments with humans and/or animals, combined with analyses of miRNA modulation.

High-intensity interval training attenuates the effects caused by arterial hypertension in the ventral prostate.

BACKGROUND: The prostatic effects induced by arterial hypertension is very controversial and its mechanism is unclear. High-intensity interval training (HIIT) is an exercise considered to be hypotensive. The objective of this work was to investigate the molecular, biochemical, and morphological effects of 8 weeks of HIIT in the prostatic tissue of spontaneously hypertensive rats (SHR). METHODS: Twenty male SHR rats, 51.4 weeks old, were used. The SHR animals were divided into two groups: spontaneously sedentary hypertensive and spontaneously hypertensive submitted to HIIT. We analyze androgens receptor and glucocorticoid receptors in the prostate. Still, we verify effects of the hypertension and HIIT on the physiopathology prostatic, for immunohistochemistry investigated BCL-2, BAX, IGF-1, FAS/CD95, data's inflammatory tumour necrosis factor α, nuclear factor kappa B and interleukin (IL)-6, anti-inflammatory IL-10. The echocardiographic evaluation was performed at the baseline and after the training period. RESULTS: Arterial hypertension promote high prostatic intraepithelial neoplasia incidence in the prostate, increases IGF-1, BCL-2 (p < 0.05), and inflammatory proteins (p < 0.05). Eight weeks of HIIT training reduced the arterial pressure and increase the concentration of tissue collagen and intracellular glycogen and showed a higher expression of BAX, FAS/CD95, and IL-10 proteins (p < 0.05), coinciding with a lower incidence of lesions and lower prostate weight (p < 0.05) and reduction of the BCL-2 and IGF-1. CONCLUSION: Our data suggested that arterial hypertension suppressed apoptosis and increased damage prostatic. On other hand, HIIT promotes morphology and function improves in the prostatic environment, inhibited inflammation, and increased apoptosis.