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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.
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Fatores de Transcrição ARNTL , Envelhecimento , Apoptose , Camundongos Endogâmicos C57BL , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Condicionamento Físico Animal , Próstata , Masculino , Animais , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Fatores de Transcrição ARNTL/metabolismo , Fatores de Transcrição ARNTL/genética , Camundongos , Condicionamento Físico Animal/fisiologia , Envelhecimento/metabolismo , Próstata/metabolismo , Próstata/patologia , Regulação para Cima , Ritmo Circadiano/fisiologiaRESUMO
The indiscriminate and, very often, incorrect use of pesticides in Brazil, as well as in other countries, results in severe levels of environmental pollution and intoxication of human life. Herein, we studied plasma membrane models (monolayer and bilayer) of the phospholipid Dioleoyl-sn-glycerol-3-phosphocholine (DOPC) using Langmuir films, and large (LUVs) and giant (GUVs) unilamellar vesicles, to determine the effect of the pesticides chlorantraniliprole (CLTP), isoxaflutole (ISF), and simazine (SMZ), used in sugarcane. CLTP affects the lipid organization of the bioinspired models of DOPC π-A isotherms, while ISF and SMZ pesticides significantly affect the LUVs and GUVs. Furthermore, the in vivo study of the gill tissue in fish in the presence of pesticides (2.0 × 10-10 mol/L for CLTP, 8.3 × 10-9 mol/L for ISF, and SMZ at 9.9 × 10-9 mol/L) was performed using optical and fluorescence images. This investigation was motivated by the gill lipid membranes, which are vital for regulating transporter activity through transmembrane proteins, crucial for maintaining ionic balance in fish gills. In this way, the presence of phospholipids in gills offers a model for understanding their effects on fish health. Histological results show that exposure to CLTP, ISF, and SMZ may interfere with vital gill functions, leading to respiratory disorders and osmoregulation dysfunction. The results indicate that exposure to pesticides caused severe morphological alterations in fish, which could be correlated with their impact on the bioinspired membrane models. Moreover, the effect does not depend on the exposure period (24h and 96h), showing that animals exposed to pesticides for a short period suffer irreparable damage to gill tissue. In summary, we can conclude that the harm caused by pesticides, both in membrane models and in fish gills, occurs due to contamination of the aquatic system with pesticides. Therefore, water quality is vital for the preservation of ecosystems.
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Brânquias , Praguicidas , Fosfolipídeos , Tilápia , ortoaminobenzoatos , Animais , Brânquias/efeitos dos fármacos , Brânquias/metabolismo , Fosfolipídeos/metabolismo , Praguicidas/toxicidade , Tilápia/metabolismo , ortoaminobenzoatos/toxicidade , Poluentes Químicos da Água/toxicidade , Membrana Celular/efeitos dos fármacos , BrasilRESUMO
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.
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Docetaxel , Neoplasias da Próstata , Masculino , Docetaxel/farmacologia , Docetaxel/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Neoplasias da Próstata/metabolismo , Humanos , Animais , Emulsões , Linhagem Celular Tumoral , Apoptose/efeitos dos fármacos , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Camundongos , Lipídeos/sangue , Progressão da Doença , Exercício Físico , Nanopartículas/química , Proliferação de Células/efeitos dos fármacos , Condicionamento Físico AnimalRESUMO
BACKGROUND: Multiple sclerosis (MS) is an important cause of acquired neurological disability in young adults, characterized by multicentric inflammation, demyelination, and axonal damage. OBJECTIVE: The objective is to investigate white matter (WM) damage progression in a Brazilian MS patient cohort, using diffusion tensor imaging (DTI) post-processed by tract-based spatial statistics (TBSS). METHODS: DTI scans were acquired from 76 MS patients and 37 sex-and-age matched controls. Patients were divided into three groups based on disease duration. DTI was performed along 30 non-collinear directions by using a 1.5T imager. For TBSS analysis, the WM skeleton was created, and a 5000 permutation-based inference with a threshold of p < .05 was used, to enable the identification of abnormalities in fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), and axial diffusivity (AD). RESULTS: Decreased FA and increased RD, MD, and AD were seen in patients compared to controls and a decreased FA and increased MD and RD were seen, predominantly after the first 5 years of disease, when compared between groups. CONCLUSION: Progressive WM deterioration is seen over time with a more prominent pattern after 5 years of disease onset, providing evidence that the early years might be a window to optimize treatment and prevent disability.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Substância Branca , Adulto Jovem , Humanos , Substância Branca/diagnóstico por imagem , Esclerose Múltipla Recidivante-Remitente/diagnóstico por imagem , Imagem de Tensor de Difusão/métodos , Brasil , Anisotropia , EncéfaloRESUMO
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.
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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.
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Treinamento Intervalado de Alta Intensidade , Hipertensão , Condicionamento Físico Animal , Bexiga Urinária , Animais , Ratos , Proteína X Associada a bcl-2 , Hipertensão/complicações , Hipertensão/terapia , Ratos Endogâmicos SHRRESUMO
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.
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Doenças Cardiovasculares , Hipertensão , Treinamento Resistido , Adulto , Humanos , Treinamento Resistido/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Hipertensão/tratamento farmacológico , Pressão Sanguínea/fisiologiaRESUMO
BACKGROUND: Head circumference (HC) correlates with brain growth and development. However, radiologists typically use their visual impressions to evaluate head dimensions, which is a purely subjective assessment. OBJECTIVE: The first objective of this paper was to analyze whether it is possible to obtain HC measurements by CT and MRI cross-sectional volumetric imaging using parameters similar to the tape measurement method, which is considered the gold standard. The second objective was to determine the most accurate method for characterizing head size: visual impression or imaging measurement. MATERIALS AND METHODS: Children who underwent HC measurement by tape and with volumetric imaging exams were selected from the Paulo Niemeyer State Brain Institute, Brazil. Two radiologists classified the children's heads using their visual impressions and by direct measurement on imaging. We used anatomical parameters similar to the tape measurement method and appropriate head growth charts and compared the absolute values obtained. RESULTS: The concordance between tape and imaging ranged 52.3-72.7% for visual impression (kappa 0.27-0.55), ≥ 95.5% for CT and ≥ 93.1% for MRI (kappa ≥ 0.92 and ≥ 0.88, respectively). Intraclass correlation coefficients ≥ 0.997 and ≥ 0.996, absolute technical error measurements of 0.20-0.31 cm and 0.24-0.29 cm, and relative technical error measurements of 0.49-0.73% and 0.58-0.70% were evidenced in the intra- and inter-rater evaluations, respectively. The means between the methods were not significantly different (P > 0.05), with high values of Pearson correlation coefficient (≥ 0.99) and Lin concordance correlation coefficient (≥ 0.99). CONCLUSION: Head circumference values obtained by cross-sectional volumetric imaging are similar to those obtained using the tape measurement method (gold standard), with high repeatability and reproducibility. Head size characterization by visual impression is less accurate than head circumference measurement by imaging and plotting the values obtained on World Health Organization normative charts.
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Encéfalo , Cabeça , Criança , Humanos , Reprodutibilidade dos Testes , Estudos Transversais , Cabeça/diagnóstico por imagem , Cabeça/anatomia & histologia , Cefalometria/métodosAssuntos
Maus-Tratos Infantis , Traumatismos Craniocerebrais , Humanos , Lactente , Criança , Hemorragia Retiniana/diagnóstico por imagem , Hemorragia Retiniana/etiologia , Traumatismos Craniocerebrais/complicações , Traumatismos Craniocerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Maus-Tratos Infantis/diagnóstico , Estudos RetrospectivosRESUMO
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.