Moderate-intensity aerobic exercise training improves CD8+ tumor-infiltrating lymphocytes effector function by reducing mitochondrial loss.

Aerobic exercise training (AET) has emerged as a strategy to reduce cancer mortality, however, the mechanisms explaining AET on tumor development remain unclear. Tumors escape immune detection by generating immunosuppressive microenvironments and impaired T cell function, which is associated with T cell mitochondrial loss. AET improves mitochondrial content and function, thus we tested whether AET would modulate mitochondrial metabolism in tumor-infiltrating lymphocytes (TIL). Balb/c mice were subjected to a treadmill AET protocol prior to CT26 colon carcinoma cells injection and until tumor harvest. Tissue hypoxia, TIL infiltration and effector function, and mitochondrial content, morphology and function were evaluated. AET reduced tumor growth, improved survival, and decreased tumor hypoxia. An increased CD8+ TIL infiltration, IFN-γ and ATP production promoted by AET was correlated with reduced mitochondrial loss in these cells. Collectively, AET decreases tumor growth partially by increasing CD8+ TIL effector function through an improvement in their mitochondrial content and function.

Impacts of the first wave of the COVID-19 pandemic on leisure and transportation physical activity among healthcare workers.

Introduction: The COVID-19 pandemic may lead to reduced physical activity (PA) in health care workers (HCWs). Objective: To evaluate leisure and transport-related PA in HCW of a COVID-19-dedicated hospital during the first wave of the COVID-19 pandemic. Methods: This is a cross-sectional study with a sample of 1,527 HCWs. Socioeconomic aspects, occupational characteristics, and engagement in leisure and transport-related PA were investigated through an online survey administered in August of 2020. Results: More than 80 % HCWs performed < 150 min/week of leisure-related PA, and 85 % performed ≤ 30 min/day transport-related PA. Being male was associated with more PA (OR: 1.93; 95 % CI:1.40-2.66) and transport-related PA; working in nursing, physical therapy, and cleaning/housekeeping services was associated with low PA (OR: 0.70; 95 % CI:0.51-0.95). Physicians and administrative staff were less active in transport-related PA. Conclusions: HCWs working in a COVID-19 hospital had low levels of PA in the domains of leisure and transportation.

Altered locomotor muscle metaboreflex control of ventilation in patients with COPD.

We investigated the locomotor muscle metaboreflex control of ventilation, circulation, and dyspnea in patients with chronic obstructive pulmonary disease (COPD). Ten patients [forced expiratory volume in 1 second (FEV1; means ± SD) = 43 ± 17% predicted] and nine age- and sex-matched controls underwent 1) cycling exercise followed by postexercise circulatory occlusion (PECO) to activate the metaboreflex or free circulatory flow to inactivate it, 2) cold pressor test to interpret whether any altered reflex response was specific to the metaboreflex arc, and 3) muscle biopsy to explore the metaboreflex arc afferent side. We measured airflow, dyspnea, heart rate, arterial pressure, muscle blood flow, and vascular conductance during reflexes activation. In addition, we measured fiber types, glutathione redox balance, and metaboreceptor-related mRNAs in the vastus lateralis. Metaboreflex activation increased ventilation versus free flow in patients (∼15%, P < 0.020) but not in controls (P > 0.450). In contrast, metaboreflex activation did not change dyspnea in patients (P = 1.000) but increased it in controls (∼100%, P < 0.001). Other metaboreflex-induced responses were similar between groups. Cold receptor activation increased ventilation similarly in both groups (P = 0.46). Patients had greater type II skeletal myocyte percentage (14%, P = 0.010), lower glutathione ratio (-34%, P = 0.015), and lower nerve growth factor (NGF) mRNA expression (-60%, P = 0.031) than controls. Therefore, COPD altered the locomotor muscle metaboreflex control of ventilation. It increased type II myocyte percentage and elicited redox imbalance, potentially producing more muscle metaboreceptor stimuli. Moreover, it decreased NGF expression, suggesting a downregulation of metabolically sensitive muscle afferents.NEW & NOTEWORTHY This study's integrative physiology approach provides evidence for a specific alteration in locomotor muscle metaboreflex control of ventilation in patients with COPD. Furthermore, molecular analyses of a skeletal muscle biopsy suggest that the amount of muscle metaboreceptor stimuli derived from type II skeletal myocytes and redox imbalance overcame a downregulation of metabolically sensitive muscle afferents.

Aerobic exercise training mitigates tumor growth and cancer-induced splenomegaly through modulation of non-platelet platelet factor 4 expression.

Exercise training reduces the incidence of several cancers, but the mechanisms underlying these effects are not fully understood. Exercise training can affect the spleen function, which controls the hematopoiesis and immune response. Analyzing different cancer models, we identified that 4T1, LLC, and CT26 tumor-bearing mice displayed enlarged spleen (splenomegaly), and exercise training reduced spleen mass toward control levels in two of these models (LLC and CT26). Exercise training also slowed tumor growth in melanoma B16F10, colon tumor 26 (CT26), and Lewis lung carcinoma (LLC) tumor-bearing mice, with minor effects in mammary carcinoma 4T1, MDA-MB-231, and MMTV-PyMT mice. In silico analyses using transcriptome profiles derived from these models revealed that platelet factor 4 (Pf4) is one of the main upregulated genes associated with splenomegaly during cancer progression. To understand whether exercise training would modulate the expression of these genes in the tumor and spleen, we investigated particularly the CT26 model, which displayed splenomegaly and had a clear response to the exercise training effects. RT-qPCR analysis confirmed that trained CT26 tumor-bearing mice had decreased Pf4 mRNA levels in both the tumor and spleen when compared to untrained CT26 tumor-bearing mice. Furthermore, exercise training specifically decreased Pf4 mRNA levels in the CT26 tumor cells. Aspirin treatment did not change tumor growth, splenomegaly, and tumor Pf4 mRNA levels, confirming that exercise decreased non-platelet Pf4 mRNA levels. Finally, tumor Pf4 mRNA levels are deregulated in The Cancer Genome Atlas Program (TCGA) samples and predict survival in multiple cancer types. This highlights the potential therapeutic value of exercise as a complementary approach to cancer treatment and underscores the importance of understanding the exercise-induced transcriptional changes in the spleen for the development of novel cancer therapies.

Thyroid hormone induces restrictive cardiomyopathy in ß1-adrenoceptor knockout mice.

The purpose of this study was to characterize the role of ß1-AR signaling and its cross-talk between cardiac renin-angiotensin system and thyroid-hormone-induced cardiac hypertrophy. T3 was administered at 0.5 mg·kg-1·day-1 for 10 days in ß1-KOT3 and WTT3 groups, while control groups received vehicle alone. Echocardiography and myocardial histology was performed; cardiac and serum ANGI/ANGII and ANP and cardiac levels of p-PKA, p-ERK1/2, p-p38-MAPK, p-AKT, p-4EBP1, and ACE were measured. WTT3 showed decreased IVSTd and increased LVEDD versus WTsal (p < 0.05). ß1-KOT3 exhibited lower LVEDD and higher relative IVSTd versus ß1-KOsal, the lowest levels of ejection fraction, and the highest levels of cardiomyocyte diameter (p < 0.05). Cardiac ANP levels decreased in WTT3 versus ß1-KOT3 (p < 0.05). Cardiac ACE expression was increased in T3-treated groups (p < 0.05). Phosphorylated-p38 MAPK levels were higher in WTT3 versus WTsal or ß1-KOT3, p-4EBP1 was elevated in ß1-KO animals, and p-ERK1/2 was up-regulated in ß1-KOT3. These findings suggest that ß1-AR signaling is crucial for TiCH.

Physical Exercise Decreases Endoplasmic Reticulum Stress in Central and Peripheral Tissues of Rodents: A Systematic Review.

Endoplasmic reticulum stress (ER stress) affects many tissues and contributes to the development and severity of chronic diseases. In contrast, regular physical exercise (PE) has been considered a powerful tool to prevent and control several chronic diseases. The present systematic review aimed to evaluate the impact of different PE protocols on ER stress markers in central and peripheral tissues in rodents. The eligibility criteria were based on PICOS (population: rodents; intervention: physical exercise/physical training; control: animals that did not undergo training; outcomes: endoplasmic reticulum stress; studies: experimental). The PubMed/Medline, Science Direct, Scopus, and Scielo databases were analyzed systematically. Quality assessment was performed using SYRCLE's risk of bias tool for animal studies. The results were qualitatively synthesized. Initially, we obtained a total of 2.490 articles. After excluding duplicates, 30 studies were considered eligible. Sixteen studies were excluded for not meeting the eligibility criteria. Therefore, 14 articles were included. The PE protocol showed decreased levels/expression of markers of ER stress in the central and peripheral tissues of rodents. PE can decrease ER stress by reducing cellular stress in the cardiac, brain, and skeletal muscle tissues in rodents. However, robust PE protocols must be considered, including frequency, duration, and intensity, to optimize the PE benefits of counteracting ER stress and its associated conditions.

Acute changes in serum and skeletal muscle steroids in resistance-trained men.

Introduction: Resistance exercise can significantly increase serum steroid concentrations after an exercise bout. Steroid hormones are involved in the regulation of several important bodily functions (e.g., muscle growth) through both systemic delivery and local production. Thus, we aimed to determine whether resistance exercise-induced increases in serum steroid hormone concentrations are accompanied by enhanced skeletal muscle steroid concentrations, or whether muscle contractions per se induced by resistance exercise can increase intramuscular steroid concentrations. Methods: A counterbalanced, within-subject, crossover design was applied. Six resistance-trained men (26 ± 5 years; 79 ± 8 kg; 179 ± 10 cm) performed a single-arm lateral raise exercise (10 sets of 8 to 12 RM - 3 min rest between sets) targeting the deltoid muscle followed by either squat exercise (10 sets of 8 to 12 RM - 1 min rest) to induce a hormonal response (high hormone [HH] condition) or rest (low hormone [LH] condition). Blood samples were obtained pre-exercise and 15 min and 30 min post-exercise; muscle specimens were harvested pre-exercise and 45 min post-exercise. Immunoassays were used to measure serum and muscle steroids (total and free testosterone, dehydroepiandrosterone sulfate, dihydrotestosterone, and cortisol; free testosterone measured only in serum and dehydroepiandrosterone only in muscle) at these time points. Results: In the serum, only cortisol significantly increased after the HH protocol. There were no significant changes in muscle steroid concentrations after the protocols. Discussion: Our study provides evidence that serum steroid concentration increases (cortisol only) seem not to be aligned with muscle steroid concentrations. The lack of change in muscle steroid after protocols suggests that resistance-trained individuals were desensitized to the exercise stimuli. It is also possible that the single postexercise timepoint investigated in this study might be too early or too late to observe changes. Thus, additional timepoints should be examined to determine if RE can indeed change muscle steroid concentrations either by skeletal muscle uptake of these hormones or the intramuscular steroidogenesis process.

Effect of stress on the chronotropic and inotropic responses to ß-adrenergic agonists in isolated atria of KOß2 mice.

Altered sensitivity to the chronotropic and inotropic effects of catecholamines and reduction in ß1/ß2-adrenoceptor (ß1/ß2-AR) ratio were reported in failing and in senescent human heart, as well as in isolated atria and ventricle of rats submitted to stress. This was due to downregulation of ß1-AR with or without up-regulation of ß2-AR. AIMS: To investigate the stress-induced behavior of ß1-AR in the heart of mice expressing a non-functional ß2-AR subtype. The guiding hypothesis is that the absence of ß2-AR signaling will not affect the behavior of ß1-AR during stress and that those are independent processes. MATERIALS AND METHODS: The chronotropic and inotropic responses to ß-AR agonists in isolated atria of stressed mice expressing a non-functional ß2-AR were analyzed. The mRNA and protein expressions of ß1- and ß2-AR were also determined. KEY FINDINGS: No deaths were observed in mice under stress protocol. Atria of stressed mice displayed reduced sensitivity to isoprenaline compared to the controls, an effect that was abolished by the ß2- and ß1-AR antagonists 50 nM ICI118,551 and 300 nM CGP20712A, respectively. Sensitivity and maximum response to the ß-agonists dobutamine and salbutamol were not altered by stress or ICI118,551. The responses to dobutamine and salbutamol were prevented by CGP20712A. The expression of ß1-AR was reduced at protein levels. SIGNIFICANCE: Collectively, our data provide evidence that the cardiac ß2-AR is not essential for survival in a stressful situation and that the stress-induced reduction of ß1-AR expression was independent of the ß2-AR presence.

Enhanced Respiratory Frequency Response to Lower Limb Mechanoreceptors Activation in Patients with Chronic Obstructive Pulmonary Disease.

PURPOSE: To investigate the mechanoreflex control of respiration and circulation in patients with chronic obstructive pulmonary disease (COPD). METHODS: Twenty-eight patients with moderate-to-severe COPD (mean ± SD: 67.0 ± 7.9 yr, 10 women) and 14 age- and sex-matched controls (67.9 ± 2.6 yr, 7 women) participated in the study. Their dominant knee was passively moved to stimulate mechanoreceptors, whereas vastus lateralis surface electrical activity checked active contractions. A differential pressure flowmeter, an electrocardiogram, and a servo-controlled finger photoplethysmograph acquired cardiorespiratory data. To gain insight into the mechanoreflex arc, we further analyzed reduced/oxidized glutathione ratio and mechanoreceptor-related gene expression in a vastus lateralis biopsy of additional nine patients (63.9 ± 8.1 yr, 33% women) and eight controls (62.9 ± 9.1 yr, 38% women). RESULTS: Patients with COPD had a greater peak respiratory frequency response (COPD: Δ = 3.2 ± 2.3 vs Controls: 1.8 ± 1.2 cycles per minute, P = 0.036) and a smaller peak tidal volume response to passive knee movement than controls. Ventilation, heart rate, stroke volume, and cardiac output peak responses, and total peripheral resistance nadir response, were unaltered by COPD. In addition, patients had a diminished glutathione ratio (COPD: 13.3 ± 3.8 vs controls: 20.0 ± 5.5 a.u., P = 0.015) and an augmented brain-derived neurotrophic factor expression (COPD: 2.0 ± 0.7 vs controls: 1.1 ± 0.4 a.u., P = 0.002) than controls. Prostaglandin E receptor 4, cyclooxygenase 2, and Piezo1 expression were similar between groups. CONCLUSIONS: Respiratory frequency response to mechanoreceptors activation is increased in patients with COPD. This abnormality is possibly linked to glutathione redox imbalance and augmented brain-derived neurotrophic factor expression within locomotor muscles, which could increase mechanically sensitive afferents' stimulation and sensitivity.

Formoterol reduces muscle wasting in mice undergoing doxorubicin chemotherapy.

Background: Even though doxorubicin (DOX) chemotherapy promotes intense muscle wasting, this drug is still widely used in clinical practice due to its remarkable efficiency in managing cancer. On the other hand, intense muscle loss during the oncological treatment is considered a bad prognosis for the disease's evolution and the patient's quality of life. In this sense, strategies that can counteract the muscle wasting induced by DOX are essential. In this study, we evaluated the effectiveness of formoterol (FOR), a ß2-adrenoceptor agonist, in managing muscle wasting caused by DOX. Methods and results: To evaluate the effect of FOR on DOX-induced muscle wasting, mice were treated with DOX (2.5 mg/kg b.w., i.p. administration, twice a week), associated or not to FOR treatment (1 mg/kg b.w., s.c. administration, daily). Control mice received vehicle solution. A combination of FOR treatment with DOX protected against the loss of body weight (p<0.05), muscle mass (p<0.001), and grip force (p<0.001) promoted by chemotherapy. FOR also attenuated muscle wasting (p<0.01) in tumor-bearing mice on chemotherapy. The potential mechanism by which FOR prevented further DOX-induced muscle wasting occurred by regulating Akt/FoxO3a signaling and gene expression of atrogenes in skeletal muscle. Conclusions: Collectively, our results suggest that FOR can be used as a pharmacological strategy for managing muscle wasting induced by DOX. This study provides new insights into the potential therapeutic use of FOR to improve the overall wellbeing of cancer patients undergoing DOX chemotherapy.

Increased sympathetic nervous system impairs prognosis in lung cancer patients: a scoping review of clinical studies.

Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer. Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational. Results: Our data indicated an increased expression of ß-2-adrenergic receptors in lung cancer, which was associated with poor prognosis. However, the use of ß-blockers as an add-on to standard treatment promoted enhanced overall survival, recurrence-free survival and reduced metastasis occurrence. Conclusion: Although the results herein seem promising, future research using high-quality prospective clinical trials is required to draw directions to guide clinical interventions.

Lung cancer is one of the most common causes of cancer-related deaths in the world, which often goes undiagnosed until it is in an advanced stage. Recently, the autonomic nervous system (sympathetic and parasympathetic nervous systems) has been identified as a regulator of cancer growth and spread, including lung cancer. In fact, preclinical studies have demonstrated that autonomic innervation in lung cancer can trigger tumor progression, metastasis, and resistance to treatment, worsening the prognosis. In this sense, add-on strategies to standard cancer treatments have been investigating and one of them has stood out: the incidental use of ß-blockers (patients who used ß-blockers for the treatment of hypertension and/or cardiovascular diseases or anxiety) before surgeries or during chemotherapy, which has been associated with improved clinical outcomes. Thus, a scoping review was conducted to summarizing the current knowledge about the quality of evidence, gaps and main results related to the role of the autonomic nervous system in human lung cancer. Data from this review indicated an increase in sympathetic nervous system receptors associated with a worse prognosis in patients with lung cancer. Indeed, those patients who took ß-blockers along with lung cancer treatment showed an increase in survival and a reduction in the occurrence of metastases. Although the results herein seem promising, further prospective clinical studies are needed to investigate the effect of the intentional and controlled use of ß-blockers as an add-on strategy on the treatment of different types and stages of lung cancer.

Muscle metabolic stress determines cancer cachexia severity in mice.

Objectives: To determine the metabolic effects of cancer-conditioned media on myotube metabolism and to understand whether the variability of these effects is associated with cancer cachexia progression. Materials and methods: We established single-cell clones from murine Lewis lung carcinoma (LLC) cells and generated conditioned media from each clonal line. Differentiated primary mouse myotubes were incubated with conditioned media derived from each individual clonal cell line. After initial analysis, we selected a specific LLC clonal cell line that failed to induce metabolic stress in myotubes for further investigation in vitro and in vivo. Results: Short-term incubation with conditioned media from 10/34 LLC clonal cells failed to affect oxygen consumption rate (OCR) in myotubes. Incubation with parental LLC-conditioned media decreased protein content and changed the expression of key regulators of muscle function in myotubes, but the incubation of conditioned media from a selected clone that failed to affect OCR in myotubes also did not affect protein content and expression of muscle regulators. Mice injected with parental LLC cells had a significantly reduced body mass and muscle wasting compared to the mice injected with cells derived from this selected LLC clone. Conclusion: Factors secreted by LLC cells induce metabolic stress in primary myotubes and induce cancer cachexia in mice. However, a selected clonal LLC cell line that failed to induce metabolic stress in myotubes also promoted weaker catabolism in mice. These novel findings establish that early disruption of muscle oxidative metabolism is associated with cancer cachexia progression.

Evidence for a neuromuscular circuit involving hypothalamic interleukin-6 in the control of skeletal muscle metabolism.

Hypothalamic interleukin-6 (IL6) exerts a broad metabolic control. Here, we demonstrated that IL6 activates the ERK1/2 pathway in the ventromedial hypothalamus (VMH), stimulating AMPK/ACC signaling and fatty acid oxidation in mouse skeletal muscle. Bioinformatics analysis revealed that the hypothalamic IL6/ERK1/2 axis is closely associated with fatty acid oxidation- and mitochondrial-related genes in the skeletal muscle of isogenic BXD mouse strains and humans. We showed that the hypothalamic IL6/ERK1/2 pathway requires the α2-adrenergic pathway to modify fatty acid skeletal muscle metabolism. To address the physiological relevance of these findings, we demonstrated that this neuromuscular circuit is required to underpin AMPK/ACC signaling activation and fatty acid oxidation after exercise. Last, the selective down-regulation of IL6 receptor in VMH abolished the effects of exercise to sustain AMPK and ACC phosphorylation and fatty acid oxidation in the muscle after exercise. Together, these data demonstrated that the IL6/ERK axis in VMH controls fatty acid metabolism in the skeletal muscle.

Muscle Stem Cell Function Is Impaired in ß2-Adrenoceptor Knockout Mice.

Knockout (ko) mice for the ß2 adrenoceptor (Adrß2) have impaired skeletal muscle regeneration, suggesting that this receptor is important for muscle stem cell (satellite cell) function. Here, we investigated the role of Adrß2 in the function of satellite cells from ß2ko mice in the context of muscle regeneration, through in vivo and in vitro experiments. Immunohistochemical analysis showed a significant reduction in the number of self-renewed Pax7+ satellite cells, proliferating Pax7+/MyoD+ myogenic precursor cells, and regenerating eMHC+ myofibers in regenerating muscle of ß2ko mice at 30, 3, and 10 days post-injury, respectively. Quiescent satellite cells were isolated by fluorescence-activated cell sorting, and cell cycle entry was assessed by EdU incorporation. The results demonstrated a lower number of proliferating Pax7+/EdU+ satellite cells from ß2ko mice. There was an increase in the gene expression of the cell cycle inhibitor Cdkn1a and Notch pathway components and the activation of Notch signaling in proliferating myoblasts from ß2ko mice. There was a decrease in the number of myogenin-positive nuclei in myofibers maintained in differentiation media, and a lower fusion index in differentiating myoblasts from ß2ko mice. Furthermore, the gene expression of Wnt/ß-catenin signaling components, the expression of nuclear ß-catenin and the activation of Wnt/ß-catenin signaling decreased in differentiating myoblasts from ß2ko mice. These results indicate that Adrß2 plays a crucial role in satellite cell self-renewal, as well as in myoblast proliferation and differentiation by regulating Notch and Wnt/ß-catenin signaling, respectively.

Walking Training Increases microRNA-126 Expression and Muscle Capillarization in Patients with Peripheral Artery Disease.

Patients with peripheral artery disease (PAD) have reduced muscle capillary density. Walking training (WT) is recommended for PAD patients. The goal of the study was to verify whether WT promotes angiogenesis in PAD-affected muscle and to investigate the possible role of miRNA-126 and the vascular endothelium growth factor (VEGF) angiogenic pathways on this adaptation. Thirty-two men with PAD were randomly allocated to two groups: WT (n = 16, 2 sessions/week) and control (CO, n = 16). Maximal treadmill tests and gastrocnemius biopsies were performed at baseline and after 12 weeks. Histological and molecular analyses were performed by blinded researchers. Maximal walking capacity increased by 65% with WT. WT increased the gastrocnemius capillary-fiber ratio (WT = 109 ± 13 vs. 164 ± 21 and CO = 100 ± 8 vs. 106 ± 6%, p < 0.001). Muscular expression of miRNA-126 and VEGF increased with WT (WT = 101 ± 13 vs. 130 ± 5 and CO = 100 ± 14 vs. 77 ± 20%, p < 0.001; WT = 103 ± 28 vs. 153 ± 59 and CO = 100 ± 36 vs. 84 ± 41%, p = 0.001, respectively), while expression of PI3KR2 decreased (WT = 97 ± 23 vs. 75 ± 21 and CO = 100 ± 29 vs. 105 ± 39%, p = 0.021). WT promoted angiogenesis in the muscle affected by PAD, and miRNA-126 may have a role in this adaptation by inhibiting PI3KR2, enabling the progression of the VEGF signaling pathway.

Cardiovascular physiology and autonomic heart control principles: the use of a station rotation strategy to recall basic cardiovascular knowledge among exercise science students

Abstract Aim: Cardiovascular physiology learned by exercise science students is often quickly forgotten. We tested whether a state rotation model would help students to recall key principles of Cardiovascular Physiology (CV). Methods: Seventy-one undergraduate students enrolled in the Exercise Physiology Course at the School of Physical Education and Sport, University of São Paulo, participated in the study. The students were randomly assigned into one of 4 stations, dedicated to recalling the concepts of the heart as a pump (e.g. preload, post-load, and contractility; station 1) and hemodynamics (e.g. serial and parallel conductance; station 2) by using the educational tool. Heart rate (HR) control by sympathetic nervous system activation (station 3) and HR control by vagal activation (station 4) were assessed by quantifying HR response to the Stroop color and word test and during face immersion in cold water, respectively. To evaluate the efficacy of the intervention, we used a Socrative app to launch eight multiple-choice questions before (PRE) and after (POST) the student's station rotation. The questions were related to the basic principles of exercise physiology and its consequences on the cardiovascular system. Results: The 4-station average score (% of corrected answers) achieved after the station rotation was higher than the score achieved before (71.21%, SD 14.50 vs. 31.07%, SD 18.04; for POST and PRE, respectively p < 0.005). Considering specific stations, the lowest score of corrected answers before the rotation was observed at station 2- hemodynamics when compared with station 1-heart as a pump and station 3/4 - autonomic control (18.9%, SD 0.9 vs. 46.5, SD 24.1 and 34.8, SD 2.1 for hemodynamics, heart as a pump and autonomic control, respectively). Interestingly, after the rotation, there was a significant increase in corrected scores for all stations (33.9, SD 9.8; 80.5, SD 4.6 and 90.2, SD 2.3, for hemodynamics, heart as a pump, and autonomic control, respectively). Conclusion: Our results suggest that the use of the educational tool was effective to recall CV principles that are essential to a better understanding of the CV responses to exercise and applying the concepts in exercise testing and prescription for different populations.

The influence of a supervised group exercise intervention combined with active lifestyle recommendations on breast cancer survivors' health, physical functioning, and quality of life indices: study protocol for a randomized and controlled trial.

BACKGROUND: Most cancer patients, under active treatment or not, are sedentary, despite increasing scientific and clinical understanding of the benefits of exercise and physical activity, such as improving quality of life, limiting disease symptoms, decreasing cancer recurrence, and increasing overall survival. Studies have shown that both supervised exercise and unsupervised physical activity programs have low adherence and limited long-term benefits among cancer survivors. Therefore, interventions focused on increasing physical activity levels have clinical and psychological relevance. The present study will examine the feasibility and efficacy of an intervention that combines supervised group exercise with active lifestyle recommendations, analyzing its clinical, psychological, physiological, functional, and immunological effects in breast cancer survivors. METHODS: Women aged 35-75 years who have completed chemotherapy, radiotherapy, and surgery for breast cancer will be recruited from the Cancer Institute of the State of Sao Paulo (ICESP) and take part in a 16-week, parallel-group, randomized, and controlled trial. They will receive a booklet with recommendations for achieving a physically active lifestyle by increasing overall daily movement and undertaking at least 150 min/week of structured exercise. Then, they will be randomized into two groups: the supervised group will take part in two canoeing group exercise sessions every week, and the unsupervised group will increase their overall physical activity level by any means, such as active commuting, daily activities, or home-based exercise. Primary outcome includes aerobic capacity. Secondary outcomes are physical activity, physical functioning, self-reported quality of life, fatigue, presence of lymphedema, body composition, immune function, adherence to physical activity guidelines, and perceptions of self-image. DISCUSSION: Results should contribute to advance knowledge on the impact of a supervised group exercise intervention to improve aspects related to health, physical functioning, and quality of life in female breast cancer survivors. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials Number: RBR-3fw9xf. Retrospectively Registered on 27 December 2018. Items from the World Health Organization Trial Registration Data Set can be accessed on http://www.ensaiosclinicos.gov.br/rg/RBR-3fw9xf/ .

Effects of Aerobic Exercise Training on MyomiRs Expression in Cachectic and Non-Cachectic Cancer Mice.

We investigated the effects of AET on myomiRs expression in the skeletal muscle and serum of colon cachectic (CT26) and breast non-cachectic (MMTV-PyMT) cancer mice models. Colon cancer decreased microRNA-486 expression, increasing PTEN in tibialis anterior muscle (TA), decreasing the PI3K/mTOR protein pathway, body and muscle wasting, fibers' cross-sectional area and muscle dysfunction, that were not preserved by AET. In contrast, breast cancer decreased those muscle functions, but were preserved by AET. In circulation, the downregulation of microRNA-486 and -206 in colon cancer, and the downregulation of microRNA-486 and upregulation of microRNA-206 expression in breast cancer might be good cancer serum biomarkers. Since the microRNA-206 is skeletal muscle specific, their expression was increased in the TA, serum and tumor in MMTV, suggesting a communication among these three compartments. The AET prevents these effects on microRNA-206, but not on microRNA-486 in MMTV. In conclusion, cancer induced a downregulation of microRNA-486 expression in TA and serum of CT26 and MMTV mice and these effects were not prevented by AET; however, to MMTV, the trained muscle function was preserved, probably sustained by the downregulation of microRNA-206 expression. Serum microRNA-206 is a potential biomarker for colon (decreased) and breast (increased) cancer to monitor the disease evolution and the effects promoted by the AET.