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BACKGROUND: Exercise is an effective method for preventing and treating osteoporosis, but it is unclear whether its effect on postmenopausal osteoporosis is related to changes in bone autophagy levels. OBJECTIVE: To observe the effects of exercise via cellular autophagy on the morphology and mechanical properties of bone tissue in ovariectomized rats, and to explore the mechanism of exercise on bone mass in ovariectomized rats from the perspective of autophagy. METHODS: A rat model of postmenopausal osteoporosis was established, and a 24-week moderate-intensity exercise was used for intervention. After the experiment, serum estradiol levels were measured by ELISA, and bone mineral density and bone microstructure of the cortical and trabecular bone were detected by micro-CT. The biomechanical indicators of the tibia were tested by a three-point bending test. Autophagosomes were observed by transmission electron microscopy. The expression of LC3 and ATG7 proteins was analyzed by western blot. RESULTS AND CONCLUSION: The serum estradiol level in the ovariectomized group was significantly lower than that of the sham-operation group and ovariectomized+exercise group (P < 0.01). The body mass of rats in each group increased, and the order was the ovariectomized group > the ovariectomized+exercise group > the sham-operation group > the sham-operation+exercise group. The bone mineral density and bone mass of rats in all groups significantly increased (P < 0.01), but the increase in the ovariectomized group was significantly lower than that of the other groups, and the increase in the ovariectomized+exercise group was significantly higher than that of the ovariectomized group. Compared with the sham-operation group, the bone mineral density of the tibial cancellous bone in the sham-operation+exercise group was significantly increased (P < 0.01), while the bone mineral density in the ovariectomized and ovariectomized+exercise groups was significantly decreased (P < 0.01). Compared with the ovariectomized+exercise group, the ovariectomized group showed significantly lower bone volume fraction, number of trabeculae, and bone mineral density of cancellous bone (P < 0.05), extremely significantly lower trabecular thickness (P < 0.01), and significantly higher mean trabecular pattern factor, trabecular separation, and structural model index (P < 0.01). Compared with the ovariectomized group, the LC3-II/LC3-I ratio and the relative expression of ATG7 protein significantly increased in the ovariectomized+exercise group (P < 0.05). Compared with the sham-operation and ovariectomized groups, the number of autophagosomes increased in the sham-operation+exercise and ovariectomized+exercise groups, respectively. To conclude, moderate-intensity treadmill exercise can improve the bone microstructure and biomechanical properties of the tibial cancellous bone and increase bone mass in ovariectomized rats by increasing serum estradiol levels and bone autophagy levels. [ABSTRACT FROM AUTHOR]

Both estrogen deprivation and diabetes mellitus are known as risk factors for neuronal damage. Using an animal model of ovariectomized and/or streptozotocin (STZ)-induced diabetes mellitus, we examined expression of apoptosis-related proteins, neuronal damage, and astrocyte activation in prefrontal cortex of rats with/without treadmill exercise. Adult female Wistar rats were divided into control, ovariectomized (Ovx, bilateral ovariectomy), diabetic (Dia, STZ 60 mg/kg; i.p.), and ovariectomized diabetic (Ovx + Dia) groups. Next, animals in each group were randomly subdivided into non-exercise and exercise subgroups. Animals in the exercise groups underwent moderate treadmill running for 4 weeks (5 days/week). Thereafter, expression of Bax, Bcl-2, and caspase-3, as apoptosis-related proteins, number of neurons, and number of glial fibrillary acidic protein (GFAP)-positive cells in prefrontal cortex were measured using immunoblotting, cresyl violet staining, and immunohistochemistry, respectively. In both Dia and Ovx + Dia groups, Bax and caspase-3 protein levels and number of GFAP-positive cells were higher than those in the control group, while Bcl-2 protein level and number of neurons compared were lower than the control group. Beneficial effects of exercise to prevent apoptosis-mediated neuronal damage and astrocyte activation were also observed in the Dia group. Based on our results, physical exercise could be beneficial to attenuate diabetes-induced neuronal damage in the prefrontal cortex via inhibition of apoptosis. [ABSTRACT FROM AUTHOR]

Exertional breathlessness is a cardinal symptom of cardiorespiratory disease. How does breathlessness abnormality, graded using normative reference equations during cardiopulmonary exercise testing (CPET), relate to self-reported and physiologic responses in people with chronic airflow limitation (CAL)? An analysis was done of people aged ≥ 40 years with CAL undergoing CPET in the Canadian Cohort Obstructive Lung Disease study. Breathlessness intensity ratings (Borg CR10 scale [0-10 category-ratio scale for breathlessness intensity rating]) were evaluated in relation to power output, rate of oxygen uptake, and minute ventilation at peak exercise, using normative reference equations as follows: (1) probability of breathlessness normality (probability of having an equal or greater Borg CR10 rating among healthy people; lower probability reflecting more severe breathlessness) and (2) presence of abnormal breathlessness (rating above the upper limit of normal). Associations with relevant participant-reported and physiologic outcomes were evaluated. We included 330 participants (44% women): mean ± SD age, 64 ± 10 years (range, 40–89 years); FEV 1 /FVC, 57.3% ± 8.2%; FEV 1 , 75.6% ± 17.9% predicted. Abnormally low exercise capacity (peak rate of oxygen uptake < lower limit of normal) was present in 26%. Relative to peak power output, rate of oxygen uptake, and minute ventilation, abnormally high breathlessness was present in 26%, 25%, and 18% of participants. For all equations, abnormally high exertional breathlessness was associated with worse lung function, exercise capacity, self-reported symptom burden, physical activity, and health-related quality of life; and greater physiologic abnormalities during CPET. Abnormal breathlessness graded using CPET normative reference equations was associated with worse clinical, physiological, and functional outcomes in people with CAL, supporting construct validity of abnormal exertional breathlessness. [ABSTRACT FROM AUTHOR]

The myocardium is a highly oxidative tissue in which mitochondria are essential to supply the energy required to maintain pump function. When pathological hypertrophy develops, energy consumption augments and jeopardizes mitochondrial capacity. We explored the cardiac consequences of chronic swimming training, focusing on the mitochondrial network, in spontaneously hypertensive rats (SHR). Male adult SHR were randomized to sedentary or trained (T: 8-week swimming protocol). Blood pressure and echocardiograms were recorded, and hearts were removed at the end of the training period to perform molecular, imaging, or isolated mitochondria studies. Swimming improved cardiac midventricular shortening and decreased the pathological hypertrophic marker atrial natriuretic peptide. Oxidative stress was reduced, and even more interesting, mitochondrial spatial distribution, dynamics, function, and ATP were significantly improved in the myocardium of T rats. In the signaling pathway triggered by training, we detected an increase in the phosphorylation level of both AKT and glycogen synthase kinase-3 β, key downstream targets of insulin-like growth factor 1 signaling that are crucially involved in mitochondria biogenesis and integrity. Aerobic exercise training emerges as an effective approach to improve pathological cardiac hypertrophy and bioenergetics in hypertension-induced cardiac hypertrophy. [ABSTRACT FROM AUTHOR]

Background: The terminal stage of ischemic heart disease develops into heart failure (HF), which is characterized by hypoxia and metabolic disturbances in cardiomyocytes. The hypoxic failing heart triggers hypoxia-inducible factor-1α (HIF-1α) actions in the cells sensitized to hypoxia and induces metabolic adaptation by accumulating HIF-1α. Furthermore, soluble monocarboxylic acid transporter protein 1 (MCT1) and mitochondrial pyruvate carrier 1 (MPC1), as key nodes of metabolic adaptation, affect metabolic homeostasis in the failing rat heart. Aerobic exercise training has been reported to retard the progression of HF due to enhancing HIF-1α levels as well as MCT1 expressions, whereas the effects of exercise on MCT1 and MPC1 in HF (hypoxia) remain elusive. This research aimed to investigate the action of exercise associated with MCT1 and MPC1 on HF under hypoxia. Methods: The experimental rat models are composed of four study groups: sham stented (SHAM), HF sedentary (HF), HF short-term exercise trained (HF-E1), HF long-term exercise trained (HF-E2). HF was initiated via left anterior descending coronary artery ligation, the effects of exercise on the progression of HF were analyzed by ventricular ultrasound (ejection fraction, fractional shortening) and histological staining. The regulatory effects of HIF-1α on cell growth, MCT1 and MPC1 protein expression in hypoxic H9c2 cells were evaluated by HIF-1α activatort/inhibitor treatment and plasmid transfection. Results: Our results indicate the presence of severe pathological remodelling (as evidenced by deep myocardial fibrosis, increased infarct size and abnormal hypertrophy of the myocardium, etc.) and reduced cardiac function in the failing hearts of rats in the HF group compared to the SHAM group. Treadmill exercise training ameliorated myocardial infarction (MI)-induced cardiac pathological remodelling and enhanced cardiac function in HF exercise group rats, and significantly increased the expression of HIF-1α (p < 0.05), MCT1 (p < 0.01) and MPC1 (p < 0.05) proteins compared to HF group rats. Moreover, pharmacological inhibition of HIF-1α in hypoxic H9c2 cells dramatically downregulated MCT1 and MPC1 protein expression. This phenomenon is consistent with knockdown of HIF-1α at the gene level. Conclusion: The findings propose that long-term aerobic exercise training, as a non- pharmacological treatment, is efficient enough to debilitate the disease process, improve the pathological phenotype, and reinstate cardiac function in HF rats. This benefit is most likely due to activation of myocardial HIF-1α and upregulation of MCT1 and MPC1. [ABSTRACT FROM AUTHOR]

Gait asymmetries are a common problem in clinical populations, such as those with a history of stroke or Parkinson's disease. The use of a split-belt treadmill is one way to enhance gait symmetry but relies on specialty (and typically expensive) equipment. Alternatively, visual cues have been shown as a method to alter gait mechanics, but their utility in altering gait symmetry has been relatively understudied. Before deploying this method to clinical populations, a proof-of-concept study is needed to explore using visual cues to alter gait symmetry in healthy adults. Therefore, the purpose of this study was to examine the extent to which healthy adults could synchronize to an asymmetric visual cue with a small or large gait asymmetry using wearable sensors to measure gait asymmetries. Seventy-two healthy adults (ages: 23.89 ± 6.08 years) walked on the treadmill for two conditions: with and without the visual cue. Each walking condition lasted 10 min at the participant's preferred walking speed. Inertial sensors were used to measure gait asymmetries. Some participants did not respond to the visual cue, and groups were separated into responders and non-responders. Participants in the small and large asymmetry-responder groups exhibited statistically significant increased asymmetries in single limb support % (p < 0.01) and step duration (s) (p < 0.05, p < 0.01, respectively). Only the large asymmetry-responder group showed statistically significant (p < 0.01) increased asymmetries in stride length. Overall, asymmetrical walking visual cues can alter gait asymmetries, and inertial sensors were sensitive enough to detect small changes in gait asymmetries. [ABSTRACT FROM AUTHOR]

Lower extremity joint kinetic factors are thought to modulate walk-to-run transition (WRT) and run-to-walk transition (RWT). This study aimed to investigate joint stiffness and energetic patterns during the WRT and RWT processes and identify whether gait transitions occur within a single step or not. Ten healthy subjects participated in treadmill WRT (1.8–2.4 m/s) and RWT (2.4–1.8 m/s) tests. We investigated two steps before transition (S–2, S–1), two steps after transition (S1, S2) and the transition step (S0). We found significant differences between S2 and S–2 for ankle joint stiffness during WRT and RWT (p < 0.001); for hip joint stiffness, we found significant differences between S1 and S–1 during WRT and RWT (p ≤ 0.001). Additionally, stance phase mechanical energy generation was observed to transfer from proximal to distal joints at S0 during WRT, and from distal to proximal at S0 during RWT. Transition step ankle kinematic and kinetic patterns were similar to the target locomotion task gait format in both WRT and RWT. Moreover, RWT required longer adaptation time compared with WRT. These findings indicate that WRT and RWT were modulated before and after the actual transitions, not within a single step. Redistribution of joint mechanical work generation was related to gait transition triggers, which modulate the WRT and RWT processes. [ABSTRACT FROM AUTHOR]

Exercise training can promote physiological cardiac growth, which has been suggested to involve changes in glucose metabolism to facilitate hypertrophy of cardiomyocytes. In this study, we used a dietary, in vivo isotope labeling approach to examine how exercise training influences the metabolic fate of carbon derived from dietary glucose in the heart during acute, active, and established phases of exercise-induced cardiac growth. Male and female FVB/NJ mice were subjected to treadmill running for up to 4 weeks and cardiac growth was assessed by gravimetry. Cardiac metabolic responses to exercise were assessed via in vivo tracing of [13C 6 ]-glucose via mass spectrometry and nuclear magnetic resonance. We found that the half-maximal cardiac growth response was achieved by approximately 1 week of daily exercise training, with near maximal growth observed in male mice with 2 weeks of training; however, female mice were recalcitrant to exercise-induced cardiac growth and required a higher daily intensity of exercise training to achieve significant, albeit modest, increases in cardiac mass. We also found that increases in the energy charge of adenylate and guanylate nucleotide pools precede exercise-induced changes in cardiac size and were associated with higher glucose tracer enrichment in the TCA pool and in amino acids (aspartate, glutamate) sourced by TCA intermediates. Our data also indicate that the activity of collateral biosynthetic pathways of glucose metabolism may not be markedly altered by exercise. Overall, this study provides evidence that metabolic remodeling in the form of heightened energy charge and increased TCA cycle activity and cataplerosis precedes cardiac growth caused by exercise training in male mice. [Display omitted] • Treadmill exercise promotes cardiac growth in male FVB/NJ mice during the first two weeks of training • Female FVB/NJ mice require a higher exercise training intensity than male mice to elicit marginal cardiac growth • Exercise augments energy charge, Krebs cycle activity, and cataplerosis before and during active cardiac growth • Differences in metabolism caused by exercise recede upon establishment of the cardiac growth phenotype [ABSTRACT FROM AUTHOR]

The vertical toe position at minimum toe clearance (MTC) in the swing phase is critical for walking safety. Consequently, the joints involved should be strictly controlled and coordinated to stabilize the foot at MTC. The uncontrolled manifold (UCM) hypothesis framework has been used to determine the existence of synergies that stabilize relevant performance variables during walking. However, no study investigated the presence of a multi-joint synergy stabilizing the foot position at MTC and the effects of age and walking speed on this synergy. Is there a multi-joint synergy stabilizing MTC during treadmill walking? Does it depend on the persons' age and walking speed? Kinematic data from 23 young and 15 older adults were analyzed using the UCM approach. The participants walked on a treadmill at three speeds: slow, self-selected, and fast. The sagittal and frontal joint angles from the swing and stance legs and pelvis obliquity were used as motor elements and the vertical toe position at MTC was the performance variable. The variances in the joint space that affected (V ORT , 'bad' variance) and did not affect (V UCM , 'good' variance) the toe position at MTC and the synergy index (ΔV) were computed. The ΔV >0 was revealed for all subjects. Walking speed did not affect ΔV in older adults, whereas ΔV reduced with speed in young adults. ΔV was higher for older than for young adults at self-selected and fast speeds, owing to a lower V ORT in the older group. The vertical toe position at MTC was stabilized by a strong multi-joint synergy. In older adults, this synergy was stronger, as they were better at limiting V ORT than young adults. Reduced V ORT in older adults could be caused by more constrained walking, which may be associated with anxiety due to walking on a treadmill. • A multi-joint synergy (ΔV Z) stabilizes the minimum toe clearance (MTC) in walking. • ΔV Z is higher and variances (V UCM and V ORT) are lower at MTC than in the first half of swing phase. • The ΔV Z and V ORT reduced in young but not in older adults when walking in fast speed. • Older adults showed higher ΔV Z and lower V ORT than young adults. • A reduced V ORT in older adults may be a compensatory strategy adopted to constraint the MTC. [ABSTRACT FROM AUTHOR]

Individuals with cerebral palsy (CP) often present with altered motor control. This can be assessed selectively during sitting/lying with the Selective Control Assessment of the Lower Extremity (SCALE), or dynamically with the dynamic motor control index during walking (walk-DMC). Both approaches suggest that altered selective motor control relate to larger gait deviations. Does the walk-DMC provide valuable information in addition to the SCALE for estimating gait deviations in individuals with CP. Retrospective, treadmill-based gait analysis data of 157 children with spastic CP (mean 11.4±3.5 years) and Gross Motor Function Classification System levels I (n=45), II (n=88) or III (n=24) were extracted. Gait kinematic deviations were evaluated using the Gait Profile Score (GPS). The SCALE, walk-DMC and GPS were extracted for the more clinically involved leg (unilateral-analysis), and for both legs together (bilateral-analysis). GPS moderately correlated with both SCALE and walk-DMC scores, unilaterally and bilaterally (r≥0.4; p<0.001). Multivariate linear regression analyses were conducted, taking into account potential confounding factors. In the unilateral analysis, 54% of the GPS variance was explained (p<0.001), with both walk-DMC and SCALE significantly contributing to the GPS variance (p=0.006 and p=0.008, respectively). In the bilateral analysis, 61% of the GPS variance was explained (p<0.001), with both walk-DMC and SCALE significantly contributing to the GPS variance (p=0.006 and p<0.001, respectively). Dimensionless walking speed and use of assistive devices were the only confounding factors included in each analysis. Both SCALE and walk-DMC significantly contribute to GPS variance, suggesting that they likely measure different components of motor control, and both may be useful in understanding the underlying relationship between motor control and deviations in gait kinematics. • Both the SCALE and walk-DMC relate to kinematic gait deviations in CP. • The SCALE and walk-DMC likely measure different components of motor control in CP. • In the absence of EMG, the SCALE can be used to quantify motor control in CP. [ABSTRACT FROM AUTHOR]

The nonlinear variability present during steady-state gait may provide a signature of health and showcase one's walking adaptability. Although treadmills can capture vast amounts of walking data required for estimating variability within a small space, gait patterns may be misrepresented compared to an overground setting. Smartphones may provide a low-cost and user-friendly estimate of gait patterns among a variety of walking settings. However, no study has investigated differences in gait patterns derived from a smartphone between treadmill walking (TW) and overground walking (OW). This study implemented a smartphone accelerometer to compare differences in temporal gait variability and gait dynamics between TW and OW. Sixteen healthy adults (8F; 24.7 ± 3.8 years) visited the laboratory on three separate days and completed three 8-minute OW and three TW trials, at their preferred speed, during each visit. The inter-stride interval was calculated as the time difference between right heel contact events located within the vertical accelerometery signals recorded from a smartphone while placed in participants front right pant pocket during walking trials. The inter-stride interval series was used to calculate stride time standard deviation (SD) and coefficient of variation (COV), statistical persistence (fractal scaling index), and statistical regularity (sample entropy). Two-way analysis of variance compared walking condition and laboratory visits for each measure. Compared to TW, OW displayed significantly (p < 0.01) greater stride time SD (0.014 s, 0.020 s), COV (1.26 %, 1.82 %), fractal scaling index (0.70, 0.79) and sample entropy (1.43, 1.63). No differences were found between visits for all measures. Smartphone-based assessment of gait provides the ability to distinguish between OW and TW conditions, similar to previously established methodologies. Furthermore, smartphones may be a low-cost and user-friendly tool to estimate gait patterns outside the laboratory to improve ecological validity, with implications for free-living monitoring of gait among various populations. • Smartphones can enable gait monitoring outside the lab and for clinical purposes. • Treadmills reduce gait variability and dynamics compared to overground setting. • Context of walking must be considered within the interpretation of the results. [ABSTRACT FROM AUTHOR]

Introduction: Perturbation-based balance training (PBT) is promising for fall prevention in older adults, mimicking real-life fall situations at a person's stability thresholds to improve reactive balance. Hence, it can be associated with anxiety, but knowledge about the acceptability of PBT is scarce. Method: This is a secondary analysis of a randomized controlled trial comparing the effects of two different PBT paradigms that aims to evaluate and compare the acceptability of those training paradigms in fall-prone older adults. Participants (74.9 ± 5.7 years) who completed the training (6 weeks, 3x/week) on either a perturbation treadmill (PBTtreadmill: n = 22) or unstable surfaces in the presence of perturbations (PBTstability: n = 27) were surveyed on the acceptability of PBT using a 21-item questionnaire addressing seven domains (perceived effectiveness, tailoring, demand, safety, burden, devices, affective attitude), based on the theoretical framework of acceptability and context-specific factors. Relative scores (% of absolute maximum) for single items and domains were calculated. Results: Median domain scores of perceived effectiveness, tailoring, safety, devices, and affective attitude were all ≥70% for both paradigms. The highest scores were obtained for tailoring (both paradigms = 100% [interquartile range 80–100%]). Domain scores of demand and burden were in the medium range (40–45%) for both paradigms. No significant differences between paradigms were found for any domain score. Two single items of safety differed significantly, with PBTtreadmill perceived as needing less support (p = 0.015) and leading less often to balance loss (p = 0.026) than PBTstability. Conclusion: PBT conducted on a perturbation treadmill or unstable surfaces is well accepted in this fall-prone older sample, even though it is conducted at individual stability thresholds. Tailoring may play a key role in achieving high levels of perceived effectiveness, appropriate levels of demand and burden, and a high sense of safety. PBT delivered on treadmills might be more appropriate for more anxious persons. [ABSTRACT FROM AUTHOR]

Background: Present study aimed to investigate the effects of swimming and treadmill exercise on demyelination, inflammation, oxidative stress, and nerve/glial antigen-2 (NG2) expression in a model of multiple sclerosis (MS). Methods: 39 male Wistar rats were divided into 5 groups including: (1) control (CON), (2) control cuprizone (CPZ), (3) cuprizone + treadmill exercise (CT), (4) cuprizone + swimming exercise (CS), and (5) delayed control cuprizone (DTXR). In the cuprizone groups, animals received a CPZ-containing diet (1% cuprizone w/w). We treated all the groups after adaptation, and we treated the delayed group (DTXR) with a delayed two weeks. For experimental studies, Immunohistochemistry, Luxol Fast Blue, and Prussian blue were applied. Results: CS and CT, compared to the control cuprizone (CPZ) group, increased re-myelination (p ≤ 0.001) and NG2 expression regulation (p ≤ 0.001). Also, there was a decreased tumor necrosis factor-α (TNF-α) (P ≤ 0.05) and iron deposition (p ≤ 0.001), and increased glutathione peroxidase (GPx) (p ≤ 0.05) in the CS and CT groups compared to the control cuprizone (CPZ) group. Conclusion: In the present study, the effectiveness of exercise in modulating and inhibiting of the progress of MS via ameliorating the inflammation and oxidative mediators, re-myelination, and the NG2-positive cells regulation was demonstrated for the first time. Also, swimming was more effective as an exercise mode compared with treadmill exercise. On the other hand, the exercise training from the initial process of demyelination was more useful than delayed exercise (DTXR) compared to (CPZ) (P ≤ 0.05). [ABSTRACT FROM AUTHOR]

Background: Mobile Applications (App) have reshaped approaches to the intervention and monitoring of physical training. The Safe Runner App is an example. However, evidence of the reliability of the Safe Runner App to obtain aerobic parameters still needs to be investigated. Aims: The present study aimed to analyze the accuracy and reproducibility of power parameters and aerobic capacity derived from incremental testing on a treadmill using an application for mobile devices. Methods: Twenty participants performed a maximum incremental test and retest. Maximum oxygen consumption (VO2MAX), maximum heart rate (HRMAX), maximum velocity (VMAX), anaerobic threshold heart rate (HRAT), and anaerobic threshold velocity (VAT) were estimated. A two-way ANOVA was used for dependent samples or the Friedman test for non-parametric data, and effect size (Cohens-d), intraclass correlation coefficient (ICC), and Bland–Altman were used to verify reliability. Results: No differences between the test and retest (p > 0.05) were observed for all variables assessed. The variables VO2MAX (d = 0.05), HRMAX (d = 0.01), and VMAX (d = 0.05) showed a trivial effect size, while HRAT (d = 0.11) and VAT (d = 0.16) showed to be trivial/low. The ICC values for VO2MAX (0.996), HRMAX (0.955), HRAT (0.939), VMAX (0.996), and VAT (0.913) demonstrated reliability. The Bland–Altman plots demonstrated an agreement of the variables. The variables VO2MAX, HRAT, and VAT were identical when comparing the Safe Runner App and Excel software. Conclusion: The Safe Runner App is reliable in identifying aerobic training parameters. [ABSTRACT FROM AUTHOR]

Introduction: There is high evidence that chronic exercise benefits overall depression severity in older adults. However, late-life depression is characterized by considerable heterogeneity in clinical manifestation emphasizing the need for more individualized exercise intervention programs. Therefore, the objective of the proposed review is to investigate the effects of chronic exercise on overall depression severity and on different symptoms of depression in randomized controlled trials (RCTs) including older adults with a mean age of at least 60 years, and by considering the moderating effects of intervention characteristics and individual characteristics. Methods: This protocol is guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols (PRISMA-P). We will use the Population-Intervention-Comparator-Outcomes-Study design (PICOS) criteria for study inclusion and will search the following database sources for relevant RCTs: Web of Science, Academic Search Complete, CINAHL, APA Psycinfo, SPORTDiscuss, Cochrane. Two independent reviewers will conduct the study selection, data extraction, and quality assessment. Disagreement will be solved by a third reviewer. Primary outcome will be changes in overall depression severity and secondary outcomes will encompass changes in symptoms of depression as defined by the DSM-5, such as sleep quality, fatigue, anxiety, mood, apathy, changes in weight, information processing speed, and executive functions, from baseline until the end of the intervention and to any available intermediary measurement or follow up. Meta-analysis will be undertaken to synthesize the effects of chronic exercise on primary and secondary outcomes. Subgroup analysis will investigate the moderating effects of intervention characteristics (frequency, intensity, duration, type of exercise, cognitive demand, social interactions, exercise supervision, behavioral change techniques, compliance, study design, dropout-rate, type of control group) and individual characteristics (age, sex, education, functional capacity, global cognition, population) on primary and secondary outcomes. Additionally, we plan to assess quality of evidence and publication bias, and to carry out sensitivity analysis. Conclusion: The results of the proposed review are anticipated to have a substantial impact on research and clinical practice. On the one hand, the review's conclusions could form the foundation for developing evidence-based recommendations for individualized exercise programs that alleviate depression in older adults. On the other hand, by revealing research gaps, the review results could encourage the formulation of research questions for further RCTs. Protocol registration number: This protocol has been published in the Prospero repository (PROSPERO 2022 CRD42022361418, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022361418) [ABSTRACT FROM AUTHOR]

Exercise enhances aspects of human cognition, but its intensity may matter. Recent animal research suggests that vigorous exercise, which releases greater amounts of lactate, activates more brain-derived neurotrophic factor (BDNF) in the hippocampus and, thus, may be optimal for supporting cognitive function. The cognitive benefits of exercise may be further augmented when combined with cognitive training. The sport of orienteering simultaneously combines exercise with spatial navigation and, therefore, may result in greater cognitive benefits than exercising only, especially at vigorous intensities. The present study aimed to examine the effects of an acute bout of orienteering at different intensities on cognition and BDNF compared to exercising only. We hypothesized that vigorous-intensity orienteering would increase lactate and BDNF and improve cognition more than moderate-intensity orienteering or vigorous exercise alone. Sixty-three recreationally active, healthy young adults (Mage = 21.10±2.75 years) with no orienteering experience completed a 1.3 km intervention course by navigating and exercising at a vigorous (80–85% of heart rate reserve) or moderate (40–50% of heart rate reserve) intensity or exercising vigorously without navigation. Exercise intensity was monitored using peak lactate, heart rate and rating of perceived exertion. Serum BDNF was extracted immediately before and after the intervention. Memory was assessed using the Mnemonic Similarity Task (high-interference memory) and the Groton Maze Learning Test (spatial memory). Both exercising and orienteering at a vigorous intensity elicited greater peak lactate and increases in BDNF than moderate-intensity orienteering, and individuals with higher peak lactate also had greater increases in BDNF. High-interference memory improved after both vigorous-intensity interventions but did not improve after the moderate-intensity intervention. Spatial memory only increased after vigorous-intensity orienteering, suggesting that orienteering at a vigorous intensity may particularly benefit spatial cognition. Overall, the results demonstrate the benefits of vigorous exercise on human cognition and BDNF. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exercise has a regulatory effect on intestinal flora dysbiosis, which can effectively protect the beneficial flora and improve the intestinal environment. However, the effect of treadmill exercise on the structure and diversity of intestinal microbial community in Parkinson’s disease and the specific mechanism are not clear. OBJECTIVE: Using 16S rDNA technique to analyze the effect of treadmill exercise on the structure and diversity of the intestinal flora of rats with Parkinson’s disease, and to investigate the mechanism of non-pharmacological treadmill exercise to improve Parkinson’s disease. METHODS: Twelve of the 18 Sprague-Dawley rats were randomly selected to make animal models of Parkinson’s disease using unilateral 2-point nigrostriatal injection of 6-hydroxydopamine. The remaining six rats were used as sham-operation group, which were injected with the same dose of saline containing 0.2% ascorbic acid using the same positioning and injection method. After successful modeling, 12 rats with Parkinson’s disease were randomly divided into model group and treadmill exercise group (n=6 per group). The treadmill exercise group was subjected to a middle and low intensity tread mill exercise, 10 m/min, 30 minutes per day, 5 days per week for 4 weeks. Fresh feces were collected and stored in liquid nitrogen 24 hour after the last exercise session, and the changes in fecal flora were analyzed by 16S rDNA sequencing technique. RESULTS AND CONCLUSION: Treadmill exercise significantly improved behavior and nigrostriatal tyrosine hydroxylase-positive cell expression in rats with Parkinson’s disease model and alleviated changes in the structure and diversity of the gut microbial community caused by Parkinson’s disease, increased the number of operational taxonomic units and modulated Alpha and Beta diversity in rats. At the phylum and genus levels, the abundance ratio of Firmicutes/ Bacteroidetes in the model group decreased compared with the sham-operated group, while beneficial bacteria such as Prevotella, Bacteroides, and Clostridium_XlV increased significantly after treadmill exercise. To conclude, treadmill exercise has a significant modulating effect on behavioral abnormalities, toxic damage to dopaminergic neurons and gut microbial imbalance caused by Parkinson’s disease, alleviates the symptoms of flora-related diseases, and has a positive effect on the improvement of Parkinson’s disease. [ABSTRACT FROM AUTHOR]

Domestic horses routinely participate in vigorous and various athletic activities. This enables the horse to serve as a model for studying athletic physiology and immunology in other species, including humans. For instance, as a model of physical efforts, such as endurance rides (long-distance running/aerobic exercise) and races (anaerobic exercise), the horse can be useful in evaluating post-exercise response. Currently, there has been significant interest in finding biomarkers, which characterize the advancement of training and adaptation to physical exercise in the horse. The parallels in cellular responses to physical exercises, such as changes in receptor expression and blood cell activity, improve our understanding of the mechanisms involved in the body's response to intense physical activity. This study focuses on the changes in levels of the pro- and anti-inflammatory cytokines and cellular response in the context of post-exercise immune response. Both the direction of changes in cytokine levels and cellular responses of the body, such as proliferation and expression of surface markers on lymphocytes, monocytes and neutrophils, show cross-functional similarities. This review reveals that horses are robust research models for studying the immune response to physical exercise in human athletes. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is characterized by continuous mucosal ulceration of the colon, starting in the rectum. 5-Aminosalicylic acid (5-ASA) is the main therapy for ulcerative colitis; however, it has side effects. Physical exercise effectively increases the number of anti-inflammatory and anti-immune cells in the body. In the current study, the effects of simultaneous treatment of treadmill exercise and 5-ASA were compared with monotherapy with physical exercise or 5-ASA in UC mice. To induce the UC animal model, the mice consumed 2% dextran sulfate sodium dissolved in drinking water for 7 days. The mice in the exercise groups exercised on a treadmill for 1 h once a day for 14 days after UC induction. The 5-ASA-treated groups received 5-ASA by enema injection using a 200 μL polyethylene catheter once a day for 14 days. Simultaneous treatment improved histological damage and increased body weight, colon weight, and colon length, whereas the disease activity index score and collagen deposition were decreased. Simultaneous treatment with treadmill exercise and 5-ASA suppressed pro-inflammatory cytokines and apoptosis following UC. The benefits of this simultaneous treatment may be due to inhibition on nuclear factor-κB/mitogen-activated protein kinase signaling activation. Based on this study, simultaneous treatment of treadmill exercise and 5-ASA can be considered as a new therapy of UC. [ABSTRACT FROM AUTHOR]

Background: Wheat-dependent exercise-induced anaphylaxis (WDEIA) is induced not by the intake of wheat-based food alone, but by the combination of exercise stress and such intake. Provocation tests have been reported to be useful for the diagnosis of this condition, but they are not always accurate. Furthermore, provocation tests are associated with the risk of anaphylactic shock, so safer testing is required. Subjects and methods: Thirty-three patients (mean age 35.5 ± 16.0 years) who underwent provocation tests from April 2019 to July 2023 were included in this study. We investigated associations of their provocation test results with their medical history, blood test results before the provocation tests, exercise load at the time of the test, and severity of the induced symptoms. Results: Symptoms were induced and the diagnosis of WDEIA was made in 28 cases, while 2 cases were confirmed not to have WDEIA. Overall, 25 of the 28 positive cases had symptoms induced by an exercise load greater than 70% of the heart rate calculated by the Karvonen formula, 7 of which required NonSteroidal Anti-Inflammatory Drugs (NSAIDs) loading to induce symptoms. None of the patients with negative wheat-specific IgE titers and positive gluten and/or ω-5 gliadin ones required NSAIDs loading. No patients required the administration of adrenaline. Conclusion: Wheat-specific IgE as well as gluten and ω-5 gliadin antibody titers are associated with WDEIA symptom severity. Exercise loading with a target heart rate of 70%–90% of that calculated by the Karvonen formula is safe and useful for diagnosis this condition. [ABSTRACT FROM AUTHOR]

Alleviating bone loss is an essential way to prevent osteoporotic fractures. Proper exercise improves bone density without the side effects of long‐term medications, but the mechanism is unclear. Our study explored the role of Antxr1/LncRNA H19/Wnt/β‐catenin axis in the process of exercise‐mediated alleviation of bone loss. Here we discovered that moderate‐intensity treadmill exercise alleviates bone loss caused by ovariectomy and ameliorates bone strength accompanied by an increased lncRNA H19 expression. Concomitantly, Antxr1, a mechanosensitive protein was found downregulated by exercise but upregulated by ovariectomy. Interestingly, knockdown expression of Antxr1 increased lncRNA H19 expression and Wnt/β‐catenin signaling pathway in bone marrow mesenchymal stem cells, whereas overexpression of Antxr1 decreased lncRNA H19 expression and Wnt/β‐catenin signaling pathway. Hence, our study demonstrates the regulation of Antxr1/LncRNA H19/Wnt/β‐catenin axis in the process of mechanical strain‐induced osteogenic differentiation, which provides further mechanistic insight into the role of mechanical regulation in bone metabolism. [ABSTRACT FROM AUTHOR]

Treadmills are important rehabilitation tools used with or without handrails. The handrails could be used to attain balance, prevent falls, and improve the walking biomechanics of stroke survivors, but it is yet unclear how the treadmill handrails impact their stability margins. Here, we investigated how 3 treadmill handrail-use conditions (no-hold, self-selected support, and light touch) impact stroke survivors' margins of stability (MoS). The anteroposterior MoS significantly increased for both legs with self-selected support while the mediolateral MoS of the unaffected leg decreased significantly when the participants walked with self-selected support in comparison to no-hold in both cases. We concluded that the contextual use of the handrail should guide its prescription for fall prevention or balance training in rehabilitation programs. [ABSTRACT FROM AUTHOR]

Background: There is a growing trend of individuals wearing cosmetics while participating in physical activities. Nonetheless, there remains a need for further understanding regarding the effects of makeup on the facial epidermis during exercise, given the existing knowledge gaps. Purpose: This study aimed to evaluate the effects of a cosmetic foundation cream on skin conditions during physical activity. Methods: Forty‐three healthy college students, 20 males (26.3 ± 1.5 years) and 23 females (23.1 ± 1.0 years), were enrolled in this study. Foundation cream was applied to participants on half of the face in two different areas (MT: makeup T zone and MU: makeup U zone). The other half of the face served as internal control (T: non‐makeup T zone and U: non‐makeup U zones). Skin levels of moisture, elasticity, pore, sebum, and oil were measured using a skin analysis device (Aramhuvis, Gyeonggi, Republic of Korea) before and after a 20‐min treadmill exercise. Paired t‐test and independent t‐test were performed for skin condition measurements at pre‐ and postexercise. Results: The skin moisture levels in both the T and MT significantly increased after exercise (p < 0.05) (pre‐T: 24.5 ± 1.3, post‐T: 38.5 ± 3.5 and pre‐MT: 18.7 ± 0.7, post‐MT: 40.4 ± 4.8). Elasticity also significantly improved in both the T and MT (p < 0.05) (pre‐T: 25.6 ± 1.3, post‐T: 41.5 ± 3.5 and pre‐MT: 20.0 ± 0.9, post‐MT: 41.7 ± 3.7). The size of the pores in the T zone observed a significant increase after exercise (p < 0.05) (pre‐T: 41.7 ± 2.1, post‐T: 47.8 ± 2.4). The sebum levels in the T zone exhibited a reduction following physical activity, whereas there was a notable increase in sebum levels in the makeup zones (p < 0.05) (pre‐MT: 2.4 ± 0.7, post‐MT:4.2 ± 0.8 and pre MU 1.8 ± 0.34, post MU 4.9 ± 0.9). The oil level was increased in the non‐makeup zones (pre‐T: 6.1 ± 1.4, post‐T: 11.8 ± 2.0 and pre‐U: 7.3 ± 1.5, post‐U: 11.9 ± 1.9; p < 0.05) and decreased in the makeup zones (pre‐MT: 13.3 ± 1.9, post‐MT: 7.4 ± 2.3 and pre‐MU: 22.1 ± 2.4, post‐MU: 3.2 ± 1.0; p < 0.05). Conclusions: The findings suggest that using foundation cream during aerobic exercise can reduce skin oil, causing dryness. Additionally, makeup can clog pores and increase sebum production. Therefore, wearing makeup may not be recommended for people with dry skin conditions based on the results of the current study. This research offers important insights to the public, encouraging them to consider the possible consequences of using makeup while exercising. [ABSTRACT FROM AUTHOR]

Introduction: High + Gz loads, the gravitational forces experienced by the body in hypergravity environments, can lead to bone loss in pilots and astronauts, posing significant health risks. Materials and methods: To explore the effect of treadmill exercise on bone tissue recovery, a study was conducted on 72 male Wistar rats. These rats were subjected to four weeks of varying levels of periodic high + Gz loads (1G, 8G, 20G) experiments, and were subsequently divided into the treadmill group and the control group. The treadmill group underwent a continuous two-week treadmill experiment, while the control group rested during this period. The mechanical properties, microstructure, and molecular markers of their tibial bone tissue were measured using three-point bending, micro-CT, and PCR. Results: The results showed that treadmill exercise improved the elastic modulus, ultimate deflection, and ultimate load of rat bone tissue. It also increased the number, density, and volume fraction of bone trabeculae, and decreased their separation. Moreover, treadmill exercise enhanced osteogenesis and inhibited osteoclastogenesis. Conclusion: This study demonstrates that treadmill exercise can promote the recovery of bone tissue in rats subjected to high + Gz loads, providing a potential countermeasure for bone loss in pilots and astronauts. [ABSTRACT FROM AUTHOR]

Post-ACLR individuals can experience repeated exposure to variable limb loading, which contributes to development of knee osteoarthritis. Variable limb loading can present as loading rate variability (LRV) and is magnified during tasks like fast walking when the system is stressed. Nonlinear measures that evaluate temporal variability have successfully detected changes in gait variability associated with altered motor control, however, appropriately describing and uncovering the nature of gait variability has been challenging. Here, Poincaré analysis, a nonlinear method unique in its ability to capture different aspects of variability, served to uncover and quantify changes in limb LRV. It was hypothesized that post-ACLR individuals' overloaded limbs would quantitatively and graphically demonstrate greater short-term stride-to-stride and long-term limb LRV during fast walking compared to the underloaded and healthy control limbs. Fourteen post-ACLR individuals and fourteen healthy controls completed a walking protocol on an instrumented treadmill where they walked at 1.0 m/s and 1.5 m/s for 5-minutes each. A Welch's test was performed to compare differences in short-term and long-term LRV metrics for the post-ACLR individuals' overloaded and underloaded limbs and the healthy controls' right limbs. Analyses revealed that the post-ACLR individuals' overloaded limb exhibited significantly greater short-term and long-term values compared to the underloaded and healthy control limbs at 1.5 m/s (p<0.05). Additionally, the loading rate data was widely scattered across the plots for the overloaded limb, indicating greater LRV. Poincaré analysis successfully identified that post-ACLR overloaded limbs exhibited impaired motor control during fast walking based on quantitative and graphical changes in variability. This highlights the clinical applications of Poincaré analysis, with the plots potentially serving as an easy-to-interpret diagnostic tool for pathological limb LRV. • Poincaré analysis detects pathological limb loading rate variability. • Post-ACLR individuals exhibit greater short- and long-term variability in one limb. • Poincaré analysis identifies impaired motor control graphically and quantitatively. • Non-linear measures better capture the true nature of gait variability. [ABSTRACT FROM AUTHOR]

BACKGROUND: The patella-patellar tendon junction is a high-incidence area of injury in patellar tendinopathy. The rabbit patella-patellar tendon injury model is a commonly used animal experimental research object. At present, the stress analysis of the injury mechanism and modeling method is not comprehensive. OBJECTIVE: Based on the previous histological and mechanical measurements, this study used micro CT to scan and model the whole patella, the patellapatellar tendon junction and the tendon quadriceps junction, to analyze the characteristics of changes in stress, and explore the potential impact of different forms of exercise on patellar tendon degeneration so as to provide a theoretical basis for injury prevention and animal model establishment. METHODS: Female healthy adult New Zealand rabbits were selected to study the patella and tendons at both ends of the left knee joint. After the material was taken, the samples were scanned and saved with micro CT. Mimics, Geomagic Studio and SolidWorks were used to establish a three-dimensional model. Finite element analysis was carried out with Ansys Workbench. The equivalent displacement, stress and strain of the target region were analyzed under different loading conditions (load size and direction changes, different action modes). RESULTS AND CONCLUSION: (1) Load direction change affected trend and value change; load size change affected value change. (2) Compared with other areas, the stress concentration was more obvious at the insertion point of the patellar tendon, and the strain value was the lowest. (3) At the insertion point of the patellar tendon, the stress concentration was greater in valgus than in varus and pronation than in extorsion. (4) The stress concentration effect and stress shielding during knee flexion and extension are the main causes of patellar tendon insertion injury. The stress in pronation and valgus states is also a potential factor leading to damage, which needs further study. The animal model established by jumping and running is more in line with the characteristics of sports injury. [ABSTRACT FROM AUTHOR]

Gait impairments negatively affect the quality of life of people with Parkinson's disease (PwPD). Aerobic exercise (AE) is an alternative to alleviate these impairments and its combination with transcranial direct current stimulation (tDCS) has demonstrated synergistic effects. However, the effect of multitarget tDCS application (i.e., motor, and prefrontal cortices simultaneously) combined with physical exercise on gait impairments is still little known. Thus, the proposed randomized clinical trial will verify the acute effects of AE combined with tDCS applied on motor and prefrontal cortices separately and simultaneously on gait (spatial-temporal and cortical activity parameters) in PwPD. Twenty-four PwPD in Hoehn & Yahr stages I-III will be recruited for this crossover study. PwPD will practice AE on treadmill simultaneously with the application of anodal tDCS during four intervention sessions on different days (∼ one week of interval). Active tDCS will be applied to the primary motor cortex, prefrontal cortex, and both areas simultaneously (multitarget), with an intensity of 2 mA for 20 min. For sham, the stimulation will remain at 2 mA for 10 s. The AE will last a total of 30 min, consisting of warm-up, main part (20 min with application of tDCS), and recovery. Exercise intensity will be controlled by heart rate. Spatial-temporal and cortical activity parameters will be acquired before and after each session during overground walking, walking with obstacle avoidance, and walking with a cognitive dual task at self-preferred velocity. An accelerometer will be positioned on the fifth lumbar vertebra to obtain the spatial-temporal parameters (i.e., step length, duration, velocity, and swing phase duration). Prefrontal cortex activity will be recorded from a portable functional near-infrared spectroscopy system and oxygenated and deoxygenated hemoglobin concentrations will be analyzed. Two-way ANOVAs with repeated measures for stimulation and moment will be performed. The findings of the study may contribute to improving gait in PwPD. Trial registration: Brazilian Clinical Trials Registry (RBR-738zkp7). [ABSTRACT FROM AUTHOR]

BACKGROUND: Low to moderate intensity aerobic exercise can help protect knee cartilage. Long-chain non-coding RNAs are crucial for gene regulation. Among them, HOTAIR can activate numerous transcriptional co-repressors to repress the activation of certain genes. OBJECTIVE: To detect the expression levels of HOX transcript antisense RNA (HOTAIR) and other related factors in chondrocytes of high fat-fed mice and after low to moderate intensity exercise intervention, and to investigate their role in cartilage injury and sports rehabilitation. METHODS: Thirty C57BL/6 male mice were randomly divided into control group (normal feeding), high fat feeding group and high fat feeding plus treadmill exercise group, with 10 mice in each group. The mice in the high fat feeding plus treadmill exercise group were subjected to an 8-week low to middle intensity treadmill exercise, and the mice in the other two groups were caged. During this period, body mass was weighed every week on Sunday. After the 8-week exercise, both lower extremities of mice were taken, and the knee joint was scanned using Micro CT to make a 3D femoral condyle image to obtain relevant parameters. Hematoxylin-eosin and safranin O-fast green staining of the knee joint were performed for Mankin and Osteoarthritis Research Society International (OARSI) scoring. RT-PCR was performed to detect the mRNA levels of cartilage metabolic indicators and lipid metabolism indicators, including type II collagen, matrix metalloproteinase 13, interleukin 1, low-density lipoprotein receptor-related protein 5, HOTAIR and its downstream factor lysine specific demethylase 1. RESULTS AND CONCLUSION: The body mass of high fat-fed mice were higher than that of the control group (P < 0.01), and the body mass of the high fat feeding plus treadmill exercise group was lower than that of the high fat feeding group (P < 0.05). The connectivity density of high fat-fed mice was higher than that of the control group (P < 0.01). Mankin and OARSI scores of the high fat feeding were higher than those of the control group (P < 0.01) and high fat feeding plus treadmill exercise group (P < 0.05). The mRNA level of type II collagen was higher in the control group than the high fat feeding plus treadmill exercise group (P < 0.05) and high fat feeding group (P < 0.01) as well as higher in the high fat feeding plus treadmill exercise group than the high fat feeding group (P < 0.01). The mRNA levels of matrix metalloproteinase 13, interleukin 1, low-density lipoprotein receptor-related protein 5, HOTAIR and lysine specific demethylase 1 were higher in the high fat feed group than the control group and high fat feeding plus treadmill exercise group (P < 0.01). To conclude, high fat feeding can increase the bone substance of the femoral condyle, lead to knee cartilage wear, and cause chondrocyte metabolism disorder. HOTAIR is highly expressed in this process. An 8-week low to middle intensity treadmill exercise can reduce body mass, alleviate knee cartilage wear, improve chondrocyte function and down-regulate HOTAIR expression in mice. [ABSTRACT FROM AUTHOR]

Activity-dependent neuroprotective protein (ADNP) is a neuroprotective protein essential for embryonic development, proper brain development, and neuronal plasticity. Its mutation causes the autism-like ADNP syndrome (also called the Helsmoortel-Van der Aa syndrome), characterized by neural developmental disorders and motor dysfunctions. Similar to the ADNP syndrome, the ADNP haploinsufficient mouse shows low synapse density, leading to motor and cognitive ability delays. Moderate physical activity (PA) has several neuroprotective and cognitive benefits, promoting neuronal survival, differentiation, neurogenesis, and plasticity. Until now, no study has investigated the effect of moderate exercise on ADNP expression and distribution in the rat brain. The aim of the current investigation was to study the effects of moderate exercise on the ADNP expression and neuronal activation measured by the microtubule protein β-Tubulin III. In pursuit of this objective, twenty-four rats were selected and evenly distributed into two categories: sedentary control rats and rats exposed to moderate physical activity on a treadmill over a span of 12 weeks. Our results showed that moderate PA increases the expression of ADNP and β-Tubulin III in the dentate gyrus (DG) hippocampal region and cerebellum. Moreover, we found a co-localization of ADNP and β-Tubulin III in both DG and cerebellum, suggesting a direct association of ADNP with adult neuronal activation induced by moderate PA. [ABSTRACT FROM AUTHOR]

Bisphosphonates are commonly used to treat and prevent bone loss, but their effects in active, juvenile populations are unknown. This study examined the effects of intramuscular clodronate disodium (CLO) on bone turnover, serum bone biomarkers (SBB), bone mineral density (BMD), bone microstructure, biomechanical testing (BT), and cartilage glycosaminoglycan content (GAG) over 165 days. Forty juvenile sheep (253 ± 6 days of age) were divided into four groups: Control (saline), T0 (0.6 mg/kg CLO on day 0), T84 (0.6 mg/kg CLO on day 84), and T0+84 (0.6 mg/kg CLO on days 0 and 84). Sheep were exercised 4 days/week and underwent physical and lameness examinations every 14 days. Blood samples were collected for SBB every 28 days. Microstructure and BMD were calculated from tuber coxae (TC) biopsies (days 84 and 165) and bone healing was assessed by examining the prior biopsy site. BT and GAG were evaluated postmortem. Data, except lameness data, were analyzed using a mixed-effects model; lameness data were analyzed as ordinal data using a cumulative logistic model. CLO did not have any measurable effects on the skeleton of sheep. SBB showed changes over time (p ≤ 0.03), with increases in bone formation and decreases in some bone resorption markers. TC biopsies showed increasing bone volume fraction, trabecular spacing and thickness, and reduced trabecular number on day 165 versus day 84 (p ≤ 0.04). These changes may be attributed to exercise or growth. The absence of a treatment effect may be explained by the lower CLO dose used in large animals compared to humans. Further research is needed to examine whether low doses of bisphosphonates may be used in active juvenile populations for analgesia without evidence of bone changes. [ABSTRACT FROM AUTHOR]

Background and purpose: In recent years, there has been extensive research on the role of exercise as an adjunctive therapy for cancer. However, the potential mechanisms underlying the anti-tumor therapy of exercise in lung cancer remain to be fully elucidated. As such, our study aims to confirm whether exercise-induced elevation of epinephrine can accelerate CD8+ T cell recruitment through modulation of chemokines and thus ultimately inhibit tumor progression. Method: C57BL/6 mice were subcutaneously inoculated with Lewis lung cancer cells (LLCs) to establish a subcutaneous tumor model. The tumor mice were randomly divided into different groups to performed a moderate-intensity exercise program on a treadmill for 5 consecutive days a week, 45 min a day. The blood samples and tumor tissues were collected after exercise for IHC, RT-qPCR, ELISA and Western blot. In addition, another group of mice received daily epinephrine treatment for two weeks (0.05 mg/mL, 200 µL i.p.) (EPI, n = 8) to replicate the effects of exercise on tumors in vivo. Lewis lung cancer cells were treated with different concentrations of epinephrine (0, 5, 10, 20 µM) to detect the effect of epinephrine on chemokine levels via ELISA and RT-qPCR. Results: This study reveals that both pre- and post-cancer exercise effectively impede the tumor progression. Exercise led to an increase in EPI levels and the infiltration of CD8+ T cell into the lung tumor. Exercise-induced elevation of EPI is involved in the regulation of Ccl5 and Cxcl10 levels further leading to enhanced CD8+ T cell infiltration and ultimately inhibiting tumor progression. Conclusion: Exercise training enhance the anti-tumor immunity of lung cancer individuals. These findings will provide valuable insights for the future application of exercise therapy in clinical practice. [ABSTRACT FROM AUTHOR]

The effects of exercise training (ET) on the heart of aortic stenosis (AS) rats are controversial and the mechanisms involved in alterations induced by ET have been poorly clarified. In this study, we analyzed the myocardial proteome to identify proteins modulated by moderate‐intensity aerobic ET in rats with chronic supravalvular AS. Wistar rats were divided into four groups: sedentary control (C‐Sed), exercised control (C‐Ex), sedentary aortic stenosis (AS‐Sed), and exercised AS (AS‐Ex). ET consisted of five treadmill running sessions per week for 16 weeks. Statistical analysis was performed by ANOVA or Kruskal–Wallis and Goodman tests. Results were discussed at a significance level of 5%. At the end of the experiment, AS‐Ex rats had higher functional capacity, lower blood lactate concentration, and better cardiac structural and left ventricular (LV) functional parameters than the AS‐Sed. Myocardial proteome analysis showed that AS‐Sed had higher relative protein abundance related to the glycolytic pathway, oxidative stress, and inflammation, and lower relative protein abundance related to beta‐oxidation than C‐Sed. AS‐Ex had higher abundance of one protein related to mitochondrial biogenesis and lower relative protein abundance associated with oxidative stress and inflammation than AS‐Sed. Proteomic data were validated for proteins related to lipid and glycolytic metabolism. Chronic pressure overload changes the abundance of myocardial proteins that are mainly involved in lipid and glycolytic energy metabolism in rats. Moderate‐intensity aerobic training attenuates changes in proteins related to oxidative stress and inflammation and increases the COX4I1 protein, related to mitochondrial biogenesis. Protein changes are combined with improved functional capacity, cardiac remodeling, and LV function in AS rats. [ABSTRACT FROM AUTHOR]

Exercise robustly increases the glucose demands of skeletal muscle. This demand is met by not only muscle glycogenolysis but also accelerated liver glucose production from hepatic glycogenolysis and gluconeogenesis to fuel mechanical work and prevent hypoglycemia during exercise. Hepatic gluconeogenesis during exercise is dependent on highly coordinated responses within and between muscle and liver. Specifically, exercise increases the rate at which gluconeogenic precursors such as pyruvate/lactate or amino acids are delivered from muscle to the liver, extracted by the liver, and channeled into glucose. Herein, we examined the effects of interrupting hepatic gluconeogenic efficiency and capacity on exercise performance by deleting mitochondrial pyruvate carrier 2 (MPC2) and/or alanine transaminase 2 (ALT2) in the liver of mice. We found that deletion of MPC2 or ALT2 alone did not significantly affect time to exhaustion or postexercise glucose concentrations in treadmill exercise tests, but mice lacking both MPC2 and ALT2 in hepatocytes (double knockout, DKO) reached exhaustion faster and exhibited lower circulating glucose during and after exercise. Use of 2H/13C metabolic flux analyses demonstrated that DKO mice exhibited lower endogenous glucose production owing to decreased glycogenolysis and gluconeogenesis at rest and during exercise. Decreased gluconeogenesis was accompanied by lower anaplerotic, cataplerotic, and TCA cycle fluxes. Collectively, these findings demonstrate that the transition of the liver to the gluconeogenic mode is critical for preventing hypoglycemia and sustaining performance during exercise. The results also illustrate the need for interorgan cross talk during exercise as described by the Cahill and Cori cycles. NEW & NOTEWORTHY Martino and colleagues examined the effects of inhibiting hepatic gluconeogenesis on exercise performance and systemic metabolism during treadmill exercise in mice. Combined inhibition of gluconeogenesis from lactate/pyruvate and alanine impaired exercise endurance and led to hypoglycemia during and after exercise. In contrast, suppressing either pyruvate-mediated or alanine-mediated gluconeogenesis alone had no effect on these parameters. These findings provide new insight into the molecular nodes that coordinate the metabolic responses of muscle and liver during exercise. [ABSTRACT FROM AUTHOR]

Spinal cord injury (SCI) presents a complex challenge in neurorehabilitation, demanding innovative therapeutic strategies to facilitate functional recovery. This study investigates the effects of treadmill training on SCI recovery, emphasizing motor function enhancement, neural tissue preservation, and axonal growth. Our research, conducted on a rat model, demonstrates that controlled treadmill exercises significantly improve motor functions post-SCI, as evidenced by improved scores on the Basso, Beattie, and Bresnahan (BBB) locomotor rating scale and enhanced electromyography readings. Notably, the training facilitates the preservation of spinal cord tissue, effectively reducing secondary damage and promoting the maintenance of neural fibers in the injured area. A key finding is the significant stimulation of axonal growth around the injury epicenter in trained rats, marked by increased growth-associated protein 43 (GAP43) expression. Despite these advancements, the study notes a limited impact of treadmill training on motoneuron adaptation and highlights minimal changes in the astrocyte and neuron–glial antigen 2 (NG2) response. This suggests that, while treadmill training is instrumental in functional improvements post-SCI, its influence on certain neural cell types and glial populations is constrained. [ABSTRACT FROM AUTHOR]

To investigate the protective effect of dihydromyricetin (DHM) against exercise-induced muscle damage (EIMD) in mice and its potential mechanism. Adult male C57BL/6J mice were randomly divided into control group (CG), exercise group (EG), and exercise + 100 mg/kg weight •d DHM (DHM) group. The intervention lasted for four weeks, during which the animals in the EG and DHM groups were subjected to exercise training for 1 h per day. The day after the training, a 90-min treadmill exercise (slope: 0 and speed: 18 m/min) was conducted in both EG and DHM groups. Samples of blood and gastrocnemius muscles were harvested from the three groups 24 h after the exercise, followed by the measurement of serum creatine kinase (CK) and lactate dehydrogenase (LDH) activities, total superoxide dismutase (T-SOD) activity, malondialdehyde (MDA), and skeletal muscle mitochondrial enzyme complex I and II activities. Histological changes in the skeletal muscle were observed by transmission electron microscopy, and the protein expressions of mitochondrial function-related pathways were detected by Western blotting. Skeletal muscle morphological changes and mitochondrial damage were alleviated in the DHM group compared to those in the EG. The activities of EIMD markers CK and LDH and the level of lipid peroxidation were notably repressed and the serum T-SOD activity was enhanced after DHM intervention. Western blotting demonstrated that the expressions of sirtuin type 3 (SIRT3), estrogen-related receptor alpha, and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha in the skeletal muscle of mice increased after the DHM intervention. DHM can relieve EIMD in mice, possibly by promoting the recovery of the mitochondrial structure and function in the skeletal muscle of mice after high-intensity exercise via the activation of the SIRT3 signaling pathway. [ABSTRACT FROM AUTHOR]

Reduced myelin stability observed in the early stages of Alzheimer's disease leads to spatial learning and memory impairment. Exercise has been shown to protect nerves, reduce the risk of Alzheimer's disease, and strengthen synaptic connectivity. However, the underlying mechanisms of how exercise can promote myelin repair and coordinate inflammation and proliferation are still uncertain. In this study, we conducted histological and biochemical assays of cortical lysates after behavioral testing to detect pathological changes, myelin sheath thickness, and mRNA and protein levels. It is notable that D-galactose model mice exhibited elevated miRNA-34a levels, overactive astrocytes, decreased myelin staining scores, increased apoptosis, and decreased synaptic plasticity in the brain. Significantly, after eight weeks of exercise, we observed improvements in LFB scores, NeuN(+) neuron counts, and myelin basic protein (MBP) expression. Additionally, exercise promoted the expression of oligodendrocyte markers Olig2 and PDFGR-α associated with brain proliferation, and improved spatial cognitive function. Furthermore, it decreased the inflammation caused by astrocyte secretions (TNF-α, Cox-2, CXCL2). Interestingly, we also observed downregulation of miR-34a and activation of the TAN1/PI3K/CREB signaling pathway. Our data shed light on a previously unsuspected mechanism by which exercise reduces miR-34a levels and protects neuronal function and survival by preventing excessive demyelination and inflammatory infiltration in the CNS. [ABSTRACT FROM AUTHOR]

Although preclinical and clinical studies have shown that exercise can inhibit bone metastasis progression, the mechanism remains poorly understood. Here, we found that non- small cell lung cancer (NSCLC) cells adjacent to bone tissue had a much lower proliferative capacity than the surrounding tumor cells in patients and mice. Subsequently, it was demonstrated that osteocytes, sensing mechanical stimulation generated by exercise, inhibit NSCLC cell proliferation and sustain the dormancy thereof by releasing small extracellular vesicles with tumor suppressor micro- RNAs, such as miR- 99b- 3p. Furthermore, we evaluated the effects of mechanical loading and treadmill exercise on the bone metastasis progression of NSCLC in mice. As expected, mechanical loading of the tibia inhibited the bone metastasis progression of NSCLC. Notably, bone metastasis progression of NSCLC was inhibited by moderate exercise, and combinations with zoledronic acid had additive effects. Moreover, exercise preconditioning effectively suppressed bone metastasis progression. This study significantly advances the understanding of the mechanism underlying exercise- afforded protection against bone metastasis progression. [ABSTRACT FROM AUTHOR]

This study aimed to investigate structural synaptic plasticity in the medial prefrontal cortex of rats under treadmill exercise pretreatment or naive conditions in a vascular dementia model, followed by recognition memory performance in a novel object recognition task. In this study, 24 Sprague–Dawley rats were obtained and randomly assigned into 4 groups as follows: control group (Con group, n = 6), vascular dementia (VD group, n = 6), exercise and vascular dementia group (Exe + VD group, n = 6), and exercise group (Exe group, n = 6). Initially, 4 weeks of treadmill exercise intervention was administered to the rats in the Exe + VD and Exe groups. Then, to establish the vascular dementia model, the rats both in the VD and Exe + VD groups were subjected to bilateral common carotids arteries surgery. One week later, open-field task and novel recognition memory task were adopted to evaluate anxiety-like behavior and recognition memory in each group. Then, immunofluorescence and Golgi staining were used to evaluate neuronal number and spine density in the rat medial prefrontal cortex. Transmission electron microscopy was used to observe the synaptic ultrastructure. Finally, microdialysis coupled with high-performance liquid chromatography was used to assess the levels of 5-HT and dopamine in the medial prefrontal cortex. The behavior results showed that 4 weeks of treadmill exercise pretreatment significantly alleviated recognition memory impairment and anxiety-like behavior in VD rats (P < 0.01), while the rats in VD group exhibited impaired recognition memory and anxiety-like behavior when compared with the Con group (P < 0.001). Additionally, NeuN immunostaining results revealed a significant decrease of NeuN-marked neuron in the VD group compared to Con group (P < 0.01), but a significantly increase in this molecular marker was found in the Exe + VD group compared to the Con group (P < 0.01). Golgi staining results showed that the medial prefrontal cortex neurons in the VD group displayed fewer dendritic spines than those in the Con group (P < 0.01), and there were more spines on the dendrites of medial prefrontal cortex cells in Exe + VD rats than in VD rats (P < 0.01). Transmission electron microscopy further revealed that there was a significant reduction of synapses intensity in the medial prefrontal cortex of rats in the VD group when compared with the Con group(P < 0.01), but physical exercise was found to significantly increased synapses intensity in the VD model (P < 0.01). Lastly, the levels of dopamine and 5-HT in the medial prefrontal cortex of rats in the VD group was significantly lower compared to the Con group (P < 0.01), and treadmill exercise was shown to significantly increased the levels of dopamine and 5-HT in the VD rats (P < 0.05). Treadmill exercise pretreatment ameliorated structural synaptic plasticity impairments of medial prefrontal cortex in VD rat and improved recognition memory. [ABSTRACT FROM AUTHOR]

BACKGROUND: Exercise is an effective strategy to prevent and treat various cardiovascular diseases and protect the heart from ischemia-reperfusion injury. Its mechanism of action needs to be studied in depth. OBJECTIVE: To observe the effect of aerobic exercise preconditioning on myocardial ischemia-reperfusion injury and to explore the effect of endothelial nitric oxide synthase (eNOS) activation (including coupling and phosphorylation). METHODS: Eighty adult Wistar rats were randomly divided into sedentary (n=40) and exercise (n=40) groups. The rats in the exercise group were subjected to aerobic exercise for 8 weeks while those in the sedentary group were quietly fed and caged. After 8 weeks of intervention, three experiments were performed. (1) Experiment 1: After the last training, cardiac function, cardiac nitric oxide metabolite content and cardiac eNOS, phosphorylated eNOS-S1177, eNOS dimer and eNOS monomer protein expression levels were detected. (2) Experiment 2: Rats were divided into sedentary control group, exercise control group, sedentary+eNOS inhibitor group, exercise+eNOS inhibitor group, all of which were subjected to an in vitro myocardial ischemia-reperfusion injury experiment. eNOS inhibitor was continuously infused into the sedentary+eNOS inhibitor group and exercise+eNOS inhibitor group 10 minutes before reperfusion, and cardiac function and myocardial infarction area were detected 3 hours after reperfusion. (3) Experiment 3: Rats were divided into sedentary control group, exercise control group, sedentary+eNOS coupler group and exercise+eNOS coupler group, all of which were subjected to an in vitro myocardial ischemiareperfusion injury experiment. The rats in the sedentary+eNOS coupler group and exercise+eNOS coupler group were treated with eNOS coupler. Myocardial infarct area, cardiac nitric oxide metabolite content, cardiac protein expression of eNOS, phosphorylated eNOS-S1177, eNOS dimer, eNOS monomer and 3-nitrotyrosine were detected 3 hours after reperfusion. The phosphorylated eNOS-S1177/eNOS ratio reflected the phosphorylated/dephosphorylated level of eNOS and eNOS dimer/monomer ratio reflected eNOS coupling/uncoupling level. RESULTS AND CONCLUSION: Experiment 1: Compared with the sedentary group, the exercise group had increased cardiac output and left ventricular ejection fraction (P < 0.05), increased nitrite and S-nitrosothiol contents (P < 0.05), upregulated phosphorylated eNOS-S1177, eNOS protein expression and phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), eNOS dimer protein expression and eNOS dimer/monomer ratios were elevated (P < 0.05). Experiment 2: Compared with the sedentary control group, left ventricular development pressure increased (P < 0.05) and myocardial infarct area decreased (P < 0.05) in the exercise control group. Compared with the exercise control group, left ventricular development pressure decreased (P < 0.05) and myocardial infarct area increased (P < 0.05) in the exercise+eNOS inhibitor group. Experiment 3: Compared with the sedentary control group, the exercise control group had increased left ventricular developmental pressure (P < 0.05), decreased myocardial infarct area (P < 0.05), decreased phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), decreased eNOS dimer/monomer ratio (P < 0.05), increased S-nitrosothiol content (P < 0.05), and decreased 3-nitrotyrosine protein expression (P < 0.05). Compared with the exercise control group, the exercise+eNOS coupler group had decreased left ventricular developmental pressure (P < 0.05), increased myocardial infarct area (P < 0.05), increased phosphorylated eNOS-S1177/eNOS ratio (P < 0.05), increased eNOS dimer/monomer ratio (P < 0.05), and elevated 3-nitro tyrosine protein expression (P < 0.05). To conclude, aerobic exercise preconditioning could induce cardioprotection, which is related to uncoupling and dephosphorylation of eNOS during cardiac ischemia-reperfusion, thereby inhibiting the excessive production of nitric oxide and reducing nitro-oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Despite a successful repair of tetralogy of Fallot (rToF) in childhood, residual lesions are common and can contribute to impaired exercise capacity. Although both cycle ergometer and treadmill protocols are often used interchangeably these approaches have not been directly compared. In this study we examined cardiopulmonary exercise test (CPET) measurements in rToF. Methods: Inclusion criteria were clinically stable rToF patients able to perform a cardiac magnetic resonance imaging (CMR) and two CPET studies, one on the treadmill (incremental Bruce protocol) and one on the cycle ergometer (ramped protocol), within 12 months. Demographic, surgical and clinical data; functional class; QRS duration; CMR measures; CPET data and international physical activity questionnaire (IPAQ) scores of patients were collected. Results: Fifty-seven patients were enrolled (53% male, 20.5 ± 7.8 years at CPET). CMR measurements included a right ventricle (RV) end-diastolic volume index of 119 ± 22 mL/m2, a RV ejection fraction (EF) of 55 ± 6% and a left ventricular (LV) EF of 56 ± 5%. Peak oxygen consumption (VO2)/Kg (25.5 ± 5.5 vs. 31.7 ± 6.9; p < 0.0001), VO2 at anaerobic threshold (AT) (15.3 ± 3.9 vs. 22.0 ± 4.5; p < 0.0001), peak O2 pulse (10.6 ± 3.0 vs. 12.1± 3.4; p = 0.0061) and oxygen uptake efficiency slope (OUES) (1932.2 ± 623.6 vs. 2292.0 ± 639.4; p < 0.001) were significantly lower on the cycle ergometer compared with the treadmill, differently from ventilatory efficiency (VE/VCO2) max which was significantly higher on the cycle ergometer (32.2 ± 4.5 vs. 30.4 ± 5.4; p < 0.001). Only the VE/VCO2 slope at the respiratory compensation point (RCP) was similar between the two methodologies (p = 0.150). Conclusions: The majority of CPET measurements differed according to the modality of testing, with the exception being the VE/VCO2 slope at RCP. Our data suggest that CPET parameters should be interpreted according to test type; however, these findings should be validated in larger populations and in a variety of institutions. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes mellitus (DM) and Alzheimer's disease (AD) are two major medical conditions that constitute a significant financial burden on most healthcare systems. Due to AD sharing "insulin resistance" mechanistic features with DM, some scientists have proposed "type 3 DM" terminology for it. This study aims to compare the prophylactic effect of exercise and metformin on cognitive brain functions in rats with type 3 DM. Material and methods: Two groups of rats were included in the study: the control group (n = 15) and the streptozotocin-induced type 2 diabetic group (n = 45). The diabetic group was subdivided into three equal subgroups: a sedentary non-treated diabetic group, an exercised group, and a metformin- treated group. We estimated step-down avoidance task latency, serum glucose, insulin, free fatty acids (FFA), cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides (TG), brain Aβ-42 and glucose, histological changes by toluidine blue, and immunohistochemistry for brain Aβ-42 and tau-positive cells. Results: Serum glucose, FFA, TG, cholesterol, LDL, brain Aβ-42, brain glucose, the number of hippocampal dark and degenerated cells, and brain Aβ-42 and tau-positive cells, were all significantly lower. In contrast, serum insulin and HDL, the number of hippocampal granular cells, and latency of the step-down avoidance task were significantly higher in exercised and metformin-treated groups compared to the diabetic group. There were significantly higher values of serum insulin and brain/plasma glucose ratio and number of brain tau-positive cells in the metformin-treated group than in the exercised group. Conclusions: We can conclude that exercise can be as effective as metformin regarding prophylaxis against the deleterious effects of type 3 DM on cognitive brain functions. [ABSTRACT FROM AUTHOR]

Previous research on the accuracy of mobile measurement systems has focused on parameters related to the whole gait cycle. Specifically, bilateral gait characteristics were primarily used as outcome measures. How accurate are unilateral gait characteristics detected using a mobile system at various fixed walking speeds? Gait analysis during treadmill walking at velocities (VEL) of 2.5 (v1), 4.5 (v2) and 6.5 km/h (v3) was performed in a population of 47 healthy young adults, consisting of 27 females (age: 23 ± 2 years, BMI: 21.4 ± 2.2 kg/m²) and 20 males (age: 22 ± 1 years, BMI: 23.3 ± 3.4 kg/m²). Spatiotemporal gait data were simultaneously determined using an instrumented treadmill (gaitway 3D) and a mobile gait analysis system (RehaGait). Besides VEL, bilateral (stride length [SL], cadence [CAD]) and unilateral (contact duration [CON], single [SS] and double support duration [DS]) outcomes were validated. Across the three VEL investigated, the correlations between both measurement systems were almost perfect in SL and CAD (r > 0.97). In addition, SL significantly differed (p < 0.01) with moderate to large effects, whereby the root mean squared error (RMSE) did not exceed 1.8 cm. RMSE in CAD was not higher than 0.33 spm and statistically significant differences were only present at v1 (d = 0.63). DS was the most erroneous unilateral parameter with values for %RMSE ranging from 9% at v1 to 14% at v3. In CON and SS %RMSE was in a magnitude of 2–4% across all VEL. Furthermore, VEL affected measurement accuracy in unilateral outcomes with moderate to large effects (F (2, 45) > 6.0, p < 0.01, η p 2 > 0.11) with consistently higher differences at lower velocities. Based on the results presented the validity of the mobile gait analysis system investigated to detect gait asymmetries must be questioned. • The device investigated provides accurate results for cadence and stride length. • The estimation of walking speed was also accurate. • Unilateral parameters were revealed to be less accurate than bilateral outcomes. • Double support duration detection showed the lowest level of accuracy. • The accuracy in contact time detection improved with walking speed. [ABSTRACT FROM AUTHOR]

OBJECTIVE To establish an orthopedic, preclinical, ovine model of controlled exercise using an equine walker. ANIMALS 20 Dorset-Polypay sheep. PROCEDURES Sheep underwent 11 weeks of exercise, 4 days per week. Exercise duration and intensity increased until sheep performed 25 minutes at 1.3 m/s and 5 min at 2.0 m/s. Physical/lameness examinations were conducted every 14 days. Blood was collected every 28 days for analysis of serum bone biomarkers (SBB): bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), carboxy-telopeptide of type I collagen cross-links (CTX-I), tartrate-resistant acid phosphatase 5b (TRAP5b), and receptor activator of nuclear factor-kβ ligand (RANKL). RESULTS Sheep adapted easily to group exercise. Animals grew taller (P = .006) but had a 4% weight loss (P = .003). RANKL was reduced on days 28 and 84 compared to day 56 (P < .05), CTX-1 was reduced on days 28 and 84 compared to days 0 and 56 (P < .05), and TRAP5b was greater on day 28 compared to day 0 (P = .009). BALP and PINP did not change. CLINICAL RELEVANCE The described preclinical model of exercising sheep has distinct advantages including ease of handling, an established lameness scale, commercially available ovine SBB assays, and the ability to alter footing characteristics and complete circular exercise. Decreasing CTX-I and RANKL with no change in BALP and PINP suggests reduced bone resorption over the study period. Future studies may include a sedentary group or utilize adult animals to alleviate any influence of growth on SBB. [ABSTRACT FROM AUTHOR]

Background and Objective: Dyspnoea is a debilitating symptom in individuals with chronic obstructive pulmonary disease (COPD) and a range of other chronic cardiopulmonary diseases and is often associated with anxiety and depression. The present study examined the effect of visually‐induced mood shifts on exertional dyspnoea in individuals with COPD. Methods: Following familiarization, 20 participants with mild to severe COPD (age 57–79 years) attended three experimental sessions on separate days, performing two 5‐min treadmill exercise tests separated by a 30‐min interval on each day. During each exercise test, participants viewed either a positive, negative or neutral set of images sourced from the International Affective Picture System (IAPS) and rated dyspnoea or leg fatigue (0–10). Heart rate (HR) and peripheral oxygen saturation (SpO2) were measured at 1‐min intervals during each test. Mood valence ratings were obtained using Self‐Assessment Manikin (SAM) scale (1–9). Results: Mood valence ratings were significantly higher when viewing positive (end‐exercise mean ± SEM = 7.6 ± 0.3) compared to negative IAPS images (2.4 ± 0.3, p < 0.001). Dyspnoea intensity (mean ± SEM = 5.8 ± 0.4) and dyspnoea unpleasantness (5.6 ± 0.3) when viewing negative images were significantly higher compared to positive images (4.2 ± 0.4, p = 0.004 and 3.4 ± 0.5, p = 0.003). Eighty‐five percent of participants (n = 17) met the minimal clinically important difference (MCID) criteria for both dyspnoea intensity and unpleasantness. HR, SpO2 and leg fatigue did not differ significantly between conditions. Conclusion: These findings indicate that the negative affective state worsens dyspnoea in COPD, thereby suggesting strategies aimed at reducing the likelihood of negative mood or improving the mood may be effective in managing morbidity associated with dyspnoea in COPD. [ABSTRACT FROM AUTHOR]

Background: The transition into medical school presents a significant source of stress for first-year medical students, potentially impacting their cardiovascular health. This study examines the effects of treadmill exercise on heart rate variability (HRV), a non-invasive measure of autonomic nervous system function, to understand the impact of physical stress on this demographic. Methods: Fifty first-year medical students from Sri Aurobindo Medical College and Postgraduate Institute participated in this study, which involved baseline and post-treadmill exercise HRV assessments. The exercise protocol aimed to induce sympathetic activation by reaching a heart rate of over 100 per minute. HRV parameters, including Mean heart rate, SDNN, LF, HF, and LF/HF ratio, were measured using an HRV analyzer. Statistical analysis involved descriptive statistics and paired t-tests to compare pre- and post-exercise HRV metrics. Results: Post-exercise HRV analysis revealed significant changes indicative of sympathetic nervous system activation. Notably, Mean heart rate significantly increased (p = 0.04), VLF power percentage and LF power (ms^2) showed significant increases (p = 0.001 and p = 0.01, respectively), suggesting heightened sympathetic activity. Conversely, parameters associated with parasympathetic activity, such as HF power, showed no significant change, indicating a stable parasympathetic response to the exercise. Conclusion: Treadmill exercise led to an evident shift towards sympathetic dominance in first-year medical students, as demonstrated by significant changes in HRV parameters. These findings suggest that physical stress from exercise induces a distinct autonomic response, highlighting the need for incorporating physical activity into medical students' routines to manage stress effectively and maintain cardiovascular health. [ABSTRACT FROM AUTHOR]

Ferroptosis is a recently identified form of programmed cell death that plays an important role in the pathophysiological process of osteoarthritis (OA). Herein, we investigated the protective effect of moderate mechanical stress on chondrocyte ferroptosis and further revealed the internal molecular mechanism. Intra-articular injection of sodium iodoacetate (MIA) was conducted to induce the rat model of OA in vivo, meanwhile, interleukin-1 beta (IL-1β) was treated to chondrocytes to induce the OA cell model in vitro. The OA phenotype was analyzed by histology and microcomputed tomography, the ferroptosis was analyzed by transmission electron microscope and immunofluorescence. The expression of ferroptosis and cartilage metabolism-related factors was analyzed by immunohistochemical and Western blot. Animal experiments revealed that moderate-intensity treadmill exercise could effectively reduce chondrocyte ferroptosis and cartilage matrix degradation in MIA-induced OA rats. Cell experiments showed that 4-h cyclic tensile strain intervention could activate Nrf2 and inhibit the NF-κB signaling pathway, increase the expression of Col2a1, GPX4, and SLC7A11, decrease the expression of MMP13 and P53, thereby restraining IL-1β-induced chondrocyte ferroptosis and degeneration. Inhibition of NF-κB signaling pathway relieved the chondrocyte ferroptosis and degeneration. Meanwhile, overexpression of NF-κB by recombinant lentivirus reversed the positive effect of CTS on chondrocytes. Moderate mechanical stress could activate the Nrf2 antioxidant system, inhibit the NF-κB p65 signaling pathway, and inhibit chondrocyte ferroptosis and cartilage matrix degradation by regulating P53, SLC7A11, and GPX4. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of aerobic treadmill training regimen of four weeks duration on oxidative stress parameters, metabolic enzymes, and histomorphometric changes in the colon of hyperhomocysteinemic rats. Male Wistar albino rats were divided into four groups (n = 10, per group): C, 0.9% NaCl 0.2 mL/day subcutaneous injection (s.c.) 2x/day; H, homocysteine 0.45 µmol/g b.w./day s.c. 2x/day; CPA, saline (0.9% NaCl 0.2 mL/day s.c. 2x/day) and an aerobic treadmill training program; and HPA, homocysteine (0.45 µmol/g b.w./day s.c. 2x/day) and an aerobic treadmill training program. The HPA group had an increased level of malondialdehyde (5.568 ± 0.872 μmol/mg protein, p = 0.0128 vs. CPA (3.080 ± 0.887 μmol/mg protein)), catalase activity (3.195 ± 0.533 U/mg protein, p < 0.0001 vs. C (1.467 ± 0.501 U/mg protein), p = 0.0012 vs. H (1.955 ± 0.293 U/mg protein), and p = 0.0003 vs. CPA (1.789 ± 0.256 U/mg protein)), and total superoxide dismutase activity (9.857 ± 1.566 U/mg protein, p < 0.0001 vs. C (6.738 ± 0.339 U/mg protein), p < 0.0001 vs. H (6.015 ± 0.424 U/mg protein), and p < 0.0001 vs. CPA (5.172 ± 0.284 U/mg protein)) were detected in the rat colon. In the HPA group, higher activities of lactate dehydrogenase (2.675 ± 1.364 mU/mg protein) were detected in comparison to the CPA group (1.198 ± 0.217 mU/mg protein, p = 0.0234) and higher activities of malate dehydrogenase (9.962 (5.752–10.220) mU/mg protein) were detected in comparison to the CPA group (4.727 (4.562–5.299) mU/mg protein, p = 0.0385). Subchronic treadmill training in the rats with hyperhomocysteinemia triggers the colon tissue antioxidant response (by increasing the activities of superoxide dismutase and catalase) and elicits an increase in metabolic enzyme activities (lactate dehydrogenase and malate dehydrogenase). This study offers a comprehensive assessment of the effects of aerobic exercise on colonic tissues in a rat model of hyperhomocysteinemia, evaluating a range of biological indicators including antioxidant enzyme activity, metabolic enzyme activity, and morphometric parameters, which suggested that exercise may confer protective effects at both the physiological and morphological levels. [ABSTRACT FROM AUTHOR]

Myonectin is a hormone that is produced mainly by skeletal muscle. We investigated the effects of exercise and energy drink (ED) administration on myonectin expression in skeletal muscle, liver and kidney tissue in rats; myonectin is produced by all three tissues. We used 28 male albino rats in four groups: untreated control (C), exercise (E), energy drink (ED) and exercise + energy drink (E + ED). The E and E + ED groups were exercised using a treadmill for 4 weeks. We also administered 3.5 ml/kg/day ED during week 1, 7 ml/kg/day during week 2 and 10 ml/kg/day during weeks 3 and 4 in the E and E + ED groups. We used ELISA to measure the levels of myonectin in skeletal muscle, liver and kidney tissues. We used immunohistochemical staining to investigate the localization and intensity of myonectin in these tissues. The amount of myonectin in skeletal muscle tissue was increased significantly in all experimental groups compared to group C. The amount of myonectin in the ED group was significantly greater than group E. No significant difference was observed in liver tissue; however, the amount of myonectin in the liver of group C was the greatest among all groups. The amount of myonectin in kidney tissue exhibited no significant difference among groups. Consumption of ED during exercise increased the amount of myonectin in kidney and skeletal muscle tissues and decreased it in liver tissue. We suggest that consumption of ED might adapt metabolism to incresed exercise by controling synthesis of myonectin in liver, kidney and skeletal muscle. [ABSTRACT FROM AUTHOR]

The effects of diet-induced visceral obesity and non-drug options of its correction on the level of sex hormones and corticosterone were evaluated in 84 female Wistar rats. During stage I, the rats received either a standard diet (STD) or a high-calorie diet (HCD) for 8 weeks. During stage II, the animals were divided into subgroups depending on obesity correction: without correction (STD control and HCD), transition from HCD to STD (HCD/STD) and/or physical activity (treadmill exercise) for the next 8 weeks (HCD/STD+exercise, STD+exercise, and HCD+exercise). Diet-induced visceral obesity resulted in hyperandrogenization and increased blood corticosterone levels in females. Transition from HCD to STD regardless of physical activity led to normalization of testosterone level and, accordingly, to return to the functional norm of estrogen-androgen balance. The positive effect of moderate physical activity on hormonal status is realized only against the background of a balanced diet or during the transition from HCD to STD. [ABSTRACT FROM AUTHOR]

Exercise is beneficial for obesity, partially through increased mitochondrial activity and raised nicotinamide adenine dinucleotide (NAD), a coenzyme critical for mitochondrial function and metabolism. Recent work has shown that increasing the availability of NAD through pharmacological means improves metabolic health in rodent models of diet-induced obesity and that the effect of these supplements when administered orally may be modulated by the gut microbiome. The gut microbiome is altered by both diet and exercise and is thought to contribute to some aspects of high-fat diet-induced metabolic dysfunction. We examined the independent and combined effects of treadmill exercise and nicotinamide mononucleotide (NMN) supplementation on the gut microbiome of female C57Bl6/J mice chronically fed a high-fat diet. We showed that 8 wk of treadmill exercise, oral-administered NMN, or combined therapy exert unique effects on gut microbiome composition without changing bacterial species richness. Exercise and NMN exerted additive effects on microbiota composition, and NMN partially or fully restored predicted microbial functions, specifically carbohydrate and lipid metabolism, to control levels. Further research is warranted to better understand the mechanisms underpinning the interactions between exercise and oral NAD þ precursor supplementation on gut microbiome. NEW & NOTEWORTHY Exercise and NAD+ precursor supplementation exerted additive and independent effects on gut microbiota composition and inferred function in female mice with diet-induced obesity. Notably, combining exercise and oral nicotinamide mononucleotide supplementation restored inferred microbial functions to control levels, indicating that this combination may improve high-fat diet-induced alterations to microbial metabolism. [ABSTRACT FROM AUTHOR]