The effect of exercise and disease status on mobilization of anti-tumorigenic and pro-tumorigenic immune cells in women with breast cancer.

Background: Mobilization of certain immune cells may improve the ability of the immune system to combat tumor cells, but the effect of acute exercise on mobilizing immune cells has been sparsely investigated in cancer patients. Therefore, we examined how acute exercise influences circulating immune cells in breast cancer patients. Methods: Nineteen newly diagnosed breast cancer patients aged 36-68 performed 30 minutes of moderate-intensity exercise with a cycle ergometer. Blood samples were collected at various time points: at rest, at 15 (E15) and 30 minutes (E30) after onset of the exercise, and at 30 and 60 minutes post-exercise. We analyzed several immune cell subsets using flow cytometry. Results: Acute exercise increased the number of total leukocytes, neutrophils, lymphocytes, monocytes, basophils, total T-cells, CD4+ T-cells, T helper (Th) 2-cells, Th 17-cells, CD8+ T-cells, CD4-CD8- T-cells, CD56+ natural killer (NK) cells, and CD14-CD16+ monocytes. Many of the changes were transient. Proportions of NK-cells and CD8+ T-cells increased, while the proportion of myeloid derived suppressor cells (MDSCs) reduced, and proportion of regulatory T-cells remained unchanged by exercise. Several associations were detected between cell mobilizations and disease state. For instance, tumor size correlated negatively with NK cell mobilization at E15, and progesterone receptor positivity correlated negatively with CD8+ T-cell mobilization. Conclusion: The findings show that the proportions of CD8+ T-cells and NK cells increased and the proportion of MDSCs proportion decreased in breast cancer patients after 30-minute exercise, suggesting a change in the profile of circulating immune cells towards more cytotoxic/anti-tumorigenic. The mobilization of some immune cells also appears to be related to the disease state.

Time-course and muscle-specific gene expression of matrix metalloproteinases and inflammatory cytokines in response to acute treadmill exercise in rats.

BACKGROUND: The extracellular matrix (ECM) of skeletal muscle plays a pivotal role in tissue repair and growth, and its remodeling tightly regulated by matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), and inflammatory cytokines. This study aimed to investigate changes in the mRNA expression of MMPs (Mmp-2 and Mmp-14), TIMPs (Timp-1 and Timp-2), and inflammatory cytokines (Il-1ß, Tnf-α, and Tgfß1) in the soleus (SOL) and extensor digitorum longus (EDL) muscles of rats following acute treadmill exercise. Additionally, muscle morphology was examined using hematoxylin and eosin (H&E) staining. METHODS AND RESULTS: Male rats were subjected to acute treadmill exercise at 25 m/min for 60 min with a %0 slope. The mRNA expression of ECM components and muscle morphology in the SOL and EDL were assessed in both sedentary and exercise groups at various time points (immediately (0) and 1, 3, 6, 12, and 24 h post-exercise). Our results revealed a muscle-specific response, with early upregulation of the mRNA expression of Mmp-2, Mmp-14, Timp-1, Timp-2, Il-1ß, and Tnf-α observed in the SOL compared to the EDL. A decrease in Tgfß1 mRNA expression was evident in the SOL at all post-exercise time points. Conversely, Tgfß1 mRNA expression increased at 0 and 3 h post-exercise in the EDL. Histological analysis also revealed earlier cell infiltration in the SOL than in the EDL following acute exercise. CONCLUSIONS: Our results highlight how acute exercise modulates ECM components and muscle structure differently in the SOL and EDL muscles, leading to distinct muscle-specific responses.

Systemic Capillary Responses to Acute Exercise in Hypertensive Seniors: Insights from a Single-Center Pilot Study.

Objective: The aim of this study was to investigate nailfold capillary parameters in community-dwelling individuals aged over 60 years who have hypertension and do not exercise regularly. Furthermore, the study examined the correlations between capillary function and other health-related indicators. DESIGN: This study was a single- center pilot trial. SETTING: The study took place in the Faculty of Health, Tsukuba University of Technology, Japan. PARTICIPANTS: Hypertensive community-dwelling elderly people took part in the study. INTERVENTION: Microcirculation was observed before and 1 min after an arm-curl exercise by means of capillary microscopy of the non-exercised limb. Additionally, we examined other health-related indicators. Methods: We measured the acute effects of reperfusion on nailfold density, flow, and diameters. Secondary outcomes included the correlations between microvascular parameters and other health-related indicators. We hypothesized that brief exercise could enhance microcirculation reperfusion and correlate with other health-related parameters. Results: There were 20 participants with a mean (SD) age of 67.1 (5.8) years. The capillary flow rate changed from 2.3 ± 6.7 to 2.7 ± 0.2 log µm/s (p < 0.01), and the capillary density changed from 0.8 ± 0.2 to 0.9 ± 0.1 log/mm (p < 0.01), which included a significant increase in the non-exercising limb. Significant correlations were observed between the nailfold capillary diameter and body fat mass, the capillary diameter and physical activity, and the capillary density and bone mineral density. Conclusions: The acute effects of exercise on high-risk elderly individuals can be safe, and even 1 of min exercise can potentially improve their nailfold capillary function, despite the brief time, compared to no exercise. The results indicate that capillaries have an impact on the function of the whole body. Thus, they may be a useful diagnostic tool for assessing nailfold capillaries.

Acute resistance exercise combined with whole body vibration and blood flow restriction: Molecular and neurocognitive effects in late-middle-aged and older adults.

Limited research exists regarding the effects of resistance exercise (RE) combined with whole body vibration (WBV), blood flow restriction (BFR), or both on the neuropsychological performance of working memory (WM) in late-middle-aged and older adults and regarding the physiological mechanisms underlying this effect. This study thus explored the acute molecular and neurophysiological mechanisms underlying WM performance following RE combined with WBV, BFR, or both. Sixty-six participants were randomly assigned into a WBV, BFR, or WBV + BFR group. Before and after the participants engaged in a single bout of isometric RE combined with WBV, BFR, or both, this study gathered data on several neurocognitive measures of WM performance, namely, accuracy rate (AR), reaction time (RT), and brain event-related potential (specifically P3 latency and amplitude), and data on biochemical indices, such as the levels of insulin-like growth factor-1 (IGF-1), norepinephrine (NE), and brain-derived neurotrophic factor (BDNF). Although none of the RE modalities significantly affected RTs and P3 latencies, ARs and P3 amplitudes significantly improved in the WBV and WBV + BFR groups. The WBV + BFR group exhibited greater improvements than the WBV group did. Following acute RE combined with WBV, BFR, or both, IGF-1 and NE levels significantly increased in all groups, whereas BDNF levels did not change. Crucially, only the changes in NE levels were significantly correlated with improvements in ARs in the WBV + BFR and WBV groups. The findings suggest that combining acute RE with WBV, BFR, or both could distinctively mitigate neurocognitive decline in late-middle-aged and older adults.

Exercise-induced cortical disinhibition mediates the relationship between fitness and memory in older adults.

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity-related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high-intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity-related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life. KEY POINTS: There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing. Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired-pulse transcranial magnetic stimulation. Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise. Cortical disinhibition completely mediated the relationship between fitness and memory. This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations.

Inverted U-shape-like functional connectivity alterations in cognitive resting-state networks depending on exercise intensity: An fMRI study.

Acute physical activity influences cognitive performance. However, the relationship between exercise intensity, neural network activity, and cognitive performance remains poorly understood. This study examined the effects of different exercise intensities on resting-state functional connectivity (rsFC) and cognitive performance. Twenty male athletes (27.3 ± 3.6 years) underwent cycling exercises of different intensities (high, low, rest/control) on different days in randomized order. Before and after, subjects performed resting-state functional magnetic resonance imaging and a behavioral Attention Network Test (ANT). Independent component analysis and Linear mixed effects models examined rsFC changes within ten resting-state networks. No significant changes were identified in ANT performance. Resting-state analyses revealed a significant interaction in the Left Frontoparietal Network, driven by a non-significant rsFC increase after low-intensity and a significant rsFC decrease after high-intensity exercise, suggestive of an inverted U-shape relationship between exercise intensity and rsFC. Similar but trend-level rsFC interactions were observed in the Dorsal Attention Network (DAN) and the Cerebellar Basal Ganglia Network. Explorative correlation analysis revealed a significant positive association between rsFC increases in the right superior parietal lobule (part of DAN) and better ANT orienting in the low-intensity condition. Results indicate exercise intensity-dependent subacute rsFC changes in cognition-related networks, but their cognitive-behavioral relevance needs further investigation.

Transcriptional Expression of Histone Acetyltransferases and Deacetylases During the Recovery of Acute Exercise in Mouse Hippocampus.

Protein acetylation, which is dynamically maintained by histone acetyltransferases (HATs) and deacetylases (HDACs), might play essential roles in hippocampal exercise physiology. However, whether HATs/HDACs are imbalanced during the recovery phase following acute exercise has not been determined. Groups of exercised mice with different recovery periods after acute exercise (0 h, 0.5 h, 1 h, 4 h, 7 h, and 24 h) were constructed, and a group of sham-exercised mice was used as the control. The mRNA levels of HATs and HDACs were detected via real-time quantitative polymerase chain reaction. Lysine acetylation on the total proteins and some specific locations on histones were detected via western blotting, as were various acylation modifications on the total proteins. Except for four unaffected genes (Hdac4, Ncoa1, Ncoa2, and Sirt1), the mRNA expression trajectories of 21 other HATs or HDACs affected by exercise could be categorized into three clusters. The genes in Cluster 1 increased quickly following exercise, with a peak at 0.5 h and/or 1 h, and remained at high levels until 24 h. Cluster 2 genes presented a gradual increase with a delayed peak at 4 h or 7 h postexercise before returning to baseline. The expression of Cluster 3 genes decreased at 0.5 h and/or 1 h, with some returning to overexpression (Hdac1 and Sirt3). Although most HATs were upregulated and half of the affected HDACs were downregulated at 0.5 h postexercise, the global or residue-specific histone acetylation levels were unchanged. In contrast, the levels of several metabolism-related acylation products of total proteins, including acetylation, succinylation, 2-hydroxyisobutyryllysine, ß-hydroxybutyryllysine, and lactylation, decreased and mainly occurred on nonhistones immediately after exercise. During the 24-h recovery phase after acute exercise, the transcriptional trajectory of HATs or the same class of HDACs in the hippocampus exhibited heterogeneity. Although acute exercise did not affect the selected sites on histone lysine residues, it possibly incurred changes in acetylation and other acylation on nonhistone proteins.

Establishing the feasibility of exercise breaks during university lectures.

It is important that principles of laboratory-based studies with implications for academic performance be implemented in naturalistic learning environments to gauge their feasibility. Here, an adaptation of a laboratory-based study of exercise breaks during a single video lecture was implemented during large, in-person lectures at Ohio State University for the duration of a semester. The rationale for this approach was based on findings that research participants who took exercise breaks during a video lecture were more likely to be on task towards the end of the lecture and performed significantly better on a multiple choice exam. The current project had three goals: (1) Establish the feasibility of integrating student-led exercise breaks during in-person lectures in a large university setting (2) Provide practical guidelines for implementing exercise breaks during in-person lectures (3) Provide preliminary evidence of positive effects of exercise breaks in a higher-education setting. One to two student-led exercise breaks (5 min each) were implemented during each 80 min, in-person lecture for the duration of a semester in four upper level Psychology courses with student enrollment ranging from 20 to 93 students (total enrollment = 223 students). Students reported that the exercise breaks were a strength of the courses and a positive experience, including self-reported improvement in attention to lecture content. Self-reported quantitative data indicated that exercise breaks improved attention, increased course enjoyment, and enhanced peer engagement. Compared to other classes, the students preferred exercise breaks during lectures. The current approach establishes the feasibility of integrating exercise breaks in a large, in-person university lecture environment for the duration of a semester with preliminary data indicating a positive impact on attention, engagement, and enjoyment. Practical guidelines for implementing exercise breaks during in-person lectures are provided.

Differential modulation of resting-state functional connectivity between amygdala and precuneus after acute physical exertion of varying intensity: indications for a role in affective regulation.

Introduction: Physical activity influences psychological well-being. This study aimed to determine the impact of exercise intensity on psychological well-being and alterations in emotion-related brain functional connectivity (FC). Methods: Twenty young, healthy, trained athletes performed a low- and high-intensity interval exercise (LIIE and HIIE) as well as a control condition in a within-subject crossover design. Before and after each condition, Positive And Negative Affect Scale (PANAS) was assessed as well as resting-state functional MRI (rs-fMRI). Voxel-wise FC was examined for bilateral amygdala seed region to whole-brain and emotion-related anatomical regions (e.g., insula, temporal pole, precuneus). Data analyses were performed using linear mixed-effect models with fixed factors condition and time. Results: The PANAS Positive Affect scale showed a significant increase after LIIE and HIIE and a significant reduction in Negative Affect after the control condition. In rs-fMRI, no significant condition-by-time interactions were observed between the amygdala and whole brain. Amygdala-precuneus FC analysis showed an interaction effect, suggesting reduced post-exercise anticorrelation after the control condition, but stable, or even slightly enhanced anticorrelation for the exercise conditions, especially HIIE. Discussion: In conclusion, both LIIE and HIIE had positive effects on mood and concomitant effects on amygdala-precuneus FC, particularly after HIIE. Although no significant correlations were found between amygdala-precuneus FC and PANAS, results should be discussed in the context of affective disorders in whom abnormal amygdala-precuneus FC has been observed.

Phosphorylation of AS160-serine 704 is not essential for exercise-increase in insulin-stimulated glucose uptake by skeletal muscles from female or male rats.

One exercise session can increase subsequent insulin-stimulated glucose uptake (ISGU) by skeletal muscle from rodents and humans of both sexes. We recently found that concurrent mutation of three key sites to prevent their phosphorylation (Ser588, Thr642, and Ser704) on Akt substrate of 160 kDa (AS160; also known as TBC1D4) reduced the magnitude of the enhancement of postexercise ISGU (PEX-ISGU) by muscle from male, but not female rats. However, we did not test the role of individual phosphorylation sites on PEX-ISGU. Accordingly, our current aim was to test whether AS160 Ser704 phosphorylation (pSer704) is required for elevated PEX-ISGU by muscle. AS160-knockout (AS160-KO) rats (female and male) were studied when either in sedentary or 3 h after acute exercise. Adeno-associated virus (AAV) vectors were used to enable muscle expression of wild-type AS160 (AAV-WT-AS160) or AS160 mutated Ser704 to alanine to prevent phosphorylation (AAV-1P-AS160). Paired epitrochlearis muscles from each rat were injected with AAV-WT-AS160 or AAV-1P-AS160. We discovered that regardless of sex 1) AS160 abundance in AS160-KO rats was similar in paired muscles expressing WT-AS160 versus 1P-AS160; 2) muscles from exercised versus sedentary rats had greater ISGU, and PEX-ISGU was slightly greater for muscles expressing 1P-AS160 versus contralateral muscles expressing WT-AS160; and 3) pAS160Thr642 was lower in muscles expressing 1P-AS160 versus paired muscles expressing WT-AS160. These results indicate that pAS160Ser704 was not essential for elevated PEX-ISGU by skeletal muscle from rats of either sex. Furthermore, elimination of the postexercise increase in pAS160Thr642 did not lessen the postexercise effect on ISGU.NEW & NOTEWORTHY The current study evaluated the role of Akt substrate of 160 kDa (AS160) phosphorylation on Ser704 in increased insulin-stimulated glucose uptake by skeletal muscle after exercise. Adeno-associated virus vectors were engineered to express either wild-type-AS160 or AS160 mutated so that it could not be phosphorylated on Ser704 in paired muscles from AS160-knockout rats. The results demonstrated that AS160 phosphorylation on Ser704 was not essential for exercise-induced elevation in insulin-stimulated glucose uptake by rats of either sex.

Influence of cardiorespiratory fitness and body composition on resting and post-exercise indices of vascular health in young adults.

Poor cardiorespiratory fitness may mediate vascular impairments at rest and following an acute bout of exercise in young healthy individuals. This study aimed to compare flow mediated dilation (FMD) and vascular augmentation index (AIx75) between young adults with low, moderate, and high levels of cardiorespiratory fitness before and after an acute bout of aerobic exercise. Forty-three participants (22 men; 21 women) between 18 and 29 years of age completed the study. Participants were classified into low, moderate, and high health-related cardiorespiratory fitness groups according to age- and sex-based relative maximal oxygen consumption (V˙O2 max) percentile rankings. FMD was performed using Doppler ultrasound and AIx75 was performed using pulse wave analysis at baseline and 60-min after a 30-min bout of treadmill running at 70% V˙O2 max. A significant interaction (p â€‹= â€‹0.047; ηp2 â€‹= â€‹0.142) was observed, with the moderate fitness group exhibiting a higher FMD post-exercise compared with baseline ([6.7% â€‹± â€‹3.1%] vs. [8.5% â€‹± â€‹2.8%], p â€‹= â€‹0.028; d â€‹= â€‹0.598). We found a significant main effect of group for AIx75 (p â€‹= â€‹0.023; ηp2 â€‹= â€‹0.168), with the high fitness group exhibiting lower AIx75 compared to low fitness group ([-10% â€‹± â€‹10%] vs. [2% â€‹± â€‹10%], respectively, p â€‹= â€‹0.019; g â€‹= â€‹1.07). This was eliminated after covarying for body fat percentage (p â€‹= â€‹0.489). Our findings suggest that resting FMD and AIx75 responses are not significantly influenced by cardiorespiratory fitness, but FMD recovery responses to exercise may be enhanced in individuals with moderate cardiorespiratory fitness levels.

The Mechanisms Underlying the Beneficial Impact of Aerobic Training on Cancer-Related Fatigue: A Conceptual Review.

Cancer-related fatigue (CRF) is a prevalent and persistent issue affecting cancer patients, with a broad impact on their quality of life even years after treatment completion. The precise mechanisms underlying CRF remain elusive, yet its multifaceted nature involves emotional, physical, and cognitive dimensions. The absence of effective medical treatments has prompted researchers to explore integrative models for potential insights. Notably, physical exercise emerges as a promising strategy for managing CRF and related symptoms, as studies showed a reduction in CRF ranging from 19% to 40%. Current recommendations highlight aerobic training at moderate intensity as beneficial, although questions about a dose-response relationship and the importance of exercise intensity persist. Despite the positive impact of exercise on CRF, the underlying mechanisms remain elusive. This review aims to provide a theoretical model explaining how aerobic exercise may alleviate CRF. Focusing on acute exercise effects, this review delves into the potential influence on peripheral and neural inflammation, immune function dysregulation, and neuroendocrine system disruptions. The objective is to enhance our understanding of the intricate relationship between exercise and CRF, ultimately paving the way for tailored interventions and potential pharmacological treatments for individuals unable to engage in physical exercise.

Fractional amplitude of low-frequency fluctuations associated with µ-opioid and dopamine receptor distributions in the central nervous system after high-intensity exercise bouts.

Introduction: Dopaminergic, opiod and endocannabinoid neurotransmission are thought to play an important role in the neurobiology of acute exercise and, in particular, in mediating positive affective responses and reward processes. Recent evidence indicates that changes in fractional amplitude of low-frequency fluctuations (zfALFF) in resting-state functional MRI (rs-fMRI) may reflect changes in specific neurotransmitter systems as tested by means of spatial correlation analyses. Methods: Here, we investigated this relationship at different exercise intensities in twenty young healthy trained athletes performing low-intensity (LIIE), high-intensity (HIIE) interval exercises, and a control condition on three separate days. Positive And Negative Affect Schedule (PANAS) scores and rs-fMRI were acquired before and after each of the three experimental conditions. Respective zfALFF changes were analyzed using repeated measures ANOVAs. We examined the spatial correspondence of changes in zfALFF before and after training with the available neurotransmitter maps across all voxels and additionally, hypothesis-driven, for neurotransmitter maps implicated in the neurobiology of exercise (dopaminergic, opiodic and endocannabinoid) in specific brain networks associated with "reward" and "emotion." Results: Elevated PANAS Positive Affect was observed after LIIE and HIIE but not after the control condition. HIIE compared to the control condition resulted in differential zfALFF decreases in precuneus, temporo-occipital, midcingulate and frontal regions, thalamus, and cerebellum, whereas differential zfALFF increases were identified in hypothalamus, pituitary, and periaqueductal gray. The spatial alteration patterns in zfALFF during HIIE were positively associated with dopaminergic and µ-opioidergic receptor distributions within the 'reward' network. Discussion: These findings provide new insight into the neurobiology of exercise supporting the importance of reward-related neurotransmission at least during high-intensity physical activity.

Aerobic Exercise and Endocannabinoids: A Narrative Review of Stress Regulation and Brain Reward Systems.

Aerobic exercise is a widely adopted practice, not solely for enhancing fitness and reducing the risk of various diseases but also for its ability to uplift mood and aid in addressing depression and anxiety disorders. Within the scope of this narrative review, we seek to consolidate current insights into the endocannabinoid-mediated regulation of stress and the brain's reward mechanism resulting from engaging in aerobic exercise. A comprehensive search was conducted across Medline, SPORTDiscus, Pubmed, and Scopus, encompassing data available until November 30, 2023. This review indicates that a bout of aerobic exercise, particularly of moderate intensity, markedly augments circulating levels of endocannabinoids - N-arachidonoyl-ethanolamine (AEA) and 2-acylglycerol (2-AG), that significantly contributes to mood elevation and reducing stress in healthy individuals.  The current understanding of how aerobic exercise impacts mental health and mood improvement is still unclear. Moderate and high-intensity aerobic exercise modulates stress through a negative feedback mechanism targeting both the hypothalamus-pituitary-adrenal (HPA) axis and the sympathetic nervous system, thereby facilitating stress regulation crucial role in endocannabinoid synthesis, ultimately culminating in the orchestration of negative feedback across multiple tiers of the HPA axis, coupled with its influence over cortical and subcortical brain structures. The endocannabinoid has been observed to govern the release of neurotransmitters from diverse neuronal populations, implying a universal mechanism that fine-tunes neuronal activity and consequently modulates both emotional and stress-related responses. Endocannabinoids further assume a pivotal function within brain reward mechanisms, primarily mediated by CB1 receptors distributed across diverse cerebral centers. Notably, these endocannabinoids partake in natural reward processes, as exemplified in aerobic exercise, by synergizing with the dopaminergic reward system. The genesis of this reward pathway can be traced to the ventral tegmental area, with dopamine neurons predominantly projecting to the nucleus accumbens, thereby inciting dopamine release in response to rewarding stimuli.

Combined effects of exercise and immuno-chemotherapy treatments on tumor growth in MC38 colorectal cancer-bearing mice.

Acute exercise induces transient modifications in the tumor microenvironment and has been linked to reduced tumor growth along with increased infiltration of immune cells within the tumor in mouse models. In this study, we aimed to evaluate the impact of acute exercise before treatment administration on tumor growth in a mice model of MC38 colorectal cancer receiving an immune checkpoint inhibitor (ICI) and chemotherapy. Six-week-old mice injected with colorectal cancer cells (MC38) were randomized in 4 groups: control (CTRL), immuno-chemotherapy (TRT), exercise (EXE) and combined intervention (TRT/EXE). Both TRT and TRT-EXE received ICI: anti-PD1-1 (1 injection/week) and capecitabine + oxaliplatin (5 times a week) for 1 week (experimentation 1), 3 weeks (experimentation 2). TRT-EXE and EXE groups were submitted to 50 minutes of treadmill exercise before each treatment administration. Over the protocol duration, tumor size has been monitored daily. Tumor growth and microenvironment parameters were measured after the intervention on Day 7 (D7) and Day 16 (D16). From day 4 to day 7, tumor volumes decreased in the EXE/TRT group while remaining stable in the TRT group (p=0.0213). From day 7 until day 16 tumor volume decreased with no significant difference between TRT and TRT/EXE. At D7 the TRT/EXE group exhibited a higher total infiltrate T cell (p=0.0118) and CD8+ cytotoxic T cell (p=0.0031). At D16, tumor marker of apoptosis, vascular integrity and inflammation were not significantly different between TRT and TRT/EXE. Our main result was that acute exercise before immuno-chemotherapy administration significantly decreased early-phase tumor growth (D0 to D4). Additionally, exercise led to immune cell infiltration changes during the first week after exercise, while no significant molecular alterations in the tumor were observed 3 weeks after exercise.

The Acute, Short-, and Long-Term Effects of Endurance Exercise on Skeletal Muscle Transcriptome Profiles.

A better understanding of the cellular and molecular mechanisms that are involved in skeletal muscle adaptation to exercise is fundamentally important to take full advantage of the enormous benefits that exercise training offers in disease prevention and therapy. The aim of this study was to elucidate the transcriptional signatures that distinguish the endurance-trained and untrained muscles in young adult males (24 ± 3.5 years). We characterized baseline differences as well as acute exercise-induced transcriptome responses in vastus lateralis biopsy specimens of endurance-trained athletes (ET; n = 8; VO2max, 67.2 ± 8.9 mL/min/kg) and sedentary healthy volunteers (SED; n = 8; VO2max, 40.3 ± 7.6 mL/min/kg) using microarray technology. A second cohort of SED volunteers (SED-T; n = 10) followed an 8-week endurance training program to assess expression changes of selected marker genes in the course of skeletal muscle adaptation. We deciphered differential baseline signatures that reflected major differences in the oxidative and metabolic capacity of the endurance-trained and untrained muscles. SED-T individuals in the training group displayed an up-regulation of nodal regulators of oxidative adaptation after 3 weeks of training and a significant shift toward the ET signature after 8 weeks. Transcriptome changes provoked by 1 h of intense cycling exercise only poorly overlapped with the genes that constituted the differential baseline signature of ETs and SEDs. Overall, acute exercise-induced transcriptional responses were connected to pathways of contractile, oxidative, and inflammatory stress and revealed a complex and highly regulated framework of interwoven signaling cascades to cope with exercise-provoked homeostatic challenges. While temporal transcriptional programs that were activated in SEDs and ETs were quite similar, the quantitative divergence in the acute response transcriptomes implicated divergent kinetics of gene induction and repression following an acute bout of exercise. Together, our results provide an extensive examination of the transcriptional framework that underlies skeletal muscle plasticity.

Effects of an acute bout of cycling on different domains of cognitive function.

The literature suggesting acute exercise benefits cognitive function has been largely confined to single cognitive domains and measures of reliant on measures of central tendencies. Furthermore, studies suggest cognitive intra-individual variability (IIV) to reflect cognitive efficiency and provide unique insights into cognitive function, but there is limited knowledge on the effects of acute exercise on IIV. To this end, this study examined the effects of acute exercise on three different cognitive domains, executive function, implicit learning, and hippocampal-dependent memory function using behavioral performance and event-related potentials (ERPs). Furthermore, this study also sought to explore the effects of an acute bout of exercise on IIV using the RIDE algorithm to separate signals into individuals components based on latency variability. Healthy adult participants (N=20; 26.3±4.8years) completed a randomized cross-over trial with seated rest or 30min of high intensity cycling. Before and after each condition, participants completed a cognitive battery consisting of the Eriksen Flanker task, implicit statistical learning task, and a spatial reconstruction task. While exercise did not affect Flanker or spatial reconstruction performance, there were exercise related decreases in accuracy (F=5.47; P=0.040), slowed reaction time (F=5.18; P=0.036), and decreased late parietal positivity (F=4.26; P=0.046). However, upon adjusting for performance and ERP variability, there were exercise related decreases in Flanker reaction time (F=24.00; P<0.001), and reduced N2 amplitudes (F=13.03; P=0.002), and slower P3 latencies (F=3.57; P=0.065) for incongruent trials. These findings suggest that acute exercise may impact cognitive IIV as an adaptation to maintain function following exercise.

Does intensity matter? A randomized crossover study of the role of acute exercise intensity on cognitive performance and motor speed and accuracy.

There is a well-recognized, yet nuanced, positive relationship between acute physical activity and cognitive function. However, the precise impact of exercise intensity remains ambiguous. We tested learning and memory, working memory and processing speed, and motor speed and accuracy across three distinct exercise intensities. A sample of 207 participants (100 female) between 18 and 44 years (mean age: 22.5±3.7years) completed all study procedures. Utilizing a within-subjects, cross-over design, participants completed moderate (35% VO2 Max), vigorous (70% VO2 Max), and sedentary (no exercise) conditions. Cognitive and motor assessments, including the Paced Auditory Serial Addition Test (PASAT), Rey Auditory Verbal Learning Test (RAVLT), Typing Speed Test, and Ten Key Data Entry Task, were conducted approximately 60min post-exercise. There were no significant differences in primary cognitive or motor outcome measures across the three exercise intensities, even with the study being strongly powered. There was, however, a small difference on the fastest trial of the PASAT, where vigorous-intensity exercise yielded slightly better performance compared to both sedentary and moderate-intensity exercise. This effect was no longer significant when including VO2 Max or maximum heart rate as indicators of fitness. There were no interactions on outcome variables by exercise intensity when including biological sex in the models. Thus, a single bout of acute exercise, regardless of its intensity, did not alter cognitive and motor performance when measured approximately 1h post-exercise. Findings highlight the importance of large samples and suggest that the temporal dynamics post-exercise might play a pivotal role in cognitive outcomes.

Aerobic exercise alters DNA hydroxymethylation levels in an experimental rodent model of temporal lobe epilepsy.

The therapeutic potential of aerobic exercise in mitigating seizures and cognitive issues in temporal lobe epilepsy (TLE) is recognized, yet the underlying mechanisms are not well understood. Using a rodent TLE model induced by Kainic acid (KA), we investigated the impact of a single bout of exercise (i.e., acute) or 4 weeks of aerobic exercise (i.e., chronic). Blood was processed for epilepsy-associated serum markers, and DNA methylation (DNAme), and hippocampal area CA3 was assessed for gene expression levels for DNAme-associated enzymes. While acute aerobic exercise did not alter serum Brain-Derived Neurotrophic Factor (BDNF) or Interleukin-6 (IL-6), chronic exercise resulted in an exercise-specific decrease in serum BDNF and an increase in serum IL-6 levels in epileptic rats. Additionally, whole blood DNAme levels, specifically 5-hydroxymethylcytosine (5-hmC), decreased in epileptic animals following chronic exercise. Hippocampal CA3 5-hmC levels and ten-eleven translocation protein (TET1) expression mirrored these changes. Furthermore, immunohistochemistry analysis revealed that most 5-hmC changes in response to chronic exercise were neuron-specific within area CA3 of the hippocampus. Together, these findings suggest that DNAme mechanisms in the rodent model of TLE are responsive to chronic aerobic exercise, with emphasis on neuronal 5-hmC DNAme in the epileptic hippocampus.