Exercise training ameliorates cognitive dysfunction in amyloid beta-injected rat model: possible mechanisms of Angiostatin/VEGF signaling.

Vascular endothelial growth factor (VEGF) regulates angio/neurogenesis and also tightly links to the pathogenesis of Alzheimer's disease (AD). Although exercise has a beneficial effect on neurovascular function and cognitive function, the direct effect of exercise on VEGF-related signaling and cognitive deficit in AD is incompletely understood. Therefore, the purpose of this study was to investigate the protective effect of exercise on angiostatin/VEGF cascade and cognitive function in AD model rats. Wistar male rats were randomly divided into five groups: control (CON), injection of DMSO (Sham-CON), CON-exercise (sham-EX), intrahippocampal injection of Aß (Aß), and Aß-exercise (Aß-EX). Rats in EX groups underwent treadmill exercise for 4 weeks, then the cognitive function was measured by the Morris Water Maze (MWM) test. mRNA levels of hypoxia-induced factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor 2 (VEGFR2), and angiostatin were determined in hippocampus by RT-PCR. We found that spatial learning and memory were impaired in Aß-injected rats, but exercise training improved it. Moreover, exercise training increased the reduced mRNA expression level of VEGF signaling, including HIF1α, VEGF, and VEGFR2 in the hippocampus from Aß-injected rats. Also, the mRNA expression level of angiostatin was elevated in the hippocampus from Aß-injected rats, and exercise training abrogated its expression. Our findings suggest that exercise training improves cognitive function in Aß-injected rats, possibly through enhancing VEGF signaling and reducing angiostatin.

Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: role of the P2Y2 receptor and endoplasmic reticulum stress.

Cerebrovascular dysfunction is a critical risk factor for the pathogenesis of Alzheimer's disease (AD). The purinergic P2Y2 receptor and endoplasmic reticulum (ER) stress are tightly associated with vascular dysfunction and the pathogenesis of AD. However, the protective effects of exercise training on P2Y2 receptor- and ER stress-associated cerebrovascular dysfunction in AD are mostly unknown. Control (C57BL/6, CON) and AD (APP/PS1dE9, AD) mice underwent treadmill exercise training (EX). 2-MeS-ATP-induced dose-dependent vasoreactivity was determined by using a pressurized posterior cerebral artery (PCA) from 10-12-mo-old mice. Human brain microvascular endothelial cells (HBMECs) were exposed to laminar shear stress (LSS) at 20 dyn/cm2 for 30 min, 2 h, and 24 h. The expression of P2Y2 receptors, endothelial nitric oxide synthase (eNOS), and ER stress signaling were quantified by Western blot analysis. Notably, exercise converted ATP-induced vasoconstriction in the PCA from AD mice to vasodilation in AD+EX mice to a degree commensurate to the vascular reactivity observed in CON mice. Exercise reduced the expression of amyloid peptide precursor (APP) and increased the P2Y2 receptor and Akt/eNOS expression in AD mice brain. Mechanistically, LSS increased the expression of both P2Y2 receptor and eNOS protein in HBMECs, but these increases were blunted by a P2Y2 receptor antagonist in HBMECs. Exercise also reduced the expression of aberrant ER stress markers p-IRE1, p/t-eIF2α, and CHOP, as well as Bax/Bcl-2, in AD mice brain. Collectively, our results demonstrate for the first time that exercise mitigates cerebrovascular dysfunction in AD through modulating P2Y2 receptor- and ER stress-dependent endothelial dysfunction.NEW & NOTEWORTHY A limited study has investigated whether exercise training can improve cerebrovascular function in Alzheimer's disease. The novel findings of the study are that exercise training improves cerebrovascular dysfunction through enhancing P2Y2 receptor-mediated eNOS signaling and reducing ER stress-associated pathways in AD. These data suggest that exercise training, which regulates P2Y2 receptor and ER stress in AD brain, is a potential therapeutic strategy for Alzheimer's disease.

Human infancy and parenting in global perspective: specificity.

We address three long-standing fundamental questions about early human development and parental caregiving within a specificity framework using data from 796 infant-mother dyads from 11 societies worldwide. Adopting a cross-society view opens a vista on universal biological origins of, and contextual influences on, infant behaviours and parenting practices. We asked: how do infant behaviours and parenting practices vary across societies? How do infant behaviours relate to other infant behaviours, and how do parent practices relate to other parent practices? Are infant behaviours and parent practices related to one another? Behaviours of firstborn five-month infants and parenting practices of their mothers were microanalysed from videorecords of extensive naturally occurring interactions in the home. In accord with behavioural specificity, biological expectations and cultural influences, we find that infants and mothers from diverse societies exhibit mean-level society differences in their behaviours and practices; domains of infant behaviours generally do not cohere, nor do domains of maternal practices; and only specific infant behaviours and mother practices correspond. Few relations were moderated by society.

Regulation of Coronary Endothelial Function by Interactions between TNF-α, LOX-1 and Adiponectin in Apolipoprotein E Knockout Mice.

BACKGROUND/AIMS: Although individual contributions of TNF-α, LOX-1 and adiponectin to the regulation of endothelial function were previously studied, their interactions in the regulation of coronary endothelial function remain unclear. The aim of this study is to investigate the interactions between TNF-α, LOX-1 and adiponectin in endothelial dysfunction in atherosclerosis. METHODS: Vasodilator function was assessed in coronary arterioles isolated from wild-type, apolipoprotein (ApoE) knockout (KO) mice, ApoE KO null for TNF-α (ApoE KOTNF-/TNF-) and ApoE KO mice treated with neutralizing antibodies to either TNF-α and LOX-1, or recombinant adiponectin. Western blot analysis and immunofluorescence staining were used for mechanistic studies. RESULTS: Acetylcholine (Ach) dilation was impaired in ApoE KO mice. KO of TNF-α, anti-TNF-α anti-LOX-1 or adiponectin restored impaired ACh vasodilation without affecting endothelium-derived hyperpolarizing factor-mediated vasodilation. Immunofluorescence staining demonstrated colocalization of TNF-α with vascular smooth muscle cells, and adiponectin with endothelial cells. ApoE KO mice showed increased protein expression of LOX-1, NF-x03BA;B, NADPH oxidase subunit NOX4 and nitrotyrosine (N-Tyr) levels in coronary arterioles. Treatment with anti-TNF-α, anti-LOX-1 and adiponectin suppressed protein expression of LOX-1, NOX4, NF-x03BA;B and N-Tyr levels. CONCLUSION: Adiponectin, anti-TNF-α and anti-LOX-1 exert vasoprotective effects in atherosclerotic ApoE KO mice.

Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise.

PURPOSE: Salivary antimicrobial proteins (sAMPs) protect the upper respiratory tract (URTI) from invading microorganisms and have been linked with URTI infection risk in athletes. While high training volume is associated with increased URTI risk, it is not known if fitness affects the sAMP response to acute exercise. This study compared the sAMP responses to various exercising workloads of highly fit experienced cyclists with those who were less fit. METHODS: Seventeen experienced cyclists (nine highly fit; eight less fit) completed three 30-min exercise trials at workloads corresponding to -5, +5 and +15 % of the individual blood lactate threshold. Saliva samples were collected pre- and post-exercise to determine the concentration and secretion of α-amylase, human neutrophil proteins 1-3 (HNP1-3) lactoferrin, LL-37, lysozyme, and salivary SIgA. RESULTS: The concentration and/or secretion of all sAMPs increased post-exercise, but only α-amylase was sensitive to exercise workload. Highly fit cyclists had lower baseline concentrations of α-amylase, HNP1-3, and lactoferrin, although secretion rates did not differ between the groups. Highly fit cyclists did, however, exhibit greater post-exercise increases in the concentration and/or secretion of a majority of measured sAMPs (percentage difference between highly fit and less fit in parentheses), including α-amylase concentration (+107 %) and secretion (+148 %), HNP1-3 concentration (+97 %) and secretion (+158 %), salivary SIgA concentration (+181 %), lactoferrin secretion (+209 %) and LL-37 secretion (+138 %). CONCLUSION: We show for the first time that fitness level is a major determinant of exercise-induced changes in sAMPs. This might be due to training-induced alterations in parasympathetic and sympathetic nervous system activation.

Planning in middle childhood: early predictors and later outcomes.

Data from 1,364 children and families who participated in the National Institute of Child Health and Human Development's Study of Early Child Care and Youth Development were analyzed to track the early correlates and later academic outcomes of planning during middle childhood. Maternal education, through its effect on parenting quality when children were 54 months old, predicts their concurrent performance on sustained attention, inhibition, and short-term verbal memory tests. This performance predicts planning in first grade, which predicts third-grade reading and mathematics attainment, but not the rate of growth in academic skills from first to fifth grades. This path was also found when the same parenting, cognitive, and academic constructs were measured at later time points.

Microvascular Function and Exercise Training: Functional Implication of Nitric Oxide Signaling and Ion Channels.

Background: Exercise training elicits indubitable positive adaptation in microcirculation in health and disease populations. An inclusive overview of the current knowledge regarding the effects of exercise on microvascular function consolidates an in-depth understanding of microvasculature. Summary: The main physiological function of microvasculature is to maintain optimal blood flow regulation to supply oxygen and nutrition during elevated physical demands in the cardiovascular system. There are several cellular and molecular alterations in resistance vessels in response to exercise intervention, an increase in nitric oxide-mediated vasodilation through the regulation of oxidative stress, inflammatory response, and ion channels in endothelial cells, thus increasing myogenic tone via voltage-gated Ca2+ channels in smooth muscle cells. Key Messages: In the review, we postulate that exercise should be considered a medicine for people with diverse diseases through a comprehensive understanding of the cellular and molecular underlying mechanisms in microcirculation through exercise training.

Factors associated with clinical nurses' preconception health behavior in Korea: a cross-sectional survey.

PURPOSE: Nurses have been reported to be at an increased risk for miscarriage and preterm labor. However, there is limited knowledge regarding nurses' preconception health behaviors. Therefore, this study aimed to identify factors influencing these behaviors. METHODS: One hundred sixty nurses, who were planning their first pregnancy within the upcoming year, participated in an online survey from August 11 to October 31, 2021. Data on preconception health behavior, perceived health status, pregnancy anxiety, nursing practice environment, and social support were analyzed using the t-test, Pearson correlation coefficients, and multiple regression analysis. RESULTS: Age (р=.024), educational level (р=.010), marital status (р=.003), work experience (р=.003), satisfaction with the work department (р<.001), smoking status (р=. 039), and previous health problems related to pregnancy outcomes (р=.004) were significantly associated with nurses' preconception health behaviors. Furthermore, perceived health status (р<.001), pregnancy anxiety (р=.011), nursing practice environment (р=.003), and social support (р<.001) showed significant correlations with preconception health behaviors. Social support (ß=. 28, р=.001), satisfaction with the work department (ß=.23, р=.032), marital status (ß=.22, р=.002), and perceived health status (ß=.23, р=.002) were confirmed as factors associated with preconception health behaviors. These factors explained 40.9% of the variance in preconception health behaviors (F=6.64, р<.001). CONCLUSION: Clinical nurses' preconception health behaviors were influenced by social support, perceived health status, satisfaction with the work department, and marital status. Interventions to improve clinical nurses' preconception health behaviors should target social support and perceived health status. A preconception health behavior education program considering clinical nurses' marital status and satisfaction with the workplace can also be implemented.

Prevalence of Metabolic Syndrome Based on Activity Type and Dietary Habits in Extremely Low-Income Individuals.

A high prevalence of metabolic syndrome (MS) and cardiovascular disease among low-income individuals has often been reported. However, there is still a lack of research on the relationship between basic livelihood security (BLS) and MS. This study investigated the prevalence of MS according to activity type, dietary habits, and the nutrient intake characteristics of individuals receiving BLS. Data from 14,803 men and 20,299 women were analyzed to assess the association between receiving BLS and MS. The associations between MS and various factors were analyzed separately in men and women by logistic regression analysis. In this cohort, 5.9% of men and 6.8% of women received BLS; of these, 46.9% and 47.7% had MS, respectively. High caloric intake, low-frequency breakfast consumption, and no nutritional education were associated with MS in both men and women. Among those with a low-frequency walking habit and strength training activity type, MS increased by 1.58 and 1.57 times in men and by 1.47 and 2.16 times in women, respectively. Men who were sedentary for 8 h or more had an increased risk of MS, but there was no association between these in women. BLS nutritional intake characteristics were high in carbohydrates and fat and low in dietary fiber and vitamin C (p < 0.05). In conclusion, establishing a healthy eating pattern through nutritional education and increasing walking and strength training may reduce the risk of MS.

Exercise intensity impacts the improvement of metabolic dysfunction-associated steatotic liver disease via variations of monoacylglycerol O-acyltransferase 1 expression.

BACKGROUND: The involvement of monoacylglycerol O-acyltransferase 1 (MOGAT1) in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD) has been recognized. While exercise is recommended for the improvement of obesity and MASLD, the impact of exercise intensity remains unclear. This study aimed to examine the influence of exercise intensity on MOGAT1 expression in high-fat diet (HFD)-induced obese mice with MASLD. METHOD: Male C57BL/6 mice aged 6 weeks were subjected to either a regular or HFD with 60 % fat content for 8 weeks. The mice were categorized into 5 groups based on their diet and exercise intensity: normal diet group (ND), HFD group, low-intensity exercise with HFD group (HFD+LIE), moderate-intensity exercise with HFD group (HFD+MIE), and high-intensity exercise (HIE) with HFD group (HFD+HIE). The duration of running was adjusted to ensure uniform exercise load across groups (total distance = 900 m): HFD+LIE at 12 m/min for 75 min, HFD+MIE at 15 m/min for 60 min, and HFD+HIE at 18 m/min for 50 min. RESULTS: Lipid droplet size and MASLD activity score were significantly lower in the HFD+HIE group compared to other exercise-intensity groups (p < 0.05). Among the 3 intensity exercise groups, the lowest MOGAT1 protein expression was found in the HFD+HIE group (p < 0.05). CONCLUSION: This study reveals that high-intensity exercise has the potential to mitigate MASLD development, partly attributed to the downregulation of MOGAT1 expression.

Effects of short-term exercise and endurance training on skeletal muscle mitochondria damage induced by particular matter, atmospherically relevant artificial PM2.5.

Introduction: This study aimed to investigate the potential of short-term aerobic exercise to mitigate skeletal muscle mitochondrial damage following ambient PM2.5 exposure, and how 12 weeks of endurance training can enhance aerobic fitness to protect against such damage. Methods: Twenty-four male C57BL/6 J mice were split into sedentary (SED, n = 12) and endurance training (ETR, n = 12) groups. The ETR group underwent 12 weeks of training (10-15 m/min, 60 min/day, 4 times/week), confirmed by an Endurance Exercise Capacity (EEC) test. Post-initial training, the SED group was further divided into SSED (SED and sedentary, n = 6) and SPE (SED and PM2.5 + Exercise, n = 6). Similarly, the ETR group was divided into EEX (ETR and Exercise, n = 6) and EPE (ETR and PM2.5 + Exercise, n = 6). These groups underwent 1 week of atmospherically relevant artificial PM2.5 exposure and treadmill running (3 times/week). Following treatments, an EEC test was conducted, and mice were sacrificed for blood and skeletal muscle extraction. Blood samples were analyzed for oxidative stress indicators, while skeletal muscles were assessed for mitochondrial oxidative metabolism, antioxidant capacity, and mitochondrial damage using western blot and transmission electron microscopy (TEM). Results: After 12 weeks of endurance training, the EEC significantly increased (p < 0.000) in the ETR group compared to the SED group. Following a one-week comparison among the four groups with atmospherically relevant artificial PM2.5 exposure and exercise treatment post-endurance training, the EEX group showed improvements in EEC, oxidative metabolism, mitochondrial dynamics, and antioxidant functions. Conversely, these factors decreased in the EPE group compared to the EEX. Additionally, within the SPE group, exercise effects were evident in HK2, LDH, SOD2, and GPX4, while no impact of short-term exercise was observed in all other factors. TEM images revealed no evidence of mitochondrial damage in both the SED and EEX groups, while the majority of mitochondria were damaged in the SPE group. The EPE group also exhibited damaged mitochondria, although significantly less than the SPE group. Conclusion: Atmospherically relevant artificial PM2.5 exposure can elevate oxidative stress, potentially disrupting the benefits of short-term endurance exercise and leading to mitochondrial damage. Nonetheless, increased aerobic fitness through endurance training can mitigate PM2.5-induced mitochondrial damage.

Vitamin D supplementation for depression in older adults: a meta-analysis of randomized controlled trials.

Background: In older adults, depression is associated with several other clinical problems such as cognitive impairment and low quality of life. Several studies have evaluated the relationship between vitamin D and depression in older adults; however, the results have been controversial thus far. Objective: This study aimed to investigate the effects of vitamin D supplementation on depressive symptom improvement among individuals aged ≥60 years with or without a diagnosis of depression or depressive symptoms based on a meta-analysis of randomized controlled trials (RCTs). Methods: RCTs were identified to analyze the relationship between vitamin D supplementation and depressive symptoms. MEDLINE, CENTRAL, Embase, and PsycINFO were systematically searched for relevant articles published from inception to November 2022. RCTs that evaluated the effect of vitamin D supplementation in participants aged ≥60 years compared to placebo were included. A random effects model was used in this meta-analysis because of the differences between the included RCTs. The quality of the RCTs was assessed using Risk of Bias 2. Results: Seven trials were included in the analyses. The primary outcome of pre-post score changes included five trials with a total of 752 participants. The secondary outcome of post-intervention score included all seven trials with a total of 4,385 participants. No significant improvement in depressive symptoms in either pre-post score changes [standardized mean difference (SMD) = -0.49; 95% confidence interval (CI) -1.07-0.09; p = 0.10] or post-intervention score (SMD = -0.10; 95% CI -0.28-0.07; p = 0.25) was found. Conclusion: Vitamin D supplementation in older adults was not associated with an improvement in depressive symptoms. More studies in older adults are needed to evaluate the association between vitamin D supplementation and depression.

Exercise Training Improves Brachial Artery Endothelial Function, but Does Not Alter Inflammatory Biomarkers in Patients with Peripheral Artery Disease: a Systematic Review and Meta-analysis.

The study aimed to systematically review the effects of exercise training (EX) on brachial artery flow-mediated dilation (FMD) and inflammatory biomarkers in patients with peripheral artery disease (PAD). Five electronic databases were searched: (i) patients with PAD aged ≥ 18; (ii) structured EX ≥ 2 weeks; (iii) measured brachial artery FMD; and (iv) measured blood inflammatory biomarkers. Eighteen studies met the inclusion criteria. EX increased FMD but had no effect on C-reactive protein, interleukin-6, and tumor necrosis factor-α. Subgroups with moderate intensity had a greater increase in FMD than subgroups with vigorous intensity. There was no difference in effect on FMD and three inflammatory biomarkers between subgroups training for ≤ 12 weeks and > 12 weeks of EX, < 50 min and ≥ 50 min of session duration, and < 150 min and ≥ 150 min of weekly volume, respectively. These results suggest that EX-induced improvement in vascular function can be independent of the improvement of systemic inflammation.

The Effectiveness of a Mobile Phone-Based Physical Activity Program for Treating Depression, Stress, Psychological Well-Being, and Quality of Life Among Adults: Quantitative Study.

BACKGROUND: Depression is a substantial global health problem, affecting >300 million people and resulting in 12.7% of all deaths. Depression causes various physical and cognitive problems, leading to a 5-year to 10-year decrease in life expectancy compared with the general population. Physical activity is known to be an effective, evidence-based treatment for depression. However, people generally have difficulties with participating in physical activity owing to limitations in time and accessibility. OBJECTIVE: To address this issue, this study aimed to contribute to the development of alternative and innovative intervention methods for depression and stress management in adults. More specifically, we attempted to investigate the effectiveness of a mobile phone-based physical activity program on depression, perceived stress, psychological well-being, and quality of life among adults in South Korea. METHODS: Participants were recruited and randomly assigned to the mobile phone intervention or waitlist group. Self-report questionnaires were used to assess variables before and after treatment. The treatment group used the program around 3 times per week at home for 4 weeks, with each session lasting about 30 minutes. To evaluate the program's impact, a 2 (condition) × 2 (time) repeated-measures ANOVA was conducted, considering pretreatment and posttreatment measures along with group as independent variables. For a more detailed analysis, paired-samples 2-tailed t tests were used to compare pretreatment and posttreatment measurements within each group. Independent-samples 2-tailed t tests were conducted to assess intergroup differences in pretreatment measurements. RESULTS: The study included a total of 68 adults aged between 18 and 65 years, who were recruited both through web-based and offline methods. Of these 68 individuals, 41 (60%) were randomly assigned to the treatment group and 27 (40%) to the waitlist group. The attrition rate was 10.2% after 4 weeks. The findings indicated that there is a significant main effect of time (F1,60=15.63; P=.003; ηp2=0.21) in participants' depression scores, indicating that there were changes in depression level across time. No significant changes were observed in perceived stress (P=.25), psychological well-being (P=.35), or quality of life (P=.07). Furthermore, depression scores significantly decreased in the treatment group (from 7.08 to 4.64; P=.03; Cohen d=0.50) but not in the waitlist group (from 6.72 to 5.08; P=.20; Cohen d=0.36). Perceived stress score of the treatment group also significantly decreased (from 2.95 to 2.72; P=.04; Cohen d=0.46) but not in the waitlist group (from 2.82 to 2.74; P=.55; Cohen d=0.15). CONCLUSIONS: This study provided experimental evidence that mobile phone-based physical activity program affects depression significantly. By exploring the potential of mobile phone-based physical activity programs as a treatment option, this study sought to improve accessibility and encourage participation in physical activity, ultimately promoting better mental health outcomes for individuals with depression and stress.

Attenuation of skeletal muscle atrophy via acupuncture, electro-acupuncture, and electrical stimulation.

Background: Accelerated skeletal muscle wasting is a shared trait among many pathologies and aging. Acupuncture has been used as a therapeutic intervention to control pain; however, little is known about its effects on skeletal muscle atrophy and function. The study's purpose was to compare the effects of acupuncture, electro-acupuncture, and electrical stimulation on cast-induced skeletal muscle atrophy. Methods: Forty female Sprague Dawley rats were randomly divided into groups: Control, casted (CAST), CAST+Acupuncture (CAST-A), 4) CAST+Electro-acupuncture (CAST-EA), and CAST+Electrical stimulation (CAST-ES) (n = 8). Plaster casting material was wrapped around the left hind limb. Acupuncture and electro-acupuncture (10 Hz, 6.4 mA) treatments were applied by needling acupoints (stomach-36 and gallbladder-34). Electrical stimulation (10 Hz, 6.4 mA) was conducted by needling the lateral and medial gastrocnemius muscles. Treatments were conducted for 15 min, three times/week for 14 days. Muscle atrophy F-box (MAFbx), muscle RING finger 1 (MuRF1), and contractile properties were assessed. Results: Fourteen days of cast-immobilization decreased muscle fiber CSA by 56% in the CAST group (p = 0.00); whereas, all treatment groups demonstrated greater muscle fiber CSA than the CAST group (p = 0.00). Cast-immobilization increased MAFbx and MuRF1 protein expression in the CAST group (p<0.01) while the CAST-A, CAST-EA, and CAST-ES groups demonstrated lower levels of MAFbx and MuRF1 protein expression (p<0.02) compared to the CAST group. Following fourteen days of cast-immobilization, peak twitch tension did not differ between the CAST-A and CON groups (p = 0.12). Conclusion: Skeletal muscle atrophy, induced by 14 days of cast-immobilization, was significantly attenuated by acupuncture, electro-acupuncture, or electrical stimulation.

Physical activity opposes coronary vascular dysfunction induced during high fat feeding in mice.

The study's purpose was to investigate if physical activity initiated with the start of high-fat feeding would oppose development of endothelial dysfunction, and if it does, then to determine some potential mechanisms. C57BL/6 female mice were randomly divided into three groups: (1) control low-fat diet (LF-SED; 15% of calories from fat), (2) high-fat diet (HF-SED; 45% of calories from fat), and (3) HF diet given access to a voluntary running wheel (HF-RUN). Our hypothesis was that HF-RUN would differ in multiple markers of endothelial dysfunction from HF-SED after 10 weeks of 45%-fat diet, but would not differ from LF-SED. HF-RUN differed from HF-SED in nine determinations in which HF-SED either had decreases in (1) acetylcholine (ACh)-induced and flow-induced vasodilatations in isolated, pressurized coronary arterioles, (2) heart phosphorylated endothelial nitric oxide synthase (p-eNOS/eNOS) protein, (3) coronary arteriole leptin (ob) receptor protein, (4) phosphorylated signal transducer and activator of transcription 3 (p-STAT3/STAT3) protein, and (5) coronary arteriole superoxide dismutase 1 protein; or had increases in (6) percentage body fat, (7) serum leptin, (8) coronary arteriole suppressor of cytokine signalling 3 (SOCS3) protein, and (9) coronary arteriole gp91(phox) protein. Higher endothelium-dependent vasodilatation by ACh or leptin was abolished with incubation of NOS inhibitor N(G)-nitro-l-arginine-methyl ester (l-NAME) in LF-SED and HF-RUN groups. Further, impaired ACh-induced vasodilatation in HF-SED was normalized by apocynin or TEMPOL to LF-SED and HF-RUN. These findings demonstrate multiple mechanisms (eNOS, leptin and redox balance) by which voluntary running opposes the development of impaired coronary arteriolar vasodilatation during simultaneous high-fat feeding.

T-cell counts in response to acute cardiorespiratory or resistance exercise in physically active or physically inactive older adults: a randomized crossover study.

T cells often undergo age-related changes, which may be offset by regular exercise training. However, the majority of literature is derived from cardiorespiratory exercise studies. The purpose of this study was to examine the effects of acute cardiorespiratory exercise and acute resistance exercise on the T-cell response among physically active (PA) older adults compared with physically inactive (PI) older adults. Twenty-four healthy older adults [PA n = 12; PI n = 12; means ± SD; age (years) PA 62 ± 5, PI 64 ± 5; body mass index (BMI; kg/m2) PA 23.9 ± 3.0, PI 25.6 ± 3.5] completed one bout each of matched intensity cardiorespiratory exercise and resistance exercise in a randomized order. Blood samples drawn preexercise, postexercise, and 1 h postexercise (recovery) were analyzed by flow cytometry for T cells and T-cell subsets. Resistance exercise mobilized more T-cell subsets in PI (10 of the measured types, including total T cells; CD45RA+ CD62L+, CD45RA- CD62L+, CD45RA- CD62L-, and CD45RA+ CD62L- T cells), whereas cardiorespiratory exercise mobilized more subsets in PA (CD45RA+ CD62L- and CD57+ CD45RA+ CD62L- CD4+ T cells). Both cardiorespiratory exercise and resistance exercise elicited a significant (P < 0.05) mobilization of highly differentiated (CD45RA+ CD62L-; CD57+ CD45RA+ CD62L-) CD8+ T cells into the circulation postexercise in both PA and PI groups. Furthermore, cardiorespiratory exercise resulted in a decrease in the number of circulating Th17 cells postexercise, whereas resistance exercise increased Th17 cell mobilization compared with the cardiorespiratory exercise response. There are differences between cardiorespiratory exercise and resistance exercise on the immune responses of T cells, particularly in PI individuals. This research study was registered at clinicaltrials.gov NCT03794050. NEW & NOTEWORTHY A bout of resistance exercise did not elicit the same T-cell responses as a bout of walking on a treadmill, and the response was also not the same for people who participate in regular exercise compared with those who do not. Although there were several similarities, these potential differences underscore the importance of careful selection of exercise protocol based on the population studied and the desired T-cell response to exercise outcome.

Exercise training improves endothelial function via adiponectin-dependent and independent pathways in type 2 diabetic mice.

Type 2 diabetes (T2D) is a leading risk factor for a variety of cardiovascular diseases including coronary heart disease and atherosclerosis. Exercise training (ET) has a beneficial effect on these disorders, but the basis for this effect is not fully understood. This study was designed to investigate whether the ET abates endothelial dysfunction in the aorta in T2D. Heterozygous controls (m Lepr(db)) and type 2 diabetic mice (db/db; Lepr(db)) were either exercise entrained by forced treadmill exercise or remained sedentary for 10 wk. Ex vivo functional assessment of aortic rings showed that ET restored acetylcholine-induced endothelial-dependent vasodilation of diabetic mice. Although the protein expression of endothelial nitric oxide synthase did not increase, ET reduced both IFN-γ and superoxide production by inhibiting gp91(phox) protein levels. In addition, ET increased the expression of adiponectin (APN) and the antioxidant enzyme, SOD-1. To investigate whether these beneficial effects of ET are APN dependent, we used adiponectin knockout (APNKO) mice. Indeed, impaired endothelial-dependent vasodilation occurred in APNKO mice, suggesting that APN plays a central role in prevention of endothelial dysfunction. APNKO mice also showed increased protein expression of IFN-γ, gp91(phox), and nitrotyrosine but protein expression of SOD-1 and -3 were comparable between wild-type and APNKO. These findings in the aorta imply that APN suppresses inflammation and oxidative stress in the aorta, but not SOD-1 and -3. Thus ET improves endothelial function in the aorta in T2D via both APN-dependent and independent pathways. This improvement is due to the effects of ET in inhibiting inflammation and oxidative stress (APN-dependent) as well as in improving antioxidant enzyme (APN-independent) performance in T2D.

Effect of PAR2 in regulating TNF-α and NAD(P)H oxidase in coronary arterioles in type 2 diabetic mice.

Protease-activated receptor-2 (PAR2) is expressed in endothelial cells and mediates endothelium-dependent vasodilation. We hypothesized that PAR2 regulates tumor necrosis factor-alpha (TNF-α)-induced coronary arteriolar dysfunction in type 2 diabetic (db/db) mice. To test this, coronary arterioles from WT control, db/db, db/db mice treated with PAR2 antagonist FSLLRY-NH2 (db/db+FSLLRY-NH2) and db/db mice null for TNF (db(TNF-)/db(TNF-)) were isolated and pressurized (60 cmH2O) without flow. Although vasodilation to the endothelium-independent vasodilator sodium nitroprusside (SNP) was not different among WT, db/db, db/db+FSLLRY-NH2 and db(TNF-)/db(TNF-), endothelium-dependent acetylcholine (ACh)- and flow-mediated vasodilation were impaired in db/db mice but were enhanced in db(TNF-)/db(TNF-) mice and db/db mice treated with PAR2 antagonist. NOS inhibitor N (G)-nitro-L-arginine-methyl ester (L-NAME) significantly reduced ACh-induced dilation in WT, db(TNF-)/db(TNF-) and db/db+FSLLRY-NH2, but did not alter the vasodilation in db/db mice. In contrast, cyclooxygenase (COX) inhibitor indomethacin (Indo) did not alter ACh-induced vasodilation in these four groups of mice. PAR2-activating peptide (PAR2-AP, 2-Furoyl-LIGRLO-am)-induced dilation was higher in db/db mice than that in WT, db(TNF-)/db(TNF-) and db/db mice treated with PAR2 antagonist. These effects were abolished by denudation, or in the presence of L-NAME or Indo. Protein expressions of TNF-α, PAR2, gp91(phox) and p47(phox) in the heart and isolated coronary arterioles were higher in db/db mice compared to WT mice. Administration of PAR2 antagonist to db/db mice reduced protein expression of TNF-α, gp91(phox) and PAR2. Protein expression of gp91(phox) and p47(phox) was lower in db(TNF-)/db(TNF-) compared to db/db mice. These results indicate that PAR2 plays a pivotal role in endothelial dysfunction in type 2 diabetes by up-regulating the expression/production of TNF-α and activating NAD(P)H oxidase subunit p47(phox).