Effects of HIIT training and HIIT combined with circuit resistance training on measures of physical fitness, miRNA expression, and metabolic risk factors in overweight/obese middle-aged women.

OBJECTIVE: The purpose of this study was to examine the effects of 10 weeks of high-intensity interval training (HIIT) and HIIT combined with circuit resistance training (HCRT) on selected measures of physical fitness, the expression of miR-9, -15a, -34a, -145, and - 155 as well as metabolic risk factors including lipid profiles and insulin resistance in middle-aged overweight/obese women. METHODS: Twenty-seven overweight/obese women aged 35-50 yrs. were randomized to HIIT (n = 14) or HCRT (n = 13) groups. The HIIT group performed running exercises (5 reps x 4 min per session) with active recovery between repetitions for 10 weeks with 5 weekly sessions. The HCRT group performed 10 weeks of HIIT and resistance training with 3 weekly HIIT sessions and 2 weekly HCRT sessions. Anthropometric measures (e.g., body mass), selected components of physical fitness (cardiovascular fitness, muscle strength), levels of miRNAs (miR-9, -15a, -34a, -145, and - 155), lipid profiles (total cholesterol; TC, Triglycerides; TG, low-density lipoprotein cholesterol; LDL-C and high-density lipoprotein cholesterol; HDL-C), and insulin resistance; HOMA-IR index, were measured at baseline and week 10. RESULTS: An ANOVA analysis indicated no significant group by time interactions (p > 0.05) for all anthropometric measures, and maximum oxygen consumption (VO2max). A significant group by time interaction, however, was found for the one-repetition maximum (IRM; p < 0.001, ES= 0.751 , moderate). A post-hoc test indicated an increase in the pre-to-post mean 1RM for HCRT (p = 0.001, ES = 1.83, large). There was a significant group by time interaction for miR-155 (p = 0.05, ES = 0.014, trivial). Levels for miR-155 underwent pre-to-post HIIT increases (p = 0.045, ES = 1.232, large). Moreover, there were also significant group by time interactions for TC (p = 0.035, ES = 0.187, trivial), TG (p < 0.001, ES = 0.586, small), LDL-C (p = 0.029, ES = 0.200, small) and HDL-C (p = 0.009, ES = 0.273, small). Post-hoc tests indicated pre-post HCRT decreases for TC (p = 0.001, ES = 1.44, large) and HDL-C (p = 0.001, ES = 1.407, large). HIIT caused pre-to-post decreases in TG (p = 0.001, ES = 0.599, small), and LDL-C (p = 0.001, ES = 0.926, moderate). CONCLUSIONS: Both training regimes did not improve cardiovascular fitness. But, HCRT improved lower/upper limb muscle strength, and HIIT resulted in an increase in miR-155 expression in peripheral blood mononuclear cells. Furthermore, HIIT and HCRT each improved selected metabolic risk factors including lipid profiles and glucose and insulin metabolism in overweight/obese middle-aged women. TRIAL REGISTRATION: OSF, October, 4th 2023. Registration DOI: https://doi.org/10.17605/OSF.IO/UZ92E . osf.io/tc5ky . "Retrospectively registered".

A Systematic Review and Meta-analysis of the Association Between ACTN3 R577X Genotypes and Performance in Endurance Versus Power Athletes and Non-athletes.

BACKGROUND: Previous studies reported differences in genotype frequency of the ACTN3 R577X polymorphisms (rs1815739; RR, RX and XX) in athletes and non-athletic populations. This systematic review with meta-analysis assessed ACTN3 R577X genotype frequencies in power versus endurance athletes and non-athletes. METHODS: Five electronic databases (PubMed, Web of Science, Scopus, Science Direct, SPORTDiscus) were searched for research articles published until December 31st, 2022. Studies were included if they reported the frequency of the ACTN3 R577X genotypes in power athletes (e.g., weightlifters) and if they included a comparison with endurance athletes (e.g., long-distance runners) or non-athletic controls. A meta-analysis was then performed using either fixed or random-effects models. Pooled odds ratios (OR) were determined. Heterogeneity was detected using I2 and Cochran's Q tests. Publication bias and sensitivity analysis tests were computed. RESULTS: After screening 476 initial registrations, 25 studies were included in the final analysis (13 different countries; 14,541 participants). In power athletes, the RX genotype was predominant over the two other genotypes: RR versus RX (OR 0.70; 95% CI 0.57-0.85, p = 0.0005), RR versus XX (OR 4.26; 95% CI 3.19-5.69, p < 0.00001), RX versus XX (OR 6.58; 95% CI 5.66-7.67, p < 0.00001). The R allele was higher than the X allele (OR 2.87; 95% CI 2.35-3.50, p < 0.00001) in power athletes. Additionally, the frequency of the RR genotype was higher in power athletes than in non-athletes (OR 1.48; 95% CI 1.25-1.75, p < 0.00001). The RX genotype was similar in both groups (OR 0.84; 95% CI 0.71-1.00, p = 0.06). The XX genotype was lower in power athletes than in controls (OR 0.73; 95% CI 0.64-0.84, p < 0.00001). Furthermore, the R allele frequency was higher in power athletes than in controls (OR 1.28; 95% CI 1.19-1.38, p < 0.00001). Conversely, a higher frequency of X allele was observed in the control group compared to power athletes (OR 0.78; 95% CI 0.73-0.84, p < 0.00001). On the other hand, the frequency of the RR genotype was higher in power athletes than in endurance athletes (OR 1.27; 95% CI 1.09-1.49, p = 0.003). The frequency of the RX genotype was similar in both groups (OR 1.07; 95% CI 0.93-1.24, p = 0.36). In contrast, the frequency of the XX genotype was lower in power athletes than in endurance athletes (OR 0.63; 95% CI 0.52-0.76, p < 0.00001). In addition, the R allele was higher in power athletes than in endurance athletes (OR 1.32; 95% CI 1.11-1.57, p = 0.002). However, the X allele was higher in endurance athletes compared to power athletes (OR 0.76; 95% CI 0.64-0.90, p = 0.002). Finally, the genotypic and allelic frequency of ACTN3 genes were similar in male and female power athletes. CONCLUSIONS: The pattern of the frequencies of the ACTN3 R577X genotypes in power athletes was RX > RR > XX. However, the RR genotype and R allele were overrepresented in power athletes compared to non-athletes and endurance athletes. These data suggest that the RR genotype and R allele, which is associated with a normal expression of α-actinin-3 in fast-twitch muscle fibers, may offer some benefit in improving performance development in muscle strength and power.

Bioinformatics Analysis Identifies Key Genes in the Effect of Resistance Training on Female Skeletal Muscle Aging.

Resistance training is used to combat skeletal muscle function decline in older adults. Few studies have been designed specific for females, resulting in very limited treatment options for skeletal muscle atrophy in aging women. Here, we analyzed the gene expression profiles of skeletal muscle samples from sedentary young women, sedentary older women, and resistance-trained older women, using microarray data from public database. A total of 45 genes that were differentially expressed during female muscle aging and reversed by resistance training were identified. Functional and pathway enrichment analysis, protein-protein interaction network analysis, and receiver operating characteristic analysis were performed to reveal the key genes and pathways involved in the effects of resistance training on female muscle aging. The collagen genes COL1A1, COL3A1, and COL4A1 were identified important regulators of female muscle aging and resistance training, by modulating multiple signaling pathways, such as PI3 kinase-Akt signaling, focal adhesions, extracellular matrix-receptor interactions, and relaxin signaling. Interestingly, the expression of CDKN1A and TP63 were increased during aging, and further upregulated by resistance training in older women, suggesting they may negatively affect resistance training outcomes. Our findings provide novel insights into the molecular mechanisms of resistance training on female muscle aging and identify potential biomarkers and targets for clinical intervention.

Effects of Passive or Active Recovery Regimes Applied During Long-Term Interval Training on Physical Fitness in Healthy Trained and Untrained Individuals: A Systematic Review.

BACKGROUND: Intermittent exercise programs characterized through intensive exercise bouts alternated with passive or active recovery (i.e., interval training), have been proven to enhance measures of cardiorespiratory fitness. However, it is unresolved which recovery type (active or passive) applied during interval training results in larger performance improvements. OBJECTIVES: This systematic review aimed to summarize recent evidence on the effects of passive or active recovery following long-term interval exercise training on measures of physical fitness and physiological adaptations in healthy trained and untrained individuals. The study protocol was registered in the Open Science Framework (OSF) platform ( https://doi.org/10.17605/OSF.IO/9BUEY ). METHODS: We searched nine databases including the grey literature (Academic Search Elite, CINAHL, ERIC, Open Access Theses and Dissertations, Open Dissertations, PsycINFO, PubMed/MEDLINE, Scopus, and SPORTDiscus) from inception until February 2023. Key terms as high-intensity interval training, recovery mode, passive or active recover were used. A systematic review rather than a meta-analysis was performed, as a large number of outcome parameters would have produced substantial heterogeneity. RESULTS: After screening titles, abstracts, and full texts, 24 studies were eligible for inclusion in our final analysis. Thirteen studies examined the effects of interval training interspersed with passive recovery regimes on physical fitness and physiological responses in trained (6 studies) and untrained (7 studies) individuals. Eleven out of 13 studies reported significant improvements in physical fitness (e.g., maximal aerobic velocity (MAV), Yo-Yo running test, jump performance) and physiological parameters (e.g., maximal oxygen uptake [VO2max], lactate threshold, blood pressure) in trained (effect sizes from single studies: 0.13 < Cohen's d < 3.27, small to very large) and untrained individuals (effect sizes: 0.17 < d < 4.19, small to very large) despite the type of interval training or exercise dosage (frequency, intensity, time, type). Two studies were identified that examined the effects of passive recovery applied during interval training in young female basketball (15.1 ± 1.1 years) and male soccer players (14.2 ± 0.5 years). Both studies showed positive effects of passive recovery on VO2max, countermovement jump performance, and the Yo-Yo running test. Eleven studies examined the effects of interval training interspersed with active recovery methods on physical fitness and physiological parameters in trained (6 studies) and untrained individuals (5 studies). Despite the type of interval training or exercise dosage, nine out of eleven studies reported significant increases in measures of physical fitness (e.g., MAV) and physiological parameters (e.g., VO2max, blood pressures) in trained (effect sizes from single studies: 0.13 < d < 1.29, small to very large) and untrained individuals (effect sizes: 0.19 < d < 3.29, small to very large). There was no study available that examined the effects of active recovery on physical fitness and physiological responses in youth. CONCLUSIONS: The results of this systematic review show that interval training interspersed with active or passive recovery regimes have the potential to improve measures of physical fitness and physiology outcomes in trained and untrained adults and trained youth. That is, the applied recovery type seems not to affect the outcomes. Nonetheless, more research is needed on the effects of recovery type on measures of physical fitness and physiological adaptations in youth.

Enhancing cardiometabolic health: unveiling the synergistic effects of high-intensity interval training with spirulina supplementation on selected adipokines, insulin resistance, and anthropometric indices in obese males.

This study investigated the combined effects of 12 weeks of high-intensity interval training (HIIT) and spirulina supplementation on adipokine levels, insulin resistance, anthropometric indices, and cardiorespiratory fitness in 44 obese males (aged 25-40 years). The participants were randomly assigned to one of four groups: control (CG), supplement (SG), training (TG), or training plus supplement (TSG). The intervention involved daily administration of either spirulina or a placebo and HIIT three times a week for the training groups. Anthropometric indices, HOMA-IR, VO2peak, and circulating adipokines (asprosin and lipocalin2, omentin-1, irisin, and spexin) were measured before and after the 12-week intervention. Post-intervention analysis indicated differences between the CG and the three interventional groups for body weight, fat-free mass (FFM), percent body fat (%BF), HOMA-IR, and adipokine levels (p < 0.05). TG and SG participants had increased VO2peak (p < 0.05). Spirulina supplementation with HIIT increased VO2peak, omentin-1, irisin, and spexin, while causing decreases in lipocalin-2 and asprosin levels and improvements in body composition (weight, %fat), BMI, and HOMA-IR. Notably, the combination of spirulina and HIIT produced more significant changes in circulating adipokines and cardiometabolic health in obese males compared to either supplementation or HIIT alone (p < 0.05). These findings highlight the synergistic benefits of combining spirulina supplementation with HIIT, showcasing their potential in improving various health parameters and addressing obesity-related concerns in a comprehensive manner.

Effects of caffeine supplementation on anaerobic power and muscle activity in youth athletes.

This study aimed to investigate the effects of caffeine ingestion on anaerobic performance and muscle activity in young athletes. In this randomized, double-blind, and placebo-controlled study, ten highly trained male post-puberal futsal players aged 15.9 ± 1.2 years conducted two laboratory sessions. Athletes performed the Wingate test 60 min after ingestion of caffeine (CAF, 6 mg/kg body mass) or placebo (PL, dextrose) (blinded administration). Peak power, mean power, and the fatigue index were assessed. During the performance of the Wingate test, electromyographic (EMG) data were recorded from selected lower limbs muscles to determine the root mean square (RMS), mean power frequency (MPF), and median power frequency (MDPF) as frequency domain parameters and wavelet (WT) as time-frequency domain parameters. Caffeine ingestion increased peak (0.80 ± 0.29 W/Kg; p = 0.01; d = 0.42) and mean power (0.39 ± 0.02 W/Kg; p = 0.01; d = 0.26) but did not significantly affect the fatigue index (52.51 ± 9.48%, PL: 49.27 ± 10.39%; p = 0.34). EMG data showed that the MPF and MDPF parameters decreased and the WT increased, but caffeine did not have a significant effect on these changes (p > 0.05). Moreover, caffeine ingestion did not significantly affect RMS changes in the selected muscles (p > 0.05). Here we showed that acute caffeine ingestion improved anaerobic performance without affecting EMG parameters in young male futsal athletes.

Effects of the Type of Exercise Training on Bone Health Parameters in Adolescent Girls: A Systematic Review.

Interventional studies offer strong evidence for exercise's osteogenic impact on bone particularly during growth. With rising osteoporosis rates in older women, enhancing bone strength early in life is crucial. Thus, investigating the osteogenic effects of different types of physical activities in young females is crucial. Despite varied findings, only two systematic reviews tried to explore this topic without examining how different types of exercise may affect bone health in adolescent girls. The first aim of this systematic review was to assess the impact of exercise training on bone health parameters in adolescent girls, and the second aim was to investigate whether the type of exercise training can modulate this effect. A systematic literature search was conducted using common electronic databases from inception - January 2023. Seven studies (355 participants) were eligible for inclusion in this systematic review. Two studies dealt with resistance training, 3 studies applied plyometric training, 1 study used team sports, and 1 study used dancing. Results indicate that plyometric training increases lumbar spine bone mass in adolescent girls. Well-designed randomized controlled trials with a proper training period (> 12 weeks) are needed to advocate a specific type of training which has the highest osteogenic effect.

Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR-expressing prostate cancer cell lines.

BACKGROUND: The androgen receptor (AR) has been studied as an approach to cancer therapy. AIMS: We used human breast cancer-derived cells with high, low, and very low expression levels of AR, in addition to prostate cancer-derived LNCaP and DU-145 cells as a positive and negative controls to examine apoptosis caused by a synthetic peptide that targets ARs. METHODS AND RESULTS: The peptide was produced to inhibit AR transactivation in breast cancer cell lines. We then measured cell viability, caspase-3 activity, and the ratio of Bax/Bcl-2. The findings indicated that the peptide (100-500 nM) in the presence of dihydrotestosterone (DHT) reduced cell growth in cells with high and low expression level of AR (p < .001), but not in cells with very low levels of AR. Treatment with 100-500 nM of peptide activated caspase-3 and increased the ratio of Bax/Bcl-2 in cells with high and low expression levels of AR. Also, increasing concentrations of the peptide (100-500 nM) reduced BrdU incorporation in the presence of DHT and promoted apoptosis in cells with high and low expression levels of AR (p < .001). CONCLUSION: The findings indicate the peptide significantly increased apoptosis in cancer cells.

Exercise training and vascular heterogeneity in db/db mice: evidence for regional- and duration-dependent effects.

Exercise training (ET) has several health benefits; however, our understanding of regional adaptations to ET is limited. We examined the functional and molecular adaptations to short- and long-term ET in elastic and muscular conduit arteries of db/db mice in relation to changes in cardiovascular risk factors. Diabetic mice and their controls were exercised at moderate intensity for 4 or 8 weeks. The vasodilatory and contractile responses of thoracic aortae and femoral arteries isolated from the same animals were examined. Blood and aortic samples were used to measure hyperglycemia, oxidative stress, inflammation, dyslipidemia, protein expression of SOD isoforms, COX, eNOS, and Akt. Short-term ET improved nitric oxide (NO) mediated vasorelaxation in the aortae and femoral arteries of db/db mice in parallel with increased SOD2 and SOD3 expression, reduced oxidative stress and triglycerides, and independent of weight loss, glycemia, or inflammation. Long-term ET reduced body weight in parallel with reduced systemic inflammation and improved insulin sensitivity along with increased SOD1, Akt, and eNOS expression and improved NO vasorelaxation. Exercise did not restore NOS- and COX-independent vasodilatation in femoral arteries, nor did it mitigate the hypercontractility in the aortae of db/db mice; rather ET transiently increased contractility in association with upregulated COX-2. Long-term ET differentially affected the aortae and femoral arteries contractile responses. ET improved NO-mediated vasodilation in both arteries likely due to collective systemic effects. ET did not mitigate all diabetes-induced vasculopathies. Optimization of the ET regimen can help develop comprehensive management of type 2 diabetes.

Spirulina Supplementation with High-Intensity Interval Training Decreases Adipokines Levels and Cardiovascular Risk Factors in Men with Obesity.

Adiposity, a state characterized by excessive accumulation of body fat, is closely linked to metabolic complications and the secretion of specific adipokines. This study explores the potential of exercise and Spirulina supplementation to mitigate these complications and modulate adipokine release associated with obesity. The primary objective of this investigation was to examine the impact of a 12-week regimen of high-intensity training combined with Spirulina supplementation on adipokine concentrations and lipid profiles in male individuals with obesity (N = 44). The participants were randomly distributed into four groups, each consisting of 11 participants: a control group (CG), a supplement group (SG), a training group (TG), and a training plus supplement group (TSG). The intervention comprised a 12-week treatment involving Spirulina supplementation (6 g capsule daily), a 12-week high-intensity interval training (HIIT) protocol with three sessions per week, or a combined approach. Following the interventions, metabolic parameters, anthropometric measurements, cardiorespiratory indices, and circulating adipokines [CRP, Sema3C, TNF-α, IL-6, MCP1, IL-8] were assessed within 48 h of the before and final training session. Statistical analyses revealed significant differences across all measures among the groups (p < 0.05). Notably, post hoc analyses indicated substantial disparities between the CG and the three interventional groups regarding body weight (p < 0.05). The combined training and supplementation approach led to noteworthy reductions in low-density lipoprotein (LDL), total cholesterol (TC), and triglyceride (TGL) levels (all p < 0.0001), coupled with an elevation in high-density lipoprotein-cholesterol (HDL-C) levels (p = 0.0001). Furthermore, adipokine levels significantly declined in the three intervention groups relative to the CG (p < 0.05). The findings from this 12-week study demonstrate that Spirulina supplementation in conjunction with high-intensity interval training reduced adipokine levels, improved body weight and BMI, and enhanced lipid profiles. This investigation underscores the potential of Spirulina supplementation and high-intensity interval training as a synergistic strategy to ameliorate obesity-related complications and enhance overall cardiometabolic well-being in obese males.

Association between "cluster of differentiation 36 (CD36)" and adipose tissue lipolysis during exercise training: a systematic review.

Fatty acid translocase (FAT/CD36) is a transmembrane glycoprotein belonging to the scavenger class B receptor family and is encoded by the cluster of differentiation 36 (CD36) gene. This receptor has a high affinity for fatty acids and is involved in lipid metabolism. An abundance of FAT/CD36 during exercise occurs in mitochondria and solitary muscles. As such, we aimed to systematically review the evidence for the relationship FAT/CD36 and adipose tissue lipolysis during exercise training. Five electronic databases were selected for literature searches until June 2022: PubMed, Web of Science, Scopus, science direct, and Google Scholar. We combined the different synonyms and used the operators ("AND", "OR", "NOT"): (CD36 gene) OR (CD36 polymorphism) OR (cluster of differentiation 36) OR (FAT/CD36) OR (fatty acid translocase) OR (platelet glycoprotein IV) OR (platelet glycoprotein IIIb) AND (adipose tissue lipolysis) OR (fatty acids) OR (metabolism lipid) OR (adipocytes) AND (physical effort) OR (endurance exercise) OR (high-intensity training). All published cross-sectional, cohort, case-control, and randomized clinical trials investigating CD36 polymorphisms and adipose tissue lipolysis during exercise in subjects (elite and sub-elite athletes, non-athletes, sedentary individuals and diabetics), and using valid methods to measure FAT/CD36 expression and other biomarkers, were considered for inclusion in this review. We initially identified 476 publications according to the inclusion and exclusion criteria, and included 21 studies investigating FAT/CD36 and adipose tissue lipolysis during exercise in our systematic review after examination of titles, abstracts, full texts, and quality assessments using the PEDro scale. There were nine studies with male-only participants, three with female-only participants, and nine studies included both female and male participants. There were 859 participants in the 21 selected studies. Studies were classified as either low quality (n = 3), medium quality (n = 13), and high quality (n = 5). In general, the data suggests an association between FAT/CD36 and adipose tissue lipolysis during exercise training. Improvements in FAT/CD36 were reported during or after exercise in 6 studies, while there were no changes reported in FAT/CD36 in 4 studies. An association between fat oxidation and FAT/CD36 expression during exercise was reported in 7 studies. No agreement was reached in 5 studies on FAT/CD36 content after dietary changes and physical interventions. One study reported that FAT/CD36 protein expression in muscle was higher in women than in men, another reported that training decreased FAT/CD36 protein in insulin-resistant participants, while another study reported no differences in FAT/CD36 in young, trained individuals with type 2 diabetes. Our analysis shows an association between FAT/CD36 expression and exercise. Furthermore, an association between whole-body peak fat oxidation and FAT/CD36 expression during exercise training was demonstrated. Systematic Review Registration: [PROSPERO], identifier [CRD42022342455].

Lower limbs micro-loading acutely attenuates repeated change-of-direction performance in male youth during small-sided soccer games.

BACKGROUND: Soccer players often wear light-weighted wearable resistance (WR) attached to different body parts during the warm-up period with the aim to improve measures of physical fitness. However, the effect of WR on physical performance is unknown. This study evaluated the effects of WR with different micro-loadings on repeated change-of-direction (RCoD) performance while executing small-sided soccer games (SSG). METHODS: Twenty male soccer players aged 16.0 ± 1.5 years (body mass 74.0 ± 7.4 kg, body-height 175.0 ± 10.0 cm) volunteered to participate in this study. Following a within-subject study design, players performed four specific warm-up protocols in randomized order with a rest of 72 h between protocols: (1) WR micro-loadings with 0.1% of body mass (WR0.1); (2) WR micro-loadings with 0.2% of body mass (WR0.2); (3) WR micro-loadings with 0.3% of body mass (WR0.3); (4) no WR (control = CONT). After the warm-up protocols, players performed 2 sets of 20-min SSG. The RCoD was collected at the 8th min of SSG (SSG 1-8 min), the 15th min of SSG1 (SSG1-15 min), and at the 15th min of SSG2 (SSG2-15 min). Outcomes included mean and total RCoD indices (i.e., mean time and total time for each condition). RESULTS: Based on the outcomes of a two-way repeated measures analysis of variance (ANOVA), WR0.1 and WR0.2 were more effective than control in dampening the decrease of RCoD's total time during SSG1-8 min, and SSG2-15 min (small ES: 0.24-0.35; p < 0.05). However, no significant differences were observed between WR0.3 and control. In addition, WR0.1 and WR0.2 significantly affected the decreases in RCoD's mean best time during SSG1 and SSG2 which was observed in the unloaded condition (CONT) and consequently displayed a lower rate of RCoD performance decrease. CONCLUSION: This study reports that wearing lower extremity WRs with micro-loads of 0.1% or 0.2% of body mass attenuates physical fatigue indicated in attenuated RCoD performance while executing SSG.

The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury.

Myocardial remodeling and dysfunction are commonly observed in type 2 diabetes mellitus (T2DM). Aerobic exercise can partly alleviate diabetes-induced myocardial dysfunction through its antioxidant actions. MOTS-c is a potential exercise mimic. This study aimed to investigate the effects of MOTS-c on improving diabetic heart function and its mechanism and to identify whether MOTS-c improved antioxidant defenses due to aerobic exercise. Herein, we established a rat model of T2DM induced by high-fat diet combined with a low-dose streptozotocin injection. Interventions were performed using intraperitoneal injections of MOTS-c (i.p. 0.5 mg/kg/day, 7 days/week) or aerobic exercise training (treadmill, 20 m/min, 60 min/day, 5 days/week) for 8 weeks. Myocardial ultrastructure was assessed using transmission electron microscopy (TEM), myocardial lipid peroxidation levels (MDA), superoxide dismutase (SOD), glutathione (GSH), and catalase (CAT) levels were assessed using colorimetric methods, and molecular analyses including MOTS-c, Kelch-like ECH-associated protein 1 (Keap1), Nuclear factor E2-related factor 2 (Nrf2), adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)and phospho-AMPK (p-AMPK) were examined using Western blot. The results showed that MOTS-c, with or without exercise, reduced myocardial ultrastructural damage and improved glucolipid metabolism and cardiac function in T2DM. Furthermore, MOTS-c increased antioxidant markers such as SOD, CAT, and the protein expression of myocardial MOTS-c, Keap1, Nrf2, and p-AMPK. MOTS-c with exercise treatment reduced myocardial MDA and increased p-AMPK significantly comparing to only exercise or MOTS-c alone. Our findings suggest that MOTS-c may be a helpful supplement for overcoming exercise insufficiency and improving myocardial structure and function in diabetes.

Physical exercise for a healthy pregnancy: the role of placentokines and exerkines.

Complications such as diabetes and preeclampsia can occur during pregnancy. Moderate-intensity exercise can prevent such complications by releasing placentokines and exerkines, such as apelin, adiponectin, leptin, irisin, and chemerin. Exercise and apelin increase thermogenesis and glucose uptake in pregnancy by activating AMPK, PI3K, PGC-1α, AKT1, UCP3, and sarcolipin. Exercise increases apelin levels to reduce preeclampsia symptoms by increasing eNOS, NO, placental growth factor (PlGF), and VEGF and decreasing levels of fms-like tyrosine kinase 1 (sFlt-1), soluble endoglin (sEng), and oxidative stress. A negative relationship has been reported between plasma leptin and VO2peak/kg and VO2peak in women with gestational diabetes. In active women, decreases in leptin levels reduce the risk of preeclampsia by ~ 40%. Higher adiponectin levels are associated with greater physical activity and lead to increased insulin sensitivity. Increased adiponectin levels in preeclampsia and exercise counteract inflammatory and atherogenic activities while also having vascular protective effects. Exercise increases irisin levels that correlate negatively with fasting glucose, insulin concentration, and glycosylated hemoglobin levels. Irisin augments mRNA expression levels of UCP1 and cell death-inducing DNA fragmentation factor-like effector A (cidea) to cause browning of adipose tissue, increased thermogenesis, and increased energy consumption. Irisin concentrations in mothers with preeclampsia in the third trimester negatively correlate with systolic and diastolic blood pressure. Expression levels of chemerin, IL-6, and TNF-α are increased in gestational diabetes, and the increases in chemerin in late pregnancy positively correlate with the ratio of sFlt-1 to PlGF as a marker of preeclampsia. The effects of physical exercise on placentokines and exerkines in women at various stages of pregnancy remain poorly understood.

The effects of ALK5 inhibition and simultaneous inhibition or activation of HIF-1α in melanoma tumor growth and angiogenesis.

BACKGROUND: Hypoxia is the most common signature of the tumor microenvironment that drives tumorigenesis through the complex crosstalk of a family of transcription factors called hypoxia-inducible factors (HIFs), with other intercellular signaling networks. Hypoxia increases transforming growth factor-beta (TGF-ß) expression. TGF-ß and HIF-1α play critical roles in several malignancies and their interactions in melanoma progression remain unknown. Therefore, the aim of this study was to assess the impact of inhibiting activin receptor-like kinase-5 (ALK5), a TGF-ß receptor, on the response to HIF-1α activation or inhibition in melanoma tumor progression. MATERIALS AND METHODS: Tumors were induced in C57BL/6J mice by subcutaneous inoculation with B16F10 melanoma cells. Mice were divided into HIF-1α inhibitor, ALK5 inhibitor (1 mg/kg) and HIF-1α inhibitor (100 mg/kg), ALK5 inhibitor, HIF-1α activator (1000 mg/kg), HIF-1α activator and ALK5 inhibitor, and control groups to receive inhibitors and activators through intraperitoneal injection. The expression of E-cadherin was evaluated by RT-qPCR. Vessel density and platelet-derived growth factor receptor beta (PDGFR)-ß+ cells around the vessels were investigated using immunohistochemistry. RESULTS: The groups receiving HIF-1α inhibitor and activator showed lower and higher tumor growth compared to the control group, respectively. E-cadherin expression decreased in all groups compared to the control group, illustrating the dual function of E-cadherin in the tumor microenvironment. Vascular density was reduced in the groups given HIF-1α inhibitor, ALK5 inhibitor, and ALK5 and HIF-1α inhibitor simultaneously. The percentage of PDGFR-ß+ cells was reduced in the presence of HIF-1α inhibitor, ALK5 inhibitor, HIF-1α and ALK5 inhibitors, and upon simultaneous treatment with HIF-1α activator and ALK5 inhibitor. CONCLUSION: Despite increased expression and interaction between TGF-ß and HIF-1α pathways in some cancers, in melanoma, inhibition of either pathway alone may have a stronger effect on tumor inhibition than simultaneous inhibition of both pathways. The synergistic effects may be context-dependent and should be further evaluated in different cancer types.

Regular soccer training improves pulmonary diffusion capacity in 6 to 10 year old boys.

BACKGROUND: Soccer is one of the most attractive sports around the globe for children and adolescents, and the benefits of soccer training are often shown. Due to the intermittent character of soccer with random changes between high-intensity activity and low-intensity play, athletes' aerobic (respiratory) capacity is specifically stimulated. However, little is known about the effects of regular soccer practice on pulmonary diffusion capacity (TL) in young players, even though it is the most popular sport in the world. OBJECTIVES: To analyze the effects of 28 weeks of regular soccer training versus a non-activity control period on the TL, the alveolar-capillary membrane diffusion capacity (DM) as well as the capillary blood volume (Vc) in healthy prepubertal boys aged 6 to 10 years. METHODS: For this purpose, boys were randomly assigned to a soccer training group (SG, n = 40) or a control group (CG, n = 40). Pre and post-intervention, all participants performed an all-out graded bicycle ergometer test to measure maximal oxygen uptake (VO2max) and maximal aerobic power (MAP). A respiratory maneuver was performed at rest and just at the end of the test to measure the TL for carbon monoxide (TLCO) and nitric oxide (TLNO), DM, as well as Vc. RESULTS: There were no significant baseline between-group differences for any of the assessed parameters (p > 0.05). Significant group-by-time interactions were found for most pulmonary parameters measured at rest (p < 0.05), with effect size (ES) values ranging from small-to-large (0.2 < ES < 4.0), except for VA (p = 0.3, ES = 0.006). Post-hoc tests indicated significant DM (p < 0.05; 0.2 < ES < 4.0), TLNO (p < 0.01; 0.22 < ES < 4.0), TLCO (p < 0,01; 0.24 < ES < 4.0) and Vc (p = 0.01; 0.404 < ES < 0.6) improvements for SG but not CG. Significant group-by-time effects were identified for HRmax and VO2max (p < 0.001; ES = 0.5 and p = 0.005; ES = 0.23 respectively). The post-hoc analyses indicated a significant decrease in HRmax and a significant increase in VO2max in the SG (p < 0.001; ES = 0.5 and p = 0.005, ES = 0.23, respectively) but not in CG. Values for TLCO increased by almost 20%; Vc of 14% DM of 8% and VA of 10% at the end of maximal exercise in SG. Furthermore, the percentage improvement was less notable in the control group (7.5% for TLCO; 2% for Vc; 5% for DM and 4% for VA). CONCLUSION: Regular soccer training significantly improves pulmonary vascular function and increases DM and Vc after exercise in prepubertal boys. The observed adaptations are most likely due to better recruitment of additional pulmonary capillary function. However, the stepwise linear regression analyses indicated that increases in pulmonary vascular function were not related to improvements in VO2max and MAP.

Neuroprotective effects of ivermectin against transient cerebral ischemia-reperfusion in rats.

Stroke is a leading cause of disability and death worldwide. Ivermectin is a broad-spectrum anti-parasitic agent with potential anti-bacterial, anti-viral, and anti-cancer effects. However, the effects of ivermectin on the brain are poorly described. This study examined the effects of ivermectin on cerebral ischemia-reperfusion (IR) in rats. A rat model of transient global IR was induced by bilateral carotid artery occlusion for 20 min. Rats received ivermectin (2 mg/kg/day, ip) one hour after inducing cerebral IR for three consecutive days at 24-h intervals. Next, we examined the effects of ivermectin on brain infarction, histopathology, malondialdehyde levels, myeloperoxidase activity, spatial learning and memory, and phospho-AMPK protein levels. The results showed that ivermectin reduced brain infarct size (P < 0.001) and histopathological changes such as cerebral leukocyte accumulation and edema (P < 0.05) compared to untreated rats with IR. Treatment with ivermectin also decreased myeloperoxidase activity (P < 0.01) and malondialdehyde levels (P < 0.05) while increasing AMPK activity (P < 0.001), memory, and learning compared to the untreated IR group. Overall, we show for the first time that ivermectin conferred neuroprotective effects in a rat model of cerebral IR. Our results indicate that three days of treatment with ivermectin reduced brain infarct size, lipid peroxidation, and myeloperoxidase activity and improved memory and learning in rats with cerebral IR. These effects likely occurred via AMPK-dependent mechanisms.

Supplementation with spinach-derived thylakoid augments the benefits of high intensity training on adipokines, insulin resistance and lipid profiles in males with obesity.

Introduction: This study investigated the effects of 12 weeks of high-intensity functional training (HIFT) combined with spinach-derived thylakoid supplementation on some selected Adipokines and insulin resistance in males with obesity. Method: Sixty-eight participants (mean age: 27.6 ± 8.4 yrs.; mean height: 168.4 ± 2.6 cm; mean weight: 95.7 ± 3.8 kg, mean BMI: 32.6 ± 2.6 kg/m2) were randomly divided into four groups of 17 per group: Control group (CG), Supplement group (SG), Training group (TG), and Training + supplement group (TSG). Following baseline measurements, the two training groups (TG and TSG) started the 12 weeks of exercise training program (3 sessions per week). A total of 36 sessions lasting up to 60 min were included in the HIFT program using the CrossFit program. The eligible participants received 5 g/day of thylakoid-rich spinach extract or matching placebo as 5 g/day of raw corn starch (one sachet, 30 min before lunch) for 12 weeks. Baseline assessments were obtained 48 hours before the start of the training protocols and 48 hours after the last training session in all groups. Results: There were significant interactions (p<0.001 for all) between exercise and time for adiponectin (ES:0.48), leptin (ES:0.46), resistin (ES:0.3), omentin (ES:0.65), vaspin (ES:0.46), visfatin (ES:0.62), apelin (ES:0.42), RBP4 (ES:0.63), chemrin (0.36) and semaphorin3c (ES: 0.5). Plasma levels of semaphorin3c were significantly correlated (p<0.05) with body weight (r= 0.57), BMI (r= 0.43), FFM (r= -0.612), FAT (r= 0.768), VO2peak (r=-0.53), insulin (r= 0.756), glucose (r= 0.623), and HOMA-IR (r= 0.727). There were also significant group differences in insulin (ES: 0.77), glucose (ES: 0.21), and HOM-IR (ES: 0.44) (p<0.05). Discussion: Our findings indicate that 12 weeks of HIFT supplemented with spinach-derived thylakoid reduced levels of leptin, resistin, vaspin, visfatin, apelin, RBP4, chemrin, semaphorin3c and insulin resistance while increasing adiponectin and omentin levels in men with obesity.