Knee Laxities Changes with Sex-steroids throughout the Menstrual Cycle Phases in Athlete and Non-athlete Females.

Objective: Our study investigated changes of knee laxities in athletes and non-athletes females and relationship between knee laxity and sex-steroid at menstrual cycle phases. Methods: Forty six healthy females, twenty four athletes and twenty two non-athletes not on hormone contraceptive pills, had no previous knee injuries and with regular menstrual cycles for 3 consecutive months, participated in the study. Medial and lateral knee laxities were determined by varus-valgus tests at follicular, ovulatory and luteal phases. Serum level of relaxin, estrogen, progesterone and testosterone were determined by ELISA and radioimmunoassay. Results: Knee laxities in athletes and non-athletes at 0° and 20° flexion were the highest in luteal phase with non-athletes possess greater laxity than athletes. Positive correlation between progesterone and relaxin levels with knee laxities were observed. Meanwhile, the levels of both hormones were highest in the luteal phase. Conclusion: Increased medial and lateral knee laxities in athletes and non-athletes associated with high serum progesterone and relaxin levels in luteal phase may contribute toward increased risk of non-contact knee injury. However, lower knee laxity in athletes than non-athletes suggest that exercise could be a protective factor.

Telocytes response to cardiac growth induced by resistance exercise training and endurance exercise training in adult male rats.

Telocytes are interstitial cells found in different tissues, including cardiac stem cell niches. The purpose of this study was to investigate the response of the telocytes to the cardiac growth that occurs in response to resistance and endurance exercise trainings using rats distributed into control, endurance, and resistance training groups. Results revealed that the ratio of heart weight to body weight, cardiomycyte number, cardiomyocyte area, thickness of the left ventricular wall were significantly higher in the training groups compared to the control group. We observed increment in the cardiomyocytes surface area and thickness of the left ventricular wall in the resistance-training group than endurance-training group. We conclude that both resistance and endurance exercise trainings will lead to an increased number of cardiac telocytes, consequently, promote activity of the cardiac stem cells, and results in physiological cardiac growth, and this response does not seem to depend on the type of exercise.

Interaction of exercise training with taurine attenuates infarct size and cardiac dysfunction via Akt-Foxo3a-Caspase-8 signaling pathway.

This research aimed to investigate the synergistic protective effect of exercise training and taurine on Akt-Foxo3a-Caspase-8 signaling related to infarct size and cardiac dysfunction. Therefore, 25 male Wistar rats with MI were divided into five groups: sham (Sh), control-MI(C-MI), exercise training-MI(Exe-MI), taurine supplementation-MI(Supp-MI), and exercise training + taurine-MI(Exe + Supp-MI). The taurine groups were given a 200 mg/kg/day dose of taurine by drinking water. Exercise training was conducted for 8 weeks (5 days/week), each session alternated 2 min with 25-30% VO2peak and 4 min with 55-60% VO2peak for 10 alternations. Then, the left ventricle tissue samples were taken from all groups. Exercise training and taurine activated Akt and decreased Foxo3a. Expression of the caspase-8 gene was increased in cardiac necrosis after MI, While, after 12 weeks of intervention decreased. Results exhibited that exercise training combined with taurine has a greater effect than either alone on activating the Akt-Foxo3a-caspase signaling pathway (P < 0.001). MI-induced myocardial injury leads to increase collagen deposition (P < 0.001) and infarct size and results in cardiac dysfunction via reduced stroke volume, ejection fraction, and fractional shortening (P < 0.001). Exercise training and taurine improved cardiac functional parameters (SV, EF, FS) and infarct size (P < 0.001) after 8 weeks of intervention in rats with MI. Also, the interaction of exercise training and taurine has a greater effect than alone on these variables. Interaction of exercise training with taurine supplementation induces a general amelioration of the cardiac histopathological profiles and improves cardiac remodeling via activating Akt-Foxo3a-Caspase-8 signaling with protective effects against MI.

High-intensity interval training ameliorates endothelial dysfunction through adropin, nitric oxide, MR-proADM, and copeptin changes in overweight subjects.

PURPOSE: The purpose of this study was to determine adropin, NO, MR-proADM, and copeptin changes following four different types of high-intensity interval training (HIIT) in men with overweight. METHODS: In the current study, 45 overweight participants were included in the pre-intervention assessments and randomly assigned to the following groups: (1) control, (2) HIIT bike, (3) HIIT short-treadmill, and (4) HIIT long-treadmill groups. The participants were given 10-min sessions of HIIT intervention between 85 and 95% of VO2peak, followed by 1-min inactive recovery at three sessions/week for 8 weeks. Body composition, VO2peak, ultrasound imaging, diabesity-related risk factors, adropin, NO, MR-proADM, and copeptin were also assessed before and following the HIIT interventions. RESULTS: There was a statistically significant elevation in adropin and NO levels (p < 0.05), while MR-proADM and copeptin were notably more decreased than those of the control group following the 8 weeks of HIIT interventions (p < 0.01). However, no statistically significant decrease was observed in carotid/femoral intima-media thickness (c/f-IMT) values following the 8-week HIIT interventions, while statistically significant reductions were demonstrated in participants who had no atherosclerotic plaque or IMT < 0.9 mm (p < 0.05). CONCLUSIONS: In conclusion, HIIT had a greater effect on IMT remodeling of the femoral artery than of the carotid artery. Decreased MR-proADM and copeptin and increased adropin levels might act as a physiological surrogate of endothelial dysfunction through increased NO-related signaling pathways in participants with overweight following high-intensity interval training.

The effect of 8 weeks of combined interval (resistance-interval training) and combined endurance (endurance-resistance training) on plasma levels of adropin and nitric oxide in males with high blood pressure.

INTRODUCTION: Nitric oxide (NO) is a vasodilator that plays an important role in blood pressure control. The purpose of the present study was to compare the effect of 8 weeks of resistance-interval and endurance-resistance trainings on plasma levels of adropin and NO in males with hypertension. METHOD: Forty-five patients with hypertension were recruited and divided into 3 groups of control (age = 51.1 ± 6.4 years, body mass = 80.4 ± 9.2 kg), resistance-interval training (age = 50.7 ± 5.5 years, body mass = 78.1 ± 11 kg), and endurance-resistance training (age = 52.8 ± 6.1 years, body mass = 79.6 ± 9.2 kg). The resistance training program was performed in 2 sets, 10 to 15 repetitions, with 50% intensity of one repetition maximum. Increasing endurance training was performed for 30-40 min at 60-70% of maximum heart rate (HRmax) on the bike. The high-intensity interval training program consisted of 4 intervals of 80 to 90% of HRmax and 3-min recovery periods of 60 to 70% of HRmax. Blood samples were collected 1 week before the start of the training program and 48 h after the last training session. Plasma levels of adropin and nitrite/nitrate were measured by ELISA before and after the exercise interventions. RESULTS: Eight weeks of resistance-interval and endurance-resistance trainings increased plasma levels of adropin and NO and decreased blood pressure (P ≤ 0.05). Furthermore, plasma levels of adropin increased in both exercise groups, whereas NO levels increased only in the endurance-resistance training. Systolic blood pressure decreased in the resistance-interval training (P ≤ 0.05) while it remained unchanged in the endurance-resistance group. CONCLUSION: Resistance-interval and endurance-resistance trainings are effective in decreasing blood pressure by increasing cardiorespiratory capacity and plasma levels of adropin and NO.

Exercise attenuates myocardial fibrosis and increases angiogenesis-related molecules in the myocardium of aged rats.

OBJECTIVES: The present study aimed to investigate the effect of two different exercise training protocols on myocardial fibrosis and the expression of some growth factors in aged rats. METHOD: Twenty-four male Wistar rats were randomly assigned to high-intensity interval training (HIIT) group, continuous exercise training (CET) group, and the control group. After 6 weeks of experiment, mRNA levels of fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), adropin proteins, and myocardial fibrosis were assessed. RESULTS: HIIT and CET induced a significant increase in the FGF-2 and adropin and a decrease in the myocardial fibrosis in compared with the control group. HIIT induced a significant increase in the VEGF if compared with the control group. There was no significant difference between CET and control group. CONCLUSION: Six weeks of HIIT and CET attenuated age-related myocardial fibrosis thereby an increase in angiogenesis-related molecules in cardiac and endothelial tissues.

High-Intensity Interval Training in Patients with Pulmonary Embolism: A Randomized Controlled Trial.

PURPOSE: High-intensity interval training (HIIT) appears to be safe and effective in cardiovascular diseases. However, there is a paucity of data on the effect of HIIT for patients with acute pulmonary embolism (PE). The present randomized controlled trial (RCT) therefore examined the efficiency and safety of HIIT in patients with acute PE. METHODS: In single-center parallel open-label RCT, 24 patients (5 women) discharged recently with a diagnosis of intermediate-high-risk acute PE were randomized (1:1) to supervised HIIT (n = 12) or control (n = 12) group. The primary outcomes were exercise capacity evaluated in terms of the estimated maximal oxygen uptake (eV˙O2max), lung function (forced expiratory volume in 1 s [FEV1]), right ventricular (RV) function (RV/left ventricular diameter [LV] ratio), and health-related quality of life (HRQoL). Safety was the secondary outcome. RESULTS: Eight weeks of HIIT improved eV˙O2max (+65%, P < 0.001), FEV1 (%) (+17%, P = 0.031), and RV/LV ratio diameter (-27%, P = 0.005), as well as HRQoL. All patients in the HIIT group tolerated exercise training without serious adverse events. The control group did not improve (P > 0.05) eV˙O2max, RV/LV ratio diameter, or HRQoL; however, FEV1 (%) was slightly reduced (-6%, P = 0.030). CONCLUSIONS: The present RCT of a tailored center-based HIIT intervention provides preliminary evidence that this intervention could improve exercise capacity, lung function, RV function, and HRQoL without serious adverse events, which could provide marked clinical benefits after PE. Further larger multicenter randomized controlled studies are needed to confirm these promising findings.

Voluntary wheel running promotes improvements in biomarkers associated with neurogenic activity in adult male rats.

In rodents, hippocampal neurogenesis and synaptogenesis phenomena are affected by exercise. However, the role of exercise parameters such as intensity, duration, and mode on molecular mechanisms involved in these processes has not been elucidated. In this study, we evaluated the effects of different intensities and modes of running on the expression of genes contributing to neuronal differentiation and synapse formation in the hippocampus of adult male rats. Adult male Wistar rats (n = 24) were randomly divided into control, low-intensity running (LIR), high-intensity running (HIR), and the voluntary wheel running (WR) conditions. Changes in the expression of microRNA-124 (miR-124), microRNA-132 (miR-132), and their respective targets, were analyzed using quantitative RT-PCR and Western blotting techniques. Our results showed that WR compared to treadmill running increased miR-124 and miR-132 expression, while reducing the expression of their respective targets, glucocorticoid receptor (GR), SRY-Box 9 (SOX9), and GTP-activated protein P250 (P250GAP). Differences in expression levels were statistically significant (ps < 0.05), except for the expression of GR in HIR (P = 0.09). Moreover, the expression level of gene coding for the transcription factor cAMP-response element binding protein (CREB) was significantly higher in the WR group compared to the treadmill running groups (P = 0.001). Western blotting techniques indicated that the level of the CREB protein was higher in WR compared to the other groups qualitatively. These findings demonstrated a more dramatic effect for voluntary running on biomarkers that are associated with stimulating neurogenesis and synapse formation in the hippocampus of male rats compared with forced treadmill running. In addition, greater positive effects were observed for lower-intensity treadmill running as compared with high-intensity running.

Aerobic Training-induced Upregulation of YAP1 and Prevention of Cardiac Pathological Hypertrophy in Male Rats.

BACKGROUND: Pathological hypertrophy is one of the negative consequences of cardiac sympathetic hyperactivity. Recent studies have shown that YAP1 plays a critical role in cardiomyocytes hypertrophy. Considering the preventive role of exercise training in cardiovascular diseases, the present study was conducted to examine the effect of aerobic exercise training on YAP1 gene expression and its upstream components. METHODS: Eighteen male Wistar rats were randomly divided into aerobic training and control groups. Aerobic training was performed one hour/day, five days per week, for eight weeks, on a treadmill at 65-75% VO2 max. Pathological hypertrophy was induced by injecting 3 mg/kg-1 of isoproterenol for seven days. The left ventricle was separated, and YAP1, 3-mercaptopyruvate sulfurtransferase (MST), large tumor suppressor (LATS), and mitogen-activated protein 4 kinase (MAP4K) gene expressions were assessed and YAP1 protein levels were also assessed by western blotting. Cell apoptosis was detected by TUNEL assays. The between-group differences were evaluated using the T-test and P value <0.05 was considered statistically significant. RESULTS: There were no significant between-group differences in MST gene expression (P = 0.061); meanwhile, in the training group, LATS and Map4K expressions were suppressed, followed by a significant increase in YAP1 expression (P < 0.001). Compared to the control group, the left ventricular weight increased significantly in the training group while the cardiomyocyte apoptosis decreased. CONCLUSIONS: The results showed that, by reducing LATS, aerobic training-induced YAP1 upregulation can help prevent the propagation of cardiomyocyte apoptosis due to pathological conditions.

Unilateral Knee and Ankle Joint Fatigue Induce Similar Impairment to Bipedal Balance in Judo Athletes.

The purpose of this study was to compare the effects of unilateral ankle fatigue versus the knee muscles with and without vision on bipedal postural control. Elite judo athletes who competed at the national level with at least 10 years of training experience, were randomised into KNEE (n = 10; 20 ± 2 years) and ANKLE (n = 9; 20 ± 3 years) groups, who performed dynamic isokinetic fatiguing contractions (force decreased to 50% of initial peak torque for three consecutive movements) of the knee flexors and extensors or ankle dorsiflexors and plantar flexors, respectively. Static bipedal postural control (French Posturology Association normative standards) with eyes open and eyes closed was examined before and immediately after the fatiguing task. Postural variables examined were the centre of pressure (CoP) sway in the medio-lateral and antero-posterior directions, total CoP area sway and CoP sway velocity. Although unilateral ankle and knee fatigue adversely affected all bipedal postural measures, with greater disturbances with eyes closed, there were no significant main group or interaction effects between KNEE and ANKLE groups. Unilateral lower limb fatigue adversely affected bipedal balance, with knee extension/flexion fatigue affecting bipedal postural control to a similar extent as unilateral ankle dorsiflexion/plantar flexion fatigue. Hence unilateral fatigue can affect subsequent bilateral performance or also have implications for rehabilitation exercise techniques. Our findings may be limited to judo athletes as other populations were not tested.

Effects of six weeks of resistance-endurance training on microRNA-29 expression in the heart of ovariectomised rats.

INTRODUCTION: Heart disease risk rises with age. However, women's symptoms become more pronounced following the onset of menopause. The aim of the present study was to evaluate the effects of six weeks of combined resistance-endurance (RE) training on microRNA-29 expression in the heart of ovariectomised rats. MATERIAL AND METHODS: Thirty female Wistar rats were divided into three groups: 1) sham (SHAM); 2) ovariectomy (OVX); and 3) OVX with RE training (OVX + RE). The effects of these treatments on cardiac microRNA-29 expression were measured using real-time PCR. Data were analysed using a 2 × 3 ANOVA and Tukey post-hoc comparisons and presented as mean ±SEM. RESULTS: Ovariectomy resulted in a significant down-regulation in the heart microRNA-29 gene expression of OVX (0.265 ±0.031 fold changes), OVX + RE (0.699 ±0.038 fold changes) in animals vs. sham animals (1 ±0 fold changes; all, p < 0.05) following six weeks of treatment. However, microRNA-29 expression in the OVX + RE group was significantly greater than in the OVX group (p < 0.05). CONCLUSIONS: Our findings suggest that the six weeks of regular RE training attenuate the reduction in heart muscle microRNA-29 expression observed in ovariectomised rates. If our findings carry over to humans, such an exercise regimen could be beneficial to the cardiovascular disease risk in women during menopause.

Effect of combined endurance-resistance training and soy extract supplementation on expression of eNOS gene in ovariectomized rats.

INTRODUCTION: Menopause is an independent risk factor for cardiovascular disease (CVD). Physical exercise and soybean diets have been suggested to reduce the risk of CVD in postmenopausal women. The purpose of this study was to investigate the effects of combined resistance and endurance (RE) training and soy extract (SOY) supplementation, both known to improve endothelial function, on expression of the eNOS gene in the heart of ovariectomized (OVX) rats. MATERIAL AND METHODS: Fifty female Wistar rats were divided into five groups: 1) sham (SHAM); 2) ovariectomy (OVX); 3) ovariectomy with soy extract supplementation (OVX + SOY); 4) OVX with RE training (OVX + RE); 5) and ovariectomy plus RE training with soy extract supplementation (OVX + RE + SOY). RE training and soy extract supplementation were administered alone or in combination for 6 weeks. The effects of these treatments on cardiac eNOS expression were measured using real-time PCR. RESULTS: Ovariectomy down-regulated cardiac eNOS gene expression; however, 6 weeks of SOY treatment or RE training reversed this effect (p ≤ 0.05). The combination of SOY plus RE was greater than RE or SOY alone in reversing estrogen-deficiency-caused eNOS down-regulation (p ≤ 0.05). CONCLUSIONS: Our data suggest that the combinatory regimen of soy extract supplementation and regular RE training may be more beneficial to cardiovascular disease risk in a menopause rat model than either exercise or soy supplementation alone.

Anticancer activity of a monobenzyltin complex C1 against MDA-MB-231 cells through induction of Apoptosis and inhibition of breast cancer stem cells.

In the present study, we examined the cytotoxic effects of Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, and C1 on MDA-MB-231 cells and derived breast cancer stem cells from MDA-MB-231 cells. The acute toxicity experiment with compound C1 revealed no cytotoxic effects on rats. Fluorescent microscopic studies using Acridine Orange/Propidium Iodide (AO/PI) staining and flow cytometric analysis using an Annexin V probe confirmed the occurrence of apoptosis in C1-treated MDA-MB-231 cells. Compound C1 triggered intracellular reactive oxygen species (ROS) production and lactate dehydrogenase (LDH) releases in treated MDA-MB-231 cells. The Cellomics High Content Screening (HCS) analysis showed the induction of intrinsic pathways in treated MDA-MB-231 cells, and a luminescence assay revealed significant increases in caspase 9 and 3/7 activity. Furthermore, flow cytometric analysis showed that compound C1 induced G0/G1 arrest in treated MDA-MB-231 cells. Real time PCR and western blot analysis revealed the upregulation of the Bax protein and the downregulation of the Bcl-2 and HSP70 proteins. Additionally, this study revealed the suppressive effect of compound C1 against breast CSCs and its ability to inhibit the Wnt/ß-catenin signaling pathways. Our results demonstrate the chemotherapeutic properties of compound C1 against breast cancer cells and derived breast cancer stem cells, suggesting that the anticancer capabilities of this compound should be clinically assessed.

Purslane (Portulaca oleracea) Seed Consumption And Aerobic Training Improves Biomarkers Associated with Atherosclerosis in Women with Type 2 Diabetes (T2D).

The aim of this study was to investigate the responses of atherosclerosis plaque biomarkers to purslane seed consumption and aerobic training in women with T2D. 196 women with T2D were assigned into; (1) placebo (PL), (2) aerobic training+placebo (AT + PL), 3) purslane seeds (PS), aerobic training+purslane seeds (AT + PS). The training program and purslane seeds consumption (2.5 g lunch and 5 g dinner) were carried out for 16 weeks. The components of purslane seed were identified and quantified by GC-MS. Blood samples were withdrawn via venipuncture to examine blood glucose, low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, triglycerides (TG), creatinine, urea, uric acid, NF-κB, GLP1, GLP1R, TIMP-1, MMP2, MMP9, CRP, CST3, and CTSS expressions. Blood glucose, LDL, cholesterol, TG, creatinine, urea, and uric acid levels in the (P), (AT), and (AT + PS) groups were significantly decreased compared to the pre-experimental levels or the placebo group, while HDL, significantly increased. Furthermore, the protein and mRNA levels of NF-κB, TIMP-1, MMP2 &9, CRP, CST3, and CTSS in the (P), (AT), (AT + PS) significantly decreased compared to pre-experimental or the placebo group, while level of GLP1 and GLP1-R increased drastically. Findings suggest that purslane seed consumption alongside exercising could improve atherosclerosis plaque biomarkers through synergistically mechanisms in T2D.

Changes in Knee Laxity and Relaxin Receptor Isoforms Expression (RXFP1/RXFP2) in the Knee throughout Estrous Cycle Phases in Rodents.

The changes in knee laxity and relaxin receptor expression at different phases of rodent estrous cycle are not known. Here, changes in the parameter were investigated in rats at different phases of the estrous cycle. Estrous cycle phases of intact female rats were determined by cytological examination of the vaginal smear. Following phase identification, blood was collected for serum hormone analyses. Knee passive range of motion (ROM) was determined by using a digital miniature goniometer. The animals were then sacrificed and patellar tendon, collateral ligaments and hamstring muscles were harvested for relaxin/insulin-like family peptide receptor 1 and 2 (RXFP1/RXFP2) analyses. Knee passive ROM was the highest at proestrus followed by diestrus and the lowest at estrus. Estrogen level was the highest at proestrus while progesterone and relaxin levels were the highest at diestrus. A strong correlation was observed between relaxin and progesterone levels. At proestrus, expression of RXFP1 and RXFP2 proteins and mRNAs were the highest at proestrus followed by diestrus and estrus. The finding shows that higher level of progesterone and relaxin in diestrus might be responsible for higher laxity of knee joint in rats.

Monobenzyltin Complex C1 Induces Apoptosis in MCF-7 Breast Cancer Cells through the Intrinsic Signaling Pathway and through the Targeting of MCF-7-Derived Breast Cancer Stem Cells via the Wnt/ß-Catenin Signaling Pathway.

Monobenzyltin Schiff base complex, [N-(3,5-dichloro-2-oxidobenzylidene)-4-chlorobenzyhydrazidato](o-methylbenzyl)aquatin(IV) chloride, C1, is an organotin non-platinum metal-based agent. The present study was conducted to investigate its effects on MCF-7 cells with respect to the induction of apoptosis and its inhibitory effect against MCF-7 breast cancer stem cells. As determined in a previous study, compound C1 revealed strong antiproliferative activity on MCF-7 cells with an IC50 value of 2.5 µg/mL. Annexin V/propidium iodide staining coupled with flow cytometry indicated the induction of apoptosis in treated cells. Compound C1 induced apoptosis in MCF-7 cells and was mediated through the intrinsic pathway with a reduction in mitochondrial membrane potential and mitochondrial cytochrome c release to cytosol. Complex C1 activated caspase 9 as a result of cytochrome c release. Subsequently, western blot and real time PCR revealed a significant increase in Bax and Bad expression and a significant decrease in the expression levels of Bcl2 and HSP70. Furthermore, a flow cytometric analysis showed that treatment with compound C1 caused a significant arrest of MCF-7 cells in G0/G1 phase. The inhibitory analysis of compound C1 against derived MCF-7 stem cells showed a significant reduction in the aldehyde dehydrogenase-positive cell population and a significant reduction in the population of MCF-7 cancer stem cells in primary, secondary, and tertiary mammospheres. Moreover, treatment with C1 down-regulated the Wnt/ß-catenin self-renewal pathway. These findings indicate that complex C1 is a suppressive agent of MCF-7 cells that functions through the induction of apoptosis, cell cycle arrest, and the targeting of MCF-7-derived cancer stem cells. This work may lead to a better treatment strategy for the reduction of breast cancer recurrence.