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.

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.

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.

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.

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.

Mental health, eating habits and physical activity levels of elite Iranian athletes during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has changed life styles of millions of people worldwide. This study investigated changes in the health, physical activity levels and eating habits of elite athletes during the COVID-19 pandemic lockdown in Iran. METHODS: 383 (248 female and 135 male) elite athletes (168.82 ± 0.07 cm; 63.92 ± 7.42 kg; the body mass index (BMI): 22.3 ± 0.78 kg/m2) participated in this study. The International Physical Activity Questionnaire (IPAQ), Depression Anxiety Stress Scales (DASS-21) and the Impact of Event Scale-Revised (IES-R) study tools were used to measure levels of physical activity and mental health status, respectively. The Emotional Eater Questionnaire (EEQ) was used to assess food consumption related to emotion. Pearson and Spearman correlation analysis test were used in data analysis. RESULTS: Levels of depression and stress were mild and moderate, while levels of anxiety were severe and very severe in most elite athletes. There were levels of low emotional eating by elite athletes during the COVID-19 pandemic. Physical activity levels were negatively correlated with psychological mood measures (p≤0.05), while there were positive correlations between emotional eating behaviours and psychological mood measures (moderate correlation; p≤0.01) and light physical activity levels (weak correlation; p≤0.05). CONCLUSION: This study provides the first preliminary evidence showing that the COVID-19 lockdown conditions negatively influenced the eating habits and levels of physical activity and mental health in elite athletes. Regular high intensity physical activity as health strategy in elite athletes and the general population remains a strategy to improve overall health during the COVID-19 pandemic. Additionally, these findings suggest the need to devise strategies to improve the life styles of elite athletes during pandemics such as the Covid-19 pandemic.

CONTEXTE: La pandémie de COVID-19 a changé les modes de vie de millions de personnes dans le monde. Cette étude a examiné certains indicateurs de bonne santé, les niveaux d'activité physique et les habitudes alimentaires d'athlètes Elite iraniens pendant le confinement lié à la pandémie de COVID-19.Méthodes : 383 (248 femmes et 135 hommes) athlètes élites (168,82 ± 0,07 cm ; 63,92 ± 7,42 kg ; indice de masse corporelle (IMC) : 22,3 ± 0,78 kg/m2) ont participé à cette étude. Le questionnaire international sur l'activité physique (IPAQ), l'échelle DASS-21 (Depression Anxiety Stress Scales) et les scores de l'auto-questionnaire Impact of Event Scale-Revised (IES-R) ont été utilisés pour mesurer les niveaux respectifs d'activité physique et de l'état de santé mentale. L'Emotional Eater Questionnaire (EEQ) a été utilisé pour évaluer les altérations de la prise alimentaire liées à l'émotion. Le test d'analyse de corrélation de Pearson et Spearman a été utilisé pour l'analyse des données.Résultats : Les niveaux de dépression et de stress étaient légers et modérés, tandis que les niveaux d'anxiété étaient sévères à très sévères chez la plupart des athlètes élites. Il y avait des niveaux de faible alimentation d'origine émotionnelle chez ces athlètes pendant la pandémie de COVID-19. Les niveaux d'activité physique étaient corrélés négativement avec les mesures de l'humeur psychologique (p≤0,05), tandis qu'il y avait des corrélations positives entre les comportements alimentaires émotionnels et les mesures de l'humeur psychologique (corrélation modérée ; p≤0,01) et les niveaux d'activité physique légère (faible corrélation ; p≤0,05). CONCLUSION: Cette étude apporte une preuve préliminaire que les conditions de confinement liées au COVID-19 ont influencé négativement les habitudes alimentaires et les niveaux d'activité physique et de santé mentale chez des athlètes élites. L'activité physique régulière à haute intensité aussi bien chez les athlètes élites que pour la population générale reste une stratégie pour améliorer la santé globale pendant la pandémie de COVID-19. De plus, ces résultats suggèrent la nécessité de concevoir des stratégies pour améliorer les styles de vie des athlètes élites lors de pandémies, telles que celle de Covid-19.

Morphine promotes migration and lung metastasis of mouse melanoma cells.

BACKGROUND: Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. METHODS: Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 µM) or in combination with a TLR4 inhibitor (morphine10 µM +CLI-095 1µM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg-1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. RESULTS: Morphine (0.1, 1, and 10 µM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 µM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). CONCLUSION: Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

MOTS-c and aerobic exercise induce cardiac physiological adaptation via NRG1/ErbB4/CEBPß modification in rats.

AIMS: To determine the effects of the mitochondrial open reading frame of the 12S ribosomal RNA type-c (MOTS-c) and aerobic exercise on cardiac structure and function and explore the role of neuregulin-1 (NRG1)- ErbB2 receptor tyrosine kinase 4(ErbB4)- CCAAT-enhancer binding protein ß (C/EBPß) in cardiac physiological adaptation induced by MOTS-c and aerobic training. MAIN METHODS: We used Hematoxylin-Eosin staining(HE)and Transmission Electron Microscope (TEM) to observe the cardiac myocardial structure, carotid artery catheterization to test cardiac function, and real-time quantitative polymerase chain reaction (qRT-PCR) and Western blotting to describe the changes of NRG1, ErbB4, C/EBPß, and Gata in cardiac physiological adaptation. KEY FINDINGS: MOTS-c and aerobic training significantly increased heart weight and heart weight index (HWI) (all p < 0.05). Aerobic exercise and MOTS-c treatment thickened myocardial fibers, with a tendency of hypertrophy. Heart rate (HR) (p < 0.001, p = 0.010, p = 0.011), the isovolumic diastolic time constant (Tau) (p < 0.001, p < 0.001, p < 0.001) in exercised (E), MOST-c treated (M) and their combination (ME) decreased significantly, while the dP/dtmax (p < 0.001, p < 0.001, p = 0.039) and dP/dtmin (p < 0.001, p < 0.001, p = 0.001) in groups E, M and ME were significantly higher than those in group C, but EDP (p = 0.903, p = 0.708, p = 0.744) remained unchanged. Moreover, C/EBPß gene levels were significantly decreased in the differential gene expression between groups C and M transcriptomics sequencing. The levels of ErbB4 mRNA (p < 0.001, p < 0.001, p < 0.001) and Gata4 mRNA (p < 0.001, p < 0.001, p = 0.001) in groups E, M and ME increased significantly, while C/EBPß mRNA expression decreased significantly (p < 0.001, p = 0.002, p = 0.001), which was consistent with the results of transcriptome sequencing. NRG1 mRNA in group E was significantly higher than that in group C (p = 0.003), but there was no significant difference between groups M and ME (p = 0.804, p = 0.320). The protein expression of NRG1 (p = 0.026, p < 0.001, p < 0.001), ErbB4 (p < 0.001, p < 0.001, p < 0.001) and Gata4 (p = 0.014, p < 0.001, p = 0.006) in groups E, M and ME increased significantly, while C/EBPß decreased significantly (p < 0.001, p = 0.001, p = 0.002). SIGNIFICANCE: Our findings suggest that MOTS-c and aerobic exercise had similar effects, improving myocardial morphology and structure and enhancing cardiac function through activation of the NRG1-ErbB4-C/EBPß pathway.

Morphine upregulates Toll-like receptor 4 expression and promotes melanomas in mice.

BACKGROUND: Morphine and other opioids are used to manage cancer-related pain; however, the role of these drugs in cancer progression remains controversial. Emerging evidence indicates that morphine can activate Toll-like receptor 4 (TLR4) and its signaling pathways, by the way the activation and expression of TLR4 can promote melanoma. In this study, we investigated the effects of morphine on the expression of TLR4 and promotion of melanoma in mice. METHODS: Mice melanoma cells (B16F10) were cultured with morphine (0.1, 1 and 10 µM) for 24 h. In the other experiment, cells were treated with morphine with or without TLR4 agonist (LPS) or antagonist (TAK-242). In in-vivo model, B16F10 cells were subcutaneously injected to C57BL/6 mice, and morphine was administrated in three different treatment protocols after developing palpable tumors (acute treatment, chronic daily injections, escalating doses of morphine). In another set of experiments, B16F10 cells were pretreated with LPS (5 µg/ml) 24 h before injection into mice. Control group received normal saline. We measured cell proliferation, the expression level of Tlr4, Nuclear factor kappa-light-chain-enhancer of activated B cells 1 (Nf-κb1) genes, TLR4 protein expression, and tumor volume. RESULTS: Chronic, acute, and escalating doses of morphine increased tumor. Morphine increased the expression of Tlr4 and Nf-κb1 regardless of the treatment protocol used. CONCLUSION: Morphine increases the progression of melanoma cancer and may be related to the increased expression of TLR4. Our results suggest that morphine should be used with caution in patients with melanoma.HighlightsMorphine increases the expression of TLR4 in melanoma.Morphine increases melanoma progression.These effects are mostly observed with chronic and escalating morphine administration.

Morphine promotes migration and lung metastasis of mouse melanoma cells

Abstract Background Morphine is an analgesic agent used for cancer pain management. There have been recent concerns that the immunosuppressant properties of morphine can also promote cancer metastasis. Morphine is an agonist for toll like receptor 4 (TLR4) that has a dual role in cancer development. The promotor or inhibitor role of morphine in cancer progression remains controversial. We investigated the effects of morphine on migration and metastasis of melanoma cells through TLR4 activation. Methods Mouse melanoma cells (B16F10) were treated with only morphine (0, 0.1, 1, and 10 μM) or in combination with a TLR4 inhibitor (morphine10 μM +CLI-095 1μM) for either 12 or 24 hours. Migration of cells was analyzed by transwell migration assays. Twenty C57BL/6 male mice were inoculated with B16F10 cells via the left ventricle of the heart and then randomly divided into two groups (n = 10 each) that received either morphine (10 mg.kg−1, sub-q) or PBS injection for 21 days (control group). Animals were euthanized and their lungs removed for evaluation of metastatic nodules. Results Morphine (0.1, 1, and 10 μM) increased cell migration after 12 hours (p < 0.001) and after 24 hours of treatment with morphine (10 μM) (p < 0.001). Treatment with CLI-095 suppressed migration compared to cells treated with morphine alone (p < 0.001). Metastatic nodules in the morphine-treated group (64 nodules) were significantly higher than in the control group (40 nodules) (p < 0.05). Conclusion Morphine increases the migration and metastasis of mouse melanoma cells by activating TLR4.

MOTS-c and Exercise Restore Cardiac Function by Activating of NRG1-ErbB Signaling in Diabetic Rats.

Pathologic cardiac remodeling and dysfunction are the most common complications of type 2 diabetes. Physical exercise is important in inhibiting myocardial pathologic remodeling and restoring cardiac function in diabetes. The mitochondrial-derived peptide MOTS-c has exercise-like effects by improving insulin resistance, combatting hyperglycemia, and reducing lipid accumulation. We investigated the effects and transcriptomic profiling of MOTS-c and aerobic exercise on cardiac properties in a rat model of type 2 diabetes which was induced by feeding a high fat high sugar diet combined with an injection of a low dose of streptozotocin. Both aerobic exercise and MOTS-c treatment reduced abnormalities in cardiac structure and function. Transcriptomic function enrichment analysis revealed that MOTS-c had exercise-like effects on inflammation, myocardial apoptosis, angiogenesis and endothelial cell proliferation and migration, and showed that the NRG1-ErbB4 pathway might be an important component in both MOTS-c and exercise induced attenuation of cardiac dysfunction in diabetes. Moreover, our findings suggest that MOTS-c activates NRG1-ErbB4 signaling and mimics exercise-induced cardio-protection in diabetes.

Thermal dysregulation in patients with multiple sclerosis during SARS-CoV-2 infection. The potential therapeutic role of exercise.

Thermoregulation is a homeostatic mechanism that is disrupted in some neurological diseases. Patients with multiple sclerosis (MS) are susceptible to increases in body temperature, especially with more severe neurological signs. This condition can become intolerable when these patients suffer febrile infections such as coronavirus disease-2019 (COVID-19). We review the mechanisms of hyperthermia in patients with MS, and they may encounter when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Finally, the thermoregulatory role and relevant adaptation to regular physical exercise are summarized.

High-intensity Interval Training Improves Lipocalin-2 and Omentin-1 Levels in Men with Obesity.

We investigated the effects of 12 weeks of high-intensity interval training (HIIT) on selected circulating adipokines and other cardiovascular diseases risks factors in men with obesity. Thirty men with obesity (age: 24.96±3.11 year, BMI: 30.92±1.04 kg/m2) were randomly assigned to HIIT and control groups. The HIIT group participated in a 12-week HIIT program (5×2 min interval bout at an intensity of 85-95% HRmax interspersed by 1 min passive recovery, three times per week), while the control group maintained their usual lifestyles. Blood lipids, insulin resistance, and select serum adipokines were assessed before and after 12 weeks of the intervention period. HIIT improved body composition and lipid profiles (p<0.05) and also decreased fasting insulin levels (p=0.001) and HOMA-IR (p=0.002) levels. Furthermore, HIIT increased levels of lipocalin-2 (p=0.002) while decreasing omentin-1 levels (p=0.001) in men with obesity. Changes in lcn2 and omentin-1 concentrations correlated with the changes in risk factors in the HIIT group (p<0.05). The results indicate that 12 weeks of supervised HIIT significantly improves both circulating concentrations of lcn2 and omentin-1, two recently described adipokines, and risk markers of cardiovascular diseases in men with obesity. Further research is necessary to understand the molecular mechanisms involved with these changes.

Effects of Exercise Training on Anabolic and Catabolic Hormones with Advanced Age: A Systematic Review.

BACKGROUND: Ageing is accompanied by decreases in physical capacity and physiological regulatory mechanisms including altered hormonal regulation compared with age-matched sedentary people. The potential benefits of exercise in restoring such altered hormone production and secretion compared to age-matched physically inactive individuals who are ageing remains unclear. OBJECTIVES: The aim of this systematic review was to summarise the findings of exercise training in modulating levels of ostensibly anabolic and catabolic hormones in adults aged > 40 years. METHODS: We searched the following electronic databases (to July 2021) without a period limit: Cochrane Library, PubMed, Science Direct, Scopus, SPORTDiscus and Web of Science. Additionally, a manual search for published studies in Google Scholar was conducted for analysis of the 'grey literature' (information produced outside of traditional commercial or academic publishing and distribution channels). The initial search used the terms 'ageing' OR 'advanced age' OR 'old people' OR 'older' OR elderly' AND 'anabolic hormones' OR 'catabolic hormones' OR 'steroid hormones' OR 'sex hormones' OR 'testosterone' OR 'cortisol' OR 'insulin' OR 'insulin-like growth factor-1' OR 'IGF-1' OR 'sex hormone-binding globulin' OR 'SHBG' OR 'growth hormone' OR 'hGH' OR 'dehydroepiandrosterone' OR 'DHEA' OR 'dehydroepiandrosterone sulfate (DHEA-S)' AND 'exercise training' OR 'endurance training' OR 'resistance training' OR ' strength training' OR 'weight-lifting' OR 'high-intensity interval training' OR 'high-intensity interval exercise' OR 'high-intensity intermittent training' OR 'high-intensity intermittent exercise' OR 'interval aerobic training' OR 'interval aerobic exercise' OR 'intermittent aerobic training' OR 'intermittent aerobic exercise' OR 'high-intensity training' OR 'high-intensity exercise' OR 'sprint interval training' OR 'sprint interval exercise' OR 'combined exercise training' OR 'anaerobic training'. Only eligible full texts in English or French were considered for analysis. RESULTS: Our search identified 484 records, which led to 33 studies for inclusion in the analysis. Different exercise training programs were used with nine studies using endurance training programs, ten studies examining the effects of high-intensity interval training, and 14 studies investigating the effects of resistance training. Most training programs lasted ≥ 2 weeks. Studies, regardless of the design, duration or intensity of exercise training, reported increases in testosterone, sex hormone-binding globulin (SHBG), insulin-like growth factor-1 (IGF-1), human growth hormone (hGH) or dehydroepiandrosterone (DHEA) (effect size: 0.19 < d < 3.37, small to very large) in both older males and females. However, there was no consensus on the effects of exercise on changes in cortisol and insulin in older adults. CONCLUSION: In conclusion, findings from this systematic review suggest that exercise training increases basal levels of testosterone, IGF-1, SHBG, hGH and DHEA in both male and females over 40 years of age. The increases in blood levels of these hormones were independent of the mode, duration and intensity of the training programs. However, the effects of long-term exercise training on cortisol and insulin levels in elderly people are less clear.

An Update on COVID-19 Vaccine Induced Thrombotic Thrombocytopenia Syndrome and Some Management Recommendations.

The thrombotic thrombocytopenia syndrome (TTS), a complication of COVID-19 vaccines, involves thrombosis (often cerebral venous sinus thrombosis) and thrombocytopenia with occasional pulmonary embolism and arterial ischemia. TTS appears to mostly affect females aged between 20 and 50 years old, with no predisposing risk factors conclusively identified so far. Cases are characterized by thrombocytopenia, higher levels of D-dimers than commonly observed in venous thromboembolic events, inexplicably low fibrinogen levels and worsening thrombosis. Hyper fibrinolysis associated with bleeding can also occur. Antibodies that bind platelet factor 4, similar to those associated with heparin-induced thrombocytopenia, have also been identified but in the absence of patient exposure to heparin treatment. A number of countries have now suspended the use of adenovirus-vectored vaccines for younger individuals. The prevailing opinion of most experts is that the risk of developing COVID-19 disease, including thrombosis, far exceeds the extremely low risk of TTS associated with highly efficacious vaccines. Mass vaccination should continue but with caution. Vaccines that are more likely to cause TTS (e.g., Vaxzevria manufactured by AstraZeneca) should be avoided in younger patients for whom an alternative vaccine is available.

A review on the role of tau and stathmin in gastric cancer metastasis.

Gastric cancer is resistant to chemotherapy, especially in the later stages. The prevalence of gastric cancer increases after the age of 40, and its peak is in the 7th decade of life. The proteins tau (tubulin associated unit) and stathmin are overexpressed in gastric cancer and contribute to the progression of the disease by increasing cancer cell proliferation, invasion, and inducing drug resistance. This review summarizes the current knowledge on the expression of tau protein and stathmin in gastric cancer and their roles in drug resistance. Medline and PubMed databases were searched from 1990 till February 2021 for the terms "tau protein", "stathmin", and "gastric cancer." Two reviewers screened all articles and assessed prognostic studies on the role of tau and stathmin proteins in gastric cancer progression. Collectively, studies reported that both proteins are expressed at different concentrations in gastric cancer and could be significant molecular biomarkers for prognosis. Both proteins could be good candidates for targeted therapy of gastric cancer and are associated with resistance to taxanes.

Physical activity and adipokine levels in individuals with type 2 diabetes: A literature review and practical applications.

We review the effects of acute and long-term physical activity on adipokine levels in individuals with type 2 diabetes (T2D). Three electronic databases were searched. Studies made in animal models were excluded, while studies based on participants with and without T2D, and also studies with type 1 diabetes were included. Of the 2,450 citations, 63 trials, including randomised control trials, cross-sectional and longitudinal studies, met our inclusion criteria. Seventy and five percent of studies reported the effects of physical activity on tumor necrosis factor-alpha (TNFα), interleukin 6 (IL-6), adiponectin, visfatin, omentin-1, and leptin levels. There are no robust results due to variations in exercise modality, intensity, duration, and also differences in cohort characteristics in the literature. Only four studies described the effects of an acute session of physical activity on adipokine levels. Overall, physical activity improves diabetes status by regulating adipokine levels. However, long-term aerobic + resistance training combined with dietary modifications is likely to be a more effective strategy for improving adipokines profiles in patients with type 2 diabetes.

Pomegranate peel attenuates dextran sulfate sodium-induced lipid peroxidation in rat small intestine by enhancing the glutathione/glutathione disulfide redox potential.

BACKGROUND: The peel of the pomegranate fruit is rich in polyphenols with antioxidant properties. We investigated the preventive effect of pomegranate peel (PP) powder against dextran sulfate sodium (DSS)-induced lipid peroxidation in the small intestine of rats. Rats were allocated to four groups: CONT group, fed a standard rodent diet; DSS group, fed a standard rodent diet and treated with DSS; as well as PP1%+DSS and PP5%+DSS groups, fed a standard rodent diet supplemented with either 1% or 5% of PP powder and treated with DSS. Rats of the four groups consumed their diets for 25 days. Lipid peroxidation was determined by measuring malondialdehyde (MDA) concentrations in plasma and MDA contents in the small intestine and liver. Glutathione/glutathione disulfide (GSH/GSSG) redox status and antioxidant enzyme activities were determined in the small intestine and liver. RESULTS: MDA content was higher (P < 0.001) in the small intestines of the DSS group compared to the CONT group. MDA content was reduced (P < 0.001) in the small intestines of the PP1%+DSS and PP5%+DSS groups compared to the DSS group. GSH contents and GSH/GSSG ratios were higher (P < 0.001) in the small intestines of the PP5%+DSS group compared to the CONT, DSS and PP1%+DSS groups. CONCLUSION: The present study demonstrates that PP powder protects the small intestine against DSS-induced lipid peroxidation by enhancing the GSH/GSSG redox potential. Powder of PP is a promising agricultural by-product containing a mixture of bioactive polyphenols that can be used for the production of functional foods aimed at the prevention of oxidative stress-induced small intestine pathogenesis. © 2021 Society of Chemical Industry.