Organokines,Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise

Sarcopenia is a disease that becomes more prevalent as the population ages, since it is directly linked to the process of senility, which courses with muscle atrophy and loss of muscle strength. Over time, sarcopenia is linked to obesity, being known as sarcopenic obesity, and leads to other metabolic changes. At the molecular level, organokines act on different tissues and can improve or harm sarcopenia. It all depends on their production process, which is associated with factors such as physical exercise, the aging process, and metabolic diseases. Because of the seriousness of these repercussions, the aim of this literature review is to conduct a review on the relationship between organokines, sarcopenia, diabetes, and other metabolic repercussions, as well the role of physical exercise. To build this review, PubMed-Medline, Embase, and COCHRANE databases were searched, and only studies written in English were included. It was observed that myokines, adipokines, hepatokines, and osteokines had direct impacts on the pathophysiology of sarcopenia and its metabolic repercussions. Therefore, knowing how organokines act is very important to know their impacts on age, disease prevention, and how they can be related to the prevention of muscle loss.     

NLRP3 Inflammasome: From Pathophysiology to Therapeutic Target in Major Depressive Disorder

Major depressive disorder (MDD) is a highly prevalent psychiatric disorder, whose pathophysiology has been linked to the neuroinflammatory process. The increased activity of the Nod-like receptor pyrin containing protein 3 (NLRP3) inflammasome, an intracellular multiprotein complex, is intrinsically implicated in neuroinflammation by promoting the maturation and release of proinflammatory cytokines such as interleukin (IL)-1β and IL-18. Interestingly, individuals suffering from MDD have higher expression of NLRP3 inflammasome components and proinflammatory cytokines when compared to healthy individuals. In part, intense activation of the inflammasome may be related to autophagic impairment. Noteworthy, some conventional antidepressants induce autophagy, resulting in less activation of the NLRP3 inflammasome. In addition, the fast-acting antidepressant ketamine, some bioactive compounds and physical exercise have also been shown to have anti-inflammatory properties via inflammasome inhibition. Therefore, it is suggested that modulation of inflammasome-driven pathways may have an antidepressant effect. Here, we review the role of the NLRP3 inflammasome in the pathogenesis of MDD, highlighting that pathways related to its priming and activation are potential therapeutic targets for the treatment of MDD.     

Circulating Extracellular Vesicles Impair Mesenchymal Stromal Cell Differentiation Favoring Adipogenic Rather than Osteogenic Differentiation in Adolescents with Obesity

Excess body weight has been considered beneficial to bone health because of its anabolic effect on bone formation; however, this results in a poor quality bone structure. In this context, we evaluated the involvement of circulating extracellular vesicles in the impairment of the bone phenotype associated with obesity. Circulating extracellular vesicles were collected from the plasma of participants with normal weight, as well as overweight and obese participants, quantified by flow cytometry analysis and used to treat mesenchymal stromal cells and osteoblasts to assess their effect on cell differentiation and activity. Children with obesity had the highest amount of circulating extracellular vesicles compared to controls. The treatment of mesenchymal stromal cells with extracellular vesicles from obese participants led to an adipogenic differentiation in comparison to vesicles from controls. Mature osteoblasts treated with extracellular vesicles from obese participants showed a reduction in differentiation markers in comparison to controls. Children with obesity who regularly performed physical exercise had a lower circulating extracellular vesicle amount in comparison to those with a sedentary lifestyle. This pilot study demonstrates how the high amount of circulating extracellular vesicles in children with obesity affects the bone phenotype and that physical activity can partially rescue this phenotype.     

有氧运动训练和姜黄素对Ⅱ型糖尿病大鼠肝糖原及糖代谢信号通路的影响

为探讨有氧运动训练和姜黄素对Ⅱ型糖尿病大鼠肝糖原及糖代谢信号通路的影响,将大鼠分为对照组（C组）,模型组（D组）、运动组（S组）、姜黄素组（H组）和姜黄素+运动组（S+H组）,S组和S+H组大鼠给予8周有氧运动训练,H组和S+H组大鼠给予8周姜黄素灌胃干预,测定其空腹血糖、口服葡萄糖耐量实验（OGTT）后各时点血糖、胰岛素分泌、胰岛素敏感性、肝糖原水平及肝脏葡萄糖代谢及胰岛素信号分子mRNA表达的变化。结果表明:与D组相比,S+H组大鼠OGTT实验后各时刻血糖值均降低（p<0.05）;且胰岛素水平、胰岛素敏感指数及肝糖原水平均较S组和H组高（p<0.05）;肝脏葡萄糖激酶（GK）、肝细胞葡萄糖载体蛋白-2（GLUT2）、肝脏胰岛素样生长因子1（IGF-1）、胰岛素受体底物1（IRS-1）、胰岛素受体底物2（IRS-2）相对表达量均较S组和H组高（p<0.05）,而人葡萄糖激酶调节蛋白（GKRP）则较S组和H组降低（p<0.05）,且联合干预效果优于单独干预。结论表明有氧运动和姜黄素可有效降低血糖水平,改善胰岛素抵抗,促进肝糖原合成。      

Implication of Irisin in Different Types of Cancer: A Systematic Review and Meta-Analysis

Cancer is a set of diseases characterized by several hallmark properties, such as increased angiogenesis, proliferation, invasion, and metastasis. The increased angiogenic activity constantly supplies the tumors with nutrients and a plethora of cytokines to ensure cell survival. Along these cytokines is a newly discovered protein, called irisin, which is released into the circulation after physical exercise. Irisin is the product of fibronectin type III domain-containing protein 5 (FNDC5) proteolytic cleavage. Recently it has been the topic of investigation in several types of cancer. In this study, we conducted a systematic review and meta-analysis to investigate its implication in different types of cancer. Our results suggest that irisin expression is decreased in cancer patients, thus it can be used as a valid biomarker for the diagnosis of several types of cancer. In addition, our results indicate that irisin may have an important role in tumor progression and metastasis since it is involved in multiple signaling pathways that promote cell proliferation and migration.     

Cardioprotective Signaling Pathways in Obese Mice Submitted to Regular Exercise: Effect on Oxysterols

Exercise induces cardioprotection against myocardial infarction, despite obesity, by restoring pro-survival pathways and increasing resistance of mitochondrial permeability transition pore (mPTP) opening at reperfusion. Among the mechanisms involved in the inactivation of these pathways, oxysterols appear interesting. Thus, we investigated the influence of regular exercise on the reperfusion injury salvage kinase (RISK) pathway, oxysterols, and mitochondria, in the absence of ischemia-reperfusion. We also studied 7β-hydroxycholesterol (7βOH) concentration (mass spectrometry) in human lean and obese subjects. Wild-type (WT) and obese (ob/ob) mice were assigned to sedentary conditions or regular treadmill exercise. Exercise significantly increased Akt phosphorylation, whereas 7βOH concentration was reduced. Moreover, exercise induced the translocation of PKCε from the cytosol to mitochondria. However, exercise did not affect the calcium concentration required to open mPTP in the mitochondria, neither in WT nor in ob/ob animals. Finally, human plasma 7βOH concentration was consistent with observations made in mice. In conclusion, regular exercise enhanced the RISK pathway by increasing kinase phosphorylation and PKCε translocation and decreasing 7βOH concentration. This activation needs the combination with stress conditions, i.e., ischemia-reperfusion, in order to inhibit mPTP opening at the onset of reperfusion. The human findings suggest 7βOH as a candidate marker for evaluating cardiovascular risk factors in obesity.     

The Effects of Exercise Training on Mitochondrial Function in Cardiovascular Diseases: A Systematic Review and Meta-Analysis

Mitochondria dysfunction is implicated in the pathogenesis of cardiovascular diseases (CVD). Exercise training is potentially an effective non-pharmacological strategy to restore mitochondrial health in CVD. However, how exercise modifies mitochondrial functionality is inconclusive. We conducted a systematic review using the PubMed; Scopus and Web of Science databases to investigate the effect of exercise training on mitochondrial function in CVD patients. Search terms included “mitochondria”, “exercise”, “aerobic capacity”, and “cardiovascular disease” in varied combination. The search yielded 821 records for abstract screening, of which 20 articles met the inclusion criteria. We summarized the effect of exercise training on mitochondrial morphology, biogenesis, dynamics, oxidative capacity, antioxidant capacity, and quality. Amongst these parameters, only oxidative capacity was suitable for a meta-analysis, which demonstrated a significant effect size of exercise in improving mitochondrial oxidative capacity in CVD patients (SMD = 4.78; CI = 2.99 to 6.57; p < 0.01), but with high heterogeneity among the studies (I² = 75%, p = 0.003). Notably, aerobic exercise enhanced succinate-involved oxidative phosphorylation. The majority of the results suggested that exercise improves morphology and biogenesis, whereas findings on dynamic, antioxidant capacity, and quality, were inadequate or inconclusive. A further randomized controlled trial is clearly required to explain how exercise modifies the pathway of mitochondrial quantity and quality in CVD patients.     

Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.     

红芸豆多糖联合运动改善饮食诱导的肥胖小鼠糖脂代谢紊乱

目的：观察红芸豆多糖（Polysaccharides from red kidney bean,PRK）联合运动（Exercise,E）改善饮食诱导的肥胖小鼠代谢紊乱,并分析其机制。方法：40只C57BL/6小鼠随机分为5组：对照组（正常饮食）、模型组（高脂饮食）、PRK组（400 mg/kg PRK）、E组（运动）、PRK+E组（400 mg/kg PRK+运动）,连续干预12周,并进行口服葡萄糖耐量试验（OGTT）,生化分析仪测定血糖、胰岛素、总胆固醇（TC）、三酰甘油（TG）、低密度脂蛋白（LDL）、高密度脂蛋白（HDL)、肝脏TC、TG、超氧化物歧化酶（SOD）、丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）水平。酶联免疫试剂盒检测胰岛素、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）、IL-1β含量。H&E染色对肝脏进行病理分析,Western Blot实验检测PPARα、FASN、Nrf2、NQO1、HO-1水平。结果：与对照组比较,模型组小鼠的体重和肝质量极显著增加（P<0.01）;与模型组比较,PRK联合运动极显著降低肥胖小鼠的体重和脂质,降低血糖和胰岛素水平（P<0.01）。与模型组比较,PRK联合运动极显著降低血清中TG、TC、LDL含量,极显著增加HDL,极显著降低肝脏TNF-α、IL-6和IL-1β水平,极显著下调肝脏TG、TC水平,极显著增加肝脏中PPARα水平,极显著降低FASN水平（P<0.01）。与模型组比较,PRK、E或PRK+E联合干预极显著提高肝脏GSH-Px和SOD水平,极显著降低MDA含量,极显著增加Nrf2、NQO1和HO-1蛋白水平,尤其PRK+E联合干预更加明显（P<0.01）。结论：PRK联合运动通过减少脂质积累、抑制炎症、氧化应激改善肥胖引起的代谢障碍,其机制与调节PGC-1α、FASN、Nrf2/NQO1/HO-1 信号通路相关。     

金融信息系统应急响应及演练

针对金融、保险等行业的信息系统的特点,提出应急响应、预案编制和演练的方法,并以银行系统为例给出具体的应急及演练方案。