Ultra‐endurance exercise induces stress and inflammation and affects circulating hematopoietic progenitor cell function

Although amateur sports have become increasingly competitive within recent decades, there are as yet few studies on the possible health risks for athletes. This study aims to determine the impact of ultra‐endurance exercise‐induced stress on the number and function of circulating hematopoietic progenitor cells (CPCs) and hematological, inflammatory, clinical, metabolic, and stress parameters in moderately trained amateur athletes. Following ultra‐endurance exercise, there were significant increases in leukocytes, platelets, interleukin‐6, fibrinogen, tissue enzymes, blood lactate, serum cortisol, and matrix metalloproteinase‐9. Ultra‐endurance exercise did not influence the number of CPCs but resulted in a highly significant decline of CPC functionality after the competition. Furthermore, Epstein‐Barr virus was seen to be reactivated in one of seven athletes. The link between exercise‐induced stress and decline of CPC functionality is supported by a negative correlation between cortisol and CPC function. We conclude that ultra‐endurance exercise induces metabolic stress and an inflammatory response that affects not only mature hematopoietic cells but also the function of the immature hematopoietic stem and progenitor cell fraction, which make up the immune system and provide for regeneration.     

The effect of hypoxia and exercise on heart rate variability,immune response,and orthostatic stress

Hypoxia with exercise is commonly used to enhance physiological adaptation in athletes, but may prolong recovery between training bouts. To investigate this, heart rate variability (HRV), systemic immune response, and response to an orthostatic challenge were measured following exercise in hypoxia and air. Eleven trained men performed a 10‐km cycling time trial breathing hypoxia (16.5 ± 0.5% O₂) or air. HRV and the heart rate response to an orthostatic challenge were measured for 3 days before and after each trial, while venous blood samples were collected pre‐, 0, 2, and 24 h post‐exercise. Hypoxia had no significant effect compared with air. Subgroup analysis of those who had a drop in oxyhemoglobin saturation (SpO₂) > 10% between hypoxia and air compared with those who did not, demonstrated a significantly altered HRV response (△HFnu: ?2.1 ± 0.9 vs 8.6 ± 9.3, △LFnu: 2.1 ± 1.0 vs ?8.6 ± 9.4) at 24 h post‐exercise and increased circulating monocytes (1.3 ± 0.2 vs 0.8 ± 0.2 × 10⁹/L) immediately post‐hypoxic exercise. Exercise and hypoxia did not change HRV or the systemic immune response to exercise. However, those who had a greater desaturation during hypoxic exercise had an attenuate recovery 24 h post‐exercise and may be more susceptible to accumulating fatigue with subsequent training bouts.     

Effects of chronic intense exercise training on the leukocyte response to acute exercise.

Circulatory leukocytes vary significantly in response to acute bouts of exercise. However, little is known concerning the adaptability of this response to chronic intense exercise training. We investigated the circulating leukocytic response to acute exercise in trained athletes during a 28-day intense exercise training program. On day 0, 14, 28 and two days after cessation of the increased training, eight trained male athletes (VO2max greater than 60 ml.kg-1.min-1) were subjected to a 20-km bicycle ergometer time trial. Blood samples were drawn before (PRE, for resting baseline values) and five minutes after (POST, response to acute exercise) the time trial. Beginning on day 0, athletes were instructed to increase the duration of their training 50%. The intense exercise training, which lasted 28 days, was verified weekly. Acute bouts of exercise caused a significant increase (p less than 0.05) in circulating white blood cells, lymphocytes, polymorphonuclear neutrophils and monocytes. The baseline resting values and the magnitude of the response to the acute bouts of exercise in the above parameters were not different during the 28 days of chronic intense exercise training or 2 days after cessation of training as compared to the values observed on day 0. Similarly there was a significant increase (p less than 0.05) in cortisol levels in response to the acute bouts of exercise during the chronic intense exercise training, but the increases were not different from that observed under baseline conditions. These results lead to the conclusion that chronic intense exercise training does not alter the circulating leukocytic response to acute exercise.     

Testosterone physiology in resistance exercise and training: the up-stream regulatory elements

Testosterone is one of the most potent naturally secreted androgenic-anabolic hormones, and its biological effects include promotion of muscle growth. In muscle, testosterone stimulates protein synthesis (anabolic effect) and inhibits protein degradation (anti-catabolic effect); combined, these effects account for the promotion of muscle hypertrophy by testosterone. These physiological signals from testosterone are modulated through the interaction of testosterone with the intracellular androgen receptor (AR). Testosterone is important for the desired adaptations to resistance exercise and training; in fact, testosterone is considered the major promoter of muscle growth and subsequent increase in muscle strength in response to resistance training in men. The acute endocrine response to a bout of heavy resistance exercise generally includes increased secretion of various catabolic (breakdown-related) and anabolic (growth-related) hormones including testosterone. The response of testosterone and AR to resistance exercise is largely determined by upper regulatory elements including the acute exercise programme variable domains, sex and age. In general, testosterone concentration is elevated directly following heavy resistance exercise in men. Findings on the testosterone response in women are equivocal with both increases and no changes observed in response to a bout of heavy resistance exercise. Age also significantly affects circulating testosterone concentrations. Until puberty, children do not experience an acute increase in testosterone from a bout of resistance exercise; after puberty some acute increases in testosterone from resistance exercise can be found in boys but not in girls. Aging beyond 35-40 years is associated with a 1-3% decline per year in circulating testosterone concentration in men; this decline eventually results in the condition known as andropause. Similarly, aging results in a reduced acute testosterone response to resistance exercise in men. In women, circulating testosterone concentration also gradually declines until menopause, after which a drastic reduction is found. In summary, testosterone is an important modulator of muscle mass in both men and women and acute increases in testosterone can be induced by resistance exercise. In general, the variables within the acute programme variable domains must be selected such that the resistance exercise session contains high volume and metabolic demand in order to induce an acute testosterone response.     

微小RNAs在分子放射生物学中的研究进展

微小RNAs (miRNAs)是一类新近发现的能调节基因表达的短小非编码RNA.miRNAs通过负性调节靶基因,在辐射诱导的凋亡、辐射耐受性、旁观者效应等辐射反应中起重要作用.越来越多的证据表明,miRNAs与放射治疗所致的辐射生物效应相关.miRNAs有可能成为改善放射治疗肿瘤疗效的潜在新靶点.     

食管癌预后相关微小RNAs分子研究进展

食管癌的诊断和手术治疗已较为成熟,但预后相关研究仍不足。许多微小RNAs（microRNAs,miRNAs）分子都与食管癌患者的预后相关。作者就目前食管癌预后相关miRNAs的研究进展作一综述,分析miRNAs分子在临床中的应用,如癌组织中变化的miRNAs表达量用于预测食管癌患者的预后、个别循环miRNAs作为新型生物标志物的潜能,应开展更多的临床试验来推进与预后相关的miRNAs分子的应用。     

Non‐invasive ventilation abolishes the IL‐6 response to exercise in muscle‐wasted COPD patients: A pilot study

Systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) has been related to the development of comorbidities. The level of systemic inflammatory mediators is aggravated as a response to exercise in these patients. The aim of this study was to investigate whether unloading of the respiratory muscles attenuates the inflammatory response to exercise in COPD patients. In a cross‐over design, eight muscle‐wasted stable COPD patients performed 40 W constant work‐rate cycle exercise with and without non‐invasive ventilation support (NIV vs control). Patients exercised until symptom limitation for maximally 20 min. Blood samples were taken at rest and at isotime or immediately after exercise. Duration of control and NIV‐supported exercise was similar, both 12.9 ± 2.8 min. Interleukin‐ 6 (IL‐6) plasma levels increased significantly by 25 ± 9% in response to control exercise, but not in response to NIV‐supported exercise. Leukocyte concentrations increased similarly after control and NIV‐supported exercise by ～15%. Plasma concentrations of C‐reactive protein, carbonylated proteins, and production of reactive oxygen species by blood cells were not affected by both exercise modes. This study demonstrates that NIV abolishes the IL‐6 response to exercise in muscle‐wasted patients with COPD. These data suggest that the respiratory muscles contribute to exercise‐induced IL‐6 release in these patients.     

Plasma leptin and exercise: recent findings

It is established that plasma leptin is associated with satiety and that leptin stimulates lipid metabolism, and increases energy expenditure. These effects implicate leptin as a major regulator of energy homeostasis, which may serve to limit excess energy storage. As plasma leptin concentrations are tightly coupled with fat mass in humans, decreases in adipose mass with weight loss coincide with decreased concentrations of circulating leptin. However, due to many confounding factors, the effects of exercise on circulating leptin are less clear. The data from investigations examining single exercise bouts suggest that serum leptin concentrations are unaltered by short duration (41 minutes or less), non-exhaustive exercise, but may be affected by short duration, exhaustive exercise. More convincingly, studies investigating long duration exercise bouts indicate that serum leptin concentrations are reduced with exercise durations ranging from one to multiple hours. These findings raise speculation that exercise-associated reductions in leptin may be due to alterations in nutrient availability or nutrient flux at the level of the adipocytes, the primary site of leptin production and secretion. Thus, one purpose of this review is to discuss the effects of exercise on circulating leptin concentrations with special emphasis on studies that have examined single exercise bouts that are associated with high levels of energy expenditure and energy deficit. In addition, a 'nutrient sensing pathway' (the hexosamine biosynthetic pathway), which regulates leptin gene expression, will be discussed as a possible mechanism by which exercise-induced energy deficit may modulate serum leptin concentrations.     

Thermal Ablation and Transarterial Chemoembolization are Characterized by Changing Dynamics of Circulating MicroRNAs

PurposeTo determine whether the levels of circulating microRNAs (miRNAs) are altered in patients undergoing thermal ablation and chemoembolization and whether these changes are predictive of a clinical outcome.Material and MethodsThis prospective study consisted of 43 patients diagnosed with hepatocellular carcinoma (n = 15) and intrahepatic colorectal cancer metastases (n = 28) treated with thermal ablation (n = 23; radiofrequency [n = 6] or microwave [n = 19]), chemoembolization using drug-eluting embolics (n = 18), or both (n = 2). Four blood samples (immediately before the intervention and 60–90 minutes, 24 hours, and 7 days after the intervention) were taken to measure the plasma concentrations of miRNAs related to hypoxia (miR-21 and miR-210), liver injury (miR-122), epithelial–mesenchymal transition (miR-200a), and apoptosis (miR-34a) using miRNA-specific TaqMan assays and quantitative real-time polymerase chain reaction. Tumor burden and treatment response at 3 months were evaluated using the modified response evaluation criteria in solid tumors. The miRNA results were compared with clinical outcomes (Mann-Whitney U test, Wilcoxon matched-pair test).ResultsDynamic changes in the circulating miRNA levels were observed following both the interventions. For thermal ablation, significant increases in miR-21, miR-210, miR-122, miR-200a, and miR-34a concentrations peaked 60–90 minutes after the intervention (P < .01). However, for transarterial chemoembolization, maximum increases in the miRNA concentrations were observed at 24 hours after the intervention for miR-21, miR-210, miR-122, miR-200a, and miR-34a (P < .05). The increased concentrations of the circulating miRNAs were followed by a subsequent decline to baseline by 7 days. For the thermal ablation (but not chemoembolization) patients, elevations in the miR-210 and miR-200a levels were associated with early progressive disease at 3 months (P = .040 and P = .012, respectively).ConclusionsIncreased but dynamic levels of circulating miRNAs are present following interventional oncologic procedures and may prove useful as biomarkers for the monitoring of clinical outcomes.     

Glucoregulation during exercise : the role of the neuroendocrine system

Under normal healthy conditions, exercise initiates simultaneous elevations in hepatic glucose production (glucose R(a)) and glucose utilisation. As a result, circulating glucose levels are maintained at a relatively constant level. This relatively simple and effective relationship between the liver and the skeletal muscle is maintained by a complex interplay of circulating and locally released neuroendocrine controllers. In large part, exercise-induced changes in the pancreatic secretion of glucagon and insulin are primarily responsible for the stimulation of glucose R(a) during moderate exercise. However, exercise imposed on an additional metabolic stress (heavy exercise and poorly controlled diabetes mellitus) can increase sympathetic drive and has been suggested for decades to play a significant role in glucoregulation. In addition, blood-borne feedback and afferent reflex mechanisms may further modulate the glucose R(a) response to exercise. This article discusses new findings from novel animal and human experiments specifically designed to examine the regulatory components of the neuroendocrine system and their influence on glucoregulation during exercise.     

Hormonal responses and adaptations to resistance exercise and training

Resistance exercise has been shown to elicit a significant acute hormonal response. It appears that this acute response is more critical to tissue growth and remodelling than chronic changes in resting hormonal concentrations, as many studies have not shown a significant change during resistance training despite increases in muscle strength and hypertrophy. Anabolic hormones such as testosterone and the superfamily of growth hormones (GH) have been shown to be elevated during 15-30 minutes of post-resistance exercise providing an adequate stimulus is present. Protocols high in volume, moderate to high in intensity, using short rest intervals and stressing a large muscle mass, tend to produce the greatest acute hormonal elevations (e.g. testosterone, GH and the catabolic hormone cortisol) compared with low-volume, high-intensity protocols using long rest intervals. Other anabolic hormones such as insulin and insulin-like growth factor-1 (IGF-1) are critical to skeletal muscle growth. Insulin is regulated by blood glucose and amino acid levels. However, circulating IGF-1 elevations have been reported following resistance exercise presumably in response to GH-stimulated hepatic secretion. Recent evidence indicates that muscle isoforms of IGF-1 may play a substantial role in tissue remodelling via up-regulation by mechanical signalling (i.e. increased gene expression resulting from stretch and tension to the muscle cytoskeleton leading to greater protein synthesis rates). Acute elevations in catecholamines are critical to optimal force production and energy liberation during resistance exercise. More recent research has shown the importance of acute hormonal elevations and mechanical stimuli for subsequent up- and down-regulation of cytoplasmic steroid receptors needed to mediate the hormonal effects. Other factors such as nutrition, overtraining, detraining and circadian patterns of hormone secretion are critical to examining the hormonal responses and adaptations to resistance training.     

运动性疲劳大鼠脑组织中一氧化氮合酶和内皮素mRNA表达的变化规律及中药“体复康”的调节作用

作为一种应激 ,运动会引起机体血液供应的重新分配。内皮素 (ET)和一氧化氮 (NO)是一对调节局部组织血液供应的拮抗因素。本实验采用递增强度的跑台运动方式 ,经过 7周训练 ,塑造了运动性疲劳大鼠模型 ;并通过原位杂交的方法 ,结合图像分析 ,观察了运动训练中不同负荷和运动后不同恢复时相的大鼠脑组织一氧化氮合酶 (NOS)和ET - 1mRNA的表达 ,以研究运动时脑组织中NOS和ETmRNA表达的动态变化规律 ,并探讨脑组织的血液供应与运动性中枢疲劳之间的关系以及纯中药制剂“体复康”的调节作用。研究结果表明 ,NOSmRNA在安静对照组大鼠脑组织海马和丘脑等部位均有基础表达 ;进行适量运动的训练对照组与安静对照组无明显差异 ,说明适量运动对大鼠脑组织中NOS活性影响不大 ;强化训练组表达明显减弱 ,说明大负荷运动会使脑组织中NOS活性减弱 ;而同样负荷的强化训练中药组表达明显强于强化训练组 ,说明该中药制剂可提高NOS活性 ;另外 ,在一次大强度的运动后即刻 ,强化训练组NOSmRNA表达明显减弱 ,至运动后 30分钟时略有恢复 ,到运动后 3小时时恢复到接近安静对照组的水平 ;而强训中药组在运动后即刻表达明显高于同时相的强化训练组 ,至运动后 30分钟时与强化训练组相同 ,到运动后 3小时时恢复到接近安静对照组的水?     

Aquatic exercise improves the monocyte pro‐ and anti‐inflammatory cytokine production balance in fibromyalgia patients

Current hypotheses of the etiology of fibromyalgia (FM) include inflammatory disorders. We evaluated the effect of a pool‐aquatic exercise program (8 months, two weekly 60‐min sessions) on the inflammatory cytokine production by isolated monocytes, and on the serum concentration of C‐reactive protein (CRP), in a group of female FM patients. Monocytes from FM patients released more IL‐1β, TNFα, IL‐6, and IL‐10 than those from an age‐matched control group of healthy women (HW). This inflammatory disorder in FM women was also manifested by high circulating concentrations of CRP. Increased IL‐6 with a concomitant decreased TNFα spontaneous release was found after 4 months (midway through) of the exercise program. At the end of the program (8 months), monocytes from FM patients showed diminished spontaneous production of pro‐/anti‐inflammatory cytokines, with a similar spontaneous release of IL‐1β and IL‐6 to that of HW, but a lower production of TNFα and higher of IL‐10. Lipopolysaccharide‐induced production of IL‐1β, TNFα, IL‐6, and IL‐10 also decreased at the end of the exercise program, although IL‐10 remained higher than HW. The anti‐inflammatory effect of the exercise program was also corroborated by a decrease in the circulating CRP concentration. Exercise also improved the health‐related quality of life of FM patients.     

Lymphocyte responses to maximal exercise: a physiological perspective

Exercise affects lymphocytes as reflected in total blood counts and the lymphocyte proliferative response. In addition, the production of immunoglobulins is impaired and during exercise the natural killer cell activity increases followed by suppression in the recovery period. Cardiopulmonary adjustments play a major role in lymphocyte response to physical activity. During intense exercise, the activated sympathetic nervous system increases blood flow to muscle as blood flow to splanchnic organs decreases. After exercise, sympathetic tone and blood pressure becomes reduced. The spleen contains lymphocytes and blood resides in gut vessels. A change in blood flow to these organs could affect the number of circulating lymphocytes. Reduced production of immunoglobulins results from suppressed B-cell function and, in response to exercise, mucosal immunity appears to decrease. Pulmonary hyperventilation and enhanced pressure in pulmonary vessels induce increased permeability of airway epithelium and stress failure of the alveolar-capillary membrane during intense exercise. A physiological perspective is of importance for evaluation of the exercise-induced change in lymphocyte function and, in turn, to post-exercise increased susceptibility to infections.     

Effects of fasted vs fed‐state exercise on performance and post‐exercise metabolism: A systematic review and meta‐analysis

The effects of nutrition on exercise metabolism and performance remain an important topic among sports scientists, clinical, and athletic populations. Recently, fasted exercise has garnered interest as a beneficial stimulus which induces superior metabolic adaptations to fed exercise in key peripheral tissues. Conversely, pre‐exercise feeding augments exercise performance compared with fasting conditions. Given these seemingly divergent effects on performance and metabolism, an appraisal of the literature is warranted. This review determined the effects of fasting vs pre‐exercise feeding on continuous aerobic and anaerobic or intermittent exercise performance, and post‐exercise metabolic adaptations. A search was performed using the MEDLINE and PubMed search engines. The literature search identified 46 studies meeting the relevant inclusion criteria. The Delphi list was used to assess study quality. A meta‐analysis and meta‐regression were performed where appropriate. Findings indicated that pre‐exercise feeding enhanced prolonged (P  = .012), but not shorter duration aerobic exercise performance (P  = .687). Fasted exercise increased post‐exercise circulating FFAs (P  = .023) compared to fed exercise. It is evidenced that pre‐exercise feeding blunted signaling in skeletal muscle and adipose tissue implicated in regulating components of metabolism, including mitochondrial adaptation and substrate utilization. This review's findings support the hypothesis that the fasted and fed conditions can divergently influence exercise metabolism and performance. Pre‐exercise feeding bolsters prolonged aerobic performance, while seminal evidence highlights potential beneficial metabolic adaptations that fasted exercise may induce in peripheral tissues. However, further research is required to fully elucidate the acute and chronic physiological adaptations to fasted vs fed exercise.     

Circulating androgens in women: exercise-induced changes

Physical exercise is known to strongly stimulate the endocrine system in both sexes. Among these hormones, androgens (e.g. testosterone, androstenedione, dehydroepiandrosterone) play key roles in the reproductive system, muscle growth and the prevention of bone loss. In female athletes, excessive physical exercise may lead to disorders, including delay in the onset of puberty, amenorrhoea and premature osteoporosis. The free and total fractions of circulating androgens vary in response to acute and chronic exercise/training (depending on the type), but the physiological role of these changes is not completely understood. Although it is commonly accepted that only the free fraction of steroids has a biological action, this hypothesis has recently been challenged. Indeed, a change in the total fraction of androgen concentration may have a significant impact on cells (inducing genomic or non-genomic signalling). The purpose of this review, therefore, is to visit the exercise-induced changes in androgen concentrations and emphasize their potential effects on female physiology. Despite some discrepancies in the published studies (generally due to differences in the types and intensities of the exercises studied, in the hormonal status of the group of women investigated and in the methods for androgen determination), exercise is globally able to induce an increase in circulating androgens. This can be observed after both resistance and endurance acute exercises. For chronic exercise/training, the picture is definitely less clear and there are even circumstances where exercise leads to a decrease of circulating androgens. We suggest that those changes have significant impact on female physiology and physical performance.     

Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training‐accustomed individuals

The influence of adenosine mono phosphate (AMP)‐activated protein kinase (AMPK) vs Akt‐mammalian target of rapamycin C1 (mTORC1) protein signaling mechanisms on converting differentiated exercise into training specific adaptations is not well‐established. To investigate this, human subjects were divided into endurance, strength, and non‐exercise control groups. Data were obtained before and during post‐exercise recovery from single‐bout exercise, conducted with an exercise mode to which the exercise subjects were accustomed through 10 weeks of prior training. Blood and muscle samples were analyzed for plasma substrates and hormones and for muscle markers of AMPK and Akt‐mTORC1 protein signaling. Increases in plasma glucose, insulin, growth hormone (GH), and insulin‐like growth factor (IGF)‐1, and in phosphorylated muscle phospho‐Akt substrate (PAS) of 160 kDa, mTOR, 70 kDa ribosomal protein S6 kinase, eukaryotic initiation factor 4E, and glycogen synthase kinase 3α were observed after strength exercise. Increased phosphorylation of AMPK, histone deacetylase5 (HDAC5), cAMP response element‐binding protein, and acetyl‐CoA carboxylase (ACC) was observed after endurance exercise, but not differently from after strength exercise. No changes in protein phosphorylation were observed in non‐exercise controls. Endurance training produced an increase in maximal oxygen uptake and a decrease in submaximal exercise heart rate, while strength training produced increases in muscle cross‐sectional area and strength. No changes in basal levels of signaling proteins were observed in response to training. The results support that in training‐accustomed individuals, mTORC1 signaling is preferentially activated after hypertrophy‐inducing exercise, while AMPK signaling is less specific for differentiated exercise.