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Mitigating disuse-induced skeletal muscle atrophy in ageing: Resistance exercise as a critical countermeasure 缓解老化过程中因失能引起的骨骼肌萎缩:阻力运动是关键对策
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-06 DOI: 10.1113/EP091937
James McKendry, Giulia Coletta, Everson A. Nunes, Changhyun Lim, Stuart M. Phillips

The gradual deterioration of physiological systems with ageing makes it difficult to maintain skeletal muscle mass (sarcopenia), at least partly due to the presence of ‘anabolic resistance’, resulting in muscle loss. Sarcopenia can be transiently but markedly accelerated through periods of muscle disuse-induced (i.e., unloading) atrophy due to reduced physical activity, sickness, immobilisation or hospitalisation. Periods of disuse are detrimental to older adults' overall quality of life and substantially increase their risk of falls, physical and social dependence, and early mortality. Disuse events induce skeletal muscle atrophy through various mechanisms, including anabolic resistance, inflammation, disturbed proteostasis and mitochondrial dysfunction, all of which tip the scales in favour of a negative net protein balance and subsequent muscle loss. Concerningly, recovery from disuse atrophy is more difficult for older adults than their younger counterparts. Resistance training (RT) is a potent anabolic stimulus that can robustly stimulate muscle protein synthesis and mitigate muscle losses in older adults when implemented before, during and following unloading. RT may take the form of traditional weightlifting-focused RT, bodyweight training and lower- and higher-load RT. When combined with sufficient dietary protein, RT can accelerate older adults' recovery from a disuse event, mitigate frailty and improve mobility; however, few older adults regularly participate in RT. A feasible and practical approach to improving the accessibility and acceptability of RT is through the use of resistance bands. Moving forward, RT must be prescribed to older adults to mitigate the negative consequences of disuse atrophy.

随着年龄的增长,生理系统逐渐退化,很难维持骨骼肌质量(肌肉疏松症),至少部分原因是存在 "合成代谢阻力",导致肌肉流失。由于体力活动减少、生病、不能活动或住院等原因,肌肉废用期(即无负荷)会导致肌肉萎缩,从而短暂但明显地加速 "肌肉疏松症 "的发生。废用期不利于老年人的整体生活质量,会大大增加他们跌倒、身体和社会依赖性以及早期死亡的风险。废用事件会通过各种机制诱发骨骼肌萎缩,包括合成代谢阻力、炎症、蛋白稳态紊乱和线粒体功能障碍,所有这些机制都会导致蛋白质负净平衡和随后的肌肉损失。令人担忧的是,老年人比年轻人更难从废用性萎缩中恢复过来。阻力训练(RT)是一种有效的合成代谢刺激,在卸载前、卸载期间和卸载后进行,可有力地刺激肌肉蛋白质合成,减轻老年人的肌肉损失。负重训练的形式包括传统的以举重为主的负重训练、体重训练以及低负荷和高负荷负重训练。如果与充足的膳食蛋白质相结合,负重训练可加快老年人从废用事件中恢复,减轻虚弱并改善活动能力;然而,很少有老年人定期参加负重训练。通过使用阻力带来提高 RT 的可及性和可接受性是一种可行且实用的方法。展望未来,必须为老年人提供康复训练,以减轻失用性萎缩的负面影响。
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引用次数: 0
Somatosensory processing in long COVID fatigue and its relations with physiological and psychological factors 长期 COVID 疲劳的体感处理及其与生理和心理因素的关系。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-06 DOI: 10.1113/EP091988
Bethan Thomas, Rachael Pattinson, Christine Bundy, Jennifer L. Davies

Fatigue is prevalent amongst people with long COVID, but is poorly understood. The sensory attenuation framework proposes that impairments in sensory processing lead to heightened perception of effort, driving fatigue. This study aims to investigate the role of somatosensory processing impairments in long COVID fatigue and quantify how sensory processing relates to other prominent symptoms of long COVID including autonomic dysfunction, mood and illness beliefs in driving the experience of fatigue. We will recruit 44 individuals with long COVID fatigue and 44 individuals with neither long COVID nor fatigue (controls). Our primary objective is to compare baseline somatosensory processing between individuals with long COVID fatigue and controls. Additionally, we will explore the associations between somatosensory processing, fatigability and the level of fatigue induced by cognitive and physical exertion. Due to the complex nature of fatigue, we will also investigate how long COVID, state fatigue, perceived effort, mood, illness beliefs, autonomic symptoms and autonomic nervous system function interact to predict trait fatigue. This comprehensive investigation aims to elucidate how sensory processing and other prominent symptoms interact to impact the experience of fatigue.

疲劳在长期慢性阻塞性脑损伤患者中十分普遍,但却鲜为人知。感觉衰减框架认为,感觉处理障碍会导致对努力的感知增强,从而引发疲劳。本研究旨在调查躯体感觉处理障碍在长期慢性阻塞性肺病疲劳中的作用,并量化感觉处理与长期慢性阻塞性肺病其他突出症状(包括自主神经功能障碍、情绪和疾病信念)在疲劳体验中的关系。我们将招募 44 名长期 COVID 疲劳患者和 44 名既无长期 COVID 也无疲劳症状的患者(对照组)。我们的主要目标是比较长期 COVID 疲劳患者和对照组之间的基线体感处理。此外,我们还将探索躯体感觉处理、疲劳度以及认知和体力消耗引起的疲劳程度之间的关联。由于疲劳的复杂性,我们还将研究长 COVID、状态疲劳、感知努力、情绪、疾病信念、自律神经症状和自律神经系统功能如何相互作用来预测特质疲劳。这项综合调查旨在阐明感觉处理和其他突出症状是如何相互作用影响疲劳体验的。
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引用次数: 0
Circadian rhythm of brain-derived neurotrophic factor in serum and plasma 血清和血浆中脑源性神经营养因子的昼夜节律。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-06 DOI: 10.1113/EP091671
Maren Ehrhardt, Stefanie Schreiber, Yves Duderstadt, Rüdiger Braun-Dullaeus, Katrin Borucki, Tanja Brigadski, Notger G. Müller, Volkmar Leßmann, Patrick Müller

The neurotrophic growth factor brain-derived neurotrophic factor (BDNF) plays a crucial role in various neurodegenerative and psychiatric diseases, such as Alzheimer's disease, schizophrenia and depression. BDNF has been proposed as a potential biomarker for diagnosis, prognosis and monitoring therapy. Understanding the factors influencing BDNF levels and whether they follow a circadian rhythm is essential for interpreting fluctuations in BDNF measurements. We aimed to investigate the circadian rhythm of BDNF by collecting multiple peripheral venous blood samples from young, healthy male participants at 12 different time points over 24 h. In addition, vital parameters, cortisol and insulin like growth factor 1 (IGF1) were measured to explore potential regulatory mechanisms, interfering variables and their correlations with BDNF concentration. The findings revealed that plasma BDNF did not exhibit any significant fluctuations over 24 h, suggesting the absence of a circadian rhythm. However, serum BDNF levels decreased during sleep. Furthermore, serum BDNF showed a positive correlation with heart rate but a negative correlation with IGF1. No significant correlation was observed between cortisol and BDNF or IGF1. Although plasma BDNF suggests steady-state conditions, the decline of serum BDNF during the nocturnal period could be attributed to physical inactivity and associated with reduced haemodynamic blood flow (heart rate reduction during sleep). The type of sample collection (peripheral venous cannula vs. blood sampling using a butterfly system) does not significantly affect the measured BDNF levels. The sample collection during the day did not significantly affect BDNF analysis, emphasizing the importance of considering activity levels rather than timing when designing standardized protocols for BDNF assessments.

神经生长因子脑源性神经营养因子(BDNF)在阿尔茨海默病、精神分裂症和抑郁症等多种神经退行性疾病和精神疾病中发挥着至关重要的作用。BDNF 已被提出作为诊断、预后和监测治疗的潜在生物标志物。了解影响 BDNF 水平的因素及其是否遵循昼夜节律对于解释 BDNF 测量值的波动至关重要。此外,我们还测量了生命参数、皮质醇和胰岛素样生长因子1(IGF1),以探索潜在的调节机制、干扰变量及其与BDNF浓度的相关性。研究结果表明,血浆 BDNF 在 24 小时内没有任何明显波动,表明没有昼夜节律。然而,睡眠时血清 BDNF 水平会下降。此外,血清 BDNF 与心率呈正相关,但与 IGF1 呈负相关。皮质醇与 BDNF 或 IGF1 之间没有明显的相关性。虽然血浆 BDNF 表明处于稳定状态,但夜间血清 BDNF 的下降可能是由于缺乏体力活动,并与血流动力学血流量减少(睡眠时心率降低)有关。样本采集类型(外周静脉插管与使用蝶形系统采血)对所测得的 BDNF 水平没有显著影响。白天采集样本对 BDNF 分析没有明显影响,这强调了在设计 BDNF 评估标准化方案时考虑活动水平而非时间的重要性。
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引用次数: 0
Feasibility of superimposed supine cycling and lower body negative pressure as an effective means of prolonging exercise tolerance in individuals experiencing persisting post-concussive symptoms: Preliminary results. 将叠加仰卧骑车和下半身负压作为一种有效手段,以延长出现持续性脑震荡后症状的人的运动耐受性的可行性:初步结果。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-05 DOI: 10.1113/EP091677
Raelyn Javra, Joel S Burma, Nathan E Johnson, Jonathan D Smirl

To examine the feasibility, utility and safety of superimposed lower body negative pressure (LBNP) and tilt during supine cycling in individuals suffering from persisting post-concussive symptoms (PPCS). Eleven individuals aged 17-31 (6 females/5 males) participated in two randomized separate visits, 1 week apart. A ramp-incremental test was performed during both visits until volitional failure. Visits included no pressure (control) or LBNP at -40 Torr (experimental) with head-up tilt at 15 degrees (females) or 30 degrees (males). Transcranial Doppler ultrasound was utilized to quantify middle cerebral artery velocity (MCAv), while symptom reports were filled out before and 0, 10, and 60 min post-exertion. Ratings of exertion and overall condition followed similar trends for participants across both tests. The relative increase in MCAv was blunted during the experimental condition (8%) compared to control (24%), while a greater heart rate (17 beats/min) was achieved during the LBNP condition (P = 0.047). Symptom severity at the 0 and 10 min post-exertion time points displayed negligible-to-small effect sizes between conditions (Wilcoxon's r < 0.11). Symptom reporting was lower at the 60 min post-exertion time point with these displaying a moderate effect size (Wilcoxon's r = 0.31). The combination of LBNP and tilt during supine cycling did not change the participants' subjective interpretation of the exertional test but attenuated the hyperpnia-induced vasodilatory MCAv response, while also enabling participants to achieve a higher heart rate during exercise and reduced symptoms 1 h later. As this protocol is safe and feasible, further research is warranted in this area for developing PPCS treatment options. HIGHLIGHTS: What is the central question of this study? What are the feasibility, safety and utility of combining head-up tilt with lower body negative pressure during supine cycling for blunting the increase in cerebral blood velocity seen during moderate-intensity exercise in individuals experiencing persisting post-concussion symptoms? What is the main finding and its importance? Although no differences were found in symptoms between conditions within the first 10 min following exertion, symptom severity scores showed a clinically meaningful reduction 60 min following the experimental condition compared to the non-experimental control condition.

目的:研究在仰卧骑车时叠加下半身负压(LBNP)和倾斜对患有持续性脑震荡后症状(PPCS)的患者的可行性、实用性和安全性。11 名年龄在 17-31 岁之间的患者(6 名女性/5 名男性)分别参加了两次随机访问,每次访问间隔 1 周。两次访问期间都进行了斜坡递增测试,直到意志衰竭。访问包括无压力(对照组)或-40 Torr的LBNP(实验组),同时头向上倾斜15度(女性)或30度(男性)。利用经颅多普勒超声波量化大脑中动脉速度(MCAv),同时填写运动前、运动后 0 分钟、10 分钟和 60 分钟的症状报告。在两次测试中,参与者对劳累程度和整体状况的评分趋势相似。与对照组(24%)相比,实验组的 MCAv 相对增加幅度较小(8%),而 LBNP 组的心率较高(17 次/分)(P = 0.047)。运动后 0 分钟和 10 分钟时点的症状严重程度在不同条件下的效应大小几乎可以忽略不计(Wilcoxon's r
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引用次数: 0
Circulating extracellular microvesicles associated with electronic cigarette use increase endothelial cell inflammation and reduce nitric oxide production 与使用电子香烟有关的循环细胞外微囊泡会增加内皮细胞炎症并减少一氧化氮的产生。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-02 DOI: 10.1113/EP091715
Nicholas G. Evanoff, Donald R. Dengel, Kelly A. Stockelman, Hannah Fandl, Noah M. DeSouza, Jared J. Greiner, Sheena R. Dufresne, Michael Kotlyar, Vinicius P. Garcia
<div> <section> <p>The purpose of this study was to determine the effect of circulating microvesicles isolated from chronic electronic (e-)cigarette users on cultured human umbilical vein endothelial cell (HUVEC) expression of nuclear factor-κB (NF-κB), cellular cytokine release, phosphorylation of endothelial nitric oxide synthase (eNOS) and NO production. The HUVECs were treated with microvesicles isolated via flow cytometry from nine non-tobacco users (five male and four female; 22 ± 2 years of age) and 10 e-cigarette users (six male and four female; 22 ± 2 years of age). Microvesicles from e-cigarette users induced significantly greater release of interleukin-6 (183.4 ± 23.6 vs. 150.6 ± 15.4 pg/mL; <i>P</i> = 0.002) and interleukin-8 (160.0 ± 31.6 vs. 129.4 ± 11.2 pg/mL; <i>P</i> = 0.01), in addition to expression of p-NF-κB p65 (Ser536) (18.8 ± 3.4 vs. 15.6 ± 1.5 a.u.; <i>P</i> = 0.02) from HUVECs compared with microvesicles from non-tobacco users. Nuclear factor-κB p65 was not significantly different between microvesicles from the non-tobacco users and from the e-cigarette users (87.6 ± 8.7 vs. 90.4 ± 24.6 a.u.; <i>P</i> = 0.701). Neither total eNOS (71.4 ± 21.8 vs. 80.4 ± 24.5 a.u.; <i>P</i> = 0.413) nor p-eNOS (Thr495) (229.2 ± 26.5 vs. 222.1 ± 22.7 a.u.; <i>P</i> = 0.542) was significantly different between microvesicle-treated HUVECs from non-tobacco users and e-cigarette users. However, p-eNOS (Ser1177) (28.9 ± 6.2 vs. 45.8 ± 9.0 a.u.; <i>P </i>< 0.001) expression was significantly lower from e-cigarette users compared with non-tobacco users. Nitric oxide production was significantly lower (8.2 ± 0.6 vs. 9.7 ± 0.9 μmol/L; <i>P</i> = 0.001) in HUVECs treated with microvesicles from e-cigarette users compared with microvesicles from non-tobacco users. This study demonstrated increased NF-κB activation and inflammatory cytokine production, in addition to diminished eNOS activity and NO production resulting from e-cigarette use.</p> </section> <section> <h3> Highlights</h3> <div> <ul> <li> <p><b>What is the central question of this study?</b></p> <p>Circulating microvesicles contribute to cardiovascular health and disease via their effects on the vascular endothelium. The impact of electronic (e-)cigarette use on circulating microvesicle phenotype is not well understood.</p> </li> <li> <p><b>What is the main finding and its importance?</b></p> <p>Circulating microvesicles from e-cigarette users increase endothelial cell inflammation and impair endothelial nitric oxide production. Endothelial infla
本研究的目的是确定从长期电子(e-)烟使用者体内分离出的循环微囊对培养的人脐静脉内皮细胞(HUVEC)的核因子-κB(NF-κB)表达、细胞因子释放、内皮一氧化氮合酶(eNOS)磷酸化和 NO 生成的影响。用流式细胞仪从 9 名非烟草使用者(5 男 4 女,22 ± 2 岁)和 10 名电子烟使用者(6 男 4 女,22 ± 2 岁)身上分离出的微囊泡处理 HUVEC。电子烟使用者的微囊泡诱导白细胞介素-6(183.4 ± 23.6 vs. 150.6 ± 15.4 pg/mL;P = 0.002)和白细胞介素-8(160.0 ± 31.6 vs. 129.4 ± 11.2 pg/mL;P = 0.003)的释放量明显增加。4 ± 11.2 pg/mL;P = 0.01),此外,与非烟草使用者的微囊泡相比,HUVEC 的 p-NF-κB p65(Ser536)表达(18.8 ± 3.4 vs. 15.6 ± 1.5 a.u.;P = 0.02)。核因子-κB p65 在非烟草使用者和电子烟使用者的微囊泡之间没有显著差异(87.6 ± 8.7 vs. 90.4 ± 24.6 a.u.;P = 0.701)。总 eNOS(71.4 ± 21.8 vs. 80.4 ± 24.5 a.u.;P = 0.413)和 p-eNOS (Thr495) (229.2 ± 26.5 vs. 222.1 ± 22.7 a.u.;P = 0.542)在经微囊处理的非烟草使用者和电子烟使用者的 HUVEC 之间均无显著差异。然而,p-eNOS(Ser1177)(28.9 ± 6.2 vs. 45.8 ± 9.0 a.u.;P
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引用次数: 0
Resistance exercise breaks during prolonged sitting augment the blood flow response to a subsequent oral glucose load in sedentary adults. 久坐时的阻力运动间歇可增强久坐成人对随后口服葡萄糖负荷的血流反应。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-02 DOI: 10.1113/EP091535
Emily M Rogers, Nile F Banks, Emma R Trachta, Morgan S Wolf, Alexander C Berry, Anna E Stanhewicz, Lucas J Carr, Bethany Barone Gibbs, Nathaniel D M Jenkins

Sitting-induced impairments in postprandial blood flow are an important link between sedentary behaviour and cardiometabolic disease risk. The objective of this work was to examine the effects of resistance exercise breaks (REB) performed every 30 min during an otherwise sedentary 3-h period on the vasodilatory response to a subsequent oral glucose load in sedentary adults. Twenty-four sedentary adults (27 ± 7 years, 16 females) completed two conditions. Fasting blood glucose, insulin, popliteal artery blood flow (PABF) and gastrocnemius perfusion were measured immediately before standardized breakfast consumption. After breakfast, the 3-h REB or uninterrupted (SIT) intervention period commenced. Participants sat at a workstation, and popliteal artery shear rate (PASR) was measured 60 and 120 min into this period. In the REB condition, participants performed a 3-min REB (3 × [20 s squats, 20 s high knees, 20 s calf raises]) every 30 min. Following the intervention period, baseline measurements were repeated. Participants then consumed a 75 g glucose beverage, and PABF and perfusion were measured every 30-60 min for the following 120 min. Relative to SIT, REB increased PASR at 60 min (+31.4 ± 9.2/s, P = 0.037) and 120 min (+37.4 ± 10.2/s, P = 0.019) into the intervention period. Insulin and glucose increased (P < 0.001) in response to glucose consumption, with no differences between conditions (P ≥ 0.299). In response to the glucose load, perfusion (1.57 vs. 1.11 mL/100 mL/min, P = 0.023) and PABF (+45.3 ± 11.8 mL/min, P = 0.001) were greater after REB versus SIT. Performing 3-min REB every 30 min during an otherwise sedentary 3-h period augmented leg blood flow responses to an oral glucose load. HIGHLIGHTS: What is the central question of this study? Can 3-min resistance exercise breaks (REB) performed during an otherwise sedentary 3-h period augment the vasodilatory response to a subsequent oral glucose load in sedentary adults? What is the main finding and its importance? Performing 3-min REB, which included squats, high knees, and calf raises, every 30 min augmented lower limb blood flow responses to a subsequent oral glucose load compared to 3 h of uninterrupted sitting in sedentary adults. Sitting-induced impairment in postprandial vasodilatory function has been identified as a link between sedentary behaviour and cardiometabolic disease. Thus, the current study presents a potentially effective strategy to offset this risk.

久坐引起的餐后血流障碍是久坐行为与心脏代谢疾病风险之间的重要联系。这项研究的目的是考察在久坐的 3 小时内每 30 分钟进行一次阻力运动休息(REB)对久坐成人随后口服葡萄糖负荷时血管舒张反应的影响。24 名久坐不动的成年人(27 ± 7 岁,16 名女性)完成了两个条件的测试。在食用标准化早餐前立即测量空腹血糖、胰岛素、腘动脉血流(PABF)和腓肠肌灌注。早餐后,开始 3 小时的 REB 或不间断(SIT)干预期。参与者坐在工作站上,在60分钟和120分钟后测量腘动脉剪切率(PASR)。在 REB 条件下,参与者每 30 分钟进行一次 3 分钟的 REB(3 × [20 秒深蹲,20 秒高抬膝,20 秒高抬小腿])。干预期结束后,重复基线测量。然后,参与者饮用 75 克葡萄糖饮料,在随后的 120 分钟内,每隔 30-60 分钟测量一次 PABF 和血流灌注。相对于 SIT,REB 在干预期的 60 分钟(+31.4 ± 9.2/s,P = 0.037)和 120 分钟(+37.4 ± 10.2/s,P = 0.019)增加了 PASR。胰岛素和葡萄糖增加(P
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引用次数: 0
An electron paramagnetic resonance time-course study of oxidative stress in the plasma of electronic cigarette exposed rats 暴露于电子香烟的大鼠血浆中氧化应激的电子顺磁共振时程研究。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-08-01 DOI: 10.1113/EP092064
Murugesan Velayutham, Amber Mills, Valery V. Khramtsov, I. Mark Olfert

The long-term consequences of electronic cigarette (Ecig) use in humans are not yet known, but it is known that Ecig aerosols contain many toxic compounds of concern. We have recently shown that Ecig exposure impairs middle cerebral artery (MCA) endothelial function and that it takes 3 days for MCA reactivity to return to normal. However, the sources contributing to impairment of the endothelium were not investigated. We hypothesized that the increased levels of oxidative stress markers in the blood are correlated with impaired MCA reactivity. We used electron paramagnetic resonance (EPR) spectroscopy to examine plasma from 4-month-old male Sprague–Dawley rats that were exposed to either air (n = 5) or 1 h Ecig exposure, after which blood samples were collected at varying times after exposure (i.e., 1–4, 24, 48 and 72 h postexposure, n = 4 or 5 in each time group). The EPR analyses were performed using the redox-sensitive hydroxylamine spin probe 1-hydroxy-3-carboxymethyl-2,2,5,5-tetramethyl-pyrrolidine (CMH) to measure the level of reactive oxidant species in the plasma samples. We found that EPR signal intensity from the CM radical was significantly increased in plasma at 1-4, 24 and 48 h (< 0.05, respectively) and returned to control (air) levels by 72 h. When evaluating the EPR results with MCA reactivity, we found a significant negative correlation (Pearson's = 0.0027). These data indicate that impaired cerebrovascular reactivity resulting from vaping is associated with the oxidative stress level (measured by EPR from plasma) and indicate that a single 1 h vaping session can negatively influence vascular health for up to 3 days after vaping.

Highlights

  • What is the central question of this study?

    Does the time course of oxidative stress triggered by electronic cigarette exposure follow the cerebral vascular dysfunction?

  • What is the main finding and its importance?

    Electron paramagnetic resonance analysis shows that the oxidative stress induced after a single 1 h exposure to electronic cigarette aerosol takes ≤72 h to return to normal, which mirrors the time course for vascular dysfunction in the middle cerebral artery that we have reported previously.

目前尚不清楚使用电子烟(Ecig)对人体的长期影响,但已知电子烟气溶胶中含有许多令人担忧的有毒化合物。我们最近的研究表明,接触电子烟会损害大脑中动脉(MCA)内皮功能,MCA反应性需要3天才能恢复正常。然而,我们并未研究导致内皮功能受损的原因。我们假设血液中氧化应激标记物水平的升高与 MCA 反应性受损有关。我们使用电子顺磁共振 (EPR) 光谱法检查了暴露于空气(n = 5)或 1 小时电子烟暴露的 4 个月大雄性 Sprague-Dawley 大鼠的血浆,然后在暴露后的不同时间收集了血液样本(即暴露后 1-4、24、48 和 72 小时,每个时间组 n = 4 或 5)。使用对氧化还原敏感的羟胺自旋探针 1-羟基-3-羧甲基-2,2,5,5-四甲基吡咯烷(CMH)进行 EPR 分析,以测量血浆样本中活性氧化物的水平。我们发现,在 1-4、24 和 48 小时内,血浆中 CM- 自由基的 EPR 信号强度明显增加(P
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引用次数: 0
Association analysis of indel variants and gene expression identifies MDM4 as a novel locus for skeletal muscle hypertrophy and power athlete status. 吲哚变异和基因表达的关联分析确定了 MDM4 是骨骼肌肥大和力量型运动员状态的新基因位点。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-07-23 DOI: 10.1113/EP091992
Hasan H Kazan, Anıl Kasakolu, Seyrani Koncagul, Mehmet A Ergun, George John, Rinat I Sultanov, Andrey V Zhelankin, Ekaterina A Semenova, Rinat A Yusupov, Nikolay A Kulemin, Andrey K Larin, Edward V Generozov, Celal Bulgay, Ildus I Ahmetov

Insertions and deletions (indels) are the second most common type of variation in the human genome. However, limited data on their associations with exercise-related phenotypes have been documented. The aim of the present study was to examine the association between 18,370 indel variants and power athlete status, followed by additional studies in 357,246 individuals. In the discovery phase, the D allele of the MDM4 gene rs35493922 I/D polymorphism was over-represented in power athletes compared with control subjects (P = 7.8 × 10-9) and endurance athletes (P = 0.0012). These findings were replicated in independent cohorts, showing a higher D allele frequency in power athletes compared with control subjects (P = 0.016) and endurance athletes (P = 0.031). Furthermore, the D allele was positively associated (P = 0.0013) with greater fat-free mass in the UK Biobank. MDM4 encodes a protein that inhibits the activity of p53, which induces muscle fibre atrophy. Accordingly, we found that MDM4 expression was significantly higher in the vastus lateralis of power athletes compared with endurance athletes (P = 0.0009) and was positively correlated with the percentage of fast-twitch muscle fibres (P = 0.0062) and the relative area occupied by fast-twitch muscle fibres (P = 0.0086). The association between MDM4 gene expression and an increased proportion of fast-twitch muscle fibres was confirmed in two additional cohorts. Finally, we found that the MDM4 DD genotype was associated with increased MDM4 gene expression in vastus lateralis and greater cross-sectional area of fast-twitch muscle fibres. In conclusion, MDM4 is suggested to be a potential regulator of muscle fibre specification and size, with its indel variant being associated with power athlete status. HIGHLIGHTS: What is the central question of this study? Which indel variants are functional and associated with sport- and exercise-related traits? What is the main finding and its importance? Out of 18,370 tested indels, the MDM4 gene rs35493922 I/D polymorphism was found to be the functional variant (affecting gene expression) and the most significant, with the deletion allele showing associations with power athlete status, fat-free mass and cross-sectional area of fast-twitch muscle fibres. Furthermore, the expression of MDM4 was positively correlated with the percentage of fast-twitch muscle fibres and the relative area occupied by fast-twitch muscle fibres.

插入和缺失(indels)是人类基因组中第二常见的变异类型。然而,关于它们与运动相关表型之间关系的数据却很有限。本研究的目的是检测 18,370 个吲哚变异与力量型运动员身份之间的关联,随后对 357,246 人进行了额外研究。在发现阶段,与对照受试者(P = 7.8 × 10-9)和耐力运动员(P = 0.0012)相比,MDM4 基因 rs35493922 I/D 多态性的 D 等位基因在力量型运动员中比例过高。这些发现在独立的队列中得到了重复,显示与对照组(P = 0.016)和耐力组(P = 0.031)相比,力量型运动员的 D 等位基因频率更高。此外,在英国生物库中,D等位基因与更大的去脂质量呈正相关(P = 0.0013)。MDM4 编码一种抑制 p53 活性的蛋白质,而 p53 可诱导肌肉纤维萎缩。因此,我们发现与耐力运动员相比,MDM4 在力量型运动员外侧肌中的表达量明显更高(P = 0.0009),并且与快速肌纤维的百分比(P = 0.0062)和快速肌纤维所占的相对面积(P = 0.0086)呈正相关。MDM4 基因表达与快肌纤维比例增加之间的关系在另外两个队列中得到了证实。最后,我们发现 MDM4 DD 基因型与外侧肌 MDM4 基因表达增加和快肌纤维横截面积增大有关。总之,MDM4 被认为是肌肉纤维规格和大小的潜在调节因子,其吲哚变体与力量型运动员身份有关。重点:本研究的核心问题是什么?哪些吲哚变异具有功能性并与运动和锻炼相关的特征有关?主要发现及其重要性是什么?在测试的 18,370 个吲哚变异中,发现 MDM4 基因 rs35493922 I/D 多态性是功能性变异(影响基因表达),也是最重要的变异,缺失等位基因与力量型运动员身份、去脂质量和快肌纤维横截面积有关。此外,MDM4 的表达与快速肌纤维的百分比和快速肌纤维所占的相对面积呈正相关。
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引用次数: 0
My sojourn with cerebral sympathetic nervous activity 我的脑交感神经活动之旅
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-07-20 DOI: 10.1113/EP092029
Patrice Brassard
<p>In 2006, I took one critical decision which would completely alter the trajectory of my career. Being in the final year of my PhD training under the mentorship of Dr Paul Poirier at Université Laval, Quebec, Canada, I decided The Copenhagen Muscle Research Center would be the place I wanted to complete my postdoctoral fellowship. Having focused my PhD work on exercise physiology in patients with type 2 diabetes (Brassard et al., <span>2006a,b</span>, <span>2007</span>; Caron et al., <span>2017</span>), I initially approached Prof. Michael Kjær at the annual meeting of the American College of Sports Medicine, which was in Denver, Colorado, in the same year. However, Prof. Kjær had recently changed his research focus away from diabetes, so it was not really possible for him to become my postdoc supervisor. During that brief meeting, he mentioned that one of his colleagues, who also happened to be present at the meeting, would most likely be interested in my profile. That colleague was Prof. Niels Secher (Aalkjaer et al., <span>2023</span>). The rest is history!</p><p>During my stay in Copenhagen in Prof. Secher's laboratory, I had the opportunity to develop a new research expertise. While I examined the influence of well-controlled type 2 diabetes on exercise responses during my PhD, I switched gears for my postdoc, and studied cerebral blood flow (CBF) regulation and cerebral metabolism in health and disease. For example, I got involved in a plethora of studies, looking at the impact of hypoxia (Avnstorp et al., <span>2015</span>; Bailey et al., <span>2017</span>; Overgaard et al., <span>2012</span>), endotoxaemia (Brassard et al., <span>2012</span>), and diabetes (Kim et al., <span>2015</span>) on CBF and cerebral oxygenation (<span></span><math> <semantics> <msub> <mi>S</mi> <mrow> <mi>c</mi> <msub> <mi>O</mi> <mn>2</mn> </msub> </mrow> </msub> <annotation>${{S}_{{mathrm{c}}{{{mathrm{O}}}_{mathrm{2}}}}}$</annotation> </semantics></math>) at rest and during exercise. We also studied the impact of acute and chronic exercise on brain-derived neurotrophic factor (Rasmussen et al., <span>2009</span>; Seifert et al., <span>2010</span>) and the influence of varying the speed of a left ventricular assist device during aerobic exercise on cerebral haemodynamics and exercise tolerance in patients in heart failure (Brassard et al., <span>2011</span>). During that time period, I was introduced to the cerebral pressure–flow relationship and dynamic cerebral autoregulation concepts. I also learned the basics of transfer function analysis with Johannes van Lieshout (Brassard et al., <span>2012</span>), a regular visiting scholar (and good friend) of Prof. Secher, who was present at the beg
埃斯勒第一次接触成功后,Esler 教授和我在接下来的几个月里定期互通电子邮件,以便我们更好地了解这项技术以及如何制备三价 NA 输液。随后,Nathalie Châteauvert女士也来了,她是我的实验室实施这项技术的另一位关键人物。她是魁北克-拉瓦尔大学心脏病和肺病研究所的药剂师兼研究药房协调员,负责制定为参与者持续输注三尖杉酯酸 NA 示踪剂的制备流程。考虑到我院的药房不具备制备这种示踪剂的条件,Nathalie Châteauvert 采取了必要的措施,确保与我院的核医学系合作。然后,我们必须找到一位经验丰富的临床医生来插入导管,尤其是逆行插入颈内静脉的导管,以便同时采集大脑静脉和动脉样本(这对脑NA溢出技术至关重要)。虽然这一程序在 Secher 教授的实验室中已是家常便饭,但我们机构中具有此类经验的临床医生却屈指可数。幸运的是,在研究开始的几个月前,一位熟人向我提到,我们机构治疗颅内压患者的麻醉师斯蒂芬-朗格文(Stephan Langevin)博士拥有在颈内静脉逆行插入导管的经验。重要的是,他非常愿意与我们合作开展这项研究。好消息!我们现在有了可以插入导管的临床医生。由于这项手术无法在我的实验室完成,我们必须与其他临床医生合作,进入手术室完成这项关键任务。我们机构的一位肺科医生马克-福尔廷(Marc Fortin)博士让我们使用了他经常使用的有创支气管镜室,包括所有必要的设备,更重要的是,他的所有员工都可以在下班前进行导管插入。早在2015年,Ainslie教授就已经知道我计划完成这项侵入性研究,因为我曾请他审查我的基金申请,重点是大脑SNA在动脉血压瞬时升高时对CBF调节作用的研究(顺便说一句,我花了5年时间才获得这项研究计划的资助!)。在整个研究期间,他毫不犹豫地将几台设备送到了我的实验室。此外,他的两名博士生迈克尔-泰姆科(Michael Tymko)和杰夫-库姆斯(Geoff Coombs)也可以参与研究,并对研究很感兴趣。这一切都是免费的。毋庸置疑,没有安斯利教授,就不可能有这项大脑 NA 溢出研究。研究团队由朱莉-德雅尔丹(Julie Desjardins)和维基-米考(Vickie Michaud)两位技术精湛的护士,以及我当时的研究生(奥德丽-德拉波(Audrey Drapeau)、劳伦斯-拉布雷克(Lawrence Labrecque)、萨拉-伊姆霍夫(Sarah Imhoff)和凯文-拉希马利(Kevan Rahimaly))和一群本科生组成。2018 年 5 月和 6 月,12 名参与者在 9 天内顺利完成了研究!这是研究团队取得的一项重要成就。但故事远未结束......例如,NA 分析最终比最初计划的要复杂得多。研究开始前,我与我所在机构的一位同事达成合作,由他负责三尖杉酯酶和非三尖杉酯酶NA的分析。遗憾的是,由于一些方法上的原因,这些分析未能完成。经过9年的筹划,我们成功完成了第一项脑NA溢出研究,但由于NA分析困难重重,我担心我们无法发表研究结果。在接下来的几个月里,我拼命寻找合作者来完成NA分析。失望之余,我做了一件我完全反对的事情:"回复所有人"。2020 年,我收到了一份邀请,希望我为自律神经系统和大脑自动调节专刊撰稿。具体地说,该期刊的特刊致力于通过不同的方法学途径和实验程序探索自律神经功能与大脑自动调节之间的联系。我毫不犹豫地使用了 "回复所有人 "选项,利用这一邀请(发送给几位国民核糖核酸(SNA)专家),向国民核糖核酸(SNA)领域的专家小组提交了我的请求。我的请求非常简单:'我想知道你们中是否有人(或你们的同事)拥有血浆和三价 NA 分析方面的专业知识?我正在积极寻找合作者。
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引用次数: 0
Apnoea as a novel method to improve exercise performance: A current state of the literature. 将呼吸暂停作为提高运动成绩的一种新方法:文献现状。
IF 2.6 4区 医学 Q2 PHYSIOLOGY Pub Date : 2024-07-19 DOI: 10.1113/EP091905
Janne Bouten, Louise Declercq, Jan Boone, Franck Brocherie, Jan G Bourgois

Acute breath-holding (apnoea) induces a spleen contraction leading to a transient increase in haemoglobin concentration. Additionally, the apnoea-induced hypoxia has been shown to lead to an increase in erythropoietin concentration up to 5 h after acute breath-holding, suggesting long-term haemoglobin enhancement. Given its potential to improve haemoglobin content, an important determinant for oxygen transport, apnoea has been suggested as a novel training method to improve aerobic performance. This review aims to provide an update on the current state of the literature on this topic. Although the apnoea-induced spleen contraction appears to be effective in improving oxygen uptake kinetics, this does not seem to transfer into immediately improved aerobic performance when apnoea is integrated into a warm-up. Furthermore, only long and intense apnoea protocols in individuals who are experienced in breath-holding show increased erythropoietin and reticulocytes. So far, studies on inexperienced individuals have failed to induce acute changes in erythropoietin concentration following apnoea. As such, apnoea training protocols fail to demonstrate longitudinal changes in haemoglobin mass and aerobic performance. The low hypoxic dose, as evidenced by minor oxygen desaturation, is likely insufficient to elicit a strong erythropoietic response. Apnoea therefore does not seem to be useful for improving aerobic performance. However, variations in apnoea, such as hypoventilation training at low lung volume and repeated-sprint training in hypoxia through short end-expiratory breath-holds, have been shown to induce metabolic adaptations and improve several physical qualities. This shows promise for application of dynamic apnoea in order to improve exercise performance. HIGHLIGHTS: What is the topic of this review? Apnoea is considered as an innovative method to improve performance. This review discusses the effectiveness of apnoea (training) on performance. What advances does it highlight? Although the apnoea-induced spleen contraction and the increase in EPO observed in freedivers seem promising to improve haematological variables both acutely and on the long term, they do not improve exercise performance in an athletic population. However, performing repeated sprints on end-expiratory breath-holds seems promising to improve repeated-sprint capacity.

急性屏气(呼吸暂停)会引起脾脏收缩,导致血红蛋白浓度短暂升高。此外,事实证明,呼吸暂停引起的缺氧会导致促红细胞生成素浓度在急性屏气后 5 小时内增加,这表明血红蛋白会长期增加。血红蛋白是氧气运输的重要决定因素,鉴于其提高血红蛋白含量的潜力,呼吸暂停被认为是提高有氧运动表现的一种新型训练方法。本综述旨在提供有关这一主题的最新文献资料。虽然呼吸暂停引起的脾脏收缩似乎能有效改善摄氧动力学,但当呼吸暂停与热身结合时,这似乎并不能立即转化为有氧运动成绩的提高。此外,只有憋气经验丰富的人在长时间和高强度的呼吸暂停方案中才会显示出促红细胞生成素和网织红细胞的增加。迄今为止,对缺乏经验的人进行的研究未能诱发呼吸暂停后促红细胞生成素浓度的急性变化。因此,呼吸暂停训练方案无法显示血红蛋白质量和有氧表现的纵向变化。从轻微的氧饱和度来看,低氧剂量可能不足以引起强烈的促红细胞生成素反应。因此,呼吸暂停似乎无助于提高有氧运动成绩。然而,呼吸暂停的变化,如在低肺活量下的低通气训练和通过短促呼气末屏气在缺氧状态下进行的重复冲刺训练,已被证明可诱导新陈代谢适应性和改善多种身体素质。这为应用动态呼吸暂停提高运动表现带来了希望。重点:本综述的主题是什么?呼吸暂停被认为是提高运动成绩的创新方法。本综述讨论了呼吸暂停(训练)对运动成绩的影响。它强调了哪些进展?虽然在自由潜水员身上观察到的呼吸暂停引起的脾脏收缩和 EPO 增加似乎有望在急性和长期改善血液变量,但它们并不能改善运动员的运动表现。不过,在呼气末屏气状态下进行重复冲刺似乎有望提高重复冲刺能力。
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