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Aerobic exercise inhibits acute lung injury: from mouse to human evidence Exercise reduced lung injury markers in mouse and in cells. 有氧运动抑制急性肺损伤:从小鼠到人类的证据表明,运动减少了小鼠和细胞中的肺损伤标志物。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2018-01-01
Nicole Cristine Rigonato-Oliveira, BreAnne Mackenzie, Andre Luis Lacerda Bachi, Manoel Carneiro Oliveira-Junior, Alana Santos-Dias, Maysa Alves Rodrigues Brandao-Rangel, Humberto Delle, Tamara Costa-Guimaraes, Nilsa Regina Damaceno-Rodrigues, Nilsa Regina Dulley, Marcela Anhesini Benetti, Christiane Malfitano, Christiane de Angelis, Regiane Albertini, Ana Paula Ligeiro Oliveira, Asghar Abbasi, Hinnak Northoff, Rodolfo Paula Vieira

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were preincubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1β, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1β, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1β, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.

急性呼吸窘迫综合征(ARDS)被定义为低氧血症性呼吸衰竭,伴有强烈的肺部炎症,涉及内皮细胞和中性粒细胞的过度活化。鉴于有氧运动(AE)的抗炎作用,本研究探讨了连续5周每天进行AE是否会抑制肺外lps诱导的ARDS。将C57Bl/6小鼠分为对照组、运动组、LPS组和运动+LPS组。AE在跑步机上进行5次/周,连续4周给予LPS。在最终AE物理测试24小时后,动物腹腔注射100ug LPS。此外,用IL-10(运动诱导的抗炎细胞因子)预孵育全血细胞、中性粒细胞和人内皮细胞。AE降低了总蛋白水平(p
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引用次数: 0
Anxiety and perceived psychological stress play an important role in the immune response after exercise. 焦虑和感知心理应激在运动后的免疫反应中起重要作用。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2018-01-01 DOI: 10.14195/2182-7087_ex2018_75
J. P. Edwards, N. Walsh, Philip C Diment, Ross Roberts
There are common pathways by which psychological stress and exercise stress alter immunity. However, it remains unknown whether psychological stress plays a role in the in vivo immune response to exercise. We examined the relationship between anxiety and perceived psychological stress reported before exercise and in vivo immunity after exercise using skin sensitisation with Diphenylcyclopropenone (DPCP). In a randomised design, sixty four, thoroughly familiarised, males completed widely used psychological instruments to assess state-anxiety and perceived psychological stress before exercise, and ran either 30 minutes at 60% (30MI) or 80% (30HI) V . O2peak, 120 minutes at 60% (120MI) V . O2peak or rested (CON) before DPCP sensitisation. Cutaneous recall to DPCP was measured as the dermal thickening response to a low-dose series DPCP challenge 4-weeks after sensitisation. After accounting for exercise (R2 = 0.20; P < 0.01), multiple-regression showed that pre-exercise state-anxiety (STAI-S; ΔR2 = 0.19; P < 0.01) and perceived psychological stress (ΔR2 = 0.13; P < 0.05) were moderately associated with the DPCP response after exercise. The STAI-S scores before exercise were considered low-to-moderate in these familiarised individuals (median split; mean STAI-S of low 25 and moderate 34). Further examination showed that the DPCP response after exercise (30MI, 30HI or 120MI) was 62% lower in those reporting low vs. moderate state-anxiety before exercise (mean difference in dermal thickening: -2.6 mm; 95% CI: -0.8 to -4.4 mm; P < 0.01). As such, the results indicate a beneficial effect of moderate (vs. low) state-anxiety and perceived psychological stress on in vivo immunity after exercise. Moreover, correlations were of comparable strength for the relationship between physiological stress (heart rate training impulse) and the summed dermal response to DPCP (r = -0.37; 95% CI: -0.05 to -0.62; P = 0.01), and state-anxiety and the summed dermal response to DPCP (r = 0.39; 95% CI: 0.08 to 0.63; P < 0.01). In conclusion, state-anxiety and perceived psychological stress levels before exercise play animportant role in determining the strength of the in vivo immune response after exercise. These findings indicate a similar strength relationship for the level of state-anxiety prior to exercise and the level of physiological stress during exercise with the in vivo immune response after exercise. Future research is required to investigate exercise-immune responses in athletes, military personnel and others in physically demanding occupations experiencing higher levels of psychological stress than those reported in this study e.g. related to important competition, military operations and major life events. Nevertheless, the present findings support the recommendation that exercise scientists should account for anxiety and psychological stress when examining the immune response to exercise.
心理压力和运动压力改变免疫力有共同的途径。然而,目前尚不清楚心理应激是否在体内对运动的免疫反应中起作用。我们使用二苯基环丙烯(DPCP)皮肤致敏,研究了运动前报告的焦虑和感知心理压力与运动后体内免疫之间的关系。在一项随机设计中,64名完全熟悉的男性在运动前完成了广泛使用的心理工具,以评估状态焦虑和感知的心理压力,并在60% (30MI)或80% (30HI) V下跑步30分钟。o2峰值,在60% (120MI) V下120分钟。DPCP致敏前o2峰值或休息(CON)。皮肤对DPCP的召回是在致敏后4周对低剂量系列DPCP刺激的皮肤增厚反应。考虑运动后(R2 = 0.20;P < 0.01),多元回归显示运动前状态焦虑(STAI-S;Δr2 = 0.19;P < 0.01)和感知心理应激(ΔR2 = 0.13;P < 0.05)与运动后DPCP反应中度相关。在这些熟悉的个体中,运动前的STAI-S评分被认为是低到中等(中位数分裂;平均STAI-S低25,中34)。进一步的检查显示,在运动前报告轻度与中度状态焦虑的患者中,运动后DPCP反应(30MI、30HI或120MI)降低62%(真皮增厚的平均差异:-2.6 mm;95% CI: -0.8 ~ -4.4 mm;P < 0.01)。因此,结果表明,适度(相对于低)的状态焦虑和感知的心理压力对运动后的体内免疫有有益的影响。此外,生理应激(心率训练脉冲)与对DPCP的总皮肤反应之间的相关性也具有相当的强度(r = -0.37;95% CI: -0.05 ~ -0.62;P = 0.01),状态焦虑和对DPCP的总皮肤反应(r = 0.39;95% CI: 0.08 ~ 0.63;P < 0.01)。综上所述,运动前的状态焦虑和感知的心理应激水平对运动后体内免疫反应的强度起着重要的决定作用。这些结果表明,运动前的状态焦虑水平和运动时的生理应激水平与运动后的体内免疫反应具有相似的强度关系。未来的研究需要调查运动员、军事人员和其他从事高体力要求职业的人的运动免疫反应,这些职业比本研究报告的心理压力水平更高,例如与重要比赛、军事行动和重大生活事件有关。然而,目前的研究结果支持了运动科学家在检查对运动的免疫反应时应该考虑焦虑和心理压力的建议。
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引用次数: 23
Toll like receptor expression induced by exercise in obesity and metabolic syndrome: A systematic review. 肥胖和代谢综合征中运动诱导Toll样受体表达:系统综述。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2018-01-01
Isabel Rada, Louise Deldicque, Marc Francaux, Hermann Zbinden-Foncea

Background: Obesity and metabolic syndrome are disorders that correlate with the activation of pro-inflammatory pathways and cytokine production, to which Toll like receptors (TLR) contribute. Exercise may act as an anti-inflammatory modulator, but there is no consensus about the role of the TLR in this tuning. The present styudy aims to systematically review the current evidence on exercise-induced TLR regulation in animals and humans suffering from obesity and metabolic syndrome.

Methods: Pubmed and Scopus databases were searched for publications from 1990 to September 2015. Search terms included: "Toll like Receptor", "TLR", "exercise", "obesity", "diabetes", and "metabolic syndrome". Elegibility criteria comprised: randomized control trials, cross-sectional and cohort studies; human or animal models with metabolic syndrome; any type of exercise; TLR expression measurement in any tissue by a clearly reported technique. The quality of selected studies was assessed using a modified version of the Downs and Black Quality Assessment Checklist. Data of study design; population; exercise type, timing and training elements; measurement technique, tissue analyzed and main outcome were extracted and categorized to facilitate data synthesis.

Results: 17 studies were included, of which 11 publications obtained a high, 5 a moderate and 1 a low score for quality assessment. A total of 8 human studies were analyzed: 6 studies used endurance continuous or interval training protocols, 1 study resistance training and the remaining study was performed following a marathon race. Blood cells were analyzed in seven studies, of which four studies sampled peripheral blood mononuclear cells (PBMC), three analyzed whole blood and one study sampled skeletal muscle. Nine animal studies were included: 8 used endurance training and 1 acute aerobic exercise. A variety of tissues samples were explored such as PBMC, skeletal muscle, adipose, vascular and nervous tissue. Globally, the animal studies showed a marked tendency towards a down-regulation of TLR2 and 4 expression accompagnied with, a reduced activation of nuclear factorkappaB (NF-κB) signaling and cytokine production, and an improvement in insulin sensitivity and body composition.

Conclusion: While animal studies showed a marked tendency towards TLR2 and 4 down-regulation after chronic endurance exercise, the current evidence in human is not sufficiently robust to conclude any role of TLR in the anti-inflammatory properties of exercise.

背景:肥胖和代谢综合征是与促炎通路激活和细胞因子产生相关的疾病,Toll样受体(TLR)参与了这一过程。运动可能是一种抗炎调节剂,但TLR在这种调节中的作用尚未达成共识。本研究旨在系统回顾目前关于运动诱导TLR调节在肥胖和代谢综合征动物和人类中的证据。方法:检索Pubmed和Scopus数据库1990 - 2015年9月的出版物。搜索词包括:“Toll样受体”、“TLR”、“运动”、“肥胖”、“糖尿病”和“代谢综合征”。入选标准包括:随机对照试验、横断面和队列研究;代谢综合征的人类或动物模型;任何类型的运动;用一种明确报道的技术测量任何组织中的TLR表达。所选研究的质量使用修改版本的Downs和Black质量评估清单进行评估。研究设计资料;人口;练习类型、时间和训练要素;对测量技术、组织分析和主要结果进行提取和分类,便于数据综合。结果:共纳入17篇文献,其中高、中、低评价文献分别为11篇、5篇和1篇。总共分析了8项人体研究:6项研究采用耐力连续或间歇训练方案,1项研究采用阻力训练,其余研究在马拉松比赛后进行。在7项研究中分析了血细胞,其中4项研究取样了外周血单个核细胞(PBMC), 3项研究取样了全血,1项研究取样了骨骼肌。9项动物研究包括:8项耐力训练和1项急性有氧运动。探索了多种组织样本,如PBMC、骨骼肌、脂肪、血管和神经组织。在全球范围内,动物研究显示,TLR2和4的表达明显下调,核因子κ b (NF-κB)信号激活和细胞因子产生减少,胰岛素敏感性和身体成分改善。结论:虽然动物实验显示慢性耐力运动后TLR2和4有明显的下调趋势,但目前在人体中的证据还不足以得出TLR在运动抗炎特性中的作用。
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引用次数: 0
Exercise induced alterations in NK-cell cytotoxicity - methodological issues and future perspectives. 运动诱导nk细胞毒性的改变——方法学问题和未来展望。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2017-01-01
Philipp Zimmer, Alexander Schenk, Markus Kieven, Michelle Holthaus, Jonas Lehmann, Lukas Lövenich, Wilhelm Bloch

With their ability to recognize and eliminate virus-infected and neoplastic cells, natural killer cells (NK-cells) represent an important part of the innate immune system. NK-cells have attracted the attention of exercise scientists for more than thirty years ago. To date, it is widely accepted that NK-cell counts in the peripheral blood are strongly influenced by acute exercise. Additionally, many studies reported effects of both, acute and chronic exercise on NK-cell cytotoxicity. However, these findings are contradictory. The inconsistence in findings may be argued with different exercise paradigms (type, duration, intensity). Moreover, strongly varying methods were used to detect NK-cell cytotoxicity. This review gives an overview of studies, investigating the impact of acute and chronic exercise on NK-cell cytotoxicity in young and old healthy adults, as well as on specific populations, such as cancer patients. Furthermore, different methodological approaches to assess NK-cell cytotoxicity are critically discussed to state on inconsistent study results and to give perspectives for further research in this field.

自然杀伤细胞(nk细胞)具有识别和消除病毒感染细胞和肿瘤细胞的能力,是先天免疫系统的重要组成部分。三十多年前,nk细胞就引起了运动科学家的注意。迄今为止,人们普遍认为外周血nk细胞计数受到急性运动的强烈影响。此外,许多研究报告了急性和慢性运动对nk细胞毒性的影响。然而,这些发现是相互矛盾的。研究结果的不一致可能与不同的运动模式(类型、持续时间、强度)有关。此外,检测nk细胞毒性的方法差异很大。本文综述了研究的总体情况,调查了急性和慢性运动对年轻和老年健康成年人以及特定人群(如癌症患者)nk细胞毒性的影响。此外,对评估nk细胞毒性的不同方法进行了批判性讨论,以说明不一致的研究结果,并为该领域的进一步研究提供观点。
{"title":"Exercise induced alterations in NK-cell cytotoxicity - methodological issues and future perspectives.","authors":"Philipp Zimmer,&nbsp;Alexander Schenk,&nbsp;Markus Kieven,&nbsp;Michelle Holthaus,&nbsp;Jonas Lehmann,&nbsp;Lukas Lövenich,&nbsp;Wilhelm Bloch","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>With their ability to recognize and eliminate virus-infected and neoplastic cells, natural killer cells (NK-cells) represent an important part of the innate immune system. NK-cells have attracted the attention of exercise scientists for more than thirty years ago. To date, it is widely accepted that NK-cell counts in the peripheral blood are strongly influenced by acute exercise. Additionally, many studies reported effects of both, acute and chronic exercise on NK-cell cytotoxicity. However, these findings are contradictory. The inconsistence in findings may be argued with different exercise paradigms (type, duration, intensity). Moreover, strongly varying methods were used to detect NK-cell cytotoxicity. This review gives an overview of studies, investigating the impact of acute and chronic exercise on NK-cell cytotoxicity in young and old healthy adults, as well as on specific populations, such as cancer patients. Furthermore, different methodological approaches to assess NK-cell cytotoxicity are critically discussed to state on inconsistent study results and to give perspectives for further research in this field.</p>","PeriodicalId":50468,"journal":{"name":"Exercise Immunology Review","volume":null,"pages":null},"PeriodicalIF":7.3,"publicationDate":"2017-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"34758379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developing a multi-component immune model for evaluating the risk of respiratory illness in athletes. 开发多组分免疫模型,评估运动员呼吸系统疾病的风险。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2017-01-01
Maree Gleeson, David B Pyne, Lisa J Elkington, Sharron T Hall, John R Attia, Christopher Oldmeadow, Lisa G Wood, Robin Callister

Clinical and laboratory identification of the underlying risk of respiratory illness in athletes has proved problematic. The aim of this study was to determine whether clinical data, combined with immune responses to standardised exercise protocols and genetic cytokine polymorphism status, could identify the risk of respiratory illness (symptoms) in a cohort of highly-trained athletes. Male endurance athletes (n=16; VO2max 66.5 ± 5.1 mL.kg-1.min-1) underwent a clinical evaluation of known risk factors by a physician and comprehensive laboratory analysis of immune responses both at rest and after two cycling ergometer tests: 60 min at 65% VO2max (LONG); and 6 x 3 min intervals at 90% VO2max (INTENSE). Blood tests were performed to determine Epstein Barr virus (EBV) status and DNA was genotyped for a panel of cytokine gene polymorphisms. Saliva was collected for measurement of IgA and detection of EBV DNA. Athletes were then followed for 9 months for self-reported episodes of respiratory illness, with confirmation of the underlying cause by a sports physician. There were no associations with risk of respiratory illness identified for any parameter assessed in the clinical evaluations. The laboratory parameters associated with an increased risk of respiratory illnesses in highly-trained athletes were cytokine gene polymorphisms for the high expression of IL-6 and IFN-ɣ; expression of EBV-DNA in saliva; and low levels of salivary IgA concentration. A genetic risk score was developed for the cumulative number of minor alleles for the cytokines evaluated. Athletes prone to recurrent respiratory illness were more likely to have immune disturbances that allow viral reactivation, and a genetic predisposition to pro-inflammatory cytokine responses to intense exercise.

临床和实验室鉴定的潜在风险的呼吸系统疾病的运动员已经证明是有问题的。本研究的目的是确定临床数据,结合对标准化运动方案的免疫反应和基因细胞因子多态性状态,是否可以识别高训练运动员队列中呼吸系统疾病(症状)的风险。男性耐力运动员(n=16;VO2max(66.5±5.1 ml .kg-1 min-1)由医生对已知危险因素进行临床评估,并对休息时和两次骑行测力仪测试后的免疫反应进行全面的实验室分析:以65% VO2max (LONG)运动60分钟;在90% VO2max (intensity)下,间隔6 x 3分钟。进行血液检测以确定eb病毒(EBV)状态,并对DNA进行基因分型以确定一组细胞因子基因多态性。采集唾液进行IgA检测和EBV DNA检测。然后对运动员进行为期9个月的自我报告的呼吸系统疾病发作,并由运动医生确认潜在原因。在临床评估中,没有发现任何参数与呼吸系统疾病的风险相关。与高训练运动员呼吸系统疾病风险增加相关的实验室参数是导致IL-6和IFN- α高表达的细胞因子基因多态性;EBV-DNA在唾液中的表达;唾液IgA浓度低。对所评估的细胞因子的次要等位基因的累积数量进行了遗传风险评分。易患复发性呼吸系统疾病的运动员更有可能出现免疫紊乱,从而导致病毒再激活,并且遗传倾向于对剧烈运动产生促炎细胞因子反应。
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引用次数: 0
A single bout of dynamic exercise enhances the expansion of MAGE-A4 and PRAME-specific cytotoxic T-cells from healthy adults. 单次动态锻炼可增强健康成人MAGE-A4和prame特异性细胞毒性t细胞的扩增。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2015-01-01
Emily C P LaVoy, Catherine M Bollard, Patrick J Hanley, James W Blaney, Daniel P O'Connor, Jos A Bosch, Richard J Simpson

The ex vivo expansion of tumor-associated-antigen (TAA)- specific cytotoxic T-cells (CTLs) from healthy donors for adoptive transfer to cancer patients is now providing additional treatment options for patients. Many studies have shown that adoptive transfer of expanded CTLs can reduce the risk of relapse in cancer patients following hematopoietic stem cell transplantation (HSCT). However, the procedure can be limited by difficulties in priming and expanding sufficient numbers of TAA-specific-CTLs. Because acute dynamic exercise mobilizes large numbers of T-cells to peripheral blood, we hypothesized that a single bout of exercise would augment the ex vivo expansion of TAA-specific-CTLs.We therefore collected lymphocytes from blood donated by healthy adults at rest and after brief maximal dynamic exercise. TAA-specific CTLs were expanded using autologous monocyte-derived-dendritic cells pulsed with melanoma-associated antigen 4 (MAGE-A4), with preferentially expressed antigen in melanoma (PRAME), and with Wilms' tumor protein (WT-1). Post exercise, 84% of the participants had a greater number of CTLs specific for at least one of the three TAA.Cells expanded from post exercise blood yielded a greater number of MAGE-A4 and PRAME-specific-cells in 70% and 61% of participants, respectively. In the 'exercise-responsive' participants (defined as participants with at least a 10% increase in TAA-specific-CTLs post-exercise), MAGEA4- and PRAME-specific-CTLs increased 3.4-fold and 6.2- fold respectively. Moreover, expanded TAA-specific CTLs retained their antigen-specific cytotoxic activity. No phenotype differences were observed between expanded cells donated at rest and postexercise. We conclude that exercise can enhance the ex vivo expansion of TAA-specific-CTLs from healthy adults without compromising cytotoxic function. Hence, this study has implications for immunotherapy using adoptive T-cell transfer of donor-derived T-cells after allogeneic HSCT.

来自健康供体的肿瘤相关抗原(TAA)特异性细胞毒性t细胞(ctl)体外扩增用于过继转移给癌症患者,现在为患者提供了额外的治疗选择。许多研究表明,扩大的ctl过继移植可以降低癌症患者造血干细胞移植(HSCT)后复发的风险。然而,由于难以启动和扩增足够数量的taa特异性ctl,该程序可能受到限制。由于急性动态运动将大量t细胞动员到外周血,我们假设单次运动将增加taa特异性ctl的体外扩增。因此,我们从健康成人在休息和短暂的最大动态运动后捐献的血液中收集淋巴细胞。taa特异性ctl扩增使用自体单核细胞衍生的树突状细胞,用黑色素瘤相关抗原4 (MAGE-A4)、黑色素瘤优先表达抗原(PRAME)和Wilms肿瘤蛋白(WT-1)脉冲。运动后,84%的参与者在三种TAA中至少有一种具有更多的特异性ctl。从运动后血液中扩增的细胞分别在70%和61%的参与者中产生了更多的MAGE-A4和prame特异性细胞。在“运动反应”参与者(定义为运动后taa特异性ctl增加至少10%的参与者)中,MAGEA4和prame特异性ctl分别增加了3.4倍和6.2倍。此外,扩增的taa特异性ctl保留了抗原特异性细胞毒活性。在休息和运动后捐赠的扩增细胞之间没有观察到表型差异。我们得出结论,运动可以增强健康成人taa特异性ctl的体外扩增,而不影响细胞毒性功能。因此,这项研究对异体造血干细胞移植后使用供体来源的t细胞进行过继t细胞移植的免疫治疗具有启示意义。
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引用次数: 0
Exercise-induced increases in cell free DNA in human plasma originate predominantly from cells of the haematopoietic lineage. 运动引起的人血浆中游离细胞DNA的增加主要来源于造血细胞。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2015-01-01
Suzan Tug, Susanne Helmig, Eva Ricarda Deichmann, Anna Schmeier-Jürchott, Eva Wagner, Tim Zimmermann, Markus Radsak, Mauro Giacca, Perikles Simon

The role of cell free DNA (cfDNA) has been intensively discussed under various pathological conditions and after acute bouts of exercise. To date, there is still no conclusive evidence concerning the cellular origin of cfDNA and the entire mechanism leading to elevated cfDNA concentrations in human plasma and serum. Here, we investigated the cellular origin of cfDNA in sex-mismatched haematopoietic stem cell transplantation (HSCT) and liver transplantation (LT) patients by determining the relative proportion of Y-chromosomal to total nuclear cfDNA. Total nuclear cfDNA and Y-chromosomal cfDNA concentrations were determined in blood plasma before and after an incremental exercise test via quantitative real-time PCR (qPCR). Female HSCT patients showed high proportions of Y-chromosomal cfDNA. Both total nuclear and Y-chromosomal cfDNA increased significantly and in a highly correlated fashion due to exercise. In male HSCT patients with female donors less than 10% of the cfDNA was of Y-chromosomal origin at any point in time and even though the total amount of cfDNA increased during exercise, no increases in Y-chromosomal DNA could be detected. The percentage of Y-chromosomal cfDNA in female LT patients with male donors was very low and levels remained unchanged during exercise. This indicates that cells not derived from the bone marrow, in this case transplanted liver cells, represented only a minor fraction of cfDNA in blood plasma and were not released during acute physical exercise. Even though many physiological conditions may be altered in transplant patients versus healthy people, our results strongly suggest that cells from the haematopoietic lineage are the main source of cfDNA released during acute bouts of exercise.

游离细胞DNA (cfDNA)在各种病理条件下和急性运动后的作用已被广泛讨论。迄今为止,关于cfDNA的细胞起源和导致人血浆和血清中cfDNA浓度升高的整个机制仍没有确凿的证据。在这里,我们通过测定y染色体与总核cfDNA的相对比例,研究了性别错配的造血干细胞移植(HSCT)和肝移植(LT)患者cfDNA的细胞来源。采用实时荧光定量PCR (quantitative real-time PCR, qPCR)测定增量运动试验前后血浆中总核cfDNA和y染色体cfDNA浓度。女性HSCT患者y染色体cfDNA比例较高。由于运动,核和y染色体cfDNA总量均显著增加,并以高度相关的方式增加。在女性供体的男性HSCT患者中,在任何时间点,少于10%的cfDNA来自y染色体,即使cfDNA总量在运动期间增加,也未检测到y染色体DNA的增加。在男性供体的女性LT患者中,y染色体cfDNA的百分比非常低,并且在运动期间水平保持不变。这表明非来自骨髓的细胞,在本例中是移植的肝细胞,只占血浆中cfDNA的一小部分,并且在急性体育锻炼期间没有释放。尽管与健康人相比,移植患者的许多生理状况可能会发生改变,但我们的研究结果强烈表明,来自造血谱系的细胞是急性运动期间释放cfDNA的主要来源。
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引用次数: 0
Influence of age and physical fitness on miRNA-21, TGF-β and its receptors in leukocytes of healthy women. 年龄和体质对健康女性白细胞中miRNA-21、TGF-β及其受体的影响
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2015-01-01
Barbara Halper, Marlene Hofmann, Stefan Oesen, Bernhard Franzke, Petra Stuparits, Claudia Vidotto, Harald Tschan, Norbert Bachl, Eva-Maria Strasser, Michael Quittan, Karl-Heinz Wagner, Barbara Wessner

The TGF-β superfamily has been shown to play an important role in a wide range of physiological as well as pathological processes including ageing, immune modulation, atherosclerosis and cancer development. The aim of the current study was to investigate (i) whether TGF-β signalling in peripheral blood mononuclear cells (PBMCs) would differ between young and old females and (ii) whether physical performance parameters of elderly women would be related to the expression of TGF-β or its receptors. Sixteen healthy young (22-28 years; YF) and 90 healthy older (65-92 years; OF) females participated in the study. In addition to several components of health-related physical fitness, circulating CRP and TGF-β levels were determined together with the mRNA expression of TGF-β, TGF-βRI, TGF-βRII, and miRNA-21 (known to interfere with TGF-β signalling) in PBMCs. Physical fitness as determined by 6-minutes walking test (YF:median 932 (range 573-1254) m; OF:360 (114-558) m), handgrip strength (YF: 32 (24-39) kg; OF:18(10-30) kg), relative isokinetic peak torque of knee extensors (YF:1.9 (1.2- 2.3) Nm/kg; OF:1.0 (0.2-1.9) Nm/kg and flexors (YF: 1.1 (0.7- 1.5) Nm/kg; OF: 0.5 (0.2-1.0) Nm/kg was substantially lower in older women (p<0.001 for all comparisons). These changes were paralleled by an increase in hs-CRP (YF: 0.9 (0.1-4.3)mg/L; OF: 2.3 (0.3-56.7)mg/L,p<0.001). Serum levels of TGF-β and TGF-β mRNA levels from PBMCs did not differ between young and old women whereas, both TGF- βRI/GAPDH (YF: 4.07 (1.38-14.60); OF: 2.08 (0.14-28.81); p=0.020) and TGF-βRII/GAPDH levels (YF: 3.16 (1.14- 10.25); OF: 1.71 (0.51-14.86); p=0.020) were lower with respect to old age. In elderly women, only TGF-βRΙ expression correlated negatively with miRNA-21 expression in PBMCs (ρ=-0.315; p=0.004). Interestingly, hs-CRP and miRNA correlated positively with handgrip strength (ρ=0.237 and ρ=243, p<0.05), while none of the TGF-β-related parameters were related to physical performance. The results suggest that age affects TGF-β signalling in leukocytes by altering the expression levels of its receptors. These changes seem to occur independently of physical fitness of old women.

TGF-β超家族已被证明在广泛的生理和病理过程中发挥重要作用,包括衰老、免疫调节、动脉粥样硬化和癌症的发展。本研究的目的是研究(1)外周血单核细胞(PBMCs)中TGF-β信号传导在年轻女性和老年女性之间是否存在差异;(2)老年女性的身体机能参数是否与TGF-β或其受体的表达有关。16名健康青年(22-28岁);90名健康老年人(65-92岁;女性参与了这项研究。除了与健康相关的几种体能成分外,还测定了pbmc中循环CRP和TGF-β水平以及TGF-β、TGF-β ri、TGF-β rii和miRNA-21(已知干扰TGF-β信号传导)的mRNA表达。6分钟步行测试(YF:中位数932(范围573-1254)m;OF:360 (114-558) m),握力(YF: 32 (24-39) kg;OF:18(10-30) kg),膝关节伸肌的相对等速峰值扭矩(YF:1.9 (1.2- 2.3) Nm/kg;OF:1.0 (0.2-1.9) Nm/kg和flexors (YF: 1.1 (0.7- 1.5) Nm/kg;老年妇女的OF: 0.5 (0.2-1.0) Nm/kg显著降低(p
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引用次数: 0
Understanding graft-versus-host disease. Preliminary findings regarding the effects of exercise in affected patients. 了解移植物抗宿主病。关于运动对患病患者影响的初步发现。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2015-01-01
Carmen Fiuza-Luces, Nuria Garatachea, Richard J Simpson, Nathan A Berger, Manuel Ramírez, Alejandro Lucia

Advances in this century regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) have led to an expanding population of long-term survivors, many of whom suffer severe side effects, particularly those related to graft-versushost disease (GVHD), a potentially multi-systemic disorder caused by immunoeffector donor lymphocytes that destroy host tissues. The GVHD, especially in its chronic form (cGVHD), generates considerable morbidity and compromises the physical capacity of patients. We have reviewed the main pathophysiological aspects of the disease as well as the data available on the effects of exercise in GVHD, based on animal and human patient research. Although exercise training as an adjunct therapy to improve health outcomes after allo-HSCT shows promise (particularly, this lifestyle intervention can improve physical fitness and possibly immune function while attenuating fatigue), there is a need for more randomized control trials that focus specifically on GVHD.

本世纪关于同种异体造血干细胞移植(alloo - hsct)的进展导致了长期幸存者群体的扩大,其中许多人遭受严重的副作用,特别是与移植物抗宿主病(GVHD)相关的副作用,这是一种由免疫效应供体淋巴细胞破坏宿主组织引起的潜在多系统疾病。GVHD,特别是慢性形式(cGVHD),会产生相当大的发病率并损害患者的身体能力。我们回顾了该疾病的主要病理生理方面,以及基于动物和人类患者研究的运动对GVHD的影响的现有数据。尽管运动训练作为一种辅助疗法来改善同种异体造血干细胞移植后的健康结果显示出希望(特别是,这种生活方式干预可以改善身体健康,并可能在减轻疲劳的同时改善免疫功能),但仍需要更多专门针对GVHD的随机对照试验。
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引用次数: 0
Exercise, skeletal muscle and inflammation: ARE-binding proteins as key regulators in inflammatory and adaptive networks. 运动、骨骼肌和炎症:are结合蛋白在炎症和适应性网络中的关键调节作用。
IF 7.3 4区 医学 Q1 Medicine Pub Date : 2015-01-01 DOI: 10.15496/PUBLIKATION-9059
T. Beiter, M. Hoene, Frauke Prenzler, F. Mooren, J. Steinacker, C. Weigert, A. Nieß, B. Munz
The role of inflammation in skeletal muscle adaptation to exercise is complex and has hardly been elucidated so far. While the acute inflammatory response to exercise seems to promote skeletal muscle training adaptation and regeneration, persistent, low-grade inflammation, as seen in a multitude of chronic diseases, is obviously detrimental. The regulation of cytokine production in skeletal muscle cells has been relatively well studied, yet little is known about the compensatory and anti-inflammatory mechanisms that resolve inflammation and restore tissue homeostasis. One important strategy to ensure sequential, timely and controlled resolution of inflammation relies on the regulated stability of mRNAs encoding pro-inflammatory mediators. Many key transcripts in early immune responses are characterized by the presence of AU-rich elements (AREs) in the 3'-untranslated regions of their mRNAs, allowing efficient fine-tuning of gene expression patterns at the post-transcriptional level. AREs exert their function by recruiting particular RNA-binding proteins, resulting, in most cases, in de-stabilization of the target transcripts. The best-characterized ARE-binding proteins are HuR, CUGBP1, KSRP, AUF1, and the three ZFP36 proteins, especially TTP/ZFP36. Here, we give a general introduction into the role of inflammation in the adaptation of skeletal muscle to exercise. Subsequently, we focus on potential roles of ARE-binding proteins in skeletal muscle tissue in general and specifically exercise-induced skeletal muscle remodeling. Finally, we present novel data suggesting a specific function of TTP/ZFP36 in exercise-induced skeletal muscle plasticity.
炎症在骨骼肌适应运动中的作用是复杂的,迄今为止几乎没有被阐明。虽然对运动的急性炎症反应似乎促进了骨骼肌训练的适应和再生,但在许多慢性疾病中,持续的低级别炎症显然是有害的。骨骼肌细胞中细胞因子产生的调控已经得到了较好的研究,但对于解决炎症和恢复组织稳态的代偿和抗炎机制知之甚少。确保炎症有序、及时和可控的解决的一个重要策略依赖于编码促炎介质的mrna的调节稳定性。早期免疫应答中的许多关键转录物的特点是在其mrna的3'-非翻译区存在富au元件(AREs),允许在转录后水平对基因表达模式进行有效的微调。AREs通过招募特定的rna结合蛋白来发挥其功能,在大多数情况下,导致目标转录物的不稳定。最具特征的是HuR、CUGBP1、KSRP、AUF1和ZFP36蛋白,尤其是TTP/ZFP36蛋白。在这里,我们一般介绍炎症在骨骼肌适应运动中的作用。随后,我们将重点关注are结合蛋白在骨骼肌组织中的潜在作用,特别是运动诱导的骨骼肌重塑。最后,我们提出了新的数据,表明TTP/ZFP36在运动诱导的骨骼肌可塑性中具有特定功能。
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引用次数: 48
期刊
Exercise Immunology Review
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