Cl097, a TLR7/8 ligand, inhibits TLR-4-dependent activation of IRAK-M and BCL-3 expression

Prolonged or repeated stimulation of Toll-like receptor (TLR) 4 leads to hyporesponsiveness of monocyte-derived macrophages, which seems to be a hallmark of immunosuppression related to sepsis and cancer. Two negative regulators of TLR-4 signaling are IL-1 receptor-associated kinase M and B-cell leukemia 3. Here, we demonstrate that the expression of both proteins is inhibited when the TLR-7/TLR-8 agonist CL097 is added to monocyte cultures despite costimulation with the TLR-4 agonist LPS or hyaluronic acid. Reduction of IL-1 receptor-associated kinase M and B-cell leukemia 3 was paralleled by a significant increased cytokine induction of TNF-[alpha], IL-10, and IL-12 observed after intracellular and extracellular TLR stimulation. In ex vivo stimulated whole blood of patients who have prolonged sepsis or metastatic cancer, TLR-7/TLR-8 agonists retained their ability of increased stimulation of TNF-[alpha]. These data might add to the understanding of sepsis and cancer-associated immune suppression in men

Is there a role for microRNAs in exercise immunology? A synopsis of current literature and future developments

With the discovery of microRNAs (miRNAs), an exceptional means of regulating gene expression was introduced a few years ago. MiRNAs function to inactivate specific messenger RNA transcripts leading to depletion of the corresponding protein, whereby computational studies have shown that about one third of all animal genes might be miRNA targets. Recent publications highlight the involvement of miRNAs in regulating the immune response. The aim of this review is to provide an overview of miRNA biogenesis and function, to illustrate their impact on both the innate as well as the adaptive immune system, to show the regulation of skeletal muscle plasticity and inflammation, and finally to present their possible role within the field of exercise immunology

Medium-term effects of a two-desk sit/stand workstation on cognitive performance and workload for healthy people performing sedentary work: a secondary analysis of a randomised controlled trial

Implementing sit/stand workstations in sedentary work environments is a common way to reduce sedentary time, but their medium-term effect on cognitive performance is unclear. To address this circumstance, eighteen office workers participated in a two-arm, randomised controlled cross-over trial (ClinicalTrials.gov Identifier: NCT02825303), either working at a traditional (sit) or an interventional (sit/stand) workplace for 23 weeks. Cognitive performance (working speed, reaction time, concentration performance, accuracy), workload and relevant covariates (salivary cortisol level, heart rate, physical activity, sitting time) were measured pre- and post-intervention under laboratory conditions. MANOVA and RMANOVA results did not show differences in performance parameters and workload, respectively, between sit/stand and traditional workplace users. Differences in text editing accuracy and cortisol levels for sit/stand workstation users indicate potential connectivity to cognitive parameters which should be further examined with large-scale studies. Practitioner summary: Medium-term effects of working at sit/stand workstations on cognitive performance and workload are unexplored. This randomised controlled trial suggests that cognitive performance and workload are unaffected for sit/stand workstation users after 23 weeks of use. However, accuracy appeared to improve and physiological stress appeared to be altered.© 2019 The Author(s

Age-specific response of skeletal muscle extracellular matrix to acute resistance exercise: A pilot study

The extracellular matrix (ECM) plays an essential role in the development, growth and repair of skeletal muscles and serves to transmit contractile force. However, its regulation is poorly understood. This study investigates the age-specificity of the effects of acute resistance exercise on ECM gene expression. To this purpose, five young (YM, 23.8 ± 2.2 yrs.) and 5 elderly (EM, 66.8 ± 4.1 yrs.) men performed one session of unilateral leg press and leg extension exercises. Six hours post-exercise, biopsies were taken from the vastus lateralis muscles of both legs. A PCR array was used to profile the expression of 84 ECM-related genes, of which 6 were validated by qPCR. The PCR array found 9 and 4 ECM-associated genes to be selectively altered (>1.5-fold change) in YM or EM only. Four further genes were upregulated in YM but downregulated in EM. Of the 6 genes validated on individual samples MMP9 expression increased in YM (9.7-fold) and decreased (0.2-fold) in EM. MMP15 was downregulated in EM only (0.6-fold). A significant correlation between leg extension 1 RM and changes in COL7A1 expression (ρ = 0.71) suggests a potential influence of fitness levels. In conclusion, acute resistance exercise affects ECM gene expression at least partly in an age-specific manner. The altered expression of genes encoding matrix metalloproteinases (MMP3, MMP9, MMP15) highlights the role of remodelling processes in the response to an acute bout of resistance exercise. Larger studies are required to verify the age-associated differences in gene expression profiles and establish their functional implications.© 2018 The Author(s

Effects of elastic band resistance training and nutritional supplementation on muscle quality and circulating muscle growth and degradation factors of institutionalized elderly women: the Vienna Active Ageing Study (VAAS)

Purpose: Regular resistance exercise training and a balanced diet may counteract the age-related muscular decline on a molecular level. The aim of this study was to investigate the influence of elastic band resistance training and nutritional supplementation on circulating muscle growth and degradation factors, physical performance and muscle quality (MQ) of institutionalized elderly. Methods: Within the Vienna Active Ageing Study, 91 women aged 83.6 (65.0–92.2) years were randomly assigned to one of the three intervention groups (RT, resistance training; RTS, resistance training plus nutritional supplementation; CT, cognitive training). Circulating levels of myostatin, activin A, follistatin, IGF-1 and GDF-15, as well as MQ and functional parameters were tested at baseline as well as after 3 and 6 months of intervention. Results: MQ of lower extremities significantly increased in the RT group (+14 %) and RTS group (+12 %) after 6 months. Performance improved in the RT and RTS groups for chair stand test (RT: +18 %; RTS: +15 %). Follistatin increased only in the RT group (+18 %) in the latter phase of the intervention, accompanied by a decrease in the activin A-to-follistatin ratio (−7 %). IGF-1, myostatin and GDF-15 levels were not affected by the intervention. Conclusion: Our data confirm that strength training improves physical performance and MQ even in very old institutionalized women. This amelioration appears to be mediated by blocking muscle degradation pathways via follistatin rather than inducing muscle growth through the IGF-1 pathway. As plasma levels of biomarkers reflect an overall status of various organ systems, future studies of tissue levels are suggested

Long-term follow-up on biological risk factors, adiposity, and cardiorespiratory fitness development in a physical education intervention: a natural experiment (CHAMPS-study DK)

Background: Schools are a key setting for large-scale primordial non-communicable disease prevention in young people, but little data on sustainability of impacts on cardiometabolic risk markers is available. Methods: Six and a half year follow-up of a natural experiment. In 2008, six public schools in the municipality of Svendborg (Denmark) augmented their curricular physical education (intervention) and four matched schools served as controls. At long term follow up in 2015 n = 312 participants aged 5–11 years had complete data (33% of children providing necessary baseline data). The intervention, that consisted of a trebling of weekly physical education lessons and courses provided to physical education teachers, was provided at intervention schools up until 6th grade. Participants attended 6th to 10th grade at follow-up. Differences in the homeostasis model assessment of insulin resistance, blood pressure, triglycerides, cholesterol ratios, cardiorespiratory fitness, waist-circumference, and a composite score of these, between participants attending intervention and control schools were analysed by mixed linear regression models. Differences in physical activity at follow-up was analysed cross-sectionally (no baseline available) in n = 495. Results: Compared to controls, children at intervention schools had a non-significant − 0.07 (− 0.32 to 0.18) standard deviations lower composite risk score 6.5 years after project initiation. Likewise, no statistically significant differences between intervention and control schools were found for any of the other outcomes (p-values ≥ 0.41). However, six of seven outcomes were in a direction favouring intervention schools. No statistically significant differences between intervention and control schools were observed for physical activity outcomes (p-values ≥ 0.13). Conclusions: An augmented physical activity program including 270 min of weekly physical education provided for three to seven years did not materialize in statistically significant differences in established risk markers in children from intervention compared to control schools. As the intervention was discontinued after 6th grade, the post-intervention effect of augmented physical education throughout adolescence is unknown. School-based physical activity programs may benefit from incorporating instruments for behaviour translation to leisure time in their intervention models to increase the probability of achieving public health relevance. Trial registration: ClinicalTrials.gov Identifier: NCT03510494.© The Author(s) 201

Regulation of Metabolic Disease-Associated Inflammation by Nutrient Sensors

Visceral obesity is frequently associated with the development of type 2 diabetes (T2D), a highly prevalent chronic disease that features insulin resistance and pancreatic β-cell dysfunction as important hallmarks. Recent evidence indicates that the chronic, low-grade inflammation commonly associated with visceral obesity plays a major role connecting the excessive visceral fat deposition with the development of insulin resistance and pancreatic β-cell dysfunction. Herein, we review the mechanisms by which nutrients modulate obesity-associated inflammation.© 2018 Alex S. Yamashita et a