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Toll-like receptor 7 (TLR7) is known for eliciting immunity against single-stranded RNA viruses, and is increased in both human and cigarette smoke (CS)-induced, experimental chronic obstructive pulmonary disease (COPD). Here we show that the severity of CS-induced emphysema and COPD is reduced in TLR7-deficient mice, while inhalation of imiquimod, a TLR7-agonist, induces emphysema without CS exposure. This imiquimod-induced emphysema is reduced in mice deficient in mast cell protease-6, or when wild-type mice are treated with the mast cell stabilizer, cromolyn. Furthermore, therapeutic treatment with anti-TLR7 monoclonal antibody suppresses CS-induced emphysema, experimental COPD and accumulation of pulmonary mast cells in mice. Lastly, TLR7 mRNA is increased in pre-existing datasets from patients with COPD, while TLR7+ mast cells are increased in COPD lungs and associated with severity of COPD. Our results thus support roles for TLR7 in mediating emphysema and COPD through mast cell activity, and may implicate TLR7 as a potential therapeutic target.

Background: Moderate calorie-restricted diets and exercise training prevent loss of lean mass and cardiovascular risk. Because adherence to routine exercise recommendation is generally poor, we utilized recreational soccer training as a novel therapeutic exercise intervention in type 2 diabetes (T2D) patients. Objective: We compared the effects of acute and chronic soccer training plus calorie-restricted diet on protein catabolism and cardiovascular risk markers in T2D. Design, setting and subjects: Fifty-one T2D patients (61.1±6.4 years, 29 females: 22 males) were randomly allocated to the soccer+diet-group (SDG) or to the dietgroup (DG). The 40-min soccer sessions were held 3 times per week for 12 weeks. Results: Nineteen participants attended 100% of scheduled soccer sessions, and none suffered any injuries. The SDG group showed higher levels of growth hormone (GH), free fatty acids and ammonia compared with DG. After 12 weeks, insulin-like growth factor binding protein (IGFPB)-3 and glucose levels were lower in SDG, whereas insulin-like growth factor (IGF)-1/ IGFBP-3 ratio increased in both groups. After the last training session, an increase in IGF-1/ IGFBP-3 and attenuation in ammonia levels were suggestive of lower muscle protein catabolism. Conclusions: Recreational soccer training was popular and safe, and was associated with decreased plasma glucose and IGFBP-3 levels, decreased ammoniagenesis, and increased lipolytic activity and IGF-1/IGFBP-3 ratio, all indicative of attenuated catabolism.

We evaluated the effects of recreational football training combined with calorie-restricted diet (football + diet) vs calorie-restricted diet alone (diet) on aerobic fitness, lipid profile, and insulin resistance indicators in type 2 diabetes (T2D) patients. Forty-four T2D patients aged 48-68 years (27 females, 17 males) were randomly allocated to the football + diet group (FDG; n = 22) or to the diet group (DG; n = 22), of whom 19 FDG and 15 DG subjects completed the study. The football training was performed for 3 × 40 min/week for 12 weeks. Dual-energy X-ray absorptiometry scanning, treadmill testing, and fasting blood samplings were performed pre and post-intervention. After 12 weeks, maximal oxygen uptake (VO2max ) was elevated (P < 0.05) by 10 ± 4% in FDG but not in DG (-3 ± 4%, P < 0.05). After 12 weeks, reductions in blood triglycerides (0.4 ± 0.1 mmol/L), total cholesterol (0.6 ± 0.2 mmol/L), low-density lipoprotein, and very low-density lipoprotein levels were observed only in FDG. Fat mass decreased (P < 0.05) by 3.4 ± 0.4 kg in FDG and 3.7 ± 0.4 kg in DG. The lower (P < 0.05) glucagon and homeostatic model assessment of insulin resistance indicated an improvement in insulin sensitivity in FDG. In conclusion, football combined with restricted diet was effective in enhancing VO2max , reducing total cholesterol and triglycerides, and increasing insulin sensitivity, potentially providing better tools for the prevention of T2D complications than diet alone.