Increased type-I interferon level is associated with liver damage and fibrosis in primary sclerosing cholangitis.

BACKGROUND: The level of type-I interferons (IFNs) in primary sclerosing cholangitis (PSC) was investigated to evaluate its association with disease activity and progression. METHODS: Bioactive type-I IFNs were evaluated in a murine model of PSC and human patients' sera using a cell-based reporter assay and ELISA techniques. In total, 57 healthy participants, 71 PSC, and 38 patients with primary biliary cholangitis were enrolled in this study. RESULTS: Bioactive type-I IFNs were elevated in the liver and serum of multidrug resistance protein 2-deficient animals and showed a correlation with the presence of CD45+ immune cells and serum alanine transaminase levels. Concordantly, bioactive type-I IFNs were elevated in the sera of patients with PSC as compared to healthy controls (sensitivity of 84.51%, specificity of 63.16%, and AUROC value of 0.8267). Bioactive IFNs highly correlated with alkaline phosphatase (r=0.4179, p<0.001), alanine transaminase (r=0.4704, p<0.0001), and gamma-glutamyl transpeptidase activities (r=0.6629, p<0.0001) but not with serum bilirubin. In addition, patients with PSC with advanced fibrosis demonstrated significantly higher type-I IFN values. Among the type-I IFN subtypes IFNα, ß and IFNω could be detected in patients with PSC with IFNω showing the highest concentration among the subtypes and being the most abundant among patients with PSC. CONCLUSIONS: The selectively elevated bioactive type-I IFNs specifically the dominating IFNω could suggest a novel inflammatory pathway that might also have a hitherto unrecognized role in the pathomechanism of PSC.

Diagnostics of νLa.max and Glycolytic Energy Contribution Indicate Individual Characteristics of Anaerobic Glycolytic Energy Metabolism Contributing to Rowing Performance.

The diagnostics of anaerobic glycolytic metabolism which play a subordinate role in elite rowing and parameters such as maximum lactate accumulation rate (νLa.max) have thus far not been associated with ergometer rowing performance. The aim of the study was to quantify the glycolytic energy metabolism (WGly) during a 2000 m ergometer rowing time trial (RTT) and νLa.max during a 10 s maximum ergometer rowing sprint test (RST) and to unravel associations between those variables and RTT performance. Combined post-exercise lactate measurements and oxygen uptake after RST and RTT were used to determine νLa.max and glycolytic energy contribution (WGly) in seven male and three female German U 23 national rowers (N = 10, 19.8 ± 0.9 years, 183.2 ± 7.0 cm height, 79.9 ± 13.3 kg body mass, 16.4 ± 5.1 % body fat). WGly during RTT ranged from 7 to 15.5% and νLa.max between 0.25 and 0.66 mmol∙L-1∙s-1. νLa.max correlated with WGly (p < 0.05, r = 0.74) and the mechanical power output (W) for the first 300 m (300first) during RTT (p < 0.05, r = 0.67). νLa.max further correlated with ∆300first-last (W) for the first and last 300 m (300last) during RTT (p < 0.01, r = 0.87) and also within the subgroup of male rowers. νLa.max displays a wide spectrum of individual differences in rowers. Due to this and its correlation to specific phases of RTT, it contributes to an individual energetic performance profile in rowing. Future studies must undermine the role of νLa.max for exercise performance and whether it serves as a marker that can be specifically targeted for a training-induced increase or decrease.

The Impact of Vegan and Vegetarian Diets on Physical Performance and Molecular Signaling in Skeletal Muscle.

Muscular adaptations can be triggered by exercise and diet. As vegan and vegetarian diets differ in nutrient composition compared to an omnivorous diet, a change in dietary regimen might alter physiological responses to physical exercise and influence physical performance. Mitochondria abundance, muscle capillary density, hemoglobin concentration, endothelial function, functional heart morphology and availability of carbohydrates affect endurance performance and can be influenced by diet. Based on these factors, a vegan and vegetarian diet possesses potentially advantageous properties for endurance performance. Properties of the contractile elements, muscle protein synthesis, the neuromuscular system and phosphagen availability affect strength performance and can also be influenced by diet. However, a vegan and vegetarian diet possesses potentially disadvantageous properties for strength performance. Current research has failed to demonstrate consistent differences of performance between diets but a trend towards improved performance after vegetarian and vegan diets for both endurance and strength exercise has been shown. Importantly, diet alters molecular signaling via leucine, creatine, DHA and EPA that directly modulates skeletal muscle adaptation. By changing the gut microbiome, diet can modulate signaling through the production of SFCA.