ABSTRACT
OBJECTIVES: The present study aimed to investigate the anti-inflammatory effects of vitamin D and resistance training in men with type 2 diabetes mellitus and vitamin D deficiency. DESIGN: This study was a randomized, placebo-controlled, double-blinded clinical trial.Trial registration code: IRCT20190204042621N1. PARTICIPANTS: Forty-eight patients with type 2 diabetes aged 40-65 (from a total of 52 volunteers in Ardabil diabetes clinic) were randomly assigned to either the vitamin D supplementation with resistance training group (VD + RT: n = 12), the resistance training group (RT: n = 12), the vitamin D supplementation group (VD: n = 12), or the control group (CON: n = 12). INTERVENTION: The subjects in VD group took vitamin D supplements at 50000 IU per 2 weeks for 3 months; the subjects in RT group exercised 3 times per week for 12 weeks; and the subjects in VD + RT group participated in both treatments. Subjects in CON group were asked to maintain normal daily life pattern for the duration of the study. MEASUREMENTS: Serum Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α) and C-reactive protein (CRP) levels were determined at pre and post-test and the data were compared among the four groups and between two tests (4 × 2) using two-way ANOVA with repeated measures. RESULTS: IL-6 decreased significantly (P = 0.001) in all groups (VD + RT = % -71.73, RT = % -65.85, VD = % -61.70). TNF-α decreased significantly (P = 0.001) in VD + RT (% -44.90) and RT (% -40) groups. CRP showed no significant change in any group (P > 0.05). CONCLUSION: Results demonstrated that vitamin D supplementation in addition to resistance training had positive effects on some inflammatory markers in T2D and vitamin D deficient men. Vitamin D supplementation was especially effective when it was complemented with exercise training.
ABSTRACT
The process of prion conversion is not yet well understood at the molecular level. The regions critical for the conformational change of PrP remain mostly debated and the extent of sequence change acceptable for prion conversion is poorly documented. To achieve progress on these issues, we applied a reverse genetic approach using the Rov cell system. This allowed us to test the susceptibility of a number of insertion mutants to conversion into prion in the absence of wild-type PrP molecules. We were able to propagate several prions with 8 to 16 extra amino acids, including a polyglycine stretch and His or FLAG tags, inserted in the middle of the protease-resistant fragment. These results demonstrate the possibility to increase the length of the loop between helices H2 and H3 up to 4-fold, without preventing prion replication. They also indicate that this loop probably remains unstructured in PrP(Sc). We also showed that bona fide prions can be produced following insertion of octapeptides in the two C-terminal turns of H2. These insertions do not interfere with the overall fold of the H2-H3 domain indicating that the highly conserved sequence of the terminal part of H2 is not critical for the conversion. Altogether these data showed that the amplitude of modifications acceptable for prion conversion in the core of the globular domain of PrP is much greater than one might have assumed. These observations should help to refine structural models of PrP(Sc) and elucidate the conformational changes underlying prions generation.
