METHODS: Expression of TRAIL and TRAIL receptor in response to insulin and glucose was determined by polymerase chain reaction. Transcriptional activity was assessed using wild-type and site-specific mutations of the TRAIL promoter. Chromatin immunoprecipitation studies were performed. VSMC proliferation and apoptosis was measured.
RESULTS: Insulin and glucose exposure to VSMC for 24 h stimulated TRAIL mRNA expression. This was also evident at the transcriptional level. Both insulin- and glucose-inducible TRAIL transcriptional activity was blocked by dominant-negative specificity protein-1 (Sp1) overexpression. There are five functional Sp1-binding elements (Sp1-1, Sp1-2, Sp-5/6 and Sp1-7) on the TRAIL promoter. Insulin required the Sp1-1 and Sp1-2 sites, but glucose needed all Sp1-binding sites to induce transcription. Furthermore, insulin (but not glucose) was able to promote VSMC proliferation over time, associated with increased decoy receptor-2 (DcR2) expression. In contrast, chronic 5-day exposure of VSMC to 1 µg/mL insulin repressed TRAIL and DcR2 expression, and reduced Sp1 enrichment on the TRAIL promoter. This was associated with increased cell death.
CONCLUSIONS: The findings of the present study provide a new mechanistic insight into how TRAIL is regulated by insulin. This may have significant implications at different stages of diabetes-associated cardiovascular disease. Thus, TRAIL may offer a novel therapeutic solution to combat insulin-induced vascular pathologies.
DESIGN: Food choice was assessed using the validated New Zealand Adolescent FFQ. Principal components analysis was used to determine dietary patterns. Trained research assistants measured participants' height and body mass. Cardiorespiratory fitness was assessed in a subset of participants using the multistage 20 m shuttle run. The level and stage were recorded, and the corresponding VO2max was calculated. Differences in mean VO2max according to sex and BMI were assessed using t tests, while associations between cardiorespiratory fitness and dietary patterns were examined using linear regression analyses adjusted for age, sex, school attended, socio-economic deprivation and BMI.
SETTING: Secondary schools in Otago, New Zealand.
SUBJECTS: Students (n 279) aged 14-18 years who completed an online lifestyle survey during a class period.
RESULTS: Principal components analysis produced three dietary patterns: 'Treat Foods', 'Fruits and Vegetables' and 'Basic Foods'. The 279 participants who provided questionnaire data and completed cardiorespiratory fitness testing had a mean age of 15·7 (sd 0·9) years. Mean VO2max was 45·8 (sd 6·9) ml/kg per min. The 'Fruits and Vegetables' pattern was positively associated with VO2max in the total sample (β=0·04; 95%CI 0·02, 0·07), girls (β=0·06; 95% CI 0·03, 0·10) and boys (β=0·03; 95% CI 0·01, 0·05).
CONCLUSIONS: These results indicate that increase in cardiorespiratory fitness was associated with a healthier dietary pattern, suggesting both should be targeted as part of a global lifestyle approach. Longitudinal studies are needed to confirm this association in relation to health outcomes in New Zealand adolescents.
METHODOLOGY: Dental pulp stem cells from healthy (DPSCs) and carious teeth (DPSCs-CT) were isolated from young donors. Both cell lines were expanded in identical culture conditions and subsequently differentiated towards DAergic-like cells using pre-defined dopaminergic cocktails. The dopaminergic efficiencies were evaluated both at gene and protein as well as at secretome levels.
RESULTS: The efficiency of DPSCs-CT to differentiate into DAergic-like cells was not equivalent to that of DPSCs. This was further reflected in both gene and protein generation whereby key neuronal markers such as nestin, NURR1 and beta-III-tubulin were expressed significantly lower as compared to differentiated DPSCs (P
METHODS: In a randomised, controlled crossover trial, ten healthy human subjects (five men, five women) were given 50 g glucose (reference food, twice); buns (0 and 10 % fenugreek seed powder); and flatbreads (0 and 10 % fenugreek seed powder) on six different occasions. Finger prick capillary blood samples were collected at 0, 15, 30, 45, 60, 90 and 120 min after the start of the meal. The palatability of the test meals was scored using Likert scales.
RESULTS: The incremental areas under the glucose curve value of buns and flatbreads with 10 % fenugreek (138 ± 17 mmol × min/L; 121 ± 16 mmol × min/L) were significantly lower than those of 0 % fenugreek bun and flatbreads (227 ± 15 mmol × min/L; 174 ± 14 mmol × min/L, P = <0.01). Adding 10 % fenugreek seed powder reduced the GI of buns from 82 ± 5 to 51 ± 7 (P