Project description:In this study, we analyse the in-vivo modulation of the transcriptome of human PBMCs by a bolus of vitamin D3 (80,000 IU) after 24 hours.
Project description:In this study, we analyse the in-vivo modulation of the transcriptome of human PBMCs over a time course by a bolus of vitamin D3 (80000 IU).
Project description:Vitamin D deficiency is a risk factor for developing multiple sclerosis (MS). Both in vitro and animal studies suggest an immunomodulatory effect of vitamin D. The PrevANZ trial, a phase IIb randomized placebo-controlled trial of oral vitamin D3 supplementation in people with a first demyelinating event (FDE), was conducted to determine if supplementation can prevent recurrent disease activity in this cohort at high risk of developing definite MS. As a sub-study of this trial, we used whole blood transcriptomic analyses to investigate the effect of vitamin D3 supplementation on peripheral immune cells in people with an FDE, and to gain insight into potential mechanisms by which vitamin D3 may regulate MS risk and disease activity. The PrevANZ trial randomized participants to 1000 IU, 5000 IU or 10,000 IU daily of oral vitamin D3 or placebo. Peripheral blood was collected at baseline and 12 weeks in PAXgene Blood RNA tubes. Transcriptomic datasets were generated by RNA sequencing.
Project description:Subjects of a randomized controlled trial (RCT) received either vitamin D3 (n = 47) in a weekly dose of 20,000 IU or placebo (n = 47) for a period of three to five years
Project description:Vitamin-D3 (VitD3) exhibits pleiotropic effects in host’s physiology by acting on several organs. To mechanistically understand how VitD3 influences the colon physiology we interrogated the gene expression profile of mouse colon in response to high or low VitD3 bioavailability. VitD3 tissue bioavailability was modulated in mice with the use of diets supplemented with different concentrations of VitD3 (0, 2 or 10 IU/g) and the use of Gc knockout mouse strain in where VitD3 bioavailability is enhanced. Vitamin-D3 (VitD3) exhibits pleiotropic effects in host’s physiology by acting on several organs. To mechanistically understand how VitD3 influences the colon physiology we interrogated the gene expression profile of mouse colon in response to high or low VitD3 bioavailability. VitD3 tissue bioavailability was modulated in mice with the use of diets supplemented with different concentrations of VitD3 (0, 2 or 10 IU/g) and the use of Gc knockout mouse strain in where VitD3 bioavailability is enhanced.
Project description:In this study, we investigated the effect of vitamin D supplementation on tumorigenesis in a thioacetamide (TAA)-induced rat intrahepatic cholangiocarcinoma model as vitamin D is known to have a spectrum of anticancer activities. Using PET, we found that tumor formation and progression were suppressed in rats fed a diet supplemented with 6 IU/g vitamin D3(+6D) as compared to the group fed a 2 IU/g vitamin D3 diet (+2D) or controls. Microarray analysis of the tumors that arose revealed that vitamin D supplementation caused significant up- and down regulation in 21 and 16 genes, respectively.
Project description:Vitamin D insufficiency may exacerbate non-specific inflammation observed in older adults. Here, we tested the hypothesis that an inflammatory gene signature present in old skin following saline injection (as model for non-specific needle injury) normalizes after oral vitamin D3 supplementation. To define the saline-induced signature, we compared gene expression in skin biopsies taken six hours after saline injection in old adults (≥65 years) to biopsies from unmanipulated skin. We then assessed signature expression in saline-injected skin of old and young adults (<40 years), and in paired samples of old adults before and after oral vitamin D3 supplementation (6400 IU/day for 14 weeks), where median serum 25-hydroxyvitamin D increased from 43 nmol/L (interquartile range 36-53 nmol/L) to 131 nmol/L (interquartile range 115-147 nmol/L). This submission comprises 112 samples from 57 individuals.
Project description:Background: In addition to its canonical functions, vitamin D has been proposed to be an important mediator of the immune system. Despite ample sunshine, vitamin D deficiency is prevalent (> 80%) in the Middle East, resulting in a high rate of supplementation. However, the underlying molecular mechanisms of the specific regimen and potential factors affecting an individual’s response to vitamin D are not well characterized. Objective: To characterize changes in blood transcriptomic and the potential mechanisms associated with vitamin D3 supplementation and response. Design: In this intervention study, one hundred vitamin D-deficient women were given a weekly oral dose (50,000 IU) of vitamin D3 for three months. A high-throughput targeted PCR, composed of 264 genes representing important blood transcriptomic fingerprints in health and disease states, was performed on pre- and post-supplementation blood samples to profile the molecular response to vitamin D3. Multivariate, network, gene ontology, and literature mining analyses were used for the interpretation of the transcriptomic profiling results. Results: We identified 54 differentially expressed genes that were strongly modulated by vitamin D3 supplementation. Network analyses showed significant changes in the immune-related pathways such as TLR4/CD14 and IFN receptors, and catabolic processes related to NFkB, which were subsequently confirmed by gene ontology enrichment analyses. We proposed a model for vitamin D3 response, using the reduced expression of the molecules involved and the receptor-mediated intra-cellular signaling leading to reduce cytokine production. Conclusions: Blood-transcriptomic profiles of vitamin D3 response were generated using a targeted blood gene panel. Vitamin D has a strong effect on the immune system, G-coupled protein receptor signaling, and the ubiquitin system. We highlighted the major molecular changes and biological processes induced by vitamin D3, which will help to further investigate the effectiveness of vitamin D supplementation among individuals in the Middle East.
Project description:In this study, we investigated the effect of vitamin D supplementation on tumorigenesis in a thioacetamide (TAA)-induced rat intrahepatic cholangiocarcinoma model as vitamin D is known to have a spectrum of anticancer activities. Using PET, we found that tumor formation and progression were suppressed in rats fed a diet supplemented with 6 IU/g vitamin D3(+6D) as compared to the group fed a 2 IU/g vitamin D3 diet (+2D) or controls. Microarray analysis of the tumors that arose revealed that vitamin D supplementation caused significant up- and down regulation in 21 and 16 genes, respectively. There are 9 tissue samples (3 rats in each group labeled as (+6), (+2) and control). Duplicate analysis were used for each sample.