Project description:In the present study, we studied the effect of dietary selenium (Se) supplementation on the transcriptomic profile of sheep. The main objective was to evaluate the effect of Se-supplementation on the overall transcriptome of sheep, the altered pathways, and the biological processes related to it . A custom oligo microarray platform (AMADID: 070119) was designed, then used to profile gene expression from 20 samples from 10 sheep at two time points (T0; before Se-supplementation, and T40; at the end of a 40-d Se-supplementation period). Isolated and purified total RNAs were individually hybridized to the custom (4x44k) DNA microarray. The comparison of control and treated animal transcriptomes revealed a large set of differentially expressed genes. After functional analysis and qPCR validation, the result showed several pathways and biological processes that have been altered following Se-supplementation to the diet.
Project description:In the present study, we studied the effect of dietray iodide (IOD) supplementation on the transcriptome's profile of sheep. The main objective was to evaluate the effect of IOD-supplementation on the overall transcriptome of sheep, the altered pathways, and the biological processes related to it . A previously custom-designed oligo microarray platform (GPL20576) was used to profile the transcriptome of 10 ewes at two time points [T0 (before supplementation) and T40 (after 40-days supplementation period). The Isolated and purified total RNAs were individually hybridized to the custom (4x44k) DNA microarray. The comparison of unsupplemented and supplemented animals' transcriptome revealed a large set of differentially expressed genes. Functional analysis showed several pathways and biological processes that have been altered following IOD-supplementation to the diet.
Project description:The licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid the adverse side-effects of clinical dosing regimes. Here we show a profound memory effect of brief rapamycin treatment. Brief, early adult treatment extended lifespan in Drosophila to the same degree as lifelong dosing. Lasting memory of earlier rapamycin treatment was mediated by elevated autophagy in enterocytes of the gut, accompanied by increased intestinal spermidine levels and improved structure and function of the ageing intestine. Brief elevation of autophagy itself induced a long-term increase in autophagy. In mice, short-term, 3-month treatment also induced a full memory effect, with enhanced autophagy in Paneth cells, improved Paneth cell architecture and gut barrier function at levels induced by chronic treatment, even 6 months after rapamycin was withdrawn. Past rapamycin treatment also enhanced the regenerative potential of aged intestine in intestinal organoids. Full geroprotective effects of chronic rapamycin treatment can thus be obtained with a brief pulse of the drug.
Project description:Inhibition of the B-cell receptor pathway, and specifically of Bruton tyrosine kinase (BTK), is a leading therapeutic strategy in chronic lymphocytic leukemia (CLL). Target occupancy has been measured as a pharmacodynamic parameter in clinical studies of covalent BTK inhibitors. However, the kinetics of BTK turnover, which determines occupancy, and the relationship between occupancy, pathway inhibition and clinical outcomes remains undefined. This randomized phase 2 study investigated the safety, efficacy, and pharmacodynamics of a selective BTK inhibitor acalabrutinib at 100 mg twice daily or 200 mg once daily in 48 patients with relapsed/refractory or high-risk treatment naïve CLL. Acalabrutinib was well tolerated and yielded an overall response rate (ORR) of partial response or better of 95.8% (95% CI 78.9%, 99.9%) and an estimated progression-free survival (PFS) rate at 24 months of 91.5% (95% CI 70.0%, 97.8%) with twice daily dosing and an ORR of 79.2% (95% CI 57.9%, 92.9%) and an estimated PFS rate at 24 months of 87.2% (95% CI 57.2%, 96.7%) with once daily dosing. BTK resynthesis was faster in CLL than in healthy volunteers. Twice daily dosing maintained higher BTK occupancy and achieved more potent pathway inhibition compared to once daily dosing. Additional follow-up is required to address the impact of dosing schedule and BTK occupancy on long-term clinical outcomes.
Project description:Origanum oil (ORO), garlic oil (GAO), and peppermint oil (PEO) were shown to effectively lower methane production, decrease abundance of methanogens, and change abundances of several bacterial populations important to feed digestion in vitro. In this study, the impact of these essential oils (EOs, at 0.50 g/L), on the rumen bacterial community composition was further examined using the recently developed RumenBactArray.