Project description:Bare-metal (BMS) and drug-eluting stents (DES) were implanted in pig coronary arteries with an overstretch during coronary angioplasty under optical coherence tomography guidance. Arteries subjected to plain old balloon angioplasty (POBA) alone served as controls. Stented/balloon dilated segments were harvested 1, 3, 7, 14 and 28 days post-intervention for proteomics analysis. At day 28 all stented arteries showed a neointima formation covering the stent struts. The evolved neointima was separated from the media and analysed in a separate proteomics analysis. In total, 31 samples were analysed for the media by LC-MS/MS (n=3 BMS/DES at each time-point 1, 3, 7 and 28 days; n=4 POBA early [day1-day3] and n=3 POBA late [day 14 - day28]). For the neointima a total of 14 samples were analysed (n=7 BMS, n=7 DES at 28 days) including the neointima of arteries of a second cohort with 4 samples each for BMS and DES day 28. The neointima samples were run in duplicates.
Project description:The main objective of this work was to evaluate the toxicity of Cd, in different genotypes of T. cacao, in scion-rootstock combinations (CCN 51-BN 34, CCN 51-PS 1319, CCN 51-PH 16, CCN 51-CCN 51), grown in soil with 150 mg Cd kg-1 soil, together with the control treatment (without addition of Cd in the soil), through proteomic profile, aiming to elucidate the influence of the scion-rootstock interaction on differential uptake and accumulation of Cd in roots and leaves.
Project description:We used quantitative mass spectrometry-based proteomics to unravel global changes in the phosphoproteome upon treatment of ASP14 cells (a Ewing Sarcoma cell line) according to the setup below. The combination of drugs were experimentally shown to infer synergy in terms of cell killing. Three experiments were performed using a triple SILAC setup (Light: Lys0,Arg0; Medium: Lys4,Arg6; and Heavy: Lys8,Arg10): Experiment 1: Light SILAC: Drug combination (90 nM Midostaurin + 20 nM BMS-754807) Medium SILAC: Midostaurin (90 nM) Heavy SILAC: 0.1% DMSO Experiment 2: Light SILAC: Drug combination (90 nM Midostaurin + 20 nM BMS-754807) Medium SILAC: Midostaurin (90 nM) Heavy SILAC: BMS-754807 (20 nM) Experiment 3: Light SILAC: Drug combination (90 nM Midostaurin + 20 nM BMS-754807) Medium SILAC: BMS-754807 (20 nM) Heavy SILAC: 0.1% DMSO ASP14 cells were starved by replacing complete SILAC medium with SILAC minimal medium without serum over night. Cells were treated with drugs as stated above for 2h; then they were stimulated with serum for 20 minutes and harvested thereafter.
Project description:The course of Crohn's disease (CD) is heterogeneous, confounding effective personalized therapy. A previous analysis of differences in gene expression between patients with versus without CD groups revealed 2 subsets of patients with CD -- a group characterized by genes more highly expressed in the colon (colon-like CD) and a group with increased expression of ileum marker genes (ileum-like CD). We compared differences in microRNAs between these groups. We performed genome-wide microRNA profile analyses of colon tissues from 18 adults with CD and 12 adults without CD (controls). We performed principal component analyses to associate levels of microRNAs with CD subtypes. Colonic epithelial cells and lamina propria immune cells were isolated from intestinal tissues and levels of microRNA 31 (miR-31) were measured by real-time quantitative PCR. We validated the differential expression of miR-31 between the subtypes by measuring miR-31 levels in an independent cohort of 32 adult patients with CD and 23 controls. We generated epithelial colonoid cultures from controls and patients with CD, and measured levels of miR-31 in crypts. We performed genome-wide microRNA profile analyses of formalin-fixed paraffin-embedded colon and ileum biopsies from 76 treatment-naive pediatric patients with CD and 51 controls (234 samples) and collected data on disease features and outcomes. In comparing miRNA expression profiles between 9 patients with colon-like CD and 9 patients with ileum-like CD, we identified 19 miRNAs with significant differences in levels. We observed a 13.5-fold difference in level of miR-31-5p between tissues from patients with colon-like vs. ileum-like CD (Padj = 1.43 x 10-18). Principal component analysis found miR-31 to be the top contributor to the variance observed. Levels of miR-31 were increased 60-fold in tissues from patients with ileum-like CD compared with controls (Padj = 2.59 × 10-51). We validated the differential expression of miR-31 between the subtypes in the independent set of tissues. Colonoids derived from patients with CD had significantly higher levels of miR-31 than colonoids derived from control tissues (day 2 P=.041 and day 6 P=.0095). Levels of miR-31 were significantly increased in colon tissues from pediatric patients with CD compared with controls (~7.8-fold, P=4.64 ×10-7) and in ileum tissues from patients with CD patients vs. controls (~1.5-fold, P=9.97 × 10-7). A high level of miR-31 in index biopsies from pediatric patients with only inflammation and no other complications at time of diagnosis associated with development of fibrostenotic ileal CD. We identified differences in miR-31 levels in colon tissues from adult and pediatric patients with CD compared with controls, and in patients with ileum-like CD compared with colon-like CD. Further studies are needed to determine the mechanisms by which miR-31 might contribute to pathogenesis of this subtype of CD, or affect response to therapy.
Project description:The glucocorticoid receptor (GR) and ten-eleven translocation 2 (TET2) respectively play a crucial role in regulating immunity and inflammation, and GR interacts with TET2. However, their syn-ergetic roles in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), remain unclear. This study aimed to investigate the co-target gene signatures of GR and TET2 in IBD and provide potential therapeutic interventions for IBD. By integrating public data, we identified 179 GR- and TET2-targeted differentially expressed genes (DEGs) in CD and 401 in UC. These genes were closely associated with immunometabolism, inflammatory responses, and cell stress pathways. In vitro inflammatory cellular models were constructed using LPS-treated HT29 and HCT116 cells, respectively. Drug repositioning based on the co-target gene signatures of GR and TET2 derived from transcriptomic data of UC, CD, and the in vitro model were performed using the Connectivity Map (CMap). BMS-536924 emerged as a top therapeutic candidate, and its validation experiment within the in vitro inflammatory model confirmed its ef-ficacy in mitigating the LPS-induced inflammatory response. This study sheds light on the path-ogenesis of IBD from a new perspective and may accelerate the development of novel therapeutic agents for inflammatory diseases including IBD.
Project description:Four small RNA libraries from two contrasting sweet sorghum genotypes were sequenced. In this study, One hundred and ninety-five conserved miRNAs belonging to 56 families and 25 putative novel miRNAs from 28 precursors were identified, among which 38 conserved and 24 novel miRNAs were differentially expressed under Cd stress and/or between H18 and L69. Two groups of them: miR169p/q-nov_23 and miR408 were further focused through the coexpression analysis and might be involved in Cd transport, cytoskeleton activity and cell wall construction by regulating their targets. This study presents new insights into the regulatory roles of miRNAs in Cd accumulation and tolerance in sweet sorghum and will help to develop high-Cd accumulation or high Cd-resistant germplasm of sweet sorghum through molecular breeding and/or genetic engineering approaches.
2023-10-12 | GSE145617 | GEO
Project description:BMS Consortium
| PRJNA1328654 | ENA
Project description:BMS-CHS101 and BMS-YUSA145 whole-genome sequencing