Single Center Randomized Trial of Orca-T alone versus Orca-T Plus Tacrolimus Prophylaxis in the Prevention of Acute Graft Versus Host Disease
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA962565 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24327000_1.fastq.gz | Fastqsanger.gz | |||
| SRR24327000_2.fastq.gz | Fastqsanger.gz | |||
| SRR24327001_1.fastq.gz | Fastqsanger.gz | |||
| SRR24327001_2.fastq.gz | Fastqsanger.gz | |||
| SRR24327002_1.fastq.gz | Fastqsanger.gz |
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Project description:Origin Recognition Complex Associated (ORCA) associates with repressive chromatin environments. We carried out H3K9me3 ChIP-seq to determine the affect of ORCA's loss on this repressive mark. Towards this end, we cultured U2OS osteosarcoma cells, performed control and ORCA knockdowns using siRNAs and then carried out H3K9me3 ChIP-seq to determine the regions in the genome which get affected upon ORCA knockdown. Examination of the levels of H3K9me3 in control and ORCA knockdown cells
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Project description:Validation of predicted gene expression of human mesangial cells after 24h Tacrolimus stimulus Objective: To evaluate tacrolimus as therapeutic option for diabetic nephropathy (DN) based on molecular profile and network-based molecular model comparisons. Materials and Methods: We generated molecular models representing pathophysiological mechanisms of DN and tacrolimus mechanism of action (MoA) based on literature derived data and transcriptomics datasets. Shared enriched molecular pathways were identified based on both model datasets. A newly generated transcriptomics dataset studying the effect of tacrolimus on mesangial cells in vitro was added to identify mechanisms in DN pathophysiology. We searched for features in interference between the DN molecular model and the tacrolimus MoA molecular model already holding annotation evidence as diagnostic or prognostic biomarker in the context of DN. Results: Thirty nine molecular features were shared between the DN molecular model, holding 252 molecular features and the tacrolimus MoA molecular model, holding 209 molecular features, with six additional molecular features affected by tacrolimus in mesangial cells. Significantly affected molecular pathways by both molecular model sets included cytokine-cytokine receptor interactions, adherens junctions, TGF-beta signaling, MAPK signaling, and calcium signaling. Molecular features involved in inflammation and immune response contributing to DN progression were significantly downregulated by tacrolimus (e.g. the tumor necrosis factor alpha (TNF), interleukin 4, or interleukin 10). On the other hand, pro-fibrotic stimuli being detrimental to renal function were induced by tacrolimus like the transforming growth factor beta 1 (TGFB1), endothelin 1 (EDN1), or type IV collagen alpha 1 (COL4A1). Conclusion: Patients with DN and elevated TNF levels might benefit from tacrolimus treatment regarding maintaining GFR and reducing inflammation. TGFB1 and EDN1 are proposed as monitoring markers to assess degree of renal damage. Next to this stratification approach, the use of drug combinations consisting of tacrolimus in addition to ACE inhibitors, angiotensin receptor blockers, TGFB1- or EDN1-receptor antagonists might warrant further studies. comparison of gene expression of human mesangial cells after 24h Tacrolimus vs. Ctrl; 4 independent experiments were conducted (4xTacrolimus 24h and 4x ctrl. 24h with Drug solvent (DMSO))
2016-08-01 | E-GEOD-84908 | biostudies-arrayexpress
Project description:Origin Recognition Complex Associated (ORCA) associates with repressive chromatin environments. We carried out H3K9me3 ChIP-seq to determine the affect of ORCA's loss on this repressive mark. Towards this end, we cultured U2OS osteosarcoma cells, performed control and ORCA knockdowns using siRNAs and then carried out H3K9me3 ChIP-seq to determine the regions in the genome which get affected upon ORCA knockdown.
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Project description:ORCA is an ORC associated protein that plays important roles in replication initiation as well as heterochromatin organization. We carried out ORCA ChIP-seq in U2OS cells synchronized at different stage of G1 phase to determine its genome wide localization. To understand the genomic features of ORCA binding regions, we also carried out Methylated DNA IP (MeDIP) followed by deep sequencing in U2OS cells to determine the genome wide localizatoin of methyl-CpG sites in U2OS cells and how ORCA bidning regions co-localize with this important repressive mark.
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