Next Generation Sequencing of Response to Mito-Tempo in Intestinal Mucosal Biopsies from Crohn's Disease patients
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE159751 | GEO | 2021/09/22
REPOSITORIES: GEO
Similar Datasets
Project description:Next Generation Sequencing of Response to Mito-Tempo in Intestinal Mucosal Biopsies from Crohn's Disease patients
| PRJNA670418 | ENA
Project description:Purpose: To uncover differentially-regulated transcripts and pathways/biological processes in newly-diagnosed, pediatric Crohn's disease in comparison to healthy controls. Methods: Intestinal epithelial cells were dissociated from ileal endoscopic biopsies, and stored at -80C in RNAlater. The polyA RNA fraction was purified, and single-end, 50 bp reads were sequenced and aligned to the Hg19 genome using the TopHat2 aligner. Differential analysis was performed using Bioconductor packages including edgeR, where significance was defined as p<0.05 and fold change>2. Results: We obtained 15788 reasonably-expressed transcripts that were included in differential analyses. Conclusions: Our study characterizes the dysregulation of intestinal epithelial cells in treatment-naïve Crohn's disease using RNA sequencing for transcriptomic profile of cells obtained through ileal endoscopic biopsies.
2018-10-30 | GSE117875 | GEO
Project description:Quantitative proteome profiling was performed on Inflammatory (ICD), stricturing and fistulizing Crohn's Disease serums using label-free Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS).
2017-05-15 | PXD001821 | Pride
Project description:A focussed microarray chip was constructed specifically for studying basal colonic gene expression in patients with Spondyloarthropathy (SpA) and Crohn's disease (CD) (ref: PMID 16476712). These focus microarrays were used 1) to study common changes in gene expression between SpA and CD, providing early markers in the follow-up study of patients with SpA and particularly these patients that evolve into clinically overt CD; and 2) to identify new candidate genes for CD by integrating gene expression data with genetic information. Keywords: Crohn's Disease, Spondylarthropathy, biopsies
2010-05-01 | GSE14442 | GEO
Project description:Crohn's disease (CD) is a chronic illness demanding better therapeutics. The marketed biologics only benefit some patients or elicit diminishing effect over time. To complement the known methods in drug development and to obtain patient specific drug responses, we optimized and validated a known human explant method to test drug candidates and pathophysiological conditions in CD intestinal biopsies. Mucosal biopsies from 27 CD patients and 6 healthy individuals were collected to validate an explant assay test where the polarized tissue was cultured on a novel metal mesh disk, slightly immersed in medium imitating an air-liquid interphase. After culture in high oxygen for 24 hours with or without biological treatment in the medium, biopsy integrity and penetration of antibodies was measured by immunohistochemistry (IHC). Nine cytokines were quantified in the conditioned medium as a read-out for degree of inflammation in individual biopsies and used to evaluate treatment efficacy. The biopsies were well-preserved, showing few structural changes. IHC revealed tissue penetration of antibodies demonstrating ability to test therapeutic antibodies. The cytokine release to the medium showed that the assay can distinguish between inflammation states and then validate the known effect of two treatment biologics confirmed by a detection panel of five specific cytokines. Our data also suggest that the assay would be able to indicate which patients are responders to anti-TNF-? therapeutics, and which are non-responders. This study demonstrates this version of an ex vivo culture as a valid and robust assay to assess inflammation in mucosal biopsies and test of the efficacy of novel drug candidates and current treatments on individual patients-potentially for a personalized medicine approach.
| S-EPMC4865152 | biostudies-literature
Project description:A focussed microarray chip was constructed specifically for studying basal colonic gene expression in patients with Spondyloarthropathy (SpA) and Crohn's disease (CD) (ref: PMID 16476712). These focus microarrays were used 1) to study common changes in gene expression between SpA and CD, providing early markers in the follow-up study of patients with SpA and particularly these patients that evolve into clinically overt CD; and 2) to identify new candidate genes for CD by integrating gene expression data with genetic information. Keywords: Crohn's Disease, Spondylarthropathy, biopsies This experiment was done in a dye-swap design in which all samples of interest were compared to a pooled sample.
2010-05-01 | E-GEOD-14442 | biostudies-arrayexpress
Project description:Mito-TAILS N-terminomics analysis of proteolytic events during EPEC infection of human epithelial cells, on whole-cell level and mitochondria.
2020-05-21 | PXD016994 | Pride
Project description:Acetaminophen (APAP) hepatotoxicity is characterized by an extensive mitochondrial oxidant stress. However, its importance as a drug target has not been clarified. To investigate this, fasted C57BL/6J mice were treated with 300 mg/kg APAP and the mitochondria-targeted antioxidant Mito-Tempo (MT) was given 1.5 h later. APAP caused severe liver injury in mice, as indicated by the increase in plasma ALT activities and centrilobular necrosis. MT dose-dependently reduced the injury. Importantly, MT did not affect APAP-protein adducts formation, glutathione depletion or c-jun N-terminal kinase activation and its mitochondrial translocation. In contrast, hepatic glutathione disulfide and peroxynitrite formation were dose-dependently reduced by MT, indicating its effective mitochondrial oxidant stress scavenging capacity. Consequently, mitochondrial translocation of Bax and release of mitochondrial intermembrane proteins such as apoptosis-inducing factor were prevented, and nuclear DNA fragmentation was eliminated. To demonstrate the importance of mitochondria-specific antioxidant property of MT, we compared its efficacy with Tempo, which has the same pharmacological mode of action as MT but lacks the mitochondria targeting moiety. In contrast to the dramatic protection by MT, the same molar dose of Tempo did not significantly reduce APAP hepatotoxicity. In contrast, even a 3 h post-treatment with MT reduced 70 % of the injury, and the combination of MT with N-acetylcysteine (NAC) provided superior protection than NAC alone. We conclude that MT protects against APAP overdose in mice by attenuating the mitochondrial oxidant stress and preventing peroxynitrite formation and the subsequent mitochondrial dysfunction. MT is a promising therapeutic agent for APAP overdose patients.
| S-EPMC5033665 | biostudies-literature
Project description:The use of gene expression signatures to classify compounds, identify efficacy or toxicity, and differentiate close analogs relies on the sensitivity of the method to identify modulated genes. We used a novel ligation-based targeted whole transcriptome expression profiling assay, TempO-Seq®, to determine whether previously unreported compound-responsive genes could be identified and incorporated into a broad but specific compound signature. TempO-Seq exhibits 99.6% specificity, single cell sensitivity, and excellent correlation with fold differences measured by RNA-Seq (R2 = 0.9) for 20,629 targets. Unlike many expression assays, TempO-Seq does not require RNA purification, cDNA synthesis, or capture of targeted RNA, and lacks a 3′ end bias. To investigate the sensitivity of the TempO-Seq assay to identify significantly modulated compound-responsive genes, we derived whole transcriptome profiles from MCF-7 cells treated with the histone deacetylase inhibitor Trichostatin A (TSA) and identified more than 9,000 differentially expressed genes. The TSA profile for MCF-7 cells overlapped those for HL-60 and PC-3 cells in the Connectivity Map (cMAP) database, suggesting a common TSA-specific expression profile independent of baseline gene expression. A 43-gene cell-independent TSA signature was extracted from cMAP and confirmed in TempO-Seq MCF-7 data. Additional genes that were not previously reported to be TSA responsive in the cMAP database were also identified. TSA treatment of 5 cell types revealed 1,136 differentially expressed genes in common, including 785 genes not previously reported to be TSA responsive. We conclude that TSA induces a specific expression signature that is consistent across widely different cell types, that this signature contains genes not previously associated with TSA responses, and that TempO-Seq provides the sensitive differential expression detection needed to define such compound-specific, cell-independent, changes in expression.
2017-05-25 | GSE91395 | GEO
Project description:Comparison of luminal and basal breast cancer cells under acute normoxia and hypoxia. Cells were plated in 96-well plates and incubated 24 hrs under normoxia or hypoxia after which the wells were washed once with cold PBS and lysed using TempO-Seq lysis buffer for 15 min at room temperature. Samples were stored at −80 °C before shipping to BioClavis for whole genome TempO-Seq analysis. For normoxia (NX) 21% oxygen was used and for hypoxia (HX) 1%oxygen was used. Each condition has 3 biological replicates.
2023-06-01 | E-MTAB-12234 | biostudies-arrayexpress