Diminished colonic health is associated with various age-related pathologies. In this study, we applied an integrative approach to reveal potential interactions between determinants of colonic health in aging C57BL/6J mice. Analysis of gut microbiota composition revealed an enrichment of various potential pathobionts, including Desulfovibrio spp., and a decline of the health-promoting Akkermansia spp. and Lactobacillus spp. during aging. Intraluminal concentrations of various metabolites varied between ages and we found evidence for an increased gut permeability at higher age. Colonic gene expression analysis suggested that during the early phase of aging (between 6 and 12 months), expression of genes involved in epithelial-to-mesenchymal transition and (re)organization of the extracellular matrix were increased. Differential expression of these genes was strongly correlated with Bifidobacterium spp. During the later phase of aging (between 12 and 28 months), gene expression profiles pointed towards a diminished antimicrobial defense and were correlated with an uncultured Gastranaerophilales spp. This study demonstrates that aging is associated with pronounced changes in gut microbiota composition and colonic gene expression. Furthermore, the strong correlations between specific bacterial genera and host gene expression may imply that orchestrated interactions take place in the vicinity of the colonic wall and potentially mediate colonic health during aging.
Integrative analysis of gut microbiota composition, host colonic gene expression and intraluminal metabolites in aging C57BL/6J mice.
Sex, Specimen part
View SamplesThe objectives of this study were to measure effects of an aspirin intervention on gene expression in normal colonic epithelial and stromal tissue in healthy humans and to determine whether response differed by UGT1A6*2 genotype. We also sought to characterize gene expression differences within colonic tissue microenvironments by identifying genes that were differentially expressed between epithelial and stromal tissue.
Tissue-specific patterns of gene expression in the epithelium and stroma of normal colon in healthy individuals in an aspirin intervention trial.
Sex, Specimen part
View SamplesEmploying microarray assays, a total of 267 genes were identified that were significantly up- or downregulated in PBMCs of WT-NOD2 patients, compared to healthy donors after challenge with vitamin D (+/-D) and/or a combination (+/-LP) of LPS (lipopolysaccharide) and PGN (peptidoglycan) (p < 0.05; threshold: 2-fold change). For further analysis by real-time PCR, 12 genes with known impact on inflammation and immunity were selected that fulfilled predefined expression criteria. In a larger cohort of patients and controls, a disease-associated expression pattern, with higher transcript levels in vitamin D-treated PBMCs from 5 patients, was observed for three of these genes, CLEC5A (p < 0.030), lysozyme (LYZ; p < 0.047) and TREM1 (p < 0.023). Six genes were found to be expressed in a NOD2- dependent manner (CD101, p < 0.002; CLEC5A, p < 0.020; CXCL5, p < 0.009; IL-24, p < 0.044; ITGB2, p < 0.041; LYZ, p < 0.042). Interestingly, the highest transcript levels were observed in patients with heterozygous NOD2 mutations.
<i>NOD2</i>- and disease-specific gene expression profiles of peripheral blood mononuclear cells from Crohn's disease patients.
Specimen part, Disease, Disease stage, Treatment
View Samples1,2-unsaturated pyrrolizidine alkaloids (PA) are plant metabolites predominantly occurring in the plant families Asteraceae and Boraginaceae. Acute and chronic PA poisoning causes severe hepatotoxicity. So far, the molecular mechanisms of PA toxicity are not well understood. To analyze its mode of action, primary human hepatocytes were exposed to a non-cytotoxic dose of 100 M of four structurally different PA: echimidine, heliotrine, senecionine, senkirkine. Changes in mRNA expression were analyzed by a whole genome microarray. Employing cut-off values with a |fold change| of 2 and a q-value of 0.01, data analysis revealed numerous changes in gene expression. In total, 4556, 1806, 3406 and 8623 genes were regulated by echimidine, heliotrine, senecione and senkirkine, respectively. 1304 genes were identified as commonly regulated. PA affected pathways related to cell cycle regulation, cell death and cancer development. The transcription factors TP53, MYC, NFB and NUPR1 were predicted to be activated upon PA treatment. Furthermore, gene expression data showed a considerable interference with lipid metabolism and bile acid flow. The associated transcription factors FXR, LXR, SREBF1/2, and PPAR// were predicted to be inhibited. In conclusion, though structurally different, all four PA significantly regulated a great number of genes in common. This proposes similar molecular mechanisms, although the extent seems to differ between the analyzed PA as reflected by the potential hepatotoxicity and individual PA structure.
Disturbance of gene expression in primary human hepatocytes by hepatotoxic pyrrolizidine alkaloids: A whole genome transcriptome analysis.
No sample metadata fields
View SamplesMYCN-high and MYCN-low neuroblastoma cells differ in their responses to Doxorubicin treatment. To explain this difference we compared the global trancriptomes of MYCN-high and MYCN-low cells before, during and after treatment. Overall design: MYCN-high cells without doxycyline and MYCN-low cells with doxycycline were treated with 0.1µg/ml Doxorubicin. Transcriptome was measured for the following time points: in untreated cells, in cells which were treated with Doxorubicin for 72 hours, and in cells collected three, eight and fourteen days after Doxorubin washout. Experiment was performed in biological duplicate.
Cell-Cycle Position of Single MYC-Driven Cancer Cells Dictates Their Susceptibility to a Chemotherapeutic Drug.
Treatment, Subject, Time
View SamplesSilver nanoparticles are used in consumer products like food contact materials, drinking water technologies and supplements, due to their antimicrobial properties. This leads to an oral uptake and exposure of intestinal cells. In contrast to other studies we found no apoptosis induction by surfactant coated silver nanoparticles in the intestinal cell model Caco-2 in a previous study, although the particles induced oxidative stress, morphological changes and cell death. Therefore, this study aimed to analyze the molecular mechanism of silver nanoparticles in Caco-2 cells. We used global gene expression profiling in differentiated Caco-2 cells, supported by verification of the microarray data by quantitative real time RT-PCR and microscopic analysis, impedance measurements and assays for apoptosis and oxidative stress. Our results revealed that the majority of surfactant coated silver nanoparticles are not taken up into differentiated Caco-2 cells. and probably affect the cells by outside-in signaling. They induce oxidative stress and have an influence on canonical pathways related to FAK, ILK, ERK, MAPK, integrins and adherence and tight junctions, thereby inducing transcription factors like AP1, NFB and NRF2, which mediate cellular reactions in response to oxidative stress and metal ions and induce changes in the cytoskeleton and cell-cell and cell-matrix contacts. The present data confirm the absence of apoptotic cell death. Non-apoptotic, necrotic cell death, especially in the intestine, can cause inflammation and influence the mucosal immune response.
Molecular mechanism of silver nanoparticles in human intestinal cells.
Cell line
View SamplesMutations of -catenin gene (CTNNB1) are frequent in adrenocortical adenomas (AA) and carcinomas (ACC). However, the target genes of CTNNB1 have not yet been identified in adrenocortical tumors.
Characterization of differential gene expression in adrenocortical tumors harboring beta-catenin (CTNNB1) mutations.
Specimen part
View SamplesGenomewide gene expression analysis of lymphoid cell lines of Hodgkin, non-Hodgkin and acute leukemia origin
High-level expression of Mastermind-like 2 contributes to aberrant activation of the NOTCH signaling pathway in human lymphomas.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Sex, Age, Specimen part, Disease, Treatment
View SamplesAcute myeloid leukemia (AML), and other myeloid malignancies, are frequently treated with hypomethylating agents like decitabine. Alterations in the epigenome, induced by decitabine, are likely to result in gene expression changes. The effects of decitabine have not been systemically studied using primary AML samples.
Genomic impact of transient low-dose decitabine treatment on primary AML cells.
Specimen part, Disease, Treatment
View Samples