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Transcription profiling of rat livers treated with pharmaceutical development compounds

ABSTRACT: We used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity. Experiment Overall Design: Compound R1 or R2, or vehicle control, was given for either 24h or 2 weeks (336h) at different doses.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Adrian Roth

PROVIDER: E-GEOD-17388 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression analysis of rat livers treated with pharmaceutical development compounds

Project description:We used microarrays to analyze gene expression changes in liver after treatment of rats with two compounds from drug development (R1, R2) to identify potential effects related to hepatotoxicity. The development cpds have been described in: Pierson et al., J Med Chem 52: 3855-62. R1 corresponds to 36, R2 corresponds to 38

2009-07-29 | GSE17388 | GEO

Project description:Altered DNA methylation patterns represent an attractive mechanism for the phenotypic changes associated with human aging. Several studies have described age-related methylation changes to various extents, but their functional significance has remained largely unclear. We have now used an integrated methylome and transcriptome sequencing approach to characterize age-related methylation changes in the human epidermis and to analyze their impact on gene expression. Our results show limited and localized methylation differences between young and old methylomes at single-base resolution. Similarly, the comparison of transcriptomes from young and old samples revealed a highly defined set of differentially expressed genes with functional annotations in skin homeostasis. Further data analysis showed a robust correlation between age-related promoter hypermethylation and gene silencing, particularly at promoters that were pre-marked with stem cell-specific chromatin features. In addition, we also observed age-related methylation changes at transcription factor binding sites, with a significant enrichment of stem cell regulatory networks. Our results provide a high-resolution analysis of age-related methylation changes and suggest that they result in highly defined alterations in the transcriptional programme of the human epidermis. Interestingly, several of our findings can be interpreted to reflect epigenetic changes in aging stem cells, thus supporting a critical role of stem cells in human aging. Whole transcriptome analysis of H. sapiens. Two samples were analyzed, one sample containing RNA from young, one sample containing RNA from old human skin.

2013-12-20 | E-GEOD-46486 | biostudies-arrayexpress

Impact of whole-body versus nose-only exposure systems on systemic, respiratory, and cardiovascular endpoints in a 2-month cigarette smoke exposure study in the ApoE-/- mouse model

Project description:In vivo inhalation toxicity is typically tested in rodents by using either whole-body (WB) or nose-only (NO) exposure systems. To assess if cigarette smoke (CS)-induced disease endpoints would be similar after exposure in either system, we exposed apolipoprotein E-deficient mice to the same target total particulate matter concentration of mainstream smoke from 3R4F reference cigarettes in NO or WB exposure chambers (EC) for 2 months, and as controls to filtered air (Sham). While CS was reproducibly delivered to both exposure systems, we observed higher nicotine and formaldehyde concentrations being delivered to NOECs than to WBECs, but similar concentrations of carbon monoxide, acetaldehyde, and acrolein. CS exposure led to the adaptive changes expected in nasal epithelia, altered lung function, increased lung inflammation, and pronounced changes in the nasal epithelial transcriptome and lung proteome. Exposure in the NOEC caused generally more pronounced or severe respiratory effects and a higher stress response. Body weight, in particular, was much lower in mice exposed in the NOEC. Aortic arch imaging revealed greater plaque area in CS-exposed mice in the WBEC group than in the respective sham group. No difference was found in aortic plaque size between CS-exposed mice in the NOEC and sham groups. As CS is a chemically and temporarily dynamic aerosol, its composition in the breathing zone was not completely comparable between the two exposure systems; however, the main disease endpoints and exposure effects were largely induced in both systems. NO exposure appeared to be more stressful for the mice than WB exposure.

2021-03-16 | E-MTAB-9248 | biostudies-arrayexpress

Comparison of R1, R2 and R3

Project description:3 samples of R1, R2 and R3 bone marrow monocytes were compared from 3 biological replicates in 3 separate experiments. R1, R2 and R3 were sorted from triplicate experiments from pools of mice

2016-11-24 | GSE90471 | GEO

A 6-month systems toxicology inhalation study in ApoE−/− mice demonstrates reduced cardiovascular effects of E-vapor aerosols compared to cigarette smoke.

Project description:Smoking cigarettes is harmful to the cardiovascular system. Considerable attention has been paid to the reduced harm potential of alternative nicotine-containing inhalable products such as e-cigarettes. We investigated the effects of E-vapor aerosols or cigarette smoke (CS) on atherosclerosis progression, cardiovascular function, and molecular changes in the heart and aorta of female ApoE−/− mice. The mice were exposed to aerosols from three different E-vapor formulations: (1) carrier (propylene glycol and vegetable glycerol), (2) base (carrier and nicotine) or (3) test (base and flavor) or to CS from 3R4F reference cigarettes for up to 6 months. Concentrations of CS and base or test aerosols were matched at 35 µg nicotine/L. Exposure to CS, compared with sham-exposed fresh air controls, accelerated atherosclerotic plaque formation, while no such effect was seen for any of the three E-vapor aerosols. Molecular changes indicated disease mechanisms related to oxidative stress and inflammation in general, plus changes in calcium regulation, and altered cytoskeletal organization and microtubule dynamics in the left ventricle. While ejection fraction, fractional shortening, cardiac output, and isovolumic contraction time remained unchanged following E-vapor aerosols exposure, the nicotine-containing base and test aerosols caused an increase in isovolumic relaxation time similar to CS. A nicotine-related increase in pulse wave velocity and arterial stiffness was also observed, but it was significantly lower for base and test aerosols than for CS. These results demonstrate that in comparison with CS, E-vapor aerosols induce substantially lower biological responses associated with smoking-related cardiovascular diseases.

2020-05-12 | E-MTAB-8578 | biostudies-arrayexpress

Bean leaves treated with benzothiadiazole (BTH)

Project description:Bean leaves treated with BTH or water. 126 = control R1, 127 = BTH R1, 128 = control R2, 129 = BTH R2, 130 = control R3, 131 = BTH R3

2019-07-31 | MSV000084162 | MassIVE

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2013-12-20 | E-GEOD-46487 | biostudies-arrayexpress

Single Cell RNA Sequencing Reveals Unique Dendritic Cell and Macrophage Subsets in the Mouse Kidney

Project description:Mononuclear phagocytes have important functions in regulating tissue injury and regeneration after AKI. We tested the hypothesis that kidney resident macrophages (R2) and infiltrative mononuclear phagocytes (R1) exist in distinct transcriptional subsets that are resolvable by single cell RNA sequencing. A further objective was to identify transcriptional signatures for those subsets. By cell sorting R2 and R1 cells from quiescent and injured mouse kidneys, we found remarkable heterogeneity among intrarenal innate immune cells. We define four subsets of dendritic cells and six subsets of R2 cells and specify differentially expressed genes that identify these cell types. Additionally, we observed subset-specific transcriptional responses to AKI. R2 cells, which express surface phenotype homogeneity, adopt distinct transcriptional programs in the steady state and after injury. Expression of MHC class II and invariant chain genes are decreased in a predominant subset of R2 cells after AKI. In contrast, other macrophage lineage-defining genes such as C1qa, b, and c, are expressed at similar levels across R2 cell subsets and their expression does not change in response to injury. This study has allowed us to identify R2 and R1 subsets that may prove to be therapeutic targets for inhibiting damaging inflammation and fibrosis or promoting tissue regeneration.

2023-09-01 | GSE157338 | GEO

A 6-Month Systems Toxicology Inhalation/Cessation Study in ApoE-/- Mice to Investigate Cardiovascular and Respiratory Exposure Effects of the Modified-Risk Tobacco Products CHTP1.2 and THS2.2 Compared with the Effects of Conventional Cigarettes [Lung iTRAQ data].

Project description:Cigarette smoke (CS) causes adverse health effects that may occur shortly after smoking initiation and lead to the development of respiratory disease (chronic obstructive pulmonary disease), cardiovascular disease, and cancer. To reduce the risk of smokers developing smoking-related diseases, Philip Morris International is developing modified risk tobacco products (MRTP). Within a systems toxicology study, we integrated multi-omics measurements with classical endpoints to assess the effects in female ApoE-/- mice of six months of exposure to CS (at 29.9 µg nicotine/L) or to aerosols from one potential and one candidate MRTP (CHTP 1.2 and THS 2.2, respectively) at matched nicotine concentrations. The impact of cessation or switching to CHTP 1.2 after three months of CS exposure was also evaluated. This data set contains the results from the analysis of proteome changes in the lung using the iTRAQ® quantification approach.

2019-06-18 | PXD010875 | Pride

2022-02-23 | PXD010874 | Pride

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