Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1230214 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32542838_1.fastq.gz | Fastqsanger.gz | |||
| SRR32542838_2.fastq.gz | Fastqsanger.gz | |||
| SRR32542839_1.fastq.gz | Fastqsanger.gz | |||
| SRR32542839_2.fastq.gz | Fastqsanger.gz | |||
| SRR32542840_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 66 |
Similar Datasets
Project description:This study investigates microorganisms participating in the biotransformation of the anti-diabetic sitagliptin in hyporheic zones. Specifically, micrcosms with spike-in of TP233 (filenames: SK_C_07, SK_C_08, SK_C_09) vs controls (filenames: SK_C_01, SK_C_02, SK_C_03) were investigated.
2026-03-03 | PXD061324 | Pride
Project description:Micropollutant biotransformation in a sequential biofiltration system comprising different redox conditions
| PRJEB32535 | ENA
Project description:This is the model of atorvastatin metabolism in hepaitc cells described in the article:
A systems biology approach to dynamic modeling and inter-subject variability of statin pharmacokinetics in human hepatocytes
Joachim Bucher , Stephan Riedmaier , Anke Schnabel , Katrin Marcus , Gabriele Vacun , Thomas S Weiss , Wolfgang E Thasler , Andreas K Nussler , Ulrich M Zanger and Matthias Reuss. BMC Systems Biology 2011, 5:66. DOI:10.1186/1752-0509-5-66
Abstract:
Background:
The individual character of pharmacokinetics is of great importance in the risk assessment of new drug leads in pharmacological research. Amongst others, it is severely influenced by the properties and inter-individual variability of the enzymes and transporters of the drug detoxification system of the liver. Predicting individual drug biotransformation capacity requires quantitative and detailed models.
Results:
In this contribution we present the de novo deterministic modeling of atorvastatin biotransformation based on comprehensive published knowledge on involved metabolic and transport pathways as well as physicochemical properties. The model was evaluated in primary human hepatocytes and parameter identifiability analysis was performed under multiple experimental constraints. Dynamic simulations of atorvastatin biotransformation considering the inter-individual variability of the two major involved enzymes CYP3A4 and UGT1A3 based on quantitative protein expression data in a large human liver bank (n=150) highlighted the variability in the individual biotransformation profiles and therefore also points to the individuality of pharmacokinetics.
Conclusions:
A dynamic model for the biotransformation of atorvastatin has been developed using quantitative metabolite measurements in primary human hepatocytes. The model comprises kinetics for transport processes and metabolic enzymes as well as population liver expression data allowing us to assess the impact of inter-individual variability of concentrations of key proteins. Application of computational tools for parameter sensitivity analysis enabled us to considerably improve the validity of the model and to create a consistent framework for precise computer-aided simulations in toxicology.
The model is parameterized for patient 1 and reproduces the time courses in figure 2 of the article.
2024-09-02 | BIOMD0000000328 | BioModels
Project description:The necrotrophic fungus Botrytis cinerea rapidly kills host tissue with its secreted proteins and metabolites. Necrotrophs can trigger the hypersensitive response (HR), which is accompanied by reactive oxygen species (ROS) production, but it remains unclear whether this ROS burst promotes or restricts B. cinerea infection. We have combined Arabidopsis RESPIRATORY BURST OXIDASE HOMOLOG D (RBOHD) mutant analysis, luminol-based in vivo assays, and the use of CRISPR-Cas generated B. cinerea ROS detoxification mutants to analyze the toxic effect of the ROS burst. In addition, RNA-sequencing, expression analyses and redox imaging were used to study RBOHD-dependent signaling and redox homeostasis. RBOHD mutants showed increased susceptibility to B. cinerea infection, and the apoplastic ROS burst was dependent on RBOHD. Fungal mutants confirmed the importance of SUPEROXIDE DISMUTASE 1 (SOD1) and ACTIVATOR PROTEIN 1 (AP1) for ROS detoxification and virulence. Unexpectedly, the transcriptomes of B. cinerea-infected Arabidopsis Col-0 and RBOHD mutant were highly similar, providing no evidence for a connection of extracellular ROS production and intracellular ROS-induced transcriptional signaling. Nevertheless, RBOHD activity was found to be involved in the maintenance of cellular redox homeostasis under phytotoxic stress. Our results demonstrate an exclusive and protective role of the RBOHD-dependent oxidative burst, but B. cinerea counteracts this response via different detoxification mechanisms.
2026-01-28 | GSE317547 | GEO
Project description:Differentially expressed genes were identified in lung endothelial cells of CLP-treated mice compared to sham-treated controls and after treatment with sitagliptin. Sitagliptin strongly reduced the inflamatory response.
2025-11-10 | GSE244815 | GEO
Project description:Differentially expressed genes were identified in lung endothelial cells of CLP-treated mice compared to sham-treated controls and after treatment with sitagliptin. Sitagliptin strongly reduced the inflamatory response.
2025-11-10 | GSE244943 | GEO
Project description:A central challenge in pharmaceutical research is to investigate genetic variation in response to drugs. The Collaborative Cross (CC) mouse reference population is a promising model for pharmacogenomic studies because of its large amount of genetic variation, genetic reproducibility, and dense recombination sites. While the CC lines are phenotypically diverse, their genetic diversity in drug disposition processes, such as detoxification reactions, is still largely uncharacterized. Here we systematically measured RNA-sequencing expression profiles from livers of 29 CC lines under baseline conditions. We then leveraged a reference collection of metabolic biotransformation pathways to map potential relations between drugs and their underlying expression quantitative trait loci (eQTLs). By applying this approach on proximal eQTLs, including eQTLs acting on the overall expression of genes and on the expression of particular transcript isoforms, we were able to construct the organization of hepatic eQTL-drug connectivity across the CC population. The analysis revealed a substantial impact of genetic variation acting on drug biotransformation, allowed mapping of potential joint genetic effects in the context of individual drugs, and demonstrated crosstalk between drug metabolism and lipid metabolism. Our findings provide a resource for investigating drug disposition in the CC strains, and offer a new paradigm for integrating biotransformation reactions to corresponding variations in DNA sequences.
2016-10-17 | GSE77715 | GEO
Project description:To investigated the therapeutic mechanism underlying the sitagliptin improves vascular endothelial function in obesity, we performed bioinformatics analyses on the expression profiles of long noncoding RNAs (lncRNAs) and message RNAs (mRNAs) in the aortae from obese mice with or without sitagliptin treatment.
2022-04-19 | GSE200814 | GEO