Project description:Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment. Vehicle control, diclofenac, and three doses of the test compound (small-molecule neurotransmitter receptor antagonist) were applied to three primary cell lines, with three biological replicates in each group. In some treatment groups read-outs were only available for two samples. All together 41 samples were profiled.
Project description:Expression profiles of 917 pathway repoter genes were determined by AmpliSeq-RNA in primary human hepatocytes treated with Diclofenac and a test compound 3 hours after treatment.
Project description:A highly specific and potent small molecule antagonist of CRTH2 (chemoattractant receptor) was used to investigate the role of this Prostaglandin D2 (PGD2) receptor in chronic models of cutaneous inflammation and the underlying immune response. These RNA samples are from mice that were in a chronic (50 day) model of atopic dermatitis. Each mouse had a section of back skin patched with a gauze, and the RNA was from the patched area of skin; the control mice had the gauze soaked in PBS, whereas all the other test mice had the gauze soaked in ovalbumin dissolved in PBS. The ovalbumin acts as an allergen and induces the experimental atopic dermatitis. The six groups of mice that received the OVA patch were treated in different ways:some received just the drug vehicle during the OVA patching, others received the test drug (compound A) at 3 different concentrations: 10 mg/kg 1 mg/kg and 0.1 mg/kg. Two other cohorts received positive control drugs: ramatroban and dexamethasone .Each different sample represents a different animal.
Project description:These samples are part of a study in which we demonstrate that mast cells express the receptor CRTH2, which is the target for our antagonist compound compound A. We want to examine whether there are differences in RNA expression when the mast cells are treated with the ligands of CRTH2 - PGD2 and DK-PGD2 - compared to no treatment. Also, we want to see if pretreating the cells with compound A can block or change differences in RNA expression induced by either DK-PGD2 or PGD2. The study also looks at Ige loaded cells exposed to antigen and dexamethasone, and cells treated with BW868c - a a highly selective DP receptor antagonist.
Project description:Through scRNA-sequencing of primary human hepatocytes (PHHs), we have identified four subgroups of hepatocytes. A phenotyping 5-probe cocktail (Sanofi-Aventis) has been used to assess their metabolic capacity. Upon cocktail treatment, the characterized four hepatocyte subgroups displayed differential gene expression profiles and exhibited xenobiotic metabolism-related specialization. Intracellular lipid accumulation achieved through loading the cells with free fatty acids (FFA, 2:1 oleic:palmitic acid), differently affected the four subgroups. Moreover, we have shown that intracellular fat accumulation diminishes the drug-related metabolic capacity of hepatocytes.
Project description:A highly specific and potent small molecule antagonist of CRTH2 (chemoattractant receptor) was used to investigate the role of this PGD2 receptor in a chronic model of airway inflammation and the underlying immune responseThis is a mouse asthma model which uses CRA (cockroach antigen) All the mice in this study were immunized with CRA followed by aerosolized CRA as a challenge. There are 3 experimental groups in this study. One cohort of mice was "simply" challenged (samples 1-3), another cohort was challenged and received the drug vehicle (samples 4-9), and the third cohort received the drug compound A prior to antigen challenge (samples 10-14). Each sample is from a different mouse. Following the aero-challenge, the mice were sacrificed, lungs harvested and RNA was made for gene expression analysis.
Project description:The transcriptomics changes induced in Primary Mouse Hepatocytes by Cyclosporin A after treatment for 24h and 48h The study investigated differential gene expression in Primary Mouse Hepatocytes mRNA following 24 and 48 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/solvent. In total 24 arrays .
Project description:This is a phase 1/1b open label, multicenter dose escalation and dose expansion study to investigate the safety, tolerability and anti-tumor activity of TPST-1120, a small molecule selective antagonist of PPARα (peroxisome proliferator activated receptor alpha) as monotherapy and in combination with a systemic anticancer agent, nivolumab, an anti-PD1 antibody, in subjects with advanced solid tumors.
Project description:The microRNA changes induced in Primary Mouse Hepatocytes of C57Bl6-mice by Cyclosporin A after treatment for 24h and 48h The study investigated differential microRNA expression in Primary Mouse Hepatocytes following 24 and 48 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/six per solvent. In total 24 arrays .
Project description:Primary human hepatocytes were treated with compounds modulating steatosis: palmitic acid, compound C and metformin qPCR miRNA expression profiling. Hepatocytes were treated as indicated in the summary. Equal amount total RNA was pooled prior to miRNA expression analysis
