Project description:To identify nasal cavity transcripts differentially expressed due to treatment with N, N-dimethyl-p-toluidine (DMPT), we collected RNA during the from male F344/N rats exposed to 120 mg/kg DMPT, 5 days after DMPT exposure for animals 5-6 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip Array. A total of 2,561 gene transcripts were differentially expressed due to DMPT treatment (false discovery rate (FDR) < 0.05).
Project description:To identify nasal cavity transcripts differentially expressed due to treatment with N, N-dimethyl-p-toluidine (DMPT), we collected RNA during the from male F344/N rats exposed to 120 mg/kg DMPT, 5 days after DMPT exposure for animals 5-6 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip Array. A total of 2,561 gene transcripts were differentially expressed due to DMPT treatment (false discovery rate (FDR) < 0.05). There were 2 groups and 5x replication for each group, for 10 total samples. The groups were (1) DMPT and (2) vehicle control. We compared vehicle control vs DMPT using ORIOGEN software. The permutation based p-values for each test were significant for FDRâ¤5%.
Project description:To identify liver transcripts differentially expressed due to treatment with N, N-dimethyl-p-toluidine (DMPT) and p-toluidine, we collected RNA during the from male F344/N rats exposed to 0, 1, 6, 20, 60 or 120 mg/kg DMPT (or p-toluidine), 5 days after exposure for animals 5-6 weeks of age. These samples were interrogated with the Affymetrix Rat Genome 230 2.0 GeneChip Array. A total of 511 gene transcripts were differentially expressed due to DMPT treatment and 354 gene transcripts were differentially expressed due to p-toluidine treatment (false discovery rate (FDR) < 0.05).
Project description:Formaldehyde, an important industrial chemical, is used for multiple commercial purposes throughout the industrialized world. This simple, one carbon aldehyde is a natural metabolite formed in cells throughput the body. However, it is also a rodent nasal carcinogen, when inhaled by rats every day for two-years at irritant concentrations. High tumor incidences occur at concentration of 10 ppm and above; no tumors are observed at concentrations below 6.0 ppm. The US Environmental Protection Agency (US EPA) is now (2007) conducting a risk assessment to try to evaluate possible cancer risks for much lower levels of human exposure. Sensitive methods are needed to evaluate tissue responses below those concentrations that are clearly irritant or carcinogenic. This microarray study was undertaken to evaluate the mode of action for nasal responses to inhaled formaldehyde in Fisher 344 rats over a range of exposure concentrations. The range of concentrations used spanned those at which virtually no tissue responses were observed (0.7 ppm) to those that represent the highest concentration in the cancer studies (15 ppm) that produced nasal tumors in half the exposed group of rats. The study identified doses at which there were no statistically significant changes in gene expression; intermediate doses with changes in a small number of genes not easily grouped by function; and then concentrations where changes were consistent with irritation and cell stress responses. Experiment Overall Design: Eight week old male F344/NCrl rats were exposed to formaldehyde through either instillation or inhalation. For animals exposed via instillation, 40 ul per nostril of 400 mM formaldehyde was instilled intranasally. Vehicle control animals were instilled with 40 ul per nostril of distilled water. All animals exposed via instillation were sacrificed 6 hours post-exposure. For animals exposed via inhalation, whole-body exposures were performed at doses of 0, 0.7, 2, 6, and 15 ppm (6 hours per day, 5 days per week). Inhalation animals were sacrified at 6 hours, 24 hours, 5 days, and 19 days following initiation of exposure except for the 15 ppm concentration which was sacrificed at only the 6 hour time point. Following sacrifice, tissue from the Level II region of the nose was dissected and digested with a mixture of proteases to remove the epithelial cells. The epithelial cells scquired from this section of the nose consisted primarily of transitional epithelium with some respiratory epithelium. Microarray analysis was performed on the epithelial cells.
Project description:Male Sprague-Dawley rats were used to establish exhausted-exercise model by motorized rodent treadmill. Yu-Ping-Feng-San at doses of 2.18 g/kg was administrated by gavage before exercise training for 10 consecutive days. Quantitative proteomics was performed for assessing the related mechanism of Yu-Ping-Feng-San.
Project description:d-serine is naturally present throughout the human body. It is also used as add-on therapy for treatment-refractory schizophrenia. d-Serine interacts with the strychnine-insensitive glycine binding site of NMDA receptor, and this interaction could lead to potentially toxic activity (i.e., excitotoxicity) in brain tissue. The transcriptomic changes that occur in the brain after d-serine exposure have not been fully explored. Affymetrix microarray technology was used to determine differential gene expression resulting from D-Serine exposure. Keywords: Dose course
Project description:To evaluate the differential impact of IFN-gamma secretion on nasal cavity epithelial cells, we compared the transcriptional profiles of nasal cavity epithelial cells (CD45-, CD3- CD11b-, CD31-, CD326+) from wildtype and IFN-gamma knockout mice at 30 days (d30) post intranasal infection with a live attenuated influenza virus expressing the immunodominant H-2Kd CD8 T cell epitope from Sendai virus nucleoprotein (LAIV-SenNP). Nasal cavity epithelial cells were also analyzed from LAIV-SenNP immunized wildtype and IFN-gamma knockout mice 3 days after intranasal administration of Sendai virus nucleoprotein peptide (d30+3). The results indicate that nasal cavity epithelial cells express genes associated with antigen presentation and antiviral function following antigen-specific T cell activation, and these alterations in transcriptional programming depend on IFN-gamma secretion.
Project description:Knee osteoarthritis (KOA), as a degenerative multifactorial disease, affects the quality of life and mental health of patients, and also brings a huge socioeconomic burden. Treating synovitis have shown promise as anti-inflammatory therapeutics in mitigating OA symptoms and disease progression. Here, by analysing synovial single-cell sequencing (scRNA-seq) data from KOA, we found that synovial fibroblasts (FLS) in OA synovium showed a distinct pro-inflammatory phenotype. We collected synovial tissue from patients with clinical OA as well as from healthy donors, and histological examination was consistent with findings in scRNA-seq. Inspired by recent cross-tissue fibroblast lineage studies, we identified by sequencing that healthy FLS in synovial tissues share transcriptome-level similarities with dermal fibroblasts (DFb). Subsequently, we revealed the local as well as systemic distribution of intra-articular injected DFbs by constructing/extracting two types of rat fibroblasts (luciferase DFbs as well as GFP DFbs). The results demonstrate that DFbs can be locally retained in the synovium for up to three weeks following targeted engrafting on it. And intra-articular injection does not result in DFbs migration to vital organs or the occurrence of histological changes in these organs. A rat model of KOA was constructed by anterior cruciate ligament transection (ACLT) in order to study the therapeutic effect of DFbs on KOA. After injection, the rats showed improvement in painful gait. In addition, histological as well as imaging results showed reduced synovitis and improvement in articular cartilage. Finally we verified the protective effect of DFbs on cytokine-stimulated chondrocytes in a co-culture system.