Project description:We are testing the ability of spironolactone as a NADPH oxidase inhibitor during an induced dietary oxalate overload by Ethylene Glycol in Sprague Dawley rats at two different time points. We looked into the development of hyperoxaluria and crystal deposition at two different time points and into differences between hyperoxaluria and crystal induced alterations in the kidneys. Eventually, we are expecting to see the role of spironolactone as an inhibitor of NADPH oxidase which is involved in the production of reactive oxygen species (ROS) which leads to oxidative stress in the living organisms leading to a plethora of vascular diseases, hypertension, and kidney diseases.
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.
Project description:We performed RNA microarray in a low protein diet (LPD) model of IUGR at three key time points of alveolarization process. IUGR and control rat pups had been studied for each time point considered: on postnatal day 4 (P4) before beginning of the alveolarization process, on P10, peak of alveolarization process and on P21 at the end of it.
Project description:In order to establish a rat embryonic stem cell transcriptome, mRNA from rESC cell line DAc8, the first male germline competent rat ESC line to be described and the first to be used to generate a knockout rat model was characterized using RNA sequencing (RNA-seq) analysis.
