Project description:Fipronil is a widely-used broad-spectrum phenylpyrazole insecticide. It has been shown that fipronil increases the hepatic metabolism of thyroid hormone in the rat, which may induce compensatory mechanisms at the level of the thyroid gland itself. Here, we studied the effect of fipronil on the transcriptome of the thyroid gland in the rat. Adult (2- to 3-month-old) female Wistar rats were treated per os with fipronil (3 mg/kg) or the vehicle alone for 14 days. The transcriptome of their thyroid gland was analyzed using Agilent 4x44K microarrays.
Project description:Fipronil is a widely-used broad-spectrum phenylpyrazole insecticide. It has been shown that fipronil increases the hepatic metabolism of thyroid hormone in the rat, which may induce compensatory mechanisms at the level of the thyroid gland itself. Here, we studied the effect of fipronil on the transcriptome of the thyroid gland in the rat. Adult (2- to 3-month-old) female Wistar rats were treated per os with fipronil (3 mg/kg) or the vehicle alone for 14 days. The transcriptome of their thyroid gland was analyzed using Agilent 4x44K microarrays. Thyroid gland gene expression was measured from female Wistar rats treated with vehicle (n = 10) or fipronil (n = 10) using a dye switch design.
Project description:Fipronil (CAS #: 120068-37-3), a widely used insecticide, has been described as a thyroid disruptor in rat inducing a marked increase in thyroxine (T4) clearance resulting in a decrease in T4 plasma concentration. These effects seem to require the bioactivation of fipronil via its biotransformation into fipronil sulfone by cytochromes P450 (CYP). Here, we hypothesized that fipronil-induced thyroid disruption may, at least in part, result from the induction of hepatic enzymes involved in the metabolism of thyroid hormones. Thus, we used microarrays to perform a genome-wide analysis of the effects of fipronil on gene expression in rat liver.
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:Fipronil (CAS #: 120068-37-3), a widely used insecticide, has been described as a thyroid disruptor in rat inducing a marked increase in thyroxine (T4) clearance resulting in a decrease in T4 plasma concentration. These effects seem to require the bioactivation of fipronil via its biotransformation into fipronil sulfone by cytochromes P450 (CYP). Here, we hypothesized that fipronil-induced thyroid disruption may, at least in part, result from the induction of hepatic enzymes involved in the metabolism of thyroid hormones. Thus, we used microarrays to perform a genome-wide analysis of the effects of fipronil on gene expression in rat liver. Liver gene expression was measured from female Wistar rats treated with vehicle (n = 7) or fipronil 3 mg/kg/day per os for 14 days (n = 8)
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.
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.