Project description:In this study, we investigated the effect of vitamin D supplementation on tumorigenesis in a thioacetamide (TAA)-induced rat intrahepatic cholangiocarcinoma model as vitamin D is known to have a spectrum of anticancer activities. Using PET, we found that tumor formation and progression were suppressed in rats fed a diet supplemented with 6 IU/g vitamin D3(+6D) as compared to the group fed a 2 IU/g vitamin D3 diet (+2D) or controls. Microarray analysis of the tumors that arose revealed that vitamin D supplementation caused significant up- and down regulation in 21 and 16 genes, respectively. There are 9 tissue samples (3 rats in each group labeled as (+6), (+2) and control). Duplicate analysis were used for each sample.
Project description:In this study, we investigated the effect of vitamin D supplementation on tumorigenesis in a thioacetamide (TAA)-induced rat intrahepatic cholangiocarcinoma model as vitamin D is known to have a spectrum of anticancer activities. Using PET, we found that tumor formation and progression were suppressed in rats fed a diet supplemented with 6 IU/g vitamin D3(+6D) as compared to the group fed a 2 IU/g vitamin D3 diet (+2D) or controls. Microarray analysis of the tumors that arose revealed that vitamin D supplementation caused significant up- and down regulation in 21 and 16 genes, respectively.
Project description:Cholangiocarcinoma (CCA) is a deadly tumour lacking effective therapies. Clinically-relevant experimental models and analysis of human samples represent the cornerstone of mechanistic cancer research. Thioacetamide (TAA)-induced intrahepatic CCA (iCCA) in rats encompasses key histological and molecular features of human iCCA. Molecular studies in bile may capture carcinogenic alterations and therapeutic vulnerabilities in CCA. We performed bile proteomic and metabolomic analyses in this model leading us to identify unrecognized mechanisms relevant to human iCCA.
Project description:The aim is to characterize rat liver fibrosis induced by thioacetamide (TAA). To induce hepatic fibrosis, Male Sprague Dawley rats (9-12 weeks of age and 380-420 g of weight upon arrival, supplied by Beijing Vital River laboratory animal Co., Ltd.) were treated with thioacetamide (TAA). Rat liver samples were collected from five groups of rats at week 1, 2, 4, 8 and 13 after TAA (300 mg/kg) administration three times per week while five control groups receive the same volume of 0.9% normal saline. Four biological replicates were used for each group.
Project description:Analysis of hormone effects on irradiated LBNF1 rat testes, which contain only somatic cells except for a few type A spermatgogonia. Rats were treated for 2 weeks with either sham treatment (group X), hormonal ablation (GnRH antagonist and the androgen receptor antagonist flutamide, group XAF), testosterone supplementation (GnRH antagonist and testosterone, group XAT), and FSH supplementation ((GnRH antagonist, androgen receptor antagonist, and FSH, group XAFF). Results provide insight into identifying genes in the somatic testis cells regulated by testosterone, LH, or FSH.
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: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:Validation of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease would provide an important resource for suggesting and testing of novel target-based therapies against this devastating cancer. In this study, comprehensive gene expression profiling in a novel orthotopic rat model of intrahepatic cholangiocarcinoma progression was carried out in an effort to identify potential therapeutic targets relevant to the progressive human cancer. Microarray analysis was performed on intrahepatic cholangiocarcinomas formed at 10, 15, and 25 days after bile duct inoculation of neu-transformed rat cholangiocytes (BDEneu cells) into rat liver and on peritoneal metastases at the 25 day time period, compared with non-cancerous right liver lobe from the same animals.
Project description:Characterization of preclinical models of intrahepatic cholangiocarcinoma progression that reliably recapitulate altered molecular features of the human disease. Here, we performed comprehensive gene expression profiling of cholangiocarcinoma tumors arising from bile duct inoculation of different grade malignant rat cholangiocytes.
