Project description:12-O-tetradecanoylphorbol-13-acetate (TPA) promotes skin carcinogenesis. CDDO is a potential antioxidative and antiinflammatory agent to prevent the TPA-induced skin cell transformation at nanomolar scale. We characterized the transcriptome, CpG methylome, and pathway network of JB6 cells treated with TPA and TPA + CDDO using RNA sequencing, methyl sequencing, and QIAGEN Ingenuity Pathway Analysis.
Project description:12-O-tetradecanoylphorbol-13-acetate (TPA) promotes skin carcinogenesis. CDDO is a potential antioxidative and antiinflammatory agent to prevent the TPA-induced skin cell transformation at nanomolar scale. We characterized the transcriptome, CpG methylome, and pathway network of JB6 cells treated with TPA and TPA + CDDO using RNA sequencing, methyl sequencing, and QIAGEN Ingenuity Pathway Analysis.
Project description:Neoplastic transformation of DPSC cultured under Hypoxia versus normoxia. Molecular characterization of cell markers associated with tumorigenicity.
Project description:Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease caused by excess fat accumulation, closely associated with obesity and metabolic syndrome.Bardoxolone methyl (2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid methyl ester, CDDO-Me) is a potent activator of nuclear factor erythroid 2-related factor 2 (Nrf2). Some clinical trials of CDDO-Me were conducted for chronic kidney diseases and pulmonary arterial hypertension, whereas the hepatoprotective effect of CDDO-Me on nonalcoholic steatohepatitis (NASH) has not yet been elucidated. The purpose of this study was to determine the hepatoprotective potential and mechanisms of CDDO-Me in a diet-induced NASH mouse model. Whole transcriptome analysis revealed that CDDO-Me markedly inhibited the expressions of chemokine ligands, Ccl3 and Ccl4, and the chemokine receptors, Ccr1 and Ccr5 that increased in NASH mice while activating Nrf2-dependent pathway. Serum protein levels of CCL3 and CCL4 upregulated in NASH mice were inhibited in a dose-dependent manner by treatment with CDDO-Me. CDDO-Me inhibited the expression levels of Ccr1 and Ccr5, and simultaneously blocked Ccl3 and Ccl4 the ligands of the receptors, respectively in RAW264.7 cell line. Taken together with the observations, CDDO-Me directly inhibits the expression of CCL3-CCR1 and CCL4-CCR5 axes in macrophages of NASH mice, which might contribute to the improvement of nonalcoholic steatohepatitis and fibrosis through the interference of monocyte-derived macrophage migration.
Project description:Neoplastic transformation of DPSC cultured under Hypoxia versus normoxia. Molecular characterization of cell markers associated with tumorigenicity. DPSC array CGH profiles of experimental (HX48h and HX72h) and reference (NX48 and NX72h) genomic DNA samples
Project description:The two-stage cell transformation assay is an in vitro model cell culture system to identify the ability of chemicals to act as initiators or promoters of cell transforma- tion and also to study the cellular and molecular mechanisms of chemically induced morphological and neoplastic cell transformation. The global gene expression profiles of 3- methylcholanthrene (MCA)+12-O-tetradecanoylphorbol-13- acetate (TPA)-transformed C3H/10T1/2 cells are not known. Therefore, we have investigated the global transcriptional profile of MCA+TPA-transformed C3H10T1/2 cells using an 8×60 k probe microarray. The study revealed a differential regulation of pathways and gene expressions. Multifold dysregulation was seen in pathways of cancer, phagosomal activity, and tumor cell microenvironment information pro- cessing systems, notably the neuroactive ligand–receptor in- teraction, actin cytoskeleton regulation, tight junction, axon guidance, and cell adhesion molecules. The genes FGF1, EIF4E1B, MAGI1,and GRIA3 showed upregulation; these encoded the pluripotent fibroblast growth factor, the transla- tion initiation factor, the tight junction scaffolding protein, and the antiapoptotic as well as the enhancer of proliferation and migration, respectively. The genes CXCL7/CXCL5/CXCL12, H2DMB1,and HSPA1A showed downregulation; these encoded the chemotactic agent protein, the protein involved