RESUMO
Genetic and epigenetic alterations accumulate in the process of hepatocellular carcinogenesis, but the role of genomic spatial organization in HCC is still unknown. Here, we performed in situ Hi-C in HCC cell line PLC/PRF/5 compared with normal liver cell line L02, together with RNA-seq and ChIP-seq of SMC3/CTCF/H3K27ac. The results indicate that there were significant compartment switching, TAD shifting and loop pattern altering in PLC/PRF/5. These spatial changes are correlated with abnormal gene expression and more opening promoter regions of the HCC cell line. Thus, the 3D genome organization alterations in PLC/PRF/5 are important in epigenetic mechanisms of HCC tumorigenesis.
Assuntos
Humanos , Carcinoma Hepatocelular/genética , Linhagem Celular , Linhagem Celular Tumoral , Genômica , Neoplasias Hepáticas/genéticaRESUMO
Objective To study the effect of tripterysium glycosides tablets on the pharmacokinetics of valsartan in rats combined with tripterysium glycosides tablets and valsartan. Methods 16 male Sprague-Dawley rats were randomly divided into two groups: the single administration group and the combined administration group. In the single administration group, the rats were given intragastric administration of valsartan (20 mg/kg) and the combined administered group was given intragastric administration of tripterysium glycosides tablets (10 mg/kg) and valsartan (20 mg/kg). Blood samples were taken at different time points and plasma concentrations of valsartan were determined by LC-MS. Pharma-cokinetic parameters were calculated. Results The maximum plasma concentration of valsartan was [(1. 57 ±0. 32) vs(1. 01±0. 28)μg/mL] and the plasma area under the curve was [(10. 01 ±0. 58) vs (6. 82±0. 77)mg·h/L], which were signifi- cantly increased in the combined administration group combined with the single administration group (P<0. 05), indicating that valsartan metabolism was significantly inhibited. Conclusion Tripterysium glycosides tablets combined with valsartan has a significant effect on the pharmacokinetics of valsartan. This study plays a guiding role in the combined administration of valsartan and tripterygium glycosides tablets, which can avoid the occurrence of clinical adverse drug interactions.