Objective To explore the effects of Chinese herbal compound, Tengmei decoction, on type II collagen-induced arthritis ( CIA) in rats, and to examine the changes of arthritis index ( AI) , limb swelling, joint tissue inflammatory infiltration, and the effects on immune-inflammatory factors.Methods Sprague-Dawley rat models of arthritis were successfully established by intradermal injection of type II collagen and Freund’ s complete adjuvant.The model rats were randomly divided into model group, positive drug group, and high-and low-dose Chinese medicine groups, 6 rats in each group.The intervention and treatment period was 12 weeks.To measure weekly the anteroposterior and transverse diameters of the rear ankles and wrists, the transverse diameter of the claw foot palm pad, the thickness and the highest point width of hind limb plantar joint swelling, and to evaluate the integrated scores of joints and limbs swelling using a vernier caliper.Results ①Compared with the normal group, the total arthritis scores and hind limbs AI scores of the model group were significantly increased ( P <0.05 or P <0.01 ) .The left forelimb AI scores were significantly increased during 10 -12 weeks ( P <0.05 ) .The anteroposterior and transverse diameters of the left hind limb, the thickness of the highest point measurement of the left hind foot pad metatarsal were significantly increased ( P<0.05 or P<0.01) in different time periods between 1-12 weeks.Compared with the model group, the total scores and the left hind limb joints AI scores of the high-and low-dose drug groups were decreased after 6 weeks (P<0.05).②Compared with the normal control group, levels of mRNA transcription and protein expression of IL-6 and TNF-αwere significantly up-regulated ( P<0.01 ) in the model group.Compared with the model group, the levels of mRNA transcription and the expression of IL-6 and TNF-αproteins were significantly down-regulated in the positive group and Chinese medicine groups ( P <0.01 ) .③ Histological examination showed that the low-dose TCM significantly improved the CIA synovial hyperplasia and inflammatory cell infiltration.Conclusions The molecular mechanism of Chinese herbal compound Tengmei decotion in improving joint pathological injury of CIA rat models may be related to its inhibitory effect on the high expression of immune-inflammatory factors in the synovial tissue of CIA rats.

OBJECTIVECellular senescence as one of the important steps against tumor is observed in many cancer patients receiving chemotherapy and is related to chemotherapeutic response. To investigate the effect of cisplatin on hepatocellular carcinoma, we treated HepG2 cells exhibiting wild-type TP53 with gradient concentrations of cisplatin.

METHODSThe inhibitory effects of cisplatin on human hepatoma HepG2 cells were detected by MTT assay and colony formation test. The changes in cell cycle were analyzed by flow cytometry, and cellular senescence was detected with senescence associated β-galactosidase (SA β-gal) staining. The relative mRNA expression levels of TP53, P21 and P19 was estimated using semi-quantitative real-time RT-PCR, and the protein expressions of P53 and P21 were detected using Western blotting.

RESULTSCisplatin induced irreversible proliferation inhibition and G1 phase arrest of HepG2 cells. Elevated levels of senescence-associated β-galactosidase was observed in HepG2 cells exposed to low doses of cisplatin. P19 expression immediately increased following cisplatin exposure and reached the maximum level at 48 h, followed then by a rapid decrease to the baseline level, whereas the expressions levels of TP53 and P21 mRNA increased continuously. Western blotting confirmed P53 and P21 expression changes similar to their mRNA expressions during cisplatin-induced cellular senescence in HepG2 cells.

CONCLUSIONOur results revealed a functional link between cisplatin and hepatocellular senescence. Cellular senescence induced by cisplatin as a stabile senescent cellular model can be used for further research.

Cell Cycle ; drug effects ; Cell Cycle Checkpoints ; drug effects ; Cellular Senescence ; Cisplatin ; pharmacology ; Cyclin-Dependent Kinase Inhibitor p19 ; metabolism ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Hep G2 Cells ; Humans ; Tumor Suppressor Protein p53 ; metabolism ; Up-Regulation