Aim To investigate the neuroprotective effects of puerarin on H2O2-induced SH-SY5Y cell ap-optosis and the molecular mechanisms underlying the neuroprotective effects. Methods Neuron injury mod-el was established in vitro through H2O2-induced SH-SY5Y injury. MTT assay was performed to detect the effect of puerarin on H2O2-induced SH-SY5Y survival rates. Hoechst 33342 staining was used to observe the cell apoptosis. JC-1 staining was employed to detect the level of mitochondria membrane poential. Caspase-3 was determined by caspase-3 catalyze the substrate specificity Ac-DEVD-pNA. Caspase-9 was determined by caspase-9 catalyze the substrate specificity Ac-LE-HD-pNA. The effects of puerarin on the protein level of Bcl-2,Bax,p-Akt and Akt were determined by West-ern blot. Results The cell survival rate significantly increased after puerarin pretreatment compared with H2O2model group. Furthermore, puerarin pretreat-ment not only inhibited the decreasing of mitochondrial membrane potential,increasing of caspase-3, caspase-9 enzymatic activity and the expression of Bax,but also promoted the expression of p-Akt and Bcl-2, which was prevented by LY294002, an inhibitor of PI3K/Akt. Conclusion Puerarin can play a neuroprotective role for SH-SY5Y cell apoptosis induced by H2O2, maybe via activating PI3K/Akt signaling pathway.

Poly (ADP-ribose) polymerase-1 (PARP-1) inhibitors and histone deacetylase (HDAC) inhibitors have recently emerged as promising anticancer drugs. The aim of this study was to investigate the effect of combination treatment with the PARP inhibitor PJ34 and HDAC inhibitor SAHA on the proliferation of liver cancer cells. Cell proliferation and apoptosis were assessed in three human liver cancer cell lines (HepG2, Hep3B and HCC-LM3) treated with PJ34 (8 μmol/L) and SAHA (1 μmol/L), alone or combined, by Cell Counting Kit-8 assay and flow cytometry, respectively. The nude mice bearing subcutaneous HepG2 tumors were administered different groups of drugs (10 mg/kg PJ34, 25 mg/kg SAHA, 10 mg/kg PJ34+25 mg/kg SAHA), and the inhibition rates of tumor growth were compared between groups. The results showed that combined use of PJ34 and SAHA could synergistically inhibit the proliferation of liver cancer cell lines HepG2, Hep3B and HCC-LM3. The apoptosis rate of HepG2 cells treated with PJ34+SAHA was significantly higher than that of HepG2 cells treated with PJ34 or SAHA alone (P<0.05). In vivo, the tumor inhibition rates were 53.5%, 61.4% and 82.6% in PJ34, SAHA and PJ34+SAHA groups, respectively. The combined use of PJ34 and SAHA could significantly inhibit the xenograft tumor growth when compared with use of PJ34 or SAHA alone (P<0.05). It was led to conclude that PJ34 and SAHA can synergistically suppress the proliferation of liver cancer cells.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Drug Synergism ; Hep G2 Cells ; Histone Deacetylase Inhibitors ; administration & dosage ; pharmacology ; Humans ; Hydroxamic Acids ; administration & dosage ; pharmacology ; Liver Neoplasms ; drug therapy ; Mice ; Phenanthrenes ; administration & dosage ; pharmacology ; Poly(ADP-ribose) Polymerase Inhibitors ; administration & dosage ; pharmacology ; Xenograft Model Antitumor Assays

Objective To determine the adherence to and its determinants of methadone maintenance treatment (MMT) among heroin addicts in Dehong prefecture in Yunnan province from 2005 to 2009. Methods A dynamic cohort analysis was conducted with the time of treatment initiation as the time of cohort entry, to calculate the proportion of adhering to the treatment at different time points after initiation of the treatment, and to study the determinants of adherence.Results A total of 3758 had been treated. Among them, 95.8% were males, 75.8% aged between 20-39 years, 90.4% were peasants or unemployed, 57.0% were ethnic minorities, 35.0% were single and 55.5% were married with spouses, 43.9% were illiterate or educated at most primary school. The age of first using drugs averaged at 23.93 years. About 96.3% of the study subjects had used heroin and 21.7% were HIV-infected. The minimum time under MMT was less than 1 month and the maximum 61 months. The median methadone dose at first delivery was 25 ml, with the minimum 1 ml and the maximum 330 ml. By the end of the study or observation period, a total of 1798 patients had withdrawn from treatment and 1960 were still under treatment. The proportions of adherence to or still being under the treatment after 1,3,6,9, 12,24, 36,48 and 60 months treatment were 0.919,0.847,0.756, 0.690, 0.637, 0.519, 0.417, 0.360 and 0.321, respectively. Multiple regression analysis using Cox proportional hazard model indicated that withdraw from the methadone maintenance treatment was significantly associated with location of the treatment clinics, year of treatment initiation, marital status, HIV infection status, methadone dose of first delivery and the result of last urine test for heroin use. Conclusion MMT attendants in Dehong prefecture had a relatively high withdraw rate and low adherence rate. More efforts are needed to provide tailored counseling and education to MMT attendants, to provide family and community support, appropriate methadone dose at first delivery, and to better coordinate with local police department.