ABSTRACT
Parkinson's disease (PD) is the most common neurodegenerative movement disease. It is featured by abnormal alpha-synuclein (α-syn) aggregation in dopaminergic neurons in the substantia nigra. Macroautophagy (autophagy) is an evolutionarily conserved cellular process for degradation of cellular contents, including protein aggregates, to maintain cellular homeostasis. Corynoxine B (Cory B), a natural alkaloid isolated from Uncaria rhynchophylla (Miq.) Jacks., has been reported to promote the clearance of α-syn in cell models by inducing autophagy. However, the molecular mechanism by which Cory B induces autophagy is not known, and the α-syn-lowering activity of Cory B has not been verified in animal models. Here, we report that Cory B enhanced the activity of Beclin 1/VPS34 complex and increased autophagy by promoting the interaction between Beclin 1 and HMGB1/2. Depletion of HMGB1/2 impaired Cory B-induced autophagy. We showed for the first time that, similar to HMGB1, HMGB2 is also required for autophagy and depletion of HMGB2 decreased autophagy levels and phosphatidylinositol 3-kinase III activity both under basal and stimulated conditions. By applying cellular thermal shift assay, surface plasmon resonance, and molecular docking, we confirmed that Cory B directly binds to HMGB1/2 near the C106 site. Furthermore, in vivo studies with a wild-type α-syn transgenic drosophila model of PD and an A53T α-syn transgenic mouse model of PD, Cory B enhanced autophagy, promoted α-syn clearance and improved behavioral abnormalities. Taken together, the results of this study reveal that Cory B enhances phosphatidylinositol 3-kinase III activity/autophagy by binding to HMGB1/2 and that this enhancement is neuroprotective against PD.
ABSTRACT
Objective To assess the effect of radiofrequency ablation ( RFA) combined with transcatheter hepatic arterial chemoemboli-zation ( TACE) and radiofrequency ablation alone for the treatment of early hepatocellular carcinoma ( HCC) with liver cirrhosis. Methods The data of all the patients that were given RFA+TACE (n=51) and RFA (n=53) treatments in our hospital from January 2008 to De-cember 2013 were analyzed. The demographic data,process of operation,postoperative complications,postoperative recovery and follow-up of the patients in two groups were carefully compared. Results The average follow-up time was (37. 6 ± 20. 7)months,38 cases were dead and 76 cases were survival. The overall survival rates of 1 years,3 years,5 years after operation were respectively 96. 5%,78. 7%,65. 9% in RFA+TACE group and 94. 3%,75. 6%,62. 3% in RFA group. Tumor-free survival rates of 1 years,3 years,5 years were 75. 4%,47. 3%, 32. 6% in RFA+TACE group,and 63. 1%,37. 2%,22. 4% in RFA group. Conclusion For patients with early hepatocellular carcinoma with liver cirrhosis,RFA combined with TACE have higher tumor free survival rate than RFA alone in the treatment of early hepatocellular carcinoma,but no difference in overall survival rate. The results still need to be validated by prospectively randomized controlled trials.
ABSTRACT
Objective:To construct the fingerprinting and analyze the genetic relationship in Gastrodia elata Bl.Methods:Inter-simple sequence repeat(ISSR) markers were used to investigate 23 populations of wild and cultivated Gastrodia elata Bl.in Guizhou Province.4 effective primers which were screened from 24 ISSR primers detected 32 loci in 23 samples,29 loci were polymorphic,amounting to 90.63% of the total loci..The average number of bands was 8 and the percentage of polymorphic loci(PPB)was from 80% to 100%.UPGMA dendrogram was analyzed by NTSYSpc,ver.2.2.Results:Similarity coefficients of the 23 populations were from 0.13 to 1.00.Individuals of the same population did not strictly cluster together and the genetic diversity of individuals in different populations was considerably high.Conclusion:Geographical distribution,variant growing conditions and artificial selection were significant factors for the rich genetic polymorphism of Gastrodia elata Bl.