RESUMEN
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.
RESUMEN
Objective To investigate the effect of applying scenario simulation practice in the professional ICU nursing students' emergency and intensive care intensified skill training before internship.Methods Totally 120 professional ICU nursing students from grade 2010 and 2011 were enrolled.Control group included 60 students from grade 2010 and experimental group included 60 students from grade 2011.Studnets in control group accepted standardized routine training while those in experimental group accepted scenario simulation practice.All students participated in skill examination after training.Two questionnaires were designed to survey nursing students and clinical teachers respectively at one month after internship.One questionnaire was to evaluate students' attitude to the training and the other one was to survey clinical teachers' evaluation of students' abilities.T test was used to statistically analyze skill examination performance and questionnaire scores between two groups.Results Skill examination performance of experimental group was better than that of control group (P＜0.01).Effects of intensified training were better in experimental group than in control group (P＜0.05,P＜0.01) including the aspects of combining theory and practice,shortening internship role transition time,enhancing selfconfidence of clinical practice and relieving tension anxiety before practice,etc.Clinical teachers thought that the experimental group's analysis ability,strain capacity,operation ability,communication ability,team cooperation ability and actively acquiring knowledge ability were stronger than those of control group (P ＜ 0.01).Conclusions Scenario simulation practice is helpful to improve operation ability and comprehensive ability.Nursing students can adapt to the clinical work better.Findings may be beneficial to the improve-ment of teachers' professional level.