ABSTRACT
Alzheimer’s disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7 ,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. T o expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/ apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.
ABSTRACT
Objective To explore the role of mindfullness in the negative life events,depression,and poor sleep quality.Methods Using five facet mindfullness questionnaire(FFMQ),adolescents self-rating life events checklist (ASLEC),self-rating depression scale (SDS) and Pittsburgh sleep quality index (PSQI) to investigate 2 792 freshmen in a medical university in Guangzhou.Results The FFMQ score (126.02±12.14) was negatively correlated with ASLEC score(23.93±19.81),SDS score(35.89±7.31) and PSQI score (3.45±2.13) (r=-0.17,r=-0.44,r=-0.26,P＜0.01).The boys in the aspects of " mindfullnessinaction" scored significantly higher than that of girls (21.20 ± 3.36,20.52±2.88,P＜0.01).The girls scored significantly higher than boys in the PSQI,SDS (3.58±2.15,3.21 ±2.08,P＜0.05;36.22±7.26,35.27±7.35,P＜0.01).Mindfullness and sleep quality showed a chain-mediated effect between negative life events and depression,and the model fitting was good (RMSEA =0.048,CFI =0.962,TLI =0.943).The total mediating effect size was 61.41％.The mediating path through mindfullness,with the effect size of 16.71％,and the chain-mediating effect was 8.94％.Conclusion The higher the level of mindfullness,the lower the individual's depression score and the better the quality of sleep.Mindfullness and the sleep quality play a role of chain-mediating effect between negative life events and depression.
ABSTRACT
Objective To explore the role of mindfullness in the negative life events,depression,and poor sleep quality.Methods Using five facet mindfullness questionnaire(FFMQ),adolescents self-rating life events checklist (ASLEC),self-rating depression scale (SDS) and Pittsburgh sleep quality index (PSQI) to investigate 2 792 freshmen in a medical university in Guangzhou.Results The FFMQ score (126.02±12.14) was negatively correlated with ASLEC score(23.93±19.81),SDS score(35.89±7.31) and PSQI score (3.45±2.13) (r=-0.17,r=-0.44,r=-0.26,P＜0.01).The boys in the aspects of " mindfullnessinaction" scored significantly higher than that of girls (21.20 ± 3.36,20.52±2.88,P＜0.01).The girls scored significantly higher than boys in the PSQI,SDS (3.58±2.15,3.21 ±2.08,P＜0.05;36.22±7.26,35.27±7.35,P＜0.01).Mindfullness and sleep quality showed a chain-mediated effect between negative life events and depression,and the model fitting was good (RMSEA =0.048,CFI =0.962,TLI =0.943).The total mediating effect size was 61.41％.The mediating path through mindfullness,with the effect size of 16.71％,and the chain-mediating effect was 8.94％.Conclusion The higher the level of mindfullness,the lower the individual's depression score and the better the quality of sleep.Mindfullness and the sleep quality play a role of chain-mediating effect between negative life events and depression.
ABSTRACT
Reversible protein phosphorylation regulates multiple biochemical events. Mycobacterium tuberculosis phosphatases play important roles in regulating the pathogen physiology and interference of host signaling. They are also involved in the evasion of host immune response and blockage of the phagosome-lysosome fusion. Selective inhibition of phosphatase represents an ideal new avenue of anti-tuberculosis drug design. In this paper, we update the progresses about the regulation network of Mycobacterium tuberculosis phosphatases including MptpA, MptpB, MstP, SapM and their inhibitors. These serve as the basis for further antituberculosis drug target.