1.Autophagy pathways and key drug targets in Parkinson's disease.
Liang OUYANG ; Lan ZHANG ; Bo LIU
Acta Pharmaceutica Sinica 2016;51(1):9-17
Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging. Great progresses have been made toward understanding the pathogenesis over the past decades. It seems that both genetic factors and environmental factors contribute to PD, while the precise pathogenesis still remains unknown. Recently, increasing evidence has suggested that autophagy dysregulation is closely related to PD. Dysregulation of the autophagic pathways has been observed in the brains of PD patients or in animal models of PD, and a number of PD-associated proteins, such as a-synuclein, Parkin and PINK1, were found to involve in autophagy, suggesting a link between autophagy and pathogenesis of PD. In this review, we summarized the role of PD-associated proteins in autophagy pathways. In addition, we described the efficacy of autophagy-modulating compounds in PD models and discussed promising strategies for PD therapy.
Animals
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Autophagy
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Humans
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Parkinson Disease
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physiopathology
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Protein Kinases
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metabolism
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Ubiquitin-Protein Ligases
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metabolism
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alpha-Synuclein
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metabolism
2.Autophagy pathways and key drug targets in Parkinson's disease.
Liang OUYANG ; Lan ZHANG ; Bo LIU
Acta Pharmaceutica Sinica 2016;51(1):9-17
Parkinson's disease (PD) is a common neurodegenerative disorder associated with aging. Great progresses have been made toward understanding the pathogenesis over the past decades. It seems that both genetic factors and environmental factors contribute to PD, while the precise pathogenesis still remains unknown. Recently, increasing evidence has suggested that autophagy dysregulation is closely related to PD. Dysregulation of the autophagic pathways has been observed in the brains of PD patients or in animal models of PD, and a number of PD-associated proteins, such as a-synuclein, Parkin and PINK1, were found to involve in autophagy, suggesting a link between autophagy and pathogenesis of PD. In this review, we summarized the role of PD-associated proteins in autophagy pathways. In addition, we described the efficacy of autophagy-modulating compounds in PD models and discussed promising strategies for PD therapy.
3.Synthesis and structure of the Salen-Mn compound
Chinese Journal of Rehabilitation Theory and Practice 2004;10(5):281-282
ObjectiveTo synthesize metal complex that exhibits superoxide dismutase (SOD)-like activity and determine its structure.MethodsThis chemical compound was synthesized by means of reflux in laboratory.Its structure was examined by infrared spectra (IR),nuclear magnetic resonance hydrogen spectra(H-NMR) and mass spectra (MS).The activity of the SOD was determine by xanthine oxidase (XOD).ResultsThe IR indicted that this complex showed a typical absorption band of -OH,C=N and benzene. The H-NMR reveals the existence of metal ion manganese (Mn3+ ,paramagnetic). The molecular weight was 365, which was obtained by EI-MS analysis. And this complex showed SOD-like activity.ConclusionA metal complex with low molecular weight and SOD-like activity has been synthesized.
4.Protective effects of the compound with low molecular weight of anti-free radical on brain injury in rats
Chinese Journal of Rehabilitation Theory and Practice 2004;10(7):406-407
Objective To study the protective effects of the compound with low molecular weight of anti free radical on brain ischemic and hypoxic injuries in rats.Methods The model of brain ischemic and hypoxic injuries in rats was established by unilateral carotid artery ligature just for 2 h. The compound was injected 30 minutes after the rats act on hypoxic state (10% O2+90%N2) for 1 h. Then the serum of rats was separated and the value of the superoxide dismutase (SOD) activity and malondiade (MDA) were determined, and the pathological changes were observed in brain tissue.Results Compared with rats in the model group, the compound decreased the concentrations of MDA in serum (P<0.05), and raised the level of SOD (P<0.05) significantly in therapy group. Otherwise, the pyramidal cells remained organized order, with only a few cells degenerated occasionally in rats of therapy group. Conclusion The compound has SOD like activity. It can scavenge the free radical and inhibit peroxidation of lipid, so it can prevent brain cells from the damage.
5.Plasma CGRP,Ang Ⅱ And ET in Healthy Offspring with Family History of Essential Hypertension
Lan LIU ; Bo ZHANG ; Junling GAO ; Yuhong ZHANG
Chinese Journal of Hypertension 2006;0(09):-
Objective To study CGRP,Ang Ⅱ and ET in healthy offsprings from different families history of essential hypertension. Methods Sixty healthy offsprings with or without a family history of essential hypertension were recruited and divided into two groups: (1) 30 from family with either one parent of essential hypertension; (2) 30 from family with both parents of essential hypertension; (3) control group,30 subjects from family with parents negative history.The levels of plasma CGRP,Ang Ⅱ and ET were determined by radioimmunoassay. Results The plasma levels of CGRP,Ang Ⅱ in one parent group were(28.3?10.4 pg/mL),(52.5?11.1 pg/mL) and (37.7?14.7 pg/mL),(58.4?9.1 pg/mL) in both parents group,which were increased significantly as compared with those in the control group (CGRP 19.9?10.5 pg/mL,Ang Ⅱ 45.3?9.9 pg/mL,P
6.A cross-lagged regression analysis between resilience, mental health and psychological stress of recruits during training
Yi MIAO ; Min LI ; Yong LAN ; Yupei ZHANG ; Bo CHEN
Chinese Journal of Behavioral Medicine and Brain Science 2012;21(1):59-62
ObjectiveTo explore the resilience and mental health of recruits during training,and to investigate mutual prediction of resilience between mental health and psychological stress to provide the scientific evidence for the mental health training and psychological selection of recruits.MethodsConnor-Davidson resilience questionnaire ( CD-RISC),symptom checklist ( SCL-90 ),psychological stress self-evaluation test ( PSET),satisfaction with life scale (SWLS),positive and negative affect scale (PANAS) were applied to 650 recruits in 2011 before starting training and after two months of training.Results ① Chinese recruits had good resilience,and the CD scores of pre-and post-test were (61.60 ± 14.36) and (61.41 ± 14.55 ) respectively.②Mental health (SCL-90) of two tests were good in recruits.③ Correlation analysis showed that the same premise of phase correlation,resilience (pre-test) could significantly predict mental health (post-test) ( β =0.070,P < 0.05 ),mental health ( pretest) could not predict resilience (post-test) (β =0.015,P > 0.05 ).Resilience (pre-test) could significantly predict psychological stress (post-test) ( β =0.075,P < 0.05 ),psychological stress (pre-test) could not predict resilience (post-test) (β =0.017,P > 0.05 ).④ Compared with high resilience group,low-resilience group of recruits had higher total score of SCL-90 and psychological stress and less positive emotion,more negative emotion and lower life satisfaction.ConclusionThe recruits training have good resilience.Resilience of recruits have predictive ability to mental health,psychological stress during training.
7.Research on the subchondral bone architecture and bone remodeling related genes change in the initial stage of osteoarthritis in rat
Guihua LAN ; Bo ZHANG ; Ping LIU ; Tujun WENG ; Manjing DENG
Chongqing Medicine 2016;45(16):2170-2172,2175
Objective To investigate the changes of microarchitecture and gene expression of subchondral bone in the initial stage of traumatic arthritis ,to explore the characteristics of subchondral bone remodeling and its role in the articular cartilage de‐generation .Methods The medial meniscal tear (MMT) was performed on the right knees of 13 SD rats to simulate the traumatic osteoarthritis ,while sham operation on the control group .Three weeks later ,all the rats were executed and dissected ,with proximal tibiae being kept and distributed into the two groups ,10 respectively .Micro‐computed tomography (micro‐CT) was adopted to re‐construct and analyze the subchondral bone .After being fixed by 4% paraformaldehyde ,all the samples were decalcified until six weeks passed ,followed by paraffin‐sectioning ,safranin O and fast green staining ,and examining and photographing under an ordina‐ry optical microscope .The RNA of another 3 SD rats′subchondral bone was extracted ,and a real‐time PCR test was carried out to illuminate the expression variation of bone‐formation marker genes (ALP ,RUNX2 ,and OCN) ,and bone‐resorption marker genes (TRAP ,CTSK and MMP9) ,between the two groups .Results Three weeks after MMT surgery ,subchondral bone disorders were observed among the experimental samples through micro‐CT scanning .There was lesser BV/TV ,Conn .D and Tb .Th(P<0 .05) and more Tb .Sp(P<0 .05) in the experimental group compared with the control group .In the pathological section ,arthritic degen‐eration was not spotted in both groups ,but trabeculae of the experimental group were found to be sparse .Compared with control group ,the level of mRNA expression of the bone‐formation marker genes of the experimental group was decreased(P<0 .05) ,while bone‐resorption related genes increased(P<0 .05) .Conclusion The model of initial traumatic osteoarthritis induced by MMT in rats′knees showed an active bone remodeling ,more bone absorbing than bone formation ,lowered bone volume ,and microarchitec‐ture changing of the subchondral bone .
8.The clinical observation and effect of HuaYu TongFu KaiQiaoFang on serum homocysteine in patients with acute cerebral infarction
Lan LI ; Li CHEN ; Yue HAN ; Bo LU ; Longhai ZHANG
Chinese Journal of Integrated Traditional and Western Medicine in Intensive and Critical Care 2013;(4):220-222
Objective To observe the clinical effect of HuaYu TongFu KaiQiaoFang on serum homocysteine (Hcy)in patients with acute cerebral infarction. Methods Sixty cases of acute cerebral infarction admitted into the comprehensive ward and intensive care unit(ICU)of the First Affiliated Hospital of Guiyang College of Traditional Chinese Medicine from December 2010 to January 2012 were randomly divided into two groups,each group including 30 cases. The control group was given conventional treatment,and based on the conventional therapy,the treatment group was additionally given HuaYu TongFu KaiQiaoFang(a traditional Chinese medicine decoction including the following ingredients:Safflower 10 g,Chishao 10 g,Chuanxiong 10 g,Notoginseng 10 g,Angelica Sinensis 10 g, Shichangpu 10 g,Polygalae 10 g,Glauber's salt 5 g,Rhubarb 6 g),one dose a day by oral or nasal administration for consecutive 14 days. Before and after treatment in the two groups,the serum Hcy level was detected by enzyme-linked immunosorbent assay(ELISA),and the clinical efficacy was assessed by Pearson or Spearman correlation analysis to observe the correlation between neurological deficit score(NDS)and Hcy levels. Results Before treatment, the difference of serum Hcy(μmol/L)and NDS levels between the two groups was not statistically significant(both P>0.05),while after treatment,the levels in the two groups were significantly decreased in comparison with those before treatment(P<0.05 or P<0.01),and the degree of descent in treatment group was more obvious compared with that in control group(Hcy:7.78±2.51 vs. 10.18±2.41,NDS:10.60±2.25 vs. 14.60±3.70,both P<0.05). After treatment,the total effective rate in the treatment group was significantly higher than that in the control group (90.0%vs. 76.7%,P<0.05). Before treatment,the NDS was positively correlated with Hcy(r=0.675,P<0.05). Conclusion HuaYu TongFu KaiQiaoFang can significantly reduce the level of serum Hcy and improve the nerve function,thus its clinical effect for treatment of acute cerebral infarction is remarkable.
9.Effect of acupuncture plus swallowing disorder therapeutic apparatus on deglutition disorder caused by early stroke
Bo LIU ; Fang ZHANG ; Yachuan LIU ; Shuang HAO ; Yun LAN
Chinese Journal of Primary Medicine and Pharmacy 2016;23(13):1986-1990
Objective To observe the effect of acupuncture plus thunder fire moxibustion plus deglutition training plus VitalStim electrical stimulation on patients with deglutition disorder of early stroke.Methods 80 patients with deglutition disorder of early stroke were randomly divided into treatment group and control group,40 cases in each group.The treatment group was treated with acupuncture plus thunder fire moxibustion plus deglutition training plus VitalStim electrical stimulation,while the control group was only treated with deglutition training.The therapeutic effects of all patients were assessed by using drinking experiment before therapy and twenty times after therapy. Results The total effective rate of the treatment group was 97.5%,which was significantly higher than 82.5% of the control group,the difference was statistically significant(χ2 =12.50,P <0.05).Watian integration of the two groups were decreased after treatment,the difference was significant(t =5.606,9.056,all P <0.05),which of the treatment group was significantly lower than the control group,the difference was statistically significant(t =3.044,P <0.05). The lung infection rate and malnutrition rates in the control group were 10.0% and 20.0%,which were significantly higher than those in the treatment group(2.5% and 5.0%),the differences were statistically significance(χ2 =4.80, 10.29,all P <0.05).Conclusion Acupuncture plus thunder fire moxibustion plus deglutition training plus VitalS-tim electrical stimulation are beneficial to the recovery of swallowing functions to early swallowing disorder in patients and could avoid the incidence of aspiration pneumonia and malnutrition.
10.Application of echocardiography in percutaneous left atrial appendage closure and for short-term follow-up
Lan ZHANG ; Qing ZHOU ; Hongning SONG ; Bo HU ; Ruiqiang GUO
Chinese Journal of Ultrasonography 2015;(8):652-656
Objective To explore the value of echocardiography in percutaneous left atrial appendage (LAA)closure for stroke prevention in patients with nonvalvular atrial fibrillation during procedure and for short-term follow-up.Methods Twenty patients were enrolled to undergo percutaneous LAA closure with the LAmbre device.Rheumatic valvular diseases were excluded by transthoracic echocardiography (TTE) and transesophageal echocardiography(TEE)before the closure procedure.TEE was performed during the procedure for the trans-septal puncture and the release of the closure device.Combined TEE with angiographic measurements,guidance for the optimal device size was provided.The closure effect and procedure-related complications were observed immediately by TEE and also evaluated by TTE at 1-day and 1-month follow-up.Results All patients underwent LAA occlusion successfully.TEE color Doppler evaluation have shown nine patients with complete closure immediately,one with a ≤ 1 mm residual LAA leak,and ten with a 1 -3 mm jet.There were no other complications during the procedure.One day after the closure,small pericardial effusions were observed for three patients while two of the three were free of the pericardial effusion at the 1-month follow-up.During the short-term follow-up,no damage was found at any anatomical structures near LAA due to the closure process,and there was no significant difference of cardiac function before and after the procedure.Conclusions With the guidance of TEE,the successful rate of percutaneous LAA closure procedure was preferable and the occurrence rate of compliance was acceptable. And TTE played an important role in patients'short-term follow-up.