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.
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.
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
3.The Guiding Thoughs of The Quality Assessment of Course Teaching in Military Medical University
Yejun RAO ; Ling OUYANG ; Yang BO ; Hong ZHOU
Chinese Journal of Medical Education Research 2006;0(11):-
The guiding thoughts and purpose of the curicular quality evaluation are expounded in this article: under the guide of Deng Xiaoping's theory adhering to the army and national political system and policy of education,adhering to Deng Xiaoping's"three faceto"educational view and methodology,we carry out the evaluation to promote the construction,to realize the purpose of course construction,teaching,learning,administration,competmon and finally to mlprove the curiculum teaching quality.
4.The study of hydrogen sulfide up-regulates the expression of ABCA1 and promotes the cholesterol efflux in foam cells
Guoshu LI ; Pingping HE ; Bo WANG ; Shouhong ZHOU ; Xinping OUYANG
Chongqing Medicine 2013;(30):3596-3598
Objective To investigate the effect of hydrogen sulfide (H2S) on the cholesterol efflux and ATP-binding cassette transporter A1 (ABCA1) expression in foam cells .Methods RAW 264 .7 macrophages were incubated with oxidized low density lipoprotein to induce foam cells .Foam cells were incubated with H2S donor sodium hydrosulfide .Cholesterol efflux from macropha-ges was tested by labed cholesterol .The cellular levels of free cholesterol (FC) ,cholesterol ester (CE) and total cholesterol (TC) were measured by high performance liquid chromatography assays .The mRNA and protein expressions of ABCA1 were detected by Real-time PCR and Western blot .Results Compared with the foam cells ,the rates of cholesterol efflux were significantly in-creased ,the levels of TC ,FC ,CE and CE/TC ratio were significantly decreased(P<0 .05) and expression of ABCA1 was signifi-cantly increased by treatment with H2S in dose-and time-dependent manner(P<0 .05) .Conclusion H2S up-regulates of expres-sion ABCA1 and promotes cholesterol efflux in RAW 264 .7 macrophage-derived foam cells .
5.The Study of the Growth Factors of Bifidobacterium sp.A04
Zhi-Jie JIANG ; Ping-Lan LI ; Qing-Bo OUYANG ;
Microbiology 1992;0(05):-
To study the stimulation effect to the growth of Bifidobac te rium sp. A04, 4 kinds of oligosaccharide, 8 kinds of Chinese traditional medi cine and 4 kinds of food raw materials were used. The results indicates that so ya bean oligosaccharide is the most effective (P
6.Methodology establishment of detection of Vibrio vulnificus by flow cytometry and aptamer
Dejing LIU ; Bo HU ; Dingfa PENG ; Shengqun OUYANG ; Lianghua WANG ; Binghua JIAO
Chinese Journal of Biochemical Pharmaceutics 2017;37(7):1-5
Objective Establish detection method to measure Vibrio vulnificus rapidly and accurately.MethodsUsing flow cytometry(FCM)and a 5'-FITC fluorescent labeled aptamer with high binding affinity to detect Vibrio vulnificus rapidly.Measure a series of concentrations of Vibrio vulnificus to identify the Limit of Blank, Lower Limit of Detection, Linearity Range, etc.ResultsCombined application of FCM and the aptamer can detect Vibrio vulnificus rapidly with the duration less than 1 hour and lower limit of detection as low as 29 CFU/mL.Conclusion The aptamer targeting Vibrio vulnificus is an excellent detective element, while FCM can realize accurate quantitative detection.The detection method has great application potential.
7.Relationship Between Mitochondrial DNA Related Factors and Traditional Chinese Medical Syndrome Types in Primary Osteoporosis Patients
Ying LI ; Hongxing HUANG ; Huoyan WU ; Zedian LI ; Jianfeng OUYANG ; Bo BAI
Journal of Guangzhou University of Traditional Chinese Medicine 2015;(4):656-660
Objective To investigate the biological characteristics of primary osteoporosis syndrome types from the perspective of mitochondrial DNA ( mtDNA) , thus to reveal the nature of osteoporosis and its traditional Chinese medical syndrome types. Methods A total of 210 osteoporosis women patients meeting the diagnostic criteria, inclusion criteria and exclusion criteria were collected from July of 2011 to October of 2013. The osteoporosis patients were differentiated into the syndrome types of yin deficiency of liver and kidney ( N=67) , yang deficiency of spleen and kidney ( N=70) and qi stagnation and blood stasis ( N=73) . And a total of 69 age-matched post-menopause non-osteoporosis patients were chosen as the control group, which were classified into the syndrome of harmony of Qi and blood. The peripheral blood was sampled for detecting mtDNA copy number with fluorescent quantitatitation PCR and for examining 8-hydroxy-2’-deoxyguanosine ( 8-OHdG) content by enzyme-linked immunosorbent assay (ELISA) . Statistical methods was used to analyze the correlation of bone mineral density (BMD) with mtDNA copy number and 8-OHdG content in different groups. Results The difference of mtDNA copy number was significant between the osteoporosis patients and non-osteoporosis patients (P<0.05), and was also significant among the three syndrome types of osteoporosis patients (P<0.05) . And 8-OHdG content showed the same features between the osteoporosis patients and non-osteoporosis patients (P<0.05) and among the three syndrome types of osteoporosis patients (P<0.05) . The correlation analysis results showed that mtDNA copy number was positively correlated with BMD, while 8-OHdG was negatively correlated with BMD in each group. Conclusion The mtDNA copy number and 8-OHdG content are correlated with the syndrome types of primary osteoporosis patients, and close correlation is shown between spleen-kidney yang deficiency and 8-OHdG, and between liver-kidney yin deficiency and mtDNA copy number.
8.The study on importance of three-dimensional radiotherapy for elderly patients with stage Ⅳ non small cell lung cancer
Bo ZHANG ; Bing LU ; Shengfa SU ; Yinxiang HU ; Weiwei OUYANG ; Huiqin LI ; Zhu MA ; Jinhua LONG
Chinese Journal of Radiation Oncology 2012;(6):504-507
Objective To evaluate the importance of three-dimensional radiotherapy for elderly patients of stage Ⅳ non-small cell lung cancer (NSCLC).Methods Comparing with treatment outcome of ≥65 years 67 patients and < 65 years 134 patients using concurrent chemotherapy and thoracic threedimensional radiotherapy during 2003 to 2010 years.Survival analysis was taken by Kaplan-Meier method.The multivariate prognosis was analyzed by Cox model.Results The follow-up was 97.8%.The percentage of ≥65 years and < 65 years patients accepted with concurrent 4-5 cycles chemotherapy were 30% and 55%,and with 42% and 49% patients with radiotherapy ≥63 Gy.The median survival time (MST) were 17 months and 14 months (x2 =0.76,P =0.384) for ≥65 years and < 65 years patients accepted with concurrent 4-5 cycles chemotherapy concurrent ≥63 Gy radiotherapy respectively.The MST and 1-,2-,3year overall survival rate were 17 months and 8 months,65% and 23%,30% and 13%,24% and 9%(x2 =7.90,P =0.005) for whole groups patients treated with chemotherapy concurrent ≥63 Gy and < 63 Gy radiotherapy.And the MST of patients ≥ 63 Gy was significantly longer than those with < 63 Gy either concurrent chemotherapy any cycles (x2 =9.54,P =0.023).The MST were 14 months and 8 months (x2 =1.82,P=0.178),17 months and 17 months (x2 =0.47,P=0.492) for ≥ 65 years and ≥ 63 Gy radiotherapy patients accepted with concurrent 4-5 cycles and 2-3 cycles chemotherapy concurrent respectively.Multivariate analysis showed local response (β =0.600,P =0.003) and numbers of tumor metastasis (β =0.670,P =0.040) were independent factors for survival.Conclusions For a part of elderly patients of stage Ⅳ NSCLC,concurrent chemotherapy and thoracic three-dimensional radiotherapy can prolong survival time with acceptable toxicity.Perhaps radiotherapy is more important.
9.A prospective study on concurrent chemotherapy and thoracic three-dimensional radiotherapy for stage Ⅳ non-small cell lung cancer (4)-The impact of response on survival
Bo ZHANG ; Bing LU ; Shengfa SU ; Weiwei OUYANG ; Yinxiang HU ; Gang WANG ; Jinhua LONG ; Huiqin LI
Chinese Journal of Radiation Oncology 2012;21(1):29-34
ObjectiveTo prospectively investigate the impact of short-time response on survival of concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC). Methods From Jan.2003 to Oct.2010,201 patients with pathologically or cytologically proven stage Ⅳ NSCLC were included.All patients received platinum-based chemotherapy.Of the 167 patients eligible for analysis,the median number of chemotherapy were 4 cycles.The median dose for planning target volume (PTV) of thoracic primary tumor was 63 Gy.Response was scored according to WHO criteria. Survival was calculated by Kaplan-Meier method and compared using the Logrank. Cox regression model were used to examine the effect of response on overall survival.ResultsThe follow-up rate of 201 patients was 97.5%.with 201,170 and 134 patients finished < 1,1 -2 and ≥3 years' follow-up.For the 167 patients eligible for analysis,the CR,PR,NC and PD rate of primary tumor was 5.4%,65.9%,21.0% and 7.7%,respectively.The effective group ( CR + PR) and ineffective group ( NC + PD) was 71.3% and 28.7%,respectively.The median survival time (MST) for patients with CR,PR,NC and PD was 22.6,13.4,8.8 and 4.8 months,respectively ( χ2 =44.79,P =0.000).The MST for effective and ineffective group was 13.9 and 7.6 months,respectively in the whole group ( χ2 =8.3 0,P =0.004 ),12.1months and 7.3 months in those treated with 2 - 3 cycles chemotherapy ( χ2 =7.71,P =0.007 ),and 13.9months and 7.9 months in those treated with 2 -5 cycles chemotherapy and radiation dose to PTV ≥36 Gy ( χ2 =4.00,P =0.045 ).No significant MST difference was detected between patients of effective group and ineffective group treated with 4 -5 cycles chemotherapy ( χ2 =0.67,P =0.413),or those treated with 4 -5 cycles of chemotherapy and radiation dose to primary lesion ≥36 Gy (χ2 =0.00,P =0.956).Multivariate analysis showed that 4-5 cycles of chemotherapy and CR and PR achieved in primary tumor (β =0.182,P=0.041 ) were independent favorable factors for survival. Conclusion CCTTRT can improve local control,and prolong the survival time for Stage Ⅳ NSCLC.
10.A prospective study on concurrent chemotherapy and thoracic three - dimensional radiotherapy for stage Ⅳ non - small cell lung cancer ( 2 ) — The impact of different metastasis organs on survival
Gang WANG ; Bing LU ; Shengfa SU ; Weiwei OUYANG ; Yinxiang HU ; Jinhua LONG ; Huiqin LI ; Bo ZHANG
Chinese Journal of Radiation Oncology 2011;20(6):473-477
Objective To prospectively evaluate the survival of different metastasis organs with concurrent chemotherapy and thoracic three-dimensional radiotherapy (CCTTRT) for stage Ⅳ non-small cell lung cancer (NSCLC).Methods Two hundred and one patients of stage Ⅳ NSCLC were enrolled from January,2003 to July,2010.Of the 182 patients eligible for analysis,The number of patients with single-organ metastasis or multiple-organ metastasis was 107 and 75,respectively.Patients were treated by platinum-based chemotherapy,the median number of cycle was 4.The median dose to planning target volume of primary tumor (DTPTv) was 63 Gy.Survival was calculated by Kaplan-Meier method and compared using the Logrank.Results The follow-up rate of 201 patients was 97.5%.with 201,170 and 134 patients finished < 1,1 -2 and ≥3 years'follow up.Of 182 patients,the 1-,2-,and 3-year overall survival (OS) rate and median survival time (MST) was 41.0%,17.0%,10.0% and 10.5 months,respectively ;with single-organ metastasis and multi-organ metastasis were 50%,20%,14% and 13 months and 29%,12%,0% and 8.5 months ( x2 =10.10,P =0.001 ),respectively; compared with multi-organ metastasis,the 1-,2-,and 3-year OS arte and MST of patients with bone,lung metastasis only was 58%,25%,16% and 14 months (x2 =10.42,P=0.001 ) and 49%,21%,21% and 11 months (x2 =6.39,P=0.011 ) respectively;patients with brain metastasis only did not show advantage of survival comparing with patients with multi-organ metastasis (49%,8%,0% and 12 months and 29%,12%,0% and 8 months,respectively;x2 =0.71,P =0.401 ) ;the 1-,2-,and 3-year OS rate and MST was 63%,23%,19% and 15 months and 42%,15%,0% and 10 months,respectively for patients with single-organ metastasis and multi-organ metastasis patients who accepted 4 - 5 cycles of chemotherapy ( x2 =6.47,P =0.011 ) ; for patients under the same metastasis and 4 - 5 cycles of chemotherapy,no matter whether single-organ or multiple-organ metastases,the 1 -,2-,3-year OS rate and MST of patients with enough radiotherapy on DTPTV ≥63 Gy were better than patients without enough radiotherapy ( DTPTV < 63 Gy ) ( 71%,25 %,25% and 16.8 months and 33%,17%,0% and 10.5 months,respectively;x2 =4.73,P =0.030 ;54%,21%,0% and 14.3 months and 29%,10%,0% and 7.6 months,respectively,x2 =8.16,P =0.004).The MST of liver metastases was 6 months,there was significantly difference when comparing with non liver matastasis ( x2 =17.21,P =0.000).Conclusions It is very important to treat stage Ⅳ NSCLC with CCTTRT,especially patients with single-organ metastasis.Liver metastases is a unfavorable prognostic factor.