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.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
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 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.
6.Case-control study on manipulation following arthroscopic capsular release for the treatment of frozen shoulder.
Yong HE ; Lian-Bo XIAO ; Nian-Hong WANG ; Gui-Lin OUYANG
China Journal of Orthopaedics and Traumatology 2014;27(4):299-302
OBJECTIVETo compare therapeutic effects between the normal rehabilitation and combined with manipulative method after arthroscopic capsular release for the treatment of severe frozen shoulder, and to evaluate the application value of manipulationp.
METHODSFrom March 2007 to July 2010,arthroscopic capsular release was performed in 48 cases (48 shoulders, 23 left side, 25 right side). All the patients were divided into two groups: control group (11 males and 15 females) and manipulation group (9 males and 13 females). The patients in the control group were treated with conventional rehabilitation procedure, and the patients in the manipulation group were treated with additional manipulation procedure. From the 2nd day after operation, the manipulation was performed for 20 minutes every time, twice daily, and it continued for 10 days. All the cases were followed up and the scale of American Shoulder and Elbow Surgeons Standardized Assessment Form (ASES self-report section) and the range of motion (ROM) were recorded.
RESULTSThe mean follow-up period was (12.54 +/- 5.78) months (ranging from 4 to 25 months). Both ASES scores and ROM in the manipulation group were better than those in the control group at the 1st month after operation, and the difference between the ASES scores and flexion of the shoulder were significant. However, there was no significan difference at the latest follow-up.
CONCLUSIONCompared with the conventional rehabilitative procedure, manipulation following arthroscopic capsular release could promote the process of joint rehabilitation and help the patient back to normal life earlier, but there is no evidence of long term advantage.
Arthroscopy ; Bursitis ; physiopathology ; surgery ; therapy ; Case-Control Studies ; Combined Modality Therapy ; Female ; Humans ; Joint Capsule Release ; Male ; Middle Aged ; Musculoskeletal Manipulations ; Range of Motion, Articular ; Treatment Outcome
7.Expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse
Bo LI ; Qingfu ZHANG ; Xueyan LIN ; Lili CHEN ; Ling OUYANG ; Shulan ZHANG
Chinese Journal of Obstetrics and Gynecology 2009;44(7):514-517
Objective To investigate the expression and significance of elastin and fibulin-5 in anterior vaginal tissue of women with pelvic organ prolapse (POP). Methods Between November 2006 and June 2008, 68 patients with POP underwent surgical treatment in Shengjing Hospital of China Medical University were enrolled in this study, who were classified into 10 patients with grade Ⅰ , 21 patients with grade Ⅱ , 25 patients with grade Ⅲ and 12 patients with grade Ⅳ in accordance with pelvic organ prolapse quantitation (POP-Q). Meanwhile, 18 cases with early cervical cancer at stage of Ⅰ b were treated by total hysterectomy and bilateral salpingo-oophorectomy, their anterior vaginal tissues were selected as controls. Immunohistochemical staining was performed to detect the expression of elastin and fibulin-5. Results (1 ) Elastin and fibulin-5 were mainly expressed at extracellular matrix(ECM). (2)The positive rate of fibulin-5 expression in anterior vaginal wall were 5% (2/37 ) in grade Ⅲ/Ⅳ and 26% (8/31 ) in grade Ⅰ/Ⅱ POP patients, which reached statistical difference (P = 0. 035). However, no statistical different expression was found between postmenopausal (13%, 8/60) and non-menopausal patients (2/8), vaginal delivery ≤ 2 (19%, 5/27 ) and > 2 patients (12%, 5/41, P > 0. 05 ). (3 ) The positive rate of elastin expression in anterior vaginal wall in POP group was 31% (21/68), which was significantly lower than 72% (13/18) of control group (P = 0. 002). Among POP group, 19% (7/37) of elastin expression in grade Ⅲ/Ⅳ POP was significantly lower than 45% (14/31 ) in grade Ⅰ/Ⅱ of POP patients. However, no statistical difference was found between postmenopausal (30%, 18/60 ) and non-menopausal patients (3/8 ), vaginal delivery ≤ 2 (26%, 7/27) and >2 patients(34%, 14/41, P>0. 05). (4)In POP group, both positive expression of fibulin-5 and elastin of anterior vaginal wall was in 6 cases, both negative expression of fibulin-5 and elastin was in 43 cases. It was illustrated that elastin and fibulin-5 had an positive relationship (P = 0. 031 ). Conclusion The decreased expression of elastin and fibolin-5 was correlated with degree of POP, which indicated that elastin and fibulin-5 may play a role in the pathogenesis of POP.
8.Early fracture external fixation in treatment of severe traumatic brain injury combined with extremity fracture
Lijun HOU ; Hai JIN ; Chengguang PAN ; Yueping OUYANG ; Yicheng LU ; Bo LI ; Hui WANG
Chinese Journal of Trauma 2009;25(3):196-198
Objective To discuss clinical effects of early (<48 hours after injury) fraeture exter-nal fixation in treatment of severe traumatic brain injury (TBI) combined with extremity fracture. Meth-ods The study involved patients with no statistical difference in aspects of age, sex, GCS, fracture ,distri-bution and general condition. According to different treatment methods at early stage (<48 hours), the pa-tients with TBI were divided into Group A (early extremity fracture external fixation) and Group B (early extremity fracture traction or cast immobilization). A comparative observation was done on complications in-cluding bedsore, pneumonia and deep venous thrombosis and on duration in ICU, hospitalization, time for fracture healing and mortality in two groups. Results Incidence rate of bedsore, pneumonia, deep ve-nous thrombosis and mortality in Group A was lower than that in Group B (P<0.05), and Group A had shorter time for ICU, hospitalization and fracture healing (P < 0.05). Conclusion For patients with se-vere TBI combined with extremity fracture, early fracture external fixation is more effective to reduce com-plications, shorten the recovery time and reduce mortality, compared with conservative methods.
9.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.
10.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.