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
;
Autophagy
;
Humans
;
Parkinson Disease
;
physiopathology
;
Protein Kinases
;
metabolism
;
Ubiquitin-Protein Ligases
;
metabolism
;
alpha-Synuclein
;
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.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 .
7.Development of Clinical Use of Biological Agents on Juvenile Idiopathic Arthritis
yu-bo, CAI ; wen-ming, ZHANG ; lan-fang, CAO
Journal of Applied Clinical Pediatrics 2004;0(09):-
Juvenile idiopathic arthritis(JIA)is the most common rheumatology disease in childhood period with poor prognosis.The biological agents are newly developed drugs with features of clear therapeutic targets and fast effects.But its use in JIA is still limited,so this article focuses on the clinical use experience,timming and sideffects of the biological agents on JIA.
8.Clinical research on intravitreal injection of triamcinolone acetonide for treating macular edema caused by pre - retinal membrane of the macular
Gui-Lan, ZHANG ; Bo-Chao, SUN ; Ming-Jie, HUANG
International Eye Science 2014;(6):1151-1153
AIM: To evaluate the efficacy and complications of intravitreal injection of triamcinolone acetonide ( TA ) for the treatment of macular edema caused by pre-retinal membrane of the macular.
METHODS: Totally 23 patients ( 24 eyes ) with macular edema caused by pre-retinal membrane of the macular were treated withintravitreal injection of 4mg TA. Best-corrected visual acuity ( BCVA ) , intraocular pressure ( IOP ) , slit - lamp examination, fundus fluorescein angiography ( FFA ) and optical coherence tomography (OCT) were performed before and after treatment. The SPSS 12. 0 software was used for statistical analysis.
RESULTS: After 10, 30, 90d of treatment of TA, as compared with before treatment, visual acuity improved significantly ( P<0. 05 ), and central macular thickness (CMT) was significantly thinner (P<0. 01). The average central macular thickness decreased from 522 ± 126μm before treatment to 264±115μm, 245±128μm, 286±131μm at 10, 30, 90d after treatment. Macular edema reduced. IOP increased in 7 eyes ( 29%) , one cataract case, no other complications associated with vitreous injection.
CONCLUSION: Intravitreal injection of TA in the treatment of macular edema caused by pre - retinal membrane of the macular is simple, safe and easy to operate. It can quickly reduce macular edema, and improve the visual acuity in the short term. Part of patients may recur after injection in the first half of the year.
9.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.
10.Transplanted hepatocytes and collagen hydrogel units subcutaneously establish engineered hepatic tissue
Zexue LI ; Lan ZHANG ; Wentao LIANG ; Kai LIANG ; Bo WEI
Chinese Journal of Tissue Engineering Research 2015;(43):6935-6939
BACKGROUND:Colagen hydrogel provides good matrix support for hepatocyte growth and tissue reconstruction, and the colagen-based engineered tissue is easy to merge the growth and form integrated tissue. OBJECTIVE:To improve the thickness of engineered hepatic tissue by dissociating hepatocytes/colagen hydrogel composite into smal hepatic units that accumulate in the subcutaneous cavity. METHODS:Freshly isolated hepatocytes from rats were mixed with colagen hydrogel to establish hepatocytes/colagen hydrogel composite. The hepatocytes/colagen hydrogel composite was dissociated into smal hepatic units after being cured. The undissociated hepatocytes/colagen hydrogel composite was taken as a control. Six Spraque-Dawley rats were enroled. Three of them were subjected to a two-thirds partial hepatectomy to induce liver regeneration. Dissociated and undissociated hepatocytes/colagen hydrogel composites were implanted into the bilateral inguinal subcutaneous cavity. Dissociated and undissociated hepatocytes/colagen hydrogel composites were implanted into the bilateral inguinal subcutaneous cavity of the other three rats. At the 7th day after transplantation, engineered hepatic tissue formation was evaluated using hematoxylin-eosin staining, immunohistochemical staining and India ink perfusion methods. RESULTS AND CONCLUSION:The grafts in these two groups al formed vascular engineered hepatic tissue in the subcutaneous cavity, but after the smal hepatic units merged, a large piece of vascular engineered hepatic tissue formed. The hepatic tissue thickness was up to 4 mm. The whole piece of implanted liver grafts only formed smal pieces of hepatic tissues, with only several layers of cels. Immunohistochemistry staining confirmed that the hepatocytes in vascular engineered hepatic tissue had the characteristics and functions of natural hepatocytes. Partial hepatectomy experiment showed that engineered hepatic tissue had the ability to respond to regenerative stimulus of partial hepatectomy. These results show that dissociating the hepatocytes/colagen hydrogel grafts into smal units that accumlate in the subcutaneous cavity can increase the thickness of the engineered hepatic tissue.