1.Effect of dimethyl fumarate on Aβ-induced oxidative stress in rat astrocytes
Beibei CAO ; Yan CHENG ; Nan ZHANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2017;19(5):532-535
Objective To study the effect of dimethyl fumarate (DMF) on Aβ-induced oxidative stress by regulating NF-E2-related factor 2 (Nrf2) expression and its mechanism.Methods Rat astrocytes were divided into Aβ group,DMF group,Nrf2 group and Nrf2 +DMF group.Expressions of Nrf2,Nqo1,Ho-1,Keap1 mRNA and HDAC were detected by RT-PCR and Western blot respectively.Results The expression levels of Nrf2,Nqo1 and HO-1 mRNA were significantly lower in Nrf2 group and Nrf2+DMF group than in Aβ group and DMF group (P<0.05) and were significantly higher in DMF group than in Aβ group (P<0.05) while the expression level of Keap1 mRNA was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (P<0.05).The expression level of HDAC was significantly lower in DMF group and Nrf2+DMF group than in Aβ group and Nrf2 group (6.41±0.43 vs 9.01±1.54,P<0.05;6.72±0.30 vs 8.76± 0.74,P<0.05).Conclusion DMF increases the Nrf2 expression by inhibiting the HDAC expression,thus reducing Aβ-induced oxidative stress in rat astrocytes.
2.Characterization of human anti-BAFF scFv-Fc that inhibits the activity of BAFF in vivo.
Meng CAO ; Peng CAO ; Shuangquan ZHANG ; Ying CHENG ; Huaijiang YAN
Acta Pharmaceutica Sinica 2012;47(10):1336-40
To investigate the effects of human anti-BAFF scFv-Fc against the hsBAFF, ICR mice were randomly divided into six groups: control, hsBAFF (1 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + Ab (1 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + Ab (2 mg x kg(-1)), hsBAFF (1 mg x kg(-1)) + human IgG (1 mg x kg(-1)) and hsBAFF (1 mg x kg(-1)) + human IgG (2 mg x kg(-1)) groups. The effects of scFv-Fc administration on the proliferation of B lymphocytes were evaluated using an MTT assay. The titres of antibody in the serum and B lymphocytes differentiation were assessed by ELISA and flow cytometry, respectively. The results showed that administration of scFv-Fc to mice injected with hsBAFF significantly prevented human BAFF-induced increases in splenic B cell numbers and serum immunoglobulin levels. Furthermore, this fully human antibody would avoid inducing the human anti-mouse antibody (HAMA) response when used in humans. These findings suggest that the compact antibody may be useful in therapeutic or diagnostic application of the BAFF-associated autoimmune diseases in human.
3.Experimental study on the in vivo biocompatibility of polypropyle ne mesh scaffolds with adipose-derived stem cells in rabbits
Hui CHENG ; Bei ZHANG ; Jie CHENG ; Yijuan CAO
Journal of Medical Postgraduates 2015;(7):692-695
Objective How to avoid the rejection of the synthetic patch and human tissue has become an urgent problem to be solved.The article investigated thein vivobiocompatibility of polypropylene mesh scaffold with adipose -derived stem cells(ADSCs) in rabbits. Methods Rabbit ADSC suspension were prepared.ADSCs were seeded onto polypropylene mesh scaffolds after passage and amplification and cultured invitro for 1 week .The polypropylene mesh and ADSC fixed polypropylene mesh were implanted respec-tively into the surface of rectus abdominis in rabbits.4 weeks later, adhesion and erosion of the meshes were evaluated, HE staining was used in histological observation and RT-PCR was applied to detect the dynamic changes of VEGF mRNA level.ADSCs were isola-ted from rabbit subcutaneous adipose tissue after collagenase digesting, filtrating and centrifuging. Results The results of flow cy-tometry showed that the expressions of CD44, CD73, CD90, CD45, CD14 and CD34 were 98.54%, 95.32%, 98.49%, 1.21%, 3.01%, 2.14%, respectively.Polypropylene mesh, ADSC-fixed polypropylene mesh had different degrees of corrosion and adhesion , but polypropylene mesh showed denser adhesion.In comparison with polypropylene,ADSC fixed polypropylene meshes induced a mil -der chronic inflammation response,with lower scores for inflammation (1.1 ±0.2 vs 0.6 ±0.1, P=0.001), higher scores for neovas-cularization (17.0 ±0.0 vs 2.6 ±0.3, P=0.000) and fibroblastic proliferation(0.9 ±0.1 vs 2.2 ±0.2, P=0.001).Relative a-mounts of VEGF mRNA of were significantly lower for ADSC-fixed polypropylene compared with the remaining polypropylene meshes (t=94.6, P<0.05). Conclusi on Polypropylene mesh scaffold with ADSCs exhibits excellent cellular compatibility and have a bright future in clinical practice.
4.Early minimally invasive treatment for biliary acute pancreatitis
Quan ZHANG ; Shujie CHENG ; Aimin ZHANG ; Shanfeng LI ; Liye CAO
Chinese Journal of General Surgery 2015;30(1):15-18
Objective To investigate the clinical effects of two minimally invasive surgical treatments for billary acute pancretitis.Method In this study,63 patients with billary acute pancretitis were prospectively divided into two groups.Patients in group A received laparoscopic cholecystectomy (LC) and laparoscopic transcyctic common bile duct exploration (LTCBDE) within 72 hours of onset,group B underwent endoscopic nasobiliary drainage (ENBD).The two groups were evaluated by blood amylase and urine amylase,alanine aminotransferase,aspartate aminotransferase on postoperative day 1,3,5,local complication and the recurrence rate within 6 months.Result Blood amylase was lower in group A than that in group B (P =0.04) on postoperative day 1.There were no significant differences in amylase,aminotransferase of two groups on postoperative day 3,5 (all P > 0.05).The incidences of local complications and pancreatic necrosis infection were 2.7%,7.7% respectively(P =0.13) ; the incidences of pancreatic pseudocyst were 5.4%,7.7% (P =0.42) ; the recurrence rate within 6 months were 2.7% and 19.2% respectively(P =0.006).Conclusions The clinical curative effects of early LC and LTCBDE or ENBD on billary acute pancretitis showed no significant differences,but the recurrence rate of acute pancretitis within 6 months revealed that early LC and LTCBDE may be more effective.
5.Prevalence of 15 skin diseases in adolescents from Liangshan prefecture in Sichuan Province
Renli WANG ; Lisheng CAO ; Cheng ZHOU ; Jianzhong ZHANG
Chinese Journal of Dermatology 2012;45(4):270-272
ObjectiveTo investigate the prevalence of 15 skin diseases in adolescents from Liangshan prefecture in Sichuan Province.Methods A stratified cluster random sampling method was used to select subjects.Adolescents from 2 urban and 3 rural middle schools were investigated,who were required to fulfill self-report questionnaires and received physical examinations by doctors.ResultsA total of 7747 adolescents aged from 12 to 20(15.86 ± 1.86) years were included in the investigation,and skin diseases were present in 6379 adolescents,with a total incidence of 82.34%.In average,each subject suffered from 1.3372 ± 0.96861 skin diseases.Of the adolescents,4698(60.64%) had acne,2219(28.64%) freckle,966(12.47%) lichen pilaris,792(10.22%) eczema or dermatitis,511(6.60%) urticaria,195(2.52%) papular urticaria,37 (0.48%) vitiligo,55 (0.71%) psoriasis,166 (2.14%) verruca vulgaris,168 (2.17%) flat wart,317 (4.09%) tinea manus and pedis,142 (1.83%) tinea corporis,62 (0.80%) chloasma,26 (0.34%) nevus flammeus,15 (0.19%) nevus of ota.Male adolescents showed a higher incidence of acne(63.91% vs.58.50%),but a lower incidence of eczema,lichen pilaris,freckle,chloasma and psoriasis compared with female adolescents.The incidence of acne,vitiligo,psoriasis and melasma were higher,while that of freckele was lower(25.93% vs.29.58% ) in Yi adolescents than in Han adolescents.Increased incidence of acne and papular urticaria and decreased prevalence of urticaria,freckle,melasma and lichen pilaris were observed in urban adolescents compared with rural adolescents.ConclusionsThe prevalence of skin diseases is high in adolescents from Liangshan prefecture.Of these 15 skin diseases,acne,freckle,lichen pilaris,eczema and urticaria are the 5 most common diseases in the area.Differences exist in the incidence of skin diseases between male and female,Han and Yi,urban and rural,adolescents.
6.Effects of the dystrophin hydrophobic regions in the pathogenesis of Duchenne muscular dystrophy A three-dimensional reconstruction verification
Yingyin LIANG ; Jiqing CAO ; Juan YANG ; Cheng ZHANG
Chinese Journal of Tissue Engineering Research 2013;(50):8703-8711
BACKGROUND:Duchenne muscular dystrophy is recognized as a fatal X-linked recessive inheritance. It is caused by the dystrophin gene mutation, resulting in the deficiency of dystrophin and consequent degeneration and necrosis of muscle fibers gradual y. Becker muscular dystrophy is also caused by the mutation of the same gene, but presented with less severe clinical symptoms compared with Duchenne muscular dystrophy. Frameshift mutation destroys the reading frames, and thus the translation cannot proceed smoothly to transcript functional proteins. In-frame mutation cannot destroy the reading frames and hence the translation can proceed smoothly. But in-frame mutation involves the whole hydrophobic regions. The three-dimensional structure of these regions and their functionality are not interpreted clearly. The effects of these regions on disease development need to be clarified in detail from the point of structure and function.
OBJECTIVE:By analyzing Kate and Dolittle scale mean hydrophobicity profile, to investigate the dystrophin hydrophobic regions using Swiss-model so as to provide the supplement explanation on the reading frame rule.
METHODS:Form 2002 to 2013, 1 038 cases diagnosed as Duchenne muscular dystrophy or Becker muscular dystrophy were col ected in the First Hospital of Sun Yat-sen University in China and Leiden DMD information database was searched with deletion of codon mutation information available. The correlation between clinical types and genotypes was analyzed upon resources col ected above. The mean hydrophobicity profile of dystrophin was analyzed by Bioedit as wel as the reconstruction of hydrophobic domains using Swiss-model. Thus, the important functional domain of dystrophin was confirmed by analysis and the correlation between clinical types and genotypes.
RESULTS AND CONCLUSION:Four hydrophobic regions were confirmed:Calponin homology domain CH2 on actin-binding domain, repeat 16 domain, Hinge Ⅲ domain and EF Hand domain. Duchenne muscular dystrophy was developed as a result of the destruction of the 1st, 2nd and 4th hydrophobic regions which were the conjunction of dystrophin and associated protein in dystrophin-glycoprotein complex. When the 3rd hydrophobic was deleted, the repeat domain located on central rob domain remained its continuity so that the clinical symptoms were less severe. These findings indicate that the dystrophin hydrophobic regions act as an important role on the pathogenesis of Duchenne muscular dystrophy.
7.The Detection of Triple Expression of Tuberculosis DNA Vaccines on the Cell Level
Ai-Li MA ; Yi-Cheng CAO ; Zhen-Wu ZHANG ;
China Biotechnology 2006;0(07):-
Objective:A novel tuberculosis DNA vaccine integrating siRNA,fusional antigen and hIL-12 triple expression units was constructed in our laboratory.Methods:To evaluate the independent expression of the three expression units,two eukaryotic expression plasmid pVAX1-siRNA-PVAE[EGFP]-hIL12 with TB fusional gene Ag85B-ESAT6(PVAE) and enhanced green fluorescent protein(EGFP),and pVAX1-siEGFP-PVAE[EGFP]-hIL12 with siRNA coding sequence targeting EGFP instead of Mcl-1L were constructed.Then two plasmids were used to transfer human embryonic kidney 293 cells.Based on EGFP report gene,it was demonstrated that siRNA expression unit and fusional antigen gene were independently expressed.Results:The hIL12 expression at 48h and 72h post transfection were also detected by ELISA analysis up to 1571.63pg/ml and 2392.25pg/ml respectively in the cell culture fluid.Conclusion:The results demonstrated that the novel DNA vaccine with siRNA,TB fusional antigen and hIL12 three expression units in the same plasmid frame is successfully constructed and independently expressed in eukaryotic cells.It laid a foundation for further animal model study on anti-tuberculosis effects of this novel DNA vaccine.
8.Atorvastatin Inhibits High Glucose-induced Oxidative Stress Injury in Human Umbilical Vein Endothelial Cells by SIRT1/NADPH Oxidase Pathway
Na CAO ; Liqi GE ; Mingyue CHENG ; Zhuoqi ZHANG ; Zhirong WANG
Chinese Circulation Journal 2014;(12):1000-1004
Objective: To explore the effect of atorvastatin (Atv) on high glucose-induced oxidative stress injury in human umbilical vein endothelial cells (HUVECs) by SIRT1/NADPH oxidase pathway with the possible mechanisms.
Methods: HUVECs were cultured in low glucose medium and then divided into 6 experimental groups:①Normal group,②Osmotic pressure control group,③High glucose (HG) group,④HG+Atv (0.1, 1.0, 10.0)μmol/L group,⑤HG+sirtinol (SIRT1 inhibitor) group,⑥HG+apocynin (NOX4 inhibitor) group, and HUVECs were further cultured for 24 hours. The cell proliferation was examined by CCK-8 kit, ROS level was detected by lfow cytometry method, protein expressions of SIRT1 and NOX4 were measured by Western blot analysis.
Results: ① Compared with Normal group, HG group had decreased HUVECs proliferation, Atv improved the HG inhibited proliferation in a does dependent manner. ② HG group had the higher level of ROS, increased NOX4 protein expression and decreased SIRT1 protein expression. ③ In HG condition, Atv up-regulated SIRT1 expression and down-regulated ROS and NOX4 expressions in a does dependent manner.④In HG condition, sirtinol decreased SIRT1 expression, increased NOX4 expression, and apocynin decreased NOX4 expression, while it had no inlfuence on SIRT1 expression.
Conclusion: Atorvastatin could resist HG-induced oxidative stress injury in HUVECs, which might be related to up-regulated SIRT1 expression, and SIRTI plays the role in NADPH oxidase at upstream.
9.Pharmacoeconomic Evaluation of Four Short-term Triple Therapeutic Schemes for Eradicating Hp
Huafeng CHENG ; Huiming CAO ; Qian CHEN ; Nansen ZHANG
China Pharmacy 1991;0(03):-
OBJECTIVE:Four different one-week triple therapeutic schemes to eradicate Helicobacter pylori were compared by pharmacoeconomic analysis to provide a scientific method for rational assignment of our limited medical fund.METHODS:According to literature reports,892 cases of duodenal ulcer and gastritis with Helicobacter pylori were selected.These patients were randomly divided into four groups which received different one-week triple therapeutic schemes:OMC(Omeprazole+Metronidazole+Clarithromycin),OFC(Omeprazole+Furazolidone+Clarithromycin),OFA(Omeprazole+Furazolidone+Amoxicillin)and BFC(Colloidal bismuth subcitrate+Furazolidone+Clarithromycin).The schemes were evaluated with pharmacoeconomic cost-effectiveness analysis.RESULTS:The cost-effectiveness ratios of OMC,OFC,OFA,BFC for gastritis or duodenal ulcer were 16.19/17.33,17.30/13.93,11.40/10.56,11.17/10.75 respectively.They changed to 16.36/17.51,17.49/14.08,8.15/7.55,11.66/11.20 by sensitivity analysis.CONCLUSION:OFA is the most effective and inexpensive one to era_dicate Hp.