1.Lipoprotein lipase Activatoor NO-1886
Chinese Pharmacological Bulletin 1987;0(03):-
NO-1886 increases LPL mRNA and LPL activity in adipose tiss ue, myocardium and skeletal muscle, resulting in an elevation of postheparin pl asma LPL activity and LPL mass in rats. NO-1886 also decreasess plasma TG con centration and causes a concomitant rise in plasma HDL-C, reduces plasma gluco se, improves insulin resistance and ?-cell dysfunction. Therefore, the LPL act ivator NO-1886 or other possible LPL activating agents are potentially benefici al for the treatment of hypertriglyceridemia, hypo-HDL cholesterolemia, and pro tection from atheroscleroosis and diabetes.
2.Influence of CTLA4Ig and CD40Ig gene local co-transfection on the survival of xenogenic renal allografts
Manbo CAI ; Jianjun LI ; Yanping WU ; Zhigang LUO
Chinese Journal of Organ Transplantation 2011;32(11):679-682
Objective To observe the efficacy of CTLA4Ig and CD40Ig gene local cotransfection on the survival of renal allografts.Methods The kidneys of guinea pig were transfected with PcDNA 3.1+-CTLA4Ig and/or PcDNA 3.1+ -CD40Ig gene by Lipo2000,and the transfected kidneys were transplanted to SD rats.The recipients were divided into group 1 (transfected with PcDNA 3.1 +,mock group),group 2 (transfected with PcDNA 3.1 + -CD40Ig,CD40Ig group),group 3 (transfected with PcDNA3.1+ -CTLA4Ig,CTLA4Ig group) and group 4 (co-transfected with PcDNA 3.1+-CD40Ig and CTLA4Ig,CTLA4Ig+ CD40Ig group).The effects of CTLA4Ig and CD40Ig transfection were determined by Western blotting.The serum creatinine (Scr) in the recipients,the pathological changes of the allografts and the survival of renal allografts were observed.Results Significantly prolonged allografts survival time was observed in group 2 (40.7 ± 10.9 days),group 3 (49.3 ± 9.5 days) and group 4 (75.7 ± 8.0 days) as compared with group 1 (6.8 ± 1.9days),especially allografts got the longest survival time in group 4 (75.7± 8.0 days).The serum creatinine level was reduced in group 4 at 30th day as compared with that in group 2 and group 3.The lymphocytes infiltrating rate in the grafts was lowest in group 4 after transplantation.Conclusion Local co-transfection of CTLA4Ig and CD40Ig genes can prolong the survival time of renal allografts significantly.
3.Effect of NO-1886 on the expression of glycogen synthase kinase 3β in the kidney of diabetic minipig model
Hongguang LI ; Yi LIU ; Xiuhong ZU ; Qinkai LI ; Manbo CAI ; Hongjie HOU ; Weidong YIN ; Zongbao WANG
Chinese Journal of Nephrology 2009;25(4):294-298
Objective To investigate the effects of lipoprotein lipase activator, NO-1886, on the mRNA and protein expression of glycogen synthase kinase-3β (GSK-3β) in the kidney of diet-induced diabetic minipigs. Methods Fifteen Guangxi Bama minipigs were randomized into three groups: C group (n=5, with the normal control diet), DM group (n=5, with the high-fat and high-sucrose diet), and NO-1886 group (n=5, with the high-fat and high-sucrose diet supplemented with 1.0% NO-1886). Plasma glucose, insulin, tfiglyceride (TG), oral glucose tolerant test, creatinine and blood urea nitrogen were measured monthly. Urinary samples in the morning were used for determination of microalbumin at month 0, 2, 4 and 5. The mRNA and protein expression of GSK-3β were measured by real time PCR, Western blot and immunohistochemistry in the kidneys obtained at the end of month 5. Results Compared with the C group, levels of plasma glucose, insulin, triglyceride and mieroalbuminuria were significantly increased in the DM group. The mRNA and protein expression of GSK-3β were increased in the kidneys of diabetic pigs (mRNA 0.0272±0.0052, protein 1.1600±0.0463, P<0.01) as compared with those of normal pigs (mRNA 0.0125±0.0045, protein 0.1385±0.0664). Compared with the DM group, the concentrations of plasma glucose, insulin, triglyceride and mieroalbuminuria obviously decreased in the NO-1886 group. The mRNA and protein expression of GSK-3β were decreased in the kidneys of the NO-1886 group (mRNA 0.0162±0.0019, protein 0.8429±0.0408, P<0.05) as compared with that of the DM group. Conclusion NO-1886 can improve disorders of glucose and TG metabolism and insulin resistance, and down-regulate the expression of GSK-3β in the kidneys, and protect renal function and morphologie damage in diet-induced diabetic minipigs.
4.Generation of thalassemia-specific integration-free induced pluripotent stem cells and determination of their differentiation ability
Manbo JIANG ; Minhui ZENG ; Jun ZAHNG ; Yanfei WEN ; Bin ZHANG ; Liuhong CAI
Chinese Journal of Pathophysiology 2015;(2):245-249
AIM:To generate thalassemia-specific integration-free induced pluripotent stem cells ( iPSC) and to detect their ability of differentiation into hematopoietic precursors .METHODS:The plasmids pEB-C5 and pEB-Tg were transfected into the fibroblast cells from hemoglobin Bart ’ s hydrops fetalis ’ s skin by the method of nuclear transfection to reprogramm the cells into iPSC .The ability of the iPSC to differentiate into 3-germ layer cells was determined .The iPSC were cocultured with mouse OP 9 cells to differentiate into hematopoietic precursors and the hematopoietic precursor specific antigens were detected .RESULTS:The integration-free iPSC from hemoglobin Bart ’ s hydrops fetalis ’ s skin fibroblasts were successfully derived, and had the ability to differentiate into 3 germ layers.When cocultured with OP9 cells for 9 d, the positive rate of hematopoietic progenitor cell marker CD 34 was 18.7%, and the CD34 and CD45 double positive rate was 12.2%.CONCLUSION:Hemoglobin Bart ’ s hydrops fetalis ’ s skin fibroblasts can be successfully induced into “in-tegration-free” iPSC.This cell line has the ability to differentiate into 3 germ layers , and can be differentiated into hemato-poietic precursors when cocultured with OP 9 cells.
5.Monte Carlo-based simulation of influence of linear accelerator beam parameter on percentage depth dose
Fan ZHANG ; Haibiao WU ; Ainong XIAO ; Xiaohong AI ; Manbo CAI ; Pian LI ; Lixiang CHENG ; Zhenchao ZHANG ; Guopu QU
Chinese Journal of Radiological Medicine and Protection 2018;38(2):145-149
Objective To determine the optimal electron beam energy at different field size through a Monte Carlo-based simulation of the therapy head of Varian X 6 MV linear accelerator so as to study the influence of radial intensity on depth dose.Methods Firstly,keeping the radial intensity unchanged for the field of interest while changing electron beam energy,compassion was carried out of calculated percentage depth doses between measured values.Thus,the optimal energy was identified for this field size.Then,the obtained energy was set the optimal value to study the radial intensity influence on the depth doses.Results The optimal electron energy for 4 cm ×4 cm,10 cm × 10 cm,20 cm × 20 cm and 30 cm × 30 cm field sizes was 5.9,6.0,6.3 and 6.4 MeV respectively.Changes in radial intensities resulted in negligible changes in percentage depth doses for4 cm ×4-cm and 10 cm × 10 cm fields,but led to observable discrepancy for 20 cm × 20 cm and 30 cm × 30 cm fields.Conclusions The optimal electron energies for different field sizes are slightly different.Change in radial intensity distribution has significant influence on the depth dose for large field.To improve simulation accuracy,the field size needs to be taken into consideration in determining the electron beam energy and radial intensity distribution.