ABSTRACT
Muhidrug resistance (MDR) is one of the important reasons for the failure of clinical anticancer drugs,involving multiple mechanisms.Among them,the classical MDR mechanism mediated by P-glycoprotein (P-gp) is closely related to the formation of MDR,which can excrete intracellular chemotherapeutic drugs through the "drug pump" effect and significantly reduce the therapeutic effect.Curcumin is mainly extracted from the underground rhizome of Chinese medicine turmeric,with a wide range of pharmacological activity.Recent studies have found that curcumin also has a role in reversing the MDR of the tumor,by inhibiting both P-gp function and expression,and this process involves a variety of signal paths.
ABSTRACT
Dihydroartemisinin (DHA),the major active metabolite of artemisinin,participates in tumor progression through the following ways:forming free radicals to induce cancer cells death dependent on iron,inducing apoptosis,inhibiting angiogenesis,tumor cells invasion and metastasis,modulating muhidrug resistance,controlling intracellular Ca2+ concentration,regulating cell cycles,cell autophagy and the immune system and so on.Generally,it is considered to be a potential anti-tumor drug.
ABSTRACT
Objective To investigate the effect of tripterygium glycosides on the resistance to immune rejection after allogeneic islet transplantation in mice.Methods Twenty C57BL/6 mice were treated with STZ diabetes mellitus and transplanted the islets from Balb/c mice donor,then recipient mice were randomly divided into two groups:triptolide group and model control group(n=10),and were intraperitoneal injected with tripterygium glycoside solutin and equivalent solvent of 5 mg·kg-1·d-1 for 14 days.Blood glucose and body weight were measured within 4 weeks after transplantation.Two weeks later,two groups of grafted islets were stained by HE staining and immunohistochemical staining,the expression of IL-2 protein were detected by Western blotting.Results The level of blood glucose were decreased to normal in the triptolide group and model control group after islet transplantation,but blood glucose gradually increased in the model control group after two weeks.Compared with the model control group,the inflammatory cells were less infiltrated and the immunohistochemical staining of insulin was deeper in the triptolide group.The expression of IL-2 in the triptolide group was significantly decreased(P<0.05).Conclusion Tripterygium glucoside could significantly decrease the inflammatory cell infiltration and inflammation factor expression in the allogeneic islet recipients to reduce the immune rejection and improve graft survival.
ABSTRACT
Objective To investigate the mechanism of islet transplantation lessening renal damage of diabetic nephropathy (DN) rat model.Method Rat DN model was established by intraperitoneal injection of a single-dose streptozotocir.The rats were divided into normal control group, DN group and islet transplant group.Islet transplantation was taken on the right renal capsule in transplantation group at 8th week after the modeling.At week 12 after the modeling, the urinary protein, urinary creatinine and blood glucose in each group were determined.The kidneys were collected, and transplant islet HE staining, immunofluorescence, kidney electron microscopy were done.Synaptopodin and transforming growth factor-β1 (TGFβ1) protein expression was observed in renal tissues of each group by immunohistochemical staining.Result The urine protein and urinary creatinine ratio in islet transplant group was significantly lower than in DN group (P＜0.001).Blood glucose level in islet transplant group had no significant difference (P＞0.05) with the control group, but was significantly lower than in DN group (P ＜ 0.05).Islet cells by HE staining and immunofluorescence staining showed new blood vessels around the islets, and the insulin secretion was exuberant.Under an electron microscope, there was local fusion of podocyte foot processes, and segmental thickening of the basement membrane in DN group;in islet transplant group, the foot processes of podocytes were neat, basement membrane structure was clear and had no thickening.Synaptopodin protein expression was significantly decreased in the glomeruli of DN group and islet transplant group as compared with the control group (P＜0.05), and that in islet transplant group was significantly enhanced (P＜0.05) as compared with DN group.The expression of TGFβ1 in DN group and islet transplant group was significantly increased (P＜0.05) as compared with control group, and that in DN group was significantly higher (P＜0.05) than in islet transplant group.Conclusion Islet transplantation can inhibit TGFβ1 pathway, improve DN podocyte injury in rats, and alleviate or even reverse proteinuria.
ABSTRACT
10.3969/j.issn.2095-4344.2013.25.011
ABSTRACT
Objective To evaluate the effect of different preparation processes on preparation of the glial cell line-derived neurotrophic factor(GDNF)loaded microspheres and observe the biological activity of GDNF.Methods With polylactide-co-glycolide(PLGA)as the coating material,the GDNF-loaded microspheres were prepared by using double emulsion(W1/O/W2).Two-factor factorial design variance analysis was done to analyze the effects of the composition proportion of lactic acid(LA)and glycolic acid(GA)in PLGA and the stirring speed of multiple emulsion on particle size,entrapment efficiency,burst release and in vitro release characteristics of the GDNF-loaded microspheres.PC-12 bioassay was employed to detect the biological activity of the released GDNF so as to determine the optimal preparation process.Results The composition proportion of PLGA could affect the microspheres'burst release(P ＜ 0.05),with no effect on particle size and entrapment efficiency.with the higher.With higher proportion of GA,the release speed of GDNF in the microspheres was increased.When the stirring speed of multiple emulsion was increased from 1 000 r/min to 3 000 r/min,the particle size of the microspheres was decrease significantly(P ＜ 0.01),the burst release was increased markedly(P ＜ 0.01)and the in vitro release rate was accelerated.The activity of GDNF in the microspheres could last for about 20 days at 37℃,which was 10 days longer than that of single GDNF.Conclusions Double emulsioncan prepare the GDNF-loaded microspheres with high entrapment efficiency and suitable in vitro release time.In the meantime,the microspheres can extend the validity of GDNF.