Effects of centella asiatica granule on the expression of TGF-β and related down-stream signals in rats with early diabetic nephropathy / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of centella asiatica (CA) granule on the expression of transform growth factor-β(TGF-β) and related down-stream signals in rats with early diabetic nephropathy(DN) and to clarify the molecular mechanisms of CA molecular mechanism of on preventing and curing early diabetic kidney disease DN by studying the effects of centella asiatica on TGF-β expression and related down-stream signals.@*METHODS@#Sixty male SD rats were divided into control group(=10) and DN model group(=50). The model rats were made a right nephrectomy. One week later, diabetic nephropathy was induced by intraperitoneal injection of streptocozin(30 mg/kg) for three consecutive days. High blood glucose level of Tail vein (fasting glucose ≥ 16.7 mmol/L) and high urinary protein level(total protein level in DN group was more than twice higher than the control group) were measured to confirm early DN in rats. In the sham operation group, the right renal capsule was damaged and the corresponding amount of saline was injected. The model rats were administrated by the means of intragastric administration. The DN model group were divided into DN group, DN+fosinopril group(1.6 mg/kg·d), DN+high CA group(16.8 mg/kg·d), DN+medium CA group(11.2 mg/kg·d) and DN+low CA group(5.6 mg/kg·d), and each group was intragastric administration one time every morning last for 16 weeks. The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3, Smad7 and the level of Smad2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.@*RESULTS@#The expressions of mRNA and protein of TGF-β, TβR1, TβR2, Smad2/3 and the level of Smad2/3 phosphorylation were significantly increased, the expressions of mRNA and protein of Smad7 were dramatically decreased. The fosinopril and high dosage CA could reverse the effects of DN.@*CONCLUSIONS@#CA plays an important role in preventing and curing DN through regulating the TGF-β/Smad signaling pathways.

Effects of centellaasiatica granule on the expression of Smad 2/3, Smad 7 and collagen Ⅳ in the mesangial cells stably expressed TGF-β1 / 中国应用生理学杂志

OBJECTIVES@#Stably expressed transforming growth factor -beta 1(TGF-β1)MCs were obtained and the effects of centellaasiatica (CA) granule on the expressions of Smad 2/3, Smad 7 and collagen Ⅳ and the level of Smad 2/3 phosphorylation were observed.@*METHODS@#Lipofectin method was used to transfect TGF-β1 vector into MC, and the stably expressed TGF-β1 cell lines were selected by G418. The cells were divided into three groups. Control group:normal MC + RPMI 1640 + 10% normal rat serum; TGF-β1 group:stably expressed TGF-β1 MC + RPMI 1640 + 10% normal rat serum; CA group:stably expressed TGF-β1 MC + RPMI 1640 + 10% rat serum containing high CA. The experiments were repeated for five times. The contents of TGF-β1 and collagen Ⅳ in the culture medium were detected with ELISA, the expressions of mRNA and protein of TGF-β1, Smad 2/3, Smad 7 and the level of Smad 2/3 phosphorylation were detected by using real time quantitative polymerase chain reaction and Western blot.@*RESULTS@#The contents of TGF-β1 and collagen Ⅳ in the culture medium of stably-expressed TGF-β1 MC were increased significantly, and the CA could reverse the effects of TGF-β1. The expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation were increased significantly in TGF-β1 transfected MC, and CA could dramatically reduce the expressions of mRNA and protein of TGF-β1, Smad 2/3 and the level of Smad 2/3 phosphorylation. The high expression of TGF-β1 decreased the expression of Smad 7 mRNA and protein, and the CA could antagonize the effect of mRNA expression.@*CONCLUSIONS@#The MCs stably-expressed TGF-β1 can activate the TGF-β1/Smad signal pathway and increase the expression of collagen Ⅳ. CA can decrease the occurrence of diabetic nephropathy(DN) by reducing the production of collagen Ⅳ through inhibiting the TGF-β1/Smad signal pathway.

Tetrandrine Exerts a Radiosensitization Effect on Human Glioma through Inhibiting Proliferation by Attenuating ERK Phosphorylation

Tetrandrine (Tet), a bisbenzylisoquinoline alkaloid, has been reported to have a radiosensitization effect on tumors. However, its effects on human glioma and the specific molecular mechanisms of these effects remain unknown. In this study, we demonstrated that Tet has a radiosensitization effect on human glioma cells. It has been hypothesized that Tet has a radiosensitization effect on glioma cells by affecting the glioma cell cycle and DNA repair mechanism and that ERK mediates these activities. Therefore, we conducted detailed analyses of the effects of Tet on the cell cycle by performing flow cytometric analysis and on DNA repair by detecting the expression of phosphorylated H2AX by immunofluorescence. We used western blot analysis to investigate the role of ERK in the effect of Tet on the cell cycle and DNA repair. The results revealed that Tet exerts its radiosensitization effect on glioma cells by inhibiting proliferation and decreasing the expression of phosphorylated ERK and its downstream proteins. In summary, our data indicate that ERK is involved in Tet-induced radiosensitization of glioma cells via inhibition of glioma cell proliferation or of the cell cycle at G0/G1 phase.

Short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and safety observation

To evaluate the short-term therapeutic effects of low-dose cytarabine plus surgical resection on elderly patients with trigeminal nerve tumor and to observe the safety. A total of 120 elderly patients with trigeminal nerve tumor were divided into a treatment group and a control group by random draw [n=60], and both groups were subjected to resection by stereotactic image-guided endoscopic nasal surgery. Afterwards, the control group was administered with high-dose cytarabine while the treatment group was given low-dose cytarabine for 14 days. Both groups completed treatment, but the effective rate of the treatment group [96.7%] was significantly higher than that of the control group [83.3%] [P < 0.05]. The pain scores of the two groups were similar at T0, T1 and T2, but the score of the treatment group at T2 was significantly different from those at T0 and T1 [P < 0.05]. During treatment, the treatment group was significantly less prone to complications such as headache, vomiting, vision impairment, nausea and local swelling than the control group [P < 0.05]. During three months of follow-up, the appetite, sleep and daily living scores were significantly higher than those of the control group [P < 0.05]. Stereotactic image-guided surgery was able to treat trigeminal nerve tumor well, and the effect was enhanced by low-dose cytarabine that improved postoperative outcomes and quality of life by dramatically decreasing complications