目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用We...目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用Western Blot检测HER2、KRAS蛋白表达,RT-PCR定量检测HER2、KRAS m RNA表达水平。结果 1Western blot检测HER2、KRAS蛋白:与空白组比较,各给药组HER2、KRAS蛋白表达不同程度下调[HER2:(1.238±0.123、1.180±0.152、1.159±0.087、0.876±0.098、0.651±0.108、0.554±0.110)比(1.482±0.101),P<0.05或P<0.01;KRAS:(0.768±0.040、0.680±0.019、0.821±0.170、0.716±0.023、0.630±0.049、0.739±0.044)比(1.015±0.033),P均<0.05];与赫赛汀组比较,中剂量联合组KRAS蛋白表达显著下调(0.630±0.049比0.759±0.029,P<0.05);2RT-PCR检测HER2、KRAS m RNA表达:与空白组比较,各给药组HER2、KRAS m RNA表达不同程度下调[HER2 m RNA:(0.916±0.026、0.783±0.061、0.846±0.021、0.741±0.079、0.660±0.079、0.673±0.045)比(1.000±0.193),P均<0.05;KRAS m RNA:(0.643±0.065、0.551±0.173、0.572±0.267、0.329±0.250、0.036±0.007、0.351±0.257)比(1.001±0.132),P<0.05或P<0.01];与赫赛汀组比较,中剂量联合组KRAS m RNA表达显著下调(0.036±0.007比0.362±0.162,P<0.01)。结论南方红豆杉水提物可通过Ras/MAPK信号通路部分下调HER2、KRAS蛋白及其m RNA表达水平,联合赫赛汀可增强其抑制作用。展开更多
Objective:To investigate the effect of Bushen Antai Granule on the mRNA and protein expression of Ras protein/mitogen activated protein kinase mediated by vascular endothelial growth factor receptor 2 with small inter...Objective:To investigate the effect of Bushen Antai Granule on the mRNA and protein expression of Ras protein/mitogen activated protein kinase mediated by vascular endothelial growth factor receptor 2 with small interference RNA interference.Methods:Method to construct the placenta microvascular endothelial cells,and the preparation of kidney fetus granule drug-containing serum,select the best drug-containing serum concentration,it can be divided into normal group,the serum siRNA-NC normal serum group,drug serum,siRNA normal serum group,siRNA drug serum group,using real-time fluorescent quantitative PCR,Western blotting,immunofluorescence test respectively the RAS/MAPK mRNA and protein expression.Results:Results there was no significant difference in Ras and MAPK mRNA and protein expression between the normal group and the negative control group(P>0.05).The mRNA and protein expressions of Ras and MAPK in the drug serum group were significantly higher than those in the normal serum group(P<0.01).Ras and MAPK mRNA and protein expression were significantly decreased in siRNA1 normal serum group compared with normal serum group(P<0.01).Ras,MAPK mRNA and protein expression in siRNA1 drug serum group were significantly different from that in siRNA1 normal serum group(P<0.01).Conclusion:Conclusion The therapeutic effect of Bushen Antai Granule on recurrent abortion may be realized by upregulation of RAS/MAPK mRNA and protein expression.展开更多
Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan(QF), a traditional Chinese medicine(TCM)formula, has been used clinically in ...Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan(QF), a traditional Chinese medicine(TCM)formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical antiinflammatory ingredients from QF, arctigenin(ATG), cholic acid(CLA), chlorogenic acid(CGA) and sinapic acid(SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines(TNF-α and IL-6) and chemokines(IL-8 and RANTES),reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively.展开更多
RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多...RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多,且临床表现相互重叠,诊断难度大。其中,矮小症是RASopathies最常见的临床表现之一,但导致矮小症的机制有待进一步探索,且生长激素治疗RASopathies的效果差异较大。本文就RASopathies及其在矮小症中的研究进展作一综述。展开更多
文摘目的探讨南方红豆杉水提物通过抑制Ras/MAPK信号通路相关靶点蛋白表达,调控裸鼠HER2阳性胃癌移植瘤生长及其机制。方法建立荷瘤裸鼠模型,将80只BALB/c裸鼠接种人表皮生长因子-2(HER2)阳性胃癌NCI-N87细胞株,并随机分组给药及取瘤,采用Western Blot检测HER2、KRAS蛋白表达,RT-PCR定量检测HER2、KRAS m RNA表达水平。结果 1Western blot检测HER2、KRAS蛋白:与空白组比较,各给药组HER2、KRAS蛋白表达不同程度下调[HER2:(1.238±0.123、1.180±0.152、1.159±0.087、0.876±0.098、0.651±0.108、0.554±0.110)比(1.482±0.101),P<0.05或P<0.01;KRAS:(0.768±0.040、0.680±0.019、0.821±0.170、0.716±0.023、0.630±0.049、0.739±0.044)比(1.015±0.033),P均<0.05];与赫赛汀组比较,中剂量联合组KRAS蛋白表达显著下调(0.630±0.049比0.759±0.029,P<0.05);2RT-PCR检测HER2、KRAS m RNA表达:与空白组比较,各给药组HER2、KRAS m RNA表达不同程度下调[HER2 m RNA:(0.916±0.026、0.783±0.061、0.846±0.021、0.741±0.079、0.660±0.079、0.673±0.045)比(1.000±0.193),P均<0.05;KRAS m RNA:(0.643±0.065、0.551±0.173、0.572±0.267、0.329±0.250、0.036±0.007、0.351±0.257)比(1.001±0.132),P<0.05或P<0.01];与赫赛汀组比较,中剂量联合组KRAS m RNA表达显著下调(0.036±0.007比0.362±0.162,P<0.01)。结论南方红豆杉水提物可通过Ras/MAPK信号通路部分下调HER2、KRAS蛋白及其m RNA表达水平,联合赫赛汀可增强其抑制作用。
基金National Natural Science Foundation of China(No.81574017)。
文摘Objective:To investigate the effect of Bushen Antai Granule on the mRNA and protein expression of Ras protein/mitogen activated protein kinase mediated by vascular endothelial growth factor receptor 2 with small interference RNA interference.Methods:Method to construct the placenta microvascular endothelial cells,and the preparation of kidney fetus granule drug-containing serum,select the best drug-containing serum concentration,it can be divided into normal group,the serum siRNA-NC normal serum group,drug serum,siRNA normal serum group,siRNA drug serum group,using real-time fluorescent quantitative PCR,Western blotting,immunofluorescence test respectively the RAS/MAPK mRNA and protein expression.Results:Results there was no significant difference in Ras and MAPK mRNA and protein expression between the normal group and the negative control group(P>0.05).The mRNA and protein expressions of Ras and MAPK in the drug serum group were significantly higher than those in the normal serum group(P<0.01).Ras and MAPK mRNA and protein expression were significantly decreased in siRNA1 normal serum group compared with normal serum group(P<0.01).Ras,MAPK mRNA and protein expression in siRNA1 drug serum group were significantly different from that in siRNA1 normal serum group(P<0.01).Conclusion:Conclusion The therapeutic effect of Bushen Antai Granule on recurrent abortion may be realized by upregulation of RAS/MAPK mRNA and protein expression.
基金supported by the National Natural Science Foundation of China(Nos.81173638 and 81373506)the Key Program of Natural Science of Foundation of TianjinChina(No.13JCZDJC31400)
文摘Gram-negative pathogen–induced nosocomial infections and resistance are a most serious menace to global public health. Qingfei Xiaoyan Wan(QF), a traditional Chinese medicine(TCM)formula, has been used clinically in China for the treatment of upper respiratory tract infections, acute or chronic bronchitis and pulmonary infection. In this study, the effects of QF on Pseudomonas aeruginosa–induced acute pneumonia in mice were evaluated. The mechanisms by which four typical antiinflammatory ingredients from QF, arctigenin(ATG), cholic acid(CLA), chlorogenic acid(CGA) and sinapic acid(SPA), regulate anti-inflammatory signaling pathways and related targets were investigated using molecular biology and molecular docking techniques. The results showed that pretreatment with QF significantly inhibits the release of cytokines(TNF-α and IL-6) and chemokines(IL-8 and RANTES),reduces leukocytes recruitment into inflamed tissues and ameliorates pulmonary edema and necrosis. In addition, ATG was identified as the primary anti-inflammatory agent with action on the PI3K/AKT and Ras/MAPK pathways. CLA and CGA enhanced the actions of ATG and exhibited synergistic NF-κB inactivation effects possibly via the Ras/MAPK signaling pathway. Moreover, CLA is speculated to target FGFR and MEK firstly. Overall, QF regulated the PI3K/AKT and Ras/MAPK pathways to inhibit pathogenic bacterial infections effectively.
文摘RASopathies是一组由于Ras/丝裂原激活蛋白激酶(Ras/mitogen activated protein kinase,MAPK)通路中的组分或调节因子的编码基因发生突变引起的一系列疾病。Ras/MAPK通路在调控细胞发育过程中发挥重要作用,因此RASopathies涉及疾病众多,且临床表现相互重叠,诊断难度大。其中,矮小症是RASopathies最常见的临床表现之一,但导致矮小症的机制有待进一步探索,且生长激素治疗RASopathies的效果差异较大。本文就RASopathies及其在矮小症中的研究进展作一综述。
