随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结...随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结合的方法,鉴定了IMRT和IMR90细胞中的差异蛋白质和差异代谢物。结果表明:在IMRT细胞中,重要代谢通路的蛋白质水平发生变化,如葡萄糖磷酸变位酶1(PGM1)、6-磷酸葡萄糖脱氢酶(G6PD)、谷胱甘肽过氧化物酶1(GPX1)、谷胱甘肽S-转移酶M2(GSTM2)等。相关通路中的代谢物,如6-磷酸葡萄糖,肉碱,磷酸胆碱,亮氨酸异亮氨酸,谷氨酰胺和丙氨酸的含量有显著变化。结合分析结果,我们在IMR90中沉默GPX1基因,促进了IMR90的衰老进程,表明GPX1在细胞衰老进程中的重要作用。展开更多
采用离子分子质谱IMR-MS(ion molecule reaction mass spectrometry)与转盘式吸烟机RM20H相连的方法,对卷烟主流烟气中气相成分建立了在线、实时、高效的逐口定量检测方法。该方法日内重复性、日间重复性结果显示除最后一口由于抽吸烟...采用离子分子质谱IMR-MS(ion molecule reaction mass spectrometry)与转盘式吸烟机RM20H相连的方法,对卷烟主流烟气中气相成分建立了在线、实时、高效的逐口定量检测方法。该方法日内重复性、日间重复性结果显示除最后一口由于抽吸烟气量不同,RSD较大外,其他抽吸口数RSD均小于15%。用该方法测定标准卷烟2R4F、3R4F和1R5F,并将结果与文献经典方法进行比较,数据显示本方法定量结果准确。展开更多
目的比较全模型迭代重建(Whole Model Iterative Reconstruction,IMR)与混合迭代重建(iDose4)对于肠系膜动脉图像质量的影响。方法对60位临床怀疑肠道疾病患者行肠道CTA检查,采用管电压80 kV、自动管电流,扫描结束后将所有动脉期数据同...目的比较全模型迭代重建(Whole Model Iterative Reconstruction,IMR)与混合迭代重建(iDose4)对于肠系膜动脉图像质量的影响。方法对60位临床怀疑肠道疾病患者行肠道CTA检查,采用管电压80 kV、自动管电流,扫描结束后将所有动脉期数据同时进行IMR和iDose^4重建,分别命名为IMR重建和iDose^4重建组,对两组图像质量进行主观评分,并测量肠系膜上动脉、肠系膜下动脉以及同层肌肉CT值,背景噪声SD值,计算肠系膜上动脉、肠系膜下动脉信噪比,对比噪声比,利用统计学软件对各组数据进行统计学分析,比较两组间不同数据差异性。结果两组重建图像在血管强化CT值均值约为462.6 HU,无明显显著性差异。肠系膜上动脉、肠系膜下动脉图像噪声IMR重建组低于iDose^4重建组,两组比较存在统计学差异,P值分别为0.000,0.016;肠系膜上动脉和肠系膜下动脉的信噪比、对比噪声比比较,IMR重建组均高于iDose^4重建组,P值分别为0.004,0.009和0.002,0.005。IMR重建组图像质量主观评分和客观评价均优与iDose^4重建组,两组差异有统计学意义(P<0.05)。结论在肠系膜动脉CTA检查中,IMR全模型迭代重建相对于iDose^4重建技术可以显著减低图像噪声,提高图像空间分辨率,在相同辐射剂量情况下可以提高图像质量。展开更多
The present study characterized the nerve growth factor (NGF)-mediated regulation of tau protein expression and transcription in IMR32 human neuroblastoma cells. Treatment of IMR32 cells with 50 ng/mL NGF resulted in ...The present study characterized the nerve growth factor (NGF)-mediated regulation of tau protein expression and transcription in IMR32 human neuroblastoma cells. Treatment of IMR32 cells with 50 ng/mL NGF resulted in increased levels of specific tau protein isoforms. A 550 bp fragment of the tau promoter was cloned and treatment of transfected IMR32 and PC12 cells with NGF also resulted in increased promoter activation, suggesting that the NGF-mediated increase in tau isoforms is regulated, at least in part, at the level of transcription. Pretreatment with the MAP kinase inhibitor U0126 or the PKC inhibitor bisindolylmaleimide 1 (BIS-1) attenuated the NGF-mediated increase in tau transcription, indicating that the NGF-mediated activation of the MAP kinase and PKC signaling pathways modulate tau transcription. Pre-treatment of cells with the Akt inhibitor, LY294002 or with NOS inhibitors Nω-nitro-L-arginine methylester (L-NAME) or s-methylisothiourea (S-MIU) had no effect on the NGF-mediated increase in tau promoter activation, suggesting that NO and the NGF-Akt signaling pathway do not modulate tau transcription. Taken together, these data demonstrate that NGF increases the levels of multiple human tau isoforms in IMR32 cells which may result, at least in part, from NGF-mediated PKC and MAP kinase-induced tau transcription.展开更多
Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious react...Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H_2O_2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri(BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against H_2O_2-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.展开更多
文摘随着高通量技术的发展,基因组学、转录组学、蛋白质组学和代谢组学等组学研究为深入了解细胞新陈代谢的机理提供了新视角。本研究先验证了整合SV40 Large T抗原基因的IMR90细胞——IMRT,表现出衰老表型。通过蛋白质组学与代谢组学相结合的方法,鉴定了IMRT和IMR90细胞中的差异蛋白质和差异代谢物。结果表明:在IMRT细胞中,重要代谢通路的蛋白质水平发生变化,如葡萄糖磷酸变位酶1(PGM1)、6-磷酸葡萄糖脱氢酶(G6PD)、谷胱甘肽过氧化物酶1(GPX1)、谷胱甘肽S-转移酶M2(GSTM2)等。相关通路中的代谢物,如6-磷酸葡萄糖,肉碱,磷酸胆碱,亮氨酸异亮氨酸,谷氨酰胺和丙氨酸的含量有显著变化。结合分析结果,我们在IMR90中沉默GPX1基因,促进了IMR90的衰老进程,表明GPX1在细胞衰老进程中的重要作用。
文摘采用离子分子质谱IMR-MS(ion molecule reaction mass spectrometry)与转盘式吸烟机RM20H相连的方法,对卷烟主流烟气中气相成分建立了在线、实时、高效的逐口定量检测方法。该方法日内重复性、日间重复性结果显示除最后一口由于抽吸烟气量不同,RSD较大外,其他抽吸口数RSD均小于15%。用该方法测定标准卷烟2R4F、3R4F和1R5F,并将结果与文献经典方法进行比较,数据显示本方法定量结果准确。
文摘The present study characterized the nerve growth factor (NGF)-mediated regulation of tau protein expression and transcription in IMR32 human neuroblastoma cells. Treatment of IMR32 cells with 50 ng/mL NGF resulted in increased levels of specific tau protein isoforms. A 550 bp fragment of the tau promoter was cloned and treatment of transfected IMR32 and PC12 cells with NGF also resulted in increased promoter activation, suggesting that the NGF-mediated increase in tau isoforms is regulated, at least in part, at the level of transcription. Pretreatment with the MAP kinase inhibitor U0126 or the PKC inhibitor bisindolylmaleimide 1 (BIS-1) attenuated the NGF-mediated increase in tau transcription, indicating that the NGF-mediated activation of the MAP kinase and PKC signaling pathways modulate tau transcription. Pre-treatment of cells with the Akt inhibitor, LY294002 or with NOS inhibitors Nω-nitro-L-arginine methylester (L-NAME) or s-methylisothiourea (S-MIU) had no effect on the NGF-mediated increase in tau promoter activation, suggesting that NO and the NGF-Akt signaling pathway do not modulate tau transcription. Taken together, these data demonstrate that NGF increases the levels of multiple human tau isoforms in IMR32 cells which may result, at least in part, from NGF-mediated PKC and MAP kinase-induced tau transcription.
基金supported by grants from the Department of Science and Technology (DST), Ministry of Science and Technology, New Delhi under order No. SR/FT/LS-163 and University with Potential for Excellence (UPE) Scheme, University Grants Commission, New Delhi
文摘Neurodegenerative diseases are the consequences of imbalance between the production of oxidative stress and its nullification by cellular defense mechanisms. Hydrogen peroxide(H_2O_2), a precursor of deleterious reactive oxygen species, elicits oxidative stress, resulting in severe brain injuries. Bacopa monnieri is well known for its nerve relaxing and memory enhancing properties. The present study was designed to evaluate the protective effects of extracts from Bacopa monnieri against H_2O_2 induced oxidative stress using a cellular model, neuroblastoma IMR32 cell line. The protective potential of methanolic, ethanolic, and water extracts of B. monnieri(BM-MEx, BM-EEx, and BM-WEx) was evaluated using MTT assay. Although, all the B. monnieri extracts were found to protect cells against H_2O_2-mediated stress but BM-MEx showed significantly greater protection. UPLC analysis of BM-MEx revealed various polyphenols, including quercetin, catechin, umbelliferone, and caffeic acid predominance. Further, BM-MEx was found to possess considerable greater neuroprotective potential in comparison to the standard polyphenols such as quercetin, catechin, umbelliferone, and caffeic acid. The levels of antioxidant enzymes were significantly elevated after the pretreatment of BM-MEx and quercetin. The expression levels of oxidative stress markers, such as NF200, HSP70, and mortalin, were significantly alleviated after the pretreatment of BM-MEx as shown by immunofluorescence and RT-PCR. In conclusion, the present study demonstrated the protective effects of BM-MEx, suggesting that it could be a candidate for the development of neuropathological therapeutics.
