目的在体内,热休克蛋白90α(heat shock protein 90α,HSP90α)对肿瘤的发生发展起着重要的作用。HSP90α抑制剂在体内可阻断肿瘤赖以生存的信号通路网络。本研究探讨HSP90α特异性抑制剂烯丙胺基-17-去甲氧基格尔德(17-allyl-amino-17-...目的在体内,热休克蛋白90α(heat shock protein 90α,HSP90α)对肿瘤的发生发展起着重要的作用。HSP90α抑制剂在体内可阻断肿瘤赖以生存的信号通路网络。本研究探讨HSP90α特异性抑制剂烯丙胺基-17-去甲氧基格尔德(17-allyl-amino-17-demethoxygeldanamycin,17-AAG)对甲状腺癌细胞增殖和迁移的影响及相关信号分子的调控机制。方法体外培养甲状腺乳头状癌细胞TPC-1和甲状腺未分化癌细胞TAK,分别给予0.001～10.000μmol/L浓度的17-AAG作用24和48h。MTT实验、划痕实验观察细胞生长和迁移情况。蛋白质印迹法检测细胞HSP90α及信号传导及转录激活因子(signal transducers and activators of transcription,STAT3)、丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)相关信号蛋白的表达及磷酸化水平变化。结果与未处理的细胞相比,经0.001～10.000μmol/L浓度的17-AAG作用24和48h的TPC-1和TAK细胞增殖能力降低,且有明显的时间和剂量依赖性。TPC-1(F=7.326,P=0.005)和TAK细胞(F=22.770,P<0.001)浓度组间比较差异有统计学意义,时间组间比较差异有统计学意义,F值分别为1 048.000和663.800,均P<0.001。与未处理的细胞相比,经0.1和1.0μmol/L浓度的17-AAG作用24h的TPC-1和TAK细胞迁移能力降低,各浓度组间比较差异有统计学意义,F=1.228,P<0.005;两细胞株间比较差异无统计学意义,F=0.365,P=0.578。经0.1和1.0μmol/L浓度的17-AAG作用24h的TPC-1和TAK细胞以及STAT3、AKT、ERK蛋白磷酸化水平降低,却对STAT3和ERK总蛋白表达影响差异无统计学意义,P>0.05。结论 17-AAG通过下调甲状腺癌细胞HSP90α相关信号蛋白STAT3/AKT/ERK磷酸化水平,从而抑制甲状腺癌细胞的增殖和迁移能力。展开更多
人肠腺病毒41（Human Adenovirus Type 41，Ad41）属于人腺病毒F组，是引起胃肠炎的病原之一，因而被称为肠腺病毒。由于在体外难于培养，又被称为难养性腺病毒。6％～8％的4岁以下婴幼儿腹泻由该病毒引起。Flewett等首次在电镜下观察得...人肠腺病毒41（Human Adenovirus Type 41，Ad41）属于人腺病毒F组，是引起胃肠炎的病原之一，因而被称为肠腺病毒。由于在体外难于培养，又被称为难养性腺病毒。6％～8％的4岁以下婴幼儿腹泻由该病毒引起。Flewett等首次在电镜下观察得到Ad41，De Jung首次成功分离Ad41的病毒株，并将其命名为Tak株。展开更多
The outcrop samples of the Tak Fa Formation(Lower Permian)in Phetchabun Province have been studied to determine their organic geochemical characteristic,depositional paleoenvironment,and hydrocarbon generation potenti...The outcrop samples of the Tak Fa Formation(Lower Permian)in Phetchabun Province have been studied to determine their organic geochemical characteristic,depositional paleoenvironment,and hydrocarbon generation potential.The total organic carbon(TOC)values ranging from 1.42 to 4.58 wt%and extractable organic matter values ranging from 76.84 to 197.65 ppm of the Tak Fa Formation were generally low and associated with low S2 values(0.00-0.50 mg HC/g rock)and hydrogen index values in range of 0-32 mg/g TOC,although this could reflect highly thermal maturity and complex tectonic history.Thus,kerogen classification can be based on a nonbiomarker study for these outcrop samples instead.The non-biomarker plot,Pr/n-C17 and Ph/n-C18 from this study indicates that organic matter originally comes from typeⅡ/III kerogen.The samples were also investigated and indicated that the organic matter inputs were derived from mixed marine and terrigenous sources and deposited under suboxic to oxic conditions.The depositional environment of the Tak Fa Formation in this study is interpreted to be an estuarine environment or restricted lagoonal carbonate platforms.This has been achieved from normal alkane and isoprenoids distributions,terpane,and sterane biomarkers.Thus,the Tak Fa Formation is considered to be a hydrocarbon source rock during the time of the deposition.Although the geochemical data in this study indicate that the Tak Fa Formation has experienced high maturation,one or more locations could meet a condition that places this formation to be an active source rock.The approach and concepts presented in this study can be applied to similar evaporite-carbonate deposits in Thailand to find more petroleum plays.展开更多
Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like re...Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.展开更多
文摘目的在体内,热休克蛋白90α(heat shock protein 90α,HSP90α)对肿瘤的发生发展起着重要的作用。HSP90α抑制剂在体内可阻断肿瘤赖以生存的信号通路网络。本研究探讨HSP90α特异性抑制剂烯丙胺基-17-去甲氧基格尔德(17-allyl-amino-17-demethoxygeldanamycin,17-AAG)对甲状腺癌细胞增殖和迁移的影响及相关信号分子的调控机制。方法体外培养甲状腺乳头状癌细胞TPC-1和甲状腺未分化癌细胞TAK,分别给予0.001～10.000μmol/L浓度的17-AAG作用24和48h。MTT实验、划痕实验观察细胞生长和迁移情况。蛋白质印迹法检测细胞HSP90α及信号传导及转录激活因子(signal transducers and activators of transcription,STAT3)、丝氨酸/苏氨酸蛋白激酶(serine/threonine protein kinase,AKT)、细胞外调节蛋白激酶(extracellular regulated protein kinases,ERK)相关信号蛋白的表达及磷酸化水平变化。结果与未处理的细胞相比,经0.001～10.000μmol/L浓度的17-AAG作用24和48h的TPC-1和TAK细胞增殖能力降低,且有明显的时间和剂量依赖性。TPC-1(F=7.326,P=0.005)和TAK细胞(F=22.770,P<0.001)浓度组间比较差异有统计学意义,时间组间比较差异有统计学意义,F值分别为1 048.000和663.800,均P<0.001。与未处理的细胞相比,经0.1和1.0μmol/L浓度的17-AAG作用24h的TPC-1和TAK细胞迁移能力降低,各浓度组间比较差异有统计学意义,F=1.228,P<0.005;两细胞株间比较差异无统计学意义,F=0.365,P=0.578。经0.1和1.0μmol/L浓度的17-AAG作用24h的TPC-1和TAK细胞以及STAT3、AKT、ERK蛋白磷酸化水平降低,却对STAT3和ERK总蛋白表达影响差异无统计学意义,P>0.05。结论 17-AAG通过下调甲状腺癌细胞HSP90α相关信号蛋白STAT3/AKT/ERK磷酸化水平,从而抑制甲状腺癌细胞的增殖和迁移能力。
文摘人肠腺病毒41（Human Adenovirus Type 41，Ad41）属于人腺病毒F组，是引起胃肠炎的病原之一，因而被称为肠腺病毒。由于在体外难于培养，又被称为难养性腺病毒。6％～8％的4岁以下婴幼儿腹泻由该病毒引起。Flewett等首次在电镜下观察得到Ad41，De Jung首次成功分离Ad41的病毒株，并将其命名为Tak株。
基金financial support from the Ratchadaphisek Somphot Endowment Fund under Outstanding Research Performance Program, Science Super Ⅲ (Department)-009, Chulalongkorn University
文摘The outcrop samples of the Tak Fa Formation(Lower Permian)in Phetchabun Province have been studied to determine their organic geochemical characteristic,depositional paleoenvironment,and hydrocarbon generation potential.The total organic carbon(TOC)values ranging from 1.42 to 4.58 wt%and extractable organic matter values ranging from 76.84 to 197.65 ppm of the Tak Fa Formation were generally low and associated with low S2 values(0.00-0.50 mg HC/g rock)and hydrogen index values in range of 0-32 mg/g TOC,although this could reflect highly thermal maturity and complex tectonic history.Thus,kerogen classification can be based on a nonbiomarker study for these outcrop samples instead.The non-biomarker plot,Pr/n-C17 and Ph/n-C18 from this study indicates that organic matter originally comes from typeⅡ/III kerogen.The samples were also investigated and indicated that the organic matter inputs were derived from mixed marine and terrigenous sources and deposited under suboxic to oxic conditions.The depositional environment of the Tak Fa Formation in this study is interpreted to be an estuarine environment or restricted lagoonal carbonate platforms.This has been achieved from normal alkane and isoprenoids distributions,terpane,and sterane biomarkers.Thus,the Tak Fa Formation is considered to be a hydrocarbon source rock during the time of the deposition.Although the geochemical data in this study indicate that the Tak Fa Formation has experienced high maturation,one or more locations could meet a condition that places this formation to be an active source rock.The approach and concepts presented in this study can be applied to similar evaporite-carbonate deposits in Thailand to find more petroleum plays.
基金financially supported by the National Natural Science Foundation of China,No.81771625(to XF)the Jiangsu Provincial Key Medical Discipline of China,No.ZDXKA2016013(to XF)the Pediatric Clinical Center of Suzhou City of China,No.Szzx201504(to XF)
文摘Secondary brain damage caused by hyperactivation of autophagy and inflammatory responses in neurons plays an important role in hypoxic-ischemic brain damage(HIBD).Although previous studies have implicated Toll-like receptor 4(TLR4)and nuclear factor kappa-B(NF-κB)in the neuroinflammatory response elicited by brain injury,the role and mechanisms of the TLR4-mediated autophagy signaling pathway in neonatal HIBD are still unclear.We hypothesized that this pathway can regulate brain damage by modulating neuron autophagy and neuroinflammation in neonatal rats with HIBD.Hence,we established a neonatal HIBD rat model using the Rice-Vannucci method,and injected 0.75,1.5,or 3 mg/kg of the TLR4 inhibitor resatorvid(TAK-242)30 minutes after hypoxic ischemia.Our results indicate that administering TAK-242 to neonatal rats after HIBD could significantly reduce the infarct volume and the extent of cerebral edema,alleviate neuronal damage and neurobehavioral impairment,and decrease the expression levels of TLR4,phospho-NF-κB p65,Beclin-1,microtubule-associated protein l light chain 3,tumor necrosis factor-α,and interleukin-1βin the hippocampus.Thus,TAK-242 appears to exert a neuroprotective effect after HIBD by inhibiting activation of autophagy and the release of inflammatory cytokines via inhibition of the TLR4/NF-κB signaling pathway.This study was approved by the Laboratory Animal Ethics Committee of Affiliated Hospital of Yangzhou University,China(approval No.20180114-15)on January 14,2018.
