目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC...目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。展开更多
目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)1...目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)10只、模型组10只、辛伐他汀预防组(辛预组)10只、连豆清脉方预防组(连预组)10只;后4组大鼠通过高脂饲料喂养建立早期AS模型,同步采用连豆清脉方、辛伐他汀,分别对大鼠AS模型进行预防性干预。并对主动脉血管壁厚度、组织PARP-1阳性细胞表达率、外周血单个核细胞TLR-4 m RNA表达、血清NF-κB水平检测计算。结果 1)光镜下大鼠主动脉血管壁厚度存在差异(P<0.01),连预组和辛预组大鼠主动脉血管壁厚度明显薄于模型组(P<0.01),但是和空预组比较差异无统计学意义。免疫组化染色光镜下大鼠左心室组织PARP-1表达具有显著差异,PARP-1阳性细胞表达率存在统计学差异(P<0.01),连预组和辛预组PARP-1阳性细胞表达率明显低于模型组(P<0.01),但是明显高于空预组(P<0.01),具有统计学差异。2)大鼠外周血单个核细胞TLR-4 m RNA表达各组间存在统计学差异(P<0.01),连预组和辛预组TLR-4 m RNA表达明显低于模型组(P<0.01),且连预组低于空预组(P<0.05)。大鼠血清NF-κB水平各组间存在差异(P=0.001);其中连预组NF-κB水平明显低于模型组(P<0.01),但与空预组比较差异无统计学意义。结论连豆清脉方可预防高脂饮食导致的AS形成;其机制与抑制NF-κB炎症信号通路PARP-1、TLR-4、NF-κB等环节有关。展开更多
Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture ...Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-repeffusion （22.5 mg/kg, initially 45 mg/kg） at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein expression.展开更多
Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4- diisothiocyanatostilbene-2,2＇-disulfonic ...Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid. Results showed that the survival rate of neurons was significantly increased after treatment with 4,4-diisothiocyanatostilbene-2,2＇-disulfonic acid, and the rate of apoptosis decreased. In addition, the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor were significantly reduced. Our experimental findings indicate that the chloride channel blocker 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid can antagonize apoptotic cell death of hippocampal neurons by inhibiting the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor.展开更多
Objective： 5-Aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly （adenosine 5＇-diphosphate ribose） polymerase, plays an important role in the tissue injury associated with ischaemia-repe...Objective： 5-Aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly （adenosine 5＇-diphosphate ribose） polymerase, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation by inhibiting the activity of poly （adenosine 5＇-diphosphate ribose） polymerase and the expression of cell adhesion molecules such as ICAM-1, P-selectin et al. But how about it in the tumor is not clear. The aim of the present study was to study the effects of 5-Aminoisoquinolinon on the adhesion of colon carcinoma line HT-29 cells to human umbilical vein endothelial cells; and the effects of 5-Aminoisoquinolinon on the expression of ICAM-1, P-selectin and the activity of poly （adenosine 5＇-diphosphate ribose） polymerase in colon carcinoma HT-29 cells. Methods： The adhesion of HT-29 cells to human umbilical vein endothelial cells was detected by adhesive experiment. Immunocytochemically Streptavidin-Peroxidase method was used to investigate the expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose）（ the product of poly （adenosine 5＇-diphosphate ribose） polymerase activation）. Results： the results of the adhesion assay of HT-29 cells to HUVEC showed that the OD570 value in each 5-AIQ-treated group was significant lower than that in the control group （5-AIQ-untreated） in a dose-dependent manner. The expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose） was significant lower in 5-Aminoisoquinolinone-treated HT-29 cell group than that in 5-Aminoisoquinolinoneuntreated groups. Conclusion： The data suggest that 5-Aminoisoquinolinone can inhibit the adhesion of HT-29 cells to human umbilical vein endothelial cells. 5-Aminoisoquinolinone also can inhibit poly （adenosine 5＇-diphosphate ribose） polymerase activation and the expressions of ICAM-1 and P-selectin in HT-29 cells. 5-Aminoisoquinolinone probably contributes to the prevention of tumor cell metastasis. Further study is needed.展开更多
文摘目的:系统评价PARPi治疗转移性去势抵抗性前列腺癌(mCRPC)的有效性及安全性,以期为临床决策供循证医学证据。方法:依据纳入和排除标准,网络检索2015年1月~2023年6月PubMed、Web of Science、Embace、Clinicial.gov中有关PARPi治疗mCRPC的随机对照试验文献,使用RevMan5.4及Stata17.0软件对数据进行Meta分析。结果:纳入7篇随机对照试验文献,共1888例患者。Meta分析结果表明,与非PARPi组比较,PARPi组(PARPi联合或不联合抗激素治疗)可提高mCRPC的放射学无进展生存期(HR=0.52,95%CI=0.34~0.78)和总生存期(HR=0.72,95%CI=0.60~0.86),差异均有统计学意义(P<0.05)。在安全性方面,PARPi组1~2级骨痛、背痛、贫血、中性粒细胞减少、恶心、呕吐、腹泻、乏力不良反应发生率明显高于非PARPi组,差异均有统计学意义(P<0.05);≥3级上述不良反应中与非PARPi组比较,PARPi组中只有恶心和贫血不良反应发生率较高,差异均有统计学意义(P<0.05),而骨痛、背痛、中性粒细胞减少、呕吐、腹泻、乏力两组间比较差异均无统计学意义(P>0.05)。结论:与非PARPi比较,PARPi联合或不联合抗激素治疗可提高mCRPC的放射学无进展生存期和总生存期,3级及以上不良反应发生率低,值得在临床上推广应用。
文摘目的研究连豆清脉方对大鼠动脉粥样硬化(AS)形成的预防作用,以及对核因子-κB(NF-κB)炎症信号通路中Toll样受体-4(TLR-4)、NF-κB、多聚二磷酸腺苷核糖聚合酶-1(PARP-1)的影响。方法 50只大鼠随机分为基础组10只、空白预防组(空预组)10只、模型组10只、辛伐他汀预防组(辛预组)10只、连豆清脉方预防组(连预组)10只;后4组大鼠通过高脂饲料喂养建立早期AS模型,同步采用连豆清脉方、辛伐他汀,分别对大鼠AS模型进行预防性干预。并对主动脉血管壁厚度、组织PARP-1阳性细胞表达率、外周血单个核细胞TLR-4 m RNA表达、血清NF-κB水平检测计算。结果 1)光镜下大鼠主动脉血管壁厚度存在差异(P<0.01),连预组和辛预组大鼠主动脉血管壁厚度明显薄于模型组(P<0.01),但是和空预组比较差异无统计学意义。免疫组化染色光镜下大鼠左心室组织PARP-1表达具有显著差异,PARP-1阳性细胞表达率存在统计学差异(P<0.01),连预组和辛预组PARP-1阳性细胞表达率明显低于模型组(P<0.01),但是明显高于空预组(P<0.01),具有统计学差异。2)大鼠外周血单个核细胞TLR-4 m RNA表达各组间存在统计学差异(P<0.01),连预组和辛预组TLR-4 m RNA表达明显低于模型组(P<0.01),且连预组低于空预组(P<0.05)。大鼠血清NF-κB水平各组间存在差异(P=0.001);其中连预组NF-κB水平明显低于模型组(P<0.01),但与空预组比较差异无统计学意义。结论连豆清脉方可预防高脂饮食导致的AS形成;其机制与抑制NF-κB炎症信号通路PARP-1、TLR-4、NF-κB等环节有关。
基金supported by the National Natural Science Foundation of China, No. 81160157the Key Program of the Science and Technology Department of Guizhou Province, No. SY20093075Nomarch Foundation for Excellent Talents in Science, Technology and Education Field of Guizhou Province, No. 201209
文摘Minocylcine, a tetracycline derivate, has been shown to cross the blood-brain barrier and enter the central nervous system. In this study, cerebral ischemia-reperfusion injury models were established using the suture method, and minocycline was immediately injected intraperitoneally after cerebral ischemia-repeffusion （22.5 mg/kg, initially 45 mg/kg） at a 12-hour interval. Results showed that after minocycline treatment, the volume of cerebral infarction was significantly reduced, the number of surviving cell in the hippocampal CA1 region increased, the number of apoptotic cells decreased, the expression of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein was down-regulated, and the escape latency in the water maze test was significantly shortened compared with the ischemia-reperfusion group. Our experimental findings indicate that minocycline can protect against neuronal injury induced by focal ischemia-reperfusion, which may be mediated by the inhibition of caspase-3 and poly（adenosine diphosphate-ribose） polymerase-1 protein expression.
基金supported by the National Natural Science Foundation of China, No. 81160157projects of Science and Technology Bureau of Guizhou Province, No.20093075, 20072127
文摘Apoptosis in cultured rat hippocampal neurons was induced using the nitric oxide donor 3-morpholinosydnonimine, and cells were treated with the chloride channel blocker, 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid. Results showed that the survival rate of neurons was significantly increased after treatment with 4,4-diisothiocyanatostilbene-2,2＇-disulfonic acid, and the rate of apoptosis decreased. In addition, the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor were significantly reduced. Our experimental findings indicate that the chloride channel blocker 4,4- diisothiocyanatostilbene-2,2＇-disulfonic acid can antagonize apoptotic cell death of hippocampal neurons by inhibiting the expression of the apoptosis-related proteins poly（adenosine diphosphate-ribose）polymerase-1 and apoptosis-inducing factor.
基金Natural Science Foundation Project of CQ CSTC (CSTC, 2006BB5288)
文摘Objective： 5-Aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly （adenosine 5＇-diphosphate ribose） polymerase, plays an important role in the tissue injury associated with ischaemia-reperfusion injury and inflammation by inhibiting the activity of poly （adenosine 5＇-diphosphate ribose） polymerase and the expression of cell adhesion molecules such as ICAM-1, P-selectin et al. But how about it in the tumor is not clear. The aim of the present study was to study the effects of 5-Aminoisoquinolinon on the adhesion of colon carcinoma line HT-29 cells to human umbilical vein endothelial cells; and the effects of 5-Aminoisoquinolinon on the expression of ICAM-1, P-selectin and the activity of poly （adenosine 5＇-diphosphate ribose） polymerase in colon carcinoma HT-29 cells. Methods： The adhesion of HT-29 cells to human umbilical vein endothelial cells was detected by adhesive experiment. Immunocytochemically Streptavidin-Peroxidase method was used to investigate the expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose）（ the product of poly （adenosine 5＇-diphosphate ribose） polymerase activation）. Results： the results of the adhesion assay of HT-29 cells to HUVEC showed that the OD570 value in each 5-AIQ-treated group was significant lower than that in the control group （5-AIQ-untreated） in a dose-dependent manner. The expression of ICAM-1, P-selectin and Poly （adenosine 5＇-diphosphate ribose） was significant lower in 5-Aminoisoquinolinone-treated HT-29 cell group than that in 5-Aminoisoquinolinoneuntreated groups. Conclusion： The data suggest that 5-Aminoisoquinolinone can inhibit the adhesion of HT-29 cells to human umbilical vein endothelial cells. 5-Aminoisoquinolinone also can inhibit poly （adenosine 5＇-diphosphate ribose） polymerase activation and the expressions of ICAM-1 and P-selectin in HT-29 cells. 5-Aminoisoquinolinone probably contributes to the prevention of tumor cell metastasis. Further study is needed.
