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基于关联网络的空间辐射防护分子靶标的辨识与预测
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作者 谢达菲 关华 +6 位作者 樊婵 胡赛 刘晓丹 谢漪 王豫 张红 周平坤 《科学通报》 EI CAS CSCD 北大核心 2020年第5期392-400,共9页
空间辐射对航天员健康的危害制约人类的空间探索活动,对其中重离子成分的医学防护研究是对抗空间辐射人体健康威胁的关键之一.本研究以地面装置模拟空间辐射环境,用0.5和2 Gy剂量的碳离子(12C^6+)辐照正常人淋巴母细胞AHH-1,照前0.5 h... 空间辐射对航天员健康的危害制约人类的空间探索活动,对其中重离子成分的医学防护研究是对抗空间辐射人体健康威胁的关键之一.本研究以地面装置模拟空间辐射环境,用0.5和2 Gy剂量的碳离子(12C^6+)辐照正常人淋巴母细胞AHH-1,照前0.5 h分别用两种已知的辐射防护药物处理细胞,照后4 h用基因表达芯片测量细胞基因表达谱,构建辐射损伤相关基因表达量调节网络.运用基于模拟退火的迭代搜索算法辨识不同剂量12C^6+辐照及防护药物作用下的辐射相关基因激活子网,依据节点的连接度预测出PPM1A, RIF1, CASP3, TFE3和RIN1等潜在的空间辐射损伤防护高关联度基因.进一步的富集分析表明,这些基因显著富集的分子功能类别主要与转录调节、激活子活性等有关;细胞定位类别主要是核体、染色体等;生物过程类别主要与信号转导、RNA代谢和细胞定位调节等有关.进一步在Hela细胞上通过Western blotting实验证明, 0.5和2 Gy剂量12C^6+辐照后, RIF1基因表达量显著上升,辐照后4 h的相对表达率达到对照组的2倍以上.这种辨识方法通过计算分析理性预测和发掘潜在的辐射损伤防护高关联度人类基因,为重离子辐射损伤医学防护研究提供了新的策略和内容.辨识所得分子靶标为有针对性地进行空间辐射损伤防护药物的研发提供了候选靶标,为细胞响应电离辐射及防护药物作用的分子机制研究提供了线索与支持,对于空间辐射损伤防护技术的提升具有重要的意义. 展开更多
关键词 基因表达谱 蛋白质相互作用网络 药物靶标 重离子 模拟退火算法
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BVAN08 enhances radiosensitivity via downregulation of DNA-PKcs towards hepatic tumor xenograft
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作者 Bo Zhang Lantao Liu +3 位作者 Sai Hu Zi-Jian Yu dafei xie Pingkun Zhou 《Radiation Medicine and Protection》 2020年第3期103-109,共7页
Objective:To study the effects of the novel vanillin derivative BVAN08 on the radiosensitivity of hepatic cancer cells for the purpose of providing evidence for its potential use as a potential radiosensitive drug.Met... Objective:To study the effects of the novel vanillin derivative BVAN08 on the radiosensitivity of hepatic cancer cells for the purpose of providing evidence for its potential use as a potential radiosensitive drug.Methods:Hepatic cancer Huh-7 cells labeled with luciferase were used to investigate the radiosensitivity induced by BVAN08 in vivo.Colony formation assays and flow cytometry were used to measure the apoptosis and radiosensitivity of Huh-7 cells in vitro produced by BVAN08.Histology and immunohistochemistry were used to evaluate the toxicity of BVAN08 in vivo.Results:BVAN08 induced apoptosis and cell cycle arrest of Huh-7 cells in a time-dependent manner.Moreover,BVAN08 combined with radiation increased the sensitivity of Huh-7 cells toγ-ray radiation and significantly inhibited tumor growth in vivo.The tumor inhibition rates of the BVAN08 treatment group,irradiation treatment group,and combined therapy group were 58%,38%,and 85%,respectively.The DNA-PKcs expression in tumor tissues of the BVAN08 treatment group was lower than that of the control group(P<0.01).BVAN08 inhibited the growth of Huh-7 cells in nude mice bearing tumors,without resulting in any noticeable side effects on bodyweight,livers,hearts,kidneys,or the number of peripheral white blood cells.Conclusions:As a natural food additive derivative,BVAN08 possesses the potential to be used as an effective anticancer drug to increase cell sensitivity to radiotherapy. 展开更多
关键词 Vanillin derivative Cell cycle Apoptosis DNA-PKCS RADIOSENSITIVITY
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