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Chemical screen identifies shikonin as a broad DNA damage response inhibitor that enhances chemotherapy through inhibiting ATM and ATR

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Acta Pharmaceutica Sinica B 2022年第3期12卷 1339-1350页

作者： Fangfang Wang sora jin Franklin Mayca Pozo Danmei Tian Xiyang Tang Yi Dai Xinsheng Yao jinshan Tang Youwei Zhang Institute of Traditional Chinese Medicine and Natural Products College of PharmacyJinan UniversityGuangzhou 510632China Guangdong Province Key Laboratory of Pharmacodynamic Constituents of Traditional Chinese Medicine and New Drug Research Jinan UniversityGuangzhou 510632China Department of Pharmacology Case Comprehensive Cancer CenterCase Western Reserve University School of MedicineClevelandOH 44106USA

DNA damage response(DDR)is a highly conserved genome surveillance mechanism that preserves cell viability in the presence of chemotherapeutic ***,small molecules that inhibit DDR are expected to enhance the anti-cancer effect of *** a recent chemical library screen,we identified shikonin as an inhibitor that strongly suppressed DDR activated by various chemotherapeutic drugs in cancer cell lines derived from different ***,shikonin inhibited the activation of ataxia telangiectasia mutated(ATM),and to a lesser degree ATM and RAD3-related(ATR),two master upstream regulators of the DDR signal,through inducing degradation of ATM and ATR-interacting protein(ATRIP),an obligate associating protein of ATR,*** a result of DDR inhibition,shikonin enhanced the anti-cancer effect of chemotherapeutic drugs in both cell cultures and in mouse *** degradation of ATRIP is proteasome dependent,that of ATM depends on caspase-and lysosome-,but not *** of ATM significantly mitigated DDR inhibition and cell death induced by shikonin and chemotherapeutic *** novel findings reveal shikonin as a pan DDR inhibitor and identify ATM as a primary factor in determining the chemo sensitizing effect of *** data may facilitate the development of shikonin and its derivatives as potential chemotherapy sensitizers through inducing ATM degradation.

关键词： Chemical screen Shikonin DNA damage Response ATM ATR ATRIP Protein degradation Chemo sensitizing

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Characterization of MAGEG2 with testis-specific expression in mice

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Asian Journal of Andrology 2017年第6期19卷 659-665页

作者： Juri Jeong sora jin Heejin Choi Jun Tae Kwon Jihye Kim Jaehwan Kim Zee Yong Park Chunghee Cho School of Life Sciences Gwangju Institute of Science and Technology Gwangju 61005 South Korea.

Male germ cell development is a well-defined process occurring in numerous seminiferous tubules of the testis. Uncovering testicular novel genes related to intrinsic regulation of spermatogenesis is essential for the understanding of spermatogenesis. In the present study, we investigated mouse Mageg2, which belongs to a group of melanoma-associated antigens （MAGEs）. Mageg2 is transcribed in the testis specifically, and its expression level is increased at the pachytene spermatocyte stage, indicating that Mageg2 is expressed predominantly in germ cells. We generated an antibody against mouse MAGEG2 for further characterization at the protein level. Immunoblot analysis suggested that MAGEG2 has specific testicular expression and the expression primarily occurred in pachytene spermatocytes. Proteomic analyses demonstrated that mouse MAGEG2 binded to testicular germ cell-specific serine/threonine-protein kinase 31 （STK31） and heat shock protein 9 （HSPA9）. Direct binding with both interaction partners was confirmed by co-immunoprecipitation. We found that STK31 and HSPA9 bind MAGEG2 directly but not with each other. Interestingly, MAGEG2 reduced the kinase activity of STK31. Our study suggests that mouse MAGEG2 has at least two functions, including chaperone activity related to HSPA9 and regulation of pachytene spermatocyte-specific kinase, STK31. Altogether, our results provide the first information about MAGEG2 at the transcript and protein levels and suggest its potential molecular functions.

关键词： heat shock proteins serine/threonine kinase spermatogenesis testis

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Accidental esophageal intubation via a large type C congenital tracheoesophageal fistula:A case report

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World Journal of Clinical Cases 2022年第30期10卷 11198-11203页

作者： Seong Min Hwang Myeong jin Kim sora Kim Saeyoung Kim Department of Anesthesiology and Pain Medicine School of MedicineKyungpook National UniversityDaegu 41944South Korea

BACKGROUND Tracheoesophageal fistula(TEF)is a congenital anomaly characterized by interruptions in esophageal continuity with or without fistulous communication to the *** management during TEF repair is challenging because of the difficulty of perioperative airway *** is important to determine the appropriate position of the endotracheal tube(ETT)for proper ventilation and to prevent excessive gastric ***,the tip of the ETT should be placed immediately below the fistula and above the *** SUMMARY A full-term,one-day-old,2.4 kg,50 cm male neonate was diagnosed with TEF type *** induction,an ETT was inserted using video laryngoscope and advanced deeply to ensure that the tip passed over the fistula,according to known *** passage of the ETT through the vocal cords was confirmed via video ***,after inflating the ETT cuff,breath sounds were not heard on bilateral lung ***,gastric sounds were *** that a large fistula(approximately 6.60 mm×4.54 mm)located 10.2mm above the carina was confirmed on preoperative tracheal computed tomography,the possibility of unintentional esophageal intubation was highly ***,we decided to uncuff and withdraw the ETT carefully for repositioning,while monitoring auscultation and end-tidal CO2 *** a certain point(9.5 cm from the lip),clear breath sounds and proper end-tidal CO_(2) readings were suddenly achieved,and adequate ventilation was *** Preanesthetic anatomical evaluation with imaging studies in TEF is necessary to minimize complications related to airway management.

关键词： Tracheoesophageal fistula Imaging study Anatomy Intubation Airway management Auscultation Case report

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Quantifying and managing regional greenhouse gas emissions: Waste sector of Daejeon, Korea

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Journal of Environmental Sciences 2014年第6期26卷 1249-1259页

作者： sora Yi Heewon Yang Seung Hoon Lee Kyoung-jin An Department of Urban Planning Research Daejeon Development Institute Department of Environmental Engineering Anyang University Faculty of Science & Technology The Technological and Higher Education Institute of Hong KongNew Territories Hong Kong China

A credible accounting of national and regional inventories for the greenhouse gas （GHG） reduction has emerged as one of the most significant current discussions. This article assessed the regional GHG emissions by three categories of the waste sector in Daejeon Metropolitan City （DMC）, Korea, examined the potential for DMC to reduce GHG emission, and discussed the methodology modified from Intergovernmental Panel on Climate Change and Korea national guidelines. During the last five years, DMC＇s overall GHG emissions were 239 thousand tons C02 eq./year from eleven public environmental infrastructure facilities, with a population of 1.52 million. Of the three categories, solid waste treatment/disposal contributes 68%, whilst wastewater treatment and others contribute 22% and 10% respectively. Among GHG unit emissions per ton of waste treatment, the biggest contributor was waste incineration of 694 kg CO2 eq./ton, followed by waste disposal of 483 kg CO2 eq./ton, biological treatment of solid waste of 209 kg CO2 eq./ton, wastewater treatment of 0.241 kg CO2 eq./m3, and public water supplies of 0.067 kg CO2 eq./m3. Furthermore, it is suggested that the potential in reducing GHG emissions from landfill process can be as high as 47.5% by increasing landfill gas recovery up to 50%. Therefore, it is apparent that reduction strategies for the main contributors of GHG emissions should take precedence over minor contributors and lead to the best practice for managing GHGs abatement.

关键词： Solid waste disposal biological treatment of solid waste waste incineration wastewater treatment public water supply

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基于BLISS和PMA的多学科可靠性设计优化

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航空学报 2013年第10期34卷 2349-2356页

作者：刘云平张俊张冰孙瑾南京信息工程大学信息与控制学院江苏南京210044 山东水利职业学院机电工程系山东日照276826 中信建设有限责任公司北京100027

针对多学科设计优化(MDO)中考虑不确定性而带来的计算复杂性问题,采用序列优化与可靠性评估(sora)法的解耦思想,提出了基于两级集成系统综合(BLISS)策略和性能测量法(PMA)的多学科可靠性设计优化(RBMDO)方法。该方法将传统的3层嵌套循环... 详细信息

针对多学科设计优化(MDO)中考虑不确定性而带来的计算复杂性问题,采用序列优化与可靠性评估(sora)法的解耦思想,提出了基于两级集成系统综合(BLISS)策略和性能测量法(PMA)的多学科可靠性设计优化(RBMDO)方法。该方法将传统的3层嵌套循环的RBMDO方法过程解耦为顺序执行的确定性多学科设计优化(DMDO)和多学科可靠性分析(MRA),DMDO和MRA均采用BLISS策略进行计算,避免了每次多学科设计优化对完整可靠性分析模型的反复调用。飞机起落架缓冲器算例结果表明,文中方法的计算效率较其他两种方法分别提高了52.01%和26.51%,验证了方法的有效性。

关键词：两级集成系统综合性能测量法多学科可靠性设计优化可靠性缓冲器

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18β-甘草次酸通过抑制信号传导与转录激活因子3的激活能够增强人肝癌细胞对索拉非尼的敏感性

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中华实验外科杂志 2018年第8期35卷 1445-1447页

作者：赵冬刘秋梦梁慧芳陈劲张必翔华中科技大学同济医学院附属武汉中心医院检验科武汉430014 华中科技大学同济医学院附属同济医院肝外科中心实验室武汉430030

目的观察18β-甘草次酸（GA）和索拉非尼单独和联合应用对人肝癌细胞株7402的增殖、凋亡和周期的影响，从对信号传导与转录激活因子3（STAT3）通路的影响探讨其可能的机制。方法用100 μmol/L的GA和10 μmol/L的索拉非尼单独和联合应用... 详细信息

目的观察18β-甘草次酸（GA）和索拉非尼单独和联合应用对人肝癌细胞株7402的增殖、凋亡和周期的影响，从对信号传导与转录激活因子3（STAT3）通路的影响探讨其可能的机制。方法用100 μmol/L的GA和10 μmol/L的索拉非尼单独和联合应用于肝癌细胞株7402，用细胞增殖活性检测（CCK-8）和平板克隆方法检测增殖，流式细胞术检测细胞周期凋亡，Western blot检测细胞周期蛋白（Cyclin D1）和STAT3通路的激活情况。结果CCK-8方法结果显示GA和索拉非尼单独处理7402后细胞生存率分别为（74.3±3.3）%和（56.7±5.0）%，联合给药细胞生存率为（42.6±2.8）%。联合给药比单独给药对细胞杀伤作用更加明显，差异均有统计学意义（P=0.000、0.000）。细胞凋亡结果显示，与对照组（5.31±1.53）%的凋亡率比较，GA和索拉非尼单独给药诱导的细胞凋亡率分别为（15.18±2.12）%和（19.18±1.30）%，联合给药细胞凋亡率为（28.29±2.58）%。与单独给药比较，联合给药能进一步增加细胞凋亡数量，差异有统计学意义（P=0.000、0.000）。机制实验中，与对照组比较，索拉非尼单独处理后磷酸化信号传导与转录激活因子3（p-STAT3）表达量变化不明显（t=2.449，P=0.070），而GA组p-STAT3表达量降低（t=34.080，P=0.000），联合给药组p-STAT3表达量显著降低（t=40.420，P=0.000）。结论GA能够通过抑制STAT3的激活增强人肝癌细胞对索拉非尼的敏感性。

关键词： 18β-甘草次酸肝癌增殖凋亡细胞周期信号传导与转录激活因子3

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弓形虫STAg不同接种途径免疫小鼠诱导的免疫应答

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中国生物制品学杂志 2008年第5期21卷 398-400页

作者：刘延庆刘晋平殷国荣马晓明孟晓丽刘红丽山西医科大学医学寄生虫学研究所寄生虫学教研室太原030001 山西农业大学动物科技学院太谷030801

目的观察弓形虫可溶性速殖子抗原（STAg）经滴鼻、灌胃和皮下注射3种途径免疫小鼠诱导的免疫应答。方法5-6周龄BALB／c小鼠32只，随机分为4组，分别以20μgSTAg滴鼻、灌胃或皮下注射免疫小鼠2次，间隔2周，对照组不作处理。末次免疫后14... 详细信息

目的观察弓形虫可溶性速殖子抗原（STAg）经滴鼻、灌胃和皮下注射3种途径免疫小鼠诱导的免疫应答。方法5-6周龄BALB／c小鼠32只，随机分为4组，分别以20μgSTAg滴鼻、灌胃或皮下注射免疫小鼠2次，间隔2周，对照组不作处理。末次免疫后14d脱颈椎处死小鼠，分离脾淋巴细胞和肠上皮内淋巴细胞（IELs）并计数，ELISA法测定血清、肠冲洗液中的弓形虫特异性抗体。结果滴鼻组和皮下注射组的脾淋巴细胞数量高于灌胃组和对照组，灌胃组与对照组相近。滴鼻组的IELs数量高于皮下注射组、灌胃组和对照组，皮下注射组和灌胃组与对照组一致。皮下注射组的血清IgG水平高于滴鼻组、灌胃组和对照组，滴鼻组略高于灌胃组和对照组，但差异无显著意义。滴鼻组的小肠冲洗液sIgA水平高于皮下注射组、灌胃组和对照组，皮下注射注射组和灌胃组略高于对照组，差异无显著意义。结论20腭STAg滴鼻免疫小鼠诱导的黏膜免疫应答优于灌胃和皮下注射；皮下注射免疫小鼠诱导的血清IgG抗体水平高于滴鼻和灌胃，但其未能诱导黏膜免疫应答。

关键词：可溶性速殖子抗原刚地弓形虫免疫应答免疫途径

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