摘要：
TNKS1BP1 is a member of the poly(ADP-ribose) polymerase (PARP) superfamily. Our previous studies have demonstrated that TNKS1BP1 plays an important role in DNA damage response. But whether and how TNKS1BP1 associates with cancer is still not clear. Here, we found that TNKS1BP1 was upregulated in human lung adenocarcinoma (LAC) tissues, and was associated with poor overall survival (OS) in LAC patients. Dysregulation of TNKS1BP1 affected the sensitivity of A549 cells to several DNA damage agents including cisplatin, bleomycin, and ionizing radiation. Mechanically, overexpression of TNKS1BP1 increased the accumulation of S phase cells, which was accompanied by a decrease in M phase cells. More importantly, we found TNKS1BP1 regulated genome stability, mainly through affecting the homologous recombination pathway of DNA double-strand breaks by inhibiting the RAD51 foci formation. Overall, our study indicates that, in LAC, aberrant expressions of TNKS1BP1 are common events, and overexpression of TNKS1BP1 might affect outcomes of cancer patients to chemotherapy and radiotherapy.
作者机构：
[Feng, Shaolong; Wang, Wuxiang; Deng, Ziyong; Zhou, Furong; Liao, Fen] Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;[Wang, Wuxiang] Univ South China, Lib, Hengyang 421001, Peoples R China.;[Feng, Yuqin] Jilin Univ, Coll Mat Sci & Engn, Changchun 130022, Peoples R China.;[Wang, Xinming] Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangzhou 510640, Guangdong, Peoples R China.
通讯机构：
[Feng, Shaolong] U;[Wang, Xinming] C;Univ South China, Sch Publ Hlth, Hengyang 421001, Peoples R China.;Chinese Acad Sci, Guangzhou Inst Geochem, State Key Lab Organ Geochem, Guangzhou 510640, Guangdong, Peoples R China.
关键词：
Fine particulate matter (PM2.5);Endothelial cell (EC);Apoptosis;p53;Guangzhou
摘要：
Exposure to airborne fine particulate matter (PM2.5) is associated with cardiovascular diseases (CVDs). Nevertheless, a comprehensive understanding of the underlying biological mechanisms by which PM2.5 exposure induces or aggravates CVD5 remain insufficiently clear. In the present study, the flow cytometry was employed to investigate the apoptosis of human umbilical vein endothelial cells (HUVECs) induced by PM2.5 in culture. The underlying apoptotic pathway was also studied through the determination of the protein expression and activation of p53, Bax, Bcl-2, caspases-9, -7, -3, and PARP by western blot. The results showed that PM2.5 could significantly induce the apoptosis of HUVECs at the tested concentrations (0.2,1, 5, 25 mu g mL(-1)), compared with the negative control (p < 0.05, p < 0.01). The apoptotic rate of HUVECs increased with the elevating levels of PM2.5 exposure, showing a clear dose-effect relationship. Moreover, the increasing phosphorylation of p53, decreasing ratio of Bcl-2/Bax, and enhancing activation of the downstream proteins caspase-9, -7, -3 and PARP, were also observed with the increasing concentrations of PM2.5 administration in the western blot, indicating that the intracellular approach of apoptosis, the p53-Bax-caspases pathway, is the major way of PM2.5-induced apoptosis in HUVECs. In conclusion, these results suggested that induction of EC apoptosis is an important mechanism by which ambient PM2.5 exposure poses adverse effects on the cardiovascular system. (C) 2017 Elsevier Ltd. All rights reserved.
作者机构：
[Zhang, Peng; Chai, Zhifang; Ma, Yuhui; Wang, Guohua; Zhang, Zhiyong; Zhang, Junzhe; Ding, Yayun; Xie, Changjian; He, Xiao; Luo, Wenhe] Chinese Acad Sci, Inst High Energy Phys, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China.;[Zhang, Zhaohui] Univ South China, Sch Publ Hlth, Hengyang, Hunan, Peoples R China.;[Qu, Meihua] Weifang Med Univ, Weifang 261042, Shandong, Peoples R China.;[Zhang, Jing; Chu, Shengqi] Chinese Acad Sci, Inst High Energy Phys, Beijing Synchrotron Radiat Facil, Beijing 100049, Peoples R China.;[Zhang, Zhiyong] Univ Chinese Acad Sci, Sch Phys Sci, Beijing 100049, Peoples R China.
通讯机构：
[Zhang, Zhiyong] C;Chinese Acad Sci, Inst High Energy Phys, Key Lab Biomed Effects Nanomat & Nanosafety, Beijing 100049, Peoples R China.
关键词：
CeO2 NPs;Phytotoxicity;Phosphate;Transformation;Agar medium
摘要：
Fate and toxicity of manufactured nanoparticles (NPs) in the living organisms and the environment are highly related to their transformation. In the present study, the effect of phosphate on the phytotoxicity and transformation of CeO2 NPs was investigated in an agar medium using head lettuce plants that are sensitive to Ce3+ ions. Plants were treated by CeO2 NPs with or without phosphate for 10 days. Results suggest that the treatments of P deficiency (P(-)) and CeO2 NPs (P(+)&Ce) could separately induce significant inhibition on the growth of lettuce seedlings and cause oxidative stress, but the inhibition was the most serious when the two conditions were combined (P(-)&Ce). In the absence of phosphate, more CeO2 NPs were transformed to Ce(III) in the roots and more Ce3+ ions were translocated to the shoots, which induced higher toxicity to head lettuce. Phosphates could alleviate the phytotoxic effect of CeO2 NPs through the precipitation of dissociated Ce3+ ions. Considering the wide existence of phosphate in the environment, phosphate-related transformation may be a critical factor in evaluating the toxicity and fate of many other metal-based NPs. (C) 2017 Elsevier Ltd. All rights reserved.
期刊：
Pathogens and Disease,2017年75(7):188-188 ISSN：2049-632X
通讯作者：
Chen, Lili
作者机构：
[Bai, Qinqin; Zeng, Xindian; Chen, Lili; Zhou, Pufan; Liu, Ziqing; Zhou, Peng; Sun, Yuanbin] Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Chen, Shenghua] Univ South China, Med Coll, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Wu, Haiying] Univ South China, Affiliated Hosp 2, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.;[Hu, Chunsheng] Hunan Prov Ctr Dis Control & Provent, Outpatient Dept, Changsha 421000, Hunan, Peoples R China.;[Chen, Yuyu] Cent S Univ, Hunan Canc Hosp, Changsha 421000, Hunan, Peoples R China.
通讯机构：
[Chen, Lili] U;Univ South China, Coll Publ Hlth, 28 West Changsheng Rd, Hengyang 421001, Hunan, Peoples R China.
会议名称：
2017年第二届全国特殊病原体学术会议
会议时间：
2017-08-13
会议地点：
南京
会议论文集名称：
2017年第二届全国特殊病原体学术会议论文集
关键词：
Chlamydia psittaci;STAT3;apoptosis;Bax/Bcl-2
摘要：
The Janus kinase-signal transducer and activator of transcription-3 (JAK-STAT3) signaling pathway is a key regulator of cell growth, motility, migration, invasion and apoptosis in mammalian cells. Infection with intracellular pathogens of the genus Chlamydia can inhibit host cell apoptosis, and here we asked whether the JAK-STAT3 pathway participates in chlamydial anti-apoptotic activity. We found that, compared with uninfected cells, levels of JAK1 and STAT3 mRNA as well as total and phosphorylated JAK1 and STAT3 protein were significantly increased in Chlamydia psittaci-infected HeLa cells. Moreover, the apoptosis rate of infected cells was higher after treatment with the tyrosine kinase inhibitor AG-490 (2-cyano-3-(3,4-dihydroxyphenyl)-N-(phenylmethyl)-2-propenamide). Immunoblotting of apoptosis-related proteins showed that C. psittaci infection reduces Bax, but increases Bcl-2, protein levels, resulting in reduced activation of caspase-3, caspase-7, caspase-9 and PARP; AG490 attenuates these effects. Together, our data suggest that the JAK/STAT3 signaling pathway facilitates the anti-apoptotic effect of C. psittaci infection by reducing the Bax/Bcl-2 apoptotic switch ratio, and by inhibiting the intracellular activation of key pro-apoptotic enzymes.
摘要：
Objectives: 4E-BP1 is a family member of eIF4E binding proteins (4E-BPs) which act as the suppressors of cap-dependent translation of RNA via competitively associating with cap-bound eIF4E. RNA translation regulation is an important manner to control the cellular responses to a series of stress conditions such as ionizing radiation (IR)-induced DNA damage response and cell cycle controlling. This study aimed to determine the mechanism of 4E-BP1 stabilization and its potential downstream target(s) in the response to IR. Methods: PI3Ks kinase inhibitors were used to determine the signaling control of 4E-BP1 phosphorylation and protein stability. shRNA strategy was employed to silence the expression of 4E-BP1 in HeLa and HepG2 cells, and determine its effect on the irradiation-induced CHK2 phosphorylation. The protein degradation/stability was investigated by western blotting on the condition of blocking novel protein synthesis by cycloheximide (CHX). Results: The phosphorylation of 4E-BP1 at Thr37/46 was significantly increased in both HepG2 and HeLa cells by ionizing radiation. Depression of 4E-BP1 by shRNA strategy resulted in an incomplete G2 arrest at the early stage of 2 hours post-irradiation, as well as a higher accumulation of mitotic cells at 10 and 12 hours post-irradiation as compared to the control cells. Consistently, the CHK2 phosphorylation at Thr68 induced by IR was also attenuated by silencing 4E-BP1 expression. Both PI3K and DNA-PKcs kinase inhibitors significantly decreased the protein level of 4E-BP1, which was associated with the accelerated degradation mediated by ubiquitination-proteasome pathway. Conclusion: PI3K kinase activity is necessary for maintaining 4E-BP1 stability. Our results also suggest 4E-BP1 a novel biological role of regulating cell cycle G2 checkpoint in responding to IR stress in association with controlling CHK2 phosphorylation.
通讯机构：
[Wan, K.] S;State Key Laboratory for Communicable Disease Prevention and Control, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China
摘要：
In human cells, ribonuclease (RNase) H2 complex is the predominant source of RNase H activities with possible roles in nucleic acid metabolism to preserve genome stability and to prevent immune activation. Dysfunction mutations in any of the three subunits of human RNase H2 complex can result in embryonic/perinatal lethality or cause Aicardi-Goutieres syndrome (AGS). Most recently, increasing findings have shown that human RNase H2 proteins play roles beyond the RNase H2 enzymatic activities in health and disease. Firstly, the biochemical and structural properties of human RNase H2 proteins allow their interactions with various partner proteins that may support functions other than RNase H2 enzymatic activities. Secondly, the disparities of clinical presentations of AGS with different AGS-mutations and the biochemical and structural analysis of AGS-mutations, especially the results from both AGS-knockin and RNase H2-null mouse models, suggest that human RNase H2 complex has certain cellular functions beyond the RNase H2 enzymatic activities to prevent the innate-immune-mediated inflammation. Thirdly, the subunit proteins RNASEH2A and RNASEH2B respectively, not related to the RNase H2 enzymatic activities, have been shown to play a certain role in the pathophysiological processes of different cancer types. In this minireview, we aims to provide a brief overview of the most recent investigations into the biological functions of human RNase H2 proteins and the underlying mechanisms of their actions, emphasizing on the new insights into the roles of human RNase H2 proteins playing beyond the RNase H2 enzymatic activities in health and disease. (C) 2015 Elsevier Ltd. All rights reserved.
摘要：
LIGHT, a costimulatory member of the immunoglobulin superfamily (Ig SF), can greatly impact T cell activation. The role of the LIGHT signaling pathway in chlamydial infection was evaluated in mice following respiratory tract infection with Chlamydia psittaci. Compared with wild type (WT) mice, LIGHT knockout (KO) mice showed significant reduction of body weight, much lower survival rate, higher bacterial burden, prolonged infection time courses and more severe pathological changes in lung tissue. The mRNA levels of IFN-gamma, TNF-alpha, IL-17 and IL-12 in the lung tissue of LIGHT KO mice were significantly lower than those in WT mice. While there was no obvious difference in the percentages of CD4(+) and CD8(+) T cells in the spleens of the two groups of mice, there was a markedly elevated percentage of CD4+ CD25(+) FoxP3(+) Treg cells in LIGHT KO mice. Together, these results demonstrate that the LIGHT signaling pathway is not only required for inflammatory cytokine production as part of the host response to chlamydial infection, but also influences the differentiation of CD4(+) CD25(+) FoxP3(+) Treg cells, both of which may be essential for control of C. psittaci respiratory tract infection. (C) 2016 Elsevier Ltd. All rights reserved.
期刊：
Environmental Toxicology and Pharmacology,2016年45:68-73 ISSN：1382-6689
通讯作者：
Zhou, Yan
作者机构：
[Zhou, Yan; Guo, Wei-Zhen; Zou, Xue-Min] Changsha Med Univ, Sch Publ Hlth, Changsha, Hunan, Peoples R China.;[Fu, Xiao-Ming] Hunan Normal Univ, Xiangnan Affiliated Hosp, Hosp Peoples Liberat Army 169, Hengyang, Hunan, Peoples R China.;[Wu, Cheng-Qiu; He, Dong-Liang] Univ South China, Sch Publ Hlth, Dept Prevent Med, Hengyang, Hunan, Peoples R China.;[He, Dong-Liang] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Nutr & Food Hyg, Wuhan, Hubei, Peoples R China.;[Feng, Wei] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, Dept Occupat & Environm Hlth, Wuhan, Hubei, Peoples R China.
通讯机构：
[Zhou, Yan] C;Changsha Med Univ, Sch Publ Hlth, Changsha, Hunan, Peoples R China.
关键词：
Comet assay;Male infertility;Male reproductive health;Metals;Sperm DNA damage
摘要：
This study aimed to examine associations between urinary metal concentrations and sperm DNA damage. Thirteen metals [arsenic (As), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe), lead (Pb), manganese (Mn), molybdenum (Mo), mercury (Hg), nickel (Ni), selenium (Se), and zinc (Zn)] were detected in urine samples of 207 infertile men from an infertility clinic using inductively coupled plasma mass spectrometry, and also, sperm DNA damage (tail length, percent DNA tail, and tail distributed moment) were assessed using neutral comet assay. We found that urinary Hg and Ni were associated with increasing trends for tail length (both p for trend < 0.05), and that urinary Mn was associated with increasing trend for tail distributed moment (p for trend = 0.02). These associations did persist even when considering multiple metals. Our results suggest that environmental exposure to Hg, Mn, and Ni may be associated with increased sperm DNA damage. (c) 2016 Elsevier B.V. All rights reserved.
作者机构：
[伍永勤; 张平芳; 陈贵梅] Department of Epidemiology and Health Statistics, School of Public Health, University of South China, Hengyang 421001, China;[贺健梅; 邹潇白; 陈曦] Department for AIDS/STD Control and Prevention, Hunan Provincial Center for Disease Control and Prevention, Changsha 410005, China;[Qin, R] Department for AIDS/STD Control and Prevention, Yongding District Center for Disease Control and Prevention, Zhangjiajie 427000, China;[江艳] Department of Epidemiology and Health Statistics, School of Public Health, Xiangnan University, Chenzhou 423000, China;[杨郁君] Department for AIDS/STD Control and Prevention, Zhangjiajie Center for Disease Control and Prevention, Zhangjiajie 427000, China
通讯机构：
[Chen, X.] D;Department for AIDS/STD Control and Prevention, Hunan Provincial Center for Disease Control and Prevention, Changsha, China
作者机构：
[奉水东] Department of Social Medicine and Health Service Management, School of Public Health, Hengyang 421001, China;[凌宏艳; 何剑琴; 张恺芳; 伍迪; 杨丝丝] Department of Physiology, School of Medicine, University of South China, Hengyang 421001, China
摘要：
Novel group quantitative structure-property relationship (QSPR) models on the thermodynamic properties of PBXTHs were presented, by the multiple linear regression (MLR) analysis method. Four thermodynamic properties were studied: the entropy (S-theta), the standard enthalpy of formation (Delta H-f(theta)), the standard Gibbs energy of formation (Delta(f)G(theta)), and the relative standard Gibbs energy of formation (Delta(R)G(theta)). The results by the formula indicate that the calculated and predicted data in this study are in good agreement with those in literature and the deviation is within the experimental errors. To validate the estimation reliability for internal samples and the predictive ability for other samples, leave-one-out (LOO) cross validation (CV) and external validation were performed, and the results show that the models are satisfactory.
