The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease （COPD）. However, just 20%-30% smokers dev...The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease （COPD）. However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 （XRCC 1）, a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 （Arg399Gln） and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype （adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028）; after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype （adjusted OR=0.39, 95% CI 0.16=0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively）. In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.展开更多
High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-...High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.展开更多
目的:探讨慢性阻塞性肺病(Chronic obstructive pulmonary disease,COPD)合并呼吸衰竭患者血清胆碱酯酶(Cholinesterase,ChE)、前白蛋白(Prealbumin,PA)、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)水平,分析其对预后的...目的:探讨慢性阻塞性肺病(Chronic obstructive pulmonary disease,COPD)合并呼吸衰竭患者血清胆碱酯酶(Cholinesterase,ChE)、前白蛋白(Prealbumin,PA)、高迁移率族蛋白B1(high mobility group protein B1,HMGB1)水平,分析其对预后的预测价值。方法:选取2021年1月至2022年12月本院收治的86例COPD合并呼吸衰竭患者为研究组,同时选取同期本院收治的82例单纯COPD患者为对照组,另选取同期于本院体检的健康志愿者56例为健康组。比较不同组别血清ChE、PA、HMGB1水平。研究组患者予以常规治疗,依据住院28 d内预后情况分为存活者、病死者。比较分析存活者、病死者治疗前、治疗7 d、治疗14 d后血清各指标水平,并分析其与急性生理学与慢性健康状况(Acute physiology and chronic health evaluationⅡ,APACHEⅡ)评分相关性及其对预后的预测价值。结果:研究组血清ChE、PA水平低于对照组、健康组,HMGB1水平高于对照组、健康组(P<0.05);病死者治疗7 d、治疗14 d后血清ChE、PA水平低于存活者,HMGB1水平高于存活者(P<0.05);治疗7 d、14 d后血清ChE、PA、HMGB1预测预后的AUC大于单项指标预测,且治疗14 d后血清各指标联合预测预后的AUC大于治疗7 d后血清各指标联合预测(P<0.05)。结论:COPD合并呼吸衰竭不同病情程度、不同预后患者血清ChE、PA、HMGB1水平存在显著差异,且与APACHEⅡ评分密切相关,联合检测其水平对预后具有一定预测价值。展开更多
基金supported by a grant from National Natural Science Foundation of China (No.30570794)
文摘The DNA damage, caused by cigarette smoking, can cause airway cell apoptosis and death, which may be associated with the development of chronic obstructive pulmonary disease （COPD）. However, just 20%-30% smokers develop COPD, which suggests that different degrees of DNA repair cause different outcomes in smokers. X-ray repair cross-complementing group 1 （XRCC 1）, a base excision repair protein, has multiple roles in repairing ROS-mediated, basal DNA damage and single-strand DNA breaks. The present study investigated the association between polymorphism in XRCC1 （Arg399Gln） and susceptibility of COPD. A total of 201 COPD cases and 309 controls were recruited and frequency-matched on age and sex. XRCC1 genotype was determined by PCR-restriction fragment length polymorphism analysis. Overall, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD had no significant difference among individuals with Trp/Trp genotype. However, after stratifying by smoking status, in former smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Trp/Trp genotype （adjusted OR=0.22, 95% CI 0.06-0.85, P=0.028）; after stratifying by smoking exposure, in light smokers, compared with those with the XRCC1 Arg/Arg genotype, the risk for COPD was significantly reduced among individuals with Arg/Trp genotype and Trp/Trp genotype （adjusted OR=0.39, 95% CI 0.16=0.94, P=0.036; 0.24, 95% CI 0.07-0.79, P=0.019, respectively）. In conclusion, XRCC1 Arg194Trp genotype is associated with a reduced risk of developing COPD among former and light smokers.
基金funded by the New Xiangya Talent Project of the Third Xiangya Hospital of Central South University(No.20150218)Program for New Century Excellent Talents in University(NCET-13-0605)+1 种基金the National Natural Science Foundation of China(No.81102512)Hunan Provincial Natural Science Foundation of China(No.14JJ7001)
文摘High mobility group box 1 (HMGB1) is a nuclear protein that can bind to DNA and act as a co-factor for gene transcription. When released into extracellular fluid, it plays a proinflammatory role by acting as a damage-associated molecular pattern molecule (DAMP) (also known as an alarmin) to initiate innate immune responses by activating multiple cell surface receptors such as the receptor for advanced glycation end-products (RAGE) and toll-like receptors (TLRs), TLR2, TLR4 or TLR9. This proinflammatory role is now considered to be important in the pathogenesis of a wide range of kidney diseases whether they result from hemodynamic changes, renal tubular epithelial cell apoptosis, kidney tissue fibrosis or inflammation. This review summarizes our current understanding of the role of HMGB1 in kidney diseases and how the HMGB1-mediated signaling pathway may constitute a new strategy for the treatment of kidney diseases. (C) 2016 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
