AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis...AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）. METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）. CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.展开更多
Sepsis and subsequent multiple organ dysfunction syndrome(MODS) are frequent complications after severe traumata or burns involving a large area,and these remain as the two most common causes of morbidity and mortalit...Sepsis and subsequent multiple organ dysfunction syndrome(MODS) are frequent complications after severe traumata or burns involving a large area,and these remain as the two most common causes of morbidity and mortality in critical illnesses.Despite the recent rapid advances in intensive展开更多
目的探讨血清高迁移率族蛋白B1(high mobility group box protein 1,HMGB1)及降钙素原(procalcitonin,PCT)水平对新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)诊断和病情评估的价值。方法选取2017年1月~2020年3月海口市妇幼...目的探讨血清高迁移率族蛋白B1(high mobility group box protein 1,HMGB1)及降钙素原(procalcitonin,PCT)水平对新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)诊断和病情评估的价值。方法选取2017年1月~2020年3月海口市妇幼保健院收治的75例新生儿NEC作为病例组和60例健康新生儿作为对照组。75例NEC新生儿根据修正Bell分期分为Ⅰ期(n=28),Ⅱ期(n=37)和Ⅲ期(n=10),根据75例患儿30天的预后情况,将其分为存活组(n=58)和死亡组(n=17)。对照组于出生3天后、病例组于治疗前检测血清HMGB1及PCT水平变化。应用ROC曲线分析血清HMGB1及PCT水平对新生儿NEC诊断及病情评估的价值。结果病例组血清HMGB1(15.60±4.85μg/L vs 3.18±1.14μg/L)及PCT(1.74±0.92ng/ml vs 0.03±0.01 ng/ml)水平明显高于对照组(t=13.628,10.427,P<0.05)。死亡组血清HMGB1(24.50±7.13μg/L vs 9.24±3.18μg/L)及PCT(3.02±1.35ng/ml vs 0.85±0.38 ng/ml)水平明显高于存活组(t=16.217,12.308,P<0.05),差异均有统计学意义。Ⅱ~Ⅲ期血清HMGB1(20.16±6.37μg/L vs 10.54±3.20μg/L)及PCT(2.85±1.30 ng/ml vs 0.94±0.42 ng/ml)水平均明显高于Ⅰ期,差异均有统计学意义(t=8.263,7.624,均P<0.05)。ROC曲线分析显示,HMGB1及PCT两项联合诊断新生儿NEC的曲线下面积(0.872,95%CI:0.814~0.930)最大,其敏感度和特异度较高,分别为87.4%和83.5%。HMGB1及PCT两项联合预测新生儿NEC死亡的曲线下面积(0.893,95%CI:0.836~0.952)最大,其敏感度和特异度较高,分别为89.0%和86.4%。结论血清HMGB1及PCT水平在新生儿NEC中明显升高,且与患儿病情严重程度相关,两项联合检测对新生儿NEC诊断及病情评估具有一定价值。展开更多
目的通过检测类风湿关节炎(RA)患者外周血单个核细胞(PBMC)、血浆中高迁移率族蛋白1(HMGB1)表达,为寻找治疗 RA 的新靶点提供依据。方法采集38例活动期 RA 患者、24例相对稳定期 RA 患者和20例健康对照者外周血。RT-PCR 检测 PBMC HMGB1...目的通过检测类风湿关节炎(RA)患者外周血单个核细胞(PBMC)、血浆中高迁移率族蛋白1(HMGB1)表达,为寻找治疗 RA 的新靶点提供依据。方法采集38例活动期 RA 患者、24例相对稳定期 RA 患者和20例健康对照者外周血。RT-PCR 检测 PBMC HMGB1mRNA 表达,Westernblot 检测 PBMC、血浆 HMGB1蛋白表达。结果与相对稳定期 RA 患者、健康对照者相比,活动期 RA患者 PBMC HMGB1mRNA 表达水平差异无统计学意义(F=1.23,P>0.05),而 HMGB1蛋白表达水平下降(F=70.91,P<0.01),血浆 HMGB1水平显著增高(P<0.001)。相对稳定期 RA 患者与健康对照者之间差异无统计学意义(P>0.05)。活动期 RA 患者血浆 HMGB1水平与 ESR(r_s=0.478,P<0.001)、C-反应蛋白(r_s=0.574,P<0.05)呈正相关。结论 HMGB1与 RA 发病密切相关,并可能成为新的治疗靶点。展开更多
Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflam...Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflammation and coagulation via two separate receptor systems.One is Toll-like receptor 4(TLR4),expressed on cell surfaces and in endosomes,and the other is the cytosolic receptor caspase-11(caspases-4 and-5 in hu-mans).Extracellular LPS binds to high mobility group box 1(HMGB1)protein,a cytokine-like molecule.The HMGB1-LPS complex is transported via receptor for advanced glycated end products(RAGE)-endocytosis to the endolysosomal system to reach the cytosolic LPS receptor caspase-11 to induce HMGB1 release,inflammation,and coagulation that may cause multi-organ failure.The insight that LPS needs HMGB1 assistance to generate severe inflammation has led to successful therapeutic results in preclinical Gram-negative sepsis studies target-ing HMGB1.However,to date,no clinical studies have been performed based on this strategy.HMGB1 is also actively released by peripheral sensory nerves and this mechanism is fundamental for the initiation and prop-agation of inflammation during tissue injury.Homeostasis is achieved when other neurons actively restrict the inflammatory response via monitoring by the central nervous system and the vagus nerve through the cholinergic anti-inflammatory pathway.The neuronal control in Gram-negative sepsis needs further studies since a deeper understanding of the interplay between HMGB1 and acetylcholine may have beneficial therapeutic implications.Herein,we review the synergistic overlapping mechanisms of LPS and HMGB1 and discuss future treatment opportunities in Gram-negative sepsis.展开更多
基金Supported by Samsung Biomedical Research Institute grant,No.SBRI C-A8-219-1
文摘AIM： To examine how High-mobility group box I （HMGB1） regulates hepatocyte apoptosis and, furthermore, to determine whether glycyrrhizin （GL）, a known HMGB1 inhibitor, prevents HMGBl-induced hepatocyte apoptosis.
基金The National Natural Science Foundation of China, No. 30600593
文摘AIM： To investigate the effect of delayed ethyl pyruvate （EP） delivery on distant organ injury, survival time and serum high mobility group box 1 （HMGB1） levels in rats with experimental severe acute pancreatitis （SAP）. METHODS： A SAP model was induced by retrograde injection of artificial bile into the pancreatic ducts of rats. Animals were divided randomly into three groups （n = 32 in each group）： sham group, SAP group and delayed EP treatment group. The rats in the delayed EP treatment group received EP （30 mg/kg） at 12 h, 18 h and 30 h after induction of SAP. Animals were sacrificed, and samples were obtained at 24 h and 48 h after induction of SAP. Serum HMGB1, aspartate arninotransferase （AST）, alanine arninotransferase （ALT）, blood urea nitrogen （BUN）, and creatinine （Cr） levels were measured. Lung wet-to-dry-weight （W/D） ratios and histological scores were calculated to evaluate lung injury. Additional experiments were performed between SAP and delayed EP treatment groups to study the influence of EP on survival times of SAP rats. RESULTS： Delayed EP treatment significantly reduced serum HMGB1 levels, and protected against liver, renal and lung injury with reduced lung W/D ratios （8.22 ±0.42 vs 9.76 ± 0.45, P 〈 0.01）, pulmonary histological scores （7.1 ± 0.7 vs 8.4 ± 1.1, P 〈 0.01）, serum AST （667 ± 103 vs 1 368 ± 271, P 〈 0.01）, ALT （446 ± 91 vs 653 ± 98, P 〈 0.01） and Cr （1.2 ± 0.3 vs 1.8 ± 0.3, P 〈 0.01） levels. SAP rats had a median survival time of 44 h. Delayed EP treatment significantly prolonged median survival time to 72 h （P 〈 0.01）. CONCLUSION： Delayed EP therapy protects against distant organ injury and prolongs survival time via reduced serum HMGBllevels in rats with experimental SAP. EP may potentially serve as an effective new therapeutic option against the inflammatory response and multiple organ dysfunction syndrome （MODS） in SAP patients.
基金Supported,in part,by Grants from the National Basic Research Program of China(No.2005CB522602)National Natural Science Foundation of China(No.30672178,30872683,30800437)National Natural Science Outstanding Youth Foundation of China(No.30125020)
文摘Sepsis and subsequent multiple organ dysfunction syndrome(MODS) are frequent complications after severe traumata or burns involving a large area,and these remain as the two most common causes of morbidity and mortality in critical illnesses.Despite the recent rapid advances in intensive
文摘目的探讨血清高迁移率族蛋白B1(high mobility group box protein 1,HMGB1)及降钙素原(procalcitonin,PCT)水平对新生儿坏死性小肠结肠炎(necrotizing enterocolitis,NEC)诊断和病情评估的价值。方法选取2017年1月~2020年3月海口市妇幼保健院收治的75例新生儿NEC作为病例组和60例健康新生儿作为对照组。75例NEC新生儿根据修正Bell分期分为Ⅰ期(n=28),Ⅱ期(n=37)和Ⅲ期(n=10),根据75例患儿30天的预后情况,将其分为存活组(n=58)和死亡组(n=17)。对照组于出生3天后、病例组于治疗前检测血清HMGB1及PCT水平变化。应用ROC曲线分析血清HMGB1及PCT水平对新生儿NEC诊断及病情评估的价值。结果病例组血清HMGB1(15.60±4.85μg/L vs 3.18±1.14μg/L)及PCT(1.74±0.92ng/ml vs 0.03±0.01 ng/ml)水平明显高于对照组(t=13.628,10.427,P<0.05)。死亡组血清HMGB1(24.50±7.13μg/L vs 9.24±3.18μg/L)及PCT(3.02±1.35ng/ml vs 0.85±0.38 ng/ml)水平明显高于存活组(t=16.217,12.308,P<0.05),差异均有统计学意义。Ⅱ~Ⅲ期血清HMGB1(20.16±6.37μg/L vs 10.54±3.20μg/L)及PCT(2.85±1.30 ng/ml vs 0.94±0.42 ng/ml)水平均明显高于Ⅰ期,差异均有统计学意义(t=8.263,7.624,均P<0.05)。ROC曲线分析显示,HMGB1及PCT两项联合诊断新生儿NEC的曲线下面积(0.872,95%CI:0.814~0.930)最大,其敏感度和特异度较高,分别为87.4%和83.5%。HMGB1及PCT两项联合预测新生儿NEC死亡的曲线下面积(0.893,95%CI:0.836~0.952)最大,其敏感度和特异度较高,分别为89.0%和86.4%。结论血清HMGB1及PCT水平在新生儿NEC中明显升高,且与患儿病情严重程度相关,两项联合检测对新生儿NEC诊断及病情评估具有一定价值。
文摘目的通过检测类风湿关节炎(RA)患者外周血单个核细胞(PBMC)、血浆中高迁移率族蛋白1(HMGB1)表达,为寻找治疗 RA 的新靶点提供依据。方法采集38例活动期 RA 患者、24例相对稳定期 RA 患者和20例健康对照者外周血。RT-PCR 检测 PBMC HMGB1mRNA 表达,Westernblot 检测 PBMC、血浆 HMGB1蛋白表达。结果与相对稳定期 RA 患者、健康对照者相比,活动期 RA患者 PBMC HMGB1mRNA 表达水平差异无统计学意义(F=1.23,P>0.05),而 HMGB1蛋白表达水平下降(F=70.91,P<0.01),血浆 HMGB1水平显著增高(P<0.001)。相对稳定期 RA 患者与健康对照者之间差异无统计学意义(P>0.05)。活动期 RA 患者血浆 HMGB1水平与 ESR(r_s=0.478,P<0.001)、C-反应蛋白(r_s=0.574,P<0.05)呈正相关。结论 HMGB1与 RA 发病密切相关,并可能成为新的治疗靶点。
文摘Gram-negative sepsis is a severe clinical syndrome associated with significant morbidity and mortality.Lipopolysaccharide(LPS),expressed on Gram-negative bacteria,is a potent pro-inflammatory toxin that induces inflammation and coagulation via two separate receptor systems.One is Toll-like receptor 4(TLR4),expressed on cell surfaces and in endosomes,and the other is the cytosolic receptor caspase-11(caspases-4 and-5 in hu-mans).Extracellular LPS binds to high mobility group box 1(HMGB1)protein,a cytokine-like molecule.The HMGB1-LPS complex is transported via receptor for advanced glycated end products(RAGE)-endocytosis to the endolysosomal system to reach the cytosolic LPS receptor caspase-11 to induce HMGB1 release,inflammation,and coagulation that may cause multi-organ failure.The insight that LPS needs HMGB1 assistance to generate severe inflammation has led to successful therapeutic results in preclinical Gram-negative sepsis studies target-ing HMGB1.However,to date,no clinical studies have been performed based on this strategy.HMGB1 is also actively released by peripheral sensory nerves and this mechanism is fundamental for the initiation and prop-agation of inflammation during tissue injury.Homeostasis is achieved when other neurons actively restrict the inflammatory response via monitoring by the central nervous system and the vagus nerve through the cholinergic anti-inflammatory pathway.The neuronal control in Gram-negative sepsis needs further studies since a deeper understanding of the interplay between HMGB1 and acetylcholine may have beneficial therapeutic implications.Herein,we review the synergistic overlapping mechanisms of LPS and HMGB1 and discuss future treatment opportunities in Gram-negative sepsis.
