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
Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a ...Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.展开更多
目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从...目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从而探讨HMGB1与大肠癌细胞增殖活性的关系。方法:免疫组织化学法检测70例大肠癌组织、70例癌旁组织、70例正常大肠组织HMGB1蛋白表达;培养SW620细胞,MTT法检测SW620细胞增殖情况,计算抑制率,绘制抑制率曲线;免疫细胞化学法检测HMGB1蛋白表达情况。结果:HMGB1在大肠癌中呈强阳性表达(80.0%),在癌旁组织中仅有微弱表达,正常大肠组织无表达;HMGB1的阳性率与癌分化程度无关(P>0.05);与肿瘤的大小、浸润、淋巴及血道转移呈正相关(P<0.01);加入不同浓度丁酸钠后,对SW620细胞生长均有抑制作用,且丁酸钠的抑制作用与药物浓度和作用时间呈现一定的正相关;同时,随着药物浓度的增加,HMGB1的表达也有所下降。结论:HMGB1在大肠癌中呈强阳性表达,HMGB1与大肠癌的转移与增殖有着密切的联系,可作为大肠癌生长、转移及预后的重要判定指标。展开更多
目的研究IL-4基因敲除小鼠脑外伤后脑水肿以及血清高迁移率组蛋白（high mobility group box1，HMGB1）和钙结合蛋白S100B的变化，以探讨IL-4对脑外伤脑组织的作用。方法雄性野生型和IL-4基因敲除BALB／cJ小鼠各20只，分别随机分为假手...目的研究IL-4基因敲除小鼠脑外伤后脑水肿以及血清高迁移率组蛋白（high mobility group box1，HMGB1）和钙结合蛋白S100B的变化，以探讨IL-4对脑外伤脑组织的作用。方法雄性野生型和IL-4基因敲除BALB／cJ小鼠各20只，分别随机分为假手术组和颅脑损伤组，每组10只。采用自由落体硬膜外撞击法建立局灶重度脑外伤模型，比较脑水肿含量；Westernblot检测各组小鼠损伤周围脑组织水通道蛋白4（aquaporin-4，APQ4）及HMGB1的表达；酶联免疫吸附（ELISA）法检测脑外伤后血清中HMGB1及S100B的表达。结果（1）脑外伤模型IL-4基因敲除BALB／cJ小鼠损伤侧脑组织含水量明显高于野生型小鼠[wT组：（80．03±0．35）％；IL-4基因敲除组：（81．93±0．41）％；P〈0．05]。（2）Westernblot结果显示，颅脑外伤后IL-4基因敲除BALB／cJ小鼠较野生型小鼠脑组织AQP4和HMGB1表达显著增高。（3）ELISA法结果显示，IL-4基因敲除BALB／cJ小鼠较野生型小鼠脑外伤后血清中HMGB1及S100B的水平明显增高[HMGB1含量：wT组：（9．21±0．74）ng／ml；IL-4基因敲除组：（13．39±1．33）ng／ml，P〈0．05；S100B蛋白含量：wT组：（11．11±0．84）pg／ml；IL-4基因敲除组：（18．11±2．02）pg／ml，P〈0．05]。结论IL-4基因敲除小鼠脑外伤后组织含水量和水通道蛋白-4的表达升高，脑组织和血清中HMGB1的水平升高，血清内钙结合蛋白S100B的含量升高。展开更多
Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proin...Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.展开更多
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
基金supported by grants from the National Natural Science Foundation of China, Nos. 81930031 (to JNZ), 81720108015 (to JNZ), 81901525 (to SZ), 82101440 (to DDS), 81801234 (to YZ) and 82071389 (to GLY)the Natural Science Foundation of Tianjin, Nos. 20JCQNJC01270 (to JWW), 20JCQNJC00460 (to GLY), 18JCQNJC81000 (to HTR)+4 种基金Scientific Research Project of Tianjin Education Commission (Natural Science), No. 2018KJ052 (to ZWZ)Tianjin Health and Health Committee Science and Technology Project, No. QN20015 (to JWW)the Science & Technology Development Fund of Tianjin Education Commission for Higher Education, No. 2016YD02 (to YW)Tianjin Key Science and Technology Projects of Innovative Drugs and Medical Devices, No. 19ZXYXSY00070 (to YW)the Clinical Research Fundation of Tianjin Medical University, No. 2018kylc002 (to YW)
文摘Neuroinflammation and the NACHT,LRR,and PYD domains-containing protein 3 inflammasome play crucial roles in secondary tissue damage following an initial insult in patients with traumatic brain injury(TBI).Maraviroc,a C-C chemokine receptor type 5 antagonist,has been viewed as a new therapeutic strategy for many neuroinflammatory diseases.We studied the effect of maraviroc on TBI-induced neuroinflammation.A moderate-TBI mouse model was subjected to a controlled cortical impact device.Maraviroc or vehicle was injected intraperitoneally 1 hour after TBI and then once per day for 3 consecutive days.Western blot,immunohistochemistry,and TUNEL(terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling)analyses were performed to evaluate the molecular mechanisms of maraviroc at 3 days post-TBI.Our results suggest that maraviroc administration reduced NACHT,LRR,and PYD domains-containing protein 3 inflammasome activation,modulated microglial polarization from M1 to M2,decreased neutrophil and macrophage infiltration,and inhibited the release of inflammatory factors after TBI.Moreover,maraviroc treatment decreased the activation of neurotoxic reactive astrocytes,which,in turn,exacerbated neuronal cell death.Additionally,we confirmed the neuroprotective effect of maraviroc using the modified neurological severity score,rotarod test,Morris water maze test,and lesion volume measurements.In summary,our findings indicate that maraviroc might be a desirable pharmacotherapeutic strategy for TBI,and C-C chemokine receptor type 5 might be a promising pharmacotherapeutic target to improve recovery after TBI.
文摘目的:研究大肠癌组织中高迁移率族蛋白1(high mobility group box 1,HMGB1)的表达,并探讨其与癌分化程度、肿瘤大小以及转移的关系。加入不同浓度丁酸钠后,观察SW620细胞中HMGB1的表达情况,以及不同药物浓度对癌细胞增殖活性的影响,从而探讨HMGB1与大肠癌细胞增殖活性的关系。方法:免疫组织化学法检测70例大肠癌组织、70例癌旁组织、70例正常大肠组织HMGB1蛋白表达;培养SW620细胞,MTT法检测SW620细胞增殖情况,计算抑制率,绘制抑制率曲线;免疫细胞化学法检测HMGB1蛋白表达情况。结果:HMGB1在大肠癌中呈强阳性表达(80.0%),在癌旁组织中仅有微弱表达,正常大肠组织无表达;HMGB1的阳性率与癌分化程度无关(P>0.05);与肿瘤的大小、浸润、淋巴及血道转移呈正相关(P<0.01);加入不同浓度丁酸钠后,对SW620细胞生长均有抑制作用,且丁酸钠的抑制作用与药物浓度和作用时间呈现一定的正相关;同时,随着药物浓度的增加,HMGB1的表达也有所下降。结论:HMGB1在大肠癌中呈强阳性表达,HMGB1与大肠癌的转移与增殖有着密切的联系,可作为大肠癌生长、转移及预后的重要判定指标。
文摘目的研究IL-4基因敲除小鼠脑外伤后脑水肿以及血清高迁移率组蛋白（high mobility group box1，HMGB1）和钙结合蛋白S100B的变化，以探讨IL-4对脑外伤脑组织的作用。方法雄性野生型和IL-4基因敲除BALB／cJ小鼠各20只，分别随机分为假手术组和颅脑损伤组，每组10只。采用自由落体硬膜外撞击法建立局灶重度脑外伤模型，比较脑水肿含量；Westernblot检测各组小鼠损伤周围脑组织水通道蛋白4（aquaporin-4，APQ4）及HMGB1的表达；酶联免疫吸附（ELISA）法检测脑外伤后血清中HMGB1及S100B的表达。结果（1）脑外伤模型IL-4基因敲除BALB／cJ小鼠损伤侧脑组织含水量明显高于野生型小鼠[wT组：（80．03±0．35）％；IL-4基因敲除组：（81．93±0．41）％；P〈0．05]。（2）Westernblot结果显示，颅脑外伤后IL-4基因敲除BALB／cJ小鼠较野生型小鼠脑组织AQP4和HMGB1表达显著增高。（3）ELISA法结果显示，IL-4基因敲除BALB／cJ小鼠较野生型小鼠脑外伤后血清中HMGB1及S100B的水平明显增高[HMGB1含量：wT组：（9．21±0．74）ng／ml；IL-4基因敲除组：（13．39±1．33）ng／ml，P〈0．05；S100B蛋白含量：wT组：（11．11±0．84）pg／ml；IL-4基因敲除组：（18．11±2．02）pg／ml，P〈0．05]。结论IL-4基因敲除小鼠脑外伤后组织含水量和水通道蛋白-4的表达升高，脑组织和血清中HMGB1的水平升高，血清内钙结合蛋白S100B的含量升高。
文摘Sepsis is an infection induced systemic inflammatory response syndrome and is a major cause of morbidity as well as mortality in intensive care units. A growing body of evidence suggests that the activation of a proinflammatory cascade is responsible for the development of immune dysfunction, susceptibility to severe sepsis and septic shock. The present theories of sepsis as a dysregulated inflammatory response and immune function, as manifested by excessive release of inflammatory mediators such as high mobility group box 1 protein （HMGB1）, are supported by increasing studies employing animal models and clinical observations of sepsis. HMGB1, originally described as a DNA-binding protein and released passively by necrotic cells and actively by macrophages/monocytes, has been discovered to be one of essential cytokines that mediates the response to infection, injury and inflammation. A growing number of studies still focus on the inflammation-regulatory function and its contribution to infectious and inflammatory disorders, recent data suggest that HMGB1 formation can also markedly influence the host cell-mediated immunity, including T lymphocytes and macrophages. Here we review emerging evidence that support extracellular HMGB1 as a late mediator of septic complications, and discuss the therapeutic potential of several HMGBl-targeting agents in experimental sepsis. In addition, with the development of traditional Chinese medicine in recent years, it has been proven that traditional Chinese herbal materials and their extracts have remarkable effective in treating severe sepsis. In this review, we therefore provide some new concepts of HMGBl-targeted Chinese herbal therapies in sepsis.
