Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial ...Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.展开更多
Avian infectious bronchitis virus(IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IB...Avian infectious bronchitis virus(IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3–5days post inoculation(dpi) and in the kidney at 8 dpi, with heavy viral loads at 1–11 and 1–28 dpi,respectively. The expression of m RNAs encoding Toll-like receptor(TLR) 3 and TLR7 were upregulated at 3–8 dpi, and that of TIR-domain-containing adapter-inducing interferon(IFN) β(TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88(My D88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor(TRAF) 3 and TRAF6 were upregulated expression in both tissues.Moreover, melanoma differentiation-associated protein 5(MDA5), laboratory of genetics and physiology 2(LGP2), stimulator of IFN genes(STING), and mitochondrial antiviral signaling protein(MAVS), as well as TANK binding kinase 1(TBK1), inhibitor of kappa B kinase(IKK) ?, IKKα, IKKβ,IFN regulatory factor(IRF) 7, nuclear factor of kappa B(NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β(MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally,consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.展开更多
AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on col...AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) risk.METHODS: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.RESULTS: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P < 0.0001), whereas the TLR4 m RNA showed a basal expression(RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P = 0.26).CONCLUSION: Our findings suggest that 展开更多
目的研究中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte Ratio,NLR)、Toll样受体-2(TLR2)及C反应蛋白/白蛋白(CRP/ALB)水平与股骨颈骨折术后感染的相关性,并分析其在预测股骨颈骨折术后感染中的临床价值。方法选取内蒙古医科大学...目的研究中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte Ratio,NLR)、Toll样受体-2(TLR2)及C反应蛋白/白蛋白(CRP/ALB)水平与股骨颈骨折术后感染的相关性,并分析其在预测股骨颈骨折术后感染中的临床价值。方法选取内蒙古医科大学第二附属医院2018.06-2021.06股骨颈骨折手术279例,根据术后感染情况分为感染组(n=30)和非感染组(n=249),同期60例健康体检合格者纳为对照组,分别在股骨颈骨折患者术后d1及对照组入组后,采集被研究者外周静脉血,电阻法检测NLR水平,酶联免疫吸附法检测TLR2以及CRP/ALB水平。分别比较各组NLR、TLR2以及CRP/ALB水平。先后行单因素及多因素Logistic回归分析,分析影响股骨颈骨折术后感染的独立危险因素。绘制受试者工作特征曲线(ROC),分析术后1 d NLR、TLR2、CRP/ALB水平在预测骨折术后感染中的价值。结果股骨颈骨折患者术后1 d NLR、TLR2、CRP/ALB水平均高于对照组,差异均具有统计学意义(P<0.001)。感染组术后d1 NLR、TLR2、CRP/ALB水平均高于非感染组,差异均具有统计学意义(P<0.05)。多因素回归分析发现,术前贫血、围术期异体输血、手术时间以及术后1 d NLR、TLR2以及CRP/ALB水平是影响股骨颈骨折术后感染的独立因素。绘制ROC曲线发现,术后1 d NLR、TLR2、CRP/ALB单独应用,在预测股骨颈骨折术后感染中,以CRP/ALB最高,其AUC=0.888,95%CI为(0.811~0.964),三指标联合应用则可提高各指标单独应用时效能,其AUC=0.900,95%CI为(0.825~0.975)。结论股骨颈骨折术后1 d外周血NLR、TLR2、CRP/ALB水平异常升高是股骨颈骨折患者术后手术部位感染的独立危险因素,并在预测股骨颈骨折术后感染中具有一定的价值。展开更多
基金supported by a grant-in-aid for Scientific Research from Japan Society for the Promotion of Science(grant number:17K10825)to HS
文摘Aneurysmal subarachnoid hemorrhage remains serious hemorrhagic stroke with high morbidities and mortalities.Aneurysm rupture causes arterial bleeding-induced mechanical brain tissue injuries and elevated intracranial pressure,followed by global cerebral ischemia.Post-subarachnoid hemorrhage ischemia,tissue injuries as well as extravasated blood components and the breakdown products activate microglia,astrocytes and Toll-like receptor 4,and disrupt blood-brain barrier associated with the induction of many inflammatory and other cascades.Once blood-brain barrier is disrupted,brain tissues are directly exposed to harmful blood contents and immune cells,which aggravate brain injuries furthermore.Blood-brain barrier disruption after subarachnoid hemorrhage may be developed by a variety of mechanisms including endothelial cell apoptosis and disruption of tight junction proteins.Many molecules and pathways have been reported to disrupt the blood-brain barrier after subarachnoid hemorrhage,but the exact mechanisms remain unclear.Multiple independent and/or interconnected signaling pathways may be involved in blood-brain barrier disruption after subarachnoid hemorrhage.This review provides recent understandings of the mechanisms and the potential therapeutic targets of blood-brain barrier disruption after subarachnoid hemorrhage.
基金supported by grants from the Natural Science Foundation of China (31360611 and 31160516)Guangxi Natural Science Foundation (2013GXNSFCA01 9010 and 2014GXNSFDA118011)
文摘Avian infectious bronchitis virus(IBV) is a Gammacoronavirus in the family Coronaviridae and causes highly contagious respiratory disease in chickens. Innate immunity plays significant roles in host defense against IBV. Here, we explored the interaction between IBV and the host innate immune system. Severe histopathological lesions were observed in the tracheal mucosa at 3–5days post inoculation(dpi) and in the kidney at 8 dpi, with heavy viral loads at 1–11 and 1–28 dpi,respectively. The expression of m RNAs encoding Toll-like receptor(TLR) 3 and TLR7 were upregulated at 3–8 dpi, and that of TIR-domain-containing adapter-inducing interferon(IFN) β(TRIF) was upregulated at 21 dpi in the trachea and kidney. Myeloid differentiation primary response protein 88(My D88) was upregulated in the trachea during early infection. Tumor necrosis factor receptor-associated factor(TRAF) 3 and TRAF6 were upregulated expression in both tissues.Moreover, melanoma differentiation-associated protein 5(MDA5), laboratory of genetics and physiology 2(LGP2), stimulator of IFN genes(STING), and mitochondrial antiviral signaling protein(MAVS), as well as TANK binding kinase 1(TBK1), inhibitor of kappa B kinase(IKK) ?, IKKα, IKKβ,IFN regulatory factor(IRF) 7, nuclear factor of kappa B(NF-κB), IFN-α, IFN-β, various interleukins(ILs), and macrophage inflammatory protein-1β(MIP-1β) were significantly upregulated in the trachea and downregulated in the kidney. These results suggested that the TLR and MDA5 signaling pathways and innate immune cytokine were induced after IBV infection. Additionally,consistent responses to IBV infection were observed during early infection, with differential and complicated responses in the kidney.
基金Supported by Grants from Brazilian agencies FAPESP,No.2012/15036-8and CNPq,No.304870/2012-9
文摘AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) risk.METHODS: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary antibodies.RESULTS: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P < 0.0001), whereas the TLR4 m RNA showed a basal expression(RQ = 0.74 vs RQ = 1, P = 0.452). Immunohistochemistry analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P = 0.26).CONCLUSION: Our findings suggest that
文摘目的研究中性粒细胞/淋巴细胞比值(neutrophil-to-lymphocyte Ratio,NLR)、Toll样受体-2(TLR2)及C反应蛋白/白蛋白(CRP/ALB)水平与股骨颈骨折术后感染的相关性,并分析其在预测股骨颈骨折术后感染中的临床价值。方法选取内蒙古医科大学第二附属医院2018.06-2021.06股骨颈骨折手术279例,根据术后感染情况分为感染组(n=30)和非感染组(n=249),同期60例健康体检合格者纳为对照组,分别在股骨颈骨折患者术后d1及对照组入组后,采集被研究者外周静脉血,电阻法检测NLR水平,酶联免疫吸附法检测TLR2以及CRP/ALB水平。分别比较各组NLR、TLR2以及CRP/ALB水平。先后行单因素及多因素Logistic回归分析,分析影响股骨颈骨折术后感染的独立危险因素。绘制受试者工作特征曲线(ROC),分析术后1 d NLR、TLR2、CRP/ALB水平在预测骨折术后感染中的价值。结果股骨颈骨折患者术后1 d NLR、TLR2、CRP/ALB水平均高于对照组,差异均具有统计学意义(P<0.001)。感染组术后d1 NLR、TLR2、CRP/ALB水平均高于非感染组,差异均具有统计学意义(P<0.05)。多因素回归分析发现,术前贫血、围术期异体输血、手术时间以及术后1 d NLR、TLR2以及CRP/ALB水平是影响股骨颈骨折术后感染的独立因素。绘制ROC曲线发现,术后1 d NLR、TLR2、CRP/ALB单独应用,在预测股骨颈骨折术后感染中,以CRP/ALB最高,其AUC=0.888,95%CI为(0.811~0.964),三指标联合应用则可提高各指标单独应用时效能,其AUC=0.900,95%CI为(0.825~0.975)。结论股骨颈骨折术后1 d外周血NLR、TLR2、CRP/ALB水平异常升高是股骨颈骨折患者术后手术部位感染的独立危险因素,并在预测股骨颈骨折术后感染中具有一定的价值。
