Colitis-associated colorectal cancer(CAC)is a major contributor to cancer-related mortality worldwide.Titanium dioxide(TiO_(2),E171),a widely used food additive,has been insufficiently studied regarding its effects on...Colitis-associated colorectal cancer(CAC)is a major contributor to cancer-related mortality worldwide.Titanium dioxide(TiO_(2),E171),a widely used food additive,has been insufficiently studied regarding its effects on macrophages within colon tumors during CAC development.In this study,CAC mouse models were used to investigate the biological impact of dietary E171 on macrophages in vivo,while lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cell lines were employed to elucidate the underlying mechanisms in vitro.We found that dietary E171 intake accelerated CAC development,exacerbated inflammatory responses and oxidative stress,and upregulated CAC-associated genes,including S100a8,S100a9,Lcn2,S100a11,Cxcl2,and interleukin-1α(Il-1α).E171 also increased the expression of S100A8,S100A9,NOD-like receptor family pyrin domain-containing 3(NLRP3),and gasdermin-D Nterminal(GSDMD-N)in macrophages within colon tumors.In inflammatory macrophages,E171 exposure enhanced cell viability,increased reactive oxygen species(ROS)levels,and elevated the expression and secretion of S100A8 and S100A9,consistent with in vivo histological observations.Furthermore,E171-induced secretion of S100A8 and S100A9 in macrophages was suppressed by specific inhibitors,including N-acetylcysteine(NAC,ROS inhibitor),MCC950(NLRP3 inhibitor),Z-YVAD-FMK(caspase 1 inhibitor),disulfiram(GSDMD inhibitor),and transfection of NLRP3 small interfering ribonucleic acid(siRNA).These results indicate that dietary E171 promotes CAC development by activating macrophages,with S100A8 and S100A9 serving as key mediators,and the NLRP3/caspase 1/GSDMD pathway acting as a critical mechanism.展开更多
目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料...目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。展开更多
基金supported by the National Natural Science Foundation of China(Nos.81974441 and 82203619)the Science and Technology Planning Project of Shenzhen Municipality(Nos.JCYJ20190814105619048 and JCYJ20220530154202005)。
文摘Colitis-associated colorectal cancer(CAC)is a major contributor to cancer-related mortality worldwide.Titanium dioxide(TiO_(2),E171),a widely used food additive,has been insufficiently studied regarding its effects on macrophages within colon tumors during CAC development.In this study,CAC mouse models were used to investigate the biological impact of dietary E171 on macrophages in vivo,while lipopolysaccharide(LPS)-stimulated RAW264.7 macrophage cell lines were employed to elucidate the underlying mechanisms in vitro.We found that dietary E171 intake accelerated CAC development,exacerbated inflammatory responses and oxidative stress,and upregulated CAC-associated genes,including S100a8,S100a9,Lcn2,S100a11,Cxcl2,and interleukin-1α(Il-1α).E171 also increased the expression of S100A8,S100A9,NOD-like receptor family pyrin domain-containing 3(NLRP3),and gasdermin-D Nterminal(GSDMD-N)in macrophages within colon tumors.In inflammatory macrophages,E171 exposure enhanced cell viability,increased reactive oxygen species(ROS)levels,and elevated the expression and secretion of S100A8 and S100A9,consistent with in vivo histological observations.Furthermore,E171-induced secretion of S100A8 and S100A9 in macrophages was suppressed by specific inhibitors,including N-acetylcysteine(NAC,ROS inhibitor),MCC950(NLRP3 inhibitor),Z-YVAD-FMK(caspase 1 inhibitor),disulfiram(GSDMD inhibitor),and transfection of NLRP3 small interfering ribonucleic acid(siRNA).These results indicate that dietary E171 promotes CAC development by activating macrophages,with S100A8 and S100A9 serving as key mediators,and the NLRP3/caspase 1/GSDMD pathway acting as a critical mechanism.
文摘目的:探讨血清高迁移率族蛋白B1(HMGB1)、S100β联合脑电双频指数(BIS)在脓毒症相关性脑病(SAE)早期诊断中的应用价值。方法:回顾性分析脓毒症病人87例临床资料,根据是否合并SAE,分为SAE组35例和非SAE组52例。比较2组病人相关临床资料和血清HMGB1、S100β水平及24 h BIS,分析脓毒症病人发生SAE的影响因素和HMGB1、S100β、BIS联合检测早期诊断SAE的临床价值。结果:SAE组病人APACHEⅡ评分、SOFA评分均明显高于非SAE组(P<0.01);SAE组血清HMGB1、S100β水平均明显高于非SAE组(P<0.01),而BIS明显低于非SAE组(P<0.01)。APACHEⅡ评分、SOFA评分和HMGB1、S100β、BIS均为脓毒症病人发生SAE的独立影响因素(P<0.01)。ROC曲线分析显示,血清HMGB1、S100β联合BIS早期诊断脓毒症病人发生SAE的AUC为0.891,敏感度为91.43%,特异度为84.62%,优于各指标独立诊断。结论:血清HMGB1、S100β联合BIS在SAE早期诊断中具有较好的临床应用价值。
