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
纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐...纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐明。本文综述了S100A9在肺、肝、肾、心脏及皮肤等主要纤维化疾病中的研究进展,重点探讨其在细胞信号通路、免疫调节及炎症反应中的作用,旨在为纤维化疾病的诊断和治疗提供新的研究思路。Fibrosis is the terminal stage of various chronic diseases, characterized by excessive accumulation of fibrous connective tissue in tissues, leading to organ structural damage and loss of function. As an important member of the S100 protein family, the role of S100A9 in various inflammatory diseases and cancers has been widely studied, but its role and mechanism in fibrotic diseases have not been fully elucidated. This article reviews the research progress of S100A9 in major fibrotic diseases such as lung, liver, kidney, heart, and skin, with a focus on exploring its role in cellular signaling pathways, immune regulation, and inflammatory response, aiming to provide new research ideas for the diagnosis and treatment of fibrotic diseases.展开更多
为探讨S100A8和S100A9对鼻咽癌细胞系CNE2的影响及是否通过Wnt/β-catenin通路而发挥作用,以培养基添加1μg/m L S100A8/S100A9培养CNE2为实验组,采用划痕、黏附和平板克隆实验分别检测S100A8/S100A9对CNE2细胞的生物学行为影响,同时运...为探讨S100A8和S100A9对鼻咽癌细胞系CNE2的影响及是否通过Wnt/β-catenin通路而发挥作用,以培养基添加1μg/m L S100A8/S100A9培养CNE2为实验组,采用划痕、黏附和平板克隆实验分别检测S100A8/S100A9对CNE2细胞的生物学行为影响,同时运用Western blotting检测CNE2细胞中β-catenin蛋白的累积。实验结果显示,S100A8/S100A9起促进CNE2细胞迁移(p<0.05,p<0.01)、基质黏附(p<0.01)和平板克隆(p<0.01)的作用,且添加S100A8/S100A9蛋白后1 h,CNE2细胞中β-catenin的累积明显上调。以上结果显示S100A8/S100A9可促进鼻咽癌细胞CNE2侵袭和迁移及细胞干性增强等生物学行为,其机制可能有Wnt/β-catenin通路的参与。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.
文摘纤维化疾病是多种慢性疾病的终末阶段,其特点是组织中纤维结缔组织的过度积累,导致器官结构破坏和功能丧失。S100A9作为S100蛋白家族的重要成员,在多种炎症性疾病和癌症中的作用已被广泛研究,但其在纤维化疾病中的作用及机制尚未完全阐明。本文综述了S100A9在肺、肝、肾、心脏及皮肤等主要纤维化疾病中的研究进展,重点探讨其在细胞信号通路、免疫调节及炎症反应中的作用,旨在为纤维化疾病的诊断和治疗提供新的研究思路。Fibrosis is the terminal stage of various chronic diseases, characterized by excessive accumulation of fibrous connective tissue in tissues, leading to organ structural damage and loss of function. As an important member of the S100 protein family, the role of S100A9 in various inflammatory diseases and cancers has been widely studied, but its role and mechanism in fibrotic diseases have not been fully elucidated. This article reviews the research progress of S100A9 in major fibrotic diseases such as lung, liver, kidney, heart, and skin, with a focus on exploring its role in cellular signaling pathways, immune regulation, and inflammatory response, aiming to provide new research ideas for the diagnosis and treatment of fibrotic diseases.
文摘为探讨S100A8和S100A9对鼻咽癌细胞系CNE2的影响及是否通过Wnt/β-catenin通路而发挥作用,以培养基添加1μg/m L S100A8/S100A9培养CNE2为实验组,采用划痕、黏附和平板克隆实验分别检测S100A8/S100A9对CNE2细胞的生物学行为影响,同时运用Western blotting检测CNE2细胞中β-catenin蛋白的累积。实验结果显示,S100A8/S100A9起促进CNE2细胞迁移(p<0.05,p<0.01)、基质黏附(p<0.01)和平板克隆(p<0.01)的作用,且添加S100A8/S100A9蛋白后1 h,CNE2细胞中β-catenin的累积明显上调。以上结果显示S100A8/S100A9可促进鼻咽癌细胞CNE2侵袭和迁移及细胞干性增强等生物学行为,其机制可能有Wnt/β-catenin通路的参与。
