Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacteria...Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella sp.have been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal models.These bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,B.fragilis toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from Salmonella.These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 MAPK.Moreover,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy process.Treatments with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different degrees.In this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial therapies.Specific bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC.These bacteria may be useful as biomarkers or therapeutic targets for CRC.展开更多
Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were inves...Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.展开更多
肝纤维化是各种慢性肝病进展至肝硬化、肝癌的关键环节,早期准确诊断和评估是逆转肝纤维化的重要前提。目前对于肝纤维化无创的理想诊断方法在不断探索中,但仍缺乏可以调控或抑制肝纤维化进展的关键靶点。白细胞介素(interleukin,IL)-33...肝纤维化是各种慢性肝病进展至肝硬化、肝癌的关键环节,早期准确诊断和评估是逆转肝纤维化的重要前提。目前对于肝纤维化无创的理想诊断方法在不断探索中,但仍缺乏可以调控或抑制肝纤维化进展的关键靶点。白细胞介素(interleukin,IL)-33是IL-1超家族成员,在多种炎症反应、自身免疫性疾病中发挥着重要的调节作用。IL-33通过与其天然受体肿瘤抑制素2(suppression of tumorigenicity 2,ST2)结合,介导免疫调控网络。文章对IL-33/ST2轴的生物学作用、调节炎症及纤维化的作用机制及作为靶点治疗肝纤维化的潜在作用进行综述。展开更多
基金This work was supported by the CAMS Innovation Fund for Medical Sciences(Grant No.2016-I2M-3-007)the National Natural Science Foundation of China(Grant No.81803584)+1 种基金the Technology Major Projects for“Major New Drugs Innovation and Development”(Grant Nos.2018ZX09711001-005-025 and 2018ZX09711001-012)the Inner Mongolian Natural Science Foundation(Grant No.2018LH08032)。
文摘Colorectal cancer(CRC)is the third most common and the second most fatal cancer.In recent years,more attention has been directed toward the role of gut microbiota in the initiation and development of CRC.Some bacterial species,such as Fusobacterium nucleatum,Escherichia coli,Bacteroides fragilis,Enterococcus faecalis,and Salmonella sp.have been associated with CRC,based upon sequencing studies in CRC patients and functional studies in cell culture and animal models.These bacteria can cause host DNA damage by genotoxic substances,including colibactin secreted by pks+Escherichia coli,B.fragilis toxin(BFT)produced by Bacteroides fragilis,and typhoid toxin(TT)from Salmonella.These bacteria can also indirectly promote CRC by influencing host-signaling pathways,such as E-cadherin/β-catenin,TLR4/MYD88/NF-κB,and SMO/RAS/p38 MAPK.Moreover,some of these bacteria can contribute to CRC progression by helping tumor cells to evade the immune response by suppressing immune cell function,creating a proinflammatory environment,or influencing the autophagy process.Treatments with the classical antibacterial drugs,metronidazole or erythromycin,the antibacterial active ingredients,M13@Ag(electrostatically assembled from inorganic silver nanoparticles and the protein capsid of bacteriophage M13),berberine,and zerumbone,were found to inhibit tumorigenic bacteria to different degrees.In this review,we described progress in elucidating the tumorigenic mechanisms of several CRC-associated bacteria,as well as progress in developing effective antibacterial therapies.Specific bacteria have been shown to be active in the oncogenesis and progression of CRC,and some antibacterial compounds have shown therapeutic potential in bacteria-induced CRC.These bacteria may be useful as biomarkers or therapeutic targets for CRC.
文摘Objective： The aim of the research was to study peptidylarginine deiminase type 4 （PAD4/PADI4） expression and its tumodgenic mechanism in hepatocellular carcinomas. Methods： Expressions of PADI4 and p53 were investigated in tumors and non-tumor tissues by Western blot in patients with hepatocellular carcinomas. We constructed plasmid of PADI4-Flag and transfected it in Hela cells to investigate the mechanism. Results： Western blot analysis showed higher PADI4 expression in hepatocellular carcinomas than in the surrounding healthy tissues. Furthermore, by Western blot, we detected decreased p53 levels in the tumor tissues of patients with hepatocellular carcinomas compared to surrounding healthy tissues. In Hela cells transfected with PcDNA3.0-Flag-PADI4 plasmid, the expression of p53 decreased obviously. Conclusion： Our results suggest that PADI4 elevated in the tissues of hepatocellular carcinomas and induced tumorigenic by down-regulating p53 expression.
文摘肝纤维化是各种慢性肝病进展至肝硬化、肝癌的关键环节,早期准确诊断和评估是逆转肝纤维化的重要前提。目前对于肝纤维化无创的理想诊断方法在不断探索中,但仍缺乏可以调控或抑制肝纤维化进展的关键靶点。白细胞介素(interleukin,IL)-33是IL-1超家族成员,在多种炎症反应、自身免疫性疾病中发挥着重要的调节作用。IL-33通过与其天然受体肿瘤抑制素2(suppression of tumorigenicity 2,ST2)结合,介导免疫调控网络。文章对IL-33/ST2轴的生物学作用、调节炎症及纤维化的作用机制及作为靶点治疗肝纤维化的潜在作用进行综述。
