Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer deve...Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer development and progression.Interleukin-8(IL-8)is overexpressed in gastric mucosa exposed to H.pylori.The expression of IL-8 directly correlates with a poor prognosis in gastric cancer.IL-8 is multifunctional.In addition to its potent chemotactic activity,it can induce proliferation and migration of cancer cells.In this review,we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer.The relationship between IL-8 and H.pylori is discussed.We also summarize the current therapeutics against IL-8 in gastric cancer.展开更多
Bile acids(BAs)are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption.There are numerous scientific reports describing BAs,especially secondary BAs,as strong car...Bile acids(BAs)are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption.There are numerous scientific reports describing BAs,especially secondary BAs,as strong carcinogens or promoters of colon cancers.Firstly,BAs act as strong stimulators of colorectal cancer(CRC)initiation by damaging colonic epithelial cells,and inducing reactive oxygen species production,genomic destabilization,apoptosis resistance,and cancer stem cells-like formation.Consequently,BAs promote CRC progression via multiple mechanisms,including inhibiting apoptosis,enhancing cancer cell proliferation,invasion,and angiogenesis.There are diverse signals involved in the carcinogenesis mechanism of BAs,with a major role of epidermal growth factor receptor,and its down-stream signaling,involving mitogen-activated protein kinase,phosphoinositide 3-kinase/Akt,and nuclear factor kappa-light-chain-enhancer of activated B cells.BAs regulate numerous genes including the human leukocyte antigen class I gene,p53,matrix metalloprotease,urokinase plasminogen activator receptor,Cyclin D1,cyclooxygenase-2,interleukin-8,and miRNAs of CRC cells,leading to CRC promotion.These evidence suggests that targeting BAs is an efficacious strategies for CRC prevention and treatment.展开更多
Bile acids(BAs)serve as physiological detergents that enable the intestinal absorption and transportation of nutrients,lipids and vitamins.BAs are primarily produced by humans to catabolize cholesterol and play crucia...Bile acids(BAs)serve as physiological detergents that enable the intestinal absorption and transportation of nutrients,lipids and vitamins.BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism,microbiota habitat regulation and cell signaling.BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy,lipid,glucose,and drug metabolism.The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism.Therefore,altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes,such as diabetes mellitus,obesity/hypercholesterolemia,and cardiovascular diseases.BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases.This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases.Moreover,we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders.Finally,we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.展开更多
基金Supported by A research grant,No.0720570,from the National Cancer Center,by the National Research Foundation of Korea(NRF)grant,Basic Research Program,No.2010-0009910MRCfor Gene Regulation,No.2011-0030132 funded by the Korea government(MSIP)
文摘Helicobacter pylori(H.pylori)is a major etiological factor in the development of gastric cancer.Large-scale epidemiological studies have confirmed the strong association between H.pylori infection and both cancer development and progression.Interleukin-8(IL-8)is overexpressed in gastric mucosa exposed to H.pylori.The expression of IL-8 directly correlates with a poor prognosis in gastric cancer.IL-8 is multifunctional.In addition to its potent chemotactic activity,it can induce proliferation and migration of cancer cells.In this review,we focus on recent insights into the mechanisms of IL-8 signaling associated with gastric cancer.The relationship between IL-8 and H.pylori is discussed.We also summarize the current therapeutics against IL-8 in gastric cancer.
文摘Bile acids(BAs)are cholesterol derivatives synthesized in the liver and then secreted into the intestine for lipid absorption.There are numerous scientific reports describing BAs,especially secondary BAs,as strong carcinogens or promoters of colon cancers.Firstly,BAs act as strong stimulators of colorectal cancer(CRC)initiation by damaging colonic epithelial cells,and inducing reactive oxygen species production,genomic destabilization,apoptosis resistance,and cancer stem cells-like formation.Consequently,BAs promote CRC progression via multiple mechanisms,including inhibiting apoptosis,enhancing cancer cell proliferation,invasion,and angiogenesis.There are diverse signals involved in the carcinogenesis mechanism of BAs,with a major role of epidermal growth factor receptor,and its down-stream signaling,involving mitogen-activated protein kinase,phosphoinositide 3-kinase/Akt,and nuclear factor kappa-light-chain-enhancer of activated B cells.BAs regulate numerous genes including the human leukocyte antigen class I gene,p53,matrix metalloprotease,urokinase plasminogen activator receptor,Cyclin D1,cyclooxygenase-2,interleukin-8,and miRNAs of CRC cells,leading to CRC promotion.These evidence suggests that targeting BAs is an efficacious strategies for CRC prevention and treatment.
文摘Bile acids(BAs)serve as physiological detergents that enable the intestinal absorption and transportation of nutrients,lipids and vitamins.BAs are primarily produced by humans to catabolize cholesterol and play crucial roles in gut metabolism,microbiota habitat regulation and cell signaling.BA-activated nuclear receptors regulate the enterohepatic circulation of BAs which play a role in energy,lipid,glucose,and drug metabolism.The gut microbiota plays an essential role in the biotransformation of BAs and regulates BAs composition and metabolism.Therefore,altered gut microbial and BAs activity can affect human metabolism and thus result in the alteration of metabolic pathways and the occurrence of metabolic diseases/syndromes,such as diabetes mellitus,obesity/hypercholesterolemia,and cardiovascular diseases.BAs and their metabolites are used to treat altered gut microbiota and metabolic diseases.This review explores the increasing body of evidence that links alterations of gut microbial activity and BAs with the pathogenesis of metabolic diseases.Moreover,we summarize existing research on gut microbes and BAs in relation to intracellular pathways pertinent to metabolic disorders.Finally,we discuss how therapeutic interventions using BAs can facilitate microbiome functioning and ease metabolic diseases.