AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar ...AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.展开更多
As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great ...As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great threat to human health.In this study,we constructed a novel fungal pathogen-responsive assembly of cuprous oxide(Cu_(2)O)nanoparticles(NPs)for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen,Candida albicans(C.albicans).This assembly was formed by coating the initial Cu_(2)O NPs with both phosphatidylethanolamine(PE)and bovine serum albumin(BSA),followed by hydrophobic/electrostatic interaction-driven formation of the Cu_(2)O-PE-BSA microaggregates.The formed microaggregates could be induced for disassembly by the fungal pathogen C.albicans,leading to close binding of the NPs to the cell wall of the pathogen.Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen,but had extreme low toxicity to mammalian cells.In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues.This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.展开更多
Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found ...Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase. Moreover, they can promote the endothelial cell proliferation, migration and angiogenesis by secreting several proteins. Fibrocytes can further differentiate into mature mesenchymocyte lineage, such as fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds. A deep understanding of the mechanism involved in fibrocyte migration and differentiation may lead to the development of a novel theory of normal physiology and pathology.展开更多
基金Supported by A GrantinAid for Scientific Research(B)to Toshikazu Yoshikawa(Grant No.21390184)Challenging Exploratory Research to Yuji Naito(No.08101559)from the Japan Society for the Promotion of Science+1 种基金A City Area Program to Toshikazu Yoshikawa and Yuji Naito from Ministry of Education,Culture,Sports,Science and Technology,JapanAn Adaptable and Seamless Technology Transfer Program through targetdriven R&D to Yuji Naito from Japan Science and Technology Agency
文摘AIM:To investigate the efficacy of rebamipide in a rat model of colitis and restitution of intestinal epithelial cells in vitro.METHODS:Acute colitis was induced with trinitrobenzene sulfonic acid(TNBS)in male Wistar rats.Rats received intrarectal rebamipide treatment daily starting on day 7 and were sacrificed on day 14 after TNBS administration.The distal colon was removed to evaluate the various parameters of inflammation.Moreover,wound healing assays were used to determine the enhanced restitution of rat intestinal epithelial(RIE)cells treated with rebamipide.RESULTS:Intracolonic administration of rebamipide accelerated TNBSinduced ulcer healing.Increases in the wet weight of the colon after TNBS administration were significantly inhibited by rebamipide.The wound assay revealed that rebamipide enhanced the migration of RIE cells through phosphorylation of extracellular signalregulated kinase(ERK)and activation of Rho kinase.CONCLUSION:Rebamipide enema healed intestinal injury by enhancing restitution of RIE cells,via ERK activation.Rebamipide might be a novel therapeutic approach for inflammatory bowel disease.
基金the National Natural Science Foundation of China(31870139 and 81873961)the Natural Science Foundation of Tianjin(19JCZDJC33800)+1 种基金the National Training Program of Innovation and Entrepreneurship for Undergraduates(201810055105)the Fundamental Research for the Central Universities。
文摘As the increasing number of the individuals suffering from AIDs,chemotherapy,and radiotherapy,pathogenic fungi,which may rapidly grow and invade the host tissues in these immune-compromised patients,is becoming great threat to human health.In this study,we constructed a novel fungal pathogen-responsive assembly of cuprous oxide(Cu_(2)O)nanoparticles(NPs)for specific targeting and inhibiting growth and biofilm formation of the representative fungal pathogen,Candida albicans(C.albicans).This assembly was formed by coating the initial Cu_(2)O NPs with both phosphatidylethanolamine(PE)and bovine serum albumin(BSA),followed by hydrophobic/electrostatic interaction-driven formation of the Cu_(2)O-PE-BSA microaggregates.The formed microaggregates could be induced for disassembly by the fungal pathogen C.albicans,leading to close binding of the NPs to the cell wall of the pathogen.Both confocal microscopy and viability assays showed that the assembly strongly inhibited growth and biofilm formation of the pathogen,but had extreme low toxicity to mammalian cells.In vivo mouse wound model further revealed that the assembly had high capacity of healing the fungus-infected wounds and reduced the fungal burden of the wound tissues.This study sheds a novel light on facile development of pathogen-responsive nano-assemblies for efficient and safe antifungal therapy.
文摘Fibrocytes are bone marrow-derived mesenchymal progenitors that co-express hematopoietic cell antigens and markers of monocytic lineage as well as fibroblast products. During wound healing, fibrocytes have been found to possess the ability of antigen-presentation to naive T cells in the inflammatory phase. Moreover, they can promote the endothelial cell proliferation, migration and angiogenesis by secreting several proteins. Fibrocytes can further differentiate into mature mesenchymocyte lineage, such as fibroblasts, myofibroblasts and adipocytes, and they may represent the systemic source of myofibroblasts that exert a contractile force required to close tissue wounds. A deep understanding of the mechanism involved in fibrocyte migration and differentiation may lead to the development of a novel theory of normal physiology and pathology.