Regenerating gene IV (RegIV),a member of the regenerating gene family discovered in 2001,has been found to be involved in malignancy in several different organs including the stomach,colorectum,pancreas and prostate,b...Regenerating gene IV (RegIV),a member of the regenerating gene family discovered in 2001,has been found to be involved in malignancy in several different organs including the stomach,colorectum,pancreas and prostate,but the overall expression profile of RegIV has not been reported. To learn more about RegIV,we evaluated its distribution by immunohistochemistry (IHC) in a total of 360 samples including 24 types of normal tissue,40 benign and malignant lesions,and 18 neuroendocrine tumors. We found that in normal tissues,in addition to its relative specificity for the gastrointestinal tract,RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation,RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma (87.5%) and peritumoral tissue (100%) but not in cancer tissue (30.8%). Among neuroendocrine tumors,RegIV had a relatively restricted expression to those of digestive system.展开更多
Objective:To explore the mechanisms of fulminant hepatitis(FH) in the early stages,and to determine the critical pathways in its initiation and progression.Methods:Twelve BALB/c mice were divided into four groups:one ...Objective:To explore the mechanisms of fulminant hepatitis(FH) in the early stages,and to determine the critical pathways in its initiation and progression.Methods:Twelve BALB/c mice were divided into four groups:one group left as negative control and sacrificed immediately after injection of phosphate-buffered saline(PBS),and another three groups with concanavalin A(Con A) administration sacrificed at 1,3,and 6 h after injection.Affymetrix GeneChip Mouse 430 2.0 Array was employed to evaluate the expression profile of each of the 12 samples.Further analysis was done on the microarray data to extract the genes that were differentially expressed.Enrichment analysis was carried out to determine relevant pathways within which regulated genes were significantly enriched.Results:A total of 393,8354 and 11 344 differentially expressed genes were found,respectively,at three time points.During 0-1 h and 1-3 h,most of the pathways enriched with regulated genes were related to immune response and inflammation,among which Toll-like receptor(TLR) signaling and mitogen-activated protein kinase(MAPK) signaling appeared during both phases,while cytokine-cytokine receptor interaction,apoptosis,T cell receptor signaling,and natural killer(NK) cell-mediated cytotoxicity pathways emerged during the second phase.Pathways found to be significant during 3-6 h were mostly related to metabolic processes.Conclusion:The TLR signaling pathway dominates the early responses of Con A-induced FH in mice.It stimulates the production of type I cytokines,therefore recruiting and activating T/NK cells.Activated T/NK cells exert their cytotoxicity on hepatocytes through inducing death receptorintermediated apoptosis,resulting in liver injury.展开更多
基金Project supported by the International Cooperation Program (No. 2007C24009)the Major Project of Natural Foundation of Zhejiang Province (No. D2080011)+1 种基金the Major Special Project of Science and Technology Found of Zhejiang Province (No. 2007C3020)the Natural Science Foundation of Zhejiang Province, China (No. Y2090152)
文摘Regenerating gene IV (RegIV),a member of the regenerating gene family discovered in 2001,has been found to be involved in malignancy in several different organs including the stomach,colorectum,pancreas and prostate,but the overall expression profile of RegIV has not been reported. To learn more about RegIV,we evaluated its distribution by immunohistochemistry (IHC) in a total of 360 samples including 24 types of normal tissue,40 benign and malignant lesions,and 18 neuroendocrine tumors. We found that in normal tissues,in addition to its relative specificity for the gastrointestinal tract,RegIV was detected in the adrenal gland and mammary gland. Among all the malignancies of various histological types under evaluation,RegIV was found mostly in adenocarcinomas. Studies on additional sets of colorectal tumor samples showed that RegIV expression was predominant in colorectal adenoma (87.5%) and peritumoral tissue (100%) but not in cancer tissue (30.8%). Among neuroendocrine tumors,RegIV had a relatively restricted expression to those of digestive system.
基金Project supported by the National Natural Science Foundation of China (No 30771918)the National Basic Research Program (973) of China (No 2007CB512905)the State S & T Projects (11th Five Year) (No 2008ZX10002-007) of China
文摘Objective:To explore the mechanisms of fulminant hepatitis(FH) in the early stages,and to determine the critical pathways in its initiation and progression.Methods:Twelve BALB/c mice were divided into four groups:one group left as negative control and sacrificed immediately after injection of phosphate-buffered saline(PBS),and another three groups with concanavalin A(Con A) administration sacrificed at 1,3,and 6 h after injection.Affymetrix GeneChip Mouse 430 2.0 Array was employed to evaluate the expression profile of each of the 12 samples.Further analysis was done on the microarray data to extract the genes that were differentially expressed.Enrichment analysis was carried out to determine relevant pathways within which regulated genes were significantly enriched.Results:A total of 393,8354 and 11 344 differentially expressed genes were found,respectively,at three time points.During 0-1 h and 1-3 h,most of the pathways enriched with regulated genes were related to immune response and inflammation,among which Toll-like receptor(TLR) signaling and mitogen-activated protein kinase(MAPK) signaling appeared during both phases,while cytokine-cytokine receptor interaction,apoptosis,T cell receptor signaling,and natural killer(NK) cell-mediated cytotoxicity pathways emerged during the second phase.Pathways found to be significant during 3-6 h were mostly related to metabolic processes.Conclusion:The TLR signaling pathway dominates the early responses of Con A-induced FH in mice.It stimulates the production of type I cytokines,therefore recruiting and activating T/NK cells.Activated T/NK cells exert their cytotoxicity on hepatocytes through inducing death receptorintermediated apoptosis,resulting in liver injury.