AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained fr...AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.展开更多
AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/D...AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing method.RESULTS VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.展开更多
Ulcerative colitis(UC)is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial.UC-associated carcinogenesis presents a different sequence of tumorigenic event...Ulcerative colitis(UC)is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial.UC-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal cancer.In fact,in UC,the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes,mutation of p53,aneuploidy,and microsatellite instability.Hypermethylation of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory carcinogenesis.Moreover,p53 is frequently mutated in the early stages of UC-associated cancer.Aneuploidy is an independentrisk factor for forthcoming carcinogenesis in UC.Epithelial cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.展开更多
Objective:To investigate the differential expression of microRNA(miRNA)in colon between ulcerative colitis(UC)and ulcerative colitis related colorectal cancer(UCRCC).Methods:An UC mouse model was built by dextran sodi...Objective:To investigate the differential expression of microRNA(miRNA)in colon between ulcerative colitis(UC)and ulcerative colitis related colorectal cancer(UCRCC).Methods:An UC mouse model was built by dextran sodium sulfate,and an UCRCC mouse model by dextran sodium sulfate and 1,2-diformylhydrazine.RNAs were extracted from the colon,purified and hybridized with fluorescence-labeled miRNA oligonucleotide gene chip.Real-time fluorescence quantitative PCR was used to verity the expression variation of miRNA.SAM was employed for the data analysis.Results:The up-regulated miRNA in colon cancer included has-miR-194,hasmiR-215,has-miR-93,has-miR-192,has-miR-92a,has-miR-29b,and has-miR-20a(median false discovery rate<5%),while the down-regulated miRNAs were has-miR-1231,has-miR-195,has-miR-143,and has-miR-145(median false discovery rate<5%).Conclusions:Significant differential expression of miRNA was found between the UC mouse and UCRCC mouse,which may be related to the onset,erosion and transfer of colorectal cancer.展开更多
目的通过观察香连片对DKK-1 m RNA、β-catenin和PCNA蛋白表达的影响,初步明确香连片预防小鼠溃疡性结肠炎癌变的作用机制。方法 48只BALB/C小鼠随机分为空白组、模型组、香连片用药组和柳氮磺胺嘧啶组,采用DMH/DSS复合法诱导小鼠溃疡...目的通过观察香连片对DKK-1 m RNA、β-catenin和PCNA蛋白表达的影响,初步明确香连片预防小鼠溃疡性结肠炎癌变的作用机制。方法 48只BALB/C小鼠随机分为空白组、模型组、香连片用药组和柳氮磺胺嘧啶组,采用DMH/DSS复合法诱导小鼠溃疡性结肠炎癌变模型,造模时间为18周,用药时间为11周。Real-time PCR检测DKK-1基因的表达,SABC免疫组织化学法检测β-catenin和PCNA蛋白的表达。结果 Real-time PCR检测结果表明香连片可以上调DKK-1 m RNA的表达,与模型组比较,差异有统计学意义(P<0.05);免疫组织化学结果表明香连片可以下调β-catenin和PCNA蛋白的表达,与模型组比较,差异具有统计学意义(P<0.05)。结论香连片预防小鼠溃疡性结肠炎癌变的作用机制与上调DKK-1的表达,阻抑Wnt/β-catenin信号通路有一定的关系。展开更多
基金Supported by National Natural Science Foundation of China,No.81072692Natural Science Foundation of Jiangsu Higher Education Institutions of China,No.10KJB320007
文摘AIM:To investigate the expression of interleukin (IL)-22 and its related proteins in biopsy specimens from patients with ulcerative colitis (UC) and UC-related carcinogenesis. METHODS:Biopsy specimens were obtained from patients with inactive (n = 10), mild-to-moderately active (n = 30), severely active (n = 34), initial (n = 30), and chronic UC (n = 44), as well as UC patients with dysplasia (n = 10). Specimens from patients without colonic abnormalities (n = 20) served as controls. Chronic colitis in experimental mice was induced by 2.5% dextran sodium sulfate. The expression levels of IL-22, IL-23, IL-22R1 and phosphorylated STAT3 (p- STAT3) were determined by immunohistochemistry. Bcl-2, cyclin D1 and survivin expression was detected by Western blotting. RESULTS:Patients with active UC had significantly more IL-22, IL-23, IL-22R1 and p-STAT3-positive cells than the patients with inactive UC and normal controls. Furthermore, IL-22 and related proteins were closely related to the severity of the colitis. The expression of IL-22 and IL-22R1 in the tissue of initial UC was stronger than in that of chronic UC, whereas the expression of p-STAT3 was significantly increased in chronic UC tissues. In dysplasia tissues, the expression level of IL-22 and related proteins was higher compared with controls. Mouse colitis model showed that expression of IL-22, IL-22R1 and IL-23 was increased with time, p-STAT3 and the downstream gene were also remarkably upregulated.CONCLUSION:IL-22/STAT3 signaling pathway may be related to UC and UC-induced carcinogenesis and IL-22 can be used as a biomarker in judging the severity of UC.
基金Supported by the National Natural Science Foundation of China,No.81370500 and No.81770559
文摘AIM To investigate the effects of VSL#3 on tumor formation, and fecal and intestinal mucosal microbiota in azoxymethane/dextran sulfate sodium(AOM/DSS) induced mice model. METHODS C57 BL/6 mice were administered AOM/DSS to develop the ulcerative colitis(UC) carcinogenesis model. Mice were treated with 5-ASA(75 mg/kg/d), VSL#3(1.5 × 109 CFU/d), or 5-ASA combined with VSL#3 by gavage from the day of AOM injection for three months(five days/week). The tumor load was compared in each group, and tumor necrosis factor(TNF-α) and interleukin(IL)-6 levels were evaluated in colon tissue. The stool and intestinal mucosa samples were collected to analyze the differences in the intestinal microbiota by 16 s rDNA sequencing method.RESULTS VSL#3 significantly reduced the tumor load in AOM/DSS-induced mice model and decreased the level of TNF-α and IL-6 in colon tissue. The model group had a lower level of Lactobacillus and higher level of Oscillibacter and Lachnoclostridium in fecal microbiota than the control group. After the intervention with 5-ASA and VSL#3, Bacillus and Lactococcus were increased, while Lachnoclostridium and Oscillibacter were reduced. 5-ASA combined with VSL#3 increased the Lactobacillus and decreased the Oscillibacter. The intestinal mucosal microbiota analysis showed a lower level of Bifidobacterium and Ruminococcaceae_UCG-014 and higher level of Al oprevotel a in the model group as compared to the control group. After supplementation with VSL#3, Bifidobacterium was increased. 5-ASA combined with VSL#3 increased the level of both Lachnoclostridium and Bifidobacterium. CONCLUSION VSL#3 can prevent UC-associated carcinogenesis in mice, reduce the colonic mucosal inflammation levels, and rebalance the fecal and mucosal intestinal microbiota.
文摘Ulcerative colitis(UC)is characterized by repeated flare-ups of inflammation that can lead to oncogenic insults to the colonic epithelial.UC-associated carcinogenesis presents a different sequence of tumorigenic events compared to those that contribute to the development of sporadic colorectal cancer.In fact,in UC,the early events are represented by oxidative DNA damage and DNA methylation that can produce an inhibition of oncosuppressor genes,mutation of p53,aneuploidy,and microsatellite instability.Hypermethylation of tumor suppressor and DNA mismatch repair gene promoter regions is an epigenetic mechanism of gene silencing that contribute to tumorigenesis and may represent the first step in inflammatory carcinogenesis.Moreover,p53 is frequently mutated in the early stages of UC-associated cancer.Aneuploidy is an independentrisk factor for forthcoming carcinogenesis in UC.Epithelial cell-T-cell cross-talk mediated by CD80 is a key factor in controlling the progression from low to high grade dysplasia in UC-associated carcinogenesis.
基金funded by the Science and Technology Planning Project of Guangdong Province,China(NO.2011B031800214)
文摘Objective:To investigate the differential expression of microRNA(miRNA)in colon between ulcerative colitis(UC)and ulcerative colitis related colorectal cancer(UCRCC).Methods:An UC mouse model was built by dextran sodium sulfate,and an UCRCC mouse model by dextran sodium sulfate and 1,2-diformylhydrazine.RNAs were extracted from the colon,purified and hybridized with fluorescence-labeled miRNA oligonucleotide gene chip.Real-time fluorescence quantitative PCR was used to verity the expression variation of miRNA.SAM was employed for the data analysis.Results:The up-regulated miRNA in colon cancer included has-miR-194,hasmiR-215,has-miR-93,has-miR-192,has-miR-92a,has-miR-29b,and has-miR-20a(median false discovery rate<5%),while the down-regulated miRNAs were has-miR-1231,has-miR-195,has-miR-143,and has-miR-145(median false discovery rate<5%).Conclusions:Significant differential expression of miRNA was found between the UC mouse and UCRCC mouse,which may be related to the onset,erosion and transfer of colorectal cancer.
文摘目的通过观察香连片对DKK-1 m RNA、β-catenin和PCNA蛋白表达的影响,初步明确香连片预防小鼠溃疡性结肠炎癌变的作用机制。方法 48只BALB/C小鼠随机分为空白组、模型组、香连片用药组和柳氮磺胺嘧啶组,采用DMH/DSS复合法诱导小鼠溃疡性结肠炎癌变模型,造模时间为18周,用药时间为11周。Real-time PCR检测DKK-1基因的表达,SABC免疫组织化学法检测β-catenin和PCNA蛋白的表达。结果 Real-time PCR检测结果表明香连片可以上调DKK-1 m RNA的表达,与模型组比较,差异有统计学意义(P<0.05);免疫组织化学结果表明香连片可以下调β-catenin和PCNA蛋白的表达,与模型组比较,差异具有统计学意义(P<0.05)。结论香连片预防小鼠溃疡性结肠炎癌变的作用机制与上调DKK-1的表达,阻抑Wnt/β-catenin信号通路有一定的关系。
