digestive/alimentary system
• colonic crypts are shorter
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• proliferating cell nuclear antigen (PCNA)-positive colonic cryptic cells are reduced to 36.6% compared to 49.7% in wild-type mice indicating a decrease in proliferating crypt cells
• mice show aberrations in the migration of crypt cells
• marker analysis indicates impaired maturation of crypt cells
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• DSS-treated mice show impaired regeneration of the intestinal epithelium and impaired healing of the colonic mucosa, with mice failing to repair the ulcers following DSS removal
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• mice show increased susceptibility to dextran sulfate sodium (DSS)-induced chronic colitis, with mice showing occult and gross bleeding, liquid diarrhea, shorter colon, more severe inflammation, large and continuous epithelial lesions such as ulcerations, and intensive infiltration of inflammatory cells throughout mucosa, submucosa, and muscle layer of the colon, diminished epithelial proliferation in ulcerated and adjacent areas, and increased collagen deposition in ulcerated areas
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immune system
• mice show increased susceptibility to dextran sulfate sodium (DSS)-induced chronic colitis, with mice showing occult and gross bleeding, liquid diarrhea, shorter colon, more severe inflammation, large and continuous epithelial lesions such as ulcerations, and intensive infiltration of inflammatory cells throughout mucosa, submucosa, and muscle layer of the colon, diminished epithelial proliferation in ulcerated and adjacent areas, and increased collagen deposition in ulcerated areas
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• colonic mucosa shows elevated IFN-gamma level
• DSS-treated mice show greatly induced IFN-gamma levels, indicating an increased inflammatory response
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• colonic mucosa shows elevated interleukin-1 beta level
• DSS-treated mice show greatly induced IL6 levels, indicating an increased inflammatory response
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neoplasm
• DSS-treated mice show predisposition to colitis-associated tumorigenesis, developing masses with fewer DSS cycles, and larger and more frequent tumors; all tumors are in the distal colon-rectum
• hyperplasia and dysplasia are 3- to 3-fold more frequent and adenomas are 5 times more frequent
• neoplasms are of a higher grade and more aggressive than in wild-type mice
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homeostasis/metabolism
• colonic mucosa shows elevated IFN-gamma level
• DSS-treated mice show greatly induced IFN-gamma levels, indicating an increased inflammatory response
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• colonic mucosa shows elevated interleukin-1 beta level
• DSS-treated mice show greatly induced IL6 levels, indicating an increased inflammatory response
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• incorporation of butyrate into phospholipids, cholesterols, and triglycerides is decreased in crypt cells indicating disrupted lipid biosynthesis from butyrate in the colonic mucosa
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• DSS-treated mice show predisposition to colitis-associated tumorigenesis, developing masses with fewer DSS cycles, and larger and more frequent tumors; all tumors are in the distal colon-rectum
• hyperplasia and dysplasia are 3- to 3-fold more frequent and adenomas are 5 times more frequent
• neoplasms are of a higher grade and more aggressive than in wild-type mice
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endocrine/exocrine glands
• colonic crypts are shorter
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cellular
• reactive oxygen species levels and lipid peroxides are higher in the mucosa of DSS-treated mice, indicating increased inflammatory oxidative stress
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