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The study of precise nutrition intervention for colorectal cancer targeting intestinal flora

ABSTRACT: Interventions: experimental group 1:Lycium barbarum polysaccharides;Experimental group 2:probiotics;experimental group 3:probiotics+ Lycium barbarum polysaccharides;Control group:placebo Primary outcome(s): Short chain fatty acids;IL-1 beta;IL-6;IL-4;IL-10;Immune interferon;tumor necrosis factor;MUC-2;Bcl-xL;NF-kB;IkB alpha;CRP;SIgA;postoperative abdominal pain;Flora richness;Flora diversity;Flora structure Study Design: Parallel

DISEASE(S): Colorectal Cancer

PROVIDER: 2696263 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:This a model from the article: Sequential polarization and imprinting of type 1 T helper lymphocytes by interferon-gamma and interleukin-12. Schulz EG, Mariani L, Radbruch A, Höfer T. Immunity.2009;30(5):666-8. 19409816, Abstract: Differentiation of naive T lymphocytes into type I T helper (Th1) cells requires interferon-gamma and interleukin-12. It is puzzling that interferon-gamma induces the Th1 transcription factor T-bet, whereas interleukin-12 mediates Th1 cell lineage differentiation. We use mathematical modeling to analyze the expression kinetics of T-bet, interferon-gamma, and the IL-12 receptor beta2 chain (IL-12Rbeta2) during Th1 cell differentiation, in the presence or absence of interleukin-12 or interferon-gamma signaling. We show that interferon-gamma induced initial T-bet expression, whereas IL-12Rbeta2 was repressed by T cell receptor (TCR) signaling. The termination of TCR signaling permitted upregulation of IL-12Rbeta2 by T-bet and interleukin-12 signaling that maintained T-bet expression. This late expression of T-bet, accompanied by the upregulation of the transcription factors Runx3 and Hlx, was required to imprint the Th cell for interferon-gamma re-expression. Thus initial polarization and subsequent imprinting of Th1 cells are mediated by interlinked, sequentially acting positive feedback loops of TCR-interferon-gamma-Stat1-T-bet and interleukin-12-Stat4-T-bet signaling. The original model was created by: Edda G. Schulz schulz@drfz.de Theoretical Biophysics, Institute of Biology, Humboldt Universität, Invalidenstrasse 42, 10115 Berlin, Germany. This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2009 The BioModels Team.For more information see the terms of use.To cite BioModels Database, please use Le Novère N., Bornstein B., Broicher A., Courtot M., Donizelli M., Dharuri H., Li L., Sauro H., Schilstra M., Shapiro B., Snoep J.L., Hucka M. (2006) BioModels Database: A Free, Centralized Database of Curated, Published, Quantitative Kinetic Models of Biochemical and Cellular Systems Nucleic Acids Res., 34: D689-D691.

Project description:In animal production the use of probiotics supplements to promote animal health is increasing. The objective of this study was to assess the impact of probiotics administration on global gene expression in dairy cows. Lactating Holstein Friesian cows (n=10) from the North Carolina Agricultural and Technical State University dairy herd were used for the study. Treatment was a 10 ml oral drench of FASTtrak microbial pack (Probiotics) (Conklin Company, Kansas City, MO) at the recommended dose in water or water only (control). This treatment was carried out for 60 days. Whole blood was collected at the beginning (Day 0) and end of the study (Day 60) for microarray analysis. We employed microarray expression profiling as a discovery platform to identify genes with potential association with probiotics supplementation in cows. Gene expression analysis identified 10,859 differentially expressed genes- 1168 upregulated genes and 9691 downregulated gene. Results for pathway analysis showed significant pathways associated with innate immunity such as the Toll-like receptor (TLR) pathway, inflammation response and Wingless (Wnt) signaling pathway. Real-time PCR was used to validate gene expression of members of the TLR and Wnt signaling pathway. Treatment affected the expression of innate and adaptive immune response, cytokine and Wnt pathway genes. Daily administration of probiotics to dairy cows impacts global gene expression and particularly the expression of innate immune genes in dairy cows. Ten animals were enrolled in the study and an initial blood sample was collected (Day 0). Animals (n=5) received either daily supplementations with FASTtrak microbial pack (Probiotics) (Conklin Company, Kansas City, MO) or water daily (control animals) for 60 days. Blood samples were collected at the end of the study from probiotics-treated and control animals for RNA extraction and microarray analysis. In vitro effect of lipopolysaccharide (LPS) endotoxin treatment was evaluated using blood samples collected from probiotics-treated animals (Day 60 samples) to serve as positive control array. A pooled sample was generated by taking equal concentration of RNA from experimental animals in each group. Pooled samples from each group was hybridized on Agilent one color bovine v2 bovine (v2) 4x44KÂ array slides.

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The study of precise nutrition intervention for colorectal cancer targeting intestinal flora

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