P143 epithelial-derived selenoprotein p protects from colitis-associated carcinogenesis

Patients with inflammatory bowel disease demonstrate selenium nutritional deficiencies and are at increased risk  for colon cancer. Previously, we determined that global loss of the selenium-containing antioxidant protein, Selenoprotein P (SELENOP), exacerbates experimental colitis-associated cancer (CAC). Using a variety of tissue-specific knockout mouse lines, we further determined that epithelial-derived SELENOP served as the primary mediator of disease severity, and Villin-Cre; Selenop f/f (Selenop ΔIEC) mice have increased tumor incidence, number, size, and dysplasia as compared to WT cohorts.
Source: Gastroenterology - Category: Gastroenterology Authors: Tags: Epithelial Cell Biology/Function in Inflammation Source Type: research

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Abstract Both human epidemiologic data and animal studies suggest that low serum vitamin D increases the risk of inflammatory bowel disease (IBD) and consequently IBD-associated colorectal cancer. We tested the hypothesis that vitamin D deficiency increases the risk for colitis-associated colon cancer (CAC) by using an established CAC mouse model, 129-Smad3tm1Par/J(Smad3-/-) mice, which have defective transforming growth factor β-signaling and develop colitis and CAC after the administration of dextran sodium sulfate (DSS). After determining a dietary regimen that induced chronic vitamin D deficiency in Smad3...
Source: Comparative Medicine - Category: Zoology Authors: Tags: Comp Med Source Type: research
Abstract Inflammatory bowel disease (IBD) involves chronic inflammation, loss of epithelial integrity, and gastrointestinal microbiota dysbiosis. Effective therapies for IBD have not been established. Accordingly, in this study, we evaluated the effects of inorganic nitrate, a potent nitric oxide (NO) donor and microbiota regulator, in a mouse model of dextran sodium sulfate (DSS)-induced colitis. Mice were pretreated with NaNO3 (2 mM) in their drinking water for 5 days, and NaCl was used as a control. Feces were collected for microbiota analyses. The results showed that oral administration of dietary nitrate co...
Source: Free Radical Biology and Medicine - Category: Biology Authors: Tags: Free Radic Biol Med Source Type: research
Conclusion: Together, our results show the potential of in silico drug discovery to combat harmful human and microbiome-derived proteins and more specifically suggests a potential for retargeting CDCA to inhibit the pro-oncogenic toxin BFT.
Source: Frontiers in cellular and infection microbiology - Category: Microbiology Source Type: research
Abstract BACKGROUND: Sirtuin 1 (SIRT1) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase that is involved in various diseases, including cancers, metabolic diseases, and inflammation-associated diseases. However, the role of SIRT1 in ulcerative colitis (UC) is still confusing. AIM: To investigate the role of SIRT1 in intestinal epithelial cells (IECs) in UC and further explore the underlying mechanisms. METHODS: We developed a coculture model using macrophages and Caco-2 cells. After treatment with the SIRT1 activator SRT1720 or inhibitor nicotinamide (NAM), the expression of oc...
Source: World Journal of Gastroenterology : WJG - Category: Gastroenterology Authors: Tags: World J Gastroenterol Source Type: research
Abstract Blueberry anthocyanins have the ability to efficiently reach the GI tract and exhibit a broad range of biochemical effects. In the context of inflammatory bowel disease (IBD), they remain a promising complement to current IBD treatments. Here, we investigated the anti-inflammatory and antioxidant capabilities of Highbush blueberries in-vitro on two normal colon epithelial cell lines, NCM 356 and CCD 841 CoN using fluorescent microscopy and flow cytometry following stimulation with a pro-inflammatory cytokine cocktail. Treatment with blueberry extract revealed a significant decrease in nuclear and cytoplas...
Source: Nutrition and Cancer - Category: Cancer & Oncology Authors: Tags: Nutr Cancer Source Type: research
In conclusion, our data show how oncogenic and tumor-suppressive drivers of cellular senescence act to regulate surveillance processes that can be circumvented to enable SnCs to elude immune recognition but can be reversed by cell surface-targeted interventions to purge the SnCs that persist in vitro and in patients. Since eliminating SnCs can prevent tumor progression, delay the onset of degenerative diseases, and restore fitness; since NKG2D-Ls are not widely expressed in healthy human tissues and NKG2D-L shedding is an evasion mechanism also employed by tumor cells; and since increasing numbers of B cells express NKG2D ...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Enterococcus faecalis strains are resident intestinal bacteria associated with invasive infections, inflammatory bowel diseases, and colon cancer. Although factors promoting E. faecalis colonization of intestines are not fully known, one implicated pathway is a phosphotransferase system (PTS) in E. faecalis strain OG1RF that phosphorylates gluconate and contains the genes OG1RF_12399 to OG1RF_12402 (OG1RF_12399-12402). We hypothesize that this PTS permits growth in gluconate, facilitates E. faecalis intestinal colonization, and exacerbates colitis. We generated E. faecalis strains containing deletions/point mutations in th...
Source: Infection and Immunity - Category: Infectious Diseases Authors: Tags: Host Response and Inflammation Source Type: research
Besides their long-known critical role in embryonic growth and in cancer development and progression, EphB (Erythropoietin-producing hepatocellular carcinoma type B) receptor tyrosine kinases and their ephrin-B ligands are involved in the modulation of immune responses and in remodelling and maintaining the integrity of the intestinal epithelial layer. These processes are critically involved in the pathogenesis of inflammatory-based disorders of the gut, like inflammatory bowel diseases (IBDs). Accordingly, our aim was to investigate the role of the EphB/ephrin-B system in intestinal inflammation by assessing the local and...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Efficient DNA repair is necessary to prevent cells from becoming dysfunctional or senescent in response to stochastic nuclear DNA damage. This is particularly important in stem cell populations, as there is no outside source to replace their losses, or repair persistent dysfunction. Researchers here note that the DNA damage response fails to trigger sufficiently in old intestinal stem cell populations, and this may be an underlying contributing cause of higher levels of cellular senescence in these cells. Aging is related to disruption of tissue homeostasis, which increases the risks of developing inflammatory bow...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
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