Increasing dietary nutrient levels modulates colon immune adaptation and alleviates inflammation in the epithelial heterogeneous nuclear ribonucleoprotein I (Hnrnp I) knockout mice.

Heterogeneous nuclear ribonucleoprotein I (HNRNP I) is an RNA-binding protein essential for neonatal immune adaptation by downregulating interleukin-1 receptor-associated kinase (IRAK1) in toll-like receptor (TLR)-mediated NF-κB signaling pathways. TLR-mediated NF-κB is associated with chronic inflammation, including the development of inflammatory bowel diseases. Meanwhile, dietary protein intake is one of the major concerns for individuals with inflammatory bowel diseases. The present study aims to investigate the effects of a protein-enriched diet on intestinal inflammation and immune responses in a mouse model with aberrant NF-κB signaling in the colon. A transgenic mouse model with intestinal-epithelial-cell (IEC) specific Hnrnp I knocked out was used to investigate the effects of protein intake on the immune system in the colon. A control diet (CON) and a nutrient-dense modified diet (MOD) were fed to both the wild-type (WT) and the knockout (KO) male mice for 14 weeks. Inflammatory markers and colonic immune responses were examined, with gene expression and protein expression levels analyzed. IEC-specific Hnrnp I knocked out mice had significantly increased expression of the active NF-κB subunit, P65, in their colons. There was a concomitant induction of mRNA expression of Il1ß, Il6, Cxcl1, and Ccl2. The number of CD4+ T cells in the distal colon was also increased in the KO mice. The results confirmed that KO mice had proinflammatory responses with aberrant NF-κB signaling in the colon. Importantly, increased nutrient density in their diets attenuated colon inflammation by decreasing the expression of proinflammatory cytokines, reducing P65 translocation, downregulating IRAK1, and limiting the number of CD4+ T cells recruited in Hnrnp I KO mice colon. In summary, this study found that a diet with increased nutrient density relieved the inflammation induced by knockout of Hnrnp I, attributable partially to the reduced expression of inflammatory and immune-modulating cytokines in the mouse distal colon.

Molecular Mechanisms Underlying the Link between Diet and DNA Methylation.

DNA methylation is a vital modification process in the control of genetic information, which contributes to the epigenetics by regulating gene expression without changing the DNA sequence. Abnormal DNA methylation-both hypomethylation and hypermethylation-has been associated with improper gene expression, leading to several disorders. Two types of risk factors can alter the epigenetic regulation of methylation pathways: genetic factors and modifiable factors. Nutrition is one of the strongest modifiable factors, which plays a direct role in DNA methylation pathways. Large numbers of studies have investigated the effects of nutrition on DNA methylation pathways, but relatively few have focused on the biochemical mechanisms. Understanding the biological mechanisms is essential for clarifying how nutrients function in epigenetics. It is believed that nutrition affects the epigenetic regulations of DNA methylation in several possible epigenetic pathways: mainly, by altering the substrates and cofactors that are necessary for proper DNA methylation; additionally, by changing the activity of enzymes regulating the one-carbon cycle; and, lastly, through there being an epigenetic role in several possible mechanisms related to DNA demethylation activity. The aim of this article is to review the potential underlying biochemical mechanisms that are related to diet modifications in DNA methylation and demethylation.

Role of food­drug interactions in neurological and psychological diseases.

Given that foods and nutrients have been shown to influence the pharmacokinetics of drugs, drugs may cause changes in the nutritional status of patients and their response to a given drug. Food­drug interactions are particularly relevant for drugs used to treat neurological and psychological diseases. This review provides an overview of food­drug interaction in the treatment of neurological and psychological diseases. A literature search was carried out by collecting data from different reviews, reports, and original articles on general or specific drug interactions with food, in patients with a variety of neurological and psychological diseases. Based on our review, we found that food­drug interactions may alter the expected impact of drug, or cause the development of a drug toxicity. Nutritional status of the patients may also be affected, particularly a change in body weight caused by a change appetite. Metabolism, absorption, and excretion of foods may also be altered, and nutritional insufficiencies may occur. Recent studies show that diet can have a strong influence on gut microbiota and thus, alter drug pharmacokinetics. Therefore, microbiota alterations should also be considered while assessing food­drug interactions. Knowledge of food­drug interactions is critical for improving health of patients with neurological and psychological diseases, and also for improving effectiveness of treatments.

The relationship of serum endocan levels and anti-TNF-alpha therapy in patients with ankylosing spondylitis.

OBJECTIVE: Endocan is a marker for vascular pathogenesis and important mediator of angiogenesis that strongly associates with inflammation and vascular diseases. Growing evidence suggest that inflammatory cytokine tumor necrosis factor (TNF-alpha) plays a role in its regulation and secretion, whereas TNF-alpha inhibitors may have the opposite influence. The aim of this research is to investigate the association between serum endocan and anti-TNF-alpha drug treatment in patients with ankylosing spondylitis (AS). METHODS: Serum endocan levels were analyzed in 42 patients with AS under anti-TNF-alpha usage. Control group consisted of 37 patients with AS who are not receiving anti-TNF drugs. Endocan is analyzed using ESM-1 ELISA kits. The blood glucose and lipid measurements of patients were also assessed. RESULTS: There was no significant change in serum endocan levels among groups. The total cholesterol, triglyceride, and LDL-C levels were higher in patients receiving anti-TNF-alpha; however, differences were not significant. There was no significant correlation between serum endocan levels and blood lipid measurements. CONCLUSION: Anti-TNF-alpha treatment does not affect serum endocan levels in patients with AS. This research has been first to evaluate the relationship between serum endocan and anti-TNF-alpha therapy in AS. Future studies are necessary to verify the exact role of anti-TNF-alpha therapy on serum endocan levels in patients with AS.