BACKGROUND/OBJECTIVES: Epigenetic regulation by nutrients can influence the development of specific diseases. This study sought to examine the effect of individual nutrients and nutrient families in the context of preventing chronic metabolic diseases via epigenetic regulation. The inhibition of lipid accumulation and inflammation by nutrients including proteins, lipids, vitamins, and minerals were observed, and histone acetylation by histone acetyltransferase (HAT) was measured. Correlative analyses were also performed.MATERIALS/METHODS: Nutrients were selected according to information from the Korean Ministry of Food and Drug Safety. Selected nutrient functionalities, including the attenuation of fatty acid-induced lipid accumulation and lipopolysaccharide-mediated acute inflammation were evaluated in mouse macrophage Raw264.7 and mouse hepatocyte AML-12 cells. Effects of the selected nutrients on in vitro HAT inhibition were also evaluated. RESULTS: Nitric oxide (NO) production correlated with HAT activity, which was regulated by the amino acids group, suggesting that amino acids potentially contribute to the attenuation of NO production via the inhibition of HAT activity. Unsaturated fatty acids tended to attenuate inflammation by inhibiting NO production, which may be attributable to the inhibition of in vitro HAT activity. In contrast to water-soluble vitamins, the lipid-soluble vitamins significantly decreased NO production. Water- and lipid-soluble vitamins both exhibited significant inhibitory activities against HAT. In addition, calcium and manganese significantly inhibited lipid accumulation, NO production, and HAT activity. CONCLUSIONS Several candidate nutrients and their family members may have roles in the prevention of diseases, including hepatic steatosis and inflammation-related diseases (i.e., nonalcoholic steatohepatitis) via epigenetic regulation. Further studies are warranted to determine which specific amino acids, unsaturated fatty acids and lipid-soluble vitamins or specific minerals influence the development of steatosis and inflammatory-related diseases.

Background and Objectives: A recent study revealed that calcitonin gene-related protein (CGRP) plays an important role in inflammatory airway diseases. However, the influence of CGRP on chronic rhinosinusitis (CRS) has not been studied. This study investigated the expression, activity, and potential pathogenic role of CGRP in patients with CRS with nasal polyposis (CRSwNP).Subjects and Method Patients with CRSwNP and control subjects were enrolled. The CRSwNP group was divided according to the presence of eosinophilic polyps and non-eosinophilic polyps. Nasal polyps (NPs) and uncinate tissues (UTs) from patients with CRSwNP and UTs from control subjects were obtained to investigate the expression of α-/β-CGRP and chromogranin A. In addition, the expression patterns of cytokines following exposure to exogenous CGRP were analyzed in dispersed nasal polyp cells (DNPCs) from patients with eosinophilic or non-eosinophilic CRSwNP. The effects of CGRP on lipopolysaccharide (LPS)-induced nuclear factor-kappa light chain enhancer of activated B cells (NF-κB) signaling change were evaluated in THP-1 cells. Results: The expression of α-/β-CGRP and number of CGRP-producing cells were significantly higher in NPs from patients with CRSwNP than in UTs from controls. Exogenous CGRP decreased the expression of inflammatory cytokines and increased that of the anti-inflammatory cytokines in DNPCs from patients with eosinophilic nasal polyps (EPs) and also increased the expression of tissue remodeling-related and anti-inflammatory cytokines in DNPCs from patients with non-eosinophilic nasal polyps (N-EPs). CGRP inhibited the nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor (IκB) phosphorylation and NF-κB translocation in LPS-stimulated M1 macrophages. Conclusion CGRP expression in NPs may play a significant role in nasal polypogenesis through inflammatory modulation, and it could be a future target to modulate certain aspects of CRSwNP.

Background: and Purpose This study aimed to evaluate whether extracellular-vesicle-incorporated microRNAs (miRNAs) are potential biomarkers for cancer-related stroke. Methods: This cohort study compared patients with active cancer who had embolic stroke of unknown sources (cancer-stroke group) with patients with only cancer, patients with only stroke, and healthy individuals (control groups). The expression profiles of miRNAs encapsulated in plasma exosomes and microvesicles were evaluated using microarray and validated using quantitative real-time polymerase chain reaction. The XENO-QTM miRNA assay technology was used to determine the absolute copy numbers of individual miRNAs in an external validation cohort. Results: This study recruited 220 patients, of which 45 had cancer-stroke, 76 were healthy controls, 39 were cancer controls, and 60 were stroke controls. Three miRNAs (miR-205-5p, miR-645, and miR-646) were specifically incorporated into microvesicles in patients with cancer-related stroke, cancer controls, and stroke controls. The area under the receiver operating characteristic curves of these three miRNAs were 0.7692–0.8510 for the differentiation of patients with cancer-stroke from cancer-controls and 0.8077–0.8846 for the differentiation of patients with cancer-stroke from stroke controls. The levels of several miRNAs were elevated in the plasma exosomes of patients with cancer, but were lower than those in plasma microvesicles. An in vivo study showed that systemic injection of miR-205-5p promoted the development of arterial thrombosis and elevation of D-dimer levels. Conclusion Stroke due to cancer-related coagulopathy was associated with deregulated expression of miRNAs, particularly microvesicle-incorporated miR-205-5p, miR-645, and miR-646. Further prospective studies of extracellular-vesicle-incorporated miRNAs are required to confirm the diagnostic role of miRNAs in patients with stroke and to screen the roles of miRNAs in patients with cancer.