Traditional Korean diet high in one-carbon nutrients increases global DNA methylation: implication for epigenetic diet.

PURPOSE: DNA methylation is a major epigenetic phenomenon through which diet affects health and disease. This study aimed to determine the epigenetic influence of the traditional Korean diet (K-diet) on global DNA methylation via one-carbon metabolism. METHODS: A crossover study was conducted on 52 women. Two diets, a K-diet, high in plant foods and low in calories and animal fat, and a control diet, similar to the diet currently consumed in Korea, were provided to all subjects alternately for 4 weeks with a 4-week washout period. Clinical parameters were measured before and after each dietary intervention. Nutrient intake was calculated by using a computer-aided nutritional analysis program. One-carbon metabolites in the serum and global DNA methylation in peripheral mononuclear cells were determined using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: The K-diet group consumed more folate (669.9 ± 6.7 µg vs. 502.7 ± 3.0, p < 0.001), B6, B12, serine, and choline, and less methionine (992.6 ± 63 vs. 1048.3 mg ± 34.1, p < 0.0001) than the control group did. In the K-diet group, the increment of plasma 5-methyltetrahydrofolate (0.08 µg/mL ± 0.11 vs 0.02 ± 0.10, p < 0.009) and decrement of L-homocysteine (- 70.7 ± 85.0 vs - 39.3 ± 69.4, p < 0.0168) were greater than those of the control group. Global DNA methylation was significantly increased in the K-diet group (6.70 ± 3.02% to 9.45 ± 3.69, p < 0.0001) but not in the control group. CONCLUSIONS: A K-diet high in one-carbon nutrients can enhance the global DNA methylation status, suggesting an epigenetic mechanism by which the K-diet conveys health effects. Trial registration Korean Clinical Trial Registry (trial number: KCT0005340, 24/08/2020, retrospectively registered).

Alleviation of Dyslipidemia via a Traditional Balanced Korean Diet Represented by a Low Glycemic and Low Cholesterol Diet in Obese Women in a Randomized Controlled Trial.

A traditional balanced Korean diet (K-diet) may improve energy, glucose, and lipid metabolism. To evaluate this, we conducted a randomized crossover clinical trial, involving participants aged 30-40 years, who were randomly assigned to two groups-a K-diet or westernized Korean control diet daily, with an estimated energy requirement (EER) of 1900 kcal. After a 4-week washout period, they switched the diet and followed it for 4 weeks. The carbohydrate, protein, and fat ratios based on energy intake were close to the target values for the K-diet (65:15:20) and control diet (60:15:25). The glycemic index of the control diet and the K-diet was 50.3 ± 3.6 and 68.1 ± 2.9, respectively, and daily cholesterol contents in the control diet and K-diet were 280 and 150 mg, respectively. Anthropometric and biochemical parameters involved in energy, glucose, and lipid metabolism were measured while plasma metabolites were determined using UPLC-QTOF-MS before and after the 4-week intervention. After the four-week intervention, both diets improved anthropometric and biochemical variables, but the K-diet significantly reduced them compared to the control diet. Serum total cholesterol, non-high-density lipoprotein cholesterol, and triglyceride concentrations were significantly lower in the K-diet group than in the control diet group. The waist circumference (p = 0.108) and insulin resistance index (QUICKI, p = 0.089) tended to be lower in the K-diet group than in the control diet group. Plasma metabolites indicated that participants in the K-diet group tended to reduce insulin resistance compared to those in the control diet group. Amino acids, especially branched-chain amino acids, tyrosine, tryptophan, and glutamate, and L-homocysteine concentrations were considerably lower in the K-diet group than in the control diet group (p < 0.05). Plasma glutathione concentrations, an index of antioxidant status, and 3-hydroxybutyric acid concentrations, were higher in the K-diet group than in the control diet group. In conclusion, a K-diet with adequate calories to meet EER alleviated dyslipidemia by decreasing insulin resistance-related amino acids and increasing ketones in the circulation of obese women.

Choosing Wisely: An idea worth sustaining.

OBJECTIVES: To evaluate the sustainability potential of Choosing Wisely (CW) to address unnecessary medical care at Ontario community hospitals. DATA SOURCES/STUDY SETTING: Ontario community hospitals and their affiliated family health teams (FHTs). STUDY DESIGN: A mixed-methods study involving the administration of a validated sustainability survey to CW implementation teams followed by their participation in focus groups. DATA COLLECTION/EXTRACTION METHODS: Survey data were collected using an Excel file with an embedded, automated scoring system. We collated individual survey scores and generated aggregate team scores. We also performed descriptive statistics for quantitative data (frequencies, means). Qualitative data were triangulated with quantitative assessments to support data interpretations using the meta-matrix method. PRINCIPAL FINDINGS: Fifteen CW implementation teams across four Ontario community hospitals and six affiliated primary care FHTs participated. CW priority areas investigated were de-prescribing of proton pump inhibitors (PPIs) and reducing Pre-Op testing and BUN/Urea lab testing. Survey results showed steady improvements in sustainability scores from baseline to final follow-up among most implementation teams: 10% increase for PPI de-prescribing (six FHTs) and 2% increase (three hospital teams); 18% increase in BUN/Urea lab testing (three hospital teams). Regardless of site or CW priority area, common facilitators were fit with existing processes and workflows, leadership support, and optimized team communication; common challenges were lack of awareness and buy-in, leadership engagement or a champion, and lack of fit with existing workflow and culture. All teams identified at least one challenge for which they co-designed and implemented a plan to maximize the sustainability potential of their CW initiative. CONCLUSIONS: Evaluating the sustainability potential of an innovation such as Choosing Wisely is critical to ensuring that they have the best potential for impact. Our work highlights that implementation teams can be empowered to influence implementation efforts and to realize positive outcomes for their health care services and patients.

A Traditional Korean Diet with a Low Dietary Inflammatory Index Increases Anti-Inflammatory IL-10 and Decreases Pro-Inflammatory NF-κB in a Small Dietary Intervention Study.

Chronic low-grade inflammation may increase the risk of chronic disease, while diets rich in anti-inflammatory components may reduce it. To determine the anti-inflammatory properties of the traditional Korean diet (K-diet) that comprises high amounts of vegetables, fiber and phytochemicals, moderate amounts of legumes, and low amounts of animal fat, ten obese women aged 50-60 years were randomly assigned to the K-diet or control diet group. The control diet was a Westernized Korean diet commonly consumed in Korea, which is high in animal fat and protein. Subjects were housed in metabolic unit-like conditions during the 2-week intervention. Plasma was collected before and after the intervention to measure inflammatory cytokines using ELISA. The dietary inflammatory index (DII) was calculated based on nutrients and food intake. The DII score for the K-diet was lower than that of the control diet (-0.94 ± 1.39 vs. 1.04 ± 1.61, p < 0.001). In the K-diet group, anti-inflammatory interleukin (IL)-10 levels increased (4.45 ± 0.34 pg/mL vs. 5.94 ± 0.33 pg/mL, p = 0.0102), whereas pro-inflammatory nuclear factor kappa B (NF-κB) levels decreased (7.70 ± 0.62 pg/mL vs. 2.71 ± 0.49 pg/mL, p = 0.0015), but not in the control group. In the K-diet group, NF-κB levels negatively correlated with IL-10 levels (r = -0.794, p = 0.006). The K-diet has anti-inflammatory properties, and IL-10 and NF-κB are putative inflammatory markers for K-diet studies.

A Traditional Korean Diet Alters the Expression of Circulating MicroRNAs Linked to Diabetes Mellitus in a Pilot Trial.

The traditional Korean diet (K-diet) is considered to be healthy and circulating microRNAs (miRs) have been proposed as useful markers or targets in diet therapy. We, therefore, investigated the metabolic influence of the K-diet by evaluating the expression of plasma and salivary miRs. Ten women aged 50 to 60 years were divided into either a K-diet or control diet (a Westernized Korean diet) group. Subjects were housed in a metabolic unit-like condition during the two-week dietary intervention. Blood and saliva samples were collected before and after the intervention, and changes in circulating miRs were screened by an miR array and validated by individual RT-qPCRs. In the K-diet group, eight plasma miRs were down-regulated by array (p < 0.05), out of which two miRs linked to diabetes mellitus, hsa-miR26a-5p and hsa-miR126-3p, were validated (p < 0.05). Among five down-regulated salivary miRs, hsa-miR-92-3p and hsa-miR-122a-5p were validated, which are associated with diabetes mellitus, acute coronary syndrome and non-alcoholic fatty liver disease. In the control diet group, validated were down-regulated plasma hsa-miR-25-3p and salivary hsa-miR-31-5p, which are associated with diabetes mellitus, adipogenesis and obesity. The K-diet may influence the metabolic conditions associated with diabetes mellitus, as evidenced by changes in circulating miRs, putative biomarkers for K-diet.

Nurse Prompting for Prescriber-Led Review of Antimicrobial Use in the Critical Care Unit.

BACKGROUND: Developing a sustainable strategy for prescriber-led review of antimicrobial use in a critical care unit may improve antimicrobial use without the need for additional resources. METHODS: Using a quality improvement framework, the researchers created a prompt for prescriber-led review of antimicrobial use. The outcome measure was antimicrobial use (days of therapy per 1000 patient days). The process measure was the proportion of relevant cases for which an antimicrobial prompt was provided. Balancing measures included mortality rate, length of stay, 48-hour readmission rates, and multiple organ dysfunction score. Interrupted time series with segmented regression analysis was used for the outcome measure. RESULTS: Process analysis identified critical care unit nurses for antimicrobial use prompting. A standard script was developed to incorporate a days of therapy prompt into nurse rounds, with primed prescriber responses. Before the intervention, monthly antimicrobial use was 804 days of therapy per 1000 patient days, with a positive trend (7.3 days of therapy per 1000 patient days, P < .05). After the intervention, there was an immediate reduction of 217 days of therapy per 1000 patient days (P < .05), with a nonsignificant negative trend, representing a 20% (95% CI, -15% to -25%) reduction. No significant change was noted in use of the control class of medications. The proportion of relevant cases for which an antimicrobial prompt was provided increased from 21% to 48% during the intervention period. Balancing measures were comparable before and after the intervention. CONCLUSIONS: Nurse prompting can lead to significant reductions in antimicrobial use, providing a sustainable mechanism for independent antimicrobial reassessment.

Walnut phenolic extracts reduce telomere length and telomerase activity in a colon cancer stem cell model.

BACKGROUND/OBJECTIVES: Telomeres are located at the chromosomal ends and progressively shortened during each cell cycle. Telomerase, which is regulated by hTERT and c-MYC, maintains telomeric DNA sequences. Especially, telomerase is active in cancer and stem cells to maintain telomere length for replicative immortality. Recently we reported that walnut phenolic extract (WPE) can reduce cell viability in a colon cancer stem cell (CSC) model. We, therefore, investigated the effect of WPE on telomere maintenance in the same model. MATERIALS/METHODS: CD133+CD44+ cells from HCT116, a human colon cancer cell line, were sorted by Fluorescence-activated cell sorting (FACS) and treated with WPE at the concentrations of 0, 10, 20, and 40 µg/mL for 6 days. Telomere lengths were assessed by quantitative real-time PCR (qRT-PCR) using telomere specific primers and DNA extracted from the cells, which was further adjusted with single-copy gene and reference DNA (ddCt ). Telomerase activity was also measured by qRT-PCR after incubating the PCR mixture with cell protein extracts, which was adjusted with reference DNA (dCt ). Transcriptions of hTERT and c-MYC were determined using conventional RT-PCR. RESULTS: Telomere length of WPE-treated cells was significantly decreased in a dose-dependent manner (5.16 ± 0.13 at 0 µg/mL, 4.79 ± 0.12 at 10 µg/mL, 3.24 ± 0.08 at 20 µg/mL and 3.99 ± 0.09 at 40 µg/mL; P = 0.0276). Telomerase activities concurrently decreased with telomere length (1.47 ± 0.04, 1.09 ± 0.01, 0.76 ± 0.08, and 0.88 ± 0.06; P = 0.0067). There was a positive correlation between telomere length and telomerase activity (r = 0.9090; P < 0.0001). Transcriptions of both hTERT and c-MYC were also significantly decreased in the same manner. CONCLUSION: In the present cell culture model, WPE reduced telomere maintenance, which may provide a mechanistic link to the effect of walnuts on the viability of colon CSCs.

Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model.

PURPOSE: Walnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism. METHODS: CD133+CD44+ HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 µg/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests. RESULTS: RNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ΔECAR = 36.98 mpH/min/ptn, p = 0.02) and oxidative pathway (ΔOCR = 29.18 pmol/min/ptn, p = 0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (ΔOCR = 111.5 pmol/min/ptn, p = 0.0006). WPE treatment also increased glucose uptake (Δ = 0.39 pmol/µL, p = 0.002) and lactate production (Δ = 0.08 nmol/µL, p = 0.005). CONCLUSIONS: WPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.

Second Medical Opinions in End-of-Life Disputes in Critical Care: An Ethics-Based Approach.

Requests for a second medical opinion (SMO) by patients or substitute decision-makers (SDMs) can arise during end-of-life disputes in critical care. Such disagreements between patients or SDMs and physicians often pertain to specific elements of the decision-making process related to withholding or withdrawing of life-sustaining treatments. When these disputes occur in the critical care setting in Canada, practicalities and policy barriers prevent an SDM from obtaining an SMO without support from healthcare providers; moreover, in a majority of these cases the SDM will require the facilitation of a physician who is often the same individual with whom they are in conflict. Institutional and a national society's policy statements propose SMOs as an important component of a conflict resolution process for end-of-life disputes (Bosslet et al. 2015; Singer et al. 2001). However, these policies do not provide specific guidance to physicians on how to fairly consider SMO requests. Given the vulnerable position of patients and their SDMs in the critical care context and in order to promote fairness, physicians should apply consistent standards in deciding whether to facilitate a request for an SMO. To guide physicians' decision-making and inform future policy development, we propose three ethical principles for considering SDM requests for an SMO in critical care at the end of life.

Iron Supplementation Reverses the Reduction of Hydroxymethylcytosine in Hepatic DNA Associated With Chronic Alcohol Consumption in Rats.

BACKGROUND: Alcohol is known to affect two epigenetic phenomena, DNA methylation and DNA hydroxymethylation, and iron is a cofactor of ten-eleven translocation (TET) enzymes that catalyze the conversion from methylcytosine to hydroxymethylcytosine. In the present study we aimed to determine the effects of alcohol on DNA hydroxymethylation and further effects of iron on alcohol associated epigenetic changes. METHODS: Twenty-four male Sprague-Dawley rats were fed either Lieber-DeCarli alcohol diet (36% calories from ethanol) or Lieber-DeCarli control diet along with or without iron supplementation (0.6% carbonyl iron) for 8 weeks. Hepatic non-heme iron concentrations were measured by colorimetric assays. Protein levels of hepatic ferritin and transferrin receptor were determined by Western blotting. Methylcytosine, hydroxymethylcytosine and unmodified cytosine in DNA were simultaneously measured by liquid chromatography/mass spectrometry method. RESULTS: Iron supplementation significantly increased hepatic non-heme iron contents (P < 0.05) but alcohol alone did not. However, both alcohol and iron significantly increased hepatic ferritin levels and decreased hepatic transferrin receptor levels (P < 0.05). Alcohol reduced hepatic DNA hydroxymethylation (0.21% ± 0.04% vs. 0.33% ± 0.04%, P = 0.01) compared to control, while iron supplementation to alcohol diet did not change DNA hydroxymethylation. There was no significant difference in methylcytosine levels, while unmodified cytosine levels were significantly increased in alcohol-fed groups compared to control (95.61% ± 0.08% vs. 95.26% ± 0.12%, P = 0.03), suggesting that alcohol further increases the conversion from hydroxymethylcytosine to unmodified cytosine. CONCLUSIONS: Chronic alcohol consumption alters global DNA hydroxymethylation in the liver but iron supplementation reverses the epigenetic effect of alcohol.