Dietary and supplemental intake of vitamins C and E is associated with altered DNA methylation in an epigenome-wide association study meta-analysis.

BACKGROUND: Dietary intake of antioxidants such as vitamins C and E protect against oxidative stress, and may also be associated with altered DNA methylation patterns. METHODS: We meta-analysed epigenome-wide association study (EWAS) results from 11,866 participants across eight population-based cohorts to evaluate the association between self-reported dietary and supplemental intake of vitamins C and E with DNA methylation. EWAS were adjusted for age, sex, BMI, caloric intake, blood cell type proportion, smoking status, alcohol consumption, and technical covariates. Significant results of the meta-analysis were subsequently evaluated in gene set enrichment analysis (GSEA) and expression quantitative trait methylation (eQTM) analysis. RESULTS: In meta-analysis, methylation at 4,656 CpG sites was significantly associated with vitamin C intake at FDR ≤ 0.05. The most significant CpG sites associated with vitamin C (at FDR ≤ 0.01) were enriched for pathways associated with systems development and cell signalling in GSEA, and were associated with downstream expression of genes enriched in the immune response in eQTM analysis. Furthermore, methylation at 160 CpG sites was significantly associated with vitamin E intake at FDR ≤ 0.05, but GSEA and eQTM analysis of the top most significant CpG sites associated with vitamin E did not identify significant enrichment of any biological pathways investigated. CONCLUSIONS: We identified significant associations of many CpG sites with vitamin C and E intake, and our results suggest that vitamin C intake may be associated with systems development and the immune response.

Bio-inspired nanoparticles mediated from plant extract biomolecules and their therapeutic application in cardiovascular diseases: A review.

Nanoparticles (NPs) have gained recognition for diagnosis, drug delivery, and therapy in fatal diseases. This review focuses on the benefits of green synthesis of bioinspired NPs using various plant extract (containing various biomolecules such as sugars, proteins, and other phytochemical compounds) and their therapeutic application in cardiovascular diseases (CVDs). Multiple factors including inflammation, mitochondrial and cardiomyocyte mutations, endothelial cell apoptosis, and administration of non-cardiac drugs, can trigger the cause of cardiac disorders. Furthermore, the interruption of reactive oxygen species (ROS) synchronization from mitochondria causes oxidative stress in the cardiac system, leading to chronic diseases such as atherosclerosis and myocardial infarction. NPs can decrease the interaction with biomolecules and prevent the incitement of ROS. Understanding this mechanism can pave the way for using green synthesized elemental NPs to reduce the risk of CVD. This review delivers information on the different methods, classifications, mechanisms and benefits of using NPs, as well as the formation and progression of CVDs and their effects on the body.

Epigenome-wide association meta-analysis of DNA methylation with coffee and tea consumption.

Coffee and tea are extensively consumed beverages worldwide which have received considerable attention regarding health. Intake of these beverages is consistently linked to, among others, reduced risk of diabetes and liver diseases; however, the mechanisms of action remain elusive. Epigenetics is suggested as a mechanism mediating the effects of dietary and lifestyle factors on disease onset. Here we report the results from epigenome-wide association studies (EWAS) on coffee and tea consumption in 15,789 participants of European and African-American ancestries from 15 cohorts. EWAS meta-analysis of coffee consumption reveals 11 CpGs surpassing the epigenome-wide significance threshold (P-value <1.1×10-7), which annotated to the AHRR, F2RL3, FLJ43663, HDAC4, GFI1 and PHGDH genes. Among them, cg14476101 is significantly associated with expression of the PHGDH and risk of fatty liver disease. Knockdown of PHGDH expression in liver cells shows a correlation with expression levels of genes associated with circulating lipids, suggesting a role of PHGDH in hepatic-lipid metabolism. EWAS meta-analysis on tea consumption reveals no significant association, only two CpGs annotated to CACNA1A and PRDM16 genes show suggestive association (P-value <5.0×10-6). These findings indicate that coffee-associated changes in DNA methylation levels may explain the mechanism of action of coffee consumption in conferring risk of diseases.

Significant amelioration of hepatitis C virus infection in a hyperendemic area: longitudinal evidence from the COMPACT Study in Taiwan.

OBJECTIVES: Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. Tzukuan, located in the southwestern area of Taiwan, is an HCV hyperendemic area (>30%). This study aimed to assess the changing epidemiological characteristics of HCV infection and to evaluate the long-term outcomes after the implementation of public health strategies for two decades. DESIGN: A population-based retrospective cohort study. SETTING: A comprehensive care programme was implemented, namely COMPACT Study, in Tzukuan since 1997. PARTICIPANTS: A total of 10 714 residents participated the screening. OUTCOME MEASURES: The HCV status, demographic and clinical profiles of the participants were recorded and validated annually from 2000 through 2019. RESULTS: The HCV infection prevalence rates were 21.1% (1076/5099) in 2000-2004, 18.8% (239/1269) in 2005-2009, 14.1% (292/2071) in 2010-2014 and 10.3% (234/2275) in 2015-2019 (p for trend test <0.0001). Among them, 1614 underwent repeated tests during the follow-up period. The annual incidence rates were 0.54% in 2005-2009, 0.4% in 2010-2014 and 0.22% in 2015-2019, respectively (p=0.01). In addition to old age, lower education level was a major risk factor for HCV infection across different periods. HCV infection prevalence rate among those illiterates reached 40.9%, followed by 28.5% in those with elementary school level, and <10% in those with high school or higher levels. The major risk factor has shifted from iatrogenic exposure in 2000-2009 to household transmission after 2010. CONCLUSIONS: HCV infection has been decreasing and the epidemiological features are changing in the hyperendemic area by continuing education, prevention and treatment strategies.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

BACKGROUND: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Brazilein suppresses migration and invasion of MDA-MB-231 breast cancer cells.

Brazilein, a bioactive compound isolated from Caesalpinia sappan L., has long been used in oriental folk medicines. Cancer metastasis is a primary cause of cancer death. However, the anti-metastatic effects of brazilein remain elusive. In this study, we found that brazilein inhibited human breast cancer MDA-MB-231 cell migration and invasion using wound-healing assay and Boyden chamber assay. The results of Western blot, gelatin zymography and reversed transcription-PCR analysis showed that brazilein suppressed matrix metalloproteinase-2 (MMP-2) expression in a concentration-dependent manner. Brazilein also decreased the nuclear protein level of nuclear factor kappaB (NF-κB). Brazilein potently suppressed the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), phosphatidylinositide-3-kinase (PI3K) and Akt, but did not affect phosphorylation of extracellular signal regulating kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK). Additionally, treatment of SB203580 (p38 MAPK inhibitor) or wortmannin (PI3K inhibitor) resulted in a reduced activity and expression of MMP-2 as well as inhibition on cell migration and invasion in MDA-MB-231 cells. Taken together, these results suggest that brazilein inhibition of MDA-MB-231 cells may be mediated through inactivation of both PI3K/Akt and p38 MAPK signaling pathways, leading to inhibitory effect on NF-κB activation. Consequently, brazilein suppresses MMP-2 expression, and thus confers anti-migration and anti-invasion of MDA-MB-231 cells.

Increased liver and lupus mortalities in 24-year follow-up of the Taiwanese people highly exposed to polychlorinated biphenyls and dibenzofurans.

BACKGROUND: A follow-up study was designed to compare the 24-year overall and disease-specific mortality in Yucheng people who were highly exposed to polychlorinated biphenyls/dibenzofurans (PCBs/PCDFs) to that in the background population in Taiwan. In 1979, the Yucheng (oil-disease in Chinese) incident occurred in central Taiwan involving approximately 2000 victims due to ingestion of rice oil contaminated with PCBs/PCDFs. Long-term follow-up of these people has been continued for 24 years. METHODS: Standardized mortality ratios were calculated using the Taiwan population as comparison group. Overall and disease-specific mortality was compared between Yucheng and background populations. RESULTS: Mortality from chronic liver disease and cirrhoses was increased in the Yucheng men, but not in women, in the early period after exposure. Cancer mortality was not increased in the Yucheng population up to 24 years after exposure. SLE in females was highly increased in the later period after PCB/PCDF exposure. Mortality from disease in any other organ system was not significantly different between Yucheng and background populations. CONCLUSIONS: The study provided a long-term mortality picture after the Taiwanese PCB/PCDF exposure incident. In addition to re-confirming the increase in liver mortality, we found high mortality of SLE among exposed population. This finding highlights the importance of further investigating the immunological effects associated with PCB/PCDF exposure.

Genetic polymorphisms in CYP1A1 and GSTM1 predispose humans to PCBs/PCDFs-induced skin lesions.

INTRODUCTION: Polychlorinated biphenyls (PCBs) and dibenzofurans (PCDFs) are ubiquitous persistent pollutants in humans. Whether people with different genotypes are with different susceptibility to these chemicals are unknown. In a group of people highly exposed to PCBs/PCDFs, we tested the hypothesis that genotypic polymorphisms affected susceptibility for development of skin manifestations. METHODS: In 1979, approximately 2000 people in central Taiwan ingested cooking oil contaminated with PCBs/PCDFs. Skin disorder such as chloracne, abnormal nail, hyperkeratosis and skin allergy were found in PCBs/PCDFs exposed group. We recruited exposed and community background exposure subjects for blood testing and telephone-interview. Single nucleotide polymorphisms, AhR Arg554Lys, CYP1A1 Ile462Val, CYP1A1 T6235C, and GSTM1/T1 deletion, were determined. Occurrence of skin manifestations was compared among people with different genotypes while stratified by PCB exposure levels by logistic regression. RESULTS: Data on exposure, medical history, and genotypes were obtained from 393 exposed and 181 background exposure groups. Skin manifestations including chloracne, allergy, abnormal nail, and hyperkeratosis were more prevalent in exposed people in a dose-related manner. Among highly exposed individuals, combined CYP1A1-MspI mutant genotype and GSTM1-null genotype were associated with increased risk of chloracne (odds ratio 2.8, 95% confidence interval 1.1-7.6). Among intermediately exposed individuals, GSTM1 null genotype was associated with skin allergy. AhR Arg554Lys genotype and GSTT1 null genotype were not related to susceptibility to skin manifestations in PCB/PCDF-exposed population. CONCLUSION: CYP1A1 and GSTM1 genotypic polymorphisms might be related to the susceptibility to PCB/PCDF-induced skin manifestations.