The MTHFR gene encodes methylenetetrahydrofolate reductase required for the metabolism of homocysteine (Hcy) – a previously reported independent risk factor for ischemic stroke (IS). In this study, we first aimed to clarify the association between DNA methylation levels in the MTHFR promoter and the risk of IS, followed by the analysis of potential interactions between environmental factors and DNA methylation levels that affect IS risk. We recruited 164 patients with hypertension and IS (case group) and 345 age- and sex-matched patients with hypertension only (control group). Demographic and clinical information was obtained using questionnaires, and blood samples were collected for biochemical analyses. Fluorescence quantitative methylation-specific PCR (qMSP) was used to detect MTHFR promoter methylation levels. A logistic regression analysis was performed to determine the relationship between environmental factors, MTHFR promoter methylation levels, and IS risk. We finally generated a receiver operating characteristic (ROC) curve to determine whether MTHFR promoter methylation levels can predict IS. The mean MTHFR methylation levels in case group (8.10 ± 6.14) were significantly lower than those in control group (17.44 ± 3.16; p < 0.05). MTHFR promoter methylation levels were also lower in patients with plasma Hcy levels ≥15 μmol/L (10.65 ± 4.05) than in those with Hcy levels <15 μmol/L (16.74 ± 4.26, p < 0.001). Finally, we found that MTHFR hypermethylation is a protective factor for IS, particular in men (OR in men: 0.07; 95% CI: 0.02–0.16; p < 0.001). Further, sex and MTHFR promoter methylation levels exhibited a preliminary interaction effect on IS risk. These results indicate that MTHFR promoter methylation status might have diagnostic value in IS.

Background Recent studies have reported conflicting associations between egg consumption and the risk of all-cause or cardiovascular disease (CVD) mortality, including ischemic heart disease (IHD) mortality and stroke mortality. With accumulating evidence, up-to-date evidence about the association should be synthesized. Objective To assess the association of the risk of all-cause and CVD mortality with egg consumption. Methods We searched PubMed, EMBASE, and Web of Science databases through November 3, 2021 for observational studies conducted in participants ≥18 y of age and provided ORs or RRs or HRs and 95% CIs for ≥3 egg consumption categories or for increased intake of egg with the associations of interest. Random-effects model was used to pool the reported risk estimates. Restricted cubic splines were used to examine the dose–response association. Results Twenty-four articles with 48 reports (25 for all-cause mortality, 11 for CVD mortality, 6 for IHD mortality, and 6 for stroke mortality) involving 11,890,695 participants were included. Intake of each 1 egg/day increment was associated with increased risk of all-cause mortality (RR 1.06; 95% CI 1.02, 1.10; P = 0.008), but the association was restricted to women, Americans, and studies with adjustments for hyperlipidemia. Egg consumption was linearly associated with CVD mortality only in participants &gt;60 y of age, Americans, studies with follow-up duration≥15 years, and adjustments for hyperlipidemia (P ≤0.018). No significant association was found between egg consumption and IHD or stroke mortality (P ≥0.080). Conclusions Egg consumption was linearly associated with a modestly risk of all-cause mortality and, in older participants, Americans, studies with longer follow-up or adjustments for hyperlipidemia, CVD mortality. These findings suggest that it may be prudent to avoid high egg consumption.

Recent studies have demonstrated the biological significance of cuproptosis modification, a newly discovered programmed cell death, in tumor progression. Nonetheless, the potential role of cuproptosis-related genes (CRGs) in the immune landscape and tumor microenvironment (TME) formation of colorectal cancer (CRC) remains unknown. We comprehensively assessed cuproptosis modification patterns of 1339 CRC samples based on 27 CRGs and systematically analyzed the correlation of these patterns with TME. The CRG-score was constructed to quantify cuproptosis characteristics by LASSO and multivariate Cox regression methods, and its predictive capability was validated in an independent cohort. We identified three distinct cuproptosis modification patterns in CRC. The TME immune cell infiltration demonstrated immune heterogeneity among these three subtypes. Enrichment for multiple metabolism signatures was pronounced in cluster A. Cluster C was significantly correlated with the signaling pathways of immune activation-related, resulting in poor prognoses. Cluster B with mixed features possibly represents a transition phenotype or intratumoral heterogeneity. Then, based on constructed eight-gene CRG-score, we found that the signature could predict the disease-free survival of CRC patients, and the low CRG-score was related to increased neoantigen load, immunity activation, and microsatellite instability-high (MSI-H). Additionally, we observed significant correlations of the CRG-score with the cancer stem cell index and chemotherapeutic drug susceptibility. This study demonstrated that cuproptosis was correlated with tumor progression, prognosis, and TME. Our findings may improve the understanding of CRGs in TME infiltration characterization of CRC patients and contribute to guiding more effective clinical therapeutic strategies.

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