Blood metabolites mediate effects of breakfast skipping on heart failure via Mendelian randomization analysis.

Numerous observational studies have suggested a potential causal relationship between skipping breakfast and cardiovascular diseases, including heart failure (HF). However, these studies are susceptible to inherent confounders and the challenge of reverse causation, and the underlying metabolic factors are not yet clear. Therefore, our aim is to assess the causal impact of breakfast skipping on HF and the role of potential mediating metabolic products from a genetic perspective, by conducting Mendelian Randomization (MR) studies and mediation analysis. We leveraged summary data from the most extensive genome-wide association studies to date on breakfast skipping (with 193,860 participants), blood metabolites (with 118,461 participants), and HF (involving 47,309 cases and 930,014 controls). To explore the causal relationship between breakfast skipping and HF, as well as the role of 249 potential blood metabolite mediators, we conducted bidirectional MR and mediation MR analyses. We primarily employed the Inverse Variance Weighted (IVW) method, complemented by various other techniques to ensure the comprehensiveness and reliability of our analysis. Our research confirms a causal association between breakfast skipping and an increased risk of HF (odds ratio [OR]: 1.378, 95% confidence interval [CI]: 1.047-1.813; p = 0.022). Furthermore, our research findings demonstrate that breakfast skipping is positively correlated with 6 blood metabolites and negatively correlated with 2 others. Notably, our mediation MR analysis further reveals that three blood metabolites act as mediators in the relationship between breakfast skipping and the risk of HF. Specifically, the mediating effects are attributed to the ratio of docosahexaenoic acid (DHA) to total fatty acids (proportion mediated = 9.41%, 95% CI: 2.10-28.61%), glucose (proportion mediated = 6.17%, 95% CI: 0.97-28.53%), and glycoprotein acetyls (GlycA) (proportion mediated = 5.68%, 95% CI: 0.94-21.62%). The combined mediating effects of these three factors total 20.53% (95%CI: 8.59-91.06%). Our research confirms the causal relationship between genetically instrumented breakfast skipping and HF, underscoring the potential mediating roles played by three key blood metabolites: ratio of DHA to total fatty acids, glucose and GlycA. This discovery offers valuable perspectives for clinical strategies targeting HF.

Causal relationship between breakfast skipping and myocardial infarction: Two-sample Mendelian randomization.

While observational studies suggest a connection between skipping breakfast and myocardial infarction (MI), the causal nature of this relationship is unclear. This study aims to investigate the genetic causal relationships between breakfast skipping and MI through Mendelian randomization (MR). Employing genetic data from a public genome-wide association study, this research focuses on genetic variations linked to breakfast skipping and MI. The primary analytical method was the inverse variance-weighted approach, complemented by additional methods like MR-Egger, weighted median, and mode analyses. It also includes heterogeneity and horizontal pleiotropy tests such as the Cochrane Q test, MR-Egger intercept, and MR-PRESSO tests, with a leave-one-out analysis for enhanced sensitivity assessment reliability. The study discovered a notable association between breakfast skipping and an increased risk of MI (odds ratios: 1.34, 95% confidence intervals: 1.03-1.76, P = .027). The test revealed no heterogeneity or multiplicity, and the sensitivity analysis confirmed the robustness of the results. Our MR analysis suggests that habitual breakfast skipping might elevate the likelihood of MI, underlining the importance of regular breakfast consumption in potentially mitigating heart attack risks.

[In vitro evaluation of cutaneous allergic reaction induced by chemicals using dendritic cells].

OBJECTIVE: To investigate the use of dendritic cells derived from mice bone marrow to evaluate the cutaneous allergic reaction induced by chemical sensitizers. METHODS: Dendritic cells derived from mice bone marrow were cultured and administrated with 2, 4-dinitrochlorobenzene (DNCB), nickel sulfate (NiSO4), sodium dodecyl sulfate (SDS) and hexyl cinnamic aldehyde (HCA), respectively. Cell membrane molecule CD86 and extracellular IL-1 beta, IL-6 and IL-12 were detected after 0, 1, 6, 12, 24, 36, 48 hour's administration, respectively. RESULTS: CD86 expression reached the highest level after exposure to DNCB for 48 h, and increased by about 279% compared with the control (P < 0.05), while it was lower than that of control after administrated with NiSO4 and HCA for 1 h and 6 h, and SDS for 36 h, respectively (P < 0.05). Extracellular IL-1 beta increased greatly after exposure to NiSO4 just for 1 h, with the maximum at 48 h (298 pg/ml, P < 0.05), and after exposure to HCA for 6 h, with maximum at 48 h (84 pg/ml, P < 0.05). However, it didn't fluctuate significantly after administrated with DNCB and SDS respectively, compared with the control. Extracellular IL-6 increased significantly after exposure to NiSO4 for 1 h, with the maximum at 24 h (2152 pg/ml, P < 0.05). After exposure to HCA, extracellular IL-6 reached the maximum at 1 h (1403 pg/ml), and then it was decreased quickly, but still higher than the control (P < 0.05), while it didn't change significantly after treatment with DNCB and SDS, compared with the control (P > 0.05). Extracellular IL-12 was not detected out among all the groups. CONCLUSION: Chemical sensitizer DNCB could induce the high expression of CD86 on DC membrane, and NiSO4 and HCA could induce DC to release IL-1 beta and IL-6. However, the irritant SDS had no such effect.