Background: Macrophage polarization and microRNA play crucial roles in the development of atherosclerosis (AS). The M1 macrophage phenotype contributes to the formation of plaques, while the M2 macrophage phenotype resolves inflammation and promotes tissue repair. MiR-126 has been found to play a role in regulating macrophage polarization in the context of AS. However, the exact mechanism of miR-126 requires further research. Methods: The foam cell model was established by stimulating THP-1 with oxidized low-density lipoprotein (ox-LDL). We transfected foam cells with miR-126 mimic and its negative control. The transfection of miR-126 was implemented by riboFECT CP transfection kit. The levels of miR-126 and M1/M2 associated genes in foam cells were quantified using reverse transcription-quantitative PCR (RT-qPCR). Additionally, the expressions of CD86⁺ and CD206⁺ cells in foam cells were determined by flow cytometry. Western blotting and RT-qPCR were used to determine the protein and mRNA levels of the vascular endothelial growth factor A (VEGFA) and the transcriptional regulator Krüppel-like factor 4 (KLF4), respectively. Additionally, we detected endothelial cell migration after co-culturing endothelial cells and macrophages. MG-132 was used to indirectly activate the expression of VEGFA, and the expression of KLF4 was also evaluated. Results: The activation of apoptosis and production of foam cells were boosted by the addition of ox-LDL. We transfected foam cells with miR-126 mimic and its negative control and observed that miR-126 greatly suppressed foam cell development and inhibited phagocytosis. Moreover, it caused pro-inflammatory M1 macrophages to switch to the anti-inflammatory M2 phenotype. This was reflected by the increase in anti-inflammatory gene expression and the decrease in pro-inflammatory gene expression. Additionally, miR-126 dramatically decreased the expressions of VEGFA and KLF4. The protein-protein interaction network analysis showed a significantly high correlation between miR-126, VEGFA, and KLF4. MiR-126 may also promote EC migration by activating macrophage PPAR γ expression and effectively suppressing macrophage inflammation. MG-132 indirectly activated the expression of VEGFA, and the expression of KLF4 also significantly increased, which indicates a direct or indirect relationship between VEGFA and KLF4. Conclusion: Our study shows that miR-126 can reverse ox-LDL-mediated phagocytosis and apoptosis in macrophages. Consequently, the potential role of miR-126 was manifested in regulating macrophage function and promoting vascular endothelial migration.

Previous research has suggested a correlation between fine particulate matter (PM2.5) and type 2 diabetes mellitus (T2DM). However, the causality was vulnerable to confounding variables. A two-sample multivariable mendelian randomization study was designed to examine the causal connection between PM2.5 and T2DM. PM2.5 trait was investigated as exposure while T2DM-related traits as outcomes. The summary data were obtained from the Finngen database and the open genome-wide association study database. The mendelian randomization estimates were obtained using the inverse-variance weighted approach, and multiple sensitivity analyses were conducted. There were potential causal relationships between PM2.5 and T2DM (OR = 2.418; P = 0.019), PM2.5 and glycated hemoglobin (HbA1c) (OR = 1.590; P = 0.041), and PM2.5 and insulin metabolism. PM2.5 was found to have no causal effect on fasting glucose and insulin, 2-h glucose, and insulin-like growth factor binding protein-1 (P > 0.05), while had a potential protective effect against some diabetes complications. Our findings indicated potential causal relationships among PM2.5 and T2DM, especially the causal relationship between PM2.5 and long-term glucose levels.

Takotsubo syndrome (TTS) is characterized by apical or left ventricular (LV) ballooning and impaired wall motion as its primary features. Although women over 55 years make up the majority of TTS patients, male patients have a greater incidence of in-hospital mortality. TTS also impacts pregnant women and children, with conflicting information regarding racial differences. TTS has an in-hospital mortality rate comparable to that of acute ST-segment elevation myocardial infarction, and higher than that in patients with myocarditis. More than 10% of patients may experience a subsequent acute episode within 5 years after the initial event. TTS exhibits symptoms such as chest pain, electrocardiograph (ECG) abnormalities, elevated B-type natriuretic peptide (BNP), and N-terminal prohormone of brain natriuretic peptide (NT-pro-BNP) levels, and changes in several imaging approaches, which may aid in early diagnosis. Fluid resuscitation, β-blockers, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), anti-anxiety or depression drugs, and cardiac rehabilitation may be employed to treat TTS, reduce recurrence rates, and improve functional exercise capacity and exercise time. After searching PubMed, Research Gate, Science Direct, and Web of Science, we summarized recent researches on epidemiology, diagnosis, treatments, and prognosis. These findings provide a theoretical basis for future clinical practice and will aid doctors and researchers investigating the unknown aspects of TTS.

Amiodarone can cause hepatic steatosis, but the relationship between treatment duration and steatosis burden and the cellular pathways involved remain unce

Objective: Previous research suggests a correlation between nontoxic goitre and type 2 diabetes mellitus (T2DM). However, the causality was vulnerable to confounding variables. Therefore, there is an urgent need for a more rigorous research approach to examine the causal connection between nontoxic goitre and T2DM.Design: Multiple exposures and outcomes two‐sample Mendelian randomization (MR) study was carried out in two stages: nontoxic goitre traits (including nontoxic diffuse goitre, NDG; nontoxic multinodular goitre, NMG; and other/unspecified nontoxic goitre, OUNG) were investigated as exposure while T2DM was investigated as an outcome in the first step, whereas the second step was reversed. The GWAS summary data for nontoxic goitre traits and T2DM were collected from the Finngen database. The summary data for fasting glucose, fasting insulin, and HbA1c were obtained from the open GWAS database established by the MRC Integrated Epidemiology Unit (IEU). The inverse‐variance weighted (IVW) approach was used to obtain MR estimates, and various sensitivity analysis was also performed.Results: NDG had a potential protective causal relationship with T2DM (OR = 0.978; 95% CI: 0.957−0.998; p = 0.034) and fasting glucose (OR = 0.995; 95% CI: 0.990−0.999; p = 0.011), while NMG had a potential protective causal relationship with T2DM (OR = 0.941; 95% CI: 0.902−0.982; p = 0.008) and HbA1c (OR = 0.992; 95% CI: 0.986−0.998; p = 0.015). OUNG was found to decrease the odds of T2DM by 4.4% (OR = 0.966; 95% CI: 0.938−0.995, p = 0.023). T2DM had a potential causal relationship with NDG (OR = 1.239; 95% CI: 1.020−1.504; p = 0.031), and a potential protective effect against NMG (OR = 0.669; 95% CI: 0.566−0.792; p < 0.001) and OUNG (OR = 0.694; 95% CI: 0.545−0.883; p = 0.004). There was no evidence of a positive association between glycemic traits and nontoxic goitre traits (p > 0.05).Conclusions: Our findings indicate a potential causal relationship between nontoxic goitre traits and T2DM. Specifically, our study addresses that NMG and T2DM may have a significant causal effect on each other in both directions.