ABSTRACT
Background: Genetic, observational, and clinical intervention studies indicate that circulating levels of remnant cholesterol (RC) are associated with cardiovascular diseases. However, the predictive value of RC for cardiovascular mortality in the general population remains unclear. Methods: Our study population comprised 19,650 adults in the United States from the National Health and Nutrition Examination Survey (NHANES) (1999-2014). RC was calculated from non-high-density lipoprotein cholesterol (non-HDL-C) minus low-density lipoprotein cholesterol (LDL-C) determined by the Sampson formula. Multivariate Cox regression, restricted cubic spline analysis, and subgroup analysis were applied to explore the relationship of RC with cardiovascular mortality. Results: The mean age of the study cohort was 46.4 ± 19.2 years, and 48.7% of participants were male. During a median follow-up of 93 months, 382 (1.9%) cardiovascular deaths occurred. In a fully adjusted Cox regression model, log RC was significantly associated with cardiovascular mortality [hazard ratio (HR) 2.82; 95% confidence interval (CI) 1.17-6.81]. The restricted cubic spline curve indicated that log RC had a linear association with cardiovascular mortality (p for non-linearity = 0.899). People with higher LDL-C (≥130 mg/dL), higher RC [≥25.7/23.7 mg/dL in males/females corresponding to the LDL-C clinical cutoff point (130 mg/dL)] and abnormal HDL-C (<40/50 mg/dL in males/females) levels had a higher risk of cardiovascular mortality (HR 2.18; 95% CI 1.13-4.21 in males and HR 2.19; 95% CI 1.24-3.88 in females) than the reference group (lower LDL-C, lower RC and normal HDL-C levels). Conclusions: Elevated RC levels were associated with cardiovascular mortality independent of traditional risk factors.
ABSTRACT
Enterovirus A71 (EV-A71) is one of the main causative agents of hand-foot-mouth disease (HFMD) and causes serious neurological complications. However, no effective therapy is currently available for treating these infections. Therefore, effective drugs to prevent and treat EV-A71 infections are urgently needed. Here, we demonstrated that treatment with Licochalcone A (LCA) significantly inhibited EV-A71 replication in a dose-dependent manner, with an EC50 of 9.30 µM in RD cells and 5.73 µM in Vero cells. The preliminary results on the inhibition mechanism showed that LCA exerted antiviral effects by interfering with the early step of viral replication. We further demonstrated that LCA showed potent antiviral activity against many enteroviruses, including EV-A71 (strain C4), EV-A71 (strain H), and coxsackievirus A16 (CV-A16). Furthermore, LCA could effectively prevent the clinical symptoms and death of virus infected mice and decreased viral load in EV-A71-infected mice. Taken together, our studies showed for the first time, that LCA is a promising EV-A71 inhibitor and provide important information for the clinical development of LCA as a potential new anti-EV-A71 agent.
