ABSTRACT
Cardiovascular disease (CVD) is the primary cause of death in humans. Atherosclerosis (AS) is the most common CVD and a major cause of many CVD-related fatalities. AS has numerous risk factors and complex pathogenesis, and while it has long been a research focus, most mechanisms underlying its progression remain unknown. Noncoding RNAs (ncRNAs) represent an important focus in epigenetics studies and are critical biological regulators that form a complex network of gene regulation. Abnormal ncRNA expression disrupts the normal function of tissues or cells, leading to disease development. A large body of evidence suggests that ncRNAs are involved in all stages of atherosclerosis, from initiation to progression, and that some are significantly differentially expressed during AS development, suggesting that they may be powerful markers for screening AS or potential treatment targets. Here, we review the role of ncRNAs in AS development and recent developments in the use of ncRNAs for AS-targeted therapy, providing evidence for ncRNAs as diagnostic markers and therapeutic targets.
ABSTRACT
Antimicrobial resistance (AMR) is a global, multifaceted crisis that poses significant challenges to the successful eradication of devastating pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA), a persistent superbug that causes devastating infections. The scarcity of new antibacterial drugs is obvious, and antivirulence strategies that reduce the pathogenicity of bacteria by weakening their virulence have become the subject of intense investigation. Alpha-hemolysin (Hla), a cytolytic pore-forming toxin, has a pivotal role in S. aureus pathogenesis. Here, we demonstrated that echinatin, a natural compound isolated from licorice, effectively inhibited the hemolytic activity of MRSA at 32 µg/mL. In addition, echinatin did not interfere with bacterial growth and had no significant cytotoxicity at the inhibitory concentration of S. aureus hemolysis. Heptamer formation tightly correlated with Hla-mediated cell invasion, whereas echinatin did not affect deoxycholic acid-induced oligomerization of Hla. Echinatin affected hemolytic activity through indirect binding to Hla as confirmed by the neutralization assay and cellular thermal shift assay (CETSA). Furthermore, qRT-PCR and western blot analyses revealed that echinatin suppressed Hla expression at both the mRNA and protein levels as well as the transcript levels of Agr quorum-sensing system-related genes. Additionally, when echinatin was added to a coculture system of A549 cells and S. aureus, it significantly reduced cell damage. Importantly, echinatin exhibited a significant therapeutic effect in an MRSA-induced mouse pneumonia model. In conclusion, the present findings demonstrated that echinatin significantly inhibits the hemolysin effect and may be a potential candidate compound for combating drug-resistant MRSA infections.
