Lanatoside C

Rapid atrial fibrillation (rapid AF) often induces or exacerbates acute heart failure (HF). However, there is controversy regarding whether β-blockers should be used to control the ventricular rate in patients during the acute HF phase. AF management guidelines generally recommend considering the addition of β-blockers when digoxin-like drugs (such as cedilanid) fail to effectively control the ventricular rate. Nevertheless, HF guidelines clearly state that β-blockers should be used with caution during the acute decompensation phase to avoid the negative inotropic effect that may exacerbate the condition. This article systematically reviews the clinical management strategies under this guideline contradiction, including: (1) Different recommendations on ventricular rate control and the use of β-blockers in domestic and international guidelines for AF and HF; (2) A pooled analysis of relevant research evidence; (3) Application strategies of β-blockers (especially short-acting agents esmolol and landiolol) in the acute phase. We focus on discussing the latest research progress and clinical application strategies of esmolol and landiolol in HF induced by rapid AF, evaluate their effectiveness and safety. Although some studies and consensus articles have focused on the management of rapid AF complicated by HF, there is currently a lack of systematic reviews on this issue. Therefore, the writing of this review has important academic value and clinical guiding significance, providing a reference for treatment decisions in this special population.

For successful viral propagation within infected cells, the virus needs to overcome the cellular integrated stress response (ISR), triggered during viral infection, which, in turn, inhibits general protein translation. This paper reports a tactic employed by viruses to suppress the ISR by upregulating host cell polyribonucleotide nucleotidyltransferase 1 (PNPT1). The propagation of adenovirus, murine cytomegalovirus and hepatovirus within their respective host cells induces PNPT1 expression. Notably, when PNPT1 is knocked down, the propagation of all three viruses is prevented. Mechanistically, the inhibition of PNPT1 facilitates the relocation of mitochondrial double-stranded RNAs (mt-dsRNAs) to the cytoplasm, where they activate RNA-activated protein kinase (PKR). This activation leads to eukaryotic initiation factor 2α (eIF2α) phosphorylation, resulting in the suppression of translation. Furthermore, by scrutinizing the PNPT1 recognition element and screening 17,728 drugs and bioactive compounds approved by the US Food and Drug Administration, lanatoside C was identified as a potent PNPT1 inhibitor. This compound impedes the propagation of adenovirus, murine cytomegalovirus and hepatovirus, and suppresses production of the severe acute respiratory syndrome coronavirus-2 spike protein. These discoveries shed light on a novel strategy to impede pan-viral propagation by activating the host cell mt-dsRNA-PKR-eIF2α signalling axis.