Discovery of new tricyclic spiroindole derivatives as potent P-glycoprotein inhibitors for reversing multidrug resistance enabled by a synthetic methodology-based library.

The discovery of novel and highly effective P-gp inhibitors is considered to be an effective strategy for overcoming tumor drug resistance. In this paper, a phenotypic screening a self-constructed synthetic methodology-based library identified a new class of tricyclic spiroindole derivatives with excellent tumor multidrug resistance reversal activity. A stereospecific compound OY-103-B with the best reversal activity was obtained based on a detailed structure-activity relationship study, metabolic stability optimization and chiral resolution.

Retrospective study on the short-term efficacy of different doses of Spironolactone in patients with heart failure of ischemic cardiomyopath and the influence of ventricular remodeling markers.

Objective: To evaluate the impact of varying dosages of Spironolactone on the short-term effectiveness and ventricular remodeling indicators in patients with Heart Failure of Ischemic Cardiomyopathy (HFIC).

Methods: A cohort of 141 HFIC patients, admitted to our hospital between October 2018 and February 2023, were enrolled for this study. Alongside the standard treatment for Chronic Congestive Heart Failure (CHF), these patients were randomly assigned to either a low-dose (20 mg/d, N=70) or a high-dose (60 mg/d, N=71) Spironolactone group.

Mitochondrial Damage-Induced Innate Immune Activation in Vascular Smooth Muscle Cells Promotes Chronic Kidney Disease-Associated Plaque Vulnerability.

Chronic kidney disease (CKD) is associated with accelerated atherosclerosis progression and high incidence of cardiovascular events, hinting that atherosclerotic plaques in CKD may be vulnerable. However, its cause and mechanism remain obscure. Here, it is shown that apolipoprotein E-deficient (ApoE) mouse with CKD (CKD/ApoE mouse) is a useful model for investigating the pathogenesis of plaque vulnerability, and premature senescence and phenotypic switching of vascular smooth muscle cells (VSMCs) contributes to CKD-associated plaque vulnerability.