Discovery of N-pyridoyl-Δ -pyrazolines as Hsp90 inhibitors.

Hsp90, as a key molecular chaperone, plays an important role in modulating the activity of many cell signaling proteins and is an attractive target for anticancer therapeutics. Herein, we report the discovery of N-pyridoyl-Δ -pyrazoline analogs as novel Hsp90 inhibitors by integrated approaches of drug design, organic synthesis, cell biology, and qualitative proteomic analysis. Novel chemical compounds were designed and optimized in the adenosine triphosphate-binding site of Hsp90; lead optimized compounds were found to have significant interactions with Asp93 and other amino acids crucial for Hsp90 inhibition.

Usefulness of Left Ventricular Strain by Cardiac Magnetic Resonance Feature-Tracking to Predict Cardiovascular Events in Patients With and Without Heart Failure.

There is controversy regarding the utility of left ventricular (LV) mechanics assessed by feature-tracking steady-state free-precession (FT-SSFP), a readily implementable technique in clinical practice. In particular, whether LV mechanics assessed by FT-SSFP predicts outcomes in subjects with heart failure (HF) with reduced ejection fraction (HFrEF), with preserved ejection fraction (HFpEF), or without HF is unknown. We aimed to assess whether LV mechanics measured with FT-SSFP cine magnetic resonance imaging (MRI) predicts adverse outcomes.

Vitamin K Status, Warfarin Use, and Arterial Stiffness in Heart Failure.

Large artery stiffening contributes to the pathophysiology of heart failure (HF) and associated comorbidities. MGP (matrix Gla-protein) is a potent inhibitor of vascular calcification. MGP activation is vitamin K-dependent.

Left Atrial Phasic Function by Cardiac Magnetic Resonance Feature Tracking Is a Strong Predictor of Incident Cardiovascular Events.

Background: The prognostic importance of left atrial (LA) dysfunction is increasingly recognized. Magnetic resonance imaging can provide excellent visualization of the LA wall. We aimed to study the association of LA dysfunction measured using feature-tracking magnetic resonance imaging with incident adverse cardiovascular events among subjects with or without heart failure (HF) at baseline.

Right Atrial Phasic Function in Heart Failure With Preserved and Reduced Ejection Fraction.

Objectives: This study researched right atrial (RA) deformation indexes and their association with all-cause mortality among subjects with or without heart failure (HF).

Background: Although left atrial dysfunction is well described in HF, patterns of RA dysfunction and their prognostic implications are unclear. Cardiac magnetic resonance (CMR) imaging can provide excellent visualization of the RA.

Poor Glycemic Control Is Associated With Increased Extracellular Volume Fraction in Diabetes.

Objective: We assessed whether poor glycemic control is associated with an increase in myocardial fibrosis among adults with diabetes.

Research Design And Methods: We studied 47 adults with type 2 diabetes and stratified them into three groups according to their hemoglobin A1c (HbA) level: <6.5% (group 1; = 12), 6.