PTX80, a novel compound targeting the autophagy receptor p62/SQSTM1 for treatment of cancer.

Cancer cells are dependent on protein quality-control mechanisms, including protein chaperones, the ubiquitin-proteasome system, and autophagy. The p62 receptor is a classical, ubiquitously expressed receptor, involved in many signal transduction pathways. Upregulation and/or reduced degradation of p62 have been implicated in tumor formation and resistance to therapy.

Chronically Elevating Circulating Ketones Can Reduce Cardiac Inflammation and Blunt the Development of Heart Failure.

Background: Previous studies have shown beneficial effects of acute infusion of the primary ketone body, β-hydroxybutyrate, in heart failure (HF). However, whether chronic elevations in circulating ketones are beneficial remains unknown.

Methods: To chronically elevate circulating ketones in mice, we deleted the expression of the ketolytic, rate-limiting-enzyme, SCOT (succinyl-CoA:3-ketoacid-CoA transferase 1; encoded by ), in skeletal muscle.

Intrauterine exposure to chronic hypoxia in the rat leads to progressive diastolic function and increased aortic stiffness from early postnatal developmental stages.

Aim: We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.

Methods: Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO ) from embryonic day E15-21 or normoxic conditions (controls).

Cardiovascular sexual dimorphism in a diet-induced type 2 diabetes rodent model, the Nile rat (Arvicanthis niloticus).

Background: The Nile rat (Arvicanthis niloticus) is an emerging laboratory model of type 2 diabetes. When fed standard rodent chow, the majority of males progress from hyperinsulinemia by 2 months to hyperglycemia by 6 months, while most females remain at the hyperinsulinemia-only stage (prediabetic) from 2 months onward. Since diabetic cardiomyopathy is the major cause of type-2 diabetes mellitus (T2DM)-related mortality, we examined whether sexual dimorphism might entail cardiac functional changes.

Resveratrol improves cardiac function and exercise performance in MI-induced heart failure through the inhibition of cardiotoxic HETE metabolites.

Numerous epidemiological studies have demonstrated that approximately 40% of myocardial infarctions (MI) are associated with heart failure (HF). Resveratrol, a naturally occurring polyphenol, has been shown to be beneficial in the treatment of MI-induced HF in rodent models. However, the mechanism responsible for the effects of resveratrol are poorly understood.