The metabolically resistant apelin-17 analog LIT01-196 reduces cardiac dysfunction and remodeling in heart failure after myocardial infarction.

Background: To protect patients after myocardial infarction (MI) and preserve cardiac function, the development of new therapeutics remains an important issue. Apelin, a neuro-vasoactive peptide, increases aqueous diuresis and cardiac contractility while reducing vascular resistance. However, its in vivo half-life is very short.

Negative urgency increases risk for coping-motivated cannabis outcomes in socially anxious male emerging adult cannabis users.

Tension reduction theory suggests that socially anxious emerging adults use cannabis to cope with negative affect. However, the literature is mixed, indicating that the effect of social anxiety on cannabis use behaviors during emerging adulthood may depend on other moderating factors, such as negative urgency. This study aimed to clarify potential moderators that may strengthen the associations between social anxiety and cannabis outcomes among emerging adults.

Molecular landscape of the overlap between Alzheimer's disease and somatic insulin-related diseases.

Alzheimer's disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.

Rational design, synthesis and pharmacological characterization of novel aminopeptidase A inhibitors.

Aminopeptidase A (APA) is a membrane-bound zinc metallopeptidase involved in the production of angiotensin III, one effector peptide of the brain renin-angiotensin system, making brain APA a relevant pharmacological target for the development of novel therapeutic treatments against hypertension and heart failure. The structure-based design of new APA inhibitors is described, based on previously developed thiol-containing inhibitors and APA crystal structure. Chemical synthesis, in vitro assessment against APA activity, pharmacological and pharmacokinetic profiling were performed, ultimately leading to a potent and selective APA inhibitor.