Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6.

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. A critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies are in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high throughput structure-based computational screening using ensemble docking for small molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein.

Angiotensin II elicits robust calcium oscillations coordinated within juxtaglomerular cell clusters to suppress renin secretion.

Background: Juxtaglomerular (JG) cells are sensors that control blood pressure and fluid-electrolyte homeostasis. In response to a decrease in perfusion pressure or changes in the composition and/or volume of the extracellular fluid, JG cells release renin, which initiates an enzymatic cascade that culminates in the production of angiotensin II (Ang II), a potent vasoconstrictor that restores blood pressure and fluid homeostasis. In turn, Ang II exerts a negative feedback on renin release, thus preventing excess circulating renin and the development of hypertension.

Small Molecule Modulators of β-arrestins.

Unlabelled: β-arrestins (βarrs) are key regulators of G protein-coupled receptors (GPCRs), essential for modulating signaling pathways and physiological processes. While current pharmacological strategies target GPCR orthosteric and allosteric sites, as well as G protein transducers, comparable tools for studying βarrs are lacking. Here, we present the discovery and characterization of novel small-molecule allosteric inhibitors of βarrs through comprehensive biophysical, biochemical, pharmacological, and structural analyses.

The expected polygenic risk score (ePRS) framework: an equitable metric for quantifying polygenetic risk via modeling of ancestral makeup.

Polygenic risk scores (PRSs) depend on genetic ancestry due to differences in allele frequencies between ancestral populations. This leads to implementation challenges in diverse populations. We propose a framework to calibrate PRS based on ancestral makeup.

Emotional Eating Interventions for Adults Living With Overweight and Obesity: A Systematic Review and Meta-Analysis of Behaviour Change Techniques.

Background: Emotional eating (EE) is a barrier to the long-term success of weight loss interventions. Psychological interventions targeting EE have been shown to reduce EE scores and weight (kg), though the mechanisms remain unclear. This review and meta-analysis aimed to identify the specific behaviour change techniques (BCTs) associated with improved outcomes.