Head-to-Head Comparison of BRAF/MEK Inhibitor Combinations Proposes Superiority of Encorafenib Plus Trametinib in Melanoma.

BRAFV600 mutations in melanoma are targeted with mutation-specific BRAF inhibitors in combination with MEK inhibitors, which have significantly increased overall survival, but eventually lead to resistance in most cases. Additionally, targeted therapy for patients with NRASmutant melanoma is difficult. Our own studies showed that BRAF inhibitors amplify the effects of MEK inhibitors in NRASmutant melanoma.

Circadian clock network desynchrony promotes weight gain and alters glucose homeostasis in mice.

Objective: A network of endogenous circadian clocks adapts physiology and behavior to recurring changes in environmental demands across the 24-hour day cycle. Circadian disruption promotes weight gain and type 2 diabetes development. In this study, we aim to dissect the roles of different tissue clocks in the regulation of energy metabolism.

Artery-Associated Sympathetic Innervation Drives Rhythmic Vascular Inflammation of Arteries and Veins.

Background: The incidence of acute cardiovascular complications is highly time-of-day dependent. However, the mechanisms driving rhythmicity of ischemic vascular events are unknown. Although enhanced numbers of leukocytes have been linked to an increased risk of cardiovascular complications, the role that rhythmic leukocyte adhesion plays in different vascular beds has not been studied.

Chronodisruption, Metabolic Homeostasis, and the Regulation of Inflammation in Adipose Tissues.

Molecular circadian clocks align daily behavioral and metabolic rhythms with the external day-night cycle. Priming energy metabolism for recurring changes on a 24-hour basis, these clocks are deeply interlinked with metabolic homeostasis and health. Circadian rhythm disruptions, as occurring in shift work or sleep disorders, are often accompanied by metabolic disturbances - from the promotion of overweight and type-2 diabetes to the development of the metabolic syndrome.

Impact of adult attention deficit hyperactivity disorder and medication status on sleep/wake behavior and molecular circadian rhythms.

Attention deficit hyperactivity disorder (ADHD) is a common neuropsychiatric condition that has been strongly associated with changes in sleep and circadian rhythms. Circadian rhythms are near 24-h cycles that are primarily generated by an endogenous circadian timekeeping system, encoded at the molecular level by a panel of clock genes. Stimulant and non-stimulant medication used in the management of ADHD has been shown to potentially impact on circadian processes and their behavioral outputs.