Evaluation of the In Vivo Efficacy of the JAK Inhibitor AZD1480 in Uterine Leiomyomas Using a Patient-derived Xenograft Murine Model.

Uterine leiomyomas are common noncancerous hormonally-dependent neoplasms comprised of uterine smooth-muscle cells and fibroblasts. Despite their significant impact on morbidity, effective non-hormonal medical treatments are lacking. In vitro studies have identified the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway as a promising target in leiomyoma cells.

Posterior Wall Thickness Associates With Survival Following Septal Myectomy for Obstructive Hypertrophic Cardiomyopathy.

Background: The left ventricular (LV) posterior wall thickness (PWT) is a predictor of sudden cardiac death in pediatric patients with hypertrophic cardiomyopathy (HCM), but the prognostic importance of PWT in adults has not been examined.

Objectives: The goal of this study was to evaluate the association of LV PWT with late survival in adult patients undergoing septal myectomy for obstructive HCM.

Methods: This single-center study reviewed 2,418 patients who underwent transaortic septal myectomy for obstructive HCM.

ZNF416 is a pivotal transcriptional regulator of fibroblast mechanoactivation.

Matrix stiffness is a central regulator of fibroblast function. However, the transcriptional mechanisms linking matrix stiffness to changes in fibroblast phenotype are incompletely understood. Here, we evaluated the effect of matrix stiffness on genome-wide chromatin accessibility in freshly isolated lung fibroblasts using ATAC-seq.

Targeting GPCR Signaling for Idiopathic Pulmonary Fibrosis Therapies.

A variety of G protein-coupled receptors (GPCRs) have been implicated in the pathogenesis of pulmonary fibrosis, largely through their promotion of profibrotic fibroblast activation. By contrast, recent work has highlighted the beneficial effects of Gαs-coupled GPCRs on reducing fibroblast activation and fibrosis. This review highlights how fibrosis-promoting and -inhibiting GPCR signaling converges on downstream signaling and transcriptional effectors, and how the diversity and dynamics of GPCR expression challenge efforts to identify effective therapies for idiopathic pulmonary fibrosis (IPF).