Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint.

The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 in immune checkpoint blockade (ICB), as MHC class I interactions mediate both activating and inhibitory functions in antitumor immunity. Loss of ERAP sensitized mouse tumor models to ICB, and this sensitivity depended on CD8 T cells and natural killer (NK) cells.

Inhibition of Aurora Kinase Induces Endogenous Retroelements to Induce a Type I/III IFN Response via RIG-I.

Unlabelled: Type I IFN signaling is a crucial component of antiviral immunity that has been linked to promoting the efficacy of some chemotherapeutic drugs. We developed a reporter system in HCT116 cells that detects activation of the endogenous IFI27 locus, an IFN target gene. We screened a library of annotated compounds in these cells and discovered Aurora kinase inhibitors (AURKi) as strong hits.

Discovery of a Potent Chloroacetamide GPX4 Inhibitor with Bioavailability to Enable Target Engagement in Mice, a Potential Tool Compound for Inducing Ferroptosis .

Compounds that inhibit glutathione peroxidase 4 (GPX4) hold promise as cancer therapeutics in their ability to induce a form of nonapoptotic cell death called ferroptosis. Our research identified , a structural analog of the potent GPX4 inhibitor RSL3, that has much better plasma stability ( > 5 h in mouse plasma). The bioavailability of provided efficacious plasma drug concentrations with IP dosing, thus enabling studies to assess tolerability and efficacy.

A multifactorial intervention to increase adherence to oral appliance therapy with a titratable mandibular advancement device for obstructive sleep apnea: a randomized controlled trial.

Purpose: Obstructive sleep apnea (OSA) is a common chronic condition, associated with several conditions that account for leading causes of mortality. Adherence to treatment of a chronic condition is, along with treatment efficacy, a major determinant of treatment outcome. The aim of this study was to test whether or not a multifactorial intervention in addition to standard care increases adherence rates in patients using a titratable oral appliance for OSA.

Referral rate for obstructive sleep apnea in a pre-doctoral dental clinic using the STOP-Bang Questionnaire.

Objectives: Obstructive sleep apnea (OSA) is a common condition that can result in significant illness when untreated. Only 10%-20% of individuals with OSA are believed to be properly diagnosed. Consequently, dentists are encouraged to identify patients at high risk for OSA.