Caspase-4 Has Potential Utility as a Colorectal Tissue Biomarker for Dysplasia and Early-Stage Cancer.

Background And Aims: Colorectal cancer (CRC) is the second most deadly cancer globally. The rapidly rising incidence rate of CRC, coupled with increased diagnoses in individuals <50 years, indicates that early detection of CRC, and those at an increased risk of CRC development, is paramount to improve the survival rates of these patients. Here, we profile caspase-4 expression across 2 distinct CRC development pathways, sporadic CRC (sCRC) and inflammatory bowel disease-associated CRC (IBD-CRC), to examine its utility as a novel biomarker for CRC risk and diagnosis.

Sleep variability and time to achieving pregnancy: findings from a pilot cohort study of women desiring pregnancy.

Objective: To determine whether chronodisruption is associated with achieving pregnancy.

Design: Pilot prospective cohort study.

Subjects: One hundred eighty-three women desiring pregnancy were recruited from the local community of an academic medical center located in the Midwest and provided sleep information between February 1, 2015, and November 30, 2017.

Synergistic Effects of the Combination of Alpelisib (PI3K Inhibitor) and Ribociclib (CDK4/6 Inhibitor) in Preclinical Colorectal Cancer Models.

The CDK4/6 inhibitor Ribociclib has shown limited efficacy as a monotherapy in colorectal cancer (CRC). However, combining Ribociclib with targeted therapies could present a viable strategy for treating CRC. This study evaluated the combination of Ribociclib and the PI3K inhibitor Alpelisib across four distinct cell lines representing different mutational statuses ( wild-type, -mutated, -mutated, and -mutated).

Structure-guided design of a peripherally restricted chemogenetic system.

Designer receptors exclusively activated by designer drugs (DREADDs) are chemogenetic tools for remotely controlling cellular signaling, neural activity, behavior, and physiology. Using a structure-guided approach, we provide a peripherally restricted Gi-DREADD, hydroxycarboxylic acid receptor DREADD (HCAD), whose native receptor is minimally expressed in the brain, and a chemical actuator that does not cross the blood-brain barrier (BBB). This was accomplished by combined mutagenesis, analoging via an ultra-large make-on-demand library, structural determination of the designed DREADD receptor via cryoelectron microscopy (cryo-EM), and validation of HCAD function.