Targeting N-Myc in neuroblastoma with selective Aurora kinase A degraders.

The N-Myc transcription factor, encoded by MYCN, is a mechanistically validated, yet challenging, target for neuroblastoma (NB) therapy development. In normal neuronal progenitors, N-Myc undergoes rapid degradation, while, in MYCN-amplified NB cells, Aurora kinase A (Aurora-A) binds to and stabilizes N-Myc, resulting in elevated protein levels. Here, we demonstrate that targeted protein degradation of Aurora-A decreases N-Myc levels.

Lower pain, less itching, and faster healing after ultrasound scalpel-assisted hemorrhoidectomy using an intimate cleaner containing chlorhexidine, acid hyaluronic acid, and natural anti-inflammatories: a multicenter observational case-control study.

Purpose: Postoperative pain is a major concern for patients undergoing ultrasound scalpel-assisted hemorrhoidectomy, potentially exacerbated by delayed wound healing. This study aimed to evaluate the impact of an intimate cleansing gel containing chlorhexidine, hyaluronic acid, and other anti-inflammatory agents (Antroclean Fisioderm) on postoperative pain, itching, and wound healing in patients who had undergone this procedure.

Methods: This multicenter observational case-control study involved a cohort of consecutive adult patients who underwent hemorrhoidectomy using an ultrasound device.

The Impact of Sugar Conformation on the Single-Stranded DNA Selectivity of APOBEC3A and APOBEC3B Enzymes.

The APOBEC3 family of polynucleotide cytidine deaminases has diverse roles as viral restriction factors and oncogenic mutators. These enzymes convert cytidine to uridine in single-stranded (ss)DNA, inducing genomic mutations that promote drug resistance and tumor heterogeneity. Of the seven human APOBEC3 members, APOBEC3A (A3A) and APOBEC3B (A3B) are most implicated in driving pro-tumorigenic mutations.

Validation of a functional human AD model with four AD therapeutics utilizing patterned ipsc-derived cortical neurons integrated with microelectrode arrays.

Preclinical methods are needed for screening potential Alzheimer's disease (AD) therapeutics that recapitulate phenotypes found in the Mild Cognitive Impairment (MCI) stage or even before this stage of the disease. This would require a phenotypic system that reproduces cognitive deficits without significant neuronal cell death to mimic the clinical manifestations of AD during these stages. Long-term potentiation (LTP), which is a correlate of learning and memory, was induced in mature human iPSC-derived cortical neurons cultured on microelectrode arrays utilizing circuit patterns connecting two adjacent electrodes.

Establishment of a Serum-Free Human iPSC-Derived Model of Peripheral Myelination.

Myelination and the formation of nodes of Ranvier are essential for the rapid conduction of nerve impulses along axons in the peripheral nervous system (PNS). While many animal-based and serum-containing models of peripheral myelination have been developed, these have limited ability when it comes to studying genetic disorders affecting peripheral myelination. We report a fully induced pluripotent stem cell (iPSC)-derived human model of peripheral myelination using Schwann cells (SCs) and motoneurons, cultured in a serum-free medium on patterned and nonpatterned surfaces.