Structure‐activity relationship study of neuroprotective complex I inhibitor CP2.

Background: We identified small molecule tricyclic pyrone compound CP2 as a mild mitochondrial complex I (MCI) inhibitor that induces neuroprotection in multiple mouse models of AD. One of the major concerns while targeting mitochondria is the production of reactive oxygen species (ROS). CP2 consists of two diastereoisomers, D1 and D2, with distinct activity and toxicity profiles.

The A to Z of Peroral Endoscopic Myotomy.

Peroral endoscopic myotomy (POEM) is a novel technique within the field of third space endoscopy. The overarching principal is creation of a mucosal incision, careful dissection of the submucosal space using an electrosurgical knife to reach the muscularis (ie, tunneling), performing a controlled myotomy, and finally, closure of the mucosal incision. POEM was first developed for the management of achalasia, and now a decade of evidence shows the procedure is safe, effective, and highly reproducible.

Pharmacological Inhibition of Astrocytic Transglutaminase 2 Facilitates the Expression of a Neurosupportive Astrocyte Reactive Phenotype in Association with Increased Histone Acetylation.

Astrocytes play critical roles in supporting structural and metabolic homeostasis in the central nervous system (CNS). CNS injury leads to the development of a range of reactive phenotypes in astrocytes whose molecular determinants are poorly understood. Finding ways to modulate astrocytic injury responses and leverage a pro-recovery phenotype holds promise in treating CNS injury.

Critical comparison of BMD and TD methods for the calculation of acceptable intakes for N-nitroso compounds.

The tumorigenic dose 50 (TD) is a widely used measure of carcinogenic potency which has historically been used to determine acceptable intake limits for carcinogenic compounds. Although broadly used, the TD model was not designed to account for important biological factors such as DNA repair and cell compensatory mechanisms, changes in absorption, etc., leading to the development of benchmark dose (BMD) approaches, which use more flexible dose-response models that are better able to account for these processes.