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Cardiac acetylcholinesterase and butyrylcholinesterase have distinct localization and function.
Am J Physiol Heart Circ Physiol
January 2025
Comenius University Bratislava, Faculty of Pharmacy, Department of Pharmacology and Toxicology, Bratislava, Slovakia.
Cholinesterase (ChE) inhibitors are under consideration to be used in the treatment of cardiovascular pathologies. A prerequisite to advancing ChE inhibitors into the clinic is their thorough characterization in the heart. The aim here was to provide a detailed analysis of cardiac ChE to understand their molecular composition, localization, and physiological functions.
View Article and Find Full Text PDFMicrobial Primer: Microbiome and thermal tolerance - a new frontier in climate resilience?
Microbiology (Reading)
January 2025
Department of Zoology, University of British Columbia, Vancouver, Canada.
Microbiome-animal host symbioses are ubiquitous in nature. Animal-associated microbiomes can play a crucial role in host physiology, health and resilience to environmental stressors. As climate change drives rising global temperatures and increases the frequency of thermal extremes, microbiomes are emerging as a new frontier in buffering vulnerable animals against temperature fluctuations.
View Article and Find Full Text PDFThe Splice Index as a prognostic biomarker of strength and function in myotonic dystrophy type 1.
J Clin Invest
January 2025
Center for Inherited Myology Research, Virginia Commonwealth University, Richmond, United States of America.
Background: Myotonic dystrophy type 1 (DM1) is a multisystemic, CTG repeat expansion disorder characterized by a slow, progressive decline in skeletal muscle function. A biomarker correlating RNA mis-splicing, the core pathogenic disease mechanism, and muscle performance is crucial for assessing response to disease-modifying interventions. We evaluated the Myotonic Dystrophy Splice Index (SI), a composite RNA splicing biomarker incorporating 22 disease-specific events, as a potential biomarker of DM1 muscle weakness.
View Article and Find Full Text PDFIdentifying and targeting key driver genes for collagen production within the 11q13/14 breast cancer amplicon.
Mol Cancer Res
January 2025
Fox Chase Cancer Center, Philadelphia, PA, United States.
Breast cancers of the IntClust-2 type, characterized by amplification of a small portion of chromosome 11, have a median survival of only five years. Several cancer-relevant genes occupy this portion of chromosome 11, and it is thought that overexpression of a combination of driver genes in this region is responsible for the poor outcome of women in this group. In this study we used a gene editing method to knock out, one by one, each of 198 genes that are located within the amplified region of chromosome 11 and determined how much each of these genes contributed to the survival of breast cancer cells.
View Article and Find Full Text PDFPopulation Pharmacokinetics of Orvacabtagene Autoleucel, an Autologous BCMA-Directed Chimeric Antigen Receptor T-Cell Product, in Patients with Relapsed/Refractory Multiple Myeloma.
Clin Cancer Res
January 2025
Bristol-Myers Squibb (United States), Summit, New Jersey, United States.
Purpose: Orvacabtagene autoleucel (orva-cel; JCARH125), a CAR T-cell therapy targeting B-cell maturation antigen (BCMA), was evaluated in relapsed/refractory multiple myeloma (RRMM) patients in the EVOLVE phase 1/2 study (NCT03430011). We applied a modified piecewise model to characterize orva-cel transgene kinetics and assessed the impact of various covariates on its pharmacokinetics (PK).
Experimental Design: The population PK analysis included 159 patients from the EVOLVE study.
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