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Discovery, Optimization, and Preclinical Pharmacology of EP652, a METTL3 Inhibitor with Efficacy in Liquid and Solid Tumor Models.
J Med Chem
January 2025
Epics Therapeutics SA, rue Adrienne Bolland 47, Gosselies 6041, Belgium.
METTL3 is the RNA methyltransferase predominantly responsible for the addition of N-methyladenosine (mA), the most abundant modification to mRNA. The prevalence of mA and the activity and expression of METTL3 have been linked to the appearance and progression of acute myeloid leukemia (AML), thereby making METTL3 an attractive target for cancer therapeutics. We report herein the discovery and optimization of small-molecule inhibitors of METTL3, culminating in the selection of as an proof-of-concept compound.
View Article and Find Full Text PDFEffects of Chemical Pretreatments of Wood Cellulose Nanofibrils on Protein Adsorption and Biological Outcomes.
ACS Appl Mater Interfaces
January 2025
Center of Translational Oral Research (TOR), Department of Clinical Dentistry, University of Bergen, Bergen 5009, Norway.
Wood-based nanocellulose is emerging as a promising nanomaterial in the field of tissue engineering due to its unique properties and versatile applications. Previously, we used TEMPO-mediated oxidation (TO) and carboxymethylation (CM) as chemical pretreatments prior to mechanical fibrillation of wood-based cellulose nanofibrils (CNFs) to produce scaffolds with different surface chemistries. The aim of the current study was to evaluate the effects of these chemical pretreatments on serum protein adsorption on 2D and 3D configurations of TO-CNF and CM-CNF and then to investigate their effects on cell adhesion, spreading, inflammatory mediator production , and the development of foreign body reaction (FBR) .
View Article and Find Full Text PDFCBX2 suppresses interferon signaling to diminish tumor immunogenicity via a noncanonical corepressor complex.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.
View Article and Find Full Text PDFImproved GOA-based fuzzy PI speed control of PMSM with predictive current regulation.
PLoS One
January 2025
Faculty of Electrical and Control Engineering, Liaoning Technical University, Huludao, Liaoning, China.
To address the susceptibility of conventional vector control systems for permanent magnet synchronous motors (PMSMs) to motor parameter variations and load disturbances, a novel control method combining an improved Grasshopper Optimization Algorithm (GOA) with a variable universe fuzzy Proportional-Integral (PI) controller is proposed, building upon standard fuzzy PI control. First, the diversity of the population and the global exploration capability of the algorithm are enhanced through the integration of the Cauchy mutation strategy and uniform distribution strategy. Subsequently, the fusion of Cauchy mutation and opposition-based learning, along with modifications to the optimal position, further improves the algorithm's ability to escape local optima.
View Article and Find Full Text PDFBone Marrow Niche in Cardiometabolic Disease: Mechanisms and Therapeutic Potential.
Circ Res
January 2025
Division of Cardiovascular Medicine, Department of Medicine (J.B.H., J.D.B., A.C.D.), Vanderbilt University Medical Center, Nashville, TN.
Cardiovascular and cardiometabolic diseases are leading causes of morbidity and mortality worldwide, driven in part by chronic inflammation. Emerging research suggests that the bone marrow microenvironment, or marrow niche, plays a critical role in both immune system regulation and disease progression. The bone marrow niche is essential for maintaining hematopoietic stem cells (HSCs) and orchestrating hematopoiesis.
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