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Design, Synthesis and Anti-Inflammatory Evaluation of 3-Substituted 5-Amidobenzoate Derivatives as Novel P2Y Receptor Antagonists via Structure-Guided Molecular Hybridization.
J Med Chem
January 2025
College of Chemistry, Zhengzhou University, Zhengzhou 450001, China.
The P2YR is activated by UDP and UDP glucose and is involved in many human inflammatory diseases. Based on the molecular docking analysis of currently reported P2YR antagonists and the crystallographic overlap study between PPTN and compound , a series of 3-substituted 5-amidobenzoate derivatives were designed, synthesized, and identified as promising P2YR antagonists. The optimal compound (methyl 3-(1-benzo[]imidazol-2-yl)-5-(2-(-tolyl) acetamido)benzoate, IC = 0.
View Article and Find Full Text PDFDNA methylation inhibitors adverse reaction characteristic analysis: an analysis based on the European spontaneous adverse event reporting system.
Front Pharmacol
January 2025
Department of Cardiology, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China.
Introduction: DNA methylation inhibitors have been approved for the prevention of Acute Myeloid Leukemia (AML), and their safety profile is not fully characterized. This study was aimed at evaluating the adverse drug reactions (ADRs) of DNA methylation inhibitors by analyzing the individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database.
Materials And Methods: The EV database managed by the European Medicines Agency was adopted.
The Ataxia-telangiectasia mutated (ATM) is the most important gene for repairing the DNA in Myelodysplastic Neoplasm.
DNA Repair (Amst)
January 2025
Cancer Cytogenomic Laboratory, Center for Research and Drug Development (NPDM), Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program in Medical Science, Federal University of Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Pathology, Federal University of Ceara, Fortaleza, Ceara, Fortaleza, Ceara, Brazil; Post-Graduate Program of Translational Medicine, Federal University of Ceara, Fortaleza, Ceara, Brazil.
Myelodysplastic Neoplasm (MDS) is a cancer associated with aging, often leading to acute myeloid leukemia (AML). One of its hallmarks is hypermethylation, particularly in genes responsible for DNA repair. This study aimed to evaluate the methylation and mutation status of DNA repair genes (single-strand - XPA, XPC, XPG, CSA, CSB and double-strand - ATM, BRCA1, BRCA2, LIG4, RAD51) in MDS across three patient cohorts (Cohort A-56, Cohort B-100, Cohort C-76), using methods like pyrosequencing, real-time PCR, immunohistochemistry, and mutation screening.
View Article and Find Full Text PDFLongitudinal Associations of PFAS Exposure With Insulin Sensitivity and β-Cell Function Among Hispanic Women With Gestational Diabetes Mellitus History.
Diabetes Care
January 2025
Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA.
Objective: We investigated associations between per- and polyfluoroalkyl substances (PFAS) and changes in diabetes indicators from pregnancy to 12 years after delivery among women with a history of gestational diabetes mellitus (GDM).
Research Design And Methods: Eighty Hispanic women with GDM history were followed from the third trimester of pregnancy to 12 years after delivery. Oral and intravenous glucose tolerance tests were conducted during follow-up.
Nelonemdaz and Patients With Acute Ischemic Stroke and Mechanical Reperfusion: The RODIN Randomized Clinical Trial.
JAMA Netw Open
January 2025
Department of Neurology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
Importance: Nelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species.
Objective: To evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy.
Design, Setting, And Participants: This multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset.
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