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HoxBlinc lncRNA reprograms CTCF-independent TADs to drive leukemic transcription and HSC dysregulation in NUP98-rearranged leukemia.
J Clin Invest
January 2025
Division of Pediatric Hematology/Oncology, Department of Pediatrics, Pennsylvania State University College of Medicine, Hershey, United States of America.
Although nucleoporin 98 (NUP98) fusion oncogenes often drive aggressive pediatric leukemia by altering chromatin structure and expression of HOX genes, underlying mechanisms remain elusive. Here, we report that a Hoxb-associated lncRNA HoxBlinc was aberrantly activated in NUP98-PHF23 fusion-driven leukemias. HoxBlinc chromatin occupancies led to elevated MLL1 recruitment and aberrant homeotic topologically associated domains (TADs) that enhanced chromatin accessibilities and activated homeotic/hematopoietic oncogenes.
View Article and Find Full Text PDFAntiproliferative activity of a series of copper(II) complexes derived from a furan-containing -acylhydrazone: monomers, dimers, charge status, and cell mechanistic studies on triple negative breast cancer cells.
Dalton Trans
January 2025
CEQUINOR (UNLP, CCT-CONICET La Plata, asociado a CIC), Departamento de Química, Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Blvd. 120 No. 1465, La Plata (1900), Argentina.
In this work, we evaluated the anticancer activity of compounds 1 (mononuclear) and 2 (dinuclear) copper(II) coordination compounds derived from the ligand 5-methylsalicylaldehyde 2-furoyl hydrazone (H2L) over MDA-MB-231 Triple-negative breast cancer (TNBC) cells, and compared their activities with that of a newly synthesized, protonated, dinuclear analogue of 2 (complex 3). Here, we report the synthesis of compound 3 and it has been characterized in the solid state (X-ray diffraction, FTIR) and in solution (EPR, UV-Vis, ESI) as well as its electrochemical profile. Complexes 1-3 impaired cell viability from 0.
View Article and Find Full Text PDFRelaxin in pregnancy: a narrative review of a pleiotropic molecule.
Minerva Obstet Gynecol
January 2025
Unit of Obstetrics and Gynecology, Department of Medical and Surgical Sciences for Mothers, Children and Adults, Policlinic University Hospital, University of Modena and Reggio Emilia, Modena, Italy.
Introduction: Relaxin is a hormone primarily produced by the corpus luteum during pregnancy, and it plays a critical role in various physiological processes related to pregnancy and childbirth.
Evidence Acquisition: Studies have suggested a possible link between relaxin levels and preterm birth. Relaxin's effects on the cervix and pelvic ligaments suggest it could influence the mode of delivery.
Exploring the Role of TRAF6-TAK1 Pathway in Podocyte Pyroptosis and Its Implications for Primary Membranous Nephropathy Therapy.
Inflammation
January 2025
Department of Nephrology, the First Affiliated Hospital of Bengbu Medical University, No. 287, Changhuai Road, Longzihu District, Bengbu, 233000, Anhui Province, China.
Primary membranous nephropathy (PMN) is a prevalent renal disorder characterized by immune-mediated damage to the glomerular basement membrane, with recent studies highlighting the significant role of pyroptosis in its progression. In this study, we investigate the molecular mechanisms underlying PMN, focusing on the role of Tumor necrosis factor receptor-associated factor 6 (TRAF6) in promoting disease advancement. Specifically, we examine how TRAF6 facilitates PMN progression by inducing the ubiquitination of Transforming growth factor-beta-activated kinase 1 (TAK1), which in turn activates the Gasdermin D (GSDMD)/Caspase-1 axis, leading to podocyte pyroptosis.
View Article and Find Full Text PDFExplanatory review on DDR inhibitors: their biological activity, synthetic route, and structure-activity relationship.
Mol Divers
January 2025
Integrated Drug Discovery Centre, Department of Pharmaceutical Chemistry, Acharya & BM Reddy College of Pharmacy, Bengaluru, 560107, Karnataka, India.
Discoidin domain receptors (DDR) are categorized under tyrosine kinase receptors (RTKs) and play a crucial role in various etiological conditions such as cancer, fibrosis, atherosclerosis, osteoarthritis, and inflammatory diseases. The structural domain rearrangement of DDR1 and DDR2 involved six domains of interest namely N-terminal DS, DS-like, intracellular juxtamembrane, transmembrane juxtamembrane, extracellular juxtamembrane intracellular kinase domain, and the tail portion contains small C-tail linkage. DDR has not been explored to a wide extent to be declared as a prime target for any particular pathological condition.
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