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DDO1002, an NRF2-KEAP1 inhibitor, improves hematopoietic stem cell aging and stress response.
Life Med
December 2024
Zhejiang Key Laboratory of Medical Epigenetics, School of Basic Medical Sciences, The Third People's Hospital of Deqing, Department of Cardiology, Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou 311121, China.
Oxidative stress diminishes the functionality of hematopoietic stem cells (HSCs) as age advances, with heightened reactive oxygen species (ROS) levels exacerbating DNA damage, cellular senescence, and hematopoietic impairment. DDO1002, a potent inhibitor of the NRF2-KEAP1 pathway, modulates the expression of antioxidant genes. Yet, the extent to which it mitigates hematopoietic decline post-total body irradiation (TBI) or in the context of aging remains to be elucidated.
View Article and Find Full Text PDFA Senescent Cluster in Aged Human Hematopoietic Stem Cell Compartment as Target for Senotherapy.
Int J Mol Sci
January 2025
Department of Medicine V, Heidelberg University, 69117 Heidelberg, Germany.
To identify the differences between aged and young human hematopoiesis, we performed a direct comparison of aged and young human hematopoietic stem and progenitor cells (HSPCs). Alterations in transcriptome profiles upon aging between humans and mice were then compared. Human specimens consist of CD34+ cells from bone marrow, and mouse specimens of hematopoietic stem cells (HSCs; Lin- Kit+ Sca1+ CD150+).
View Article and Find Full Text PDFComprehensive Characterization of Overt Myelofibrosis in an Asian Cohort: Phenotype, Mutation Landscape and Discordance Among Scoring Systems.
Hematol Oncol
January 2025
Division of Hematology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
Various prognostic scoring systems in myelofibrosis (MF) have been developed to guide clinical decision-making in MF. However, discrepancies between different scoring systems for individual patients remain poorly understood, which can result in conflicting treatment recommendations. Moreover, data regarding there applicability in Asian populations remain scarce.
View Article and Find Full Text PDFClonal hematopoiesis of indeterminate potential and type 2 diabetes mellitus among patients with STEMI: from a prospective cohort study combing bidirectional Mendelian randomization.
Cardiovasc Diabetol
January 2025
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, No.167, Beijing, 100037, China.
Aim: Both clonal hematopoiesis of indeterminate potential (CHIP) and type 2 diabetes mellitus (T2DM) are conditions closely associated with advancing age. This study delves into the possible implications and prognostic significance of CHIP and T2DM in patients diagnosed with ST-segment elevation myocardial infarction (STEMI).
Methods: Deep-targeted sequencing employing a unique molecular identifier (UMI) for the analysis of 42 CHIP mutations-achieving an impressive mean depth of coverage at 1000 × -was conducted on a cohort of 1430 patients diagnosed with acute myocardial infarction (473 patients with T2DM and 930 non-DM subjects).
Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography.
JAMA Netw Open
January 2025
Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Importance: Disease characteristics of genetically mediated coronary artery disease (CAD) on coronary angiography and the association of genomic risk with outcomes after coronary angiography are not well understood.
Objective: To assess the angiographic characteristics and risk of post-coronary angiography outcomes of patients with genomic drivers of CAD: familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP).
Design, Setting, And Participants: A retrospective cohort study of 3518 Mass General Brigham Biobank participants with genomic information who underwent coronary angiography was conducted between July 18, 2000, and August 1, 2023.
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