Possible impacts of cosmic radiation on leukemia development during human deep space exploration

Leukemia, Journal Year: 2025, Volume and Issue: unknown

Published: April 24, 2025

Language: Английский

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Macrophage WEE1 Directly Binds to and Phosphorylates NF‐κB p65 Subunit to Induce Inflammatory Response and Drive Atherosclerosis

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: April 9, 2025

Abstract Atherosclerosis has an urgent need for new therapeutic targets. Protein kinases orchestrate multiple cellular events in atherosclerosis and may provide targets atherosclerosis. Here, a protein kinase, WEE1 G2 checkpoint kinase (WEE1), promoting inflammation is identified. Kinase enrichment analysis experimental evidences reveal macrophage phosphorylation at S642 human mouse atherosclerotic tissues. RNA‐seq analysis, combined with experiment studies using mutant plasmids, shows that phosphorylation, rather than expression, mediated oxLDL‐induced macrophages. Macrophage‐specific deletion of or pharmacological inhibition activity attenuates by reducing mice. Mechanistically, co‐immunoprecipitation followed proteomics are used to explore the mechanism substrate WEE1. p‐WEE1 promoted inflammatory response through activating NF‐κB shown further revealed can directly bind p65 subunit. It confirmed interacts RHD domain phosphorylates S536, thereby facilitating subsequent activation The findings demonstrate drives phosphorylating S536. This study identifies as upstream potential target

Language: Английский

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Genomic variant profiling in blast‐phase paediatric chronic myeloid leukaemia: Predisposing and driving alterations

British Journal of Haematology, Journal Year: 2025, Volume and Issue: unknown

Published: May 8, 2025

Summary Paediatric blast‐phase chronic myeloid leukaemia (CML‐BP) is a rare and serious condition. Of 231 paediatric patients enrolled in the German CML‐PAED‐II registry between January 2007 September 2023, 25 individuals (11%) were diagnosed with CML‐BP. To identify genetic variants associated early onset disease transformation, we performed whole genome sequencing (WGS), deep targeted cytogenetic analyses 19 cases de novo ( n = 11) or secondary 8) CML‐BP sufficient available biomaterial. Copy number (CNVs) more frequent than single nucleotide (SNVs) prevalent Recurrent pathogenic somatic SNVs observed ABL1 5, 24%), RUNX1 2, 12%) ASXL1 12%). Nine (47%) carried germline 1) either of genes ATM , CHEK2 FANCM HERC2 NBN RAD54B RECQL4 SETD2 TP63 belonging to DNA damage response (DDR). Within comparison cohort phase CML, only one individual (5%) exhibited DDR variant. Our study provides novel pathogenetic insights into The identification DDR‐associated suggests predisposition potential implications for families concerning cancer treatment surveillance.

Language: Английский

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Mitochondrial DNA damage, repair, and replacement in cancer

Trends in cancer, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 1, 2024

Language: Английский

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