Histone methylation plays a key function in modulating gene expression, and preserving genome integrity and epigenetic inheritance. However, aberrations of histone methylation are commonly observed in human diseases, especially cancer. Lysine methylation mediated by histone methyltransferases can be reversed by lysine demethylases (KDMs), which remove methyl marks from histone lysine residues. Currently, drug resistance is a main impediment for cancer therapy. KDMs have been found to mediate drug tolerance of many cancers via altering the metabolic profile of cancer cells, upregulating the ratio of cancer stem cells and drug-tolerant genes, and promoting the epithelial-mesenchymal transition and metastatic ability. Moreover, different cancers show distinct oncogenic addictions for KDMs. The abnormal activation or overexpression of KDMs can alter gene expression signatures to enhance cell survival and drug resistance in cancer cells. In this review, we describe the structural features and functions of KDMs, the KDMs preferences of different cancers, and the mechanisms of drug resistance resulting from KDMs. We then survey KDM inhibitors that have been used for combating drug resistance in cancer, and discuss the opportunities and challenges of KDMs as therapeutic targets for cancer drug resistance.
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http://dx.doi.org/10.1002/med.21955 | DOI Listing |
Medicine (Baltimore)
January 2025
Department of Respiratory and Critical Care Medicine, Zhongshan City People's Hospital, Zhongshan, Guangdong Province, China.
Rationale: ROS proto-oncogene 1 (ROS1) fusion is a rare but important driver mutation in non-small cell lung cancer, which usually shows significant sensitivity to small molecule tyrosine kinase inhibitors. With the widespread application of next-generation sequencing (NGS), more fusions and co-mutations of ROS1 have been discovered. Non-muscle myosin heavy chain 9 (MYH9) is a rare fusion partner of ROS1 gene as reported.
View Article and Find Full Text PDFJ Infect Dis
January 2025
Department of Medical and Surgical Sciences, Alma Mater Studiorum, University of Bologna, Italy.
Background: To assess the impact of attaining aggressive beta-lactam pharmacokinetic/pharmacodynamic (PK/PD) targets on clinical efficacy in critical orthotopic liver transplant (OLT) recipients with documented early Gram-negative infections.
Methods: OLT recipients admitted to the post-transplant ICU between June 2021 and May 2024 having documented Gram-negative infections treated with targeted therapy continuous infusion (CI) beta-lactams, and undergoing therapeutic drug monitoring (TDM)-guided beta-lactam dosing adjustment in the first 72 hours were prospectively enrolled. Free steady-state concentrations (fCss) of beta-lactams (BL) and/or of beta-lactamase inhibitors (BLI) were calculated, and aggressive PK/PD target attainment was measured.
PLoS One
January 2025
Department of Microbiology and Hygiene, Mymensingh, Bangladesh.
Pseudomonas aeruginosa (P. aeruginosa) is a major pathogen associated conditions like septicaemia, respiratory disorders, and diarrhoea in poultry, particularly in Japanese quail (Coturnix japonica). The infection causes huge economical losses due to its high transmissibility, mortality and zoonotic potential.
View Article and Find Full Text PDFPLoS One
January 2025
Department of Biochemistry and Molecular Biology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania.
Escherichia coli is one of the critical One Health pathogens due to its vast array of virulence and antimicrobial resistance genes. This study used multiplex PCR to determine the occurrence of virulence genes bfp, ompA, traT, eaeA, and stx1 among 50 multidrug-resistant (MDR) E. coli isolates from humans (n = 15), animals (n = 29), and the environment (n = 6) in Dar es Salaam, Tanzania.
View Article and Find Full Text PDFPLoS Biol
January 2025
Department of Internal Medicine, Teikyo University School of Medicine, Tokyo, Japan.
The unique architecture of the liver consists of hepatic lobules, dividing the hepatic features of metabolism into 2 distinct zones, namely the pericentral and periportal zones, the spatial characteristics of which are broadly defined as metabolic zonation. R-spondin3 (Rspo3), a bioactive protein promoting the Wnt signaling pathway, regulates metabolic features especially around hepatic central veins. However, the functional impact of hepatic metabolic zonation, regulated by the Rspo3/Wnt signaling pathway, on whole-body metabolism homeostasis remains poorly understood.
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