Resistance to standard and novel therapies remains the main obstacle to cure in acute myeloid leukaemia (AML) and is often driven by metabolic adaptations which are therapeutically actionable. Here we identify inhibition of mannose-6-phosphate isomerase (MPI), the first enzyme in the mannose metabolism pathway, as a sensitizer to both cytarabine and FLT3 inhibitors across multiple AML models. Mechanistically, we identify a connection between mannose metabolism and fatty acid metabolism, that is mediated via preferential activation of the ATF6 arm of the unfolded protein response (UPR). This in turn leads to cellular accumulation of polyunsaturated fatty acids, lipid peroxidation and ferroptotic cell death in AML cells. Our findings provide further support to the role of rewired metabolism in AML therapy resistance, unveil a connection between two apparently independent metabolic pathways and support further efforts to achieve eradication of therapy-resistant AML cells by sensitizing them to ferroptotic cell death.
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http://dx.doi.org/10.1038/s41467-023-37652-0 | DOI Listing |
Stem Cells Dev
December 2024
Department of Neurology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Ninety-nine percent of alpha-synuclein (α-syn) in the human body is distributed in erythrocytes. However, the role that α-syn plays in erythropoiesis remains unclear. To determine the effect of α-syn on erythroid differentiation, the erythroid cells, derived from human CD34+ progenitors in the umbilical cord, were cultured in a system composed of a series of cytokines and harvested after 6 days.
View Article and Find Full Text PDFBMC Plant Biol
December 2024
College of Horticulture, Sichuan Agricultural University, Chengdu, 611130, China.
Melatonin (MT) can improve plant resistance and fruit quality. The mechanism by which MT affects soluble sugar and organic acids accumulation in drupe fruits is not clear. In this study, 100 µmol/L MT was sprayed on the leaves of plum trees at the second stage of rapid fruit expansion (90 and 97 d after flowering), and the effects of MT on plum fruit quality and its effects on the soluble sugar-organic acid metabolism were investigated.
View Article and Find Full Text PDFAn Acad Bras Cienc
December 2024
Universidade Federal do Ceará, Departamento de Bioquímica e Biologia Molecular, Laboratório de Moléculas Biologicamente Ativas, Rua José Aurelio Camara, s/n, 60440-970 Fortaleza, CE, Brazil.
Understanding lectin-carbohydrate interactions at the structural and molecular levels is crucial to the field of lectins, as the diverse roles and biological activities exhibited by these proteins are fundamentally linked to their specific binding to target glycoconjugates. This study aimed to apply molecular dynamics to analyze the structure and binding properties of Parkia lectins. 3D structures of Parkia platycephala and P.
View Article and Find Full Text PDFJ Diabetes Metab Disord
June 2025
Department of Internal Medicine, University of Ioannina, Stavrou Niarchou Avenue, Ioannina, 45500 Greece.
Objectives: SGLT-2 inhibitors have been shown to exert cardio- and renoprotective actions. We aimed to investigate the underlying mechanisms using H-NMR based metabolomics in patients with type-2 diabetes mellitus who received dapagliflozin.
Methods: 50 patients with type 2 diabetes mellitus, inadequately controlled on metformin monotherapy (HbA1c > 7%) received dapagliflozin for 3 months and 30 matched patients received insulin degludec for 3 months.
J Nanobiotechnology
December 2024
Ultrasound Medical Center, Gansu Province Clinical Research Center for Ultrasonography, Gansu Province Medical Engineering Research Center for Intelligence Ultrasound, Lanzhou University Second Hospital, Lanzhou, 730030, P.R. China.
Background: The progression of triple-negative breast cancer is shaped by both tumor cells and the surrounding tumor microenvironment (TME). Within the TME, tumor-associated macrophages (TAMs) represent a significant cell population and have emerged as a primary target for cancer therapy. As antigen-presenting cells within the innate immune system, macrophages are pivotal in tumor immunotherapy through their phagocytic functions.
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