Functional contributions of individual cellular components of the bone-marrow microenvironment to myelofibrosis (MF) in patients with myeloproliferative neoplasms (MPNs) are incompletely understood. We aimed to generate a comprehensive map of the stroma in MPNs/MFs on a single-cell level in murine models and patient samples. Our analysis revealed two distinct mesenchymal stromal cell (MSC) subsets as pro-fibrotic cells. MSCs were functionally reprogrammed in a stage-dependent manner with loss of their progenitor status and initiation of differentiation in the pre-fibrotic and acquisition of a pro-fibrotic and inflammatory phenotype in the fibrotic stage. The expression of the alarmin complex S100A8/S100A9 in MSC marked disease progression toward the fibrotic phase in murine models and in patient stroma and plasma. Tasquinimod, a small-molecule inhibiting S100A8/S100A9 signaling, significantly ameliorated the MPN phenotype and fibrosis in JAK2V617F-mutated murine models, highlighting that S100A8/S100A9 is an attractive therapeutic target in MPNs.
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http://dx.doi.org/10.1016/j.stem.2020.11.004 | DOI Listing |
Cancer Cell Int
December 2024
Department of Applied Chemistry, Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Taiwan.
Introduction: Chronic alcohol consumption and tobacco usage are major risk factors for esophageal squamous cell carcinoma (ESCC). Excessive tobacco and alcohol consumption lead to oxidative stress and the generation of reactive carbonyl species (RCS) which induce DNA damage and cell apoptosis. This phenomenon contributes to cell damage and carcinogenesis in various organs including ESCC.
View Article and Find Full Text PDFDiabet Med
December 2024
Department of Biomolecular Pharmacology, Hoshi University, Tokyo, Japan.
Aims: Skin disorders occur more frequently with sodium-dependent glucose cotransporter type 2 (SGLT2) inhibitors than with other antidiabetic drugs. We conducted basic research using ipragliflozin, with the aim of identifying new measures to prevent skin disorders caused by SGLT2 inhibitors.
Methods: db/db type 2 diabetes model mice were orally administered ipragliflozin (10 mg/kg or 30 mg/kg) once a day for 28 days and skin function genes were analysed by real-time RT-PCR or Western blotting.
Toxicol Appl Pharmacol
December 2024
Department of Infectious Diseases, The First Affiliated Hospital of Harbin Medical University, Harbin 150001, Heilongjiang, People's Republic of China. Electronic address:
Non-alcoholic fatty liver disease (NAFLD) is a major cause of chronic liver disease. The present work aimed to explore the function of regulator of Calcineurin 2 (RCAN2) in NAFLD and its related mechanisms. Mice were fed with high-fat diet (HFD) to construct NAFLD model.
View Article and Find Full Text PDFInt J Biochem Cell Biol
December 2024
Institute of Biology and Medicine, College of Life Science and Health, Wuhan University of Science and Technology, Wuhan, Hubei 430081, China; College of Biomedicine and Health, College of Life Science and Technology, Huazhong Agricultural University, Wuhan, Hubei 430070, China. Electronic address:
Considering the high degree of malignancy, recurrence rate and poor prognosis, exploring promising targets is an imperious strategy for colorectal carcinoma therapy. Recent studies have indicated that GABPα plays a role in cancer aggressiveness, but its exact function and regulatory mechanisms in colorectal cancer progression remain unclear. This study aims to explore the biological role of GABPα and its upstream regulator, miR-378a-5p, in modulating cancer progression.
View Article and Find Full Text PDFExp Eye Res
December 2024
Department of Biochemistry, Post-Graduate Program in Biochemistry and Post-Graduate Program in Pharmacology, Federal University of Santa Catarina (UFSC), Florianópolis, Santa Catarina, Brazil. Electronic address:
High intraocular pressure (HIOP) and high glucose levels are associated with oxidative stress. Although physical exercise protects against oxidative damage, its specific impact on eye health remains unclear. Thus, this study aimed to assess the impact of physical exercise on the oxidative status of whole eyes in male Swiss mice subjected to HIOP model and cafeteria diet (CD).
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