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doi: 10.3389/fphys.2021.702826 Received 30 April 2021 Accepted 24 June 2021 Published 20 July 2021 Volume 12 - 2021 Edited by Enrique Jaimovich, University of Chile, Chile Reviewed by Alexis Diaz, The University of Sydney, Australia

doi: 10.1074/jbc.M109.041376 26

3.2 Hyperactivation of glycolytic pathways in RA synoviocytes The hyperactivation of glycolysis in RA synoviocytes is centered on HK2, whose mitochondrial-bound state drives pathological processes through the dual role of catalyzing glucose phosphorylation and regulating apoptosis ( HK2 gene could significantly inhibit the migration and invasion of FLS as well as lactate production, while its overexpression enhanced its pro-inflammatory function and positively correlated with tumor-like transformation characteristics ( The HK2-selective inhibitors (such as 3-BrPA) could specifically inhibit FLS invasiveness in animal models without interfering with normal cellular metabolism ( 3.3 Multidimensional effects of lipid metabolism imbalance in RA Dysregulation of RA lipid metabolism is characterized by elevated LDL-C levels, impaired HDL-C function, and abnormal PCSK9 accumulation, which directly drive inflammation and immune dysregulation

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