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A limitation of our study was the absence of muscle biopsy, which could have provided additional data regarding intramuscular LCR levels as well as molecular and cellular responses, including proteins involved in the mTOR pathway

Furthermore, in line with the recent elucidation of the mechanism by which fumarate accumulation in these cells induces epithelial-to-mesenchymal-transition (EMT) 40 , the protein expression data showed a clear EMT signature exemplified by downregulation of E-cadherin ( Cdh1 ) and epithelial cell adhesion molecule ( Epcam ), as well as upregulation of vimentin ( Vim ) (Fig

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In contrast, in macrophage-like cells, synthetic ICA derivatives (at concentrations of 10.821.6 M) elicit a distinct response: within 4 hours of exposure, they activate endosomal TLR3 and surface TLR4 (164), triggering cascades of type I interferons (e.g., IFNB1) and proinflammatory cytokines (e.g., IL6, IL12A/B) that amplify innate antiviral immunityunderscoring ICAs context-dependent functional plasticity