International Journal of Molecular Medical Science, 2025, Vol.15, No.1, 20-32 http://medscipublisher.com/index.php/ijmms 24 Figure 2 (A) CF-related over-represented terms; DEGs obtained from Myr-treated and untreated A. fumigatus-infected CF monocytes; the comparisons were used for performing over-representation analysis (ORA) using GO, KEGG, and MSigDB terms. Here are shown the enriched terms (adjustedp-value<0.05) matching the top functional categories related to CF including autophagy, infection, inflammation, and lipid metabolism. On the x-axis, the number of DEGs belonging to the enriched term. (B) Volcano plot showing DEGs distribution between up- and downregulated genes with labels for the top 20 significant DEGs. On the x-axis, the log2Fold change, and on the y-axis the adjusted p-value (-log10). (C) STRING analysis of up regulated DEGs in treated versus untreated comparison (Adopted from Mingione et al., 2020a) Chronic inflammation in CF patients drives protein catabolism, leading to muscle wasting and reduced physical strength. The inflammatory cytokines produced in response to persistent infections and defective CFTR function contribute to the breakdown of muscle proteins, exacerbating malnutrition and weakening the immune response (Lara-Reyna et al., 2019; Feng et al., 2023). 4.4 Oxidative stress and redox imbalance Oxidative stress plays a critical role in the exacerbation of CF symptoms. The imbalance between the production of Reactive Oxygen Species (ROS) and the body's antioxidant defenses leads to cellular damage and inflammation. This oxidative stress is a key factor in the progression of lung disease and other complications in CF patients (Lara-Reyna et al., 2019; Scholte et al., 2019; Veltman et al., 2021). CF patients exhibit dysregulation of antioxidant defenses, including impaired glutathione metabolism. Glutathione is a crucial antioxidant that helps mitigate oxidative stress. In CF, the reduced availability of glutathione exacerbates oxidative damage and inflammation, highlighting the need for therapeutic strategies that enhance antioxidant defenses (Lara-Reyna et al., 2019; Scholte et al., 2019; Veltman et al., 2021).
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