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Mechanistically, PYC inhibits NF-B activation, leading to decreased transcription of pro-inflammatory mediators such as TNF-, ICAM-1, and vascular cell adhesion molecule-1, thereby modulating cytokine-driven inflammatory responses and endothelial activation ( Network pharmacology and protein-protein interaction analyses have identified IL-6, TNF, IL-1B, prostaglandin endoperoxide synthase 2, and NF-B1 as core molecular targets of PYC, with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment highlighting the IL-17 and TNF signaling pathways as key anti-inflammatory mechanisms

Risk factors for greater lean tissue loss likely include advanced age, rapid or large absolute weight loss, low dietary protein intake, sedentary lifestyle, and comorbid conditions such as chronic kidney disease or long-standing diabetes [15]

Although ponatinib is an FDA-approved TKI that directly targets T315I-Bcr-Abl leukemia, its association with cardiovascular toxicity is a significant concern in clinical therapy

1, July 2007, pp