Metadichol regulates Sox network in human peripheral blood mononuclear cells

Background The SOX (SRY-related HMG-box) family of transcription factors comprises 20 master regulators essential for development, cellular differentiation, stem cell maintenance, and immune function. Metadichol, a nanoemulsion derived from long-chain alcohols, has demonstrated pleiotropic biological activities through comprehensive activation of nuclear receptors (NRs), Toll-like receptors (TLRs), sirtuins, and circadian regulatory networks, but its orchestrated effects on SOX gene expression remain unexplored. Objective To systematically evaluate the dose-dependent effects of Metadichol on the complete SOX transcription factor family expression in human peripheral blood mononuclear cells (PBMCs) and elucidate the synergistic mechanisms involving nuclear receptor signaling, sirtuin activation, TLR modulation, KLF factors, and circadian networks. Methods Human PBMCs were isolated using density gradient centrifugation and treated with Metadichol at concentrations of 1 pg/ml, 100 pg/ml, 1 ng/ml, and 100 ng/ml for 24 hours. Total RNA was extracted and subjected to quantitative real-time PCR (qPCR) analysis targeting 20 SOX family genes (SOX1-21, SOX30, and SRY) using GAPDH as the reference gene. Gene expression was calculated using the 2^(-ΔΔCt) method with appropriate statistical validation. Bioinformatics analysis was performed to identify transcriptional network interactions and pathway enrichment. Results Metadichol treatment resulted in coordinated upregulation of 16 SOX genes at the optimal 100 pg/ml concentration, with fold changes ranging from 1.49 to 3.80-fold (mean ± SEM: 2.45 ± 0.18). The most significantly upregulated genes included SOX10 (3.80-fold, p < 0.001), SOX7 (3.37-fold, p < 0.001), and SOX4 (3.46-fold, p < 0.001). Two genes showed downregulation: SOX12 (0.19-fold, 5.26-fold decrease) and SOX30 (0.60-fold, 1.67-fold decrease), while SOX9 and SRY remained stable. Dose-response analysis revealed an inverted U-shaped pattern with maximal efficacy at 100 pg/ml, consistent with Metadichol's established nuclear receptor and TLR activation profiles. Conclusions Metadichol exhibits unprecedented comprehensive modulation of SOX transcription factor expression through orchestrated activation of multiple regulatory networks, including nuclear receptors, sirtuins, TLRs, and circadian factors. This multi-target approach suggests potential therapeutic applications in regenerative medicine, immunomodulation, and age-related diseases through coordinated transcriptional reprogramming.