Discovering the role of sulfur against atopic dermatitis via the AC010336.1/miR-3929/GPI axis with a machine-learning power.

Sulfur is clinically used for treating scabies and pruritus and shows potential in treating atopic dermatitis (AD), though its mechanism remains unclear. The potential targets of sulfur and the differentially expressed genes of AD in the GSE237920 and GSE121212 datasets from the Gene Expression Omnibus database were identified. The intersecting genes were analyzed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes. A protein-protein interaction network was established using the Search Tool for the Retrieval of Interacting Genes/Proteins database. Through Least Absolute Shrinkage and Selection Operator, Random Forest, and Support Vector Machine-Recursive Feature Elimination algorithms, we screened the core targets. The core genes were validated using receiver operating characteristic analysis, gene set enrichment analysis, and immune cell infiltration analysis. Long noncoding RNA (lncRNA)-microRNA (miRNA)-mRNA bioinformatics networks were predicted using databases. The core lncRNA-miRNA-mRNA axis was identified by intersecting bioinformatics networks with GSE168694. Subsequently, the expression of each node in the axis was verified through animal experiments. Using machine learning and bioinformatics analysis, glucose-6-phosphate isomerase (GPI) was identified as a core target. We then predicted 5 miRNAs and 141 lncRNAs. By validating the results using the GSE168694 dataset, the AC010336.1/miR-3929/GPI axis was identified as the key competing endogenous RNA regulatory axis. Animal experiments demonstrated that sulfur exerted therapeutic effects against AD by restoring epidermal barrier function, reducing immune cell infiltration, and mitigating pruritus. Additionally, animal experiments confirmed that sulfur alleviated AD by modulating the AC010336.1/miR-3929/GPI axis. These novel findings provide valuable insights and guidance for future investigations on the competing endogenous RNA mechanism of traditional Chinese medicine in AD therapy. SIGNIFICANCE STATEMENT: This study investigates the therapeutic mechanisms of sulfur, a traditional Chinese medicine, in the treatment of atopic dermatitis, with elucidate extending to the single-gene regulatory level.