Mycoplasma genitalium is a significant sexually transmitted pathogen, and its clinical management is increasingly complicated by the global distribution of mutations associated with macrolide and fluoroquinolone resistance. To characterize the molecular resistance landscape in a routine diagnostic setting, we retrospectively analyzed residual clinical specimens collected during routine sexually transmitted infection testing between January and December 2024. Among 374,021 specimens screened, we included 4019 M. genitalium-positive samples containing sufficient residual material. Using multiplex polymerase chain reaction assays, we detected mutations associated with macrolide and fluoroquinolone resistance in the 23S rRNA and parC genes, respectively. Frequent substitutions included A2059G and A2058G in the 23S rRNA gene (1253 samples) and substitutions at positions 248 and 259 in the parC gene (1306 samples). Mutations in the predefined 23S rRNA and/or parC targets were identified in approximately 44% of the analyzed samples, with distinct patterns of mutation distribution and co-occurrence. Although phenotypic susceptibility and clinical outcomes were not assessed, this large-scale, assay-based analysis provides a comprehensive overview of resistance-associated mutation patterns in M. genitalium derived from routine diagnostics, supporting molecular surveillance for monitoring antimicrobial resistance trends.

Glioblastoma (GBM) is a highly aggressive and lethal brain tumor characterized by metabolic reprogramming and epigenetic dysregulation. In GBM, the expression levels of Enhancer of Zeste Homolog 2 (EZH2) and dipeptidyl peptidase 4 (DPP4) are inversely correlated, significantly influencing tumor progression. To investigate these reports, the therapeutic potential of digitoxin, a plant-derived bioactive glycoside, was studied in combination with the chemotherapeutic agents temozolomide (TMZ) or romidepsin. We evaluated the EZH2-DPP4 axis and pro-apoptotic signaling using qPCR, western blot, and ELISA. The synergistic effects were assessed through cell viability assays, flow cytometry, and an orthotopic xenograft mouse model utilizing 18F-FDG PET imaging. Digitoxin effectively downregulated EZH2 while restoring DPP4 expression, thereby inhibiting tumor cell growth and enhancing apoptosis. Notably, the combination therapy effectively inhibited tumor progression and reduced tumor burden in vivo, resulting in significantly prolonged survival. Consistent effects were observed in EZH2-knockdown cells, confirming that digitoxin targets the EZH2-DPP4 pathway. These findings suggest that digitoxin acts as a novel epigenetic-regulatory agent, representing a promising integrative medicine and therapeutic strategy to overcome chemoresistance in GBM management.