Resveratrol ameliorates sepsis-induced immune dysfunction by targeting GADD45A to maintain hematopoietic stem cell homeostasis: A predictive study integrating ensemble machine learning, single-cell tr
2 days ago
- #Sepsis
- #GADD45A
- #Resveratrol
- Resveratrol (RES) may help improve sepsis-induced immune dysfunction by targeting GADD45A to maintain hematopoietic stem cell (HSC) homeostasis.
- The study used network pharmacology, ensemble machine learning, single-cell transcriptomics, and molecular dynamics simulations.
- Four key genes (JAK1, GADD45A, MAPK14, ARG1) were identified, with GADD45A showing the highest predictive weight.
- Sepsis causes a myeloid shift in immune cells, and GADD45A is enriched in myeloid subclusters.
- Virtual knockout simulations suggest GADD45A impairment may worsen inflammatory responses by affecting HSC differentiation.
- Molecular dynamics simulations confirmed RES-GADD45A binding stability, supporting its potential as a pharmacological target.
- Resveratrol may help restore immune balance in sepsis by regulating GADD45A-mediated HSC transcriptional programs.