Project description:This study explored the regulatory effect of D-mannose on host immunometabolic responses after viral infection. The results showed that D-mannose can compete with glucose for transporters and hexokinase, inhibiting glycolysis, reducing mitochondrial reactive oxygen species and succinate-induced HIF-1α, thereby reducing virus-induced inflammatory cytokine production. Even with delayed combinatorial treatment of D-mannose and antiviral monotherapy after viral infection, a synergistic effect was still observed in mouse models. Phosphomannose isomerase (PMI) activity determines the benefits of D-mannose, as simultaneous PMI depletion and mannose supplementation impaired cell viability. PMI inhibition can suppress replication of various viruses by affecting host and viral surface protein glycosylation. However, D-mannose does not inhibit PMI activity or viral fitness. In summary, PMI-centered therapeutic strategies can eliminate viral infections, while D-mannose treatment reprograms glycolysis to control collateral damage.
Project description:Using chromatin immunoprecipitation and next-generation sequencing (ChIP-seq), we assessed the effects of acute exposure to oligomeric amyloid-beta on 82-kDa ChAT and SATB1 genome association in human SH-SY5Y neural cells, finding that Aβ-exposure increased 82-kDa ChAT and SATB1 association with gene promoters, introns and matrix attachment regions. We found that both SATB1 and 82-kDa ChAT associate with synapse and cell stress related genes after amyloid-beta exposure.
