RESUMEN
Post-translational modifications (PTMs), as epigenetic modifications, are significant in the interaction between virus and its host. However, it is unclear whether rotavirus (RV) causes changes in both the host cell epigenetic protein modification and the regulatory mechanism of viral replication. Here, we analyzed the proteome of Caco-2 cells to determine if acetylation modification occurred within the cells after RV infection. We found that glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a protein involved in glycolysis, was deacetylated at lysine 219 via histone deacetylase 9 (HDAC9) in 50 h after the RV infection. Remarkably, the deacetylation of GAPDH promoted RV replication. Finally, we found that glycolysis was alterable in Caco-2 cells by RV or the deacetylation of GAPDH lysine 219, using the Seahorse XF Glycolysis Stress Test. In conclusion, our results demonstrate for the first time that RV infection promoted deacetylation of GAPDH at lysine 219 in order to increase its own viral replication in Caco-2 cells.
RESUMEN
Genistein (Gen), a kind of natural isoflavone drug monomer with poor water solubility and low oral absorption, was incorporated into oral nanoparticles with a new mesoporous carrier material, NH2-MCM-41, which was synthesized by copolycondensation. When the ratio of Gen to NH2-MCM-41 was 1:0.5, the maximum adsorption capacity of Gen was 13.15%, the maximum drug loading was 12.65%, and the particle size of the whole core-shell structure was in the range of 370 nm-390 nm. The particles were characterized by a Malvern particle size scanning machine, XRD, Fourier transform infrared spectroscopy, scanning electron microscopy, and nitrogen adsorption and desorption. Finally, Gen-NH2-MCM-41 was encapsulated by sodium alginate (SA), and the chimerism of this material, denoted as GEN-NH2-MCM-41@SA, was investigated. In vitro release experiments showed that, after 5 h in artificial colon fluid (pH = 8.0), the cumulative release reached 99.56%. In addition, its anti-rotavirus (RV) effect showed that the maximum inhibition rate was 62.24% at a concentration of 30 µM in RV-infected Caco-2 cells, and it significantly reduced the diarrhea rate and diarrhea index in an RV-infected-neonatal mice model at a dose of 0.3 mg/g, which was better than the results of Gen. Ultimately, Gen-NH2-MCM-41@SA was successfully prepared, which solves the problems of low solubility and poor absorption and provides an experimental basis for the application of Gen in the clinical treatment of RV infection.