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In in vitro experiments on cultures of human multipotent stem cells from the human bone arrow and dental pulp, we studied direct reprogramming towards neuro-glial lineage cells using a cocktail of small molecules. Reprogramming by the previously published protocol (with a cocktail containing β-mercaptoethanol, LIF, VPA, CHIR99021, and RepSox) and by the optimized protocol (VPA, RG108, А83-01, dorsomorphin, thiazovivin, CHIR99021, forskolin, and Isx9) allows obtaining cells with immunophenotypic and genetic signs of neural stem cells. However, neither the former, nor the optimized protocols allowed preparing neural progenitors capable of adequate terminal differentiation from both bone marrow-derived mesenchymal stem cells and nestin-positive neural crest-derived mesenchymal stem cells. Real-time PCR demonstrated the expression of some neurogenesis markers, but neural stem cell-specific expression pattern was not observed. The findings lead us to a conclusion that reprogramming with small molecules without additional factors modifying gene expression does not allow reproducible production of human neural stem cell-like progenitors that can be used as the source of neural tissue for the regenerative therapy. [ABSTRACT FROM AUTHOR]

Phenytoin diminished production of nitric oxide stimulated by lethal γ-irradiation in mouse liver, intestinal mucosa, lungs, heart, and brain 6 and 24 h postirradiation. This inhibition directly depended on the degree of stimulation of nitric oxide production by γ-irradiation in studied tissues. [ABSTRACT FROM AUTHOR]