SummaryThe core functions of stem cells (SCs) are critically regulated by their cellular redox status. Glutathione is the most abundant non-protein thiol functioning as an antioxidant and a redox regulator. However, an investigation into the relationship between glutathione-mediated redox capacity and SC activities is hindered by lack of probe. Here, we demonstrate that cyanoacrylamide-based coumarin derivatives are ratiometric probes suitable for the real-time monitoring of glutathione levels in living SCs. These probes revealed that glutathione levels are heterogeneous among subcellular organelles and among individual cells and show dynamic changes and heterogeneity in repopulating SCs depending on oxidative stress or culture conditions. Importantly, a subpopulation of SCs with high glutathione levels exhibited increased stemness and migration activities in vitro and showed improved therapeutic efficiency in treating asthma. Our results indicate that high glutathione levels are required for maintaining SC functions, and monitoring glutathione dynamics and heterogeneity can advance our understanding of the cellular responses to oxidative stress.

Improving the stability, bioavailability, and processability of active pharmaceutical ingredients (APIs) has been the key research goal in the field of pharmaceutical crystallization. Cocrystallization has been considered as an effective route to achieve this goal, and intense research over decades has revealed cocrystals of many APIs. However, most cocrystal formers have been designed based primarily on their molecular interactions not their health benefits. Herein, we choose naringenin (N), a natural flavonoid, as a novel cocrystal former as it has many health efficacies and the ability to form specific interactions. At a 1:1 stoichiometric ratio, N successfully forms a cocrystal with carbamazepine (CBZ), whose plasma concentration is known to be improved by natural flavonoids such as N. The resorcinol functional group of N and the urea functional group of CBZ are connected through hydrogen bonds, and the improved stability of the cocrystal seems to originate from this structure. The melting temperature of the cocrystal is 262 °C, which is higher than those of CBZ and N, and the better stability of the cocrystal is further confirmed by the observation of enhanced hydration stability (up to 30 days at 93% RH). This novel strategy of cocrystallization using natural flavonoids could improve the commercialization potential of API cocrystals.