RESUMO
Enhancer of zeste homolog 2 (EZH2) and Bruton's tyrosine kinase (BTK) are both key factors involved in the development and progression of hematological malignancies. Clinical studies have demonstrated the potential of various EZH2 inhibitors, which target the methyltransferase activity of EZH2, for the treatment of lymphomas. However, despite their ability to effectively reduce the H3K27me3 levels, these inhibitors have shown limited efficacy in blocking the proliferation of lymphoma cells. To overcome this challenge, we employed a hydrophobic tagging approach utilizing MS1943, a selective EZH2 degrader. In this study, we investigated the inhibitory effects of two drugs, the FDA-approved EZH2 inhibitor Tazemetostat, currently undergoing clinical trials, and the novel drug MS1943, on Burkitt's lymphoma. Furthermore, we assessed the potential synergistic effect of combining these drugs with the BTK inhibitor Ibrutinib. In this study, we evaluated the effects of combination therapy with MS1943 and Ibrutinib on the proliferation of three Burkitt's lymphoma cell lines, namely RPMI1788, Ramos, and Daudi cells. Our results demonstrated that the combination of MS1943 and Ibrutinib significantly suppressed cell proliferation to a greater extent compared to the combination of Tazemetostat and Ibrutinib. Additionally, we investigated the underlying mechanisms of action and found that the combination therapy of MS1943 and Ibrutinib led to the upregulation of miR29B-mediated p53-upregulated modulator of apoptosis PUMA, BAX, cleaved PARP, and cleaved caspase-3 in Burkitt's lymphoma cells. These findings highlight the potential of this innovative therapeutic strategy as an alternative to traditional EZH2 inhibitors, offering promising prospects for improving treatment outcomes in Burkitt's lymphoma.
RESUMO
Ammonia is a suitable hydrogen carrier with each molecule accounting for up to 17.65% of hydrogen by mass. Among various potential ammonia production methods, we adopt the photoelectrochemical (PEC) technique, which uses solar energy as well as electricity to efficiently synthesize ammonia under ambient conditions. In this article, we report MoS2@La2Zr2O7 heterostructures designed by incorporating two-dimensional (2D)-MoS2 nanoflakes on La2Zr2O7 nanofibers (MoS2@LZO) as photoelectrocatalysts. The MoS2@LZO heterostructures are synthesized by a facile hydrothermal route with electrospun La2Zr2O7 nanofibers and Mo precursors. The MoS2@LZO heterostructures work synergistically to amend the drawbacks of the individual MoS2 electrocatalysts. In addition, the harmonious activity of the mixed phase of pyrochlore/defect fluorite-structured La2Zr2O7 nanofibers generates an interface that aids in increased electrocatalytic activity by enriching oxygen vacancies in the system. The MoS2@LZO electrocatalyst exhibits an enhanced Faradaic efficiency and ammonia yield of approximately 2.25% and 10.4 µg h-1 cm-2, respectively, compared to their corresponding pristine samples. Therefore, the mechanism of improving the PEC ammonia production performance by coupling oxygen-vacant sites to the 2D-semiconductor-based electrocatalysts has been achieved. This work provides a facile strategy to improve the activity of PEC catalysts by designing an efficient heterostructure interface for PEC applications.
