RESUMEN
Suppressor of fused (SUFU) is widely regarded as a key negative regulator of the sonic hedgehog (SHH) morphogenic pathway and a known tumor suppressor of medulloblastoma (MB). However, we report here that SUFU expression was markedly increased in 75% of specimens compiled in a tissue array comprising 49 unstratified MBs. The SUFU and GLI1 expression levels in this MB array showed strong positive correlation, which was also identified in a large public data set containing 736 MBs. We further report that increasing Sufu gene dosage in mice caused preaxial polydactyly, which was associated with the expansion of the Gli3 domain in the anterior limb bud and heightened Shh signaling responses during embryonic development. Increasing Sufu gene dosage also led to accelerated cerebellar development and, when combined with ablation of the Shh receptor encoded by Patched1 (Ptch1), promoted MB tumorigenesis. These data reveal multifaceted roles of SUFU in promoting MB tumorigenesis by enhancing SHH signaling. This revelation clarifies potentially counterintuitive clinical observation of high SUFU expression in MBs and may pave way for novel strategies to reduce or reverse MB progression.
Asunto(s)
Neoplasias Cerebelosas , Meduloblastoma , Polidactilia , Ratones , Animales , Meduloblastoma/genética , Meduloblastoma/patología , Proteínas Represoras/genética , Proteínas Represoras/metabolismo , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Transformación Celular Neoplásica/genética , Factores de Transcripción , Neoplasias Cerebelosas/genética , Polidactilia/genéticaRESUMEN
The development of sustainable technologies for efficient nitrate removal has attracted increasing attention, because excessive nitrate emissions can result in serious environmental, economic, and health effects. Herein, we propose to utilize FeSiBC metallic glass (MG) powders as a potential solution for nitrate removal. In terms of removal efficiency and reusability, our results show that the MG powders, as special zero-valent iron carriers, are 2-3 orders of magnitude more efficient in nitrate removal than the previous studies, while maintaining more than 50% nitrate removal efficiency after 9 cycles of reaction. Moreover, the optimal FeSiBC MG dosage, pH value, and temperature for nitrate removal are determined. The mechanism of nitrate removal is also revealed. The present study offers a promising approach to remediate nitrate, one of the world's most widespread water pollutants.
RESUMEN
Propofol is a neuroprotective anesthetic. Whether propofol can promote spinal cord injury repair by bone marrow mesenchymal stem cells remains poorly understood. We used rats to investigate spinal cord injury repair using bone marrow mesenchymal stem cell transplantation combined with propofol administration via the tail vein. Rat spinal cord injury was clearly alleviated; a large number of newborn non-myelinated and myelinated nerve fibers appeared in the spinal cord, the numbers of CM-Dil-labeled bone marrow mesenchymal stem cells and fluorogold-labeled nerve fibers were increased and hindlimb motor function of spinal cord-injured rats was markedly improved. These improvements were more prominent in rats subjected to bone marrow mesenchymal cell transplantation combined with propofol administration than in rats receiving monotherapy. These results indicate that propofol can enhance the therapeutic effects of bone marrow mesenchymal stem cell transplantation on spinal cord injury in rats.
