RESUMEN
Glycolytic activity and in vitro effect of the pyruvate kinase activator AG-946 in red blood cells from low-risk myelodysplastic syndromes patients. Data showed decreased glycolytic activity in red blood cells of 2/3 of patients with lower-risk MDS. These results highlight a potential effect of the PK activator in this setting.
Asunto(s)
Eritrocitos , Glucólisis , Síndromes Mielodisplásicos , Piruvato Quinasa , Humanos , Síndromes Mielodisplásicos/tratamiento farmacológico , Síndromes Mielodisplásicos/sangre , Glucólisis/efectos de los fármacos , Eritrocitos/metabolismo , Eritrocitos/efectos de los fármacos , Anciano , Masculino , Femenino , Persona de Mediana Edad , Prueba de Estudio Conceptual , Anciano de 80 o más AñosRESUMEN
Glioblastoma (GBM) is a severe form of brain tumor that has a high fatality rate. It grows aggressively and most of the time results in resistance to traditional treatments like chemo- and radiotherapy and surgery. Biodiversity, beyond representing a big resource for human well-being, provides several natural compounds that have shown great potential as anticancer drugs. Many of them are being extensively researched and significantly slow GBM progression by reducing the proliferation rate, migration, and inflammation and also by modulating oxidative stress. Here, the use of some natural compounds, such as Allium lusitanicum, Succisa pratensis, and Dianthus superbus, was explored to tackle GBM; they showed their impact on cell number reduction, which was partially given by cell cycle quiescence. Furthermore, a reduced cell migration ability was reported, accomplished by morphological cytoskeleton changes, which even highlighted a mesenchymal-epithelial transition. Furthermore, metabolic studies showed an induced cell oxidative stress modulation and a massive metabolic rearrangement. Therefore, a new therapeutic option was suggested to overcome the limitations of conventional treatments and thereby improve patient outcomes.
Asunto(s)
Neoplasias Encefálicas , Glioblastoma , Glioblastoma/tratamiento farmacológico , Glioblastoma/patología , Humanos , Neoplasias Encefálicas/tratamiento farmacológico , Neoplasias Encefálicas/patología , Movimiento Celular/efectos de los fármacos , Línea Celular Tumoral , Estrés Oxidativo/efectos de los fármacos , Productos Biológicos/farmacología , Productos Biológicos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Extractos Vegetales/farmacología , Antineoplásicos Fitogénicos/farmacología , Transición Epitelial-Mesenquimal/efectos de los fármacos , Antineoplásicos/farmacologíaRESUMEN
Neuronal differentiation is regulated by nerve growth factor (NGF) and other neurotrophins. We explored the impact of NGF on mitochondrial dynamics and metabolism through time-lapse imaging, metabolomics profiling, and computer modeling studies. We show that NGF may direct differentiation by stimulating fission, thereby causing selective mitochondrial network fragmentation and mitophagy, ultimately leading to increased mitochondrial quality and respiration. Then, we reconstructed the dynamic fusion-fission-mitophagy cycling of mitochondria in a computer model, integrating these processes into a single network mechanism. Both the computational model and the simulations are able to reproduce the proposed mechanism in terms of mitochondrial dynamics, levels of reactive oxygen species (ROS), mitophagy, and mitochondrial quality, thus providing a computational tool for the interpretation of the experimental data and for future studies aiming to detail further the action of NGF on mitochondrial processes. We also show that changes in these mitochondrial processes are intertwined with a metabolic function of NGF in differentiation: NGF directs a profound metabolic rearrangement involving glycolysis, TCA cycle, and the pentose phosphate pathway, altering the redox balance. This metabolic rewiring may ensure: (a) supply of both energy and building blocks for the anabolic processes needed for morphological reorganization, as well as (b) redox homeostasis.