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The NADPH oxidase 1 (NOX1) complex formed by proteins NOX1, p22phox, NOXO1, NOXA1, and RAC1 plays an important role in the generation of superoxide and other reactive oxygen species (ROS) which are involved in normal and pathological cell functions due to their effects on diverse cell signaling pathways. Cell migration and invasiveness are at the origin of tumor metastasis during cancer progression which involves a process of cellular de-differentiation known as the epithelial-mesenchymal transition (EMT). During EMT cells lose their polarized epithelial phenotype and express mesenchymal marker proteins that enable cytoskeletal rearrangements promoting cell migration, expression and activation of matrix metalloproteinases (MMPs), tissue remodeling, and cell invasion during metastasis. In this work, we explored the importance of the peroxiredoxin 6 (PRDX6)-NOX1 enzyme interaction leading to NOXA1 protein stabilization and increased levels of superoxide produced by NOX in hepatocarcinoma cells. This increase was accompanied by higher levels of N-cadherin and MMP2, correlating with a greater capacity for cell migration and invasiveness of SNU475 hepatocarcinoma cells. The increase in superoxide and the associated downstream effects on cancer progression were suppressed when phospholipase A2 or peroxidase activities of PRDX6 were abolished by site-directed mutagenesis, reinforcing the importance of these catalytic activities in supporting NOX1-based superoxide generation. Overall, these results demonstrate a clear functional cooperation between NOX1 and PRDX6 catalytic activities which generate higher levels of ROS production, resulting in a more aggressive tumor phenotype.

Objetivo. Generar el modelo de competencias del profesor para ejercer la docencia de alto nivel en Medicina. Materiales y métodos. Para generar el modelo se analizó la bibliografía, el propósito del plan de estudio por competencias y se utilizó el método Developing a Curriculum (DACUM), con la participación de 35 expertos que integraron mediante consenso el trabajo que debe realizar un docente de medicina para cumplir con éxito el propósito del plan de estudio. Resultados. Se identificaron las funciones básicas de los profesores de medicina, así como las actividades para su cumplimiento. Se conformó el modelo con seis competencias: disciplinaria, de investigación, psicopedagógica, de comunicación, académico-administrativa y humanística. Conclusiones. El modelo pretende guiar las acciones de los profesores que actualmente participan en el programa y aquellos que aspiran a formar parte del proceso educativo; elaborar programas para la formación de profesores que favorezcan el desarrollo de competencias académicas; identificar elementos que se deben considerar para la evaluación del desempeño docente; orientar el diseño de indicadores útiles para otorgar reconocimientos y estímulos a los profesores cuyo desempeño académico sea excepcional; orientar al estudiante, en la relación profesor-alumno, sobre las funciones y actividades que puede esperar del profesor.Aim. To create a competency model for the medical professor in order to exert teaching at its highest level. Materials and methods. To create such model, we analyzed current literature on teaching, the aim of the curricula for competencies and we used the DACUM method whose letters stand for Developing a Curriculum. 35 experts who participated in this project reached a consensus regarding the duties that have to be carried out by a medical professor in order to successfully fulfill the aim of the curricula. Results. We identified the basic functions of medical professors as well as the related duties for its fulfillment. The model comprises six competencies: disciplinary, research, psico-pedagogy, communicative, academic-administrative and humanistic competencies. Conclusion. This model pretends to guide the actions of medical professors who are currently participating in this program and those who want to become part of the education process. It also pretends to create programs favoring the professors´ training benefiting the development of academic competencies; to identify the elements to be considered for the assessment of the professors´ development; to guide the design of useful indicators to grant awards and incentives to those professors whose academic development be exceptional; to guide the student within the professor-student relationship, on the duties and activities that they can expect from the professor.

Background: NO has an antiproliferative action on HepG2 cells and Thioredoxin (Trx) and Glutaredoxin (Grx) have denitrosilase and deglutathionylase activities. Aims: To ascertain whether Trx and/or Grx systems intermediate the anti-proliferative effect of NO on hepatoblastoma cells by modulating the redox-state of key proteins. Methods: HepG2 cells overexpressing Nitric Oxide Synthase-3 (NOS-3) were transfected with specific siRNA to silence Trx1 and Grx1. The expression and thiolic redox state of proteins were determined by Western blot and redox mobility shift assay. Results: Overexpression of NOS3 increased the levels and activities of proteins of the redoxin systems, Trx1, Grx1, TrxR1 and TxnIP, and the levels of signaling proteins (Akt1, pAkt1-Ser473, MapK, pMapK, Stat3, Fas). The thiolic redox state of Trx1, Grx1 and Akt1 shifted to more oxidized. Increases were also observed in Pro-apoptotic Caspase-3 fragment levels; caspase 3, 8 and 9 activities; antiapoptotic (Bcl-2); mitochondrial energetic (Aco2) and heme (Urod) metabolism; Glycolysis (Pkm2); and pentose phosphate pathway (Tkt). However, two cytosolic proteins related to iron (Aco1) and one carbon (Mat2) metabolism decreased markedly. Moreover, the redox state of Urod and Aco1 shifted to more oxidized cysteines.Trx1 or Grx1 silencing augmented Tyr nitration and diminished cell proliferation in WT cells, but attenuated the antiproliferative effect on NO, the increase of Fas, Akt1 and pAkt1-Ser473 and the oxidative modification of Akt1 in NOS3 cells. Conclusions: Trx1 and Grx1 exert contradictory influences on HepG2 cells. They are required for proliferation but they also contribute to antiproliferative effect of NO, associated to Akt1 redox changes.

Objetivo. Generar el modelo de competencias del profesor para ejercer la docencia de alto nivel en Medicina. Materiales y métodos. Para generar el modelo se analizó la bibliografía, el propósito del plan de estudio por competencias y se utilizó el método Developing a Curriculum (DACUM), con la participación de 35 expertos que integraron mediante consenso el trabajo que debe realizar un docente de medicina para cumplir con éxito el propósito del plan de estudio. Resultados. Se identificaron las funciones básicas de los profesores de medicina, así como las actividades para su cumplimiento. Se conformó el modelo con seis competencias: disciplinaria, de investigación, psicopedagógica, de comunicación, académico-administrativa y humanística. Conclusiones. El modelo pretende guiar las acciones de los profesores que actualmente participan en el programa y aquellos que aspiran a formar parte del proceso educativo; elaborar programas para la formación de profesores que favorezcan el desarrollo de competencias académicas; identificar elementos que se deben considerar para la evaluación del desempeño docente; orientar el diseño de indicadores útiles para otorgar reconocimientos y estímulos a los profesores cuyo desempeño académico sea excepcional; orientar al estudiante, en la relación profesor-alumno, sobre las funciones y actividades que puede esperar del profesor.

Cancer cells have unlimited replicative potential, insensitivity to growth-inhibitory signals, evasion of apoptosis, cellular stress, and sustained angiogenesis, invasiveness and metastatic potential. Cancer cells adequately adapt cell metabolism and integrate several intracellular and redox signaling to promote cell survival in an inflammatory and hypoxic microenvironment in order to maintain/expand tumor phenotype. The administration of tyrosine kinase inhibitor (TKI) constitutes the recommended therapeutic strategy in different malignancies at advanced stages.There are important interrelationships between cell stress, redox status, mitochondrial function, metabolism and cellular signaling pathways leading to cell survival/death. The induction of apoptosis and cell cycle arrest widely related to the antitumoral properties of TKIs result from tightly controlled events involving different cellular compartments and signaling pathways. The aim of the present review is to update the most relevant studies dealing with the impact of TKI treatment on cell function. The induction of endoplasmic reticulum (ER) stress and Ca2+ disturbances, leading to alteration of mitochondrial function, redox status and phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and AMP-activated protein kinase (AMPK) signaling pathways that involve cell metabolism reprogramming in cancer cells will be covered. Emphasis will be given to studies that identify key components of the integrated molecular pattern including receptor tyrosine kinase (RTK) downstream signaling, cell death and mitochondria-related events that appear to be involved in the resistance of cancer cells to TKI treatments.