Role of Kynurenine Pathway in Glioblastoma

In brain, the tryptophan degradation products through the kynurenine pathway exhibit neuromodulatory and inflammatory effects and have been related to the progression of neurodegenerative disorders, furthermore, their protagonism on the modulation of immune response and in cancer development has been reported. The immunosuppressive role of kynurenines has been described on glioblastoma models. In patients, the elevated activity of indoleamine-2,3-dioxygenase (IDO) such as the increase of kynurenine/tryptophan ratio have been also reported, suggesting that activation of kynurenine pathway is present during glioblastoma formation and can be related with tumor progression. The importance of the kynurenine pathway during cancer development has encouraged recent studies to the use of IDO inhibitors as a therapeutic strategy for treatment of breast, lung and ovarian cancer, until to get its use in clinical trials. IDO inhibitors also have been used in in vitro and in vivo models of glioblastoma showing promising results. The effect of kynurenines on glioblastoma offer a new perspective about the tryptophan metabolism during cancer. Due to the relevance of the kynurenine pathway in brain homeostasis, immunomodulation and cancer, we discuss the relevance of the kynurenine pathway on the development of glioblastoma multiforme as well as a possible molecular target for glioblastoma treatment

Evaluation of vitamin D serum levels in asthmatic adults and their relationship with asthma control

Antecedentes: Los niveles disminuidos de vitamina D infl uyen en el control y la gravedad del asma. Objetivo: Evaluar la relación entre niveles séricos de vitamina D y control del asma, así como estado nutricional, calidad de vida y comorbilidades del paciente. Métodos: Estudio transversal, observacional y descriptivo de 43 pacientes asmáticos mayoresde 18 años. Se realizó análisis de varianza multivariados de regresión logística múltiple y lineal múltiples; se consideró estadísticamente signifi cativa una p ≤ 0.05. Resultados: Se determinaron niveles insufi cientes de vitamina D en 83.7 % de los pacientes; 93 % presentó al menos una exacerbación asmática en el último año. No se evidenció relación entre los niveles séricos de vitamina D y control del asma medido por el Asthma Control Test (ACT) y el volumen espiratorio forzado el primer segundo (FEV1). Se obtuvo asociación signifi cativa entre el índice de masa corporal y niveles de vitamina D (p = 0.013). Con un cuestionario de calidad de vida en adultos asmáticos se registró que 76.7 % tenía mala calidad de vida. Conclusiones: No se observó relación entre los niveles séricos de vitamina D y el control del asma en los pacientes. La mayoría de los pacientes tenía niveles séricos de vitamina D insufi cientes, asma descontrolada y mala calidad de vida. El sobrepeso y la obesidad grado I se asociaron con niveles insufi cientes de vitamina D. ABSTRACT Background: Decreased levels of vitamin D infl uence on the control and severity of asthma. Objective: To evaluate the relationship between vitamin D serum levels and asthma control, as well as nutritional status, quality of life and patient comorbidities. Methods: Cross-sectional, observational, descriptive study of 43 asthmatic patients older than 18 years of age. Multiple logistic and multiple linear regression multivariate analyses of variance were performed; a p-value ≤ 0.05 was considered to be statistically signifi cant. Results: Insuffi cient vitamin D levels were determined in 83.7 % of patients; 93 % had at least one asthma exacerbation in the previous year. There was no relationship between vitamin D serum levels and asthma control as measured by ACT and FEV1. There was a signifi cant association between body mass index and vitamin D levels (p = 0.013). With a quality of life questionnaire for asthmatic adults, 76.7 % were recorded to have a poor quality of life. Conclusions: No relationship was observed between vitamin D serum levels and asthma control in the patients. Most patients had insuffi cient vitamin D serum levels, uncontrolled asthma, and poor quality of life. Overweight and grade I obesity were associated with vitamin D insuffi cient levels

Evaluación de los niveles séricos de vitamina D en adultos asmáticos y su relación con el control de asma

Abstract Background: Decreased levels of vitamin D infl uence on the control and severity of asthma. Objective: To evaluate the relationship between vitamin D serum levels and asthma control, as well as nutritional status, quality of life and patient comorbidities. Methods: Cross-sectional, observational, descriptive study of 43 asthmatic patients older than 18 years of age. Multiple logistic and multiple linear regression multivariate analyses of variance were performed; a p-value ≤ 0.05 was considered to be statistically signifi cant. Results: Insuffi cient vitamin D levels were determined in 83.7 % of patients; 93 % had at least one asthma exacerbation in the previous year. There was no relationship between vitamin D serum levels and asthma control as measured by ACT and FEV1. There was a signifi cant association between body mass index and vitamin D levels (p = 0.013). With a quality of life questionnaire for asthmatic adults, 76.7 % were recorded to have a poor quality of life. Conclusions: No relationship was observed between vitamin D serum levels and asthma control in the patients. Most patients had insuffi cient vitamin D serum levels, uncontrolled asthma, and poor quality of life. Overweight and grade I obesity were associated with vitamin D insuffi cient levels

The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival

Endometrial cancer (EC) is the most common type of gynecologic cancer in women of developed countries. Despite surgery combined with chemo-/radiotherapy regimens, overall survival of patients with high-risk EC tumors is poor, indicating a need for novel therapies. The MEK5-ERK5 pathway is activated in response to growth factors and to different stressors, including oxidative stress and cytokines. Previous evidence supports a role for the MEK5-ERK5 pathway in the pathology of several cancers. We investigated the role of ERK5 in EC. In silico analysis of the PanCancer Atlas dataset showed altera- tions in components of the MEK5-ERK5 pathway in 48% of EC patients. Here, we show that ERK5 inhibition or silencing decreased EGF-induced EC cell proliferation, and that genetic deletion of MEK5 resulted in EC impaired proliferation and reduced tumor growth capacity in nude mice. Pharmacologic inhibition or ERK5 silencing impaired NF-kB pathway in EC cells and xenografts. Furthermore, we found a positive correlation between ERK5 and p65/RELA protein levels in human EC tumor samples. Mechanistically, genetic or pharmacologic impairment of ERK5 resulted in downregulation of NEMO/ IKKγ expression, leading to impaired p65/RELA activity and to apoptosis in EC cells and xenografts, which was rescued by NEMO/IKKγ overexpression. Notably, ERK5 inhibition, MEK5 deletion or NF-kB inhibition sensitized EC cells to standard EC chemotherapy (paclitaxel/carboplatin) toxicity, whereas ERK5 inhibition synergized with paclitaxel to reduce tumor xenograft growth in mice. Together, our results suggest that the ERK5-NEMO-NF-κB pathway mediates EC cell prolifera- tion and survival. We propose the ERK5/NF-κB axis as new target for EC treatment.The online version contains supplementary material available at 10.1007/s00018-022-04541-

EstuPlan: Methodology for the development of creativity in the resolution of scientific and social problems

Creative thinking is necessary to generate novel ideas and solve problems."EstuPlan" is a methodology in which knowledge and creativity converge for the resolution of scientific problems with social projection. It is a training programme that integrates teachers, laboratory technicians and PhD students, master and undergraduate students which form working groups for the development of projects. Projects have a broad and essential scope and projection in terms of environmental problems, sustainable use of natural resources, food, health, biotechnology or biomedicine. The results show the success of this significant learning methodology using tools to develop creativity in responding to scientific and social demand for problem-solving to transfer academic knowledge to different professional environments. Bioplastics, Second Life of Coffee, LimBio, Algae oils, Ecomers, Caring for the life of your crop and Hate to Deforestate are currently being developed

Compromising between European and US allergen immunotherapy schools: Discussions from GUIMIT, the Mexican immunotherapy guidelines

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, see Supplementary data) concluded the following: Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50–200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed

Guía Mexicana de Práctica Clínica de Inmunoterapia 2011

Existen varias guías internacionales para la práctica clínica de in- munoterapia, que aplican solo parcialmente en México. La primera guía mexicana de inmunoterapia data de 1998

Post-Franco Theatre

In the multiple realms and layers that comprise the contemporary Spanish theatrical landscape, “crisis” would seem to be the word that most often lingers in the air, as though it were a common mantra, ready to roll off the tongue of so many theatre professionals with such enormous ease, and even enthusiasm, that one is prompted to wonder whether it might indeed be a miracle that the contemporary technological revolution – coupled with perpetual quandaries concerning public and private funding for the arts – had not by now brought an end to the evolution of the oldest of live arts, or, at the very least, an end to drama as we know it

Puntos de encuentro. Investigaciones de posgrado en proceso (II)

Puntos de encuentro. Investigaciones de posgrado en proceso (II) es la continuación del proyecto de innovación docente “Puntos de encuentro. Investigaciones de posgrado en proceso” desarrollado durante el curso 2017-18. Dicho proyecto trataba de generar una comunidad de aprendizaje a través de encuentros periódicos, seminarios y actividades comunes entre directores de tesis, profesores y doctorandos. El desarrollo del mismo ha puesto de manifiesto la necesidad de continuar las dinámicas instauradas, así como la articulación de otros posibles modos de ensayar metodologías colaborativas, que son la base de la propuesta. Teniendo en cuenta los resultados obtenidos durante el curso 2017-18 el desarrollo de este proyecto ha estado condicionado por el interés de mantener y propiciar la comunidad de aprendizaje generada. Por otra parte, ha sido fundamental la experimentación en procesos de tutorización entre pares y colectivos, en un periodo formativo definido, en el campo de estudio propuesto por procesos de investigación de carácter individual. El desarrollo de las actividades desarrolladas ha puesto en práctica metodologías colaborativas capaces de ensayar otras aproximaciones a procesos de aprendizaje para las nuevas generaciones de estudiantes. El equipo de trabajo ha estado compuesto por los miembros que ya habían participado en el anterior proyecto (22 doctorandos y 10 docentes) y por nuevas incorporaciones que demostraron interés en formar parte del grupo (28 doctorandos y 14 docentes). En este sentido, cabe destacar que la comunidad no únicamente se ha mantenido sino que se ha visto incrementada. Al igual que el curso anterior el desarrollo de las investigaciones en curso se inscriben en distintos campos de conocimiento afines lo que ha permitido seguir articulando espacios transdisciplinares de encuentro que dieran lugar al debate y al diálogo, así como la creación de redes propiciadas por las afinidades entre distintos miembros del grupo. Esta memoria recoge la valoración de los resultados obtenidos haciendo mención a los objetivos alcanzados, a la metodología empleada, al grupo de trabajo adscrito al proyecto y a las actividades desarrolladas a lo largo del curso 2018-19. Presenta a modo de anexo una serie de imágenes de los encuentros realizados y los documentos de difusión del seminario de investigación