Effect of DNA repair deficiencies on the cytotoxicity of resveratrol

Numerous preclinical studies have shown that the naturally-occurring polyphenol resveratrol may produce health-beneficial effects in a variety of disorders, including cancer, diabetes, Alzheimer, and cardiovascular diseases. Resveratrol has entered clinical trials for the prevention and treatment of several of these disorders. This polyphenol is also available in the market as a dietary supplement. Experimental data have shown, however, that resveratrol induces DNA damage in a variety of cells. Here we review such evidence and evaluate the cytotoxicity of resveratrol (MTT assay) in cells deficient in several major DNA repair pathways (i.e., homologous recombination, non-homologous end joining, base excision repair, nucleotide excision repair, mismatch repair, and Fanconi anemia repair). Cells deficient in base excision repair (EM9), nucleotide excision repair (UV4 and UV5) and Fanconi Anemia (KO40) were slightly hypersensitive to resveratrol-induced cytotoxicity with respect to their parental cells (AA8). Our results suggest that these pathways may participate in the repair of the DNA damage induced by resveratrol and that deficiencies in these pathways may confer hypersensitivity to the genotoxic activity of this dietary constituen

Realizzazione di seminari a distanza mediante l’uso dello strumento blackboard (lavagna virtuale) (wimbaclassroom del webct) per la conoscenza delle applicazioni e dei progressi scientifici delle colture cellulari in ambito lavorativo

La asignatura de Cultivos Celulares impartida en la Licenciatura de Biología de la Universidad de Sevilla, proporciona a los alumnos información teórica y práctica en esta materia. El gran avance tecnológico de los cultivos celulares aconseja complementar la información. Para ello hemos realizado una actividad formativa que ha permitido a profesionales procedentes de otras universidades o empresas, proporcionar de forma directa y sin desplazarse, conocimientos sobre las técnicas más innovadoras en cultivos celulares. Se han realizado dos conferencias a distancia mediante el uso de la herramienta Wimba Classroom. Se evaluó el grado de comprensión de las conferencias por parte de los alumnos mediante las herramientas tarea y examen de WebCT, así como la posible repercusión en la nota final. Los resultados obtenidos mostraron un incremento en el número de aprobados y de presentados a examen en el grupo experimental con respecto al control, así como un aumento de la nota media obtenida (5,92 frente a 4,01). Los alumnos evaluaron distintos aspectos de la actividad mediante encuestas a través de la plataforma, en las cuales se obtuvo un grado de valoración de la misma muy positivo. Los resultados indican que el uso de Wimba Classroom es adecuado para el objetivo propuesto.Cell Cultures is a subject included in the Biologist Degree at Sevilla University, that provides theoretical and practical information in this area. Due to the quick technological development in this field, we consider that is important to contribute complementary information to students who are cursing this subject. By means of the present project, specialists from biotechnological companies, who directly use and work with cell cultures, have provided lectures about different innovative applications in this area. The conferences have been carried out without the physical presence of the speakers by the use of the Wimba Classroom online tool. The level of understanding of the conferences was tested by means of WebCT evaluation tools, and the possible impact in the final califications got by students was analized. The results show that the the group of students that actively participated in the activity got higher final calification than the group who did not participate (5,92 and 4,01 respectively). Students could evaluate different aspects of the activity by answering a WebCT survey online. The results show that Wimba Classroom is adequate for this purpose and that evaluation of the formative activity by students is quite positive.Il corso Colture Cellulari impartito nel corso di Laurea in Biologia dell’Università di Siviglia, fornisce agli alunni informazioni teoriche e pratiche su questa materia. Il grande progresso tecnologico delle colture cellulari suggerisce di ampliare l’offerta formativa. Per questo motivo abbiamo realizzato un’attività formativa che ha permesso a professionisti provenienti da altre Università o imprese, di fornire in forma diretta e senza bisogno di lezioni in presenza, conoscenze sulle tecniche più innovatrici nella coltivazione cellulare. Sono state realizzate due conferenze a distanza mediante l’uso dello strumento Aula Virtuale. È stato valutato il grado di comprensione delle conferenze da parte degli alunni per mezzo dello strumento compito e esame del WEbCT, così come è stata valutata la possibile ripercussione sul voto finale. I risultati ottenuti mostrano un incremento nel numero dei promossi e di coloro i quali si sono presentati all’esame nel gruppo sperimentale rispetto al gruppo controllo, così come l’aumento del voto medio ottenuto (5,92 su 4,01). Gli alunni hanno valutato diversi aspetti dell’attività mediante questionari forniti dalla piattaforma, nei quali si è ottenuto un livello di valutazione molto positivo della stessa. I risultati indicano che l’uso dell’Aula Virtuale è adeguato all’obiettivo proposto

A hydroalcoholic extract from the leaves of Nerium oleander inhibits glycolysis and induces selective killing of lung cancer cells

Recent evidence suggests that cardiac glycosides might be used for the treatment of cancer. The ornamental shrub Nerium oleander has been used in traditional medicine for treating several disorders including cancer, and extracts from the leaves of this plant have already entered phase I clinical trials. In this communication, we have prepared a hydroalcoholic extract from the leaves of Nerium oleander (containing 4.75 ± 0.32 % of cardenolides) and have assessed its cytotoxic activity in A549 lung cancer cells vs. MRC5 nonmalignant lung fibroblasts. The results showed that the cytotoxicity of the Nerium oleander extract against the cancer cell line was significantly higher than that against the nonmalignant cell line, with a potency and selectivity similar to those of the anticancer drug cisplatin. Pretreatment of A549 cells with the antioxidants N-acetylcysteine and catalase slightly prevented the cytotoxicity of the extract, therefore suggesting that the formation of reactive oxygen species participates in its cytotoxic activity but does not play a major role. Nerium oleander extract-induced cytotoxicity and DNA damage (gamma-H2AX focus formation) were slightly higher in cells lacking BRCA2 (deficient in homologous recombination repair) than in parental cells; this indicates that the induction of DNA damage may also play a role in the cytotoxicity of the extract. Nerium oleander extract induced a marked inhibition of glycolysis (glucose consumption and lactate production) in A549 cells, comparable to that of the glycolysis inhibitor dichloroacetate (currently in clinical development for cancer therapy). Because platinum compounds are widely used in the treatment of lung cancer, we tested the cytotoxicity of several combinations of cisplatin with the extract and found a moderate synergism when Nerium oleander extract was administered after cisplatin but a moderate antagonism when it was added before cisplatin. Our results suggest that extracts from Nerium oleander might induce anticancer effects in patients with lung cancer and support their possible advancement into phase II clinical trials for the treatment of this type of cancer

Cells Deficient in the Fanconi Anemia Protein FANCD2 are Hypersensitive to the Cytotoxicity and DNA Damage Induced by Coffee and Caffeic Acid

Epidemiological studies have found a positive association between coffee consumption and a lower risk of cardiovascular disorders, some cancers, diabetes, Parkinson and Alzheimer disease. Coffee consumption, however, has also been linked to an increased risk of developing some types of cancer, including bladder cancer in adults and leukemia in children of mothers who drink coffee during pregnancy. Since cancer is driven by the accumulation of DNA alterations, the ability of the coffee constituent caffeic acid to induce DNA damage in cells may play a role in the carcinogenic potential of this beverage. This carcinogenic potential may be exacerbated in cells with DNA repair defects. People with the genetic disease Fanconi Anemia have DNA repair deficiencies and are predisposed to several cancers, particularly acute myeloid leukemia. Defects in the DNA repair protein Fanconi Anemia D2 (FANCD2) also play an important role in the development of a variety of cancers (e.g., bladder cancer) in people without this genetic disease. This communication shows that cells deficient in FANCD2 are hypersensitive to the cytotoxicity (clonogenic assay) and DNA damage (γ-H2AX and 53BP1 focus assay) induced by caffeic acid and by a commercial lyophilized coffee extract. These data suggest that people with Fanconi Anemia, or healthy people who develop sporadic mutations in FANCD2, may be hypersensitive to the carcinogenic activity of coffee

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans - joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, ‘Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,’ is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation-induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios.VII Programa Marco de Investigación y Desarrollo (VIIPM) de la Unión Europea. nº 295513European Radiation Dosimetry Group (EURADOS) de la Unión Europea. EURADOS WG1

Conducting seminars distance using blackboard tools (Wimbaclassroom of webct) for specific applications and progress of cell cultures in relation to the workplace

[ES] La asignatura de Cultivos Celulares impartida en la Licenciatura de Biología de la Universidad de Sevilla, proporciona a los alumnos información teórica y práctica en esta materia. El gran avance tecnológico de los cultivos celulares aconseja complementar la información. Para ello hemos realizado una actividad formativa que ha permitido a profesionales procedentes de otras universidades o empresas, proporcionar de forma directa y sin desplazarse, conocimientos sobre las técnicas más innovadoras en cultivos celulares. Se han realizado dos conferencias a distancia mediante el uso de la herramienta Wimba Classroom. Se evaluó el grado de comprensión de las conferencias por parte de los alumnos mediante las herramientas tarea y examen de WebCT, así como la posible repercusión en la nota final. Los resultados obtenidos mostraron un incremento en el número de aprobados y de presentados a examen en el grupo experimental con respecto al control, así como un aumento de la nota media obtenida (5,92 frente a 4,01). Los alumnos evaluaron distintos aspectos de la actividad mediante encuestas a través de la plataforma, en las cuales se obtuvo un grado de valoración de la misma muy positivo. Los resultados indican que el uso de Wimba Classroom es adecuado para el objetivo propuestoEN] Cell Cultures is a subject included in the Biologist Degree at Sevilla University, that provides theoretical and practical information in this area. Due to the quick technological development in this field, we consider that is important to contribute complementary information to students who are cursing this subject. By means of the present project, specialists from biotechnological companies, who directly use and work with cell cultures, have provided lectures about different innovative applications in this area. The conferences have been carried out without the physical presence of the speakers by the use of the Wimba Classroom online tool. The level of understanding of the conferences was tested by means of WebCT evaluation tools, and the possible impact in the final califications got by students was analized. The results show that the the group of students that actively participated in the activity got higher final calification than the group who did not participate (5,92 and 4,01 respectively). Students could evaluate different aspects of the activity by answering a WebCT survey online. The results show that Wimba Classroom is adequate for this purpose and that evaluation of the formative activity by students is quite positive.[IT] l corso Colture Cellulari impartito nel corso di Laurea in Biologia dell’Università di Siviglia, fornisce agli alunni informazioni teoriche e pratiche su questa materia. Il grande progresso tecnologico delle colture cellulari suggerisce di ampliare l’offerta formativa. Per questo motivo abbiamo realizzato un’attività formativa che ha permesso a professionisti provenienti da altre Università o imprese, di fornire in forma diretta e senza bisogno di lezioni in presenza, conoscenze sulle tecniche più innovatrici nella coltivazione cellulare. Sono state realizzate due conferenze a distanza mediante l’uso dello strumento Aula Virtuale. È stato valutato il grado di comprensione delle conferenze da parte degli alunni per mezzo dello strumento compito e esame del WEbCT, così come è stata valutata la possibile ripercussione sul voto finale. I risultati ottenuti mostrano un incremento nel numero dei promossi e di coloro i quali si sono presentati all’esame nel gruppo sperimentale rispetto al gruppo controllo, così come l’aumento del voto medio ottenuto (5,92 su 4,01). Gli alunni hanno valutato diversi aspetti dell’attività mediante questionari forniti dalla piattaforma, nei quali si è ottenuto un livello di valutazione molto positivo della stessa. I risultati indicano che l’uso dell’Aula Virtuale è adeguato all’obiettivo proposto.El proyecto de docencia que se ha presentado ha sido subvencionado por la Universidad de Sevilla dentro del I Plan de docencia de la US, línea de Innovación y mejora docente. La participación en el congreso ha recibido subvención del mismo plan en la línea de Divulgación de proyectos de investigación, innovación y mejora de la actividad docenteDomínguez García, I.; Reina Del Pozo, M.; Castro Feo, B.; Mateos Cordero, S.; Torreblanca López, J. (2011). Realización de seminarios a distancia mediante el uso de herramientas de blackboard (wimbaclassroom de webct) para conocer las aplicaciones y avances de los cultivos celulares en relación al ámbito laboral. REDU. Revista de Docencia Universitaria. 8(2):161-174. https://doi.org/10.4995/redu.2010.6201OJS16117482ÁLVAREZ‐ÁLVAREZ, B., GONZÁLEZ‐MIERES C., GARCÍA‐RODRÍGUEZ N. (2007). La motivación y los métodos de evaluación como variables fundamentales para estimular el aprendizaje autónomo. Red U. Revista de Docencia Universitaria, número 2. http://www.um.es/ead/Red_U/2/ESCALONA ORCAO, A.I., & LOSCERTALES PALOMAR, B. (2008). Pautas y materiales para la renovación metodológica en la docencia universitaria. En: V.V. A.A. II Jornadas de Innovación Docente, Tecnologías de la Información y Comunicación, e Investigación Educativa de la Universidad de Zaragoza. (Eds.) Instituto de Ciencias de la Educación. Universidad de Zaragoza.FORÉS, A., BORGES, F., BAUTISTA, G. (2006). Didáctica Universitaria en entornos virtuales de enseñanza‐aprendizaje (1st ed.). Madrid: Narcea, S. A. de Ediciones.LEÓN DE MORA, C. (2006). Planificación, diseño de cursos y docencia a través de Internet con WebCTE6. Secretariado de Publicaciones de la Universidad de Sevilla.LEÓN DE MORA, C. (2007). Wimba Classroom. Secretariado de Publicaciones de la Universidad de Sevilla.ZARAGOZA, J., LUIS PASCUAL, J.C., MANRIQUE, J.C. (2009). Experiencias de innovación en docencia universitaria: resultados de la aplicación de sistemas de evaluación formativa. Red U. Revista de Docencia Universitaria, número 4. http://www.redu.um.es/red_U/4

Arginine deprivation alters microglial polarity and synergizes with radiation to eradicate non-arginine-auxotrophic glioblastoma tumors

New approaches for the management of glioblastoma (GBM) are an urgent and unmet clinical need. Here, we illustrate that the efficacy of radiotherapy for GBM is strikingly potentiated by concomitant therapy with the arginine-depleting agent ADI-PEG20 in a non-arginine-auxotrophic cellular background (argininosuccinate synthetase 1 positive). Moreover, this combination led to durable and complete radiological and pathological response, with extended disease-free survival in an orthotopic immune-competent model of GBM, with no significant toxicity. ADI-PEG20 not only enhanced the cellular sensitivity of argininosuccinate synthetase 1–positive GBM to ionizing radiation by elevated production of nitric oxide (˙NO) and hence generation of cytotoxic peroxynitrites, but also promoted glioma-associated macrophage/microglial infiltration into tumors and turned their classical antiinflammatory (protumor) phenotype into a proinflammatory (antitumor) phenotype. Our results provide an effective, well-tolerated, and simple strategy to improve GBM treatment that merits consideration for early evaluation in clinical trials.Fondo de Desarrollo Regional (FEDER). Programa Operativo Epiro 2014-2020National Strategic Reference Frameworks de la Unión Europea. NSRF 2014-2020-5033092Ministerio de Ciencia, Innovación y Universidades de España y fondos FEDER. RTI2018-098645-B-100Consejería de Economía y Conocimiento de la Junta de Andalucía y fondos FEDER. P18- RT-1372Universidad de Sevilla. US-126480

Integration of new biological and physical retrospective dosimetry methods into EU emergency response plans : joint RENEB and EURADOS inter-laboratory comparisons

Purpose: RENEB, 'Realising the European Network of Biodosimetry and Physical Retrospective Dosimetry,' is a network for research and emergency response mutual assistance in biodosimetry within the EU. Within this extremely active network, a number of new dosimetry methods have recently been proposed or developed. There is a requirement to test and/or validate these candidate techniques and inter-comparison exercises are a well-established method for such validation. Materials and methods: The authors present details of inter-comparisons of four such new methods: dicentric chromosome analysis including telomere and centromere staining; the gene expression assay carried out in whole blood; Raman spectroscopy on blood lymphocytes, and detection of radiation induced thermoluminescent signals in glass screens taken from mobile phones. Results: In general the results show good agreement between the laboratories and methods within the expected levels of uncertainty, and thus demonstrate that there is a lot of potential for each of the candidate techniques. Conclusions: Further work is required before the new methods can be included within the suite of reliable dosimetry methods for use by RENEB partners and others in routine and emergency response scenarios

Enhanced hydrogen production from thermochemical processes

To alleviate the pressing problem of greenhouse gas emissions, the development and deployment of sustainable energy technologies is necessary. One potentially viable approach for replacing fossil fuels is the development of a H2 economy. Not only can H2 be used to produce heat and electricity, it is also utilised in ammonia synthesis and hydrocracking. H2 is traditionally generated from thermochemical processes such as steam reforming of hydrocarbons and the water-gas-shift (WGS) reaction. However, these processes suffer from low H2 yields owing to their reversible nature. Removing H2 with membranes and/or extracting CO2 with solid sorbents in situ can overcome these issues by shifting the component equilibrium towards enhanced H2 production via Le Chatelier's principle. This can potentially result in reduced energy consumption, smaller reactor sizes and, therefore, lower capital costs. In light of this, a significant amount of work has been conducted over the past few decades to refine these processes through the development of novel materials and complex models. Here, we critically review the most recent developments in these studies, identify possible research gaps, and offer recommendations for future research

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac