106 research outputs found

    The multifaceted role of vitamin b6 in cancer: drosophila as a model system to investigate dna damage

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    A perturbed uptake of micronutrients, such as minerals and vitamins, impacts on different human diseases, including cancer and neurological disorders. Several data converge towards a crucial role played by many micronutrients in genome integrity maintenance and in the establishment of a correct DNA methylation pattern. Failure in the proper accomplishment of these processes accelerates senescence and increases the risk of developing cancer, by promoting the formation of chromosome aberrations and deregulating the expression of oncogenes. Here, the main recent evidence regarding the impact of some B vitamins on DNA damage and cancer is summarized, providing an integrated and updated analysis, mainly centred on vitamin B6. In many cases, it is difficult to finely predict the optimal vitamin rate that is able to protect against DNA damage, as this can be influenced by a given individual's genotype. For this purpose, a precious resort is represented by model organisms which allow limitations imposed by more complex systems to be overcome. In this review, we show that Drosophila can be a useful model to deeply understand mechanisms underlying the relationship between vitamin B6 and genome integrity

    Epidemiología de las quemaduras pediátricas: seis años de experiencia en una unidad especializada de alta complejidad

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    Introducción: Las lesiones por quemaduras son una patología grave, que pueden conducir a una gran morbilidad y una mortalidad significativa, pero también tienen un impacto sanitario-económico considerable. El objetivo de este estudio fue describir epidemiológicamente la población hospitalizada en la Unidad de Quemados del Hospital de Pediatría “Prof. Dr. Juan P. Garrahan” entre los años 2015 y 2020. Material y métodos: Estudio observacional, descriptivo- analítico, transversal, con evaluación y análisis de datos registrados en base de datos de historias clínicas digitalizadas. Resultados: La serie incluyó 214 pacientes, 60,3% sexo masculino, mediana de edad 4.6 años (0-16,6), 63% provenientes de la provincia de Buenos Aires, 78% de traslados se hicieron por vía terrestre con tiempo promedio de 55,6 minutos (DS 81,9), 52,8% ingresaron en los meses de otoño-invierno, 80% carecían de cobertura social. La etiología lesional fue fuego y variantes (69,2%) y escaldaduras (25,7%). El 49% reunieron criterios de lesión inhalatoria. La mediana de superficie corporal quemada (SCQ) fue 30% (0-100%), lesiones tipo B (profundas) 16,2% (0-100%) y gravedad crítica (37,4%) y grave (19,2%), requiriendo una mediana de 5 actos quirúrgicos (0-55). El 87,3% de los ingresos fue en Cuidados Intensivos, con mediana de estancia hospitalaria de 33 días (1-243) y relación promedio %SCQ/días internación 1,9 (DS 2,1). El uso de Asistencia Respiratoria Mecánica (ARM) fue 68,7% con una mediana de 7.5 días (1-100). La mortalidad de la serie fue 9,8% y estuvo asociada estadísticamente a lesión inhalatoria (p=0,0001), profundidad lesional B (p=0,00001) y uso de ARM (p=0,0011). Conclusion: Los resultados de este estudio concluyen que el sexo masculino, la franja etaria < 5 años, los ingresos en otoño-invierno, las lesiones por fuego, el grupo de gravedad crítico y la utilización de ARM son datos epidemiológicos predominantes correspondientes a una Unidad de Quemados de Alta Complejidad y deben ser tenidos en cuenta para la planificación y adecuación de los recursos asistenciales.Burn injuries are a serious pathology, which can lead to high morbidity and significant mortality, but also have a considerable health-economic impact. The objective of this study was to epidemiologically describe the population hospitalized in the Burn Unit of the Pediatric Hospital “Prof. Dr. Juan P. Garrahan” between 2015 and 2020. Material and method: Observational, descriptive-analytical, cross-sectional study, with evaluation and analysis of data recorded in a database of digitized medical records. Results: The series included 214 patients, 60,3% male, median age 4,6 years (0-16,6), 63% from the province of Buenos Aires, 78% of transfers were made by land with an average time of 55,6 minutes (DS 81,9), 52,8% entered in the fall-winter months, 80% lacked social coverage. The lesional etiology was fire and variants (69,2%) and scalds (25,7%). 49% met criteria for inhalation injury. The median body surface area burned (SCQ) was 30% (0-100%), type B (deep) injuries 16,2% (0-100%) and critical (37,4%) and severe (19,2%) severity, requiring a median of 5 surgical acts (0-55). 87,3% of the admissions were in Intensive Care, with a median hospital stay of 33 days (1-243) and average ratio %SCQ/days hospitalization 1,9 (DS 2,1). The use of Mechanical Respiratory Assistance (MRA) was 68,7% with a median of 7,5 days (1-100). Mortality in the series was 9,8% and was statistically associated with inhalation injury (p=0,0001), injury depth B (p=0,00001) and use of MRA (p=0,0011). Conclusion: The results of this study conclude that male sex, the age group <5 years, admissions in autumn-winter, fire injuries, the critical severity group and the use of MRA are predominant epidemiological data corresponding to a Unit of High Complexity Burns and must be taken into account for the planning and adaptation of care resources

    The moonlighting RNA-binding activity of cytosolic serine hydroxymethyltransferase contributes to control compartmentalization of serine metabolism

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    Enzymes of intermediary metabolism are often reported to have moonlighting functions as RNA-binding proteins and have regulatory roles beyond their primary activities. Human serine hydroxymethyltransferase (SHMT) is essential for the one-carbon metabolism, which sustains growth and proliferation in normal and tumour cells. Here, we characterize the RNA-binding function of cytosolic SHMT (SHMT1) in vitro and using cancer cell models. We show that SHMT1 controls the expression of its mitochondrial counterpart (SHMT2) by binding to the 5'untranslated region of the SHMT2 transcript (UTR2). Importantly, binding to RNA is modulated by metabolites in vitro and the formation of the SHMT1-UTR2 complex inhibits the serine cleavage activity of the SHMT1, without affecting the reverse reaction. Transfection of UTR2 in cancer cells controls SHMT1 activity and reduces cell viability. We propose a novel mechanism of SHMT regulation, which interconnects RNA and metabolites levels to control the cross-talk between cytosolic and mitochondrial compartments of serine metabolism

    Murine and Bovine γδ T Cells Enhance Innate Immunity against Brucella abortus Infections

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    γδ T cells have been postulated to act as a first line of defense against infectious agents, particularly intracellular pathogens, representing an important link between the innate and adaptive immune responses. Human γδ T cells expand in the blood of brucellosis patients and are active against Brucella in vitro. However, the role of γδ T cells in vivo during experimental brucellosis has not been studied. Here we report TCRδ−/− mice are more susceptible to B. abortus infection than C57BL/6 mice at one week post-infection as measured by splenic colonization and splenomegaly. An increase in TCRγδ cells was observed in the spleens of B. abortus-infected C57BL/6 mice, which peaked at two weeks post-infection and occurred concomitantly with diminished brucellae. γδ T cells were the major source of IL-17 following infection and also produced IFN-γ. Depletion of γδ T cells from C57BL/6, IL-17Rα−/−, and GMCSF−/− mice enhanced susceptibility to B. abortus infection although this susceptibility was unaltered in the mutant mice; however, when γδ T cells were depleted from IFN-γ−/− mice, enhanced susceptibility was observed. Neutralization of γδ T cells in the absence of TNF-α did not further impair immunity. In the absence of TNF-α or γδ T cells, B. abortus-infected mice showed enhanced IFN-γ, suggesting that they augmented production to compensate for the loss of γδ T cells and/or TNF-α. While the protective role of γδ T cells was TNF-α-dependent, γδ T cells were not the major source of TNF-α and activation of γδ T cells following B. abortus infection was TNF-α-independent. Additionally, bovine TCRγδ cells were found to respond rapidly to B. abortus infection upon co-culture with autologous macrophages and could impair the intramacrophage replication of B. abortus via IFN-γ. Collectively, these results demonstrate γδ T cells are important for early protection to B. abortus infections

    Heart rate variability at bedtime predicts subsequent sleep features

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    Getting enough sleep during the night is important for preventing adverse short- and long-term health outcomes. The sympathetic-parasympathetic autonomic balance, characteristics of the pre-bed time resting period, correlates with sleep efficiency. We investigated in healthy subjects whether Low/High Frequencies (LF/HF) and other Heart Rate Variability (HRV) metrics, extracted in the period immediately before sleep onset, are able to predict quality/architecture sleep parameters in the sample group and in the Evening-/Intermediate-chronotype subgroups. Linear correlations were found between HRV metrics and the investigated quality/architecture sleep parameters. The possibility to predict sleep parameters from the HRV metrics while falling asleep might pave the way to behavioral interventions during the bedtime period to increase the quality of sleep
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