Neuroprotective Effects of Resveratrol in Ischemic Brain Injury

Cerebral ischemia represents the third cause of death and the first cause of disability inadults. This process results from decreasing cerebral blood flow levels as a result of the occlusionof a major cerebral artery. This restriction in blood supply generates low levels of oxygen andglucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, andfinally, neurological deterioration. Currently, blood restoration of flow is the only effective approachas a therapy in terms of ischemic stroke. However, a significant number of patients still have apoor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS)during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided bymodulating mitochondrial function and have been identified as potential targets for the treatmentof cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols againstcerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has beenshown to markedly decrease brain damage caused by ischemia in numerous studies. According toin vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways,including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronalautophagy activation, and de novo SUR1 expression inhibition. In this review, we summarize therecent outcomes based on the neuroprotective effect of RSV itself and RSV-loaded nanoparticlesin vitro and in vivo models focusing on such mechanisms of action as well as describing the potentialtherapeutic strategies in which RSV plays an active role in cases of ischemic brain injuryFil: Machado, Noelia Daiana. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; Argentina. Universidad Nacional de Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación y Desarrollo en Ingeniería de Procesos y Química Aplicada; ArgentinaFil: Villena Armas, Gorka. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-Orgánica "Antonio González"; EspañaFil: Fernández, Mariana Adela. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Departamento de Química Orgánica; ArgentinaFil: Grijalvo, Santiago. Institute For Advanced Chemistry Of Catalonia; España. Biomedical Research Networking Center in Bioengineering, Biomaterials and Nanomedicine; EspañaFil: Díaz Díaz, David. Universidad de la Laguna. Departamento de Química Orgánica. Instituto Universitario de Bio-Orgánica "Antonio González"; España. Universitat Regensburg; Alemani

Secondary phytohaemagglutinin (PHA) swelling response is a good indicator of T-cell-mediated immunity in free-living birds

El phytohaemagglutinin (PHA) se prueba para medir la inmunidad adquirida y es uno de los métodos más utilizados; actualmente, está siendo debatido a raíz de los nuevos conocimientos sobre la compleja fisiología del proceso. Como respuesta secundaria reiterada a los mayores desafíos vinculados a los aumentos de los niveles de linfocitos T circulantes sería indicativo de una respuesta inmune mediada por células, se realizó por primera vez un experimento bajo condiciones naturales con repetidas PHA desafíos en libre-viviendo los pájaros adultos y polluelos para arrojar luz sobre este tema. Hemos encontrado significativamente más fuerte respuesta a PHA inyección secundaria independiente del sexo o la edad, mientras que el control de la condición corporal, la segunda respuesta es en promedio 90% más grande que el primero. Igualmente, los recuentos de linfocitos fueron significativamente superiores en el segundo reto de PHA, mientras que no se encontraron diferencias significativas entre las aves no tratadas. Las correlaciones positivas significativas entre la PHA respuesta y ambos recuentos de linfocitos y los niveles de proteínas plasmáticas (principalmente albúmina, globulina (precursor) fueron recuperados, mientras que no hubo diferencias significativas en los niveles de proteínas plasmáticas recuperados entre los retos. Nuestros resultados son consistentes con las aves cautivas, apoyando la validez del PHA de la hinchazón de la piel como prueba precisa de haber adquirido células T como la inmunidad en aves.The validity of using the phytohaemagglutinin (PHA) test to measure acquired immunity, one of the most widely used methods, is currently being debated due to new knowledge on the complex physiology of the process. As a greater secondary response to repeated challenges linked to increases of circulating lymphocyte levels would be indicative of a T-cell-mediated immune response, we performed for the first time an experiment under natural conditions with repeated PHA challenges in free-living adult birds and chicks to shed light on this topic. We found significantly stronger secondary response to PHA injection independent of sex or age, while controlling for body condition, the second response being on average 90% larger than the first. Likewise, lymphocyte counts were significantly higher in the second PHA challenge, whereas no significant differences were found among untreated birds. Significant positive correlations between the PHA response and both lymphocyte counts and plasma protein levels (mainly albumin, globulin (precursor) were recovered, whereas no significant differences were recovered in plasma protein levels between challenges. Our results are consistent with those from captive birds, supporting the validity of the PHA skin-swelling test as an accurate gauge of acquired T-cell-mediated immunity in birds.Trabajo patrocinado por: Fondo Mejicano para Conservación de la Naturaleza. Proyecto PIE 2012 A-P-C-IGSI-12-12 Gobierno de Extremadura. CONACYT (I010/176/2012) y becas PO10014 y RE12002 Gobierno de Extremadura. Dirección General de Vida Silvestre. SGPA/ DGVS/08559/11peerReviewe

Las Cruces en la red y en la calle

No se pueden entender las Cruces de Mayo sin la calle, pues es ahí donde tienen su máxima expresión. Pero en los tiempos que corren, tampoco se pueden entender sin Internet, donde se publican noticias y reportajes en los diversos diarios cibernéticos; donde se "cuelgan" vídeos en Youtube; donde se publican fotos en Facebook, etc

LXR Nuclear receptors are transcriptional regulators of dendritic cell chemotaxis

The liver X receptors (LXRs) are ligand-activated nuclear receptors with established roles in the maintenance of lipid homeostasis in multiple tissues. LXRs exert additional biological functions as negative regulators of inflammation, particularly in macrophages. However, the transcriptional responses controlled by LXRs in other myeloid cells, such as dendritic cells (DCs), are still poorly understood. Here we used gain- and loss-of-function models to characterize the impact of LXR deficiency on DC activation programs. Our results identified an LXR-dependent pathway that is important for DC chemotaxis. LXR-deficient mature DCs are defective in stimulus-induced migration in vitro and in vivo. Mechanistically, we show that LXRs facilitate DC chemotactic signaling by regulating the expression of CD38, an ectoenzyme important for leukocyte trafficking. Pharmacological or genetic inactivation of CD38 activity abolished the LXR-dependent induction of DC chemotaxis. Using the low-density lipoprotein receptor-deficient (LDLR−/−) LDLR−/− mouse model of atherosclerosis, we also demonstrated that hematopoietic CD38 expression is important for the accumulation of lipid-laden myeloid cells in lesions, suggesting that CD38 is a key factor in leukocyte migration during atherogenesis. Collectively, our results demonstrate that LXRs are required for the efficient emigration of DCs in response to chemotactic signals during inflammation

Unraveling the effect of silent, intronic and missense mutations on VWF splicing : contribution of next generation sequencing in the study of mRNA

Large studies in von Willebrand disease patients, including Spanish and Portuguese registries, led to the identification of >250 different mutations. It is a challenge to determine the pathogenic effect of potential splice site mutations on VWF mRNA. This study aimed to elucidate the true effects of 18 mutations on VWF mRNA processing, investigate the contribution of next-generation sequencing to in vivo mRNA study in von Willebrand disease, and compare the findings with in silico prediction. RNA extracted from patient platelets and leukocytes was amplified by RT-PCR and sequenced using Sanger and next generation sequencing techniques. Eight mutations affected VWF splicing: c.1533+1G>A, c.5664+2T>C and c.546G>A (p.=) prompted exon skipping; c.3223-7_3236dup and c.7082-2A>G resulted in activation of cryptic sites; c.3379+1G>A and c.7437G>A) demonstrated both molecular pathogenic mechanisms simultaneously; and the p.Cys370Tyr missense mutation generated two aberrant transcripts. Of note, the complete effect of three mutations was provided by next generation sequencing alone because of low expression of the aberrant transcripts. In the remaining 10 mutations, no effect was elucidated in the experiments. However, the differential findings obtained in platelets and leukocytes provided substantial evidence that four of these would have an effect on VWF levels. In this first report using next generation sequencing technology to unravel the effects of VWF mutations on splicing, the technique yielded valuable information. Our data bring to light the importance of studying the effect of synonymous and missense mutations on VWF splicing to improve the current knowledge of the molecular mechanisms behind von Willebrand disease. identifier:02869074

Towards a dynamic checklist of lichen-forming, lichenicolous and allied fungi of Ecuador – using the <i>Consortium of Lichen Herbaria</i> to manage fungal biodiversity in a megadiverse country

peer reviewedA checklist of Lichen-forming, Lichenicolous and Allied Fungi of Ecuador is presented with a total of 2599 species, of which 39 are reported for the first time from the country. The names of three species, Hypotrachyna montufariensis, H. subpartita and Sticta hypoglabra, previously not validly published, are validated. Pertusaria oahuensis, originally introduced by Magnusson as ‘ad interim’, is validated as Lepra oahuensis. The form Leucodermia leucomelos f. albociliata is validated. Two new combinations, Fissurina tectigera and F. timida, are made, and Physcia mobergii is introduced as a replacement name for the illegitimate P. lobulata Moberg non (Flörke) Arnold. In an initial step, the checklist was compiled by reviewing literature records of Ecuadorian lichen biota spanning from the late 19th century to the present day. Subsequently, records were added based on vouchers from 56 collections participating in the Consortium of Lichen Herbaria, a Symbiota-based biodiversity platform with particular focus on, but not exclusive to, North and South America. Symbiota provides sophisticated tools to manage biodiversity data, such as occurrence records, a taxonomic thesaurus, and checklists. The thesaurus keeps track of frequently changing names, distinguishing taxa currently accepted from ones considered synonyms. The software also provides tools to create and manage checklists, with an emphasis on selecting vouchers based on occurrence records that can be verified for identification accuracy. Advantages and limitations of creating checklists in Symbiota versus traditional ways of compiling these lists are discussed. Traditional checklists are well suited to document current knowledge as a ‘snapshot in time’. They are important baselines, frequently used by ecologists and conservation scientists as an established naming convention for citing species reported from a country. Compiling these lists, however, requires an immense effort, only to inadequately address the dynamic nature of scientific discovery. Traditional checklists are thus quickly out of date, particularly in groups with rapidly changing taxonomy, such as lichenized fungi. Especially in megadiverse countries, where new species and new occurrences continue to be discovered, traditional checklists are not easily updated; these lists necessarily fall short of efficiently managing immense data sets, and they rely primarily on secondary evidence (i.e. literature records rather than specimens). Ideally, best practices make use of dynamic database platforms such as Symbiota to assess occurrence records based both on literature citations and voucher specimens. Using modern data management tools comes with a learning curve. Systems like Symbiota are not necessarily intuitive and their functionality can still be improved, especially when handling literature records. However, online biodiversity data platforms have much potential in more efficiently managing and assessing large biodiversity data sets, particularly when investigating the lichen biota of megadiverse countries such as Ecuador

Elevated circulating levels of succinate in human obesity are linked to specific gut microbiota

Gut microbiota-related metabolites are potential clinical biomarkers for cardiovascular disease (CVD). Circulating succinate, a metabolite produced by both microbiota and the host, is increased in hypertension, ischemic heart disease, and type 2 diabetes. We aimed to analyze systemic levels of succinate in obesity, a major risk factor for CVD, and its relationship with gut microbiome. We explored the association of circulating succinate with specific metagenomic signatures in cross-sectional and prospective cohorts of Caucasian Spanish subjects. Obesity was associated with elevated levels of circulating succinate concomitant with impaired glucose metabolism. This increase was associated with specific changes in gut microbiota related to succinate metabolism: a higher relative abundance of succinate-producing Prevotellaceae (P) and Veillonellaceae (V), and a lower relative abundance of succinate-consuming Odoribacteraceae (O) and Clostridaceae (C) in obese individuals, with the (P + V/O + C) ratio being a main determinant of plasma succinate. Weight loss intervention decreased (P + V/O + C) ratio coincident with the reduction in circulating succinate. In the spontaneous evolution after good dietary advice, alterations in circulating succinate levels were linked to specific metagenomic signatures associated with carbohydrate metabolism and energy production with independence of body weight change. Our data support the importance of microbe-microbe interactions for the metabolite signature of gut microbiome and uncover succinate as a potential microbiota-derived metabolite related to CVD risk

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe