The Role of Nrf2 Signaling in PPARβ/δ-Mediated Vascular Protection against Hyperglycemia-Induced Oxidative Stress

Hyperglycemia induces oxidative stress and plays a substantial role in the progression of vascular diseases. Here, we demonstrated the potentiality of peroxisome proliferator-activated receptor (PPAR)β/δ activation in attenuating high glucose-induced oxidative stress in endothelial cells and diabetic rats, pointing to the involvement of nuclear factor erythroid 2-related factor 2 (Nrf2). HUVECs exposed to high glucose showed increased levels of reactive oxygen species (ROS) and upregulated NOX-2, NOX-4, Nrf2, and NQO-1 effects that were significantly reversed by the PPARβ/δ agonists GW0742 and L165041. Both PPARβ/δ agonists, in a concentration-dependent manner, induced transcriptional and protein upregulation of heme oxygenase-1 (HO-1) under low- and high-glucose conditions. All effects of PPARβ/δ agonists were reversed by either pharmacological inhibition or siRNA-based downregulation of PPARβ/δ. These in vitro findings were confirmed in diabetic rats treated with GW0742. In conclusion, PPARβ/δ activation confers vascular protection against hyperglycemia-induced oxidative stress by suppressing NOX-2 and NOX-4 expression plus a direct induction of HO-1; with the subsequent downregulation of the Nrf2 pathway. Thus, PPARβ/δ activation could be of interest to prevent the progression of diabetic vascular complications.This work was supported by Grants from Ministerio de Economía y Competitividad and Fondo Europeo de Desar- rollo Regional (FEDER) (SAF2010-22066-C02-01, SAF2010-22066-C02-02, SAF2011-28150, SAF2014-55523- R), Junta de Andalucía (Proyecto de excelencia, P12-CTS- 2722), and Instituto de Salud Carlos III (RIC RD12/0042/ 0011), Spain

Mycophenolate mediated remodeling of gut microbiota and improvement of gut-brain axis in spontaneously hypertensive rats

This work was supported by Grants from Comisi´on Interministerial de Ciencia y Tecnología, Ministerio de Economía y competitividad (SAF2017-84894-R), Junta de Andalucía (CTS-164) with funds from the European Union, Ministerio de Economia y Competitividad, Instituto de Salud Carlos III (CIBER-CV), Spain. M.T. is a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program). I.R.-V. is a predoctoral fellow of MINECO. The cost of this publication was paid in part with funds from the European Union (Fondo Europeo de Desarrollo Regional, FEDER, “FEDER una manera de hacer Europa”).Microbiota has a role in the host blood pressure (BP) regulation. The immunosuppressive drug mofetil mycophenolate (MMF) ameliorates hypertension. The present study analyzes whether MMF improves dysbiosis in a genetic model of hypertension. Twenty weeks old male spontaneously hypertensive rats (SHR) and Wistar Kyoto rats (WKY) were randomly divided into three groups: untreated WKY, untreated SHR, and SHR treated with MMF for 5 weeks. MMF treatment restored gut bacteria from the phyla Firmicutes and Bacteroidetes, and acetate- and lactate-producing bacteria to levels similar to those found in WKY, increasing butyrate-producing bacteria. MMF increased the percentage of anaerobic bacteria in the gut. The improvement of gut dysbiosis was associated with an enhanced colonic integrity and a decreased sympathetic drive in the gut. MMF inhibited neuroinflammation in the paraventricular nuclei in the hypothalamus. MMF increased the lower regulatory T cells proportion in mesenteric lymph nodes and Th17 and Th1 infiltration in aorta, improved aortic endothelial function and reduced systolic BP. This study demonstrates for the first time that MMF reduces gut dysbiosis in SHR. This effect could be related to its capability to improve gut integrity due to reduced sympathetic drive in the gut associated to the reduced brain neuroinflammation.Comision Interministerial de Ciencia y Tecnologia, Ministerio de Economia y competitividad SAF201784894RJunta de Andalucia CTS-164European CommissionSpanish GovernmentInstituto de Salud Carlos III (CIBERCV) , SpainEuropean Union (Fondo Europeo de Desarrollo Regional, FEDER, "FEDER una manera de hacer Europa"

Critical Role of the Interaction Gut Microbiota – Sympathetic Nervous System in the Regulation of Blood Pressure

Association between gut dysbiosis and neurogenic diseases, such as hypertension, has been described. The aim of this study was to investigate whether changes in the gut microbiota alter gut-brain interactions inducing changes in blood pressure (BP). Recipient normotensive Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) were orally gavaged with donor fecal contents from SHR and WKY. We divided the animals into four groups: WKY transplanted with WKY microbiota (W-W), SHR with SHR (S-S), WKY with SHR (W-S) and SHR with WKY (S-W). Basal systolic BP (SBP) and diastolic BP (DBP) were reduced with no change in heart rate as a result of fecal microbiota transplantation (FMT) from WKY rats to SHR. Similarly, FMT from SHR to WKY increased basal SBP and DBP. Increases in both NADPH oxidase-driven reactive oxygen species production and proinflammatory cytokines in brain paraventricular nucleus linked to higher BP drop with pentolinium and plasmatic noradrenaline (NA) levels were found in the S-S group as compared to the W-W group. These parameters were reduced by FMT from WKY to SHR. Increased levels of pro-inflammatory cytokines, tyrosine hydroxylase mRNA levels and NA content in the proximal colon, whereas reduced mRNA levels of gap junction proteins, were found in the S-S group as compared to the W-W group. These changes were inhibited by FMT from WKY to SHR. According to our correlation analyses, the abundance of Blautia and Odoribacter showed a negative correlation with high SBP. In conclusion, in SHR gut microbiota is an important factor involved in BP control, at least in part, as consequence of its effect on neuroinflammation and the sympathetic nervous system activity.This work was funded by grants from Comisión Interministerial de Ciencia y Tecnología, Ministerio de Economía y Competitividad (MINECO) (SAF2017-8489-R, AGL2015-67995- C3-3-R, and SAF2014-55523-R), Junta de Andalucía (Proyecto de Excelencia P12-CTS-2722 and CTS-164) with support from the European Union, and Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (CIBER-CV, CIBER-EHD), Spain. MS is a postdoctoral fellow of Junta de Andalucía. MR is postdoctoral fellow of University of Granada. IR-V is a predoctoral fellow of MINECO. The cost of this publication was paid in part with FEDER funds

Physiological, morphological and behavioural responses of self-feeding precocial chicks copying with contrasting levels of water salinity during development

Combined physiological and behavioural responses to salt loads during development have rarely been studied in air-breathing vertebrates able to inhabit hypersaline habitats, but they may be of particular importance in understanding, for example, the differences among species in patterns of habitat use or ontogenetic diet switches. Here, we compared the physiological and behavioural responses of self-feeding precocial chicks developed in contrasting levels of water salinity. The model species was the Black-winged Stilt (Himantopus himantopus) a precocial shorebird that breeds in a range of habitats from freshwater to hypersaline wetlands. Specifically, we compared resting metabolic rate (RMR), heat shock proteins (Hsp70), plasma ions, hematocrit, body mass, body size, growth rate and headshaking behaviour of captive-reared Black-winged Stilt fledglings developed under fresh (0 ½), saline (20 ½), and hypersaline (60 ½) water. Contrary to expectations, none of the physiological and morphological variables measured differed significantly among treatments. Likewise, the RMR of wild and captive-reared fledglings was similar. Surprisingly, the saltgland mass of wild fledglings from freshwater and those from hypersaline habitats was also similar. However, head-shaking, a behavioural response associated to minimize salt intake and to expel the secretions of salt glands, differed according to salinity source: head-shaking rate increased with increasing salinity. The results of this study support the key role of behavioural osmoregulation in avoiding salt stress during development.Trabajo financiado por: Fundacão para a Ciência e Tecnologia. Ayuda SFRH / BD / 74228 / 2010 y UID/MAR/04292/2013 para Afonso Duarte dos Reis Rocha Ministerio de Ciencia e Innovación. Ayuda CGL2011-27485 Junta de Extremadura y Fondos FEDER. Ayuda GR15080peerReviewe

Control de plantas de destilación por membranas con apoyo de energía solar

La destilación por membranas es una tecnología de desalación de agua no implantada industrialmente y en la que existen numerosas incógnitas sobre su funcionamiento y producción en condiciones intermitentes de operación como las que se pueden alcanzar cuando se usa energía solar como fuente primaria de energía. Una de las pocas plantas piloto actuales está ubicada en la Plataforma Solar de Almería (PSA). En este trabajo se incluye una descripción sobre la instalación y los esquemas de control que se han propuesto para conseguir unas condiciones adecuadas de flujo másico y temperatura a la entrada del sistema de destilación. En la segunda parte se expondrán resultados representativos

Use ultrasonography for cyst fibrosis in breast of young university

Se realizó un estudio en universitarias del área de la salud de la Universidad del Estado de México, las edades de las participantes oscilan entre 19 a 24 años, aparentemente sanas. El objetivo fue, determinar la relación de proporción de fibrosis quística en mama, por medio de imágenes ultrasonográficas. Fue un estudio de corte transversal cualitativo, conformado por una muestra de 32 estudiantes femeninas. Los resultados son, el 65% presentó nódulos del tipo fibroadenoma y quistes de mama, de este porcentaje, el 100% señalo haber utilizado hormonas para el control natal, 19.4% utilizó levonorgestrel (Pildora anticonceptiva de emergencia) de forma recurrente, 12.5% tiene antecedentes heredo familiares y solo el 18% de la muestra indico que se realiza autoexploración mamaria. Una de las principales causas de la fibrosis quística, es el consumo de anticonceptivos hormonales, se le suma un estilo de vida poco saludable. Las participantes son estudiantes del área de la salud y durante su formación profesional, las universitarias han realizado actividades de promoción y educación para la salud sobre el cáncer de mama, por lo tanto, cuentan con los conocimientos para llevar a cabo la autoexploración, sin embargo, menos del 20% se responsabiliza de su cuidado en la salud.The study was carried out in university students of the health area of the University of the State of Mexico. The range ages are 19 to 24 years old and appear to be healthy. The purpose of the research was to determine the ratio of cystic fibrosis in the breast, through ultrasonographic images. It is a qualitative cross-sectional study with a sample size of 32 individuals, using a sampling for convenience. The results found were that 65% had fibroadenoma-like nodules and breast cysts, of this percentage, 100% reported using hormones for birth control, 19.4% used levonorgestrel (Emergency Contraceptive Pile) recursively, 12.5% indicated having a family history, on the other hand, only 18% of the sample indicated that breast self-examination is performed. It is concluded that one of the main causes of cystic fibrosis is the use of hormonal contraceptives and added to this is an unhealthy lifestyle. It should be noted that the participants are students in the area of health and in the course of their professional training, university students have carried out health promotion and education on breast cancer, therefore, they have the knowledge to carry out self-exploration and less than 20% are responsible for their health care

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

All-Path Bridging: Path Exploration Protocols for Data Center and Campus Networks

Today, link-state routing protocols that compute multiple shortest paths predominate in data center and campus networks, where routing is performed either in layer three or in layer two using link-state routing protocols. But current proposals based on link-state routing do not adapt well to real time traffic variations and become very complex when attempting to balance the traffic load. We propose All-Path bridging, an evolution of the classical transparent bridging that forwards frames over shortest paths using the complete network topology, which overcomes the limitations of the spanning tree protocol. All-Path is a new frame routing paradigm based on the simultaneous exploration of all paths of the real network by a broadcast probe frame, instead of computing routes on the network graph. This paper presents All- Path switches and their differences with standard switches and describes ARP-Path protocol in detail, its path recovery mechanisms and compatibility with IEEE 802.1 standard bridges. ARP-Path is the first protocol variant of the All-Path protocol family. ARP-Path reuses the standard ARP Request and Reply packets to explore reactively the network and find the fastest path between two hosts. We compare its performance in terms of latency and load distribution with link-state shortest-path routing bridges, showing that ARP-Path distributes the load more evenly and provides lower latencies. Implementations on different platforms prove the robustness of the protocol. The conclusion is that All-Path bridging offer a simple, resilient and scalable alternative to path computation protocols

All-Path Bridging: Path Exploration Protocols for Data Center and Campus Networks

Today, link-state routing protocols that compute multiple shortest paths predominate in data center and campus networks, where routing is performed either in layer three or in layer two using link-state routing protocols. But current proposals based on link-state routing do not adapt well to real time traffic variations and become very complex when attempting to balance the traffic load. We propose All-Path bridging, an evolution of the classical transparent bridging that forwards frames over shortest paths using the complete network topology, which overcomes the limitations of the spanning tree protocol. All-Path is a new frame routing paradigm based on the simultaneous exploration of all paths of the real network by a broadcast probe frame, instead of computing routes on the network graph. This paper presents All- Path switches and their differences with standard switches and describes ARP-Path protocol in detail, its path recovery mechanisms and compatibility with IEEE 802.1 standard bridges. ARP-Path is the first protocol variant of the All-Path protocol family. ARP-Path reuses the standard ARP Request and Reply packets to explore reactively the network and find the fastest path between two hosts. We compare its performance in terms of latency and load distribution with link-state shortest-path routing bridges, showing that ARP-Path distributes the load more evenly and provides lower latencies. Implementations on different platforms prove the robustness of the protocol. The conclusion is that All-Path bridging offer a simple, resilient and scalable alternative to path computation protocols