Silk fibroin nanoparticles constitute a vector for controlled release of resveratrol in an experimental model of inflammatory bowel disease in rats.

Purpose: We aimed to evaluate the intestinal anti-inflammatory properties of silk fibroin nanoparticles, around 100 nm in size, when loaded with the stilbene compound resveratrol, in an experimental model of rat colitis. Methods: Nanoparticles were loaded with resveratrol by adsorption. The biological effects of the resveratrol-loaded nanoparticles were tested both in vitro, in a cell culture of RAW 264.7 cells (mouse macrophages), and in vivo, in the trinitrobenzenesulfonic acid model of rat colitis, when administered intracolonically. Results: The resveratrol liberation in 1× phosphate-buffered saline (PBS; pH 7.4) was characterized by fast liberation, reaching the solubility limit in 3 hours, which was maintained over a period of 80 hours. The in vitro assays revealed immunomodulatory properties exerted by these resveratrol-loaded nanoparticles since they promoted macrophage activity in basal conditions and inhibited this activity when stimulated with lipopolysaccharide. The in vivo experiments showed that after evaluation of the macroscopic symptoms, inflammatory markers, and intestinal barrier function, the fibroin nanoparticles loaded with resveratrol had a better effect than the single treatments, being similar to that produced by the glucocorticoid dexamethasone. Conclusion: Silk fibroin nanoparticles constitute an attractive strategy for the controlled release of resveratrol, showing immunomodulatory properties and intestinal anti-inflammatory effects

Protocol for the detection and nutritional management of high-output stomas

Introduction: An issue of recent research interest is excessive stoma output and its relation to electrolyte abnormalities. Some studies have identified this as a precursor of dehydration and renal dysfunction. A prospective study was performed of the complications associated with high-output stomas, to identify their causes, consequences and management.Materials and methods: This study was carried out by a multidisciplinary team of surgeons, gastroenterologists, nutritionists and hospital pharmacists. High-output stoma (HOS) was defined as output ≥1500 ml for two consecutive days. The subjects included in the study population, 43 patients with a new permanent or temporary stoma, were classified according to the time of HOS onset as early HOS (<3 weeks after initial surgery) or late HOS (≥3 weeks after surgery). Circumstances permitting, a specific protocol for response to HOS was applied. Each patient was followed up until the fourth month after surgery.Results: Early HOS was observed in 7 (16 %) of the sample population of 43 hospital patients, and late HOS, in 6 of the 37 (16 %) non-early HOS population. By type of stoma, nearly all HOS cases affected ileostomy, rather than colostomy, patients. The patients with early HOS remained in hospital for 18 days post surgery, significantly longer than those with no HOS (12 days). The protocol was applied to the majority of EHOS patients and achieved 100 % effectiveness. 50 % of readmissions were due to altered electrolyte balance. Hypomagnesaemia was observed in 33 % of the late HOS patients.Conclusion: The protocol developed at our hospital for the detection and management of HOS effectively addresses possible long-term complications arising from poor nutritional status and chronic electrolyte alteration

Ten millennia of hepatitis B virus evolution

Hepatitis B virus (HBV) has been infecting humans for millennia and remains a global health problem, but its past diversity and dispersal routes are largely unknown. We generated HBV genomic data from 137 Eurasians and Native Americans dated between ~10,500 and ~400 years ago. We date the most recent common ancestor of all HBV lineages to between ~20,000 and 12,000 years ago, with the virus present in European and South American hunter-gatherers during the early Holocene. After the European Neolithic transition, Mesolithic HBV strains were replaced by a lineage likely disseminated by early farmers that prevailed throughout western Eurasia for ~4000 years, declining around the end of the 2nd millennium BCE. The only remnant of this prehistoric HBV diversity is the rare genotype G, which appears to have reemerged during the HIV pandemic

Anti-inflammatory bowel effect of industrial orange by-products in DSS-treated mice

This work addresses the role of different by-products derived from the industrial extraction of orange juice in a possible anti-inflammatory effect in mice with colitis induced by dextran sulfate sodium (DSS). Fresh orange residue (FOR), dry orange residue (DOR), orange liqueur (OL) and animal feed (AF), as well as commercial citrus pectin (CP), were administered to C57BL/6J mice for 15 days before starting the DSS treatment. Analysis of macroscopic parameters such as the Disease Activity Index (DAI) and the colonic weight/length ratio revealed an anti-inflammatory effect following intake of FOR, AF or CP. Moreover, q-PCR of RNA from colonic tissue indicated measurable changes in the expression of TNF-α, IL-1β, iNOS, and intercellular adhesion molecules ICAM I, as well as in intestinal barrier proteins such as MUC-3, occludin, and ZO-1. Pectin, phenolic compounds and/or Maillard reaction products formed at initial steps were identified as relevant components exerting the ascribed beneficial effects. Our findings could open up the further application of a variety of orange by-products as food supplements in the potential amelioration of inflammatory bowel diseases.The authors are grateful to the García Carrión SA for providing samples and funding projects AGL2014-53445-R (MINECO) and ALIBIRD-CM S-2013/ABI-272 (CAM). M. T. P. thanks the National Secretary of Higher Education, Science, Technology and Innovation of Ecuador (SENESCYT).Peer reviewe

Effect of orange by-products on inflammatory indicators in a DSS mouse model

Trabajo presentado al XII Congreso Internacional Nutrición, Alimentación y Dietética, celebrado en Madrid el 11 y 12 de abril de 2018.[Introducción] Inflammation is a response triggered by damage to living tissues. The mechanisms involved in the initiation and perpetuation of inflammatory bowel disease (IBD) are not known exactly; however, there are mediators released in the early stages and may act as indicators of the disease. Colonic cytokines production and macroscopic indicators such as weight loss, reduction of food consumption, soft stools, among others, allow to evaluate the degree of IBD. Orange by-products (OBP) namely: fresh residue (FOR), dry residue (DOR), liquor (OL) and animal feed (AF), analysed in a previous study contain: phenols, pectin and/or furosine (Maillard reaction product). These compounds can show anti-oxidant, anti-bacterial and anti-cancer effect, but its anti-inflammatory activity is still little studied.[Objetivos] In consequence the aim of this work was to study the effect of OBP ingestion on IBD, using a DSS mice model; which exhibits similar characteristics to those present in human Crohn´s disease.[Métodos] 2-Furoylmethyl-Amino Acids (2-FM-AA) were analyzed by ionpair RP-HPLC-UV, and monosaccharides through hydrolysis with 2 M trifluoroacetic acid and subsequent formation of trimethylsilyloximes derivatives, by GC-FID. Male C57BL/6 mice (Janvier, St Berthevin Cedex, France) were distributed in 7 groups: healthy, DSS control, FOR, DOR, OL, AF and Citrus pectin (CP) (CEAMSA, O Porriño, Spain) was used as standard. Animals pre-treatment start 15 days before induction of colitis with DSS (2,7%) on drinking water. On day 22, animals were euthanized and colon samples were obtained. Macroscopic indicators were observed every day (body weigth, food consumption, disease activity index (DAI)), and tissue pro-inflammatory cytoquines and intestinal protective proteins were determined by Real-Time quantitative PCR (EcoTM Real-Time PCR System, Illumina, CA, USA).[Resultados] Weights lost was high for DSS control group and CP, AF and FOR significantly reduced the drop. In addition, FOR and CP groups, presented low disease activity index (DAI) values vs. DSS control group (p < 0.05). On the contrary, DOR and OL groups showed a DAI value similar to non-treated groups. Colonic weight/length ratio was significantly less in all the OBP or CP treated mice vs the DSS group. Colonic inflammatory cytokines expression as TNF-α, IL-1β, IL-6 and NOS were significantly reduced in AF and CP group and expression of protein with intestinal barrier functions as ICAM I, MUC 3, occludin, and ZO-1 were also positively modified in mice treated with FOR, AF and CP (p < 0.05).[Discusión] Analyzing the consumption effect of AF vs. CP; CP intake allowed to obtain, a better anti-inflammatory response, which could be due to its greatest content of soluble dietary fiber SDF and N-fructosyl-lysine.[Conclusiones] In general, CP and AF intake allowed to obtain a better anti-inflammatory response in DSS model of IBD compared with other OBP products assayed, which could be due to its greatest content of furosine. The product namely FOR also show a beneficial effect in some parameters measured probably due at its biggest phenols content. The evaluated indicators underline the potential role of pectin and Maillard reaction compounds in ameliorating some IBD symptoms. However, in order to reach more accurate conclusions, the analysis of additional biochemical indicators should be conducted.Peer reviewe

Patterns of human occupation during the early Holocene in the Central Ebro Basin (NE Spain) in response to the 8.2 ka climatic event

28 páginas, 4 figuras, 2 tablasThe Central Ebro River Basin (NE Spain) is the most northern area of truly semi-arid Mediterranean climate in Europe and prehistoric human occupation has been strongly influenced by these unique environmental conditions. The Bajo Aragón region (SE Ebro River Basin) was intensively populated during the Early Holocene (9400 – 8200 cal. yr B.P.) but the settlements were abandoned abruptly at around 8200 cal. yr B.P. Modern climate conditions single out this region due to the harsh environment, characterized by the highest absolute summer temperatures of the Ebro River Basin. We propose that this “archaeological silence” was caused by the regional impact of the global abrupt 8.2 ka cold event. Available regional paleoclimate archives demonstrate the existence of an aridity crisis 8200 years ago that interrupts the humid Early Holocene. That environmental crisis would have forced hunter-gatherers groups from the Bajo Aragón to migrate to regions with more favourable conditions (i.e. more humid mountainous areas) and only return in the Neolithic. Coherently, archaeological sites persist during this crisis in the nearby Iberian Range (Maestrazgo) and the North Ebro River area (Pre-Pyrenean mountains and along the northwestern Ebro Basin).This work was part of the projects: “Palinología y Paleoclima: Cambios Climáticos y/o Antropogénicos y Evolución de la vegetación” funded by CSIC (Programa Intramural 2007-2008); “Los cambios climáticos abruptos y su influencia en los ecosistemas y las sociedades humanas en el Pirineo central y occidental” funded by the Aragón Regional Government (DGA) and two projects funded by the Spanish Inter-Ministry Commission of Science and Technology (CICYT): “Cambios climáticos rápidos en la Peninsula Ibérica basados en calibración de indicadores, series instrumentales largas y análisis de alta resolución de registros lacustres (Subproyecto CGL2006-13327-C04-01/CLI)” and “Cazadores-Recolectores del valle del Ebro (HUM 2005-02882)”. A. Moreno, M. Morellón, M. Sebastián and MC. Sopena have benefited from a Marie Curie Outgoing International Fellowships (proposal 021673-IBERABRUPT), a DGA fellowship, a FPI fellowship and a FSE-MEC contract, respectively.Peer reviewe

Territorial mobility and subsistence strategies during the Ebro Basin Late Neolithic-Chalcolithic: A multi-isotope approach from San Juan cave (Loarre, Spain)

The use of isotopic analysis in human and animal remains from the Holocene has proved to be a very useful tool to explore the exploitation and adaptation of past populations to different environments. In this study we present isotopic analysis results of carbon, nitrogen and strontium from the Late Neolithic-Chalcolithic site of San Juan cave (Loarre, Spain). We analysed 33 humans, divided in adult and subadult groups, and 16 animals recovered from the same archaeological context. Stable isotope analysis of carbon and nitrogen has allowed to distinguish an homogeneous subsistence pattern during the Late Neolithic-Chalcolithic transition. The use of strontium isotopes (87Sr/86Sr) in human dental enamel suggests 19% (4 out of 21) are non-local individuals, based on comparison with the local bioavailable 87Sr/86Sr range calculated using microfauna teeth from the archaeological context, modern plants and snails. This new study gives information about Late Neolithic communities located in the north-east of the Iberian Peninsula, and it allows inference of the socio-economic structure, territorial mobility and individual provenance of humans.Fil: Villalba Mouco, Vanessa. Universidad de Zaragoza; EspañaFil: Sauqué Latas, Víctor. Universidad de Zaragoza; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Antropología de Córdoba. Universidad Nacional de Córdoba. Facultad de Filosofía y Humanidades. Instituto de Antropología de Córdoba; ArgentinaFil: Sarasketa Gartzia, Izaskun. Universidad del País Vasco; EspañaFil: Pastor, M. Victoria. Universidad de Zaragoza; EspañaFil: le Roux, Petrus J.. Cape Town Universtity; SudáfricaFil: Vicente, Diana. Universidad de Zaragoza; EspañaFil: Utrilla, Pilar. Universidad de Zaragoza; EspañaFil: Salazar García, Domingo C.. Cape Town Universtity; Sudáfrica. Universidad del País Vasco; Españ

The metabolic and vascular protective effects of olive (Olea europaea L.) leaf extract in diet-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties.

Many studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition. C57BL/6J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25 mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At the end of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers of intestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed. OLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-α, Il-1β, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administration was able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelial dysfunction. OLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.his work was supported by the Junta de Andalucía (CTS 164) and by the Spanish Ministry of Economy and Competitiveness (AGL2015-67995-C3-3-R) with funds from the European Union. A. Rodriguez-Nogalesis a postdoctoral fellow of Instituto de Salud Carlos III (Sara Borrell Program);J. Garrido-Mesa and F. Algieri are postdoctoral fellows of University of Granada; T. Vezza is a postdoctoral fellow from Instituto de Investigación Biosanitaria de Granada. The CIBER-EHD and the “Red de Investigación en SIDA”are funded by the Instituto de Salud Carlos IIIS