Progranulin as a biomarker and potential therapeutic agent

Progranulin is a cysteine-rich secreted protein with diverse pleiotropic actions and participates in several processes, such as inflammation or tumorigenesis. Progranulin was first identified as a growth factor and, recently, it was characterised as an adipokine implicated in obesity, insulin resistance and rheumatic disease. At a central level, progranulin acts as a neurotropic and neuroprotective factor and protects from neural degeneration. In this review, we summarise the most recent research advances concerning the potential role of progranulin as a therapeutic target and biomarker in cancer, neurodegenerative and inflammatory diseases

Evaluation of bacterial adherence of clinical isolates of Staphylococcus sp. using a competitive model: An in vitro approach to the "race for the surface" theory

Objectives Implant-related infection is one of the most devastating complications in orthopaedic surgery. Many surface and/or material modifications have been developed in order to minimise this problem; however, most of the in vitro studies did not evaluate bacterial adhesion in the presence of eukaryotic cells, as stated by the 'race for the surface' theory. Moreover, the adherence of numerous clinical strains with different initial concentrations has not been studied. Methods We describe a method for the study of bacterial adherence in the presence of preosteoblastic cells. For this purpose we mixed different concentrations of bacterial cells from collection and clinical strains of staphylococci isolated from implant-related infections with preosteoblastic cells, and analysed the minimal concentration of bacteria able to colonise the surface of the material with image analysis. Results Our results show that clinical strains adhere to the material surface at lower concentrations than collection strains. A destructive effect of bacteria on preosteoblastic cells was also detected, especially with higher concentrations of bacteria. Conclusions The method described herein can be used to evaluate the effect of surface modifications on bacterial adherence more accurately than conventional monoculture studies. Clinical strains behave differently than collection strains with respect to bacterial adherence.This work was funded by the following grants from the Spanish MINECO (MAT2013- 48224-C2-2-R and MAT2013-48224-C2-1-R). M. Martínez-Pérez reports funding received from EFORT 2015 congress: travel supported by PFIZER, which is related to this article. J. Esteban and E. Gómez-Barrena report funding received from several companies for travel, expenses and grants, none of which is related to this articl

The novel adipokine progranulin counteracts IL-1 and TLR4-driven inflammatory response in human and murine chondrocytes via TNFR1

Progranulin (PGRN) is a recently identified adipokine that is supposed to have anti-inflammatory actions. The proinflammatory cytokine interleukin-1? (IL1?) stimulates several mediators of cartilage degradation. Toll like receptor-4 (TLR4) can bind to various damage-associated molecular patterns, leading to inflammatory condition. So far, no data exist of PGRN effects in inflammatory conditions induced by IL1? or lipopolysaccharide (LPS). Here, we investigated the anti-inflammatory potential of PGRN in IL1?- or LPS-induced inflammatory responses of chondrocytes. Human osteoarthritic chondrocytes and ATDC-5 cells were treated with PGRN in presence or not of IL1? or LPS. First, we showed that recombinant PGRN had no effects on cell viability. We present evidence that PGRN expression was increased during the differentiation of ATDC-5 cell line. Moreover, PGRN mRNA and protein expression is increased in cartilage, synovial and infrapatellar fat pad tissue samples from OA patients. PGRN mRNA levels are upregulated under TNF? and IL1? stimulation. Our data showed that PGRN is able to significantly counteract the IL1?-induced expression of NOS2, COX2, MMP13 and VCAM-1. LPS-induced expression of NOS2 is also decreased by PGRN. These effects are mediated, at least in part, through TNFR1. Taken together, our results suggest that PGRN has a clear antiinflammatory function

Role of type of fibre on intestinal microbiota and performance in rabbits

ABSTRACT -In this work is reviewed the new approaches and methods to the dietary fibre concept and its relation with the intestinal microbiota. Fibre is the largest dietary fraction in rabbit diets. It influences rate of passage and constitutes an significant substrate for intestinal microbiota that might affect rabbit health and performance. However, the definition of fibre, its separation in different fractions and the way to quantify and characterize it is still under discussion. Besides, new molecular techniques have been developed to improve the study of intestinal microbiota that might help to understand better its relationship with the level and type of fibre. Recent data seems to indicate the important role of dietary soluble fibre level, as well as its balance with insoluble fibre, in minimizing the effects of epizootic rabbit enteropathy

Radon and material radiopurity assessment for the NEXT double beta decay experiment

The Neutrino Experiment with a Xenon TPC (NEXT), intended to investigate the neutrinoless double beta decay using a high-pressure xenon gas TPC filled with Xe enriched in 136Xe at the Canfranc Underground Laboratory in Spain, requires ultra-low background conditions demanding an exhaustive control of material radiopurity and environmental radon levels. An extensive material screening process is underway for several years based mainly on gamma-ray spectroscopy using ultra-low background germanium detectors in Canfranc but also on mass spectrometry techniques like GDMS and ICPMS. Components from shielding, pressure vessel, electroluminescence and high voltage elements and energy and tracking readout planes have been analyzed, helping in the final design of the experiment and in the construction of the background model. The latest measurements carried out will be presented and the implication on NEXT of their results will be discussed. The commissioning of the NEW detector, as a first step towards NEXT, has started in Canfranc; in-situ measurements of airborne radon levels were taken there to optimize the system for radon mitigation and will be shown too.Comment: Proceedings of the Low Radioactivity Techniques 2015 workshop (LRT2015), Seattle, March 201

NEXT-100 Technical Design Report (TDR). Executive Summary

In this Technical Design Report (TDR) we describe the NEXT-100 detector that will search for neutrinoless double beta decay (bbonu) in Xe-136 at the Laboratorio Subterraneo de Canfranc (LSC), in Spain. The document formalizes the design presented in our Conceptual Design Report (CDR): an electroluminescence time projection chamber, with separate readout planes for calorimetry and tracking, located, respectively, behind cathode and anode. The detector is designed to hold a maximum of about 150 kg of xenon at 15 bar, or 100 kg at 10 bar. This option builds in the capability to increase the total isotope mass by 50% while keeping the operating pressure at a manageable level. The readout plane performing the energy measurement is composed of Hamamatsu R11410-10 photomultipliers, specially designed for operation in low-background, xenon-based detectors. Each individual PMT will be isolated from the gas by an individual, pressure resistant enclosure and will be coupled to the sensitive volume through a sapphire window. The tracking plane consists in an array of Hamamatsu S10362-11-050P MPPCs used as tracking pixels. They will be arranged in square boards holding 64 sensors (8 times8) with a 1-cm pitch. The inner walls of the TPC, the sapphire windows and the boards holding the MPPCs will be coated with tetraphenyl butadiene (TPB), a wavelength shifter, to improve the light collection.Comment: 32 pages, 22 figures, 5 table

The CD14 (−159 C/T) SNP is associated with sCD14 levels and allergic asthma, but not with CD14 expression on monocytes

LPS-ligation to CD14/TLR-4 on monocytes/macrophages triggers the production of IL-12-family cytokines. IL12/18 promote TH1-differentiation, counteracting the TH2-driven asthma. Therefore, CD14 modulation could alter the TH2-differentiation and should be taken into account when studying asthma. To analyse the alteration in CD14 levels and its association with CD14 (−159 C/T) SNP (rs2569190) in Caucasian adults with stable allergic asthma, we performed a cross-sectional study (277 healthy subjects vs. 277 patients) where clinical parameters, CD14 values and the CD14 (−159 C/T) SNP were studied. Apart from typical biomarkers, we found an increment of neuron-specific enolase (NSE) in allergic asthma, probably linked to monocyte activity. Indeed, we evidenced increased monocyte numbers, but lower CD14 expression and normalised sCD14 values in patients. Moreover, we noticed an association of the T allele (P = 0.0162) and TT genotype (P = 0.0196) of the CD14 SNP with a decreased risk of allergic asthma and augmented sCD14 levels. In conclusion, monocyte CD14 expression and normalized sCD14 values were reduced in stable state asthmatics, and this could be related to the presence of an expanded CD14low monocyte subset. This study also demonstrates that the CD14 (−159 C/T) polymorphism is a risk factor for moderate-severe allergic asthma in adult CaucasiansThis study was funded by grants from Sociedad Española de Neumología y Cirugía Torácica, (SEPAR) (121/2012) and Instituto de Salud Carlos III, Ministerio de Economía y Competitividad (Fondo de Investigación Sanitaria, FIS; co-financed by European Union ERDF funds) (PI13/02046). JJNF is a recipient of a Xunta de Galicia Fellowship (Co-financed by European Social Fund (ESF))S