NIRS potential use for the determination of natural resources quality from dehesa (acorn and grass) in Montanera system for Iberian pigs.

NIRS technology has been used as an alternative to conventional methods to determinate the content of nutrients of acorns and grass from dehesa ecosystem. Dry matter (DM), crude fat (CF), crude protein (CP), starch, total phenolic compounds (TP), α-tocopherol, γ-tocopherol, fatty acids, neutral detergent fiber (NDF), total antioxidant activity (TAA) and total energy (TE) were determined by conventional methods for later development of NIRS predictive equations. The NIR spectrum of each sample was collected and for all studied parameters, a predictive model was obtained and external validated. Good prediction equations were obtained for moisture, crude fat, crude protein, total energy and γ-tocopherol in acorns samples, with high coefficients of correlation (1-VR) and low standard error of prediction (SEP) (1-VR=0.81, SEP=2.62; 1-VR=0.92, SEP=0.54; 1-VR=0.86, SEP=0.47; 1-VR=0.84, SEP=0.2; 1-VR=0.88, SEP=5.4, respectively) and crude protein, NDF, α-tocopherol and linolenic acid content in grass samples (1-VR=0.9, SEP=1.99; 1-VR=0.87, SEP=4.13; 1-VR=0.76, SEP=10.9; 1-VR=0.82, SEP=0.6, respectively). Therefore, these prediction models could be used to determinate the nutritional composition of Montanera natural resources

Engineered Contrast Agents in a Single Structure for T1-T2 Dual Magnetic Resonance Imaging

[EN] The development of contrast agents (CAs) for Magnetic Resonance Imaging (MRI) with T-1-T-2 dual-mode relaxivity requires the accurate assembly of T-1 and T-2 magnetic centers in a single structure. In this context, we have synthesized a novel hybrid material by monitoring the formation of Prussian Blue analogue Gd(H2O)(4)[Fe(CN)(6)] nanoparticles with tailored shape (from nanocrosses to nanorods) and size, and further protection with a thin and homogeneous silica coating through hydrolysis and polymerization of silicate at neutral pH. The resulting Gd(H2O)(4)[Fe(CN)(6)]@SiO2 magnetic nanoparticles are very stable in biological fluids. Interestingly, this combination of Gd and Fe magnetic centers closely packed in the crystalline network promotes a magnetic synergistic effect, which results in significant improvement of longitudinal relaxivity with regards to soluble Gd3+ chelates, whilst keeping the high transversal relaxivity inherent to the iron component. As a consequence, this material shows excellent activity as MRI CA, improving positive and negative contrasts in T-1- and T-2-weighted MR images, both in in vitro (e.g., phantom) and in vivo (e.g., Sprague-Dawley rats) models. In addition, this hybrid shows a high biosafety profile and has strong ability to incorporate organic molecules on the surface with variable functionality, displaying great potential for further clinical application.Financial support of the Spanish Ministry of Economy and Competitiveness (projects TEC2016-80976-R and SEV-2016-0683) is gratefully acknowledged. Dr E. M. Rivero thanks the Cursol Foundation for a post-doctoral scholarship. A. C. G. also thanks the La Caixa Foundation for a Ph.D. scholarship. We fully appreciate the assistance of the Electron Microscopy Service of the UPV and INSCANNER S.L.Cabrera-García, A.; Checa-Chavarria, E.; Pacheco-Torres, J.; Bernabeu-Sanz, A.; Vidal Moya, JA.; Rivero-Buceta, EM.; Sastre Navarro, GI.... (2018). Engineered Contrast Agents in a Single Structure for T1-T2 Dual Magnetic Resonance Imaging. Nanoscale. 10(14):6349-6360. https://doi.org/10.1039/c7nr07948fS634963601014Bolan, P. J., Nelson, M. T., Yee, D., & Garwood, M. (2005). Imaging in breast cancer: Magnetic resonance spectroscopy. Breast Cancer Research, 7(4). doi:10.1186/bcr1202Mitchell, R. E., Katz, M. H., McKiernan, J. M., & Benson, M. C. (2005). The evaluation and staging of clinically localized prostate cancer. Nature Clinical Practice Urology, 2(8), 356-357. doi:10.1038/ncpuro0260Colombo, M., Carregal-Romero, S., Casula, M. F., Gutiérrez, L., Morales, M. P., Böhm, I. B., … Parak, W. J. (2012). Biological applications of magnetic nanoparticles. Chemical Society Reviews, 41(11), 4306. doi:10.1039/c2cs15337hMi, P., Kokuryo, D., Cabral, H., Wu, H., Terada, Y., Saga, T., … Kataoka, K. (2016). A pH-activatable nanoparticle with signal-amplification capabilities for non-invasive imaging of tumour malignancy. Nature Nanotechnology, 11(8), 724-730. doi:10.1038/nnano.2016.72Cheng, W., Ping, Y., Zhang, Y., Chuang, K.-H., & Liu, Y. (2013). Magnetic Resonance Imaging (MRI) Contrast Agents for Tumor Diagnosis. Journal of Healthcare Engineering, 4(1), 23-46. doi:10.1260/2040-2295.4.1.23Lauffer, R. B. (1987). Paramagnetic metal complexes as water proton relaxation agents for NMR imaging: theory and design. Chemical Reviews, 87(5), 901-927. doi:10.1021/cr00081a003Caravan, P., Ellison, J. J., McMurry, T. J., & Lauffer, R. B. (1999). Gadolinium(III) Chelates as MRI Contrast Agents:  Structure, Dynamics, and Applications. Chemical Reviews, 99(9), 2293-2352. doi:10.1021/cr980440xDavis, M. E., Chen, Z., & Shin, D. M. (2008). Nanoparticle therapeutics: an emerging treatment modality for cancer. Nature Reviews Drug Discovery, 7(9), 771-782. doi:10.1038/nrd2614Lee, N., & Hyeon, T. (2012). Designed synthesis of uniformly sized iron oxide nanoparticles for efficient magnetic resonance imaging contrast agents. Chem. Soc. Rev., 41(7), 2575-2589. doi:10.1039/c1cs15248cHasebroock, K. M., & Serkova, N. J. (2009). Toxicity of MRI and CT contrast agents. Expert Opinion on Drug Metabolism & Toxicology, 5(4), 403-416. doi:10.1517/17425250902873796Khawaja, A. Z., Cassidy, D. B., Al Shakarchi, J., McGrogan, D. G., Inston, N. G., & Jones, R. G. (2015). Revisiting the risks of MRI with Gadolinium based contrast agents—review of literature and guidelines. Insights into Imaging, 6(5), 553-558. doi:10.1007/s13244-015-0420-2Lee, N., Yoo, D., Ling, D., Cho, M. H., Hyeon, T., & Cheon, J. (2015). Iron Oxide Based Nanoparticles for Multimodal Imaging and Magnetoresponsive Therapy. Chemical Reviews, 115(19), 10637-10689. doi:10.1021/acs.chemrev.5b00112Zhou, Z., Bai, R., Munasinghe, J., Shen, Z., Nie, L., & Chen, X. (2017). T1–T2 Dual-Modal Magnetic Resonance Imaging: From Molecular Basis to Contrast Agents. ACS Nano, 11(6), 5227-5232. doi:10.1021/acsnano.7b03075Shin, T.-H., Choi, Y., Kim, S., & Cheon, J. (2015). Recent advances in magnetic nanoparticle-based multi-modal imaging. Chemical Society Reviews, 44(14), 4501-4516. doi:10.1039/c4cs00345dBae, K. H., Kim, Y. B., Lee, Y., Hwang, J., Park, H., & Park, T. G. (2010). Bioinspired Synthesis and Characterization of Gadolinium-Labeled Magnetite Nanoparticles for Dual ContrastT1- andT2-Weighted Magnetic Resonance Imaging. Bioconjugate Chemistry, 21(3), 505-512. doi:10.1021/bc900424uPeng, Y.-K., Lui, C. N. P., Chen, Y.-W., Chou, S.-W., Raine, E., Chou, P.-T., … Tsang, S. C. E. (2017). Engineering of Single Magnetic Particle Carrier for Living Brain Cell Imaging: A Tunable T1-/T2-/Dual-Modal Contrast Agent for Magnetic Resonance Imaging Application. Chemistry of Materials, 29(10), 4411-4417. doi:10.1021/acs.chemmater.7b00884Choi, J., Lee, J.-H., Shin, T.-H., Song, H.-T., Kim, E. Y., & Cheon, J. (2010). Self-Confirming «AND» Logic Nanoparticles for Fault-Free MRI. Journal of the American Chemical Society, 132(32), 11015-11017. doi:10.1021/ja104503gShin, T.-H., Choi, J., Yun, S., Kim, I.-S., Song, H.-T., Kim, Y., … Cheon, J. (2014). T1andT2Dual-Mode MRI Contrast Agent for Enhancing Accuracy by Engineered Nanomaterials. ACS Nano, 8(4), 3393-3401. doi:10.1021/nn405977tCheng, K., Yang, M., Zhang, R., Qin, C., Su, X., & Cheng, Z. (2014). Hybrid Nanotrimers for Dual T1 and T2-Weighted Magnetic Resonance Imaging. ACS Nano, 8(10), 9884-9896. doi:10.1021/nn500188yZhou, Z., Huang, D., Bao, J., Chen, Q., Liu, G., Chen, Z., … Gao, J. (2012). A Synergistically EnhancedT1-T2Dual-Modal Contrast Agent. Advanced Materials, 24(46), 6223-6228. doi:10.1002/adma.201203169Huang, G., Li, H., Chen, J., Zhao, Z., Yang, L., Chi, X., … Gao, J. (2014). Tunable T1and T2contrast abilities of manganese-engineered iron oxide nanoparticles through size control. Nanoscale, 6(17), 10404. doi:10.1039/c4nr02680bPerrier, M., Kenouche, S., Long, J., Thangavel, K., Larionova, J., Goze-Bac, C., … Guari, Y. (2013). Investigation on NMR Relaxivity of Nano-Sized Cyano-Bridged Coordination Polymers. Inorganic Chemistry, 52(23), 13402-13414. doi:10.1021/ic401710jPerera, V. S., Yang, L. D., Hao, J., Chen, G., Erokwu, B. O., Flask, C. A., … Huang, S. D. (2014). Biocompatible Nanoparticles of KGd(H2O)2[Fe(CN)6]·H2O with Extremely HighT1-Weighted Relaxivity Owing to Two Water Molecules Directly Bound to the Gd(III) Center. Langmuir, 30(40), 12018-12026. doi:10.1021/la501985pCai, X., Gao, W., Ma, M., Wu, M., Zhang, L., Zheng, Y., … Shi, J. (2015). A Prussian Blue-Based Core-Shell Hollow-Structured Mesoporous Nanoparticle as a Smart Theranostic Agent with Ultrahigh pH-Responsive Longitudinal Relaxivity. Advanced Materials, 27(41), 6382-6389. doi:10.1002/adma.201503381Yang, L., Zhou, Z., Liu, H., Wu, C., Zhang, H., Huang, G., … Gao, J. (2015). Europium-engineered iron oxide nanocubes with high T1and T2contrast abilities for MRI in living subjects. Nanoscale, 7(15), 6843-6850. doi:10.1039/c5nr00774gCabrera-García, A., Vidal-Moya, A., Bernabeu, Á., Sánchez-González, J., Fernández, E., & Botella, P. (2015). Gd–Si oxide mesoporous nanoparticles with pre-formed morphology prepared from a Prussian blue analogue template. Dalton Transactions, 44(31), 14034-14041. doi:10.1039/c5dt01928aCabrera-García, A., Vidal-Moya, A., Bernabeu, Á., Pacheco-Torres, J., Checa-Chavarria, E., Fernández, E., & Botella, P. (2016). Gd-Si Oxide Nanoparticles as Contrast Agents in Magnetic Resonance Imaging. Nanomaterials, 6(6), 109. doi:10.3390/nano6060109Botella, P., Corma, A., & Quesada, M. (2012). Synthesis of ordered mesoporous silica templated with biocompatible surfactants and applications in controlled release of drugs. Journal of Materials Chemistry, 22(13), 6394. doi:10.1039/c2jm16291aMascharak, P. K. (1986). Convenient synthesis of tris(tetraethylammonium) hexacyanoferrate(III) and its use as an oxidant with tunable redox potential. Inorganic Chemistry, 25(3), 245-247. doi:10.1021/ic00223a001Clemments, A. M., Muniesa, C., Landry, C. C., & Botella, P. (2014). Effect of surface properties in protein corona development on mesoporous silica nanoparticles. RSC Adv., 4(55), 29134-29138. doi:10.1039/c4ra03277bOyane, A., Kim, H.-M., Furuya, T., Kokubo, T., Miyazaki, T., & Nakamura, T. (2003). Preparation and assessment of revised simulated body fluids. Journal of Biomedical Materials Research, 65A(2), 188-195. doi:10.1002/jbm.a.10482Blüml, S., Schad, L. R., Stepanow, B., & Lorenz, W. J. (1993). Spin-lattice relaxation time measurement by means of a TurboFLASH technique. Magnetic Resonance in Medicine, 30(3), 289-295. doi:10.1002/mrm.1910300304Hennig, J., & Friedburg, H. (1988). Clinical applications and methodological developments of the RARE technique. Magnetic Resonance Imaging, 6(4), 391-395. doi:10.1016/0730-725x(88)90475-4Hennig, J., Nauerth, A., & Friedburg, H. (1986). RARE imaging: A fast imaging method for clinical MR. Magnetic Resonance in Medicine, 3(6), 823-833. doi:10.1002/mrm.1910030602Yamada, M., & Yonekura, S. (2009). Nanometric Metal−Organic Framework of Ln[Fe(CN)6]: Morphological Analysis and Thermal Conversion Dynamics by Direct TEM Observation. The Journal of Physical Chemistry C, 113(52), 21531-21537. doi:10.1021/jp907180eNavarro, M. C., Pannunzio-Miner, E. V., Pagola, S., Gómez, M. I., & Carbonio, R. E. (2005). Structural refinement of Nd[Fe(CN)6]·4H2O and study of NdFeO3 obtained by its oxidative thermal decomposition at very low temperatures. Journal of Solid State Chemistry, 178(3), 847-854. doi:10.1016/j.jssc.2004.11.026Ding, Y., Chu, X., Hong, X., Zou, P., & Liu, Y. (2012). The infrared fingerprint signals of silica nanoparticles and its application in immunoassay. Applied Physics Letters, 100(1), 013701. doi:10.1063/1.3673549Botella, P., Abasolo, I., Fernández, Y., Muniesa, C., Miranda, S., Quesada, M., … Corma, A. (2011). Surface-modified silica nanoparticles for tumor-targeted delivery of camptothecin and its biological evaluation. Journal of Controlled Release, 156(2), 246-257. doi:10.1016/j.jconrel.2011.06.039Na, H. B., Lee, J. H., An, K., Park, Y. I., Park, M., Lee, I. S., … Hyeon, T. (2007). Development of aT1 Contrast Agent for Magnetic Resonance Imaging Using MnO Nanoparticles. Angewandte Chemie International Edition, 46(28), 5397-5401. doi:10.1002/anie.200604775Deng, Y., Li, E., Cheng, X., Zhu, J., Lu, S., Ge, C., … Pan, Y. (2016). Facile preparation of hybrid core–shell nanorods for photothermal and radiation combined therapy. Nanoscale, 8(7), 3895-3899. doi:10.1039/c5nr09102kBottrill, M., Kwok, L., & Long, N. J. (2006). Lanthanides in magnetic resonance imaging. Chemical Society Reviews, 35(6), 557. doi:10.1039/b516376pZhang, W., Martinelli, J., Peters, J. A., van Hengst, J. M. A., Bouwmeester, H., Kramer, E., … Djanashvili, K. (2017). Surface PEG Grafting Density Determines Magnetic Relaxation Properties of Gd-Loaded Porous Nanoparticles for MR Imaging Applications. ACS Applied Materials & Interfaces, 9(28), 23458-23465. doi:10.1021/acsami.7b05912Li, Y., Chen, T., Tan, W., & Talham, D. R. (2014). Size-Dependent MRI Relaxivity and Dual Imaging with Eu0.2Gd0.8PO4·H2O Nanoparticles. Langmuir, 30(20), 5873-5879. doi:10.1021/la500602xT. L. Riss , R. A.Moravec , A. L.Niles , S.Duellman , H. A.Benink , T. J.Worzella and L.Minor , Cell Viability Assays , in Assay Guidance Manual , Eli Lilly & Company and the National Center for Advancing Translational Sciences , Bethesda, MD , 2012Mahmoudi, M., Lynch, I., Ejtehadi, M. R., Monopoli, M. P., Bombelli, F. B., & Laurent, S. (2011). Protein−Nanoparticle Interactions: Opportunities and Challenges. Chemical Reviews, 111(9), 5610-5637. doi:10.1021/cr100440gLu, J., Liong, M., Li, Z., Zink, J. I., & Tamanoi, F. (2010). Biocompatibility, Biodistribution, and Drug-Delivery Efficiency of Mesoporous Silica Nanoparticles for Cancer Therapy in Animals. Small, 6(16), 1794-1805. doi:10.1002/smll.20100053

Fast degrading polymer networks based on carboxymethyl chitosan

[EN] In this work macroporous membrane for mesenchymal stem cells, MSCs, transplant has been developed. The membranes support cell seeding and proliferation and completely degrade in less than one week in "in vitro" culture. The biodegradable material is a polymer network based on carboxymethyl chitosan( a water soluble modification of chitosan) crosslinked by poly(epsilon-caprolactone) PCL, fragments which are susceptible to hydrolytic degradation. Synthesis was performed in solution in a common solvent for the two components of the network. The gel fraction was assessed by extraction in selective solvents. Physical characterization of networks of varying composition included water sorption capacity and the crystallinity of poly(epsilon-caprolactone) in the network. In this way polymer networks are synthesized that lose between 66 +/- 5% and 89 +/- 1% of their mass when immersed in water for 28 days. The same weight loss is attained in enzymatic medium in only 4 days. Porcine bone marrow MSCs were seeded in macroporous membranes to show cell viability, and proliferation up to 7 days culture when the biomaterial is completely dissolved in the medium.Gamiz Gonzalez, MA.; Guldrís-Prada, P.; Antolinos Turpín, CM.; Ródenas Rochina, J.; Vidaurre, A.; Gómez Ribelles, JL. (2017). Fast degrading polymer networks based on carboxymethyl chitosan. Materials Today Communications. 10:54-66. doi:10.1016/j.mtcomm.2017.01.005S54661

A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability

Oral administration of camptothecin (Cm) derivatives and other antitumoral agents is being actively developed in order to improve the quality of life of patients with cancer. Though several lipophilic derivatives of CPT have shown interesting oral bioavailability in preclinical and clinical studies, only Topotecan has been approved for this route of administration. Semisynthesis, antitumor activity, biological inhibition mechanism, and in situ intestinal permeability of 9, 10-[1,3]-Dioxinocamptothecin (CDiox), an unexplored CPT derivative, have been studied in this paper. The hexacyclic analog was as effective as Topotecan and CPT in different tumor cell lines, showing an expected similar apoptosis cell mechanism and high ability to inhibit DNA synthesis in HeLa, Caco-2, A375 and MDA-MB-231 cell lines. Furthermore, in vitro and in situ pharmacokinetics transport values obtained for CDiox displayed more favorable absorption profile than CPT and Topotecan. (C) 2014 Elsevier Masson SAS. All rights reserved.G.R.-B. acknowledges Instituto de Tecnologia Quimica for a scholarship; Consolider-Ingenio 2010 (proyecto MULTICAT), Sub-programa de Apoyo a Centros de Excelencia Severo Ochoa, and Agencia de Gestico, d'Ajuts Universiteris i de Recerca (2009 SGR 758, to S.S.) I.G.-A., V.M.-S., M.G.-A. and M. B. acknowledge financial support from the European Financial Commission (Red bioFarma DCI-ALA/19.09.01/10/21526/245-297/ALFA III (2010)). J.L.G.-G. acknowledges the financial support of the CIBERER (Biomedical Network Research Center for Rare Diseases) ISCIII.Rodríguez Berna, G.; Mangas Sanjuan, V.; Gonzalez Alvarez, M.; Gonzalez Álvarez, I.; Garcia Gimenez, JL.; Díaz Cabañas, MJ.; Bermejo, M.... (2014). A promising camptothecin derivative: Semisynthesis, antitumor activity and intestinal permeability. European Journal of Medicinal Chemistry. 83:366-373. doi:10.1016/j.ejmech.2014.06.050S3663738

Validation of the spanish version of the multiple sclerosis international quality of life (musiqol) questionnaire

<p>Abstract</p> <p>Background</p> <p>The Multiple Sclerosis International Quality Of Life (MusiQoL) questionnaire, a 31-item, multidimensional, self-administrated questionnaire that is available in 14 languages including Spanish, has been validated using a large international sample. We investigated the validity and reliability of the Spanish version of MusiQoL in Spain.</p> <p>Methods</p> <p>Consecutive patients with different types and severities of multiple sclerosis (MS) were recruited from 22 centres across Spain. All patients completed the MusiQoL questionnaire, the 36-Item Short Form (SF-36) health survey, and a symptoms checklist at baseline and 21 days later. External validity, internal consistency, reliability and reproducibility were tested.</p> <p>Results</p> <p>A total of 224 Spanish patients were evaluated. Dimensions of MusiQoL generally demonstrated a high internal consistency (Cronbach's alpha: 0.70-0.92 for all but two MusiQoL domain scores). External validity testing revealed that the MusiQoL index score correlated significantly with all SF-36 dimension scores (Pearson's correlation: 0.46-0.76), reproducibility was satisfactory (intraclass correlation coefficient: 0.60-0.91), acceptability was high, and the time taken to complete the 31-item questionnaire was reasonable (mean [standard deviation]: 9.8 [11.8] minutes).</p> <p>Conclusions</p> <p>The Spanish version of the MusiQoL questionnaire appears to be a valid and reliable instrument for measuring quality of life in patients with MS in Spain and constitutes a useful instrument to measure health-related quality of life in the clinical setting.</p

Analysis of the Promoters Involved in Enterocin AS-48 Expression

The enterocin AS-48 is the best characterized antibacterial circular protein in prokaryotes. It is a hydrophobic and cationic bacteriocin, which is ribosomally synthesized by enterococcal cells and post-translationally cyclized by a head-to-tail peptide bond. The production of and immunity towards AS-48 depend upon the coordinated expression of ten genes organized in two operons, as-48ABC (where genes encoding enzymes with processing, secretion, and immunity functions are adjacent to the structural as-48A gene) and as-48C1DD1EFGH. The current study describes the identification of the promoters involved in AS-48 expression. Seven putative promoters have been here amplified, and separately inserted into the promoter-probe vector pTLR1, to create transcriptional fusions with the mCherry gene used as a reporter. The activity of these promoter regions was assessed measuring the expression of the fluorescent mCherry protein using the constitutive pneumococcal promoter PX as a reference. Our results revealed that only three promoters PA, P2(2) and PD1 were recognized in Enterococcus faecalis, Lactococcus lactis and Escherichia coli, in the conditions tested. The maximal fluorescence was obtained with PX in all the strains, followed by the P2(2) promoter, which level of fluorescence was 2-fold compared to PA and 4-fold compared to PD1. Analysis of putative factors influencing the promoter activity in single and double transformants in E. faecalis JH2-2 demonstrated that, in general, a better expression was achieved in presence of pAM401-81. In addition, the P2(2) promoter could be regulated in a negative fashion by genes existing in the native pMB-2 plasmid other than those of the as-48 cluster, while the pH seems to affect differently the as-48 promoter expression.This work was supported in part by the Ministerio de Ciencia e Innovación project BIO2008-01708, the Plan Propio from the University of Granada (Spain) and by the Research Plan Group (BIO 160)

TRAIL/TRAIL Receptor System and Susceptibility to Multiple Sclerosis

The TNF-related apoptosis inducing ligand (TRAIL)/TRAIL receptor system participates in crucial steps in immune cell activation or differentiation. It is able to inhibit proliferation and activation of T cells and to induce apoptosis of neurons and oligodendrocytes, and seems to be implicated in autoimmune diseases. Thus, TRAIL and TRAIL receptor genes are potential candidates for involvement in susceptibility to multiple sclerosis (MS). To test whether single-nucleotide polymorphisms (SNPs) in the human genes encoding TRAIL, TRAILR-1, TRAILR-2, TRAILR-3 and TRAILR-4 are associated with MS susceptibility, we performed a candidate gene case-control study in the Spanish population. 59 SNPs in the TRAIL and TRAIL receptor genes were analysed in 628 MS patients and 660 controls, and validated in an additional cohort of 295 MS patients and 233 controls. Despite none of the SNPs withstood the highly conservative Bonferroni correction, three SNPs showing uncorrected p values<0.05 were successfully replicated: rs4894559 in TRAIL gene, p = 9.8×10−4, OR = 1.34; rs4872077, in TRAILR-1 gene, p = 0.005, OR = 1.72; and rs1001793 in TRAILR-2 gene, p = 0.012, OR = 0.84. The combination of the alleles G/T/A in these SNPs appears to be associated with a reduced risk of developing MS (p = 2.12×10−5, OR = 0.59). These results suggest that genes of the TRAIL/TRAIL receptor system exerts a genetic influence on MS