Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapy

[EN] Carbon nanohorns are suitable platforms for use in biological applications. Their high surface areas allow the incorporation of molecular entities, such as polyamidoamine dendrimers. In this work, we report the synthesis, structural characterization and biological data of new hybrid systems of carbon nanohorns that hold polyamidoamine dendrimers. One of these derivatives has been employed as an agent for gene delivery. The system is able to release interfering genetic material diminishing the levels of a house-keeping protein and a protein directly involved in prostate cancer development. Importantly, this hybrid material is also far less toxic than the corresponding free dendrimer. These results allow us to conclude that these nanomaterials can be exploited as useful non-viral agents for gene therapy.M.A.H., N.R., M.L. and E.V. are grateful to DGICYT of Spain for funding through the Project CTQ2007-60037/BQU and to Consejeria de Educacion y Ciencia (JCCM) for funding projects PBI-06-0020 and PCI08-0040. J.G. also acknowledges the Ministerio de Ciencia e Innovacion (MICINN) (Spain) (BFU2011-30161-C02-02), MICINN (Spain)-Fondo Europeo de Desarrollo Regional (FEDER, European Union) (Project CTQ2006-08871) and JCCM (Project PCI08-0033). This work has been supported, in part, by Grants PI081434 from Fondo de Investigaciones Sanitarias, BFU2011-30161-C02-01 from MICINN and PII1109-0163-4002 and POII10-0274-3182 from Consejeria de Educacion, JCCM to V.C. J.G., F.C.P.-M and B.C. are recipients of Torres-Quevedo research contracts funded by MICINN (Spain) and Nano-Drugs S.L. Authors are very grateful to Dr. V. Sue Myers at UT-Austin and Claudio Gamboz of Settore Microscopia Elettronica at University of Trieste for their help with the TEM measurements. We also thank Ana Belen Garcia for her expert technical assistance. Authors are also very grateful to Dr. Sonia Merino and Dr. Prado Sanchez-Verdti for fruitful discussions.Guerra, J.; Herrero, MA.; Carrión, B.; Pérez-Martínez, FC.; Lucío, MI.; Rubio, N.; Meneghetti, M.... (2012). Carbon nanohorns functionalized with polyamidoamine dendrimers as efficient biocarrier materials for gene therapy. Carbon. 50(8):2832-2844. https://doi.org/10.1016/j.carbon.2012.02.0502832284450

Immunization with the HisAK70 DNA Vaccine Induces Resistance against Leishmania Amazonensis Infection in BALB/c Mice

Leishmania amazonensis is the aetiological agent of a broad spectrum of leishmaniosis in South America. It can cause not only numerous cases of cutaneous leishmaniosis but also diffuse cutaneous leishmaniosis. Considering the diversity of parasite species causing different forms of the disease that coexist in the same region, it is desirable to develop a vaccine capable of eliciting cross-protection. We have previously described the use of HisAK70 DNA vaccine for immunization of mice to assess the induction of a resistant phenotype against Leishmania major and infantum infections. In this study, we extended its application in the murine model of infection by using L. amazonensis promastigotes. Our data revealed that 14 weeks post-infection, HisAK70-vaccinated mice showed key biomarkers of protection, such as higher iNOS/arginase activity, IFN-γ/IL-10, IFN-γ/IL-4, and GM-CSF/IL-10 ratios, in addition to an IgG2a-type response when compared to the control group. These findings correlated with the presentation of lower footpad swelling and parasite burdens in the immunized compared to the control mice. Overall, this study suggests that immunization with HisAK70 may be considered a suitable tool to combat leishmaniosis as it is able to induce a potent cellular immune response, which allows to control the infection caused by L. amazonensis

Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector

[EN] New detector approaches in Positron Emission Tomography imaging will play an important role in reducing costs, lowering administered radiation doses, and improving overall performance. PETALO employs liquid xenon as the active scintillating medium and UV-sensitive silicon photomultipliers for scintillation readout. The scintillation time in liquid xenon is fast enough to register time-of-flight information for each detected coincidence, and sufficient scintillation is produced with low enough fluctuations to obtain good energy resolution. The present simulation study examines a full-body-sized PETALO detector and evaluates its potential performance in PET image reconstruction.This work was supported by the European Research Council under grant ID 757829 and by Ministerio de Economia y Competitividad for grant FPA2016-78595-C3-1-R.Renner, J.; Romo-Luque, C.; Aliaga, RJ.; Álvarez-Puerta, V.; Ballester Merelo, FJ.; Benlloch-Rodríguez, J.; Carrión, J.... (2022). Monte Carlo characterization of PETALO, a full-body liquid xenon-based PET detector. Journal of Instrumentation. 17(5):1-14. https://doi.org/10.1088/1748-0221/17/05/P0504411417

II Jornadas de la Sociedad Española para la Conservación y Estudio de Los Mamíferos (SECEM) Soria 7-9 diciembre 1995

Seguimiento de una reintroducción de corzo (Capreolus capreolus) en ambiente mediterráneo. Dispersión y área de campeoModelos de distribución de los insectívoros ern la Península IbéricaDieta anual del zorro, Vulpes vulpes, en dos hábitats del Parque Nacional de DoñanaDesarrollo juvenil del cráneo en las poblaciones ibéricas de gato montés, Felis silvestris Schreber, 1777Presencia y expansión del visón americano (Mustela vison) en las provincias de Teruel y Castellón (Este de España).Preferencias de hábitat invernal de la musaraña común (Crocidura russula) en un encinar fragmentado de la submeseta norteUso de cámaras automáticas para la recogida de información faunística.Dieta del lobo en dos zonas de Asturias (España) que difieren en carga ganadera.Consumo de frutos y dispersión de semillas de serbal (Sorbus aucuparia L.) por zorros y martas en la cordillera Cantábrica occidentalEvaluación de espermatozoides obtenidos postmorten en el ciervo.Frecuencia de aparición de diferentes restos de conejo en excrementos de lince y zorroAtlas preliminar de los mamíferos de Soria (España)Censo y distribución de la marmota alpina (Marmota marmota) en Navarra.Trampeo fotográfico del género Martes en el Parque Nacional de Aigüestortes i Estany de Sant Maurici (Lleida)Peer reviewe

Treatment with tocilizumab or corticosteroids for COVID-19 patients with hyperinflammatory state: a multicentre cohort study (SAM-COVID-19)

Objectives: The objective of this study was to estimate the association between tocilizumab or corticosteroids and the risk of intubation or death in patients with coronavirus disease 19 (COVID-19) with a hyperinflammatory state according to clinical and laboratory parameters. Methods: A cohort study was performed in 60 Spanish hospitals including 778 patients with COVID-19 and clinical and laboratory data indicative of a hyperinflammatory state. Treatment was mainly with tocilizumab, an intermediate-high dose of corticosteroids (IHDC), a pulse dose of corticosteroids (PDC), combination therapy, or no treatment. Primary outcome was intubation or death; follow-up was 21 days. Propensity score-adjusted estimations using Cox regression (logistic regression if needed) were calculated. Propensity scores were used as confounders, matching variables and for the inverse probability of treatment weights (IPTWs). Results: In all, 88, 117, 78 and 151 patients treated with tocilizumab, IHDC, PDC, and combination therapy, respectively, were compared with 344 untreated patients. The primary endpoint occurred in 10 (11.4%), 27 (23.1%), 12 (15.4%), 40 (25.6%) and 69 (21.1%), respectively. The IPTW-based hazard ratios (odds ratio for combination therapy) for the primary endpoint were 0.32 (95%CI 0.22-0.47; p < 0.001) for tocilizumab, 0.82 (0.71-1.30; p 0.82) for IHDC, 0.61 (0.43-0.86; p 0.006) for PDC, and 1.17 (0.86-1.58; p 0.30) for combination therapy. Other applications of the propensity score provided similar results, but were not significant for PDC. Tocilizumab was also associated with lower hazard of death alone in IPTW analysis (0.07; 0.02-0.17; p < 0.001). Conclusions: Tocilizumab might be useful in COVID-19 patients with a hyperinflammatory state and should be prioritized for randomized trials in this situatio

Ahora / Ara

La cinquena edició del microrelatari per l’eradicació de la violència contra les dones de l’Institut Universitari d’Estudis Feministes i de Gènere «Purificación Escribano» de la Universitat Jaume I vol ser una declaració d’esperança. Aquest és el moment en el qual les dones (i els homes) hem de fer un pas endavant i eliminar la violència sistèmica contra les dones. Ara és el moment de denunciar el masclisme i els micromasclismes començant a construir una societat més igualitària. Cadascun dels relats del llibre és una denúncia i una declaració que ens encamina cap a un món millor

Mechanisms of immunity to Leishmania major infection in mice: The contribution of DNA vaccines coding for two novel sets of histones (H2A–H2B or H3–H4)

The immune phenotype conferred by two different sets of histone genes (H2A-H2B or H3-H4) was assessed. BALB/c mice vaccinated with pcDNA3H2AH2B succumbed to progressive cutaneous leishmaniosis (CL), whereas vaccination with pcDNA3H3H4 resulted in partial resistance to Leishmania major challenge associated with the development of mixed T helper 1 (Th1)/Th2-type response and a reduction in parasite-specific Treg cells number at the site of infection. Therefore, the presence of histones H3 and H4 may be considered essential in the development of vaccine strategies against CL based on the Leishmania histones.Ministerio de Educación y CienciaAGL2007-62207Depto. de Sanidad AnimalFac. de VeterinariaTRUEpu

Solid Lipid Nanoparticles Enhancing the Leishmanicidal Activity of Delamanid

Author Contributions Conceptualization, J.S.-A. and M.L.F.; methodology, J.S.-A., M.A.M., D.J., A.P. and J.C.; validation, M.A.M., J.S.-A., A.P., J.C. and M.L.F.; formal analysis, J.S.-A., J.C. and M.L.F.; investigation, J.S.-A., D.J., M.A.M., A.P. and J.C.; resources, M.L.F.; data curation, J.S.-A. and M.L.F.; writing, review and editing, J.S.-A. and M.L.F.; funding acquisition, M.L.F. All authors have read and agreed to the published version of the manuscript. Funding M.L.F. acknowledges the financial support of the AEI and European Regional Development Fund, “Investing in your future”, Grants TED2021-129248B-I00 and CA21111 “One Health drugs against parasitic vector-borne diseases in Europe and beyond (OneHealthdrugs)” COST action, the Spanish Nanomedicine network RED2022-134560-T MICIN/AEI/1013039/501100011033 “NanoCARE 2.0”, and IDIVAL for the INNVAL 17/11 project. J.S.-A. acknowledges the financial support of the Universidad Central del Ecuador, during his PhD studies.Leishmaniasis, a zoonotic parasitic disease transmitted by infected sandflies, impacts nearly 1 million people yearly and is endemic in many countries across Asia, Africa, the Americas, and the Mediterranean; despite this, it remains a neglected disease with limited effective treatments, particularly in impoverished communities with limited access to healthcare. This study aims to repurpose approved drugs for an affordable leishmaniasis treatment. After the screening of potential drug candidates by reviewing databases and utilizing molecular docking analysis, delamanid was chosen to be incorporated into solid lipid nanoparticles (SLNPs). Both in cellulo and in vivo tests confirmed the successful payload release within macrophages and through the epidermis following topical application on murine skin. The evaluation of macrophages infected with L. infantum amastigotes showed that the encapsulated delamanid exhibited greater leishmanicidal activity compared with the free drug. The process of encapsulating delamanid in SLNPs, as demonstrated in this study, places a strong emphasis on employing minimal technology, ensuring energy efficiency, cost-effectiveness, and reproducibility. It enables consistent, low-cost production of nanomedicines, even on a small scale, offering a promising step toward more accessible and effective leishmaniasis treatments.European CommissionMinisterio de Ciencia y Innovación (España)Instituto de Investigación Valdecilla (España)Depto. de Sanidad AnimalFac. de VeterinariaTRUEpu

The Receptor Slamf1 on the Surface of Myeloid Lineage Cells Controls Susceptibility to Infection by Trypanosoma cruzi

Author Contributions Conceived and designed the experiments: J. Calderon, E. Maganto-Garcia, M. Fresno. Performed the experiments: J. Calderon, E. Maganto-Garcia, C. Punzon, J. Carrion. Analyzed the data: J. Calderon, E. Maganto-Garcia, C. Terhorst, M. Fresno. Contributed reagents/materials/analysis tools: C. Terhorst. Wrote the paper: C. Terhorst, M. Fresno.Trypanosoma cruzi, the protozoan parasite responsible for Chagas' disease, causes severe myocarditis often resulting in death. Here, we report that Slamf1-/- mice, which lack the hematopoietic cell surface receptor Slamf1, are completely protected from an acute lethal parasite challenge. Cardiac damage was reduced in Slamf1-/- mice compared to wild type mice, infected with the same doses of parasites, as a result of a decrease of the number of parasites in the heart even the parasitemia was only marginally less. Both in vivo and in vitro experiments reveal that Slamf1-defIcient myeloid cells are impaired in their ability to replicate the parasite and show altered production of cytokines. Importantly, IFN-γ production in the heart of Slamf1 deficient mice was much lower than in the heart of wt mice even though the number of infiltrating dendritic cells, macrophages, CD4 and CD8 T lymphocytes were comparable. Administration of an anti-Slamf1 monoclonal antibody also reduced the number of parasites and IFN-γ in the heart. These observations not only explain the reduced susceptibility to in vivo infection by the parasite, but they also suggest human Slamf1 as a potential target for therapeutic target against T. cruzi infection.Ministerio de Ciencia e InnovaciónSAF2005-02220,SAF2007-61716SAF2010-18733CSIC-CONICETBSCH/UAMComunidad de MadridS2010/BMD-2332RED RECAVARED RICETRD06/0014/1013RD06/0021/0016Depto. de Sanidad AnimalFac. de VeterinariaTRUEpu

Subtilase cytotoxin-encoding subAB2 variants in verotoxin-producing Escherichia coli strains isolated from goats and sheep

Subtilase cytotoxin (SubAB) is a cytotoxin which might contribute to the virulence of verotoxin-producing Escherichia coli (VTEC) strains in humans. Three variants of SubAB encoding genes have been described (subAB1, subAB2-1, and subAB2-2) and it has been suggested that the strains positive for two variants of subAB may be more pathogenic for humans. In this study, 188 subAB2-positive VTEC strains isolated from goats and sheep were investigated for the presence of the subAB2-1 and subAB2-2 variants by PCR. Eighty-one of the 132 (61.4%) caprine strains and 36 of the 56 (64.3%) ovine strains possessed the subAB2-1 variant and all ovine and caprine strains, except one, were positive for the subAB2-2 variant. The results of this study show for first time that the subAB2-1 and subAB2-2 variants are found in caprine subAB2-positive VTEC strains and confirm that both subAB2 variants are detected in ovine subAB2-positive VTEC strains. Since no significant difference in the presence of both subAB2 variants was found among strains belonging to serotypes associated with severe illness in humans and strains not belonging to these serotypes, the occurrence of two subAB2 variants seems not to be associated with a higher risk of severe disease in humans.Universidad Complutense de Madrid / Banco Santander Central Hispano (INBAVET 920338)Depto. de Sanidad AnimalFac. de VeterinariaTRUEpu