233 research outputs found

    Correlation Between Endoglin and Malignant Phenotype in Human Melanoma Cells: Analysis of hsa-mir-214 and hsa-mir-370 in Cells and Their Extracellular Vesicles.

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    Endoglin (CD105) is an auxiliary receptor of transforming growth factor (TGF)-ÎČ family members that is expressed in human melanomas. It is heterogeneously expressed by primary and metastatic melanoma cells, and endoglin targeting as a therapeutic strategy for melanoma tumors is currently been explored. However, its involvement in tumor development and malignancy is not fully understood. Here, we find that endoglin expression correlates with malignancy of primary melanomas and cultured melanoma cell lines. Next, we have analyzed the effect of ectopic endoglin expression on two miRNAs (hsa-mir-214 and hsa-mir-370), both involved in melanoma tumor progression and endoglin regulation. We show that compared with control cells, overexpression of endoglin in the WM-164 melanoma cell line induces; (i) a significant increase of hsa-mir-214 levels in small extracellular vesicles (EVs) as well as an increased trend in cells; and (ii) significantly lower levels of hsa-mir-370 in the EVs fractions, whereas no significant differences were found in cells. As hsa-mir-214 and hsa-mir-370 are not just involved in melanoma tumor progression, but they can also target endoglin-expressing endothelial cells in the tumor vasculature, these results suggest a complex and differential regulatory mechanism involving the intracellular and extracellular signaling of hsa-mir-214 and hsa-mir-370 in melanoma development and progression.S

    V- and Nb-containing tungsten bronzes catalysts for the aerobic transformation of ethanol and glycerol. Bulk and supported materials

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    [EN] This work report the applicability of reflux to the synthesis of supported tungsten bronzes (i.e. W-V-O and W-Nb-O), using mesoporous KIT-6 as inert support. For comparison, the corresponding bulk materials prepared by reflux or by hydrothermal synthesis have been also prepared. The catalysts were characterized by several techniques (X-ray diffraction, N-2 adsorption, temperature programmed desorption (NH3), and Raman and FTIR spectroscopies) and tested in the selective aerobic transformation of ethanol and glycerol. These results demonstrate the formation of V- and Nb-containing tungsten oxide bronzes in all of the heat-treated samples (bulk and supported materials), as well as the effective incorporation of metals (V or Nb) in the framework of tungsten bronzes. During the aerobic transformation of ethanol, diethyl ether and ethylene (in Nb-containing catalysts) and acetaldehyde, diethyl ether and ethylene (in V-containing catalysts) were the main reaction products, with very small formation of carbon oxides. During the aerobic transformation of glycerol, acrolein was mainly formed over Nb-containing catalysts, whereas acrylic acid, acrolein and COx were mainly observed over V-containing catalysts. The differences between bulk and supported catalysts have been explained according to changes in their physico-chemical properties: V-containing catalysts presenting both acid and redox sites; and Nb-containing catalysts presenting acid sites. In this way, supported materials seems to be effective in both redox and acid reactions due to the small modifications of the acid characteristics of catalysts.The authors would like to acknowledge the DGICYT (CTQ2015-68951-C3-1-R) and Secretary of State for International Cooperation in Spain (Project AP/040992/11). N.S and D.D thank "Conselho Nacional de Desenvolvimento Cientifico y Tecnologico (CNPq)" in Brasil and Severo Ochoa Excellence Program (SVP-2014-068669) in Spain, respectively, for their fellowships. Authors are also grateful to the Electron Microscopy Service (Universitat Politecnica de Valencia) for facilities.La Salvia, N.; Delgado-Muñoz, D.; Ruiz-Rodríguez, L.; Nadji, L.; Massó Ramírez, A.; López Nieto, JM. (2017). V- and Nb-containing tungsten bronzes catalysts for the aerobic transformation of ethanol and glycerol. Bulk and supported materials. Catalysis Today. 296:2-9. https://doi.org/10.1016/j.cattod.2017.04.009S2929

    Outcomes of COVID-19 Patients Admitted to the Intermediate Respiratory Care Unit: Non-Invasive Respiratory Therapy in a Sequential Protocol

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    The intermediate respiratory care units (IRCUs) have a pivotal role managing escalation and de-escalation between the general wards and the intensive care units (ICUs). Since the COVID-19 pandemic began, the early detection of patients that could improve on non-invasive respiratory therapies (NRTs) in IRCUs without invasive approaches is crucial to ensure proper medical management and optimize limiting ICU resources. The aim of this study was to assess factors associated with survival, ICU admission and intubation likelihood in COVID-19 patients admitted to IRCUs. Observational retrospective study in consecutive patients admitted to the IRCU of a tertiary hospital from March 2020 to April 2021. Inclusion criteria: hypoxemic respiratory failure (SpO(2) = 25 rpm with FiO(2) > 50% supplementary oxygen) due to acute COVID-19 infection. Demographic, comorbidities, clinical and analytical data, and medical and NRT data were collected at IRCU admission. Multivariate logistic regression models assessed factors associated with survival, ICU admission, and intubation. From 679 patients, 79 patients (12%) had an order to not do intubation. From the remaining 600 (88%), 81% survived, 41% needed ICU admission and 37% required intubation. In the IRCU, 51% required non-invasive ventilation (NIV group) and 49% did not (non-NIV group). Older age and lack of corticosteroid treatment were associated with higher mortality and intubation risk in the scheme, which could be more beneficial in severe forms. Initial NIV does not always mean worse outcomes

    Constraints on HIV-1 evolution and immunodominance revealed in monozygotic adult twins infected with the same virus

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    The predictability of virus–host interactions and disease progression in rapidly evolving human viral infections has been difficult to assess because of host and genetic viral diversity. Here we examined adaptive HIV-specific cellular and humoral immune responses and viral evolution in adult monozygotic twins simultaneously infected with the same virus. CD4 T cell counts and viral loads followed similar trajectories over three years of follow up. The initial CD8 T cell response targeted 17 epitopes, 15 of which were identical in each twin, including two immunodominant responses. By 36 months after infection, 14 of 15 initial responses were still detectable in both, whereas all new responses were subdominant and remained so. Of four responses that declined in both twins, three demonstrated mutations at the same residue. In addition, the evolving antibody responses cross-neutralized the other twin's virus, with similar changes in the pattern of evolution in the envelope gene. These results reveal considerable concordance of adaptive cellular and humoral immune responses and HIV evolution in the same genetic environment, suggesting constraints on mutational pathways to HIV immune escape

    An ALMA survey of submillimetre galaxies in the COSMOS field: The extent of the radio-emitting region revealed by 3 GHz imaging with the Very Large Array

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    We determine the radio size distribution of a large sample of 152 SMGs in COSMOS that were detected with ALMA at 1.3 mm. For this purpose, we used the observations taken by the VLA-COSMOS 3 GHz Large Project. One hundred and fifteen of the 152 target SMGs were found to have a 3 GHz counterpart. The median value of the major axis FWHM at 3 GHz is derived to be 4.6±0.44.6\pm0.4 kpc. The radio sizes show no evolutionary trend with redshift, or difference between different galaxy morphologies. We also derived the spectral indices between 1.4 and 3 GHz, and 3 GHz brightness temperatures for the sources, and the median values were found to be α=−0.67\alpha=-0.67 and TB=12.6±2T_{\rm B}=12.6\pm2 K. Three of the target SMGs, which are also detected with the VLBA, show clearly higher brightness temperatures than the typical values. Although the observed radio emission appears to be predominantly powered by star formation and supernova activity, our results provide a strong indication of the presence of an AGN in the VLBA and X-ray-detected SMG AzTEC/C61. The median radio-emitting size we have derived is 1.5-3 times larger than the typical FIR dust-emitting sizes of SMGs, but similar to that of the SMGs' molecular gas component traced through mid-JJ line emission of CO. The physical conditions of SMGs probably render the diffusion of cosmic-ray electrons inefficient, and hence an unlikely process to lead to the observed extended radio sizes. Instead, our results point towards a scenario where SMGs are driven by galaxy interactions and mergers. Besides triggering vigorous starbursts, galaxy collisions can also pull out the magnetised fluids from the interacting disks, and give rise to a taffy-like synchrotron-emitting bridge. This provides an explanation for the spatially extended radio emission of SMGs, and can also cause a deviation from the well-known IR-radio correlation.Comment: 32 pages (incl. 5 appendices), 17 figures, 7 tables; accepted for publication in A&A; abstract abridged for arXi

    Cellular HIV-1 DNA Levels in Drug Sensitive Strains Are Equivalent to Those in Drug Resistant Strains in Newly-Diagnosed Patients in Europe

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    Background HIV-1 genotypic drug resistance is an important threat to the success of antiretroviral therapy and transmitted resistance has reached 9% prevalence in Europe. Studies have demonstrated that HIV-1 DNA load in peripheral blood mononuclear cells (PBMC) have a predictive value for disease progression, independently of CD4 counts and plasma viral load. Methodology/Principal Findings Molecular-beacon-based real-time PCR was used to measure HIV-1 second template switch (STS) DNA in PBMC in newly-diagnosed HIV-1 patients across Europe. These patients were representative for the HIV-1 epidemic in the participating countries and were carrying either drug-resistant or sensitive viral strains. The assay design was improved from a previous version to specifically detect M-group HIV-1 and human CCR5 alleles. The findings resulted in a median of 3.32 log10HIV-1copies/106PBMC and demonstrated for the first time no correlation between cellular HIV-1 DNA load and transmitted drug-resistance. A weak association between cellular HIV-1 DNA levels with plasma viral RNA load and CD4+T-cell counts was also reconfirmed. Co-receptor tropism for 91% of samples, whether or not they conferred resistance, was CCR5. A comparison of pol sequences derived from RNA and DNA, resulted in a high similarity between the two. Conclusions/Significance An improved molecular-beacon-based real-time PCR assay is reported for the measurement of HIV-1 DNA in PBMC and has investigated the association between cellular HIV-1 DNA levels and transmitted resistance to antiretroviral therapy in newly-diagnosed patients from across Europe. The findings show no correlation between these two parameters, suggesting that transmitted resistance does not impact disease progression in HIV-1 infected individuals. The CCR5 co-receptor tropism predominance implies that both resistant and non-resistant strains behave similarly in early infection. Furth

    Food hypersensitivity : an examination of factors influencing symptoms and temporal changes in the prevalence of sensitization in an adult sample

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    Funding Information: HCYL is supported by the Medical Research Council Centre for Environment and Health. NSI is supported by the Centre for Food and Allergy Research (NHMRC Centre of Research Excellence) PhD scholarship and the Melbourne Children’s LifeCourse top-up PhD scholarship (Royal Children’s Hospital Foundation grant #2018-984). ISGlobal acknowledges support from the Spanish Ministry of Science and Innovation through the “Centro de Excelencia Severo Ochoa 2019-2023” Program (CEX2018-000806-S), and the Generalitat de Catalunya through the CERCA Program. Publisher Copyright: © 2023, The Author(s).Background/Objectives: Food hypersensitivity (FHS) is common, but little is known about the factors associated with severe reactions, age of onset and whether sensitization persists. This study examines the factors associated with self-reported severe food reactions, onset age and the changes in prevalence of sensitization to foods over time in an adult sample. Subjects/Methods: We used data from adults taking part in the European Community Respiratory Health Survey (ECRHS) III (2010–2014) who provided information on food hypersensitivity, including symptoms, suspected culprit food and onset age (n = 4865). A subsample from six countries had serum food-specific IgE tested for 25 core foods and also in 10 years earlier (ECRHS II). We applied logistic regression and McNemar’s test for analyses. Results: The prevalence of self-reported FHS was 13.5% at ECRHS III. Of those providing information on symptoms (n = 611), 26.4% reported severe reactions. About 80% of 1033 reported food-specific reactions (reported by 596 participants) began after age 15. History of asthma (odds ratio OR 2.12 95% confidence interval CI 1.13–3.44) and a younger age of onset of FHS (OR 1.02, 95% CI 1.01–1.03, per year) were associated with higher risks of a lifetime experience of severe food reactions. In the subsample with IgE tested in both surveys (n = 1612), the overall prevalence of sensitization to foods did not change over 10 years. Conclusion: Our findings support previous observations of more severe food reactions in people with asthma and that most FHS reported by this sample started after age 15. We found no evidence of changes in the prevalence of sensitization to food in adults followed for 10 years.Peer reviewe

    Water intake, hydration status and 2-year changes in cognitive performance: a prospective cohort study

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    BackgroundWater intake and hydration status have been suggested to impact cognition; however, longitudinal evidence is limited and often inconsistent. This study aimed to longitudinally assess the association between hydration status and water intake based on current recommendations, with changes in cognition in an older Spanish population at high cardiovascular disease risk.MethodsA prospective analysis was conducted of a cohort of 1957 adults (aged 55-75) with overweight/obesity (BMI between >= 27 and = 300 mmol/L (dehydrated). Water intake was assessed as total drinking water intake and total water intake from food and beverages and according to EFSA recommendations. Global cognitive function was determined as a composite z-score summarizing individual participant results from all neuropsychological tests. Multivariable linear regression models were fitted to assess the associations between baseline hydration status and fluid intake, continuously and categorically, with 2-year changes in cognitive performance.ResultsThe mean baseline daily total water intake was 2871 +/- 676 mL/day (2889 +/- 677 mL/day in men; 2854 +/- 674 mL/day in women), and 80.2% of participants met the ESFA reference values for an adequate intake. Serum osmolarity (mean 298 +/- 24 mmol/L, range 263 to 347 mmol/L) indicated that 56% of participants were physiologically dehydrated. Lower physiological hydration status (i.e., greater serum osmolarity) was associated with a greater decline in global cognitive function z-score over a 2-year period (beta: - 0.010; 95% CI - 0.017 to - 0.004, p-value = 0.002). No significant associations were observed between water intake from beverages and/or foods with 2-year changes in global cognitive function.ConclusionsReduced physiological hydration status was associated with greater reductions in global cognitive function over a 2-year period in older adults with metabolic syndrome and overweight or obesity. Future research assessing the impact of hydration on cognitive performance over a longer duration is needed
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