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  • Acceso AbiertoArtículo
    The PNPLA3 genetic variant rs738409 influences the progression to cirrhosis in hiv/hepatitis c virus coinfected patients
    (Public Library of Science (PLoS), 2016-12-14) Núñez-Torres, Rocío; Macías Sánchez, Juan; Mancebo, María; Frías, Mario; Dolci, Giovanni; Téllez, Francisco; Merchante Gutiérrez, Nicolás; Gómez Mateos, Jesús María; Pineda Vergara, Juan Antonio; Real Navarrete, Luis Miguel; Medicina; Bioquímica Médica y Biología Molecular e Inmunología; Junta de Andalucía; Gobierno de España; Instituto de Salud Carlos III; Ministerio de Economia, Industria y Competitividad (MINECO). España
    Contradictory data about the impact of the rs738409 steatosis-related polymorphism within PNPLA3geneonliver fibrosis progression in HIV/hepatitis C virus (HIV/HCV)-coinfected patients have been reported. Our objective was to test whether this, and other polymor phisms previously related to fatty liver disease in HIV infection linked to SAMM50 or LPPR4 genes, influence liver fibrosis progression in HIV/HCV-coinfected individuals. Three hun dred andthirty two HIV/HCV-coinfected patients who consecutively attended four Spanish university hospitals from November 2011 to July 2013 were included. A liver stiffness cut-off of 14.6 kPa, as determined by transient elastography, was used to diagnose cirrhosis. Liver stiffness progression was studied in 171 individuals who had two available LS determina tions without anti-HCV treatment between them. Moreover, 28 HIV/HCV-coinfected patients whounderwent liver transplant, as well as 19 non-cirrhotic coinfected individuals used as controls, were included in an additional study. Only rs738409 was associated with cirrhosis: 45 (29.6%) of 152 Gallele carriers versus 36 (20.0%) of 180 CC carriers showed cirrhosis (multivariate p = 0.018; adjusted odds ratio = 1.98; 95% confidence interval = 1.123.50). Also, 21 (30.4%) of 69 Gallele carriers versus 16 (15.7%) of 102 CC patients showed signifi cant liver stiffness progression (adjusted p-value = 0.015; adjusted odds ratio = 2.89; 95% confidence interval = 1.236.83). Finally, the proportion of rs738409 G allele carriers was significantly higher in transplanted individuals than in controls (p = 0.044, odds ratio = 3.43; 95%confidence interval = 1.0111.70). Our results strongly suggest that the rs738409 poly morphism is associated with liver fibrosis progression in HIV/HCV-coinfected patients.
  • Acceso AbiertoArtículo
    Vaccination prepartum enhances the beneficial effects of melatonin on the immune response and reduces platelet responsiveness in sheep
    (BioMed Central, 2012-06-20) Regodón, Sergio; Ramos, Asunción; Míguez, María P.; Carrillo Vico, Antonio; Rosado, Juan A.; Jardín, Isaac; Bioquímica Médica y Biología Molecular e Inmunología; Junta de Extremadura; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Ministerio de Ciencia e Innovación (MICIN). España
    Background: Melatonin regulates several physiological processes and its powerful action as antioxidant has been widely reported. Melatonin acts modulating the immune system, showing a protective effect on the cardiovascular system and improving vaccine administration as an adjuvant-like agent. Here, we have investigated the role of melatonin as an adjuvant of the Clostridium perfringens vaccine in prepartum sheep and whether melatonin modulates platelet physiology during peripartum. Results: The experiments were carried out in peripartum sheep from a farm located in an area of Mediterranean-type ecosystem. Plasma melatonin levels were determined by ELISA and sheep platelet aggregation was monitored using an aggregometer. Here we demonstrated for the first time that plasma melatonin concentration were higher in pregnant (125 pg/mL) than in non-pregnant sheep (15 pg/mL; P < 0.05). Administration of melatonin prepartum did not significantly modify platelet function but significantly improved the immune response to vaccination against C. perfringens. Conclusion: Administration of melatonin as an adjuvant provides a significant improvement in the immune response to vaccine administration prepartum against C. perfringens.
  • Acceso AbiertoArtículo
    Structure and Nonlinear Optical Properties of TeO2–WO3–PbO Thin Film Glasses
    (Elsevier, 2025) Gorni, G.; Muñoz Martín, D.; Ruiz de la Cruz, A.; Martin Diaconescu, V.; Simonelli, L.; García López, Francisco Javier; Fernández Navarro, J. M.; Solís, J.; Gonzalo, J.; Física Atómica, Molecular y Nuclear; Agencia Estatal de Investigación. España; European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER); Consejo Superior de Investigaciones Científicas (CSIC); Ministerio de Ciencia e Innovación (MICIN). España
    Lead tungsten tellurite thin film glasses have been produced by pulsed laser deposition in a broad TeO2 compositional range (50–85 mol%). Films present high transparency with an optical band gap Eg =3.3–3.4 eV, large refractive index (n >2) and reduced absorption (k <10 4) in the visible and near infrared ranges, whereas their nonlinear optical response (∣χ(3)∣) is found to be ≥10 12 esu at 1.3 μm. The dependence of n, Eg and ∣χ(3)∣ with film composition is analyzed and compared with the values determined for the parent bulk glasses. ∣χ(3)∣ increases as the TeO2 content in the film glasses decreases, while it remains constant for bulk glasses. This behaviour is analyzed in the frame of Line’s model and correlated to the structural differences between bulk and film glasses. In the case of bulk glasses, X-ray absorption spectroscopy results at the W L3 and L1-edges clearly indicate the presence of W6+ions in a distorted octahedral coordination, with the coordination environment and W–O bond distance remaining unchanged regardless of the WO3 content. Raman analysis suggests that films have a structure close to that of bulk glasses, with a moderate WO3 and PbO enrichment, and a relative increase of the non-bridging oxygen fraction that are proposed to be responsible for the observed increase of ∣χ(3)∣ in the films.
  • Acceso AbiertoArtículo
    Quantitative Determination of the Order Phase Transitions of Multicaloric Materials: The Validity of n-overshoot
    (Elsevier, 2025) Reis Junior, Mario de Souza; Jia Yan, Law; Franco García, Victorino; Física de la Materia Condensada; Agencia Estatal de Investigación. España; Air Force Office of Scientific Research. United States; European Union (UE); Junta de Andalucía
    Caloric materials have a significant response (adiabatic temperature change or isothermal entropy change) in the vicinity of a phase transition, with the magnitude and characteristics of this response being strongly dependent on the nature of the transition. It is therefore important to be able to quantitatively ascertain the order of the transition (first or second order) to predict if the phase transformation implies a significant hysteresis, which is detrimental from the application point of view. In the case of magnetocalorics, the overshoot above two of the exponent , describing the field dependence of the isothermal entropy change, has been demonstrated to be a suitable fingerprint of first order phase transitions. In this work, we demonstrate that the criterion holds for multicaloric materials in which the magnetocaloric transformation is altered by pressure.
  • Acceso AbiertoArtículo
    Leptin Is an Anti-Apoptotic Effector in Placental Cells Involving p53 Downregulation
    (Ed. Public Library of Science (PLoS), 2014-06-12) Toro, Ayelén Rayen; Maymó, Julieta Lorena; Ibarbalz, Federico Matías; Pérez Pérez, Antonio; Maskin, Bernardo; Faletti, Alicia Graciela; Sánchez Margalet, Víctor; Varone, Cecilia Laura; Bioquímica Médica y Biología Molecular e Inmunología; ANPCyT; CONICET; CONICET fellowship; Fundacion Florencio Fiorini, Buenos Aires, Argentina; Instituto de Salud Carlos III; Universidad de Buenos Aires (UBACYT)
    Leptin, a peripheral signal synthetized by the adipocyte to regulate energy metabolism, can also be produced by placenta, where it may work as an autocrine hormone. We have previously demonstrated that leptin promotes proliferation and survival of trophoblastic cells. In the present work, we aimed to study the molecular mechanisms that mediate the survival effect of leptin in placenta. We used the human placenta choriocarcinoma BeWo and first trimester Swan-71 cell lines, as well as human placental explants. We tested the late phase of apoptosis, triggered by serum deprivation, by studying the activation of Caspase-3 and DNA fragmentation. Recombinant human leptin added to BeWo cell line and human placental explants, showed a decrease on Caspase-3 activation. These effects were dose dependent. Maximal effect was achieved at 250 ng leptin/ml. Moreover, inhibition of endogenous leptin expression with 2 µM of an antisense oligonucleotide, reversed Caspase-3 diminution. We also found that the cleavage of Poly [ADP-ribose] polymerase-1 (PARP-1) was diminished in the presence of leptin. We analyzed the presence of low DNA fragments, products from apoptotic DNA cleavage. Placental explants cultivated in the absence of serum in the culture media increased the apoptotic cleavage of DNA and this effect was prevented by the addition of 100 ng leptin/ml. Taken together these results reinforce the survival effect exerted by leptin on placental cells. To improve the understanding of leptin mechanism in regulating the process of apoptosis we determined the expression of different intermediaries in the apoptosis cascade. We found that under serum deprivation conditions, leptin increased the anti-apoptotic BCL-2 protein expression, while downregulated the pro-apoptotic BAX and BID proteins expression in Swan-71 cells and placental explants. In both models leptin augmented BCL-2/BAX ratio. Moreover we have demonstrated that p53, one of the key cell cycle-signaling proteins, is downregulated in the presence of leptin under serum deprivation. On the other hand, we determined that leptin reduced the phosphorylation of Ser-46 p53 that plays a pivotal role for apoptotic signaling by p53. Our data suggest that the observed anti-apoptotic effect of leptin in placenta is in part mediated by the p53 pathway. In conclusion, we provide evidence that demonstrates that leptin is a trophic factor for trophoblastic cells


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