Protein Expression Knockdown in Cancer Cells Induced by a Gemini Cationic Lipid Nanovector with Histidine-Based Polar Heads

A histidine-based gemini cationic lipid, which had already demonstrated its efficiency as a plasmid DNA (pDNA) nanocarrier, has been used in this work to transfect a small interfering RNA (siRNA) into cancer cells. In combination with the helper lipid monoolein glycerol (MOG), the cationic lipid was used as an antiGFP-siRNA nanovector in a multidisciplinary study. Initially, a biophysical characterization by zeta potential (ζ) and agarose gel electrophoresis experiments was performed to determine the lipid effective charge and confirm siRNA compaction. The lipoplexes formed were arranged in Lα lamellar lyotropic liquid crystal phases with a cluster-type morphology, as cryo-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS) studies revealed. Additionally, in vitro experiments confirmed the high gene knockdown efficiency of the lipid-based nanovehicle as detected by flow cytometry (FC) and epifluorescence microscopy, even better than that of Lipofectamine2000*, the transfecting reagent commonly used as a positive control. Cytotoxicity assays indicated that the nanovector is non-toxic to cells. Finally, using nano-liquid chromatography tandem mass spectrometry (nanoLC-MS/MS), apolipoprotein A-I and A-II followed by serum albumin were identified as the proteins with higher affinity for the surface of the lipoplexes. This fact could be beyond the remarkable silencing activity of the histidine-based lipid nanocarrier herein presentedThis work has been funded by the Spanish Ministry of Science, Innovation and Universities (MICIU) (Grant RTI2018-095844-B-I00 and CTQ2017-88948-P), the University Complutense of Madrid (Spain) (project number UCMA05-33-010), and the Regional Government of Madrid (Grant P2018/NMT-4389). P.T. thanks Agencia Estatal de Investigación (AEI) through the Project MAT2016-80266-R and Xunta de Galicia (Grupo de Referencia Competitiva ED431C 2018/26; Agrupación Estratégica en Materiales-AEMAT ED431E 2018/08). ERDF funds are all greatly acknowledged. The proteomic analysis was performed in the Proteomics Unit of Complutense University of Madrid, a member of ProteoRed and is supported by grant PT17/0019, of the PE I+D+i 2013-2016, funded by ISCIII and ERDFS

Molecular Oxygen Lignin Depolymerization: An Insight into the Stability of Phenolic Monomers

This is the peer reviewed version of the following article: Y. Mathieu, J. D. Vidal, L. Arribas Martínez, N. Abad Fernández, S. Iborra, A. Corma, ChemSusChem 2020, 13, 4743, which has been published in final form at https://doi.org/10.1002/cssc.202001295. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.[EN] During oxidative depolymn. of lignin in aq. alk. medium using mol. oxygen as oxidant, the highly functionalized primary phenolic monomers are not stable products, owing to various not fully identified secondary reaction mechanisms. However, better understanding of the mechanisms responsible for the instability of the main part of the products of interest derived from lignin is of much interest. Evaluation of their individual reactivities under oxidative conditions should significantly help to find a better way to valorize the lignin polymer and to maximize the yields of target value-added products. Consequently, the main objective of this study is to assess the individual stabilities of some selected ligninbased phenolic compds., such as vanillin, vanillic acid, and acetovanillone, together with some other pure chem. compds. such as phenol and anisole to give an insight into the mechanisms responsible for the simultaneous formation and repolymn. of those products and the influence of the oxidn. conditions. Various complementary strategies of stabilization are proposed, discussed, and applied for the oxidative depolymn. reactions of a tech. lignin extd. from pinewood with a high content of b-O-4 interconnecting bonds to try to obtain enhanced yields of value-added products.The authors thank Tecnicas Reunidas for material and financial support. We also acknowledge the Spanish Ministry of Science, Innovation, and Universities for funding through the "Severo Ochoa" Excellence Program (SEV 2016-0683) and the LIGNO-PRIZED project from the Spanish Centre for the Development of Industrial Technology (CDTI) in the framework of the Strategic Program of National Business Research Consortia (CIEN-2016). Special and kindly thanks are also given to Dr. Dalgi Sunith Barbosa Trillos and Dr. Jakob Mottweiler for their priceless help during the elaboration of the present work.Mathieu, Y.; Vidal, JD.; Arribas Martínez, L.; Abad Fernández, N.; Iborra Chornet, S.; Corma Canós, A. (2020). Molecular Oxygen Lignin Depolymerization: An Insight into the Stability of Phenolic Monomers. ChemSusChem. 13(17):4743-4758. https://doi.org/10.1002/cssc.202001295S474347581317BP. energy outlook2019 https://www.bp.com/content/dam/bp/business-sites/en/global/corporate/pdfs/energy-economics/energy-outlook/bp-energy-outlook-2019.pdf.J. Bluestein J. 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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

Epidemiological trends of HIV/HCV coinfection in Spain, 2015-2019

Altres ajuts: Spanish AIDS Research Network; European Funding for Regional Development (FEDER).Objectives: We assessed the prevalence of anti-hepatitis C virus (HCV) antibodies and active HCV infection (HCV-RNA-positive) in people living with HIV (PLWH) in Spain in 2019 and compared the results with those of four similar studies performed during 2015-2018. Methods: The study was performed in 41 centres. Sample size was estimated for an accuracy of 1%. Patients were selected by random sampling with proportional allocation. Results: The reference population comprised 41 973 PLWH, and the sample size was 1325. HCV serostatus was known in 1316 PLWH (99.3%), of whom 376 (28.6%) were HCV antibody (Ab)-positive (78.7% were prior injection drug users); 29 were HCV-RNA-positive (2.2%). Of the 29 HCV-RNA-positive PLWH, infection was chronic in 24, it was acute/recent in one, and it was of unknown duration in four. Cirrhosis was present in 71 (5.4%) PLWH overall, three (10.3%) HCV-RNA-positive patients and 68 (23.4%) of those who cleared HCV after anti-HCV therapy (p = 0.04). The prevalence of anti-HCV antibodies decreased steadily from 37.7% in 2015 to 28.6% in 2019 (p < 0.001); the prevalence of active HCV infection decreased from 22.1% in 2015 to 2.2% in 2019 (p < 0.001). Uptake of anti-HCV treatment increased from 53.9% in 2015 to 95.0% in 2019 (p < 0.001). Conclusions: In Spain, the prevalence of active HCV infection among PLWH at the end of 2019 was 2.2%, i.e. 90.0% lower than in 2015. Increased exposure to DAAs was probably the main reason for this sharp reduction. Despite the high coverage of treatment with direct-acting antiviral agents, HCV-related cirrhosis remains significant in this population

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Megaproyectos urbanos y productivos. Impactos socio-territoriales

El desarrollo de megaproyectos productivos trae consigo oportunidades para el crecimiento económico, la generación de empleos y el desarrollo regional. No obstante, en la actualidad, los grandes temas como la expansión urbana, el desarrollo industrial, las cementeras, la minería, el uso intensivo del agua y demás recursos naturales, preocupan a las comunidades por los impactos generados y porque en lo general, no consideran la racionalidad y responsabilidad ambiental y social hacia el entorno. En este contexto son diversos los estudios científicos que, en el marco de la política de económica imperante, intentan posicionarse como alternativas a proyectos económicos que confrontan los intereses particulares y comunitarios y que afectan la salud humana y ambiental. Megaproyectos urbanos y productivos. Impactos socio-territoriales, reúne veinticinco textos académicos sobre las afectaciones que éstos emprendimientos tienen para la sociedad y el entorno. Los temas expuestos recogen experiencias en el desarrollo urbano, industrial, turístico, portuario y aeroportuario, entre otros. Así mismo se retoman temas como la ética, la dialéctica, la política y la economía y su relación en el emprendimiento de megaproyectos. La búsqueda de esquemas productivos racionales y responsables con el entorno, que reivindiquen el derecho de las comunidades a un medio ambiente sano, a la preservación del territorio y sus recursos y de las formas de vida tradicionales, son los referentes para la realización del presente libro. Como elemento central se concibe el territorio como contenedor de identidad y vida, siendo preocupación y tema de estudio de la comunidad académica, las organizaciones de la sociedad civil y las redes de activistas organizados.UAEM, CONACyT, se

GEODIVULGAR: Geología y Sociedad

Fac. de Ciencias GeológicasFALSEsubmitte