Valorisation of the invasive macroalgae Undaria pinnatifida (Harvey) Suringar for the green synthesis of gold and silver nanoparticles with antimicrobial and antioxidant potential

Bacterial and fungal infections are a challenging global problem due to the reported increasing resistance of pathogenic microorganisms to conventional antimicrobials. Nanomaterials are a promising strategy to fight infections caused by multidrug-resistant microbes. In this work, gold (Au@UP) and silver (Ag@UP) nanoparticles were produced for the first time by green synthesis using an aqueous extract of the invasive macroalgae Undaria pinnatifida (UP). The nanoparticles were characterized by a wide range of physicochemical techniques. Au@UP and Ag@UP demonstrated to be spherical and crystalline with an average size of 6.8 ± 1.0 nm and 14.1 ± 2.8 nm, respectively. Carbohydrates and proteins of the UP extract may participate in the synthesis and capping of the nanoparticles. The UP extract, Ag@UP, and Au@UP were assessed for their antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans, and Candida auris. Ag@UP showed the highest antimicrobial activity with very low MIC and MBC values for all the tested bacteria, and Au@UP demonstrated to be very effective against biofilm-producing bacteria. The antifungal properties of both Ag@UP and Au@UP were remarkable, inhibiting hyphae formation. This study points towards a very promising biomedical exploitation of this invasive brown algae.Ministerio de Universidades | Ref. 33.50.460A.752Xunta de Galicia | Ref. ED431C2018UK Research and Innovation | Ref. 10073017Fundação para a Ciência e a Tecnologia | Ref. UIDB/04050/202

Toxicity in vitro and in zebrafish embryonic development of gold nanoparticles biosynthesized using cystoseira macroalgae extracts

Introduction: Research on gold nanoparticles (AuNPs) occupies a prominent place in the field of biomedicine nowadays, being their putative toxicity and bioactivity areas of major concern. The green synthesis of metallic nanoparticles using extracts from marine organisms allows the avoidance of hazardous production steps while maintaining features of interest, thus enabling the exploitation of their promising bioactivity. Objective: To synthesize and characterize AuNPs using, for the first time, macroalga Cystoseira tamariscifolia aqueous extract (Au@CT). Methods: Algal aqueous extracts were used for the synthesis of AuNPs, which were characterized using a wide panel of physicochemical techniques and biological assays. Results: The characterization by UV-Vis spectroscopy, transmission electron microscopy, Z-potential and infrared spectroscopy confirmed that Au@CT were stable, spherical and polycrystalline, with a mean diameter of 7.6 ± 2.2 nm. The antioxidant capacity of the extract, prior to and after synthesis, was analyzed in vitro, showing that the high antioxidant potential was not lost during the synthesis. Subsequently, in vitro and in vivo toxicity was screened, by comparing two species of the genus Cystoseira (C. tamariscifolia and C. baccata) and the corresponding biosynthesized gold nanoparticles (Au@CT and Au@CB). Cytotoxicity was tested in mouse (L929) and human (BJ5ta) fibroblast cell lines. In both cases, only the highest (nominal) test concentration of both extracts (31.25 mg/mL) or Au@CB (12.5 mM) significantly affected cell viability, as measured by the MTT assay. These results were corroborated by a Fish Embryo Acute Toxicity (FET) test. Briefly, it was shown that, at the highest (nominal) tested concentration (31.25 mg/mL), CT extract induced significantly higher cytotoxicity and embryotoxicity than CB extract. However, it was demonstrated that Au@CT, but not Au@CB, were generally non-toxic. At sub-lethal (nominal) test concentrations (1.25 and 2.5 mM), Au@CT affected zebrafish embryonic development to a much lesser extent than Au@CB. In vitro wound healing assays also revealed that, while other experimental conditions did not impact cell migration, CT and Au@CT displayed a moderate positive effect. Conclusion: Au@CT and Au@CB display promising features, desirable for biomedical applications, as wound healing.This work was supported by the strategic program UID/BIA/04050/2020, funded by national funds through the FCT, IP, and the project "FUN2CYT: Harnessing the Potential for Biomedical Applications of Pleiotropic Cytokines LIF and Oncostatin M" (POCI-01-0145-FEDER-030568), supported by Programa Operacional Competitividade e Internacionalizacao (FEDER) and FCT, IP. This work was further supported by Xunta de Galicia ED431C 2018/54-GRC. A. Goncalves holds a fellowship from Fundacao para a Ciencia e a Tecnologia I.P. (FCT, IP) (SFRH/BD/146807/2019). We are extremely grateful to Dr. Andre da Costa for critical revision of the manuscript

Long-Term Systemic Expression of a Novel PD-1 Blocking Nanobody from an AAV Vector Provides Antitumor Activity without Toxicity

Immune checkpoint blockade using monoclonal antibodies (mAbs) able to block programmed death-1 (PD-1)/PD-L1 axis represents a promising treatment for cancer. However, it requires repetitive systemic administration of high mAbs doses, often leading to adverse effects. We generated a novel nanobody against PD-1 (Nb11) able to block PD-1/PD-L1 interaction for both mouse and human molecules. Nb11 was cloned into an adeno-associated virus (AAV) vector downstream of four different promoters (CMV, CAG, EF1α, and SFFV) and its expression was analyzed in cells from rodent (BHK) and human origin (Huh-7). Nb11 was expressed at high levels in vitro reaching 2–20 micrograms/mL with all promoters, except SFFV, which showed lower levels. Nb11 in vivo expression was evaluated in C57BL/6 mice after intravenous administration of AAV8 vectors. Nb11 serum levels increased steadily along time, reaching 1–3 microgram/mL two months post-treatment with the vector having the CAG promoter (AAV-CAG-Nb11), without evidence of toxicity. To test the antitumor potential of this vector, mice that received AAV-CAG-Nb11, or saline as control, were challenged with colon adenocarcinoma cells (MC38). AAV-CAG-Nb11 treatment prevented tumor formation in 30% of mice, significantly increasing survival. These data suggest that continuous expression of immunomodulatory nanobodies from long-term expression vectors could have antitumor effects with low toxicity

Local delivery of optimized nanobodies targeting the PD-1/PD-L1 axis with a self-amplifying RNA viral vector induces potent antitumor responses

Despite the success of immune checkpoint blockade for cancer therapy, many patients do not respond adequately. We aimed to improve this therapy by optimizing both the antibodies and their delivery route, using small monodomain antibodies (nanobodies) delivered locally with a self-amplifying RNA (saRNA) vector based on Semliki Forest virus (SFV). We generated nanobodies against PD-1 and PD-L1 able to inhibit both human and mouse interactions. Incorporation of a dimerization domain reduced PD-1/PD-L1 IC50 by 8- and 40-fold for antiPD-L1 and anti-PD-1 nanobodies, respectively. SFV viral particles expressing dimeric nanobodies showed a potent antitumor response in the MC38 model, resulting in >50% complete regressions, and showed better therapeutic efficacy compared to vectors expressing conventional antibodies. These effects were also observed in the B16 melanoma model. Although a short-term expression of nanobodies was observed due to the cytopathic nature of the saRNA vector, it was enough to generate a strong proinflammatory response in tumors, increasing infiltration of NK and CD8+ T cells. Delivery of the SFV vector expressing dimeric nanobodies by local plasmid electroporation, which could be more easily translated to the clinic, also showed a potent antitumor effect

Optimization of lipase production by solid-state fermentation of olive pomace: from flask to laboratory-scale packed-bed bioreactor

Lipases are versatile catalysts with many applications and can be produced by solid-state fermentation (SSF) using agro-industrial wastes. The aim of this work was to maximize the production of Aspergillus ibericus lipase under SSF of olive pomace (OP) and wheat bran (WB), evaluating the effect on lipase production of C/N ratio, lipids, phenols, content of sugars of substrates and nitrogen source addition. Moreover, the implementation of the SSF process in a packed-bed bioreactor and the improvement of lipase extraction conditions were assessed. Low C/N ratios and high content of lipids led to maximum lipase production. Optimum SSF conditions were achieved with a C/N mass ratio of 25.2 and 10.2% (w/w) lipids in substrate, by the mixture of OP:WB (1:1) and supplemented with 1.33% (w/w) (NH4)2SO4. Studies in a packed-bed bioreactor showed that the lower aeration rates tested prevented substrate dehydration, improving lipase production. In this work, the important role of Triton X-100 on lipase extraction from the fermented solid substrate has been shown. A final lipase activity of 223 ± 5 U g1 (dry basis) was obtained after 7 days of fermentation.Felisbela Oliveira acknowledges the financial support from Fundação para a Ciência e Tecnologia (FCT) of Portugal through grant SFRH/BD/87953/2012. José Manuel Salgado was supported by grant CEB/N2020–INV/01/2016 from Project ‘‘BIOTECNORTE-Underpinning Biotechnology to foster the north of Portugal bioeconomy’’ (NORTE-01-0145-FEDER-000004). Luı ´s Abrunhosa was supported by grant UMINHO/BPD/51/2015 from project UID/BIO/04469/2013 financed by FCT/MEC (OE). This study was supported by the Portuguese Foundation for Science and Technology (FCT) under the scope of the strategic funding of UID/BIO/04469/2013 unit and COMPETE 2020 (POCI-01-0145-FEDER006684) and BioTecNorte operation (NORTE-01-0145-FEDER000004) funded by the European Regional Development Fund under the scope of Norte2020–Programa Operacional Regional do Norte. Noelia Pérez-Rodríguez acknowledges the financial support of FPU fellowship from the Spanish Ministry of Education, Culture and Sports. The authors thank the Spanish Ministry of Economy and Competitiveness for the financial support of this work (Project CTQ2015-71436-C2-1-R), which has partial financial support from the FEDER funds of the European Union.info:eu-repo/semantics/publishedVersio

Decisions of refusal Intensive Care Units' admission as a measure of limitation of life support treatments: geographical variability in Spain

From a post hoc analysis of the ADENI-UCI study (multicenter, observational, cohort, prospective study, with a follow-up period of 13 months, in 62 Intensive Medicine Services in Spain. geographical differences in the reason for denial of income in UCI as a LTSV measure are analyzed. A total of 2284 with an average age of 75.25 (12.45) years were included. 59.43% male. By means of multinominal regression adjusted by age, sex, APACHE and SOFA, was evident (by choosing the northern for reference) that age in the south was a less significantly exposed reason (OR: 0.48 (IC95%: 0.35-0.65). p

Hyperoxemia and excess oxygen use in early acute respiratory distress syndrome : Insights from the LUNG SAFE study

Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Concerns exist regarding the prevalence and impact of unnecessary oxygen use in patients with acute respiratory distress syndrome (ARDS). We examined this issue in patients with ARDS enrolled in the Large observational study to UNderstand the Global impact of Severe Acute respiratory FailurE (LUNG SAFE) study. Methods: In this secondary analysis of the LUNG SAFE study, we wished to determine the prevalence and the outcomes associated with hyperoxemia on day 1, sustained hyperoxemia, and excessive oxygen use in patients with early ARDS. Patients who fulfilled criteria of ARDS on day 1 and day 2 of acute hypoxemic respiratory failure were categorized based on the presence of hyperoxemia (PaO2 > 100 mmHg) on day 1, sustained (i.e., present on day 1 and day 2) hyperoxemia, or excessive oxygen use (FIO2 ≥ 0.60 during hyperoxemia). Results: Of 2005 patients that met the inclusion criteria, 131 (6.5%) were hypoxemic (PaO2 < 55 mmHg), 607 (30%) had hyperoxemia on day 1, and 250 (12%) had sustained hyperoxemia. Excess FIO2 use occurred in 400 (66%) out of 607 patients with hyperoxemia. Excess FIO2 use decreased from day 1 to day 2 of ARDS, with most hyperoxemic patients on day 2 receiving relatively low FIO2. Multivariate analyses found no independent relationship between day 1 hyperoxemia, sustained hyperoxemia, or excess FIO2 use and adverse clinical outcomes. Mortality was 42% in patients with excess FIO2 use, compared to 39% in a propensity-matched sample of normoxemic (PaO2 55-100 mmHg) patients (P = 0.47). Conclusions: Hyperoxemia and excess oxygen use are both prevalent in early ARDS but are most often non-sustained. No relationship was found between hyperoxemia or excessive oxygen use and patient outcome in this cohort. Trial registration: LUNG-SAFE is registered with ClinicalTrials.gov, NCT02010073publishersversionPeer reviewe

Handbook of Active Ageing and Quality of Life: From Concepts to Applications

La edición de este libro estuvo a cargo de Fermina Rojo-Pérez y Gloria Fernández-Mayoralas.El documento adjunto contiene la cubierta, portada e índice del libro.This handbook presents an overview of studies on the relationship of active ageing and quality of life. It addresses the new challenges of ageing from the paradigm of positive ageing (active, healthy and successful) for a better quality of life. It provides theoretical perspectives and empirical studies, including scientific knowledge as well as practical experiences about the good ageing and the quality of later life around the world, in order to respond to the challenges of an aged population. The handbook is structured in 4 sections covering theoretical and conceptual perspectives, social policy issues and research agenda, methods, measurement instrument-scales and evaluations, and lastly application studies including domains and geographical contexts.Peer reviewe

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