2,563 research outputs found

    Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer

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    Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applicationsThis research was funded by the Instituto de Salud Carlos IIIISCIII and the European Regional Development Fund (FEDER) (AC18/00107, AC18/00045, PI18/00176); by the ERA-NET EURONANOMED III project METASTARG (Grant Number JTC 2018-045) and the ERA-NET EURONANOMED III project PANIPAC (Grant Number JTC 2018/041); and by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria (IN607B2021/14). RP was supported by Roche-Chus Joint Unit (IN853B 2018/03) funded by Axencia Galega de Innovación (GAIN), Consellería de Economía, Emprego e Industria. SL, PH, and AP-L. were funded by a Predoctoral fellowship (IN606A-2019/003, IN606A-2018/019 and ED481A-2018/095) from Axencia Galega de Innovación (GAIN, Xunta de Galicia).S

    Determination of Methane Oxidation in Landfill Fugitive Emissions by 13C Isotope Measurements

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    Still today, the final destiny of a large part of the waste dumped is landfilling, which is an important source of methane. Quantifying the amount of methane that is oxidized when the landfill gas passes through the seal, it can provide valuable information when determining the total GHG potential emission of a landfill. In this work, methane oxidation has been determined for landfill gas samples taken on the surface of three Spanish landfills. For this, it has been determined the 13C isotopic signal in methane by cavity ring-down spectroscopy (CRDS-WS). Previously, the preference of methanotrophic bacteria for 12C isotope versus 13C has been quantified using soil samples from the three landfills. The results obtained show a great variability, ranging from 0 to 70% of methane oxidized. This variability can be explained with the specific characteristics of each sample, suggesting a consistent methodology

    Adherence to the Mediterranean Diet in Pregnancy and Its Benefits on Maternal-Fetal Health: A Systematic Review of the Literature

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    Introduction: Pregnancy is a transcendent period for the mother and the fetus, characterized by an increase on energy requirements. Mediterranean diet (MD) is considered a healthy eating pattern that can provide the nutritional requirements of pregnancy and protect from the development of obstetric pathologies. Objective: To know the relationship between adherence to the MD and its maternal-fetal benefits. Methodology: A systematic review was conducted by identifying articles in the PubMed and Cochrane databases. The publication date of the studies was between 2010 and 2020, and the inclusion criteria established were that the articles were written in English and Spanish and were accessible in full text. Studies concerning assisted reproduction, gene modulation, conference abstracts, systematic reviews, and pilot studies were excluded. Results: Finally, a total of 14 studies were included in the review. The association between the MD and the reduction of some pathologies of pregnancy, such as gestational diabetes, overweight or obesity, sleep quality, complications of childbirth, urinary tract infections (UTIs), and alterations in fetal growth was demonstrated, as well as perinatal problems, including birth weight, prematurity, gastroschisis, and other childhood problems. Conclusion: The MD is an optimal diet to consume during pregnancy

    A Review of the Role of Micronutrients and Bioactive Compounds on Immune System Supporting to Fight against the COVID-19 Disease

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    Micronutrients are critical for an adequate function of the immune system and play a vital role in promoting health and nutritional well-being. The present work is aimed at reviewing (1) the role of micronutrients in helping the immune system to fight against the COVID-19 disease through the diet with food or food supplements and (2) the potential use of food health claims regarding immune function according to the European Food Safety Authority (EFSA) requirements. Till date, there are some health claims authorized by the European Commission that refer to the role of certain essential nutrients (vitamins B6 , B9 , B12, A, D, C, and Cu, Fe, Se) to contribute to the proper functioning of the immune system. Vitamins D, C, Zn, and Se, have been thoroughly studied as a strategy to improve the immune system to fight against COVID-19 disease. From all the micronutrients, Vitamin D is the one with more scientific evidence suggesting positive effects against COVID-19 disease as it is linked to a reduction of infection rates, as well as an improved outcomes in patients. To validate scientific evidence, different clinical trials are ongoing currently, with promising preliminary results although inconclusive yet

    Influence of the Mediterranean diet on seminal quality—a systematic review

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    Currently, there is a growing interest in the study of fertility because fertility-related problems affect up to 15% of the world’s population. The aim of this study was to determine the influence of the Mediterranean diet on seminal quality in men of reproductive age. For this purpose, a systematic review of the literature was carried out following the PRISMA method. Electronic searches were carried out in the international databases PubMed, Scopus, the Cochrane Library, and Web of Science. In total, 10 articles with 2032 men were included. As inclusion criteria, articles published between 2012 and 2022 were selected, including those that included men aged between 18 and 55 years. Nutritional status was assessed through weight, height, and BMI. Dietary habits were evaluated through different indexes and food frequency questionnaires, and finally, semen quality was evaluated by measuring sperm concentration and motility (progressive and non-progressive). In six (60%) of the included articles, a positive relationship between adherence to the Mediterranean diet and semen quality was demonstrated; in two (20%) of the articles, no association was found; and finally, in two (20%) of the included articles, the relationship between dietary patterns typical of DM and semen quality was evaluated. Dietary habits influence semen quality. Adherence to the Mediterranean diet can improve male reproductive health, as it is a diet with antioxidant and anti-inflammatory effects. This is the first systematic review about the influence of the Mediterranean diet on semen quality, and the results are positive. These findings may allow us to provide better advice to our patients and to establish interventions with the aim of improving the results of assisted reproduction techniques

    Aplastic anemia and severe pancytopenia during treatment with peg-interferon, ribavirin and telaprevir for chronic hepatitis C

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    Telaprevir and Boceprevir are the first direct acting antivirals approved for chronic hepatitis C in combination with peg-interferon alfa and ribavirin. Pancytopenia due to myelotoxicity caused by these drugs may occur, but severe hematological abnormalities or aplastic anemia (AA) have not been described. We collected all cases of severe pancytopenia observed during triple therapy with telaprevir in four Spanish centers since approval of the drug in 2011. Among 142 cirrhotic patients receiving treatment, 7 cases of severe pancytopenia (5%) were identified and three were consistent with the diagnosis of AA. Mean age was 59 years, five patients had compensated cirrhosis and two patients had severe hepatitis C recurrence after liver transplantation. Severe pancytopenia was diagnosed a median of 10 wk after the initiation of therapy. Three patients had pre-treatment hematological abnormalities related to splenomegaly. In six patients, antiviral treatment was interrupted at the onset of hematological abnormalities. Two patients died due to septic complications and one patient due to acute alveolar hemorrhage. The remaining patients recovered. Severe pancytopenia and especially AA, are not rare during triple therapy with telaprevir in patients with advanced liver disease. Close monitoring is imperative in this setting to promptly detect serious hematological disorders and to prevent further complications

    Determination of methane and carbon dioxide surface emissions in a Spanish landfill

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    Fugitive emissions from the surface of landfills constitute an important source of carbon dioxide and methane that are emitted to the atmosphere and contribute to the greenhouse effects. Quantifying those emissions can give valuable information, not only, on the amount of those gases which are released into the atmosphere but on their environmental consequences. They can also help to evaluate another aspects related to the landfill management like the seal efficiency or the gas recovery. Quantifying these emissions is not an easy task, due to the heterogeneity of the waste into the landfills, their huge dimensions and the influence of others factors like the site meteorology. Several measurement methods as well as prediction models for determine this type of emissions can be found in the bibliography. In this study a process in two steps, as described on the Guidance on monitoring landfill gas surface emissions (EA 2010), was followed in order to obtain the fugitive emissions of two landfill sites in Madrid (Spain). The first step consists on a walkover survey. At this stage the gas concentration close to the surface is monitored and zones with equal concentrations are defined. At the same time, significant emission sources and failures in the gas collection system are identified. All this information is used to choose the sample points for the second step, the flux box study. A flux box or flux chamber is a well known volume dispositive that allows to accumulate and to quantify over time emissions emanating from a given area of the landfill. To measure the composition of methane inside the flux box, a portable detector based on Infrared (IR) Absorption Spectroscopy (Sensit PMD) in combination with an electronic narrow band pass filter technology is being used. Carbon dioxide emissions were obtained using a passive IR sensor for CO2 (Kimo HQ210). Some preliminary results show the possibility of quantifying emissions rates from less than 1 mg/m2h to 104 mg/m2h or even higher. From a number of measures of this type in the selected emissions points the total amount of the surface emission of the landfill could be estimated. This method has been used in two landfills. The first one is a closed landfill that has been exploited for almost 40 years and was closed in 2000. In this case the landfill gas extracted is being used to generate electricity. The other one corresponds to a landfill which is still in use and the extracted gas is being burnt in a flare. Another critical difference between the two landfills is the type of cover used. In the closed landfill there is a high density polyethylene film while in the other one there is only a clay and sand barrier as cover. The walkover survey results show lower concentrations of methane on the closed landfill. This is an evidence of the effectiveness of a good seal combined with the active extraction and use of the gas to reduce methane release
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