1,721,134 research outputs found

    Genetics and Glaucoma: the state of the art

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    Glaucoma is the second leading cause of irreversible blindness worldwide. Although genetic background contributes differently to rare early-onset glaucoma (before age 40) or common adult-onset glaucoma, it is now considered an important factor in all major forms of the disease. Genetic and genomic studies, including GWAS, are contributing to identifying novel loci associated with glaucoma or to endophenotypes across ancestries to enrich the knowledge about glaucoma genetic susceptibility. Moreover, new high-throughput functional genomics contributes to defining the relevance of genetic results in the biological pathways and processes involved in glaucoma pathogenesis. Such studies are expected to advance significantly our understanding of glaucoma's genetic basis and provide new druggable targets to treat glaucoma. This review gives an overview of the role of genetics in the pathogenesis or risk of glaucoma

    Vitamin E and neurodegenerative diseases.

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    Vitamin E is essential for neurological function. This fact, together with a growing body of evidence indicating that neurodegenerative processes are associated with oxidative stress, lead to the convincing idea that several neurological disorders may be prevented and/or cured by the antioxidant properties of vitamin E. In this review, some aspects related to the role of vitamin E against Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis and ataxia with vitamin E deficiency will be presented

    MiRNA Regulation of Glutathione Homeostasis in Cancer Initiation, Progression and Therapy Resistance

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    Glutathione (GSH) is the most abundant antioxidant that contributes to regulating the cellular production of Reactive Oxygen Species (ROS) which, maintained at physiological levels, can exert a function of second messengers in living organisms. In fact, it has been demonstrated that moderate amounts of ROS can activate the signaling pathways involved in cell growth and proliferation, while high levels of ROS induce DNA damage leading to cancer development. Therefore, GSH is a crucial player in the maintenance of redox homeostasis and its metabolism has a role in tumor initiation, progression and therapy resistance. Our recent studies have demonstrated that neuroblastoma cells resistant to etoposide, a common chemotherapeutic drug, show a partial monoallelic deletion of the locus coding for miRNA 15a and 16-1. leading to a loss of these miRNAs and the activation of GSH-dependent responses. Therefore, the aim of this review is to highlight the role of specific miRNAs in the modulation of intracellular GSH levels in order to take into consideration the use of modulators of miRNA expression as a useful strategy to better sensitize tumors to current therapies

    Polyester-Based Dendrimer Nanoparticles Combined with Etoposide Have an Improved Cytotoxic and Pro-Oxidant Effect on Human Neuroblastoma Cells

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    Etoposide (ETO) is a cytotoxic drug that exerts its effect by increasing reactive oxygen species (ROS) production. Although ETO is widely used, fast metabolism, poor solubility, systemic toxicity, and multi-drug resistance induction all limit its administration dosage and its therapeutic efficiency. In order to address these issues, a biodegradable dendrimer was prepared for entrapping and protecting ETO and for enhancing its solubility and effectiveness. The achieved dendrimer complex with ETO (CPX 5) showed the typical properties of a well-functioning delivery system, i.e., nanospherical morphology (70 nm), optimal Z-potential (−45 mV), good drug loading (37%), very satisfying entrapment efficiency (53%), and a remarkably improved solubility in biocompatible solvents. In regards to its cytotoxic activity, CPX 5 was tested on neuroblastoma (NB) cells with very promising results. In fact, the dendrimer scaffold and ETO are able to exert per se a cytotoxic and pro-oxidant activity on human NB cells. When CPX 5 is combined with ETO, it shows a synergistic action, slowly releasing the drug over time and significantly improving and protracting bioactivity. On the basis of these findings, the prepared ETO reservoir represents a novel biodegradable and promising device for the delivery of ETO into NB cells

    Development of a Fast, Low‐Cost, Conservative and Ecological Method for Quantifying Gallic Acid in Polymeric Formulations by FTIR Spectroscopy in Solution

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    The beneficial polyphenol gallic acid (GA) is often loaded in polymeric systems to improve its poor bioavailability and low stability, therefore quantifying its concentration is mandatory. Chromatography is expensive, time long and non-ecological; partial least square-based near-infrared technique requires interpretative chemometrics tools; ultraviolet/visible (UV-Vis) method is non-specific and destructive. Herein, using Fourier transform infrared (FTIR) spectroscopy, a fast, low-cost, ecological and conservative method for quantifying GA in polymer matrices was developed, by acquiring spectra of GA solutions at different GA concentrations (CGAs). Selected spectral data and CGAs were used to build a linear regression model by least squares approach, subsequently validated adopting samples of three different GA polymer formulations, as validation sets. Test samples were analyzed by FTIR technique and the model was used to determine CGAs, which were predicted with minimal absolute errors (0.01-0.03). This method is robust and extendable also to other precious polymeric matrices or valuable substances
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