1,721,031 research outputs found

    Nanoparticelle Glicosilate Di Mucina Covalentemente Reticolate Come Sistemi Per La Veicolazione Ed Il Rilascio Di Farmaci E Biomolecole

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    The patented technology consists of nanoparticles with particular characteristics capable of conveying different types of drugs to a specific site. It is a new strategy to fight infectious diseases and counteract antimicrobial resistance. Infectious diseases represent a stubborn and major public-health problem all over the world. Worsening this situation is the rise of antimicrobial resistance which hampers the effective prevention and treatment of a wide range of infections. In light of this, we need new strategies to fight pathogens and better ways to efficiently deliver new or existing drugs. NanoMugs are multifunctional nanoparticles, intrinsically glycosylated and with mucoadhesive properties, able to incorporate drugs. The one-step synthesis method allows to obtain a triple effect in one single product: 1) Persistence at the site of infection by mucoadhesion; as NanoMug are made of a highly glycosilated protein, the main component of mucus, they are naturally mucoadhesive. 2) Bacterial and viral engagement by glycan-mediated binding: we used a highly glycosylated protein. The production method preserves these characteristics and the nanoparticles themselves are equipped with oligosaccharides on their surface. 3) Targeted drug delivery and release; molecules with different molecular weight, charge and chemistry can be efficiently loaded during the one-step synthesis. As drugs are not covalently bound to NanoMug, they can be released over time

    From tissue engineering to engineering tissues: the role and application of in vitro models

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    Engineered models have emerged as relevant in vitro tools to foresee the translational potential of new therapies from the bench to the bedside in a fast and cost-effective fashion. The principles applied to the development of tissue-engineered constructs bring the foundation concepts to engineer relevant in vitro models. Engineered models often face scepticism, because regularly these do not include the extreme complexity of nature, but rather a simplification of a phenomenon. While engineering in vitro models, a hypothesis is imposed towards which defined parameters are included to assess the degree of similarity between the in vitro model and the native phenomenon, keeping in mind their intrinsic limitations. The development of in vitro models has been highly supported and disseminated by different regulatory agencies. This review aims at defining and exploring the multifaceted potential of tangible, not theoretical, models within the biomedical field to represent physiological tissues and organ-related phenomena

    Bioinspired in vitro intestinal mucus model for 3D-dynamic culture of bacteria

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    : The intestinal mucus is a biological barrier that supports the intestinal microbiota growth and filters molecules. To perform these functions, mucus possesses optimized microstructure and viscoelastic properties and it is steadily replenished thus flowing along the gut. The available in vitro intestinal mucus models are useful tools in investigating the microbiota-human cells interaction, and are used as matrices for bacterial culture or as static component of microfluidic devices like gut-on-chips. The aim of this work is to engineer an in vitro mucus models (I-Bac3Gel) addressing in a single system physiological viscoelastic properties (i.e., 2-200 Pa), 3D structure and suitability for dynamic bacterial culture. Homogeneously crosslinked alginate hydrogels are optimized in composition to obtain target viscoelastic and microstructural properties. Then, rheological tests are exploited to assess a priori the hydrogels capability to withstand the flow dynamic condition. We experimentally assess the suitability of I-Bac3Gels in the evolving field of microfluidics by applying a dynamic flow to a bacterial-loaded mucus model and by monitoring E. coli growth and survival. The engineered models represent a step forward in the modelling of the mucus, since they can answer to different urgent needs such as a 3D structure, bioinspired properties and compatibility with dynamic system

    Ligand-based design, in silico ADME-Tox filtering, synthesis and biological evaluation to discover new soluble 1,4-DHP-based CFTR activators

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    The altered gating of the mutant CFTR chloride channel cystic fibrosis (CF) may be corrected by small molecules called potentiators. We present a molecular scale simulation system for the discovery of ΔF508-CFTR soluble potentiators. Results report the design, ADME-Tox prediction, synthesis, solubility determination and in vitro biological evaluation of two 1,4-dihydropyridines (DHPs). Compound 1 shows a promising ADME-Tox profile and good potency

    Three-dimensional substrate for microbial cultures

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    The present invention relates to a three-dimensional substrate with structural and compositional gradient for microbial cultures and cocultures, and to a method for preparing it, where said three-dimensional substrate comprises: - a diffusion system (1) which comprises a first compartment (2) and a second compartment (3), where said first compartment (2) is placed above said second compartment (3), said first and second compartments (2, 3) being separated by a semipermeable membrane (4); - a base solution which comprises polysaccharides, proteins and salts or a preformed hydrogel which comprises polysaccharides, proteins and salts; - a cross-linking medium which comprises salts, culture media and distilled water

    Insight into the interaction of inhaled corticosteroids with human serum albumin: A spectroscopic-based study

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    It is well known that the safety and efficacy profile of an inhaled cortocosteroid (ICS) is influenced by the pharmacokinetic properties and associated pharmacodynamic effects of the drug. Freely circulating, protein unbound, and active ICS can cause systemic adverse effects. Therefore, a detailed investigation of drug-protein interaction could be of great interest to understand the pharmacokinetic behaviour of corticosteroids and for the design of new analogues with effective pharmacological properties. In the present work, the interaction between some corticosteroids and human serum albumin (HSA) has been studied by spectroscopic approaches. UV–Vis spectroscopy confirmed that all the investigated corticosteroids can bind to HSA forming a protein-drug complex. The intrinsic fluorescence of HSA was quenched by all the investigated drugs, which was rationalized in terms of a static quenching mechanism. The thermodynamic parameters determined by the Van’t Hoff analysis of the binding constants (negative ΔH and ΔS values) clearly indicate thathydrogen bonds and van der Waals forces play a major role in the binding process between albumin and betamethasone, flunisolide and prednisolone, while hydrophobic forces may play a major role in stabilizing albumin-triamcinolone complexes

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed

    Variations on the Author

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    “Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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