1,721,001 research outputs found

    Nonclassic endogenous regulators of angiogenesis

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    Angiogenesis, the process through which new blood vessels arise from preexisting ones, is regulated by several "classic" factors, among which the most studied are vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2). In recent years, investigations showed that, in addition to the classic factors, numerous endogenous peptides play a relevant regulatory role in angiogenesis. Such regulatory peptides, each of which exerts well-known specific biological activities, are present, along with their receptors, in the blood vessels and may take part in the control of the "angiogenic switch." An in vivo and in vitro proangiogenic effect has been demonstrated for erythropoietin, angiotensin II (ANG-II), endothelins (ETs), adrenomedullin (AM), proadrenomedullin N-terminal 20 peptide (PAMP), urotensin-II, leptin, adiponectin, resistin, neuropeptide-Y, vasoactive intestinal peptide (VIP), pituitary adenylate cyclase-activating polypeptide (PACAP), and substance P. There is evidence that the angiogenic action of some of these peptides is at least partly mediated by their stimulating effect on VEGF (ANG-II, ETs, PAMP, resistin, VIP and PACAP) and/or FGF-2 systems (PAMP and leptin). AM raises the expression of VEGF in endothelial cells, but VEGF blockade does not affect the proangiogenic action of AM. Other endogenous peptides have been reported to exert an in vivo and in vitro antiangiogenic action. These include somatostatin and natriuretic peptides, which suppress the VEGF system, and ghrelin, that antagonizes FGF-2 effects. Investigations on "nonclassic" regulators of angiogenesis could open new perspectives in the therapy of diseases coupled to dysregulation of angiogenesis

    Surface nanostructuring of bioresorbable implants to induce osteogenic differentiation of human mesenchymal stromal cells

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    Surface nanostructuring of bioresorbable polymers is a promising solution for tissue regeneration therapies, as such nanostructured implants non-toxically degrade after producing localized and prolonged stimuli. In this work, a process chain for the fabrication of bioresorbable polymer implants was developed and validated. The implants present surface arrays of nanopillars whose main design parameters were optimized to induce the osteogenic differentiation of human stem cells. In vitro and in vivo cell experiments provided evidence for the potential application in tissue regeneration and revealed that nanopillars' diameter, height, and spacing need to be independently optimized to effectively promote osteogenic differentiation

    Biological behavior of endothelial cells on Human Elastin-like Polypeptide-based biomaterials

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    Bioinspired artificial proteins modelled on tropoelastin represent an attractive tool for many biotechnological and biomedical applications. In this work, a recombinant Human Elastin-like Polypeptide (HELP) comprising the most regularly repeated hexapeptidic motif of human tropoelastin, has been employed to prepare HELP-based or –coated biomaterials. In vitro characterization of the polypeptide based materials was aimed to evaluate their potential application for blood vessel reconstruction

    Engineering the tumor environment in vitro using peptide-enriched, hyaluronic acid-based hydrogels

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    Electrochemotherapy (ECT) is a clinically used and effective treatment in the care of melanoma, and recently it was suggested as a promising tool for the treatment of other deep-seated solid tumors (e.g., liver tumors). In general, ECT efficacy is evaluated in vitro on cell suspensions or in adhesion, and in vivo on animal models. Nevertheless, the first two mentioned approaches completely lack extracellular matrix (ECM) components, leading to unreliable results because they do not reflect the natural tissue architecture. To overcome this issue, several three-dimensional (3D) in vitro models, such as spheroids and hydrogel-based cultures, have been proposed to mimic the complex tumor microenvironment. In this frame, a new synthetic scaffold based on hyaluronic acid (HA) and self-assembling peptides (EAbuK) is proposed as an advantageous alternative. HA-EAbuK scaffolds promote spheroids formation where cells experiment cell-cell interactions, but also improve cell-ECM interactions. Liver cancer (HepG2) cell lines were cultured on HA and HA-EAbuK scaffolds and preliminary bioassays were carried out to assess cell viability and spheroids formation. Then, cells were electroporated at different electric field amplitudes. 3D cultures on HA scaffolds and cells in adhesion (2D cultures), electroporated using culture medium or phosphate-based EP buffer, were taken as controls. Our data showed that HepG2 cells cultured on HA-EAbuK scaffolds were already completely electroporated at 800 V/cm, whereas cells cultured on HA started to be electroporated at 1200 V/cm. In 2D cultures, HEPG2 cells were electroporated at 1000 V/cm and 1200 V/cm in EP buffer and in culture medium, respectively. Collectively, our preliminary results suggest that HepG2 cell cultures on HA-EAbuK hydrogels may represent a promising tool for in vitro evaluation of EP efficiency

    Photochemical and photobiological properties of 4,8-dimethyl-5′-acetylpsoralen

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    The photochemical and photobiological properties of 4,8-dimethyl-5'-acetylpsoralen (AcPso), proposed for the photochemotherapy of some skin diseases, were investigated. The photoreaction of AcPso with DNA is weaker in the presence of air than in a nitrogen atmosphere, in terms of total photobinding and DNA cross-linking; when UVA irradiation is performed in air, AcPso behaves as a monofunctional reagent. The quenching effect of oxygen is related to the high capacity of AcPso to produce singlet oxygen. Furthermore, it is demonstrated that AcPso photoadducts are better producers of singlet oxygen than free AcPso in solution. Using DNA sequencing methodology, two modes of DNA photo-sensitization by AcPso are shown, these lead to the formation of photoadducts mainly at T residues (and at C to a lesser extent) and to photo-oxidized G residues probably via singlet oxygen. Chemical or enzymatic cleavage were used as probes in these experiments. A rapid assay for the detection of the photodynamic effect of a photosensitizer on DNA, involving oxygen, is also described. Finally, the cytotoxicity and genotoxicity of AcPso on E. coli WP2 cells appear to be related to its ability to form photoadducts, in particular cross-links, rather than to its capacity to produce singlet oxygen

    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

    Appropriate Similarity Measures for Author Cocitation Analysis

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    We provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
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