1,720,964 research outputs found

    Shear Stress and Its Effect on the Interaction of Myoblast Cells with Nanosized Drug Delivery Vehicles

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    An important aspect to ensure progress in biomedicine is the fundamental understanding of the interaction of cells and tissue with (bio)­materials. The consideration of shear stress in drug delivery and/or tissue engineering remains largely unexplored. To illustrate the fundamental relevance, we employ a microfluidic setup to evaluate the myoblast cell response to two prominent drug carrier systems, namely, liposomes and nanoparticles, in the presence of low shear stress. We show that positively charged carriers have an enhanced interaction with myoblast cells in the presence of shear stress. This effect can be translated into improved therapeutic response in terms of reduction in cell viability when delivering a cytotoxic compound or into a better translocation efficiency when using lipoplexes. Taken together, our fundamental findings open up new possibilities in tissue engineering and drug delivery by considering an additional parameter when delivering beneficial compounds

    Tyrosinase-Loaded Multicompartment Microreactor toward Melanoma Depletion

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    Melanoma is malignant skin cancer occurring with increasing prevalence with no effective treatment. A unique feature of melanoma cells is that they require higher concentrations of ltyrosine (l-tyr) for expansion than normal cells. As such, it has been demonstrated that dietary l-tyr restriction lowers systemic l-tyr and suppresses melanoma advancement in mice. Unfortunately, this diet is not well tolerated by humans. An alternative approach to impede melanoma progression will be to administer the enzyme tyrosinase (TYR), which converts l-tyr into melanin. Herein, a multicompartment carrier consisting of a polymer shell entrapping thousands of liposomes is employed to act as a microreactor depleting l-tyr in the presence of melanoma cells. It is shown that the TYR enzyme can be incorporated within the liposomal subunits with preserved catalytic activity. Aiming to mimic the dynamic environment at the tumor site, l-tyr conversion is conducted by co-culturing melanoma cells and microreactors in a microfluidic setup with applied intratumor shear stress. It is demonstrated that the microreactors are concurrently depleting l-tyr, which translates into inhibited melanoma cell growth. Thus, the first microreactor where the depletion of a substrate translates into antitumor properties in vitro is reported

    Silica Replicas Derived from Mammalian Cells as an Innovative Approach to Physically Direct Cell Lineage Decisions of Mesenchymal Stem Cells

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    By means of a “live-cell” template strategy, silica replicas displaying the same morphology and topography of the mammalian cells used as templates are fabricated. The replicas are used as substrates to direct the differentiation of mesenchymal stem cells (MSCs) to predefined cell lineages. Upregulation of specific genes shows how the silica replica-based substrates have the ability to induce the molecular characteristics of the mature cell types from which they have been derived from. Thus, MSCs cultured in the presence of silica replicas of human osteoblasts (HObs) differentiate into HObs-like cells, as shown by the upregulation of specific osteogenic genes. Likewise, when MSCs are incubated with silica replicas derived from human chondrocytes, an enhanced expression of chondrogenic markers is observed. Importantly, the effects of the silica replicas are cell type-specific since the incubation of MSCs with HObs silica replicas does not result in upregulation of chondrogenic markers and vice versa. What is more, for both cases, the differentiation rate is enhanced when the silica replicas are used in combination with growth factors, suggesting a potential synergistic effect. These results demonstrate the potential of this innovative method as an efficient and cheap approach with the potential to eliminate, or at least reduce, the use of biochemically soluble compounds in stem cells research

    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

    Metal-Phenolic Networks as Broad-Spectrum Antioxidant Coatings for Hemoglobin Nanoparticles Working as Oxygen Carriers

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    Timely administration of donor red blood cells (RBCs) is a crucial and life-saving procedure to restore tissue oxygenation in patients suffering from acute blood loss. However, important drawbacks of using allogenic RBCs are their limited availability and portability, specific storage requirements, short shelf life, or the need for blood type matching. These limitations result in serious logistical challenges that make the transfusion of donor RBCs difficult in extreme life-threatening situations prior to hospital admission. Thus, the engineering of hemoglobin (Hb) nanoparticles (Hb-NPs), which are free from the aforementioned limitations, has emerged as a promising strategy to create RBC substitutes to be used when donor blood is not available. Despite the tremendous progress achieved in recent years, many challenges still need to be overcome. For example, it is still difficult to create Hb-NPs with a high Hb content while also preventing the autoxidation of Hb into nonfunctional methemoglobin (metHb). Herein, the fabrication of small, solid Hb-NPs with an antioxidant coating is reported. By desolvation precipitation, Hb-NPs with an average hydrodynamic diameter of ∼250 nm and a polydispersity index of ∼0.2 are fabricated. A metal-phenolic network (MPN) layer consisting of a phenolic ligand (i.e., tannic acid) cross-linked through iron(III) ions is deposited onto the Hb-NPs surface to render antioxidant protection. The resulting MPN-coated Hb-NPs (MPN@Hb-NPs) maintain the ability of the encapsulated Hb to reversibly bind and release oxygen. The antioxidant properties are demonstrated, showing that MPN@Hb-NPs can effectively scavenge multiple reactive oxygen and nitrogen species, both in solution and in the presence of human RBCs and two relevant cell lines, namely, macrophages and endothelial cells. Importantly, these outstanding antioxidant properties resulting from the MPN translate into decreased metHb conversion. Finally, the newly reported MPN@Hb-NPs are also biocompatible, as shown by hemolysis rate and cell viability studies and can be used to protect the cells from oxidative damage. All in all, we have identified a novel strategy to minimize heme-mediated oxidative reactions that could potentially bring this new generation of Hb-based oxygen carriers a step closer to the clinic

    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

    Confined Multiple Enzymatic (Cascade) Reactions within Poly(dopamine)-based Capsosomes

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    The design of compartmentalized carriers as artificial cells is envisioned to be an efficient tool with potential applications in the biomedical field. The advent of this area has witnessed the assembly of functional, bioinspired systems attempting to tackle challenges in cell mimicry by encapsulating multiple compartments and performing controlled encapsulated enzymatic catalysis. Although capsosomes, which consist of liposomes embedded within a polymeric carrier capsule, are among the most advanced systems, they are still amazingly simple in their functionality and cumbersome in their assembly. We report on capsosomes by embedding liposomes within a poly­(dopamine) (PDA) carrier shell created in a solution-based single-step procedure. We demonstrate for the first time the potential of PDA-based capsosomes to act as artificial cell mimics by performing a two-enzyme coupled reaction in parallel with a single-enzyme conversion by encapsulating three different enzymes into separated liposomal compartments. In the former case, the enzyme uricase converts uric acid into hydrogen peroxide, CO2 and allantoin, followed by the reaction of hydrogen peroxide with the reagent Amplex Ultra Red in the presence of the enzyme horseradish peroxidase to generate the fluorescent product resorufin. The parallel enzymatic catalysis employs the enzyme ascorbate oxidase to convert ascorbic acid into 2-L-dehydroascorbic acid

    Dispelling the Myths Behind First-author Citation Counts

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    We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more sophisticated methods
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