1,720,956 research outputs found

    Development of 3D breast cancer model to study extracellular vesicle crosstalk

    No full text
    3D model systems are crucial in establishing novel therapeutics and understanding cell interactions in the tumor microenvironment. Extracellular vesicles (EVs) are promising carriers of therapeutic cargo for tumor-targeted delivery, and biocompatible hydrogels offer controlled EV delivery. The three core elements of this study included generation and scale up of GFP-EVs in a FiberCell bioreactor, followed by assessment of EV encapsulation and release from hyaluronic acid hydrogels and finally establishing a dynamic 3D breast cancer model that mimics the tumor niche. MDA-MB-231 cells were genetically modified to produce CD63-GFP-labeled EVs. 1x109 of these cells were cultured in a 20kD bioreactor with the introduction of serum free media once stable culture was established. Over five weeks, multiple collections of GFP-labeled EVs were isolated by size exclusion chromatography and characterized by Nanoparticle Tracking Analysis (NTA), western blot, and Transmission Electron Microscopy (TEM). Furthermore, tyramine modified hyaluronic acid (HA-TA) hydrogels were established with hydrogen peroxide and horse radish peroxidase crosslinkers to investigate EV release patterns in static and dynamic conditions. To establish a dynamic 3D multicellular model of breast cancer, isolation and characterization of patient-derived tumor and lymph node stromal cells was performed. Mixed stromal/epithelial tumor spheroids and lymph node spheroids encapsulated in alginate hydrogels were formed. Spheroid viability was assessed and these were introduced into a dynamic multi in vitro organ (MIVO®) system with their respective endothelial barriers to establish crosstalk and support secretome analysis using angiogenesis arrays and ELISA. GFP expression was demonstrated in transduced cells with longitudinal expression confirmed in cells throughout bioreactor culture. NTA and TEM revealed both plasma-EVs and GFP-EVs in the size range of 30-200nm with an intact lipid bilayer were successfully isolated. Initial harvests of GFP-EVs contained subpopulations in a higher size range which disappeared within a few days of serum withdrawal, highlighting initial serum contamination. Western blot confirmed the expression of EV markers CD63, TSG101, CD81, CD 82. Successful incorporation and release of plasma-derived EVs from the hydrogels was demonstrated, with release patterns dependent on loaded EV concentrations and hydrogel formulations. Further investigation into EV release patterns using GFP-EVs under static and dynamic conditions highlighted a significant increase in EV release under fluidic flow conditions. Characterization of tumor and LN stromal populations confirmed presence of stromal markers and absence of hematopoietic markers. Spheroid growth within the alginate gel was monitored maintenance of an intact structure, cell viability and metastatic potential shown. Secretome analysis of the spheroid culture in the dynamic fluidic system supported the tumor-mimicking characteristics of the 3D breast cancer model system. These preliminary findings demonstrate the potential of the fibercell bioreactor system that supported efficient, serum free and reproducible scale up of GFP-EV production which will facilitate tracking EV transfer in the cancer setting. HA-TA hydrogels also showed promise for incorporation and sustained release of EVs. Finally, the 3D organoids in the dynamic system mimicked the tumor niche, demonstrating compelling potential for future study of intercellular EV trafficking and therapeutic potential prior to clinical translation.2025-01-2

    Beyond Physical Exercise: The Role of Nutrition, Gut Microbiota and Nutraceutical Supplementation in Reducing Age-related Sarcopenia

    No full text
    Sarcopenia, a commonly prevalent geriatric condition mainly characterized by progressive loss of the skeletal muscle mass that result in noticeable reduced muscle strength and quality. Most of the geriatric population of above 60 years of age are overweight leading to the accumulation of fat in the muscles resulting in abated muscle function. The increased loss of muscle mass is associated with high rates of disability, poor motility, frailty and mortality. The excessive degeneration of muscles is now also being observed in middle aged people. Therefore, geriatrics has recently started shifting towards the identification of early stages of the disability in order to expand the life span of the patient and reduce physical dependence. Recent findings have indicated that patients with increased physical activity are also affected by sarcopenia, therefore indicating the role of nutritional supplements to enhance muscle health which in turn helps to counteract sarcopenia. Various interventions with physical trainings haven't provided substantial improvements of this disorder thereby highlighting the crucial role of nutritional supplementation in enhancing muscle mass and strength. Nutritional supplementation has not only shown to enhance the positive effects of physical interventions but also have a profound impact on the gut microbiome that has come forward as a key regulator of muscle mass and function. This brief review throws light upon the efficiency of nutrients and nutraceutical supplementation by highlighting their ancillary effects in physical interventions as well as improving the gut microbiome status in sarcopenic adults thereby giving rise to a multimodal intervention for the treatment of sarcopenia

    Going Beyond Counting First Authors in Author Co-citation Analysis

    Full text link
    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

    Full text link
    “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

    Full text link
    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

    Dispelling the Myths Behind First-author Citation Counts

    Full text link
    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

    Author Index

    No full text
    Nao informado

    koamabayili/VECTRON-author-checklist: VECTRON author checklist

    No full text
    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
    corecore