1,721,059 research outputs found
Exosome-Delivered MiR-126 as potential therapy for Malignant Pleural Mesothelioma: a cancer stroma model to evaluate the anticancer effect of exosomal MiR-126
Get PDFIl miR-126 risulta sotto espresso in diversi tipi di tumori, tra cui il mesotelioma maligno (MM), una delle neoplasie più difficili da trattare. Studi precedenti hanno dimostrato come la restaurazione del miR-126 porti alla perdita di malignità. I livelli di miR-126 possono essere restaurati con diversi sistemi. Tra i metodi di trasporto più studiati ci sono gli esosomi, vescicole endocitotiche naturalmente prodotte dalle cellule. Poiché il miR-126 è altamente espresso nelle cellule endoteliali, gli esosomi endoteliali e gli esosomi endoteliali arricchiti di miR-126 sono stati utilizzati per veicolare e restaurare i livelli di questo miRNA nelle cellule di MM. La tesi si focalizza sulla valutazione degli effetti del miR-126 veicolato dagli esosomi nello stroma tumorale. Il modello di stroma è stato realizzato coltivando i fibroblasti e le cellule endoteliali con le cellule di MM (miR-126 responsive o miR-126 non-responsive) ed è stato valutato l’effetto del miR-126 esosomiale sulle vie di segnalazione, sulla proliferazione cellulare e sull’ angiogenesi. Nel microambiente di MM miR-126 responsivo, i livelli di miR-126 aumentano nelle cellule di MM e nelle cellule endoteliali mentre diminuiscono nei fibroblasti. Inoltre, le variazioni dei livelli di miR-126 nelle diverse componenti cellulari in seguito ai trattamenti provocano da un lato la sotto espressione di VEGF e EGFL7 con conseguente inibizione dell’angiogenesi, mentre dall’altro l’inibizione della via IRS1/AKT/MAPK con conseguente arresto del ciclo cellulare. In conclusione, il miR-126 veicolato dagli esosomi endoteliali ha un effetto oncosoppressore nelle cellule di MM, suggerendo un possibile utilizzo degli esosomi veicolanti miRNA (eso-miR) nella terapia contro il cancro.MiR-126 was found frequently downregulated in many types of cancer, including malignant mesothelioma (MM), which represents one of the most challenging neoplastic diseases.
Previous studies show that miR-126 restoration is associated with the loss of malignancy. The levels of miRNAs can be restored by various ways. One of the most studied methods is the administration of miRNAs through exosomes, endocytic vesicles naturally produced by cells. Since miR-126 is highly expressed in endothelial cells, endothelial-derived exosomes and endothelial-derived exosomes miR-126-enriched have been used to deliver and restore miR-126 in MM cells. The thesis is focused on evaluation of the effect of miR-126 using exosomes as carrier on the stroma microenvironment. A stroma model was performed culturing fibroblasts and endothelial cells with MM cells (miR-126 responsive or miR-126 non-responsive cells), and the tumour-suppressive functions of miR-126 delivered by exosomes on cell signaling modulation, cell proliferation, and angiogenesis were evaluated after treatments. In the miR-126 responsive MM environment, the miR-126 introduced by treatments increased level of miR-126 in MM cells and endothelial cells while a reduction of miR-126 was observed in fibroblasts. Moreover, alteration of miR-126 levels after treatments produces VEGF and EGFL7 downregulation with consequent inhibition of angiogenesis, and inhibition of IRS1/AKT/MAPK pathway with consequent arrest of cell growth. In conclusion miR-126 delivered by endothelial-derived exosomes promotes anti-tumour responses in MM cells, suggesting that exo-miR treatment represent a promising cancer therapy strategy
HIGH EFFICACY ONCOLOGICAL THERAPY BASED ON MIRNA
No full textThe reintroduction of a tumor suppressor miRNA into the tumor has been proposed as a new cancer therapy, but the efficiency of this treatment is partially compromised by the low transport efficiency in vivo. Current approaches are mainly based on liposomal, polymeric and viral based vehicles, but still exhibit some toxicity. Exosomes are similar to liposomes, but their biogenesis guarantees excellent biocompatibility and low toxicity. Malignant mesothelioma is sensitive to mir-126 treatment. Mir-126, inserted inside the exosomes, is effectively incorporated by the cancer cells, but at the same time, it is eliminated by the cells themselves by releasing the exosomes. Treatment of malignant mesothelioma with an exosomal release inhibitor followed by treatment with exosomes enriched in miR-126 allows for the accumulation of miRNA in tumor cells, thus inducing massive cell death. Massive cell death (100% death in 48h) was observed by treating the tumor masses with an exosomal inhibitor (GW4869) and exo-miR-126
Epigenetic Regulation of miRNA Expression in Malignant Mesothelioma: miRNAs as Biomarkers of Early Diagnosis and Therapy
No full textAsbestos exposure leads to epigenetic and epigenomic modifications that, in association with ROS-induced DNA damage, contribute to cancer onset. Few miRNAs epigenetically regulated in MM have been described in literature; miR-126, however, is one of them, and its expression is regulated by epigenetic mechanisms. Asbestos exposure induces early changes in the miRNAs, which are reversibly expressed as protective species, and their inability to reverse reflects the inability of the cells to restore the physiological miRNA levels despite the cessation of carcinogen exposure. Changes in miRNA expression, which results from genetic/epigenetic changes during tumor formation and evolution, can be detected in fluids and used as cancer biomarkers. This article has reviewed the epigenetic mechanisms involved in miRNA expression in MM, focusing on their role as biomarkers of early diagnosis and therapeutic effects
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe 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
Get PDF“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
Get PDFWe 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
Get PDFWe 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
Envisioning gamification in anesthesia, pain management, and critical care: basic principles, integration of artificial intelligence, and simulation strategies
No full textAbstract Unlike traditional video games developed solely for entertainment purposes, game-based learning employs intentionally crafted approaches that seamlessly merge entertainment and educational content, resulting in captivating and effective learning encounters. These pedagogical methods include serious video games and gamification. Serious games are video games utilized as tools for acquiring crucial (serious) knowledge and skills. On the other hand, gamification requires integrating gaming elements (game mechanics) such as points, leaderboards, missions, levels, rewards, and more, into a context that may not be associated with video gaming activities. They can be dynamically (game dynamics) combined developing various strategic approaches. Operatively, gamification adopts simulation elements and leverages the interactive nature of gaming to teach players specific skills, convey knowledge, or address real-world issues. External incentives stimulate internal motivation. Therefore, these techniques place the learners in the central role, allowing them to actively construct knowledge through firsthand experiences. Anesthesia, pain medicine, and critical care demand a delicate interplay of technical competence and non-technical proficiencies. Gamification techniques can offer advantages to both domains. Game-based modalities provide a dynamic, interactive, and highly effective opportunity to learn, practice, and improve both technical and non-technical skills, enriching the overall proficiency of anesthesia professionals. These properties are crucial in a discipline where personal skills, human factors, and the influence of stressors significantly impact daily work activities. Furthermore, gamification can also be embraced for patient education to enhance comfort and compliance, particularly within pediatric settings (game-based distraction), and in pain medicine through stress management techniques. On these bases, the creation of effective gamification tools for anesthesiologists can present a formidable opportunity for users and developers. This narrative review comprehensively examines the intricate aspects of gamification and its potentially transformative influence on the fields of anesthesiology. It delves into theoretical frameworks, potential advantages in education and training, integration with artificial intelligence systems and immersive techniques, and also addresses the challenges that could arise within these contexts
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