1,721,015 research outputs found
Therapeutic efficacy of adipose-derived MSC in chronic experimental autoimmune encephalomyelitis
Full text linkLe cellule staminali mesenchimali (CSM) rappresentano un promettente approccio terapeutico per le patologie neurologiche a carattere autoimmune. In lavori precedenti è stato dimostrato che il trattamento con CSM da midollo osseo in un modello di encefalite autoimmune sperimentale (EAS), modello animale di sclerosi multipla, ha un effetto immunomodulate ed è in grado di ridurre la gravità della malattia.
In questo lavori dimostriamo che la somministrazione di CSM da tessuto adiposo (CSA) prima dell'insorgenza della malattia è in grado di ridurre significativamente la gravità della malattia, diminuendo infiammazione e demielinizzazione a livello del midollo attraverso un effetto immunomodulante. Le CSA migrano preferibilmente negli organi linfoidi, ma sono in grado di penetrare anche nel sistema nervoso centrale (SNC). Ancora più importante, la somministrazione di CSA in fase cronica di EAS migliora significativamente l'andamento clinico e riduce sia demielinizzazione che perdita assonale, e induce uno shift delle cellule T verso un fenotipo Th2. Abbiamo evidenziato inoltre che una consistente sottopopolazione di CSA esprime l’integrina α4 attivata e tramite microscopia intravitale abbiamo visto che le CSA sono in grado di aderire ai vasi cerebrali infiammati. La bioluminescence imaging conferma che l’inegrina α4 regola la migrazione delle CSA nel SNC infiammato. Dopo esser migrate nelle lesioni di EAS, le CSA portano ad un aumento significativo del numero dei progenitori degli oligodendrociti endogeni.
Per quanto riguarda i meccanismo molecolari che stanno alla base di questo effetto, abbiamo visto che le CSA sono in grado di produrre in coltura vascular endothelial growth factor, insulin growth factor-I, basic fibroblast growth factor, brain-derived growth factor e platelet-derived growth factor-AB, sia in condizioni basali che dopo stimoli infiammatori. E’ interessante notare che tutte queste molecole sono coinvolte nella proliferazione sia dei precursori degli oligodendrociti che delle CSA stesse.
In conclusione, abbiamo mostrato che le CSA presentano un chiaro effetto terapeutico attraverso un duplice meccanismo: sono in grado sia di sopprimere la risposta immunitaria nelle prime fasi della malattia, sia di indurre una neuro-rigenerazione locale agendo sui progenitori endogeni quando la malattia ha raggiunto una fase cronica.
I nostri dati suggeriscono quindi che le CSA possano rappresentare un valido strumento per le terapie cellulari nel trattamento di patologie infiammatorie croniche del SNC.Mesenchymal stem cells (MSC) represent a promising therapeutic approach for neurological autoimmune diseases; previous studies have shown that treatment with bone marrow-derived MSC induces immune modulation and reduces disease severity in
experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis.
Here we show that intravenous administration of adipose-derived MSC (ASC) before disease onset significantly reduces the severity of EAE and decreases spinal cord inflammation and demyelination by immune modulation. ASC preferentially home into lymphoid organs, but migrates also inside the central nervous system (CNS). Most importantly, administration of ASC in chronic established EAE significantly ameliorates the disease course and reduces both demyelination and axonal loss, and induces a Th2-type cytokine shift in T cells. Interestingly, a relevant subset of ASC expresses activated α4 integrins and adheres to inflamed brain venules in intravital microscopy experiments. Bioluminescence imaging confirms that α4 integrins control ASC accumulation in inflamed CNS. After penetration within EAE lesions, ASC induce a significant increase of the number of endogenous oligodendrocyte progenitors. As for the mechanisms responsible for such effect, we found that ASC cultures produce vascular endothelial growth factor, insulin growth factor-I, basic fibroblast growth factor, brain-derived growth factor and platelet-derived growth factor-AB both in basal condition and after inflammatory stimulus. Interestingly, these molecules are all involved in the proliferation of both oligodendrocyte precursors and ASC themselves. In conclusion, we show that ASC display clear therapeutic effect by a bimodal mechanism, by suppressing the autoimmune response in early phases of disease as well as by inducing local neuro-regeneration by activating endogenous progenitors in animals with established disease.
Overall our data suggest that ASC represent a valuable tool for stem cell-based therapy in chronic inflammatory diseases of the CNS
L'anticorpo monoclonale Trastuzumab (Tz) modula il contenuto proteico delle Vescicole Extracellulari (EVs) rilasciate da cellule di carcinoma mammario ErbB2 positive
No full textCancers overexpressing the ERBB2 oncogene are aggressive and associated with a poor prognosis. Trastuzumab is a ERBB2 specific recombinant antibody employed for the treatment of these diseases since it blocks ERBB2 signaling causing growth arrest and survival inhibition. While the effects of Trastuzumab on ERBB2 cancer cells are well known, those on the extracellular vesicles released from these cells are scarce. This study focused on ERBB2+ breast cancer cells and aimed to establish what type of EVs they release and whether Trastuzumab affects their morphology and molecular composition. To these aims, we performed immunoelectron microscopy, immunoblot, and high-resolution mass spectrometry analyses on EVs purified by differential centrifugation of culture supernatant. Here we show that EVs released from ERBB2+ breast cancer cells are polymorphic in size and appearance, and that ERBB2 is preferentially associated with large (120 nm) EVs. Moreover, we report that Tz induces the expression of a specific glycosylated 50 kDa isoform of the CD63 tetraspanin and modulates the expression of 51 EVs proteins, including TOP1. As these pro- teins are functionally associated with organelle organization, cytokinesis, and response to lipids, we suggest that Tz may influence these cellular processes in target cells at distant sites via modified EVs
In silico study of airway/lung mechanics in normal human breathing
Full text linkThe airway/lung mechanics is usually represented with nonlinear 0-D models based on a pneumatic-electrical analogy. The aim of this work is to provide a detailed description of the human respiratory mechanics in healthy and diseased conditions. The model used for this purpose employs some known constitutive functions of the main components of the respiratory system. We give a detailed mathematical description of these functions and subsequently derive additional key ones. We are interested not only in the main output such as airflow at the mouth or alveolar pressure and volume, but also in other quantities such as resistance and pressure drop across each element of the system and even recoil and compliance of the chest wall. Pathological conditions are simulated by altering the parameters of the constitutive functions. Results show that increased upper airway resistance induces airflow reduction with concomitant narrowing of volume and pressure ranges without affecting lung compliance. Instead, increased elastic recoil leads to low volumes and decreased lung compliance. The model could be used in the study of the interaction between respiratory and cardiovascular systems in pathophysiological conditions
Effect of Intracellular Diffusion on Current–Voltage Curves in Potassium Channels
No full textWe study the effect of intracellular ion diffusion on ionic currents
permeating through the cell membrane. Ion flux across the cell membrane is
mediated by specific channels, which have been widely studied in recent years
with remarkable results: very precise measurements of the true current across
a single channel are now available. Nevertheless, a complete understanding of
this phenomenon is still lacking, though molecular dynamics and kinetic models
have provided partial insights. In this paper we demonstrate, by analyzing the
KcsA current-voltage currents via a suitable lattice model, that intracellular
diffusion plays a crucial role in the permeation phenomenon. We believe that
the interplay between the channel behavior and the ion diffusion in the cell is
a key ingredient for a full explanation of the current-voltage curves
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe 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 linkWe 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 linkWe 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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