1,720,975 research outputs found
Extracellular vesicles in endothelial cells: from mediators of cell-to-cell communication to cargo delivery tools
No full textNrf2 transcription factor activation modulates endothelial inflammatory response triggered by TNF-alpha
No full textOxidants are one of the etiologies of multiple diseases and disorders. Cells are continously exposed
to the deleterious consequences of reactive oxigen species generated endogenously and
exogenously. However, cells have developed multiple stress adaptive responses, including the
system regulated by the transcription factor Nrf2 that modulates a set of cytoprotective genes (such
as HO-1, NQO1, γ-GCS). Up today there are few data supporting the atheroprotective and antiinflammatory
activity of the Nrf2 pathway in endothelial cells. Since activation of endogenous
cellular defense mechanisms can represent an innovative approach to therapeutic intervention in
pathological conditions characterized by chronic tissue damage, a better understanding of adaptive
response mechanisms at the cellular and molecular levels can lead to novel strategies for the
prevention and treatment of many different diseases. Thus, to test the potential atheroprotective and
anti-inflammatory role of the Nrf2 pathway we have investigated if some changes in the
intracellular redox status, such as those related to endogenous antioxidants depletion, might be able
to alter the response to the inflammatory cytokine TNF-α in cultured human endothelial cells
through the activation of this pathway.
In this study, we revealed that an oxidative intracellular status consequent to an intracellular
glutathione depletion induced by HUVECs exposure to buthionine sulfoximine (BSO), an inhibitor
of γ-glutamylcysteine synthetase (γ-GCS), a rate-limiting enzyme in glutathione biosynthesis, is
able to induce a cellular adaptive response. Interestingly we demonstrated that, in our experimental
conditions, activation of Nrf2 pathway is able to reduce endothelial dysfunction by decreasing NFkB
nuclear translocation and adhesion molecules gene expression in HUVECs. Furthermore, we
confirmed that Nrf2 nuclear translocation activated by GSH depletion is dependent on extracellular
signal-regulated kinases 1/2 phosphorylation. In conclusion, we showed that the coordinate
induction of endogenous cytoprotective proteins through activation of the Nrf2 pathway might serve
as a new therapeutic approach for prevention or treatment of endothelial dysfunction.
Corresponding author: Antonio Speciale ([email protected]
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
Cyanidin-3-O-glucoside ameliorates palmitate-induced insulin resistance by modulating IKK and JNK induced serine IRS-1 phosphorylation
No full textModulation of nuclear factor-kB signalling pathway by anthocyanins in human intestinal Caco-2 cells exposed to Tnf-α
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Blueberry-derived exosome-like nanoparticles counters the response to TNF-α-induced change on gene expression in ea.Hy926 cells
No full textExosome-like nanoparticles (ELNs) are attracting interest as important vehicles of intercellular communication, both in prokaryotes and eukaryotes. Recently, dietary nanoparticles similar to mammalian exosomes have attracted attention for these features. In particular they appear to be relevant in the modulation of several cellular processes as well as candidate carriers of bioactive molecules (proteins, lipids, and nucleic acids, including miRNAs) with therapeutic value. Herein, we investigated the cellular uptake of blueberry-derived ELNs (B-ELNs) by a human stabilized endothelial cell line (EA.hy926) and the ability of B-ELNs to modulate the expression of inflammatory genes as the response of tumor necrosis factor-α (TNF-α). Our results indicate that 1) EA.hy926 cells internalize B-ELNs in a dose-dependent manner; 2) pretreatment with B-ELNs counters TNF-α-induced reactive oxygen species (ROS) generation and loss of cell viability and modulates the differential expression of 29 genes (fold change > 1.5) induced by TNF-α compared to control; 3) pathway analysis reveals their involvement in a total of 340 canonical pathways, 121 KEGG pathways, and 121 GO Biological processes; and 4) the intersection between differentially expressed (DE) genes and miRNAs contained in B-ELNs unveils a set of candidate target genes, such as prostaglandin I2 synthase (PTGIS), mitogen-activated protein kinase 14 (MAPK14), and phosphodiesterase 7A (PDE7A), for ELNs-contained cargo. In conclusion, our study indicates that B-ELNs can be considered candidate therapeutic carriers of bioactive compounds potentially able to protect vascular system against various stressors
Caffeic Acid modulates oxidative stress induced by high-glucose exposure in endothelial cells: involvement of Nrf2 pathway
No full textVariations 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
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