1,720,996 research outputs found
Nitric Oxide/Cyclic GMP-Dependent Calcium Signalling Mediates IL-6- and TNF-α-Induced Expression of Glial Fibrillary Acid Protein
Full text linkAstrocyte activation is characterized by hypertrophy with increased glial fibrillary acidic protein (GFAP), whose expression may involve pro-inflammatory cytokines. In this study, the effects of pro-inflammatory IL-6 and TNF-α and anti-inflammatory cytokines IL-4 and IL-10 on nitric oxide (NO)/cyclic guanosine monophosphate (cGMP) signalling, intracellular calcium concentration ([Ca2+]i) and GFAP expression were investigated. In human glioblastoma astrocytoma U-373 MG cells, IL-6 and TNF-α, but not IL-4 or IL-10, increased iNOS, cGMP, [Ca2+]i and GFAP expression. The inhibitors of iNOS (1400 W), soluble guanylyl cyclase (ODQ) and IP3 receptors (ryanodine and 2-APB) reversed the increase in cGMP or [Ca2+]i, respectively, and prevented GFAP expression. In rat striatal slices, IL-6 and TNF-α, at variance with IL-4 and IL-10, promoted a concentration-dependent increase in Ca2+ efflux, an effect prevented by 1400 W, ODQ and RY/2APB. These data were confirmed by in vivo studies, where IL-6, TNF-α or the NO donor DETA/NO injected in the striatum of anaesthetised rats increased cGMP levels and increased GFAP expression. The present findings point to NO/cGMP-dependent calcium signalling as part of the mechanism mediating IL-6- and TNF-α-induced GFAP expression. As this process plays a fundamental role in driving neurotoxicity, targeting NO/cGMP-dependent calcium signalling may constitute a new approach for therapeutic interventions in neurological disorders
A nitric oxide/Ca2+/Calmodulin/ERK1/2 mitogen-activated protein kinase pathway is involved in the mitogenic effect of IL-1beta in human astrocytoma cells
No full textBackground and purpose: Evidence is accumulating to support a role for interleukin-1b (IL-1b) in astrocyte proliferation.
However, the mechanism by which this cytokine modulates this process is not fully elucidated.
Experimental approach: In this study we used human astrocytoma U-373MG cells to investigate the role of nitric oxide (NO),
intracellular Ca2þ concentration ([Ca2þ]i), and extracellular signal-regulated protein kinase (ERK) in the signalling pathway
mediating IL-1b-induced astrocyte proliferation.
Key results: Low IL-1b concentrations induced dose-dependent ERK activation which paralleled upregulation of cell division,
whereas higher concentrations gradually reversed both these responses by promoting apoptosis. Pretreatment with the
nonspecific NOS inhibitor, N-o-nitro-l-arginine methyl ester (L-NAME) or the selective iNOS inhibitor, N-[[3-(aminomethyl)-
phenyl]methyl]-ethanimidamide dihydrochloride (1400W), antagonized ERK activation and cell proliferation induced by IL-1b.
Inhibition of cGMP formation by the guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ),
partially inhibited ERK activation and cell division. Functionally blocking Ca2þ release from endoplasmic reticulum with
ryanodine or 2-aminoethoxydiphenylborane (2-APB), inhibiting calmodulin (CaM) activity with N-(6-aminohexyl)-5-chloro-1-
naphthalenesulphonamide hydrochloride (W7) or MAPK kinase activity with 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthiol]
butadiene (U0126) downregulated IL-1b-induced ERK activation as well as cell proliferation. The cytokine induced a
transient and time-dependent increase in intracellular NO levels which preceded elevation in [Ca2þ]i.
Conclusions and implications: These data identified the NO/Ca2þ/CaM/ERK signalling pathway as a novel mechanism
mediating the mitogenic effect of IL-1b in human astrocytes. As astrocyte proliferation is a hallmark of reactive astrogliosis, our
results reveal a new potential target for therapeutic intervention in neuroinflammatory disorders
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
Ozonated oils as functional dermatological matrices: Effects on the wound healing process using SKH1 mice
Full text linkWound tissue repair is a complex and dynamic process of restoring cellular structures and tissue layers.Improvement of this process is crucial for several pathologies characterized by chronic delayed woundclosure such as diabetes, and the investigation of new approaches aimed to ameliorate the wound healingprocess is under continuous evolution. Recently, the usage of vegetable matrices in the form of ozonatedoils has been proposed and several researchers have shown a positive effect in the wound, based on theirbactericidal, antiviral, and antifungal properties. The present study was undertaken to compare the effectthat different ozonated oils (olive, sesame and linseed) with the same level of ozonation have on woundhealing rate in SKH1 mice. Several histological parameters and the level of key proteins such as VEGF andPCNA have been analyzed. Only treatment with ozonated sesame oil shows a faster wound closure in thefirst 7 days. This effect paralleled with the increased VEGF and PCNA levels, NFkB nuclear translocationand 4-HNE formation. The present study shows that not only the ozonation grade is of importance for the improvement of wound healing process but also the typical composition of the oil
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
Rottlerin exhibits antiangiogenic effects in vitro.
No full textRottlerin, a natural product purified from Mallotus philippinensis, has a number of target molecules and biological effects. We recently found that Rottlerin caused growth arrest in MCF-7 breast cancer cells and human immortalized keratinocytes, through inhibition of NFκB and downregulation of cyclin D-1. To evaluate whether this effect could be generalized to primary cells, human microvascular endothelial cells were treated with Rottlerin. In this study, we demonstrated that Rottlerin prevents basal and TNFα-stimulated NFκB nuclear migration and DNA binding also in human microvascular endothelial cell, where NFκB inhibition was accompanied by the downregulation of NFκB target gene products, such as cyclin D-1 and endothelin-1, which are essential molecules for endothelial cell proliferation and survival. Rottlerin, indeed, inhibited human microvascular endothelial cells proliferation and tube formation on Matrigel. Rottlerin also increases cytoplasmic free calcium and nitric oxide levels and downregulates endothelin converting enzyme-1 expression, thus contributing to the drop in endothelin-1 and growth arrest. These results suggest that Rottlerin may prove useful in the development of therapeutic agents against angiogenesis
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
Modulation of scavenger receptor B1 (SRB1) levels in human keratynocites by cigarette smoke The role of H202
No full textThe pathological effects of cigarette smoke (CS) have been extensively documented. The CS produces over 4,000 compounds in gaseous and particulate states that are able to induce oxidative stress to the cells.
Skin acts as a first line of defense against environmental trauma. The upper layer of the skin, the stratum corneum, is composed by a lipid barrier.The alteration of the skin lipids composition by the exposure to environmental stressors can affect the capacity of the SC to protect us from dehydration and external dangers.
Scavenger Receptor B1 (SR-B1) has been shown to be involved in the uptake of cholesterol from HDL to peripheral tissues therefore its role in skin homeostasis is crucial.
In the present work we studied the effects of CS and some of its products such as acrolein, 4HNE and H2O2 on SR-B1 expression in human keratinocytes. CS exposure decreased SR-B1 level and induced the formation of aldehydes adducts.
By contrast, cells treated with several doses of acrolein or 4HNE or H2O2 did not affect SR-B1. The treatment with glucose oxidase induces the same effect of CS as to concern SR-B1 levels and this was reversed by catalase.
In addition, CS induced the activation of NADPH oxidase measured as p67 translocation to the membrane.
The data from this study show the decreased levels of SR-B1 after CS exposure is mainly driven by the production of H2O2 (exogenous and endogenous), this could lead to the disturbance of the skin lipid barrier affecting skin physiology and be a possible cause of disorders such as skin aging and wound healing linked to CS exposure
The PDE4 inhibitor CHF6001 prevents keratinocytes proliferation by modulating cellular inflammation pathways
No full textPsoriasis is a skin disease characterized by abnormal keratinocyte proliferation and inflammation. Currently, there are no cures for this disease, so the goal of treatment is to decrease inflammation and slow down the associated rapid cell growth and shedding. Recent advances have led to the usage of phosphodiesterase 4 (PDE4) inhibitors for treatment of this condition. For example, apremilast is an oral, selective PDE4 inhibitor that is able to reduce skin inflammation and is Food and Drug Administration (FDA)-approved to treat adults with moderate to severe psoriasis and/or psoriatic arthritis. However, common target-related adverse events, including diarrhea, nausea, headache, and insomnia limit the usage of this drug. To circumvent these effects, the usage of PDE4 inhibitors specifically designed for topical treatment, such as CHF6001, may combine local anti-inflammatory activity with limited systemic exposure, improving tolerability. In this study, we showed that CHF6001, currently undergoing clinical development for COPD, suppresses human keratinocyte proliferation as assessed via BrdU incorporation. We also observed decreased re-epithelialization in a scratch-wound model after CHF6001 treatment. At the molecular level, CHF6001 inhibited translocation of phosphorylated NF-κB subunit p65, promoting loss of nuclear cyclin D1 accumulation and an increase of cell cycle inhibitor p21. Furthermore, CHF6001 decreased oxidative stress, measured by assessing lipid peroxidation (4-HNE adduct formation), through the inactivation of the NADPH oxidase. These results suggest that CHF6001 has the potential to treat skin disorders associated with hyperproliferative keratinocytes, such as psoriasis by targeting oxidative stress, abnormal re-epithelization, and inflammation
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