1,720,977 research outputs found
Copaifera langsdorffii Desf.: in vitro investigation on anti-Helicobacter pylori and anti-inflammatory activities of oleoresin and fruit methanolic extract
No full textCopaifera langsdorffii Desf. has been used in the traditional medicine of Brazil for centuries to treat a wide range of conditions, including infections, wounds and inflammation. The aim of this study is to compare the effects of C. langsdorffii bark oleoresin and a methanolic extract of the fruit for their anti-Helicobacter pylori (HP) activity and gastroprotective effects. We analyzed the in vitro anti-HP activity against three HP strains: CCUG 39500 (cagA+) and two clinical isolates, G21 and 10 K (cagA + and cagA–, respectively). The effect of C. langsdorffii products on IL-6 release in lipopolysaccharide-stimulated human peripheral blood mononuclear cells was also evaluated. Finally, the toxicity of the samples was evaluated in vitro and in vivo. Both the samples showed an interesting anti-HP activity, acting on different virulence strains, with the oleoresin reaching a minimum bactericidal concentration of 98 μg/ml against cagA– strain. Moreover, an interesting reduction in IL-6 release was observed, which could be helpful for reducing HP-induced inflammation, thus, preventing complications such as ulcer and irritation of the gastric mucosa. Toxicity was not observed up to 2000 μg/ml. Even if more studies must be conducted, this work supports the use of C. langsdorffii in the management of HP-related gastric disorders
Consensus screening for a challenging target: the quest for P-glycoprotein inhibitors
No full textATP-binding cassette (ABC) transporters are a large family of proteins involved in membrane transport of a wide variety of substrates. Among them, ABCB1, also known as MDR-1 or P-glycoprotein (P-gp), is the most characterized. By exporting xenobiotics out of the cell, P-gp activity can affect the ADME properties of several drugs. Moreover, P-gp has been found to mediate multidrug resistance in cancer cells. Thus, the inhibition of P-gp activity may lead to increased absorption and/or intracellular accumulation of co-administered drugs, enhancing their effectiveness. Using the human-mouse chimeric cryoEM 3D structure of the P-gp in the inhibitor-bound intermediate form (PDBID: 6qee), approximately 200 000 commercially available natural compounds from the ZINC database were virtually screened. To build a model able to discriminate between substrate and inhibitors, two datasets of compounds with known activity, including P-gp inhibitors, substrates, and inactive molecules were also docked. The best docking pose of selected substrates and inhibitors were used to generate 3D common feature pharmacophoric models that were combined with the Autodock Vina binding energy values to prioritize compounds for visual inspection. With this consensus approach, 13 potential candidates were identified and then tested for their ability to inhibit P-gp, using zosuquidar, a third generation P-gp inhibitor, as a reference drug. Eight compounds were found to be active with 6 of them having an IC50 lower than 5 μM in a membrane-based ATPase activity assay. Moreover, the P-gp inhibitory activity was also confirmed by two different cell-based in vitro methods. Both retrospective and prospective results demonstrate the ability of the combined structure-based pharmacophore modeling and docking-based virtual screening approach to predict novel hit compounds with inhibitory activity toward P-gp. The resulting chemical scaffolds could serve as inspiration for the optimization of novel and more potent P-gp inhibitors
Effect of in vitro simulated digestion on the anti-Helicobacter pylori activity of different propolis extracts
No full textCannabidiol-enriched Cannabis sativa L. extract modulates inflammatory-induced human peripheral mononuclear cells response
No full textRecent studies propose non-psychotropic Cannabis sativa L. as a candidate drug having a role in the pathogenic mechanisms involved in inflammation [1]. In order to evaluate the biological effect of a chemically standardized extract of C. sativa var. carmagnola dried female inflorescences (CSE) and its main constituents, the purpose of this study was to investigate the modulation of cannabinoid receptors (CBr) and pro-inflammatory cytokines in an acute inflammatory stress in vitro model. CSE was chemically characterized by HPLC-DAD and GC. The CSE biological effect was investigated on human peripheral blood mononuclear cells (PBMC) firstly exposed to the endotoxin LPS (2, 6, 24 hours) in order to evaluate CBr and cytokines regulation. Then, cells were pre-treated with CSE and its main components at the concentration of 1 μg/ml, followed by a 2 hours stimulation with the endotoxin LPS.
CSE was found to contain cannabidiol (CBD) >20%, THC <0.6% and β-caryophyllene as principal sesquiterpene; flavonoids were found only <0.1%. Short term exposure to LPS significantly downregulated CB1r and CB2r gene expression and induced IL-1β, IL-6 and TNF-α release. CBr transcription resulted attenuat by pre-treatment with CSE, and more with CBD. Moreover, the LPS-induced release of the pro-inflammatory cytokine IL-6 was attenuated by CSE and CBD treatment.
C. sativa extract and its main constituent CBD were able to regulate the LPS-induced inflammatory PBMC response through the modulation of CBr expression. These results contribute to support the role of the non-psychotropic cannabis compounds in the management of the inflammatory mechanisms
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
Novel Therapeutic Approach for the Management of Mood Disorders: In Vivo and In Vitro Effect of a Combination of L-Theanine, Melissa officinalis L. and Magnolia officinalis Rehder & E.H. Wilson
Full text linkMood disorders represent one of the most prevalent and costly psychiatric diseases worldwide. The current therapies are generally characterized by several well-known side effects which limit their prolonged use. The use of herbal medicine for the management of several psychiatric conditions is becoming more established, as it is considered a safer support to conventional pharmacotherapy. The aim of this study was to investigate the possible anxiolytic and antidepressant activity of a fixed combination of L-theanine, Magnolia officinalis, and Melissa officinalis (TMM) in an attempt to evaluate how the multiple modulations of different physiological systems may contribute to reducing mood disorders. TMM showed an anxiolytic-like and antidepressant-like activity in vivo, which was related to a neuroprotective effect in an in vitro model of excitotoxicity. The effect of TMM was not altered by the presence of flumazenil, thus suggesting a non-benzodiazepine-like mechanism of action. On the contrary, a significant reduction in the effect was observed in animals and neuronal cells co-treated with AM251, a cannabinoid receptor type 1 (CB1) antagonist, suggesting that the endocannabinoid system may be involved in the TMM mechanism of action. In conclusion, TMM may represent a useful and safe candidate for the management of mood disorders with an innovative mechanism of action, particularly as an adjuvant to conventional therapies
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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