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    Tanshinones from Salvia miltiorrhiza Bunge revert chemotherapy-induced neuropathic pain and reduce glioblastoma cells malignancy

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    Medicinal plants and herbal extracts from traditional Chinese medicine are used increasingly commonly worldwide for their benefits to health and quality of life as dietary supplements or as ingredients in functional foods. Among them, Salvia miltiorrhiza Bunge (a natural strong remedy for the treatment of a variety of conditions) is traditionally used for centuries in Asian countries as antioxidant, anticancer, and anti-inflammatory agent. In this context, several evidences support the hypothesis that some tanshinones (in particular tanshinone IIA and cryptotanshinone) extracted from the roots (Danshen) of Salvia miltiorrhiza exert neuroprotective and analgesic activities. Oxaliplatin (OXA), a platinum-based drug used for the treatment of solid tumors, induces neuropathic pain which hampers the chemotherapy success. While several attempts were made to prevent oxaliplatin-induced painful neuropathy, a growing number of evidences look to natural sources as an effective remedy to counterbalance the OXA-mediated side effects. The aim of the present study was to investigate the pain-relieving profile of Danshen and its active constituents tanshinone IIA (TIIA) and cryptotanshinone (CRY) in animal models of neuropathic pain induced by OXA, anticancer drug characterized by a dose-limiting neurotoxicity. Contextually, the neuroprotective and anticancer activities of the selected compounds were tested in different cells lines. A single administration per os of CRY (30 mg mg/kg) significantly, in a dose dependent manner, attenuated chemotherapy-induced pain. A 7 days repeated administrations highlighted the effectiveness and potency of both CRY and TIIA (10 mg/kg). On the other hand, Danshen showed a painkiller profile against oxaliplatin-induced neuropathy. Contextually, Danshen and its active constituents showed remarkable and selective inhibitory activities on glioblastoma cells lines LN-229 (IC50: 50.0 ± 4.0, 48.2 ± 4.9 and 51.9 ± 2.3 μM respectively for Danshen standardized extract, TIIA and CRY) next to healthy but high proliferative cell lines enterocytes (IC50:> 250 μM for TIIA and CRY) and keratinocytes (IC50: >100 and 97 ± 2 μM respectively for TIIA and CRY). Taken together the results reported here demonstrated the long-lasting pain-relieving effects of Danshen and its related bioactive constituents in animal models of neuropathic pain and their selective in vitro neuroprotective properties on certain central malignancy cells lines. Thus, suggest that S. miltiorrhiza roots could be considered as a new potential source of active diterpenoidic compounds useful for pharmaceutical or nutraceutical industries and beneficial as food complements

    Bioengineered lipophilic Ru(III) complexes as potential anticancer agents

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    Lipid-conjugated Ru(III) complexes – designed to obtain lipophilic analogues of the low molecular weight derivative AziRu, which is a NAMI-A-like anticancer agent – have been synthesized and fully characterized. A detailed biophysical investigation, including multiple, integrated techniques, allowed determining their molecular and self-assembling properties in aqueous solutions mimicking the extracellular environment, showing that our design produced a protective effect from hydrolysis of the Ru(III) complexes. In vitro biological experiments, carried out in comparison with AziRu, demonstrated that, among the novel lipophilic Ru(III) complexes synthesized, the compounds derivatized with palmitic and stearic acid, that we named PalmiPyRu and StePyRu respectively, showed attractive features and a promising antiproliferative activity, selective on specific breast cancer phenotypes. To get a deeper insight into their interactions with potential biomacromolecular targets, their ability to bind both bovine serum albumin (BSA), an abundant serum carrier protein, and some DNA model systems, including duplex and G-quadruplex structures, has been investigated by spectroscopic techniques. Inductively coupled plasma-mass spectrometry (ICP-MS) analysis of the ruthenium amount incorporated in human MCF-7 and MDA-MB-231 breast cancer cells, after incubation in parallel experiments with PalmiPyRu and AziRu, showed a markedly higher cell uptake of the lipophilic Ru(III) complex with respect to AziRu. These data confirmed that the proper lipidic tail decorating the metal complex not only favoured the formation of aggregates in the extracellular media but also improved their cell membrane penetration, thus leading to higher antiproliferative activity selective on breast cancer cells

    Lipophilicity profiling and cell viability assessment of a selected panel of endocrine disruptors

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    Endocrine disruptors are chemicals widely used worldwide by industries in a variety of applications. Routinely exposure to these chemicals, even if at low doses, can cause damage effects on human health. In the present study, we evaluated toxic effects of nine chemicals, among which phthalates, using various cell lines to inspect their capability to interfere with cell proliferation and viability.Alongside, we investigated their affinity for phospholipids to assess the possible passage through biomembranes. Experimentally determined logkwIAM.MG values ranged from 1.37 to 3.49 whilst calculated log kwIAM.DD2 spanned from 1.80 to 5.21, supporting the target contaminants to exhibit lipophilicity moderate or very high. The achieved results were related to pharmacokinetic and toxicological properties by ADMET predictor™ and EPI Suite™ software. Triclosan and 4-Nonylphenol were found to be the most toxic against all cell lines screened, showing an IC50 of 30 μM for triclosan on human keratinocytes and of 50 μM for 4-Nonylphenol on human colorectal adenocarcinoma cells. Overall, even if the phthalates showed higher IC50 values (ranging from 170 μM to 280 μM), we can assert that all contaminants herein tested were able to interfere with cell growth and viability

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The 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

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    “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

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    We 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

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    We 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

    Author Index

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    koamabayili/VECTRON-author-checklist: VECTRON author checklist

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    We have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
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