1,721,011 research outputs found

    Castanea Sativa Mill. bark extract exerts chemopreventive properties triggering extrinsic apoptotic pathway in Jurkat cells

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    Chemoprevention represents the possibility to prevent, stop or reverse the cancerogenetic process. In this context the interest towards natural extracts has grown due to their phytochemical content. Castanea Sativa Mill. (CSM) bark extracts showed to exert positive effect in the counteraction of chronic/degenerative diseases, therefore, we evaluated its potential chemopreventive effect. Flow cytometry (FCM) analyses of Jurkat cells treated with CSM bark extract 0-500 μg/mL for 24-72h allowed to evaluate its cytotoxicity and ability to induce apoptosis. Moreover, to define if CSM bark extract was selective towards cancer cells, its cytotoxic and proapoptotic effect was evaluated in human lymphocytes (PBL) from healthy donors. CSM bark extract induced apoptosis in Jurkat cells in a dose- and time- dependent manner by activating the extrinsic pathways as evidenced by the activation of caspae 8. Moreover, at 24h treatment IC50 resulted 304 and 128 μg/mL in PBL and Jurkat cells respectively. CSM bark extract resulted a partially selective chemopreventive agent thanks to its ability to induce apoptosis in cancer cells at concentrations lower than in non-transformed cells

    Flow cytometry vs optical microscopy in the evaluation of the genotoxic potential of xenobiotic compounds

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    Background: It is now recognized that mutational events play a key role in the development of pathological processes like cancer, cardiovascular, and neurodegenerative disease. Therefore, it is crucial to have Genetics Toxicology tests that allow rapid and accurate identification of the mutagenic potential of a xenobiotic. Currently the most widely used technique is the "In vitro mammalian cell micronucleus test" performed by optical microscopy, but some problems have been highlighted, including the number of cells analyzed, the high subjectivity of the reading at the microscope and the long analysis times. Aim: The aim of this work was to develop a study protocol, for the automation of the "In vitro mammalian cell micronucleus test", by flow cytometry (FCM) analysis, to overcome the limits that afflict the optical microscopy. Methods: The study was conducted on peripheral blood lymphocytes treated with three known clastogens and three known aneugens. Results: The results obtained by the proposed FCM technique compared with those obtained through the validated method, demonstrated that the increase of micronuclei percentage is perfectly comparable between the two methods. Conclusions: This fact, in view of results supported by a high number of cells analyzed and obtained by an accurate and objective reading, with a considerable reduction of the analysis time, can support a future request for validation of the micronucleus analysis by FCM

    Sulforaphane as a promising molecule for fighting cancer

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    Cancer is a complex disease characterized by multiple genetic and molecular alterations involving transformation, deregulation of apoptosis, proliferation, invasion, angiogenesis, and metastasis. To grow, invade, and metastasize, tumors need host components and primary dysfunction in the tumor microenvironment, in addition to cell dysfunction, can be crucial for carcinogenesis. A great variety of phytochemicals have been shown to be potentially capable of inhibiting and modulating several relevant targets simultaneously and is therefore non-specific. Because of the enormous biological diversity of cancer, this pleiotropism might constitute an advantage. Phytochemicals, in particular diet-derived compounds, have therefore been proposed and applied in clinical trials as cancer chemopreventive/chemotherapeutic agents. Sulforaphane (SFN) is an isothiocyanate found in cruciferous vegetables. SFN has proved to be an effective chemoprotective agent in cell culture, in carcinogen-induced and genetic animal cancer models, as well as in xenograft models of cancer. It promoted potent cytostatic and cytotoxic effects orchestrated by the modulation of different molecular targets. Cell vulnerability to SFN-mediated apoptosis was subject to regulation by cell-cycle-dependent mechanisms but was independent of a mutated p53 status. Moreover, combination of SFN with cytotoxic therapy potentiated the cytotoxic effect mediated by chemotherapy in vitro, thus suggesting its potential therapeutic benefit in clinical settings. Overall, SFN appears to be an effective and safe chemopreventive molecule and a promising tool to fight cancer

    Anthraquinones: Genotoxic until Proven Otherwise? A Study on a Substance-Based Medical Device to Implement Available Data for a Correct Risk Assessment

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    A genotoxicological study was carried out on a substance-based medical device (SMD) containing anthraquinones in order to evaluate its potential mutagenic effect. The “In Vitro Mammalian Cell Micronucleus Test” was performed on human TK6 cells by flow cytometry. Cultures were treated with concentrations of SMD tested in the range of 0–2 mg/mL for short treatment time (3 h) both in the absence and presence of an exogenous metabolic activation system, followed by a recovery period in fresh medium (23 h) and for extended treatment time (26 h) without an exogenous metabolic activation system. At the end of both treatment times, cytotoxicity, cytostasis, apoptosis and micronuclei (MNi) frequency were analysed in treated cultures and then compared with those measured in concurrent negative control cultures. The SMD did not induce a statistically significant increase MNi frequency under any of experimental conditions tested. The negative outcome shows that the SMD is non-mutagenic in terms of its ability to induce chromosomal aberrations both in the absence and presence of an exogenous metabolic activation system. The study ended by analyzing intracellular ROS levels to exclude the pro-oxidant ability, typically linked to DNA damage. On the contrary, our results demonstrated the ability the SMD to counteract oxidative stress

    LATONA. Functional, toxicological and technological characterization of Limosilactobacillus vaginalis BC17

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    This dataset contains data collected in the PoC MISE - AlmaValue project “LATONA” (“Lattobacilli della donna quali agenti bioterapeutici per promuovere il corretto sviluppo del microbiota intestinale e del sistema immunitario nel neonato”), funded by Ministero dello Sviluppo Economico on PNRR funds and within the framework of the European Commission's Next Generation EU programme. In particular, the research focused on the vaginal strain Limosilactobacillus vaginalis BC17 and its derivatives (cell-free supernatant and heat-killed cells), and some health-promoting features were considered: (i) L. vaginalis BC17 was indagated for the ability to adhere to intestinal cells (i.e. Caco-2 and HT-29 cells) and to survive in co-incubation with them. (ii) The absence of cytotoxicity of the strain and its derivatives was demonstrated on intestinal cells lines (i.e. Caco-2 and HT-29). (iii) Any genotoxicity effects of cell-free supernatant and heat-killed cells were excluded. (iv) L. vaginalis BC17 and its derivatives were sought for the capacity to favour the adhesion of beneficial Bifidobacterium spp. and to inhibit the adhesion of enteropathogens (i.e. enterotoxigenic E. coli, Salmonella enterica, and Yersinia enterocolitica) to Caco-2 cells. (v) Anti-inflammatory properties were highlighted both on intestinal cells and macrophages models. Moreover, the dataset provides the data relative to the development of freeze-dried tablets containing L. vaginalis BC17 or heat-killed cells in the presence of cell-free supernatant and maltodextrin. In particular, the dataset supplies raw data in terms of diameter, thickness and weight of tablets resulting from a screening procedure of different ratios of maltodextrin and cell-free supernatant. It also contains the characterization of the selected tablets in terms of diameter, thickness, weight, pH at dissolution, content uniformity, and disintegration time in different media at different temperatures. Moreover, the data set includes the stability of the selected tablets’ physical features (diameter, thickness, and weight), functional properties (impact on intestinal cells viability, impact on Bifidobacterium spp. and E. coli adhesion to Caco-2 cells, anti-inflammatory activities) and BC17 viability (only for the tablet containing the viable probiotic) over three months

    Genotoxicity Evaluation of The Novel Psychoactive Substance MTTA

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    MTTA, also known as mephtetramine, is a stimulant novel psychoactive substance characterized by a simil-cathinonic structure. To date, little has been studied on its pharmaco-toxicological profile, and its genotoxic potential has never been assessed. In order to fill this gap, the aim of the present work was to evaluate its genotoxicity on TK6 cells in terms of its ability to induce structural and numerical chromosomal aberrations by means of a cytofluorimetric protocol of the "In Vitro Mammalian Cell Micronucleus (MN) test". To consider the in vitro effects of both the parental compound and the related metabolites, TK6 cells were treated with MTTA in the absence or presence of an exogenous metabolic activation system (S9 mix) for a short-term time (3 h) followed by a recovery period (23 h). No statistically significant increase in the MNi frequency was detected. Specifically, in the presence of S9 mix, only a slight increasing trend was observable at all tested concentrations, whereas, without S9 mix, at 75 μM, almost a doubling of the negative control was reached. For the purposes of comprehensive evaluation, a long-term treatment (26 h) was also included. In this case, a statistically significant enhancement in the MNi frequency was observed at 50 μM

    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
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