1,721,005 research outputs found
Suberoylanilide Hydroxamic Acid Analogs with Heteroaryl Amide Group and Different Chain Length: Synthesis and Effect on Histone Deacetylase
No full textThis review covers the last 25 years of the literature on analogs of suberoylanilide hydroxamic acid (SAHA, known also as vorinostat) acting as an HDAC inhibitor. In particular, the topic has been focused on the synthesis and biological activity of compounds where the phenyl group (the surface recognition moiety, CAP) of SAHA has been replaced by an azaheterocycle through a direct bond with amide nitrogen atom, and the methylene chain in the linker region is of variable length. Most of the compounds displayed good to excellent inhibitory activity against HDACs and in many cases showed antiproliferative activity against human cancer cell lines
Lactobacillus crispatus interferes with Chlamydia trachomatis infectivity through modulation of integrin exposure in cervical cells
No full textIn women, urogenital CT infections are often asymptomatic, thus remaining unnoticed and untreated. This can lead to complications and sequelae including pelvic inflammatory disease, tubal infertility and ectopic pregnancy (1, 2). A normal vaginal microbiota, dominated by lactobacilli, is crucial for the prevention of several urogenital and sexually transmitted infections, including Chlamydia (3, 4, 5). This aspect is strengthened by the demonstration that in case of bacterial vaginosis, a clinical condition characterized by the depletion of lactobacilli, a higher risk of STI transmission and acquisition is reported (6).
This study aimed to elucidate the molecular bases of the interaction among lactobacilli, Chlamydia trachomatis and epithelial cells. We evaluated the capacity of lactobacilli cells and supernatants to interfere with C. trachomatis infectivity in HeLa cells, by means of competition, exclusion and displacement mechanisms. Lactobacilli cells were the most active fraction, by means of an exclusion strategy. We investigated the potential mechanism of protection in Lactobacillus crispatus BC5 (model strain), and we demonstrated that the incubation of HeLa cell line with BC5 cells induces important modifications al the level of the epithelial plasma membrane, by altering lipid composition and α5 integrin subunit exposure. When α5 integrin subunits were masked by a specific blocking antibody, Chlamydia infection was precluded. α5 integrin subunit is thus crucial for the pathogen penetration into HeLa cells, and the anti-Chlamydia activity of BC5 can be directly linked to membrane properties modifications in epithelial cells. In conclusion, we identified a potential molecular mechanism at the basis of the protection exerted by Lactobacillus against the sexually transmitted pathogen Chlamydia trachomatis, getting insights into the role of the vaginal microbiota for the woman’s health
“Synthesis and Antiproliferative study of Ru(II) – Hydroxy Stearic Acids ”
No full textProspectives on Ruthenium anticancer agents are encouraging since Ru(II) can directly interact on tumor cells via multiple mechanisms provoking their death. The selection of ligands plays a key role in anticancer activity, the addition of hydrophobic species such as PPh3 to a metal center increases drug uptake in cancer cells and could allow the intercalation in DNA nucleobases pairs. Metallodrugs often show an enhanced anticancer activity compared to free ligands.
In this context, ligands with well-established antitumor activity as 7- and (R)-9-Hydroxy stearic acid (HSA) were selected and reacted with mer-[Ru(H)2(CO)(PPh3)3] to give Ru(II) anticancer species.2 The anticancer in vitro properties of this class of metallo-prodrugs could be ascribed to synergistic effects between the metal center and bioactive ligands. The results have been compared with the analogously coordinated innocuous 12-HSA. The three novel Ru(II)-HSA complexes were fully characterized spectroscopically by using ESI-MS, IR, UV-Vis, and NMR techniques. The nature of Ru-12-HSA was also determined by single crystal X-ray diffraction, Cytotoxicity, cell proliferation, and DNA damage tests were performed demonstrating the biological activity of Ru-7-HSA and Ru-9-HSA
Histone post-translational modifications by HPLC-ESI-MS after HT29 cell treatment with HDAC inhibitors
No full textThe goal of the present work is to establish a correlation between the degree of histone post-translational modifications and the effects caused by treatment of HT29 colon cancer cells with class I-selective (MS-275 and MC1855), class II-selective (MC1568), and non-selective (suberoylanilide hydroxamic acid (SAHA) histone deacetylase inhibitors (HDACi). This correlation could afford a mean to better understand the mechanism of action of new, more potent, and selective HDACi directly on the cells. To this end, LC coupled to MS was applied in studies of time and concentration-dependent treatment with HDACi in HT29 cells. The results were correlated to their potency of histone deacetylase inhibition and to their effects on the cell cycle. The results indicate that the four tested inhibitors show a different pattern of time- and concentration-dependent modification after treatment of HT29 cells. At the selected concentrations, they cause different histone hyperacetylation and different cell cycle effects. In particular, SAHA (non-selective HDACi) affected hyperacetylation of all histones and caused massive cell death. MC1855 (class I-selective HDACi, hydroxamate) proved to be more potent and less toxic (cell arrest in G2/M phase) than SAHA. MS-275 (class I-selective HDACi, benzamide) exhibited a higher degree of hyperacetylation of H4 and a lower degree of H2A, H2B, and H3 acetylation, causing a cell arrest in G0/G1 phase. On the contrary, MC1568 (class II-selective HDACi) produced only a modest hyperacetylation of H4, was ineffective on the other histones, and showed no effect on cell cycle in HT29 cells
Vaginal Lactobacillus strains interfere with Chlamydia trachomatis infection
No full textLactobacilli play a pivotal role in the maintenance of the homeostasis of the vaginal ecosystem, establishing mutualistic synergies with the female host and preventing the overgrowth of exogenous pathogens, including sexually transmitted microorganisms. Chlamydia trachomatis is an obligate intracellular bacterium and represents a leading cause of sexually transmitted disease worldwide; if left untreated, can induce severe sequelae in women, as pelvic inflammatory disease and infertility.
We investigated the in vitro activity of a panel of vaginal Lactobacillus strains (belonging to L. crispatus, L. gasseri, and L. vaginalis species) against C. trachomatis infectivity in human cervical cells (HeLa cells). We demonstrated that vaginal lactobacilli are effective in inhibiting C. trachomatis infectious process, the antagonistic activity is specific for Lactobacillus and L. crispatus is the most active species. We then focused on the molecular basis of the anti-Chlamydia activity exerted by L. crispatus, and we showed that Lactobacillus induces modifications in the lipid organization of HeLa plasma membrane and reduces 51 integrin exposure.
We thus identified a molecular mechanism underlying the protective effect of vaginal Lactobacillus towards C. trachomatis infection, getting insights into the role of cervico-vaginal microbiota in woman’s health
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
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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