24 research outputs found

    Cardiopoietic cell therapy for advanced ischemic heart failure: results at 39 weeks of the prospective, randomized, double blind, sham-controlled CHART-1 clinical trial

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    Cardiopoietic cells, produced through cardiogenic conditioning of patients' mesenchymal stem cells, have shown preliminary efficacy. The Congestive Heart Failure Cardiopoietic Regenerative Therapy (CHART-1) trial aimed to validate cardiopoiesis-based biotherapy in a larger heart failure cohort

    The risk of developing a CIN2+ lesion in women with HPV16 and 18, versus women with other HPV types: follow up study

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    Of the 12 known carcinogenic HPV types, HPV16 is by far the most carcinogenic in terms of numbers of cases of cervical cancer and its immediate precursor, cervical intraepithelial neoplasia grade 3 (CIN3). HPV18 is second in terms of etiologic importance (but is disproportionately important for adenocarcinomas)(1-3). Aims:Our study compares the risk of developing a CIN2+ lesions in women with HPV16 and 18, versus women with other HPV types. Sensitivity, specificity and their respective 95% confidence intervals (95%CI), positive predictive values (PPV) and negative predictive values (NPV) were also calculated on the basis of the results of cytologic and histologic follow-up

    Structure-based virtual screening allows the identification of efficient modulators of E-cadherin-mediated cell-cell adhesion

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    Cadherins are a large family of transmembrane calcium-dependent cell adhesion proteins that orchestrate adherens junction formation and are crucially involved in tissue morphogenesis. Due to their important role in cancer development and metastasis, cadherins can be considered attractive targets for drug discovery. A recent crystal structure of the complex of a cadherin extracellular portion and a small molecule inhibitor allowed the identification of a druggable interface, thus providing a viable strategy for the design of cadherin dimerization modulators. Here, we report on a structure-based virtual screening approach that led to the identification of efficient and selective modulators of E-cadherin-mediated cell-cell adhesion. Of all the putative inhibitors that were identified and experimentally tested by cell adhesion assays using human pancreatic tumor BxPC-3 cells expressing both E-cadherin and P-cadherin, two compounds turned out to be effective in inhibiting stable cell-cell adhesion at micromolar concentrations. Moreover, at the same concentrations, one of them also showed anti-invasive properties in cell invasion assays. These results will allow further development of novel and selective cadherin-mediated cell-cell adhesion modulators for the treatment of a variety of cadherin-expressing solid tumors and for improving the efficiency of drug delivery across biological barriers

    Computational analysis of cysteine and methionine metabolism and its regulation in dairy starter and related bacteria.

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    Item does not contain fulltextSulfuric volatile compounds derived from cysteine and methionine provide many dairy products with a characteristic odor and taste. To better understand and control the environmental dependencies of sulfuric volatile compound formation by the dairy starter bacteria, we have used the available genome sequence and experimental information to systematically evaluate the presence of the key enzymes and to reconstruct the general modes of transcription regulation for the corresponding genes. The genomic organization of the key genes is suggestive of a subdivision of the reaction network into five modules, where we observed distinct differences in the modular composition between the families Lactobacillaceae, Enterococcaceae, and Leuconostocaceae, on the one hand, and the family Streptococcaceae, on the other. These differences are mirrored by the way in which transcription regulation of the genes is structured in these families. In the Lactobacillaceae, Enterococcaceae, and Leuconostocaceae, the main shared mode of transcription regulation is methionine (Met) T-box-mediated regulation. In addition, the gene metK, encoding S-adenosylmethionine (SAM) synthetase, is controlled via the S(MK) box (SAM). The S(MK) box is also found upstream of metK in species of the family Streptococcaceae. However, the transcription control of the other modules is mediated via three different LysR-family regulators, MetR/MtaR (methionine), CmbR (O-acetyl[homo]serine), and HomR (O-acetylhomoserine). Redefinition of the associated DNA-binding motifs helped to identify/disentangle the related regulons, which appeared to perfectly match the proposed subdivision of the reaction network.1 juli 201
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