672 research outputs found

    Expression of Alpha-Enolase (ENO1), Myc Promoter-Binding Protein-1 (MBP-1) and Matrix Metalloproteinases (MMP-2 and MMP-9) Reflect the Nature and Aggressiveness of Breast Tumors

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    Breast cancer is a complex and heterogeneous disease: Several molecular alterations cause cell proliferation and the acquisition of an invasive phenotype. Extracellular matrix (ECM) is considered essential for sustaining tumor growth and matrix metalloproteinases (MMPs) have been identified as drivers of many aspects of the tumor phenotype. Mounting evidence indicates that both α-enolase (ENO1) and Myc promoter-binding protein-1 (MBP-1) also played pivotal roles in tumorigenesis, although as antagonists. ENO1 is involved in cell growth, hypoxia tolerance and autoimmune activities besides its major role in the glycolysis pathway. On the contrary, MBP-1, an alternative product of ENO1, suppresses cell proliferation and the invasive ability of cancer cells. Since an important task in personalized medicine is to discriminate a different subtype of patients with different clinical outcomes including chances of recurrence and metastasis, we investigated the functional relationship between ENO1/MBP-1 expression and MMP-2 and MMP-9 activity levels in both tissues and sera of breast cancer patients. We focused on the clinical relevance of ENO1 and MMPs (MMP-2 and MMP-9) overexpression in breast cancer tissues: The association between the higher ENO1, MMP-2 and MMP-9 expression with a worse prognosis suggest that the elevated ENO1 and MMPs expression are promising biomarkers for breast cancer. A relationship seems to exist between MBP-1 expression and the decrease in the activity levels of MMP-9 in cancer tissues and MMP-2 in sera. Moreover, the sera of breast cancer patients grouped for MBP-1 expression differentially induced, in vitro, cell proliferation and migration. Our findings support the hypothesis of patient's stratification based on ENO1, MBP-1 and MMPs expression. Elucidating the molecular pathways through which MBP-1 influences MMPs expression and breast cancer regression can lead to the discovery of new management strategies

    Independent Developers: The invisible urban regenerators

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    Most of today’s urban development and regeneration is being provided by the private sector. Cities are being regenerated and redeveloped by institutional developers with projects that can change entire neighbourhoods and city centres. The majority of these developers are interested primarily in institutional properties and other buildings that are large enough to generate the required returns and revenues without bearing too much risks. There are also areas and neighbourhoods that do not experience institutional development and investment because their developmental values and sites are not encouraging to them. Nevertheless, some of these areas gained economic growth and were regenerated without any institutional developers being involved. These kinds of regenerations are either a result of community development or they are the outcome of independent development. This type of development culture is not much studied yet. Independent developers are the invisibles working in the shadows of the big institutional property developers that are often covered in the media and literature. Hardly anybody notices and writes about these small and independent developers that, although developing smaller projects, still have an impact on and are important for urban regeneration. This analysis of independent developers and their projects will provide information on their approach to property development. The report will discuss the major differences between institutional and independent development and how they each address topics like location, market, intervention and funding. By drawing on examples from interviews, literature and other publications, the report will examine independent property developers in more detail and try to analyse their role and their contribution to urban regeneration

    Site-Specific RNA Editing of Stop Mutations in the CFTR mRNA of Human Bronchial Cultured Cells

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    It is reported that about 10% of cystic fibrosis (CF) patients worldwide have nonsense (stop) mutations in the CFTR gene, which cause the premature termination of CFTR protein synthesis, leading to a truncated and non-functional protein. To address this issue, we investigated the possibility of rescuing the CFTR nonsense mutation (UGA) by sequence-specific RNA editing in CFTR mutant CFF-16HBEge, W1282X, and G542X human bronchial cells. We used two different base editor tools that take advantage of ADAR enzymes (adenosine deaminase acting on RNA) to edit adenosine to inosine (A-to-I) within the mRNA: the REPAIRv2 (RNA Editing for Programmable A to I Replacement, version 2) and the minixABE (A to I Base Editor). Immunofluorescence experiments show that both approaches were able to recover the CFTR protein in the CFTR mutant cells. In addition, RT-qPCR confirmed the rescue of the CFTR full transcript. These findings suggest that site-specific RNA editing may efficiently correct the UGA premature stop codon in the CFTR transcript in CFF-16HBEge, W1282X, and G542X cells. Thus, this approach, which is safer than acting directly on the mutated DNA, opens up new therapeutic possibilities for CF patients with nonsense mutations

    Synthesis and antibacterial activity of iron-hexacyanocobaltate nanoparticles

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    This paper deals with the synthesis and characterization of iron-hexacyanocobaltate (FeHCC) and its antibacterial properties. The nanoparticles were prepared by a facile co-precipitation technique. Crystal structure, particle morphology, and elemental composition were determined using X-ray Powder Diffraction, X-ray fluorescence spectroscopy, Transmission Electron Microscopy (TEM), and Infrared Spectroscopy (IR). The antibacterial activity of the FeHCC nanoparticles was tested against Escherichia coli and Staphylococcus aureus as models for Gram-negative and Gram-positive bacteria, respectively, by bacterial counting method and microscopic visualization (TEM, FEG-SEM, and fluorescence microscopy). The results showed that the FeHCC nanoparticles bind to the bacterial cells, inhibit bacterial growth in a dose- and time-dependent manner, inducing a loss of the membrane potential, the production of reactive oxygen species and the release of macromolecules (nucleic acids and proteins) in the extracellular environment. To the best of our knowledge, this is the first study reporting the antimicrobial effects of metal-hexacyanometallates suggesting practical uses of these materials in different areas, such as self-cleaning surfaces or food packaging
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