538 research outputs found

    Sodium Thiosulfate Prevents Chondrocyte Mineralization and Reduces the Severity of Murine Osteoarthritis.

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    Calcium-containing crystals participate in the pathogenesis of OA. Sodium thiosulfate (STS) has been shown to be an effective treatment in calcification disorders such as calciphylaxis and vascular calcification. This study investigated the effects and mechanisms of action of STS in a murine model of OA and in chondrocyte calcification. Hydroxyapatite (HA) crystals-stimulated murine chondrocytes and macrophages were treated with STS. Mineralization and cellular production of IL-6, MCP-1 and reactive oxygen species (ROS) were assayed. STS's effects on genes involved in calcification, inflammation and cartilage matrix degradation were studied by RT-PCR. STS was administered in the menisectomy model of murine OA, and the effect on periarticular calcific deposits and cartilage degeneration was investigated by micro-CT-scan and histology. In vitro, STS prevented in a dose-dependent manner calcium crystal deposition in chondrocytes and inhibited Annexin V gene expression. In addition, there was a reduction in crystal-induced IL-6 and MCP-1 production. STS also had an antioxidant effect, diminished HA-induced ROS generation and abrogated HA-induced catabolic responses in chondrocytes. In vivo, administration of STS reduced the histological severity of OA, by limiting the size of new periarticular calcific deposits and reducing the severity of cartilage damage. STS reduces the severity of periarticular calcification and cartilage damage in an animal model of OA via its effects on chondrocyte mineralization and its attenuation of crystal-induced inflammation as well as catabolic enzymes and ROS generation. Our study suggests that STS may be a disease-modifying drug in crystal-associated OA

    Efek Daun Sirih Merah (Piper Crocatum) Terhadap Kadar Gula Darah Dan Gambaran Morfologi Endokrin Pankreas Tikus Wistar (Rattus Norvegicus)

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    : Leaves of 'sirih merah‘ (Piper Crocatum) contain compounds such as flavonoid, alkaloid and tannin, wich are capable of lowering blood sugar levels. This study aimed to investigate the effects of the administration of ‘sirih merah' broth on blood sugar levels and histopathological features of pancreatic endocrine. This was a laboratory experimental study which was conducted for five month using 12 wistar rats as objects. The rats were divided into four groups: Group A (negative control), which received no treatment; group B, which were given the broth of ‘sirih merah' at 2,4 ml; Group C, which were given sugar solution at 2,4 ml; and Group D, which were given the broth (1,2 ml) and sugar solution (1,2 ml). The results revealed that the levels of blood sugar decreased in rats in Groups B and D but increased in Group C. When compared with rats in Group A, the size and the number of Langerhans islets increased in Group C (more than twice). On the contrary, the number of Langerhans islets in Group D was relatively similar with that of Group A. Conclusion: The administration of the broth of ‘sirih merah' leaves is able to lower blood sugar levels and to cause hyperplasia of pancreatic Langerhans islets

    A new insight into MYC action: control of RNA polymerase II methylation and transcription termination

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    MYC oncoprotein deregulation is a common catastrophic event in human cancer and limiting its activity restrains tumor development and maintenance, as clearly shown via Omomyc, an MYC-interfering 90 amino acid mini-protein. MYC is a multifunctional transcription factor that regulates many aspects of transcription by RNA polymerase II (RNAPII), such as transcription activation, pause release, and elongation. MYC directly associates with Protein Arginine Methyltransferase 5 (PRMT5), a protein that methylates a variety of targets, including RNAPII at the arginine residue R1810 (R1810me2s), crucial for proper transcription termination and splicing of transcripts. Therefore, we asked whether MYC controls termination as well, by affecting R1810me2S. We show that MYC overexpression strongly increases R1810me2s, while Omomyc, an MYC shRNA, or a PRMT5 inhibitor and siRNA counteract this phenomenon. Omomyc also impairs Serine 2 phosphorylation in the RNAPII carboxyterminal domain, a modification that sustains transcription elongation. ChIP-seq experiments show that Omomyc replaces MYC and reshapes RNAPII distribution, increasing occupancy at promoter and termination sites. It is unclear how this may affect gene expression. Transcriptomic analysis shows that transcripts pivotal to key signaling pathways are both up- or down-regulated by Omomyc, whereas genes directly controlled by MYC and belonging to a specific signature are strongly down-regulated. Overall, our data point to an MYC/PRMT5/RNAPII axis that controls termination via RNAPII symmetrical dimethylation and contributes to rewiring the expression of genes altered by MYC overexpression in cancer cells. It remains to be clarified which role this may have in tumor development

    Tuning morphology and magnetism in epitaxial L10-FePt films

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    In this work, well-ordered epitaxial FePt thin ¿lms have been grown by RF sputtering on two different substrates (MgO (100) and SrTiO3 (100)) and the effect of different lattice parameters between the substrate and FePt ¿lm on morphology and magnetic behavior has been considered. Growth conditions have been optimized to obtain different morphologies and magnetic behaviors

    High performance platinum contacts on high-flux CdZnTe detectors

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    The need for direct X-ray detection under high photon flux with moderate or high energies (30–100 keV range) has strongly increased with the rise of the 4th Generation Synchrotron Light Sources, characterised by extremely brilliant beamlines, and of other applications such as spectral computed tomography in medicine and non-destructive tests for industry. The novel Cadmium Zinc Telluride (CZT) developed by Redlen Technologies can be considered the reference material for high-flux applications (HF-CZT). The enhanced charge transport properties of the holes allow the mitigation of the effects of radiation induced polarization phenomena, typically observed in standard CZT materials (LF-CZT) under high photon flux. However, standard LF-CZT electrical contacts led to inacceptable high dark leakage currents on HF-CZT devices. In this work, a detailed study on the characteristics of new optimized sputtered platinum electrical contacts on HF-CZT detectors is reported. The results from electrical and spectroscopic investigations, showed the best performances on HF-CZT detectors with platinum anode, coupled with both platinum or gold cathode. The morphology, structure, and composition of Pt/CZT contact have been analysed by means of Transmission Electron Microscopy (TEM) on microscopic lamellas obtained by Focused Ion Beam (FIB), highlighting the presence of CdTeO3 oxide at the metal semiconductor interface

    Reverse Micelle Strategy for the Synthesis of MnOx-TiO2Active Catalysts for NH3-Selective Catalytic Reduction of NOxat Both Low Temperature and Low Mn Content

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    MnOx-TiO2catalysts (0, 1, 5, and 10 wt % Mn nominal content) for NH3-SCR (selective catalytic reduction) of NOxhave been synthesized by the reverse micelle-assisted sol-gel procedure, with the aim of improving the dispersion of the active phase, usually poor when obtained by other synthesis methods (e.g., impregnation) and thereby lowering its amount. For comparison, a sample at nominal 10 wt % Mn was obtained by impregnation of the (undoped) TiO2sample. The catalysts were characterized by using an integrated multitechnique approach, encompassing X-ray diffraction followed by Rietveld refinement, micro-Raman spectroscopy, N2isotherm measurement at −196 °C, energy-dispersive X-ray analysis, diffuse reflectance UV-vis spectroscopy, temperature-programmed reduction technique, and X-ray photoelectron spectroscopy. The obtained results prove that the reverse micelle sol-gel approach allowed for enhancing the catalytic activity, in that the catalysts were active in a broad temperature range at a substantially low Mn loading, as compared to the impregnated catalyst. Particularly, the 5 wt % Mn catalyst showed the best NH3-SCR activity in terms of both NOxconversion (ca. 90%) and the amount of produced N2O (ca. 50 ppm) in the 200-250 °C temperature range

    Effects of the Brookite Phase on the Properties of Different Nanostructured TiO2 Phases Photocatalytically Active Towards the Degradation of N-Phenylurea

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    Different sol-gel synthesis methods were used to obtain four nanostructured mesoporous TiO2 samples for an efficient photocatalytic degradation of the emerging contaminant N-phenylurea under either simulated solar light (1 Sun) or UV light. Particularly, two TiO2 samples were obtained by means of as many template-assisted syntheses, whereas other two TiO2 samples were obtained by a greener template-free procedure, implying acidic conditions and, then, calcination at either 200 °C or 600 °C. In one case, anatase was obtained, whereas in the other three cases mixed crystalline phases were obtained. The four TiO2 samples were characterized by X-ray powder diffraction (followed by Rietveld analysis); Transmission Electron Microscopy; N2 adsorption/desorption at −196 °C; Diffuse Reflectance UV/Vis spectroscopy and ζ-potential measurements. A commercial TiO2 powder (i. e., Degussa P25) was used for comparison. Differences among the synthesized samples were observed not only in their quantitative phase composition, but also in their nanoparticles morphology (shape and size), specific surface area, pore size distribution and pHIEP (pH at isoelectric point), whereas the samples band-gap did not vary sizably. The samples showed different photocatalytic behavior in terms of N-phenylurea degradation, which are ascribed to their different physico-chemical properties and, especially, to their phase composition, stemming from the different synthesis conditions
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