102 research outputs found

    VEGF is a chemoattractant for FGF-2–stimulated neural progenitors

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    Mmigration of undifferentiated neural progenitors is critical for the development and repair of the nervous system. However, the mechanisms and factors that regulate migration are not well understood. Here, we show that vascular endothelial growth factor (VEGF)-A, a major angiogenic factor, guides the directed migration of neural progenitors that do not display antigenic markers for neuron- or glia-restricted precursor cells. We demonstrate that progenitor cells express both VEGF receptor (VEGFR) 1 and VEGFR2, but signaling through VEGFR2 specifically mediates the chemotactic effect of VEGF. The expression of VEGFRs and the chemotaxis of progenitors in response to VEGF require the presence of fibroblast growth factor 2. These results demonstrate that VEGF is an attractive guidance cue for the migration of undifferentiated neural progenitors and offer a mechanistic link between neurogenesis and angiogenesis in the nervous system

    Sivelestat sodium attenuates acute lung injury by inhibiting JNK/NF-ÎşB and activating Nrf2/HO-1 signaling pathways

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    Sivelestat sodium (SIV), a neutrophil elastase inhibitor, is mainly used for the clinical treatment of acute respiratory distress syndrome (ARDS) or acute lung injury (ALI). However, studies investigating the effects of SIV treatment of ALI are limited. Therefore, this study investigated the potential molecular mechanism of the protective effects of SIV against ALI. Human pulmonary microvascular endothelial cells (HPMECs) were stimulated with tumor necrosis factor α (TNF-α), and male Sprague-Dawley rats were intratracheally injected with Klebsiella pneumoniae (KP) and treated with SIV, ML385, and anisomycin (ANI) to mimic the pathogenetic process of ALI in vitro and in vivo, respectively. The levels of inflammatory cytokines and indicators of oxidative stress were assessed in vitro and in vivo. The wet/dry (W/D) ratio of lung tissues, histopathological changes, inflammatory cells levels in bronchoalveolar lavage fluid (BALF), and survival rates of rats were analyzed. The JNK/NF-κB (p65) and Nrf2/HO-1 levels in the HPMECs and lung tissues were analyzed by western blot and immunofluorescence analyses. Administration of SIV reduced the inflammatory factors levels, intracellular reactive oxygen species (ROS) production, and malondialdehyde (MDA) levels and increased the levels of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in lung tissues. Meanwhile, SIV alleviated pathological injuries, decreased the W/D ratio, and inflammatory cell infiltration in lung tissue. In addition, SIV also inhibited the activation of JNK/NF-κB signaling pathway, promoted nuclear translocation of Nrf2, and upregulated the expression of heme oxygenase 1 (HO-1). However, ANI or ML385 significantly reversed these changes. SIV effectively attenuated the inflammatory response and oxidative stress. Its potential molecular mechanism was related to the JNK/NF-κB activation and Nrf2/HO-1 signaling pathway inhibition. This further deepened the understanding of the protective effects of SIV against ALI

    Modelling human choices: MADeM and decision‑making

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    Research supported by FAPESP 2015/50122-0 and DFG-GRTK 1740/2. RP and AR are also part of the Research, Innovation and Dissemination Center for Neuromathematics FAPESP grant (2013/07699-0). RP is supported by a FAPESP scholarship (2013/25667-8). ACR is partially supported by a CNPq fellowship (grant 306251/2014-0)

    Synthesis and crystal structures of <i>N</i>-(2,3,4,6<i>-</i>Tetra-<i>O</i>-acetyl-<i>β</i>-<i>D</i>-glycosyl)thiocarbamoyl <span style="font-size:12.0pt;line-height:115%;font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";mso-ansi-language:NL;mso-fareast-language: EN-IN;mso-bidi-language:HI" lang="NL">methylene diamine</span>

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    1072-1075The structure of N-(2,3,4,6-Tetra-O-acetyl-β-D-glycosyl)thiocarbamoyl methylene diamine, C16H25N3O9S has been determined by X-ray diffraction method. It crystallizes in the monoclinic system, space group P2l, with lattice parameters a = 7.6560(2), b = 10.3113(3), c = 14.1813(1)Å, β = 100.879 (2)o, and Z = 2. The hexapyranosyl ring adopts a chair conformation. All the ring substituents are in the equatorial position. The acetoxylmethyl group is in the gauche- gauche conformation. The S atom is in synperiplanar conformation, while the N-C-N-C linkage is antiperiplanar. The N-H...O intermolecular hydrogen bonds link the molecules into infinite chains and these are connected by C-H...O interaction
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