Plos One
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Critically ill patients frequently develop acute lung injury (ALI). Disturbed alveolar fibrin turnover, a characteristic feature of ALI, is the result of both activation of coagulation and inhibition of fibrinolysis. Nebulized fibrinolytic agents could exert lung-protective effects, via promotion of fibrinolysis as well as anti-inflammation. ⋯ Local treatment with rtPA or anti-PA1-1 affects pulmonary fibrinolysis but not inflammation in models of direct or indirect ALI in rats.
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A knock-in (KI) mouse model of FHM-1 expressing the R192Q missense mutation of the Cacna1a gene coding for the α1 subunit of CaV2.1 channels shows, at the level of the trigeminal ganglion, selective functional up-regulation of ATP -gated P2X3 receptors of sensory neurons that convey nociceptive signals to the brainstem. Why P2X3 receptors are constitutively more responsive, however, remains unclear as their membrane expression and TRPV1 nociceptor activity are the same as in wildtype (WT) neurons. Using primary cultures of WT or KI trigeminal ganglia, we investigated whether soluble compounds that may contribute to initiating (or maintaining) migraine attacks, such as TNFα, CGRP, and BDNF, might be responsible for increasing P2X3 receptor responses. ⋯ Nonetheless, on cultures made from both genotypes, exogenous TNFα enhanced TRPV1 receptor-mediated currents expressed by a few neurons, suggesting transient amplification of TRPV1 nociceptor responses. CGRP increased P2X3 receptor currents only in WT cultures, although prolonged CGRP receptor antagonism or BDNF neutralization reduced KI currents to WT levels. Our data suggest that, in KI trigeminal ganglion cultures, constitutive up-regulation of P2X3 receptors probably is already maximal and is apparently contributed by basal CGRP and BDNF levels, thereby rendering these neurons more responsive to extracellular ATP.
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Helium is a noble gas with a low density, allowing for lower driving pressures and increased carbon dioxide (CO2) diffusion. Since application of protective ventilation can be limited by the development of hypoxemia or acidosis, we hypothesized that therefore heliox facilitates ventilation in an animal model of ventilator-induced lung injury. ⋯ Heliox allowed for a reduction in respiratory rate and respiratory minute volume during VILI, while maintaining normal acid-base balance. Use of heliox may be a useful approach when protective tidal volume ventilation is limited by the development of severe acidosis.
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Systematic reviews of the literature occupy the highest position in currently proposed hierarchies of evidence. The aims of this study were to assess whether citation classics exist in published systematic review and meta-analysis (SRM), examine the characteristics of the most frequently cited SRM articles, and evaluate the contribution of different world regions. ⋯ Since the late 1970s, the USA, UK, and Canada have taken leadership in the production of citation classic papers. No first author from low or middle-income countries (LMIC) led one of the most cited 100 SRM.
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Exosomes are small membrane vesicles released by a variety of cell types. Exosomes contain genetic materials, such as mRNAs and microRNAs (miRNAs), implying that they may play a pivotal role in cell-to-cell communication. Mesenchymal stem cells (MSCs), which potentially differentiate into multiple cell types, can migrate to the tumor sites and have been reported to exert complex effects on tumor progression. ⋯ The results demonstrated that MSC-derived exosomes significantly down-regulated the expression of vascular endothelial growth factor (VEGF) in tumor cells, which lead to inhibition of angiogenesis in vitro and in vivo. Additionally, miR-16, a miRNA known to target VEGF, was enriched in MSC-derived exosomes and it was partially responsible for the anti-angiogenic effect of MSC-derived exosomes. The collective results suggest that MSC-derived exosomes may serve as a significant mediator of cell-to-cell communication within the tumor microenvironment and suppress angiogenesis by transferring anti-angiogenic molecules.