380 research outputs found

    Alpha-tocopherol exerts protective function against the mucotoxicity of particulate matter in amphibian and human goblet cells

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    Exposure to particulate matter (PM) in ambient air is known to increase the risk of cardiovascular disorders and mortality. The cytotoxicity of PM is mainly due to the abnormal increase of reactive oxygen species (ROS), which damage cellular components such as DNA, RNA, and proteins. The correlation between PM exposure and human disorders, including mortality, is based on long-term exposure. In this study we have investigated acute responses of mucus-secreting goblet cells upon exposure to PM derived from a heavy diesel engine. To this end, we employed the mucociliary epithelium of amphibian embryos and human Calu-3 cells to examine PM mucotoxicity. Our data suggest that acute exposure to PM significantly impairs mucus secretion and results in the accumulation of mucus vesicles in the cytoplasm of goblet cells. RNA-seq analysis revealed that acute responses to PM exposure significantly altered gene expression patterns; however, known regulators of mucus production and the secretory pathway were not significantly altered. Interestingly, pretreatment with alpha-tocopherol nearly recovered the hyposecretion of mucus from both amphibian and human goblet cells. We believe this study demonstrates the mucotoxicity of PM and the protective function of alpha-tocopherol on mucotoxicity caused by acute PM exposure from heavy diesel engines

    Prolonged Activation of ERK Contributes to the Photorejuvenation Effect in Photodynamic Therapy in Human Dermal Fibroblasts

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    Photodynamic therapy (PDT) is known to be effective in the photorejuvenation of photoaged skin. However, the molecular mechanisms of rejuvenation by PDT remain elusive. In this study, we aimed to understand the molecular events occurring during the photorejuvenation after PDT in dermal fibroblasts in vitro. First, we found that PDT conditions resulted in an increased fibroblast proliferation and motility in vitro. Under this condition, cells had increased intracellular reactive oxygen species (ROS) production. Importantly, PDT induced a prolonged activation of extracellular signalā€“regulated kinase (ERK) with a corresponding increase in matrix metalloproteinase (MMP)-3 and collagen type IĪ± messenger RNA and protein. Moreover, inhibition of PDT-induced ERK activation significantly suppressed fibroblast proliferation and expression of MMP-3 and collagen type IĪ± following PDT. In addition, NAC (an antioxidant) inhibited PDT-induced fibroblast proliferation and ERK activation indicating that prolonged ERK activation and intracellular ROS contribute to the proliferation of fibroblasts and the dermal remodeling process for skin rejuvenation. We also identified increased collagen volume and decreased elastotic materials that are used as markers of photoaging in human skin samples using histochemical studies. Results from this study suggest that intracellular ROS stimulated by PDT in dermal fibroblasts lead to prolonged activation of ERK and, eventually, fibroblast proliferation and activation. Our data thus reveal a molecular mechanism underlying the skin rejuvenation effect of PDT

    Implementation of central line-associated bloodstream infection prevention bundles in a surgical intensive care unit using peer tutoring

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    This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Abstract Background Central line-associated bloodstream infections (CLABSIs) can be prevented through well-coordinated, multifaceted programs. However, implementation of CLABSI prevention programs requires individualized strategies for different institutional situations, and the best strategy in resource-limited settings is uncertain. Peer tutoring may be an efficient and effective method that is applicable in such settings. Methods A prospective intervention was performed to reduce CLABSIs in a surgical intensive care unit (SICU) at a tertiary hospital. The core interventions consisted of implementation of insertion and maintenance bundles for CLABSI prevention. The overall interventions were guided and coordinated by active educational programs using peer tutoring. The CLABSI rates were compared for 9Ā months pre-intervention, 6Ā months during the intervention and 9Ā months post-intervention. The CLABSI rate was further observed for three years after the intervention. Results The rate of CLABSIs per 1000 catheter-days decreased from 6.9 infections in the pre-intervention period to 2.4 and 1.8 in the intervention (6Ā m; PĀ =Ā 0.102) and post-intervention (9Ā m; PĀ =Ā 0.036) periods, respectively. A regression model showed a significantly decreasing trend in the infection rate from the pre-intervention period (PĀ <Ā 0.001), with incidence-rate ratios of 0.348 (95% confidence interval [CI], 0.98ā€“1.23) in the intervention period and 0.257 (95% CI, 0.07ā€“0.91) in the post-intervention period. However, after the 9-month post-intervention period, the yearly CLABSI rates reverted to 3.0ā€“5.4 infections per 1000 catheter-days over 3Ā years. Conclusions Implementation of CLABSI prevention bundles using peer tutoring in a resource-limited setting was useful and effectively reduced CLABSIs. However, maintaining the reduced CLABSI rate will require further strategies

    Multimodal MRI-Based Triage for Acute Stroke Therapy: Challenges and Progress

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    Revascularization therapies have been established as the treatment mainstay for acute ischemic stroke. However, a substantial number of patients are either ineligible for revascularization therapy, or the treatment fails or is futile. At present, non-contrast computed tomography is the first-line neuroimaging modality for patients with acute stroke. The use of magnetic resonance imaging (MRI) to predict the response to early revascularization therapy and to identify patients for delayed treatment is desirable. MRI could provide information on stroke pathophysiologies, including the ischemic core, perfusion, collaterals, clot, and bloodā€“brain barrier status. During the past 20 years, there have been significant advances in neuroimaging as well as in revascularization strategies for treating patients with acute ischemic stroke. In this review, we discuss the role of MRI and post-processing, including machine-learning techniques, and recent advances in MRI-based triage for revascularization therapies in acute ischemic stroke

    Role of Amphipathic Helix of a Herpesviral Protein in Membrane Deformation and T Cell Receptor Downregulation

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    Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip) of T lymphotropic Herpesvirus saimiri (HVS) is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM) domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation
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