Molecular medicine reports
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Basic fibroblast growth factor (bFGF) has proven useful for neural stem and progenitor cells during the transplantation‑mediated therapeutic effect of bone mesenchymal stem cells (BMSCs). Endogenous bFGF expression levels increase during brain development and gradually diminish with aging. ⋯ The neuronal differentiation rate was not consistent with neurological functional recovery rate over time. bFGF may promote the transplantation‑mediated therapeutic effect of BMSCs more significantly and rapidly in rats following TBI, with a small proportion of differentiated neurons. In conclusion, exogenous bFGF functions as a booster of the transplantation‑mediated therapeutic effect of BMSCs following TBI.
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Randomized Controlled Trial
Effects of nitrous oxide on the production of cytokines and chemokines by the airway epithelium during anesthesia with sevoflurane and propofol.
The aim of this study was to evaluate the effects of nitrous oxide (a gaseous anesthetic) on the in vivo production of inflammatory cytokines and chemokines by the airway epithelium, when combined with sevoflurane or propofol. Subjects undergoing simple or segmental mastectomy were randomly assigned to the sevoflurane and nitrous oxide, sevoflurane and air, propofol and nitrous oxide, or propofol and air group (all n=13). Epithelial lining fluid (ELF) was obtained using the bronchoscopic microsampling method prior to and following the mastectomy to enable measurement of the pre- and post-operative levels of certain inflammatory cytokines and chemokines using a cytometric bead array system. ⋯ Furthermore, the IL-12p70 levels were significantly reduced in the ELF following the operations that involved the inhalation of sevoflurane and air, although the IL-12p70 levels were not significantly changed by the inhalation of nitrous oxide and sevoflurane. These observations suggest that the combination of sevoflurane and nitrous oxide induces an inflammatory response (increased production of IL-1β, IL-8 and MCP-1) and suppresses the anti-inflammatory response (reduced production of IL-12p70) in the local milieu of the airway. Thus, the combination of these compounds should be carefully administered for anesthesia.
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Airway remodeling is characterized by airway wall thickening, subepithelial fibrosis, increased smooth muscle mass, angiogenesis and an increase in mucous glands, which may lead to a chronic and obstinate asthma with pulmonary function depression. In the present study, we observed substantially thickened lung tissue with extensive fibrosis in ovalbumin-sensitized mice, which was interrelated with transforming growth factor-β1 (TGF-β1) expression in bronchoalveolar lavage fluid. ⋯ Of note, a significantly increased synthesis of fibronectin was observed following TGF-β1 treatment, which further supported the hypothesis that EMT is a pivotal factor in peribronchial fibrosis. In combination, the results indicated that myofibroblasts deriving from bronchial epithelial cells via EMT may contribute to peribronchial fibrosis and that Snail may be an important factor in this phenomenon.
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Erythropoietin (EPO) has been shown to be neuroprotective in various models of neuronal injury. The aim of the present study was to investigate the beneficial effect of recombinant human EPO (rhEPO) following intracerebral hemorrhage (ICH) and the underlying molecular and cellular mechanisms. ICH was induced using autologous blood injection in adult rats. rhEPO (5000 IU/kg) or vehicle was administered to rats with ICH 2 h following surgery and every 24 h for 1 or 3 days. ⋯ Inhibiting the PI3K pathway with wortmannin abolished the rhEPO‑mediated neuroprotective effects. Moreover, western blot analysis showed that rhEPO induced the upregulation of Akt phosphorylation and downregulation of glycogen synthase kinase (GSK)‑3β phosphorylation, which were reversed by pretreatment with wortmannin, indicating the involvement of PI3K signaling in rhEPO-mediated anti-apoptotic and anti-inflammatory effects following ICH. In conclusion, these results suggested that rhEPO may exert its beneficial effects in ICH through the activation of the PI3K signaling pathway.
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Myeloid-derived suppressor cells (MDSCs) and dendritic cells (DCs) are important in the immune response. In vitro, DCs are derived from myeloid precursors by stimulation with granulocyte macrophage colony‑stimulating factor and interleukin‑4. ⋯ In the present study, MPL was used to disturb DC differentiation from myeloid precursors and it was observed that prolonged stimulation with MPL led to the accumulation of MDSCs in vitro and in vivo. In conclusion, it was demonstrated that stimulation by MPL from the beginning of cell differentiation disturbed the development of DCs and led to the accumulation of MDSCs.