Shock : molecular, cellular, and systemic pathobiological aspects and therapeutic approaches : the official journal the Shock Society, the European Shock Society, the Brazilian Shock Society, the International Federation of Shock Societies
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The aim of the present study was to examine the effect and possible mechanism of salvianolic acid B (SalB) on pulmonary microcirculation disturbance induced by lipopolysaccharide (LPS) in rat. Male Sprague-Dawley rats were subjected to thoracotomy under continuous anesthesia and mechanical ventilation. Albumin leakage from pulmonary capillary and the numbers of leukocytes adherent to the pulmonary capillary wall were determined for 60 min by an upright microscope upon LPS (2 mg · kg(-1) · h(-1)) infusion with or without administration of SalB (5 mg · kg(-1) · h(-1)). ⋯ In addition, LPS increased pulmonary tissue wet-to-dry weight ratio and tumor necrosis factor α and interleukin 8 levels in plasma and bronchoalveolar lavage fluid enhanced the expression of E-selectin, intercellular adhesion molecule 1, myeloperoxidase, MMP-2, and MMP-9, whereas it decreased the expression of AQP-1 and AQP-5 in pulmonary tissue, all of which were attenuated by SalB pretreatment. Salvianolic acid B pretreatment improves pulmonary microcirculation disturbance and lung injury on LPS exposure. More studies are required to evaluate the potential of SalB as an option for protecting lung from endotoxemia.
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Postconditioning prevents cardiomyocytes from ischemia/reperfusion-induced apoptosis. However, little is known about the molecular mechanisms that mediate the cardioprotective effect of postconditioning. ⋯ In addition, p53 is involved in the regulatory role of postconditioning in PUMA expression. Our data reveal a cardioprotective pathway of postconditioning in which it represses PUMA.
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Streptococcal toxic shock syndrome is most frequently associated with Streptococcus pyogenes of the M1 serotype. Simvastatin protects against M1 protein-induced acute lung damage, although downstream mechanisms remain elusive. Herein, we hypothesized that geranylgeranylation might regulate proinflammatory effects in M1 protein-induced lung injury. ⋯ Notably, GGTI-2133 abolished M1 protein-induced gene expression of CXC chemokines in alveolar macrophages. These novel findings indicate that geranylgeranyl transferase is an important regulator of neutrophil recruitment and CXC chemokine production in the lung. Thus, targeting geranylgeranyl transferase might be a potent way to ameliorate streptococcal M1 protein-triggered acute lung injury.
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A recent study showed that the injection of mitochondria isolated from a nonischemic region mitigated myocardial injury. We tested the protective effects of infusing isolated mitochondria on the reperfusion injury in the liver of rats. A partial liver ischemia-reperfusion (I/R) model in male Wistar rats was used. ⋯ Our results show that the elevation of serum alanine aminotransferase (414.3 ± 67.1 vs. 208.8 ± 30.2 U/L), the necrosis of hepatocytes on hematoxylin-eosin staining, increase in positive counts in TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) staining (59.5% ± 4.4% vs. 24.6% ± 9.1%), the expression of cytosolic cytochrome c, cleaved caspase 9, and 4-hydroxynonenal were all reduced in the I/R-mito group, compared with the I/R-vehicle group. The membrane potential of the isolated mitochondria measured by JC-1 fluorescence remained high, and the infused mitochondria were distributed in the liver parenchyma at 240 min after reperfusion. These results demonstrate that an intrasplenic infusion of viable mitochondria isolated from the donor before reperfusion significantly reduced I/R injury in the liver.
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Chronic lung diseases cause serious morbidity and mortality, and effective treatments are limited. Induced pluripotent stem cells (iPSCs) lacking the reprogramming factor c-Myc (3-gene iPSCs) can be used as ideal tools for cell-based therapy because of their low level of tumorigenicity. In this study, we investigated whether 3-gene iPSC transplantation could rescue bleomycin-induced pulmonary fibrosis. ⋯ Furthermore, IP-10 neutralization via treatment with IP-10-neutralizing antibodies ameliorated the reparative effect of either 3-gene iPSCs or iPSC-CM on collagen content, neutrophil and monocyte accumulation, pulmonary fibrosis, and recipient survival. Intravenous delivery of 3-gene iPSCs/iPSC-CM alleviated the severity of histopathologic and physiologic impairment in bleomycin-induced lung fibrosis. The protective mechanism was partially mediated by the early moderation of inflammation, reduced levels of cytokines and chemokines that mediate inflammation and fibrosis, and an increased production of antifibrotic IP-10 in the injured lungs.