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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Most gene expression studies of sepsis have used either whole blood or specific leukocyte fractions as source tissues for RNA. Data regarding the relative utility of these different tissue sources are lacking. ⋯ Our results support the use of whole blood to derive gene expression data in sepsis studies investigating novel diagnostics and subtype discovery. This strategy has a number of practical advantages, and the resulting data also have potential utility in developing molecular classifications of sepsis syndromes.
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During abdominal sepsis, the inhibition of gastrointestinal (GI) motility together with mucosal barrier dysfunction will lead to increased bacterial translocation and maintenance of sepsis. The activation of the vagal anti-inflammatory pathway remains an appealing therapeutic strategy in sepsis. In this respect, selective alpha7 nicotinic acetylcholine receptor (α7nAChR) agonists have shown anti-inflammatory properties in several animal models of inflammation. ⋯ Our results show that peripheral targeting of the vagal anti-inflammatory pathway proves beneficial in an animal model of polymicrobial abdominal sepsis. A major role is allocated to splenic immune cells in the development of sepsis, as preventive splenectomy was protective for the development of sepsis. Data on the Chrna7 mice suggest that the beneficial effects mediated by GTS-21 on inflammation and motility might be related to activation of other receptors besides the α7nAChR.
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Lung fibrosis is an aggressive disease with uncontrolled fibrotic response and no effective therapeutic treatment. Epithelial-to-mesenchymal transition (EMT) has been proved to be an important pathological feature in lung fibrosis. In this study, we investigated whether MaR1, a kind of proresolving lipid mediators, could inhibit TGF-β1-induced EMT in vitro and lung fibrosis in vivo. ⋯ TGF-β1 concentration in bronchoalveolar lavage and fibrotic markers (fibronectin and α-SMA) in lung tissues are inhibited by MaR1 administration. These data indicate that MaR1 inhibits TGF-β1-induced EMT and attenuates bleomycin-induced pulmonary fibrosis. MaR1 may be a promising strategy for alleviation of lung fibrosis.
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Acute alterations in skeletal muscle protein metabolism are a well-established event associated with the stress response to burns. Nevertheless, the long-lasting effects of burn injury on skeletal muscle protein turnover are incompletely understood. This study was undertaken to investigate fractional synthesis (FSR) and breakdown (FBR) rates of protein in skeletal muscle of pediatric burn patients (n = 42, >30% total body surface area burns) for up to 1 year after injury. ⋯ Therefore, net protein balance was lower in burn patients compared with healthy men from 2 weeks to 12 months post-injury (P < 0.05). These findings show that skeletal muscle protein turnover stays elevated for up to 1 year after burn, an effect attributable to simultaneous increases in FBR and FSR. Muscle FBR exceeds FSR during this time, producing a persistent negative net protein balance, even in the post-prandial state, which likely contributes to the prolonged cachexia seen in burned victims.
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Infectious complications, sepsis, and multiple organ dysfunction syndrome (MODS) remain important causes for morbidity and mortality in patients who survive the initial trauma. Increasing evidence suggests that genetic variants, particularly single nucleotide polymorphisms (SNPs), are critical determinants for interindividual differences in both inflammatory responses and clinical outcome in sepsis patients. Although the effect of SNPs on sepsis and MODS has been studied in many populations and diseases, this review aimed to summarize the current knowledge on the effect of SNPs on infectious complication specifically in trauma patients. ⋯ A number of genetic variations have so far been studied in cohorts of trauma patients. Studies are often unique and numbers sometimes small. No definitive conclusions can be reached at this time about the influence of specific sequence variations on outcome in trauma patients.