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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Sepsis results from a dysregulated host immune response to infection and is responsible for ~11 million deaths each year. In the laboratory, many aspects of sepsis can be replicated using a cecal ligation and puncture model, which is considered the most clinically relevant rodent model of sepsis. ⋯ Treatment of mice with 10 μg of a synthetic 68-amino acid peptide derived from an immunomodulatory molecule secreted by a parasitic worm of humans and livestock, F. hepatica , termed F. hepatica helminth defense molecule, potently suppressed the systemic inflammatory profile, protected mice against acute kidney injury, and improved survival between 48 and 72 h after procedure. These results suggest that the anti-inflammatory parasite-derived F. hepatica helminth defense molecule peptide has potential as a biotherapeutic treatment for sepsis.
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Background : New strategies are needed to mitigate further tissue injury during traumatic limb ischemia in cases requiring damage control resuscitation (DCR). Little is known about the pathophysiology and injury course in acute limb ischemia (ALI) with DCR in polytraumatized casualties. We therefore investigated the effects of therapeutic limb hypothermia in a swine model of ALI and DCR. ⋯ Mean nerve histology scores did not differ between the 5°C and paired control limbs, or between the mean muscle and nerve histology scores of the 15°C and paired control limbs. Conclusion : Cooling to 15°C significantly reduced local tissue metabolites compared to paired controls, while producing no significant increase in histologic damage, whereas cooling to 5°C increased histologic muscle damage. These results suggest an approach to prevention of ischemic injury through local hypothermia but warrant further functional testing.
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Mice used in biomedical research are typically housed at ambient temperatures (22°C-24°C) below thermoneutrality (26°C-31°C). This chronic cold stress triggers a hypermetabolic response that may limit the utility of mice in modeling hypermetabolism in response to burns. To evaluate the effect of housing temperature on burn-induced hypermetabolism, mice were randomly assigned to receive sham, small, or large scald burns. ⋯ Locomotion was significantly reduced in mice with large burns compared to sham and small burn groups, irrespective of sex or housing temperature ( P < 0.05). Housing at 30°C revealed sexual dimorphism in terms of the impact of burns on body mass and composition, where males with large burns displayed marked cachexia, whereas females did not. Collectively, this study demonstrates a sex-dependent role for housing temperature in influencing energetics and body composition in a rodent model of burn trauma.
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Background: Growing evidence has found the critical role of circular RNAs (circRNAs) in sepsis-induced acute kidney injury (S-AKI). CircTMCO3 has been found to be involved in tumor microenvironment changes of ovarian cancer. This study aimed to explore whether circTMCO3 functions in S-AKI, and if so, to elucidate the molecular mechanism. ⋯ ZEB2 was identified to be a target of miR-218-5p; its downregulation not only reversed the impacts of miR-218-5p inhibitor on S-AKI, but also mitigated the effects mediated by circTMCO3 upregulation in vitro. Conclusions: CircTMCO3 protects against S-AKI by regulating miR-218-5p/ZEB2 axis, thereby mediating antiapoptotic, antioxidant, and anti-inflammatory activities. This indicates that increasing circTMCO3 expression might be a future therapeutic method for S-AKI.