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 is one of the leading causes of morbidity and mortality worldwide. Monocytes seem to undergo functional reprogramming during sepsis, resulting in dysregulated host immune response. To clarify this dysregulation mechanism, we investigated three histone modifications found in promoters of genes involved in innate immune response, and associated these findings with gene transcription in septic patients. ⋯ In addition, we found moderate to strong correlation between gene transcription and the enzymes that modulate these histone modifications in the transcriptome data sets. Our study, one of the pioneering by evaluating septic patients' samples, suggests that epigenetic enzymes modulate the prevalent histone marks in promoters of genes involved in the immune-inflammatory response, altering the transcription of these specific genes during sepsis. Furthermore, nonsurviving sepsis patients have a more pronounced epigenetic dysregulation compared with survivors, suggesting a more dysfunctional response.
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Objective: This study evaluated the feasibility of a combination of pelvic binder and rectal balloon compression in managing fatal venous hemorrhage in a canine model of pelvic fracture. Methods: Rectums from humans (rectal cancer patients), swine, and canines were retrieved to determine their elasticity by measuring their stress and strain. Canines were selected as the animal model in this study because their rectum demonstrated more reversible strain than swine rectum. ⋯ Results: Our results showed that after the reproducible injuries in both internal iliac veins, the combination of pelvic binder and rectal balloon compression was associated with the best survival rate and survival time compared with the other treatment groups. In addition, the combination of pelvic binder and rectal balloon compression exhibited more stable hemodynamics than the pelvic binder or rectal balloon compression treatment alone. Conclusions: This study demonstrated the potential feasibility of using pelvic binder combined with rectal balloon compression to manage the fatal venous bleeding in pelvic fractures.
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Background: The kidney is the most common extrapulmonary organ injured in sepsis. The current study examines the ability of aerosolized nanochemically modified tetracycline 3 (nCMT-3), a pleiotropic anti-inflammatory agent, to attenuate acute kidney injury (AKI) caused by intratracheal LPS. Methods: C57BL/6 mice received aerosolized intratracheal nCMT-3 (1 mg/kg) or saline, followed by intratracheal LPS (2.5 mg/kg) to induce acute lung injury-induced AKI. ⋯ Lipopolysaccharide-treated mice demonstrated renal injury with increased levels of inflammatory cytokines (IL-1β, IL-6), active MMP-2 and MMP-9, proapoptotic proteins (cytochrome C, Bax/Bcl-2 ratio, cleaved caspase-3), apoptotic cells, inflammasome activation (NLRP3, caspase-1), and p38 signaling. Intratracheal nCMT-3 significantly attenuated all the measured markers of renal injury, inflammation, and apoptosis. Conclusions: Pretreatment with aerosolized nCMT-3 attenuates LPS-induced AKI by inhibiting renal NLRP3 inflammasome activation, renal inflammation, and apoptosis.
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Background : Systemic inflammation acts as a contributor to neurologic deficits after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). Extracellular cold-inducible RNA-binding, protein (CIRP) has been demonstrated to be responsible in part for the inflammation through binding to toll-like receptor 4 (TLR4) after cerebral ischemia. The short peptide C23 derived from CIRP has a high affinity for TLR4, we hypothesize that C23 reduces systemic inflammation after CA/CPR by blocking the binding of CIRP to TLR4. ⋯ In addition, C23 treatment can reduce the apoptosis of hippocampus neurons ( P < 0.05). Finally, the rats in the C23 group have improved survival rate and neurological prognosis ( P < 0.05). Conclusions: These findings suggest that C23 can reduce systemic inflammation and it has the potential to be developed into a possible therapy for post-CA syndrome.
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Objectives: This study investigated the role and potential involvement of pulmonary vascular glycocalyx degradation in acute lung injury in rats with severe heatstroke (HS). Methods: Rats in an established HS model were exposed to a heated environment for 60 min in an incubator (temperature, 40°C ± 2°C; humidity, 65% ± 5%). Following pretreatment with heparanase III (HPSE III) or heparin, pathological lung injury, arterial blood gas, alveolar barrier disruption, and hemodynamic changes were evaluated. ⋯ Moreover, TNF-α and IL-6 were overexpressed following heat stress. Furthermore, apoptosis of pulmonary tissues and the concentration of malondialdehyde in rat lungs increased in the HS and HPSE groups. Conclusions : Heatstroke induced pulmonary glycocalyx degradation, which increased vascular permeability and aggravated vascular endothelial dysfunction, contributing to apoptosis, inflammation, and oxidation in the pulmonary tissues.