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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Severe burn injuries induce acute and chronic susceptibility to infections, which is largely attributed to a hyper-pro-inflammatory response followed by a chronic anti-inflammatory response. Concurrent inhalation injury (B + I) causes airway inflammation. Pulmonary macrophages and neutrophils are "hyperactive" with increased reactive oxygen (ROS) and nitrogen species (RONS) activity, but are unable to clear infection, causing airway damage upon activation. ⋯ BI-injured mice that received Combo-MP an hour after injury, inoculated 48 h later with Pseudomonas aeruginosa (PAO1), and sacrificed 48 h after infection, displayed significantly decreased bacterial counts in the lungs and liver versus untreated B + I mice. This reduction in infection was accompanied by significantly altered lung and plasma cytokine profiles and immune reprogramming of pulmonary and splenic cells. Our findings strongly suggest that multimodal MP-based therapy holds considerable promise for reprogramming the immune response after burn injuries, particularly by mitigating the hyper-inflammatory phase, and preventing subsequent susceptibility to infection.
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In natural disasters such as earthquakes and landslides, the main problem that wounded survivors are confronted with is Crush Syndrome (CS). The aim of this study was to explore more convenient and effective early treatment measures for it. In the present study, we investigated the protective effect of fasciotomy combined with different concentration of hypertonic saline flushing with CS rats. ⋯ Among them, alternating flushing with 3%-0.45% saline had the best therapeutic effect on CS. Finally, it can be found that 3%-0.45% saline treatment regimen dramatically raised the survival rate of CS rats. All in all, this study suggests that fasciotomy combined with hypertonic saline flushing is a good therapeutic approach for CS.
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Acute kidney injury (AKI) is a common, fatal complication of acute cholangitis (AC). The link between AC and AKI is poorly understood. ⋯ AKI often follows AC and is strongly associated with poor prognosis and increased healthcare utilization. Healthcare professionals should make more efforts to identify patients with AC at risk of AKI and start management promptly to limit adverse outcomes.
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This study aimed to investigate the protective effect of pentoxifylline (PTX) on vascular endothelial dysfunction in uraemia. The human aortic endothelial cells (HAECs) required for the experiments were all obtained from the National Collection of Authenticated Cell Cultures (Salisbury, UK). The permeability of HAECs was assessed. ⋯ The expression of NLRP3 (0.810 ± 0.032, p = 0.02) and caspase-1 (0.580 ± 0.041, p = 0.03) was increased, whereas the expression of ZO-1 (0.255 ± 0.038, p = 0.03) and VE-cadherin (0.0546 ± 0.053, p = 0.02) was decreased in the uraemia group; compared with the healthy volunteer group, treated with PTX (NLRP3, 0.298 ± 0.042, p = 0.03; caspase-1, 0.310 ± 0.021, p = 0.03; ZO-1, 0.412 ± 0.028, p = 0.02; VE-cadherin, 0.150 ± 0.034, p = 0.02) and MCC950 (NLRP3, 0.432 ± 0.022, p = 0.03; caspase-1, 0.067 ± 0.031, p > 0.05; ZO-1, 0.457 ± 0.026, p = 0.03; VE-cadherin, 0.286 ± 0.017, p = 0.03) lessened this trend. Pentoxifylline promoted the HAEC permeability mediated by uremic toxins (1.507 ± 0.012, p = 0.02). In conclusion, PTX enhances the release of HMGB1, which is dependent on NLRP3 activation, and consequently exerts positive effects on interconnecting proteins, ultimately leading to an improvement in vascular permeability.
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Sepsis is a life-threatening organ dysfunction that occurs due to a dysregulated host response to infection. Septic-associated liver injury (SALI) has been closely linked to the prognosis and mortality of sepsis. Recent investigations have delved into the gut-liver axis and its association with SALI, identifying its pivotal role in the gut microbiota. ⋯ Moreover, their metabolites might exacerbate or initiate SALI by modulating immune responses. Nevertheless, interventions to restore the balance of the gut microbiota, such as the administration of probiotics, fecal microbiota transplantation, or dietary adjustments, may ameliorate SALI and enhance the prognosis and survival rates of septic patients. This review aimed to elucidate the function of the gut microbiota in the genesis and procession of SALI and its potential therapeutic value, offering a deeper understanding of the pathogenesis and therapeutic avenues for SALI.