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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To uncover critical active proteins influencing sepsis outcomes through multi-omics analysis. ⋯ The study's findings advance the understanding of sepsis pathophysiology by linking differentially active proteins to patient prognosis, paving the way for targeted therapeutic strategies.
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Observational Study
Immunosuppression correlates with the deterioration of sepsis-induced disseminated intravascular coagulation.
Background: The dysregulated host responses play a crucial role in the pathophysiology process of sepsis-induced disseminated intravascular coagulation (DIC). The study aimed to characterize the dynamic alternation of immune-related biomarkers and their relationship with the progression of DIC during sepsis. Methods: A prospective, observational study was conducted in a tertiary care academic hospital. ⋯ The patients with overt DIC displayed pronounced immune disorders from D1 to D7 upon sepsis, which was characterized by the decreased percentage of monocyte HLA-DR (mHLA-DR), increased percentage of regulatory T cells, the levels of procalcitonin, neutrophil CD64 index, and systemic inflammatory cytokines relative to nonovert DIC or non-DIC patients. In multivariate analysis, the combination of anti-inflammatory cytokine IL-10 and mHLA-DR at D1 upon enrollment had a superior predictive value for predicting DIC deterioration in sepsis (area under the curve = 0.87, P < 0.0001). Conclusion: These data illustrate that immunosuppression can crosstalk with coagulation disorder during sepsis and present an additional evaluation tool to predict DIC deterioration.
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Background: Sepsis is a type of life-threatening organ dysfunction that is caused by a dysregulated host response to infection. The lung is the most vulnerable target organ under septic conditions. Pulmonary microvascular endothelial cells (PMVECs) play a critical role in acute lung injury (ALI) caused by severe sepsis. ⋯ Treatment with the sarco/endoplasmic reticulum Ca 2+ adenosine triphosphatase inhibitor, thapsigargin, resulted in a significant reduction in cell viability as well as a reduction in the expression of junctional proteins, including vascular endothelial-cadherin and occludin. Treatment with the store-operated Ca 2+ entry inhibitor, YM-58483 (BTP2), increased the cell viability and expression of junctional proteins. Conclusions: The present study suggested that H 2 treatment alleviates LPS-induced PMVEC dysfunction by inhibiting store-operated Ca 2+ entry mediated by STIM1 and Orai1 in vitro and in vivo .
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Background: Despite advancements in sepsis treatment, mortality remains high. Plasmapheresis (PE) targeting multiple pathways simultaneously seems to be a potential treatment option, but evidence is insufficient. We aimed to investigate the efficacy of PE for sepsis with multiple organ failure (MOF). ⋯ Compared with the conventional group, the sequential organ failure assessment, norepinephrine dosage, prothrombin time, actate dehydrogenase, total bilirubin, white blood cells, and immature granulocytes in the PE group significantly decreased over time, while platelets, red blood cells, and hemoglobin significantly increased over time. Conclusions: Plasmapheresis demonstrated an association with reduced risks of 28-day, in-hospital and 1-year mortality in septic patients with MOF. Moreover, plasmapheresis might exhibit the potential to improve outcomes by improving organ function, hemodynamics, and restoring several indicators, such as coagulation, anemia, and inflammation.
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Background: Recent studies have shown that ferroptosis is involved in the evolution of acute lung injury (ALI), a serious respiratory pathological process leading to death. However, the regulatory mechanisms underlying ferroptosis in ALI remain largely unknown. The current study analyzed and identified a ferroptosis-related gene signature for ALI. ⋯ Besides, the ferroptosis-related molecules GPX4 and ACSL4 showed remarkable difference in these models. Conclusion: These results indicate that PROK2 , IL6 , TNF , and SLC7A11 may be key regulatory targets of ferroptosis during ALI. This study proved that ferroptosis is a common pathophysiological process in three ALI models.