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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Nitrosative stress is widely involved in cell injury via inducing the nitration modification of a variety of proteins. This study aimed to investigate whether inhibition of nitrosative stress attenuated myocardial injury and improved outcomes in a rat model of cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). ⋯ Inhibition of nitrosative stress is a novel molecular target to alleviate myocardial injury and improve outcomes in a rat model of CA/CPR.
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As a global major health problem and a leading cause of death, sepsis is defined as a failure of homeostasis, which is mainly initiated by an infection and followed by sustained excessive inflammation until immune suppression. Despite advances in the identification and management of clinical sepsis, morbidity, and mortality remain high. ⋯ Here we summarize mechanisms of several forms of RCD in sepsis including necroptosis, pyroptosis, ferroptosis. In conclusion, targeting RCD is considered a promising approach to treat sepsis.
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Severe microcirculatory disturbance is common in patients with cardiogenic shock necessitating extracorporeal membrane oxygenation (ECMO), however, biomarkers linked to microcirculation and clinical outcome are scarce. Herein we identified a circular RNA, hsa_circ_0007367, rooted from the ubiquitin-associated protein 2 (UBAP2) gene, namely circUBAP2, and evaluated its biological function and the associations with microcirculation and the prognosis. ⋯ The expression of circUBAP2 correlates with microcirculatory perfusion and has the potential in predicting outcomes for on-ECMO patients with cardiogenic shock.
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Sepsis is a fatal health issue induced by an aberrant host response to infection, and it correlates with organ damage and a high mortality rate. Endothelial barrier dysfunction and subsequent capillary leakage play major roles in sepsis-induced multiorgan dysfunction. Anaerobic glycolysis is the primary metabolic mode in sepsis and the pyruvate dehydrogenase complex (PDHC) serves as a critical hub in energy regulation. ⋯ The LPS-treated HUVEC model showed that DCA reversed LPS-induced phosphorylation of pyruvate dehydrogenase E1α Ser293 and Ser300 to restore PDHC activity. Immunoprecipitation results showed that LPS treatment increased the acetylation level of PDH E1α in HUVECs. Our study suggested that activation of PDHC may represent a therapeutic target for treatment of LPS-induced endothelial barrier dysfunction.
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Sepsis and septic shock usually show a high mortality rate and frequently need of intensive care unit admissions. After fluid resuscitation, norepinephrine (NE) is the first-choice vasopressor in septic shock patients. However, high-NE doses are associated with increased rates of adverse effects and mortality. ⋯ Only few clinical data actually support selepressin administration in this setting. Here, we review the current literature on this topic analyzing some pathophysiological aspects, the rationale about the use of NAV, the possible use of selepressin differentiating animal, and human studies. Various issues remain unresolved and future trials should be focused on early interventions based on a multimodal activation of the vasopressive pathways using both alpha and V1A receptors pathways.