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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Introduction: Sulforaphane (SFN), known as the activator of the nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway, has been proven to protect the lung against various pathological stimuli. The present study aimed to investigate the effect of SFN on lung injury induced by systemic ischemia reperfusion after cardiac arrest and resuscitation. Methods: After animal preparation, 24 pigs were randomly divided into sham group (n = 6), cardiopulmonary resuscitation group (CPR, n = 9), or CPR + SFN group (n = 9). ⋯ After resuscitation, the indicators of lung injury (ELWI, PVPI, and oxygenation index) were all better in the CPR + SFN group than in the CPR group, in which the differences in ELWI and PVPI at 2, and 4 h after resuscitation were significant between the two groups. In addition, SFN significantly reduced lung injury score, improved oxidative imbalance (superoxide dismutase, malondialdehyde), decreased pyroptosis-related proinflammatory cytokines (IL-1β, IL-18), downregulated pyroptosis-related proteins (NOD-like receptor pyrin domain 3, cleaved caspase 1, GSDMD, GSDMD N-terminal), and activated the Nrf2/HO-1 pathway when compared with the CPR group. Conclusion: SFN produced effective postresuscitation lung protection through alleviating lung pyroptosis possibly via activating the Nrf2/HO-1 pathway in pigs.
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Background: Aberrant expression of circular RNAs (circRNAs) has been revealed to have crucial roles in the pathological processes of cardiovascular disease. Here, this study aimed to investigate the role and mechanism of circ_0001379 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury to explore the potential action of circ_0001379 in acute myocardial infarction (AMI). Methods: Levels of genes and proteins were examined by quantitative real-time polymerase chain reaction and western blot. ⋯ Further rescue experiments showed that inhibition of miR-98-5p reversed the protective effects of circ_0001379 silencing on H/R-induced cardiomyocytes. Besides that, miR-98-5p overexpression abolished H/R-evoked cardiomyocyte apoptosis and inflammatory response, while this condition was abated by SOX6. Conclusion: Circ_0001379 silencing protects cardiomyocytes from H/R-induced apoptosis and inflammatory response by miR-98-5p/SOX6 axis, suggesting a novel therapeutic strategy for AMI prevention.
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The depletion of peripheral blood B cells is associated with immunosuppression and poor prognosis during sepsis, and selective depletion occurs when B cell subsets are specifically targeted. In this study, we examined the mechanisms underlying the selective depletion of B cell subsets in the immunosuppressive phase of septic shock patients. Thirty-two septic shock patients were recruited as a septic shock group and 10 healthy volunteers as a control group. ⋯ Activated caspase-1 levels in IM B cells were higher compared with activated caspase-3 in septic shock patients, whereas the levels of activated caspase-1 in AM B cells were lower compared with activated caspase-3. Moreover, in vitro experiments showed that Z-DEVD-FMK and VX-765 could alleviate the depletion of IM, AM, and RM B cells. The selective reduction of circulating B cell subsets in septic shock patients could be attributed to intrinsic and extrinsic apoptosis as well as pyroptosis.
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Background: Pneumonia is a frequent complication after polytrauma. This study aims to evaluate the ability of different serum markers to identify patients at risk of developing pneumonia after polytrauma. Methods: A retrospective analysis of prospectively collected data in polytraumatized patients with concomitant thoracic trauma (Injury Severity Score ≥16, Abbreviated Injury Scale Thorax ≥ 3) was performed. ⋯ No statistically significant difference could be observed for serum levels of CYFRA 21-1, Ang-2, PTX-3, sRAGE, IL-6, and IL-10 between the groups (pneumonia vs. no pneumonia) on all days. Logistic regression revealed a combination of IL-6, IL-10, sRAGE, and PTX-3 to be eventually helpful to identify patients at risk of developing pneumonia and our newly developed score was significantly higher on day 0 in patients developing pneumonia ( P < 0.05). Conclusion: The investigated serum markers alone are not helpful to identify polytraumatized patients at risk of developing pneumonia, while a combination of IL-6, IL-10, PTX-3, and sRAGE might be.
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Background: Sepsis is marked by a dysregulated immune response to an infection. Invariant natural killer T cells ( i NKT cells) are a pluripotent lymphocyte subpopulation capable of affecting and coordinating the immune response to sepsis. The spleen is an important site of immune interactions in response to an infection. ⋯ With respect to PD-1 ligands upon phagocytes, PD-1 ligand expression was unaffected, whereas PD-L2 expression was significantly affected by the presence of PD-1. Conclusions: Invariant natural killer T cells play a distinct role in the spleen response to sepsis, an effect mediated by the checkpoint protein PD-1. Given that modulators are available in clinical trials, this offers a potential therapeutic target in the setting of sepsis-induced immune dysfunction.