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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Background: The association between sepsis and noninfectious respiratory diseases is well-documented, yet the specific causal link between the two remains unclear. In order to explore this relationship further, we employed a Mendelian randomization (MR) analysis utilizing data from the UK Biobank and FinnGen Biobank. Methods: We analyzed the summary statistics of a genome-wide association study summary statistics for chronic obstructive pulmonary disease (COPD), asthma, pulmonary embolism (PE), idiopathic pulmonary fibrosis (IPF), obstructive sleep apnea (OSA), lung cancer, sepsis, and sepsis-related mortality. ⋯ IPF and OSA were not significantly associated with sepsis or sepsis-related mortality ( P > 0.05). Conclusion: Our MR analysis offers new insights into potential links between noninfectious respiratory diseases and the risk of sepsis. However, additional investigation into the underlying mechanisms and clinical studies are necessary to confirm these findings.
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Background: Myocardial infarction (MI) is a severe condition that typically results from the ischemia and necrosis of heart muscle. Kruppel-like factor 6 (KLF6) can aggravate myocardial ischemia/reperfusion injury. This work aims to reveal its role and mechanism in hypoxia/reoxygenation (H/R)-induced cardiomyocyte injury. ⋯ Additionally, WTAP stabilized KLF6 mRNA by regulating its m6A modification. Furthermore, WTAP knockdown rescued H/R-induced AC16 cell apoptosis, inflammatory response, oxidative stress, and ferroptosis by decreasing KLF6 expression. Conclusion: WTAP-mediated m6A modification of KLF6 aggravated hypoxia/reoxygenation-induced apoptosis, inflammatory response, oxidative stress, and ferroptosis of human cardiomyocytes, providing a therapeutic strategy for MI.
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Background: The inability to evaluate host immunity in a rapid quantitative manner in patients with sepsis has severely hampered development of novel immune therapies. The enzyme-linked immunospot (ELISpot) assay is a functional bioassay that measures the number of cytokine-secreting cells and the relative amount of cytokine produced at the single-cell level. A key advantage of ELISpot is its excellent dynamic range enabling a more precise quantifiable assessment of host immunity. ⋯ Conclusion: ELISpot offers a unique capability to assess the functional status of both adaptive and innate immunity over time. The results presented herein demonstrate that ELISpot can also be used to detect and follow the in vivo effects of drugs to ameliorate sepsis-induced immune dysfunction. This capability would be a major advance in guiding new immune therapies in sepsis.
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Background: The recruitment of neutrophils to sites of localized injury or infection is initiated by changes on the surface of endothelial cells located in proximity to tissue damage. Inflammatory mediators, such as TNF-α, increase surface expression of adhesive ligands and receptors on the endothelial surface to which neutrophils tether and adhere. Neutrophils then transit through the activated endothelium to reach sites of tissue injury with little lasting vascular injury. ⋯ Similar findings were demonstrated on fibronectin, collagen I, collagen IV, and laminin, suggesting that neutrophil surface VLA-3 and CD151 are responsible for endothelial damage regardless of substrata and are likely to be operative in all bodily tissues. Conclusion: This report identifies VLA-3 and CD151 on the activated human neutrophil, which are responsible for damage to endothelial function. Targeting these molecules in vivo may demonstrate preservation of organ function during critical illness.
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Background: Pulmonary artery catheterization (PAC) has been widely used in critically ill patients, yielding mixed results. Prior studies on cardiogenic shock (CS) predominantly included patients with acute myocardial infarction. This study aims to examine the effect of PAC use in patients with nonischemic CS. ⋯ After inverse probability of treatment weighting, patients in the PAC group had significantly lower in-hospital mortality (24.8% vs. 35.3%, P < 0.001), renal replacement therapy (10.7% vs. 12.4%, P = 0.002), in-hospital cardiac arrest (7.1% vs. 9.6%, P < 0.001), and mechanical ventilation (44.6% vs. 50.4%, P < 0.001) compared to non-PAC group. In contrast, the PAC group had higher use of intra-aortic balloon pump (15.4% vs. 3.4%, P < 0.001), percutaneous ventricular assist devices (12.6% vs. 2.6%, P < 0.001), extracorporeal membrane oxygenation (3.9% vs. 2.5%, P < 0.001), and heart transplantation (2.1% vs. 0.4%, P < 0.001). Conclusion: In the real-world setting, invasive hemodynamic monitoring with PAC in patients with nonischemic CS is associated with survival benefits and a reduction in adverse events, including reduced need for renal replacement therapy, mechanical ventilation and risk of in-hospital cardiac arrest.