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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Hemorrhagic shock (HS) is accompanied by a pronounced activation of the inflammatory response in which acute lung injury (ALI) is one of the most frequent consequences. Among the pivotal orchestrators of this inflammatory cascade, extracellular cold-inducible RNA-binding protein (eCIRP) emerges as a noteworthy focal point, rendering it as a promising target for the management of inflammation and tissue injury. Recently, we have reported that oligonucleotide poly(A) mRNA mimic termed A 12 selectively binds to the RNA binding region of eCIRP and inhibits eCIRP binding to its receptor TLR4. ⋯ A 12 treatment also decreased lung levels of TNF-α, MIP-2, and KC mRNA expressions. Lung histological injury score, neutrophil infiltration (Ly6G staining and myeloperoxidase activity), and lung apoptosis were significantly attenuated after A 12 treatment. Our study suggests that the capacity of A 12 in attenuating HS-induced ALI and may provide novel perspectives in developing efficacious pharmaceutics for improving hemorrhage prognosis.
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Sepsis-associated encephalopathy (SAE) is a serious complication of sepsis, which is characterized by cognitive dysfunction, a poor prognosis, and high incidences of morbidity and mortality. Substantial levels of systemic inflammatory factors induce neuroinflammatory responses during sepsis, ultimately disrupting the central nervous system's (CNS) homeostasis. This disruption results in brain dysfunction through various underlying mechanisms, contributing further to SAE's development. ⋯ They serve an important regulatory role in CNS homeostasis and can be activated through multiple pathways. Consequently, activated microglia are involved in several pathogenic mechanisms related to SAE and play a crucial role in its development. This article discusses the role of microglia in neuroinflammation, dysfunction of neurotransmitters, disruption of the blood-brain barrier, abnormal control of cerebral blood flow, mitochondrial dysfunction, and reduction in the number of good bacteria in the gut as main pathogenic mechanisms of SAE and focuses on studies targeting microglia to ameliorate SAE to provide a theoretical basis for targeted microglial therapy for SAE.
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Background: Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. There is currently no simple immune-imbalance-driven indicator for patients with sepsis. Methods: This study was conducted in Peking Union Medical College Hospital. ⋯ In trend analysis, as the trend of D1-D3-D7 IL-6/LY# decreases, the morality rate is lower than increase or fluctuate group (42.1% vs. 58.3%, 37.9% vs. 43.8%, 37.5% vs. 38.5% in high, moderate, and low D1 IL-6/LY# group separately). Conclusion: IL-6/LY# examined on first day in intensive care unit can be used as an immune-imbalance alert to identify sepsis patients with higher risk of 28-day mortality. Decreasing trend of IL-6/LY# suggests a lower 28-day mortality rate of sepsis patients.
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Objective : Numerous epidemiological studies have identified a potential link between sepsis and a variety of autoimmune disorders. The primary objective of this study is to delve deeper into this connection, investigating the potential causal relationship between sepsis and autoimmune disorders through the application of Mendelian randomization (MR). Methods : To assess the potential genetic impact on sepsis risk relating to susceptibility toward immune-related outcomes, we used summary data from the largest European genome-wide association studies (GWAS) on these conditions using a two-sample MR framework. ⋯ Conclusion : Our MR research, centered on a European population, does not validate a correlation between susceptibility to the majority of autoimmune disorders and sepsis risk. Associations discerned in epidemiological studies may owe partly to shared biological or environmental confounders. The risk susceptibility for primary sclerosing cholangitis does relate to sepsis risk, opening doors for personalized precision treatments in the future.
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Introduction: Hypertension is a prevalent condition in the United States and leads to an increased risk of developing various comorbidities. However, the impact of new-onset hypertension after severe burns on patient outcomes is not known. We posit that hypertension onset after severe burn is associated with increased risk of developing comorbidities and mortality. ⋯ Age grouping indicated an elevated risk of developing AKI, heart failure, acute MI, and death. Conclusion: New-onset hypertension diagnosis in severely burned patients is associated with acute kidney injury, heart failure, acute MI, and death. Overall, males, older patients, and those with a higher % TBSA burned are at a higher risk of developing these comorbidities.