Modeling lung endothelial dysfunction in sepsis‐associated ARDS using a microphysiological system

Physiological Reports, Journal Year: 2024, Volume and Issue: 12(13)

Published: July 1, 2024

Endothelial dysfunction is a critical feature of acute respiratory distress syndrome (ARDS) associated with higher disease severity and worse outcomes. Preclinical in vivo models sepsis ARDS have failed to yield useful therapies humans, perhaps due interspecies differences inflammatory responses heterogeneity human host responses. Use microphysiological systems (MPS) investigate lung endothelial function may shed light on underlying mechanisms targeted treatments for ARDS. We assessed the response plasma from critically ill patients our MPS through measurement permeability, expression adhesion molecules, cytokine secretion. Sepsis induced areas cell (EC) contraction, loss cellular coverage, luminal defects. EC barrier was significantly following incubation compared healthy plasma. ICAM-1 expression, IL-6 soluble secretion increased more after Plasma who developed further sICAM-1 without Our results demonstrate proof concept that can enable interrogation specific promote patients.

Language: Английский

Spatiotemporal regulation of neutrophil heterogeneity in health and disease

Human Molecular Genetics, Journal Year: 2025, Volume and Issue: unknown

Published: April 27, 2025

Abstract Neutrophils are the most abundant leukocytes in humans and indispensable for innate immunity. They short-lived, terminally differentiated cells. However, mounting evidence indicates that neutrophils heterogeneous health disease: they young or aged a steady state, while their heterogeneity becomes more diverse disease conditions, such as cancer, sepsis, thromboinflammation. Although presence of distinct neutrophil subsets is well recognized, it not fully understood how have functional phenotypic what mechanisms control it. This review will focus on our current understanding molecular basis pathophysiological conditions. In addition, we discuss possibility targeting specific subset to attenuate inflammation tissue damage without compromising immune responses.

Language: Английский

Advances in neutrophil extracellular traps and ferroptosis in sepsis-induced cardiomyopathy

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: April 28, 2025

Sepsis-induced cardiomyopathy is a reversible non-ischemic acute cardiac dysfunction associated with sepsis. It strongly an abnormal immune response. emerges as vital threat to public health owing its high mortality rate. However, the exact pathogenesis requires further investigation. In recent years, NETosis and ferroptosis, which are novel modes of programmed cell death, have been identified found play important roles in sepsis-related organ damage. This article outlines mechanisms these two discusses role neutrophil extracellular traps myocardial injury importance ferroptosis sepsis-induced cardiomyopathy, reviews potential interconnection between types death cardiomyopathy.

Language: Английский