Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU...Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU)patients is approximately 10%,with mortality rates ranging from 35%to 45%and exceeding 50%in severe cases.[1]Identifying and controlling risk factors for ARDS is critical for early prevention.Smoking remains a significant global public health issue,affecting one-third of adults and 40%of children through exposure to secondhand smoke.[2]In an animal study,cigarette smoke impaired lung endothelial barrier function through oxidative stress and exacerbated lipopolysaccharide-induced increases in vascular permeability in vivo.This finding is consistent with the pathological changes observed in ARDS.[3]Although many observational studies have suggested a potential link between smoking and ARDS,the causal relationship remains unclear.This study uses Mendelian randomization(MR)to explore whether smoking behavior causally influences ARDS and investigates the mechanisms by which smoking may contribute to ARDS development through transcriptomic analysis of the Gene Expression Omnibus(GEO)database.展开更多
Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to i...Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient （LDLR^-/-） mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy （TEM） at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TEM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. Experiments with endocytosis inhibitors and small interfering RNA （siRNA） revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.展开更多
基金funded by the Hunan Provincial Natural Science Foundation of China(2024JJ2038,2024JJ9161)the Central Government Guides Local Science and Technology Development Fund Projects(2024ZYC031)+4 种基金the Hunan Health High-Level Talent Project(R2023073)the National Key Clinical Specialty Scientific Research Project(Z2023114)the Young Doctor Foundation of Hunan Provincial People’s Hospital(BSJJ202209)the Key Cultivation Project of Hunan Provincial People’s Hospital(RS2022A06)the Clinical Research Center for Emergency and Critical Care in Hunan Province(2021SK4011).
文摘Acute respiratory distress syndrome(ARDS)is a severe clinical condition characterized by acute respiratory failure due to widespread pulmonary inflammation and edema.The incidence of ARDS among intensive care unit(ICU)patients is approximately 10%,with mortality rates ranging from 35%to 45%and exceeding 50%in severe cases.[1]Identifying and controlling risk factors for ARDS is critical for early prevention.Smoking remains a significant global public health issue,affecting one-third of adults and 40%of children through exposure to secondhand smoke.[2]In an animal study,cigarette smoke impaired lung endothelial barrier function through oxidative stress and exacerbated lipopolysaccharide-induced increases in vascular permeability in vivo.This finding is consistent with the pathological changes observed in ARDS.[3]Although many observational studies have suggested a potential link between smoking and ARDS,the causal relationship remains unclear.This study uses Mendelian randomization(MR)to explore whether smoking behavior causally influences ARDS and investigates the mechanisms by which smoking may contribute to ARDS development through transcriptomic analysis of the Gene Expression Omnibus(GEO)database.
文摘Very small superparamagnetic iron oxide nanoparticles （VSOPs） rapidly accumulate in atherosclerotic lesions, thereby enabling plaque visualization by magnetic resonance imaging （MRI）. This study was performed to identify the uptake mechanisms of VSOPs into atherosclerotic plaques. Low-density lipoprotein receptor-deficient （LDLR^-/-） mice with advanced atherosclerosis were analyzed using MRI and transmission electron microscopy （TEM） at various time points after intravenous administration of VSOPs. Post-mortem MRI detected VSOP labeling of atherosclerotic plaques 10 min after injection, and the signal increased over the first 3 h. TEM revealed that the intensive plaque labeling was mediated by accelerated transcytosis of VSOPs through endothelial cells overlaying atherosclerotic lesions. Experiments with endocytosis inhibitors and small interfering RNA （siRNA） revealed a dynamin-dependent mechanism involving both clathrin- and caveolin-mediated processes. In cell culture experiments, endothelial VSOP uptake was enhanced under proatherogenic flow and TNFα stimulation, conditions that are both present in plaque areas. Our study demonstrates that VSOPs enable non-invasive MRI assessment of accelerated endothelial transcytosis, an important pathomechanism in atherosclerotic plaque formation.
