Recently Published Documents
AbstractUnderstanding the respiratory mechanics of ARDS patients is crucial to avoid ventilator-induced lung injury (VILI), and this is much more challenging if not only lung compliance is altered but the whole compliance of the respiratory system is abnormal, as in obese patients. We face this problem daily in the ICU, and to optimize ventilation, we estimate respiratory mechanics using an oesophageal balloon. The balloon position is crucial to assess reliable values. In the present technical note, we describe the use of echocardiography to confirm the correct position of this instrument.
Abstract Background The adverse health effects of fine particulate matter (PM2.5) exposure are associated with marked inflammatory responses. Adipose-derived stem cells (ADSCs) have immunosuppressive effects, and ADSC transplantation could attenuate pulmonary fibrosis in different animal disease models. However, whether ADSCs affect PM2.5-induced lung injury has not been investigated. Method C57BL/6 mice were exposed to PM2.5 every other day via intratracheal instillation for 4 weeks. After that, the mice received tail vein injections of ADSCs every 2 weeks. Results ADSC transplantation significantly attenuated systemic and pulmonary inflammation, cardiac dysfunction, fibrosis, and cell death in PM2.5-exposed mice. RNA-sequencing results and bioinformatic analysis suggested that the downregulated differentially expressed genes (DEGs) were mainly enriched in inflammatory and immune pathways. Moreover, ADSC transplantation attenuated PM2.5-induced cell apoptosis and pyroptosis in the lungs and hearts. Conclusion ADSCs protect against PM2.5-induced adverse health effects through attenuating pulmonary inflammation and cell death. Our findings suggest that ADSC transplantation may be a potential therapeutic approach for severe air pollution-associated diseases.
Polydatin alleviates severe traumatic brain injury induced acute lung injury by inhibiting S100B mediated NETs formation
Kidney-lung crosstalk during SARS-CoV-2 infection: In silico hypothesis-generating method for COVID-19 models
Abstract BackgroundPublicly available genomics datasets have been growing drastically during the past decades. Although most of these datasets were initially generated to answer a pre-defined scientific question, their re-purposing became useful when new challenges such as COVID-19 arise. While the establishment and use of experimental models of COVID-19 are in progress, the potential hypotheses for mechanisms of onset and progression of COVID-19 can be generated by using in silico analysis of known COVID-19 conditions and SARS-CoV-2 targets. MethodsSelecting condition: COVID-19 infection leads to acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). There is increasing data demonstrating mechanistic links between AKI and ARDS. Selecting targets: SARS-CoV-2 uses angiotensin-converting enzyme 2 (ACE2) and transmembrane protease, serine 2 (TMPRSS2) for cell entry. We hypothesized that modeling AKI and ARDS would lead to changes in kidney and lung ACE2 and TMPRSS2. We therefore evaluated expression of ACE2 and TMPRSS2 as well as other novel molecular players of AKI and AKI-lung cross-talk in publicly available microarray datasets GSE6730 and GSE60088, which represented gene expression of lungs and kidneys in mouse models that resembled lung-kidney injury seen during SARS-CoV-2 infection.ResultsExpression of COVID-19 related genes ACE2 and TMPRSS2 was downregulated in lungs at early stages of injury. At a later stage, the expression of ACE2 decreased further, while expression of TMPRSS2 recovered. In kidneys, both genes were downregulated by AKI, but not by distant lung injury. We also identified 53 kidney genes upregulated by pneumonia and mechanical ventilation (PMV); and 254 lung genes upregulated by AKI, 9 genes of which were common to both organs. 3 of 9 genes were previously linked to kidney-lung cross-talk: Lcn2 (Fold Change (FC)Lung(L) =18.6, FCKidney(K) =6.32), Socs3 (FCL =10.5, FCK =10.4), Inhbb (FCL =6.20, FCK =6.17). This finding validates the current approach and reveals new 6 candidates, including Maff (FCL =7.21, FCK =5.98).ConclusionsUsing our in-silico approach, we identified changes in COVID-19 related genes ACE2 and TMPRSS2 in traditional mouse models of AKI and lung cross-talk. We also found changes in the new candidate genes, which could be involved in the combined kidney-lung injury during COVID-19
Vaping or E-cigarettes were created to deliver nicotine-containing aerosol to users with a flavoring agent without agents such as tars, oxidant gases, and carbon monoxide smoke found in traditional tobacco cigarettes. The use of E-cigarettes is steadily increasing in the United States, especially among the young population. Electronic cigarettes seem capable of causing various injury patterns in the lungs, collectively called E-cigarettes or vaping-associated lung injury (EVALI). Spontaneous pneumomediastinum (SPM) is a rare finding in EVALI. Here, we report a case of spontaneous pneumomediastinum secondary to vaping in a young man with no past medical history except for daily vaping and a recent untreated influenza infection.
Size and surface modification of silica nanoparticles affect the severity of lung toxicity by modulating endosomal ROS generation in macrophages
Abstract Background As the application of silica nanomaterials continues to expand, increasing chances of its exposure to the human body and potential harm are anticipated. Although the toxicity of silica nanomaterials is assumed to be affected by their physio-chemical properties, including size and surface functionalization, its molecular mechanisms remain unclear. We hypothesized that analysis of intracellular localization of the particles and subsequent intracellular signaling could reveal a novel determinant of inflammatory response against silica particles with different physico-chemical properties. Results We employed a murine intratracheal instillation model of amorphous silica nanoparticles (NPs) exposure to compare their in vivo toxicities in the respiratory system. Pristine silica-NPs of 50 nm diameters (50 nm-plain) induced airway-centered lung injury with marked neutrophilic infiltration. By contrast, instillation of pristine silica particles of a larger diameter (3 μm; 3 μm-plain) significantly reduced the severity of lung injury and neutrophilic infiltration, possibly through attenuated induction of neutrophil chemotactic chemokines including MIP2. Ex vivo analysis of alveolar macrophages as well as in vitro assessment using RAW264.7 cells revealed a remarkably lower cellular uptake of 3 μm-plain particles compared with 50 nm-plain, which is assumed to be the underlying mechanism of attenuated immune response. The severity of lung injury and neutrophilic infiltration was also significantly reduced after intratracheal instillation of silica NPs with an amine surface modification (50 nm-NH2) when compared with 50 nm-plain. Despite unchanged efficacy in cellular uptake, treatment with 50 nm-NH2 induced a significantly attenuated immune response in RAW264.7 cells. Assessment of intracellular redox signaling revealed increased reactive oxygen species (ROS) in endosomal compartments of RAW264.7 cells treated with 50 nm-plain when compared with vehicle-treated control. In contrast, augmentation of endosomal ROS signals in cells treated with 50 nm-NH2 was significantly lower. Moreover, selective inhibition of NADPH oxidase 2 (NOX2) was sufficient to inhibit endosomal ROS bursts and induction of chemokine expressions in cells treated with silica NPs, suggesting the central role of endosomal ROS generated by NOX2 in the regulation of the inflammatory response in macrophages that endocytosed silica NPs. Conclusions Our murine model suggested that the pulmonary toxicity of silica NPs depended on their physico-chemical properties through distinct mechanisms. Cellular uptake of larger particles by macrophages decreased, while surface amine modification modulated endosomal ROS signaling via NOX2, both of which are assumed to be involved in mitigating immune response in macrophages and resulting lung injury.