Acute Lung Injury
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2021 ◽  
Vol 24 (4) ◽  
Fen Hu ◽  
Xianfeng Dong ◽  
Weixin Li ◽  
Jianfa Lv ◽  
Feng Lin ◽  

Antioxidants ◽  
2021 ◽  
Vol 10 (8) ◽  
pp. 1221
Alvaro Martinez Mesa ◽  
Eva Cabrera César ◽  
Elisa Martín-Montañez ◽  
Esther Sanchez Alvarez ◽  
Pilar Martinez Lopez ◽  

Introduction: SARS-CoV-2 (COVID-19) patients who develop acute respiratory distress syndrome (ARDS) can suffer acute lung injury, or even death. Early identification of severe disease is essential in order to control COVID-19 and improve prognosis. Oxidative stress (OS) appears to play an important role in COVID-19 pathogenesis; we therefore conceived a study of the potential discriminative ability of serum biomarkers in patients with ARDS and those with mild to moderate disease (non-ARDS). Method: 60 subjects were enrolled in a single-centre, prospective cohort study of consecutively admitted patients: 29 ARDS/31 non-ARDS. Blood samples were drawn and marker levels analysed by spectrophotometry and immunoassay techniques. Results: C-reactive protein (CRP), lactate dehydrogenase (LDH), and ferritin were significantly higher in ARDS versus non-ARDS cases at hospital admission. Leukocytes, LDH, ferritin, interleukin 6 (IL-6) and tumour necrosis factor alpha (TNF-α) were also significantly elevated in ARDS compared to non-ARDS patients during the hospital stay. Total thiol (TT) was found to be significantly lower in ARDS. Conversely, D-dimer, matrix metalloproteinase-9 (MMP-9) and advanced glycosylated end products (AGE) were elevated. Leukocytes, LDH, CRP, ferritin and IL-6 were found to be significantly higher in non-survivors. However, lymphocyte, tumour necrosis factor beta (TGF-β), and TT were lower. Conclusion: In summary, our results support the potential value of TT, ferritin and LDH as prognostic biomarkers for ARDS development in COVID-19 patients, distinguishing non-ARDS from ARDS (AUCs = 0.92; 0.91; 0.89) in a fast and cost-effective manner. These oxidative/inflammatory parameters appear to play an important role in COVID-19 monitoring and can be used in the clinical management of patients.

2021 ◽  
Vol 12 ◽  
Jacob Herrmann ◽  
Sarah E. Gerard ◽  
Wei Shao ◽  
Yi Xin ◽  
Maurizio Cereda ◽  

Rationale: Intratidal changes in regional lung aeration, as assessed with dynamic four-dimensional computed tomography (CT; 4DCT), may indicate the processes of recruitment and derecruitment, thus portending atelectrauma during mechanical ventilation. In this study, we characterized the time constants associated with deaeration during the expiratory phase of pressure-controlled ventilation in pigs before and after acute lung injury using respiratory-gated 4DCT and image registration.Methods: Eleven pigs were mechanically ventilated in pressure-controlled mode under baseline conditions and following an oleic acid model of acute lung injury. Dynamic 4DCT scans were acquired without interrupting ventilation. Automated segmentation of lung parenchyma was obtained by a convolutional neural network. Respiratory structures were aligned using 4D image registration. Exponential regression was performed on the time-varying CT density in each aligned voxel during exhalation, resulting in regional estimates of intratidal aeration change and deaeration time constants. Regressions were also performed for regional and total exhaled gas volume changes.Results: Normally and poorly aerated lung regions demonstrated the largest median intratidal aeration changes during exhalation, compared to minimal changes within hyper- and non-aerated regions. Following lung injury, median time constants throughout normally aerated regions within each subject were greater than respective values for poorly aerated regions. However, parametric response mapping revealed an association between larger intratidal aeration changes and slower time constants. Lower aeration and faster time constants were observed for the dependent lung regions in the supine position. Regional gas volume changes exhibited faster time constants compared to regional density time constants, as well as better correspondence to total exhaled volume time constants.Conclusion: Mechanical time constants based on exhaled gas volume underestimate regional aeration time constants. After lung injury, poorly aerated regions experience larger intratidal changes in aeration over shorter time scales compared to normally aerated regions. However, the largest intratidal aeration changes occur over the longest time scales within poorly aerated regions. These dynamic 4DCT imaging data provide supporting evidence for the susceptibility of poorly aerated regions to ventilator-induced lung injury, and for the functional benefits of short exhalation times during mechanical ventilation of injured lungs.

Guang Li ◽  
Bo Wang ◽  
Xiangchao Ding ◽  
Xinghua Zhang ◽  
Jian Tang ◽  

AbstractExtracellular vesicles (EVs) can be used for intercellular communication by facilitating the transfer of miRNAs from one cell to a recipient cell. MicroRNA (miR)-210-3p is released into the blood during sepsis, inducing cytokine production and promoting leukocyte migration. Thus, the current study aimed to elucidate the role of plasma EVs in delivering miR-210-3p in sepsis-induced acute lung injury (ALI). Plasma EVs were isolated from septic patients, after which the expression of various inflammatory factors was measured using enzyme-linked immunosorbent assay. Cell viability and apoptosis were measured via cell counting kit-8 and flow cytometry. Transendothelial resistance and fluorescein isothiocyanate fluorescence were used to measure endothelial cell permeability. Matrigel was used to examine the tubulogenesis of endothelial cells. The targeting relationship between miR-210-3p and ATG7 was assessed by dual-luciferase reporter assays. The expression of ATG7 and autophagy-related genes was determined to examine autophagic activation. A sepsis mouse model was established by cecal ligation and puncture (CLP)-induced surgery. The level of miR-210-3p was highly enriched in septic EVs. MiR-210-3p enhanced THP-1 macrophage inflammation, BEAS-2B cell apoptosis, and HLMVEC permeability while inhibiting angiogenesis and cellular activity. MiR-210-3p overexpression reduced ATG7 and LC3II/LC3I expression and increased P62 expression. Improvements in vascular density and autophagosome formation, increased ATG7 expression, and changes in the ratio of LC3II/LC3I were detected, as well as reduced P62 expression, in adenovirus-anti-miR-210-3p treated mice after CLP injury. Taken together, the key findings of the current study demonstrate that plasma EVs carrying miR-210-3p target ATG7 to regulate autophagy and inflammatory activation in a sepsis-induced ALI model.

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Wenhui Wu ◽  
Huiqing Lin ◽  
Ailing Yin ◽  
Cunsi Shen ◽  
Hongliang Zhou ◽  

Compatibility remains among the crucial and significant characteristics of traditional Chinese medicines. The Gardeniae Fructus (FG)-Forsythiae Fructus (FF) herb pair, an epitome of formulations for heat-clearing and detoxification, is extensively used to treat bacterial pneumonia in clinical settings. However, there are few reports on their synergistic effects. This study thus investigated their compatibility by GC-MS based metabolomics using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Differential metabolites were identified by both variable importance in the projection (VIP) > 1 in orthogonal partial least-squares discriminant analysis (OPLS-DA) mode and P < 0.05 . Results of biochemistry and histopathology indicated that FG-FF herb pair exerted more promising lung protective effect than its individual decoction against the LPS-induced ALI model. From the metabolomics study, 32 differential metabolites in vehicle vs. model groups, 21 differential metabolites in FF vs. model groups, 21 differential metabolites in FG vs. model groups, and 20 differential metabolites in FG-FF herb pair vs. model groups were found. Among them, the levels of 3-hydroxybutyric acid, alanine, isophthalic acid, and terephthalic acid were restored significantly in the FF group, while silanol and cholesterol were restored significantly in the FG group. For FG-FF treatment, the amount of behenic acid, a metabolite with anti-inflammatory properties, was increased, while palmitic acid, a proinflammatory metabolite, was decreased. Meanwhile, the two biomarkers were restored more significantly than that by FG or FF treatment, which indicated that the synergistic effects by FF coupled with FG might be attributed to restoring fatty acids metabolic pathway.

2021 ◽  
Vol 142 ◽  
pp. 111949
Dan Song ◽  
Min Zhao ◽  
Liuxiang Feng ◽  
Pingyi Wang ◽  
Yimei Li ◽  

2021 ◽  
Benkun Zou ◽  
Michael Goodwin ◽  
Danial Saleem ◽  
Wei Jiang ◽  
Jianguo Tang ◽  

Oxidized phospholipids have diverse biological activities, many of which can be pathological, yet how they are inactivated in vivo is not fully understood. Here we present evidence that a previously unsuspected lipase, acyloxyacyl hydrolase (AOAH), can play a significant role in reducing the pro-inflammatory activities of two prominent products of phospholipid oxidation, 1-palmitoyl-2-glutaryl-sn-glycero-3-phosphocholine (PGPC) and 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-3-phosphocholine (POVPC). AOAH removed the sn-2 and sn-1 acyl chains from both lipids and reduced their ability to induce macrophage inflammasome activation and cell death in vitro and acute lung injury in vivo. In addition to transforming Gram-negative bacterial lipopolysaccharide from stimulus to inhibitor, its most studied activity, AOAH can inactivate these important danger-associated molecular pattern (DAMP) molecules and reduce tissue inflammation and cell death.

2021 ◽  
Vol 14 (1) ◽  
Robert Ruemmler ◽  
Alexander Ziebart ◽  
Elisabeth Britten ◽  
Moritz Gosling ◽  
Rene Rissel ◽  

Abstract Objective Extracellular histones have been identified as one molecular factor that can cause and sustain alveolar damage and were linked to high mortality rates in critically ill patients. In this pilot study, we wanted to validate the proinflammatory in vivo effects of local histone application in a prospective translational porcine model. This was combined with the evaluation of an experimental acute lung injury model using intrabronchial lipopolysaccharides, which has been published previously. Results The targeted application of histones was successful in all animals. Animals showed decreased oxygenation after instillation, but no differences could be detected between the sham and histone treatments. The histologic analyses and inflammatory responses indicated that there were no differences in tissue damage between the groups.

2021 ◽  
Vol 22 (15) ◽  
pp. 7853
Athanassios Fragoulis ◽  
Kristina Biller ◽  
Stephanie Fragoulis ◽  
Dennis Lex ◽  
Stefan Uhlig ◽  

qRT-PCR still remains the most widely used method for quantifying gene expression levels, although newer technologies such as next generation sequencing are becoming increasingly popular. A critical, yet often underappreciated, problem when analysing qRT-PCR data is the selection of suitable reference genes. This problem is compounded in situations where up to 25% of all genes may change (e.g., due to leukocyte invasion), as is typically the case in ARDS. Here, we examined 11 widely used reference genes for their suitability in commonly used models of acute lung injury (ALI): ventilator-induced lung injury (VILI), in vivo and ex vivo, lipopolysaccharide plus mechanical ventilation (MV), and hydrochloric acid plus MV. The stability of reference gene expression was determined using the NormFinder, BestKeeper, and geNorm algorithms. We then proceeded with the geNorm results because this is the only algorithm that provides the number of reference genes required to achieve normalisation. We chose interleukin-6 (Il‑6) and C-X-C motif ligand 1 (Cxcl-1) as the genes of interest to analyse and demonstrate the impact of inappropriate normalisation. Reference gene stability differed between the ALI models and even within the subgroup of VILI models, no common reference gene index (RGI) could be determined. NormFinder, BestKeeper, and geNorm produced slightly different, but comparable results. Inappropriate normalisation of Il-6 and Cxcl1 gene expression resulted in significant misinterpretation in all four ALI settings. In conclusion, choosing an inappropriate normalisation strategy can introduce different kinds of bias such as gain or loss as well as under- or overestimation of effects, affecting the interpretation of gene expression data.

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