Prevention Of Lung Injury Research Articles

MOTS-c mimics remote ischemic preconditioning in protecting against lung ischemia-reperfusion injury by alleviating endothelial barrier dysfunction.

Remote ischemic preconditioning (RIPC) induces the expression of unidentified protective cytokines that mitigate lung ischemia-reperfusion injury (LIRI). This study hypothesizes that MOTS-c, a mitokine with potent protective effects against mitochondrial damage, contributes to RIPC-mediated protection by alleviating endothelial barrier dysfunction. In human lung transplantation patients, serum levels of MOTS-c significantly decreased following IR injury but were markedly increased when RIPC was performed prior to transplantation. Similarly, in a mouse model of LIRI, RIPC restored serum MOTS-c levels and improved lung injury outcomes. Intravenous administration of MOTS-c in mice replicated the protective effects observed with RIPC. Mechanistic studies demonstrated that repeated hypoxia in human primary skeletal muscle immortalized cells (HPSMIC) led to the secretion of conditioned media that protected HUVECs from OGD/R-induced injury; silencing MOTS-c abolished these protective effects. Further investigations using nuclear factor erythroid 2-related factor 2 (Nrf2) knockout mice and the Nrf2 inhibitor ML385 revealed that MOTS-c exerts its protective function by increasing Nrf2 protein levels, thereby maintaining endothelial barrier integrity. In conclusion, this study identifies MOTS-c as a novel mediator of RIPC's protective effects against LIRI and highlights its potential as a therapeutic alternative for preventing lung injury and preserving vascular endothelial function.

Staged Approach: The Role of Delayed Repair Following Complete Unifocalization of Major Aortopulmonary Collateral Arteries with Ventricular Septal Defect and Pulmonary Atresia.

The presentation of pulmonary vasculature in pulmonary atresia with ventricular septal defect and major aortopulmonary collateral arteries (PA/VSD/MAPCA) is highly variable-as is the number, size and position of the MAPCAs and their relationship with the native pulmonary artery system. The priority in the management of this disease should be attaining timely and complete unifocalization, as opposed to single-stage full repair in every case. The merit of early unifocalization is that it secures the pulmonary vascular bed by (a) avoiding loss of lung segments from progressive stenosis/atresia of MAPCA origins, (b) preventing lung injury from high pressure/flow in areas fed by large, unobstructed MAPCAs, and (c) restoring central continuity of the pulmonary vasculature. Furthermore, there are a small but important group of patients with poorly developed vessels (about 10%-15% of the population) and/or diminutive native pulmonary artery vasculature that require initial shunt procedures to promote rehabilitation and growth of vessels before unifocalization can be attempted. During unifocalization, patients not suitable for single stage repair can be identified by intraoperative flow studies and can be successfully managed with staged strategies that provide time for growth and reinterventions on the pulmonary vasculature. Over 85% of patients can achieve unifocalization. Deferring closure of the VSD to a subsequent procedure is safe and these cases have similar survival to primary repair. Some patients (15%-20%) may never achieve VSD closure with this strategy but can still maintain a good quality of life with a restrictive right ventricular to pulmonary artery conduit and open VSD.

Heparan sulfate acts in synergy with tight junction through STAT3 signaling to maintain the endothelial barrier and prevent lung injury development.

Damage to glycocalyx and tight junction are key determinants of endothelial permeability, which is the main pathological feature of acute respiratory distress syndrome (ARDS). However, the effect of glycocalyx heparan sulfate (HS) on tight junction proteins occludin and ZO-1 has not been revealed. In this study, the mice exposed to LPS results showed that FITC-albumin infiltration, HS shedding, and tight junction protein impairment were most severe at 6h of LPS treatment compared with those in other treatment times. The in vitro and vivo experiments revealed that tight junction damage, FITC-albumin infiltration, and pathological injury induced by LPS were significantly alleviated via protection of glycocalyx HS shedding. mRNA sequencing analysis demonstrated that the STAT signaling pathways played a crucial role in the inhibition of LPS-induced HS shedding in mice. Supplementation of exogenous HS in human umbilical vein endothelial cells (HUVECs) and mice ameliorated LPS-induced the tight junction barrier defect by inhibiting STAT3 phosphorylation. Further analysis uncovered that intervention of STAT3 signaling significantly alleviated LPS-induced tight junction proteins damage and vascular permeability in HUVECs and mice. Mechanistically, HS modulated tight junction proteins by STAT3 signaling, which might directly bind to the promoter regions of occludin and ZO-1. In conclusion, glycocalyx HS played an important role in protecting endothelial barrier function and preventing injury development, in synergy with tight junction through STAT3 signaling, which further alleviated pulmonary edema.

SignalingviaCD131 regulates pulmonary inflammation, alveolar cell death and emphysema in COPD

BackgroundChronic Obstructive Pulmonary Disease (COPD) is a heterogenous disease where chronic inflammation is implicated in airway remodeling and emphysema. The CD131 receptor is indispensable for signaling by the beta common (βc) family of cytokines encompassing GM-CSF, IL-5 and IL-3, which instigate both Type-2 and non-Type-2 inflammatory responses. This study aims to determine whether antagonising CD131 signaling can prevent pulmonary inflammation, alveolar cell death and emphysema development.MethodsWe performed in-house andin silicotranscriptomic analysis to investigate the gene expression of CD131 (CSF2RB) and pathway enrichment for βc cytokine signaling in blood, sputum and lung biopsies of COPD patients. To model emphysema, transgenic mice expressing human CD131 were exposed to elastase or cigarette smoke (CS) and a fully human monoclonal antibody (CSL311) was employed to inhibit CD131 signaling.ResultsCD131 gene expression was significantly increased in COPD, along with an enrichment of gene set for βc cytokine signaling. In transgenic mice subjected to emphysema models, CD131 antagonism effectively prevented lung injury, alveolar cell death and emphysema development. Mechanistically, RNA sequencing identified pathway enrichment for myeloid cell activation, Type-2 immune response and macrophage alternative activation in elastase-induced emphysematous mice, mirroring human COPD. Blocking CD131 signaling almost completely reversed the global gene expression alterations associated with emphysema development.ConclusionsCD131 signaling orchestrates pulmonary inflammation in COPD, resulting in immunopathology that underpins emphysema and lung function decline. Antagonising CD131 therefore represents a unique strategy to simultaneously target multiple pathogenic myeloid cell populations.

Integrative Analysis of Pharmacology and Transcriptomics Predicts Resveratrol Will Ameliorate Microplastics-Induced Lung Damage by Targeting Ccl2 and Esr1.

Microplastics (MPs) are ubiquitous on earth, posing a growing threat to human health. Previous studies have shown that the lung is a primary organ for MPs exposure. Resveratrol (RES) is a common dietary polyphenol that exhibits anti-inflammatory and antioxidant effects. However, whether RES exerts a protective effect against MPs-induced lung damage is still unknown. The targets of RES were retrieved from five databases. Differentially expressed genes (DEGs) were identified through comprehensive bioinformatic analysis. Multiple algorithms were employed to screen for the core targets. Ultimately, molecular docking analysis and molecular dynamics (MD) simulations were utilized to confirm the binding affinity between RES and the core targets. In total, 1235 DEGs were identified in the transcriptomes. After removing duplicates, a total of 739 RES targets were obtained from five databases, and 66 of these targets intersected with DEGs. The potential core targets (Esr1, Ccl2) were further identified through topological analysis and machine learning. These findings were subsequently verified by molecular docking and MD simulations. This study demonstrated that RES may mitigate lung injury induced by MPs by targeting Esr1 and Ccl2. Our research offers a novel perspective on the prevention and treatment of MPs-induced lung injury.

Emerging roles of mechanosensitive ion channels in ventilator induced lung injury: a systematic review.

The pathogenetic mechanisms of ventilator-induced lung injury (VILI) still need to be elucidated. The mechanical forces during mechanical ventilation are continually sensed and transmitted by mechanosensitive ion channels (MSICs) in pulmonary endothelial, epithelial, and immune cells. In recent years, MSICs have been shown to be involved in VILI. A systematic search across PubMed, the Cochrane Library, Web of Science, and ScienceDirect was performed from inception to March 2024, and the review was conducted in accordance with PRISMA guidelines. The potential eligible studies were evaluated by two authors independently. Study characteristics, quality assessment, and potential mechanisms were analyzed. We included 23 eligible studies, most of which were performed with murine animals in vivo. At the in vitro level, 52% and 48% of the experiments were conducted with human or animal cells, respectively. No clinical studies were found. The most reported MSICs include Piezo channels, transient receptor potential channels, potassium channels, and stretch-activated sodium channels. Piezo1 has been the most concerned channel in the recent five years. This study found that signal pathways, such as RhoA/ROCK1, could be enhanced by cyclic stretch-activated MSICs, which contribute to VILI through dysregulated inflammation and immune responses mediated by ion transport. The review indicates the emerging role of MSICs in the pathogenesis of VILI, especially as a signal-transmitting link between mechanical stretch and pathogenesis such as inflammation, disruption of cell junctions, and edema formation. Mechanical stretch stimulates MSICs to increase transcellular ion exchange and subsequently generates VILI through inflammation and other pathogeneses mediated by MSICs signal-transmitting pathways. These findings make it possible to identify potential therapeutic targets for the prevention of lung injury through further exploration and more studies. https://inplasy.com/inplasy-2024-10-0115/, identifier INPLASY2024100115.

Synergistic Antioxidant Activity of Lycium barbarum Polysaccharide and Chlorogenic Acid and Its Effect on Inflammatory Response of NR8383 Cells.

It is inevitable for polyphenols and polysaccharides to interact during food preparation. Modifications in microstructure can lead to changes in the physical and chemical properties of food systems, which in turn may influence the nutritional characteristics and functional activities of the food. Recent studies have shown that, in addition to traditional Chinese medicine compounds, certain natural polysaccharides and polyphenols exhibit significant anti-inflammatory and antioxidant properties. These compounds are also associated with beneficial therapeutic effects for the prevention and treatment of acute lung injury. The objective of this study was to examine the synergistic antioxidant effects of chlorogenic acid (CA) and Lycium barbarum polysaccharide (LBP) in various ratios, along with their combined antioxidant and anti-inflammatory effects on LPS-induced inflammation in rat alveolar macrophages. Using the Combination Index (CI), which quantifies the synergistic or antagonistic effect of two substances, all four combinations showed synergistic antioxidant properties over a range of concentrations by in vitro antioxidant property experiments. However, based on comparing them, the four group ratios exhibited the highest antioxidant activity of the infusion at CA:LBP = 1:7, indicating synergistic interactions (CI < 1). In addition, the antioxidant and anti-inflammatory effects of the CA-LBP complex were observed to alleviate cellular inflammatory injury by reducing LPS-induced nitric oxide and reactive oxygen species production and inhibiting the release of inflammatory factors such as TNF-α and IL-6.

Association of toll-like receptors with the airway-intestinal microbiota and pneumonia development in preterm infants - A case control study

BackgroundThe prevention and treatment of pneumonia and lung injury in preterm infants are major challenges for pediatricians worldwide. Few studies have analyzed the composition of bacterial colonies in the airway and intestine and their relationship with toll-like receptors (TLRs) as it relates to pneumonia in preterm infants. MethodsThis study included 70 infants born at 32–35 weeks gestation. Oral-tracheal aspirates at the time of birth, first-pass meconium, and serum specimens were collected. Bacterial deoxyribonucleic acid (DNA) was extracted from the Oral-tracheal aspirates and meconium, and 16S ribosomal ribonucleic acid (rRNA) genes were amplified and sequenced. The levels of TLR2 and TLR4 were analyzed using an enzyme-linked immunosorbent assay. Preterm infants were classified into non-pneumonia (A) and pneumonia (B) groups according to their clinical manifestations. ResultsSignificant differences in the alpha and beta diversities were observed between the two groups. Infants with pneumonia had less bacterial diversity in the airways and intestinal flora at birth than those without pneumonia. The three most predominant phyla in the airways at birth were Proteobacteria, Firmicutes, and Actinobacteria. The levels of TLR2 and TLR4 in oral-tracheal aspirates were higher in infants with pneumonia than in those without pneumonia, although serum TLR2 and TLR4 levels did not differ between the groups. Streptococcus in the oral tracheal aspirate was negatively correlated with TLR2 and TLR4 levels, and Ureaplasma in the oral-tracheal aspirate was negatively correlated with TLR4 levels in the airway. ConclusionReduced perinatal microbiota diversity is associated with the levels of TLR2 and TLR4, and may also have a significant impact on the development of pneumonia.

Control of inflammatory lung injury and repair by metabolic signaling in endothelial cells.

Sepsis-induced inflammatory lung injury includes acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). There are currently no effective treatments for ALI/ARDS, but clinical outcomes could be improved by inhibiting lung injury and/or promoting post-sepsis vascular repair. In this review, we describe studies of endothelial cell metabolic pathways in sepsis-induced ALI/ARDS and vascular repair and identify areas of research that deserve attention in future studies. We also describe studies of metabolic interventions that aim to inhibit ALI/ARDS and/or promote post-sepsis vascular repair, including those that target endothelial cell metabolites, endothelial cell metabolic signaling pathways, and endothelial cell metabolism. Endothelial cells are integral to both the injury and repair phases of ALI/ARDS. During the injury phase of ALI/ARDS, lung endothelial cell survival decreases, and lung endothelial cell-to-endothelial cell (EC-EC) junctions are weakened. During the repair phase after sepsis-induced lung injury, lung endothelial cell proliferation and lung EC-EC junction reannealing occur. These crucial aspects of ALI/ARDS and post-sepsis vascular repair, that is, endothelial cell viability, growth, and junction integrity, are controlled by a myriad of metabolites and metabolic signaling pathways in endothelial cells. Metabolic signaling pathways in endothelial cells represent a novel class of putative targets for the prevention and treatment of sepsis-induced inflammatory lung injury. Therapies that target metabolic signaling in endothelial cells are currently being explored as potential treatments for sepsis-induced inflammatory lung injury.

Nebulized Heparin for Prevention of Acute Lung Injury in Adult Patients Suffering Smoke Inhalation Injury: A Randomized Controlled Trial

Abstract Background Nebulized heparin (NH) has been used for treatment of inhalation injury- induced acute respiratory distress syndrome (ARDS) but its benefit for prevention of severe ARDS in those patients is not known. Aim of the Work The aim of this study was to examine the effect of NH on prevention of severe ARDS and on survival in patients suffering inhalation injury. Methods Eighty-eight adults suffering inhalation injury were randomized to receive 5,000 IU of heparin in 3 ml normal saline (n = 44) or to normal saline only (n = 44) by nebulization every 4 hours until successful extubation or death, whichever was earlier, to a maximum of 14 days. Primary outcomes were occurrence of severe ARDS (PaO2/FiO2 ratio &amp;lt;100) and survival to ICU discharge. Secondary outcomes were failed weaning from mechanical ventilation (reintubation in 48 hours after extubation) and occurrence of heparin-related side effects. Results There was no statistically significant difference between both groups as regards occurrence of severe ARDS (p-value =.233), mortality (p-value = .354), reintubation within 48 hours (p-value = .419) or thrombocytopenia (p-value = .777). None of the patients developed abnormal prolongation of prothrombin time (PTT). Estimated marginal mean PaO2/FiO2 ratio was significantly higher (p-value &amp;lt; .001) and mean platelet count was significantly lower (p-value = .005) in the nebulized heparin group, with no statistically significant difference in mean PTT (p-value = .074). Conclusions Nebulized heparin was associated with improved oxygenation but was did not reduce the incidence of severe ARDS, failed weaning from mechanical ventilation or mortality in patients suffering inhalation injury. Nebulized heparin had no effect on prothrombin time but could be associated with clinically unimportant reduction in platelet count.

MFSD7C protects hemolysis-induced lung impairments by inhibiting ferroptosis

Hemolysis drives susceptibility to lung injury and predicts poor outcomes in diseases, such as malaria and sickle cell disease (SCD). However, the underlying pathological mechanism remains elusive. Here, we report that major facilitator superfamily domain containing 7 C (MFSD7C) protects the lung from hemolytic-induced damage by preventing ferroptosis. Mechanistically, MFSD7C deficiency in HuLEC-5A cells leads to mitochondrial dysfunction, lipid remodeling and dysregulation of ACSL4 and GPX4, thereby enhancing lipid peroxidation and promoting ferroptosis. Furthermore, systemic administration of MFSD7C mRNA-loaded nanoparticles effectively prevents lung injury in hemolytic mice, such as HbSS-Townes mice and PHZ-challenged 7 C−/− mice. These findings present the detailed link between hemolytic complications and ferroptosis, providing potential therapeutic targets for patients with hemolytic disorders.

DUSP6 protein action and related hub genes prevention of sepsis-induced lung injury were screened by WGCNA and Venn

During a sepsis infection, the lung is extremely susceptible to damage. A condition known as acute respiratory distress syndrome (ARDS) may develop in extreme circumstances. The primary objective of this research is to identify important genes that are related with both sepsis and lung injury. These genes have the potential to act as novel biomarkers in the investigation of sepsis-induced lung injury prevention strategies. It was possible to download from GEO data both the sepsis-related dataset (GSE64457) and the lung injury-related dataset (GSE40839). In the GSE64457 dataset, using the “limma” package in R revealed 429 differentially expressed genes (DEGs) with logFC values more than or equal to −1 and p values <0.05. There were 266 genes that were up-regulated and 163 genes that were down-regulated. Through the use of Gene Ontology (GO), it was discovered that the majority of the DEGs were associated with the inflammatory response (BP terms), a particular granule lumen (CC terms), and protein binding (MF terms). By doing a pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes (KEGG), researchers were able to identify DEGs that were mostly associated with the NOD-like receptor signalling pathway, the TNF signalling pathway, and Epstein-Barr virus infection. Within the GSE40839 dataset, Weighted Gene Co-Expression Network Analysis (WGCNA) yielded a total of 7 modules, from which it was possible to screen out 2 critical modules and 693 key genes. The important genes and DEGs were both subjected to a Venn analysis. Finally, 14 genes that overlapped (ARL4A, LAIR1, MTHFD2, TSPAN13, DUSP6, PECR, CBS, TES, ASNS, SYNE1, FGF13, LCN2, KLF10, BCAT1) were closely associated to the incidence and development of sepsis-induced lung injury. This indicates that these genes are the essential genes to avoid the occurrence of sepsis-induced lung injury. This study provides novel strategies for preventing lung harm brought on by sepsis.

Antioxidant Activity of Baby Java Citrus Peel Extract Promotes Lung Tissue Repair in Mice Challenged by Lipopolysaccharides

Acute lung injury tends to be induced by infection or sepsis that disrupts alveolar and vascular permeability, neutrophil influx, and edema. Those impairments are worsened by the increase of oxidative stress along with hyperinflammation response. Oxidative stress in lung tissue could be indicated by malondialdehyde (MDA) and nuclear fac-tor erythroid 2-related factor 2 (Nrf2) expression. This research aimed to evaluate the efficacy of Baby Java citrus peel extract (BJE) in suppressing oxidative stress and preventing lung injury in lipopolysaccharides (LPS)-induced mice. Twenty-five male BALB/c mice were divided into five groups consisting of untreated (N), LPS (A), and LPS-induced followed by treatment using BJE at various doses: 75 mg/kg BW (BJE-1), 105 mg/kg BW (BJE-2), and 150 mg/kg BW (BJE-3). Lungs were isolated for histopathological analysis also detection of MDA and Nrf2 using flow cytometry. BJE at the dose of 105 mg/kg BW could inhibit the alteration of lung histology following LPS challenge including alveolar and interstitial neutrophil infiltration, proteinaceous debris, and septal thickening. The same dose also showed good potency in suppressing MDA and Nrf2 levels as oxidative stress indicators. Our findings demonstrated the protective effects of Baby Java citrus peel in acute lung injury and oxidative stress prevention after LPS exposure

Human pulmonary microvascular endothelial cells respond to DAMPs from injured renal tubular cells.

Acute kidney injury (AKI) causes distant organ dysfunction through yet unknown mechanisms, leading to multiorgan failure and death. The lungs are one of the most common extrarenal organs affected by AKI, and combined lung and kidney injury has a mortality as high as 60%-80%. One mechanism that has been implicated in lung injury after AKI involves molecules released from injured kidney cells (DAMPs, or damage-associated molecular patterns) that promote a noninfectious inflammatory response by binding to pattern recognition receptors (PRRs) constitutively expressed on the pulmonary endothelium. To date there are limited data investigating the role of PRRs and DAMPs in the pulmonary endothelial response to AKI. Understanding these mechanisms holds great promise for therapeutics aimed at ameliorating the devastating effects of AKI. In this study, we stimulate primary human microvascular endothelial cells with DAMPs derived from injured primary renal tubular epithelial cells (RTECs) as an ex-vivo model of lung injury following AKI. We show that DAMPs derived from injured RTECs cause activation of Toll-Like Receptor and NOD-Like Receptor signaling pathways as well as increase human primary pulmonary microvascular endothelial cell (HMVEC) cytokine production, cell signaling activation, and permeability. We further show that cytokine production in HMVECs in response to DAMPs derived from RTECs is reduced by the inhibition of NOD1 and NOD2, which may have implications for future therapeutics. This paper adds to our understanding of PRR expression and function in pulmonary HMVECs and provides a foundation for future work aimed at developing therapeutic strategies to prevent lung injury following AKI.

An active peptide from yak inhibits hypoxia-induced lung injury via suppressing VEGF/MAPK/inflammatory signaling

Pulmonary vascular remodeling and inflammation play an important role in the hypoxic-induced lung diseases. Our previous investigations showed that peptide from yak milk residues could alleviate inflammation. In this study, our results suggest that peptide (LV) from yak milk residues peptide had protective effect of lung in the animal models of hypoxic-induced lung injury. LV Gavage could improve pulmonary vascular remodeling in the lung tissues of hypoxic mice. A comprehensive analysis of metabolomics and transcriptomics revealed that 5-KETE, 8,9-EET, and 6-keto-prostaglandin F1a might be potential targets to prevent lung injury in the hypoxic mice. These metabolites can be regulated by MAPK/VEGF and inflammatory pathways. Our data indicated that LV treatment could inhibit apoptosis and inflammation via Nrf2/NF-κB/MAPK/PHD-2 pathway and protected hypoxic-induced lung epithelial cells injury. Taken together, our results suggest that LV provides a novel therapeutic clue for the prevention of hypoxia-induced lung injury and inflammation-related lung diseases.

Current State of Ventilator Setting and Their Relationship with Mortality Rate in Patients under Mechanical Ventilation: A Cross-Sectional Study

Background: Given the importance of implementing lung protective strategies to prevent lung injury caused by ventilators and death of patients, it is necessary to monitor the current condition of hospitals and examine the relationship between the parameters set on the ventilators and patient mortality. This study conducted to determine the current state of ventilator setting and their relationship with mortality rate in patients under mechanical ventilation: a cross-sectional study. Methods: This is a cross-sectional study that was conducted between June to December 2020 in one of the hospitals affiliated to Tehran University of Medical Sciences. The initial tidal volume set on the ventilator was recorded for 304 patients under mechanical ventilation and then, their heights were measured and their tidal volumes were determined based on the standard formula. Other parameters set on the ventilator as well as systolic and diastolic blood pressures of patients were also recorded and their survival rate was investigated. The data was analyzed by SPSS software, using descriptive statistics and logistic regression model. Results: Among patients, who were under mechanical ventilation, 77.6% were hospitalized in intensive care units and the rest were hospitalized in general wards. The mean adjusted tidal volume for patients was 472.91 ± 32.13 ml. The mean peak inspiratory pressure and plateau pressure were 28.00±6.98 and 13.88±4.93 CmH2O, respectively. Also, 37.2% of patients died during the hospitalization. The results of adjusted odds ratio based on multivariate logistic regression model for predictors of mortality rate showed that the variables of patients' age [OR=1.040 (1.019-1.062)], the hospital’s general ward in comparison with the ICU [OR=11.379 (5.130-25.240)] and the peak inspiratory pressure [OR=1.072 (1.007-1.141)] had a direct and significant relationship with mortality rate (in all cases P&lt;0.05). Meanwhile, the plateau pressure [OR=0.886 (0.808 -0.972)] had an inverse and significant relationship with mortality rate (P&lt;0.05). Conclusion: Despite the recommendations regarding lung protective strategies, in some cases, some parameters set in the ventilator are outside the recommended levels, which can effect on patients mortality. So monitoring and controlling the implementation of lung protective strategies and paying attention to controlling pressures set on the ventilator are among measures that should be taken in medical centers in order to prevent lung injuries and maintain patient safety.

Emodin alleviates intestinal ischemia/reperfusion-induced lung injury by upregulating HO-1 expression via PI3K/AkT pathway

BackgroundEmodin, a natural anthraquinone derivative found in various Chinese medicinal herbs, has been proved to be an effective therapeutic agent in the treatment of many diseases. However, its effect on lung injury after intestinal ischemia/reperfusion injury remains unknown. This research was designed to investigate whether emodin protects against intestinal ischemia/reperfusion-induced lung injury and to elucidate the underlying molecular mechanisms in vivo and in vitro. MethodsIntestinal ischemia/reperfusion injury was induced by occluding the superior mesenteric artery in mice, and mouse lung epithelial-12 cells were subjected to oxygen-glucose deprivation and reoxygenation to establish an in vitro model. ResultsOur data indicated that emodin treatment reduced intestinal ischemia/reperfusion-induced oxidative stress, inflammation and apoptosis in lung tissues and alleviated lung injury. However, the protective effects of emodin on intestinal ischemia/reperfusion-induced lung injury were reversed by the protein kinase B inhibitor triciribine or the heme oxygenase-1 inhibitor tin protoporphyrin IX. The protein kinase inhibitor triciribine also downregulated the expression of heme oxygenase-1. ConclusionIn conclusion, our data suggest that emodin treatment protects against intestinal ischemia/reperfusion-induced lung injury by enhancing heme oxygenase-1 expression via activation of the PI3K/protein kinase pathway. Emodin may act as a potential therapeutic agent for the prevention and treatment of lung injury induced by intestinal ischemia/reperfusion.

Adipose-derived stem cells ameliorate radiation-induced lung injury by activating the DDAH1/ADMA/eNOS signaling pathway

BackgroundIonizing radiation-induced lung injury is caused by the initial inflammatory reaction and leads to advanced fibrosis of lung tissue. Adipose-derived stem cells (ASCs) are a type of mesenchymal stem cell that can differentiate into various functional cell types with broad application prospects in the treatment of tissue damage. The purpose of this study was to explore the protective effect of ASCs against radiation-induced lung injury and to provide a novel basis for prevention and treatment of radiation-induced lung injury. Materials and methodsFifty mice were randomly divided into a control group (Ctrl), radiation exposure group (IR), radiation exposure plus ASC treatment group (IR + ASC), radiation exposure plus L-257 group (IR + L-257), and radiation exposure plus ASC treatment and L-257 group (IR + ASC + L-257). Mice in IR, IR + ASC, and IR + ASC + L-257 groups were exposed to a single whole-body dose of 5 Gy X-rays (160 kV/25 mA, 1.25 Gy/min). Within 2 h after irradiation, mice in IR + ASC and IR + ASC + L-257 groups were injected with 5 × 106 ASCs via the tail vein. Mice in IR + L-257 and IR + ASC + L-257 groups were intraperitoneally injected with 30 mg/kg L-257 in 0.5 mL saline. ResultsThe mice in the IR group exhibited lung hemorrhage, edema, pulmonary fibrosis, and inflammatory cell infiltration, increased release of proinflammatory cytokines, elevation of oxidative stress and apoptosis, and inhibition of the dimethylarginine dimethylamino hydratase 1 (DDAH1)/ADMA/eNOS signaling pathway. ASC treatment alleviated radiation-induced oxidative stress, apoptosis, and inflammation, and restored the DDAH1/ADMA/eNOS signaling pathway. However, L-257 pretreatment offset the protective effect of ASCs against lung inflammation, oxidative stress, and apoptosis. ConclusionsThese data suggest that ASCs ameliorate radiation-induced lung injury, and the mechanism may be mediated through the DDAH1/ADMA/eNOS signaling pathway.

Necroptosis blockade prevents lung injury in severe influenza.

Severe influenza A virus (IAV) infections can result in hyper-inflammation, lung injury and acute respiratory distress syndrome1-5 (ARDS), for which there are no effective pharmacological therapies. Necroptosis is an attractive entry point for therapeutic intervention in ARDS and related inflammatory conditions because it drives pathogenic lung inflammation and lethality during severe IAV infection6-8 and can potentially be targeted by receptor interacting protein kinase 3 (RIPK3) inhibitors. Here we show that a newly developed RIPK3 inhibitor, UH15-38, potently and selectively blocked IAV-triggered necroptosis in alveolar epithelial cells in vivo. UH15-38 ameliorated lung inflammation and prevented mortality following infection with laboratory-adapted and pandemic strains of IAV, without compromising antiviral adaptive immune responses or impeding viral clearance. UH15-38 displayed robust therapeutic efficacy even when administered late in the course of infection, suggesting that RIPK3 blockade may provide clinical benefit in patients with IAV-driven ARDS and other hyper-inflammatory pathologies.

Research trends and hotspots in the field of electrical impedance tomography for mechanical ventilation: a bibliometric analysis.

Electrical impedance tomography (EIT) is a relatively recent functional imaging technique that is both noninvasive and radiation free. EIT measures the associated voltage when a weak current is applied to the surface of the human body to determine the distribution of electrical resistance within tissues. We performed a bibliometrics-based review to explore the geographic hotspots of current research and future trends developing in the field of EIT for mechanical ventilation. The Web of Science database was searched from its inception to June 25, 2023. CiteSpace software was used to visualize and analyze the relevant literature and identify the most impactful literature, trends, and hotspots. 363 articles describing EIT use in mechanical ventilation were identified. A fluctuating growth in the number of publications was observed from 1998 to 2023. Germany had the highest number of articles (n=154), followed by Italy (n=53) and China (n=52). A cluster analysis of keyword co-occurrence revealed that "titration", "ventilator-related lung injury", and "oxygenation" were the most actively researched terms associated with the use of EIT in mechanically ventilated patients. Significant progress has been made in EIT research for mechanical ventilation. EIT research is limited to a small number of countries with a present research focus on the prevention and treatment of ventilator-related lung injury, oxygenation status, and prone ventilation. These topics are expected to remain research hotspots in the future.