scholarly journals Seawater-drowning-induced acute lung injury: From molecular mechanisms to potential treatments

2017 ◽  
Vol 13 (6) ◽  
pp. 2591-2598 ◽  
Author(s):  
Faguang Jin ◽  
Congcong Li
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms

Molecular Mechanisms in Acute Lung Injury

1993 ◽  
pp. 275-292 ◽  
Author(s):  
Peter A. Ward ◽  
Michael S. Mulligan
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms

scholarly journals Basic and clinical research progress in acute lung injury/acute respiratory distress syndrome

2018 ◽  
Vol 7 (2) ◽  
pp. 38-43 ◽  
Author(s):  
Tong Wang
Keyword(s):  
Acute Respiratory Distress Syndrome ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Respiratory Distress Syndrome ◽  
Respiratory Distress ◽  
Molecular Mechanisms ◽  
Distress Syndrome ◽  
Severe Infection ◽  
Research Progress ◽  
Severe Stage

Abstract Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) is an acute progressive respiratory failure caused by severe infection, trauma, shock, poisoning, inhaled harmful gas, acute pancreatitis, and pathological obstetrics. ALI and ARDS demonstrate similar pathophysiological changes. The severe stage of ALI is defined as ARDS. At present, a significant progress has been achieved in the study of the pathogenesis and pathophysiology of ALI/ARDS. Whether or not ALI/ARDS patients can recover depends on the degree of lung injury, extra-pulmonary organ damage, original primary disease of a patient, and adequacy in supportive care. Conservative infusion strategies and protective lung ventilation reduce ARDS disability and mortality. In this study, the pathogenesis of ALI/ARDS, lung injury, molecular mechanisms of lung repair, and conservative infusion strategies and pulmonary protective ventilation are reviewed comprehensively.

Differential modulation of surfactant protein D under acute and persistent hypoxia in acute lung injury

2012 ◽  
Vol 303 (1) ◽  
pp. L43-L53 ◽  
Author(s):  
Koji Sakamoto ◽  
Naozumi Hashimoto ◽  
Yasuhiro Kondoh ◽  
Kazuyoshi Imaizumi ◽  
Daisuke Aoyama ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
De Novo ◽  
Acute Hypoxia ◽  
Surfactant Protein ◽  
Surfactant Protein D ◽  
Alveolar Cells ◽  
Mesenchymal Transition ◽  
Twist Expression

Hypoxia contributes to the development of fibrosis with epithelial-mesenchymal transition (EMT) via stimulation of hypoxia-inducible factor 1α (HIF-1α) and de novo twist expression. Although hypoxemia is associated with increasing levels of surfactant protein D (SP-D) in acute lung injury (ALI), the longitudinal effects of hypoxia on SP-D expression in lung tissue injury/fibrosis have not been fully evaluated. Here, the involvement of hypoxia and SP-D modulation was evaluated in a model of bleomycin-induced lung injury. We also investigated the molecular mechanisms by which hypoxia might modulate SP-D expression in alveolar cells, by using a doxycycline (Dox)-dependent HIF-1α expression system. Tissue hypoxia and altered SP-D levels were present in bleomycin-induced fibrotic lesions. Acute hypoxia induced SP-D expression, supported by the finding that Dox-induced expression of HIF-1α increased SP-D expression. In contrast, persistent hypoxia repressed SP-D expression coupled with an EMT phenotype and twist expression. Long-term expression of HIF-1α caused SP-D repression with twist expression. Ectopic twist expression repressed SP-D expression. The longitudinal observation of hypoxia and SP-D levels in ALI in vivo was supported by the finding that HIF-1α expression stabilized by acute hypoxia induced increasing SP-D expression in alveolar cells, whereas persistent hypoxia induced de novo twist expression in these cells, causing repression of SP-D and acquisition of an EMT phenotype. Thus this is the first study to demonstrate the molecular mechanisms, in which SP-D expression under acute and persistent hypoxia in acute lung injury might be differentially modulated by stabilized HIF-1α expression and de novo twist expression.

scholarly journals Lung biopsy cells transcriptional landscape from COVID-19 patient stratified lung injury in SARS-CoV-2 infection through impaired pulmonary surfactant metabolism

2020 ◽  
Author(s):  
Abul Bashar Mir Md. Khademul Islam ◽  
Md. Abdullah-Al-Kamran Khan
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Biopsy ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Gene Expression Pattern ◽  
Viral Proteins ◽  
Cytokine Signaling ◽  
Surfactant Metabolism

AbstractClinical management of COVID-19 is still complicated due to the lack of therapeutic interventions to reduce the breathing problems, respiratory complications and acute lung injury – which are the major complications of most of the mild to critically affected patients and the molecular mechanisms behind these clinical features are still largely unknown. In this study, we have used the RNA-seq gene expression pattern in the COVID-19 affected lung biopsy cells and compared it with the effects observed in typical cell lines infected with SARS-CoV-2 and SARS-CoV. We performed functional overrepresentation analyses using these differentially expressed genes to signify the processes/pathways which could be deregulated during SARS-CoV-2 infection resulting in the symptomatic impairments observed in COVID-19. Our results showed that the significantly altered processes include inflammatory responses, antiviral cytokine signaling, interferon responses, and interleukin signaling etc. along with downmodulated processes related to lung’s functionality like-responses to hypoxia, lung development, respiratory processes, cholesterol biosynthesis and surfactant metabolism. We also found that the viral protein interacting host’s proteins involved in similar pathways like: respiratory failure, lung diseases, asthma, and hypoxia responses etc., suggesting viral proteins might be deregulating the processes related to acute lung injury/breathing complications in COVID-19 patients. Protein-protein interaction networks of these processes and map of gene expression of deregulated genes revealed that several viral proteins can directly or indirectly modulate the host genes/proteins of those lung related processes along with several host transcription factors and miRNAs. Surfactant proteins and their regulators SPD, SPC, TTF1 etc. which maintains the stability of the pulmonary tissue are found to be downregulated through viral NSP5, NSP12 that could lead to deficient gaseous exchange by the surface films. Mitochondrial dysfunction owing to the aberration of NDUFA10, NDUFAF5, SAMM50 etc. by NSP12; abnormal thrombosis in lungs through atypical PLAT, EGR1 functions by viral ORF8, NSP12; dulled hypoxia responses due to unusual shift in HIF-1 downstream signaling might be the causative elements behind the acute lung injury in COVID-19 patients. Our study put forward a distinct mechanism of probable virus induced lung damage apart from cytokine storm and advocate the need of further research for alternate therapy in this direction.

Validation of novel hub genes and molecular mechanisms in acute lung injury using an integrative bioinformatics approach

2021 ◽  
Author(s):  
Qingchun Liang ◽  
Qin Zhou ◽  
Jinhe Li ◽  
Zhugui Chen ◽  
Zhihao Zhang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
Molecular Biomarkers ◽  
Functional Enrichment ◽  
Lung Injury Score ◽  
Control Group ◽  
High Morbidity ◽  
Hub Genes

Abstract Acute lung injury (ALI) is an inflammatory pulmonary disease that can easily develop into serious acute respiratory distress syndrome, which has high morbidity and mortality. However, the molecular mechanism of ALI remains unclear, and few molecular biomarkers for diagnosis and treatment have been identified. In this study, we aimed to identify novel molecular biomarkers using a bioinformatics approach. Gene expression data were obtained from the Gene Expression Omnibus database, co-expressed differentially expressed genes (CoDEGs) were identified using R software, and further functional enrichment analyses were conducted using the online tool Database for Annotation, Visualization, and Integrated Discovery. A protein–protein interaction network was established using the STRING database and Cytoscape software. Lipopolysaccharide (LPS)-induced ALI mouse model was constructed and verified. The hub genes were screened and validated in vivo. The transcription factors (TFs) and miRNAs associated with the hub genes were predicted using the NetworkAnalyst database. In total, 71 CoDEGs were screened and found to be mainly involved in the cytokine–cytokine receptor interactions, and the tumor necrosis factor and malaria signaling pathways. Animal experiments showed that the lung injury score, bronchoalveolar lavage fluid protein concentration, and wet-to-dry weight ratio were higher in the LPS group than those in the control group. Real-time polymerase chain reaction analysis indicated that most of the hub genes such as colony-stimulating factor 2 (Csf2) were overexpressed in the LPS group. A total of 20 TFs including nuclear respiratory factor 1 (NRF1) and two miRNAs were predicted to be regulators of the hub genes. In summary, Csf2 may serve as a novel diagnostic and therapeutic target for ALI. NRF1 and mmu-mir-122-5p may be key regulators in the development of ALI.

scholarly journals Repair after acute lung injury: molecular mechanisms and therapeutic opportunities

Critical Care ◽  
2012 ◽  
Vol 16 (2) ◽  
pp. 209 ◽  
Author(s):  
Adrián González-López ◽  
Guillermo M Albaiceta
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms

scholarly journals Panaxydol attenuates ferroptosis against LPS-induced acute lung injury in mice by Keap1-Nrf2/HO-1 pathway

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jiucui Li ◽  
Kongmiao Lu ◽  
Fenglan Sun ◽  
Shanjuan Tan ◽  
Xiao Zhang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Molecular Mechanisms ◽  
Pulmonary Inflammation ◽  
Epithelial Cell Line ◽  
High Morbidity ◽  
Regulated Necrosis ◽  
The Impact

Abstract Background Acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) induces uncontrolled and self-amplified pulmonary inflammation, and has high morbidity and mortality rates in critically ill patients. In recent years, many bioactive ingredients extracted from herbs have been reported to effectively ameliorate ALI/ARDS via different mechanisms. Ferroptosis, categorized as regulated necrosis, is more immunogenic than apoptosis and contributes to the progression of ALI. In this study, we examined the impact of panaxydol (PX), isolated from the roots of Panax ginseng, on lipopolysaccharide (LPS)-induced ALI in mice. Methods In vivo, the role of PX on LPS-induced ALI in mice was tested by determination of LPS-induced pulmonary inflammation, pulmonary edema and ferroptosis. In vitro, BEAS-2B cells were used to investigate the molecular mechanisms by which PX functions via determination of inflammation, ferroptosis and their relationship. Results Administration of PX protected mice against LPS-induced ALI, including significantly ameliorated lung pathological changes, and decreased the extent of lung edema, inflammation, and ferroptosis. In vitro, PX inhibited LPS-induced ferroptosis and inflammation in bronchial epithelial cell line BEAS-2B cells. The relationship between ferroptosis and inflammation was investigated. The results showed that ferroptosis mediated inflammation in LPS-treated BEAS-2B cells, and PX might ameliorate LPS-induced inflammation via inhibiting ferroptosis. Meanwhile, PX could upregulate Keap1-Nrf2/HO-1 pathway, and selective inhibition of Keap1-Nrf2/HO-1 pathway significantly abolished the anti-ferroptotic and anti-inflammatory functions of PX in LPS-treated cells. Conclusion PX attenuates ferroptosis against LPS-induced ALI via Keap1-Nrf2/HO-1 pathway, and is a promising novel therapeutic candidate for ALI.

scholarly journals Cellular Signal Transduction Pathways Involved in Acute Lung Injury Induced by Intestinal Ischemia-Reperfusion

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Guangyao Li ◽  
Yingyi Zhang ◽  
Zhe Fan
Keyword(s):  
Signal Transduction ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Intestinal Ischemia ◽  
Molecular Mechanisms ◽  
Ischemia Reperfusion ◽  
Organ Injury ◽  
Intestinal Barrier Function ◽  
Signal Transduction Pathways ◽  
Intestinal Ischemia Reperfusion

Intestinal ischemia-reperfusion (II/R) injury is a common type of tissue and organ injury, secondary to intestinal and mesenteric vascular diseases. II/R is characterized by a high incidence rate and mortality. In the II/R process, intestinal barrier function is impaired and bacterial translocation leads to excessive reactive oxygen species, inflammatory cytokine release, and even apoptosis. A large number of inflammatory mediators and oxidative factors are released into the circulation, leading to severe systemic inflammation and multiple organ failure of the lung, liver, and kidney. Acute lung injury (ALI) is the most common complication, which gradually develops into acute respiratory distress syndrome and is the main cause of its high mortality. This review summarizes the signal transduction pathways and key molecules in the pathophysiological process of ALI induced by II/R injury and provides a new therapeutic basis for further exploration of the molecular mechanisms of ALI induced by II/R injury. In particular, this article will focus on the biomarkers involved in II/R-induced ALI.

scholarly journals Cissus subtetragona Planch. Ameliorates Inflammatory Responses in LPS-induced Macrophages, HCl/EtOH-induced Gastritis, and LPS-induced Lung Injury via Attenuation of Src and TAK1

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 6073
Author(s):  
Laily Rahmawati ◽  
Nur Aziz ◽  
Jieun Oh ◽  
Yo Han Hong ◽  
Byoung Young Woo ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Mouse Models ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Raw264.7 Cells ◽  
Acute Gastritis ◽  
Anti Inflammatory

Several Cissus species have been used and reported to possess medicinal benefits. However, the anti-inflammatory mechanisms of Cissus subtetragona have not been described. In this study, we examined the potential anti-inflammatory effects of C. subtetragona ethanol extract (Cs-EE) in vitro and in vivo, and investigated its molecular mechanism as well as its flavonoid content. Lipopolysaccharide (LPS)-induced macrophage-like RAW264.7 cells and primary macrophages as well as LPS-induced acute lung injury (ALI) and HCl/EtOH-induced acute gastritis mouse models were utilized. Luciferase assays, immunoblotting analyses, overexpression strategies, and cellular thermal shift assay (CETSA) were performed to identify the molecular mechanisms and targets of Cs-EE. Cs-EE concentration-dependently reduced the secretion of NO and PGE2, inhibited the expression of inflammation-related cytokines in LPS-induced RAW264.7 cells, and decreased NF-κB- and AP-1-luciferase activity. Subsequently, we determined that Cs-EE decreased the phosphorylation events of NF-κB and AP-1 pathways. Cs-EE treatment also significantly ameliorated the inflammatory symptoms of HCl/EtOH-induced acute gastritis and LPS-induced ALI mouse models. Overexpression of HA-Src and HA-TAK1 along with CETSA experiments validated that inhibited inflammatory responses are the outcome of attenuation of Src and TAK1 activation. Taken together, these findings suggest that Cs-EE could be utilized as an anti-inflammatory remedy especially targeting against gastritis and acute lung injury by attenuating the activities of Src and TAK1.

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