ABSTRACT
The effective remission of acute respiratory distress syndrome- (ARDS-) caused pulmonary fibrosis determines the recovery of lung function. Inositol can relieve lung injuries induced by ARDS. However, the mechanism of myo-inositol in the development of ARDS is unclear, which limits its use in the clinic. We explored the role and mechanism of myo-inositol in the development of ARDS by using an in vitro lipopolysaccharide- (LPS-) established alveolar epithelial cell inflammation model and an in vivo ARDS mouse model. Our results showed that inositol can alleviate the progression of pulmonary fibrosis. More significantly, we found that inositol can induce autophagy to inhibit the progression pulmonary fibrosis caused by ARDS. In order to explore the core regulators of ARDS affected by inositol, mRNA-seq sequencing was performed. Those results showed that transcription factor HIF-1α can regulate the expression of SLUG, which in turn can regulate the key gene E-Cadherin involved in cell epithelial-mesenchymal transition (EMT) as well as N-cadherin expression, and both were regulated by inositol. Our results suggest that inositol activates autophagy to inhibit EMT progression induced by the HIF-1α/SLUG signaling pathway in ARDS, and thereby alleviates pulmonary fibrosis.
Subject(s)
Pulmonary Fibrosis , Respiratory Distress Syndrome , Mice , Animals , Pulmonary Fibrosis/drug therapy , Pulmonary Fibrosis/chemically induced , Inositol/adverse effects , Signal Transduction , Respiratory Distress Syndrome/drug therapy , Cadherins/metabolism , Autophagy , Epithelial-Mesenchymal Transition , Lipopolysaccharides/pharmacologyABSTRACT
Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 infection. This study aims to examine the changes in peripheral blood parameters during the early stages of COVID-19 and influenza. We analyzed the peripheral blood parameters of 169 COVID-19 patients and 131 influenza patients during the early-onset stage. Results from the patients with COVID-19 were compared with those from healthy controls and influenza patients. In addition, results from patients with common and severe COVID-19 were further compared. There were significant differences between COVID-19 and influenza patients in terms of age, white blood cell count, platelet count, percentage of neutrophils, percentage of lymphocytes, percentage of monocytes, percentage of eosinophils, percentage of basophils, neutrophil, count and monocyte count. Two parameters (monocyte count and percentage of basophils) were combined to clarify the diagnostic efficacy of COVID-19 and influenza and the area under the curve was found to be 0.772. Comparison of peripheral blood parameters from common COVID-19, severe COVID-19, and influenza patients revealed many differences during the early disease stages. The diagnostic formula developed by this study will be of benefit for physicians in the differentiation of COVID-19 and influenza.
Subject(s)
COVID-19/blood , COVID-19/diagnosis , Influenza, Human/blood , Influenza, Human/diagnosis , Adolescent , Adult , Aged , China , Diagnosis, Differential , Female , Humans , Leukocyte Count , Lymphocytes/cytology , Male , Middle Aged , Monocytes/cytology , Neutrophils/cytology , Platelet Count , Young AdultABSTRACT
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-a new coronavirus that has led to a worldwide pandemic1-has a furin cleavage site (PRRAR) in its spike protein that is absent in other group-2B coronaviruses2. To explore whether the furin cleavage site contributes to infection and pathogenesis in this virus, we generated a mutant SARS-CoV-2 that lacks the furin cleavage site (ΔPRRA). Here we report that replicates of ΔPRRA SARS-CoV-2 had faster kinetics, improved fitness in Vero E6 cells and reduced spike protein processing, as compared to parental SARS-CoV-2. However, the ΔPRRA mutant had reduced replication in a human respiratory cell line and was attenuated in both hamster and K18-hACE2 transgenic mouse models of SARS-CoV-2 pathogenesis. Despite reduced disease, the ΔPRRA mutant conferred protection against rechallenge with the parental SARS-CoV-2. Importantly, the neutralization values of sera from patients with coronavirus disease 2019 (COVID-19) and monoclonal antibodies against the receptor-binding domain of SARS-CoV-2 were lower against the ΔPRRA mutant than against parental SARS-CoV-2, probably owing to an increased ratio of particles to plaque-forming units in infections with the former. Together, our results demonstrate a critical role for the furin cleavage site in infection with SARS-CoV-2 and highlight the importance of this site for evaluating the neutralization activities of antibodies.