Comparative analysis of clinical features of lower respiratory tract infection with respiratory syncytial virus and influenza virus in adults: a retrospective study.

BACKGROUND: Respiratory syncytial virus (RSV) infection in adults remains less recognized and understood, both socially and clinically, compared to influenza virus infection. This retrospective study aims to delineate and compare the clinical manifestations of adult RSV and influenza virus infections in the lower respiratory tract, thereby enhancing awareness of RSV lower respiratory tract infection and providing strategic insights for its prevention and treatment. METHODS: Clinical data from January 2019 to December 2020 were analyzed for 74 patients with RSV and 129 patients with influenza A/B virus lower respiratory tract infections who were admitted to respiratory or intensive care units. All patients had complete clinical data with positive IgM and negative IgG viral antibodies. Comparison parameters included onset timing, baseline data, clinical manifestations, supplementary examination results, treatment methods, and prognosis, while logistic regression was employed to ascertain the correlation of clinical features between the two patient groups. RESULTS: In comparison to the influenza group, the RSV group presented less frequently with fever at admission but exhibited a higher incidence of dyspnea and wheezing on pulmonary auscultation (P < 0.01). RSV infection was more prevalent among patients with underlying diseases, particularly chronic obstructive pulmonary disease (COPD) and demonstrated a higher probability of co-infections, most notably with Mycoplasma (P < 0.01). The RSV group had significantly higher lymphocyte counts (P < 0.01) and exhibited more incidences of pleural thickening, pulmonary fibrosis, and emphysema (P < 0.05). The use of non-invasive mechanical ventilation was more common, and hospital stays were longer in the RSV group compared to the influenza group (P < 0.05). Logistic multivariate regression analysis further revealed that age and tachypnea incidence were significantly higher in the RSV group (P < 0.05). CONCLUSION: Compared to influenza virus infection, adults with COPD are more susceptible to RSV infection. Moreover, RSV infection elevates the risk of co-infection with Mycoplasma and may lead to conditions such as pleural thickening, pulmonary fibrosis, and emphysema. The requirement for non-invasive mechanical ventilation is higher in RSV-infected patients, who also tend to have longer hospital stays. Therefore, greater awareness and preventive strategies against RSV infection are imperative.

Using biological information to analyze potential miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer.

BACKGROUND: Lung cancer is the most common malignant tumor, and it has a high mortality rate. However, the study of miRNA-mRNA regulatory networks in the plasma of patients with non-small cell lung cancer (NSCLC) is insufficient. Therefore, this study explored the differential expression of mRNA and miRNA in the plasma of NSCLC patients. METHODS: The Gene Expression Omnibus (GEO) database was used to download microarray datasets, and the differentially expressed miRNAs (DEMs) were analyzed. We predicted transcription factors and target genes of the DEMs by using FunRich software and the TargetScanHuman database, respectively. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used for GO annotation and KEGG enrichment analysis of downstream target genes. We constructed protein-protein interaction (PPI) and DEM-hub gene networks using the STRING database and Cytoscape software. The GSE20189 dataset was used to screen out the key hub gene. Using The Cancer Genome Atlas (TCGA) and UALCAN databases to analyze the expression and prognosis of the key hub gene and DEMs. Then, GSE17681 and GSE137140 datasets were used to validate DEMs expression. Finally, the receiver operating characteristic (ROC) curve was used to verify the ability of the DEMs to distinguish lung cancer patients from healthy patients. RESULTS: Four upregulated candidate DEMs (hsa-miR199a-5p, hsa-miR-186-5p, hsa-miR-328-3p, and hsa-let-7d-3p) were screened from 3 databases, and 6 upstream transcription factors and 2253 downstream target genes were predicted. These genes were mainly enriched in cancer pathways and PI3k-Akt pathways. Among the top 30 hub genes, the expression of KLHL3 was consistent with the GSE20189 dataset. Except for let-7d-3p, the expression of other DEMs and KLHL3 in tissues were consistent with those in plasma. LUSC patients with high let-7d-3p expression had poor overall survival rates (OS). External validation demonstrated that the expression of hsa-miR-199a-5p and hsa-miR-186-5p in peripheral blood of NSCLC patients was higher than the healthy controls. The ROC curve confirmed that the DEMs could better distinguish lung cancer patients from healthy people. CONCLUSION: The results showed that miR-199a-5p and miR-186-5p may be noninvasive diagnostic biomarkers for NSCLC patients. MiR-199a-5p-KLHL3 may be involved in the occurrence and development of NSCLC.

Characterization of the fatty acid metabolism-related genes in lung adenocarcinoma to guide clinical therapy.

BACKGROUND: Lung adenocarcinoma (LUAD) is a common cancer with a bad prognosis. Numerous investigations have indicated that the metabolism of fatty acids plays an important role in the occurrence, progression, and treatment of cancer. Consequently, the objective of the current investigation was to elucidate the role and prognostic significance of genes associated with fatty acid metabolism in patients diagnosed with LUAD. MATERIALS AND METHODS: The data files were acquired from The Cancer Genome Atlas database and GSE31210 dataset. Univariate Cox and least absolute shrinkage and selection operator regression analyses were conducted to establish a prognostic risk scoring model depending on fatty acid metabolism-associated genes to predict the prognosis of patients with LUAD. pRRophetic algorithm was utilized to evaluate the potential therapeutic agents. Gene set variation analysis combined with cell-type identification based on the estimation of relative subsets of RNA transcript and single-sample gene set enrichment analysis was used to determine the association between immune cell infiltration and risk score. Tumor immune dysfunction and exclusion algorithm was employed to predict immunotherapeutic sensitivity. RESULTS: To forecast the prognosis of patients with LUAD, a risk scoring model based on five genes associated with fatty acid metabolism was developed, including LDHA, ALDOA, CYP4B1, DPEP2, and HPGDS. Using the risk score algorithm, patients were divided into higher- and lower-risk categories. Patients classified as minimal risk showed superior prognosis than those with elevated risk. In addition, individuals in the higher-risk group had a proclivity toward chemoresistance and amenable to immunotherapy. CONCLUSION: The prognostic risk scoring model aids in estimating the prognosis of LUAD patients. It may also provide new insights into LUAD carcinogenesis and therapeutic strategies.

A glycolysis-based three-gene signature predicts survival in patients with lung squamous cell carcinoma.

BACKGROUND: Lung cancer is one of the most lethal and most prevalent malignant tumors worldwide, and lung squamous cell carcinoma (LUSC) is one of the major histological subtypes. Although numerous biomarkers have been found to be associated with prognosis in LUSC, the prediction effect of a single gene biomarker is insufficient, especially for glycolysis-related genes. Therefore, we aimed to develop a novel glycolysis-related gene signature to predict survival in patients with LUSC. METHODS: The mRNA expression files and LUSC clinical information were obtained from The Cancer Genome Atlas (TCGA) dataset. RESULTS: Based on Gene Set Enrichment Analysis (GSEA), we found 5 glycolysis-related gene sets that were significantly enriched in LUSC tissues. Univariate and multivariate Cox proportional regression models were performed to choose prognostic-related gene signatures. Based on a Cox proportional regression model, a risk score for a three-gene signature (HKDC1, ALDH7A1, and MDH1) was established to divide patients into high-risk and low-risk subgroups. Multivariate Cox regression analysis indicated that the risk score for this three-gene signature can be used as an independent prognostic indicator in LUSC. Additionally, based on the cBioPortal database, the rate of genomic alterations in the HKDC1, ALDH7A1, and MDH1 genes were 1.9, 1.1, and 5% in LUSC patients, respectively. CONCLUSION: A glycolysis-based three-gene signature could serve as a novel biomarker in predicting the prognosis of patients with LUSC and it also provides additional gene targets that can be used to cure LUSC patients.

Specific Lung Squamous Cell Carcinoma Prognosis-Subtype Distinctions Based on DNA Methylation Patterns.

BACKGROUND Lung squamous cell carcinoma (LUSC) is one of the major types of non-small-cell lung cancer. Epigenetic alterations, such as DNA methylation, have been recognized to be closely associated with the tumorigenesis and progression. MATERIAL AND METHODS In this study, we investigated the prognosis subgroups and assessed their correlation with clinical characteristics in LUSC using a methylation array acquired from The Cancer Genome Atlas (TCGA) database. RESULTS A total of 196 DNA methylation sites exhibited a significant association with patient prognosis, and patients were further stratified into 7 prognosis subgroups based upon the consensus clustering. The patients in every subgroup were different in terms of prognosis and TNM stage. In addition, we found these 196 significant methylation sites corresponded to 258 genes. The function enrichment analysis revealed that these 258 genes enriched in biological pathways were closely related to cancers, such as DNA methylation and demethylation, cell cycle DNA replication, regulation of signal transduction by p53 class mediator, and genetic imprinting. Subsequently, we determined the levels of methylation sites in 7 subgroups, and found 24 intra-subgroup-specific methylation sites. Meanwhile, we selected 3 subgroups-specific methylation sites to construct the prognosis model for LUSC patients using multivariate Cox proportional risk regression model analysis. This model can effectively predict the prognosis of LUSC patients. CONCLUSIONS Our study identified a new classification of LUSC into 7 prognosis subgroups on the basis of DNA methylation data in TCGA, which demonstrated that molecular subtypes are independent factor for prognosis in LUSC. This may provide a more detailed explanation for LUSC heterogeneity. Additionally, this classification will contribute to discovery of new biomarkers of LUSC and provide more accurate subdivision of LUSC. Furthermore, these specific DNA methylation sites and corresponding genes can serve as biomarkers for early diagnosis, accurate therapy, and prognosis prediction.

The prognostic relevance of 14-3-3ξ expression in cancers: A meta-analysis.

OBJECTIVE: To gain an enhanced understanding of the prognostic importance of 14-3-3ξ levels in cancer patients. METHODS: The meta-analysis and systematic review was conducted in October 2019. Two reviewers independently reviewed Web of Science, Embase and PubMed databases to identify published studies using relevant key words. The correlation between the level of 14-3-3ξ and cancer patient survival was assessed based upon pooled hazard ratios and 95% confidence intervals derived from the selected studies. Data was analysed using STATA 12. RESULTS: Of the 244 studies initially identified, 22(9%) were included, and they comprised 2,676 patients. Elevated 14-3-3ξ level correlated significantly with poorer overall survival (hazard ratio: 1.93; 95% confidence interval: 1.42-2.61) in cancer patients. With respect to disease-free survival, the pooled hazard ratio for cancer patients expressing high levels of 14-3-3ξ was 1.89 (95% confidence interval: 1.56-2.30). Patients with elevated 14-3-3ξ expression also exhibited reduced cancer-specific survival (hazard ratio: 3.47; 95% confidence interval: 2.12-5.69). CONCLUSIONS: Higher level of 14-3-3ξ correlated with poorer patient prognosis in a range of cancer types.

IL-32 induces epithelial-mesenchymal transition by triggering endoplasmic reticulum stress in A549 cells.

BACKGROUND: Epithelial-mesenchymal transition (EMT) is a key process in the onset and development of idiopathic pulmonary fibrosis (IPF) with unclear mechanisms. Our previous studies found that bleomycin and tunicamycin could induce ER stress and consequently trigger EMT accompanying with IL-32 overexpression. This study was aimed to investigate the effects of IL-32 on EMT and ER stress to elucidate the pathogenesis of IPF. METHODS: Human lung adenocarcinoma A549 cells were treated with recombinant human (rh)IL-32, IL-32 siRNA and EMT inducer tunicamycin, or 4-phenylbutyric acid (4-PBA), respectively. Then the cell morphology was observed and the expression of ER-related markers and EMT-related markers were detected by RT-qPCR or western blotting. RESULTS: Stimulation of A549 cells with rhIL-32 led to a morphological change from a pebble-like shape to an elongated shape in a portion of the cells, accompanied by down regulated expression of the epithelial cell marker E-cadherin and up regulated expression of the mesenchymal cell markers N-cadherin, Vimentin, and Zeb-1. However, these rhIL-32 induced changes were inhibited by the ER stress inhibitor 4-PBA. Suppression of IL-32 expression with siRNA inhibited TM-induced EMT. Further stimulation of the A549 cells with rhIL-32 demonstrated an increase in the expression of GRP78, although this increase was also inhibited by 4-PBA. CONCLUSIONS: These results suggest that IL-32 induces EMT in A549 cells by triggering ER stress, and IL-32 may be a novel marker for IPF.

Histone Deacetylases Promote ER Stress Induced Epithelial Mesenchymal Transition in Human Lung Epithelial Cells.

BACKGROUND/AIMS: Epithelial to mesenchymal transition (EMT) is a crucial process involved in pulmonary fibrosis. This study aimed to explore the role of histone deacetylases (HDACs) and endoplasmic reticulum (ER) stress in EMT in human lung epithelial cells. METHODS: Human lung adenocarcinoma A549 cells were treated with bleomycin and tunicamycin to induce EMT. The proliferation of A549 cells was detected by MTT assay. The expression of HDACs and EMT markers was detected by PCR and Western blot analysis. The secretion of TGF-ß1 and collagen I was examined by ELISA. RESULTS: A549 cells switched from a cobblestone-like appearance to an elongated fibroblast like appearance after exposure to tunicamycin or bleomycin, accompanied by increased expression of N-cadherin, α-SMA and Collagen I. Meanwhile, GRP78 was upregulated in A549 cells exposed to tunicamycin or bleomycin. These changes induced by tunicamycin or bleomycin could be abrogated by 4-PBA. Moreover, tunicamycin and bleomycin promoted the expression of HDAC2 and HDAC6, and HDACs inhibitor SAHA abrogated the morphological and biochemical changes in A549 cells. 4-PBA and SAHA inhibited the upregulation of pulmonary fibrosis factors TGF-ß1 and IL-32 and the activation of Smad pathway induced by tunicamycin or bleomycin. CONCLUSIONS: We provide the first evidence that tunicamycin and bleomycin induce ER stress and EMT in lung epithelial cells via the upregulation of HDACs. HDACs inhibitor could inhibit ER stress induced upregulation of pulmonary fibrosis factors and the activation of Smad pathway. HDACs inhibitors are promising agents for the therapy of pulmonary fibrosis.

Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis.

Arsenic trioxide (As2O3) induces cell apoptosis and reduces the invasive and metastatic activities in various cancer types. However, the role of As2O3 in ovarian cancer angiogenesis remains unclear. In this study, we investigated the role of As2O3 in ovarian cancer angiogenesis and found that a low concentration of As2O3 causes no effects on epithelial ovarian cancer cell viability or apoptosis. Moreover, we found that As2O3-treated epithelial ovarian cancer cells demonstrate a reduced tube formation of endothelial cells in Matrigel. In addition, As2O3-treated epithelial ovarian cancer cells show a decreased VEGFA, VEGFR2 and CD31 mRNA expression. As per the underlying mechanisms involved in As2O3 treatment, we found that As2O3 inhibits VEGFA and VEGFR2 expression that thereby inhibits the VEGFA-VEGFR2-PI3K/ERK signaling pathway. This leads to a suppression in both VEGFA synthesis and angiogenesis-related gene expression. A decreased VEGFA synthesis and secretion also inhibits the VEGFA-VEGFR2-PI3K/ERK signaling pathway in human umbilical vein endothelial cells (HUVECs). In summary, our results may provide strategies for the use of As2O3 in the prevention of tumor angiogenesis.

Effect of sivelestat sodium in patients with acute lung injury or acute respiratory distress syndrome: a meta-analysis of randomized controlled trials.

BACKGROUND: Sivelestat is widely used in treating acute lung injury (ALI)/acute respiratory distress syndrome (ARDS), although the clinical efficacy of sivelestat remains controversial. This study aimed to evaluate the impact of sivelestat in patients with ALI/ARDS. METHODS: Electronic databases, PubMed, Embase, and the Cochrane Library, were searched to identify trials through April 2017. Randomized controlled trials (RCTs) were included irrespective of blinding or language that compared patients with and without sivelestat therapy in ALI/ARDS. A random-effects model was used to process the data, and the relative risk (RR) and standard mean difference (SMD) with corresponding 95% confidence intervals (CIs) were used to evaluate the effect of sivelestat. RESULTS: Six RCTs reporting data on 804 patients with ALI/ARDS were included. Overall, no significant difference was found between sivelestat and control for the risk of 28-30 days mortality (RR: 0.94; 95% CI: 0.71-1.23; P = 0.718). Sivelestat therapy had no significant effect on ventilation days (SMD: 0.05; 95% CI: -0.27 to 0.38; P = 0.748), arterial oxygen partial pressure (PaO2)/fractional inspired oxygen (FiO2) level (SMD: 0.48; 95% CI: -0.45 to 1.41; P = 0.315), and intensive care unit (ICU) stays (SMD: -9.87; 95% CI: -24.30 to 4.56; P = 0.180). The results of sensitivity analysis indicated that sivelestat therapy might affect the PaO2/FiO2 level in patients with ALI/ARDS (SMD: 0.87; 95% CI: 0.39 to 1.35; P < 0.001). CONCLUSIONS: Sivelestat therapy might increase the PaO2/FiO2 level, while it had little or no effect on 28-30 days mortality, ventilation days, and ICU stays. These findings need to be verified in large-scale trials.

Zunyimycins B and C, New Chloroanthrabenzoxocinones Antibiotics against Methicillin-Resistant Staphylococcus aureus and Enterococci from Streptomyces sp. FJS31-2.

This study performed an optimization of the fermentation conditions to activate the expression of the zunyimycin family biosynthesis genes of the zunyimycin-producing streptomycetes strain Streptomyces sp. FJS31-2. Bioassay-guided isolation and purification by varied chromatographic methods yielded two new compounds of the zunyimycin derivatives, namely, 31-2-7 and 31-2-8, accompanied with three known anthrabenzoxocinones family members of zunyimycin A, BE24566B, and chloroanthrabenzoxocinone. Their structures were elucidated by NMR, HRESIMS, IR, UV, and CD. Results showed that these two compounds were structurally similar to the previously reported compound zunyimycin A but differed in positions and number of chlorine atom substitution. The two novel compounds were called zunyimycins B and C. Antibacterial activity assay indicated that zunyimycin C showed a good inhibitory effect on the methicillin-resistant Staphylococcus aureus and Enterococci.

Expression of B and T Lymphocyte Attenuator in Patients with Severe Community-Acquired Pneumonia and the Effect of Steroid Therapy in a Mouse Model.

BACKGROUND: Severe community-acquired pneumonia (CAP) remains a clinical problem, and the identification of new therapeutic targets may increase the rate of successfully treating patients with severe CAP. B and T lymphocyte attenuator (BTLA) is an immunoglobulin-related membrane protein that may play a vital role in the pathogenesis of infection. However, the effects of BTLA in related to severe CAP involved are unknown. In this study, we investigated potential changes in BTLA expression on lymphocytes in patients with severe CAP and determined how BTLA expression affects a model of LPS-induced acute lung inflammation. METHODS: The percentages of circulating BTLA+CD4+ lymphocytes were determined in patients with severe CAP and in an LPS-induced acute lung inflammation model. Bronchoalveolar lavage fluid (BALF) was collected from mice and analyzed for leukocyte counts and by enzyme-linked immunosorbent assay (ELISA). Lung tissue samples were collected and assessed via Western blotting, immunohistochemistry and HE staining. RESULTS: The percentages of circulating BTLA+CD4+ lymphocytes were significantly higher in patients with severe CAP and in mice with LPS-induced acute lung inflammation than in the control groups. After treatment with either dexamethasone or the agonistic anti-BTLA antibody 6A6, BTLA expression was significantly higher than that in the control mice with LPS-induced acute lung inflammation. Moreover, both dexamethasone and the agonistic anti-BTLA antibody 6A6 attenuated inflammatory responses and nuclear factor (NF)-κB pathway activation. CONCLUSIONS: These results demonstrated that BTLA may be a therapeutic target for the treatment of severe CAP and that BTLA expression may reflect the body's immune status and guide decisions regarding steroid therapy for treating severe CAP.

[Effect of Curcumin on TGF-ß2 Regulated PPAR-γ/PDGF-ß Signaling Pathway in Lung Fibroblasts of Mice].

OBJECTIVE: To explore the effect of curcumin on TGF-ß2 regulated peroxisome proliferater activated receptor y (PPAR-γ)/platelet derived growth factor ß (PDGF-ß) signaling pathway in lung fibroblasts of mice. METHODS: C57BL/6 mouse lung fibroblasts were in vitro cultured with TGF-ß2, curcumin, or TGF-ß2 plus curcumin. The cell proliferation was detected by cell growth counting in the blank control group, low, middle, and high dose curcumin groups (5, 25, 50 µmol/L), the TGF-ß2 (10 ng/mL) group, TGF-ß2 (10 ng/mL) plus curcumin (5, 25, 50 µmol/L) groups. mRNA expressions of PPAR-γ, platelet-derived growth factor receptor ß (PDGFR-ß), fibroblast growth factor R1 (FGFR1) were detected using reverse transcription PCR. Protein levels of PPAR-γ and collagen-1 were detected using Western blot and ELISA in the blank control group, the TGF-ß2 group, the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group. RESULTS: Compared with the blank control group, curcumin 50 µmol/L showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the TGF-ß2 group, TGF-ß2 (10 ng/mL) plus curcumin 50 mol/L also showed the most significant inhibition on cell proliferation at 48 h and 72 h. Compared with the blank control group, mRNA expressions of PPAR-γ and PDGF-ß, as well as protein expression of PPAR-γ increased, the collagen-1 expression also increased in the TGF-ß2 group (P < 0.05). Compared with the TGF-ß2 group, mRNA expressions of PPAR-γ obviously increased in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group, higher than that in the TGF-ß2 (10 ng/mL) plus curcumin 5 [µmol/L group (P < 0.05). mRNA expressions of PPAR-γ was higher in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). mRNA expressions of PDGF-ß was lower in TGF-ß2 (10 ng/mL) plus curcumin groups than in the TGF-ß2 group (P < 0.05). Besides, PDGF-ß mRNA expressions were lower in the TGF-ß2 (10 ng/mL) plus curcumin 50 µmol/L group than in the TGF-ß2 (10 ng/mL) plus curcumin 5 µmol/L group and the TGF-ß2 (10 ng/mL) plus curcumin 25 µmol/L group (P < 0.05). There was no statistical difference in FGFR1 mRNA expressions between the TGF-ß2 group and 3 TGF-ß2 plus curcumin groups (P > 0.05). Compared with the TGF-ß2 group, PPAR-γ protein expressions increased and collagen-1 protein expressions decreased in the TGF-ß2 (10 ng/mL) plus curcumin 50 µLmol/L group (P < 0.05, P < 0.01). CONCLUSIONS: Curcumin not only could inhibit TGF-ß2 induced proliferation of lung fibroblasts, but also could inhibit the synthesis of collagens. These might be associated with up-regulating PPAR-γ expressions and down-regulating PDGF-ß expressions. Therefore, curcumin might inhibit the occurrence and developing of lung fibrosis through blocking PPAR-γ/PDGF-ß signaling pathway.

A novel function of claudin-5 in maintaining the structural integrity of the heart and its implications in cardiac pathology.

This study aims to investigate the role of claudin-5 (Cldn5) in cardiac structural integrity. Proteomic analysis was performed to screen the protein profiles in enlarged left atrium from atrial fibrillation (AF) patients. Cldn5 shRNA adeno-associated virus (AAV) or siRNA was injected into the mouse left ventricle or added into HL1 cells respectively to knockdown Cldn5 in cardiomyocytes to observe whether the change of Cldn5 influences cardiac morphology and function, and affects those protein expressions stem from the proteomic analysis. Mitochondrial density and membrane potential were also measured by Mitotracker staining and JC-1 staining under the confocal microscope in HL1 cells. Cldn5 was reduced in cardiomyocytes from the left atrial appendage of AF patients compared to non-AF donors. Proteomic analysis showed 83 proteins were less abundant and 102 proteins were more abundant in AF patients. KEGG pathway analysis showed less abundant CACNA2D2, CACNB2, MYL2 and MAP6 were highly associated with dilated cardiomyopathy. Cldn5 shRNA AAV injection caused severe cardiac atrophy, dilation and myocardial dysfunction in mice. The decreases in mitochondrial numbers and mitochondrial membrane potentials in HL1 cells were observed after Cldn5 knockdown. We demonstrated for the first time the mechanism of Cldn5 downregulation-induced myocyte atrophy and myocardial dysfunction might be associated with the downregulation of CACNA2D2, CACNB2, MYL2 and MAP6, and mitochondrial dysfunction in cardiomyocytes.

N 6-methyladenosine modification contributes to respiratory syncytial virus infection.

Background: Respiratory syncytial virus (RSV) is the second leading cause of death due to lower respiratory tract infections. Effective prevention and treatment measures are lacking, posing a huge socioeconomic burden to the world. N 6-methyladenosine (m6A) is the most common internal modification in messenger RNA and noncoding RNA. Numerous recent studies have shown that the dysregulation of m6A modification is associated with diseases caused by pathogenic viruses. Methods: The changes in m6A modification were evaluated using m6A RNA methylation assay. The differences in gene expression levels of various m6A-modifying enzymes were observed using Quantitative Real-time PCR (qRT-PCR) during RSV infection. The autophagosomes were observed using transmission electron microscopy, and the expression of autophagy-associated protein Microtubule Associated Protein 1 Light Chain 3 Beta Ⅱ/Ⅰ (LC3B Ⅱ/Ⅰ) and Beclin1 in Human Normal Lung Epithelial Cells (BEAS-2B) cells using Western blot during RSV infection. The significantly differentially expressed genes were screened guided by bioinformatics. Their relationship with m6A-modifying enzymes was analyzed through protein-protein interaction network and expression correlation analysis. Results: The m6A abundance decreased and demethylase Fat Mass and Obesity- Associated Protein (FTO) significantly increased during RSV infection after 24 h. We also found that the DNA Damage-Inducible Transcript 3 Protein (DDIT3) level significantly increased during RSV infection after 24 h and observed autophagosomes in BEAS-2B cells. In addition, RSV infection could cause the upregulation of LC3B Ⅱ/Ⅰ and Beclin1. The expression correlation analysis showed that DDIT3 levels were positively correlated with the FTO level, and Methyltransferase Like 3 (METTL3), RNA Binding Motif Protein 15B (RBM15B), YTH Domain-Containing Family Protein 1 (YTHDF1), and levels were negatively correlated with the DDIT3 level. Conclusions: We uncovered a significant role for m6A modification during RSV infection. Also, a correlation was found between m6A and autophagy, providing new ideas for therapeutic advancements in RSV treatment.

Comprehensive analysis of an endoplasmic reticulum stress-related gene prediction model and immune infiltration in idiopathic pulmonary fibrosis.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic progressive interstitial lung disease. This study aimed to investigate the involvement of endoplasmic reticulum stress (ERS) in IPF and explore its correlation with immune infiltration. Methods: ERS-related differentially expressed genes (ERSRDEGs) were identified by intersecting differentially expressed genes (DEGs) from three Gene Expression Omnibus datasets with ERS-related gene sets. Gene Set Variation Analysis and Gene Ontology were used to explore the potential biological mechanisms underlying ERS. A nomogram was developed using the risk signature derived from the ERSRDEGs to perform risk assessment. The diagnostic value of the risk signature was evaluated using receiver operating characteristics, calibration, and decision curve analyses. The ERS score of patients with IPF was measured using a single-sample Gene Set Enrichment Analysis (ssGSEA) algorithm. Subsequently, a prognostic model based on the ERS scores was established. The proportion of immune cell infiltration was assessed using the ssGSEA and CIBERSORT algorithms. Finally, the expression of ERSRDEGs was validated in vivo and in vitro via RT-qPCR. Results: This study developed an 8-ERSRDEGs signature. Based on the expression of these genes, we constructed a diagnostic nomogram model in which agouti-related neuropeptide had a significantly greater impact on the model. The area under the curve values for the predictive value of the ERSRDEGs signature were 0.975 and 1.000 for GSE70866 and GSE110147, respectively. We developed a prognostic model based on the ERS scores of patients with IPF. Furthermore, we classified patients with IPF into two subtypes based on their signatures. The RT-qPCR validation results supported the reliability of most of our conclusions. Conclusion: We developed and verified a risk model using eight ERSRDEGs. These eight genes can potentially affect the progression of IPF by regulating ERS and immune responses.

Association between inflammatory biomarkers and acute respiratory distress syndrome or acute lung injury risk : A systematic review and meta-analysis.

BACKGROUND: The relationship between acute respiratory distress syndrome (ARDS)/acute lung injury (ALI) and levels of certain inflammatory factors remains controversial. The purpose of this meta-analysis was to summarize the available studies evaluating the association between levels of inflammatory factors and ARDS/ALI incidence. METHODS: We searched the PubMed, EmBase, and Cochrane databases for studies published up to July 2017. For each inflammatory factor, a random effects model was employed to pool results from different studies. RESULTS: We identified 63 studies that included 6243 patients in our meta-analysis. Overall, the results indicated that the levels of angiopoietin (ANG)-2 (standard mean difference, SMD: 1.34; P < 0.001), interleukin (IL)-1ß (SMD: 0.92; P = 0.012), IL­6 (SMD: 0.66; P = 0.005), and tumor necrosis factor (TNF)-α (SMD: 0.98; P = 0.001) were significantly higher in patients with ARDS/ALI than in unaffected individuals. No significant differences were observed between patients with ARDS/ALI and unaffected individuals in terms of the levels of IL­8 (SMD: 0.61; P = 0.159), IL-10 (SMD: 1.10; P = 0.231), and plasminogen activator inhibitor (PAI)-1 (SMD: 0.70; P = 0.060). CONCLUSIONS: ARDS/ALI is associated with a significantly elevated levels of ANG­2, IL-1ß, IL­6, and TNF­α, but not with IL­8, IL-10, and PAI­1 levels.

Ultrasound imaging features of bronchial anthracofibrosis: A case-control study.

To determine the ultrasound imaging characteristics of patients with bronchial anthracofibrosis (BAF) and identify clinical markers for prevention and treatment. We randomly selected 1243 participants (113 with BAF) who underwent bronchoscopy and received treatment at our institution between April 2018 and October 2019. BAF was classified as flat, deep-seated retracted, or black mucosal protruding based on microscopic findings. Ultrasound probes were used to determine the maximum thickness of the tube walls and submucosa. The average values of the submucosal and bony tissue areas in the BAF subtypes were compared. The BAF group included 13 participants with a history of tuberculosis (11.5%) and 57 participants with biofuel exposure (50.4%). The average exposure time was 17.4 ± 6.2 years; BAF accounted for 10% of the bronchoscopies performed. The maximum tube-wall thicknesses of the deep-seated retracted (17.3 ± 5.7) and black mucosal protruding (19.3 ± 5.4) groups were significantly greater than those of the flat group (12.5 ± 5.0; P < .05). The maximum thicknesses of the submucosa in the deep-retracted (9.8 ± 3.0) and black mucosal protruding (14.5 ± 5.0) groups were significantly greater than that of the flat group (6.6 ± 3.5; P < .05). The ratios of bone tissue in the flat and black mucosal protruding groups were 33.3 ± 9.3% and 34.9% ± 12.1%, respectively. The ratio in the deep-seated retracted group (65.2% ± 8.7%) was significantly reduced (P < .05). The flat group showed no significant change (P > .05). Differences in BAF airway remodeling among different subtypes may lead to varying clinical symptoms. Analyzing the characteristics of BAF airway remodeling and the regulatory pathway may provide new clues for treatment.

Pulmonary hypertension secondary to seronegative rheumatoid arthritis overlapping antisynthetase syndrome: A case report.

BACKGROUND: Polyarthritis is the most frequent clinical manifestation in antisynthetase syndrome (ASS) forms of idiopathic inflammatory myositis and may be misdiagnosed as rheumatoid arthritis (RA), particularly in patients with seronegative RA (SNRA). It is unclear whether there is an overlap between ASS and RA, or if ASS sometimes mimics RA. Pulmonary hypertension (PAH) is common in connective tissue diseases (CTDs). However, published reports on CTD-PAH do not include overlapping CTDs, and its incidence and impact on patient prognosis are unclear. CASE SUMMARY: We report the case of a 63-year-old woman who presented with a 3-mo history of symptom aggravation of recurrent symmetrical joint swelling and pain that had persisted for over 10 years. The patient was diagnosed with RA and interstitial lung disease. The patient repeatedly presented to the hospital's respiratory and rheumatology departments with arthralgia, plus shortness of breath after activity. Relevant tests indicated that anti-CCP and RF remained negative, while anti-J0-1 and anti-Ro-52 were strongly positive. It was not until recently that we recognized that this could be an unusual case of SNRA with concurrent ASS. Joint pain was relieved after regular anti-rheumatic treatment. Chest computed tomography scans showed that pulmonary interstitial changes did not progress significantly over several years; however, they showed gradual widening of the pulmonary artery, and cardiac ultrasound indicated elevated pulmonary artery systolic pressure. The prescribed treatment of PAH was not effective in improving shortness of breath. CONCLUSION: Overlap of RA and ASS may be missed. Further research is necessary to facilitate early diagnosis, effective evaluation, and prognosis.