Circadian clock gene Clock-Bmal1 regulates cellular senescence in Chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disease. COPD is associated with accelerated lung aging. Circadian clock is believed to play important roles in COPD. Although the circadian molecular clock regulates cellular senescence, there is no information available regarding the impact of COPD. The aim of this study is to investigate the role of the circadian clock protein BMAL1 and CLOCK in cellular senescence in order to understand the cellular mechanisms of accelerated aging of COPD. Bmal1 and Clock levels were assessed in the plasma samples of non-smokers, smokers, and patients with COPD. The regulation of ciracadian clock expression and cell senescence by cigarette smoke extract (CSE) was studied in vitro, and small interfering RNA (siRNA) and overexpression of Bmal1 or Clock were employed to investigate the role of circadian clock on cell senescence. Herein, patients with COPD showed lower Bmal1 and Clock expression in the plasma. Interestingly, CSE exposure contributed to the increased cell senescence, decreased Clock and Bmal1 in human bronchial epithelial cells (Beas-2B cells). We found that knockdown of Clock or Bmal1 lead to upregulation of cell senescence in Beas-2B cells, while overexpression of Clock or Bmal1 inhibited cell senescence in Beas-2B cells, which is through the MAPK pathways. Therefore, our findings indicated that Bmal1 or Clock deficiency may be a significant factor to increase cellular senescence of the lung to develop COPD.

BOLA3 is a prognostic-related biomarker and correlated with immune infiltrates in lung adenocarcinoma.

BACKGROUD: BolA gene family contains three members, high expression of BolA family member 2 (BOLA2) has been reported to be associated with prognosis of several cancers. However, the relationship between BOLA3 and lung adenocarcinoma (LUAD) remains unclear. METHODS: Expression of BOLA3 was analyzed by online database. Co-expressed genes and gene set enrichment analysis (GSEA) were performed using LinkedOmics. Diagnostic value was assessed using receiver operating characteristic (ROC) curves. The prognostic value of BOLA3 was analyzed using Prognoscan and Kaplan-Meier Plotter. The Tumor Immune Estimation Resource (TIMER) and Single-sample Gene Set Enrichment Analysis (ssGSEA) were used to explore the relationship between BOLA3 and tumor immune infiltration. RESULTS: The results showed that the expression of BOLA3 was significantly higher in LUAD than in normal tissues. High expression of BOLA3 was associated with T stage, N stage, pathologic stage (all P < 0.001). In addition, elevated expression of BOLA3 was associated with overall survival (OS) and progression-free survival (PFS) in LUAD ((OS:HR = 2.58, log-rank P = 1.3e - 11; PFS:HR = 2.36, log-rank P = 4.1e - 05). BOLA3 expression level has negative correlations with infiltrating levels of B cells, CD4 +T cells, macrophages, neutrophils, and dendritic cells (DCs). GSEA analysis showed BOLA3 joined mainly in mitochondrial respiratory chain complex assembly, translational initiation, etc. CONCLUSIONS: These results showed up-regulated in BOLA3 was correlated with poor prognosis and immune infiltrates in LUAD, BOLA3 can be served as a potential immunotherapy target.

Study on the Red Blood Cell Distribution Width in Connective Tissue Disease Associated with Interstitial Lung Disease.

BACKGROUND: Connective tissue disease (CTD) associated with interstitial lung disease (ILD) affects the lungs and can lead to considerable morbidity and shortened survival. Red blood cell distribution width (RDW) is a readily available parameter that is routinely reported with complete blood cell count (CBC) This study aimed to investigate the predictive value of RDW in CTD-ILD. METHODS: A retrospective analysis was performed on 180 patients with CTD-ILD and 202 patients with CTD but without ILD between April 2016 and December 2018. Baseline demographics, laboratory results, imaging examinations, and results of ultrasound scans were analysed. RESULTS: In comparison with patients without ILD, patients with CTD-ILD displayed a larger RDW (14.65 ± 2.08 vs. 14.17 ± 1.63, P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (r = 0.349; P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (r = 0.349; P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (r = 0.349; P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (P=0.002), and RDW shared positive relationships with pulmonary artery systolic pressure (. CONCLUSIONS: RDW was significantly increased in patients with CTD-ILD under various CTD backgrounds and may be a promising biomarker that may help physicians predict CTD-ILD risk.

Red Blood Cell Distribution Width Predicts Pulmonary Hypertension Secondary to Chronic Obstructive Pulmonary Disease.

Purpose: This study aims at investigating the predictive value of red blood cell distribution width (RDW) in pulmonary hypertension (PH) secondary to chronic obstructive pulmonary disease (COPD). Methods: 213 eligible in-hospital COPD patients were reviewed between May 2016 and May 2018, including 39 cases with PH and 174 without PH. Clinical data including demographic characteristics, comorbidities, and results of ultrasound scans, imaging examinations, and laboratory tests were recorded. Results: Increased RDW level was observed in COPD patients with PH compared with COPD patients without PH, with 15.10 ± 1.72% versus 13.70 ± 1.03%, respectively (p < 0.001). RDW shared positive relationships with brain natriuretic peptide (BNP) (p=0.001, r = 0.513), pulmonary artery (PA) systolic pressure (p=0.014, r = 0.390), and PA-to-ascending aorta (A) ratio (PA : A) (p=0.001, r = 0.502). Multivariate analysis indicated that RDW, BNP, and PA : A > 1 were the independent risk factors of PH secondary to COPD (p < 0.05). The AUC of the RDW in patients with PH was 0.749 ± 0.054 (p < 0.001). The optimal cutoff value of RDW for predicting PH was 14.65, with a sensitivity and a specificity value of 69.2% and 82.8%, respectively. Conclusion: RDW is significantly increased in COPD patients with PH and thus may be a useful biomarker for PH secondary to COPD.

The Effect of Polydopamine on an Ag-Coated Polypropylene Nonwoven Fabric.

A practical method for preparing multifunctional polypropylene (PP) nonwoven fabrics with excellent stability and durability was explored. First, the PP nonwoven fabric was sputtered by a magnetron sputtering system to form an Ag film on the surface of the fabric. Subsequently, the coated fabric was treated with dopamine. The fabrics were characterized by scanning electron microscopy (SEM), an energy dispersive spectrometer (EDS), electrical conductivity, electromagnetic interference shielding effectiveness (EMI SE), antibacterial activity, stability, and laundering durability. The results of the study revealed that the fabric was coated with Ag, and after the treatment with dopamine, the surfaces of Ag-coated fibers were coated with polydopamine (PDA). The fabrics still had a sheet resistance below ~15 Ω/sq and exhibited excellent EMI SE above ~25 dB, though few differences existed from the single Ag-coated sample. After the treatment with dopamine, the antibacterial activity of the fabric was enhanced. Meanwhile, the treated samples exhibited excellent resistance against sodium sulfide corrosion, which could enhance the stability of the Ag-coated fabric. Moreover, the laundering durability of the treated fabric was improved in the same process, whose lowest sheet resistance was ~18 Ω/sq and the EMI SE was ~8 dB more than single Ag-coated PP nonwoven fabrics. In conclusion, this method was considered to be effective in fabricating multifunctional, stable, and durable fabrics.

Quantitative proteomic characterization of lung tissue in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, eventually fatal disease. IPF is characterized by excessive accumulation of the extracellular matrix (ECM) in the alveolar parenchyma and progressive lung scarring. The pathogenesis of IPF and whether the ECM involved in the process remain unknown. METHODS: To identify potential treatment target and ECM associated proteins that may be involved in the development of IPF, we employed isobaric tag for relative and absolute quantitation (iTRAQ) combined liquid chromatography-tandem mass spectrometry (LC-MS/MS) approach to examine protein expression in lung tissues from IPF patients. RESULTS: A total of 662 proteins with altered expression (455 upregulated proteins and 207 downregulated proteins) were identified in lung tissue of IPF patients compared with control. KEGG pathway enrichment analysis showed that the altered proteins in lung tissue mainly belonged to the PI3K-Akt signaling, focal adhesion, ECM-receptor interaction, and carbon metabolism pathways. According to the bioinformatic definition of the matrisome, 229 matrisome proteins were identified in lung tissue. These proteins comprised the ECM of lung, of which 104 were core matrisome proteins, and 125 were matrisome-associated proteins. Of the 229 ECM quantified proteins, 56 significantly differentially expressed proteins (19 upregulated proteins and 37 downregulated proteins) were detected in IPF lung tissue samples. In addition to proteins with well-known functions such as COL1A1, SCGB1A1, TAGLN, PSEN2, TSPAN1, CTSB, AGR2, CSPG2, and SERPINB3, we identified several novel ECM proteins with unknown function deposited in IPF lung tissue including LGALS7, ASPN, HSP90AA1 and HSP90AB1. Some of these differentially expressed proteins were further verified using Western blot analysis and immunohistochemical staining. CONCLUSIONS: This study provides a list of proteomes that were detected in IPF lung tissue by iTRAQ technology combined with LC-MS/MS. The findings of this study will contribute better understanding to the pathogenesis of IPF and facilitate the development of therapeutic targets.

Idiopathic pulmonary fibrosis with chronic necrotizing pulmonary aspergillosis: a case report.

OBJECTIVE: IPF with CNPA is rare, and its clinical manifestations and radiologic features lack specificity compared with other types of pulmonary aspergillosis. This study aims to assess the clinical features of idiopathic pulmonary fibrosis (IPF) with chronic necrotizing pulmonary aspergillosis (CNPA). METHODS: One case of IPF with CNPA is reported and literature review is performed. RESULTS: The patient had a history of intermittent hemoptysis without history of smoking and alcohol. CT scan of the chest showed bilateral ILD and nodules in the upper lobes of bilateral lungs and middle lobe of the right lung of the patient. CT-guided pulmonary puncture biopsy using microscopy revealed mold hyphae. Based on combined medical history and radiologic findings, the patient was diagnosed with CNPA. CONCLUSION: A discriminating pathological feature favors the discovery of aspergillus hyphae in pulmonary tissues, which provides assistance for the early anti-fungal therapy.