Expression of Siglec-9 in peripheral blood neutrophils was increased and associated with disease severity in patients with AECOPD.

BACKGROUND: The pathogenesis and treatment strategies for chronic obstructive pulmonary disease (COPD) require further exploration. Abnormal neutrophil inflammation and the overexpression of neutrophil extracellular traps (NETs) are closely associated with acute exacerbations of COPD (AECOPD). Siglec-9, a specific receptor expressed on neutrophils that inhibits their function, prompted us to investigate its relationship with NETs found in induced sputum and the severity of the disease. METHODS: We collected clinical data from patients with AECOPD and assessed the expression of Siglec-9 in peripheral blood neutrophils and the presence of NETs in induced sputum. We then observed the correlation between Siglec-9, the inflammatory response, and the severity of AECOPD. RESULTS: We observed an increase in the expression of Siglec-9 in the peripheral blood neutrophils of patients with AECOPD. Concurrently, these patients exhibited more severe clinical symptoms, higher systemic inflammation levels, and a reduced quality of life compared to those with induced sputum NET expression. Further subgroup analysis of AECOPD patients with high Siglec-9 expression revealed worsened quality of life and more severe inflammation, particularly in indicators such as the BODE index, CRP, peripheral blood neutrophil count, IL-6, IL-8, TNF-α expression, and others. Furthermore, we noted a significant increase in NET-specific expression in the sputum of patients with high Siglec-9 expression levels. In comparison to patients with low Siglec-9 expression, those with high expression experienced more systemic inflammatory reactions and a lower quality of life. Correlation analysis of the aforementioned indicators revealed that the expression ratio of Siglec-9 in the peripheral blood of patients correlated with lung function, quality of life, and NETs in the induced sputum of patients with AECOPD. CONCLUSION: The increased expression of Siglec-9 in peripheral blood neutrophils of AECOPD patients leads to elevated NET expression in induced sputum, exacerbating the systemic inflammatory response and worsening lung function and quality of life in these patients.

Research progress of N6-methyladenosine in colorectal cancer: A review.

Colorectal cancer is the third most common malignant tumor worldwide, causing serious harm to human health. Epigenetic modification, especially RNA methylation modification, plays a critical role in the occurrence and development of colorectal cancer via post-transcriptional regulation of mRNA and non-coding RNA expression. Among these, N6-methyladenosine (m6A) is the most common chemical modification in mammals, which plays an important role in the progress of cancer, including colorectal cancer. m6A is a dynamic and reversible process and is mainly regulated by m6A methyltransferase ("writers"), m6A demethylases ("erasers"), and m6A binding proteins ("readers"). Herein, we reviewed recent advances in the role of m6A modification in colorectal cancer and focused on the factors affecting m6A modification. Furthermore, we discussed the clinical application of m6A modifications for colorectal cancer diagnosis, prognosis, and treatment and provided guides in clinical practice. m6A modification and m6A regulators play significant roles in the occurrence and development of colorectal cancer by regulating the stability and translation of mRNAs, the maturation of miRNAs, and the function of lncRNAs. m6A regulators can play biological roles in colorectal cancer through m6A-dependent manner or m6A-independent manner. Multiplies of internal factors, including miRNAs and lncRNAs, and external factors can also regulate the m6A modification by completing with m6A regulators in a base complement manner, regulating the expression of m6A and mutating the m6A site. m6A regulators and m6A modificantion are diagnostic and prognostic markers for CRC. Therefore, m6A regulators and m6A modificantion may be potential therapeutic target for CRC in the future.

A novel defined pyroptosis-related gene signature predicts prognosis and correlates with the tumour immune microenvironment in lung adenocarcinoma.

Lung adenocarcinoma (LUAD) is one of the most common causes of cancer-related death. The role of pyroptosis in LUAD remains unclear. Our study aimed to identify a prognostic signature of pyroptosis-related genes (PRGs) and explore the connection of PRGs with the tumour microenvironment in LUAD. Gene expression and clinical information were obtained from The Cancer Genome Atlas database. Consensus clustering was applied to classify LUAD patients. The least absolute shrinkage and selection operator Cox and multivariate Cox regression models were used to generate a PRG-related prognostic signature. The correlations between PRGs and tumour-infiltrating immune cells or the tumour mutational burden were analysed by Spearman's correlation analysis. In this study, 44 PRGs significantly differed in expression between LUAD and normal tissues. Based on these genes, patients were clustered into three clusters with significantly different distributions of tumour-infiltrating immune cells and immune checkpoint regulators. A total of four PRGs (NLRP1, HMGB1, CYCS, and BAK1) were used to construct a prognostic model. Significant correlations were observed between these prognostic PRGs and immune cell infiltration or the tumour mutational burden. Predictive nomogram results showed that BAK1 could be an independent prognostic biomarker in LUAD. Additionally, the expression level of BAK1 was validated in two independent Gene Expression Omnibus cohorts. Our identified prognostic PRG signature may provide insight for future studies targeting pyroptosis and the tumour microenvironment in LUAD. Future studies are needed to verify our current findings.

Identification of potential biomarkers and pathogenesis in neutrophil-predominant severe asthma: A comprehensive bioinformatics analysis.

BACKGROUND: Airway neutrophilia has been associated with asthma severity and asthma exacerbations. This study attempted to identify biomarkers, pathogenesis, and therapeutic molecular targets for severe asthma in neutrophils using bioinformatics analysis. METHODS: Fifteen healthy controls and 3 patients with neutrophilic severe asthma were screened from the Gene Expression Omnibus (GEO) database. Based on the analysis of differentially expressed genes (DEGs), functional and pathway enrichment analyses, gene set enrichment analysis, protein-protein interaction network construction, and analysis were performed. Moreover, small-molecule drug candidates have also been identified. RESULTS: Three hundred and three upregulated and 59 downregulated genes were identified. Gene ontology function enrichment analyses were primarily related to inflammatory response, immune response, leukocyte migration, neutrophil chemotaxis, mitogen-activated protein kinase cascade, Jun N-terminal kinase cascade, I-kappaB kinase/nuclear factor-κB, and MyD88-dependent toll-like receptor signaling pathway. Pathway enrichment analyses and gene set enrichment analysis were mainly involved in cytokine-cytokine receptor interaction, the TNF signaling pathway, leukocyte transendothelial migration, and the NOD-like receptor signaling pathway. Furthermore, 1 important module and 10 hub genes (CXCL8, TLR2, CXCL1, ICAM1, CXCR4, FPR2, SELL, PTEN, TREM1, and LEP) were identified in the protein-protein interaction network. Moreover, indoprofen, mimosine, STOCK1N-35874, trapidil, iloprost, aminoglutethimide, ajmaline, levobunolol, ethionamide, cefaclor, dimenhydrinate, and bethanechol are potential drugs for the treatment of neutrophil-predominant severe asthma. CONCLUSION: This study identified potential biomarkers, pathogenesis, and therapeutic molecular targets for neutrophil-predominant severe asthma.

Efficacy of Liuzijue Qigong in patients with chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND: Liuzijue is a traditional Qigong exercise that is commonly performed in China. However, the treatment effects of Liuzijue Qigong are controversial. The aim of this systematic review was to evaluate the efficacy of Liuzijue Qigong in patients with chronic obstructive pulmonary disease (COPD). METHODS: Randomised controlled trials were identified by searching several English and Chinese databases from inception to August 8, 2020. Study selection and data extraction were independently performed by two investigators. Data synthesis and analysis were carried out with Review Manager software 5.2. Quality assessment for each study was based on the modified Jadad scale. RESULTS: Forty studies with 3137 participants were included. Significant improvements were observed in the following outcomes (mean difference, 95% confidence interval): forced expiratory volume in 1 s (0.17, 0.09-0.25) and its percent predicted normal value (6.04, 3.43-8.65), forced expiratory volume in 1 s to forced volume capacity ratio (6.95, 3.06-10.83), 6-min walking distance (33.06, 23.73-42.38), 30-s sit-to-stand test (2.65, 0.98-4.32), COPD assessment test score (- 2.04, - 2.77 to - 1.30), modified Medical Research Council dyspnea scale (- 0.34, - 0.48 to - 0.20), Medical Research Council dyspnea scale (- 0.37, - 0.57 to - 0.18), Traditional Chinese Medicine syndrome score (- 1.85, - 2.86 to - 0.85), Hamilton Anxiety Scale (- 2.31, - 3.04 to - 1.59), Hamilton Depression Scale (- 2.08, - 2.45 to - 1.71) and St. George's Respiratory Questionnaire (- 6.94, - 9.20 to - 4.67). CONCLUSIONS: Liuzijue Qigong may be an effective adjuvant therapy for the improvement of lung function, exercise capacity, health status, mental status and quality of life in patients with COPD.

Sialic acid-binding immunoglobulin-like lectin 9 as a potential therapeutic target for chronic obstructive pulmonary disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) has become the third-leading cause of death worldwide, which is a severe economic burden to the healthcare system. Chronic bronchitis is the most common condition that contributes to COPD, both locally and systemically. Neutrophilic inflammation predominates in the COPD airway wall and lumen. Logically, repression of neutrophilia is an essential fashion to COPD treatment. However, currently available anti-neutrophilic therapies provide little benefit in COPD patients and may have serious side effects. Thus, there is an urgent need to explore an effective and safe anti-neutrophilic approach that might delay progression of the disease. Sialic acid-binding immunoglobulin-like lectin (Siglec)-9 is a member of the Siglec cell surface immunoglobulin family. It is noteworthy that Siglec-9 is highly expressed on human neutrophils and monocytes. Ligation of Siglec-9 by chemical compounds or synthetic ligands induced apoptosis and autophagic-like cell death in human neutrophils. Furthermore, administration of antibody to Siglec-E, mouse functional ortholog of Siglec-9, restrained recruitment and activation of neutrophils in mouse models of airway inflammation in vivo. Given the critical role that neutrophils play in chronic bronchitis and emphysema, targeting Siglec-9 could be beneficial for the treatment of COPD, asthma, fibrosis, and related chronic inflammatory lung diseases.

Apatinib sensitizes chemoresistant NSCLC cells to doxetaxel via regulating autophagy and enhances the therapeutic efficacy in advanced and refractory/recurrent NSCLC.

The prognosis of advanced non­small cell lung cancer (NSCLC) is poor; therefore, identifying novel treatment strategies for patients with NSCLC is important. The present study aimed to investigate the efficacy of apatinib plus docetaxel vs. docetaxel alone, as well as their effects on regulating autophagy markers in patients with advanced NSCLC. Furthermore, it was evaluated whether apatinib sensitized chemoresistant NSCLC cells to docetaxel via regulating autophagy. A total of 39 patients with advanced NSCLC were consecutively enrolled and treated with apatinib plus docetaxel (n=19) or docetaxel alone (n=20) for four treatment cycles. The treatment response, adverse events and expression levels of autophagy markers [(light chain 3 α (LC3A) and Beclin­1] were evaluated in tumor samples, which were obtained via biopsy, before treatment and after 2­cycle treatment. In addition, in a mechanistic in vitro experiment, apatinib, docetaxel, the autophagy activator rapamycin and the autophagy inhibitor 3­methyladenine (3­MA) were used to treat docetaxel­resistant A549 (A549/DTX) cells alone or in various combinations. The expression levels of LC3A, Beclin­1, poly (ADP) ribose polymerase (PARP) and phosphorylated (p)­AKT were detected via western blotting, while the cell apoptosis rate was detected with an Annexin V/PI assay. The overall remission rate (37 vs. 10%; P=0.047) and disease control rate (84 vs. 45%; P=0.011) were increased in the Apatinib plus docetaxel group compared with the Docetaxel group. Most of the adverse events were mild and tolerable, and there was no difference between the two groups except for total hypertension and hand­foot syndrome, which were higher in the Apatinib plus docetaxel group). Compared with the levels prior to treatment, Beclin­1 and LC3A remained unchanged post­treatment in the Apatinib plus docetaxel group, while they were increased in the Docetaxel group. Docetaxel increased LC3A, Beclin­1 and p­AKT expression levels, PARP cleavage and the cell apoptosis rate in A549/DTX cells, and rapamycin further enhanced, while 3­MA reduced these effects of docetaxel. Moreover, apatinib repressed LC3A, Beclin­1, p­AKT expression levels and promoted the cell apoptosis rate in A549/DTX cells and docetaxel­treated A549/DTX cells. In conclusion, apatinib synergize the effect of docetaxel in treating patients with advanced NSCLC and chemoresistant NSCLC cells via inhibiting autophagy.

LncRNA NEAT1/miR-204/NUAK1 Axis is a Potential Therapeutic Target for Non-Small Cell Lung Cancer.

BACKGROUND: Long non-coding RNA (lncRNA) is a key part of non-coding RNA, and more and more evidence has revealed that it plays a vital role in tumors. NEAT1 is a lncRNA discovered in the early stage. However, it is still unclear whether NEAT1 and miR-204 play a regulatory role in lung cancer (LC). This research aimed to determine the biological function of NEAT1/miR-204 in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: In order to research the function of NEAT1 in NSCLC, RT-PCR, Western blot, luciferase assay and RNA immunoprecipitation assay were used to determine the relationship between NEAT1, miR-204 and NUAK1. CCK8 test, cell migration and invasion test were used to explore the influence of NEAT1 on proliferation and metastasis of LC cells. Tumor allotransplantation was used to detect the influence of NEAT1 on the growth of LC. RESULTS: The results revealed that NEAT1 was obviously enhanced in LC cell lines. Further functional analysis showed that low expression of NEAT1 obviously suppressed the growth, migration and invasion of NSCLC and facilitated cell apoptosis. Determination of luciferase reporter gene revealed that miR-204 was the direct target of NEAT1 in LC. In addition, NUAK1 was called the direct target of miR-204, and miR-204/NUAK1 had saved the role of NEAT1 in NSCLC cells. Tumor allotransplantation experiments showed that knocking down NEAT1 could inhibit the growth of LC. CONCLUSION: In summary, our results showed that the down-regulation of NEAT1 in NSCLC inhibited its growth, migration and invasion through the miR-204/NUAK1 axis.