Association between the Reduced Expression of RECK and Neutrophilic Inflammation in Chronic Obstructive Pulmonary Disease.

INTRODUCTION: Reversion-inducing cysteine-rich protein with Kazal motifs (RECK), a recently discovered inhibitor of matrix metalloproteinase (MMP). There is a large number of chronic obstructive pulmonary disease (COPD) patients worldwide; however, the role of RECK on COPD has not been studied. This study explored the expression of RECK in COPD patients and its effect on neutrophil function to provide a new scientific basis for the prevention and treatment of COPD. METHOD: Fifty patients with acute exacerbation of COPD and fifty healthy controls were enrolled in the study. RECK was detected in lung tissue, sputum, and plasma of subjects as well as in BEAS-2B cells stimulated with cigarette smoke extract (CSE) by immunohistochemistry, ELISA, and qRT-PCR. Meanwhile, lung function (FEV1%pred) and inflammatory cytokines (IL-6 and IL-8) were examined, and correlation analysis was performed with RECK expression. The effect of RECK on proliferation, apoptosis, migration, and inflammatory cytokines and its potential mechanism was further quantified by neutrophil stimulated with recombinant human RECK protein (rhRECK) combined with CSE using CCK8, flow cytometry, Transwell assay, qRT-PCR, ELISA, and Western analysis. RESULTS: RECK was mainly expressed on airway epithelial cells in normal lung tissue and was significantly diminished in COPD patients. The levels of RECK in sputum and plasma were also significantly decreased in COPD patients. Pearson correlation analysis showed that RECK level in plasma was positively correlated with FEV1%pred (r = 0.458, p < 0.001) and negatively correlated with IL-6 and IL-8 (r = -0.386, -0.437; p = 0.006, 0.002) in COPD patients. The expression of RECK was decreased in BEAS-2B stimulated with CSE. The migration, inflammation, and MMP-9 expression of neutrophils were promoted by CSE, while inhibited by rhRECK. CONCLUSION: RECK is low expressed in COPD patients and negatively correlated with inflammation. It may inhibit the inflammation and migration of neutrophils by downregulating MMP-9.

Design, synthesis and biological evaluation of 5-fluorouracil-derived benzimidazoles as novel type of potential antimicrobial agents.

A series of 5-fluorouracil benzimidazoles as novel type of potential antimicrobial agents were designed and synthesized for the first time. Bioactive assay manifested that some of the prepared compounds exhibited good or even stronger antibacterial and antifungal activities against the tested strains in comparison with reference drugs norfloxacin, chloromycin and fluconazole. Noticeably, 3-fluorobenzyl benzimidazole derivative 5c gave remarkable antimicrobial activities against Saccharomyces cerevisiae, MRSA and Bacillus proteus with MIC values of 1, 2 and 4µg/mL, respectively. Experimental research revealed that compound 5c could effectively intercalate into calf thymus DNA to form compound 5c-DNA complex which might block DNA replication and thus exert antimicrobial activities. Molecular docking indicated that compound 5c should bind with DNA topoisomerase IA through three hydrogen bonds by the use of fluorine atom and oxygen atoms in 5-fluorouracil with the residue Lys 423.

Infection caused by Cupriavidus gilardii in a convalescent COVID-19 patient.

Cupriavidus gilardii is an aerobic, gram-negative bacillus that can opportunistically infect immunocompromised patients or those undergoing invasive procedures. We reported a case caused by C. gilardii in a previously basic healthy 78-year-old male, who had COVID-19 and had used corticosteroids recently. The bacterium was identified as C. gilardii by the metagenomic next-generation sequencing from the patient's bronchoalveolar lavage fluid and blood. In addition, this is the first time that we isolated C. gilardii from bronchoalveolar lavage fluid, which provides clinical experience in rare bacterial infections.

Effect of Singing on Symptoms in Stable COPD: A Systematic Review and Meta-Analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic lung disease which feature is progressive airflow obstruction. Singing is a popular and convenient activity that requires people to manage their lung volumes and airflow actively. Despite the well-known benefits of singing to healthy people, the specific effect still remains unclear. Objective: To investigate the mental and psychological benefits of singing in patients with stable COPD. Search Methods: We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses Guidelines (PRISMA) on randomized controlled trials (RCTs) including singing exercise as the main intervention in stable COPD. We searched 8 electronic databases, including Web of Science, PubMed, Embase, Cochrane Library, Clinical Trials.gov, and the Physical Therapy Evidence Database (PEDro), CNKI, and Wanfang Database from inception until May 2022. The searching languages was English or Chinese. Data extraction using standardized templates was performed by two independent reviewers. The quality of the studies was assessed using the PEDro scale. Data synthesis was performed with Revman 5.4. The pooled effect sizes are reported by MD and 95% CI. Results: Five RCTs involving 333 patients with stable COPD were included in this meta-analysis. Singing was regarded as the main intervention in the experimental group. Meta-analysis revealed that singing improves quality of life on Short Form 36 physical component summary (SF-36 PCS) (MD = 12.63, 95% CI: 5.52 to 19.73, P < 0.01) and respiratory muscle in maximal expiratory pressure (PEmax) (MD = 14.30, 95% CI: 0.87 to 27.73, P = 0.04) in patients with COPD. However, it has limited effects on Short Form 36 mental component summary (SF-36 MCS), lung function, exercise capability, and adverse mental state. Conclusion: Based on results of the meta-analysis, singing could be used to improve quality of life (SF-36 PCS) and respiratory muscles (PEmax) in patients with COPD.