メチシリン耐性黄色ブドウ球菌の臨床分離株における抗菌薬耐性遺伝子分布とゲンタマイシン、クリンダマイシン、ミノサイクリン感受性の関連についての解析

広島大学(Hiroshima University)博士(医学)Doctor of Philosophy in Medical Sciencedoctora

Correlation Analysis between Antibiotic Resistance Gene Profile and Susceptibility to Gentamicin, Clindamycin, and Minocycline in Clinically Isolated Methicillin-resistant Staphylococcus aureus

This study aimed to elucidate retrospectively the correlations between the genome and phenotype in clinical methicillin-resistant Staphylococcus aureus (MRSA) gentamicin (GEN), clindamycin (CLI), and minocycline (MIN) susceptibility using next-generation sequencing (NGS) technology. Ninety two MRSA strains were isolated from individual inpatients treated in Hiroshima University Hospital, Hiroshima, Japan, extracted for their genomic DNA, and sequenced using an Illumina® MiSeq sequencer to obtain their de novo whole-genome assembly. An in silico analysis using ResFinder was performed to obtain the genomic antimicrobial susceptibility profile which was analyzed together with GEN, CLI, and MIN minimum inhibitory concentration (MIC) levels. This study found aac(6’)aph(2”)+, spc+, ermA+, tetM+ MRSA strains were predominant (42/92) and were shown to exhibit >16 mg/L GEN (40/42), >4 mg/L CLI (26/42), and >8 mg/L MIN MIC levels (30/42). Associations between aac(6’)aph(2”) detections and GEN MIC levels (p <0.001), ermA detections and CLI MIC levels (p <0.001), and tetM detections and MIN MIC levels (p <0.001) were revealed in this study. Correlations between simultaneous detections of aac(6’) aph(2”)-spc-ermA-tetM and GEN MIC levels (φc= 0.398, p <0.001), CLI MIC levels (φc= 0.448, p <0.001), and MIN MIC levels (φc= 0.515, p <0.001) were revealed in this study. The genomicphenotypic correlation analyses in this study provided an insight of a rapid antimicrobial detection in MRSA using in silico genomic antimicrobial susceptibility profiling.This research was partially supported by a Grant-in-Aid for Scientific Research (A) (No.15H02567) from the Ministry of Education, Culture, Sports, Science, and Technology and those from Ministry of Health, Labor, and Welfare of the Government of Japan

The utility of salivary CRP and IL-6 as a non-invasive measurement evaluated in patients with COVID-19 with and without diabetes [version 3; peer review: 2 approved]

Background The available evidence suggests that inflammatory responses, in both systemic and oral tissue, contribute to the pathology of COVID-19 disease. Hence, studies of inflammation biomarkers in oral fluids, such as saliva, might be useful to better specify COVID-19 features. Methods In the current study, we performed quantitative real-time PCR to measure salivary levels of C-reactive protein (CRP) and interleukin-6 (IL-6) in saliva obtained from patients diagnosed with mild COVID-19, in a diabetic group (DG; n = 10) and a non-diabetic group (NDG; n = 13). All participants were diagnosed with periodontitis, while six participants with periodontitis but not diagnosed with COVID-19 were included as controls. Results We found increases in salivary total protein levels in both the DG and NDG compared to control patients. In both groups, salivary CRP and IL-6 levels were comparable. Additionally, the levels of salivary CRP were significantly correlated with total proteins, in which a strong and moderate positive correlation was found between DG and NDG, respectively. A linear positive correlation was also noted in the relationship between salivary IL-6 level and total proteins, but the correlation was not significant. Interestingly, the association between salivary CRP and IL-6 levels was positive. However, a moderately significant correlation was only found in COVID-19 patients with diabetes, through which the association was validated by a receiver operating curve. Conclusions These finding suggest that salivary CRP and IL-6 are particularly relevant as potential non-invasive biomarker for predicting diabetes risk in mild cases of COVID-19 accompanied with periodontitis

Differentially Expressed Genes Study Shown Potential for BCG Stimulation in Reducing the Severity of COVID-19

The incidence of COVID-19 infection and death is known to be lower in tuberculosis (TB) endemic countries than in nonendemic countries. The Bacillus Calmette-Guerin (BCG) vaccination, which is commonly administered in TB endemic countries, was previously reported to have a nonspecific protective effect against several infections, including COVID-19. In this study, we used a differentially expressed genes (DEG) approach to analyze the genes modulated by BCG vaccination and COVID-19 infection. The Gene Expression Omnibus (GEO) database was used to select a COVID-19 gene expression data set with GSE164805, GSE14408, and GSE58636, and DEG in each data set were identified using the GEO2R online tools and selected using the adjusted p value (padj) 0.05 criteria. The protein-protein interaction (PPI) network was constructed from DEGs with the same trend of expression (upregulation or downregulation) using STRING version 11. The PPI network was performed by using the highest confidence number (0.9). DEGs that have a high-trust network were collected and functional cluster analysis of biological processes from Gene Ontology (GO), pathway analysis from the Human KEGG pathway, and COVID-19-related gene analysis was carried out using the Enrichr database. We found that either BCG or tuberculin increased the expression of several genes related to hyperinflammation, such as CCL3, CCL4, CSF2, IL1B, and LTA. In severe COVID-19, these genes were downregulated. This leads to the hypothesis that revaccination may have a protective effect against the severity of COVID-19 by reducing the hyperinflammatory status

Differentially Expressed Genes Analysis in the Human Small Airway Epithelium of Healthy Smokers Shows Potential Risks of Disease Caused by Oxidative Stress and Inflammation and the Potentiality of Astaxanthin as an Anti-Inflammatory Agent

Cigarette smoke (CS) was known for its effect of increasing oxidative stress that could trigger tissue injury and endothelial dysfunction mediated by free radicals and reactive oxygen species (ROS). ROS itself is a key signaling molecule that plays a role in the development of inflammatory disorders. Nuclear factor erythroid2 related factor2 (Nrf2) is the main regulator of antioxidant cellular response to cell and tissue-destroying components caused by CS. Nrf2 protein that is significantly activated in the smokers’ small airway epithelium is followed by a series of gene expression changes in the same cells. This study aims to observe differentially expressed genes (DEGs) in the human small airway epithelium of smokers compared to genes whose expression changes due to astaxanthin (AST) treatment, an antioxidant compound that can modulate Nrf2. Gene expression data that was stored in the GEO browser (GSE 11952) was analyzed using GEO2R to search for DEG among smokers and nonsmokers subject. DEG was further compared to those genes whose expression changes due to astaxanthin treatment (AST) that were obtained from the Comparative Toxicogenomics Database (CTD; https://ctdbase.org/). DEG (p<0.05) analysis result shows that there are 23 genes whose expression regulation is reversed compared to gene expression due to AST treatment. The gene function annotations of the 23 DEGs showed the involvement of some of these genes in chemical and oxidative stress, reactive oxygen species (ROS), and apoptotic signaling pathways. All of the genes were involved/associated with chronic bronchitis, adenocarcinoma of the lung, non-small-cell lung carcinoma, carcinoma, small cell lung carcinoma, type 2 diabetes mellitus, emphysema, ischemic stroke, lung diseases, and inflammation. Thus, AST treatment for smokers could potentially decrease the development of ROS and oxidative stress that leads to inflammation and health risks associated with smoking

Video‐assisted surgical diagnosis and pleural adhesion management in catamenial pneumothorax: A case and literature review

Abstract Catamenial pneumothorax is a rare primary spontaneous pneumothorax associated with the menstrual phase and is the most common manifestation of thoracic endometriosis syndrome. We report a case of a 32‐year‐old woman with a history of endometriosis who presented to the emergency ward with a chief complaint of dyspnea and right‐sided chest pain, and a chest X‐ray showed a right pneumothorax. Initial management was by placing a chest tube to expand the right lung. The patient underwent a video‐assisted thoracoscopy and talc pleurodesis, during which we found multiple perforations in the tendinous part of the diaphragm. A partial resection of the tendinous part of the diaphragm was done. Our review indicated that primary spontaneous pneumothorax in women should be suspected as catamenial pneumothorax due to thoracic endometriosis. The gold standard procedure for diagnosis and treatment is surgery. Hormonal therapy is an effective choice to prevent and reduce post‐operative recurrence

Xanthine Oxidase-Induced Inflammatory Responses in Respiratory Epithelial Cells: A Review in Immunopathology of COVID-19

Xanthine oxidase (XO) is an enzyme that catalyzes the production of uric acid and superoxide radicals from purine bases: hypoxanthine and xanthine and is also expressed in respiratory epithelial cells. Uric acid, which is also considered a danger associated molecule pattern (DAMP), could trigger a series of inflammatory responses by activating the inflammasome complex path and NF-κB within the endothelial cells and by inducing proinflammatory cytokine release. Concurrently, XO also converts the superoxide radicals into hydroxyl radicals that further induce inflammatory responses. These conditions will ultimately sum up a hyperinflammation condition commonly dubbed as cytokine storm syndrome (CSS). The expression of proinflammatory cytokines and neutrophil chemokines may be reduced by XO inhibitor, as observed in human respiratory syncytial virus (HRSV)-infected A549 cells. Our review emphasizes that XO may have an essential role as an anti-inflammation therapy for respiratory viral infection, including coronavirus disease 2019 (COVID-19)