Association between dysbiotic perio-pathogens and inflammatory initiators and mediators in COVID-19 patients with diabetes.

It has been suggested that a corona virus infection is linked to chronic periodontitis (COVID-19). Our objectives were to look at the expression of angiotensin-converting enzyme-2 (ACE2) in periodontal compartments containing periodontal infections to determine if ACE2 is directly or indirectly responsible for the inflammation in periodontal tissues getting worse. In this study, six non-COVID-19 periodontitis patients without diabetes served as controls, and 23 hospitalized periodontitis patients were admitted with PCR-confirmed COVID-19 with diabetes mellitus (Group 1/G1, n = 10), and without diabetes (Group 2/G2, n = 13). We evaluated the mRNA expression of ACE2, IL-6, IL-8, complement C3, and LL-37, as well as the relative proportion of Porphyromonas gingivalis, Fusobacterium nucleatum, and Veillonella parvula to represent the dysbiosis condition in periodontal microenvironment using subgingival plaque and gingival crevicular fluids (GCF) samples and quantitative real time PCR (qPCR). Every analysis was done to ascertain how they related to one another. The area under the curve (AUC) and receiver operating characteristic (ROC) curve were used to determine the sensitivity and specificity of inflammatory indicators. All the grouped patients had ACE2 detected, according to our findings, but only the G1 patients had a positive correlation (p < 0.05) between ACE2 expression and the inflammatory markers. The combination of IL-6 and C3 mRNAs was found to be 0.78 and 0.55 for the G1 group and the G2 group, respectively, based on the ROC and AUC values. According to our research, the relationship between complement C3 and IL-6 may be able to predict the degree of periodontal inflammation in COVID-19 patients who also have diabetes.

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.

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.

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.

Clinical characteristics and quality of life of persistent symptoms of COVID-19 syndrome in Indonesia.

Introduction: Coronavirus disease-2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) manifests in a broad clinical spectrum. COVID-19 survivors report various symptoms up to several months after being infected. The purpose of this study was to determine the prevalence of persistent COVID-19 syndrome in Indonesia, the factors that influence the incidence, and the quality of life. Methods: This was a cross-sectional study with an online questionnaire conducted in January 2021. Inclusion criteria were: adult Indonesian citizens who had recovered from COVID-19, and were confirmed negative by RT-PCR of nasal swabs or had undergone an isolation period for a minimum of 14 days. Data analysis was performed by the Chi-square test, followed by multivariate analysis with the backward likelihood ratio method. Results: From a total of 385 respondents, 256 (66.5%) experienced persistent COVID-19 syndrome. The most prevalent symptoms were fatigue (29.4%), cough (15.5%), and muscle pain (11.2%). Of the five aspects of quality of life, the most commonly reported aspects were pain/discomfort and anxiety/depression. The risk of persistent COVID-19 syndrome was significantly higher in subjects with older age, comorbidities, higher clinical severity, previous treatment in hospital, presence of pneumonia, and those who had required oxygen therapy. In the multivariate analysis, the most influential factor for the incidence of persistent COVID-19 syndrome was pneumonia (aOR 2.31, 95% CI 1.29-4.11, p<0.002). Conclusions: The prevalence of the persistent COVID-19 syndrome in Indonesia was high, which affects the quality of life of COVID-19 survivors. Pneumonia was the main factor that influenced the incidence of persistent COVID-19 syndrome. Further research with a larger sample size and a longer study time is recommended to control COVID-19 and its impact on the health and quality of life of COVID-19 survivors.

ACE2 expression in saliva of patients with COVID-19 and its association with Candida albicans and Aggregatibacter actinomycetemcomitans.

Background: A relationship between oral microbiota and susceptibility to SARS-CoV-2 infection has been extensively studied. However, the relationship between oral commensal flora and expression of angiotensin-converting enzyme 2 ( ACE2) remains to be established. In this observational study, we collected saliva from patients with COVID-19 and evaluated the relationship between ACE2 expression and Candida albicans as well as with selected gram-negative bacteria ( Aggregatibacter actin o mycetemcomitans, Fusobacterium nucleatum, and Veillonella parvula). We investigated how this may be directly or indirectly involved in oral dysbiosis in patients with COVID-19. Methods: We included 23 hospitalized patients admitted to Universitas Indonesia Hospital with PCR-confirmed COVID-19, with six healthy participants serving as controls. Saliva and tongue surface swabs were collected from patients with diabetes (DG) and without diabetes (NDG) and subject controls. Using quantitative PCR (qPCR) we assessed the mRNA expression of ACE2, the abundance of C. albicans, and the transcription levels of its biofilm-associated genes, agglutinin-like protein 3 ( ALS3), hyphal wall protein 1 ( HWP1), and yeast-form wall protein 1 ( YWP1). We also counted the relative proportion of the three selected gram-negative oral bacteria in saliva. All analyses were performed to determine the relationship between ACE2 expression and C. albicans and gram-negative bacteria. Results: ACE2 mRNA expression was significantly higher in tongue swab samples than in saliva. However, no significant difference was observed between the patient groups. Conversely, DG patients had a significantly higher abundance of C. albicans in saliva compared to NDG patients and control group patients. The correlation and sensitivity/specificity relationship between ACE2 expression and C. albicans or the selected oral bacteria were also observed. Conclusions: The data show that ACE2 expression can be detected in saliva of patients with COVID-19 and its association with C. albicans and gram-negative oral bacteria might contribute toward developing an oral dysbiosis based predictor for prognosis of COVID-19 severity.

Virtual screening of Indonesian herbal compounds as COVID-19 supportive therapy: machine learning and pharmacophore modeling approaches.

BACKGROUND: The number of COVID-19 cases continues to grow in Indonesia. This phenomenon motivates researchers to find alternative drugs that function for prevention or treatment. Due to the rich biodiversity of Indonesian medicinal plants, one alternative is to examine the potential of herbal medicines to support COVID therapy. This study aims to identify potential compound candidates in Indonesian herbal using a machine learning and pharmacophore modeling approaches. METHODS: We used three classification methods that had different decision-making processes: support vector machine (SVM), multilayer perceptron (MLP), and random forest (RF). For the pharmacophore modeling approach, we performed a structure-based analysis on the 3D structure of the main protease SARS-CoV-2 (3CLPro) and repurposed SARS, MERS, and SARS-CoV-2 drugs identified from the literature as datasets in the ligand-based method. Lastly, we used molecular docking to analyze the interactions between the 3CLpro and 14 hit compounds from the Indonesian Herbal Database (HerbalDB), with lopinavir as a positive control. RESULTS: From the molecular docking analysis, we found six potential compounds that may act as the main proteases of the SARS-CoV-2 inhibitor: hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4'-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside. CONCLUSIONS: Our layered virtual screening with machine learning and pharmacophore modeling approaches provided a more objective and optimal virtual screening and avoided subjective decision making of the results. Herbal compounds from the screening, i.e. hesperidin, kaempferol-3,4'-di-O-methyl ether (Ermanin); myricetin-3-glucoside, peonidin 3-(4'-arabinosylglucoside); quercetin 3-(2G-rhamnosylrutinoside); and rhamnetin 3-mannosyl-(1-2)-alloside are potential antiviral candidates for SARS-CoV-2. Moringa oleifera and Psidium guajava that consist of those compounds, could be an alternative option as COVID-19 herbal preventions.

Bronchoscopy Findings of Severe and Critical COVID-19 Patients Treated in ICU: A Year of Experience in a Developing Country.

Background: Bronchoscopy procedure in patients with COVID-19 poses significant challenges, especially in a developing country with limited resources. Objectives: We aim to describe the clinical characteristics of severe and critical COVID-19 patients treated in an intensive care unit (ICU) and their bronchoscopy findings. Methods: We performed a retrospective analysis of clinical data of ICU patients with COVID-19 treated and received bronchoscopy procedures. This study retrospectively included all consecutive patients who underwent bronchoscopy at a teaching hospital in Depok, Indonesia, from May, 2020, until May, 2021. Results: A total of 57 bronchoscopy procedures in 54 patients were performed in this study. Primary procedure indications were retained mucus (68.4%) and ventilatory support weaning failure (15.8%). Bronchoscopic findings were mostly hyperaemic mucosa (95.00%) and purulent secretion (50.90%). Microbiological findings from bronchoalveolar samples were Acinetobacter baumanii, Klebsiella pneumoniae, and Candida albicans (33.3%, 26.6%, and 10.5%, respectively). The most common fungal isolated were Candida albicans (28%), followed by Candida tropicalis (16%) and Aspergillus sp. (8%). The overall length of hospital stay was 24 days, and the in-ICU stay was 22.06 ± 10.99 days. The patients' survival of 28-days postprocedural outcome was 25.9% (14 subjects). Follow-up found that 20.4% of patients survived after sixty days of hospitalization. Conclusion: Diagnostic and therapeutic bronchoscopy in ICU patients with COVID-19 was safe and feasible to perform in developing countries with limited resources. It could help bronchial mucous clearance and confirm microbiological infection. The procedures should be strictly performed for patients with indications and comply with safety standards.

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).