Natural antibodies targeting LPS in pleural effusions of various etiologies.

BACKGROUND: Respiratory infection, cancer and heart failure can cause abnormal accumulation of fluid in the pleural cavity. The immune responses within the cavity are orchestrated by leucocytes that reside in the serosal associated lymphoid tissue. Natural antibodies (NAbs) are abundant in the serum having a major role in systemic and mucosal immunity, however their occurrence in pleural fluid remains an open question. Our aim herein was to detect and measure the levels of NAbs targeting LPS of M, G, and A class in both, the pleural fluid and the serum of 78 patients with pleural effusions (PEs) of various etiologies. METHODS: The values of anti-LPS NAb activity were extracted through a normalization step regarding the total IgM, IgG and IgA levels and in addition the ratio of PF/S values were analyzed further with other critical biochemical parameters from biopsies. RESULTS: Anti-LPS NAbs of all Ig classes were detected in most of the samples, while a significant increase of anti-LPS activity was observed in infectious and non-infectious compared to malignant PEs. Multivariate linear regression confirmed a negative correlation of IgM and IgA anti-LPS PF/S ratio with malignancy. Moreover, anti-LPS NAbs PF/S measurements led to increased positive and negative predictive power in ROC curves generated for the discrimination between benign and malignant PEs. CONCLUSIONS: Our results highlight a potential role of anti-LPS NAbs in the pleural cavity that should be further explored.

Investigation of admission serum creatinine as a predictor of hospital length of stay in triple-vaccinated COVID-19 inpatients.

BACKGROUND: This study assessed the association between admission kidney function and the duration of hospitalization in triple-vaccinated coronavirus disease 2019 (COVID-19) inpatients during the omicron surge in Larissa, central Greece. METHODS: Regression analysis was used to estimate the effect of kidney function biomarkers on hospital length of stay (LoS) within a dataset from a cohort of 51 subjects. RESULTS: Sex- and age-adjusted admission serum creatinine was associated with hospital LoS (p=0.034). CONCLUSIONS: Serum creatinine concentration on admission should be further evaluated as a possible clinical predictor of hospital LoS among triple-vaccinated COVID-19 inpatients both at the country and global level.

Differential effects of biocompatible peritoneal dialysis fluids on human mesothelial and endothelial cells in 2D and 3D phenotypes.

INTRODUCTION: Peritoneal dialysis (PD) is a life maintaining treatment in patients with end-stage renal disease. Its chronic application leads to peritoneal mesothelial layer denudation and fibrotic transformation along with vascular activation of inflammatory pathways. The impact of different PD fluids (PDF) on mesothelial and endothelial cell function and repair mechanisms are not comprehensively described. MATERIALS AND METHODS: Mesothelial (MeT-5A) and endothelial cells (EA.hy926) were cultured in 1:1 ratio with cell medium and different PDF (icodextrin-based, amino acid-based, and glucose-based). Cell adhesion, cell migration, and cell proliferation in 2D and spheroid formation and collagen gel contraction assays in 3D cell cultures were performed. RESULTS: Cell proliferation and cell-mediated gel contraction were both significantly decreased in all conditions. 3D spheroid formation was significantly reduced with icodextrin and amino acid PDF, but unchanged with glucose PDF. Adhesion was significantly increased by amino acid PDF in mesothelial cells and decreased by icodextrin and amino acid PDF in endothelial cells. Migration capacity was significantly decreased in mesothelial cells by all three PDF, while endothelial cells remained unaffected. CONCLUSIONS: In 3D phenotypes the effects of PDF are more uniform in both mesothelial and endothelial cells, mitigating spheroid formation and gel contraction. On the contrary, effects on 2D phenotypes are more uniform in the icodextrin and amino acid PDF as opposed to glucose ones and affect mesothelial cells more variably. 2D and 3D comparative assessments of PDF effects on the main peritoneal membrane cell barriers, the mesothelial and endothelial, could provide useful translational information for PD studies.

2-Deoxy-glucose ameliorates the peritoneal mesothelial and endothelial barrier function perturbation occurring due to Peritoneal Dialysis fluids exposure.

Peritoneal dialysis (PD) and prolonged exposure to PD fluids (PDF) induce peritoneal membrane (PM) fibrosis and hypervascularity, leading to functional PM degeneration. 2-deoxy-glucose (2-DG) has shown potential as PM antifibrotic by inhibiting hyper-glycolysis induced mesothelial-to-mesenchymal transition (MMT). We investigated whether administration of 2-DG with several PDF affects the permeability of mesothelial and endothelial barrier of the PM. The antifibrotic effect of 2-DG was confirmed by the gel contraction assay with embedded mesothelial (MeT-5A) or endothelial (EA.hy926) cells cultured in Dianeal® 2.5 % (CPDF), BicaVera® 2.3 % (BPDF), Balance® 2.3 % (LPDF) with/without 2-DG addition (0.2 mM), and qPCR for αSMA, CDH2 genes. Moreover, 2-DG effect was tested on the permeability of monolayers of mesothelial and endothelial cells by monitoring the transmembrane resistance (RTM), FITC-dextran (10, 70 kDa) diffusion and mRNA expression levels of CLDN-1 to -5, ZO1, SGLT1, and SGLT2 genes. Contractility of MeT-5A cells in CPDF/2-DG was decreased, accompanied by αSMA (0.17 ± 0.03) and CDH2 (2.92 ± 0.29) gene expression fold changes. Changes in αSMA, CDH2 were found in EA.hy926 cells, though αSMA also decreased under LPDF/2-DG incubation (0.42 ± 0.02). Overall, 2-DG mitigated the PDF-induced alterations in mesothelial and endothelial barrier function as shown by RTM, dextran transport and expression levels of the CLDN-1 to -5, ZO1, and SGLT2. Thus, supplementation of PDF with 2-DG not only reduces MMT but also improves functional permeability characteristics of the PM mesothelial and endothelial barrier.

The effect of cigarette smoke extract exposure on the size and sexual behaviour of Drosophila melanogaster.

Drosophila melanogaster is a widely used animal model in human diseases and to date it has not been applied to the study of the impact of tobacco use on human sexual function. Hence, this report examines the effects of different concentrations of cigarette smoke extract (CSE) exposure on the size and sexual behavior of D. melanogaster. Wild-type flies were held in vials containing CSE-infused culture media at concentrations of 10%, 25%, and 50% for three days, and their offspring were reared under the same conditions before measuring their body size and mating behavior. CSE exposure during development reduced the tibia length and body mass of emerging adult flies and prolonged the time required for successful courtship copulation success, while courtship behaviors (wing extension, tapping, abdomen bending, attempted copulation) remained largely unchanged. Our findings indicate that CSE exposure negatively affects the development of flies and their subsequent reproductive success. Future experiments should investigate the CSE effect on male female fertility.

Identification of Genes and miRNAs Associated with TAFI-Related Thrombosis: An in Silico Study.

Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) is a carboxypeptidase B-like proenzyme encoded by the CPB2 gene. After thrombin activation, TAFI downregulates fibrinolysis, thus linking the latter with coagulation. TAFI has been shown to play a role in venous and arterial thrombotic diseases, yet, data regarding the molecular mechanisms underlying its function have been conflicting. In this study, we focused on the prediction and functional enrichment analysis (FEA) of the TAFI interaction network and the microRNAs (miRNAs) targeting the members of this network in an attempt to identify novel components and pathways of TAFI-related thrombosis. To this end, we used nine bioinformatics software tools. We found that the TAFI interactome consists of 28 unique genes mainly involved in hemostasis. Twenty-four miRNAs were predicted to target these genes. Co-annotation analysis of the predicted interactors with respect to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and transcription factors (TFs) pointed to the complement and coagulation cascades as well as neutrophil extracellular trap formation. Cancer, stroke, and intracranial aneurysm were among the top 20 significant diseases related to the identified miRNAs. We reason that the predicted biomolecules should be further studied in the context of TAFI-related thrombosis.

Changes in Smoking Habits in Greece During the Lockdown Measures Due to COVID-19.

INTRODUCTION: During lockdown, people are experiencing higher than usual levels of stress related to social isolation, employment, and finances that may result in lifestyle changes. Here, we aim to assess whether smoking habits changed during the lockdown measures due to coronavirus disease 2019 (COVID-19). METHODS: For the purpose of the survey, an online questionnaire was distributed from the tenth of April to the second of May 2020, among a Greek population, by using an online platform. RESULTS: Two hundred smokers/vapers participated in the present survey (62.5% women, 44% of 36-45 years, 29% of 16-55 years, 15.5% 26-35 years). The daily number of cigarettes smoked before the onset of the COVID-19 pandemic is 15.06 ± 9.84, while during the restrictive measures due to COVID-19, the daily number of cigarettes smoked is 14.52 ± 10.13 (p > 0.05). Vapers consumed an average of 0.54 ± 2.43 mL vapor per day before the COVID-19 pandemic and 0.61 ± 2.81 mL during lockdown. Males smoked more cigarettes per day before (16.31 ± 11.87) and during the lockdown (15.33 ± 12.17) versus females (14.30 ± 8.36) and 14.04 ± 8.70, respectively) (p > 0.05 for both genders). Before versus during the restrictive measures, subjects that were primary school graduates smoked more cigarettes per day (28.00 ± 9.09 and 27.50 ± 9.57, respectively), followed by subjects that were high school graduates (16.90 ± 9.33 and 15.97 ± 9.50, respectively), university graduates (14.17 ± 10.14 and 13.93 ± 10.66, respectively), postgraduates (12.96 ± 9.52 and 12.25 ± 9.90, respectively) and middle school graduates (12.89 ± 8.22 and 14.22 ± 7.93, respectively).The self-reported reason for the change in the mL vaporized and the cigarettes smoked are confinement at home (36.3%), stress about COVID-19 (34.09%), free time (20.45%), boredom (4.54%), stress about the work status (2.27%), and participation in online lucky games (2.27%). DISCUSSION: We did not observe significant differences in the daily consumption of smoke/vaping during the lockdown measures. More studies are needed to assess the long-term effects of the pandemic in smoking habits.

Changes in expression of mesothelial BBS genes in 2D and 3D after lithium chloride and ammonium sulphate induction of primary cilium disturbance: a pilot study.

BACKGROUND: Malignant pleural mesothelioma (MPM), a rare and aggressive pleural tumor, has significant histological and molecular heterogeneity. Primary Cilium (PC), an organelle of emerging importance in malignancies, has been scarcely investigated in MPM. A critical molecular complex for the PC function is the BBSome and here we aimed at assessing its expression patterns in ordinary 2D and spheroid 3D cell cultures. METHODS: A human benign mesothelial cell line (MeT-5A), MPM cell lines (M14K, epithelioid MPM; MSTO, biphasic MPM), and primary MPM cells (pMPM) were used. Primers specific for the human BBS1, 2, 4, 5, 7, 9, 18 transcripts were designed, and quantitative real-time PCR (qRT-PCR) was done with ß-actin as the gene of reference. The relative gene expression across 2D and 3D cultures was analyzed by the expression factor (mean of 1/ΔCt values). With the 2-∆∆Ct method the gene expression fold changes were assessed from qRT-PCR data. Molecular changes using the PC-modulating drugs ammonium sulfate (AS) and lithium chloride (LC) were also determined. RESULTS: PC was present in all cells used in the study at approximately 15% of the observed area. BBSome transcripts were differentially expressed in different dimensions of cell culture (2D vs. 3D) in all cell lines and pMPM. Treatment with AS and LC affected the expression of the ciliary BBS2 and BBS18 genes in the benign as well as in the MPM cells. CONCLUSIONS: These data indicate distinct BBSome molecular profiles in human benign and MPM cells cultured in 2D and 3D dimensions and support the notion that PC genes should be investigated as potential MPM therapeutic targets.

A Hypertonic Seawater Nasal Irrigation Solution Containing Algal and Herbal Natural Ingredients Reduces Viral Load and SARS-CoV-2 Detection Time in the Nasal Cavity.

Nasal irrigation is thought to decrease the viral load present in the nasal cavity. Our aim was to assess the effect of a hypertonic seawater solution [with algal and herbal natural ingredients (Sinomarin®)] on the viral load of nasopharynx in patients hospitalized with severe COVID-19 pneumonia. We conducted a prospective, randomized, controlled trial from June 2022 to December 2022. We allocated 56 patients with COVID-19 pneumonia into two groups (28 in each group)-the hypertonic seawater group [nasal irrigations with a hypertonic seawater solution (Sinomarin®) every 4 h for 16 h per day, for two consecutive days] and the control group (no nasal irrigations). A second nasopharyngeal swab was collected 48 h after the baseline nasopharyngeal swab (8 h after the last wash in the hypertonic seawater group) to estimate the SARS-CoV-2 viral load as determined by cycle threshold (Ct) values. In the hypertonic seawater group, the mean Ct values significantly increased two days after the initial measurement [ΔCt 48-0 h = 3.86 ± 3.03 cycles, p < 0.001 (95%CI: 2.69 to 5.04)]. No significant differences in the Ct values were observed in the control group [ΔCt 48-0 h = -0.14 ± 4.29, p = 0.866 (95%CI: -1.80 to -1.52)]. At follow-up, 17 patients from the hypertonic seawater group had negative test results compared to only 9 patients from the control group (p = 0.03). Nasal irrigations with a hypertonic seawater solution containing algal and herbal natural ingredients significantly decreased nasopharyngeal viral load and the detection time of SARS-CoV-2 in the nasal cavity.

Natural autoimmunity in oligoarticular juvenile idiopathic arthritis.

BACKGROUND: Oligoarticular juvenile idiopathic arthritis (oligo-JIA) is considered as an antigen-driven lymphocyte-mediated autoimmune disease. Natural antibodies (NAbs) are pre-immune antibodies produced in the absence of exogenous antigen stimulation, participating in both, innate and adaptive immunity. Considering their major immunoregulatory role in homeostasis and autoimmune pathogenesis, we designed this study to further elucidate their role in oligo-JIA pathogenesis. METHODS: Seventy children with persistent oligo-JIA and 20 healthy matched controls were enrolled in the study. Serum IgM and IgA antibodies against human G-actin, human IgG F(ab΄)2 fragments and the hapten TriNitroPhenol (TNP) as well as the total concentration of serum IgM and IgA were measured by in-house enzyme-immunoassays. Kolmogorov-Smirnov normality test, Kruskal-Wallis H and Mann-Whitney tests were used to assess data distribution, and significant differences of non-parametric data between groups of the study. Backward regression analysis was used to analyze the effect of multiple factors (age, gender, disease activity, anti-nuclear antibody positivity, presence of uveitis) on continuous dependent variables (activities and activity/ concentration ratios of IgM and IgA NAbs). RESULTS: The ratios of IgA anti-TNP, anti-actin and anti-F(ab΄)2 levels to total serum IgA concentration were found to be significantly increased in patients with oligo-JIA compared to healthy subjects. Significantly elevated levels of IgM anti-TNP antibodies were also found in children with inactive oligo-JIA compared to those of children with active disease and of healthy controls. In the presence of anterior uveitis, IgM anti-TNP levels were significantly higher than in patients without uveitis or in healthy controls. Backward regression analysis revealed that the disease activity and the presence of anterior uveitis independently affect IgM anti-TNP levels. CONCLUSUIONS: Our findings are in accordance with the hypothesis that NAbs contribute to the pathogenesis of autoimmune diseases and provide additional evidence that disturbances in natural autoimmunity may contribute to the as yet unclarified pathogenesis of oligo-JIA.

Effects of pharmacological primary cilium disturbance in the context of in vitro 2D and 3D malignant pleura mesothelioma.

INTRODUCTION: Primary cilium (PC) is a single non-motile antenna-like organelle composed of a microtubule core axon originating from the mother centriole of the centrosome. The PC is universal in all mammalian cells and protrudes to the extracellular environment receiving mechanochemical cues that it transmits in the cell. AIM: To investigate the role of PC in mesothelial malignancy in the context of two-dimensional (2D) and three-dimensional (3D) phenotypes. MATERIALS AND METHODS: The effect of pharmacological deciliation [using ammonium sulphate (AS) or chloral hydrate (CH)] and PC elongation [using lithium chloride (LC)] on cell viability, adhesion, and migration (2D cultures) as well as in mesothelial sphere formation, spheroid invasion and collagen gel contraction (3D cultures) was investigated in benign mesothelial MeT-5A cells and in malignant pleural mesothelioma (MPM) cell lines, M14K (epithelioid) and MSTO (biphasic), and primary malignant pleural mesothelioma cells (pMPM). RESULTS: Pharmacological deciliation or elongation of the PC significantly affected cell viability, adhesion, migration, spheroid formation, spheroid invasion and collagen gel contraction in MeT-5A, M14K, MSTO cell lines and in pMPM cells compared to controls (no drug treatment). CONCLUSIONS: Our findings indicate a pivotal role of the PC in functional phenotypes of benign mesothelial cells and MPM cells.

Pertussis Prevalence in Adult Population in Greece: A Seroprevalence Nationwide Study.

The reported cases of pertussis vary considerably globally. In the present nationwide study, we aimed to record the Bordetella pertussis prevalence in Greece by measuring serum IgG specific antibody levels to pertussis toxin (anti-PT IgG). General practitioners and laboratories participated in this study from 12 regions of Greece. A geographically stratified sampling plan based on regional units (NUTS level 2) was applied in order to produce a representative sample, taking into consideration age group (30−39, 40−49, 50−59, 60−69, 70−79 and 80+) and sex. In total, 1169 subjects participated in the study. The percentage of participants with anti-PT IgG antibodies higher than 50 IU/mL was 3.7%. The levels of anti-PT IgG antibodies of total sample ranged between 1.46 IU/mL to 126.60 IU/mL, with mean 17.74 IU/mL and standard deviation 14.03 U/mL (p-value < 0.001). The total seroprevalence of Greek regions for pertussis disease varied significantly among prefectures. The region with the highest seroprevalence was Peloponnese 21.3%, followed by the region of Central Greece 15.3%. The proportion of adults who have pertussis specific antibodies <50 IU/mL has been >90%, suggesting that a large number of adults may be vulnerable to infection of pertussis despite well-established vaccination programs in Greece. Despite the fact that vaccination reduced the number of reported pertussis cases in the last decades in Greece, our seroprevalence study may indicate that the herd immunity level among Greek adults is suboptimal.

Predictors of SARS-CoV-2 IgG Spike Antibody Responses on Admission and Clinical Outcomes of COVID-19 Disease in Fully Vaccinated Inpatients: The CoVax Study.

BACKGROUND: SARS-CoV-2 vaccines have shown high efficacy in protecting against COVID-19, although the determinants of vaccine effectiveness and breakthrough rates are yet to be determined. We aimed at investigating several factors affecting the SARS-CoV-2 IgG Spike (S) antibody responses on admission and clinical outcomes of COVID-19 disease in fully vaccinated, hospitalized patients. METHODS: 102 subjects were enrolled in the study. Blood serum samples were collected from each patient upon admission for the semiquantitative determination of the SARS-CoV-2 IgG S levels with lateral flow assays. Factors influencing vaccine responses were documented. RESULTS: 27 subjects had a negative antibody test upon hospital admission. Out of the 102 patients admitted to the hospital, 88 were discharged and 14 died. Both the absence of anti-S SARS-CoV-2 antibodies and poor clinical outcomes of COVID-19 disease were associated with older age, lower Ct values, and a shorter period between symptom onset and hospital admission. Ct values and time between symptom onset and hospitalization were independently associated with SARS-CoV-2 IgG S responses upon admission. The PaO2/FiO2 ratio was identified as an independent predictor of in-hospital mortality. CONCLUSIONS: Host- and disease-associated factors can predict SARS-CoV-2 IgG S responses and mortality in hospitalized patients with breakthrough SARS-CoV-2 Infection.

Incorporating Biomarkers in COPD Management: The Research Keeps Going.

Globally, chronic obstructive pulmonary disease (COPD) remains a major cause of morbidity and mortality, having a significant socioeconomic effect. Several molecular mechanisms have been related to COPD including chronic inflammation, telomere shortening, and epigenetic modifications. Nowadays, there is an increasing need for novel therapeutic approaches for the management of COPD. These treatment strategies should be based on finding the source of acute exacerbation of COPD episodes and estimating the patient's own risk. The use of biomarkers and the measurement of their levels in conjunction with COPD exacerbation risk and disease prognosis is considered an encouraging approach. Many types of COPD biomarkers have been identified which include blood protein biomarkers, cellular biomarkers, and protease enzymes. They have been isolated from different sources including peripheral blood, sputum, bronchoalveolar fluid, exhaled air, and genetic material. However, there is still not an exclusive biomarker that is used for the evaluation of COPD but rather a combination of them, and this is attributed to disease complexity. In this review, we summarize the clinical significance of COPD-related biomarkers, their association with disease outcomes, and COPD patients' management. Finally, we depict the various samples that are used for identifying and measuring these biomarkers.

Prediction and enrichment analyses of the Homo sapiens-Drosophila melanogaster COPD-related orthologs: potential for modeling of human COPD genomic responses with the fruit fly.

The significant similarities in airway epithelial cells between mammals and the fruit fly Drosophila melanogaster have rendered the latter an important model organism for studies of chronic inflammatory lung diseases. Focusing on the chronic obstructive pulmonary disease (COPD), we here mapped human gene orthologs associated with this disease in D. melanogaster to identify functionally equivalent genes for immediate, further screening with the fruit fly model. The DIOPT-DIST tool was accessed for the prediction of the COPD-associated orthologs between humans and Drosophila. Enrichment analyses with respect to pathways of the retrieved functional homologs were performed using the ToppFun and FlyMine tools, identifying 73 unique human genes as well as 438 fruit fly genes. The ToppFun analysis verified that the human gene list is associated with COPD phenotypes. Furthermore, the FlyMine investigation highlighted that the Drosophila genes are functionally connected mainly with the "ABC-family proteins mediated transport" and the "ß-catenin-independent WNT signaling pathway." These results suggest an evolutionarily conserved role toward responses to inhaled toxicants and CO2 in both species. We reason that the predicted orthologous genes should be further studied in the Drosophila models of cigarette smoke-induced COPD.

Temporal Associations of the SARS-CoV-2 NP Antigen and Anti-Spike Total Ig Levels with Laboratory Parameters in a Greek Cohort of Hospitalized COVID-19 Patients.

Background: The direct effect of SARS-CoV-2 on the lungs results in increased hospitalization rates of patients with pneumonia. Severe COVID-19 patients often develop ARDS which is associated with poor prognosis. Assessing risk factors for COVID-19 severity is indispensable for implementing and evaluating therapeutic interventions. We investigated the temporal associations between the SARS-CoV-2 antigen (Ag), total Immunoglobulin (Ig) levels, and several laboratory parameters in hospitalized patients with varying degrees of COVID-19 severity. Methods: The SARS-CoV-2 nucleocapsid protein (NP) and total Ig Spike (S) protein-specific antibodies were determined for each patient with lateral flow assays through repeated sampling every two days. Hematological and biochemical parameters were evaluated at the same time points. Results: 40 Greek COVID-19 patients (31 males, 9 females) with a median age of 59.50 ± 16.21 years were enrolled in the study. The median time from symptom onset to hospitalization was 8.0 ± 4.19 days. A significant negative correlation was observed between the SARS-CoV-2 Ag and total Ig levels. The temporal correlation patterns of the SARS-CoV-2 NP Ag and anti-S total Ig levels with laboratory markers varied among patients with differing degrees of COVID-19 severity. Severe-critical cases had lower SARS-CoV-2 Ag and increased total Ig levels as compared to mild-moderate cases. Conclusions: Distinct temporal profiles of the SARS-CoV-2 NP Ag and anti-S total Ig levels may distinguish different groups of COVID-19 severity.

In silico investigation of the viroporin E as a vaccine target against SARS-CoV-2.

Viroporins, integral viral membrane ion channel proteins, interact with host-cell proteins deregulating physiological processes and activating inflammasomes. Severity of COVID-19 might be associated with hyperinflammation, thus we aimed at the complete immunoinformatic analysis of the SARS-CoV-2 viroporin E, P0DTC4. We also identified the human proteins interacting with P0DTC4 and the enriched molecular functions of the corresponding genes. The complete sequence of P0DTC4 in FASTA format was processed in 10 databases relative to secondary and tertiary protein structure analyses and prediction of optimal vaccine epitopes. Three more databases were accessed for the retrieval and the molecular functional characterization of the P0DTC4 human interactors. The immunoinformatics analysis resulted in the identification of 4 discontinuous B-cell epitopes along with 1 linear B-cell epitope and 11 T-cell epitopes which were found to be antigenic, immunogenic, nonallergen, nontoxin, and unable to induce autoimmunity thus fulfilling prerequisites for vaccine design. The functional enrichment analysis showed that the predicted host interactors of P0DTC4 target the cellular acetylation network. Two of the identified host-cell proteins - BRD2 and BRD4 - have been shown to be promising targets for antiviral therapy. Thus, our findings have implications for COVID-19 therapy and indicate that viroporin E could serve as a promising vaccine target against SARS-CoV-2. Validation experiments are required to complement these in silico results.

Investigation and Functional Enrichment Analysis of the Human Host Interaction Network with Common Gram-Negative Respiratory Pathogens Predicts Possible Association with Lung Adenocarcinoma.

Haemophilus influenzae (Hi), Moraxella catarrhalis (MorCa) and Pseudomonas aeruginosa (Psa) are three of the most common gram-negative bacteria responsible for human respiratory diseases. In this study, we aimed to identify, using the functional enrichment analysis (FEA), the human gene interaction network with the aforementioned bacteria in order to elucidate the full spectrum of induced pathogenicity. The Human Pathogen Interaction Database (HPIDB 3.0) was used to identify the human proteins that interact with the three pathogens. FEA was performed via the ToppFun tool of the ToppGene Suite and the GeneCodis database so as to identify enriched gene ontologies (GO) of biological processes (BP), cellular components (CC) and diseases. In total, 11 human proteins were found to interact with the bacterial pathogens. FEA of BP GOs revealed associations with mitochondrial membrane permeability relative to apoptotic pathways. FEA of CC GOs revealed associations with focal adhesion, cell junctions and exosomes. The most significantly enriched annotations in diseases and pathways were lung adenocarcinoma and cell cycle, respectively. Our results suggest that the Hi, MorCa and Psa pathogens could be related to the pathogenesis and/or progression of lung adenocarcinoma via the targeting of the epithelial cellular junctions and the subsequent deregulation of the cell adhesion and apoptotic pathways. These hypotheses should be experimentally validated.