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 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.

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.

Knowledge, Attitudes, and Practices of Primary Care Physicians towards COVID-19 in Greece: A Cross-Sectional Study.

The aim of this study was to investigate the knowledge, attitudes, and practices of primary care physicians and residents towards the COVID-19 pandemic in Greece. A cross-sectional questionnaire-based study was conducted in Greece during March 2021. The population frame for the study was a list of currently practicing primary care physicians and residents who were registered within one of the main associations of general/family medicine in Greece. Hierarchical multiple logistic regression analysis was performed for practices at higher levels (vs. lower) in relation to knowledge, attitudes, and general characteristics of participants. Overall, 194 participants completed the survey (e-response rate: 38.4%). In total, 94% of participants were familiar with official recommendations regarding SARS-CoV-2, and 88.7% were vaccinated against SARS-CoV-2 or promptly intended to be. Physicians working in the private sector had a higher average practices score when compared to physicians working in the public sector (87.6 vs. 81.9, p < 0.05). Higher levels of attitudes predicted greater odds for higher levels of practices (odds ratio = 4.18, p < 0.05). Despite the relatively high COVID-19 vaccination rate of physicians, several participants were unvaccinated due to a then unscheduled first dose appointment. Attitudes were the only determinant for more proper practices towards the prevention of COVID-19.

Self-reported risk of obstructive sleep apnea syndrome, and awareness about it in the community of 4 insular complexes comprising 41 Greek Islands.

Obstructive Sleep Apnea Syndrome (OSAS) is a chronic disease that significantly increases morbidity and mortality of the affected population. There is lack of data concerning the OSAS prevalence in the insular part of Greece. The purpose of this study was to investigate the self-reported prevalence of OSAS in 4 Greek insular complexes comprising 41 islands, and to assess the awareness of the population regarding OSAS and its diagnosis. Our study comprised 700 participants from 41 islands of the Ionian, Cyclades, Dodecanese and Northeast Aegean island complexes that were studied by means of questionnaires via a telephone randomized survey (responsiveness rate of 25.74%). Participants were assessed by the Berlin Questionnaire (BQ) for evaluation of OSA risk, by the Epworth Sleepiness Scale (ESS) for evaluation of excessive daytime sleepiness, and by 3 questions regarding the knowledge and diagnosis of OSAS. The percentage of participants at high risk according to BQ was 27.29% and the percentage of people who were at high risk according to ESS was 15.43%. A percentage of 6.29% of the population was at high risk for OSAS (high risk both in BQ and ESS). A high percentage of 73.43%, were aware of OSAS as a syndrome however a significantly less percentage (28.00%) was aware of how a diagnosis of OSAS is established. The community prevalence of OSAS in Greek islands in combination with the low-level awareness of the OSAS diagnostic methods highlights the need for development of health promotion programs aiming at increasing the detection of patients at risk while increasing the awareness of OSAS.

Smoking Patterns and Anxiety Factors Among Women Expressing Perinatal Depression.

Background: Relationships among perinatal depression occurring a number of weeks before and after childbirth and smoking have been identified. Depression may lead to the inability to abstain from smoking during pregnancy. Objectives: This study aims to determine factors affecting smoking during pregnancy revealing potential relationships between depression and smoking patterns during and after pregnancy. Methods: A total of 206 mothers participated in the study. Data were collected through self-reporting as respondents were asked to answer questionnaires during the 12th week of pregnancy, during the 30th week of pregnancy, after childbirth, and during the period after pregnancy. Relationships between smoking behavior, sociodemographic variables, and feelings of perinatal depression were examined using chi-square test and binary logistic regression analysis. A follow-up investigation has been conducted after 2 years revealing the percentage of women returning to their smoking habits. Results: Smokers before (B = 0.568; p = 0.026) and during pregnancy (B = 1.238; p = 0.009) were more likely to express depression before childbirth. Average daily cigarette consumption before (B = 1.110; p = 0.001) and during pregnancy (B = 1.167; p = 0.002) was associated with depression during pregnancy. Women who smoked during pregnancy reported significantly more depressive symptoms after pregnancy (B = 1.757; p = 0.005) compared with nonsmokers and smokers who abstained during pregnancy. Average daily cigarette consumption during pregnancy (B = 1.402; p = 0.002) affects the expression of depression after pregnancy. Women who smoked before pregnancy (B = 0.568; p = 0.025) and their average daily cigarette consumption before pregnancy (B = 1.465; p = 0.025) were highly associated with the inability to abstain from smoking during pregnancy. However, the knowledge of risks of maternal smoking during pregnancy (B = -1.110; p = 0.001) and medical consult on abstaining (B = -1.238; p = 0.009) reinforced the maternal attempt to quit smoking. The follow-up investigation revealed an elevated amount of women returning to previous smoking patterns. Discussion: Perinatal depression is associated with smoking patterns during pregnancy. Assessment of depression and smoking is needed throughout perinatal period to support the health of women.

Cross Sectional Study of the Community Self-Reported Risk of Obstructive Sleep Apnoea (OSA) and Awareness in Thessaly, Greece.

The purpose of this study was to investigate the self-reported risk of obstructive sleep apnea syndrome (OSAS) in the municipality of Thessaly, Greece, and the level of awareness of both the disease and its diagnosis. Inhabitants of Thessaly (254 total; 84 men and 170 women) were studied by means of questionnaires via a telephone-randomized survey. This comprised: (a) the Berlin questionnaire for evaluation of OSAS risk; (b) the evaluation of daytime sleepiness by the Epworth Sleepiness Scale; and (c) demographic and anthropometric data. The percentage of participants at high risk for OSA was 26.77%, and the percentage of people who were at high risk of excessive daytime sleepiness was 10.63%. High risk for OSAS was found to be 3.94%. No significant differences were found between high- and low-risk OSAS participants associated with age, smoking and severity of smoking. Regarding the knowledge of the community about OSAS, the majority of the sample was aware of the entity (64.17%), while fewer had knowledge about the diagnosis (18.50%) and polysomnography (24.80%). The high risk of OSA prevalence and the low awareness of the diagnosis of OSA highlights the need for the development of health promotion programs aiming at increasing the disease awareness in the general population in order to address OSA more effectively.

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.

Association between Interleukin-6 and vitamin D serum levels in patients with obstructive sleep apnea syndrome and impact of long-term continuous positive airway pressure therapy on biomarker levels.

OBJECTIVE: Hypoxia induces interleukin-6 (IL-6) production in obstructive sleep apnea syndrome (OSAS). Low serum 25 hydroxyvitamin D (25(OH)D) levels have been linked to OSAS susceptibility. Serum 25(OH)D levels have been negatively correlated with serum IL-6 levels in patients with chronic inflammation. No data exist to assess whether there is a correlation between 25(OH)D and IL-6 serum levels in OSAS, while the impact of continuous positive airway pressure (CPAP) therapy on IL-6 or 25(OH)D levels needs further investigation. We aimed to compare the serum 25(OH)D and IL-6 levels between OSAS patients and controls, examine a possible correlation between 25(OH)D and IL-6 levels and the changes of their concentrations after twelve months of CPAP therapy in OSAS patients. METHODS: 15 newly-diagnosed OSAS patients and 15 non-apneic controls were recruited. Serum IL-6 and 25(OH)D levels were measured in the study population at baseline and twelve months after CPAP initiation in OSAS patients. RESULTS: IL-6 levels were elevated in OSAS patients than controls and were positively and negatively correlated with body mass index (BMI) and minimum oxyhemoglobin saturation (minSpO2), respectively. Diabetes mellitus, BMI and minSpO2 independently predicted IL-6 levels. No difference was found in 25(OH)D levels between groups. No correlation between IL-6 and 25(OH)D levels was detected. Effective CPAP therapy did not impact IL-6 or 25(OH)D levels after one year in OSAS patients. CONCLUSIONS: No correlation between IL-6 and 25(OH)D levels was found. IL-6 levels were significantly elevated in OSAS patients than the controls and positively correlated with BMI, diabetes mellitus, and nocturnal hypoxemia.

HΜGB1/sRAGE levels differ significantly between transudates and exudates.

High mobility group box 1(HMGB1) protein operates as an alarmin with multiple roles in immunity and cell homeostasis. It is highly expressed in epithelial barrier sites and acts via the binding to the receptor for advanced glycation end products (RAGE). Production of HMGB1 and soluble RAGE (sRAGE), a decoy receptor for HMGB1, has been implicated in several pulmonary diseases, but both have been scarcely investigated in pleural diseases. The aim of this study was to determine the levels of HMGB1 and sRAGE in transudative, malignant and parapneumonic pleural effusions (PEs) and to investigate the effect of low and high HMGB1 pleural fluid levels on MeT-5A cell adhesion, migration and spheroid formation, in each group. HMGB1 and sRAGE levels were significantly lower and higher in transudative PEs compared to malignant and parapneumonic PEs, respectively. Patients above 65 years of age had significantly lower HMGB1 and higher sRAGE levels compared to patients below 65 years old. Furthermore, incubation of MeT-5A cells with malignant or parapneumonic PEs bearing low or high levels of HMGB1 yielded significant differential effects on MeT-5A cell adhesion, migration and spheroid formation. In all types of effusions, high HMGB1 levels correlated with more adherence compared to low HMGB1 levels. In transudative and malignant PEs high HMGB1 levels correlated with decreased migration of MeT-5A cells while in parapneumonic ones the effect was the opposite. Only samples from parapneumonic PEs high in HMGB1 achieved uniform spheroid formation. These results reveal a clinical context-dependent effect of the HMGB1/sRAGE axis in PEs.

Serum vitamin D levels in patients with obstructive sleep apnea syndrome and level changes after continuous positive airway pressure therapy.

PURPOSE: Patients with obstructive sleep apnea syndrome (OSAS) have been found to exhibit lower serum vitamin D levels, even when the control groups are matched for confounding conditions. However, contradictory studies are also present. This study aimed to compare serum 25-hydroxyvitamin D (25(OH)D) levels between adult patients with OSAS and non-apneic controls and to evaluate the changes in 25(OH)D levels after 3 and 12 months of continuous positive airway pressure (CPAP) therapy. METHODS: The study was comprised of 30 patients with OSAS and 30 controls. Serum 25(OH)D levels were determined at baseline and after 3 and 12 months of CPAP therapy in all patients with OSAS. For analysis, patients with OSAS were divided into subgroups by adherence, with adherence defined as CPAP usage for > 4 h per night on at least 70% of nights. RESULTS: The 25(OH)D levels were not significantly different between OSAS and control groups at baseline. 25(OH)D levels did not change after 3 and 12 months of CPAP therapy. Patients who were CPAP-adherent showed less reduction in 25(OH)D levels compared with non-adherent ones (21.18 ± 9.3 vs. 12.13 ± 3.8 ng/mL, p = 0.022) after 1 year. The 25(OH)D levels were significantly correlated with higher daily CPAP usage at 3 and 12 months. Mean daily CPAP usage was a significant predictor of serum 25(OH)D levels at 12 months. CONCLUSIONS: Patients with OSAS who demonstrated good CPAP adherence showed significantly higher 25(OH)D levels after 1 year compared with those not adequately using CPAP. Long-term good CPAP adherence and highly daily CPAP usage positively affected 25(OH)D levels in patients with OSAS.

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.

The Drosophila septate junctions beyond barrier function: Review of the literature, prediction of human orthologs of the SJ-related proteins and identification of protein domain families.

The involvement of Septate Junctions (SJs) in critical cellular functions that extend beyond their role as diffusion barriers in the epithelia and the nervous system has made the fruit fly an ideal model for the study of human diseases associated with impaired Tight Junction (TJ) function. In this study, we summarized current knowledge of the Drosophila melanogaster SJ-related proteins, focusing on their unconventional functions. Additionally, we sought to identify human orthologs of the corresponding genes as well as protein domain families. The systematic literature search was performed in PubMed and Scopus databases using relevant key terms. Orthologs were predicted using the DIOPT tool and aligned protein regions were determined from the Pfam database. 3-D models of the smooth SJ proteins were built on the Phyre2 and DMPFold protein structure prediction servers. A total of 30 proteins were identified as relatives to the SJ cellular structure. Key roles of these proteins, mainly in the regulation of morphogenetic events and cellular signalling, were highlighted. The investigation of protein domain families revealed that the SJ-related proteins contain conserved domains that are required not only for cell-cell interactions and cell polarity but also for cellular signalling and immunity. DIOPT analysis of orthologs identified novel human genes as putative functional homologs of the fruit fly SJ genes. A gap in our knowledge was identified regarding the domains that occur in the proteins encoded by eight SJ-associated genes. Future investigation of these domains is needed to provide functional information.

Pleural effusion osmolality correlation with pH and glucose level of pleural fluid and its effects on the pleural membrane permeability.

BACKGROUND AND AIM: Pleural effusions (PE) are a common clinical entity resulting from pathologies that affect the pleural space such as congestive heart failure, malignancy and pneumonia. The osmolality of the pleural fluid has never been studied as well as the effects of its changes on the pleural membrane. The purpose of this study was to identify the osmolality levels of PEs of different etiologies and to assess the potential effects of osmolality imbalance on the pleural permeability. MATERIALS AND METHODS: We measured the osmolality of the PEs of 64 consecutive patients (6 with transudative, 11 with parapneumonic and 47 with malignant pleural effusions) that were hospitalized in the University Hospital of Larissa. Subsequently, we selected clinically relevant hyper- and hypo- osmolality levels and performed assessment of the permeability of sheep parietal pleura by means of Ussing chamber experiments. RESULTS: The mean pleural fluid osmolality was 291.7 ± 24.89 mOms/Kg (95 % CI: 285.4-297.9), and it varied among the three groups of PEs (p = 0.05). Transformed osmolality values were associated with pH and glucose levels in the PEs. After exposure of the sheep parietal pleura to 240 mOsm/kg (hyposmolar) the transmesothelial resistance (RTM) significantly increased (p < 0.05) while at 340 mOsm/kg (hyperosmolar) the RTM was not significantly altered. CONCLUSIONS: PEs osmolality differs depending on the underlying pathology and is linked to PE pH and glucose. Hypo-osmotic PEs can lead to decreased pleural permeability. These results warrant further study of the PEs osmolality levels on the function of the pleural mesothelial cells.

Cell and extracellular matrix interaction models in benign mesothelial and malignant pleural mesothelioma cells in 2D and 3D in-vitro.

Malignant pleural mesothelioma (MPM) is an aggressive tumour that grows in the pleural cavity. MPM spheroids released in the pleural fluid can form new tumour foci. Cell-cell, cell-extracellular matrix (ECM) interactions in 2D and 3D impact malignant cell behaviour during cell adhesion, migration, proliferation and epithelial-mesenchymal transition (EMT). In this study, epithelioid, biphasic and sarcomatoid MPM cell types as well as benign mesothelial cells were tested with regards to the above phenotypes. Fibronectin (FN) and homologous cell-derived extracellular matrix (hcd-ECM) treated substratum differentially affected the above phenotypes. 3D MPM spheroid invasion was higher in FN-collagen matrices in the epithelioid and biphasic cells, while 3D cell cultures of epithelioid and sarcomatoid MPM cells in FN-collagen showed a higher contractility compared to hcd-ECM-collagen. Cell aggregates demonstrated invasive behaviour in hcd-ECM matrices alone. Our results suggest that ECM and the dimensionality affect malignant cell behaviour during cell culture studies.

25-hydroxyvitamin D levels in patients with obstructive sleep apnea and continuous positive airway pressure treatment: a brief review.

The aim of the present study is to summarize the information available, to time, regarding the relationship between obstructive sleep apnea (OSA) and vitamin-D (vD) levels. Moreover, the association between vD deficiency and OSA severity will also be examined. At the end of the present study the possible advantageous effect of CPAP on vD-levels will be summarized. Extensive literature search was conducted in PubMed, Scopus, The Cochrane Library and Embase database. 13 articles were found concerning OSA and vD, of which 2 articles included treatment with a CPAP. Patients with OSA exhibit low levels of vD in the blood serum, and women present an even lower mean value than men. Lack of VD in blood serum seems to be related to the severity of the OSA syndrome, and to the short duration of sleep. OSA patients with concurrent metabolic syndrome exhibit lower serum vD-levels, as compared with those without metabolic syndrome. Long-term continuous positive airway pressure treatment (CPAP) treatment can increase vD-levels in male OSA patients while no change is observed in women. OSA patients demonstrate lower levels of vD in multiple studies. The severity of the OSA may be associated with vD-levels and deficiency, however more studies are needed to assess that relationship due to contradictions in current bibliography. CPAP can increase vD-levels in male patients. The relation between vD and OSA and/or CPAP is important but recent; therefore further research is needed about the exact relationship to be clarified. Also, the effect of gender hormones on vD regulation in OSA patients should be further investigated.

Interactome networks between the human respiratory syncytial virus (HRSV), the human metapneumovirus (ΗMPV), and their host: In silico investigation and comparative functional enrichment analysis.

BACKGROUND AND OBJECTIVES: Human respiratory syncytial virus (HRSV) and human metapneumovirus (HMPV) are leading causes of upper and lower respiratory tract infections in non-immunocompetent subjects, yet the mechanisms by which they induce their pathogenicity differ significantly and remain elusive. In this study we aimed at identifying the gene interaction networks between the HRSV, HMPV respiratory pathogens and their host along with the different cell-signaling pathways associated with the above interactomes. MATERIALS AND METHODS: The Viruses STRING database (http://viruses.string-db.org/) was used for the identification of the host-viruses interaction networks. The two lists of the predicted functional partners were entered in the FunRich tool (http://www.funrich.org) for the construction of the Venn diagram and the comparative Funcional Enrichment Analysis (FEA) with respect to biological pathways. The sets of the common and unique human genes identified in the two networks were also analyzed. The computational predictions regarding the shared human genes in the host-HRSV and the host-HMPV interactomes were further evaluated via the analysis of the GSE111732 dataset. miRNA transcriptomics data were mapped to gene targets using the miRNomics pipeline of the GeneTrail2 database (https://genetrail2.bioinf.uni-sb.de/). RESULTS: Eleven out of twenty predicted human genes were common in the two interactomes (TLR4, SOCS3, SFXN1, AKT1, SFXN3, LY96, SFXN2, SOCS7, CISH, SOCS6, SOCS1). FEA of these common genes identified the kit receptor and the GH receptor signaling pathways as the most significantly enriched annotations. The remaining nine genes of the host-HRSV and the host-HMPV interaction networks were the IFIH1, DDX58, NCL, IRF3, STAT2, HSPA4, CD209, KLF6, CHKA and the MYD88, SOCS4, SOCS2, SOCS5 AKT2, AKT3, SFXN4, SFXN5 and TLR3 respectively. Distinct cell-signaling pathways were enriched per interactome. The comparative FEA highlighted the association of the host-HRSV functional partners with the negative regulation of RIG-I/MDA5 signaling. The analysis with respect to miRNAs mapping to gene targets of the GSE111732 dataset indicated that nine out of the eleven common host genes are either enriched or depleted in the sample sets (HRSV or HMPV infected) as compared with the reference set (non-infected), although with no significant scores. CONCLUSIONS: We have identified both shared and unique host genes as members of the HRSV and HMPV interaction networks. The disparate human genes likely contribute to distinct responses in airway epithelial cells.

Alzheimer's Disease in Patients with Obstructive Sleep Apnea Syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is a disorder with high prevalence among adults and is an independent risk factor for various diseases, especially those affecting the central nervous system (CNS). Continuous positive airway pressure (CPAP) is usually the optimal choice of treatment for OSAS. Alzheimer's disease (AD) is a neurodegenerative disease affecting a large proportion of the elderly population. The purpose of this study was to collect information concerning the two pathological entities and investigate the effectiveness of CPAP in the treatment of AD. MATERIALS AND METHODS: In this review, Twenty articles were found concerning OSAS and AD, of which one article was about treatment with donepezil and seven articles considered treatment with CPAP. RESULTS: Serious OSAS and short sleep duration are associated with a high risk of developing dementia. Respiratory distress during sleep is associated with developing mild cognitive impairment at younger ages. The cerebrovascular damage of AD patients is correlated with the severity of OSAS. Lower cerebrospinal fluid levels are associated with memory disturbances and oxygen saturation parameters in patients with OSAS-AD. Continuous use of CPAP is related to the delayed onset of cognitive impairment and is suggested as an effective method of protecting cognitive function, depression, sleep quality and architecture, and daytime sleepiness in AD patients with good compliance. Treatment of CPAP patients with OSAS-AD is suggested as an effective method of protecting cognitive function. CONCLUSION: Clinicians dealing with AD patients should consider CPAP treatment when OSAS coexists.