Publications by authors named "Sotirios G Zarogiannis"

68 Publications

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

Am J Physiol Lung Cell Mol Physiol 2021 Apr 6. Epub 2021 Apr 6.

Department of Physiology, University Of Thessaly, Greece.

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, non-allergen, non-toxin 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 anti-viral 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.
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http://dx.doi.org/10.1152/ajplung.00443.2020DOI Listing
April 2021

Outside-in induction of the IFITM3 trafficking system by infections, including SARS-CoV-2, in the pathobiology of Alzheimer's disease.

Brain Behav Immun Health 2021 Jul 26;14:100243. Epub 2021 Mar 26.

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, Larissa, 41500, Greece.

Background: IFITM3 is a viral restriction protein that enables sequestration of viral particles and subsequent trafficking to lysosomes. Recently, IFITM3 upregulation was found to induce gamma - secretase activity and the production of amyloid beta. The purpose of this study was to determine whether dysregulation of IFITM3-dependent pathways was present in neurons and peripheral immune cells donated by AD patients. As a secondary aim, we sought to determine whether these perturbations could be induced by viruses, including SARS-CoV-2.

Methods: Gene set enrichment analyses (GSEA) previously performed on publicly available transcriptomic data from tissues donated by AD patients were screened for enriched pathways containing IFITM3. Subsequently, signature containing IFITM3, derived from entorhinal cortex (EC) neurons containing neurofibrillary tangles (NFT) was screened for overlap with curated, publicly available, viral infection-induced gene signatures (including SARS-CoV-2).

Results: GSEA determined that IFITM3 gene networks are significantly enriched both in CNS sites (entorhinal and hippocampal cortices) and in peripheral blood mononuclear cells (PBMCs) donated by AD patients. Overlap screening revealed that IFITM3 signatures are induced by several viruses, including SARS-CoV, MERS-CoV, SARS-CoV-2 and HIV-1 (adjusted p-value <0.001; Enrichr Database).

Discussion: A data-driven analysis of AD tissues revealed IFITM3 gene signatures both in the CNS and in peripheral immune cells. GSEA revealed that an IFITM3 derived gene signature extracted from EC/NFT neurons overlapped with those extracted from publicly available viral infection datasets, including SARS-CoV-2. Our results are in line with currently emerging evidence on IFITM3's role in AD, and SARS-CoV-2's potential contribution in the setting of an expanded antimicrobial protection hypothesis.
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http://dx.doi.org/10.1016/j.bbih.2021.100243DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997139PMC
July 2021

The role of nitric oxide in pleural disease.

Respir Med 2021 Apr 23;179:106350. Epub 2021 Feb 23.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.

Nitric oxide (NO) regulates various physiological and pathophysiological functions in the lungs. However, there is much less information about the effects of NO in the pleura. The present review aimed to explore the available evidence regarding the role of NO in pleural disease. NO, has a double-edged role in the pleural cavity. It is an essential signaling molecule mediating various physiological cell functions such as lymphatic drainage of the serous cavities, the immune response to intracellular multiplication of pathogens, and downregulation of neutrophil migration, but also induces genocytotoxic and mutagenic effects when present in excess. NO is implicated in the pathogenesis of asbestos-related or exudative pleural disease and mesothelioma. From a clinical point of view, the fraction of exhaled NO has been suggested as a potential non-invasive tool for the diagnosis of benign asbestos-related disorders. Under experimental conditions, NO-mimetics were found to attenuate hypoxia-induced therapy resistance in mesothelioma. Similarly, hybrid agents consisting of an NO donor coupled with a parent anti-inflammatory drug showed an enhancement of the anti-inflammatory activity of anti-inflammatory drugs. However, given the paucity of research work performed over the last years in this area, further research should be undertaken to establish reliable conclusions with respect to the feasibility of determining or targeting the NO signaling pathway for pleural disease diagnosis and therapeutic management.
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http://dx.doi.org/10.1016/j.rmed.2021.106350DOI Listing
April 2021

HΜGB1/sRAGE levels differ significantly between transudates and exudates.

Cytokine 2021 May 16;141:155469. Epub 2021 Feb 16.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece; Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece. Electronic address:

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.
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http://dx.doi.org/10.1016/j.cyto.2021.155469DOI Listing
May 2021

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

Clin Exp Pharmacol Physiol 2021 Apr 17;48(4):543-552. Epub 2020 Dec 17.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.

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.
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http://dx.doi.org/10.1111/1440-1681.13446DOI Listing
April 2021

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

Respir Physiol Neurobiol 2021 Mar 12;285:103581. Epub 2020 Nov 12.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece; Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece. Electronic address:

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 (R) significantly increased (p < 0.05) while at 340 mOsm/kg (hyperosmolar) the R 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.
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http://dx.doi.org/10.1016/j.resp.2020.103581DOI Listing
March 2021

Double hit viral parasitism, polymicrobial CNS residency and perturbed proteostasis in Alzheimer's disease: A data driven, in silico analysis of gene expression data.

Mol Immunol 2020 11 21;127:124-135. Epub 2020 Sep 21.

Department of Neurology, Athens Naval Hospital, P.C. 115 21, Athens, Greece.

The aim of this study was to determine the interaction of peripheral immunity vs. the CNS in the setting of AD pathogenesis at the transcriptomic level in a data driven manner. For this purpose, publicly available gene expression data from the GEO Datasets repository. We performed differential gene expression and functional enrichment analyses were performed on the five retrieved studies: (a) three hippocampal cortex (HC) studies (b) one study of peripheral blood mononuclear cells (PBMC) and (c) one involving neurofibrillary tangle - containing neurons of the entorhinal cortex (NFT EC). Subsequently, BLAST was used to determine protein conservation between human proteins vs. microbial, whereas putative protein / oligopeptide antigenicity were determined via RANKPep. Gene ontology and pathway analyses revealed significantly enriched viral parasitism pathways in both PBMC and NFT - EC datasets, mediated by ribosomal protein families and epigenetic regulators. Among these, a salient viral pathway referred to Influenza A infection. NFT - EC annotations included leukocyte chemotaxis and immune response pathways. All datasets were significantly enriched for infectious pathways, as well as pathways involved in impaired proteostasis and non - phagocytic cell phagosomal cascades. In conclusion, our in silico analysis outlined an ad hoc model of AD pathophysiology in which double hit (PBMC and NFT-EC) viral parasitism is mediated by eukaryotic translational hijacking, and may be further implicated by impaired immune responses. Overall, our results overlap with the antimicrobial protection hypothesis of AD pathogenesis and support the notion of a pathogen - driven etiology.
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http://dx.doi.org/10.1016/j.molimm.2020.08.021DOI Listing
November 2020

Alanyl-Glutamine Restores Tight Junction Organization after Disruption by a Conventional Peritoneal Dialysis Fluid.

Biomolecules 2020 08 13;10(8). Epub 2020 Aug 13.

Division of Pediatric Nephrology, Center for Pediatric and Adolescent Medicine, University Hospital Heidelberg, 69120 Heidelberg, Germany.

Understanding and targeting the molecular basis of peritoneal solute and protein transport is essential to improve peritoneal dialysis (PD) efficacy and patient outcome. Supplementation of PD fluids (PDF) with alanyl-glutamine (AlaGln) increased small solute transport and reduced peritoneal protein loss in a recent clinical trial. Transepithelial resistance and 10 kDa and 70 kDa dextran transport were measured in primary human endothelial cells (HUVEC) exposed to conventional acidic, glucose degradation products (GDP) containing PDF (CPDF) and to low GDP containing PDF (LPDF) with and without AlaGln. Zonula occludens-1 (ZO-1) and claudin-5 were quantified by Western blot and immunofluorescence and in mice exposed to saline and CPDF for 7 weeks by digital imaging analyses. Spatial clustering of ZO-1 molecules was assessed by single molecule localization microscopy. AlaGln increased transepithelial resistance, and in CPDF exposed HUVEC decreased dextran transport rates and preserved claudin-5 and ZO-1 abundance. Endothelial clustering of membrane bound ZO-1 was higher in CPDF supplemented with AlaGln. In mice, arteriolar endothelial claudin-5 was reduced in CPDF, but restored with AlaGln, while mesothelial claudin-5 abundance was unchanged. AlaGln supplementation seals the peritoneal endothelial barrier, and when supplemented to conventional PD fluid increases claudin-5 and ZO-1 abundance and clustering of ZO-1 in the endothelial cell membrane.
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http://dx.doi.org/10.3390/biom10081178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464725PMC
August 2020

Epigenetic regulation of apoptosis via the PARK7 interactome in peripheral blood mononuclear cells donated by tuberculosis patients vs. healthy controls and the response to treatment: A systems biology approach.

Tuberculosis (Edinb) 2020 07 31;123:101938. Epub 2020 May 31.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Mezourlo, 41110, Larisa, Greece.

Aims: The aims of our study were to determine for the first time differentially expressed genes (DEGs) and enriched molecular pathways involving the PARK7 interactome in PBMCs donated from tuberculosis patients.

Methods: Data on a previously reconstructed PARK7 interactome (Vavougios et al., 2017) from datasets GDS4966 (Case-Control) and GDS4781 (Treatment Series) were retrieved from the Gene Expression Omnibus (GEO) repository. Gene Enrichment analysis was performed via the STRING algorithm and the GeneTrail2 software.

Results: 17 and 22 PARK7 interactores were determined as DEGs in the active TB vs HD and Treatment Series subset analyses, correspondingly, associated with significantly enriched pathways (FDR <0.05) involving p53 and PTEN mediated, stress responsive apoptosis regulation pathways. The treatment subset was characterized by the emergence of an additional layer of transcriptional regulation mediated by polycomb proteins among others, as well as TLR-mediated and cytokine survival signaling. Finally, the enrichment of a Parkinson's disease signature including PARK7 interactors was determined by its differential regulation both in the exploratory analyses (FDR = 0.024), as well as the confirmatory analyses (FDR = 1.81e).

Conclusions: Our in silico analysis revealed for the first time the role of PARK7's interactome in regulating the epigenetics of the PBMC lifecycle and Mtb symbiosis.
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http://dx.doi.org/10.1016/j.tube.2020.101938DOI Listing
July 2020

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.

Acta Physiol (Oxf) 2021 01 5;231(1):e13527. Epub 2020 Aug 5.

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, Larissa, Greece.

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.
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http://dx.doi.org/10.1111/apha.13527DOI Listing
January 2021

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

Microb Pathog 2020 Apr 25;141:104000. Epub 2020 Jan 25.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece; Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41334, Larissa, Greece. Electronic address:

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.
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http://dx.doi.org/10.1016/j.micpath.2020.104000DOI Listing
April 2020

Encapsulating Peritoneal Sclerosis: Pathophysiology and Current Treatment Options.

Int J Mol Sci 2019 Nov 16;20(22). Epub 2019 Nov 16.

Division of Nephrology and Hypertension, 1st Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece.

Encapsulating peritoneal sclerosis (EPS) is a life-threatening complication of long-term peritoneal dialysis (PD), which may even occur after patients have switched to hemodialysis (HD) or undergone kidney transplantation. The incidence of EPS varies across the globe and increases with PD vintage. Causative factors are the chronic exposure to bioincompatible PD solutions, which cause long-term modifications of the peritoneum, a high peritoneal transporter status involving high glucose concentrations, peritonitis episodes, and smoldering peritoneal inflammation. Additional potential causes are predisposing genetic factors and some medications. Clinical symptoms comprise signs of intestinal obstruction and a high peritoneal transporter status with incipient ultrafiltration failure. In radiological, macro-, and microscopic studies, a massively fibrotic and calcified peritoneum enclosed the intestine and parietal wall in such cases. Empirical treatments commonly used are corticosteroids and tamoxifen, which has fibrinolytic properties. Immunosuppressants like azathioprine, mycophenolate mofetil, or mTOR inhibitors may also help with reducing inflammation, fibrin deposition, and collagen synthesis and maturation. In animal studies, N-acetylcysteine, colchicine, rosiglitazone, thalidomide, and renin-angiotensin system (RAS) inhibitors yielded promising results. Surgical treatment has mainly been performed in severe cases of intestinal obstruction, with varying results. Mortality rates are still 25-55% in adults and about 14% in children. To reduce the incidence of EPS and improve the outcome of this devastating complication of chronic PD, vigorous consideration of the risk factors, early diagnosis, and timely discontinuation of PD and therapeutic interventions are mandatory, even though these are merely based on empirical evidence.
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http://dx.doi.org/10.3390/ijms20225765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6887950PMC
November 2019

The health impact of Saharan dust exposure.

Int J Occup Med Environ Health 2019 Nov 8;32(6):749-760. Epub 2019 Oct 8.

Hellenic Mediterranean University, Heraklion, Greece (Nursing Department).

Air pollution is a high priority global health concern. The health damaging effects of ambient particulate matter (PM), a component of air pollution, are extensively documented, with 1.4% of deaths worldwide resulting from exposure to PM. A growing body of evidence suggests that mineral dust, found in PM, may contribute to some of these deleterious health impacts. Approximately half of atmospheric mineral dust originates from the Sahara Desert. This systematic but concise review summarizes the findings from recent literature exploring the adverse health effects of Saharan dust particles worldwide. The authors have shown that 1) PM contributes to all-cause and cause-specific mortality and morbidity; 2) the PM arising from Saharan dust contributes to excess all-cause and cause-specific mortality and morbidity; and 3) larger particle sizes may be more harmful than smaller particle sizes. However, there remain many questions regarding their effects on vulnerable patient populations, underlying mechanisms of action, and regional variations in both environmental and health effects. This review highlights the urgent need for continued and deeper analyses of this emerging public health issue. Int J Occup Med Environ Health. 2019;32(6):749-60.
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http://dx.doi.org/10.13075/ijomeh.1896.01466DOI Listing
November 2019

In Vitro Characterization of Cisplatin and Pemetrexed Effects in Malignant Pleural Mesothelioma 3D Culture Phenotypes.

Cancers (Basel) 2019 Sep 27;11(10). Epub 2019 Sep 27.

Department of Physiology, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece.

Malignant pleural mesothelioma (MPM) is an aggressive cancer with poor prognosis. The main treatment for MPM is doublet chemotherapy with Cisplatin and Pemetrexed, while ongoing trials test the efficacy of pemetrexed monotherapy. However, there is lack of evidence regarding the effects of Cisplatin and Pemetrexed on MPM cell phenotypes, especially in three-dimensional (3D) cell cultures. In this study, we evaluated the effects Cisplatin and Pemetrexed on cell viability using homologous cell derived extracellular matrix (hECM) as substratum and subsequently in the following 3D cell culture phenotypes: tumor spheroid formation, tumor spheroid invasion, and collagen gel contraction. We used benign mesothelial MeT-5A cells as controls and the MPM cell lines M14K (epithelioid), MSTO (biphasic), and ZL34 (sarcomatoid). Cell viability of all cell lines was significantly decreased with all treatments. Mean tumor spheroid perimeter was reduced after treatment with Pemetrexed or the doublet therapy in all cell lines, while Cisplatin reduced the mean spheroid perimeter of MeT-5A and MSTO cells. Doublet treatment reduced the invasive capacity of spheroids of cell lines into collagenous matrices, while Cisplatin lowered the invasion of the MSTO and ZL34 cell lines, and Pemetrexed lowered the invasion of MeT-5A and ZL34 cell lines. Treatment with Pemetrexed or the combination significantly reduced the collagen gel contraction of all cell lines, while Cisplatin treatment affected only the MeT-5A and M14K cells. The results of the current study can be used as an in vitro 3D platform for testing novel drugs against MPM for ameliorating the effects of first line chemotherapeutics.
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http://dx.doi.org/10.3390/cancers11101446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6826727PMC
September 2019

Pleural Effusion IL-33/sST2 Levels and Effects of Low and High IL-33/sST2 Levels on Human Mesothelial Cell Adhesion and Migration.

Inflammation 2019 Dec;42(6):2072-2085

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500, Larissa, Greece.

Interleukin 33 (IL-33) is an alarmin with multiple roles in immunity and cell homeostasis, highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). Production of IL-33 and soluble ST2 (sST2), a decoy receptor for IL-33, 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 IL-33 and sST2 in transudative (TrPEs), malignant (MPEs), and parapneumonic (PPEs) pleural effusions (PEs) and investigate the effect of PE fluids from each group with low and high IL-33/sST2 levels on MeT-5A cell adhesion and migration. IL-33 and sST2 pleural fluid levels were similar among TrPEs, MPEs, and PPEs. However, a significant correlation was found between IL-33 and LDH and in sST2 levels with lymphocyte counts in TrPEs. Additionally, in MPEs the levels of IL-33 correlated with the levels of sST2 and with the red blood cell counts. Furthermore, incubation of MeT-5A cells with MPEs and PPEs bearing low or high levels of IL-33/sST2 yielded significant differential effects on MeT-5A cell adhesion and migration. In MPEs, high IL-33/sST2 levels led to increased adhesion and migration of MeT-5A cells, while in PPEs the effect was the opposite, while no effect in both cell phenotypes was determined for TrPEs. These results reveal a clinical context dependent effect of the IL-33/sST2 axis in PEs.
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http://dx.doi.org/10.1007/s10753-019-01070-6DOI Listing
December 2019

Risk Assessment for Self Reported Obstructive Sleep Apnea and Excessive Daytime Sleepiness in a Greek Nursing Staff Population.

Medicina (Kaunas) 2019 Aug 12;55(8). Epub 2019 Aug 12.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.

: The risk assessment of Obstructive Sleep Apnea (OSA) and Excessive Daytime Sleepiness (EDS) in specific occupational populations is important due to its association with morbidity. The aim of the present study was to identify the risk of OSA development and EDS in a Greek nursing staff population. : In this cross-sectional study a total of 444 nurses, 56 males (age = 42.91 ± 5.76 years/BMI = 27.17 ± 4.32) and 388 females (age = 41.41 ± 5.92 years/BMI = 25.08 ± 4.43) working in a Greek secondary and tertiary hospital participated during the period from 18 January 2015 to 10 February 2015. The participants completed the Berlin Questionnaire (BQ), concerning the risk for OSA and the Epworth Sleepiness Scale (ESS), concerning the EDS. The work and lifestyle habits of the participants were correlated with the results of the questionnaires. : According to the BQ results 20.5% ( = 91) of the nursing staff was at high risk for OSA. Increased daytime sleepiness affected 27.7% ( = 123) of the nurses according to ESS results. Nurses at risk for Obstructive Sleep Apnea Syndrome (OSAS), positive for both BQ and ESS, were 7.66% ( = 34). Out of the nurses that participated 77% ( = 342) were working in shifts status and had significant meal instability (breakfast < 0.0001, lunch < 0.0001, dinner = 0.0008). : The population at high risk for OSA and EDS in the nursing staff was found to be 20% and 28% respectively. High risk for OSAS was detected in 7.66% of the participants. The high risk for OSA and EDS was the same irrespective of working in shift status. In specific, nursing population age was an independent predictor for high risk for OSA and skipping lunch an independent predictor of daytime sleepiness.
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http://dx.doi.org/10.3390/medicina55080468DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723047PMC
August 2019

Mesothelioma Mortality Rates in Greece for the Period 2005-2015 Is Increased Compared to Previous Decades.

Medicina (Kaunas) 2019 Jul 30;55(8). Epub 2019 Jul 30.

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.

To present summary statistics regarding malignant mesothelioma (MM) mortality in Greece during the period 2005-2015 and compare it with previous decades, along with gender, age and geographical area analysis. : The Hellenic Statistical Authority provided the data, which included all deaths for the period 1983 to 2015 that mentioned MM as the death cause in the corresponding death certificate. MM mortality rates have been calculated with respect to gender, age, and geographical location in Greece. Furthermore, a comparison analysis was made among three eleven consecutive year periods, in order to assess potential changes in the mortality rates. : The MM mortality rate has significantly increased during the period 2005-2015 both in males and females compared to earlier decades. The maximum number of MM deaths has shifted to an older age group of 70-80 years during the 2005-2015 period as compared to that of 1983-2004 in both genders. Additionally, MM mortality rates have significantly increased in all geographical areas except for the Epirus Prefecture. : Our results demonstrate an increased MM mortality rate in Greece for the decade 2005-2015 as compared to the two previous decades. This increase is possibly due to the fact that the peak in asbestos production and use in Greece was in mid 1990s, while the asbestos ban came in effect in 2005. Based on these findings the MM epidemic in Greece has not yet peaked, therefore it is important to implement screening strategies for early MM detection.
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http://dx.doi.org/10.3390/medicina55080419DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724054PMC
July 2019

In-Depth Bioinformatic Study of the CLDN16 Gene and Protein: Prediction of Subcellular Localization to Mitochondria.

Medicina (Kaunas) 2019 Jul 26;55(8). Epub 2019 Jul 26.

Department of Physiology, Faculty of Medicine, University of Thessaly, Biopolis, 41500 Larissa, Greece.

The defects in the gene are a cause of primary hypomagnesemia (FHHNC), which is characterized by massive renal magnesium wasting, resulting in nephrocalcinosis and renal failure. The mutations occur throughout the gene's coding region and can impact on intracellular trafficking of the protein or its paracellular pore forming function. To gain more understanding about the mechanisms by which mutations can induce FHHNC, we performed an in-depth computational analysis of the CLDN16 gene and protein, focusing specifically on the prediction of the latter's subcellular localization. The complete nucleotide or amino acid sequence of CLDN16 in FASTA format was entered and processed in 14 databases. One CpG island was identified. Twenty five promoters/enhancers were predicted. The interactome was found to consist of 20 genes, mainly involved in kidney diseases. No signal peptide cleavage site was identified. A probability of export to mitochondria equal to 0.9740 and a cleavable mitochondrial localization signal in the N terminal of the CLDN16 protein were predicted. The secondary structure prediction was visualized. Νo phosphorylation sites were identified within the CLDN16 protein region by applying DISPHOS to the functional class of transport. The KnotProt database did not predict any knot or slipknot in the protein structure of CLDN16. Seven putative miRNA binding sites within the 3'-UTR region of CLDN16 were identified. This is the first study to identify mitochondria as a probable cytoplasmic compartment for CLDN16 localization, thus providing new insights into the protein's intracellular transport. The results relative to the interactome underline its role in renal pathophysiology and highlight the functional dependence of CLDNs-10, 14, 16, 19. The predictions pertaining to the miRNAs, promoters/enhancers and CpG islands of the gene indicate a strict regulation of its expression both transcriptionally and post-transcriptionally.
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http://dx.doi.org/10.3390/medicina55080409DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6723856PMC
July 2019

2-Deoxy-glucose Enhances the Effect of Cisplatin and Pemetrexed in Reducing Malignant Pleural Mesothelioma Cell Proliferation But Not Spheroid Growth.

Anticancer Res 2019 Jul;39(7):3809-3814

Department of Respiratory Medicine, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece

Background/aim: Malignant pleural mesothelioma (MPM) is a therapy-resistant neoplasm of the pleura. Standard chemotherapy consists of a combination of cisplatin (CPDD) and pemetrexed (PEM). The aim of this study was to assess whether inhibition of aerobic glycolysis by 2-deoxy-glucose (2DG) would enhance the effects of standard chemotherapy.

Materials And Methods: MeT-5A, M14K, MSTO and ZL34 cell lines were used. Cell viability with 2DG and cell proliferation and spheroid formation with CPDD+PEM alone and with 2-DG were tested.

Results: Viability with 2-DG was dose-dependent. Cell proliferation with CPDD+PEM on 2D surface was reduced in all cell types, 2-DG inclusion demonstrated a synergistic effect in MSTO and ZL34 cells. Spheroid growth in 3D with CPDD+PEM or CPDD+PEM+2-DG lowered spheroid growth in all cell types.

Conclusion: 2-DG synergizes with CPDD+PEM in lowering MPM cell proliferation in 2D to <20%. In 3D MPM spheroid growth 2-DG synergism with CPDD+PEM treatment is not maintained.
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http://dx.doi.org/10.21873/anticanres.13530DOI Listing
July 2019

In Silico Transcriptomic Analysis of Wound-Healing-Associated Genes in Malignant Pleural Mesothelioma.

Medicina (Kaunas) 2019 Jun 12;55(6). Epub 2019 Jun 12.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, 41500 Larissa, Greece.

Malignant pleural mesothelioma (MPM) is a devastating malignancy with poor prognosis. Reliable biomarkers for MPM diagnosis, monitoring, and prognosis are needed. The aim of this study was to identify genes associated with wound healing processes whose expression could serve as a prognostic factor in MPM patients. We used data mining techniques and transcriptomic analysis so as to assess the differential transcriptional expression of wound-healing-associated genes in MPM. Moreover, we investigated the potential prognostic value as well as the functional enrichments of gene ontologies relative to microRNAs (miRNAs) of the significantly differentially expressed wound-healing-related genes in MPM. Out of the 82 wound-healing-associated genes analyzed, 30 were found significantly deregulated in MPM. Kaplan-Meier analysis revealed that low gene expression could serve as a prognostic factor favoring survival of MPM patients. Finally, gene ontology annotation enrichment analysis pointed to the members of the hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members as important regulators of the deregulated wound healing genes. 30 wound-healing-related genes were significantly deregulated in MPM, which are potential targets of hsa-miR-143, hsa-miR-223, and the hsa-miR-29 miRNA family members. Out of those genes, ITGAV gene expression was a prognostic factor of overall survival in MPM. Our results highlight the role of impaired tissue repair in MPM development and should be further validated experimentally.
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http://dx.doi.org/10.3390/medicina55060267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6631992PMC
June 2019

Benign Pleural Mesothelial Cells Have Higher Osmotic Water Permeability than Malignant Pleural Mesothelioma Cells and Differentially Respond to Hyperosmolality.

Cell Physiol Biochem 2019 ;52(4):869-878

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece.

Background/aims: Cell volume regulation is a critical mechanism for cell homeostasis and depends on the osmotic water permeability (P) of the cell plasma membrane. The P of human mesothelial cells is unknown although they contribute to serosal fluid turnover.

Methods: In this study we measured the osmotic water permeability of benign human mesothelial cells (MeT-5A) and of epithelioid (M14K) and sarcomatoid (ZL34) malignant pleural mesothelioma (MPM) cells in response to acute hyperosmotic stress. We also assessed the changes in their P after preconditioning with 4% glucose for 24 hours. In both cases we also assessed the role of AQP1 inhibition (0.1 mM HgCl) on the P. Finally, we assessed corresponding changes in the AQP1 plasma membrane availability by immunofluorescence.

Results: We report that MeT-5A cells have a significantly higher P as compared to M14K and ZL34 MPM cells [4.85E-03±2.37E-03 cm/sec (n=17) versus 2.74E-03±0.74E-03 cm/sec (n=11) and 2.86E-03±0.11E-03 cm/sec (n=11)]. AQP1 inhibition significantly decreased the P in all cells lines (p<0.001 in all cases). High glucose preconditioning for 24 hours significantly increased MeT-5A P (p<0.001), did not influence M14K P (p=0.19) and significantly reduced ZL34 P (p=0.02). Comparing cell lines after high glucose preconditioning, MeT-5A P was significantly higher than that of M14K and ZL34 MPM cells and the AQP1 inhibition effect was significant in MeT-5A and M14K cells. These results were corroborated by AQP1 immunofluorescence.

Conclusion: We provide evidence for a differential regulation of P in benign and MPM cells that require further mechanistic investigation.
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http://dx.doi.org/10.33594/000000060DOI Listing
April 2019

Mechanisms of engineered nanoparticle induced neurotoxicity in Caenorhabditis elegans.

Environ Toxicol Pharmacol 2019 Apr 22;67:29-34. Epub 2019 Jan 22.

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, 41500, Greece. Electronic address:

The wide-spread implementation of nanoparticles poses a major health concern. Unique biokinetics allow them to transfer to neurons throughout the body and inflict neurotoxicity, which is challenging to evaluate solely in mammalian experimental models due to logistics, financial and ethical limitations. In recent years, the nematode Caenorhabditis elegans has emerged as a promising nanotoxicology experimental surrogate due to characteristics such as ease of culture, short life cycle and high number of progeny. Most importantly, this model organism has a well conserved and fully described nervous system rendering it ideal for use in neurotoxicity assessment of nanoparticles. In that context, this mini review aims to summarize the main mechanistic findings on nanoparticle related neurotoxicity in the setting of Caenorhabditis elegans screening. The injury pathway primarily involves changes in intestinal permeability and defecation frequency both of which facilitate translocation at the site of neurons, where toxicity formation is linked partly to oxidative stress and perturbed neurotransmission.
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http://dx.doi.org/10.1016/j.etap.2019.01.010DOI Listing
April 2019

Pleural effusions induced by human herpesviruses in the immunocompetent host.

Infect Dis (Lond) 2019 Mar 24;51(3):189-196. Epub 2019 Jan 24.

b Department of Physiology , Faculty of Medicine, University of Thessaly, BIOPOLIS , Larissa , Greece.

Methods: A computer-based search of the English literature for articles relative to Human Herpesviruses (HHVs) infection and pleural effusions (PEs) in the immunocompetent host was performed in PubMed and Scopus. The reference lists of the retrieved articles were also reviewed for relevant articles.

Results: A total of 20 articles satisfied the selection criteria and were included in the study. In the majority of the articles, PEs were reported as clinical complications of systemic HHV-induced infection. The frequency of HHVs within the reported cases was five for HHV-1/2, one for HHV-3, six for HHV-4, six for HHV-5 and one for HHV-6. One case involved HHV-4 and HHV-5 co-infection. No case of HHV-7 or HHV-8 related PE in the immunocompetent host was retrieved.

Conclusions: Pleural effusions in the immunocompetent host occur in severe viral infections and can be due to comorbidities (or septic complications) or due to the direct HHV pathogenicity although research relative to the susceptibility of pleural mesothelial cells to HHV infection is lacking. HHV pathogenicity needs to be studied further as it could explain undiagnosed PEs.
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http://dx.doi.org/10.1080/23744235.2018.1551620DOI Listing
March 2019

IL-33/ST2 Axis in Organ Fibrosis.

Front Immunol 2018 24;9:2432. Epub 2018 Oct 24.

Department of Respiratory Medicine, Faculty of Medicine, School of Health Sciences, University of Thessaly, BIOPOLIS, Larissa, Greece.

Interleukin 33 (IL-33) is highly expressed in barrier sites, acting via the suppression of tumorigenicity 2 receptor (ST2). IL-33/ST2 axis has long been known to play a pivotal role in immunity and cell homeostasis by promoting wound healing and tissue repair. However, it is also involved in the loss of balance between extensive inflammation and tissue regeneration lead to remodeling, the hallmark of fibrosis. The aim of the current review is to critically evaluate the available evidence regarding the role of the IL-33/ST2 axis in organ fibrosis. The role of the axis in tissue remodeling is better understood considering its crucial role reported in organ development and regeneration. Generally, the IL-33/ST2 signaling pathway has mainly anti-inflammatory/anti-proliferative effects; however, chronic tissue injury is responsible for pro-fibrogenetic responses. Regarding pulmonary fibrosis mature IL-33 enhances pro-fibrogenic type 2 cytokine production in an ST2- and macrophage-dependent manner, while full-length IL-33 is also implicated in the pulmonary fibrotic process in an ST2-independent, Th2-independent fashion. In liver fibrosis, evidence indicate that when acute and massive liver damage occurs, the release of IL-33 might act as an activator of tissue-protective mechanisms, while in cases of chronic injury IL-33 plays the role of a hepatic fibrotic factor. IL-33 signaling has also been involved in the pathogenesis of acute and chronic pancreatitis. Moreover, IL-33 could be used as an early marker for ulcer-associated activated fibroblasts and myofibroblast trans-differentiation; thus one cannot rule out its potential role in inflammatory bowel disease-associated fibrosis. Similarly, the upregulation of the IL-33/ST2 axismay contribute to tubular cell injury and fibrosis via epithelial to mesenchymal transition (EMT) of various cell types in the kidneys. Of note, IL-33 exerts a cardioprotective role via ST2 signaling, while soluble ST2 has been demonstrated as a marker of myocardial fibrosis. Finally, IL-33 is a crucial cytokine in skin pathology responsible for abnormal fibroblast proliferation, leukocyte infiltration and morphologic differentiation of human endothelial cells. Overall, emerging data support a novel contribution of the IL-33/ST2 pathway in tissue fibrosis and highlight the significant role of the Th2 pattern of immune response in the pathophysiology of organ fibrosis.
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http://dx.doi.org/10.3389/fimmu.2018.02432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6207585PMC
October 2019

The emerging epigenetics of PARK7 and its implication in neurodegenerative disease.

Neural Regen Res 2018 Sep;13(9):1542-1543

Department of Physiology, Faculty of Medicine, University of Thessaly, Larissa, Greece.

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http://dx.doi.org/10.4103/1673-5374.237117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6126139PMC
September 2018

Carbon Nanotubes and Other Engineered Nanoparticles Induced Pathophysiology on Mesothelial Cells and Mesothelial Membranes.

Front Physiol 2018 29;9:295. Epub 2018 Mar 29.

Department of Physiology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, Greece.

Nanoparticles have great potential for numerous applications due to their unique physicochemical properties. However, concerns have been raised that they may induce deleterious effects on biological systems. There is accumulating evidence that, like asbestos, inhaled nanomaterials of >5 μm and high aspect ratio (3:1), particularly rod-like carbon nanotubes, may inflict pleural disease including mesothelioma. Additionally, a recent set of case reports suggests that inhalation of polyacrylate/nanosilica could in part be associated with inflammation and fibrosis of the pleura of factory workers. However, the adverse outcomes of nanoparticle exposure to mesothelial tissues are still largely unexplored. In that context, the present review aims to provide an overview of the relevant pathophysiological implications involving toxicological studies describing effects of engineered nanoparticles on mesothelial cells and membranes studies primarily emphasize on simulating cellular uptake and toxicity of nanotubes on benign or malignant cell lines. On the other hand, studies focus on illustrating endpoints of serosal pathology in rodent animal models. From a molecular aspect, some nanoparticle categories are shown to be cytotoxic and genotoxic after acute treatment, whereas chronic incubation may lead to malignant-like transformation. At an organism level, a number of fibrous shaped nanotubes are related with features of chronic inflammation and MWCNT-7 is the only type to consistently inflict mesothelioma.
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http://dx.doi.org/10.3389/fphys.2018.00295DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884948PMC
March 2018

Editorial: Mesothelial Physiology and Pathophysiology.

Front Physiol 2018 22;9:263. Epub 2018 Mar 22.

Department of Physiology, Faculty of Medicine, BIOPOLIS, University of Thessaly, Larissa, Greece.

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http://dx.doi.org/10.3389/fphys.2018.00263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5874514PMC
March 2018

Identification of a prospective early motor progression cluster of Parkinson's disease: Data from the PPMI study.

J Neurol Sci 2018 04 31;387:103-108. Epub 2018 Jan 31.

Division of Basic Neurosciences, Biomedical Research Foundation of the Academy of Athens, Athens, Greece; Second Department of Neurology, National and Kapodistrian University of Athens Medical School, Athens, Greece.

Aim: The aim of our study is to phenotype PD motor progression, and to detect whether serum, cerebrospinal fluid (CSF), neuroimaging biomarkers and neuropsychological measures characterize PD motor progression phenotypes.

Methods: We defined motor progression as a difference of at least one point in the Hoehn & Yahr (H&Y) scale between the baseline (Visit 0, V0), 12 months (Visit 04, V04) and 36 months (Visit 08, V08) milestones of the Progression Markers Initiative (PPMI) study. H&Y progression events were recorded at each milestone in order to be used as cluster analysis variables, in order to produce progression phenotypes. Subsequently, cross-cluster comparisons prior to and following (pairwise) propensity score matching were performed in order to assess phenotype - defining characteristics.

Results: Four progression clusters where identified: SPPD: Secondarily Progressive PD, H&Y progression between V04 and V08; EPPD: Early Progressive PD. H&Y progression between V0 and V04; NPPD: Non Progressive PD, no H&Y progression; MIPD: Minimally Improving PD, i.e. Minimal H&Y improvement H&Y progression between V04 and V08;. Independent Samples Mann Whitney U tests determined CSF aSyn (p = 0.006, adj p-value = 0.036. I) and Semantic Animal fluency T-score (SFT, p = 0.003, adjusted p-value = 0.016.) as statistically significant cross-cluster characteristics. Following Propensity Score Matching, SFT, Hopkins Verbal Learning Test (Retention/Recall), Serum IGF1, CSF aSyn, DaT-SPECT binding ratios (SBRs) and the Benton Judgement of Line Orientation Test (BJLOT) were determined as statistically significant predictors of cluster differentiation (p < 0.05).

Discussion: SFT, Serum IGF1, CSF aSyn and DaT-SPECT-derived, basal ganglia Striatal Binding Ratios warrant further investigation as possible motor progression biomarkers.
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http://dx.doi.org/10.1016/j.jns.2018.01.025DOI Listing
April 2018

The putative interplay between DJ-1/NRF2 and Dimethyl Fumarate: A potentially important pharmacological target.

Mult Scler Relat Disord 2018 Apr 26;21:88-91. Epub 2018 Feb 26.

Department of Neurology, Athens Naval Hospital, Deinokratous 70, Athens, Greece.

Recent research has outlined that Dimethyl Fumarate (DMF) functions as a gene regulator via multiple pathways, critical among which is the NRF2 cytoprotective cascade. PARK7/DJ-1 is a multifunctional protein that acts as a redox sensor and effector of multiple cytoprotective pathways, including NRF2. Specifically, it prevents the association of NRF2 with its inhibitor KEAP1, allowing NRF2 to enter the nucleus and mediate cytoprotective and antioxidant cascades. It is our hypothesis that while the NRF2-KEAP1 inhibitory complex is reported the main pharmacological target for DMF's NRF dependent functions, no study to date has explored the effects of DMF on DJ-1's expression, and vice-versa, the possibility of a regulatory inadequacy in the upstream, oxidant-responsive DJ-1 activator of the NRF2 cascade.
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http://dx.doi.org/10.1016/j.msard.2018.02.027DOI Listing
April 2018

Silver Nanoparticles Alter Cell Adhesion and Proliferation of Sheep Primary Mesothelial Cells.

In Vivo 2018 Jan-Feb;32(1):109-112

Department of Physiology, Faculty of Medicine, University of Thessaly, BIOPOLIS, Larissa, Greece

Background: Human exposure to engineered nanoparticles has been linked to pleural effusion, inflammation and fibrosis. Silver nanoparticles (AgNPs) are widely used in medical and domestic products, increasing the risk of occupational and domestic exposure. We assessed the influence of AgNPs on adhesion and proliferation of sheep primary pleural mesothelial cells.

Materials And Methods: Cells were used for cell adhesion (90 min) and proliferation experiments (3 days) while exposed to 20 nm and 60 nm AgNPs (0.2 μg/ml and 2 μg/ml) using colorimetric assays.

Results: Exposure to 0.2 μg/ml of 20 nm and 60 nm AgNPs significantly increased cell adhesion, while at 2 μg/ml this effect was not elicited. Cell proliferation was significantly increased by both 20 nm and 60 nm AgNPs at 0.2 μg/ml, while at 2 μg/ml this effect was only elicited by the 60 nm AgNPs.

Conclusion: AgNPs alter the adhesive and proliferative properties of primary pleural mesothelial cells.
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http://dx.doi.org/10.21873/invivo.11211DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5892624PMC
August 2018