George Kolios
Democritus University of Thrace, Medicine, Faculty Member
- Gastroenterologist - Clinical Pharmacologistedit
Research Interests: Medicine, Inflammatory Bowel Disease, Case Report, Humans, Low Dose, and 15 moreRandomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase(Randomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase)
(Randomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase)
Research Interests: Immunology, Probiotics, Treatment Outcome, Medicine, Saccharomyces cerevisiae, and 15 moreInflammatory Bowel Disease, Humans, Escherichia coli, Chronic Disease, Female, Disease, Digestion, Lactobacillus, Male, Immune system, Review article, Gut Flora, Bifidobacterium, Inflammatory Bowel Diseases, and Pharmacology and pharmaceutical sciences
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Research Interests: Medicine, Inflammatory Bowel Disease, Case Report, Humans, Low Dose, and 15 moreRandomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase(Randomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase)
(Randomised Controlled Trial, Aspirin, Recurrence, Randomized Controlled Trial, Combination drug therapy, In Vitro Studies, Crohn Disease, Inflammatory Bowel Diseases, Acute Disease, Adverse effect, Database Search, Exacerbation, Adrenal cortex hormones, Pharmacology and pharmaceutical sciences, and Cyclooxygenase)
The intestinal microflora is a large bacterial community that colonizes the gut, with a metabolic activity equal to an organ and various functions that affect the physiology and pathology of the host's mucosal immune system.... more
The intestinal microflora is a large bacterial community that colonizes the gut, with a metabolic activity equal to an organ and various functions that affect the physiology and pathology of the host's mucosal immune system. Intestinal bacteria are useful in promotion of human health, but certain components of microflora, in genetically susceptible individuals, contribute to various pathological disorders, including inflammatory bowel disease. Clinical and experimental observations indicate an imbalance in protective and harmful microflora components in these disorders. Manipulation of gut flora to enhance its protective and beneficial role represents a promising field of new therapeutic strategies of inflammatory bowel disease. In this review, we discuss the implication of gut flora in the intestinal inflammation that justifies the role of probiotics and prebiotics in the prevention and treatment of inflammatory bowel disease and we address the evidence for therapeutic benefits...
Research Interests: Immunology, Probiotics, Treatment Outcome, Medicine, Saccharomyces cerevisiae, and 15 moreInflammatory Bowel Disease, Humans, Escherichia coli, Chronic Disease, Female, Disease, Digestion, Lactobacillus, Male, Immune system, Review article, Gut Flora, Bifidobacterium, Inflammatory Bowel Diseases, and Pharmacology and pharmaceutical sciences
Atrial fibrillation (AF) is a prevalent cardiac arrhythmia worldwide and is characterized by a high risk of thromboembolism, ischemic stroke, and fatality. The precise molecular mechanisms of AF pathogenesis remain unclear. The purpose of... more
Atrial fibrillation (AF) is a prevalent cardiac arrhythmia worldwide and is characterized by a high risk of thromboembolism, ischemic stroke, and fatality. The precise molecular mechanisms of AF pathogenesis remain unclear. The purpose of this study was to use bioinformatics tools to identify novel key genes in AF, provide deeper insights into the molecular pathogenesis of AF, and uncover potential therapeutic targets. Four publicly available raw RNA-Seq datasets obtained through the ENA Browser, as well as proteomic analysis results, both derived from atrial tissues, were used in this analysis. Differential gene expression analysis was performed and cross-validated with proteomics results to identify common genes/proteins between them. A functional enrichment pathway analysis was performed. Cross-validation analysis revealed five differentially expressed genes, namely FGL2, IGFBP5, NNMT, PLA2G2A, and TNC, in patients with AF compared with those with sinus rhythm (SR). These genes p...
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The probiotics Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 seem to promote wound healing when applied topically. Our aim was to investigate their effect on the mRNA expression... more
The probiotics Lactiplantibacillus plantarum UBLP-40, Lactobacillus rhamnosus UBLR-58 and Bifidobacterium longum UBBL-64 seem to promote wound healing when applied topically. Our aim was to investigate their effect on the mRNA expression of pro-inflammatory, healing and angiogenetic factors during the healing process of a standardized excisional wound model in rats. Rats subjected to six dorsal skin wounds were allocated to Control; L. plantarum; combined formula of L. rhamnosus plus B. longum; L. rhamnosus; and B. longum treatments, applied every two days, along with tissue collection. The pro-inflammatory, wound-healing, and angiogenetic factors of mRNA expression were assessed by qRT-PCR. We found that L. plantarum exerts a strong anti-inflammatory effect in relation to L. rhamnosus–B. longum, given alone or in combination; the combined regime of L. rhamnosus–B. longum, works better, greatly promoting the expression of healing and angiogenic factors than L. plantarum. When separa...
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Background Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the alimentary tract, primarily manifested as Crohn’s disease and Ulcerative colitis. Dysbiosis of the intestinal microbial microflora is a... more
Background Inflammatory Bowel Disease (IBD) is a chronic inflammatory condition of the alimentary tract, primarily manifested as Crohn’s disease and Ulcerative colitis. Dysbiosis of the intestinal microbial microflora is a well-established characteristic of IBD. The microbiota metabolism ends in the production of several metabolites that participate in interactions with the host and ultimately influence its physiology. Our aim is to investigate whether metabolite receptor expression differs between IBD and healthy individuals and unravel their possible interactions with inflammatory and fibrotic pathways in the intestine. Methods RNA-sequencing data from over 2500 intestinal biopsy samples were collected from publicly available datasets via the Sequence Read Archive. Bioinformatics analysis of metabolite receptor genes was performed using the RaNA-seq online platform which included normalization, alignment and differential expression. In addition, correlation analysis between the ta...
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ABSTRACTNon-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells... more
ABSTRACTNon-alcoholic steatohepatitis (NASH) constitutes a significant cause of deaths, liver transplantations and economic costs worldwide. Despite extended research, investigations on the role of erythrocytes are scarce. Red blood cells from experimental animals and human patients with NASH, present phosphatidylserine exposure which is then recognized by Kupffer cells. This event leads to erythrophagocytosis, and amplification of inflammation through iron disposition. In addition, it has been shown that erythrocytes from NASH patients release the chemokine MCP1, leading to increased TNF-α release from macrophages RAW 264.7. However, erythrophagocytosis can also be caused by reduced CD47 levels. In addition, increased MCP1 release could be either signal-induced, or caused by higher MCP1 levels on the erythrocyte membrane. Finally, erythrocyte efferocytosis could provide additional inflammatory metabolites. In this study, we measured the erythrocyte membrane levels of CD47 and MCP1 ...
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Objective: To measure plasma glutamine (GLN) levels in systemic and portal circulation after combined enteral and parenteral administration in early endotoxemic swine. We hypothesized that this combination will be more efficient than... more
Objective: To measure plasma glutamine (GLN) levels in systemic and portal circulation after combined enteral and parenteral administration in early endotoxemic swine. We hypothesized that this combination will be more efficient than intravenous administration alone in restoring plasma levels during the course of endotoxemia. Materials and Methods: Endotoxemia was induced with Escherichia coli O111:B4 lipopolysaccharide (LPS) (250 μg/kg body weight) in 16 anesthetized, fasted swine and maintained by constant infusion (2 μg/kg/h) over 180 min. Another 16 swine served as controls. After infusion with LPS or placebo, GLN was administered intravenously, enterally or in combination (0.5 g/kg i.v. plus 0.5 g/kg enterally) over 30 min. At 0, 15, 30, 45, 60, 120 and 180 min, blood was drawn from the systemic and portal circulation for colorimetric assessment of GLN. Results: In healthy, placebo-alone swine, GLN levels remained stable throughout the study. Intravenous and combined infusion ...
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Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent).... more
Stem cells are a population of undifferentiated cells characterized by the ability to extensively proliferate (self-renewal), usually arise from a single cell (clonal), and differentiate into different types of cells and tissue (potent). There are several sources of stem cells with varying potencies. Pluripotent cells are embryonic stem cells derived from the inner cell mass of the embryo and induced pluripotent cells are formed following reprogramming of somatic cells. Pluripotent cells can differentiate into tissue from all 3 germ layers (endoderm, mesoderm, and ectoderm). Multipotent stem cells may differentiate into tissue derived from a single germ layer such as mesenchymal stem cells which form adipose tissue, bone, and cartilage. Tissue-resident stem cells are oligopotent since they can form terminally differentiated cells of a specific tissue. Stem cells can be used in cellular therapy to replace damaged cells or to regenerate organs. In addition, stem cells have expanded ou...
Research Interests: Genetics, Developmental Biology, Stem Cells, Reprogramming, Biology, and 15 moreCell Biology, Stem Cell, Regenerative Medicine, Medicine, Mesenchymal stem cells, Humans, Embryonic Stem Cell, Lung Diseases, Respiration, Integrated Approach, Stem cells and Regenerative Medicine, Induced Pluripotent Stem Cells, Adult Stem Cell, Stem Cell Biology and Regenerative Medicine, and Cardiovascular medicine and haematology(Cell Biology, Stem Cell, Regenerative Medicine, Medicine, Mesenchymal stem cells, Humans, Embryonic Stem Cell, Lung Diseases, Respiration, Integrated Approach, Stem cells and Regenerative Medicine, Induced Pluripotent Stem Cells, Adult Stem Cell, Stem Cell Biology and Regenerative Medicine, and Cardiovascular medicine and haematology)
(Cell Biology, Stem Cell, Regenerative Medicine, Medicine, Mesenchymal stem cells, Humans, Embryonic Stem Cell, Lung Diseases, Respiration, Integrated Approach, Stem cells and Regenerative Medicine, Induced Pluripotent Stem Cells, Adult Stem Cell, Stem Cell Biology and Regenerative Medicine, and Cardiovascular medicine and haematology)
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Idiopathic pulmonary fibrosis (IPF) is caused by progressive lung tissue impairment due to extended chronic fibrosis, and it has no known effective treatment. The use of conditioned media (CM) from an immortalized human adipose... more
Idiopathic pulmonary fibrosis (IPF) is caused by progressive lung tissue impairment due to extended chronic fibrosis, and it has no known effective treatment. The use of conditioned media (CM) from an immortalized human adipose mesenchymal stem cell line could be a promising therapeutic strategy, as it can reduce both fibrotic and inflammatory responses. We aimed to investigate the anti-inflammatory and anti-fibrotic effect of CM on human pulmonary subepithelial myofibroblasts (hPSM) and on A549 pulmonary epithelial cells, treated with pro-inflammatory or pro-fibrotic mediators. CM inhibited the proinflammatory cytokine-induced mRNA and protein production of various chemokines in both hPSMs and A549 cells. It also downregulated the mRNA expression of IL-1α, but upregulated IL-1β and IL-6 mRNA production in both cell types. CM downregulated the pro-fibrotic-induced mRNA expression of collagen Type III and the migration rate of hPSMs, but upregulated fibronectin mRNA production and th...
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Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are characterized by chronic and relapsing inflammation, while their pathogenesis remains mostly unelucidated. Gut commensal microbiota seem to be one of the... more
Inflammatory bowel disease (IBD), Crohn’s disease, and ulcerative colitis are characterized by chronic and relapsing inflammation, while their pathogenesis remains mostly unelucidated. Gut commensal microbiota seem to be one of the various implicated factors, as several studies have shown a significant decrease in the microbiome diversity of patients with IBD. Although the question of whether microbiota dysbiosis is a causal factor or the result of chronic inflammation remains unanswered, one fact is clear; active inflammation in IBD results in the disruption of the mucus layer structure, barrier function, and also, colonization sites. Recently, many studies on IBD have been focusing on the interplay between mucosal and luminal microbiota, underlining their possible beneficial effect on mucosal healing. Regarding this notion, it has now been shown that specific probiotic strains, when administrated, lead to significantly decreased inflammation, amelioration of colitis, and improved ...
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Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity... more
Regenerative medicine is a novel scientific field that employs the use of stem cells as cell-based therapy for the regeneration and functional restoration of damaged tissues and organs. Stem cells bear characteristics such as the capacity for self-renewal and differentiation towards specific lineages and, therefore, serve as a backup reservoir in case of tissue injuries. Therapeutically, they can be autologously or allogeneically transplanted for tissue regeneration; however, allogeneic stem cell transplantation can provoke host immune responses leading to a host-versus-transplant reaction. A probable solution to this problem is stem cell encapsulation, a technique that utilizes various biomaterials for the creation of a semi-permeable membrane that encases the stem cells. Stem cell encapsulation can be accomplished by employing a great variety of natural and/or synthetic hydrogels and offers many benefits in regenerative medicine, including protection from the host’s immune system ...
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Even though anti-TNF therapy significantly improves the rates of remission in inflammatory bowel disease (IBD) patients, there is a noticeable subgroup of patients who do not respond to treatment. Dysbiosis emerges as a key factor in IBD... more
Even though anti-TNF therapy significantly improves the rates of remission in inflammatory bowel disease (IBD) patients, there is a noticeable subgroup of patients who do not respond to treatment. Dysbiosis emerges as a key factor in IBD pathogenesis. The aim of the present study is to profile changes in the gut microbiome and transcriptome before and after administration of the anti-TNF agent Infliximab (IFX) and investigate their potential to predict patient response to IFX at baseline. Mucosal biopsy samples from 20 IBD patients and nine healthy controls (HC) were examined for differences in microbiota composition (16S rRNA gene sequencing) and mucosal gene expression (RT-qPCR) at baseline and upon completion of IFX treatment, accordingly, via an in silico pipeline. Significant differences in microbiota composition were found between the IBD and HC groups. Several bacterial genera, which were found only in IBD patients and not HC, had their populations dramatically reduced after ...
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Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in... more
Cervical cancer is strongly related to certain high-risk types of human papilloma virus infection. Breast cancer metastasis suppressor 1 (BRMS1) is a tumor suppressor gene, its expression being regulated by DNA promoter methylation in several types of cancers. This study aims to evaluate the methylation status of BRMS1 promoter in relation to high-risk types of human papilloma virus infection and the development of pre-cancerous lesions and describe the pattern of BRMS1 protein expression in normal, high-risk types of human papilloma virus–infected pre-cancerous and malignant cervical epithelium. We compared the methylation status of BRMS1 in cervical smears of 64 women with no infection by high-risk types of human papilloma virus to 70 women with proven high-risk types of human papilloma virus infection, using real-time methylation-specific polymerase chain reaction. The expression of BRMS1 protein was described by immunohistochemistry in biopsies from cervical cancer, pre-cancerou...
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The stress neuropeptides, corticotropin-releasing hormone (CRH) and urocortin (UCN), modulate the inflammatory response via the hypothalamus-pituitary-adrenal axis and locally, in a paracrine manner, act on mast and macrophage cells.... more
The stress neuropeptides, corticotropin-releasing hormone (CRH) and urocortin (UCN), modulate the inflammatory response via the hypothalamus-pituitary-adrenal axis and locally, in a paracrine manner, act on mast and macrophage cells. Kupffer cells (KCs) are the resident macrophages of the liver. They represent the bulk of tissue macrophages in the body and they are the first to face invading noxious agents reaching the body via the portal circulation. The aim of the present report was to study the expression of the CRH system in rat KC and test its functionality. Our findings are as follows: (1) In highly purified KCs the transcripts of UCN, of its receptors CRHR1, CRHR2 and that of the pseudoreceptor CRH-binding protein (CRHBP) were present while that of CRH was not detectable. (2) Similarly, immunoreactive UCN, CRHR1, CRHR2 and CRHBP were easily detectable by immunohistochemistry and immunofluorescence in sections of whole rat liver (localized in KC) as well as in purified KC while CRH was again not detectable. (3) Exposure of purified KC to CRH or UCN suppressed lipopolysaccharide-induced tumor necrosis factor alpha production, an effect completely prevented by the CRHR1 and CRHR2 receptor antagonist astressin. Our data demonstrate the presence of UCN and its receptors in rat KC, the absence of CRH, and the functionality of these receptors. We propose that a UCN-based system may affect local inflammatory phenomena in the liver acting in a paracrine manner.
Research Interests: Endocrinology, Neuroendocrinology, Biology, Immunohistochemistry, Medicine, and 15 moreCorticotropin Releasing Hormone, Inflammatory Immune Response, Lipopolysaccharide, Internal Medicine, Animals, Male, Clinical Sciences, Neuropeptide Y, Rat, Protein Binding, Neurosciences, Gene Expression Regulation, Kupffer cells, Inflammatory response, and Neuropeptide
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Introduction Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis... more
Introduction Regenerative medicine and particular adult stem cells represent an alternative option with several fruitful therapeutic applications in patients suffering from chronic lung diseases including idiopathic pulmonary fibrosis (IPF). Nevertheless, lack of knowledge regarding the origin and the potential of mesenchymal stem cells (MSCs) to differentiate into fibroblasts has limited their use for the treatment of this dismal disease. Patients and methods To this end, we conducted a phase Ib, non-randomized, clinical trial to study the safety of three endobronchial infusions of autologous adipose derived stromal cells (ADSCs)-stromal vascular fraction (SVF) (0.5 million cells per kgr of body weight per infusion) in patients with IPF (n=14) of mild to moderate disease severity (forced vital capacity –FVC>50% predicted value and diffusion lung capacity for carbon monoxide-DLCO>35% of predicted value). Our primary end-point was incidence of treatment emergent adverse events ...
Research Interests: Flow Cytometry, Inflammation, Medicine, Translational Medicine, Adipose tissue, and 13 moreProspective studies, Humans, Female, Male, Radionuclide imaging, Lung, Aged, Middle Aged, Stromal Cells, Idiopathic Pulmonary Fibrosis, Mesenchymal Stromal Cells, Respiratory function tests, and Medical and Health Sciences
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Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with ineffective treatment. Mycophenolate mofetil (MMF) is an immunomodulatory agent which inhibits lymphocyte proliferation. Objective.... more
Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with ineffective treatment. Mycophenolate mofetil (MMF) is an immunomodulatory agent which inhibits lymphocyte proliferation. Objective. We sought to determine the safety and efficacy profile of MMF in IPF patients. Methods. We retrospectively identified ten patients, who met the ATS/ERS 2000 criteria for IPF and received MMF 2 gr/day for 12 months. All of them had routine laboratory, pulmonary function and radiological (high resolution computed tomography-HRCT) data available and were enrolled in the study. Forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity of the lung for carbon monoxide (DL(CO)), 6-minute walking distance (6MWD), HRCT scans and routine laboratory data at treatment onset were compared with respective values 12 months after treatment onset. Results. There were no significant alterations in FVC, TLC, DL(CO) and 6MWD pre- and 6 and 12 months pos...
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Research Interests: Chemistry, Gastroenterology, Biology, Membrane Proteins, Enzyme Inhibitors, and 15 moreMedicine, Inflammatory Bowel Disease, Humans, Intestinal Mucosa, Mitogen Activated Protein Kinase, High Performance Liquid Chromatography, Clinical Sciences, Homeostasis, Nitric Oxide Synthase, Liquid Chromatography, Isoenzymes, Neurosciences, Enzyme Linked Immunosorbent Assay, Inducible Nitric Oxide Synthase, and Interleukin(Medicine, Inflammatory Bowel Disease, Humans, Intestinal Mucosa, Mitogen Activated Protein Kinase, High Performance Liquid Chromatography, Clinical Sciences, Homeostasis, Nitric Oxide Synthase, Liquid Chromatography, Isoenzymes, Neurosciences, Enzyme Linked Immunosorbent Assay, Inducible Nitric Oxide Synthase, and Interleukin)
(Medicine, Inflammatory Bowel Disease, Humans, Intestinal Mucosa, Mitogen Activated Protein Kinase, High Performance Liquid Chromatography, Clinical Sciences, Homeostasis, Nitric Oxide Synthase, Liquid Chromatography, Isoenzymes, Neurosciences, Enzyme Linked Immunosorbent Assay, Inducible Nitric Oxide Synthase, and Interleukin)
Research Interests: Cognitive Science, Survival Analysis, Medicine, Humans, Internal Medicine, and 9 moreFemale, Male, DNA methylation, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, and Stomach neoplasms(Female, Male, DNA methylation, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, and Stomach neoplasms)
(Female, Male, DNA methylation, Clinical Sciences, Aged, Middle Aged, Adult, Prognosis, and Stomach neoplasms)
Summary Human colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known... more
Summary Human colonic epithelial cells express T helper type 1 (Th1)-associated chemoattractants, yet little is known about the production of Th2-associated chemoattractants. CCL11/eotaxin-1, CCL24/eotaxin-2 and CCL26/eotaxin-3 are known to attract CCR3-expressing, Th2-polarized lymphocytes. We studied constitutive and inflammation-induced expression and production of CCR3 together with its ligands in the colon and peripheral blood of patients with inflammatory bowel disease (IBD) by flow cytometry, reverse transcription–polymerase chain reaction (RT–PCR) and enzyme-linked immunosorbent assay (ELISA). We further defined the regulated expression of these chemokines by RT–PCR and ELISA using cultured human epithelial cell lines. A higher fraction of peripheral T lymphocytes were found to be positive for CCR3 in patients with ulcerative colitis (UC) compared to Crohn's disease (CD), while almost no CCR3+ T cells were found in normal controls (NC). Similarly, higher and more frequen...
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Nitric oxide (NO) production is increased in the human colonic mucosa in intestinal inflammation. We examined the effect of corticosteroids and the role of mononuclear cells in this production. Colonic biopsies from patients with... more
Nitric oxide (NO) production is increased in the human colonic mucosa in intestinal inflammation. We examined the effect of corticosteroids and the role of mononuclear cells in this production. Colonic biopsies from patients with ulcerative colitis and normal controls were cultured with either budesonide or prednisolone in the presence of proinflammatory cytokines. Human mixed mononuclear cells (MMCs) were cocultured with HT-29 cells stimulated with IFN-γ and LPS in the presence or absence of corticosteroids. Nitrite production was measured in supernatants by a modification of the Griess reaction, and inducible NO synthase (iNOS) mRNA expression was studied in colonic tissue by RT-PCR. Both steroids significantly suppressed the nitrite production and iNOS mRNA expression in inflamed colonic biopsies from ulcerative colitis patients and in cytokine-stimulated normal colonic biopsies but not in cytokine-stimulated HT-29 cells. Nitrite production by HT-29 cells was significantly increa...
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Crohn’s disease and ulcerative colitis, the two most common inflammatory bowel diseases (IBD), arecharacterized by chronic relapsing inflammation. Although recent progress regarding the therapeutic approachto these diseases has been made... more
Crohn’s disease and ulcerative colitis, the two most common inflammatory bowel diseases (IBD), arecharacterized by chronic relapsing inflammation. Although recent progress regarding the therapeutic approachto these diseases has been made in the development of biologic therapies, not every patient responds well,resulting in a high percentage of ineffectiveness. Even though the immunological cascades range between thecurrent pharmacological agents for IBD treatment and the constant research for more possible pharmacologicaltargets, a lot of progress still needs to be made regarding the correct therapeutical choice for each individualpatient. Therefore, it is still important to find proper, inexpensive, and measurable biomarkers, in order to beable to assess the efficacy of these therapies, to make personalized choices, as well as to avoid potential adversedrug reactions and side effects. The biomarkers that are available in the present vary; metabolic, microbial,cytokine-related, gene...
Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in... more
Inflammatory Bowel Diseases (IBDs) are characterized by chronic intestinal inflammation and fibrosis, the latter being the predominant denominator for long-term complications. Epithelial and mesenchymal 2D cultures are highly utilized in vitro models for the preclinical evaluation of anti-inflammatory and antifibrotic therapies. More recently, human intestinal organoids (HIOs), a new 3D in vitro model derived from pluripotent stem cells, have the advantage to closely resemble the architecture of the intestinal mucosa. However, the appropriate timing for the study of inflammatory and fibrotic responses, during HIO development, has not been adequately investigated. We developed HIOs from the human embryonic stem cell line, H1, and examined the expression of mesenchymal markers during their maturation process. We also investigated the effect of inflammatory stimuli on the expression of fibrotic and immunological mediators. Serial evaluation of the expression of mesenchymal and extracel...
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ABSTRACTBACKGROUNDNon-Alcoholic Fatty Liver Disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of... more
ABSTRACTBACKGROUNDNon-Alcoholic Fatty Liver Disease (NAFLD) constitutes a global pandemic. An intricate network among cytokines and lipids possesses a central role in NAFLD pathogenesis. Red blood cells comprise an important source of both cytokines and signaling lipids and have an important role in the molecular crosstalk during immunometabolic deregulation. However, their role in NAFLD has not been investigated in deep.METHODSConditioned media from erythrocytes derived from 10 NAFLD patients (4 men, 6 women, aged 57.875±15,16) and 10 healthy controls (4 men, 6 women, aged 39.3±15.55) were produced and used for the analysis of 9 cytokines (IFN-γ, TNF-α, CCL2, CCL5, IL-8, IL-1β, IL-12p40, IL-17, MIP-1β), 2 signaling lipids (Sphingosine 1-phosphate and Lysophosphatidic Acid), and cholesterol. Their effect on the cytokine profile released by RAW 264.7 macrophages was also studied.RESULTSErythrocytes from patients with NAFLD augmented the levels of MCP1 in the growth medium in comparis...
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Background/Aim: Colon cancer is one of the most common cancer types and the second leading cause of death due to cancer. Many efforts have been performed towards the investigation of molecular alterations during colon cancer progression.... more
Background/Aim: Colon cancer is one of the most common cancer types and the second leading cause of death due to cancer. Many efforts have been performed towards the investigation of molecular alterations during colon cancer progression. However, the identification of stage-specific molecular markers remains a challenge. The aim of this study was to develop a novel computational methodology for the analysis of alterations in differential gene expression and pathway deregulation across colon cancer stages in order to reveal stage-specific biomarkers and reinforce drug repurposing investigation. Materials and Methods: Transcriptomic datasets of colon cancer were used to identify (a) differentially expressed genes with monotonicity in their fold changes (MEGs) and (b) perturbed pathways with ascending monotonic enrichment (MEPs) related to the number of the participating differentially expressed genes (DEGs), across the four colon cancer stages. Through an in silico drug repurposing pipeline we identified drugs that regulate the expression of MEGs and also target the resulting MEPs. Results: Our methodology highlighted 15 MEGs and 32 candidate repurposed drugs that affect their expression. We also found 51 MEPs divided into two groups according to their rate of DEG content alteration across colon cancer stages. Focusing on the target MEPs of the highlighted repurposed drugs, we found that one of them, the neuroactive ligand-receptor interaction, was targeted by the majority of the candidate drugs. Moreover, we observed that two of the drugs (PIK-75 and troglitazone) target the majority of the resulting MEPs. Conclusion: These findings highlight significant genes and pathways that can be used as stage-specific biomarkers and facilitate the discovery of new potential repurposed drugs for colon cancer. We expect that the computational methodology presented can be applied in a similar way to the analysis of any progressive disease.
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Several studies have gathered interest in the relationship between gut microbiota and atherosclerosis. Gut microbiota and its metabolites, such as trimethylamine-N-oxide, and gut dysbiosis play an important role in the development of... more
Several studies have gathered interest in the relationship between gut microbiota and atherosclerosis. Gut microbiota and its metabolites, such as trimethylamine-N-oxide, and gut dysbiosis play an important role in the development of atherosclerosis. Also, inflammation, derived by the intestinal tract, adds another mechanism through which the ecosystem of the human body affects the metabolic diseases and, furthermore, cardiovascular diseases. The scientific world should fixate the understanding of the exact physiologic and pathophysiologic mechanisms for atherogenesis by gut microbiota and through that, new ways for novel therapeutic targets will be available in the coming years. This review summarizes the latest data on this matter.
Research Interests: Medicine()
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Osteoporosis is a systemic disease that affects the skeleton, causing reduction of bone density and mass, resulting in destruction of bone microstructure and increased risk of bone fractures. Since osteoporosis is a disease affecting the... more
Osteoporosis is a systemic disease that affects the skeleton, causing reduction of bone density and mass, resulting in destruction of bone microstructure and increased risk of bone fractures. Since osteoporosis is a disease affecting the elderly and the aging of the world’s population is constantly increasing, it is expected that the incidence of osteoporosis and its financial burden on the insurance systems will increase continuously and there is a need for more understanding this condition in order to prevent and/or treat it. At present, available drug therapy for osteoporosis primarily targets the inhibition of bone resorption and agents that promote bone mineralization, designed to slow disease progression. Safe and predictable pharmaceutical means to increase bone formation have been elusive. Stem cell therapy of osteoporosis, as a therapeutic strategy, offers the promise of an increase in osteoblast differentiation and thus reversing the shift towards bone resorption in osteop...
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Abstract Adhesions formation is considered a significant clinical entity implicating the healing process following major abdominal surgery, with serious clinical consequences and need for substantial health care expenditures. Several... more
Abstract Adhesions formation is considered a significant clinical entity implicating the healing process following major abdominal surgery, with serious clinical consequences and need for substantial health care expenditures. Several agents and substances applied either locally or systematically could potentially function as inhibitors of the formation of peritoneal adhesions endowed by limiting tissue apposition during the critical stages of mesothelial repair. Phospholipids are identified as surfactant‐like substances, acting as a temporary membrane‐like coverage of serosal defects. The experimental use of phospholipids for adhesions formation totals 24 publications. All retrieved studies, out of two, demonstrated the efficacy of phospholipids use in adhesions prevention. A single intraperitoneal dose of approximately 75 mg/kg of phosphatidylcholine, for a 30‐min exposure time, emerges as the standard practice in terms of efficacy in both surgical alone or combined to peritonitis settings. The findings revealing an unimpeded healing of anastomoses and laparotomy wounds support the safety of this agent. The two additional properties of intraperitoneal use of phospholipids involve the inhibition of bacterial adherence/growth following impregnation of intra‐abdominal drainages with phospholipids, without influencing bacterial translocation and the elimination of peritoneal carcinosis, through inhibition of intraperitoneal adhesion of tumor cells. The latter effect is achieved by a dose of phospholipids equal to 150 mg/kg. These experimental data, support that the intraperitoneal phospholipids administration can forestall adhesions formation following intra‐abdominal surgical trauma, with no considerable overdosing‐related adverse effects. Furthermore, these substances could possibly attenuate posttraumatic inflammation, and inhibit intraperitoneal tumor cell adhesion.
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Colonic subepithelial myofibroblasts (cSEMFs) are mesenchymal cells with a pivotal role in the pathophysiology of Crohn's disease (CD) fibrosis. Here, we demonstrate for the first time a complete expression mapping of cytokine... more
Colonic subepithelial myofibroblasts (cSEMFs) are mesenchymal cells with a pivotal role in the pathophysiology of Crohn's disease (CD) fibrosis. Here, we demonstrate for the first time a complete expression mapping of cytokine receptors, implicated in inflammatory bowel diseases, in primary human cSEMFs and how pro-inflammatory cytokines regulate this expression. Furthermore, we show the effect of Th1-, Th2-, Th17- and Treg-related cytokines on a fibrosis-related phenotype of cSEMFs. Colonic subepithelial myofibroblasts were isolated from healthy individuals' colonic biopsies. Interleukin (IL)-1α- and/or tumor necrosis factor (TNF)-α-induced mRNA and protein expression of cytokine receptors was assayed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and immunofluorescence, respectively. Th-related cytokine effects on mRNA and protein profibrotic factor expression were analyzed by qRT-PCR and/or colorimetric assays and on the wound-healing capacity o...
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The BioEnterics Intragastric Balloon [BIB] is a reliable, non-invasive technique to manage obesity for subjects who refuse or are unsuitable for bariatric surgery. In a prior study, BIB placed in the antrum [A] was found to have... more
The BioEnterics Intragastric Balloon [BIB] is a reliable, non-invasive technique to manage obesity for subjects who refuse or are unsuitable for bariatric surgery. In a prior study, BIB placed in the antrum [A] was found to have significantly better results on weight loss in relation to that in fundus [F], but many balloons initially placed in the F were eventually found in the A. The aim of the present analysis was to evaluate whether the balloon position [firmly in F, firmly in A, or transient from F to A [FA]] influences the 3- and 6-month weight loss. Six hundred sixty-eight patients that underwent successful BIB treatment were assigned into three groups: group F [n = 354], group A [n = 159], and group AF [n = 155]. Weight loss parameters were recorded and analyzed at 3 and 6 months. In all three groups, there was a significant, progressive reduction of BMI at 3 and 6 months. At 6 months, BMI reduction between groups F and A, and F and FA [p = 0.001] and groups A and FA [p = 0.0...
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Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the... more
Echinocandins are recommended for the treatment of suspected or confirmed invasive candidiasis (IC) in adults. Less is known about the use of echinocandins for the management of IC in children. The aim of this study was to investigate the overall efficacy and safety of echinocandin class in neonatal and pediatric patients with IC. PubMed, Cochrane Central, Scopus and Clinical trial registries were searched up to July 27, 2017. Eligible studies were randomized trials (RCTs) that evaluated the efficacy and safety of any echinocandin versus agents of other antifungal classes for the treatment of IC in pediatric patients. The primary outcome was treatment success with resolution of symptoms and signs, and absence of IC. In the meta-analysis a random effects model was used, and the odds ratio (OR) and 95% confidence intervals (CI) were calculated. Four randomized clinical trials (324 patients), 2 confirmed IC (micafungin vs. liposomal amphotericin B and caspofungin vs. liposomal amphoter...
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Research Interests: Medicine()
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