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Origin and genomic characteristics of SARS-CoV-2 and its interaction with angiotensin converting enzyme type 2 receptors, focusing on the gastrointestinal tract

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World Journal of Gastroenterology 2020年第41期26卷 6335-6345页

作者： Michail Galanopoulos Aris Doukatas maria gazouli Department of Gastroenterology 401 General Military Hospital of AthensAthens 11525AttikiGreece Medical Office of Hellenic Army General Staff 401 General Military Hospital of AthensAthens 11525AttikiGreece Laboratory of Biology School of MedicineNational and Kapodistrian University of AthensAthens 11527AttikiGreece

The emergence of coronavirus disease-2019 induced by a newly identified bcoronavirus, namely severe acute respiratory syndrome coronavirus 2(SARSCoV-2) has constituted a public health emergency. Even though it was considered a zoonotic disease, the virus has also spread among humans via respiratory secretions. The expression and distribution of angiotensin converting enzyme type 2(ACE2) in various human organs might also show other possible infection routes. High ACE2 ribonucleic acid expression has been identified in the gastrointestinal tract(GI) indicating its importance as a possible infection pathway of SARS-CoV-2. ACE2 induces viral entry into the host and most importantly has been found to be associated with the function of the gut. Its deficiency has been implicated in several pathologies such as colorectal inflammation. The renin-angiotensin system(RAS) is an essential regulatory cascade operating both at a local tissue level and at the systemic or circulatory level. The RAS may be important in the pathogenesis of chronic liver disease and is associated with the up-regulation of ACE2. Thus, the aim of this review is firstly, the analysis of some important general and genome characteristics of SARS-CoV-2 and secondly, and most importantly, to focus on the utility of ACE2 receptors in both SARS-CoV-2 replication and pathogenesis, especially in the GI tract.

关键词： SARS-CoV-2 COVID-19 Gastrointestinal tract Angiotensin converting enzyme type 2 Angiotensin converting enzyme type 2 receptor Renin-angiotensin system Angiotensin converting enzyme

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Clock genes:Their role in colorectal cancer

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World Journal of Gastroenterology 2014年第8期20卷 1986-1992页

作者： Theodoros Karantanos George Theodoropoulos Dimitrios Pektasides maria gazouli First Department of Propaedeutic Surgery School of MedicineUniversity of Athens11725 AthensGreece Second Pathology Department School of MedicineUniversity of Athens11725 AthensGreece Department of Basic Medical Science Laboratory of BiologySchool of MedicineUniversity of Athens11725 AthensGreece

Clock genes create a complicated molecular time-keeping system consisting of multiple positive and negative feedback loops at transcriptional and translational levels. This circadian system coordinates and regulates multiple cellular procedures implicated in cancer development such as metabolism, cell cycle and DNA damage response. Recent data support that molecules such as CLOCK1, BMAL1 and PER and CRY proteins have various effects on c-Myc/p21 and Wnt/β-catenin pathways and influence multiple steps of DNA damage response playing a critical role in the preservation of genomic integrity in normal and cancer cells. Notably, all these events have already been related to the development and progression of colorectal cancer (CRC). Recent data highlight critical correlations between clock genes’ expression and pathogenesis, progression, aggressiveness and prognosis of CRC. Increased expression of positive regulators of this circadian system such as BMAL1 has been related to decrease overall survival while decreased expression of negative regulators such as PER2 and PER3 is connected with poorer differentiation, increased aggressiveness and worse prognosis. The implications of these molecules in DNA repair systems explain their involvement in the development of CRC but at the same time provide us with novel targets for modern therapeutic approaches for patients with advanced CRC.

关键词： Clock genes Colorectal cancer Development Prognosis

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Influence of environmental factors in the development of inflammatory bowel diseases

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World Journal of Gastrointestinal Pharmacology and Therapeutics 2016年第1期7卷 112-125页

作者： Evangelia Legaki maria gazouli Department of Basic Medical Sciences Laboratory of Biology School of Medicine University of Athens

Idiopathic inflammatory bowel diseases (IBD), Crohn’s disease (CD) and ulcerative colitis (UC), are multifactorial diseases that are manifested after disruption of a genetic predisposed individual and its intestinal microflora through an environmental stimulus. Urbanization and industrialization are associated with IBD. Epidemiological data, clinical observations and family/immigrants studies indicate the significance of environmental influence in the development of IBD. Some environmental factors have a different effect on the subtypes of IBD. Smoking and appendectomy is negatively associated with UC, but they are aggravating factors for CD. A westernized high fat diet, full of refined carbohydrates is strongly associated with the development of IBD, contrary to a high in fruit, vegetables and polyunsaturated fatty acid-3 diet that is protective against these diseases. High intake of nonsteroidal antiinflammatory drug and oral contraceptive pills as well as the inadequacy of vitamin D leads to an increased risk for IBD and a more malignant course of disease. Moreover, other factors such as air pollution, psychological factors, sleep disturbances and exercise influence the development and the course of IBD. Epigenetic mechanism like DNA methylation, histone modification and altered expression of miRNAS could explain the connection between genes and environmental factors in triggering the development of IBD.

关键词： Crohn&rsquo s disease Ulcerative colitis Epigenetics Environment

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Contribution of ghrelin to functional gastrointestinal disorders' pathogenesis

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World Journal of Gastroenterology 2019年第5期25卷 539-551页

作者： Tilemachos Koutouratsas Theodora Kalli Georgios Karamanolis maria gazouli Department of Basic Medical Science Laboratory of Biology School of Medicine University of Athens Gastroenterology Department Larnaca General Hospital Gastroenterology Unit 2nd Department of Surgery "Aretaieio"University Hospital School of Medicine University of Athens

Functional gastrointestinal disorders(FGID) are heterogeneous disorders with a variety of clinical manifestations, primarily defined by signs and symptoms rather than a definite underlying cause. Their pathophysiology remains obscure and, although it is expected to differ according to the specific FGID, disruptions in the brain-gut axis are now thought to be a common denominator in their pathogenesis. The hormone ghrelin is an important component of this axis,exerting a wide repertoire of physiological actions, including regulation of gastrointestinal motility and protection of mucosal tissue. Ghrelin's gene shows genetic polymorphism, while its protein product undergoes complex regulation and metabolism in the human body. Numerous studies have studied ghrelin's relation to the emergence of FGIDs, its potential value as an index of disease severity and as a predictive marker for symptom relief during attempted treatment. Despite the mixed results currently available in scientific literature, the plethora of statistically significant findings shows that disruptions in ghrelin genetics and expression are plausibly related to FGID pathogenesis. The aim of this paper is to review current literature studying these associations, in an effort to uncover certain patterns of alterations in both genetics and expression, which could delineate its true contribution to FGID emergence, either as a causative agent or as a pathogenetic intermediate.

关键词： Functional gastrointestinal disorders Functional colonic diseases Irritable bowel syndrome Cyclic vomiting syndrome Infantile colic Gastrointestinal disease Ghrelin Genetics Epigenetic processes

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Undefined familial colorectal cancer

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World Journal of Gastrointestinal Oncology 2009年第1期1卷 12-20页

作者： Constantinos Pantelis Zambirinis George Theodoropoulos maria gazouli First Propaedeutic Surgical Department Hippocration University HospitalSchool of MedicineUniversity of Athens Department of Biology School of MedicineUniversity of Athens

Colorectal cancer(CRC),one of the most common cancers of the world,is actually a spectrum of several subtypes,with different molecular profiles,clinicopathological characteristics and possibly separate pathways of *** is estimated that in approximately 25-35 of cases,a familial component exists,so they are classified as familial CRC(fCRC).However the known hereditary CRC syndromes justify only up to *** rest are attributed to some inherited genetic predisposition passed to offspring through lowpenetrance genes,which in the proper environmental setting can bring on ***,part of the familial clustering may be attributed to *** of the complexity regarding the etiology of CRC,the clinician is sometimes faced with obscure patient data,and cannot be sure if they are dealing with fCRC or sporadic *** elucidation of what is going on with the as yet "undefined" portion of CRC will aid not only in the diagnosis,classification and treatment of CRC,but more importantly in the proper adjustment of the screening guidelines and in genetic counselling of patients.

关键词： Colorectal cancer Familial Undefined Type X Polymorphisms

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Single nucleotide polymorphisms of OCTN1, OCTN2, and DLG5 genes in Greek patients with Crohn's disease

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World Journal of Gastroenterology 2005年第47期11卷 7525-7530页

作者： maria gazouli Gerassimos Mantzaris Athanassios J Archimandritis George Nasioulas Nicholas P Anagnou Department of Biology School of MedicineUniversity of AthensAthens 11725Greece Department of Gastroenterology Evagelismos HospitalAthens 11521Greece Department of Internal Medicine Hippokration General HospitalSchool of MedicineUniversity of AthensAthens 11527Greece Molecular Biology Department Research Center HYGEIA "Antonis Papayiannis" AthensGreece

AIM: To validate novel single nucleotide polymorphisms (SNPs) in Greek patients with Crohn's disease (CD).METHODS: A total of 120 patients with CD, 85 patients with UC, and 100 unrelated healthy controls were genotyped. Genotyping was performed by allele-specific PCR or by PCR-RFLP ***: Our results showed that the 1672T and -207C alleles were obviously over-represented in CD patients only (P＜0.01 and P＜0.05, respectively) compared to the control population. The G113A polymorphism was completely absent in our studied population. The odds ratio for the carriage of the TC haplotype was 2.21 for CD patients as compared with controls. Additionally, the frequency of the TC haplotype was increased in patients with ileocolitis or colitis, and was mainly associated with the fibrostenotic phenotype of the disease. Furthermore, when the TC haplotype was compared jointly with the carriage of at least one mutation of the NOD2/CARD15 gene, there was an increased risk for CD, but not for UC, compared to controls. Regarding the location of the disease, the concomitant presence of the TC haplotype and NOD2/CARD15 mutations was mainly associated with ileocolitis or ileitis. CONCLUSION: Collectively, our results suggest that the 1672T variant of the OCTN1 gene and the -207C variant of the OCTN2 gene represent risk factors for CD in the Greek population.

关键词： Crohn's disease SNPs OCTN1 OCTN2 DLG5

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Role of exercise in preventing and restoring gut dysbiosis in patients with inflammatory bowel diseases:A review

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World Journal of Gastroenterology 2021年第30期27卷 5037-5046页

作者： Tilemachos Koutouratsas Anastassios Philippou George Kolios Michael Koutsilieris maria gazouli Department of Basic Medical Sciences Laboratory of BiologyMedical SchoolNational and Kapodistrian University of AthensAthens 11527Greece Department of Basic Medical Sciences Laboratory of PhysiologySchool of MedicineNational and Kapodistrian University of AthensAthens 11527Greece Department of Medicine Laboratory of PharmacologyDemocritus University of ThraceAlexandroupolis 68100Greece

Inflammatory bowel diseases(IBD)include a spectrum of chronic inflammatory disorders of the gastrointestinal tract whose pathogenesis is yet to be *** intestinal microbiome has been studied as a causal component,with certain microbiotic alterations having been observed in subtypes of *** exercise is a modulator of the intestinal microbiome,causing shifts in its composition that are partially corrective of those observed in IBD;furthermore,physical exercise may be beneficial in patients with certain IBD *** review studies the effects of physical exercise on the human gut microbiome while investigating pathophysiologic mechanisms that could explain physical activity’s clinical effects on patients with IBD.

关键词： Inflammatory bowel disease Ulcerative colitis Crohn’s disease Pouchitis Microbiome Exercise

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Molecular basis of the irritable bowel syndrome

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World Journal of Gastroenterology 2014年第2期20卷 376-383页

作者： Anna Vaiopoulou Georgios Karamanolis Theodora Psaltopoulou George Karatzias maria gazouli Department of Basic Medical Science Laboratory of BiologySchool of MedicineUniversity of Athens11527 AthensGreece 2~(nd) Department of Surgery "Aretaieio" University HospitalSchool of MedicineUniversity of Athens11527 AthensGreece Department of Hygiene Epidemiology and Medical StatisticsSchool of MedicineUniversity of Athens11527 AthensGreece

Irritable bowel syndrome(IBS)is a functional disorder characterized by abdominal pain,discomfort and *** pathophysiology of IBS is poorly understood,but the presence of psychosocial basis is now *** is an increasing number of publications supporting the role of genetics in *** of the variations are found in genes associated with the brain-gut axis,revealing the strong correlation of brain-gut axis and ***,which play critical roles in physiological processes,are not well studied in ***,so far there is found an involvement of alterations in miRNA expression or sequence,in IBS *** phenotype is affected by epigenetic alteration and *** in DNA and histone methylation are observed in patients who suffered childhood trauma or abuse,resulting in altered gene expression,such as the glucocorticoid receptor ***,diet is another factor associated with IBS,which may contribute to symptom *** foods may affect on bacterial metabolism and epigenetic modifications,predisposing to IBS.

关键词： Irritable bowel syndrome Gastrointestinal diseases Genetics Epigenetics Diet

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Safety of anti-tumor necrosis factor therapy during pregnancy in patients with inflammatory bowel disease

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World Journal of Gastroenterology 2015年第47期21卷 13205-13211页

作者： Ioannis Androulakis Christos Zavos Panagiotis Christopoulos George Mastorakos maria gazouli Endocrine Unit Aretaieion Hospital University of Athens Medical School Department of Basic Biological Sciences Laboratory of Biology School of Medicine University of Athens

Treatment of inflammatory bowel disease has significantly improved since the introduction of biological agents, such as infliximab, adalimumab, certolizumab pegol, and golimumab. The Food and Drug Administration has classified these factors in category B, which means that they do not demonstrate a fetal risk. However, during pregnancy fetuses are exposed to high anti-tumor necrosis factor(TNF) levels that are measurable in their plasma after birth. Since antibodies can transfer through the placenta at the end of the second and during the third trimesters, it is important to know the safety profile of these drugs, particularly for the fetus, and whether maintaining relapse of the disease compensates for the potential risks of fetal exposure. The limited data available for the anti-TNF drugs to date have not demonstrated any significant adverse outcomes in the pregnant women who continued their therapy from conception to the first trimester of gestation. However, data suggest that antiTNFs should be discontinued during the third trimester, as they may affect the immunological system of the newborn baby. Each decision should be individualized, based on the distinct characteristics of the patient and her disease. Considering all the above, there is a need for more clinical studies regarding the effect of antiTNF therapeutic agents on pregnancy outcomes.

关键词： Anti-tumor necrosis factor Pregnancy Adverse effects Crohn's disease Ulcerative colitis Inflammatory bowel disease

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Abnormal DNA methylation as a cell-free circulating DNA biomarker for colorectal cancer detection:A review of literature

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World Journal of Gastrointestinal Oncology 2017年第4期9卷 142-152页

作者： Michail Galanopoulos Nikolaos Tsoukalas Ioannis S Papanikolaou maria Tolia maria gazouli Gerassimos J Mantzaris Department of Gastroenterology 'Evaggelismos-Ophthalmiatreion Athinon-Polycliniki' Department of Medical Oncology Veterans Hospital (417 NIMTS) Hepatogastroenterology Unit Second Department of Internal Medicine and Research InstituteAttikon University General HospitalMedical SchoolNational and Kapodistrian University of Athens Department of Radiotherapy/Radiation Oncology Faculty of MedicineSchool of Health SciencesUniversity of Thessaly Department of Basic Medical Sciences Laboratory of Biology Medical SchoolNational and Kapodistrian University of Athens

Colorectal cancer(CRC) is one of the most prevalent malignancies in the world. CRC-associated morbidity and mortality is continuously increasing, in part due to a lack of early detection. The existing screening tools such as colonoscopy, are invasive and yet high cost, affecting the willingness of patients to participate in screening programs. In recent years, evidence is accumulating that the interaction of aberrant genetic and epigenetic modifications is the cornerstone for the CRC development and progression by alternating the function of tumor suppressor genes, DNA repair genes and oncogenes of colonic cells. Apart from the understanding of the underlying mechanism(s) of carcinogenesis, the aforementioned interaction has also allowed identification of clinical biomarkers, especially epigenetic, for the early detection and prognosis of cancer patients. One of the ways to detect these epigenetic biomarkers is the cell-free circulating DNA(circ DNA), a blood-based cancer diagnostic test, mainly focusing in the molecular alterations found in tumor cells, such as DNA mutations and DNA *** this brief review, we epitomize the current knowledge on the research in circ DNA biomarkers-mainly focusing on DNA methylation-as potential blood-based tests for early detection of colorectal cancer and the challenges for validation and globally implementation of this emergent technology.

关键词： Colorectal cancer early detection Colorectal cancer screening Circulating free DNA Colorectal cancer blood-based biomarkers DNA methylation blood biomarkers

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