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Spontaneous and antiviral-induced cutaneous lesions in chronic hepatitis B virus infection

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World Journal of Gastroenterology 2014年第42期20卷 15860-15866页

作者： Ioana Grigorescu Dan Lucian Dumitrascu 2nd Department of internal medicine University of Medicine and Pharmacy "Iuliu Hatieganu"

AIM: To describe spontaneous, or interferon (IFN)- or immunization-induced skin lesions in hepatitis B virus (HBV) infection.

关键词： Hepatitis B Skin diseases Adverse effects Immunization

Issues and opportunities of stem cell therapy in autoimmune diseases

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World Journal of Stem Cells 2019年第4期11卷 212-221页

作者： Gy?rgyi M?zes Ferenc Sipos Immunology Team 2nd Department of Internal MedicineSemmelweis University

The purpose of regenerative medicine is to restore or enhance the normal function of human cells, tissues, and organs. From a clinical point of view, the use of stem cells is more advantageous than differentiated cells because they can be collected more easily and in larger quantities, their proliferation capacity is more pronounced, they are more resistant in cell culture, their aging is delayed, they are able to form a number of cell lines, and they are able to promote vascularization of tissue carriers. The therapeutic use of stem cells for disease modification, immunomodulation, or regenerative purposes are undoubtedly encouraging, but most studies are still in their early stages, and the clinical results reported are not clear with regard to therapeutic efficacy and potential side effects. Uniform regulation of the clinical application of stem cells is also indispensable for this highly customizable, minimally invasive, individualized therapeutic method to become a successful and safe treatment alternative in many different autoimmune and autoinflammatory disorders.

关键词： Stem cell therapy Autoimmune Autoinflammatory Immunomodulation Disease modification

Therapeutic aspects of c-MYC signaling in inflammatory and cancerous colonic diseases

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World Journal of Gastroenterology 2016年第35期22卷 7938-7950页

作者： Ferenc Sipos Gábor Firneisz Györgyi Mũzes 2nd Department of internal medicine Semmelweis UniversityH-1088 Budapest Hungary

Colonic inflammation is required to heal infections, wounds, and maintain tissue homeostasis. As the seventh hallmark of cancer, however, it may affect all phases of tumor development, including tumor initiation, promotion, invasion and metastatic dissemination, and also evasion immune surveillance. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability, and, further, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Both sporadical and colitis-associated colorectal carcinogenesis are multi-step, complex processes arising from the uncontrolled proliferation and spreading of malignantly transformed cell clones with the obvious ability to evade the host's protective immunity. In cells upon DNA damage several protooncogenes, including c-MYC are activated in parelell with the inactivation of tumor suppressor genes. The target genes of the c-MYC protein participate in different cellular functions, including cell cycle, survival, protein synthesis, cell adhesion, and microRNA expression. The transcriptional program regulated by c-MYC is context dependent, therefore the final cellular response to elevated c-MYC levels may range from increased proliferation to augmented apoptosis. Considering physiological intestinal homeostasis, c-MYC displays a fundamental role in the regulation of cell proliferation and crypt cell number. However, c-MYC gene is frequently deregulated in inflammation, and overexpressed in both sporadic and colitis-associated colon adenocarcinomas. Recent results demonstrated that endogenous c-MYC is essential for efficient induction of p53-dependent apoptosis following DNA damage, but c-MYC function is also involved in and regulated by autophagy-related mechanisms, while its expression is affected by DNA-methylation, or histone acetylation. Molecules directly targeting c-MYC, or agents acting on other genes involved in the c-MYC pathway could be sele

关键词： c-MYC Therapy Apoptosis Autophagy Colon Inflammation Colorectal cancer

Nonalcoholic fatty liver disease and polycystic ovary syndrome

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World Journal of Gastroenterology 2014年第26期20卷 8351-8363页

作者： Evangeline Vassilatou Endocrine Unit 2nd Department of Internal Medicine - Propaedeutic"Attikon" University Hospital

Nonalcoholic fatty liver disease(NAFLD)is the most common cause of chronic liver disease in the Western world comprising a spectrum of liver damage from fatty liver infiltration to end-stage liver disease,in patients without significant alcohol *** prevalence of NAFLD has been reported in patients with polycystic ovary syndrome(PCOS),one of the most common endocrinopathies in premenopausal women,which has been redefined as a reproductive and metabolic disorder after the recognition of the important role of insulin resistance in the pathophysiology of the ***,in particular central adiposity and insulin resistance are considered as the main factors related to NAFLD in ***,existing data support that androgen excess,which is the main feature of PCOS and is interrelated to insulin resistance,may be an additional contributing factor to the development of *** the natural history of NAFLD remains unclear and hepatic steatosis seems to be a relatively benign condition in most patients,limited data imply that advanced stage of liver disease is possibly more frequent in obese PCOS patients with *** patients,particularly obese patients with features of the metabolic syndrome,should be submitted to screening for NAFLD comprising assessment of serum aminotransferase levels and of hepatic steatosis by abdominal *** modifications including diet,weight loss and exercise are the most appropriate initial therapeutic interventions for PCOS patients with *** pharmacologic therapy is considered,metformin may be used,although currently there is no medical therapy of proven benefit for ***-term follow up studies are needed to clarify clinical implications and guide appropriate diagnostic evaluation,follow-up protocol and optimal treatment for PCOS patients with NAFLD.

关键词： Nonalcoholic fatty liver disease Polycystic ovary syndrome Insulin resistance Obesity Hyperandrogenism Premenopausal women

Intratumoral functional heterogeneity and chemotherapy

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World Journal of Gastroenterology 2014年第10期20卷 2429-2432页

作者： Ferenc Sipos Miklós Constantinovits Gyrgyi Müzes 2nd Department of internal medicine Semmelweis University 1088 Budapest Hungary

Intratumoral heterogeneity including genetic and nongenetic mechanisms refers to biological differences amongst malignant cells originated within the same ***,cell differentiation hierarchy and stochasticity in gene expression and signaling pathways may result in phenotypic differences of cancer *** a tumor consists of cancer cell clones that display distinct behaviours,changes in clonal proliferative behavior may also contribute to the phenotypic variability of tumor *** is a need to reveal molecular actions driving chemotherapeutic resistance in colon cancer *** general,it is widely hypothesized that therapeutic resistance in colorectal cancer is a consequence of the preferential survival of cancer stem ***,recent data regarding colorectal cancer suggest that resistance to anticancer therapy and post-therapeutic tumor reappearence could be related to variations of clonal *** the interaction of genetic and nongenetic determinants influencing the functional diversity and therapy response of tumors should be a future direction for cancer research.

关键词： Colorectal cancer Clonal dynamics Functional heterogeneity Chemotherapy Xenograft Oxaliplatin

Endoscopic hemostasis using self-expandable metal stent combinedwith PuraStat® for patient with high risk of post-endoscopicsphincterotomy bleeding (with video)

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Hepatobiliary & Pancreatic Diseases International 2024年第1期23卷 94-96页

作者： Takeshi Ogura Yuki Uba Masahiro Yamamura Nobu Nishioka Hiroki Nishikawa 2nd Department of internal medicine Osaka Medical and Pharmaceutical UniversityOsakaJapan

To the Editor:Endoscopic sphincterotomy(EST)is an established technique for removal of bile duct stones and self-expandable metal stent(SEMS)***,bleeding can be considered an adverse event after EST,particularly for patients with high risk of bleeding such as those on *** the various techniques reported for obtaining endoscopic hemostasis[1-3].

关键词： bleeding stasis endoscopic

Interplay of autophagy and innate immunity in Crohn's disease: A key immunobiologic feature

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World Journal of Gastroenterology 2013年第28期19卷 4447-4454页

作者： Gyrgyi Müzes Zsolt Tulassay Ferenc Sipos 2nd Department of internal medicine Semmelweis University 1088 Budapest Hungary

Crohn's disease representing a clinical phenotype of inflammatory bowel disease is a polygenic immune disorder with complex multifactor etiology. Recent genome-wide association studies of susceptibility loci have highlighted on the importance of the autophagy pathway, which previously had not been implicated in disease pathology. Autophagy represents an evolutionarily highly conserved multi-step process of cellular self-digestion due to sequestration of excessive, damaged, or aged proteins and intracellular organelles in double-membranous vesicles of autophagosomes, terminally self-digested in lysosomes. Autophagy is deeply involved in regulation of cell development and differentiation, survival and senescence, and it also fundamentally affects the inflammatory pathways, as well as the innate and adaptive arms of immune responses. Autophagy is mainly activated due to sensors of the innate immunity, i.e., by pattern recognition receptor signaling. The interplay of genes regulating immune functions is strongly influenced by the environment, especially gut resident microbiota. The basic challenge for intestinal immune recognition is the requirement of a simultaneous delicate balance between tolerance and responsiveness towards microbes. On the basis of autophagy-related risk genetic polymorphisms (ATG16L1, IRGM , NOD2 , XBP1 ) impaired sensing and handling of intracellular bacteria by innate immunity, closely interrelated with the autophagic and unfolded protein pathways seem to be the most relevant immunobiologic events. Autophagy is now widely considered as a key regulator mechanism with the capacity to integrate several aspects of Crohn's disease pathogenesis. In this review, recent advances in the exciting crosstalk of susceptibility coding variants-related autophagy and innate immunity are discussed.

关键词： Crohn’s disease Innate immunity Autophagy genes Autophagy Gut microbiota

Endoscopic treatment and follow-up of gastrointestinal Dieulafoy's lesions

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World Journal of Gastroenterology 2005年第38期11卷 6022-6026页

作者： Panagiotis Katsinelos George Paroutoglou Kostas Mimidis Athanasios Beltsis Basilios Papaziogas George Gelas Yiannis Kountouras Department of Endoscopy and Motility Unit 2nd Surgical clinic 2nd Department of internal medicine

AIM: To investigate retrospectively the clinical and endoscopic features of bleeding Dieulafoy's lesions and to assess the short- and long-term effectiveness of endoscopic ***: Twenty-three patients who had gastrointestinal bleeding from Dieulafoy's lesions underwent endoscopic therapy. Demographic data, mode of presentation, riskfactors for gastrointestinal bleeding, blood transfusion requirements, endoscopic findings, details of endoscopic therapy, recurrence of bleeding, and mortality rates were collected and analyzed ***: Hemostasis was attempted by dextrose 50% plus epinephrine in 10 patients, hemoclipping in 8 patients,heater probe in 2 patients and ethanolamine oleate in 2 patients. Comorbid conditions were present in 17 patients (74%). Overall permanent hemostasis was achieved in 18 patients (78%). Initial hemostasis was successful with no recurrent bleeding in patients treated with hemoclipping, heater probe or ethanolamine injection. In the group of patients who received dextrose 50% plus epinephrine injection treatment, four (40%) had recurrent bleeding and one (10%) had unsuccessful initial *** the four patients who had rebleeding, three had unsuccessful hemostasis with similar treatment. Surgical treatment was required in five patients (22%) owing to uncontrolled bleeding, recurrent bleeding with unsuccessful retreatment and inability to approach the lesion. One patient (4.3%) died of sepsis after operation during hospitalization. There were no side-effects related to endoscopic therapy. None of the patients in whom permanent hemostasis was achieved presented with rebleeding from Dieulafoy's lesion over a mean long-term follow-up of 29.8 ***: Bleeding from Dieulafoy's lesions can be managed successfully by endoscopic methods, which should be regarded as the first choice. Endoscopic hemoclipping therapy is recommended for bleeding Dieulafoy's lesions.

关键词： Endoscopic treatment Dieulafoy lesion Gastrointestinal tract

Pharmacotherapy for Non-alcoholic Fatty Liver Disease Associated with Diabetes Mellitus Type 2

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Journal of clinical and Translational Hepatology 2022年第5期10卷 965-971页

作者： Emmanouil S.Koullias John Koskinas 2nd Department of internal medicine National and Kapodistrian University of AthensHippokration General HospitalAthensGreece

Non-alcoholic fatty liver disease(NAFLD)and diabetes mellitus type 2 commonly coexist as a manifestation of metabolic *** presence of diabetes promotes the progression of simple fatty liver to non-alcoholic steatohepatitis(NASH)and cirrhosis,and the presence of NAFLD increases the risk of diabetic *** coexistence affects a large part of the population,imposing a great burden on health care systems *** from diet modification and exercise,recent advances in the pharmacotherapy of diabetes offer new prospects regarding liver steatosis and steatohepatitis improvement,enriching the existing algorithm and supporting a multifaceted approach to diabetic patients with fatty liver *** agents mainly include members of the families of glucagon-like peptide-1 analogues and the sodium-glucose co-transporter-2 *** addition,agents acting on more than one receptor simultaneously are presently under study,in an attempt to further enhance our available options.

关键词： NAFLD/NASH Diabetes mellitus type 2 Steatosis SGLT2 GLP1