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Glucagon-like peptide 1 agonists are potentially useful drugs for treating metabolic dysfunction-associated steatotic liver disease

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World Journal of Gastroenterology 2024年第30期30卷 3541-3547页

作者： Maurizio Soresi lydia giannitrapani Department of Health Promotion Sciences Maternal and Infant CareInternal Medicine and Medical Specialties(PROMISE)University of PalermoPalermo 90127Italy

In this editorial,we comment on Yin et al’s recently published Letter to the *** particular,we focus on the potential use of glucagon-like peptide 1 receptor agonists(GLP-1RAs)alone,but even more so in combination therapy,as one of the most promising therapies in metabolic dysfunction-associated steatotic liver disease(MASLD),the new definition of an old condition,non-alcoholic fatty liver disease,which aims to better define the spectrum of steatotic *** is well known that GLP-1RAs,having shown outstanding performance in fat loss,weight loss,and improvement of insulin resistance,could play a role in protecting the liver from progressive *** clinical trials have shown that,among GLP-1RAs,semaglutide is a safe,well-studied therapeutic choice for MASLD patients;however,most studies demonstrate that,while semaglutide can reduce steatosis,including steatohepatitis histological signs(in terms of inflammatory cell infiltration and hepatocyte ballooning),it does not improve *** of therapies with different but complementary mechanisms of action are considered the best way to improve efficiency and slow disease progression due to the complex pathophysiology of the *** particular,GLP-1RAs associated with antifibrotic drug therapy,dual glucose-dependent insulinotropic polypeptide(GIP)/GLP-1RA or GLP-1 and glucagon RAs have promoted greater improvement in hepatic steatosis,liver biochemistry,and non-invasive fibrosis tests than ***,although to date there are no definitive indications from international drug agencies,there is the hope that soon the therapeutic lines in the most advanced phase of study will be able to provide a therapy for MASLD,one that will certainly include the use of GLP-1RAs as combination therapy.

关键词： Non-alcoholic fatty liver disease Glucagon-like peptide 1 Semaglutide Liver fibrosis Therapy

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Non invasive tools for the diagnosis of liver cirrhosis

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World Journal of Gastroenterology 2014年第48期20卷 18131-18150页

作者： Maurizio Soresi lydia giannitrapani Melchiorre Cervello Anna Licata Giuseppe Montalto Unit of Internal Medicine Biomedical Department of Internal Medicine and Specialties Di Bi MIS University of Palermo 90127 Palermo Italy Institute of Biomedicine and Molecular Immunology "A. Monroy" National Research Council (CNR) 90146 Palermo Italy

Liver cirrhosis(LC),the end stage of many forms of chronic hepatitis of different etiologies is a diffuse process characterized by fibrosis and the conversion of normal liver architecture into structurally abnormal nodules surrounded by annular *** chronic progressive clinical condition,leads to liver cell failure and portal hypertension,which can favour the onset of hepatocellular *** the phase of the natural history is crucial for therapeutic choice and *** biopsy is currently considered the best available standard of reference but it has some limits,so alternative tools have been developed to substitute liver biopsy when assessing liver *** markers offer a cost-effective alternative to liver biopsy being less invasive and theoretically without *** can be classified into direct and indirect markers which may be used alone or in combination to produce composite *** imaging includes a number of instruments and techniques to estimate liver fibrosis and cirrhosis like ultrasound(US),US Doppler,contrast enhanced US *** could be used for the diagnosis of advanced LC while is not able to evaluate progression of fibrosis,in this case Elastography is more *** review aims to revise the most recent data from the literature about non invasive methods useful in defining liver fibrosis.

关键词： Liver fibrosis Liver biopsy Ultrasound Elastography Serum markers

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Genetic association of interleukin-6 polymorphism (-174 G/C) with chronic liver diseases and hepatocellular carcinoma

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World Journal of Gastroenterology 2013年第16期19卷 2449-2455页

作者： lydia giannitrapani Maurizio Soresi Daniele Balasus Anna Licata Giuseppe Montalto Unit of Internal Medicine Biomedical Department of Internal Medicine and Specialties DiBiMIS University of Palermo

Interleukin-6 (IL-6) is a pleiotropic cytokine which is expressed in many inflammatory cells in response to different types of stimuli, regulating a number of biological processes. The IL-6 gene is polymorphic in both the 5' and 3' flanking regions and more than 150 single nucleotide polymorphisms have been identified so far. Genetic polymorphisms of IL-6 may affect the outcomes of several diseases, where the presence of high levels of circulating IL-6 have been correlated to the stage and/or the progression of the disease itself. The -174 G/C polymorphism is a frequent polymorphism, that is located in the upstream regulatory region of the IL-6 gene and affects IL-6 production. However, the data in the literature on the genetic association between the -174 G/C polymorphism and some specific liver diseases characterized by different etiologies are still controversial. In particular, most of the studies are quite unanimous in describing a correlation between the presence of the high-producer genotype and a worse evolution of the chronic liver disease. This is valid for patients with hepatitis C virus (HCV)-related chronic hepatitis and liver cirrhosis and hepatocellu-lar carcinoma (HCC) whatever the etiology. Studies in hepatitis B virus-related chronic liver diseases are not conclusive, while specific populations like non alcoholic fatty liver disease/non-alcoholic steatohepatitis, autoimmune and human immunodeficiency virus/HCV coinfected patients show a higher prevalence of the lowproducer genotype, probably due to the complexity of these clinical pictures. In this direction, a systematic revision of these data should shed more light on the role of this polymorphism in chronic liver diseases and HCC.

关键词： Single nucleotide polymorphisms Interleukin-6 Chronic hepatitis Liver cirrhosis Hepatocellular carcinoma

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Nanotechnology applications for the therapy of liver fibrosis

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World Journal of Gastroenterology 2014年第23期20卷 7242-7251页

作者： lydia giannitrapani Maurizio Soresi Maria Luisa Bondì Giuseppe Montalto Melchiorre Cervello Unit of Internal Medicine Biomedical Department of Internal Medicine and Specialties DiBiMISUniversity of Palermo90127 PalermoItaly Institute for Nanostructured Materials Studies National Research Council (CNR)90146 PalermoItaly Institute of Biomedicine and Molecular Immunology "A.Monroy" National Research Council (CNR)90146 PalermoItaly

Chronic liver diseases represent a major global health problem both for their high prevalence worldwide and,in the more advanced stages,for the limited available curative treatment *** fact,when lesions of different etiologies chronically affect the liver,triggering the fibrogenesis mechanisms,damage has already occurred and the progression of fibrosis will have a major clinical impact entailing severe complications,expensive treatments and death in end-stage liver *** significant advances in the understanding of the mechanisms of liver fibrinogenesis,the drugs used in liver fibrosis treatment still have a limited therapeutic *** drugs showing potent antifibrotic activities in vitro often exhibit only minor effects in vivo because insufficient concentrations accumulate around the target cell and adverse effects result as other non-target cells are *** stellate cells play a critical role in liver fibrogenesis,thus they are the target cells of antifibrotic *** application of nanoparticles has emerged as a rapidly evolving area for the safe delivery of various therapeutic agents(including drugs and nucleic acid)in the treatment of various pathologies,including liver *** this review,we give an overview of the various nanotechnology approaches used in the treatment of liver fibrosis.

关键词： Liver fibrosis Nanotechnology Nanoparticles Hepatic stellate cells Antifibrotic drugs Cirrhosis

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Interleukin-6 and its soluble receptor in patients with liver cirrhosis and hepatocellular carcinoma

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World Journal of Gastroenterology 2006年第16期12卷 2563-2568页

作者： Soresi Maurizio giannitrapani lydia D'Antona Fabio Florena Ada Maria La Spada Emanuele Terranova Angela Cervello Melchiorre D'Alessandro Natale Montalto Giuseppe Dipartimento di Medicina Clinica e delle Patologie Emergenti Policlinico UniversitarioPalermoItaly Istituto di Anatomia ed Istologia Patologica Policlinico UniversitarioPalermoItaly Istituto di Biomedicina ed Immunologia Molecolare C.N.R.PalermoItaly Dipartimento di Scienze Farmacologiche Pohclinico UniversitarioPalermoItaly

AIM： To evaluate the immunohistochemical localization of interleukin-6 （IL-6） and IL-6 receptor （IL-6R） on tumor tissue specimens from patients with hepatocellular carcinoma （HCC） and the serum levels of IL-6 and sIL-6R in a group of patients with HCC as well as liver cirrhosis （LC） in a group of patients with LC alone and in a control group. METHODS： Three groups of subjects were studied： group Ⅰ （n =83） suffering from HCC and LC, group Ⅱ （n = 72） suffering from LC alone and group Ⅲ （n =42） as healthy controls. All patients had hepatitis C virus infection. Serum IL-6 and IL-6R levels were determined using a commercially available ELISA kit. Immunohistochemistry was performed using the streptavidin-biotin complex and rabbit polyclonal antibodies against IL-6 and IL-6R. RESULTS： Immunohistochemistry analysis showed a medium to strong cytoplasmic and membrane reactivity for IL-6 and IL-6R respectively, in at least 40% of cases of HCC, whereas liver cirrhosis patients and controls were negative for IL-6 or showed a very mild and focal dot-like cytoplasmic reaction for IL-6R. Serum IL-6 levels in HCC group were significantly higher than those in LC and control groups （P〈 0.0001）. There was no significant difference in sIL-6R concentrations among 3 groups. When the patients with HCC were divided into groups according to Okuda＇s classification, a significant serum increase of IL-6 and slL-6R level was observed from stage Ⅰ to stage Ⅲ （P〈0.02, P〈0.0005）. When HCC and LC patients were divided into 3 classes of cirrhosis severity according to Child-Pugh, values in HCC patients were significantly higher than those in LC patients for each corresponding class （P〈 0.01）. CONCLUSION： IL-6 serum levels in HCC patients are higher than those in LC patients and controls, suggesting an increased production of this cytokine by neoplastic cells, sIL-6R values are similar in all groups, increasing only in stage III HCC patients. These data suggest that they have a closer relationship wit

关键词： Interleukin-6 Cytokine Chronic liver disease Immunohistochemistry

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Magnetic resonance imaging of the cirrhotic liver in the eraof gadoxetic acid

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World Journal of Gastroenterology 2016年第1期22卷 103-111页

作者： Francesco Agnello Marco Dioguardi Burgio Dario Picone Federica Vernuccio Giuseppe Cabibbo lydia giannitrapani Adele Taibbi Antonino Agrusa Tommaso Vincenzo Bartolotta Massimo Galia Roberto Lagalla Massimo Midiri Giuseppe Brancatelli Section of Radiological Sciences DIBIMEDUniversity of Palermo90127 PalermoItaly Section of Gastroenterology DIBIMISUniversity of Palermo90127 PalermoItaly Section of Internal Medicine DIBIMISUniversity of Palermo90127 PalermoItaly Department of General Surgery Urgencyand Organ TransplantationUniversity of Palermo90127 PalermoItaly

Gadoxetic acid improves detection and characterization of focal liver lesions in cirrhotic patients and can estimate liver function in patients undergoing liver *** purpose of this article is to describe the optimal gadoxetic acid study protocol for the liver,the unique characteristics of gadoxetic acid,the differences between gadoxetic acid and extra-cellular gadolium chelates,and the differences in phases of enhancement between cirrhotic and normal liver using gadoxetic *** also discuss how to obtain and recognize an adequate hepatobiliary phase.

关键词： Hepatobiliary contrast materials Gadoxeticacid Cirrhosis Magnetic resonance imaging Liver

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Architecture of Collaborating Frameworks：Simulation,Visualisation,User Interface and Analysis

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International Conference on Computing in High Energy and Nuclear Physics 2001年第1期 518-521页

作者： A.Pfeiffer R.giannitrapani 等 CERN，Geneva Switzerland UniversitadiUdineandINFNsezionediTrieste Italy

In modern high energy and astrophysics experiments the variety of user requirements and the complexity of the problem domain often involve the collaboration of several software frameworks,and different components are responsible for providing the functionalities related to each *** instance,a common use case consists in studying the physics effects and the detector performance,resulting from primary events,in a given detector configuration,to evaluate the physics reach of the experiment or optimise the detector design,Such a study typically involves various components:simulation,Visualisation,Analysis and (interactive)User *** focus on the design aspects of the collaboration of these frameworks and on the technologies that help to simplify the complex process of software design.

关键词：软件开发高能物理实验天文物理实验

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