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Therapeutic Perspectives of IL1 Family Members in Liver Diseases:An Update

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Journal of Clinical and Translational Hepatology 2022年第6期10卷 1186-1193页

作者： Ines Bilić Ćurčić Tomislav Kizivat Ana Petrović Robert Smolić Ashraf Tabll George Y.Wu Martina Smolić Faculty of Medicine osijek University of OsijekOsijekCroatia University Hospital osijek OsijekCroatia Faculty of Den-tal Medicine and health osijek University of OsijekOsijekCroatia National Research center GizaEgypt Egypt center for Research and Regenerative Medicine(ECRRM) CairoEgypt University of Connecticut health center FarmingtonCTUSA

Interleukin(IL)1 superfamily members are a cornerstone of a variety of inflammatory processes occurring in various organs including the *** of acute and chronic liver diseases regardless of etiology depends on the stage of hepatocyte damage,the release of inflammatory cytokines and disturbances in gut ***1 cytokines and re-ceptors can have pro-or anti-inflammatory roles,even dual functionalities conditioned by the ***-oping novel therapeutic strategies to block the IL1/IL1R sign-aling pathways seems like a reasonable *** mode of action is now exploited by anakinra and canakinumab,which are used to treat different inflammatory illnesses,and studies in liver diseases are on the *** this mini review,we have focused on the IL1 superfamily members,given their cru-cial role in liver inflammation diseases,specifically discussing their potential role in developing new treatment strategies.

关键词： Interleukin 1 superfamily members Inflammation Acute liver dis-ease Chronic liver disease Therapy

Noninvasive Fibrosis Assessment in Chronic Hepatitis C Infection: An Update

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Journal of Clinical and Translational Hepatology 2023年第5期11卷 1228-1238页

作者： Kristina Bojanic Mirta Sudaric Bogojevic Sonja Vukadin Renata Sikora Gordana Ivanac Nikola Raguz Lucic Martina Smolic Ashraf ATabll George YWu Robert Smolic Faculty of Dental Medicine and health osijek Josip Juraj Strossmayer University of OsijekOsijekCroatia Faculty of Medicine osijek Josip Juraj Strossmayer University of OsijekOsijekCroatia health center osijek-Baranja County OsijekCroatia Department of Biology Josip Juraj Strossmayer University of OsijekOsijekCroatia University Hospital Dubrava ZagrebCroatia School of Medicine University of ZagrebZagrebCroatia Microbial Biotechnology Department Biotechnology Research InstituteNational Research CenterGizaEgypt Egypt center for Research and Regenerative Medicine(ECRRM) CairoEgypt University of Connecticut health center FarmingtonCTUSA

Liver biopsy is historically the gold standard for liver fibrosis assessment of chronic hepatitis C ***,with the introduction and validation of noninvasive tests(NITs)to evaluate advanced fibrosis,and the direct-acting antiviral agents for treatment of chronic hepatitis C virus(HCV),the role of NITs have become even more *** is now need for longitudinal monitoring and elucidation of cutoff values for prediction of liver-related complication after sustained virological *** aim of this report is to provide a critical overview of the various NITs available for the assessment of liver fibrosis in HCV patients.

关键词： Hepatitis C virus Fibrosis Noninvasive serum fibrosis markers Transient elastography Shear wave elastography Magnetic resonance elastography Steatohepatitis

Anabolic androgenic steroid-induced liver injury:An update

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World Journal of Gastroenterology 2022年第26期28卷 3071-3080页

作者： Ana Petrovic Sonja Vukadin Renata Sikora Kristina Bojanic Robert Smolic Davor Plavec George Y Wu Martina Smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Dental Medicine Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Dental Medicine Health Center Osijek-Baranja CountyOsijek 31000Croatia Department of Otorhinolaryngology Neurosurgery and RadiologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijek 31000Croatia Department of Radiology Health Center Osijek-Baranja CountyOsijek 31000Croatia Research Department Srebrnjak Children's HospitalZagreb 10000Croatia Department of Medicine Division of Gastrenterology/HepatologyUniversity of Connecticut Health CenterFarmingtonCT 06030United States

Anabolic androgenic steroids(AASs)are a group of molecules including endogenous testosterone and synthetic derivatives that have both androgenic and anabolic *** properties make them therapeutically beneficial in medical conditions such as ***,they are commonly bought illegally and misused for their anabolic,skeletal muscle building,and performanceenhancing *** and long-term use of AASs affects all organs,leading to cardiovascular,neurological,endocrine,gastrointestinal,renal,and hematologic *** is one of the major concerns regarding AASs treatment and *** and its derivatives have been most often shown to induce a specific form of cholestasis,peliosis hepatis,and hepatic benign and malignant *** is currently believed that mechanisms of pathogenesis of these disorders include disturbance of antioxidative factors,upregulation of bile acid synthesis,and induction of hepatocyte *** toxicity cases are treated with supportive measures and liver function normalizes with discontinuation of ***,some long-term consequences are ***-induced liver injury should be taken in consideration in patients with liver disorders,especially with the increasing unintentional ingestion of supplements containing *** this paper,we review the most current knowledge about AAS-associated adverse effects on the liver,and their clinical presentations,prevalence,and pathophysiological mechanisms.

关键词： Androgens Steroids Cholestasis Fibrosis Liver Chemical and drug induced liver injury

Mechanisms of Hepatic Cholestatic Drug Injury

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Journal of Clinical and Translational Hepatology 2019年第1期7卷 86-92页

作者： Tea Omanovic Kolaric Vjera Nincevic Robert Smolic Martina Smolic George Y Wu Department of Pharmacology Faculty of Medicine OsijekOsijekCroatia Department of Pharmacology Faculty of Dental Medicine and HealthOsijekCroatia Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Drug-induced cholestasis represents a form of drug-induced liver disease that can lead to severe impairment of liver *** drugs have been shown to cause cholestasis and consequently bile duct ***,there is still lack of therapeutic tools that can prevent progression to advanced stages of liver *** review focuses on the various pathological mechanisms by which drugs expresstheir hepatotoxic effects,as well as consequences of increased bile acid and toxin accumulation in the hepatocytes.

关键词： Drug-induced liver injury Bile acids Cholestasis

An Update on Efficacy and Safety of Emerging Hepatic Antifibrotic Agents

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Journal of Clinical and Translational Hepatology 2021年第1期9卷 60-70页

作者： Vinka Rupcic Rubin Kristina Bojanic Martina Smolic Jurica Rubin Ashraf Tabll Robert Smolic Department of Gynaecology and Obstetrics Osijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Radiology Health Center OsijekOsijekCroatia Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of Gastroenterology/HepatologyUniversity Hospital OsijekOsijekCroatia Microbial Biotechnology Department Genetic Engineering and Biotechnology Research DivisionNational Research CentreDokkiEgypt Department of immunology Egypt Center for Research and RegenerativeMedicine(ECRRM)CairoEgypt Department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia

Liver fibrosis represents a response to chronic liver *** dysfunction-associated fatty liver disease and metabolic dysfunction-associated steatohepatitis are the most common chronic liver diseases,both with increasing ***,there is a great impetus for development of agents targeting these *** data on possible treatment options for liver fibrosis are emerging in the ***,despite extensive research and much effort in the field,approved agents for liver fibrosis are still *** this critical review,we have summarized the main data about specific treatment options for liver fibrosis gained from ongoing clinical trials,with an emphasis on efficacy and safety of these agents.

关键词： Liver fibrosis MAFLD MASH Clinical trials Antifibrotic agents Efficacy Safety

Targeting the Wnt Signaling Pathway in Liver Fibrosis for Drug Options:An Update

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Journal of Clinical and Translational Hepatology 2021年第6期9卷 960-971页

作者： Kristina Duspara Kristina Bojanic Josipa Ivanusic Pejic Lucija Kuna Tea Omanovic Kolaric Vjera Nincevic Robert Smolic Aleksandar Vcev Marija Glasnovic Ines Bilic Curcic Martina Smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Biophysics and Radiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Radiology Health Center OsijekOsijekCroatia Department of Medi-cine Division of Gastroenterology/HepatologyUniversity Hospital OsijekOsijekCroatia Department of Pathophysiology Physiology and ImmunologyFaculty of Dental Medicine and Health OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Family Medicine and History of MedicineFaculty of Medicine OsijekJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of EndocrinologyUniversity Hospital OsijekOsijekCroatia

morbidity and mortality for healthcare systems *** imparts an enormous economic burden to societies,making continuous research and informational updates about its pathogenesis and treatment *** review′s focus is on the current knowledge about the Wnt signaling path-way,serving as an important pathway in liver fibrosis development and activation of hepatic stellate cells(HSCs).Two types of Wnt pathways are distinguished,namely the ß-catenin-dependent canonical and non-canonical Ca^(2+) or planar cell polarity(PCP)-dependent *** dynamic balance of physiologically healthy liver and hepatocytes is disturbed by repeated liver *** of theß-catenin Wnt pathway prevents the regeneration of hepatocytes by the replacement of extracellular matrix(ECM),leading to the appearance of scar tissue and the formation of regenerated nodular hepatocytes,lacking the original function of healthy ***,liver function is reduced due to the severely advanced *** inhibition ofß-catenin inhibits inflammatory processes(since chemokines and pro-inflammatory cytokines are produced during Wnt activation),reduces growth of activated HSCs and reduces collagen synthesis and angiogenesis,thereby reducing the progression of liver fibrosis in *** the canonical Wnt pathway is usually inactive in a physiologically healthy liver,it shows activity during cell regeneration or renewal and in certain pathophysiological conditions,such as liver diseases and *** blocking of some of the basic components of the Wnt path-way is a therapeutic *** include the frizzled transmembrane receptor(Fz)receptors using the secreted frizzled-related protein family(sFRP),Fz-coreceptors low-density LRP 5/6 through dickkopf-related protein 1(DKK1)or niclosamide,glycogen kinase-3 beta(GSK-3β)using SB-216763,cyclic-AMP response element-binding protein(CBP)using PRI-724 and ICG-001,the lymphoid enhancer binding factor(LEF)/T cell-spec

关键词： Liver fibrosis Wnt signaling pathway Hepatic stellate cell Therapeutic solutions

HCV Extrahepatic Manifestations

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Journal of Clinical and Translational Hepatology 2019年第2期7卷 172-182页

作者： Lucija Kuna Jelena Jakab Robert Smolic George Y Wu Martina Smolic Department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology and Physiology with Immunology Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department of Internal Medicine Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Pharmacology Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Medicine Division of Gastroenterology-HepatologyUniversity of Connecticut Health CenterFarmingtonCTUSA

Hepatitis C virus(HCV)has been shown to affect many tissues other than ***,of the many extrahepatic manifestations(EMs)that have been associated with HCV,including cryoglobulinemia,lymphoma,insulin resistance,type 2 diabetes and neurological disorders,only a few have been shown to be directly related to HCV infection of extrahepatic ***-triggered immune-mediated mechanisms account for most of the *** is estimated that up to 74%of patients with chronic hepatitis C can develop at least one *** HCV patients with EMs should be considered for antiviral therapy,although not all will resolve with sustained virological response.

关键词： Hepatitis C virus Hepatic stellate cells B cell lymphomas pancreatic B cell TGF-β-dependent signaling pathway Extrahepatic manifestations Direct-acting antivirals

Understanding the multifaceted etiopathogenesis of foot complications in individuals with diabetes

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World Journal of Clinical Cases 2023年第8期11卷 1669-1683页

作者： Tatjana Matijević Jasminka Talapko Tomislav Meštrović Marijan Matijević Suzana Erić Ivan Erić IvanaŠkrlec Department of Dermatology and Venereology University Hospital Center OsijekOsijek 31000Croatia Faculty of Dental Medicine and health Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia University Centre Varaždin University NorthVaraždin 42000Croatia Institute for health Metrics and Evaluation and the Department for health Metrics Sciences University of Washington School of MedicineSeattleWA 98195United States Department of Surgery National Memorial Hospital VukovarVukovar 32000Croatia Faculty of Medicine Josip Juraj Strossmayer University of OsijekOsijek 31000Croatia Department of Radiotherapy and Oncology Clinical Hospital Center OsijekOsijek 31000Croatia Department of Surgery Osijek University Hospital CentreOsijek 31000Croatia

Diabetes mellitus,a chronic disease of metabolism,is characterized by a disordered production or cellular utilization of *** foot disease,which comprises the spectrum of infection,ulceration,and gangrene,is one of the most severe complications of diabetes and is the most common cause of hospitalization in diabetic *** aim of this study is to provide an evidence-based overview of diabetic foot *** to neuropathy,diabetic foot infections can occur in the form of ulcers and minor skin *** patients with diabetic foot ulcers,ischemia and infection are the main causes of non-healing ulcers and *** compromises the immune system of individuals with diabetes,leading to persistent inflammation and delayed wound *** addition,the treatment of diabetic foot infections is challenging due to difficulty in accurate identification of pathogenic microorganisms and the widespread issue of antimicrobial *** a further complicating factor,the warning signs and symptoms of diabetic foot problems can easily be *** associated with diabetic foot complications include peripheral arterial disease and osteomyelitis;accordingly,the risk of these complications in people with diabetes should be assessed *** antimicrobial agents represent the mainstay of treatment for diabetic foot infections,if peripheral arterial disease is present,revascularization should be considered to prevent limb amputation.A multidisciplinary approach to the prevention,diagnosis,and treatment of diabetic patients,including those with foot ulcers,is of the utmost importance to reduce the cost of treatment and avoid major adverse consequences such as amputation.

关键词： Diabetic foot Diabetes mellitus Foot ulcer Infection Peripheral arterial disease

Obesity Paradox in Chronic Liver Diseases:Product of Bias or a Real Thing?

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Journal of Clinical and Translational Hepatology 2019年第3期7卷 275-279页

作者： Ines Bilic Curcic Maja Cigrovski Berkovic Lucija Kuna Hrvoje Roguljic Robert Smolic Silvija Canecki Varzic Lucija Virovic Jukic Martina Smolic Department of Pharmacology Faculty of MedicineJ.J.Strossmayer University of OsijekOsijekCroatia Department of Diabetes Endocrinology and Metabolism DisordersOsijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department for Endocrinology Diabetes and Metabolism University Hospital Center"Sestre Milosrdnice"ZagrebCroatia Department of Pharmacology and Biochemistry Faculty of Dental Medicine and HealthJ.J.Strossmayer University of OsijekOsijekCroatia Department for Cardiovascular Disease Osijek University HospitalOsijekCroatia Department of Gastroenterology and Hepatology Osijek University Hospital CentreFaculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Pathophysiology Faculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Internal Medicine Faculty of MedicineJosip Juraj Strossmayer University of OsijekOsijekCroatia Department of Gastroenterology and Hepatology Sisters of Mercy University HospitalUniversity of Zagreb School of MedicineZagrebCroatia Department of Pharmacology J.J.Stross-mayer University of Osijek Faculty of Medicine OsijekJ.Huttlera 4Osijek 31000Croatia

In recent years,evidence supporting the theory of obesity paradox has increased,showing that obese/overweight people with prevalent chronic diseases experience lower mortality compared with patients of normal *** far,evidence is most comprehensive in cardiovascular and chronic renal diseases;however,published studies are prone to many biases,enabling us to reach a definite *** data in chronic liver disease is scarce and *** is traditionally associated with nonalcoholic fatty liver disease and steatosis in viral hepatitis and as such one would not expect the obesity paradox to be a real possibility in liver ***,there seem to be new data indicating the opposite-the obesity paradox exists in severe and end-stage liver cirrhosis,which could be attributed to a better lean mass in patients with higher body mass index,meaning that sarcopenia,as one of the most important prognostic factors of survival,is less likely to be ***,the problem of various methodological problems addressing the association between body weight and mortality,which is present both in liver disease and other chronic diseases,are preventing us from attaining an unanimous ***,we should be aware that the obesity paradox might be true,especially in severe and end-stage *** suggests focusing our efforts toward preserving or building up fat-free mass and decreasing infiammatory activity responsible for catabolism and sarcopenia,and implying that the underlaying cause should be treated.

关键词： Obesity paradox Chronic liver disease NAFLD NASH Cirrhosis