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An update on the role of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways in pediatric diseases

World Journal of Pediatrics 2019年第1期15卷 4-11页

作者： Giacomina Brunetti Gabriele D'Amato Mariancgela Chiarito Apollonia Tullo Graziana Colaianni Silvia Colucci Maria Grano Maria Felicia Faienza Section of Human Anatomy and Histology Department of Basic Medical SciencesNeuroscience and Sense Organs.University"A.Moro”of Bari.Piazza G.Cesare 11 70124 BariItaly Neonatal Intensive Care Unit Di Venere HospitalBariItaly Pediatric Section Department of Biomedical Sciences and Human Oncology.University"A.Moro”of BariPiazza G.Cesare 1 170124 BariItaly Institute of Biomembranes Bioenergetics and Molecular Biotechnologies—IBIOMCNR70126 BariItaly department of Emergency and Organ transplantation University“A.Moro”of Bari.Bari.Italy

Background Bone remodeling is a lifelong process due to the balanced activity of osteoclasts (OCs),the bone-reabsorbing cells,and osteoblasts (OBs),and the bone-forming *** equilibrium is regulated by numerous cytokines,but it has been largely demonstrated that the RANK/RANKL/osteoprotegerin and Wnt/β-catenin pathways play a key role in the control of osteoclastogenesis and osteoblastogenesis,*** pro-osteoblastogenic activity of the Wnt/β-catenin can be inhibited by sclerostin and Dickkopf-1 (DKK-1).RANKL,sclerostin and DKKs-1 are often up-regulated in bone diseases,and they are the target of new monoclonal *** sources The authors performed a systematic literature search in PubMed and EMBASE to June 2018,reviewed and selected articles,based on pre-determined selection *** We re-evaluated the role of RANKL,osteoprotegerin,sclerostin and DKK-1 in altered bone remodeling associated with some inherited and acquired pediatric diseases,such as type 1 diabetes mellitus (T1DM),alkaptonuria (AKU),hemophilia A,osteogenesis imperfecta (OI),21-hydroxylase deficiency (21 OH-D) and Prader-Willi syndrome (PWS).To do so,we considered recent clinical studies done on pediatric patients in which the roles of RANKL-RANK/osteoprotegerin and WNT-β-catenin signaling pathways have been investigated,and for which innovative therapies for the treatment of osteopenia/osteoporosis are being *** The case studies taken into account for this review demonstrated that quite frequently both bone reabsorbing and bone deposition are impaired in pediatric ***,for some of them,bone damage began in childhood but only manifested with *** use of denosumab could represent a valid alternative therapeutic approach to improve bone health in children,although further studies need to be carried out.

关键词： RANKL-RANK/Osteoprotegerin WNT-β-catenin signaling Pediatric diseases

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Cochlear stem cell transplantation for hearing recovery in a rat model of sensorineural hearing loss

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Neural Regeneration Research 2010年第11期5卷 833-837页

作者： Hongyan Zheng Haoqing Tai Shuilin Zeng department of Anatomy Nanjing University of Traditional Chinese Medicine Nanjing 210029 Jiangsu Province China Institute of Neurobiology Southeast University Medical School Nanjing 210009 Jiangsu Province China

BACKGROUND： transplantation of in vitro, cultured, neural stem cells or bone marrow stem cells into the cochlear wall or oval window has been used to observe survival, proliferation, and differentiation of cochlear stem cells, as well as migration of differentiated hair cells in scala tympani over a short period of time. OBJECTIVE： To investigate the relationship between survival, proliferation, differentiation, and migration of transplanted cochlear stem cells and hearing recovery from sensorineural hearing loss. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment was performed at the Laboratory of Neurobiology, Southeast University in 2009. MATERIALS： Stem cells were isolated from neonatal rats, followed by primary and passaged cultures. METHODS： A total of 30 adult, male rats with normal hearing were treated with gentamicin sulfate to establish models of sensorineural hearing loss. The model rats were randomly assigned to cochlear stem cell transplantation and control groups, which were respectively injected with a 10μL cochlear stem cell suspension （1 × 10^5μL） and phosphate-buffered saline into the scala tympani. MAIN OUTCOME MEASURES： Rat hearing recovery was detected by brainstem auditory-evoked potential at 1, 9, and 15 months following transplantation. The location of stem cells was detected using nestin immunofluorescence, proliferative capacity was detected using bromodeoxyuridine immunofluorescence, and hair cell differentiation was detected using Myosin VIIA immunofluorescence. RESULTS： Cochlear stem cells migrated from the needle track to the spiral organ along the scala tympani following transplantation, and the hair cell-like cells migrated to the basal membrane and organ of Corti. The threshold of brainstem auditory-evoked potential increased with increasing time （P 〈 0.05）. CONCLUSION： Transplanted cochlear stem cells from the internal ear migrated to the basal membrane and reached the injury site. The cells differentiated into ce

关键词： cochlear stem cells transplantation hearing recovery sensorineural hearing loss neural regeneration rats

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Pathological conditions re-shape physiological Tregs into pathological Tregs

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Burns & Trauma 2015年第1期3卷 10-20页

作者： William Y Yang Ying Shao Jahaira Lopez-Pastrana Jietang Mai Hong Wang Xiao-feng Yang Centers for Metabolic Disease Research Cardiovascular Researchand Thrombosis ResearchDepartment of PharmacologyTemple University School of MedicineMERB 10593500 North Broad StreetPhiladelphiaPA 19140USA department of Microbiology and Immunology Temple University School of MedicinePhiladelphiaPA 19140USA

CD4^(+)FOXP3^(+)regulatory T cells(Tregs)are a subset of CD4 T cells that play an essential role in maintaining peripheral immune tolerance,controlling acute and chronic inflammation,allergy,autoimmune diseases,and anti-cancer immune *** the past 20 years,a significant progress has been made since Tregs were first characterized in *** concepts and principles regarding Tregs generation,phenotypic features,subsets(tTregs,pTregs,iTregs,and iTreg35),tissue specificity(central Tregs,effector Tregs,and tissue resident Tregs),homeostasis(highly dynamic and apoptotic),regulation of Tregs by receptors for PAMPs and DAMPs,Treg plasticity(re-differentiation to other CD4 T helper cell subsets,Th1,Th2,Tfh,and Th17),and epigenetic regulation of Tregs phenotypes and functions have been *** this concise review,we want to briefly analyze these eight new progresses in the study of *** have also proposed for the first time a novel concept that“physiological Tregs”have been re-shaped into“pathological Tregs”in various pathological *** of the improvement in our understanding on this important cellular component about the immune tolerance and immune suppression would lead to the future development of novel therapeutics approaches for acute and chronic inflammatory diseases,allergy,allogeneic transplantation-related immunity,sepsis,autoimmune diseases,and cancers.

关键词： Regulatory T cells Immune suppression Epigenetic mechanisms Histone modifications Metabolic cardiovascular diseases

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Eliminating viral hepatitis in children after liver transplants:How to reach the goal by 2030

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World Journal of Gastroenterology 2022年第3期28卷 290-309页

作者： Palittiya Sintusek Kessarin Thanapirom Piyawat Komolmit Yong Poovorawan The Thai Pediatric Gastroenterology Hepatology and Immunology(TPGHAI)Research UnitChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of PediatricsFaculty of MedicineKing Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand Division of Gastroenterology Department of MedicineLiver Fibrosis and Cirrhosis Research UnitFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalThai Red Cross SocietyBangkok 10330Thailand Center of Excellence in Liver Diseases King Chulalongkorn Memorial HospitalChulalongkorn UniversityBangkok 10330Thailand Center of Excellence in Clinical Virology Faculty of MedicineChulalongkorn UniversityBangkok 10330Thailand

Viral hepatitis infections are a great burden in children who have received liver *** viruses can cause liver inflammation that can develop into liver graft fibrosis and cirrhosis over the long *** reactions due to viral hepatitis infections are associated with or can mimic graft rejection,rendering the condition difficult to *** strategies using vaccinations are agreeable to patients,safe,cost-effective and ***,strategies to eliminate viral hepatitis A and B focus mainly on immunization programmes for children who have received a liver *** a vaccine has been developed to prevent hepatitis C and E viruses,its use is not licensed ***,eliminating hepatitis C and E viruses mainly involves early detection in children with suspected cases and effective treatment with antiviral *** hygiene and sanitation are also important to prevent hepatitis A and E *** blood products and liver grafts should be screened for hepatitis B,C and E in children who are undergoing liver *** research on early detection of viral hepatitis infections should include molecular techniques for detecting hepatitis B and ***,novel antiviral drugs for eradicating viral hepatitis that are highly effective and safe are needed for children who have undergone liver transplantation.

关键词： Viral hepatitis Children Adolescent Liver transplantation Infection Elimination

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Urinary Neutrophil Gelatinase Associated Lipocalin as a Marker of Tubular Damage in Type 2 Diabetic Patients with and without Albuminuria

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Open Journal of nephrology 2014年第1期4卷 37-46页

作者： Abeer A. Al-Refai Safaa I. Tayel Ahmed Ragheb Ashraf G. Dala Ahmed Zahran Biochemistry department Faculty of Medicine Menofia University Shibin El Kom Egypt Internal medicine department Faculty of Medicine Menofia University Shibin El Kom Egypt

Background: Neuttrophil gelatinase associated lipocalin (NGAL) was shown to be a good marker for predicting acute kidney injury (AKI). Some recent reports demonstrated that NGAL may be an early biomarker for kidney affection in diabetic patients. The aim of this work is to investigate urinary NGAL (UNGAL) in type 2 diabetic patients with and without albuminuria. Methods: This study included 46 type 2 diabetic patients and 15 healthy age and sex matched individuals as the control group. Diabetic patients were divided into three groups according to urinary albumin excretion (UAE), normoalbuminuria, microalbuminuria and macroalbuminuria. UNGAL was measured in all populations and corrected to urinary creatinine to account for day to day variation in urine volume and transformed log. Comparison between 4 groups (control, normoalbuminuria, microalbuminuria and macroalbuminuria) was done. Results: Log UNGAL/Creatinine ratio showed significant difference when comparing control group (0.70 ± 0.58) versus normoalbuminuria (1.71 ± 1.06), microalbuminuria (1.57 ± 0.72) and macroalbuminuria (1.92 ± 0.63), however, there was no significant difference among diabetic groups. Pearson’s correlation showed that log UNGAL/Creatinine ratio positively correlated with glycated hemoglobin (HbA1c) and inversely with estimated glomerular filtration rate (eGFR). Regression analysis showed that HbA1c, urinary creatinine and eGFR were the independent predictors of log UNGAL/Creatinine ratio. Conclusion: Tubular markers like UNGAL may be early elevated in type 2 diabetic patients even before the incidence of glomerular injury detected by microalbuminuria and it can be used as an early marker for detection of kidney involvement in diabetic patients.

关键词： Neutrophil Gelatinase Associated Lipocalin (NGAL) Diabetic Nephropathy Albuminuria Tubular Markers

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Latent tuberculosis:Risk factors,screening and treatment in liver transplantation recipients from an endemic area

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World Journal of transplantation 2021年第12期11卷 512-522页

作者： Isabela Dias Lauar Luciana Costa Faria Roberta Maia de Castro Romanelli Wanessa Trindade Clemente medicine department Universidade Josédo Rosário VellanoBelo Horizonte 31710030Minas GeraisBrazil Internal medicine department Faculdade de MedicinaUniversidade Federal de Minas Gerais(UFMG)Belo Horizonte 30130100Minas GeraisBrazil Pediatrics department Faculdade de MedicinaUniversidade Federal de Minas Gerais(UFMG)Belo Horizonte 30130100Minas GeraisBrazil department of Laboratory medicine Faculdade de MedicinaUniversidade Federal de Minas Gerais(UFMG)Belo Horizonte 30130100Minas GeraisBrazil

BACKGROUND Patients undergoing solid organ transplantation,particularly those who live or have lived in tuberculosis(TB)endemic areas,are at a high risk of developing *** majority of post-transplantation TB cases are associated with reactivation of latent TB infection(LTBI).Brazil is in a single position with overlapping areas of high TB endemicity and high transplant *** liver transplant(LT),one should be aware of the potential hepatotoxicity associated with the treatment regimens for *** To evaluate the frequency of LTBI in LT patients and treatment-related *** This was a retrospective analysis of a cohort of cirrhotic patients aged≥18 years,who underwent LT at a high-complexity teaching hospital from January 2005 to December *** Overall,429 patients underwent LT during the study *** these,213(49.7%)underwent the tuberculin skin test(TST)during the pre-transplant period,and 35(16.4%)of them had a positive *** treatment for LTBI was initiated after LT in 12(34.3%)of the TST-positive patients;in 3(25.0%),treatment was maintained for at least 6 *** The prevalence of LTBI was lower than *** and completion of LTBI treatment was limited by difficulties in the management of these special patients.

关键词： Latent tuberculosis Liver transplantation Tuberculosis Infection transplantation Risk factors

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Contrast Agents and Contrast-Induced Nephropathy

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International Journal of Clinical medicine 2015年第7期6卷 451-457页

作者： Mohammad Hassan Ghadiani Pooneh Dehghan department of nephrology Taleghani Hospital Shahid Beheshti University of Medical Sciences Tehran Iran Taleghani Hospital Research Development Unit Department of Imaging Shahid Beheshti University of Medical Sciences Tehran Iran

Recent advances in medical sciences, especially in imaging, have dramatically increased the use of contrast agents. The constantly changing nature of medicine and the availability of new information, such as new pharmaceutical formulations, have necessitated periodic revisions and drafting of new guidelines for the safe use of intravenous contrast agents in radiology. This study examined the majority of guidelines, articles, and authoritative references available on the use of intravenous contrast agents in adults to reduce the risk of contrast-induced nephropathy. The search engines of PubMed, Web of Science, Scopus, and Google Scholar were used, and relevant English articles cited at least twice between 1979 and 2014 were studied. Review of the collected papers showed no consensus among them for guidelines on the incidence of contrast-induced nephropathy in patients at risk. Different formulas were used to calculate estimated glomerular filtration rate, which could be problematic in some cases. Further studies are needed for unification of existing guidelines.

关键词： Contrast-Induced Nephropathy Contrast Agents Acute Kidney Injury

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Management of Hepatocellular Carcinoma: Updated Review

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Journal of Cancer Therapy 2013年第2期4卷 536-545页

作者： Tamer Elbaz Mohamed El Kassas Gamal Esmat Endemic medicine and Hepatogastroenterology department Faculty of Medicine Cairo University Cairo Egypt Hepatology department National Hepatology and Tropical Medicine Research Institute Cairo Egypt.

Hepatocellular carcinoma (HCC) represents one of the most challenging potentially curable tumors with high incidence, prevalence and mortality rates. For proper assessment, prognosis estimation and treatment decisions, at least seven important guidelines and staging systems were designated. Proper treatment needs the interaction of multidisciplinary HCC clinic to choose the most appropriate line of treatment. The different modalities of management include resection (surgery or transplantation), local ablation, chemoembolization, radioembolization and molecular targeted therapies with a wide range of investigational drugs that developed after the FDA approved sorafenib. Downstaging and bridging are two important strategies to manage HCC patients who will undergo liver transplantation to improve their postoperative survival. Finally, survival and prognosis depends on several prognostic factors that are either patient related or tumor related. In our study, we aim to provide an updated comprehensive review of the different aspects of liver cancer management starting from staging systems to the different applied treatment modalities.

关键词： Hepatocellular Carcinoma Staging Molecular Targeted Therapies

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Liver transplantation in alcoholic liver disease current status and controversies

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World Journal of Gastroenterology 2013年第36期19卷 5953-5963页

作者： Ashwani K Singal Khushdeep S Chaha Khalid Rasheed Bhupinderjit S Anand Division of Gastroenterology and Hepatology Department of Medicine University of Alabama at Birmingham department of medicine UAB Huntsville Program Huntsville department of medicine UAB Montgomery Program Montgomery department of Gastroenterology and Hepatology Michael DeBakey VA Center Baylor College of Medicine Houston

Alcoholic cirrhosis remains the second most common indication for liver transplantation.A comprehensive medical and psychosocial evaluation is needed when making a decision to place such patients on the transplant *** transplant centers worldwide need a minimum of 6 mo of alcohol abstinence for listing these *** with alcohol dependence are at high risk for relapse to alcohol use after transplantation(recidivism).These patients need to be identified and require alcohol rehabilitation treatment before *** to the level of harmful drinking is reported in about 15%-20%***,recurrent cirrhosis and graft loss from recidivism is rare,occurring in less than 5%of all alcoholic cirrhosis-related transplants,harmful drinking in the post-transplant pe-riod does impact the long-term *** development of metabolic syndrome with cardiovascular events and de novo malignancy are important contributors to non liver-related mortality amongst transplants for alcoholic liver *** protocols for earlier detection of de novo malignancy are needed to improve the long-term *** need for a minimum of 6 mo of abstinence before listing makes transplant a nonviable option for patients with severe alcoholic hepatitis who do not respond to *** data from retrospective and prospective studies has challenged the 6 mo rule,and beneficial effects of liver transplantation have been reported in select patients with a first episode of severe alcoholic hepatitis who are unresponsive to steroids.

关键词： Alcoholic liver disease Liver transplantation Transplant evaluation Recidivism Six months rule Alcoholic hepatitis

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Safety of interferon β treatment for chronic HCV hepatitis

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World Journal of Gastroenterology 2004年第1期10卷 12-16页

作者： DFesti LSandri GMazzella ERoda AColecchia TSacco TStaniscia SCapodicasa AVestito department of Internal medicine and Gastroenterology University of BolognaBolognaItaly department of medicine and Aging University G.d'AnnunzioChietiItaly

Hepatitis C is a major cause of liver-related morbidity and mortality worldwide. In fact, chronic hepatitis C is considered as one of the primary causes of chronic liver disease, cirrhosis and hepatocellular carcinoma, and is the most common reason for liver transplantation. The primary objectives for the treatment of HCV-related chronic hepatitis is to eradicat einfection and prevent progression of the disease. The treatment has evolved from the use of m-interferon (IFNα) alone to the combination of IFNα plus ribavirin, with a significant improvement in the overall efficacy, and to the newer PEG-IFNs which have further increased the virological response, used either alone or in combination with ribavirin. Despite these positive results, in terms of efficacy, concerns are related to the safety and adverse events. Many patients must reduce the dose of PEG-IFN or ribavirin, others must stop the treatment and a variable percentage of subjectsare not suitable owing to intolerance toward drugs. IFNβ represents a potential therapeutic alternative for the treatment of chronic viral hepatitis and in some countries it plays an important role in therapeutic protocols. Aim of the present paper was to review available data on the safety ofIFNβ treatment in HCV-related chronic hepatitis. The rates of treatment discontinuation and/or dose modification due to the appearance of severe side effects during IFNβ are generally low and in several clinical studies no requirements for treatment discontinuation and/or dose modifications have been reported. The most frequent side effects experienced during IFNβ treatment are flu-like syndromes, fever, fatigue and injection-site reactions. No differences in terms of side-effect frequency and severity between responders and non-responders have been reported.A more recent study, performed to compare IFNβ alone or in combination with ribavirin, confirmed the good safety profile of both treatments. Similar trends of adverse event frequency have

关键词：慢性丙型肝炎干扰素β 药物疗法病毒复制免疫抑制剂

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