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Renin angiotensin system in liver diseases: Friend or foe?

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World Journal of Gastroenterology 2017年第19期23卷 3396-3406页

作者： ana cristina Simoes e Silva Aline S Miranda Natália P Rocha Antonio L Teixeira Department of Pediatrics Faculty of MedicineFederal University of Minas Gerais Interdisciplinary Laboratory of Medical Investigation Faculty of MedicineUFMG Laboratory of Neurobiology Department of MorphologyInstitute of Biological SciencesUFMG Neuropsychiatry Program Department of Psychiatry and Behavioral SciencesMcGovern Medical SchoolUniversity of Texas Health Science Center at Houston

In the last three decades,the understanding of the renin angiotensin system(RAS)has been changed by the discoveries of functional local systems,novel biologically active peptides,additional specific receptors,alternative pathways of angiotensin(Ang)?Ⅱ?generation,and new roles for enzymes and precursor components other than those in Ang?Ⅱ?*** this regard,the discovery that Ang-(1-7)opposes the pressor,proliferative,pro-fibrotic,and pro-inflammatory effects mediated by Ang?Ⅱ?has contributed to the realization that the RAS is composed of two *** first axis consists of the angiotensin-converting enzyme(ACE),with Ang?Ⅱ?as the end product,and the angiotensin type 1(AT1)receptor as the main effector mediating the biological actions of Ang?Ⅱ.The second axis results from ACE2-mediated hydrolysis of Ang?Ⅱ,leading to the production of Ang-(1-7),with the Mas receptor as the main effector conveying the vasodilatory,antiproliferative,anti-fibrotic,and anti-inflammatory effects of Ang-(1-7).Experimental and clinical studies have shown that both axes of the RAS may take part in the pathogenesis of liver *** this manuscript,we summarize the current evidence regarding the role of RAS in hepatic cirrhosis and its complications,including hemodynamic changes and hepatorenal *** therapeutic potential of the modulation of RAS molecules in liver diseases is also discussed.

关键词： Renin angiotensin system Angiotensin Ⅱ Angiotensin-(1-7) Hepatic cirrhosis Liver fibrosis Hepatorenal syndrome

Management of hepatitis C in patients with chronic kidney disease

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World Journal of Gastroenterology 2015年第2期21卷 408-422页

作者： Roberto J Carvalho-Filho ana cristina CA Feldner Antonio Eduardo B Silva Maria Lucia G Ferraz Division of Gastroenterology Hepatology SectionFederal University of Sao PauloSao PauloSP 04023-900Brazil

Hepatitis C virus(HCV) infection is highly prevalent among chronic kidney disease(CKD) subjects under hemodialysis and in kidney transplantation(KT) recipients, being an important cause of morbidity and mortality in these patients. The vast majority of HCV chronic infections in the hemodialysis setting are currently attributable to nosocomial transmission. Acute and chronic hepatitis C exhibits distinct clinical and laboratorial features, which can impact on managementand treatment decisions. In hemodialysis subjects, acute infections are usually asymptomatic and anicteric; since spontaneous viral clearance is very uncommon in this context, acute infections should be treated as soon as possible. In KT recipients, the occurrence of acute hepatitis C can have a more severe course, with a rapid progression of liver fibrosis. In these patients, it is recommended to use pegylated interferon(PEG-IFN) in combination with ribavirin, with doses adjusted according to estimated glomerular filtration rate. There is no evidence suggesting that chronic hepatitis C exhibits a more aggressive course in CKD subjects under conservative management. In these subjects, indication of treatment with PEG-IFN plus ribavirin relies on the CKD stage, rate of progression of renal dysfunction and the possibility of a preemptive transplant. HCV infection has been associated with both liver disease-related deaths and cardiovascular mortality in hemodialysis patients. Among those individuals, low HCV viral loads and the phenomenon of intermittent HCV viremia are often observed, and sequential HCV RNA monitoring is needed. Despite the poor tolerability and suboptimal efficacy of antiviral therapy in CKD patients, many patients can achieve sustained virological response, which improve patient and graft outcomes. Hepatitis C eradication before KT theoretically improves survival and reduces the occurrence of chronic graft nephropathy, de novo glomerulonephritis and post-transplant diabetes mellitus.

关键词： Hepatitis C virus Chronic kidney disease End-stage

Acute liver failure with hemolytic anemia in children with Wilson’s disease:Genotype-phenotype correlations?

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World Journal of Hepatology 2021年第10期13卷 1428-1438页

作者： Tudor Lucian Pop Alina Grama ana cristina Stefanescu Claudia Willheim Peter Ferenci 2^(nd) Pediatric Discipline Department of Mother and ChildIuliu Hatieganu University of Medicine and PharmacyCluj-Napoca 400177Romania 2^(nd) Pediatric Clinic Center of Expertise in Pediatric Liver Rare DisordersEmergency Clinical Hospital for ChildrenCluj-Napoca 400177Romania Department of Internal Medicine Ⅲ Gastroenterology and HepatologyMedical University of ViennaWien A-1090Austria

BACKGROUND Wilson’s disease(WD)is a rare autosomal recessive inherited disorder of copper *** liver failure(ALF)and hemolytic anemia represent the most severe presentation of WD in *** clear genotype-phenotype correlations exist in ***-truncating nonsense,frame-shift,or splice-site variants may be associated with more severe *** contrast,missense variants may be associated with late-onset,less severe disease,and more neurological ***,a gene variant(HSD17B13:TA,rs72613567)with a possible hepatic protective role against toxins was associated with a less severe hepatic phenotype in *** To analyze the possible genotype-phenotype correlations in children with WD presented with ALF and non-immune hemolytic *** The medical records of children with WD diagnosed and treated in our hospital from January 2006 to December 2020 were retrospectively *** clinical manifestations(ALF with non-immune hemolytic anemia or other less severe forms),laboratory parameters,copper metabolism,ATP7B variants,and the HSD17B13:TA(rs72613567)variant were reviewed to analyze the possible genotype-phenotype *** We analyzed the data of 51 patients with WD,26 females(50.98%),with the mean age at the diagnosis of 12.36±3.74 *** and Coombs-negative hemolytic anemia was present in 8 children(15.67%),all adolescent *** Kayser-Fleisher ring was present in 9 children(17.65%).The most frequent variants of the ATP7B gene were ***1069Gln(c.3207A>G)in 38.24% of all alleles,***1341Asp(c.4021G>A)in 26.47%,***939Cys(c.2817G>T)in 9.80%,and ***844Ter(c.2530A>T)in 4.90%.In ALF with hemolytic anemia,***939Cys(c.2817G>T)and ***844Ter(c.2530A>T)variants were more frequent than in other less severe forms,in which ***1069Gln(c.3207A>G)was more ***1341Asp(c.4021G>A)has a similar frequency in all hepatic *** 33 of the patients,the HSD17B13 genotype was *** overall HSD17B13:TA a

关键词： Wilson’s disease Children Acute liver failure Hemolytic anemia ATP7B variant Genotype-phenotype correlation

TLR2 and TLR4 polymorphisms influence m RNA and protein expression in colorectal cancer

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World Journal of Gastroenterology 2015年第25期21卷 7730-7741页

作者： Marcela Alcantara Proenca Juliana Garcia de Oliveira Aline cristina Targa Cadamuro Maysa Succi Joao Gomes Netinho Eny Maria Goloni-Bertolo érika cristina Pavarino ana Elizabete Silva Department of Biology UNESPSao Paulo State University USC-Sacred Heart University PróReitoria de Pesquisa e Pós Graduacao Department of Surgery School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil UPGEM School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil

AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) ***: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary ***: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P analysis of TLR2 and TLR4 protein expression was concordant with the findings of m RNA expression. In addition, the TLR2-196 to-174 del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P

关键词： Toll-like receptor 2 Toll-like receptor 4 Colorectal cancer Protein expression Gene expression Genetic polymorphisms

Synthesis and applications of lanthanoid complexes of pentadentate and hexadentate N_(5) and N_(6) macrocycles:A review

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Journal of Rare Earths 2024年第1期42卷 1-15,I0001页

作者： Julio Corredoira-Vázquez cristina González-Barreira Paula Oreiro-Martínez ana M.García-Deibe Jesús Sanmartín-Matalobos Matilde Fondo Departamento de Química Inorganica Facultade de QuímicaUniversidade de Santiago de CompostelaCampus Vida15782Santiago de CompostelaSpain Phantom-g CICECO-Aveiro Institute of MaterialsDepartment of PhysicsUniversity of Aveiro3810-193AveiroPortugal Institute of Materials(iMATUS) Universidade de Santiago de Compostela15782Santiago de CompostelaSpain

In this paper,the lanthanoid complexes of N_(5) and N_(6) macrocycle ligands,without pendant arms or additional heteroatoms,are *** review covers the period from 2015 to the current date,since in 2014 Schiff base macrocyclic ligands incorporating the pyridine moiety,and their complexes,were revised,and in 2015 the chemistry of pentaaza macrocycle ligands with rare earth metals was also *** and phthalocyanine ligands are not included in this review,which primarily focuses on complexes with Schiff bases and amines without pendant arms or any additional donor other than *** synthetic methods,structural characterization,based on single X-ray crystal data,and properties of the lanthanoid complexes,with special attention to magneto-structural correlations,are presented herein.

关键词： Lanthanoid N_(5),N_(6)macrocycle Coordination chemistry Chirality Biological activity Molecule magnet

Trypanosoma rangeli:growth in mammalian cells in vitro and action of a repositioned drug(17-AAG)and a natural extract(Artemisia *** oil)

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BIOCELL 2019年第1期43卷 13-19页

作者： ana Laura CIMADOR Emeli Luciana GALANTE Lucila Ibel MUNOZ Patricia Silvia ROMANO Antonella Denisse LOSINNO Maria cristina VANRELL Facultad de Farmacia y Bioquimica Universidad Juan Agustin Maza.MendozaArgentina Facultad de Ciencias Medicas Universidad Nacional de Cuyo.MendozaArgentina Laboratorio de Biologia de Trypanosoma cruzi y la celula hospedadora-Instituto de Histologia y Embriologia“Dr.Mario H.Burgos”IHEM-CONICET-Universidad Nacional de Cuyo.Mendoza Argentina

Trypanosoma rangeli and *** are both parasitic unicellular species that infect *** ***,the causative agent of Chagas disease,*** is an infective and non-pathogenic parasite for humans,but pathogenic for vectors from the Rhodnius *** both species can coexist in different hosts and overlap their infective cycles but very little is known about the infection of *** in mammalian cells,we decided to characterize both the development of this parasite in cell culture and the effect of therapeutic agents with potential trypanocidal action on *** found that *** exhibits a cycle of infection in Vero cells similar to that for *** and that the repurposed drug,17-AAG,and the natural extract Artemisia *** oil produce a toxic effect on epimastigotes showing a trypanocidal action from the fifth day of *** treatments also affected the infection of trypomastigotes and reduced the capacity of replication of amastigotes of *** ***/*** coinfection cases have been reported,the finding of drugs with potential activity against both species could be significant in the ***,studies of susceptibility of both species to drugs could also help to know the different mechanisms of pathogenicity in humans displayed by *** that are absent in ***.

关键词： Life-cycle Treatment Trypanosoma rangeli

Hepatocellular carcinoma after direct-acting antiviral hepatitis C virus therapy:A debate near the end

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World Journal of Gastroenterology 2020年第43期26卷 6770-6781页

作者： cristina Maria Muzica Carol Stanciu Laura Huiban ana-Maria Singeap Catalin Sfarti Sebastian Zenovia Camelia Cojocariu Anca Trifan Department of Gastroenterology Grigore T.Popa University of Medicine and PharmacySt.Spiridon Emergency HospitalIasi 700115Romania

Direct acting antivirals(DAAs)have revolutionized the treatment of hepatitis C virus(HCV)infection,achieving high rates(≥95%)of sustained virological response,with a good safety profile and high compliance ***,it had been expected that viral clearance will reduce morbidity and mortality rates,as well as the risk of hepatocellular carcinoma(HCC).However,since 2016,concerns have been raised over an unexpected high rate of HCC occurrence and recurrence after DAA therapy,which led to an avalanche of studies with contradictory *** aimed to review the most recent and relevant articles regarding the risk of HCC after DAA treatment and identify the associated risk factors.

关键词： Hepatocellular carcinoma Direct acting antivirals therapy Hepatitis C virus infection Sustained virological response Risk factors of hepatocellular carcinoma Review

Retrospective study of HIV drug resistance in Mexican children with vertically transmitted infection

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World Journal of Pediatrics 2022年第7期18卷 505-510页

作者： cristina de Jesus Herrera-Castillo Angelica Maldonado-Rodriguez Othon Rojas-Montes ana Maria Cevallos JoséGuillermo Vazquez-Rosales Rosalia Lira Infectious Diseases Department Pediatrics Hospital"Silvestre Frenk Freund"National Medical Center"Siglo ⅩⅪ".Mexican Social Sccurity Instiute(IMSS).Mexico City.Mexico Infectious and Parasitie Dise ases Medical Research Unit Pediatrics Hospital"Silvestre Frenk Freund"National Medical Center“Siglo ⅩⅪ”Mexican Social Security Institute(IMSS).Col.Cuauhtemoc.Av.Cuauhtemoc 33006720 Mexico CityMexico Departament of Molecular Biology and Biotechnology Biomedical Research InstituteNational Autonomous University of MexicoUNAMMexico City.Mexico

According to World Health Organization(WHO)estimates,in 2020,there were 1.8 million human immunodeficiency virus(HIV)-infected children below 15 years old living with HIV and 150,000 children who acquired the infection[1].Every year,110,000 children die as a consequence of acquired immune deficiency syndrome-related causes[2].As in adults,optimal management of infected children depends on early diagnosis and treatment with antiretroviral drugs based on their viral genotype.

关键词： infection diagnosis drugs

Inherited Fanconi syndrome

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World Journal of Pediatrics 2023年第7期19卷 619-634页

作者： Anna Luiza Braga Albuquerque Rafael dos Santos Borges ana Flavia Conegundes Erika Emmylaine dos Santos Frederico Moreira Man Fu Clara Tavares Araujo Pedro Alves Soares Vaz de Castrol ana cristina Simoes e Silva Interdisciplinary Laboratory of Medical Investigation Unit of Pediatric NephrologyFaculty of MedicineFederal University of Minas Gerais(UFMG)Belo HorizonteBrazil Department of Pediatrics Faculty of MedicineUFMGAlfredo Balena Avenue1902Nd FloorRoom#281Belo HorizonteMG 30130-100Brazil

Background Fanconi-Debré-de Toni syndrome(also known as Fanconi renotubular syndrome,or FRST)profoundly increased the understanding of the functions of the proximal convoluted tubule(PCT)and provided important insights into the pathophysiology of several kidney diseases and drug *** sources We searched Pubmed and Scopus databases to find relevant articles about *** review article focuses on the physiology of the PCT,as well as on the physiopathology of FRST in children,its diagnosis,and *** FRST encompasses a wide variety of inherited and acquired PCT alterations that lead to impairment of PCT *** children,FRST often presents as a secondary feature of systemic disorders that impair energy supply,such as Lowe's syndrome,Dent's disease,cystinosis,hereditary fructose intolerance,galactosemia,tyrosinemia,Alport syndrome,and Wilson's *** rare,congenital causes of FRST greatly impact the morbidity and mortality of patients and impose diagnostic ***,its treatment is diverse and considers the ability of the clinician to identify the correct etiology of the *** The early diagnosis and treatment of pediatric patients with FRST improve the prognosis and the quality of life.

关键词： Cystinosis Fanconi syndrome Fanconi renotubular syndrome Fanconi-Debre-de Toni syndrome Proximal tubule Renal tubular transport-Rickets