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Signaling Networks Controlling HCC Onset and Progression: Influence of Microenvironment and Implications for Cancer Gene Therapy

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Journal of Cancer Therapy 2013年第2期4卷 353-358页

作者： Alessandra Marchetti Carla Cicchini Laura Santangelo angela Maria Cozzolino Viviana costa Marco Tripodi Laura Amicone Pasteur Institute—Cenci Bolognetti Foundation Department of Cellular Biotechnologies and Hematology Sapienza University Rome Italy

Hepatocarcinogenesis, as other epithelial malignancies, has been proved to be a multistep process that, starting from mutagenic events, allows the transformed liver cell to evolve towards a more aggressive phenotype, characterized by the acquisition of migratory/invasive and stem-cell-like properties. Hepatocellular carcinoma(HCC)can originate from both mature hepatocytes and liver precursor/stem cells. Whatever its origin, a common feature of advanced-stage HCC is the reduction or lack of expression of master genes of epithelial/hepatocyte differentiation, i.e. members of the liver enriched transcription factors(LEFTs)family like HNF4α, and conversely an increased expression of epithelial-to-mesenchymal transition(EMT)master genes, i.e. the transcriptional repressors belonging to the Snail family. Recently, it has emerged as members of these families are capable to directly repress each other and to regulate in opposite manner target genes involved in stemness and in hepatocyte differentiation, thus influencing cell outcome between epithelial/differentiated/poor aggressive and mesenchymal/undifferentiated/aggressive phenotype. Consequently, the restoration of LEFT functions in invasive HCC could represent an important goal for anti-cancer therapies. However, any strategy based on gene transfer needs to take in account the influence of micro-environmental factors in HCC tumor niche, like TGFb, responsible for shifting the described balance in tumor cell towards the acquisition of stem-cell like properties and invasiveness, through Snail/EMT induction and LEFTs downregulation. The presence of this cytokine, indeed, was shown to override both anti-EMT and tumor suppressor activity of the ectopically expressed HNF4α protein. In this review, the rationale to propose implementation of HCC gene therapy will be discussed.

关键词： HNF4 Snail TGFβ microRNA EMT Cancer Stem Cell

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Landscape Structural Indicators as a Tool to Assess Land Use Changes in Planning for Sub-Basin Sustainability (Southeastern Brazil)

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Journal of Water Resource and Protection 2016年第4期8卷 482-492页

作者： angela Terumi Fushita José Eduardo dos Santos Imyra Maíra Martins de Souza Eduarda Romanini Rômulo Theodoro costa Analysis and Environmental Planning Laboratory Department of Hydrobiology Federal University of S&#227o Carlos (UFSCar) S&#227o Carlos Brazil Pos-Graduate Programme in Ecology and Natural Resources Federal Universityof S&#227o Carlos (UFSCar) S&#227o Carlos Brazil

Land use is shaped by the interactions between nature and society, and these interactions can inhibit environmental sustainability and deplete the natural capital that provides the ecosystem services upon which humans depend. Urbanity Index and Landscape Vulnerability Indicator have been proposed to improve the impact interpretability of land use changes on sub-basin sustainability for local scenarios of biodiversity conservation. A time series of LandSat 5 Thematic Mapper remote sensing data from São Carlos municipality, Southeastern Brazil, for the years 1989, 2004 and 2014 revealed that land use changes in the sub-basins do not take place in a progressive and gradual way. Over the 25-year period, the main trends showed the loss and increase of forest cover so that it has remained quantitatively similar over time due to reduced agricultural land use. The aggregation of both indicators enabled the identification of greater naturalness and lower vulnerability, as well as lower naturalness and higher vulnerability under local sub-basin conditions, pointing the need for different strategies for sub-basin biodiversity conservation and sustainability. These preliminary scenarios provide a way to communicate problems of environmental sustainability at different landscape scales to the scientific community as well as to planners, policy makers and the broader public.

关键词： Land Use Quantifiable Indicator Urbanity Index Landscape Vulnerability Indicator

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Roots and rhizomes of wild Asparagus:Nutritional composition,bioactivity and nanoencapsulation of the most potent extract

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Food Bioscience 2022年第1期45卷 349-360页

作者： Khaoula Adouni Ana Júlio Celestino Santos-Buelga Ana M.Gonzalez-Paramas Patrícia Filipe Patricia Rijo Sofia A.costa Lima Salette Reis angela Fernandes Isabel C.F.R.Ferreira Virginia Fernandez-Ruiz Patricia Morales Guido Flamini Lotfi Achour Pedro Fonte Laboratoire de Recherche“Bioressources:Biologie Integrative&Valorisation” Institut Superieur de Biotechnologie de MonastirAvenue Tahar HaddedBP 74Universite de Monastir5000MonastirTunisia CBIOS-Research Center for Biosciences&Health Technologies Universidade Lusofona de Humanidades e TecnologiasCampo Grande 3761749-024LisbonPortugal Department of Biomedical Sciences University of Alcal´aCtra.Madrid-Barcelona Km.33.60028871Alcala de HenaresMadridSpain Grupo de Investigacion en Polifenoles(GIP-USAL) Facultad de FarmaciaUniversidad de SalamancaCampus Miguel de UnamunoE-37007SalamancaSpain Research Institute for Medicines(iMed.ULisboa) Faculty of PharmacyUniversidade de LisboaAv.Professor Gama Pinto1649-003LisboaPortugal LAQV REQUIMTEDepartment of Chemical Sciences–Applied Chemistry LabFaculty of Pharmacy10 University of PortoRua Jorge de Viterbo Ferreira 2284050-313PortoPortugal Centro de Investigacao de Montanha(CIMO) Instituto Politecnico de BragancaCampus de Santa Apolonia5300-253BragancaPortugal Department of Nutrition and Food Science Faculty of PharmacyComplutense University of Madrid(UCM)Plaza Ramon y Cajal s/n28040MadridSpain Dipartimento di Farmacia University of Pisavia Bonanno 656126PisaItaly Centro Interdipartimentale di Ricerca“Nutraceutica e Alimentazione per la Salute”University of Pisa Via del Borghetto 8056124PisaItaly Center for Marine Sciences(CCMar) University of AlgarveGambelas Campus8005-139FaroPortugal Department of Chemistry and Pharmacy Faculty of Sciences and TechnologyUniversity of AlgarveGambelas Campus8005-139FaroPortugal iBB-Institute for Bioengineering and Biosciences Department of BioengineeringInstituto Superior TecnicoUniversidade de Lisboa1049-001LisboaPortugal Associate Laboratory i4HB—Institute for Health and Bioeconomy at Instituto Superior Tecnico Universidade de LisboaAv.Rovisco Pais1049-001LisboaPortugal

The nutritional composition and bioactive properties of roots and rhizomes of Asparagus stipularis were *** activity of extracts obtained by infusion was evaluated using free radicals scavenging and reducing power *** liver primary cell was used to check the hepatotoxicity of *** revealed that Asparagus samples are likely a source of nutrients,such as dietary fibre and essential fatty ***-daD-ESI/MS characterization of infusions allowed the identification and quantitation of 7 phenolic compounds,all hydroxycinnamoyl derivatives,with caffeic acid as the most *** infusion contained the highest amounts of these *** also exhibited the highest antioxidant activity in all assays,with EC_(50) values of 0.44±0.01,0.98±0.03 and 0.64±0.01 mg/mL for DPPH,ABTS and FRAP assays,respectively,with no toxicity towards PLP2 primary cell cultures(GI_(50)>400μg/mL).PLGA nanoparticles loaded with root extract were prepared using solvent-evaporation double emulsion *** size was about 260 nm and a polydispersity index around 0.1,with a zeta potential of about-36 mV,as well as a good encapsulation efficiency of approximately 83%.Their morphology was analysed by SEM and spherical polymeric nanoparticles with a smooth surface were *** and DSC were also performed,which allowed corroborating the efficacy of the encapsulation and to confirm the production of a stable and robust system to load Asparagus *** developed nanoparticles are expected to be used as delivery systems for bioactive compounds of *** and they could be used as an innovative dietary supplement.

关键词： Asparagus stipularis Nutritional composition Antioxidant activity Nanoparticles PLGA

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GLI ISOTOPI DELL'OSSIGENO COME INFORMATORI PALEOCLIMATICI—— Alcuni dati sperimentali

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Natural Disaster Reduction in China 1989年第1期 331-337页

作者： DONATELLA D'angela Istituto

Studi precedenti hanno permesso di definite l’esistenza di una retazione diretta e quantita-tiva che lega la composizione isotopica dell’ossigeno (18O/16O) nel fosfato delle ossa di diverse speciedi mammiferi con la temperatura media annua al suolo delle località di provenienza di tali *** applicare tale relazione a campioni di mammiferi vissuti in età preistorica risulta evidente lapossibilità di compiere studi di tipo paleoclimatico e paleoidrologico. Si presentano i risuhati ottenuti da campioni provenienti da alcuni siti preistorici della Pianura Pada-na e dal villaggio di Fossacesia Marina sulla costa Adriatica. I dati isotopici si accordano bene con le informazioni sulla situazione climatica durante l’Atlanticoottenute con altre metodologie di studio; eventuali variazioni e fluttuazioni locali vengono *** isotopes as climatic indicators. Some experimental data. Oxygen isotope composi-tion (18O/16O) of bone phosphate from different mammal species coming from some prehistoric sitesof the Po Valley and from the Neolithic village of Fossacesia Marina （CH） have been carried on. Previousstudies have demonstrated the existence of a direct, quantitative relationship between oxygen isotopiccomposition of bone phosphate and mean annual temperature. The existence of such relationship allowsto study the ancient environment and climate. The trend of climate, during prehistoric periods, agrees well with the data obtained from other me-thodology of study; some fluctuations of climate in the studied sites are also discussed.

关键词： area Pi GLI ISOTOPI DELL’OSSIGENO COME INFORMATORI PALEOCLIMATICI Alcuni dati sperimentali MN Perl

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Effect of Adjunct Culture <i>Lactobacillus helveticus</i>(B02) on the Composition, Proteolysis, Free Amino Acids Release and Sensory Characteristics of Prato Cheese

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Food and Nutrition Sciences 2017年第5期8卷 512-525页

作者： Natália Chinellato de Azambuja Izildinha Moreno darlila Aparecida Gallina Leila Maria Spadoti Eliana Maria Pettirossi Motta Maria Teresa Bertolodo Pacheco angela Lima Menêses de Queiroz Adriane Elisabete costa Antunes Faculdade de Ciências Aplicadas Universidade Estadual de Campinas (FCA/UNICAMP) Limeira Brazil Centro de Tecnologia de Laticínios Instituto de Tecnologia de Alimentos (TECNOLAT/ITAL) Campinas Brazil Faculdade de Engenharia de Alimentos Universidade Estadual de Campinas (FEA/UNICAMP) Campinas Brazil Centro de Ciência e Qualidade de Alimentos Instituto de Tecnologia de Alimentos (CCQA/ITAL) Campinas Brazil Centro de Tecnologia Universidade Federal da Paraíba Jo&#227o Pessoa Brazil

At semi-industrial scale it was obtained two cheeses, one with aromatic culture (CHN) and the other with also L. helveticus (CHN + LH). Proteolysis during ripening was evaluated using proteolytic indices, electrophoretic profile Urea-PAGE and release of free amino acids. Sensory evaluation was performed by acceptability test. It was observed a 5-fold increase in the fraction corresponding to αs1-I-casein in the CHN cheese and 6.5 times in the CHN + LH cheese and 7.2 and 8.2 increase respectively, for total amino acids. Prato cheese with the adjunct culture showed higher acceptability in terms of overall aroma and flavor.

关键词： Amino Acids Cheese L. helveticus Ripening Sensory Analysis

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Predictors of surgical complications in boys with hypospadias:data from an international registry

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World Journal of Pediatric Surgery 2023年第4期6卷 217-223页

作者： Kathryn Scougall Jillian Bryce Federico Baronio Rachel L Boal Jose Roberto Castera Sebastián Castro Tim Cheetham Eduardo Correa costa Feyza darendeliler Justin H davies Mirjam Dirlewanger Gabriella Gazdagh Evgenia Globa Gil Guerra-Junior Tulay Guran Gloria Herrmann Paul-Martin Holterhus Ahsen KaragözlüAkgül Renata Markosyan Kenneth McElreavey Marcio Lopes Miranda Anna Nordenstrom Stuart O’Toole Sukran Poyrazoglu Gianni Russo Valerie Schwitzgebel Marianna Stancampiano Michael Steigert S Faisal Ahmed angela K Lucas-Herald University of Glasgow GlasgowUK IRCCS Azienda Ospedaliero-Universitaria di Bologna Policlinico S Orsola BolognaItaly Great North Children's Hospital Newcastle Upon TyneUK Hospital de Ninos Ricardo Gutiérrez Buenos AiresArgentina Hospital de Clinicas de Porto Alegre Porto AlegreBrazil Istanbul University IstanbulTurkey Southampton Children's Hospital SouthamptonUK University Hospital of Geneva GenevaSwitzerland Ukrainian Research Center of Endocrine Surgery Endocrine Organs and Tissue Transplantation KyivUkraine State University of Campinas CampinasBrazil Marmara University IstanbulTurkey University Medical Centre UlmGermany University Hospital of Schleswig-Holstein Campus Kiel/Christian-Albrechts-University of Kiel KielGermany Marmara University Faculty of Medicine IstanbulTurkey Yerevan State Medical University Endocrinology Clinic YerevanArmenia Institut Pasteur ParisFrance Karolinska University Hospital StockholmSweden Royal Hospital for Children GlasgowUK IRCCS Ospedale San Raffaele MilanoItaly Graubunden Cantonal Hospital ChurSwitzerland

Background Complications are frequently reported after hypospadias repair and there is a need to understand the factors that influence their *** data from boys with hypospadias born between 2000 and 2020 were obtained from the International Disorders of Sex Development(l-DSD)*** regressions,fisher's exact tests and spearman's correlation tests were performed on the data to assess associations between clinical factors and complication *** Of the 551 eligible boys,data were available on 160(29%).Within the cohort,the median(range)External Masculinization Score(EMS)was 6(2,9).All presented with one or more additional genital malformation and 61(38%)presented with additional extragenital *** of androgen action,androgen synthesis and gonadal development were diagnosed in 28(18%),22(14%)and 9(6%)boys,*** remaining 101(62%)patients were diagnosedas having non-specific 46,XY Disorders of Sex ***(50%)boys had evidence of abnormal biochemistry,and gene variants were identified in 42(26%).Median age at first hypospadias surgery was 2 years(0,9),and median length of follow-up was 5 years(0,17).Postsurgical complications were noted in 102(64%)*** were no significant associations with postsurgical *** Boys with proximal hypospadias in the I-DSD Registry have high rates of additional comorbidities and a high risk of postoperative *** clinical factors were significantly associated with complication *** complication rates with no observable cause suggest the involvement of other factors which need investigation.

关键词： complications surgical involvement

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<i>Angiostrongylus costaricensis</i>: Systematic Review of Case Reports

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Advances in Infectious Diseases 2014年第1期4卷 36-41页

作者： angela Romero-Alegría Moncef Belhassen-García Virginia Velasco-Tirado Ana Garcia-Mingo Lucia Alvela-Suárez Javier Pardo-Lledias Miguel Cordero Sánchez Department of Internal Medicine CAUSA IBSAL Salamanca Spain Department of Internal Medicine CAUSA IBSAL Salamanca Spain CIETUS University of Salamanca Salamanca Spain Department of Internal Medicine General Hospital of Palencia “Río Carrión” Palencia Spain

Introduction: Abdominal angiostrongyliasis is an infrequently diagnosed disease because it is little known and is usually well tolerated. Methods: We carried out a systematic review with PubMed as a search engine for the MedLine database, and we analysed the clinical, epidemiological and analytical parameters of this disease. Results: In total, reports of 27 case have been found, together with a series of 116 patients, which were later augmented up to 194 patients. In the results, we have observed a predominance of male patients, and costa Rica, Brazil and the United States as the main countries of origin. Typical symptoms include abdominal pain on the right iliac fossa, with leukocytosis and eosinophilia. Discussion: There are some serological diagnostic methods, although lack of standardization leads to most of the diagnoses being reached via pathology. Surgery is the usual treatment approach. Although there are medical options, this is a controversial subject because of the low number of cases published in the literature, which implies an absence of solid studies.

关键词： Angiostrongylus costaricensis Abdominal Angiostrongyliasis Acute Abdomen Eosinophilia

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