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Decellularized extracellular matrix as scaffold for cancer organoid cultures of colorectal peritoneal metastases

Journal of Molecular Cell Biology 2022年第11期14卷 36-49页

作者： Luca Varinelli Marcello Guaglio Silvia Brich Susanna Zanutto Antonino Belfiore Federica Zanardi Fabio Iannelli Amanda Oldani elisa costa Matteo Chighizola Ewelina Lorenc Simone P.Minardi Stefano Fortuzzi Martina Filugelli Giovanna Garzone Federica Pisati Manuela Vecchi Giancarlo Pruneri Shigeki Kusamura Dario Baratti Laura Cattaneo Dario Parazzoli Alessandro Podestà Massimo Milione Marcello Deraco Marco A.Pierotti Manuela Gariboldi Department of Research Fondazione IRCCS Istituto Nazionale dei Tumorivia G.Venezian 120133 MilanItaly Peritoneal Surface Malignancies Unit Colon and Rectal SurgeryFondazione IRCCS Istituto Nazionale dei Tumorivia G.Venezian 120133 MilanItaly Department of Pathology and Laboratory Medicine Clinical Research lABoratory(CRAB)Fondazione IRCCS Istituto Nazionale dei Tumorivia G.Venezian 120133 MilanItaly Bioinformatics Core Unit IFOM ETSThe AIRC Institute of Molecular Oncologyvia Adamello 1620139 MilanItaly Imaging Technological Development Unit IFOM ETSThe AIRC Institute of Molecular Oncologyvia Adamello 1620139 MilanItaly C.I.Ma.I.Na.and Dipartimento di Fisica‘Aldo Pontremoli’ Universitàdegli Studi di Milanovia G.Celoria 1620133 MilanItaly Cogentech Ltd Benefit Corporation with a Sole Shareholder via Adamello 1620139 MilanItaly Pathology and Laboratory Medicine Department Fondazione IRCCS Istituto Nazionale dei Tumorivia G.Venezian 120133 MilanItaly

Peritoneal metastases (PM) from colorectal cancer (CRC) are associated with poor survival. The extracellular matrix (ECM) plays a fundamental role in modulating the homing of CRC metastases to the peritoneum. The mechanisms underlying the interactions between metastatic cells and the ECM, however, remain poorly understood, and the number of in vitro models available for the study of the peritoneal metastatic process is limited. Here, we show that decellularized ECM of the peritoneal cavity allows the growth of organoids obtained from PM, favoring the development of three-dimensional (3D) nodules that maintain the characteristics of in vivo PM. Organoids preferentially grow on scaffolds obtained from neoplastic peritoneum, which are characterized by greater stiffness than normal scaffolds. A gene expression analysis of organoids grown on different substrates reflected faithfully the clinical and biological characteristics of the organoids. An impact of the ECM on the response to standard chemotherapy treatment for PM was also observed. The ex vivo 3D model, obtained by combining patient-derived decellularized ECM with organoids to mimic the metastatic niche, could be an innovative tool to develop new therapeutic strategies in a biologically relevant context to personalize treatments.

关键词： colorectal cancer peritoneal metastasis organoids extracellular matrix(ECM) decellularized extracellular matrix engineered disease model ECM stiffness

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Analysis of genetic relationship among Arbutus unedo L. genotypes using RAPD and SSR markers

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Journal of Forestry Research 2013年第2期24卷 227-236页

作者： Filomena Gomes Rita costa Maria M. Ribeiro elisa Figueiredo Jorge M. Canhoto CERNAS Departamento Florestal Escola Superior Agrária Coimbra INRB Instituto Nacional de Recursos Biológicos Departamento de Recursos Naturais e Desenvolvimento Sustentável Escola Superior Agrária Centre of Functional Ecology Department of Life Sciences University of Coimbra

The strawberry tree （Arbutus unedo L.） is an underutilized, drought tolerant, fire resistant species with a south western distribution in Europe, and with ecological and putative socio-economical impact in Portugal and Mediterranean countries. Our aim was to develop an appropriate set of molecular markers to enable genetic diversity to be assessed and to fingerprint Arbutus unedo genotypes for breeding and conservation purposes in Portugal. Twenty-seven trees from a broad geographic range were screened with 20 random amplified polymorphic DNA （RAPD primers） and 11 microsatellite markers （SSR）. The RAPDs generated 124 bands, 57.3% of which were polymorphic, with an expected heterozygosity of 27%. We cross-amplified 11 SSR primers developed for Vaccinium spp., and 5 were found to be polymorphic in A. unedo, with 75% of expected heterozygosity, a number of alleles of 11.6, a null allele frequency of 7.6% and a polymorphic information content of 71%. Although the SSRs were more polymorphic and informative than the RAPDs, both markers displayed high genetic variability with the gathered data. No geographic pattern was observed in the genetic variation distribution based on both marker systems, and the lack of correlation between genetic and geographical matrices was confirmed by Mantel tests. Likely, no correlation was found between pairwise SSR and RAPD band-sharing matrices. These results and their implications on A. unedo breeding and conservation programs are discussed.

关键词： Ericaceae fingerprinting geographic pattern molecular markers strawberry tree.

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Intestinal anti-inflammatory activity of Ground Cherry(Physalis angulata L.)standardized CO2 phytopharmaceutical preparation

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World Journal of Gastroenterology 2017年第24期23卷 4369-4380页

作者： luiz domingues almeida junior ana elisa valencise quaglio celso acácio rodrigues de almeida costa Luiz Claudio Di Stasi laboratory of phytomedicines pharmacology and biotechnology(phytopharmatech)department of pharmacologyinstitute of biosciencesuniversidade estadual paulista unespbotucatusao paulocep 18618-970

AIM To investigate the effects of Ground Cherry(Physalis angulata L.)standardized supercritical CO_2 extract in trinitrobenzenesulphonic acid(TNBS)model of rat intestinal *** The animals were divided into groups that received vehicle or *** extract(PACO_2)orally at the doses 25,50 and 100 mg/kg daily by 5 d before TNBS *** effects of PACO_2 were assessed by macroscopic analysis,biochemical determinations of the levels of myeloperoxidase(MPO),alkaline phosphatase(ALP),glutathione and cytokines(such as INF-γ,IL-1β,IL-6,IL-10 and TNF-α),gene expression evaluation(including Hsp70,heparanase,NF-κB,mitogenactivated protein kinases(Mapk)1,3,6 and 9,and the mucins genes Muc 1,2,3 and 4)and histopathological studies using optical,and electronic(transmission and scanning)*** PACO2 extract promoted a significant reduction in MPO and ALP activities,reducing oxidative stress and neutrophil *** effects were accompanied by significant reduction of colonic levels of IFN-γand IL-6 and down-regulation of heparanase,Hsp70,Mapk3,Mapk9,Muc1 and Muc2 genes expression when compared with TNBS-control *** addition,protective effects were also evidenced by reduced neutrophil infiltration,recovery of cell architecture and replacement of mucin by histopathological and ultrastructural *** Physalis angulata supercritical CO2 extract is an intestinal anti-inflammatory product that modulates oxidative stress,immune response and expression of inflammatory mediators,with potentially utility for treating inflammatory bowel disease.

关键词： Intestinal disease Inflammatory bowel disease Physalis angulata L.trinitrobenzenesulphonic acid

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King's College criteria and the Clichy-Villejuif criteria require adjustments for assessing acute liver failure due to yellow fever

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World Journal of Transplantation 2025年第1期15卷 124-134页

作者： Bruno da Silva Athanasio Antonio Marcio de Faria Andrade Vivian Vasconcelos costa Juliano Felix Castro Silverio Leonardo Macedo Garcia Mauro Martins Teixeira Daniele da Gloria Souza Paula Vieira Teixeira Vidigal Cristiano Xavier Lima Department of Surgery Federal University of Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil Liver Transplantation Unit Felicio Rocho HospitalBelo Horizonte 30110-934Minas GeraisBrazil Department of Morphology Federal University of Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil Department of Biochemistry and Immunology Federal University of Minas GeraisBelo Horizonte 31270-901Minas GeraisBrazil Department of Pathology Federal University of Minas GeraisBelo Horizonte 30130-100Minas GeraisBrazil

BACKGROUND Acute liver failure(ALF)is a severe condition characterized by rapid deterioration of liver function in individuals without preexisting liver *** transplantation(LT)is the most impactful *** fever(YF)is an infectious disease that primarily affects the liver and has a high mortality ***,LT can be a viable option for treating rare cases with extensive liver ***,the criteria for assessing the severity of ALF and determining the indications for transplantation have not been specifically validated for cases caused by *** To present necessary adjustments to established scoring systems for ALF secondary to *** This was an observational,retrospective,single-center *** consecutive patients with confirmed ALF due to YF were monitored in the intensive care unit by a specialized liver transplant team during a three-month epidemic outbreak in *** hospitalization,general supportive therapeutic measures were implemented,and the patients were regularly assessed using the King's College criteria and the Clichy-Villejuif criteria to determine the severity of liver *** is considered a viable measure for patients with signs of end-stage liver *** Eight of 14(57%)patients developed severe neurological alterations within the first 96 hours after hospital *** patients underwent emergency LT,and despite a moderate viral infection of the graft after transplantation,the 5-year survival rate was 50%.Although the King's College criteria and the Clichy-Villejuif criteria are the main scoring systems for ALF,they are insufficient for predicting the risk of mortality in this context,primarily because of low serum bilirubin levels in the final stage of the disease and significant disparities between coagulation abnormalities and patient *** To ensure good applicability in cases of YF-induced ALF,the authors suggest adaptations to the King's College and Clichy-Vill

关键词： Yellow fever Acute liver failure Liver transplantation King's College criteria Clichy-Villejuif criteria

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EFFECTIVE NETWORKS FOR REAL-TIME DISTRIBUTED PROCESSING

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Journal of Systems Science & Complexity 2011年第1期24卷 39-50页

作者： Gonzalo TRAVIESO Luciando da Fontoura costa Instituto de Fisica de Sao Carlos Universidade de Sao Paulo Av. do Trabalhador SSo-Carlensc 400 13566 - 590 Sao Carlos SP Brazil.

This paper applies the concepts and methods of complex networks to the development of models and simulations of master-slave distributed real-time systems by introducing an upper bound in the allowable delivery time of the packets with computation results. Two representative intercom nection models are taken into account： Uniformly random and scale free （Barabasi-Albert）, including the presence of background traffic of packets. The obtained results include the identification of the uniformly random interconnectivity scheme as being largely more efficient than the scale-free counterpart. Also, increased latency tolerance of the application provides no help under congestion.

关键词： Complex networks distributed computing real-time.

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Pathogenesis and clinical management of arboviral diseases

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World Journal of Virology 2025年第1期14卷 9-50页

作者： Victoria Cenci Dietrich Juan Marcos Caram costa Marina Maria Gomes Leite Oliveira Carlos Eduardo Oliveira Aguiar Luis Guilherme de Oliveira Silva Marcel Silva Luz Fabian Fellipe Bueno Lemos Fabrício Freire de Melo Instituto Multidisciplinar em Saúde Universidade Federal da BahiaVitória da Conquista 45029-094BahiaBrazil

Arboviral diseases are viral infections transmitted to humans through the bites of arthropods,such as mosquitoes,often causing a variety of pathologies associated with high levels of morbidity and *** the past decades,these infections have proven to be a significant challenge to health systems worldwide,particularly following the considerable geographic expansion of the dengue virus(DENV)and its most recent outbreak in Latin America as well as the difficult-tocontrol outbreaks of yellow fever virus(YFV),chikungunya virus(CHIKV),and Zika virus(ZIKV),leaving behind a substantial portion of the population with complications related to these ***,the world is experiencing a period of intense globalization,which,combined with global warming,directly contributes to wider dissemination of arbovirus vectors across the ***,all continents remain on high alert for potential new ***,this review aims to provide a comprehensive understanding of the pathogenesis of the four main arboviruses today(DENV,ZIKV,YFV,and CHIKV)discussing their viral characteristics,immune responses,and mechanisms of viral evasion,as well as important clinical aspects for patient *** includes associated symptoms,laboratory tests,treatments,existing or developing vaccines and the main associated complications,thus integrating a broad historical,scientific and clinical approach.

关键词： Arboviruses Arbovirus infections Dengue Zika virus Yellow fever Chikungunya virus Clinical diagnosis Pathogenesis Flavivirus Togaviridae infections

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Ethylene-auxin crosstalk regulates postharvest fruit ripening process in apple

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Fruit Research 2021年第1期1卷 116-128页

作者： Nicola Busatto Alice Tadiello Marco Moretto Brian Farneti Francesca Populin Urska Vrhovsek Mauro Commisso elisa Sartori Paolo Sonego Franco Biasioli Guglielmo costa Flavia Guzzo Paolo Fontana Kristof Engelen Fabrizio costa Research and Innovation Centre Fondazione Edmund Machvia Mach 138098 San Michele all'AdigeTrentoItaly Department of Biotechnology University of VeronaStrada le Grazie 15CàVignal 137134 VeronaItaly Department of Agricultural Science University of BolognaVia Fanin 4640127BolognaItaly Center Agriculture Food Environment C3A University of TrentoVia Mach 138098 San Michele all'AdigeTrentoItaly

The ripening of climacteric fruits,such as apple,is represented by a series of genetically programmed events orchestrated by the action of several *** this study,we investigated the existence of a hormonal crosstalk between ethylene and auxin during the post-harvest ripening of three internationally known apple cultivars:‘Golden Delicious',‘Granny Smith'and‘Fuji'.The normal climacteric ripening was impaired by the exogenous application of 1-methylcyclopropene(1-MCP)that affected the production of ethylene and the physiological behaviour of specific ethylene-related quality traits,such as fruit texture and the production of volatile organic *** application of 1-MCP induced,moreover,a de-novo accumulation of *** RNA-Seq wide-transcriptome analysis evidenced as the competition at the level of the ethylene receptors induced a cultivar-dependent transcriptional *** DEGs annotation carried out through the KEGG database identified as most genes were assigned to the plant hormone signaling transduction category,and specifically related to auxin and *** interplay between these two hormones was further assessed through a candidate gene analysis that highlighted a specific activation of GH3 and ILL genes,encoding key steps in the process of the auxin homeostasis *** results showed that a compromised ethylene metabolism at the onset of the climacteric ripening in apple can stimulate,in a cultivar-dependent fashion,an initial de-novo synthesis and de-conjugation of auxin as a tentative to restore a normal ripening progression.

关键词： crosstalk cultivar process

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Oxidative stress in N88S seipinopathy:novel insights into the mechanisms of neurodegeneration and therapeutic avenues

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Neural Regeneration Research 2023年第8期18卷 1719-1720页

作者： Vítor costa Vitor Teixeira i3S-Instituto de Investigação e Inovação em Saúde Universidade do PortoPortoPortugal Yeast Signalling Networks IBMC-Instituto de Biologia Molecular e CelularUniversidade do PortoPortoPortugal ICBAS Instituto de Ciências Biomédicas Abel SalazarUniversidade do PortoPortoPortugal

Lipid droplets (LDs) are ubiquitous cellular orga nelles that perform functions mostly dedicated to energy homeostasis and lipid *** neutral lipid depots (triacylglycerol,sterol esters),they can be rapidly mobilized through lipase-mediated hydrolysis (lipolysis) or via lipophagy,a specific form of autophagy devoted to consumption of LDs inside the lysosome.

关键词： hydrolysis insight devoted

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Prenatal and postnatal drug exposure:focus on persistent central effects

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Neural Regeneration Research 2023年第8期18卷 1697-1702页

作者： Giulia costa Alexia E.Pollack Department of Biomedical Sciences Section of NeuroscienceUniversity of CagliariCagliariItaly Department of Biology University of Massachusetts-BostonBostonMAUSA

Clinical studies indicate significant use of prescription,nonprescription and social/recreational drugs by women during pregnancy;however,limited knowledge exists about the detrimental effects that this practice may have on the developing central nervous system of the ***,few experimental and clinical data are available on how gestational exposure could exacerbate the effects of the same or a different drug consumed by the offspring later in *** present review summarizes recent findings on the central toxicity elicited by several classes of drugs,administered prenatally and postnatally in experimental animals and humans,focusing on prescription and nonprescription analgesics,anti-inflammatory agents,alcohol and nicotine.

关键词： 3 4-methylenedioxymethamphetamine acetaminophen alcohol chlorpyrifos dexamethasone ibuprofen methadone neuroinflammation neurotoxicity nicotine

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Structure,stability,catalytic activity,and polarizabilities of small iridium clusters

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Chinese Physics B 2018年第6期27卷 225-230页

作者： Francisco E Jorge José R da costa Venaancio Unidade Academica dc Ffsica Universidade Federal de Campina Grande 58429-900 Campina Grande Brazil Departamento de Ffsica Universidade Federal do Espfrito Santo 29060-900 Vitoria Brazil

At the second order Douglas–Kroll–Hess（DKH2） level, the B3 PW91 functional in conjunction with the relativistic all-electron basis set of valence triple zeta quality plus polarization functions are employed to compute bond lengths, dissociation energies, vertical ionization potentials, and the highest occupied molecular orbital-lowest unoccupied molecular orbital energy gaps of the small iridium clusters（Irn, n≤8）. These results are compared with the experimental and theoretical data available in the literature. Our results confirm the theoretical predictions made by Feng et al. about the catalytic activities of the Ir4 and Ir6 clusters. From the optimized geometries, DKH2 calculations of static electric mean dipole polarizabilities and polarizability anisotropies are also carried out. It is the first time that the polarizabilities of small iridium clusters have been studied. For n≤4, the mean dipole polarizabilities per atom present an odd–even oscillatory behavior,whereas from Ir5 to Ir8, they decrease with the cluster size increasing. The dependence of the polarizability anisotropy on the structure symmetry of the iridium cluster is verified.

关键词： B3PW91 functional all-electron basis sets DKH2 calculations iridium clusters polarizabilities

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