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Up-regulation of tumor necrosis factor-a pathway survival genes and of the receptor TNFR2 in gastric cancer

World Journal of Gastrointestinal Oncology 2019年第4期11卷 281-294页

作者： Ana Flavia Teixeira Rossi Julia Cocenzo Contiero fernanda da silva manoel-caetano Fabio Eduardo Severino Ana Elizabete silva Department of Biology Sao Paulo State University–UNESP Department of Surgery and Orthopedics Faculty of Medicine Sao Paulo State University–UNESP

BACKGROUND Gastric carcinogenesis can be induced by chronic inflammation triggered by Helicobacter pylori(H. pylori) infection. Tumor necrosis factor(TNF)-α and its receptors(TNFR1 and TNFR2) regulate important cellular processes, such as apoptosis and cell survival, and the disruption of which can lead to cancer. This signaling pathway is also modulated by microRNAs(miRNAs), altering gene *** To evaluate the mRNA and miRNAs expression involved in the TNF-α signaling pathway in gastric cancer(GC) tissues and its *** Quantitative polymerase chain reaction(qPCR) by TaqMan? assay was used to quantify the RNA transcript levels of TNF-α signaling pathway(TNF, TNFR1,TNFR2, TRADD, TRAF2, CFLIP, NFKB1, NFKB2, CASP8, CASP3) and miRNAs that targets genes from this pathway(miR-19 a, miR-34 a, miR-103 a, miR-130 a,miR-181 c) in 30 GC fresh tissue samples. Molecular diagnosis of H. pylori was performed by nested PCR for gene HSP60. A miRNA:mRNA interaction network was construct using Cytoscape v3.1.1 from the in silico analysis performed using public *** Up-regulation of cellular survival genes as TNF, TNFR2, TRADD, TRAF2, CFLIP,and NFKB2, besides CASP8 and miR-34 a was observed in GC tissues, whereas mediators of apoptosis such as TNFR1 and CASP3 were down-regulated. When the samples were stratified by histological type, the expression of miR-103 a and miR-130 a was significantly increased in the diffuse-type of GC compared to the intestinal-type. However, no influence of H. pylori infection was observed on the expression levels of mRNA and miRNAs analyzed. Moreover, the miRNA:mRNA interaction network showed several interrelations between the miRNAs and their target genes, highlighting miR-19 a and miR-103 a, which has as predicted or validated target a large number of genes in the TNF-α pathway,including TNF, TNFR1, TNFR2, CFLIP, TRADD, CASP3 and *** Our findings show that cell survival genes mediated by TNF/TNFR2 binding

关键词： Gastric cancer Tumor necrosis factor-a signaling TNFR1 TNFR2 Cellular survival MicroRNAs

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Downregulation of TNFR2 decreases survival gene expression,promotes apoptosis and affects the cell cycle of gastric cancer cells

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World Journal of Gastroenterology 2022年第24期28卷 2689-2704页

作者： Ana Flávia Teixeira Rossi fernanda da silva manoel-caetano Joice Matos Biselli Ágata silva Cabral Marilia de Freitas Calmon Saiki Marcelo Lima Ribeiro Ana Elizabete silva Department of Biological Sciences Sao Paulo State University(UNESP)São Josédo Rio Preto 15054-000São PauloBrazil Clinical Pharmacology and Gastroenterology Unit São Francisco University(USF)Bragança Paulista 12916-900São PauloBrazil

BACKGROUND Chronic inflammation due to Helicobacter pylori(***)infection promotes gastric *** necrosis factor-α(TNF-α),a key mediator of inflammation,induces cell survival or apoptosis by binding to two receptors(TNFR1 and TNFR2).TNFR1 can induce both survival and apoptosis,while TNFR2 results only in cell *** dysregulation of these processes may contribute to *** To evaluate the effects of TNFR1 and TNFR2 downregulation in AGS cells treated with *** extract on the TNF-α*** AGS cell lines containing TNFR1 and TNFR2 receptors downregulated by specific shRNAs and nonsilenced AGS cells were treated with *** extract for 6 ***,quantitative polymerase chain reaction with TaqMan®assays was used for the relative quantification of the mRNAs(TNFA,TNFR1,TNFR2,TRADD,TRAF2,CFLIP,NFKB1,NFKB2,CASP8,CASP3)and miRNAs(miR-19a,miR-34a,miR-103a,miR-130a,miR-181c)related to the TNF-αsignalling *** cytometry was employed for cell cycle analysis and apoptosis *** In nonsilenced AGS cells,*** extract treatment increased the expression of genes involved in cell survival and inhibited both apoptosis(NFKB1,NFKB2 and CFLIP)and the TNFR1 ***1 downregulation significantly decreased the expression of the TRADD and CFLIP genes,although no change was observed in the cellular process or miRNA *** contrast,TNFR2 downregulation decreased the expression of the TRADD and TRAF2 genes,which are both important downstream mediators of the TNFR1-mediated pathway,as well as that of the NFKB1 and CFLIP genes,while upregulating the expression of miR-19a and ***,a reduction in the number of cells in the G0/G1 phase and an increase in the number of cells in the S phase were observed,as well as the promotion of early *** Our findings mainly highlight the important role of TNFR2 in the TNF-αpathway in gastric cancer,indicating that silencing it can reduce the

关键词： Gastric cancer Helicobacter pylori Tumour necrosis factor-αsignalling pathway TNFR1 TNFR2 miRNAs

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Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans

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Neural Regeneration Research 2025年第2期20卷 343-353页

作者： Ana Milena silva Olaya fernanda Martins Almeida Ana Maria Blanco Martinez Suelen Adriani Marques PhD Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Biomedical Science Institute Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy Federal University of Rio de JaneiroRio de JaneiroBrazil Graduate Program in Pathological Anatomy(PPGAP/UFRJ) Department of Neurobiology/Institute of BiologyCampus do GragoatáNiteróiRio de JaneiroBrazil

Spinal cord injury results in the loss of sensory,motor,and autonomic functions,which almost always produces permanent physical ***,in the search for more effective treatments than those already applied for years,which are not entirely efficient,researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach,seeking to promote neuronal recovery after spinal cord *** of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and,consequently,boosting functional *** the majority of experimental research has been conducted in rodents,there is increasing recognition of the importance,and need,of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in *** article is a literature review from databases(PubMed,Science Direct,Elsevier,Scielo,Redalyc,Cochrane,and NCBI)from 10 years ago to date,using keywords(spinal cord injury,cell therapy,non-human primates,humans,and bioengineering in spinal cord injury).From 110 retrieved articles,after two selection rounds based on inclusion and exclusion criteria,21 articles were ***,this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans,aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

关键词： bioengineering biomaterials cell therapy humans non-human primates spinal cord injury stem cell therapy

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Upregulation of the APE1 and H2AX genes and miRNAs involved in DNA damage response and repair in gastric cancer

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Genes & Diseases 2019年第2期6卷 176-184页

作者： fernanda S.manoel-caetano Ana Flávia T.Rossi Gabriela Calvet de Morais Fábio Eduardo Severino Ana Elizabete silva Department of Biology UNESPSāo Paulo State UniversityCampus of Sāo Josédo Rio PretoRua Cristòvāo Colombo226515.054-000Sāo Josédo Rio PretoSāo PauloBrazil Department of Surgery and Orthopedics Faculty of MedicineUNESPSāo Paulo State UniversityCampus of BotucatuAv.Prof.Mário Rubens Guimarāes Montenegros/n18.618-687BotucatuSāo PauloBrazil

Gastric cancer remains one of the leading causes of cancer-related death worldwide,and most of the cases are associated with Helicobacter pylori *** bacterium promotes the production of reactive oxygen species(ROS),which cause DNA damage in gastric epithelial *** this study,we evaluated the expression of important genes involved in the recognition of DNA damage(ATM,ATR,and H2AX)and ROS-induced damage repair(APE1)and the expression of some miRNAs(miR-15a,miR-21,miR-24,miR-421 and miR-605)that target genes involved in the DNA damage response(DDR)in 31 fresh tissues of gastric *** v3.1.1 was used to construct the postulated miRNA:mRNA interaction *** performed by real-time quantitative PCR exhibited significantly increased levels of the APE1(RQ=2.55,pdamage,which could confer an advantage to cell survival and proliferation in the tumor microenvironment.

关键词： DNA damage response DNA repair Gastric cancer Gene expression microRNA

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Differences in viral kinetics between genotypes 1 and 3 of hepatitis C virus and between cirrhotic and non-cirrhotic patients during antiviral therapy

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World Journal of Gastroenterology 2006年第45期12卷 7271-7277页

作者： José Eymard Medeiros-Filho Isabel Maria Vicente Guedes de Carvalho Mello Joo Renato Rebello Pinho Avidan U Neumann fernanda de Mello Malta Luiz caetano da silva Flair José Carrilho Hepatology Branch Department of Gastroenterology University of So Paulo School of Medicine So Paulo Brazil Viral Immu-nology Laboratory Instituto Butantan So Paulo Brazil Hepatology Branch Department of Gastroenterology University of S?o Paulo School of Medicine So Paulo Brazil Faculty of Life Sciences Bar-Ilan Univer-sity Ramat-Gan Israel Virology Branch Instituto Adolfo Lutz So Paulo Brazil

AIM： TO evaluate the impact of hepatitis C virus （HCV） infection with genotype 1 or 3 and the presence or absence of liver cirrhosis （LC） in the early viral kinetics response to treatment. METHODS： Naive patients （n = 46） treated with interferon-α （IFN-α） and ribavirin and followed up with frequent early HCV-RNA determinations were analysed. Patients were infected with genotype 1 （n = 28, 7 with LC） or 3 （n = 18, 5 with LC）. RESULTS： The first phase decline was larger in genotype 3 patients than in genotype 1 patients （1.72 vs 0.95 log IU/mL, P 〈 0.001）. The second phase slope decline was also larger in genotype 3 patients than in genotype 1 patients （0.87 vs 0.15 log/wk, P 〈 0.001）. Differences were found in both cirrhotic and non-cirrhotic patients. Genotype 1 cirrhotic patients had a slower 2^nd phase slope than non-cirrhotic patients （0.06 vs 0.18 log/wk, P 〈 0,02）. None of genotype 1 cirrhotic patients had a 1^st phase decline larger than 1 log （non-cirrhotic patients： 55%, P 〈 0.02）. A similar trend toward a slower 2nd phase slope was observed in genotype 3 cirrhotic patients but the 1^st phase slope decline was not different. Sustained viral response was higher in genotype 3 patients than in genotype 1 patients ,（72% vs 14%, P 〈 0.001） and in genotype 1 non-cirrhotic patients than in genotype 1 cirrhotic patients （19% vs 0%）. A second phase decline slower than 0.3 log per week was predictive of non-response in all groups. CONCLUSION： Genotype 3 has faster early viral decline than genotype 1. Cirrhosis correlates with a slower 2nd phase decline and possibly with a lower 1^st phase slope decline in genotype 1 patients.

关键词： Hepatitis C virus Treatment Early kinetics Cirrhosis Genotypes

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Red deer as a disperser of native,but not invasive plants’seeds

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Integrative Zoology 2023年第5期18卷 859-866页

作者： fernanda GARCIA António ALVES da silva Ruben HELENO JoséPaulo SOUSA Joana ALVES Centre for Functional Ecology(CFE) TERRA Associate LaboratoryDepartment of Life SciencesUniversity of CoimbraCoimbraPortugal

INTRODUCTION Seed dispersal is a key process in the life cycle of most plants,with ecological and evolutionary consequences that go beyond vegetation dynamics and cascade to entire ecosystem functioning and stability(Traveset et al.2014).Seed dispersal largely constrains plant recruitment and the distribution of future plant cohorts,thus playing a critical role in the restoration of disturbed sites(Cain et al.2000;Higgins et al.2003).It can also threaten plant diversity by facilitating plant invasions(Vavra et al.2007;Heleno 2020).

关键词： consequences disperse disturbed

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Incidence of hepatocellular carcinoma in outpatients with cirrhosis in Brazil: A 10-year retrospective cohort study

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World Journal of Gastroenterology 2016年第46期22卷 10219-10225页

作者： Marcelo Campos Appel-da-silva Suelen Aparecida da silva Miozzo Isabella de Azevedo Dossin Cristiane Valle Tovo fernanda Branco Angelo Alves de Mattos Graduate Program:Hepatology Universidade Federal de Ciências da Saúde de Porto Alegre(UFCSPA)Porto AlegreRS 900150-170Brazil Ultrasound Imaging Servince Hospital Santa Casa de Porto AlegrePorto AlegreRS 90050-170Brazil

AIM To determine the incidence of hepatocellular carcinoma(HCC) and the impact of HCC surveillance on early diagnosis and survival of cirrhotic outpatients. METHODS In this retrospective cohort study, cirrhotic outpatients undergoing HCC surveillance between March 2005 and March 2014 were analyzed. Exclusion criteria were HIV coinfection; previous organ transplantation; diagnosis of HCC at first consultation; missing data in the medical chart; and less than 1 year of follow-up. Surveillance was carried out every six months using ultrasound and serum alpha-fetoprotein determination. Ten-year cumulative incidence and survival were estimated through Kaplan-Meier analysis. RESULTS Four hundred and fifty-three patients were enrolled, of which 57.6% were male. Mean age was 55 years. Hepatitis C virus and heavy use of alcohol were the main etiologic agents of cirrhosis. HCC was diagnosed in 75 patients(16.6%), with an estimated cumulative incidence of 2.6% in the 1st year, 15.4% in the 5th year, and 28.8% in the 10 th year. Median survival was estimated at 17.6 mo in HCC patients compared to 234 mo in non-HCC patients(P < 0.001). Early-stage HCC was more often detected in patients who underwent surveillance every 6 mo or less(P = 0.05). However, survival was not different between patients with early stage vs non-early stage tumors [HR = 0.54(0.15-1.89), P = 0.33].CONCLUSION HCC is a frequent complication in patients with cirrhosis and adherence to surveillance programs favors early diagnosis.

关键词： Liver cirrhosis Hepatocellular carcinoma Epidemiology Surveillance Survival

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Non-Polar Chemical Constituents of Atemoya and Evaluation of the Cytotoxic and Antimicrobial Activity

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Phyton-International Journal of Experimental Botany 2021年第3期90卷 921-931页

作者： Suzana Vieira Rabêlo fernanda Granja da silva Oliveira Michele Miriam Calixto de Lira Livia Macedo Dutra Adilson Sartoratto Marta Cristina Teixeira Duarte Maria Claudia dos Santos Luciano Maria Francilene Souza silva Cláudia doÓPessoa manoel Odorico de Moraes Filho Emmanoel Vilaça Costa Jackson Roberto Guedes da silva Almeida Post-Graduate Program in Biotechnology(RENORBIO) Federal Rural University of PernambucoRecifePernambuco52171-900Brazil Post-Graduate Program in Biotechnology State University of Feira de SantanaFeira de SantanaBahia44036-900Brazil Center for Studies and Research of Medicinal Plants(NEPLAME) Federal University of San Francisco ValleyPetrolinaPernambuco56304-205Brazil Multidisciplinary Center of Chemical Biological and Agricultural Research(CPQBA)Campinas State UniversityCampinasSão Paulo13083-970Brazil National Laboratory of Experimental Oncology(LabNOE) Federal University of CearáFortalezaCeará60020-181Brazil Departament of Chemistry Federal University of AmazonasManausAmazonas69067-005Brazil

This study aimed to identify the chemical composition of essential oil from fruits(EOAF)and the hexanic crude extract from aerial parts(At-Hex)of atemoya(Annona cherimola x Annona squamosa),a hybrid belonging to the Annonaceae *** and antimicrobial activity was also *** was obtained by hydrodistillation using a Clevenger apparatus,and their composition was analyzed by gas chromatography-mass spectrometry(GC-MS)*** was tested against human tumor cell lines HCT-116(colon carcinoma),SF-295(glioblastoma),OVCAR-8(ovarian carcinoma)and HL60(leukemia)using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide(MTT)assay,while antimicrobial activity was conducted by bioauthography method against eleven microorganisms ***-four compounds were identified in the EOAF and twenty-nine in *** monoterpenes linalool(25.70%),α-pinene(10.38%),β-pinene(9.12%),transocimene(7.43%),and the sesquiterpene bicyclogermacrene(12.58%)were the major constituents of EOAF,whereas the sesquiterpene spathulenol(13.91%)was the main compound of ***-Hex showed a high cytotoxicity against SF-295(glioblastoma).These findings show an important chemotaxonomic contribution for the Annonaceae family,mainly for the Annona *** proved to be a promising source of substances with potential cytotoxic activity.

关键词： Annona GC-MS volatile compounds terpenoids biologic activities

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Gangliosides in nervous system development,regeneration,and pathologies

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Neural Regeneration Research 2023年第1期18卷 81-86页

作者： Juliana F.Vasques Renata Guedes de Jesus Gonçalves Almir Jordão da silva-Junior Robertta silva Martins fernanda Gubert Rosalia Mendez-Otero Instituto de Ciências Biomédicas Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Instituto de Biofísica Carlos Chagas Filho Universidade Federal do Rio de JaneiroRio de JaneiroBrazil Programa Redes de Pesquisa em Saúde no Estado do Rio de Janeiro Rio de JaneiroBrazil Programa Rede NanoSaúde do Estado do Rio de Janeiro Rio de JaneiroBrazil Instituto Nacional de Ciência e Tecnologia em Medicina Regenerativa Rio de JaneiroBrazil

Gangliosides,sialic acid-containing sphingolipids,are major constituents of neuronal *** to the number of sialic acids and the structure of the oligosaccharide chain,gangliosides can be classified as simple or complex and grouped in different *** of gangliosides have been identified in vertebrate cells,with different expression patterns during development and related to several physiological processes,especially in the nervous *** GD3 and its O-acetylated form,9acGD3,are highly expressed in early developmental stages,GM1,GD1a,GD1b,and GT1b are the most abundant ganglioside species in the mature nervous *** in enzymes involved in ganglioside metabolism can lead to the accumulation of specific species,a condition termed gangliosidosis and usually marked by severe neurological *** in ganglioside levels have also been described in several neurodegenerative diseases,such as Alzheimer’s and Parkinson’*** this review,we summarized recent information about the roles of GD3,9acGD3,GM1,GD1a,GD1b,GT1b,and other ganglioside species in nervous system development and regeneration,as well as clinical trials evaluating possible therapeutic applications of these molecules.

关键词： 9acGD3 gangliosides GD1a GD1b GD3 glycolipids GM1 GM2 GM3 GM4 GT1b

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Microbiological biostimulant promotes rooting of olive cuttings

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International Journal of Agricultural and Biological Engineering 2021年第6期14卷 207-212页

作者： Giovana Ritter Fabíola Villa daniel Fernandes da silva Odair Alberton fernanda Jaqueline Menegusso Tatiane Eberling Joyce Dória Western ParanáState University(Unioeste) Campus Marechal Cândido Rondon.Marechal Cândido RondonPR85960-000Brazil Paranaense University(UNIPAR) UmuaramaPR87502-210Brazil Federal University of Lavras LavrasMG37200-000Brazil

The most widely used method of olive propagation is cutting,although for some cultivars the technique is still *** objective of this work was to evaluate the use of plant growth promoter bacteria and arbuscular mycorrhizal fungi in the rooting of olive *** experiments were conducted from October 2017 to January 2018 with cuttings from 4 olive cultivars(Ascolano 315,Koroneiki,Maria da Féand Picual)from four-year-old *** first experiment consisted of 4 olive cultivars and 3 mycorrhizal species plus the control and the second experiment of 3 concentrations of commercial inoculant(Nitro1000®),containing Azospirillum brasilense plus *** cuttings were treated with 3000 mg/L of indolebutyric acid(IBA).The experimental design used in the two experiments was randomized blocks,in a 4×4 factorial scheme,containing 25 stakes per replicate and 3 *** cuttings were kept under weaver conditions and within a low rooting *** 75 d,the percentage of rooted cuttings,callus and sprouts,length of the largest root,number and length of shoots were *** use of FMA in Maria da Féand Picual has a positive response to cutting rooting and the fungi benefit the quality of the seedlings by the higher number of shoots and larger root *** relation of Azospirillum brasilense cultivar is specific,being that,the cultivar Picual does not respond to inoculation of the bacterium having less viability in the propagation by *** da Féand Koroneiki have the best percentages of rooting with the use of 75.00 and 52.00 mL/L of inoculant,respectively.

关键词： Azospirillum brasilense Arbuscular mycorrhizal fungi Propagation Olea europaea L. microorganism

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