28492 research outputs found
Sort by
ETV4 plays a role on the primary events during the adenoma-adenocarcinoma progression in colorectal cancer
No full textColorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause
of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition.
As methods: ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene
expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients. In the results, gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelialmesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples.
This way, our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special
emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration
Avaliação de marcadores de ativação imune e inflamação associados ao risco de desenvolvimento de doença cardiovascular em controladores do HIV
No full textA infecção pelo HIV-1 é caracterizada pela desregulação do sistema imune, resultando em níveis aumentados de ativação imune e inflamação persistente. Alguns indivíduos denominados controladores do HIV-1 (HICs), no entanto, apresentam controle espontâneo da replicação viral e indícios de preservação da resposta imune. Entre HICs, dados discordantes existem acerca dos níveis de ativação imune e da frequência de subpopulações de linfócitos T, incluindo Treg e Th17. Além disso, alguns estudos indicaram inflamação persistente e maior incidência de aterosclerose e hospitalização em HICs comparados com a população geral. Sabendo que fenômenos associados com ativação imune e inflamação participam da gênese de doenças cardiovasculares (CVD), o presente estudo avaliou a extensão da imunopatogênese em HICs através de diversos marcadores de ativação imune e inflamação e caracterizados como alterados na infecção pelo HIV-1 e em indivíduos com CVD. Para tal, perfis de ativação e diferenciação de linfócitos T, níveis de ativação plaquetária, frequência de agregados monócitos plaquetas, o balanço de subpopulações de monócitos e a concentração de marcadores séricos foram avaliados em dois grupos de HICs com diferentes níveis de controle da viremia \2013 Controladores de Elite (EC) e Controladores Virêmicos (VC) \2013 e comparados com os dados de dois grupos controle - indivíduos infectados pelo HIV-1 em tratamento antirretroviral (cART) e indivíduos HIV-1 negativos (HIVneg). Ao avaliar parâmetros da ativação imune, ECs demonstraram níveis similares de linfócitos T ativados em comparação com HIVneg, enquanto cART e VCs apresentaram níveis elevados dessas células. Nas análises de subpopulações de células T CD4+ em ECs, apenas células T de memória transicional apresentaram frequências alteradas em relação a HIVneg No entanto, VCs apresentaram frequências maiores de linfócitos terminalmente efetores, naive e T de memória tronco, além de frequências menores de linfócitos de memória transicional e memória central comparado com HIVneg. Entre os linfócitos T CD8+ , ECs apresentaram frequências aumentadas de linfócitos T de memória tronco, enquanto VCs apresentaram altas frequências de células terminalmente efetoras. ECs apresentaram frequências altas de Tregs ativadas em comparação com os grupos controle, apesar dos HICs apresentarem menores frequências de Tregs totais em comparação com HIVneg. Altas frequências de linfócitos Th17 e razões Th17/Treg ainda foram observadas em ECs, indicando preservação de células Th17 neste grupo. Ao avaliar parâmetros inflamatórios, os dois grupos de HICs apresentaram maior expressão de CD62P em plaquetas comparados com HIVneg. Diferenças na frequência de agregados monócitos plaquetas não foram observadas. Menores frequências de monócitos clássicos em VCs e maiores frequências de monócitos não clássicos em VCs e ECs em comparação com HIVneg foram observadas mesmo após ajuste para variáveis confundidoras. Entre os marcadores séricos, níveis elevados em comparação com HIVneg foram observadas para D-dímero, ST2,VCAM-1 e ICAM-1 em VCs, VCAM-1 e ICAM-1 em cART e VCAM-1 em ECs, mesmo após ajuste para fatores confundidores. No conjunto, VCs apresentaram níveis elevados de diversos marcadores de ativação imune e inflamação, enquanto ECs apresentam evidências de equilíbrio do sistema imune e controle da ativação celular, apesar de inflamação persistente. Os níveis de inflamação em ECs, no entanto, são comparáveis ao de cART indicando que esses indivíduos podem se beneficiar de terapias alternativas à cART que visem diminuir a inflamaçãoThe HIV-1 infection is characterized by immune system deregulation, resulting in increased levels of immune activation and persistent inflammation. However, some individuals denominated HIV-1 Controllers (HICs) present spontaneous control of viral replication and preservation of immune response. Among HICs, discordant data exist about the levels of immune activation and the frequency of T lymphocytes subsets, including Treg and Th17. Moreover, some studies indicated persistent inflammation and a higher incidence of atherosclerosis and hospitalization in HICs compared to the general population. Knowing that phenomena associated with immune activation and inflammation participate in the genesis of cardiovascular diseases (CV), this study evaluated the extension of immunopathogenesis in HICs through several markers associated with the immune activation and inflammation and characterized as increased in the HIV-1 infection and individuals with CVD. For this, activation and differentiation profiles of T lymphocytes, levels of platelet activation, frequency of monocyte-platelet aggregates, the balance of monocyte subsets, and the concentration of serum markers were evaluated in two groups of HICs with different levels of viremia control \2013 Elite controllers (ECs) and Viremic Controllers (VCs) \2013 and compared with the data obtained from two control groups - HIV-1 infected individuals under antiretroviral therapy (cART) and non-infected individuals (HIVneg). For immune activation analyses, ECs showed similar levels of activated T lymphocytes when compared to HIVneg, while cART and VCs showed elevated levels of these cells In T CD4+ subset analyses on ECs, only transitional memory T cells had altered frequencies in comparison to HIVneg, while VCs displayed higher frequencies of terminally effector, naïve and stem memory T cells and lower frequencies of transitional memory and central memory T cells when compared to HIVneg. Among T CD8+ T cells, ECs showed increased frequencies of stem memory T cells, while VCs presented higher frequencies of terminally effector T cells. ECs also presented higher frequencies of activated Tregs in comparison to control groups, although HICs had lower frequencies of total Tregs compared to control groups. Higher frequencies of Th17 cells and increased Th17/Tregs ratios were also observed for ECs, indicating preservation of Th17 cells in this group. For inflammatory parameters, both HICs groups presented higher expression. Of CD62P in platelets when compared to HIVneg. Differences in the frequencies of monocyte-platelet aggregates were not observed among the groups. Lower frequencies of classical monocytes in VCs and higher frequencies of nonclassical monocytes in VCs and ECs when compared to HIVneg were observed even after statistical adjustment for confusing variables. Among serum markers concentrations, increased levels when compared to HIVneg were observed for D-dimer, ST2, VCAM-1, ICAM-1 in VCs, VCAM-1, and ICAM-1 in cART and VCAM-1 in ECs after statistical adjustments. As a whole, VCs presented alterations at several markers of immune activation and inflammation, while ECs presented evidence an equilibrated immune system and control of cellular activation, despite persistent inflammation. The levels of inflammation in ECs, however, are comparable to the observed in cART, indicating that those individuals can benefit themselves from alternative therapies that intend to lower inflammation2022-07-1
The role of Mannose-binding lectin in leprosy: A systematic review
Get PDFLeprosy is an infectious disease that may present different clinical forms depending on host immune response to Mycobacterium leprae. Mannose-binding lectin (MBL) is an acute phase protein associated with the pathophysiology of leprosy. Some studies have shown that there is a correlation between serum levels of MBL and polymorphisms in its gene associated with susceptibility per se and to different clinical forms. The aim of this study was to conduct a systematic review of publications in the literature that studied the association of MBL with leprosy. Databases were searched until December 2020 (PROSPERO: CRD42020158458), and additional searches were conducted scanning the reference lists of the articles. Two independent reviewers assessed the study quality using the Newcastle-Ottawa Quality Assessment Scale. Finally, 10 eligible articles were included in the study. The overall results indicated that both low MBL serum levels and polymorphisms in the structural or promoter region of its gene seem to be associated as protective factors against the development of severe forms. The results suggest that MBL may play a role in the clinical progression of leprosy
NMReDATA: Tools and applications
Get PDFO formato de dados extraídos por ressonância magnética nuclear (NMReDATA) foi proposto como uma forma de armazenar, trocar e disseminar dados de ressonância magnética nuclear (RMN) e metadados físicos e químicos de compostos químicos. Neste artigo, relatamos fluxos de trabalho analíticos que aproveitam o formato NMReDATA uniforme e padronizado. Também damos acesso a um repositório de dados de amostra, que pode servir para validar pacotes de software que codificam ou decodificam arquivos no formato NMReDATA.The nuclear magnetic resonance extracted data (NMReDATA) format has been proposed as a way to store, exchange, and disseminate nuclear magnetic resonance (NMR) data and physical and chemical metadata of chemical compounds. In this paper, we report on analytical workflows that take advantage of the uniform and standardized NMReDATA format. We also give access to a repository of sample data, which can serve for validating software packages that encode or decode files in NMReDATA format
NDM-1-encoding plasmid in Acinetobacter chengduensis isolated from coastal water
Get PDFBackground: Acinetobacter spp. may cause difficult-to-treat nosocomial infections due to acquisition of carbapenemases, including New Delhi metallo-β-lactamase (NDM). This genus has been pointed out as a possible actor in the early dissemination of blaNDM, and this gene has been documented in a variety of species.
Objective: Here we describe an Acinetobacter chengduensis (isolate FL51) carrying blaNDM recovered from coastal water in Brazil.
Methods: In vitro techniques included antimicrobial susceptibility and minimum inhibitory concentration tests, PCR, plasmid profile and matting-out/transformation assays. In silico approaches comprised comparative genomic analyses using appropriate databases.
Results: FL51 grew at room temperature in a variety of culture media, excluding MacConkey. It showed resistance to all beta-lactams tested and to ciprofloxacin. blaNDM-1 was identified, and a single replicon was observed in plasmid profile. In silico DNA hybridization revealed Acinetobacter FL51 as being Acinetobacter chengduensis. blaNDM-1 was flanked upstream by ISAba14-aphA6-ISAba125 and downstream by bleMBL-trpF-Δtat, inserted in a 41,068 bp non typeable plasmid named pNDM-FL51. This replicon showed high coverage and identity with other sequences present in plasmids deposited on the GenBank database, recovered almost exclusively from Acinetobacter spp., associated with hospital settings and animal sources.
Conclusion: We described a recently described environmental Acinetobacter species carrying a plasmid-borne blaNDM associated with a Tn125-like structure. Our findings suggest that replicon may play an important role in blaNDM dissemination among distinct settings within this genus and may support the theory of blaNDM emergence from an environmental Acinetobacter
First paleoparasitological study on human remains from the province of Córdoba (late Holocene)
No full textPaleoparasitology in Argentina has produced a number of studies, especially from Patagonia. However, investigations on parasites in past populations from the central region of the country are absent. In this regard, we performed the first research on parasitosis in human remains from archaeological sites of the province of Córdoba. Thirteen individuals from four archaeological sites, dated of 2562 ± 47 to 533 ± 57 14C years BP, were examined. Paleoparasitological analyses were conducted on 20 sediment samples from the pelvic cavity, using spontaneous sedimentation, disaggregation in hydrochloric acid, and sucrose flotation techniques. We found structures suggestive of helminth eggs of Ascaridoidea and Heterakoidea superfamilies, and of unidentified nematode eggs. As animals are the definitive hosts of the parasites found, the results could suggest the occurrence of false parasitism in the individuals from the region. The close interaction between humans and animals, incorporated as part of the diet, is supported by previous isotopic and zooarchaeological studies. The scarcity of parasite findings in this study would be attributed to taphonomic processes and the environmental characteristics of the sites.La Paleoparasitología en la Argentina ha producido un gran número de trabajos, especialmente en Patagonia. Sin embargo, hay ausencia de estos estudios en las poblaciones de la región central del país. En este sentido, realizamos la primera investigación sobre parasitosis en restos humanos de sitios arqueológicos de la provincia de Córdoba. Se estudiaron 13 individuos de 4 sitios arqueológicos, datados entre 2562 ± 47 y 533 ± 57 14C años AP. Los análisis paleoparasitológicos se aplicaron sobre 20 muestras de sedimentos provenientes de la cavidad pélvica, empleando las técnicas de sedimentación espontánea, disgregación en ácido clorhídrico y flotación en sacarosa. Se hallaron estructuras sugestivas de huevos de helmintos de las superfamilias Ascaridoidea y Heterakoidea, y otros de nemátodos no identificados. Debido a que los animales son los huéspedes definitivos de estos parásitos, los resultados podrían sugerir la presencia de falso parasitismo en los individuos de la región. La relación cercana de los humanos con los animales, utilizados como parte de la dieta, se sustenta en estudios isotópicos y zooarqueológicos previos. La escasez de hallazgos parasitarios en este estudio posiblemente se debe a factores tafonómicos y a las características ambientales de los sitios
Participação em museus de ciências e em ecomuseus: apontamentos a partir da Nova Museologia
No full textA presente pesquisa, de caráter qualitativo, objetiva, de um lado, analisar em que medida existiriam influências da nova museologia em museus de ciências e, de outro, como os seus postulados habitam os ecomuseus. Através de um levantamento de instituições museais no estado do Rio de Janeiro \2013 a partir do Cadastro Nacional de Museus (CNM) e da plataforma Museusbr \2013 e da definição de critérios de elegibilidade, delimitou-se como campo empírico o Museu da Vida e oMuseu da Maré. Enfocando-se os setores educativos destas instituições, a partir da realização de entrevistas com seus gestores e educadores e da revisão da literatura, um primeiro objetivo específico da pesquisa foi analisar em que medida a nova museologia se apresenta nos discursos dos gestores e educadores do Museu da Vida sobre as práticas de mediação e participação da instituição; um segundo objetivo foi compreender de que maneira os gestores e educadores do Museu da Maré identificam os fundamentos da nova museologia em suas práticas de mediação e participação; o terceiro, por fim, foi identificar as implicações do arcabouço teórico da nova museologia para o campo da educação museal, e particularmente para a educação em museus de ciências. A análise dos dados indicou que, no caso do Museu da Vida, não existe uma visão consensual sobre o tema, mas a maioria dos entrevistados considera o paradigma da nova museologia pertinente e que ele é parcialmente adotado pela instituição, reconhecendo que ainda existem muitos desafios a serem enfrentados para a sua efetiva adoção. O diálogo com a literatura permite identificar o Museu da Vida com a terceira geração de museus de ciências, marcada pela valorização da interatividade e que não apresenta aproximações com a perspectiva da nova museologia. Por outro lado, a instituição busca se atualizar frente as demandas sociais contemporâneas, se aproximando do conceito de quarta geração de museus de ciências, que apresenta alguns pontos consoantes com este paradigma. No caso do Museu da Maré, a nova museologia se apresenta, no discurso dos entrevistados, pelo viés da autonomia dos visitantes, da formação majoritária da equipe por moradores e ex-moradores da Maré, e da veiculação de narrativas que valorizam os espaços favelados e a história da Maré contada pela visão de seus moradores, em uma perspectiva que poderíamos chamar decolonial. Para o campo da educação museal e particularmente para as ações educativas dos museus de ciências, a análise indicou que a nova museologia pode contribuir para a superação da perspectiva da interatividade como forma de gerar um deslumbramento acrítico pela ciência, orientando para uma maior autonomia dos sujeitos no espaço museal, para a valorização de seus saberes e interesses e para o pensamento crítico sobre ciência.CAPESThe present research, of qualitative character, aims, by the one hand, to analyze to what measure there would be influences of the new museology in science museums and, by the other hand, how its postulates inhabit ecomuseums. Through a survey of museum institutions in the state of Rio de Janeiro - based on the Cadastro Nacional de Museus (National Museum Register) (CNM) and the Museusbr platform - and the definition of eligibility criteria, The Museu da Vida (The Museum of Life) and the Museu da Maré (Mare Museum) were defined as empirical field. Focusing on the educational sectors of these institutions, starting with interviews with museum´s managers and educators and reviewing the literature, a first specific objective of the research was to analyze to what measures the new museology appears in the speeches of the Museu da Vida´s managers and educators about the institution's mediation and participation practices; a second objective was to understand how Museu da Maré´s managers and educators identify the foundations of the new museology in their mediation and participation practices; the third, finally, was to identify the implications of the theoretical framework of the new museology for the field of museum education, and particularly for education in science museums. The analysis of the data indicated that, in the case of the Museu da Vida, there is no consensus view about the theme, but the majority of the interviewed considered the paradigm of the new museology pertinent and that it is partially adopted by the institution, recognizing that there are still many challenges to be faced for its effective adoption. The dialogue with literature shows the Museu da Vida can be identified with the third generation of science museums, marked by the valorization of interactivity and which does not present any approximations with the perspective of the new museology. By the other hand, the institution seeks to update itself in the face of contemporary social demands, approaching the concept of the fourth generation of science museums, which presents some consonants points with this paradigm. According to the interviewees in the Museu da Maré, the new museology is present due the visitors' autonomy, in the majority of the team being residents and former residents of Maré, and the transmission of narratives which value the favela spaces and the history of Maré told by the resident´s point of view, in a perspective that we could call decolonial. In the field of museum education and particularly for the educational actions of science museums, the analysis indicated that the new museology can contribute to overcoming to the perspective of interactivity as a way of generating an uncritical dazzle by science, aiming at greater autonomy of the subjects in the museum space, the valorization of their knowledge and interests and for critical thinking about science
Ética: pesquisa com seres humanos no Brasil
No full textdubladoVídeo integrante do Curso Princípios básicos do cultivo de células de mamíferos, que aborda a subtema Ética: Pesquisa com seres humanos no BrasilFiocruzMP4Tópicos em cultura de células de mamíferosPrograma de Pós-Graduação em Biociências e Biotecnologi
Impact of HIV status on systemic inflammation during pregnancy Running Head: Inflammation in pregnant women with HIV
No full text1Department of Epidemiology, Columbia University Mailman School of Public Health, New
York, USA
2Department of Medicine, Weill Cornell Medical College, New York, USA
3Department of Biostatistics, Columbia University Mailman School of Public Health, New
York, USA
4Department of Obstetrics and Gynecology, Byramjee Jeejeebhoy Government Medical
College, Pune, India
5Byramjee-Jeejeebhoy Government Medical college-Johns Hopkins University Clinical
Research Site, Pune, India
6Instituto Goncalo Moniz, Fundação Oswaldo Cruz, Salvador, Brazil
7Multinational Organization Network Sponsoring Translational and Epidemiological
Research, (MONSTER) Initiative, Salvador, Brazil
8Faculdade de Medicina, Universidade Federal da Bahia, Salvador, Brazil
9Curso de Medicina, Faculdade de Tecnologia e Ciências, Salvador, Brazil
10Universidade Salvador (UNIFACS), Laureate Universities, Salvador, Brazil
11Escola Bahiana de Medicina e Saúde Pública (EBMSP), Salvador, Brazil
12National Institutes of Health, National Institute for Research in Tuberculosis, International
Center for Excellence in Research, Chennai, India
13Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, USA.Eunice Kennedy Shriver
National Institute of Child Health and Human Development of the National Institutes of
Health under award number R00HD089753 to RS and R01HD081929 to AG. JSM received
support from NIAID (K23AI129854). Additional support for this work was the NIH-funded
Johns Hopkins Baltimore-Washington-India Clinical Trials Unit for NIAID Networks
(UM1AI069465 to AG). BBA is a senior investigator from the Conselho Nacional de
Desenvolvimento Científico e Tecnológico (CNPq), Brazil. MAP received a research
fellowship from the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES;
finance code 001).There are limited studies on the «association» of «HIV infection» with systemic
«inflammation» during «pregnancy».
Design: A «cohort study» (N=220) of «pregnant women» with «HIV» (N=70) (all on antiretroviral
«therapy») and without «HIV» (N=150) were enrolled from an antenatal clinic in Pune, «India».
«Methods»: The following systemic inflammatory markers were measured in «plasma» samples
using «immunoassays»: soluble CD163 (sCD163), «soluble CD14» («sCD14»), intestinal fatty acidbinding
«protein» (I-FABP), «C-reactive protein» (CRP), «alpha 1-acid glycoprotein» (AGP),
«interferon»-β (IFNβ), «interferon»-γ (IFNγ), «interleukin» (IL)-1β, «IL-6», «IL-13», «IL-17A» and «tumor»
«necrosis» factor α (TNFα). Generalized estimating equation (GEE) and «linear regression»
models were used to assess the «association» of «HIV» status with each inflammatory marker
during «pregnancy» and by trimester, respectively.
Results: «Pregnant women» with «HIV» had higher levels of markers for gut «barrier» dysfunction
(I-FABP), «monocyte» activation («sCD14») and markers of systemic «inflammation» («IL-6» and
TNFα), but surprisingly lower levels of AGP, an «acute phase protein», compared to pregnant
«women» without «HIV», with some trimester-specific differences.
Conclusions: Our data show that «women» with «HIV» had higher levels of markers of gut
«barrier» dysfunction, «monocyte» activation and systemic «inflammation». These markers, some of
which are associated with «preterm birth», might help explain the increase in adverse «birth»
outcomes in «women» with «HIV» and could suggest targets for potential interventions
Development of human angiotensin converting enzyme-2 (hACE2) as a strategy to face COVID-19
No full textOs autores externos submeteram sua publicação para apresentação de trabalho no evento “International Symposium on Immunobiologicals”, que foi coordenado e organizado pelo Instituto de Tecnologia em Imunobiológicos (Bio-Manguinhos), da Fundação Oswaldo Cruz