Percorrer por autor "Valente, Ana"
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- Aleitamento materno e peso à nascença – fatores protetores ou de risco para a obesidade infantil? - Estudo COSI Portugal 2010 .Publication . Baleia, Joana; Valente, Ana; Rito, AnaIntrodução: A obesidade continua a ser uma doenças mais prevalentes na infância e um sério desafio de saúde pública a nível mundial. Devido ao seu carácter preditivo de obesidade na idade adulta e co-morbilidades, fatores inerentes ao início da vida têm vindo a ser estudados pelo seu potencial papel determinante no risco de desenvolver obesidade na infância. Objetivos: O presente trabalho pretende estudar o aleitamento materno e o peso à nascença, como possíveis fatores protetores ou de risco para a obesidade infantil. Métodos: O estudo compreende 3637 crianças dos 6-8 anos avaliadas na 2ª fase do COSI Portugal 2010. Os dados do peso à nascença e da amamentação foram obtidos por um questionário familiar. A prevalência de obesidade e excesso de peso foi determinada aplicando o critério da Organização Mundial de Saúde. Resultados: Segundo os critérios estabelecidos pela Organização Mundial de Saúde, no ano de 2010 o excesso de peso afetava 39% das crianças portuguesas, das quais 16,4% eram obesas. No que concerne ao peso à nascença, os resultados mostraram que 8,3% das crianças nasceram com baixo peso (<2500g) e 5,4% apresentaram macrossomia (>4000g) no momento do nascimento. Cerca de 52% das crianças foram amamentadas por um período inferior a 6 meses. Nesta amostra o baixo peso à nascença não constituiu um risco do excesso de peso nas crianças portuguesas (OR = 0,74; IC95% 0,57-0,98) no entanto, as crianças com macrossomia apresentaram uma maior probabilidade de ter excesso de peso (OR = 1,41; IC95% 1,05 1,90) e as crianças com alimentação artificial exclusiva desde o nascimento, maior risco de obesidade (OR = 1,39; IC95% 1,09-1,77). Conclusões: Maior peso à nascença e a ausência de amamentação revelaram ser factores de risco para a prevalência de excesso de peso e de obesidade infantil.
- Avaliação da ingestão de micronutrientes em diabéticos tipo 2Publication . Valente, Ana; Bicho, Manuel; Duarte, Rui; Raposo, João F.; Costa, H.S.
- Comparative analysis of hybrid‑SNP microarray and nanopore sequencing for detection of large‑sized copy number variants in the human genomePublication . Silva, Catarina; Ferrão, José; Marques, Bárbara; Pedro, Sónia; Correia, Hildeberto; Valente, Ana; Rodrigues, António Sebastião; Vieira, LuísBackground: Nanopore sequencing is a technology that holds great promise for identifying all types of human genome variations, particularly structural variations. In this work, we used nanopore sequencing technology to sequence 2 human cell lines at low depth of coverage to call copy number variations (CNV), and compared the results variant by variant with chromosomal microarray (CMA) results. Results: We analysed sequencing data using CuteSV and Sniffles2 variant callers, compared breakpoints based on hybrid-SNP microarray, nanopore sequencing and Sanger sequencing, and analysed CNV coverage. From a total of 48 high confidence variants (truth set), variant calling detected 79% of the truth set variants, increasing to 86% for interstitial CNV. Simultaneous use of the 2 callers slightly increased variant calling. Both callers performed better when calling CNV losses than gains. Variant sizes from CMA and nanopore sequencing showed an excellent correlation, with breakpoints determined by nanopore sequencing differing by only 20 base pairs on average from Sanger sequencing. Nanopore sequencing also revealed that four variants concealed genomic inversions undetectable by CMA. In the 10 CNV not called in nanopore sequencing, 8 showed coverage evidence of genomic loss or gain, highlighting the need to improve SV calling algorithms performance. Conclusions: Nanopore sequencing offers advantages over CMA for structural variant detection, including the identification of multiple variant types and their breakpoints with increased precision. However, further improvements in variant calling algorithms are still needed for nanopore sequencing to become a highly robust and standardized approach for a comprehensive analysis of genomic structural variation.
- Effects of TiO2 Nanoparticles on the Genome-Wide Methylation of Human Epithelial Intestinal CellsPublication . Valente, Ana; Vieira, Luís; Silva, Catarina; Louro, Henriqueta; Silva, Maria João; Ventura, CéliaIntroduction: Titanium dioxide nanoparticles (TiO2NP) have multiple applications in industry (e.g., engineering, cosmetics, food additives), and biomedicine (e.g., targeted drug delivery and biosensing). Food-grade TiO2 (E171) is applied as a food additive to whiten and improve the opacity of food products, while also having the ability to enhance its flavour. In 2021, EU member states banned E171 from all food products, since there is doubts about its genotoxicity. Nevertheless, the ingestion of TiO2NPs may still occur through to other sources, such as contaminated food or water, consumer products (e.g., toothpaste and lipstick) or pharmaceutics. To date, there is some in vitro evidence that TiO2NP may induce changes in DNA methylation. However, very few studies were performed, and none used genome-wide approaches to identify possible differentially methylated genes induced by TiO2NP exposure, and its impact on molecular pathways. Methodology: Caco-2 epithelial intestinal cells were exposed to 14 μg/ml of anatase, rutile or brookite phase TiO2NP for 24h. Genomic DNA was extracted from exposed and non-exposed cells. DNA libraries were generated using the Premium Reduced Representative Bisulfite Sequencing (RRBS) kit (Diagenode) and sequenced on the NextSeq 550 system (Illumina) using 100 bp paired reads. The Galaxy platform was used for read treatment and mapping, methylation calling and assessing of differentially methylated regions between exposed and non-exposed cells. Pathway analysis was performed using Reactome, and gene ontology analysis with the ClueGO plugin in Cytoscape. Results: Significant differential methylation (p ≤ 0.05) of 92 genes (21 hyper- and 71 hypo-methylated), 70 genes (12 hyper- and 58 hypo-methylated) and 88 genes (21 hyper- and 67 hypo-methylated) was observed for the anatase, rutile and brookite phase TiO2NP, respectively. Functional pathway analysis of these methylation changes identified several relevant cellular pathways that may be altered by exposure, such as G alpha signalling events, being some associated to colon cancer. Conclusions: All types of TiO2NP induce changes in genome methylation of intestinal cells, which may affect cell proliferation, differentiation and survival. Moreover, although some dysfunctional pathways are shared between the three TiO2NP, many are type-specific, suggesting different molecular mechanisms of action for each TiO2NP.
- Epigenomics as a novel approach to explore the toxic effects of nanomaterialsPublication . Ventura, Célia; Vieira, Luís; Valente, Ana; Fernandes, Camila; Silva, Catarina; Louro, Henriqueta; Ferreira, Paulo J.T.; Silva, Maria JoãoIn recent years, there has been a huge development of innovative engineered nanomaterials with potential use in industrial and biomedical applications. This increased widespread use raised concerns that nanomaterials may elicit human adverse health effects through occupational, environmental or consumer exposure. Many toxicity studies, mainly in vitro, have showed that some nanomaterials, such as carbon nanotubes or titanium dioxide nanoparticles (TiO 2 NP), may cause genotoxicity, inflammation, and associated adverse health effects. Nevertheless, few studies have focused on the nanomaterials effect s on the epigenome, namely, modifications of histone tails, microRNA expression or DNA methylation. Here we wil l present two “omics” studies based on next generation sequencing , one focusing on the effect of three nanocellulose s derived from Eucaliptus globulus kraft pulp on the microRNA expression of BEAS 2B, and an other one focusing on the effect of three types of TiO 2 NP on the DNA methylation of Caco 2 cells. Regarding the former 24h exposure to fibrillar micro/nanocellulose s did not induced significant (FDR ≤ 0.05) differentially expressed microRNAs, as compared to non exposed cells. By contrast, the crystalline nanocelul l ose induced the over and under expression of 22 and 30 microRNAs, respectively. These microRNAs can be f urther explored as potential biomarkers for human biomonitoring and co ntribute to elucidate the mechanisms of action of crystalline nanocellulose. As to the genome wide methylation study Reduced Representative Bisulfite Sequencing allowed the identification of significant ( p ≤ 0.05) differential methylation of 92, 70, and 88 gene sequences for the anatase, rutile and brookite phase TiO 2 NP exposures, respectively. Functional pathway analysis of these methylation changes showed that all TiO 2 NP may affect cell proliferation, differentiation, and survival, and suggested different molecular mechanisms of action for each type of TiO 2 NP. In conclusion, epigenomics revealed to be a powerful tool to understand the key molecular events underlying nanomaterials effects.
- Frequência de polimorfismos genéticos de enzimas envolvidas no metabolismo da homocisteína em diabéticos tipo 2Publication . Valente, Ana; Bicho, Manuel; Duarte, Rui; Raposo, João F.; Costa, H.S.INTRODUÇÃO: A hiperhomocisteinémia tem vindo a ser associada com polimorfismos genéticos das enzimas 5,10-metilenotetrahidrofolato (MTHF), cistationina β-sintetase (CBS) e dihidrofolato redutase (DHFR). São escassos os dados epidemiológicos de distribuição dos polimorfismos C677T da MTHFR, 844ins68 da CBS e deleção de 19 pares de bases do gene da DHFR em diabéticos tipo 2. Conhecer a variação polimórfica destas enzimas e sua relação com outros factores de risco cardiovascular pode ajudar a definir medidas de prevenção e contribuir de forma relevante para uma nutrição clínica personalizada. OBJECTIVO: Avaliar a distribuição dos polimorfismos C677T da MTHFR, 844ins68 da CBS e deleção de 19 pares de bases do gene da DHFR em diabéticos tipo 2, bem como a frequência da presença simultânea de dois ou mais destes polimorfismos. MÉTODOS: Estudo epidemiológico observacional tipo caso-controlo em 134 adultos caucasianos com idades entre 40-75 anos. Foram constituídos dois grupos: GI - 69 diabéticos tipo 2 com angiopatia; GII - 65 diabéticos tipo 2 sem angiopatia. Os polimorfismos genéticos foram identificados por PCR e/ou RFLP. A análise estatística foi realizada em SPSS®, versão 20.0 (SPSS Inc, Chicago). RESULTADOS: A frequência do polimorfismo da CBS, em heterozigotia foi no GI: 28,4% e no GII: 18,5%. No polimorfismo da MTHFR, os genótipos CT e TT foram mais frequentes no GI (46,4%; 7,2%) do que no GII (41,5%; 6,2%). A prevalência de homozigóticos no polimorfismo da DHFR foi 19,7% (GI) e 16,9% (GII). O genótipo da heterozigotia foi o mais prevalente (GI: 53%; GII: 73,9%). Os diabéticos do GI com o polimorfismo da MTHFR apresentaram com maior frequência hiperhomocisteinémia (OR = 5,37; P = 0,040) em comparação com o GII. O mesmo se verificou para a CBS (OR = 6,71; P = 0,018). A presença simultânea dos polimorfismos da MTHFR e da DHFR foi a mais frequente (GI: 41% vs. GII: 43%). A frequência conjunta dos 3 polimorfismos foi superior no GI (9,1%) em relação ao GII (4,6%). CONCLUSÃO: A elevada frequência isolada do polimorfismo de delecção de 19 pares de bases do gene da DHFR e combinada com o polimorfismo C677T da MTHFR, são condições que têm vindo a ser associadas com uma maior susceptibilidade à ocorrência de eventos cérebro-cardiovasculares. Os polimorfismos C677T da MTHFR e 844ins68 da CBS estão associados com a hiperhomocisteinémia e a sua identificação poderá ser muito relevante em nutrição clínica.
- Genome-wide methylation changes upon Caco-2 cells exposure to undigested and digested titanium dioxide nanoparticlesPublication . Ventura, Célia; Valente, Ana; Vieira, Luís; Silva, Catarina; Rolo, Dora; Silva, Maria Joao; Louro, HenriquetaIntroduction: Titanium dioxide nanoparticles (TiO2NPs) are relevant nanomaterials (NMs) for biomedicine and industry, which raise concerns about its effects on human health, particularly through ingestion. Several studies found that exposure to NMs can lead to DNA methylation changes. DNA methylation regulates gene expression, playing a vital role in development and disease, with aberrant methylation linked to cancer and other health conditions. Aim: We aimed at identifying DNA methylation changes in intestinal cells exposed to three TiO2NPs (NM-102, NM-103, NM-105), either digested or undigested. Their cellular effects were investigated by functional pathway and gene ontology (GO) analysis. Results: 48, 41, 55 differentially methylated genes (DMG) were identified after exposure to undigested NM-102, NM-103, NM-105; 71, 65, 55 DMG in the digested counterparts. Undigested TiO2NPs affected many G-proteins/adenylate cyclase-related pathways (PKA, glucagon, GPER1, CREB1, ADORA2B); the digested had lower impact. Cancer-related pathways were shared. Enriched molecular functions were mainly transcription-related; different biological processes were enriched if TiO2NPs were digested or not. Conclusions: TiO2NPs exposure causes DNA methylation changes that have a functional impact on intestinal cells, which differs with its physicochemical properties and digestion. NM-105 caused hypermethylation, unlike the other TiO2NPs. This study highlights DNA methylation relevance in assessing NMs’ toxicity.
- Perspetiva do consumidor relativa aos efeitos na saúde associados ao consumo de sumos detoxPublication . Santos, Inês Carvalho; Costa, H.S.; Silva, Mafalda A.; Valente, Ana; Albuquerque, T.G.Os sumos detox são uma nova tendência alimentar associada à perda de peso e a um estilo de vida saudável. São constituídos por frutas e hortícolas, alimentos naturalmente ricos em antioxidantes, compostos bioativos e vitaminas, cujo consumo está associado à redução de fatores de risco de doenças crónicas. O objetivo deste trabalho foi avaliar a perceção dos consumidores relativamente aos efeitos na saúde associados ao consumo de sumos detox. Foi desenvolvido e aplicado um questionário online a 285 indivíduos com idades compreendidas entre os 18 e os 84 anos. Os resultados obtidos indicaram que a maioria da população inquirida já ouviu falar em sumos detox e considera que estes não constituem uma boa opção para substituir refeições, embora lhes associe diversos benefícios. Relativamente aos benefícios nutricionais dos sumos detox, os inquiridos destacaram a sua riqueza vitamínica (80,7%), o seu poder de hidratação (61,4%), a sua riqueza mineral (57,9%) e seu teor de fibra (52,6%).
- Presença de listeria monocytogenes em queijos de pasta mole da região a sul do TejoPublication . Gonçalves, Magda; Furtado, Rosália; Coelho, Anabela; Belo Correia, Cristina; Valente, AnaIntrodução: Nas últimas décadas, o número de casos de infeções de origem alimentar provocadas por Listeria monocytogenes tem vindo a aumentar. Objetivo: Deteção e quantificação de Listeria monocytogenes em queijos de pasta mole produzidos na região a Sul do Tejo. Metodologia: Foram analisadas 30 amostras de queijos de pasta mole de diferentes fabricantes, dos quais 66,7% produzidas a partir de leite de ovelha cru. Resultados: Das amostras analisadas, 10% (n = 3) estavam contaminadas com Listeria monocytogenes e 17% (n=5) com Listeria innocua. Conclusão: O consumo de queijos de pasta mole está associado com o aumento do risco de ocorrência de listeriose.
- The Effect of Nanomaterials on DNA Methylation: A ReviewPublication . Valente, Ana; Vieira, Luís; Silva, Maria João; Ventura, CéliaDNA methylation is an epigenetic mechanism that involves the addition of a methyl group to a cytosine residue in CpG dinucleotides, which are particularly abundant in gene promoter regions. Several studies have highlighted the role that modifications of DNA methylation may have on the adverse health effects caused by exposure to environmental toxicants. One group of xenobiotics that is increasingly present in our daily lives are nanomaterials, whose unique physicochemical properties make them interesting for a large number of industrial and biomedical applications. Their widespread use has raised concerns about human exposure, and several toxicological studies have been performed, although the studies focusing on nanomaterials’ effect on DNA methylation are still limited. The aim of this review is to investigate the possible impact of nanomaterials on DNA methylation. From the 70 studies found eligible for data analysis, the majority were in vitro, with about half using cell models related to the lungs. Among the in vivo studies, several animal models were used, but most were mice models. Only two studies were performed on human exposed populations. Global DNA methylation analyses was the most frequently applied approach. Although no trend towards hypo- or hyper-methylation could be observed, the importance of this epigenetic mechanism in the molecular response to nanomaterials is evident. Furthermore, methylation analysis of target genes and, particularly, the application of comprehensive DNA methylation analysis techniques, such as genome-wide sequencing, allowed identifying differentially methylated genes after nanomaterial exposure and affected molecular pathways, contributing to the understanding of their possible adverse health effects.