Browsing by Issue Date, starting with "2021-02"
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- Desenvolvimento de abordagens terapêuticas de RNA em Doenças Lisossomais de SobrecargaPublication . Sandra, AlvesSobre o desenvolvimento de abordagens terapêuticas de RNA em Doenças Lisossomais de Sobrecarga.
- 1+Million Genomes Initiative /Beyond 1 Million Genomes CSA UpdatePublication . Vicente, AstridThe 1+ Million Genomes initiative has the potential to improve disease prevention, allow for more personalised treatments and support groundbreaking research. The '1+ Million Genomes' (1+MG) initiative aims to enable secure access to genomics and the corresponding clinical data across Europe for better research, personalised healthcare and health policy making. Since the Digital Day 2018, 22 EU countries, the UK and Norway signed Member States’ declaration on stepping up efforts towards creating a European data infrastructure for genomic data and implementing common national rules enabling federated data access. The initiative forms part of the EU’s agenda for the Digital Transformation of Health and Care and is aligned with the goals of the European Health Data Space.
- Functional characterization of variants associated with Familial HypercholesterolemiaPublication . Alves, Ana CatarinaFamilial hypercholesterolemia is a cardiovascular disease risk condition since its characterized by elevated lipid values since childhood. In this work we stratified CVD risk in a sample of FH patients and the general population and analysed both cohorts in terms of lipid lowering therapy used and attainment of lipid therapeutic target levels.
- Development of an antisense oligonucleotides-based therapy for mucolipidosis type II α/β: in vivo studiesPublication . Gonçalves, Mariana; Matos, Liliana; Santos, Juliana Inês; Coutinho, Maria Francisca; Prata, Maria João; Pires, Maria João; Oliveira, Paula; Alves, SandraIntroduction: The RNA molecule has become an increasingly promising target for the therapy of various diseases. Mucolipidosis type II α/β (ML II α/β) is one of the most severe Lysosomal Storage Disorders and is caused by the deficiency of the enzyme GlcNAc-1- phosphotransferase. This enzyme is responsible for the addition of the mannose 6-phosphate (M6P) marker to lysosomal enzymes, which allow their targeting to lysosomes. GlcNAc-1- phosphotransferase is encoded by the GNPTAB and GNPTG genes. Of the several mutations that occur in ML II α/β, the deletion of 2 nucleotides from GNPTAB exon19 (c.3503_3504del) is the most frequent, being a good target for a mutation specific therapy as there is no therapy for this disease 1,2. In this study, we explored the possibility of an innovative therapeutic strategy based on the use of antisense oligonucleotides (AOs) for ML II. In a previous in vitro study in ML II patient fibroblasts, AOs were used to promote the exon 19 skipping from the GNPTAB pre-mRNA, resulting successfully in the production of an in-frame mRNA 3. Currently, our objective is to evaluate the therapeutic potential of this approach in vivo in mice (Mus musculus) of the strain C57BL/6. Material & Methods: Eighteen animals with an average body mass of 25 g were used. During the study, individual body weight, food and water intake were recorded. The animals were divided into 6 groups: groups 1 and 4 were injected with saline solution, groups 2 and 5 were injected with AO at 25 mg / kg and groups 3 and 6 were injected with AO at 50 mg / kg. All animals were injected intraperitoneally and sacrificed after 4 days (groups 1, 2 and 3) or after 7 days (groups 4, 5 and 6). At the end of the experiment, the organs were collected, weighted and frozen at -80ºC, for later RNA extraction, cDNA synthesis and PCR. Statistical analysis was performed using the GraphPad Prism® for Windows program. Statistical significance between groups was determined by analysis of variance (ANOVA), followed by a Bonferroni test. All ethical issues were followed by the guidelines of the Portuguese General Directorate of Food and Veterinary. Results: Our results show that mice from groups 5 and 6 have a lower liver mass compared to the other groups, with significant differences (p <0.05). Liver of animals from group 3 has a lower weight compared to the liver of animals from group 2 and group 4, with a statistically significant difference. However, exon 19 skipping was not observed in any organ sample using any of the tested doses or incubation periods. Conclusions: To explain these first in vivo results we can theorize that the doses administered were not sufficient to achieve a response or the AO may have had a high clearance rate or did not recognize the target RNA. Moreover, the collected organs should have been preserved in liquid nitrogen to maintain RNA integrity. Other experiments will be done in the near future to overcome these preliminary data. References: [1] R. V. Velho et al. Human mutation. [2] M. F. Coutinho, et al. Biochemistry research international [3] L. Matos, et al. Human Gene Therapy.
- Seroprevalence of SARS-CoV-2 Infection in Portugal in May-July 2020: Results of the First National Serological Survey (ISNCOVID-19)Publication . Kislaya, Irina; Gonçalves, Paulo; Barreto, Marta; De Sousa, Rita; Garcia, Ana Cristina; Matos, Rita; Guiomar, Raquel; Rodrigues, Ana Paula; ISNCOVID-19 groupIntroduction: The aim of this study was to estimate and describe the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) specific antibodies (immunoglobulin M and/or immunoglobulin G) in Portugal in May-July 2020. Material and methods: A cross-sectional seroepidemiological survey was developed after the peak of the first epidemic wave on a sample of 2301 Portuguese residents, aged 1 year or older. Survey sample was selected using a two-stage stratified non-probability sampling design (quota sampling). SARS-CoV-2 immunoglobulin M and immunoglobulin G antibodies were measured in serum samples by enzyme-linked immunosorbent assay. Seroprevalence estimates of immunoglobulin M and/or immunoglobulin G and 95% confidence intervals were stratified by sex, age group, health region and education. Results: Overall, seroprevalence was 2.9% (95% confidence interval: 2.0% - 4.2%). Higher prevalence rates were observed in male (4.1%, 95% confidence interval: 2.6% - 6.6%) and those with secondary education (6.4%, 95% confidence interval: 3.2% - 12.5%). Differences in seroprevalence by age group and region were not statistically significant. Discussion: The estimated seroprevalence of SARS-CoV-2 was higher than the cumulative incidence reported by the National Surveillance System but far from necessary to reach herd immunity. Conclusion: Our results support limited extent of infection by SARS-CoV-2 in the study population possibly due to early lockdown measures implemented in Portugal and support the need to continue monitoring of SARS-CoV-2 seroprevalence in order to increase our knowledge about the evolution of the epidemic and to estimate the proportion of the susceptible population over time.
- Cellular Mechanisms of Toxicity of Ingested NanomaterialsPublication . Vieira, Adriana Isabel Ramos; Louro, Maria Henriqueta; Silva, Maria JoãoTitanium dioxide (TiO2) nanomaterials (NMs) are used in a variety of consumer products, namely in the food sector, but their application has raised some concerns regarding their negative impacts on human health and particularly, on the gastrointestinal tract (GIT) following digestion, as this may be a major route of exposure. However, the toxicity studies currently available in the literature are contradictory and the majority do not consider the influence of human digestion in the ingested NMs safety assessment. This work aimed to understand the potential toxic effects of three TiO2 NMs (NM-102, NM-103 and NM-105) with distinct physicochemical properties, in the intestine, using human intestinal cells (Caco-2 and HT29-MTX-E12) as in vitro models. It was also intended to comprehend the impact of an in vitro simulated human digestion process on the NMs’ characteristics and to correlate these differences with the toxicity induced by digested TiO2 NMs, in comparison with undigested NMs. Regarding the cytotoxicity, both undigested and digested NM-105 led to a decrease in HT29-MTX-E12 cell viability, which was more pronounced in the digested sample, concomitantly with a decrease in its hydrodynamic size. Furthermore, digested NM-105 induced an increase in the DNA strand break level in both cell lines and in oxidative DNA damage, only in HT29-MTX-E12 cells, thus being classified as potentially genotoxic, through the comet assay. Digested NM-103 showed also an equivocal genotoxic response in Caco-2 cells. FPG-modified comet assay revealed an induction of DNA oxidative base lesions in Caco-2 and HT29-MTX-E12 exposed to undigested NM-103 and NM-102. Lastly, through the micronucleus assay, increased chromosomal damage effects were observed following treatment with some of the undigested and digested NMs. The present results reinforce the conception that NMs biological interactions are context-dependent, since their physicochemical properties can be changed after the digestion process, consequently leading to different biological effects.
- Exposure to Xenobiotics and Gene-Environment Interactions in Autism Spectrum Disorder: A Systematic Review [CHAPTER 7]Publication . Xavier Santos, João; Rasga, Célia; Moura Vicente, AstridHeritability estimates indicate that genetic susceptibility does not fully explain Autism Spectrum Disorder (ASD) risk variance, and that environmental factors may play a role in this disease. To explore the impact of the environment in ASD etiology, we performed a systematic review of the literature on xenobiotics implicated in the disease, and their interactions with gene variants. We compiled 72 studies reporting associations between ASD and xenobiotic exposure, including air pollutants, persistent and non-persistent organic pollutants, heavy metals, pesticides, pharmaceutical drugs and nutrients. Additionally, 9 studies reported that interactions between some of these chemicals (eg. NO2, particulate matter, manganese, folic acid and vitamin D) and genetic risk factors (eg. variants in the CYP2R1, GSTM1, GSTP1, MET, MTHFR and VDR genes) modulate ASD risk. The chemicals highlighted in this review induce neuropathological mechanisms previously implicated in ASD, including oxidative stress and hypoxia, dysregulation of signaling pathways and endocrine disruption. Exposure to xenobiotics may be harmful during critical windows of neurodevelopment, particularly for individuals with variants in genes involved in xenobiotic metabolization or in widespread signaling pathways. We emphasize the importance of leveraging multilevel data collections and integrative approaches grounded on artificial intelligence to address gene–environment interactions and understand ASD etiology, towards prevention and treatment strategies.
- Drinking Green Tea: Despite the Risks Due to Mycotoxins, Is It Possible to Increase the Associated Health Benefits?Publication . Assunção, Ricardo; Twarużek, M; Kosicki, R.; Viegas, C.; Viegas, S.Tea has been consumed for thousands of years. Despite the different varieties, particular emphasis has been placed on green tea (GT), considering the associated health benefits following its regular consumption, some of which are due to its polyphenol constituents, such as epigallocatechin- 3-gallate (EGCG). Tea is not prone to the growth of microorganisms, except fungus, when proper storage, handling, and packing conditions are compromised. Consequently, mycotoxins, secondary metabolites of fungi, could contaminate tea samples, affecting human health. In the present study, we aimed to assess the balance between risks (due to mycotoxins and high levels of EGCG) and benefits (due to moderate intake of EGCG) associated with the consumption of GT. For this, 20 GT samples (10 in bulk and 10 in bags) available in different markets in Lisbon were analyzed through a LC–MS/MS method, evaluating 38 different mycotoxins. Six samples revealed detectable values of the considered toxins. Current levels of mycotoxins and EGCG intake were not associated with health concerns. Scenarios considering an increasing consumption of GT in Portugal showed that drinking up to seven cups of GT per day should maximize the associated health benefits. The present study contributes to the future establishment of GT consumption recommendations in Portugal.
- Nutrient profile models a useful tool to facilitate healthier food choices: A comprehensive reviewPublication . Santos, Mariana; Rito, Ana Isabel; Matias, Filipa Nunes; Assunção, Ricardo; Castanheira, Isabel; Loureiro, IsabelBackground: The term “nutrient profile” (NP) has been associated with several concepts arising from the need to regulate the choice of food products, and to allow consumers to make informed and healthier food choices. The use of NP models as a policy tool to improve public health nutrition and reduce the prevalence of non-communicable diseases, is receiving increasing attention. Scope and approach: To clarifying the importance of NP models as tools to establish public health interventions concerning consumers’ food choices, a literature review of the guiding principles to implement NP models was conducted. The covered topics include main characteristics, advantages, disadvantages, and associated gaps of the considered NP models. Key findings and conclusions: From the selected studies, a total of 85 documents were included. Nutrient profiling has a wide range of applications including front-of-pack (FoP) food labelling, regulation of food marketing to children, regulation of health and nutrition claims and school food standards. Sodium, saturated fatty acids (SFA), and total sugars were the nutrients most frequently to limit; on the contrary fibre was the most used qualifying nutrient. This review gathers, through a holistic approach, the scientific basis behind the development of the NP model, reinforcing the importance of these tools, and enabling regulators with information to establish an appropriate model.
- The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confoundersPublication . Milić, Mirta; Ceppi, Marcello; Bruzzone, Marco; Azqueta, Amaya; Brunborg, Gunnar; Godschalk, Roger; Koppen, Gudrun; Langie, Sabine; Møller, Peter; Teixeira, João Paulo; Alija, Avdulla; Anderson, Diana; Andrade, Vanessa; Andreoli, Cristina; Asllani, Fisnik; Bangkoglu, Ezgi Eyluel; Barančoková, Magdalena; Basaran, Nursen; Boutet-Robinet, Elisa; Buschini, Annamaria; Cavallo, Delia; Costa Pereira, Cristiana; Costa, Carla; Costa, Solange; Da Silva, Juliana; Del Boˊ, Cristian; Dimitrijević Srećković, Vesna; Djelić, Ninoslav; Dobrzyńska, Malgorzata; Duračková, Zdenka; Dvořáková, Monika; Gajski, Goran; Galati, Serena; García Lima, Omar; Giovannelli, Lisa; Goroshinskaya, Irina A.; Grindel, Annemarie; Gutzkow, Kristine B.; Hernández, Alba; Hernández, Carlos; Holven, Kirsten B.; Ibero-Baraibar, Idoia; Ottestad, Inger; Kadioglu, Ela; Kažimirová, Alena; Kuznetsova, Elena; Ladeira, Carina; Laffon, Blanca; Lamonaca, Palma; Lebailly, Pierre; Louro, Henriqueta; Mandina Cardoso, Tania; Marcon, Francesca; Marcos, Ricard; Moretti, Massimo; Moretti, Silvia; Najafzadeh, Mojgan; Nemeth, Zsuzsanna; Neri, Monica; Novotna, Bozena; Orlow, Irene; Paduchova, Zuzana; Pastor, Susana; Perdry, Hervé; Spremo-Potparević, Biljana; Ramadhani, Dwi; Riso, Patrizia; Rohr, Paula; Rojas, Emilio; Rossner, Pavel; Safar, Anna; Sardas, Semra; Silva, Maria João; Sirota, Nikolay; Smolkova, Bozena; Staruchova, Marta; Stetina, Rudolf; Stopper, Helga; Surikova, Ekaterina I.; Ulven, Stine M.; Ursini, Cinzia Lucia; Valdiglesias, Vanessa; Valverde, Mahara; Vodicka, Pavel; Volkovova, Katarina; Wagner, Karl-Heinz; Živković, Lada; Dušinská, Maria; Collins, Andrew R.; Bonassi, StefanoThe alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.
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