Browsing by Author "Faria, Ana"
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- Adipose tissue dysfunction as a central mechanism leading to dysmetabolic obesity triggered by chronic exposure to p,p’-DDEPublication . Pestana, Diogo; Teixeira, Diana; Meireles, Manuela; Marques, Cláudia; Norberto, Sónia; Sá, Carla; Fernandes, Virgínia; Correia-Sá, Luísa; Faria, Ana; Guardão, Luísa; Guimarães, João T.; Cooper, Wendy N.; Sandovici, Ionel; Domingues, Valentina; Delerue-Matos, Cristina; Monteiro, Rosário; Constância, Miguel; Calhau, ConceiçãoEndocrine-disrupting chemicals such as p,p'-dichlorodiphenyldichloroethylene (p,p'-DDE), are bioaccumulated in the adipose tissue (AT) and have been implicated in the obesity and diabetes epidemic. Thus, it is hypothesized that p,p'-DDE exposure could aggravate the harm of an obesogenic context. We explored the effects of 12 weeks exposure in male Wistar rats' metabolism and AT biology, assessing a range of metabolic, biochemical and histological parameters. p,p'-DDE -treatment exacerbated several of the metabolic syndrome-accompanying features induced by high-fat diet (HF), such as dyslipidaemia, glucose intolerance and hypertension. A transcriptome analysis comparing mesenteric visceral AT (vAT) of HF and HF/DDE groups revealed a decrease in expression of nervous system and tissue development-related genes, with special relevance for the neuropeptide galanin that also revealed DNA methylation changes at its promoter region. Additionally, we observed an increase in transcription of dipeptidylpeptidase 4, as well as a plasmatic increase of the pro-inflammatory cytokine IL-1β. Our results suggest that p,p'-DDE impairs vAT normal function and effectively decreases the dynamic response to energy surplus. We conclude that p,p'-DDE does not merely accumulate in fat, but may contribute significantly to the development of metabolic dysfunction and inflammation. Our findings reinforce their recognition as metabolism disrupting chemicals, even in non-obesogenic contexts.
- Brominated flame retardants effect in MCF-7 cells: Impact on vitamin D pathwayPublication . Sousa, Sara; Maia, Maria Luz; Pestana, Diogo; Teixeira, Diana; Ângelo-Dias, Miguel; Martins, Catarina; Borrego, Luís Miguel; Delerue-Matos, Cristina; Calhau, Conceição; Domingues, Valentina; Faria, AnaBrominated flame retardants (BFRs) are persistent environmental pollutants, allowing a constant human exposure which carries several health risks, including the occurrence of breast cancer and vitamin D deficiency. Vitamin D inhibits cell growth and is negatively associated with breast cancer risk. The effect of BFRs in breast cancer and vitamin D pathway is still poorly understood. MCF-7 cells were treated with hexabromocyclododecane (HBCD), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB), hexabromobenzene (HBB) and pentabromotoluene (PBT) using short and long-term exposure protocols. Viability, proliferation, migration, cell cycle and gene expression were assessed. Gene expression of hVDBP and hCYP2R1 was also evaluated in hepatocytes. Long-term exposure of MCF-7 cells to HBB increased cell proliferation and migration, consequently increasing MMP-9 expression. The vitamin D pathway was also altered by BFRs: cells appeared less prepared to activate and transport vitamin D and the signaling, action and inactivation mechanisms were diminished in the presence of BFRs. Untreated MCF-7 cells showed cell cycle arrest in phase G0/G1 in the presence of activated vitamin D. However, when MCF-7 cells were exposed to BFRs, cell cycle was arrested in phase G2/M, possibly due to DNA damage. Nonetheless, calcitriol seems to be able to mitigate the effect of some BFRs exposure, e.g. PBT
- Effects of Environmental Organochlorine Pesticides on Human Breast Cancer: Putative Involvement on Invasive Cell AbilityPublication . Pestana, Diogo; Teixeira, Diana; Faria, Ana; Domingues, Valentina; Monteiro, Rosário; Calhau, ConceiçãoHuman exposure to persistent organic pollutants (POPs) is a certainty, even to long banned pesticides like o,p′-dichlorodiphenyltrichloroethane (o,p′-DDT), and its metabolites p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE), and p,p′-dichlorodiphenyldichloroethane (p,p′-DDD). POPs are known to be particularly toxic and have been associated with endocrine-disrupting effects in several mammals, including humans even at very low doses. As environmental estrogens, they could play a critical role in carcinogenesis, such as in breast cancer. With the purpose of evaluating their effect on breast cancer biology, o,p′-DDT, p,p′-DDE, and p,p′-DDD (50–1000 nM) were tested on two human breast adenocarcinoma cell lines: MCF-7 expressing estrogen receptor (ER) α and MDA-MB-231 negative for ERα, regarding cell proliferation and viability in addition to their invasive potential. Cell proliferation and viability were not equally affected by these compounds. In MCF-7 cells, the compounds were able to decrease cell proliferation and viability. On the other hand, no evident response was observed in treated MDA-MB-231 cells. Concerning the invasive potential, the less invasive cell line, MCF-7, had its invasion potential significantly induced, while the more invasive cell line MDA-MB-231, had its invasion potential dramatically reduced in the presence of the tested compounds. Altogether, the results showed that these compounds were able to modulate several cancer-related processes, namely in breast cancer cell lines, and underline the relevance of POP exposure to the risk of cancer development and progression, unraveling distinct pathways of action of these compounds on tumor cell biology.
- Holistic Security and Safety for Factories of the FuturePublication . Maia, Eva; Wannous, Sinan; Dias, Tiago; Praça, Isabel; Faria, AnaThe accelerating transition of traditional industrial processes towards fully automated and intelligent manufacturing is being witnessed in almost all segments. This major adoption of enhanced technology and digitization processes has been originally embraced by the Factories of the Future and Industry 4.0 initiatives. The overall aim is to create smarter, more sustainable, and more resilient future-oriented factories. Unsurprisingly, introducing new production paradigms based on technologies such as machine learning (ML), the Internet of Things (IoT), and robotics does not come at no cost as each newly incorporated technique poses various safety and security challenges. Similarly, the integration required between these techniques to establish a unified and fully interconnected environment contributes to additional threats and risks in the Factories of the Future. Accumulating and analyzing seemingly unrelated activities, occurring simultaneously in different parts of the factory, is essential to establish cyber situational awareness of the investigated environment. Our work contributes to these efforts, in essence by envisioning and implementing the SMS-DT, an integrated platform to simulate and monitor industrial conditions in a digital twin-based architecture. SMS-DT is represented in a three-tier architecture comprising the involved data and control flows: edge, platform, and enterprise tiers. The goal of our platform is to capture, analyze, and correlate a wide range of events being tracked by sensors and systems in various domains of the factory. For this aim, multiple components have been developed on the basis of artificial intelligence to simulate dominant aspects in industries, including network analysis, energy optimization, and worker behavior. A data lake was also used to store collected information, and a set of intelligent services was delivered on the basis of innovative analysis and learning approaches. Finally, the platform was tested in a textile industry environment and integrated with its ERP system. Two misuse cases were simulated to track the factory machines, systems, and people and to assess the role of SMS-DT correlation mechanisms in preventing intentional and unintentional actions. The results of these misuse case simulations showed how the SMS-DT platform can intervene in two domains in the first scenario and three in the second one, resulting in correlating the alerts and reporting them to security operators in the multi-domain intelligent correlation dashboard.
- Immediate effects of suboccipital myofascial induction on postural stability: a pilot studyPublication . Pinheiro, Ana Rita; Faria, Ana; Mesquita Montes, António; Crasto, Carlos; Silva, Cláudia; Carvalho, Paulo; Santos, Rubim; Cunha, ChristineStanding is a constant postural challenge due to high position of the center of mass regarding the small size of base of support. Somatosensory, vestibular and visual inputs are crucial to preserve the upright orientation and stability]
- Impact of brominated flame retardants on lipid metabolism: An in vitro approachPublication . Maia, Maria Luz; Sousa, Sara; Pestana, Diogo; Faria, Ana; Teixeira, Diana; Delerue-Matos, Cristina; Domingues, Valentina; Calhau, ConceiçãoBrominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.
- Inflammatory and Cardiometabolic Risk on Obesity: Role of Environmental XenoestrogensPublication . Teixeira, Diana; Pestana, Diogo; Santos, Cristina; Correia-Sá, Luísa; Marques, Cláudia; Norberto, Sónia; Meireles, Manuela; Faria, Ana; Silva, Ricardo; Faria, Gil; Sá, Carla; Freitas, Paula; Taveira-Gomes, António; Domingues, Valentina; Delerue-Matos, Cristina; Calhau, Conceição; Monteiro, RosárioContext: Some chemicals used in consumer products or manufacturing (eg, plastics, pesticides) have estrogenic activities; these xenoestrogens (XEs) may affect immune responses and have recently emerged as a new risk factors for obesity and cardiovascular disease. However, the extent and impact on health of chronic exposure of the general population to XEs are still unknown. Objective: The objective of the study was to investigate the levels of XEs in plasma and adipose tissue (AT) depots in a sample of pre- and postmenopausal obese women undergoing bariatric surgery and their cardiometabolic impact in an obese state. Design and Participants: We evaluated XE levels in plasma and visceral and subcutaneous AT samples of Portuguese obese (body mass index ≥ 35 kg/m2) women undergoing bariatric surgery. Association with metabolic parameters and 10-year cardiovascular disease risk was assessed, according to menopausal status (73 pre- and 48 postmenopausal). Levels of XEs were determined by gas chromatography with electron-capture detection. Anthropometric and biochemical data were collected prior to surgery. Adipocyte size was determined on tissue sections obtained during surgery. Results: Our data show that XEs are pervasive in this obese population. Distribution of individual and concentration of total XEs differed between plasma, visceral AT, and subcutaneous AT, and the pattern of accumulation was different between pre- and postmenopausal women. Significant associations between XE levels and metabolic and inflammatory parameters were found. In premenopausal women, XEs in plasma seem to be a predictor of 10-year cardiovascular disease risk. Conclusions: Our findings point toward a different distribution of XE between plasma and AT in pre- and postmenopausal women, and reveal the association between XEs on the development of metabolic abnormalities in obese premenopausal women
- Optimization and validation of organochlorine compounds in adipose tissue by SPE-gas chromatographyPublication . Fernandes, Virgínia C.; Pestana, Diogo; Monteiro, Rosário; Faria, Gil; Meireles, Manuela; Correia-Sá, Luísa; Teixeira, Diana; Faria, Ana; Calhau, Conceição; Domingues, Valentina F.; Delerue-Matos, CristinaScientific evidence has shown an association between organochlorine compounds (OCC) exposure and human health hazards. Concerning this, OCC detection in human adipose samples has to be considered a public health priority. This study evaluated the efficacy of various solid-phase extraction (SPE) and cleanup methods for OCC determination in human adipose tissue. Octadecylsilyl endcapped (C18-E), benzenesulfonic acid modified silica cation exchanger (SA), poly (styrene-divinylbenzene (EN) and EN/RP18 SPE sorbents were evaluated. The relative sample cleanup provided by these SPE columns was evaluated using gas chromatography with electron capture detection (GC–ECD). The C18-E columns with strong homogenization were found to provide the most effective cleanup, removing the greatest amount of interfering substance, and simultaneously ensuring good analyte recoveries higher than 70%. Recoveries>70% with standard deviations (SD)<15% were obtained for all compounds under the selected conditions. Method detection limits were in the 0.003–0.009 mg/kg range. The positive samples were confirmed by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The highest percentage found of the OCC in real samples corresponded to HCB, o,p′-DDT and methoxychlor, which were detected in 80 and 95% of samples analyzed respectively. Copyright © 2012 John Wiley & Sons, Ltd.
- Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals - Depot differences and dysmetabolism implicationsPublication . Pestana, Diogo; Faria, Gil; Sá, Carla; Fernandes, Virgínia C.; Teixeira, Diana; Norberto, Sónia; Faria, Ana; Meireles, Manuela; Marques, Cláudia; Correia-Sá, Luísa; Cunha, Ana; Guimarães, João T.; Taveira-Gomes, António; Santos, Ana Cristina; Domingues, Valentina F.; Delerue-Matos, Cristina; Monteiro, Rosário; Calhau, ConceiçãoBackground: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens.