Publications by authors named "Ana M Gil"

Objectives: The association between SARS-CoV-2 infection and new onset of immune-mediated diseases is of interest given the conflicting evidence. This study aims to gather evidence and estimate the risk of immune-mediated diseases following SARS-CoV-2 infection.

Methods: Analytical observational studies reporting immune-mediated diseases after confirmed SARS-CoV-2 infection, compared to individuals without infection history, were included.

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Mesenchymal stem cell (MSC) osteodifferentiation is accompanied by important lipid metabolic adaptations, which may reveal relevant biomarkers and potential osteoinductive species. However, high donor variability remains a challenge for biomarker identification. This work unveiled shared lipid features of human adipose-tissue MSC (hAMSC) for three independent donors, using an untargeted NMR spectroscopy methodology.

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Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals that are recognized for their environmental persistence and potential toxicity. As regulatory pressure increases on legacy PFAS, emerging alternatives are being increasingly used. However, their environmental toxicological profiles remain poorly understood.

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The application of vibrational microspectroscopy to the study of in vitro mesenchymal stem cells (MSC) osteogenic differentiation is a promising approach towards the understanding of the molecular processes involved in bone fabrication. Both infrared (IR) and Raman microspectroscopies have been applied, with a clear predominance of the latter. Bone marrow MSC have been the target of most studies, followed by those originating from dental/oral and adipose tissues.

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Background: Mesenchymal stem cells (MSC) are pivotal bioengineering tools, offering significant promise for applications in bone regeneration. However, their therapeutic potential is limited by inter-donor variability and experimental issues. This study aimed to identify robust metabolic markers of osteodifferentiation applicable across multiple donors, while providing insight into the metabolic pathways actively involved in the process.

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Metabolic dysfunction-associated steatotic liver disease (MASLD) can be recapitulated in mice fed a high-fat diet. The development of MASLD and the diet can both perturb metabolism in key extrahepatic tissues such as the heart, kidney, and skeletal muscle. To date, these alterations have not been well described in this animal model of diet-induced MASLD.

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Breast cancer is the most common type of cancer in women and the second leading cause of death by cancer. Despite recent advances, the mortality rate remains high, underlining the need to develop new therapeutic approaches. The complex interaction between cancer cells and the tumor microenvironment (TME) is crucial in determining tumor progression, therapy response, and patient prognosis.

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Background: Breast cancer is a heterogeneous malignant disease with a varying prognosis and is classified into four molecular subtypes. It remains one of the most prevalent cancers globally, with the tumor microenvironment playing a critical role in disease progression and patient outcomes.

Methods: This study evaluated tumor samples from 40 female patients with luminal A and B breast cancer, utilizing flow cytometry to phenotypically characterize the immune cells and tumor cells present within the tumor tissue.

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In this study, untargeted Nuclear Magnetic Resonance (NMR) metabolomics was applied for the first time, to our knowledge, to assess the metabolic impact of direct and transgenerational exposure (F0 and F3 generations, respectively) of amphipods Gammarus locusta to simvastatin (SIM), a pharmaceutical widely prescribed for the treatment of hypercholesterolemia. Results revealed the important gender-dependent nature of each of these effects. Directly exposed males showed enhanced glucose catabolism and tricarboxylic acid (TCA) cycle activity, in tandem with adaptations in osmotic regulation and glyoxylate metabolism.

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Per- and polyfluoroalkyl substances (PFAS) are synthetic chemicals known for their persistence and bioaccumulation, leading to widespread environmental contamination. Despite their recognised environmental risks, particularly to aquatic wildlife, including marine invertebrates, detailed impact studies are limited. PFAS can be categorised according to the length of the compound chain, with short-chain PFAS announced as a safer alternative to the more commonly used long-chain PFAS.

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Given the general increase in legume consumption worldwide, there is a need to characterize the resulting human metabolic adaptations in order to demonstrate potential legume diet/health relationships. A nuclear magnetic resonance (NMR) metabolomics urine study was carried out on a small cohort ( = 18) to characterize the excretory effects of a pilot longitudinal 8-week legume-based dietary intervention. Despite the expected high interindividual variability in the excreted metabolome, the results suggested a nonlinear metabolic response, with higher metabolic activity in the first 4 weeks and a tendency toward baseline at the end of the intervention.

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Background & Aims: Legumes intake is known to be associated with several health benefits the origins of which is still a matter of debate. This paper addresses a pilot small cohort to probe for metabolic aspects of the interplay between legumes intake, human metabolism and gut microbiota.

Methods: Untargeted nuclear magnetic resonance (NMR) metabolomics of blood plasma and fecal extracts was carried out, in tandem with qPCR analysis of feces, to assess the impact of an 8-week pilot legumes diet intervention on the fecal and plasma metabolomes and gut microbiota of 19 subjects.

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Article Synopsis
  • This pilot study examined how replacing a traditional lunch with a vegetarian legume-based meal impacted blood and body measurements in omnivorous adults over 8 weeks.
  • Participants (26 individuals) consumed a median of 79.8 grams of legumes per meal, with half meeting the Portuguese legume intake recommendations, but no significant changes were found in body measurements.
  • While the study showed a reduction in total and LDL cholesterol levels, there were increases in triglycerides and glucose-related markers, indicating a need for more extensive research on the dietary effects using larger groups.
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Cisplatin (cDDP) resistance is a matter of concern in triple-negative breast cancer therapeutics. We measured the metabolic response of cDDP-sensitive (S) and -resistant (R) MDA-MB-231 cells to PdSpermine(Spm) (a possible alternative to cDDP) compared to cDDP to investigate (i) intrinsic response/resistance mechanisms and (ii) the potential cytotoxic role of PdSpm. Cell extracts were analyzed by untargeted nuclear magnetic resonance metabolomics, and cell media were analyzed for particular metabolites.

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This work investigated the mechanisms of action of conventional drugs, cisplatin and oxaliplatin, and the potentially less deleterious drug PdSpermine (Spm) and its Pt(II) analog, against osteosarcoma MG-63 cells, using nuclear-magnetic-resonance metabolomics of the cellular lipidome. The Pt(II) chelates induced different responses, namely regarding polyunsaturated-fatty-acids (increased upon cisplatin), suggesting that cisplatin-treated cells have higher membrane fluidity/permeability, thus facilitating cell entry and justifying higher cytotoxicity. Both conventional drugs significantly increased triglyceride levels, while PtSpm maintained control levels; this may reflect enhanced apoptotic behavior for conventional drugs, but not for PtSpm.

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Untargeted nuclear magnetic resonance (NMR) metabolomics was used to evaluate compositional changes during yogurt fermentation upon lupin enrichment compared to traditional conditions. Lupin significantly changed the sample metabolic profile and its time course dynamics, seemingly delaying microbial action. The levels of organic and amino acids were significantly altered, along with those of some sugars, nucleotides, and choline compounds.

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This work compared the metabolic profile of a parental MDA-MB-231 cisplatin-sensitive triple negative breast cancer (TNBC) cell line with that of a derived cisplatin-resistant line, to characterize inherent metabolic adaptations to resistance, as a means for marker and new TNBC therapies discovery. Supported by cytotoxic, microscopic and biochemical characterization of both lines, Nuclear Magnetic Resonance (NMR) metabolomics was employed to characterize cell polar extracts for the two cell lines, as a function of time (0, 24 and 48 h), and identify statistically relevant differences both between sensitive and resistant cells and their time course behavior. Biochemical results revealed a slight increase in activation of the NF-κB pathway and a marked decrease of the ERK signaling pathway in resistant cells.

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The lipid metabolism adaptations of estrogen and progesterone receptor-positive breast cancer tumors from a mouse syngeneic model are investigated in relation to differences across the transition from hormone-dependent (HD) to hormone-independent (HI) tumor growth and the acquisition of endocrine therapy (ET) resistance (HIR tumors). Results are articulated with reported polar metabolome results to complete a metabolic picture of the above transitions and suggest markers of tumor progression and aggressiveness. Untargeted nuclear magnetic resonance metabolomics was used to analyze tumor and mammary tissue lipid extracts.

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This paper reports on an NMR metabolomics study of lipophilic extracts of clams exposed to the hormonal contaminant 17-α-ethinylestradiol (EE2), at 17 °C and 21 °C. The results reveal that exposure at 17 °C triggers a weak response at low EE2 concentrations, suggestive of a slight increase in membrane rigidity, followed by lipid metabolic stability at higher EE2 concentrations. On the other hand, at 21 °C, lipid metabolism begins to respond at 125 ng/L EE2, with antioxidant docosahexaenoic acid (DHA) helping to tackle high-oxidative-stress conditions, in tandem with enhanced storage of triglycerides.

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Adopting eco-friendly diets will demand the consumption of more plant-based protein food sources such as legumes. However, assessing the impact of such a dietary shift on the dietary and nutritional intake of traditionally omnivorous populations is needed. The objective of this study was to assess the impact of substituting a traditional omnivorous-based lunch for a vegetarian, legume-based meal on the daily dietary and nutritional intake in a group of omnivorous adults in the city of Porto, Portugal.

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Untargeted Nuclear Magnetic Resonance metabolomics was employed to study the effects of warming conditions (17-21 °C) and exposure to 17-α-ethinylestradiol (EE2) on the polar metabolome of Ruditapes philippinarum clams, to identify metabolic markers for monitoring/prediction of deviant environmental conditions. Warming alone triggered changes in alanine/aspartate/glutamate, aromatic amino acids, taurine/hypotaurine and homarine/trigonelline pathways, as well as in energy metabolism, suggesting osmoregulatory adaptations and glycolytic/tricarboxylic acid (TCA) cycle activation, possibly accompanied to some extent by gluconeogenesis to preserve glycogen reserves. At 17 °C, the lowest EE2 concentration (5 ng/L) specifically engaged branched-chain and aromatic amino acids to activate the glycolysis/TCA cycle.

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Up to the present day, studies on the therapeutic properties of camel ( spp.) urine and the detailed characterization of its metabolomic profile are scarce and often unrelated. Information on inter individual variability is noticeably limited, and there is a wide divergence across studies regarding the methods for sample storage, pre-processing, and extract derivatization for metabolomic analysis.

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This paper describes an untargeted NMR metabolomics study to identify potential intracellular donor-dependent and donor-independent metabolic markers of proliferation and osteogenic differentiation of human adipose mesenchymal stem cells (hAMSCs). The hAMSCs of two donors with distinct proliferating/osteogenic characteristics were fully characterized regarding their polar endometabolome during proliferation and osteogenesis. An 18-metabolites signature (including changes in alanine, aspartate, proline, tyrosine, ATP, and ADP, among others) was suggested to be potentially descriptive of cell proliferation, independently of the donor.

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Cisplatin (cDDP)-based chemotherapy is often limited by severe deleterious effects (nephrotoxicity, hepatotoxicity and neurotoxicity). The polynuclear palladium(II) compound PdSpermine (PdSpm) has emerged as a potential alternative drug, with favorable pharmacokinetic/pharmacodynamic properties. This paper reports on a Nuclear Magnetic Resonance metabolomics study to (i) characterize the response of mice brain and liver to PdSpm, compared to cDDP, and (ii) correlate brain-liver metabolic variations.

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Chitosan-genipin (Ch-Ge) films have been proposed for the replacement of sulfur dioxide (SO) in white wines preservation to circumvent the adverse health consequences caused by SO intake. To assess the effects of different-sized Ch-Ge films (25 and 100 cm) on wine composition compared to SO-treated and untreated wines, nuclear magnetic resonance metabolomics was applied. Relative to SO, 100 cm films induced significant changes in the levels of organic acids, sugars, amino acids, 5-hydroxymethylfurfural, among other compounds, while 25 cm films appeared to induce only small variations.

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