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result(s) for
"Fraga, M"
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The effect of exposure to nanoparticles and nanomaterials on the mammalian epigenome
by
Sierra, Marta I.
,
Valdés, Adolfo
,
Fernandez, Agustin F.
in
Animals
,
Biomedical materials
,
Carbon
2016
Human exposure to nanomaterials and nanoparticles is increasing rapidly, but their effects on human health are still largely unknown. Epigenetic modifications are attracting ever more interest as possible underlying molecular mechanisms of gene-environment interactions, highlighting them as potential molecular targets following exposure to nanomaterials and nanoparticles. Interestingly, recent research has identified changes in DNA methylation, histone post-translational modifications, and noncoding RNAs in mammalian cells exposed to nanomaterials and nanoparticles. However, the challenge for the future will be to determine the molecular pathways driving these epigenetic alterations, the possible functional consequences, and the potential effects on health.
Journal Article
World Congress of Trauma and Emergency Leagues (WCTEL): looking for the future
by
Calderan, Thiago R. A.
,
Marttos, Antônio C.
,
Fraga, Andréa M. A.
in
Brazil
,
Congresses as Topic - trends
,
Convention centers
2026
The first World Congress of Trauma and Emergency Leagues (WCTEL) was held at the University of Campinas (Unicamp), Brazil, on July 3rd to 6th, 2025. The meeting was organized by undergraduate medical and nurse students, guided by their professors, and with a support of Brazilian and international societies. Pre-congress activities included a Students World Championship in Emergency and Trauma Simulation. More than 1000 participants from 19 countries attended the WCTEL, enabling exchanges of experiences and the possibility of cooperation between students. This new kind of congress could be a good way to attract young people to work with trauma and emergency surgery in the future.
Journal Article
Challenges for future food systems: From the Green Revolution to food supply chains with a special focus on sustainability
2023
Finding a food system to feed the growing worldwide population remains a challenge, especially in the current era, where natural resources are being dramatically depleted. From a historical point of view, the Green Revolution, together with biofortification and sustainable intensification, was established as a possible solution to counter hunger and malnutrition during the second half of the 20th century. As a solution, to overcome the limitations attributed to the Green Revolution, food supply chains were developed. The current food system, based on the long food supply chain (LFSC), is characterized by globalization, promoting several advantages for both producers and consumers. However, LFSC has been demonstrated to be unable to feed the global population and, furthermore, it generates negative ecological, environmental, logistical, and nutritional pressures. Thus, novel efficient food systems are required to respond to current environmental and consumers’ demands, as is the case of short food supply chain (SFSC). As a recently emerging food system, the evaluation of SFSC sustainability in terms of environmental, economic, and social assessment is yet to be determined. This review is focused on the evolution of food supply systems, starting from the Green Revolution to food supply chains, providing a significant perspective on sustainability.
Journal Article
Effects of short-term high-fat overfeeding on genome-wide DNA methylation in the skeletal muscle of healthy young men
2012
Aims/hypothesis
Energy-dense diets that are high in fat are associated with a risk of metabolic diseases. The underlying molecular mechanisms could involve epigenetics, as recent data show altered DNA methylation of putative type 2 diabetes candidate genes in response to high-fat diets. We examined the effect of a short-term high-fat overfeeding (HFO) diet on genome-wide DNA methylation patterns in human skeletal muscle.
Methods
Skeletal muscle biopsies were obtained from 21 healthy young men after ingestion of a short-term HFO diet and a control diet, in a randomised crossover setting. DNA methylation was measured in 27,578 CpG sites/14,475 genes using Illumina's Infinium Bead Array. Candidate gene expression was determined by quantitative real-time PCR.
Results
HFO introduced widespread DNA methylation changes affecting 6,508 genes (45%), with a maximum methylation change of 13.0 percentage points. The HFO-induced methylation changes were only partly and non-significantly reversed after 6–8 weeks. Alterations in DNA methylation levels primarily affected genes involved in inflammation, the reproductive system and cancer. Few gene expression changes were observed and these had poor correlation to DNA methylation.
Conclusions/interpretation
The genome-wide DNA methylation changes induced by the short-term HFO diet could have implications for our understanding of transient epigenetic regulation in humans and its contribution to the development of metabolic diseases. The slow reversibility suggests a methylation build-up with HFO, which over time may influence gene expression levels.
Journal Article
Effects of different arachidonic acid supplementation on psychomotor development in very preterm infants; a randomized controlled trial
by
de Pipaón, Miguel Sáenz
,
Couce, María L.
,
Baña, Ana M.
in
Analysis
,
Arachidonic Acid - administration & dosage
,
Arachidonic Acid - analysis
2015
Background & aims
Nutritional supplementation with polyunsaturated fatty acids is important in preterm infants neurodevelopment, but it is not known if the omega-6/omega-3 ratio affects this process. This study was designed to determine the effects of a balanced contribution of arachidonic acid in very preterm newborns fed with formula milk.
Methods
This was a randomized trial, in which newborns <1500 g and/or <32 weeks gestational age were assigned to one of two groups, based on the milk formula they would receive during the first year of life. Initially, 60 newborns entered the study, but ultimately, group A was composed of 24 newborns, who were given formula milk with an ω-6/ω-3 ratio of 2/1, and Group B was composed of 21 newborns, given formula milk with an ω-6/ω-3 ratio of 1/1. The infants were followed up for two years: growth, visual-evoked potentials, brainstem auditory-evoked potentials, and plasma fatty acids were periodically measured, and psychomotor development was assessed using the Brunet Lézine scale at 24 months corrected age. A control group, for comparison of Brunet Lézine score, was made up of 25 newborns from the SEN1500 project, who were fed exclusively with breast milk.
Results
At 12 months, arachidonic acid values were significantly higher in group A than in group B (6.95 ± 1.55 %
vs.
4.55 ± 0.78 %), as were polyunsaturated fatty acids (41.02 ± 2.09 %
vs.
38.08 ± 2.32 %) achieved a higher average. Group A achieved a higher average Brunet Lézine score at 24 months than group B (99.9 ± 9
vs.
90.8 ± 11,
p
=0.028). The Brunet Lézine results from group A were compared with the control group results, with very similar scores registered between the two groups (99.9 ± 9
vs.
100.5 ± 7). There were no significant differences in growth or evoked potentials between the two formula groups.
Conclusions
Very preterm infants who received formula with an ω-6/ω-3 ratio of 2/1 had higher blood levels of essential fatty acids during the first year of life, and better psychomotor development, compared with very preterm newborns who consumed formula with an ω-6/ω-3 of 1/1. Therefore, formula milk with an arachidonic acid quantity double that of docosahexaenoic acid should be considered for feeding very preterm infants.
Trial registration
ClinicalTrials.gov Identifier
NCT02503020
.
Journal Article
Salermide, a Sirtuin inhibitor with a strong cancer-specific proapoptotic effect
2009
Sirtuin 1 (Sirt1) and Sirtuin 2 (Sirt2) belong to the family of NAD+ (nicotinamide adenine dinucleotide-positive)-dependent class III histone deacetylases and are involved in regulating lifespan. As cancer is a disease of ageing, targeting Sirtuins is emerging as a promising antitumour strategy. Here we present Salermide (
N
-{3-[(2-hydroxy-naphthalen-1-ylmethylene)-amino]-phenyl}-2-phenyl-propionamide), a reverse amide with a strong
in vitro
inhibitory effect on Sirt1 and Sirt2. Salermide was well tolerated by mice at concentrations up to 100 μ
M
and prompted tumour-specific cell death in a wide range of human cancer cell lines. The antitumour activity of Salermide was primarily because of a massive induction of apoptosis. This was independent of global tubulin and K16H4 acetylation, which ruled out a putative Sirt2-mediated apoptotic pathway and suggested an
in vivo
mechanism of action through Sirt1. Consistently with this, RNA interference-mediated knockdown of Sirt1, but not Sirt2, induced apoptosis in cancer cells. Although p53 has been reported to be a target of Sirt1, genetic p53 knockdowns showed that the Sirt1-dependent proapoptotic effect of Salermide is p53-independent. We were finally able to ascribe the apoptotic effect of Salermide to the reactivation of proapoptotic genes epigenetically repressed exclusively in cancer cells by Sirt1. Taken together, our results underline Salermide's promise as an anticancer drug and provide evidence for the molecular mechanism through which Sirt1 is involved in human tumorigenesis.
Journal Article
Epigenetic inactivation of the Wnt antagonist DICKKOPF-1 (DKK-1) gene in human colorectal cancer
by
García, J M
,
Paz, M F
,
Aguilera, O
in
Adaptor Proteins, Signal Transducing
,
Adenomatous polyposis coli
,
Adenomatous Polyposis Coli Protein - genetics
2006
Colorectal cancer is a major cause of cancer death worldwide. A number of key oncogenes and tumor suppressor genes have been proposed to drive progression from healthy colonic epithelia to malignant tumors, including members of the Wnt/
β
-catenin pathway. Recently, CpG island promoter hypermethylation was shown to cause inactivation of two extracellular Wnt inhibitors in colon cancer: secreted frizzled-related proteins (sFRPs) and Wnt inhibitory factor-1 (WIF-1). Here, we show for the first time that another extracellular Wnt inhibitor, the
DICKKOPF-1
(
DKK-1
) gene, is transcriptionally silenced by CpG island promoter hypermethylation in colon cancer cell lines (
n
=9), whereas treatment with the DNA-demethylating agent 5-aza-2-deoxycytidine restored
DKK-1
expression. Restoration of DKK-1 function in non-expressing cells bearing a truncated
APC
(
Adenomatous Polyposis Coli
) gene had no effect on
β
-catenin/T-cell factor-dependent transcription, but induced tumor suppressor-like features such as reduced colony formation density and tumor growth inhibition in nude mice. These results suggest additional functions for DKK-1 other than inhibiting canonical Wnt signaling. In primary colorectal tumors,
DKK-1
was found hypermethylated in 17% (nine of 54) of cases. Furthermore, while for both
SFRP-1
and
WIF-1
methylation-associated silencing occurred across the whole spectrum of colorectal tumorigenesis,
DKK-1
promoter was selectively hypermethylated in advanced colorectal neoplasms (Duke's C and D tumors).
Journal Article
Anorexia Nervosa and Autism Spectrum Disorder: what links them?
2023
IntroductionAccording to the literature, about 35% of patients with Anorexia Nervosa (AN) also have a diagnosis of Autism Spectrum Disorder (ASD), and this comorbidity occurs more frequently in males.ObjectivesWith this work, the authors intend to address the characteristics present in this comorbidity and what is the impact of this comorbidity in the diagnosis, approach and prognosis of AN.MethodsNon-systematic research of the literature through the PubMed database with the terms “autism spectrum disorder” and “anorexia nervosa”. Only surveys conducted in the last 10 years were considered for inclusion.ResultsAlthough AN and ASD may seem to be quite distinct conditions, the studies found suggest the existence of four characteristics that overlap the two diagnoses: deficits in theory of mind, inability to switch between courses of action fluently, inability to see the whole pictures to the detriment of detail and alexithymia. Studies also point to greater resistance to treatment in AN when an ASD is present in comorbidity.ConclusionsScientific evidence suggests that autistic characteristics in people with AN are not a consequence of being underweight, but rather stable characteristics present before and after the onset of AN. The studies thus conclude that comorbidity between the two disorders exists and is frequent enough to warrant greater attention to the diagnosis of ASD in people with AN. However, there are still no specific guidelines for the treatment of AN in people with ASD, which leads to a worse response to treatment, evolution and prognosis of AN in people with ASD.Disclosure of InterestNone Declared
Journal Article
Insect Antifeedant Benzofurans from Pericallis Species
2023
In this work, we have studied the benzofurans of Pericallis echinata (aerial parts and transformed roots), P. steetzii (aerial parts and transformed roots), P. lanata (aerial parts), and P. murrayi (aerial parts and roots). This work has permitted the isolation of the new benzofurans 10-ethoxy-11-hydroxy-10,11-dihydroeuparin (10), (-)-eupachinin A ethyl ether (12), 11,15-didehydro-eupachinin A (13), 10,12-dihydroxy-11-angelyloxy-10,11-dihydroeuparin (14), 2,4-dihydroxy-5-formyl-acetophenone (15) isolated for the first time as a natural product, 11-angelyloxy-10,11-dihydroeuparin (16), and 12-angelyloxyeuparone (17), along with several known ones (1–9, 11). In addition, the incubation of the abundant component, 6-hydroxytremetone (1), with the fungus Mucor plumbeus has been studied. Benzofurans in the tremetone series (1, 1a, 2–5, 18, 18a), the euparin series (6, 7, 7a, 8–10, 14, 16), and the eupachinin-type (11, 12) were tested for antifeedant effects against the insect Spodoptera littoralis. The antifeedant compounds (1, 4, 6, 11, 12) were further tested for postingestive effects on S. littoralis larvae. The most antifeedant compounds were among the tremetone series, with 3-ethoxy-hydroxy-tremetone (4) being the strongest antifeedant. Glucosylation of 1 by its biotransformation with Mucor plumbeus gave inactive products. Among the euparin series, the dihydroxyangelate 14 was the most active, followed by euparin (6). The eupachinin-type compounds (11, 12) were both antifeedants. Compounds 4, 11, and 12 showed antifeedant effects without postingestive toxicity to orally dosed S. littoralis larvae. Euparin (6) had postingestive toxicity that was enhanced by the synergist piperonyl butoxide.
Journal Article
New Pharmacological Strategies against Pancreatic Adenocarcinoma: The Multifunctional Thiosemicarbazone FA4
by
Fraga Rodrigues, Stephanie M.
,
Niso, Mauro
,
Anobile, Dario P.
in
Apoptosis
,
Binding sites
,
Cancer therapies
2022
A new sigma-2 (σ2) receptor ligand (FA4) was efficiently synthesized and evaluated for cytotoxic, proapoptotic, and antimigratory activity on pancreatic ductal adenocarcinoma (PDAC) primary cell cultures, which restrained the aggressive and chemoresistant behavior of PDAC. This compound showed relevant antiproliferative activity with half maximal inhibitory concentration (IC50) values ranging from 0.701 to 0.825 μM. The cytotoxic activity was associated with induction of apoptosis, resulting in apoptotic indexes higher than those observed after exposure to a clinically relevant concentration of the gemcitabine, the first-line drug used against PDAC. Interestingly, FA4 was also able to significantly inhibit the migration rate of both PDAC-1 and PDAC-2 cells in the scratch wound-healing assay. In conclusion, our results support further studies to improve the library of thiosemicarbazones targeting the σ-2 receptor for a deeper understanding of the relationship between the biological activity of these compounds and the development of more efficient anticancer compounds against PDAC.
Journal Article