Browsing by Author "Costa, Raquel"
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- Anti-Angiogenic Properties of Cafestol and Kahweol Palmitate Diterpene EstersPublication . Moeenfard, Marzieh; Cortez, Alice; Machado, Vera; Costa, Raquel; Luís, Carla; Coelho, Pedro; Soares, Raquel; Alves, Arminda; Borges, Nuno; Santos, AlejandroEpidemiological studies support the association of coffee-specific diterpenes, with various beneficial health effects. Although anti-antiangiogenic properties of free cafestol and kahweol have been recently described, available data regarding their esterified form, in particular palmitate esters as the main diterpene esters present in coffee, are still rare. Given that angiogenesis plays an important role in many pathological conditions, including cancer growth and metastasis, this study aimed to assess and compare the potential anti-angiogenic effects of cafestol palmitate (CP) and kahweol palmitate (KP) in an in vitro angiogenesis model. According to our findings, both compounds inhibited angiogenesis steps on human microvascular endothelial cells (HMVECs), although a more significant effect was observed for KP. Compared to control, HMVECs viability decreased in a dose-dependent manner upon incubation either with CP or KP. Concentrations of 75 and 100 μM of each compound were cytotoxic. Cell proliferation was also dramatically reduced by both diterpene esters at 50 μM, although KP had a stronger inhibitory effect. However, CP and KP did not induce apoptosis on HMVECs. Both compounds reduced cell migration, but this effect was only statistically significant after KP incubation. Inhibition of VEGFR2 expression and its downstream effector Akt, but not Erk, was also observed in CP- and KP-treated HMVECs. These findings were confirmed using ELISA assay for phosphorylated (active) VEGFR-2. Taken together, these data indicate that both CP and KP can be considered potent compounds against angiogenesis-dependent disorders. Our findings further indicate that KP exerts more potent anti-angiogenic effects than CP, in most of assays.
- Bioaerogels: promising nanostructured materials in fluid management, healing and regeneration of woundsPublication . G. Bernardes, Beatriz; Del Gaudio, Pasquale; Alves, Paulo; Costa, Raquel; A. Garcia-Gonzalez, Carlos; Leite Oliveira, AnaWounds affect one’s quality of life and should be managed on a patient-specific approach, based on the particular healing phase and wound condition. During wound healing, exudate is produced as a natural response towards healing. However, excessive production can be detrimental, representing a challenge for wound management. The design and development of new healing devices and therapeutics with improved performance is a constant demand from the healthcare services. Aerogels can combine high porosity and low density with the adequate fluid interaction and drug loading capacity, to establish hemostasis and promote the healing and regeneration of exudative and chronic wounds. Bio-based aerogels, i.e., those produced from natural polymers, are particularly attractive since they encompass their intrinsic chemical properties and the physical features of their nanostructure. In this work, the emerging research on aerogels for wound treatment is reviewed for the first time. The current scenario and the opportunities provided by aerogels in the form of films, membranes and particles are identified to face current unmet demands in fluid managing and wound healing and regeneration.
- EEG signatures during pregnancy and their role on parenting-related measures: scoping reviewPublication . Braga, Patrícia Vilela; Amaoui, Sofia; Lamela, Diogo; Jongenelen, Inês; Costa, Raquel; Oliveira, Jorge; Pasion, Rita; Pinto, Tiago Miguel; Paiva, Tiago Oliveira; Campos, Carlos; Campos, CarlosThis scoping review aims to map and synthesise the current research evidence targeting the electroencephalography (EEG) neural correlates during pregnancy and its association with parenting-related measures during pregnancy and postpartum period. Pregnancy is characterised by a wide range of biological changes associated with adaptation to parenthood. A growing body of literature has examined the neural correlates of pregnancy using EEG, revealing distinct patterns in pregnant females, with these EEG metrics changing throughout gestation and postpartum. Due to the heterogeneity of the evidence, the current literature lacks an organised synthesis, making it difficult to understand the neural correlates during pregnancy and their association with parentingrelated measures during pregnancy and postpartum period. Studies will be included if they contain a quantitative EEG metric in their assessment in pregnant women. Studies will be included if they involve clinical or community samples. No sociodemographic, obstetric, or health exclusion criteria will be applied. The scoping review will be conducted following the Joanna Briggs Institute’s (JBI) guidelines and will be reported following Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. Searches will be conducted in 7 databases (Cochrane for Trials and Reviews, PsycInfo, PubMed, Psychological and Behavioural Science Collection, Scopus and Web of Science Core Collection) for articles published in English, Portuguese, or Spanish with no limitation on the region or publication time frame. Two independent reviewers will screen each record following a standardised flowchart using asreview lab. Data extraction will be performed by the two reviewers using charting tables in Excel. Disagreements at any step will be resolved via consensus or by a third reviewer. Results will be reported using tables and graphs along with a descriptive analysis, according to the research questions.
- Exploring the anti-cancer properties of pomegranate peel aqueous extractPublication . Luís, Carla; Sousa, André P.; Costa, Raquel; Maduro, Ana T.; Pais, Patrick J.; Sá, Sara; Gestoso, Álvaro; Fernandes, Flávia; Jerónimo, Eliana; Soares, Raquel; Fernandes, Rúben; Baylina, Pilar; Duarte, Maria F.The objective of this work is to evaluate the influence of pomegranate peel extract (PPE) in the behavior of breast cell lines (epithelial and tumor type) and related oxidative metabolism. Fruitbased functional foods have been the target of increasing scientific research for their physiological and pathophysiological properties. Pomegranate (Punica granatum) is a suitable example with both prophylactic and medicinal effects. MCF-7 cell line from tumor breast carcinoma, and MCF-10A cell line from normal epithelial mammary gland were used and subjected to different concentrations of PPE, ranging from 1 to 5 mM of gallic acid equivalents (GAE). Viability, proliferation, mobility, and cytotoxicity assays were performed along with the quantification of antioxidant enzymes, namely, catalase, superoxide dismutase (SOD) and reduced (GSH) and oxidized (GSSG) glutathione. We observed a decrease in viability and proliferation of MCF-7 cells, at higher concentrations of PPE, with no influence in epithelial cells. Interestingly, in a concentration-dependent manner, PPE triggered a significant decrease in migration on both cell lines, with a more pronounced effect in breast cancer cell line. Regarding antioxidant enzyme activity, on tumor cells higher concentrations of PPE decreased catalase activity and significantly increased SOD activity. Regarding GSH and GSSG, we observed different expression levels between MCF-7 and MCF-10A, with MCF-7 presenting lower levels compared to MCF-10A. GSH/GSSG ratio was notably higher in MCF-7 at 5 mM GAE. PPE exhibits anti-tumor effects without significantly affecting normal epithelial cells. Our work strengthens the potential antitumoral effect of PPE by reducing MCF-7 cell viability and proliferation through the imbalance of antioxidant enzymes.
- Fattymess: fat diet-induced obesity in melanoma metastasisPublication . Correia, Joana; Costa, Raquel; Prudêncio, Cristina; Soares, Raquel; Coelho, PedroMelanoma is the most aggressive skin cancer characterized by a high metastatic potential and poor survival rate, leading to major morbidity/mortality. Overweight, obesity and diet composition have been identified as risk factors for many types of cancers. However, there are cancers where obesity is associated with favorable outcomes and this has been coined the “obesity paradox”. Preliminary data obtained by our research group disclosed paradoxical findings unveiling that obesity act as a two-edged sword in melanoma: potentiating primary tumor growth, and vascularity/angiogenesis, but at the same time decrease metastatic potential, thus preventing secondary tumor growth. In this exploratory research project, we propose to further explore and deepen the impact that fat-rich diets and obesity partake in melanoma etiology
- Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?Publication . Ramalho, Renata; Almeida, Joana; Beltrão, Marília; Pirraco, Ana; Costa, Raquel; Sokhatska, Oksana; Guardão, Luísa; Palmares, Carmo; Guimarães, João Tiago; Delgado, Luís; Moreira, André; Soares, RaquelA number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R2 = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.
- Neurokinin-1 receptor, a new modulator of lymphangiogenesis in obese-asthma phenotypePublication . Ramalho, Renata; Almeida, Joana; Fernandes, Rúben; Costa, Raquel; Pirraco, Ana; Guardão, Luísa; Delgado, Luís; Moreira, André; Soares, RaquelAims Obesity and asthma are widely prevalent and associated disorders. Recent studies of our group revealed that Substance P (SP) is involved in pathophysiology of obese-asthma phenotype in mice through its selective NK1 receptor (NK1-R). Lymphangiogenesis is impaired in asthma and obesity, and SP activates contractile and inflammatory pathways in lymphatics. Our aim was to study whether NK1-R expression was involved in lymphangiogenesis on visceral (VAT) and subcutaneous (SAT) adipose tissues and in the lungs, in obese-allergen sensitized mice. Main methods Diet-induced obese and ovalbumin (OVA)-sensitized Balb/c mice were treated with a selective NK1-R antagonist (CJ 12,255, Pfizer Inc., USA) or placebo. Lymphatic structures (LYVE-1 +) and NK1-R expression were analyzed by immunohistochemistry. A semi-quantitative score methodology was used for NK1-R expression. Key findings Obesity and allergen-sensitization together increased the number of LYVE-1 + lymphatics in VAT and decreased it in SAT and lungs. NK1-R was mainly expressed on adipocyte membranes of VAT, blood vessel areas of SAT, and in lung epithelium. Obesity and allergen-sensitization combined increased the expression of NK1-R in VAT, SAT and lungs. NK1-R antagonist treatment reversed the effects observed in lymphangiogenesis in those tissues. Significance The obese-asthma phenotype in mice is accompanied by increased expression of NK1-R on adipose tissues and lung epithelium, reflecting that SP released during inflammation may act directly on these tissues. Blocking NK1-R affects lymphangiogenesis, implying a role of SP, with opposite physiological consequences in VAT, and in SAT and lungs. Our results provide a clue for a novel SP role in the obese-asthma phenotype.
- Neurophysiological markers of cardiac interoceptive processing in expectant parents: a study with heartbeat-evoked potentialsPublication . Braga, Patrícia Vilela; Marshall, Amanda; Lamela, Diogo; Jongenelen, Inês; Rocha, Nuno Barbosa; Costa, Raquel; Pasion, Rita; Schütz-Bosbach, Simone; Pinto, Tiago Miguel; Feldman, Ruth; Campos, Carlos; Campos, Carlos; Rocha, NunoPregnancy and parenthood are associated with functional and morphological brain changes. Specifically, the parental caregiving network encompasses key structures implicated in interoception, that is, the ability to perceive and subjectively experience inner bodily states. Interoceptive processing may be critical for successful caregiving, allowing parents to integrate perceived changes in their own bodily states with information stemming from their child. Thus, it is feasible to hypothesize that pregnancy-related neurophysiological changes can modify interoception in expectant parents. Objective: To compare neural markers of cortical interoceptive processing (heartbeat-evoked potentials; HEP) between first-time expectant parents (mothers and fathers) and matched non-parents. First-time expectant heterosexual couples at 26-34 weeks gestational age (n = 70) and matched non-parents (n = 140, 70 female) will complete a multilevel interoception assessment protocol. Neural markers of interoception will be indexed by HEP, that is, neurophysiological responses to cardiac afferent inputs which are obtained through electroencephalography recordings (EEG) time-locked to electrocardiography events (ECG). HEP will be recorded while participants complete the Baby Face Repetition Suppression Paradigm in which sad or neutral infant facial expressions are either repeated or alternated in a 500 ms interstimulus interval. This manipulation induces an emotion-specific repetition modulation on HEP amplitude (differential effects for sad vs. neutral facial expressions). A condition with adult facial expressions will be employed to examine domain-general vs. infant-specific effects. Expectant parents will display increased allocation of neural resources to interoceptive inputs (larger repetition-induced HEP modulation) in contrast to non-parents, particularly when considering infant facial expressions. Effect sizes will be larger when contrasting sad vs. neutral infant facial expressions. Findings from this pioneering study will provide further understanding of the parental brain and the role of interoception during pregnancy, contributing to the comprehension of complex processes involved in caregiving and the development of the parent-infant bond.
- Neurophysiological markers of cardiac interoceptive processing in first-time expectant mothersPublication . Braga, Patrícia Vilela; Marshall, Amanda; Lamela, Diogo; Jongenelen, Inês; Rocha, Nuno Barbosa; Costa, Raquel; Pasion, Rita; Schütz-Bosbach, Simone; Pinto, Tiago Miguel; Feldman, Ruth; Campos, Carlos; Campos, Carlos; Rocha, NunoPregnancy is a complex biological phenomenon where two distinct pathways may produce changes in interoception (ability to perceive and subjectively experience inner bodily states). First, pregnancy modifies the parental caregiving brain network, which includes key regions for interoceptive processing, particularly the insula. Second, pregnancy also changes the strength, frequency, and/or nature of interoceptive signals across different modalities (e.g., cardiac, respiratory, gastric). This study investigates pregnancy-related changes in neural markers of cortical interoceptive processing, specifically heartbeat-evoked potentials (HEP), by comparing first-time expectant mothers with non-pregnant, age-matched females. Data were collected from first-time expectant mothers (n = 13; Mage = 32.15 years) and matched controls (n = 8; mean age = 30.88 years) at 28–32 weeks of gestation. EEG recordings, time-locked to R-peaks (ECG), were obtained while participants completed the Infant Face Repetition Suppression Task. This paradigm was designed to induce an emotion (sad vs. neutral) and age-specific (infant vs. adult) modulation of HEP amplitude. A cluster mass permutation test was employed to identify the electrodes and time-windows where HEP amplitude was effectively modulated (right frontal-central; 308 - 600 ms). Repetition-suppression effects on HEP amplitude were observed for adult stimuli (p = .049, d = 0.499), while no modulation was observed in the infant condition (p = .471, d = 0.174). Pregnant participants displayed significantly lower HEP amplitude in adult trials in comparison to non-pregnant controls (p = .046, g = 0.997). Despite significant differences only emerging in the adult trials, pregnant women displayed lower HEP amplitude across all conditions. These findings suggest that pregnancy modifies cardiac interoceptive processing, leading to an overall decrease in HEP amplitude. Contrary to our hypothesis, expectant mothers did not exhibit infant- or emotion-specific changes in neural markers of cardiac interoception.
- Role of oxidative stress-induced systemic and cavernosal molecular alterations in the progression of diabetic erectile dysfunctionPublication . Castela, Angela; Gomes, Pedro; Domingues, Valentina F.; Paíga, Paula; Costa, Raquel; Vendeira, Pedro; Costa, CarlaBackground Erectile dysfunction (ED) is a prevalent complication of diabetes, and oxidative stress is an important feature of diabetic ED. Oxidative stress-induced damage plays a pivotal role in the development of tissue alterations. However, the deleterious effects of oxidative stress in the corpus cavernosum with the progression of diabetes remain unclear. The aim of this study was to evaluate systemic and penile oxidative stress status in the early and late stages of diabetes. Methods Male Wistar streptozotocin-diabetic rats (and age-matched controls) were examined 2 (early) and 8 weeks (late) after the induction of diabetes. Systemic oxidative stress was evaluated by urinary H2O2 and the ratio of circulating reduced/oxidized glutathione (GSH/GSSG). Penile oxidative status was assessed by H2O2 production and 3-nitrotyrosine (3-NT) formation. Cavernosal endothelial nitric oxide synthase (eNOS) was analyzed by quantitative immunohistochemistry. Dual immunofluorescence was also performed for 3-NT and α-smooth muscle actin (α-SMA) and eNOS–α-SMA. Results There was a significant increase in urinary H2O2 levels in both diabetic groups. The plasma GSH/GSSG ratio was significantly augmented in late diabetes. In cavernosal tissue, H2O2 production was significantly increased in late diabetes. Reactivity for 3-NT was located predominantly in cavernosal smooth muscle (SM) and was significantly reduced in late diabetes. Quantitative immunohistochemistry revealed a significant decrease in eNOS levels in cavernosal SM and endothelium in late diabetes. Conclusions The findings indicate that the noxious effects of oxidative stress are more prominent in late diabetes. Increased penile protein oxidative modifications and decreased eNOS expression may be responsible for structural and/or functional deregulation, contributing to the progression of diabetes-associated ED.