39 research outputs found

    On the use of polynomial models in multiobjective directional direct search

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    FCT - Fundacao para a Ciencia e a Tecnologia PTDC/MAT-APL/28400/2017; UIDB/00297/2020.Polynomial interpolation or regression models are an important tool in Derivative-free Optimization, acting as surrogates of the real function. In this work, we propose the use of these models in the multiobjective framework of directional direct search, namely the one of Direct Multisearch. Previously evaluated points are used to build quadratic polynomial models, which are minimized in an attempt of generating nondominated points of the true function, defining a search step for the algorithm. Numerical results state the competitiveness of the proposed approach.authorsversionpublishe

    Optimização / Investigação Operacional

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    Editor Convidado: Ana Luísa Custódio João Gouveia, Richard Z. Robinson e Rekha Thomas, "Representações mínimas de polítopos" Teresa Grilo, Fernando Lobo Pereira e Sílvio Gama, "Controlo óptimo de sistemas dinâmicos impulsionados por escoamentos de Couette" Marta Pascoal e Marisa Resende, "Informação imprecisa na forma de conjuntos aproximativos – aplicação à otimização em redes" Susana Fernandes, "Representação proporcional – um problema de otimização inteira

    Sapwood of carob tree (Ceratonia siliqua L.) as a potential source of bioactive compounds

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    Methanol (ME) and hot water extracts (WE) of carob tree sapwood (Ceratonia siliqua L.) exhibited high antioxidant activity and were rich in phenolic compounds, with the main compounds identified by HPLC/DAD as gentisic acid and (-)-epicatechin. The ME displayed a high in vitro antitumor activity against human tumoural cell lines and reduced intracellular ROS production by HeLa cells after treatment with H2O2. (-)-Epicatechin was shown to contribute to the cytotoxic activity of the ME. This is the first report on the biological activity of carob tree sapwood

    Metastatic Renal Cell Carcinoma: The Importance of Immunohistochemistry in Differential Diagnosis

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    Introduction: Clear cell carcinoma accounts for 75% of all types of renal neoplasms. Approximately one third presents with metastatic disease at diagnosis. Immunohistochemical studies play a significant diagnostic role. Case Report: We report the case of a 48-year-old heavy smoker who presented with productive cough and progressive dyspnea. The study revealed a renal mass and lung alterations compatible with primary tumor of the lung. The patient underwent a right complete nephrectomy. The anatomopathological exam showed clear cell renal carcinoma (pT1bN0Mx). After transthoracic needle aspiration biopsy, the clinical diagnosis was stage IV adenocarcinoma of the lung. Initially, the patient received one cycle of chemotherapy (cisplatin/pemetrexed). Two weeks later, the immunohistochemistry tests revealed a secondary lesion with probable renal origin. Chemotherapy was stopped and the patient was started on sunitinib treatment. After two cycles the disease progressed. A second-line treatment with everolimus was proposed; however, the patient died 2 weeks later due to terminal respiratory insufficiency. Discussion: Clear cell renal cell carcinoma remains one of the great mimickers in pathology. Immunohistochemistry is a valuable tool in the differential diagnosis of lung carcinomas. With the help of thyroid transcription factor 1, it is possible to distinguish a primary lung tumor from a metastasis with a reasonable degree of certainty. The present case report illustrates the challenge of making a definitive and adequate diagnosis. The immunohistochemistry added information that changed the whole treatment strategy. For the best treatment approach, it is fundamental that clinicians await all possible test results, before establishing a treatment plan

    In vitro cytotoxic effects and apoptosis induction by a methanol leaf extract of carob tree (Ceratonia siliqua L.)

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    This research evaluated the in vitro apoptotic inducing properties of a methanol leaf extract of carob tree (Ceratonia siliqua L.) on a human cervical adenocarcinoma cell line (HeLa). The cell viability effect on a prostate (DU-145), breast (MDA-MB-231) and colon cell line (HCT-166) was also assessed. The effect of the extract on reactive oxygen species (ROS) production by HeLa cells was studied, and a phytochemical evaluation was made by high performance liquid chromatography with diode array detection (HPLC). Total mean yield of identified phenols was 261.1 mg/g DW, and (+)-catechin was the major compound (76.8 mg/g DW). The extract decreased cell viability in a dose-and time-dependent manner, and a more pronounced effect on HeLa line was observed. In vitro cytotoxic activity was associated with apoptosis, but not to the increase of ROS production. Among the tested compounds identified in the extract, the highest activity was detected with gallic acid (GA), (+)-catechin and quercetin, with reductions in HeLa cells viability down to 8.0, 11.9 and 27.1%, respectively. This is the first report on the apoptotic activity of a leaf extract of carob tree on a human cancer cell line, suggesting that it may be a potential source of chemopreventive compounds

    Isololiolide, a carotenoid metabolite isolated from the brown alga Cystoseira tamariscifolia, is cytotoxic and able to induce apoptosis in hepatocarcinoma cells through caspase-3 activation, decreased Bcl-2 levels, increased p53 expression and PARP cleavage

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    Background: Brown macroalgae have attracted attention because they display a wide range of biological activities, including antitumoral properties. In this study we isolated isololiolide from Cystoseira tamariscifolia for the first time.Purpose: To examine the therapeutical potential of isololiolide against tumor cell lines.Methods/Study design: The structure of the compound was established and confirmed by 1D and 2D NMR as well as HRMS spectral analysis. The in vitro cytotoxicity was analyzed by colorimetric 3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyltetrazolium bromide assay in tumoral as well as in non-tumoral cell lines. Cell cycle arrest and induction of apoptosis were assessed by flow cytometry. Alteration of expression levels in proteins important in the apoptotic cascade was analyzed by western blotting.Results: Isololiolidewas isolated for the first time from the brown macroalga C. tamariscifolia. Isololiolide exhibited significant cytotoxic activity against three human tumoral cell lines, namely hepatocarcinoma HepG2 cells, whereas no cytotoxicity was found in non-malignant MRC-5 and HFF-1 human fibroblasts. Isololiolide completely disrupted the HepG2 normal cell cycle and induced significant apoptosis. Moreover, western blot analysis showed that isololiolide altered the expression of proteins that are important in the apoptotic cascade, increasing PARP cleavage and p53 expression while decreasing procaspase-3 and Bcl-2 levels.Conclusion: Isololiolide isolated from C. tamariscifolia is able to exert a selective cytotoxic activity on hepatocarcinoma HepG2 cells as well as induce apoptosis through the modulation of apoptosis-related proteins. (C) 2016 Elsevier GmbH. All rights reserved

    Further evidence of possible therapeutic uses of Sambucus nigra L. extracts by the assessment of the In Vitro and In Vivo anti-inflammatory properties of Its PLGA and PCL-Based Nanoformulations

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    Sambucus nigra L. is widely used in traditional medicine with different applications. However, confirmative studies are strongly required. This study aimed to assess the biological activities of the S. nigra flower’s extract encapsulated into two different types of nanoparticles for optimizing its properties and producing further evidence of its potential therapeutic uses. Different nanoparticles (poly(lactide-co-glycolide, PLGA) and poly-Ɛ-caprolactone (PCL), both with oleic acid, were prepared by emulsification/solvent diffusion and solvent-displacement methods, respectively. Oleic acid was used as a capping agent. After the nanoparticles’ preparation, they were characterized and the biological activities were studied in terms of collagenase, in vitro and in vivo anti-inflammatory, and in vitro cell viability. Rutin and naringenin were found to be the major phenolic compounds in the studied extract. The encapsulation efficiency was higher than 76% and revealed to have an impact on the release of the extract, mainly for the PLGA. Moreover, biochemical and histopathological analyses confirmed that the extract-loaded PLGA-based nanoparticles displayed the highest anti-inflammatory activity. In addition to supporting the previously reported evidence of potential therapeutic uses of S. nigra, these results could draw the pharmaceutical industry’s interest to the novelty of the nanoproducts.Authors also gratefully acknowledge the Régiefrutas and Fundação para a Ciência e a Tecnologia (FCT) (UIDB/04138/2020, UIDB/00100/2020, UIDP/50017/2020+UIDB/50017/2020) and Portugal 2020 to the Portuguese Mass Spectrometry Network (LISBOA-01-0145-FEDER-402-022125) for financial support. Furthermore, the authors are also grateful to the work supported by the FCT and the Portuguese National and Regional Budget, through CCMAR/Multi/04326/2019 project. Finally, Luísa Custódio was supported by the FCT Scientific Employment Stimulus (CEECIND/00425/2017).info:eu-repo/semantics/publishedVersio

    Bacillary Prostatitis after Intravesical Immunotherapy: A Rare Adverse Effect

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    Nowadays, the most efficient form of intravesical immunotherapy for superficial transitional cell carcinoma of the urinary bladder is the instillation of bacillus Calmette-Guérin (BCG), proceeding from an attenuated strain of Mycobacterium bovis. In up to 40% of cases, its instillation is associated with significantly elevated prostate-specific antigen (PSA) levels. In these cases, prostate biopsy should be withheld for 3 months and PSA should be monitored. Bacillary prostatitis is a rare occurrence in patients treated with intravesical BCG immunotherapy. Although symptomatic bacillary prostatitis is even rarer, it is the worst type of this condition. The aims of this study are to report a case of bacillary prostatitis as a rare adverse effect of intravesical BCG immunotherapy and to make a theoretical review about how to manage this complication. A 58-year-old man, former smoker, underwent a transurethral resection of the bladder in February 2004 because of a papillary transitional cell carcinoma of the bladder (pT1G2N0M0). After surgery, BCG instillation therapy was given in a total of 15 instillations, the last one in March 2007. In the last 3 months of therapy, until May 2007, a progressive increase in his PSA level was registered, and he underwent a prostate biopsy revealing granulomatous prostatitis of bacillary etiology. The semen culture was positive for M. bovis. After 3 months of a two-drug (isoniazid and rifampin) antituberculous regimen, the semen culture became negative and the PSA level decreased. The early identification of intravesical BCG immunotherapy complications allows their effective treatment. However, when a histological diagnosis of asymptomatic granulomatous prostatitis is made, the execution and type of treatment are controversial

    Growth performance, in vitro antioxidant properties and chemical composition of the halophyte Limonium algarvense Erben are strongly influenced by the irrigation salinity

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    Limonium algarvense Erben (sea lavender) is a halophyte species with potential to provide natural ingredients with in vitro antioxidant, anti-inflammatory, neuroprotective and antidiabetic properties. This study reports for the first time the 1) cultivation of sea lavender in greenhouse conditions under irrigation with freshwater (approx. 0 mM NaCl) and saline aquaculture wastewater (300 and 600 mM NaCl), and 2) the influence of the irrigation salinity on the plant performance (e.g growth, number of produced leaves and flowers), in vitro antioxidant properties [radical scavenging activity (DPPH and ABTS), ferric reducing antioxidant power (FRAP), metal chelating properties on copper (CCA) and iron (ICA)], toxicity (in vitro on three mammalian cell lines) and chemical composition (determined by LC-ESI-HRMS/MS). The freshwater-irrigated plants had better growth performance than those irrigated with saltwater. Extracts from wild plants, had the highest antioxidant activity, but those from cultivated ones kept high in vitro antioxidant properties and interesting chemical profile. The flowers' extracts of plants irrigated with 300 mM NaCl had the highest antioxidant activities against DPPH, whereas those from freshwater-irrigated plants were more active on ABTS, CCA and FRAP. Most of the extracts showed nil toxicity. The flowers' extracts displayed the highest diversity of compounds, mainly quercetin, apigenin, luteolin, naringenin and their glycoside derivatives. Moreover, their abundance varied with the irrigation salinity. These data indicate that sea lavender plants can be successfully cultivated in greenhouse conditions under fresh- and saltwater irrigation, maintaining interesting biological and chemical properties.Funding Agency Portuguese Foundation for Science and Technology Portuguese National Budget CCMAR/Multi/04326/2019 GreenVet project ALG-01-0145-FEDER-028876 XtrerneAquaCrops FA-05-2017-028 Lisboa-01-0145-FEDER-022125-RNEM-IST ID/QUI/00100/201 Portuguese Foundation for Science and Technology SFRH/BD/116604/2016 CEECIND/00425/2017info:eu-repo/semantics/publishedVersio

    Conversando sobre Património Industrial e outras Histórias: palavras, espaços e imagens

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    O conjunto de entrevistas apresentadas neste livro procura dar uma nova visão acerca do património industrial. Com uma abordagem aos estudos e às trajectórias de diversos estudiosos do Brasil e de Portugal, aos percursos de formação de cada autor (a), às suas várias temporalidades e vinculações institucionais distintas, a obra valoriza as narrativas orais de quem viveu o processo de construção e consolidação dessa área de pesquisa nos dois países. O objectivo é contribuir para o debate complexo e contínuo sobre o património e possibilita uma ampliação do nosso entendimento dos modos como esta área se firmou e se vem afirmando em diversos espaços, dentro e fora das universidades
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