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- ItemAcesso aberto (Open Access)Análise do perfil lipidômico em pacientes com câncer colorretal em estádios avançados(Universidade Federal de São Paulo (UNIFESP), 2017-07-31) Figueiredo, Adiel Goes de [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; http://lattes.cnpq.br/7314943504526739; http://lattes.cnpq.br/5873178563768279; Universidade Federal de São Paulo (UNIFESP)Abstract In the last 10 years the incidence of colorectal cancer (CRC) has been increasing in developing countries. The search for molecular markers that reduce the need for invasive examinations for the diagnosis of colorectal cancer and the follow-up of treated patients advanced with the use of analytical technologies such as mass spectrometry (MS), which allowed the search for lipid metabolites as Candidates for probable biomarkers. The objective was to establish the lipid profile of patients with locally advanced, unresectable or metastatic colorectal cancer. Peripheral blood was collected from patients with colorectal cancer and patients with normal colonoscopy. After lipid extraction, the samples were processed and analyzed in the MALDI TOF / TOF equipment. From the data matrix, the statistical analyzes were performed by the principal component analysis methods and the least squares discriminant analysis. The importance of the variable in the projection was used to identify the ions that had the greatest discriminatory effect between the groups. Eight lipids were identified as potential biomarkers and a multiple logistic regression model was proposed to calculate the performance of the test where we observed values of AUC 0.87, sensitivity 88.33% and specificity 83.78% and for a validation test with 1000 permutations a p <0.001. The classes of lipids found were sphingolipids, glycerophospholipids and policetidia. The strength of the association between the peak intensities of these lipids and the presence of colorectal cancer make these metabolites candidates for possible biomarkers. We found that sphingolipid (m / z = 742.98869) could be a biomarker in monitoring patients with CRC. In the survival analysis, three lipids showed a prognostic value for colorectal cancer, sphingolipid (m / z = 857,11525) and policetidios (m / z = 876,20796) and glycerophospholipid (m / z = 1031.54773).
- ItemAcesso aberto (Open Access)Análises de glicoesfingolipídeos em diferentes espécies do fungo patogênico do gênero Aspergillus(Universidade Federal de São Paulo (UNIFESP), 2018-06-28) Rodrigues, Karolina Marques [UNIFESP]; Takahashi, Helio Kiyoshi [UNIFESP]; http://lattes.cnpq.br/8090231917635170; Universidade Federal de São Paulo (UNIFESP)incidence of serious fungal infections has increased in the last decade, mainly due to the increase in the number of immunocompromised patients, representing a serious cause of morbidity and mortality in this population. Recent works show that fungi are vulnerable to inhibitors of sphingolipid biosynthesis, which led us to study the structures of fungal glycosphingolipids, in order to obtain relevant information on the biosynthesis and functional roles of these molecules and to propose new potential targets for antifungal treatment. Glycosylinositol phosphorilceramides (GIPCs), inositolphosphoryl ceramides (IPCs), and monohexosyl ceramides (CMHs) from A. fumigatus, A. flavus, A. niger and A. nidulans, filamentous fungi causing aspergillosis, were extracted, purified and characterized using methods chromatography, biochemistry and mass spectrometry. By mass spectrometry using electrospray ionization (EISMS) in positive mode, two major peaks corresponding to CMHs of 754 m/z and 756 m/z were identified for all species analyzed. By collisioninduced dissociation (CID), m/z fragments of m/z: 736, 574, 556 and 276 were identified for CMH 754 m/z. Similarly for CMH m/z 756 fragments of m/z 738, 576, 558 and 276. The fragmentation pattern for both CMHs corresponds respectively to [M+H1H2O]+, [M+H1H2OHex]+, [M+H2H2OHex]+, [M+H2H2Oacyl]+, the fragments associated with ceramidecontaining CMH, with structures not described in mammalian CMH, d19:2/h18:1 and d19:2/18:0, respectively. Glucosylceramide and galactosylceramide were characterized by high resolution thin layer chromatography (HPTLC). It was possible to identify 2 different species of IPCs [M+H]+, 926 m/z, and 954 m/z, presenting 282 m/z and 310 m/z fragments for sphingosine t18:0 and t20:0, respectively. The presence of inositol was confirmed using 241 m/z precursor ion mass spectrometry, referring to the inositol phosphate group of these structures. For the characterization of the GIPCs in the different Aspergillus species, we used collision induced dissociation (DIC) in tandem MS with eletrotron ionization (ESI), in positive mode [M+H]+. In this way we were able to detect the 1088 m/z and 1116 m/z ions corresponding to GIPCs with 1 hexose; 1250 m/z and 1278 m/z, GIPCs with 2 hexoses; 1412 m/z and 1440 m/z, corresponding to GIPCs containing 3 hexoses. The GIPCs present A. fumigatus, A. flavus and A. niger were derived from the IPC 926 m/z (containing ceramide 666 m/z) and the IPC 954 m/z (containing ceramid 694 m/z), on the other hand, the A. nidulans GIPCs are derived only from the IPC 926 m/z. The presence of galactofuranose residues in GIPCs was confirmed using the monoclonal antibody MEST1 which recognizes terminal residues of galactofuranose. By immunostaining the HPTLC plates with MEST1 the A. fumigatus, A. flavus and A. niger GIPCs, which had a component recognized by mAb MEST1, have the same chromatographic migration as GIPC called Pb1 of Paracoccidioides brasiliensis. As for A. nidulans, only small reactivity with mAb MEST1 was detected. These results indicate that in the four species studied, both CMHs, IPCs and GIPCs have structures not expressed in mammals, indicating that these molecules as well as the specific enzymes involved in the metabolism of these sphingolipids can be considered as targets for antifungal treatment .
- ItemSomente MetadadadosThe antiviral effect of mollusk mucus on measles virus(Elsevier Science Bv, 2016) de Toledo-Piza, Ana Rita; Figueiredo, Cristina Adelaide; de Oliveira, Maria Isabel; Negri, Giuseppina [UNIFESP]; Namiyama, Gislene; Tonelotto, Mariana; Villar, Karina de Senna; Rofatto, Henrique Krambeck; Mendonca, Ronaldo ZucatelliMeasles is a viral disease highly contagious spread by respiratory transmission. Although infection can be controlled by vaccination, numerous cases of measles have been registered in many areas of the world, highlighting the need for additional interventions. Terrestrial gastropods exude mucus on their body surface when traveling, to protect the body from mechanical injury, desiccation or contact with harmful substances. The mucus of mollusks has been studied as a source of new natural compounds with diverse biological activities. In this study, the antiviral activity of the mucus of the land slug P. boraceiensis was demonstrated in vitro using Vero cells infected with measles virus. The crude sample and four fractions were tested in cultures infected with measles virus and the antiviral activity was assessed by the cytopathic effect in infected cell cultures as well as by immunofluorescence and qPCR. Fractions 39 and 50 of the mucus from P. boraceiensis were analyzed by HPLC-DAD-ESI-MS/MS and infrared spectroscopy. A mixture of polyunsaturated fatty acids was found in the two fractions. A reduction in the growth of the measles virus was observed, measured by qPCR, with a protection index of 80% in Vero cells infected with measles and treated with fraction 39. Fraction 39 exhibited the best antiviral action in vitro and high contents of hydroxy-tritriacontapentaenoic acid and hydroxy-pentatriacontapentaenoic acid were found in this fraction. (C) 2016 Elsevier B.V. All rights reserved.
- ItemAcesso aberto (Open Access)Associação entre os lipídeos alimentares e os ácidos graxos séricos com sintomas depressivos e de ansiedade de adolescentes com obesidade: um estudo transversal exploratório(Universidade Federal de São Paulo, 2023-08-11) Silva, Sandra Maria Chemin Seabra da [UNIFESP]; Caranti, Danielle Arisa [UNIFESP]; http://lattes.cnpq.br/4760019839583649; http://lattes.cnpq.br/4994112947147521; Universidade Federal de São Paulo (UNIFESP)Introdução: A obesidade, o transtorno de ansiedade e a depressão são doenças complexas e multifatoriais com alta prevalência e incidência, sendo estabelecidas, atualmente, como um problema de saúde pública global. Todas apresentam a inflamação crônica e o padrão alimentar como importantes fatores. Neste sentido, os ácidos graxos circulantes merecem destaque, especialmente pelos seus efeitos anti e pró-inflamatórios. Objetivo: Verificar o grau de associação entre os lipídeos obtidos por meio da alimentação, lipídeos séricos e mediadores inflamatórios com os sintomas de depressão e a ansiedade-traço de adolescentes com obesidade. Métodos: Trata-se de uma pesquisa retrospectiva de coorte, que visitou o banco com os dados de 399 adolescentes com obesidade, pertencente a um estudo realizado no período de 2008 a 2012, conduzido pelo Grupo de Estudos da Obesidade (GEO) da Universidade Federal de São Paulo (UNIFESP). Este estudo foi aprovado pelo Comitê de Ética e Pesquisa UNIFESP. Este banco era composto pelos dados de massa corporal, estatura, composição corporal, glicemia, insulinemia e perfil lipídico (p. ex., triglicérides, colesterol total e frações), concentração plasmática de leptina, adiponectina, fator de necrose tumoral alfa (TNF-), inibidor da ativador do plasminogênio-1 (PAI-1), proteína C reativa (PCR), interleucinas (IL) 1, 6 e 10, perfil de ácidos graxos séricos livres, dados do consumo alimentar e dados do Inventário de depressão de Beck (BDI) e do Inventário de Ansiedade Traço e Estado (IDATE). Resultados: Artigo 1) A amostra foi composta por 138 adolescentes, com idade média de 16,38 anos (± 1,49), Índice de Massa Corporéa médio de 35,78 kg/m2 (± 4.79), sendo 38,4% do gênero masculino e 61,6% do gênero feminino. Tendo os sintomas de depressão como variável desfecho (dependente), as análises de associação foram feitas para verificar o grau de predição das variáveis independentes (p. ex., composição corporal, metabolismo da glicose, perfil lipídico, perfil de ácidos graxos, concentração de leptina, adiponectina, interleucina IL-6, IL-10, TNF-α, PCR, PAI-1). Os sintomas depressivos foram verificados em 54,6% da amostra. Além disso, houve correlação positiva entre os sintomas depressivos e o teor sérico de ácidos graxos saturados (AGS), gordura corporal e adipocinas inflamatórias, como leptina, IL-6 e a relação leptina/ adiponectina. Por outro lado, a correlação foi negativa entre os sintomas de depressão e o total de ácidos graxos poliinsaturados (AGP) do tipo -3. Artigo 2) Para este estudo foram analisados os dados de 125 adolescentes com obesidade, relacionando a ansiedade-traço com a composição corporal, citocinas e ácidos graxos séricos, massa de gordura visceral e massa de gordura subcutânea, concentrações séricas de glicose, insulina, triglicerídeos, colesterol total e fração (VLDL, HDL, LDL, HDL), alanina aminotransferase, aspartato aminotransferase, γ-glutamil transferase, leptina, adiponectina, PAI-1, PCR, e sintomas de Ansiedade-traço. Foi estudado também a associação da Ansiedade-traço com a ingestão de energia e macronutrientes. Os grupos foram criados com base nos percentis de ingestão total de lipídios. No entanto, não houve associação dos lipídios consumidos ou dos ácidos graxos séricos com ansiedade-traço. Conclusão: Os AGS foram positivamente correlacionados aos sintomas depressivos, ao passo que os AGP apresentaram correlação inversa. Contudo, nenhuma correlação foi verificada com ansiedade-traço, nem com lipídios consumidos. Estes resultados indicam que são necessários estudos novos estudos longitudinais, a fim de confirmar a causalidade entre os AG séricos e depressão e a não causalidade com ansiedade-traço em indivíduos com obesidade.
- ItemSomente MetadadadosCaracterização de vesículas extracelulares exportadas pelo fungo(Universidade Federal de São Paulo (UNIFESP), 2012) Vallejo, Milene Carmes [UNIFESP]; Puccia, Rosana [UNIFESP]Este trabalho resultou no estudo de vesículas extracelulares do fungo patogênico Paracoccidioides brasiliensis na fase de levedura. Estas estruturas foram caracterizadas nos isolados Pb3 e Pb18 que pertencem a grupos filogenéticos diferentes e provocam um perfil distinto de infecção em camundongos B10.A. Vesículas extracelulares de 20 a 200 nm transportam antígenos, como visto nas reações de immunoblot com soro de pacientes com paracoccidioidomicose. Um novo epitopo de α-galactosil foi identificado nas vesículas extracelulares, como também na parede celular e em vacúolos intracelulares P. brasiliensis. Proteínas do sobrenadante de cultura do isolado Pb18 foram separadas em frações de vesículas (ves) e livre de vesículas (ves-free), e analisadas por cromatografia líquida acoplada à espectrometria de massas (LC-MS/MS). Foram identificadas, com dois ou mais peptídeos, 205 proteínas de vesículas, contra 260 de ves-free incluindo 120 compartilhadas. A proporção de proteínas de vesículas e ves-free classificadas como secretadas foi aproximadamente 70%, a maioria utilizando o transporte por vias não convencionais. Analisamos proteínas das frações de vesículas de P. brasiliensis com ortólogos em vesículas de H. capsulatum, C. neoformans e S. cerevisiae. Foram identificadas 72 proteínas de vesículas de Pb18 (35%) com ortólogos em pelo menos duas das outras espécies analisadas. Entre elas, sequências que participam de processos metabólicos de carboidrato e proteína, atividade antioxidante, tradução, sinalização e transporte foram enriquecidos nas vesículas. Com esse trabalho, fornecemos uma comparação completa com outros proteomas de vesículas fúngicas e ampliamos a visão sobre proteomas extracelulares em fungos. Nossa análise lipidômica identificou 36 espécies de fosfolipídeos nas vesículas extracelulares dos isolados Pb3 e Pb18, incluindo fosfatidilcolina, fosfatidiletalonamina, ácido fosfatídico, fosfatidilserina, fosfatidilinositol e fosfatidilglicerol. O ácido graxo C18:1 predominou nas vesículas do Pb3, enquanto nas vesículas de Pb18 o C18:2 foi mais abundante. O esterol predominante nas vesículas de Pb3 e Pb18 foi o brassicasterol, seguido por ergostetol e lanosterol. Foram identificadas nas vesículas dos dois isolados 2 espécies de monohexosilceramidas. As preparações de vesículas de ambos os isolados foram capazes de estimular a produção de citocinas em macrófagos RAW264.7. A produção de TNF-α foi maior em células estimuladas com vesículas do Pb3, ao contrário da expressão de IL-10 que foi maior ao estímulo com vesículas de Pb18. Acreditamos que nosso trabalho adiciona dados ao entendimento futuro da biologia das vesículas extracelulares, incluindo sua biogênese e função na interação patógeno-hospedeiro.
- ItemSomente MetadadadosComportamento do glicogênio e dos lipídeos totais nos hepatócitos de ratas albinas prenhes e de seus conceptos, tratados com diferentes doses de cloridrato de 2 (1-Naftilmetil) - imidazolina: estudo histoquímico(Universidade Federal de São Paulo (UNIFESP), 1982) Weckx, Luc Louis Maurice [UNIFESP]; Pontes, Paulo Augusto de Lima [UNIFESP]
- ItemSomente MetadadadosEfeito da fragmentação de dna espermático no desenvolvimento e no perfil lipídico de blastocistos de camundongos(Universidade Federal de São Paulo (UNIFESP), 2019-12-17) Melo, Augusto Azzolini De [UNIFESP]; Lopes, Paula Intasqui [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: To evaluate the effect of sperm DNA fragmentation on the development and metabolism of mice blastocysts. Method: Male FVB/NJ and female C57BL/6J mice were used. Initially, a study to validate an experimental model of sperm DNA fragmentation induction was performed. For this, thirteen males were submitted to testicular heat stress (Heat stress group, n=13), and fourteen males, not submitted to heat stress, formed the control group (n=14). In these groups, sperm concentration, motility and DNA fragmentation by an alkaline comet assay were analyzed. With the validation of this model, two substudies were performed, to evaluate the effect of sperm DNA fragmentation on: (1) embryos produced by in vitro fertilization and cultivated until the blastocyst stage, and (2) embryos fertilized in vivo and collected on blastocyst stage. Embryos from the Control and Heat stress groups were evaluated regarding their development, using cleavage rate, blastocyst rate, and viability rate, and lipid profile, by mass spectrometry (microQTOF-QII). Groups were compared using an unpaired Student’s t test or the Mann-Whitney test (p<0.05). Results: In the validation of the experimental model, groups did not differ regarding sperm concentration and motility. However, the Heat stress group presented an increase in sperm DNA fragmentation. In both substudies, groups did not differ regarding cleavage rate (only for substudy 1), blastocyst rate and percentage of viable cells. On the other hand, blastocysts from the Heat stress group presented a decrease in total cell count when compared to those of the Control group. In substudy 1, the Heat stress group presented an increase in the flavonoids class of lipids. In substudy 2, this group presented a decrease in the glycerolipids, fatty acids, sphingolipids, and glycerophospholipids categories. Conclusion: The proposed experimental model of sperm DNA fragmentation induction through heat stress allowed the study of the effects of sperm DNA fragmentation on embryo development. Embryos generated with sperm from mice induced to high sperm DNA fragmentation do no present alterations on their development, but present a decreased total number of cells. On the other hand, embryo lipid profile is altered due to sperm DNA fragmentation.
- ItemSomente MetadadadosEfeito do hormônio luteinizante (LH) adicionado ao estímulo ovariano no perfil lipídico do líquido folicular de mulheres em tratamento para infertilidade(Universidade Federal de São Paulo (UNIFESP), 2013-07-31) Costa, Livia do Vale Teixeira da [UNIFESP]; Fraietta, Renato Fraietta [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: Using Lipidomics approach to identify the follicular fluid lipid profile of women submitted to different ovarian stimulation protocols for in vitro fertilization treatments. Method: We conducted the study using 28 self-paired samples of follicular fluid from women who presented only tubal factor as a cause of female infertility. The patients were divided into (i) FSH group, consisting of 14 patients who received FSH hormone during controlled ovarian stimulation, and (ii) FSH + LH group, composed of the same 14 patients who have returned to the sector of Assisted Human Reproduction to receive a new stimulus, which corresponded to the addition of LH to the previous protocol. Lipidomics analysis was performed by MSE mass spectrometry. Possible lipids were identified by the software SimLipid 3.4. Results: Clinical data analysis showed that there are no statistically significant differences between groups. Lipids were identified in relation to their groups, so that in the FSH group we found wax monoesters, anthocyanidins and CoA fatty acyls, while in FSH + LH group we found sphingomyelin. Conclusion: Differences were found between the two groups concerning lipid profiles analyzed in follicular fluid. These findings contributed to deepen the understanding of the molecular mechanisms involved in the administration of different hormonal stimuli for patients undergoing treatments for infertility, and so to the establishment of the best protocol for each women considering the identification of potential biomarkers.
- ItemAcesso aberto (Open Access)Efeitos do treinamento de alta intensidade de corredores profissionais na saúde cardiovascular(Universidade Federal de São Paulo (UNIFESP), 2016-12-21) Bittencourt, Celia Regina de Oliveira [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; http://lattes.cnpq.br/2393476657163442; http://lattes.cnpq.br/2334390725647030; Universidade Federal de São Paulo (UNIFESP)Introduction: Physical activity has been universally recommended for cardiovascular disease prevention. However, the effects of intensive physical activity on cardiovascular protection are less reported. Objectives : To examine biochemical, nutritional, and ergo-respiratory parameters, and, particularly, to quantify the percentage of circulating endothelial progenitor cells (EPC) and amount of endothelial (EMP) and platelet (PMP) microparticles among professional runners. These parameters were compared with healthy non-athlete controls. Methods: Case control study includes professional runners and age and gender matched controls. Circulating EPC, EMP and PMP were quantified by flow-cytometry using specific antibodies. Lean and fat corporal mass were estimated by bioimpedance. Biochemical parameters were obtained fast after routine exercise in the day before. Results: Athletes had lower BMI, better metabolic and lipid profile (all p<0.05 vs. controls). Higher CEP (%) was observed in athletes (CD34/KDR+, p=0.038 vs. controls; CD133+/KDR+, p=0.018 vs. controls; but did not differ for CD34+/CD133+, p=0.51). Microparticles (EMP and PMP) were similar between athletes and controls. Athletes had higher mean (SE) VO2 peak group [59 (4) vs 48 (3) ml/kg.min, p<0.05). Conclusions: Intensive exercise is associated with increased circulating EPC without increase in microparticles. This favorable balance of vascular biomarkers is still associated with better anthropometric and biochemical parameters.
- ItemAcesso aberto (Open Access)Estudo da interação do poligodial em modelos de membrana de microorganismos(Universidade Federal de São Paulo, 2018-04-09) Gonçalves, Giulia Elisa Guimarães [UNIFESP]; Caseli, Luciano [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)In this study, polygodial, a natural product belonging to the group of sesquiterpenes, was isolated from hexane extract of leaves of Drimys brasiliensis (Winteraceae). Due to the promising results regarding the antiparasitic potential, we sought to study its interaction with the membrane models through Langmuir monolayers. Tensiometric, spectroscopic and morphological techniques were used to characterize the pure and mixed lipid monolayers. The lipids adopted in this study were choosen because they have different chemical natures, including: DPPC (dipalmitoylphosphatidylcholine), DMPC (dimyristoylphosphatidylcholine), DOPC (dioleoylphosphatidylcholine); DODAB (dioctadecyldimethylammonium bromide); DPPS (dipalmitoylphosphatidylserine); DPPG (dipalmitoylphosphatidylglycerol); DPPE (dipalmitoylphosphatidylalonamine) and cholesterol. The results show that the DPPG monolayer condenses in the presence of the compound, while as other monolayers expand. The presence of the polygodial is able to plot greater instability for a DPPG monolayer - recorded by adsorption kinetics curves and also by its PM-IRRAS spectrum; while, it also brings an apparent stability to the DOPC and cholesterol monolayers. Here, the behavior of some of this monolayers in presence of polygodial isomer(epi-polygodial) was also compared. Spectra in the infrared region allowed us to evaluate the factor “relative intensity”, especially in the bands related to the asymmetric and symmetrical stretches of the methylene group, which are related to a greater or less organization of the monolayer. On the other hand, images of the monolayers by Brewster angle microscopy showed the morphology of the film with the incorporation of the polygodial and epipolygodial. Particularly, there is an increase in the number of domains for DODAB in the presence of polygodial and a different behavior of DPPE monolayer for the two compounds. As conclusion, a presence of a polar head group as well as an unsaturation in the alkyl chain influenced in the intermolecular forces between the polygodial and the lipid monolayer, besides bringing characteristics of greater or lesser fluidity to the monolayer, depending on the lipid. More fluid monolayers, such as DOPC and DODAB, appeared to incorporate the compound better because of more flexible molecular rearrangement. In addition, a change in the configuration of a stereogenic carbon also seems to contribute to changes in the interactions between lipid-compound, being necessary more studies to better clarify the extensions caused by this change.
- ItemSomente Metadadados"Estudo Lipidômico De Pacientes Com Câncer Colorretal"(Universidade Federal de São Paulo (UNIFESP), 2018-08-30) Muniz, Pamela Carvalho [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background: Colorectal Cancer Is A Major Public Health Problem Worldwide. Data On A Pathogenesis And Pathophysiology Of Colorectal Carcinoma Have Been Stimulated The Development Of Testes That Are Sensitive, Specific And Reproducible To Screening, Diagnose, And Follow Up The Risk Population. Objectives And Methods: Comparing The Serum Lipid Profile Of Colorectal Cancer Patients On Pre-Operative And On Their Late Follow-Up And Identifying Lipid Biomarkers. It Was Collected Peripheral Blood From 15 Patients With Crc At The Time Of Onset And 3 Years After Treatment (Surgery, Chemo And / Or Radiotherapy). The Lipid Extraction Was Realized, And The Analysis Was Performed By Esi-Ms. After The Acquisition Of The Spectra The Analyzes Were Done Through The Software Metaboanalyst 3.0, With Evaluation Of The Main Components And Partial Least Squares Regression. The Importance Of The Variable In The Projection Was Used To Identify The Ions That Had The Greatest Discriminatory Effect Between The Groups. Results: Statistic
- ItemSomente MetadadadosEstudo lipidômico de pacientes com câncer gástrico(Universidade Federal de São Paulo (UNIFESP), 2019-07-30) Silva, Gislaine Fernandes [UNIFESP]; Forones, Nora Manoukian [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Introduction: Gastric cancer is the third cause of cancer death in the world. Early detection markedly improves the prognosis, however, the diagnosis of early stage lesions is made only in 5% of the cases. Recently, many attempts have been made to identify molecular markers that may help in the early diagnosis of this cancer. Objectives and methods: Comparing the plasma lipid profile of patients with gastric cancer to a control group without cancer and to identifying possible lipid biomarkers capable of differentiating the groups. Peripheral blood was collected from patients with gastric cancer at the time of diagnosis and from patients with no evidence of neoplasia. Lipid extraction was realized and ESI-MS analysis performed. The statistical analyzes of the obtained spectra were performed using MetaboAnalyst 3.0 software, with evaluation of the main components and discriminant analysis of least squares. The importance of the variable in the projection was used to identify the ions that presented the greatest discriminatory effect between the groups. Results: Eight lipids in the positive mode were identified as potential biomarkers, all of them hyperrepresented in the gastric cancer group. The classes of lipids found were sterol lipids, glycerolipids, sphingolipids and glycerophospholipids. To estimate the diagnostic value of the potential biomarkers, the ROC analysis was performed, showing that the sphingolipid (m / z 651.4502) could be a biomarker for the diagnosis of gastric cancer, with AUC value 0,998, sensitivity 100% and specificity 96%. In addition to this sphingolipid, all other lipids showed sensitivity and specificity above 92% and 88%, respectively. Conclusion: We identified eight potential lipid biomarkers capable of differentiating patients with gastric cancer from individuals without neoplasia, with a high sensitivity, specificity and accuracy. These results may provide important information for the development of a quick and safe examination for the diagnosis of gastric cancer.
- ItemAcesso aberto (Open Access)A Euterpe oleracea (açaí) modifica o metabolismo de esteróis e atenua a aterosclerose induzida experimentalmente(Universidade Federal de São Paulo (UNIFESP), 2011-10-26) Feio, Claudine Maria Alves [UNIFESP]; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Background: Euterpe oleracea (acai) is a fruit from the Amazon region, whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe oleracea would reduce therosclerosis development by a decrease in cholesterol absorption and synthesis. Methods: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe oleracea extract or water plus a 0.05% cholesterol-enriched diet for additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry. Results: At sacrifice, animals treated with Euterpe oleracea had lower levels of total cholesterol (p=0.03) and non-HDL-cholesterol (p=0.03) as compared to controls. These animals had smaller atherosclerotic plaque area in their aortas (p=0.001) and a smaller intima/media ratio (p=0.002) in comparison with controls. At the end of the study, campesterol, ƒÀ-sitosterol, and desmosterol plasma levels did not differ between groups. However, animals treated with Euterpe oleracea showed lower values for the desmosterol/campesterol (p=0.026) and desmosterol/ƒÀ-sitosterol (p=0.006) ratios as compared to controls. Conclusion: Consumption of Euterpe oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.
- ItemAcesso aberto (Open Access)Euterpe Oleracea (Acai) Modifies Sterol Metabolism and Attenuates Experimentally-Induced Atherosclerosis(Japan Atherosclerosis Soc, 2012-01-01) Feio, Claudine Maria Alves [UNIFESP]; Izar, Maria Cristina de Oliveira [UNIFESP]; Ihara, Silvia Saiuli Miki [UNIFESP]; Kasmas, Soraia Hani [UNIFESP]; Martins, Celma Muniz [UNIFESP]; Feio, Max N.; Maues, Luis A.; Borges, Ney C.; Moreno, Ronilson Agnaldo; Póvoa, Rui Manuel dos Santos [UNIFESP; Fonseca, Francisco Antonio Helfenstein [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Fed Univ Para; SynchropharAim: Euterpe oleracea (acai) is a fruit from the Amazon region whose chemical composition may be beneficial for individuals with atherosclerosis. We hypothesized that consumption of Euterpe oleracea would reduce atherosclerosis development by decreasing cholesterol absorption and synthesis.Methods: Male New Zealand rabbits were fed a cholesterol-enriched diet (0.5%) for 12 weeks, when they were randomized to receive Euterpe oleracea extract (n=15) or water (n=12) plus a 0.05% cholesterol-enriched diet for an additional 12 weeks. Plasma phytosterols and desmosterol were determined by ultra-performance liquid chromatography and mass spectrometry. Atherosclerotic lesions were estimated by computerized planimetry and histomorphometry.Results: At sacrifice, animals treated with Euterpe oleracea had lower levels of total cholesterol (p=0.03), non-HDL-cholesterol (p=0.03) and triglycerides (p=0.02) than controls. These animals had smaller atherosclerotic plaque area in their aortas (p=0.001) and a smaller intima/media ratio (p=0.002) than controls, without differences in plaque composition. At the end of the study, campesterol, beta-sitosterol, and desmosterol plasma levels did not differ between groups; however, animals treated with Euterpe oleracea showed lower desmosterol/campesterol (p=0.026) and desmosterol/beta-sitosterol (p=0.006) ratios than controls.Conclusions: Consumption of Euterpe oleracea extract markedly improved the lipid profile and attenuated atherosclerosis. These effects were related in part to a better balance in the synthesis and absorption of sterols.
- ItemSomente MetadadadosFollicular fluid lipid fingerprinting from women with PCOS and hyper response during IVF treatment(Springer, 2015-01-01) Cordeiro, Fernanda Bertuccez [UNIFESP]; Cataldi, Thais Regiani [UNIFESP]; Teixeira da Costa, Livia do Vale [UNIFESP]; Lima, Camila Bruna de [UNIFESP]; Stevanato, Juliana [UNIFESP]; Zylbersztejn, Daniel Suslik [UNIFESP]; Ferreira, Christina Ramires; Eberlin, Marcos Nogueira; Cedenho, Agnaldo Pereira [UNIFESP]; Lo Turco, Edson Guimaraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder that leads to lower natural reproductive potential and presents a challenge for assisted reproductive medicine because patients may exhibit immature oocyte retrieval and a higher risk of ovarian hyper stimulation syndrome during in vitro fertilization (IVF) treatment. This study aimed to identify potential lipid biomarkers for women with PCOS and a hyper response to controlled ovarian stimulation.Follicular fluid samples were collected from patients who underwent IVF, including normal responder women who became pregnant (control group, n = 11), women with PCOS and a hyper response to gonadotropins (PCOS group, n = 7) and women with only hyper response to gonadotropins (HR group, n = 7). A lipidomic analysis was performed by electrospray ionization mass spectrometry, and candidate biomarkers were analyzed by tandem mass spectrometry experiment.The lipid profiles indicated particularities related to differences in phosphatidylcholine (PCOS and HR), phosphatidylserine, phosphatydilinositol and phosphatidylglycerol (control), sphingolipids (PCOS) and phosphatidylethanolamine (control and HR).These findings contribute to the understanding of the molecular mechanisms associated with lipid metabolism in the PCOS-related hyper response, and strongly suggest that these lipids may be useful as biomarkers, leading to the development of more individualized treatment for pregnancy outcome.
- ItemSomente MetadadadosHigh-intensity statin monotherapy versus moderate-intensity statin plus ezetimibe therapy: Effects on vascular biomarkers(Elsevier B.V., 2015-02-01) Ferreira, C. E. S. [UNIFESP]; Franca, C. N. [UNIFESP]; Izar, M. C. O. [UNIFESP]; Camargo, L. M. [UNIFESP]; Roman, R. M.; Fonseca, F. A. H. [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Albert Einstein Israeli Hosp; Univ Fed Rio Grande do Sul
- ItemSomente MetadadadosHyaluronidase Alters the Lipid Profile of Cumulus Cells as Detected by MALDI-TOF MS and Multivariate Analysis(Springer, 2014-09-01) Montani, Daniela Antunes [UNIFESP]; Regiani, Thais [UNIFESP]; Victorino, Amanda Begati [UNIFESP]; Camillo, Jacqueline [UNIFESP]; Pilau, Eduardo Jorge; Gozzo, Fabio Cesar; Zylbersztejn, Daniel Suslik [UNIFESP]; Ferreira, Christina Ramires; Lo Turco, Edson Guimaraes [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade Estadual de Campinas (UNICAMP)This research aimed to study the changes in lipid composition in cumulus cells using hyaluronidase according to the intracytoplasmic sperm injection protocol commonly used in human reproduction clinics. the lipid extraction was performed by the Blight-Dyer protocol and the lipid profiles were obtained by MALDI-TOF MS in positive and negative modes. the mass spectra data were processed with MassLynx and the statistical analysis was performed using MetaboAnalyst 2.0. Fifteen ions were selected for each mode as potential markers for differences between the groups. These ions were identified in the human metabolome database as phosphatidylserine with and without treatment, phosphatidylethanolamine in the after treatment group and phosphatidylinositol in the before treatment group, which are lipids that may be involved in cell apoptosis and signaling. We concluded that MALDI-TOF MS coupled with multivariate analysis can be utilized as a strategy to obtain and study the lipid profiles of cumulus cells and as a tool to study the metabolic state of cumulus cells.
- ItemAcesso aberto (Open Access)Influência do consumo alimentar de ácidos graxos trans no perfil de lipídios séricos em nipo-brasileiros de Bauru, São Paulo, Brasil(Escola Nacional de Saúde Pública Sergio Arouca, Fundação Oswaldo Cruz, 2006-02-01) Bertolino, Carla Novaes; Castro, Teresa Gontijo; Sartorelli, Daniela Saes; Ferreira, Sandra Roberta Gouvea [UNIFESP]; Cardoso, Marly Augusto; Universidade de São Paulo (USP); Universidade Federal de São Paulo (UNIFESP)This study describes the contribution of changes in trans fatty acid intake in relation to serum lipoproteins. A total of 328 Japanese-Brazilians of the first (Issei) and second (Nisei) generations, aged 40-79 years in 1993, were assessed in two cross-sectional surveys on health and nutritional status in 1993 and 2000. Multiple linear regression models were used with changes (2000/ 1993) in serum lipoproteins as the dependent variable and changes in dietary trans fatty acids (adjusted for total calories) as independent variable. In both genders a significant reduction was observed in total intake of trans fatty acids with lower LDL and increased HDL serum levels during 7-year follow-up. The mean intakes of trans fatty acids (% of total energy) in 1993 and 2000 were: 5.1% and 3.4% for women and 4.7% and 3.3% for men, respectively. Although the association between changes in dietary trans fatty acids and serum lipoprotein was not statistically significant, on average the intake of this trans fat was higher than the WHO recommendation (up to 1% of total energy).
- ItemAcesso aberto (Open Access)Interaction of 10-(octyloxy) decyl-2-(trimethylammonium) ethyl phosphate with mimetic membranes and cytotoxic effect on leukemic cells(Elsevier B.V., 2010-09-01) Santos, G. A. dos; Thomé, Carolina Hassibe [UNIFESP]; Ferreira, Germano A; Yoneda, Juliana Sakamoto; Nobre, Thatyane Morimoto; Perez, Katia Regina [UNIFESP]; Scheucher, Priscila Santos; Gimenes-Teixeira, Hamilton Luiz; Constantino, Maurício Gomes; Oliveira, Kleber Thiago de; Faça, Vítor Marcel; Falcão, Roberto Passetto; Greene, Lewis Joel [UNIFESP]; Rego, Eduardo Magalhães; Ciancaglini, Pietro; Universidade de São Paulo (USP); Inst Nacl Ciencia & Tecnol Celulas Tronco & Terap; Universidade Federal de São Paulo (UNIFESP); Universidade Federal de São Carlos (UFSCar)10-(Octyloxy) decyl-2-(trimethylammonium) ethyl phosphate (ODPC) is an alkylphospholipid that can interact with cell membranes because of its amphiphilic character. We describe here the interaction of ODPC with liposomes and its toxicity to leukemic cells with an ED-50 of 5.4, 5.6 and 2.9 pM for 72 h of treatment for inhibition of proliferation of NB4, U937 and K562 cell lines, respectively, and lack of toxicity to normal hematopoietic progenitor cells at concentrations up to 25 pM. the ED-50 for the non-malignant HEK-293 and primary human umbilical vein endothelial cells (HUVEC) was 63.4 and 60.7 mu M, respectively. the critical micellar concentration (CMC) of ODPC was 200 mu M. Dynamic light scattering indicated that dipalmitoylphosphatidylcholine (DPPC) liposome size was affected only above the CMC of ODPC. Differential calorimetric scanning (DCS) of liposomes indicated a critical transition temperature (T(c)) of 41.5 degrees C and an enthalpy (Delta H) variation of 7.3 kcal mol(-1). the presence of 25 mu M ODPC decreased T(c) and Delta H to 393 degrees C and 4.7 kcal mol(-1), respectively. ODPC at 250 mu M destabilized the liposomes (36.3 degrees C. 0.46 kcal mol(-1)). Kinetics of 5(6)-carboxyfluorescein (CF) leakage from different liposome systems indicated that the rate and extent of CF release depended on liposome composition and ODPC concentration and that above the CMC it was instantaneous. Overall, the data indicate that ODPC acts on in vitro membrane systems and leukemia cell lines at concentrations below its CMC, suggesting that it does not act as a detergent and that this effect is dependent on membrane composition. (C) 2010 Elsevier B.V. All rights reserved.
- ItemSomente MetadadadosLipid fingerprinting in women with early-onset preeclampsia: A first look(Elsevier B.V., 2012-07-01) De Oliveira, Leandro [UNIFESP]; Camara, Niels Olsen S.; Bonetti, Tatiana [UNIFESP]; Lo Turco, Edson G. [UNIFESP]; Bertolla, Ricardo Pimenta [UNIFESP]; Moron, Antonio F. [UNIFESP]; Sass, Nelson [UNIFESP]; Cotrim Guerreiro Da Silva, Ismael Dale [UNIFESP]; Universidade Federal de São Paulo (UNIFESP); Universidade de São Paulo (USP); Hosp Maternidade Vila Nova CachoeirinhaObjectives: the aim of this preliminary study was to characterize the plasma lipid profiling of women with preeclampsia.Design and methods: Plasma samples of 8 pregnant women with early-onset preeclampsia and 8 normal pregnant women were evaluated. Lipids were extracted from plasma using the Bligh-Dyer protocol. the extracts were subjected to MALDI-MS. Data matrix was exported for partial least squares discriminant analysis (PLS-DA) and a parameter VIP was employed to reflect the variable importance in the discriminant analysis. the major discriminant variables were selected and underwent to Mann-Whitney U test.Results: A total of 1290 ions were initially identified and twelve m/z signals were highlighted as the most important lipids for the discrimination of patients with preeclampsia. the identification of these differential lipids was carried out through Lipid Database Search.Conclusions: the main classes identified were glycerophosphocholines [GP01], glycerophosphoserines [GP03], glycerophosphoglycerols [GP04], glycosyldiradylglycerols [GL05] and glycerophosphates [GP10]. (C) 2012 the Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.