Impacto da dieta cetogênica rica em MUFAS e PUFAS e suplementada com DHA sobre parâmetros oxidativos, inflamatórios e comportamentais / Impact of a ketogenic diet rich in MUFAS and PUFAS and supplemented with DHA on oxidative, inflammatory and behavioral parameters

Introdução - A dieta cetogênica (DC) tem sido utilizada como tratamento adjuvante da epilepsia fármaco resistente e tem se popularizado no manejo de outras doenças neurológicas e metabólicas (obesidade, diabetes e dislipidemias). Entretanto, também está associada a efeitos adversos que precisam ser melhor compreendidos. Objetivo - Avaliar o potencial efeito protetor de uma dieta cetogênica modificada (DCM), rica em ácidos graxos monoinsaturados (MUFAs) e ácidos graxos poli-insaturados (PUFAs), e suplementada com ácido docosahexaenóico (DHA), sobre a neuroinflamação e o estresse oxidativo e suas repercussões no comportamento de ratos. Materiais e Métodos - Estudo experimental com 18 ratos Wistar, alocados em 3 grupos de 6 animais. No grupo da dieta padrão (DP), os animais consumiram dieta comercial. No grupo da dieta cetogênica clássica (DCC), os animais consumiram uma dieta rica em gorduras saturadas. No grupo DCM, os animais consumiram dieta rica em MUFAs e PUFAs e enriquecida com DHA. Após 100 dias de intervenção foram realizados testes comportamentais e, após a eutanásia, foram feitos extratos lipídico e aquoso do lobo frontal e do hipocampo para análise de ácidos graxos e parâmetros oxidativos e inflamatórios. Resultados - Os animais DCC apresentaram um comportamento mais ansioso que ao animas DP, segundo os testes de Labirinto em Cruz Elevado e Medo ao Contexto. O grupo DCC teve mais incorporação de ácidos graxos saturados (AGs) no lobo frontal e no hipocampo em relação ao DCM. O grupo DCM teve maior incorporação de PUFAs, com destaque para o aumento de DHA no hipocampo. As citocinas inflamatórias IL1-ß e IL-6 tiveram menor concentração nos grupos DCM e DCC em relação ao grupo DP no lobo frontal, perfil semelhante ao observado com a IL-6 no hipocampo, e diferente da IL1-ß que foi reduzida significativamente apenas no DCM. Não houve diferença da concentração da Neuroprotectina D (NPD) e da enzima antioxidante Superóxido Dismutase (SOD) entre os grupos. A LDLox teve menor concentração nos grupos DCC e DCM em relação ao DP. A enzima catalase (CAT) foi menor no grupo DCM em relação ao grupo DP. Conclusão - Embora a modulação da composição de ácidos graxos da DC possa ser promissora, uma vez que a DCC induziu a um estado mais ansioso, não foi possível explicar essa diferença pelas vias inflamatória e antioxidante avaliadas.

Introduction - The ketogenic diet (KD) has been applied as an adjuvant treatment for drug-resistant epilepsy and has become popular in the management of other neurological and metabolic diseases (obesity, diabetes and dyslipidemia). However, it is also associated with adverse effects that need to be better understood. Objective - To evaluate the potential protective effect of a modified ketogenic diet (MKD), rich in monounsaturated fatty acids (MUFAs) and polyunsaturated fatty acids (PUFAs), and supplemented with docosahexaenoic acid (DHA), on neuroinflammation and oxidative stress and their repercussions on the behavior of rats. Materials and Methods - Experimental study with 18 Wistar rats, allocated into 3 groups of 6 animals. In the standard diet (SD) group, the animals consumed a commercial diet. In the classical ketogenic diet (CKD) group, the animals consumed a diet rich in saturated fats. In the MKD group, the animals consumed a diet rich in MUFAs and PUFAs and enriched with DHA. After 100 days of intervention, behavioral tests were carried out and, after euthanasia, lipid and aqueous extracts were made from the frontal lobe and hippocampus for analysis of fatty acids and oxidative and inflammatory parameters. Results - The CKD animals showed more anxious behavior than the DP animals, according to the Elevated Cross Maze and Context Fear tests. The CKD group had more incorporation of saturated fatty acids (SFAs) in the frontal lobe and hippocampus compared to MKD. The MKD group had greater incorporation of PUFAs, with emphasis on the increase in DHA in the hippocampus. The inflammatory cytokines IL1-ß and IL-6 had lower concentrations in the MKD and CKD groups compared to the PD group in the frontal lobe, a profile similar to that observed with IL-6 in the hippocampus, and different from IL1-ß, which was significantly reduced in the MKD. There was no difference in the concentration of Neuroprotectin D (NPD) and the antioxidant enzyme Superoxide Dismutase (SOD) between the groups. LDLox had a lower concentration in the CKD and MKD groups compared to the DP. The catalase enzyme was lower in the MKD group compared to the DP group. Conclusion - Although the modulation of the fatty acid composition of KD may be promising, since CKD induced a more anxious state, it was not possible to explain this difference through the inflammatory and antioxidant pathways evaluated.

Associations between plasma n-3 polyunsaturated fatty acids and gestational diabetes mellitus in the second trimester / 中华预防医学杂志

Objective: To examine the associations between plasma n-3 polyunsaturated fatty acids (PUFAs) in the second trimester and gestational diabetes mellitus (GDM) among Chinese pregnant women. Methods: Based on data from the Tongji-Shuangliu Birth Cohort enrolled from 2017 to 2019 in the Shuangliu Maternal and Child Health Hospital, it conducted a case-control study among 269 GDM cases who were diagnosed by 75 g oral glucose tolerance test, and 538 non-GDM controls matched at a 1∶2 ratio on maternal age and gestational weeks. The age range of the 807 women was 18-40 years. Fasting plasma n-3 PUFAs were determined by gas chromatography-mass spectrometry in the second trimester (24-28 weeks). Participants were categorized into quartiles (Q1-Q4) of plasma n-3 PUFAs based on distributions in the control group. Conditional logistic regression models were applied to estimate the associations between plasma n-3 PUFAs and GDM. Results: The median (interquartile) relative concentrations of plasma n-3 PUFA C22∶5n-3 was significantly lower in women with GDM 0.87 (0.72, 1.07) compared with women without GDM 0.94 (0.75, 1.19)(P=0.001). Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM, with an OR (95%CI) of 0.75 (0.62-0.90) for each SD increase of relative concentration. Compared with the Q1 group, the OR values and 95%CIs of Q2, Q3, and Q4 groups were 0.97 (0.62-1.51), 0.72 (0.45-1.15), and 0.54 (0.32-0.90), respectively (Ptrend<0.05). However, there were no significant associations of C18∶3n-3, C20∶5n-3, C22∶6n-3, and total n-3 PUFAs with GDM. Conclusion: Plasma n-3 PUFA C22∶5n-3 was inversely associated with GDM during the second trimester.

Metabolismo e importancia de los ácidos grasos poliinsaturados en la gestación y lactancia / Metabolism and importance of polyunsaturated fatty acids in pregnancy and lactation

Introducción: Los ácidos grasos polinsaturados de cadena larga son esenciales en la nutrición del feto y del recién nacido. Objetivo: Examinar la importancia de los ácidos grasos poliinsaturados durante el embarazo y la lactancia, para destacar los requerimientos, las recomendaciones y fuentes alimentarias. Métodos: Se realizó una revisión sistemática de la literatura internacional de los últimos 15 años en bases de datos, en español y en inglés. Se utilizaron las siguientes palabras clave: embarazo, lactancia, ácidos grasos poliinsaturados, omega 3/6, fuentes y requerimientos. Se identificaron los aspectos más relevantes y controversiales. Resultados: El ácido araquidónico y docosahexaenoico influyen sobre el perfil lipídico, la sensibilidad a la insulina, la proliferación y diferenciación de los preadipocitos. Sus concentraciones durante la gestación resultan uno de los principales factores responsables de la programación fetal, que son las adaptaciones metabólicas que condicionan la evolución de la salud futura. Concentraciones óptimas de ácidos grasos omega 3 y 6 son vitales para el desarrollo neurológico del feto y del recién nacido. La funcionalidad de la placenta puede afectar la adiposidad y los niveles fetales de nutrientes clave, como los ácidos grasos poliinsaturados de cadena larga. Conclusiones: La dieta es uno de los principales factores ambientales durante la gestación. La lactancia materna es la mejor alternativa nutricional durante el primer año de vida, por eso es fundamental promocionarla. Es importante ofrecer una asistencia adecuada y generar estrategias que estimulen el consumo de ácidos omega-3 como una herramienta de prevención a largo plazo(AU)

Introduction: Long-chain polyunsaturated fatty acids are essential in the nutrition of the fetus and newborns. Objective: Examine the importance of polyunsaturated fatty acids during pregnancy and lactation to highlight food requirements, recommendations and sources. Methods: A systematic review of the international literature of the last 15 years was carried out in databases, in Spanish and English, using the following keywords: pregnancy, lactation, polyunsaturated fatty acids, omega 3/6, sources and requirements. The most relevant and controversial aspects were identified. Results: Arachydonic and docosahexaenoic acid influence lipid profile, insulin sensitivity, proliferation and differentiation of preadipocytes. Their levels during gestation are one of the main factors responsible for fetal programming that are metabolic adaptations conditioning the evolution of future health. Optimal levels of omega-3 and 6 fatty acids are vital for the neurological development of the fetus and newborn. Placenta´s functionality can affect adiposity and fetal levels of key nutrients, such as long-chain polyunsaturated fatty acids. Conclusions: Diet is one of the main environmental factors during gestation. Breastfeeding is the best nutritional alternative during the first year of life, which is why it is essential to promote it. It is important to provide adequate assistance and generate strategies that stimulate the consumption of omega-3 acids as a long-term prevention tool(AU)

Chemical composition, larvicidal and cytotoxic activity of Annona salzmannii (Annonaceae) seed oil

The seed oil of Annona salzmannii A. DC. was analyzed by GC-MS and 1H qNMR, revealing a mixture of unsaturated (80.5%) and saturated (18.7%) fatty acids. Linoleic (45.3%) and oleic (33.5%) acid were the major unsaturated fatty acids identified, while palmitic acid (14.3%) was the major saturated fatty acid. The larvicidal effects of A. salzmannii seed oil were evaluated against third-instar larvae of Aedes aegypti (Linn.). The oil exhibited moderate larvicidal activity, with a LC50 of 569.77 ppm (95% CI = 408.11 to 825.88 ppm). However, when the cytotoxic effects of the oil were evaluated, no expressive antiproliferative effects were observed in tumor cell lines B16-F10 (mouse melanoma), HepG2 (human hepatocellular carcinoma), K562 (human chronic myelocytic leukemia), HL-60 (human promyelocytic leukemia), and non-tumor cell line PBMC (peripheral blood mononuclear cells), with IC50 values > 50 µg·mL-1. This is the first study to evaluate the chemical composition, larvicidal and cytotoxic activity of A. salzmannii seed oil

Oxidative stability of Echium plantagineum oil / Estabilidade Oxidativa do óleo de echium plantagineum

The evidences about the cardioprotective effects of omega-3 fatty acids (n-3 FA), especially EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid), have increased the consumption of these fatty acids. Echium plantagineum is a plant from Boragenacea family, known as potential source of non-marine omega-3 fatty acids (n-3 FA). Echium seeds presents 12-16% of stearidonic acid (SDA), that can be converted to EPA and DHA at a more elevated rate than the conversion obtained from α-linolenic acid (ALA), present in several other vegetable oils. However, echium oil is highly susceptible to oxidation because it has a high proportion of polyunsaturated fatty acids. Thus, the objective of this study was to combine three natural strategies to inhibit the oxidative damage in echium oil. In the first step, a mixture containing hydrophilic (HM: synaptic + ascorbic + citric acids) or lipophilic (LM: α-tocopherol + ascorbyl palmitate + citric acid) antioxidants was applied in the flaxseed oil, kept at 40oC/ 15 days. The oxidative markers were compared with the oil added of TBHQ (120 ppm) and EDTA (75 ppm), both artificial compounds. The results showed that LM and HM had an oxidative protection similar to the artificial antioxidants and that, HM promoted a better protection than LM. Based on this result, HM was selected as a strategy to be applied in the next step. In the second part of this study, Echium oil was obtained by two process: continuous screew pressing (PRESS) and extraction using hexane (SOLV). Both samples were added of HM combined with a high oleic sunflower oil and kept at different temperatures during storage. Two conditions were analyzed: 6 months into sealed flasks and 30 days into opened flasks. Oxidation reaction was followed by measuring the concentration of hydroperoxide, malondialdehyde, tocopherol and volatile compounds. In general, results showed that temperature reduction was enough to keep the oils stability during storage. Thus, the focus of the strategy's combination was directed toward samples after exposition to oxygen. In this context, better results were obtained by blending 20% of high oleic sunflower oil and the hydrophilic antioxidant mixture (500 ppm of synaptic acid, 250 ppm of ascorbic acid and 150 ppm of citric acid). In this condition it was observed 37-41% reduction in the hydroperoxide values and 40-75% in the malondialdehyde concentration in the samples prepared according to the optimized condition, when compared with the standard conditions by which the oil is currently extracted and processed

As evidências do efeito cardioprotetor dos ácidos graxos ômega 3 (AG n-3), principalmente do ácido eicosapentenoico (EPA) e docosahexaenoico (DHA), tem aumentado o consumo desses ácidos graxos. Echium plantagineum é uma planta da família Boragenacea, conhecida como uma fonte potencial AG n-3 de origem não marinha. As sementes de Echium apresentam 12-16% de ácido estearidônico (SDA), que pode ser convertido em EPA e DHA a uma maior taxa que a obtida através do consumo do ácido alfa linolênico (ALA), presente em diversos óleos vegetais. Porém, o óleo de echium é extremamente suscetível à oxidação, por ter um alto teor de ácidos graxos poli-insaturados. Portanto, o objetivo desse estudo foi combinar três estratégias naturais para inibir a oxidação no óleo de echium. Na primeira parte do estudo, misturas contendo antioxidantes hidrofílicos (HM: ácido sinápico + ácido ascórbico + ácido cítrico) ou lipofílicos (LM: alfa-tocoferol + palmitado de ascobila + ácido cítrico) foram aplicados no óleo de linhaça, e mantidos a 40oC por 15 dias. Os marcadores de oxidação foram comparados com óleo de linhaça no qual foram adicionados compostos artificiais: TBHQ (120 ppm) e EDTA (75 ppm). Os resultados mostraram que LM e HM apresentaram uma proteção antioxidante similar ao efeito apresentado pelos compostos artificiais, e que a mistura HM promoveu uma melhor proteção antioxidante que a mistura LM. A partir desse resultado, a mistura HM foi selecionada como estratégia a ser aplicada na etapa seguinte. Assim, na segunda parte do estudo, o óleo de echium foi obtido por dois processos de extração: prensagem mecânica continua (PRESS) e extração usando hexano (SOLV). A mistura HM e o óleo de girassol alto oleico foram selecionados como estratégias antioxidantes, além da redução de temperatura de estocagem. Duas condições foram analisadas: 6 meses em frascos fechados e 30 dias em frascos abertos. A oxidação foi quantificada através da determinação das concentrações de hidroperóxido, malonaldeído, tocoferol e compostos voláteis. No geral, os resultados mostraram que a redução de temperatura foi suficiente para manter a estabilidade do óleo durante o estoque. Portanto, objetivou-se combinar estratégias para aumentar a estabilidade oxidativa das amostras expostas ao oxigênio. Neste contexto, os melhores resultados foram obtidos quando 20% de óleo de girassol alto oleico foi combinado com a mistura hidrofílica de antioxidantes naturais (500 ppm de ácido sinápico, 250 ppm de ácido ascórbico e 150 ppm de ácido cítrico). Nessa condição, foi observada uma redução de 37-41% nos valores de hidroperóxidos e 40-75% na concentração de malonaldeído, quando comparado com a condição padrão

Effect of long-term consumption of oxidized polyunsaturated fatty acids on atherosclerotic lesion in LDL receptor knockout mice / Efeito do consumo crônico de ácidos graxos poliinsaturados oxidados na aterosclerose em camundongos knockout para receptor de LDL

Polyunsaturated fatty acids (PUFA) are susceptible to enzymatic and non-enzymatic oxidation, leading to the production of secondary compounds that present different physiological effects. Among the PUFA, the products formed from Omega 6 (n-6 FA) and Omega 3 (n-3 FA) fatty acids oxidation can modulate inflammation, dyslipidemia and oxidative stress preventing or reducing the atherosclerosis progression. In fact, the effect of chronic intake of edible oils containing products of polyunsaturated fatty acids oxidation (POPs) on atherosclerosis is still controversial. In general POPs from n-6 FA have a more pro-inflammatory profile than POPs from n-3 FA. Thus, the objective of this study was to compare the chronic intake of partially oxidized n-6 FA and n-3 FA rich oils on atherosclerosis biomarkers. Initially, six edible oils containing a higher amount of n-6 and n-3 FA were submitted to oxidative conditions, simulating the steps of transport, storage and consume. It was observed that oxidative reaction started in all oils since the first step and at the moment of consumption, some oxidative chemical markers were out the legal range suggested by the Official Agencies. In addition, it was possible to identify the type of secondary product formed from each precursor oil, providing a better information for oils quality control. After this step, fish and soybean oils were chosen as n-3 FA and n-6 FA rich oils, respectively. Using LDLr(-/-) mice, the effect of three oxidative levels of soybean oil was evaluated after 24 weeks of supplementation. Animals fed with the oil with the highest level of oxidation (fried and reused oil) showed no body weight gain, suggesting that POPs from soybean oil at this level could promote a browning effect on white adipose tissue by increasing UCP-1 expression. This group also showed the highest concentration of lipoproteins in plasma. However, these metabolic differences did not accelerate atherosclerosis in the animals. Finally, the effect of POPs from n-3 FA and n-6 FA oxidation were compared also using LDLr(-/-) mice as model for experimental atherosclerosis. Some alterations observed after n-3 FA supplementation, such as the increase of liver weight, IL-6, SONPC, 8-HETE and 15-F2-Isop and the decrease of BAT and glucose, were reversed by their POPs. In addition, POPs from n-6 FA caused increased of LDL and 5-HETE. As observed in the previous study, these metabolic alterations were not enough to prevent or accelerate atherosclerosis, as measured by histological analysis of the lesion size in the aorta. These results suggest that although a significant amount of POPs are being consumed by diet, their metabolic effects did not influence atherosclerotic plaques in the animal model. However, besides lesion area in the aortas, new studies should also evaluate the plaques stability

Os ácidos graxos poliinsaturados (PUFA) são suscetíveis à oxidação enzimática e não enzimática, levando à produção de compostos secundários que apresentam diferentes efeitos fisiológicos. Entre os PUFA, os produtos formados a partir da oxidação dos ácidos graxos ômega 6 (n-6 FA) e ômega 3 (n-3 FA) podem modular a inflamação, dislipidemia e estresse oxidativo, impedindo ou reduzindo a progressão da aterosclerose. De fato, o efeito da ingestão crônica de óleos contendo produtos da oxidação de ácidos graxos poliinsaturados (POPs) na aterosclerose ainda é controverso. Em geral, os POPs dos n-6 FA têm um perfil mais pró-inflamatório do que os POPs dos n-3 FA. Assim, o objetivo deste estudo foi comparar a ingestão crônica de POPs provenientes de óleos ricos em n-6 FA e n-3 FA em biomarcadores de aterosclerose. Inicialmente, seis óleos ricos em n-6 FA e n-3 FA foram submetidos a condições oxidativas, simulando as etapas de transporte, armazenamento e consumo. Observou-se que a reação oxidativa iniciou-se em todos os óleos desde a primeira etapa e, no momento do consumo, alguns marcadores oxidativos estavam fora da faixa legal sugerida pelas agências reguladoras. Além disso, foi possível identificar o tipo de produto secundário formado a partir de cada óleo precursor, fornecendo melhores informações para o controle de qualidade dos óleos. Após esta etapa, os óleos de peixe e soja foram escolhidos como óleos ricos em n-3 FA e n-6 FA, respectivamente. Utilizando camundongos LDLr(-/-), o efeito de três níveis oxidativos de óleo de soja foi avaliado após 24 semanas de suplementação. Os animais alimentados com o óleo com maior nível de oxidação (óleo frito e de reuso) não apresentaram ganho de peso corporal, sugerindo que os POPs do óleo de soja nesse nível de oxidação pudessem promover um efeito de Browning no tecido adiposo branco, aumentando a expressão de UCP-1. Este grupo também mostrou a maior concentração de lipoproteínas no plasma. No entanto, essas diferenças metabólicas não aceleraram a aterosclerose nos animais. Finalmente, o efeito de POPs da oxidação de óleos ricos em n-3 FA e n-6 FA foi comparado também usando camundongos LDLr(-/-), como modelo para aterosclerose experimental. Algumas alterações observadas após a suplementação com óleo de peixe fresco, como aumento do peso hepático, IL-6, SONPC, 8-HETE e 15-F2-IsoP e diminuição da BAT e glicose, foram revertidas por seus POPs. Além disso, os POPs do óleo de soja causaram aumento de LDL e 5-HETE. Como observado no estudo anterior, essas alterações metabólicas não foram suficientes para prevenir ou acelerar a aterosclerose, medida pela análise histológica do tamanho da lesão na aorta. Esses resultados sugerem que, embora uma quantidade significativa de POPs esteja sendo consumida pela dieta, seus efeitos metabólicos não influenciaram as placas ateroscleróticas no modelo animal. Porém, além da área de lesão nas aortas, novos estudos também devem avaliar a estabilidade das placas

2-Hexyl-4-Pentylenic Acid (HPTA) Stimulates the Radiotherapy-induced Abscopal Effect on Distal Tumor through Polarization of Tumor-associated Macrophages / 生物医学与环境科学（英文）

Objective@#The aim of this study was to explore the effects of 2-hexyl-4-pentylenic acid (HPTA) in combination with radiotherapy (RT) on distant unirradiated breast tumors.@*Methods@#Using a rat model of chemical carcinogen (7,12-dimethylbenz[a]anthracene,DMBA)-induced breast cancer, tumor volume was monitored and treatment response was evaluated by performing HE staining, immunohistochemistry, immunofluorescence, qRT-PCR, and western blot analyses.@*Results@#The results demonstrated that HPTA in combination with RT significantly delayed the growth of distant, unirradiated breast tumors. The mechanism of action included tumor-associated macrophage (TAM) infiltration into distant tumor tissues, M1 polarization, and inhibition of tumor angiogenesis by IFN-γ.@*Conclusion@#The results suggest that the combination of HPTA with RT has an abscopal effect on distant tumors

Research advances in the effect of long-chain polyunsaturated fatty acids on neonates / 中国当代儿科杂志

Adequate supply of long-chain polyunsaturated fatty acids (LCPUFAs) is of great importance for neonates, especially preterm infants. In particular,

The effect of n- 3 polyunsaturated fatty acid supplementation on immune and reproductive parameters in dairy cows: a review / O efeito da suplementação de ácidos graxos poliinsaturados n-3 sobre os parâmetros imunológicos e reprodutivos em vacas leiteiras: revisão de literatura

In dairy cattle, supplementation with polyunsaturated fatty acids (PUFAs) is considered to be an important tool to decrease the negative energy balance of periparturient dairy cows and improve the reproductive and immune systems. The most common PUFAs added to ruminant diets are omega 3 (n-3 PUFA) as linolenic acid and omega 6 (n-6 PUFA) as linoleic acid. This paper aims to review the potential effects of n-3 PUFA. We consider the effects of n-3 PUFA on the bovine immune system, especially on immune cells, and on in vivo and in vitro reproductive parameters, emphasizing how n-3 PUFAs act as modulators through one or more molecular mechanisms. The incorporation of n-3 PUFA in the dairy cow diet has positive effects on animal fertility and immunity. Future research on n-3 PUFA should be more explored concerning reproduction and immune function, starting from the investigation of basic biology to their potential for application in the clinical and preventive medicine fields.(AU)

Em rebanhos leiteiros, a suplementação com ácidos graxos poliinsaturados (PUFAs) é considerada uma ferramenta importante para diminuir o balanço energético negativo de vacas leiteiras durante o periparto e contribuir para a reprodução e sistema imunológico. Os efeitos da suplementação com PUFA sobre estes sistemas têm sido pouco explorados na literatura. Os PUFAs mais comuns na dieta dos ruminantes são Ômega-3 (n-3 PUFA) como ácido linolênico e Ômega-6 (n-6 PUFA) como ácido linoleico. Esta revisão abordará os aspectos gerais do n-3 PUFA, seus efeitos mais relevantes no sistema imune, principalmente seus efeitos nas células imunes, bem como seus efeitos na parte reprodutiva, tanto in vivo como in vitro, enfatizando a ação do n-3 PUFA através de mecanismos moleculares. A incorporação de n-3 PUFAs na dieta de vacas leiteiras exerce efeitos positivos na fertilidade e imunidade. Mais estudos a fim de explorar a função do n-3 PUFA na modulação do sistema imune e parâmetros reprodutivos, desde a investigação da biologia básica até a aplicação a campo de modo clínico e preventivo, devem ser requeridos.(AU)

Relative validation of a food frequency questionnaire to assess dietary fatty acid intake / Validación relativa de un cuestionario de frecuencia de alimentos para evaluar la ingesta dietaria de ácido graso

OBJECTIVES: This study aimed to develop and validate a Food Frequency Questionnaire (FFQ) for assessing consumption of fatty acids among pregnant women. METHODS: Two lists of foods were created according to percent contribution of each nutrient estimated by three 24-hour recalls: a long and short version FFQ to estimate long-chain polyunsaturated fatty acids (LCPUFAs). Student paired t-test and Pearson correlation coefficients were used to verify the differences in mean consumption of nutrients from the FFQ and 24-hour recall. The concordance between the consumption values of the two methods was assessed using the Bland-Altman method and quartiles concordance. RESULTS: For the FFQ - long version, correlation values ranged from 0.33 (<0.05) to 0.62 (<0.01) for docosahexaenoic acid (DHA) and linoleic acid (LA), respectively. Eicosapentaenoic acid (EPA) and docosapentaenoic acid (DPA) were not correlated. Exact concordance ranged from 49.0% (energy) to 22.4% (EPA), and discordance ranged from 14.3% (DPA) to 2.0% (Saturated). The FFQ - short version had high correlations for LCPUFAs. Exact concordance ranged from 36.7% (n-3 LCPUFA) to 16.3% (DHA); and discordance from 12.2% (DPA) to 2.0% (arachidonic acid). Bland-Altman analysis showed good concordance for both versions. CONCLUSION: This nutrient-specific FFQ is a valid instrument to be used to estimate the level of consumption of fatty acids among pregnant women.

OBJETIVO: Este estudio tuvo como objetivo desarrollar y validar un cuestionario de frecuencia de consumo de alimentos para evaluar el consumo de ácidos grasos en gestantes. MÉTODOS: Dos listas de alimentos fueron creadas de acuerdo con la contribución porcentual de cada nutriente estimado por 3 recordatorios de 24 horas: CFC - versión larga y CFC - versión corta para estimar ácidos grasos poliinsaturados de cadena larga (AGPICL). La prueba de t pareada de Student y el coeficiente de correlación de Pearson se utilizaron para verificar las diferencias entre el consumo medio de nutrientes de del CFC y el recordatorio de 24 horas. La concordancia entre los valores de consumo de los dos métodos se evaluó mediante el método de Bland-Altman y la concordancia de cuartiles. RESULTADOS: En CFC - versión larga, los valores de correlación oscilaron entre 0.33 (<0.05) y 0.62 (<0.01) para ácido docosahexaenoico (DHA) y ácido linoleico (LA), respectivamente. Ácido eicosapentaenoico (EPA) y ácido docosapentaenoico (DPA) no presentaron correlación. La concordancia exacta varió de 49,0% (energía) a 22,4% (EPA), y la discordancia varió de 14,3% (DPA) a 2,0% (saturado). CFC: la versión corta mostró los mejores valores de correlaciones para los AGPICL. La concordancia exacta varió de 36,7 (n-3 LCPUFA) a 16,3% (DHA); y discordancia de 12,2% (DPA) a 2,0% (ácido araquidónico). El análisis de Bland-Altman mostró una buena concordancia para ambas versiones. CONCLUSIÓN: Este método CFC específico de nutrientes es un instrumento válido que se utiliza para estimar el nivel de consumo de ácidos grasos en mujeres gestantes.

Suplementação com óleos ricos em ácidos graxos poli-insaturados na dieta de leitões na fase de creche: efeitos no desempenho, na resposta inflamatória, no perfil lipídico e no "status" oxidativo / Supplementation with oils rich in polyunsaturated fatty acids in the diet of pigs in the nursery phase: effects on performance, inflammatory response, lipid profile and oxidative "status"

Nos sistemas de produção, os produtos naturais vêm se destacando na substituição a produtos sintéticos, dentre eles podemos ressaltar os óleos vegetais ricos em ácido graxos poli-insaturados (PUFA), que são conhecidos, popularmente, por seus efeitos benéficos. Dessa forma, o objetivo com este trabalho foi avaliar os efeitos da suplementação dos óleos de pequi (Caryocar brasiliense) e girassol (Helianthus annus) sobre parâmetros fisiológicos em leitões na fase de creche. Foram utilizados 180 leitões alojados em granja comercial, distribuídos em três grupos (n=60) conforme suplementação alimentar: óleo de pequi, óleo de girassol e controle negativo. Amostras de sangue e o peso dos animais foram obtidos nos intervalos de quatro trocas de rações da fase de creche para avaliação do desempenho, da resposta inflamatória, do perfil lipídico e do "status" oxidativo. Os parâmetros fisiológicos mensurados demonstraram que os óleos interferiram positivamente na resposta inflamatória sistêmica, por meio dos leucócitos totais e da relação neutrófilo/linfócito (P<0,05); no equilíbrio oxidante-antioxidante, por mensuração de óxido nítrico e do malondialdeído (P<0,05); e no metabolismo lipídico, com a avaliação de colesterol total e triglicérides (P<0,05). Por outro lado, esses óleos vegetais interferiram no ganho de peso e no consumo de ração (P<0,05). Assim, concluí-se que a suplementação com óleos de pequi e girassol melhora a saúde dos animais, mas tem impacto negativo no desempenho zootécnico de leitões na fase de creche.(AU)

In production systems, natural products have been outstanding in replacing synthetic products, among them, we can highlight the vegetable oils rich in polyunsaturated fatty acids (PUFA) that are popularly known for their beneficial effects. Thus, the objective of this study was to evaluate the effects of pequi (Caryocar brasiliense) and sunflower (Helianthus annus) oil supplementation on nursery physiological parameters. We used 180 piglets housed in a commercial farm, distributed in 3 groups (n=60) according to food supplementation: pequi oil, sunflower oil and negative control. Blood samples and animal weight were obtained at intervals of four nursery phase rations to evaluate performance, inflammatory response, lipid profile and oxidative status. The physiological parameters measured showed that the oils positively interfered in the systemic inflammatory response through total leukocytes and neutrophil / lymphocyte ratio (P<0.05), in the oxidant-antioxidant balance by measuring nitric oxide and malondialdehyde (P<0.05). and lipid metabolism with the assessment of total cholesterol and triglycerides (P<0.05). On the other hand, these vegetable oils interfered with weight gain and feed intake (P<0.05). Thus, it can be concluded that supplementation with pequi and sunflower oils improves animal health, but has a negative impact on the piglet's performance in the nursery phase.(AU)

Proximate and Nutritional Content of Rainbow Trout (Oncorhynchus mykiss) Flesh Cultured in a Tropical Highland Area

Abstract The present study was performed to assess the proximate and nutrient content of rainbow trout flesh, cultured in the Doi Inthanon Fisheries Research Unit, Chiang Mai Inland Fisheries Research and Development Center, Thailand. 240 fish were randomly distributed across 12 cages with 20 fish cage-1. Sixteen individual fish from each cage were randomly collected at different ages of 10, 12 and 24 months. Body composition, pH, water-holding capacity, shear force, collagen content analysis, sensory, lipid oxidation, and fatty acids profile were evaluated. The results indicated that body composition and carcass length were significantly higher in fish aged 24 months, except for carcass and viscero-somatic index percentages (P ≤ 0.05). Fish at 24 months showed significantly higher pH, moisture, fat, shear force, thiobarbituric acid reactive substances, and total collagen content values than fish at 10 and 12 months (P ≤ 0.05). However, protein percentage, sensory measurement and water-holding capacity were significantly higher in younger fish at 10 and 12 months. The average lipid content and n-6/n-3 ratios were significantly greater in fish at 12 months and in ventral fillets (P ≤ 0.05). However, polyunsaturated fatty acids: saturated fatty acid ratio was higher in fish at 24 months and in dorsal fillets. In conclusion, rainbow trout cultured in sub-tropical, montane conditions can be valuable sources of protein, unsaturated fatty acids, eicosapentaenoic acids, and docosahexaenoic acids.

The benefits of omega-3 fatty acid nanocapsulation for the enrichment of food products: a review / Os benefícios da nanoencapsulação de ácidos graxos da classe ômega-3 para o enriquecimento de produtos alimentícios: uma revisão

ABSTRACT Polyunsaturated fatty acids oxidize easily due to their chemical structure, causing a reduction of their nutritional properties. Nanostructured systems may be an alternative to protect fatty acids against oxidation, improving solubility and stability. Consequently, nutritional value of food is maintained as well as the sensory characteristics (color, flavor, texture, and aroma) when fatty acids are added to food products. The present study is a narrative review to introduce the potential benefits of omega-3 unsaturated fatty acids nanoparticles incorporated in food products. The literature review includes publications in English and Portuguese issued between March 1985 and March 2019, in PubMed, ScienceDirect and Web of Science databases. Manual searches were conducted in the articles references lists of the articles included to identify other relevant studies. There were studies that evaluated the stability of fatty acids in food products such as bread, fruit juice, milk, yogurt, and meat. In this study, the most used nanostructured systems for the incorporation of fatty acids were the nanocapsules and the nanoliposomes. Currently, the nanostructured system demonstrates a potential to improve protection of polyunsaturated fatty acids against oxidization and thermal degradation. In this way, they maintain their functional properties and their bioavailability increases and therapeutic efficacy and sensory properties are improved. There are several methodologies being tested, which makes it difficult to identify the most efficient formulation to protect fatty acids. Nanostructured systems seem to be the best alternative to protect polyunsatured fatty acids from oxidization. The encapsulation efficiency, particle's size and type are relevant factors to be considered to evaluate oxidization. In conclusion, the review showed that currently it is impossible to determine the most efficient methodology. Besides, nanoformulations should follow international guidelines to present more standardized and therefore more efficient particles.

RESUMO Os ácidos graxos poli-insaturados são facilmente oxidados devido à sua estrutura química, o que acarreta a diminuição de suas propriedades nutricionais. Nesse contexto, o sistema nanoestruturado pode ser uma alternativa para protegê-los contra a oxidação, melhorando a solubilidade e estabilidade. Consequentemente, quando são adicionados a produtos alimentares, o valor nutricional é mantido, bem como as características sensoriais (cor, sabor, textura e aroma). O presente estudo é uma revisão narrativa para apresentar os potenciais benefícios das nanopartículas com ácidos graxos insaturados da classe ômega-3 incorporados a produtos alimentícios. A literatura consultada incluiu publicações em inglês e em português, considerando o período entre março de 1985 e março de 2019, utilizando as bases de dados PubMed, ScienceDirect e Web of Science. Foram realizadas buscas manuais nas referências dos artigos incluídos, a fim de identificar outros estudos relevantes. Foram encontradas pesquisas que avaliaram a estabilidade dos ácidos graxos em produtos alimentícios, como pães, suco de fruta, leite, iogurte e carne. Neste estudo, as nanoestruturas mais utilizadas para a incorporação dos ácidos graxos foram as nanocápsulas e os nanolipossomas. Atualmente, o sistema nanoestruturado demonstra um potencial para melhorar a proteção desses ácidos poli-insaturados contra a oxidação e degradação térmica. Dessa forma, eles mantêm suas propriedades funcionais, aumenta-se sua biodisponibilidade e há melhora da eficácia terapêutica e das propriedades sensoriais. Existem diversas metodologias sendo testadas, o que dificulta a identificação de qual seria a formulação mais eficiente nessa proteção, mas os sistemas nanoestruturados parecem ser a melhor alternativa para proteger os ácidos graxos insaturados da oxidação. A eficiência de encapsulação bem como o tamanho e o tipo de partícula são fatores importantes a considerar na avaliação da oxidação. Em conclusão, a revisão demonstrou que atualmente a metodologia mais eficiente não é possível de ser identificada. Ademais, as nanoformulações devem seguir diretrizes do protocolo internacional para apresentar partículas mais padronizadas e, assim, eficientes.

Pumpkin seeds (Cucurbita maxima): a review of functional attributes and by-products / Semillas de calabaza (Cucurbita máxima): una revisión de sus propiedades funcionales y sub-productos

ABSTRACT The need to obtain nutritious foods from new sources and lower waste in industry has created a high interest in studying different parts of plants or foods that today are considered waste, but could be considered by-products with high nutritional value with potential use in human diets. Pumpkin seeds are commonly considered as waste but they have a high content of fatty and amino acids, which when used as a by-product or ingredient can add value to food products. The aim of this work was to perform a wide review of the nutritional and functional properties of Cucurbita maxima seeds and their potential medicinal influence.

RESUMEN La necesidad de obtener alimentos nutritivos de nuevas fuentes y menores desperdicios en la industria ha generado un gran interés en el estudio de diferentes partes de plantas o alimentos que hoy en día se consideran desechos, pero que podrían considerarse subproductos con alto valor nutricional y uso potencial en alimentación humana. Las semillas de calabaza se consideran comúnmente como desechos, pero tienen un alto e importante contenido de ácidos grasos y aminoácidos, que cuando se utilizan como subproducto o ingrediente pueden aportar un alto valor agregado a los productos alimenticios. El objetivo de este trabajo es realizar una amplia revisión de las propiedades nutricionales y funcionales de las semillas de Cucurbita maxima y su potencial influencia medicinal asociada a ellas.

Efeito da suplementação de ômega 3 isolado ou associado em pacientes com doença de Alzheimer: uma revisão sistemática da literatura científica / Effect of omega 3 supplementation alone or associated in patients with Alzheimer's disease: a systematic literature review

Introdução: O envelhecimento da população está associado ao aumento da incidência da doença de Alzheimer (DA), a qual causa graves complicações ao paciente. Os nutrientes imunomoduladores, como os ácidos graxos poli-insaturados (PUFAs) da série ômega 3 (w-3) podem auxiliar na melhora do quadro clínico da DA. Objetivo: Analisar o efeito da suplementação de PUFAs w-3 isolado ou associado na população idosa com DA. Material e Métodos: Trata-se de uma revisão sistemática de literatura científica nas bases de dados Pubmed e Science Direct, que englobou ensaios clínicos em idosos com provável e/ou comprovado diagnóstico de DA e suplementados com PUFAS w-3 isolado ou associado, no idioma inglês e com os seguintes descritores em saúde (DECs): brain, Alzheimer's disease, fatty docosahexaenoic acid(DHA), polyunsaturated fatty acids (PUFA), older and elderly people e termo de pesquisa: eicosapentaenoic acid (EPA). O recorte temporal das publicações foi delimitado de 2006 a 2017. Resultados: foram selecionados 10 ensaios clínicos, cuja suplementação de w-3 favoreceu menor declínio no score de miniexame de estado mental (MEEM), retardo da disfunção, melhora no domínio de agitação do inventário neuropsiquiátrico (NPI) e melhora dos sintomas depressivos pela Escala de Depressão de Montgomery-Asberg (MADRS). Foram observadas mudanças significativas como aumento de apetite, peso, índice de massa corporal (IMC), EPA e DHA, além de reduções nos níveis séricos de albumina, ácido araquidônico (AA), ácido mirístico, interleucina-6 (IL- 6), interleucina 1 ß (IL-1ß) e fator estimulante de colônias de granulócitos (G-CSF) e redução na liberação de prostaglandina F2α (PGF2α). Foram relatadas alterações positivas em alguns genes e em outros, redução de sua expressão, além de hipometilação de importantes genes. Conclusão: A suplementação de PUFAs w-3 exerceu efeito positivo em pacientes com DA grau leve a moderado.

Introduction: Aging of the population is associated with an increased incidence of Alzheimer's disease (AD), which causes severe complications to the patient. Immunomodulatory nutrients such as polyunsaturated fatty acids (PUFAs) of the omega-3 (w-3) series may help improve the clinical picture of AD. Objective: To analyze the effect of supplementation of isolated or associated w-3 PUFAs in patients with AD. Material and Methods: This is a systematic review of the scientific literature in the Pubmed and Science Direct databases, which included clinical trials in elderly people with probable and / or proven diagnosis of AD supplemented with isolated or associated PUFAS w-3, in English and with the following health descriptors (DECs): brain, Alzheimer's disease, fatty docosahexaenoic acid (DHA), polyunsaturated fatty acids (PUFA), older and elderly people and search term: eicosapentaenoic acid (EPA).The time cut of publications was delimited from 2006 to 2017. Results: a total of 10 clinical trials were selected, whose w-3 supplementation favored a smaller decline in the Mini Mental Status Examination (MMSE) score, delayed dysfunction, improved neuropsychiatric inventory (NPI) agitation, and improved depressive symptoms by the Montgomery-Asberg Depression Scale (MADRS). Significant changes were observed as increased appetite, weight, body mass index (BMI), EPA and DHA, as well as reductions in serum albumin levels, arachidonic acid (AA), myristic acid, interleukin-6 (IL-6), interleukin 1ß (IL-1ß), and granulocyte colony stimulating factor (G-CSF) and reduced clearance of prostaglandin F2α (PGF2α). Positive alterations have been reported in some genes and in others, reduction of their expression, besides hypomethylation of important genes. Conclusion: Supplementation of PUFAs w-3 had a positive effect in patients with mild to moderate AD.

Therapeutic potential of omega fatty acids in breast cancer. Review / Potencial terapéutico de ácidos grasos omega en cáncer de mama. Revisión

Background: Breast cancer is the second cause of death in women in developed and undeveloped countries, including Colombia. A high percentage of these tumors is estrogen dependent, for which the hormonal treatment is the most used therapy in breast cancer. Currently, the first line treatment for breast tumor in postmenopausal women is the letrozole, an aromatase enzyme inhibitor that avoids the transformation of androgens to estrogens. Since letrozole produced adverse effects on patients, there is a requirement for new alternative treatments. Furthermore, omega fatty acids (ω-FA), essential as they are obtained from the normal diet or from dietary supplements, have demonstrated nutraceutical potential because of their anti-inflammatory or pro-inflammatory activity. Nonetheless, there is controversy in in vitro, in vivo and epidemiologic reports regarding their preventive or inducing activities of carcinogenesis in animals and humans, depending on the structure of the ω-FA. Objectives: This review aims to show the main in vitro, in vivo and epidemiologic evidences of the chemotherapeutic potential of ω-3 and ω-6 FA in different types of neoplasm, particularly in breast cancer, in individual or combined treatments with diverse antineoplastics. Methods: PubMed and Science Direct databases revealed the most representative studies, published during the last two decades, about ω-3 and ω-6 FA, breast cancer and the principal therapeutic strategies for this neoplasm. Findings were presented in separated topics to provide an overview of ω-FA and their potential in treatments for breast cancer. Results: Patients treated with estrogens and progesterone derivate have shown predisposition to develop breast cancer after two years of continued therapy. Furthermore, ω-FA with known nutraceutical potential have demonstrated their potential as adjuvants in the treatment against different neoplasms, like hepatic and colon cancer. Conclusions: Current therapies for breast cancer and their low efficacy in the long term led to explore new alternative treatments with ω-FA. These essential fatty acids in daily consumption could enhance the antineoplastic agent effect. Nevertheless, metabolism of the ω-FA must be considered for this use.

Antecedentes: el cáncer de mama es la segunda causa de muerte de mujeres en países desarrollados y no desarrollados, incluido Colombia. La mayoría de estos tumores son dependientes de estrógeno por esa razón, la terapia más utilizada es la hormonal. Actualmente, el tratamiento de primera línea en mujeres posmenopáusicas es el letrozol, inhibidor de la enzima aromatasa, que evita la conversión de andrógenos en estrógenos. El letrozol causa efectos adversos en las pacientes, lo cual motiva la búsqueda de nuevas alternativas que disminuyan estos efectos. Los ácidos grasos omega, esenciales en la dieta regular o suplementaria, han mostrado su potencial nutracéutico ambivalente, como antiinflamatorios o proinflamatorios. Debido a esto, existe controversia en distintos reportes a nivel in vitro, in vivo y epidemiológicos sobre la actividad preventiva o quimioterapéutica de los ω-3 y ω-6 AGOs. Objetivos: el aporte de este artículo, es mostrar las principales evidencias in vitro, in vivo y epidemiológicas del potencial quimioterapéutico de los AGOs en tratamientos individuales y combinados con antineoplásicos, en distintos tipos de cánceres, particularmente en el cáncer de mama. Métodos: se revisaron las bases de datos PubMed y Science Direct y se seleccionaron los estudios más representativos de las dos últimas décadas sobre ω-3 y ω-6 AGOs y las principales estrategias usadas en el cáncer de mama. Los hallazgos se presentan en temas separados, primero una visión general de los AGOs y luego su potencial bioactivo en tratamientos contra el cáncer de mama. Resultados: la mayoría de los estudios en pacientes con cáncer de mama, tratadas con estrógenos y derivados de progesterona, han mostrado predisposición a desarrollar cáncer de mama después de dos años de terapia continua. De otro lado, los AGOs han demostrado su potencial como adyuvantes en el tratamiento en diferentes cánceres como el de colon y hepático. Conclusiones: las terapias actuales para el cáncer de mama y su baja eficacia a largo plazo exigen explorar nuevas alternativas de terapias, que incluyen los AGOs podrían potenciar fármacos, no obstante, es necesario tener en cuenta, el metabolismo de los AGOs, para uso

Effect of Eicosapentaenoic Acid Supplementation on Paraoxonase 2 Gene Expression in Patients with Type 2 Diabetes Mellitus: a Randomized Double-blind Clinical Trial

Type 2 diabetes mellitus (T2DM) is recognized as one of the most prevalent metabolic diseases, and it is mostly associated with oxidative stress, atherosclerosis and dyslipidemia. Paraoxonase 2 (PON2) due to its antioxidant properties may play a role in the atherosclerosis development. Although long-chain omega-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA) have been shown to reduce the risk of cardiovascular disease, the exact mechanism of action is still unknown. Our goal in this study was to determine the effect of EPA administration on gene expression of PON2 in patients with T2DM. Present study was a randomized, controlled double-blind trial. Thirty-six patients with T2DM were randomly allocated to receive 2 g/day EPA (n = 18) or placebo (n = 18) for 8 weeks. There were no significant differences between 2 groups concerning demographic or biochemical variables, and dietary intakes as well (p > 0.05). However, patients received EPA showed a significant increase in the gene expression of PON2 compared with placebo group (p = 0.027). In addition, high-density lipoprotein cholesterol increased and fasting blood sugar decreased significantly after EPA supplementation compared with control group. Taken together, supplementation with 2 g/day EPA could be atheroprotective via the upregulation of PON2 in patients with T2DM. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03258840

Rasfonin inhibits proliferation and migration of osteosarcoma 143B cells / 北京大学学报(医学版)

OBJECTIVE@#To investigate the effects of rasfonin, a fungal secondary metabolite, on the proliferation and migration of osteosarcoma 143B cells.@*METHODS@#3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt (MTS) assay was performed to examine 143B cell viability following treatment of rasfonin. Using dimethyl sulfoxide (DMSO) group as control, cell viability was detected when 143B cells were treated with rasfonin (3 μmol/L and 6 μmol/L) for 12 or 24 hours. The effect of rasfonin on colony forming ability was detected by clone formation assay. 143B cells treated with DMSO or rasfonin (3 μmol/L) for one week, and the number of clones formed in the two groups was counted. Wound healing and transwell assay were employed to analyze cell invasion and migration upon rasfonin challenge. The DMSO group was used as control while rasfonin (3 μmol/L) was used for 24 hours. The wound healing rate and the number of invasive cells were compared between the two groups. The intracellular autophagosomes were monitored by transmission electron microscopy when 143B cells were treated with DMSO or rasfonin (3 μmol/L) for 4 hours. The expression of p62, microtubule-associated protein 1 light chain 3 fusion protein (LC3) and poly (ADP-ribose) polymerase-1 (PARP-1) in response to rasfonin were detected by immunoblotting assay.@*RESULTS@#Rasfonin reduced the viability of 143B cells in a dose-dependent manner (12 h: F=31.36, P<0.01; 24 h: F=67.07, P<0.01). Rasfonin (3 μmol/L) completely inhibited the clonal formation of 143B cells (P<0.01). The wound healing result revealed that rasfonin significantly decreased migratory ability of 143B cells (33.91%±0.83% vs. 65.11%±0.94%, P<0.01), whereas its treatment significantly reduced the number of 143B cells penetrating through Matrigel-containing basement membrane (21.33±1.45 vs. 49.33±2.40, P<0.01). Compared with the control group, rasfonin markedly increased the number of autophagic vacuoles. The immunoblotting results revealed that rasfonin increased LC3-II accumulation and decreased p62 levels. Choloroquine (CQ), an often used autophagic inhibitor, further accumulated rasfonin-induced LC3-II. In addition, rasfonin appeared to cause the cleavage of PARP-1.@*CONCLUSION@#Rasfonin induced autophagy and activated caspase-dependent apoptosis in 143B cells concurring with suppressing the proliferation and migration of the cells; these results provide an experimental basis for rasfonin as a potential therapeutic agent for osteosarcoma.

Dietary intake of n-3 and n-6 polyunsaturated fatty acids in Korean toddlers 12–24 months of age with comparison to the dietary recommendations

BACKGROUND/OBJECTIVES: Adequate dietary fatty acid intake is important for toddlers between 12–24 months of age, as this is a period of dietary transition in conjunction with rapid growth and development; however, actual fatty acid intake during this period seldom has been explored. This study was conducted to assess the intake status of n-3 and n-6 polyunsaturated fatty acids by toddlers during the 12–24-month period using 2010–2015 Korea National Health and Nutrition Examination Survey data. SUBJECTS/METHODS: Twenty-four-hour dietary recall data of 12–24-month-old toddlers (n = 544) was used to estimate the intakes of α-linolenic acid (ALA; 18:3n-3), eicosapentaenoic acid (EPA; 20:5n-3), docosahexaenoic acid (DHA; 22:6n-3), linoleic acid (LA; 18:2n-6), and arachidonic acid (AA; 20:4n-6), as well as the major dietary sources of each. The results were compared with the expected intake for exclusively breastfed infants in the first 6 months of life and available dietary recommendations. RESULTS: Mean daily intakes of ALA, EPA, DHA, LA, and AA were 529.9, 22.4, 37.0, 3907.6, and 20.0 mg/day, respectively. Dietary intakes of these fatty acids fell below the expected intake for 0–5-month-old exclusively breastfed infants. In particular, DHA and AA intakes were 4 to 5 times lower. The dietary assessment indicated that the mean intake of essential fatty acids ALA and LA was below the European and the FAO/WHO dietary recommendations, particularly for DHA, which was approximately 30% and 14–16% lower, respectively. The key sources of the essential fatty acids, DHA, and AA were soy (28.2%), fish (97.3%), and animals (53.7%), respectively. CONCLUSIONS: Considering the prevailing view of DHA and AA requirements on early brain development, there remains considerable room for improvement in their intakes in the diets of Korean toddlers. Further studies are warranted to explore how increasing dietary intakes of DHA and AA could benefit brain development during infancy and early childhood.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy / 대한소아소화기영양학회지

PURPOSE: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. METHODS: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. RESULTS: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p < 0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p < 0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p < 0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p < 0.05, r=0.381). CONCLUSION: Calcium supplementation may improve neurocognitive development in malnourished infants.