Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 8.615
Filtrar
1.
Anticancer Res ; 40(4): 1833-1841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32234871

RESUMO

BACKGROUND/AIM: Time-restricted feeding (TRF) during the dark phase of the day restores metabolic homeostasis in mice. MATERIALS AND METHODS: We performed untargeted metabolomic analysis on plasma from mice subjected to TRF that attenuates high-fat diet-enhanced spontaneous metastasis of Lewis lung carcinoma (LLC). RESULTS: Twenty-four of 152 identified metabolites differed among the four dietary groups (non-LLC-bearing mice fed the AIN93G diet and LLC-bearing mice fed the AIN93G, the high-fat diet (HFD), or TRF of the HFD). Component 1 of sparse partial least squares-discriminant analysis showed a clear separation between non-LLC-bearing and LLC-bearing mice. Major metabolites responsible for the changes were elevations in α-tocopherol, docosahexaenoic acid, cholesterol, dihydrocholestrol, isoleucine, leucine, and phenylalanine and decreases in lactic acid and pyruvic acid in LLC-bearing mice particularly those fed the HFD. Time-restricted feeding shifted the metabolic profile of LLC-bearing mice towards that of non-LLC-bearing controls. CONCLUSION: Time-restricted feeding improves metabolic profile of LLC-bearing mice.


Assuntos
Carcinoma Pulmonar de Lewis/sangue , Jejum/sangue , Metabolômica , Animais , Carcinoma Pulmonar de Lewis/dietoterapia , Colestanol/sangue , Colesterol/sangue , Dieta Hiperlipídica/efeitos adversos , Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/sangue , Jejum/fisiologia , Humanos , Insulina/sangue , Isoleucina/sangue , Ácido Láctico/sangue , Leucina/sangue , Camundongos , Metástase Neoplásica , Fenilalanina/sangue , Ácido Pirúvico/sangue , alfa-Tocoferol/sangue
3.
Mol Pharmacol ; 97(5): 304-313, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132133

RESUMO

Free-fatty acid receptor-4 (FFA4), previously termed GPR120, is a G protein-coupled receptor (GPCR) for medium and long-chained fatty acids, agonism of which can regulate a myriad of metabolic, sensory, inflammatory, and proliferatory signals. Two alternative splice isoforms of FFA4 exist that differ by the presence of an additional 16 amino acids in the longer (FFA4-L) transcript, which has been suggested to be an intrinsically ß-arrestin-biased GPCR. Although the shorter isoform (FFA4-S) has been studied more extensively, very little is known about mechanisms of regulation or signaling of the longer isoform. Because ß-arrestin recruitment is dependent on receptor phosphorylation, in the current study, we used the endogenous agonist docosahexaenoic acid (DHA) to examine the mechanisms of FFA4-L phosphorylation, as well as DHA-dependent ß-arrestin recruitment and DHA-dependent extracellular-signal regulated kinase-1/2 (ERK1/2) signaling in human embryonic kidney 293 cells. Our results reveal differences in basal phosphorylation of the two FFA4 isoforms, and we show that DHA-mediated phosphorylation of FFA4-L is primarily regulated by G protein-coupled receptor kinase 6, whereas protein kinase-C can also contribute to agonist-induced and heterologous phosphorylation. Moreover, our data demonstrate that FFA4-L phosphorylation occurs on the distal C terminus and is directly responsible for recruitment and interactions with ß-arrestin-2. Finally, using CRISPR/Cas9 genome-edited cells, our data reveal that unlike FFA4-S, the longer isoform is unable to facilitate phosphorylation of ERK1/2 in cells that are devoid of ß-arrestin-1/2. Together, these results are the first to demonstrate phosphoregulation of FFA4-L as well as the effects of loss of phosphorylation sites on ß-arrestin recruitment and ERK1/2 activation. SIGNIFICANCE STATEMENT: Free-fatty acid receptor-4 (FFA4) is a cell-surface G protein-coupled receptor for medium and long-chained fatty acids that can be expressed as distinct short (FFA4-S) or long (FFA4-L) isoforms. Although much is known about FFA4-S, the longer isoform remains virtually unstudied. Here, we reveal the mechanisms of docosahexaenoic acid-induced phosphorylation of FFA4-L and subsequent ß-arrestin-2 recruitment and extracellular-signal regulated kinase-1/2 activity.


Assuntos
Processamento Alternativo , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Sistema de Sinalização das MAP Quinases , Receptores Acoplados a Proteínas-G/química , Receptores Acoplados a Proteínas-G/metabolismo , beta-Arrestina 2/metabolismo , Processamento Alternativo/efeitos dos fármacos , Sequência de Aminoácidos , Ácidos Docosa-Hexaenoicos/farmacologia , Quinases de Receptores Acoplados a Proteína G/metabolismo , Subunidades alfa Gq-G11 de Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação/efeitos dos fármacos , Isoformas de Proteínas/química , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Proteína Quinase C/metabolismo , Receptores Acoplados a Proteínas-G/genética , Transdução de Sinais/efeitos dos fármacos
4.
Sci Total Environ ; 710: 136448, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32050374

RESUMO

Docosahexaenoic acid plays a vital role in human health as it is essential for the proper function of the nervous system and for visual functions. To decrease the cost of docosahexaenoic acid production by Schizochytrium, the cost of the medium should be further decreased. In this study, the use of tofu whey wastewater to culture Schizochytrium sp. for docosahexaenoic acid production was tested, with the goal of reducing the medium cost. The results indicated that tofu whey wastewater presented a better culture performance with respect to biomass, lipid, and docosahexaenoic acid production compared with three traditional media. Through simple pH adjustment, the biomass and docosahexaenoic acid productivity reached 1.89 and 0.24 g/L/day, respectively, which were much higher than those obtained using traditional medium. The removal efficiency of chemical oxygen demand, total nitrogen, and total phosphorus reached 64.7, 66.0, and 59.3%, respectively. Due to the rich nutrients in tofu whey wastewater, the use of extra nitrogen source was avoided and the total medium cost for docosahexaenoic acid production in cultures using tofu whey wastewater was <1/3 of that of traditional media. This result indicated that tofu whey wastewater is an effective and economic basal medium for docosahexaenoic acid production by Schizochytrium sp.


Assuntos
Alimentos de Soja , Soro do Leite , Biomassa , Ácidos Docosa-Hexaenoicos , Fermentação , Nutrientes , Águas Residuárias
5.
Bioresour Technol ; 303: 122899, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32028216

RESUMO

Omega-3 fatty acids have become a commodity of high nutritional and commercial value; intensive fishing and its environmental and social cost has led researchers to seeking alternative more sustainable ways of producing them. Heterotrophic microalgae such as Crypthecodinium cohnii, a marine dinoflagellate, have the ability to utilize various substrates and accumulate high amounts of docosahexaenoic acid (DHA). In this work, a mild oxidative organosolv pretreatment of beechwood pulps was employed that allowed up to 95% of lignin removal in a single stage, thus yielding a cellulose-rich solid fraction. The enzymatic hydrolysates were evaluated for their ability to support the growth and lipid accumulation of C. cohnii in batch and fed-batch cultures; the results verified the successful microalgae growth, while DHA reached up to 43.5% of the cell's total lipids. The proposed bioprocess demonstrated the utilization of non-edible biomass towards high added value food supplements in a sustainable and efficient manner.


Assuntos
Dinoflagelados , Ácidos Graxos Ômega-3 , Microalgas , Biomassa , Ácidos Docosa-Hexaenoicos , Ácidos Graxos , Lignina
6.
PLoS One ; 15(2): e0229435, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32107491

RESUMO

A collection of evidence suggests that conjugation of double bonds of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids, omega-3 polyunsaturated fatty acids (n-3 PUFAs), increases their anticarcinogenic activity; however, the effect of such conjugation on vascular tone activity remains unknown. We propose that the mixture of conjugated PUFAs exerts higher vasorelaxation activity than the corresponding mixture of nonconjugated PUFAs. The vascular response to different concentrations of conjugated and nonconjugated isomers of EPA and DHA, among other fatty acids (FAs) naturally present in shark oil, and the role of nitric oxide (NO) as a vasorelaxant agent were investigated. Both conjugated EPA (CEPA) and conjugated DHA (CDHA) were prepared by alkaline isomerization of all PUFAs contained in shark oil. Different concentrations of conjugated and nonconjugated PUFAs were placed in contact with precontracted aortic rings of Wistar rats to assess their effect on vascular tone. All tested samples exerted a vasorelaxant effect. Compared to nonconjugated PUFAs, conjugated isomers exhibited an increase in the dilatation of the aortic rings (P<0.001) in a dose-dependent manner (P<0.001). In addition, nonconjugated PUFAs produced nitric oxide (NO) in a dose-dependent manner, while conjugated PUFAs did not, suggesting that their dilatation mechanism is not totally dependent on NO.


Assuntos
Aorta Torácica/fisiologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Óleos de Peixe/farmacologia , Óxido Nítrico/metabolismo , Vasodilatação/fisiologia , Animais , Aorta Torácica/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/química , Ácido Eicosapentaenoico/química , Endotélio Vascular/efeitos dos fármacos , Endotélio Vascular/fisiologia , Ácidos Graxos/metabolismo , Óleos de Peixe/química , Isomerismo , Masculino , Ratos , Ratos Wistar , Tubarões , Vasodilatação/efeitos dos fármacos
7.
Food Chem ; 313: 126139, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-31927203

RESUMO

Based on various antioxidant mechanisms, four kinds of antioxidants including ascorbyl palmitate (AP), vitamin E (VE), phytic acid (PA) and one of the polyphenols (antioxidant of bamboo leaves, tea polyphenol palmitate or tea polyphenols (TP)) were used in combination to improve oxidative stability of docosahexaenoic acid (DHA) algae oil. To achieve the best effect, the formulations and mixture ratios of the antioxidant combinations were optimized. The effects were monitored by peroxide value, thiobarbituric acid-reactive substances, acid value, free radicals, Rancimat induction time and fatty acid composition of DHA algae oil undergoing accelerated storage. Finally, the DHA algae oil containing 80 mg/kg AP, 80 mg/kg VE, 40 mg/kg PA and 80 mg/kg TP had the highest oxidative stability. Furthermore, the shelf life of DHA algae oil containing the optimum composite antioxidant was predicted by using accelerated shelf life testing coupled with Arrhenius model, which was 3.80-fold longer than the control sample.


Assuntos
Antioxidantes/química , Ácidos Docosa-Hexaenoicos/química , Óleos/química , Ácido Ascórbico/análogos & derivados , Ácido Ascórbico/química , Armazenamento de Alimentos , Oxirredução , Folhas de Planta/química , Polifenóis/química , Sasa/química , Chá/química , Substâncias Reativas com Ácido Tiobarbitúrico/química , Vitamina E/química
8.
Biosci Biotechnol Biochem ; 84(4): 743-756, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31889475

RESUMO

The current study aimed to investigate the antitumor and antiangiogenesis effects of apatinib in triple-negative breast cancer in vitro and also whether the combination of docosahexaenoic acid (DHA) and apatinib is more effective than apatinib monotherapy. The cell counting kit-8 assay was used to measure cell proliferation. Flow cytometry was utilized to determine the cell apoptosis rate. A wound healing assay was utilized to assess cell migration. Western blot analysis was carried out to determine the effects of apatinib and DHA on Bcl-2, BAX, cleaved caspase-3, caspase-3, phosphorylated protein kinase B (p-Akt), and Akt expression. DHA in combination with apatinib showed enhanced inhibitory effects on cell proliferation and migration compared with apatinib or DHA monotherapy. Meanwhile, DHA combined with apatinib strongly increased the cell apoptosis percentage. DHA was observed to enhance the antitumor and antiangiogenesis effects of apatinib via further downregulation of p-Akt expression.Abbreviations: FITC: fluorescein isothiocyanate; PI: propidium iodide.


Assuntos
Antineoplásicos/uso terapêutico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Piridinas/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antineoplásicos/administração & dosagem , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ácidos Docosa-Hexaenoicos/administração & dosagem , Ácidos Docosa-Hexaenoicos/farmacologia , Sinergismo Farmacológico , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Piridinas/administração & dosagem , Piridinas/farmacologia , Neoplasias de Mama Triplo Negativas/patologia
9.
Appl Biochem Biotechnol ; 190(1): 218-231, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31332676

RESUMO

Yeast surface display has emerged as a viable approach for self-immobilization enzyme as whole-cell catalysts. Herein, we displayed Candida rugosa lipase 1 (CRL LIP1) on the cell wall of Pichia pastoris for docosahexaenoic acid (DHA) enrichment in algae oil. After a 96-h culture, the displayed CRL LIP1 achieved the highest activity (380 ± 2.8 U/g) for hydrolyzing olive oil under optimal pH (7.5) and temperature (45 °C) conditions. Additionally, we improved the thermal stability of displayed LIP1, enabling retention of 50% of its initial bioactivity following 6 h of incubation at 45 °C. Furthermore, the content of DHA enhanced from 40.61% in original algae oil to 50.44% in glyceride, resulting in a 1.24-fold increase in yield. The displayed CRL LIP1 exhibited an improved thermal stability and a high degree of bioactivity toward its native macromolecule substrates algae oil and olive oil, thereby expanding its potential for industrial applications in fields of food and pharmaceutical. These results suggested that surface display provides an effective strategy for simultaneous convenient expression and target protein immobilization.


Assuntos
Proteínas de Bactérias/metabolismo , Candida/enzimologia , Ácidos Docosa-Hexaenoicos/metabolismo , Temperatura Alta , Lipase/metabolismo , Estabilidade Enzimática , Enzimas Imobilizadas/metabolismo
10.
Biosci Biotechnol Biochem ; 84(3): 633-639, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31710276

RESUMO

To evaluate the suitability of the new nutritional composition of renewed commercial Formula A (protein reduced to 2.2 g/100 kcal, arachidonic acid increased to 13.2 mg/100 kcal, and docosahexaenoic acid maintained at 20 mg/100 kcal), we examined whether the growth of Formula A-fed infants was equivalent to that of breastfed infants. In this observational study, 1,053 infants were followed-up to 12 months. Growth, stool consistency, and the health condition of 99 infants fed with Formula A and 295 breastfed infants were compared. Body weight, body mass index, and head circumference of Formula A-fed infants were similar to those of breastfed infants. Additionally, there were no differences in the stool consistency and the health condition (infection and allergy prevalence) between the two groups. Formula A-fed infants grew as well as breastfed infants, suggesting the appropriate nutritional composition of Formula A. The findings may contribute to further improvements in infant formulas.


Assuntos
Desenvolvimento Infantil , Proteínas na Dieta/administração & dosagem , Ingestão de Energia , Fórmulas Infantis/química , Ácido Araquidônico/metabolismo , Peso Corporal , Aleitamento Materno , Ácidos Docosa-Hexaenoicos/metabolismo , Seguimentos , Nível de Saúde , Humanos , Lactente , Recém-Nascido
11.
Bioresour Technol ; 297: 122402, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761627

RESUMO

This study reports comparative evaluation of the growth and DHA productivity of the thraustochytrid strain Thraustochytriidae PKU#Mn16 fermented with seven different substrate feeding strategies. Of these strategies, fed-batch fermentation of the mixed substrate (glucose & glycerol) yielded the maximum growth (52.2 ±â€¯1.5 g/L), DHA yield (Yp/s: 8.65) and productivity (100.7 ±â€¯2.9 mg/L-h), comparable with those of previously reported Aurantiochytrium strains. Transcriptomics analyses revealed that glucose upregulated some genes of the fatty acid synthase pathway whereas glycerol upregulated a few genes of the polyketide synthase pathway. Co-fermentation of the mixed substrate differentially regulated genes of these two pathways and significantly enhanced the DHA productivity. Furthermore, some genes involved in DNA replication, phagosome, carbon metabolism, and ß-oxidation were also found to alter significantly during the mixed-substrate fermentation. Overall, this study provides a unique strategy for enhancing growth and DHA productivity of the strain PKU#Mn16 and the first insight into the mechanisms underlying mixed-substrate fermentation.


Assuntos
Carbono , Ácidos Docosa-Hexaenoicos , Vias Biossintéticas , Ácidos Graxos , Fermentação
12.
Ambio ; 49(4): 865-880, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31512173

RESUMO

Docosahexaenoic acid (DHA) is an essential, omega-3, long-chain polyunsaturated fatty acid that is a key component of cell membranes and plays a vital role in vertebrate brain function. The capacity to synthesize DHA is limited in mammals, despite its critical role in neurological development and health. For humans, DHA is most commonly obtained by eating fish. Global warming is predicted to reduce the de novo synthesis of DHA by algae, at the base of aquatic food chains, and which is expected to reduce DHA transferred to fish. We estimated the global quantity of DHA (total and per capita) currently available from commercial (wild caught and aquaculture) and recreational fisheries. The potential decrease in the amount of DHA available from fish for human consumption was modeled using the predicted effect of established global warming scenarios on algal DHA production and ensuing transfer to fish. We conclude that an increase in water temperature could result, depending on the climate scenario and location, in a ~ 10 to 58% loss of globally available DHA by 2100, potentially limiting the availability of this critical nutrient to humans. Inland waters show the greatest potential for climate-warming-induced decreases in DHA available for human consumption. The projected decrease in DHA availability as a result of global warming would disproportionately affect vulnerable populations (e.g., fetuses, infants), especially in inland Africa (due to low reported per capita DHA availability). We estimated, in the worst-case scenario, that DHA availability could decline to levels where 96% of the global population may not have access to sufficient DHA.


Assuntos
Ácidos Docosa-Hexaenoicos , Aquecimento Global , Animais , Aquicultura , Pesqueiros , Peixes , Humanos
13.
Bioresour Technol ; 298: 122562, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838241

RESUMO

Exergy analysis is powerful tool for process optimization and mechanism analysis. In this study, exergy analysis was performed for docosahexaenoic acid (DHA) fermentation process. More than 86% of input exergy was contributed by glucose. The exergy of biomass was about 64.66% of the total output exergy when the phosphate concentration was 4 g L-1. The exergy efficiencies of DHA (ηDHA) for the starting strains and the evolved strains under high oxygen concentration, low temperature, and two-factor conditions were also investigated. The ηDHA in the collected experimental data was not more than 20.9%. It was proved that there was a positive correlation between ηDHA and the biomass yield. It was indicated that adaptive laboratory evolution (ALE) improved biomass yield which had the most important effect on enhancing ηDHA and DHA yield (or DHA productivity). It is necessary to improve ηDHA through process optimization and ALE in future.


Assuntos
Ácidos Docosa-Hexaenoicos , Estramenópilas , Biomassa , Fermentação , Fosfatos
14.
Food Chem ; 308: 125607, 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-31677599

RESUMO

Lipid sources as alternatives to fish oil could alter the nutritional value and flavor quality of crab meat affecting consumer preferences. Herein, an 8-week nutritional trial was designed to investigate the effects of dietary lipid sources including fish oil (FO), krill oil (KO), palm oil, rapeseed oil, soybean oil and linseed oil on profiles of amino acids, fatty acids and volatiles in muscle of swimming crab (Portunus trituberculatus). Volatiles of crab muscle were characterized by headspace solid-phase microextraction and gas chromatography-tandem mass spectrometry. Results revealed that crabs fed FO and KO had significantly higher levels of protein, indispensable amino acids, eicosapentaenoic acid and docosahexaenoic acid in muscle. Principal component analysis and hierarchical cluster analysis demonstrated that muscle volatiles of crabs fed different dietary oils exhibited significant variations. Dietary FO and KO significantly increased the relative levels of 3-methylbutanal, heptanal, benzaldehyde and nonanal in muscle, which may produce more pleasant flavors.


Assuntos
Braquiúros/química , Aromatizantes/análise , Animais , Gorduras na Dieta/análise , Ácidos Docosa-Hexaenoicos/análise , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/análise , Ácidos Graxos/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Estado Nutricional , Valor Nutritivo , Alimentos Marinhos/análise , Microextração em Fase Sólida , Natação , Paladar
15.
J Exp Clin Cancer Res ; 38(1): 498, 2019 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-31856871

RESUMO

BACKGROUND: The MYCN amplification is a defining hallmark of high-risk neuroblastoma. Due to irregular oncogenes orchestration, tumor cells exhibit distinct fatty acid metabolic features from non-tumor cells. However, the function of MYCN in neuroblastoma fatty acid metabolism reprogramming remains unknown. METHODS: Gas Chromatography-Mass Spectrometer (GC-MS) was used to find the potential target fatty acid metabolites of MYCN. Real-time PCR (RT-PCR) and clinical bioinformatics analysis was used to find the related target genes. The function of the identified target gene ELOVL2 on cell growth was detected through CCK-8 assay, Soft agar colony formation assay, flow Cytometry assay and mouse xenograft. Chromatin immunoprecipitation (ChIP) and Immunoprecipitation-Mass Spectrometer (IP-MS) further identified the target gene and the co-repressor of MYCN. RESULTS: The fatty acid profile of MYCN-depleted neuroblastoma cells identified docosahexaenoic acid (DHA), an omega-3 polyunsaturated fatty acid with anti-tumor activity, significantly increased after MYCN depletion. Compared with MYCN single-copy neuroblastoma cells, DHA level was significantly lower in MYCN-amplified neuroblastoma cells. RT-PCR and clinical bioinformatics analysis discovered that MYCN interfered DHA accumulation via ELOVL fatty acid elongase 2 (ELOVL2) which is a rate-limiting enzyme of cellular DHA synthesis. Enforced ELOVL2 expression in MYCN-amplified neuroblastoma cells led to decreased cell growth and counteracted the growth-promoting effect of MYCN overexpression both in vitro and vivo. ELOVL2 Knockdown showed the opposite effect in MYCN single-copy neuroblastoma cells. In primary neuroblastoma, high ELOVL2 transcription correlated with favorable clinical tumor biology and patient survival. The mechanism of MYCN-mediated ELOVL2 inhibition contributed to epigenetic regulation. MYCN recruited PRC1 (Polycomb repressive complex 1), catalysed H2AK119ub (histone 2A lysine 119 monoubiquitination) and inhibited subsequent ELOVL2 transcription. CONCLUSIONS: The tumor suppressive properties of DHA and ELOVL2 are repressed by the MYCN and PRC1 jointly, which suggests a new epigenetic mechanism of MYCN-mediated fatty acid regulation and indicates PRC1 inhibition as a potential novel strategy to activate ELOVL2 suppressive functions.


Assuntos
Ácidos Docosa-Hexaenoicos/biossíntese , Elongases de Ácidos Graxos/genética , Proteína Proto-Oncogênica N-Myc/metabolismo , Neuroblastoma/genética , Neuroblastoma/metabolismo , Complexo Repressor Polycomb 1/metabolismo , Animais , Linhagem Celular Tumoral , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Xenoenxertos , Histonas/metabolismo , Humanos , Camundongos , Modelos Biológicos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Complexo Repressor Polycomb 1/genética
16.
Internist (Berl) ; 60(12): 1319-1327, 2019 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-31591673

RESUMO

BACKGROUND: Confusion reigns about omega­3 fatty acids and their effects. Scientific investigations did not appear to clarify the issue. Guidelines and regulatory authorities contradict each other. OBJECTIVE: This article provides clarity by considering not intake but levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in erythrocytes as a percentage of all fatty acids measured (omega­3 index). CURRENT DATA: The largest database of all methods of fatty acid analyses has been generated with the standardized HS-Omega­3 Index® (Omegametrix, Martinsried, Deutschland). The omega­3 index assesses the in EPA+DHA status of a person, has a minimum of 2%, a maximum of 20%, and is optimal between 8% and 11%. In many western countries but not in Japan or South Korea, mean levels are suboptimal. Suboptimal levels correlate with increased total mortality, sudden cardiac death, fatal and non-fatal myocardial infarction, other cardiovascular diseases, cognitive impairment, major depression, premature birth and other health issues. Interventional studies on surrogate and intermediary parameters demonstrated many positive effects, correlating with the omega­3 index when measured. Due to issues in methodology that became apparent from the perspective of the omega­3 index many, even large interventional trials with clinical endpoints were not positive, which is reflected in pertinent meta-analyses. In contrast, interventional trials without issues in methodology the clinical endpoints mentioned were reduced. CONCLUSION: All humans have levels of EPA+DHA that if methodologically correctly assessed in erythrocytes, are optimal between 8% and 11%. Deficits can cause serious health issues that can be prevented by optimal levels.


Assuntos
Ácidos Docosa-Hexaenoicos/sangue , Ácido Eicosapentaenoico/sangue , Eritrócitos/metabolismo , Ácidos Graxos Ômega-3/sangue , Morte Súbita Cardíaca , Humanos , Infarto do Miocárdio
17.
Mar Drugs ; 17(10)2019 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-31614820

RESUMO

Marine ecosystems are the most prevalent ecosystems on the planet, providing a diversity of living organisms and resources. The development of nanotechnology may provide solutions for utilizing these thousands of potential compounds as marine pharmaceuticals. Here, we designed a liposomal glycol chitosan formulation to load both doxorubicin (DOX) and rapamycin (RAPA), and then evaluated its therapeutic potential in a prepared drug-resistant cell model. We explored the stability of the drug delivery system by changing the physiological conditions and characterized its physicochemical properties. The electrostatic complexation between DOX-glycol chitosan and docosahexaenoic acid RAPA-liposomes (GC-DOX/RAPA ω-liposomes) was precisely regulated, resulting in particle size of 131.3 nm and zeta potential of -14.5 mV. The well-characterized structure of GC-DOX/RAPA ω-liposomes led to high loading efficiencies of 4.1% for DOX and 6.2% for RAPA. Also, GC-DOX/RAPA ω-liposomes exhibited high colloidal stability under physiological conditions and synergistic anti-cancer effects on DOX-resistant MDA-MB-231 cells, while showing pH-sensitive drug release behavior. Our results provided a viable example of marine pharmaceuticals with therapeutic potential for treating drug-resistant tumors using an efficient and safe drug delivery system.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Quitosana/química , Ácidos Docosa-Hexaenoicos/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lipossomos/química , Sirolimo/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos/efeitos dos fármacos , Ecossistema , Feminino , Humanos , Nanopartículas/química , Tamanho da Partícula
18.
Neurol Res ; 41(11): 1008-1014, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31573411

RESUMO

Objective: To investigate the effects of propofol used in early pregnancy on brain development and function of offspring, and further to explore the effects of docosahexaenoic acid (DHA) intervention. Methods: Forty pregnant rats were randomly divided into four groups: control group (C), propofol group (P), DHA intervention group (D), and propofol + DHA group (P + D). The DHA treatment was before propofol was administered. Morris water maze test was performed 30 days after delivery. The levels of amyloid beta (Aß), IL-1ß and reactive oxygen species (ROS) in hippocampus were detected by enzyme-linked immunosorbent assay (ELISA). The expression of brain-derived neurotrophic factor (BDNF) and tyrosine kinase-B (Trk-B), protein kinase B (Akt), p-Akt and cAMP response element-binding protein (CREB) in hippocampus were detected by western blot. Results: The learning and memory abilities of the rats in P group were reduced. The levels of Aß, IL-1ß and ROS were increased, while the levels of BDNF, Trk-B and CREB, and p-Akt/Akt ratio were reduced. In addition, compared with P group, DHA in P + D group reversed or alleviated adverse changes caused by propofol. Conclusions: Application of general anesthesia with propofol during the early stage of pregnancy can negatively affect the brain development of the offspring to reduce the learning and memory ability, while DHA can reverse it.


Assuntos
Peptídeos beta-Amiloides/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Memória/efeitos dos fármacos , Propofol/farmacologia , Anestesia Geral/métodos , Animais , Animais Recém-Nascidos , Encéfalo/crescimento & desenvolvimento , Feminino , Hipocampo/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Gravidez , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
Clin Interv Aging ; 14: 1481-1492, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31616139

RESUMO

Nutritional factors can influence the risk of developing Alzheimer's disease (AD) and its rate of progression, and there is, therefore, increasing interest in nutrition as a modifiable risk factor for the disease. Synaptic loss is an important feature of early AD, and the formation of new synapses is dependent on key nutritional elements that are known to be deficient in patients with AD. The daily medical food, Souvenaid, contains Fortasyn Connect, a multinutrient combination developed to specifically address these deficiencies, comprising docosahexaenoic acid, eicosapentaenoic acid, uridine monophosphate, choline, phospholipids, selenium, folic acid, and vitamins B12, B6, C, and E. Although yielding heterogeneous findings, clinical studies of Fortasyn Connect provide preliminary evidence of clinically relevant benefits on cognitive outcomes in prodromal and early AD. The LipiDiDiet trial investigated the effects of Fortasyn Connect on cognition and related measures in prodromal AD, and is the first randomized, controlled, double-blind, multicenter trial study of a non-pharmacological intervention in this setting. The primary efficacy endpoint was change over 24 months in a composite score of cognitive performance using a neuropsychological test battery. Fortasyn Connect had no significant effect on this endpoint, but demonstrated a significant benefit on secondary endpoints, including domains of cognition affected by AD (attention, memory, executive function) and hippocampal atrophy, suggesting a potential benefit on disease progression. Other studies have demonstrated benefits for Fortasyn Connect on nutritional markers and levels of plasma homocysteine. Taken together, current evidence indicates that Fortasyn Connect may show benefit on domains of cognition affected by AD and nutritional measures that influence risk factors for its progression; that it has greater potential for benefit earlier rather than later in the disease; and that it is safe and well tolerated, alone or in combination with AD medications. Further research into its potential role in AD management is therefore warranted.


Assuntos
Doença de Alzheimer/dietoterapia , Suplementos Nutricionais , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácido Eicosapentaenoico/uso terapêutico , Estado Nutricional , Fosfolipídeos/uso terapêutico , Idoso , Doença de Alzheimer/fisiopatologia , Progressão da Doença , Método Duplo-Cego , Feminino , Humanos , Masculino , Testes Neuropsicológicos
20.
Nat Commun ; 10(1): 3945, 2019 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-31477726

RESUMO

Neuroinflammation is one of the hallmarks of Parkinson's disease (PD) and may contribute to midbrain dopamine (DA) neuron degeneration. Recent studies link chronic inflammation with failure to resolve early inflammation, a process operated by specialized pro-resolving mediators, including resolvins. However, the effects of stimulating the resolution of inflammation in PD - to modulate disease progression - still remain unexplored. Here we show that rats overexpressing human α-synuclein (Syn) display altered DA neuron properties, reduced striatal DA outflow and motor deficits prior to nigral degeneration. These early alterations are coupled with microglia activation and perturbations of inflammatory and pro-resolving mediators, namely IFN-γ and resolvin D1 (RvD1). Chronic and early RvD1 administration in Syn rats prevents central and peripheral inflammation, as well as neuronal dysfunction and motor deficits. We also show that endogenous RvD1 is decreased in human patients with early-PD. Our results suggest there is an imbalance between neuroinflammatory and pro-resolving processes in PD.


Assuntos
Modelos Animais de Doenças , Ácidos Docosa-Hexaenoicos/administração & dosagem , Inflamação/prevenção & controle , Degeneração Neural/prevenção & controle , Doença de Parkinson/prevenção & controle , Animais , Ácidos Docosa-Hexaenoicos/genética , Ácidos Docosa-Hexaenoicos/metabolismo , Neurônios Dopaminérgicos/efeitos dos fármacos , Neurônios Dopaminérgicos/metabolismo , Humanos , Masculino , Microglia/efeitos dos fármacos , Microglia/metabolismo , Doença de Parkinson/genética , Doença de Parkinson/metabolismo , Ratos , Ratos Sprague-Dawley , Ratos Transgênicos , Substância Negra/efeitos dos fármacos , Substância Negra/metabolismo , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA