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.

Effect of docosahexaenoic acid on microglial activation during oxygen-glucose deprivation and restoration injury / 中华麻醉学杂志

Objective@#To evaluate the effect of docosahexaenoic acid (DHA) on microglial activation during oxygen-glucose deprivation and restoration (OGD/R) injury.@*Methods@#N9 microglia were inoculated in 96-well culture plates at a density of 104 cells/well for 3-5 days and divided into 3 groups (n=18 each) using a random number table method: control group (group C), group OGD/R and DHA+ OGD/R group. The cells were cultured for 24 h in an incubator at 37 ℃ (95% air-5% CO2) in group C. In OGD/R and DHA groups, the culture medium was replaced by glucose-free culture medium, the cells were cultured for 12 h in an incubator at 37 ℃ (95% N2-5% CO2), and then cells were returned to the normal culture medium and cultured for 24 h in an incubator at 37 ℃ (95% air-5% CO2) to establish the OGD/R injury model. The cells in group DHA were incubated with 25 μmol/L DHA at 12 h before OGD/R. The cell viability was detected using the methyl thiazolyl tetrazolium assay, the activity of lactate dehydrogenase (LDH) was measured by using chemical colorimetric method, activated microglia were counted by immunofluorescence staining, the expression of microglia activation marker iba-1 was detected by Western blot, and the concentrations of tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6) and IL-4 and IL-10 in culture medium were determined using enzyme-linked immunosorbent assay.@*Results@#Compared with the group C, the cell viability was significantly decreased, the LDH activity was increased, the number of activated microglia was increased, and the expression of iba-1 was up-regulated in OGD/R and DHA+ OGD/R groups, the concentrations of TNF-α and IL-6 were significantly increased in group OGD/R, and the concentrations of TNF-α, IL-6, IL-4 and IL-10 were significantly increased in group DHA+ OGD/R (P<0.05). Compared with group OGD/R, the cell viability was significantly increased, the LDH activity was decreased, the number of activated microglia was decreased, the expression of iba-1 was down-regulated, TNF-α and IL-6 concentrations were decreased, and IL-4 and IL-10 concentrations were increased in group DHA (P<0.05).@*Conclusion@#The mechanism by which DHA reduces OGD/R injury may be related to inhibiting activation of microglia and to reducing inflammatory responses.

Effect of docosahexaenoic acid on microglial activation during oxygen-glucose deprivation and restoration injury / 中华麻醉学杂志

Objective To evaluate the effect of docosahexaenoic acid (DHA) on microglial activation during oxygen-glucose deprivation and restoration (OGD/R) injury.Methods N9 microglia were inoculated in 96-well culture plates at a density of 104 cells/well for 3-5 days and divided into 3 groups (n=18 each) using a random number table method:control group (group C),group OGD/R and DHA+OGD/R group.The cells were cultured for 24 h in an incubator at 37 ℃ (95％ air-5％ CO2) in group C.In OGD/R and DHA groups,the culture medium was replaced by glucose-free culture medium,the cells were cultured for 12 h in an incubator at 37 ℃ (95％ N2-5％ CO2),and then cells were returned to the normal culture medium and cultured for 24 h in an incubator at 37 ℃ (95％ air-5％ CO2) to establish the OGD/R injury model.The cells in group DHA were incubated with 25 μmol/L DHA at 12 h before OGD/R.The cell viability was detected using the methyl thiazolyl tetrazolium assay,the activity of lactate dehydrogenase (LDH)was measured by using chemical colorimetric method,activated microglia were counted by immunofluorescence staining,the expression of microglia activation marker iba-1 was detected by Western blot,and the concentrations of tumor necrosis factor-α (TNF-α),interleukin 6 (IL-6) and IL-4 and IL-10 in culture medium were determined using enzyme-linked immunosorbent assay.Results Compared with the group C,the cell viability was significantly decreased,the LDH activity was increased,the number of activated microglia was increased,and the expression of iba-1 was up-regulated in OGD/R and DHA+OGD/R groups,the concentrations of TNF-α and IL-6 were significantly increased in group OGD/R,and the concentrations of TNF-α,IL-6,IL-4 and IL-10 were significantly increased in group DHA+OGD/R (P＜0.05).Compared with group OGD/R,the cell viability was significantly increased,the LDH activity was decreased,the number of activated microglia was decreased,the expression of iba-1 was down-regulated,TNF-α and IL-6 concentrations were decreased,and IL-4 and IL-10 concentrations were increased in group DHA (P＜0.05).Conclusion The mechanism by which DHA reduces OGD/R injury may be related to inhibiting activation of microglia and to reducing inflammatory responses.

Deficiency or activation of peroxisome proliferator-activated receptor α reduces the tissue concentrations of endogenously synthesized docosahexaenoic acid in C57BL/6J mice

BACKGROUND/OBJECTIVES: Docosahexaenoic acid (DHA), an n-3 long chain polyunsaturated fatty acid (LCPUFA), is acquired by dietary intake or the in vivo conversion of α-linolenic acid. Many enzymes participating in LCPUFA synthesis are regulated by peroxisome proliferator-activated receptor alpha (PPARα). Therefore, it was hypothesized that the tissue accretion of endogenously synthesized DHA could be modified by PPARα. MATERIALS/METHODS: The tissue DHA concentrations and mRNA levels of genes participating in DHA biosynthesis were compared among PPARα homozygous (KO), heterozygous (HZ), and wild type (WT) mice (Exp I), and between WT mice treated with clofibrate (PPARα agonist) or those not treated (Exp II). In ExpII, the expression levels of the proteins associated with DHA function in the brain cortex and retina were also measured. An n3-PUFA depleted/replenished regimen was applied to mitigate the confounding effects of maternal DHA. RESULTS: PPARα ablation reduced the hepatic Acox, Fads1, and Fads2 mRNA levels, as well as the DHA concentration in the liver, but not in the brain cortex. In contrast, PPARα activation increased hepatic Acox, Fads1, Fads2 and Elovl5 mRNA levels, but reduced the DHA concentrations in the liver, retina, and phospholipid of brain cortex, and decreased mRNA and protein levels of the brain-derived neurotrophic factor in brain cortex. CONCLUSIONS: LCPUFA enzyme expression was altered by PPARα. Either PPARα deficiency or activation-decreased tissue DHA concentration is a stimulus for further studies to determine the functional significance.

Oral omega 3 in different proportions of EPA, DHA, and antioxidants as adjuvant in treatment of keratoconjunctivitis sicca in dogs / Ômega 3 oral em diferentes proporções de EPA, DHA e antioxidantes como adjuvante no tratamento de ceratoconjuntivite seca em cães

ABSTRACT Purpose: To compare the efficacy of 0.03% to­pical tacrolimus in combination with oral omega (ω) 3 with different ratios of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and antioxidants as adjuvant in the treatment of keratoconjunctivitis sicca (KCS) in dogs. Methods: Forty-five dogs with KCS were evaluated monthly for 6 months. Evaluations included performance of the Schirmer tear, fluorescein, and lissamine green tests. Tear film break-up time (TBUT) was assessed. Conjunctival cytology was evaluated at the beginning, middle, and end of the study. Conjunctiva was biopsied at the beginning and end of the study. Dogs were randomly assigned to one of the three groups (n=15): Group T (topical tacrolimus 0.03%), Group TO (topical tacrolimus + ω-1.5 EPA: 1 DHA), or Group TOA (topical tacrolimus + ω-1 EPA:4.5 DHA + antioxidants). Results: There was a significant improvement in clinical signs in all groups. TBUT increased throughout treatment in all groups; this effect was most pronounced in Group TO. Cytological analysis performed at the end of the study period, showed decreased levels of lymphocytes, neutrophils, and metaplastic and squamous cells in Groups T, TO, and TOA. Histological analysis performed at the end of the study period showed decreased levels of lymphocytes and neutrophils and increased levels of goblet cells. These effects were most pronounced in Group TO. Conclusion: Oral treatment with ω-3 containing a higher proportion of EPA than DHA increased the effectiveness of topical tacrolimus 0.03% in the treatment of keratoconjunctivitis sicca in dogs.

RESUMO Objetivo: Comparar a eficácia do tacrolimus 0,03% tópico associado ao ômega 3 oral, com diferentes proporções de ácido eicosapentaenoico (EPA), ácidos docosa-hexaenoicos (DHA) e antioxidantes, como adjuvante no tratamento de cães acometidos por ceratoconjuntivite seca. Métodos: Quarenta e cinco cães atendidos no Hospital Veterinário da UNOESTE portadores de ceratoconjuntivite seca foram avaliados mensalmente por 6 meses pelo Teste Lacrimal de Schirmer, Teste de Fluoresceína, Tempo de Ruptura do Filme Lacrimal, Teste de Rosa Bengala, citologia da conjuntiva no início, meio e fim do projeto e biopsia da conjuntiva no início e final do projeto. Os cães foram distribuídos aleatoriamente em 3 grupos (n=15): grupo T (tacrolimus 0,03% tópico), grupo TO (tacrolimus + ômegas 1.5 EPA/1 DHA oral) e grupo TOA (tacrolimus + ômegas 1 EPA/4,5 DHA + antioxidantes oral). Resultados: Houve uma melhora significativa nos sinais clínicos em ambos os grupos. No tempo de ruptura do filme lacrimal todos os grupos apresentaram aumento no decorrer do tratamento, sendo que o grupo TO foi o que apresentou melhor resultado em todos momentos quando comparado aos demais grupos. Ao final do experimento, os grupos T, TO e TOA apresentaram na análise citológica, diminuição de linfócitos, neutrófilos, células metaplásicas e escamosas, e na análise histopatológica, diminuição de linfócitos e neutrófilos e aumento das células caliciformes, com o grupo TO com melhor desempenho. Conclusão: O tratamento oral com ω-3 contendo uma maior proporção de EPA do que o DHA aumentou a eficácia do tacrolimus tópico 0,03% no tratamento de ceratoconjuntivite sicca em cães.

Effect of exogenous resolvin D2 on radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation / 中华麻醉学杂志

Objective To evaluate the effect of exogenous resolvin D2 on radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation.Methods Thirty-six clean-grade healthy male Sprague-Dawley rats,aged 8 weeks,weighing 230-270 g,were divided into 3 groups (n=12 each) using a random number table method:sham operation group (group S),radicular pain induced by non-compressive lumbar intervertebral disc herniation group (group P) and exogenous resolvin D2 group (group R).The right L5 dorsal root ganglions were covered by autologous nucleus pulposus tissues to establish the model of non-compressive lumbar disc herniation in P and R groups.The corresponding surgical site was only exposed in group S.The corresponding drugs were intrathecally injected within 3 days after establishing the model,phosphate buffer solution 10 μl was injected in group P,1 ng/μl resolvin D2 solution 10 μl was injected in group R,and normal saline 10 μl was given for pipe washing after administration in the three groups.The mechanical paw withdrawal threshold (MWT) was measured on 1 day before establishing the model and 1-7 days after establishing the model.The spinal dorsal horns of lumbar enlargement segments were removed on day 7 after establishing the model for determination of the expression of glial fibrillary acidic protein (GFAP) (by Western blot) and co-expression of G-protein-coupled receptor 18 with GFAP (by double-label immunofluorescence).Results Compared with group S,the MWT was significantly decreased at 1-7 days after establishing the model,and the expression of GFAP was up-regulated in group P (P＜0.05).Compared with group P,the MWT was significantly increased at 3-7 days after establishing the model,and the expression of GFAP was down-regulated in group R (P＜0.05).G-protein-coupled receptor 18 was co-expressed with GFAP.Conclusion Exogenous resolvin D2 can reduce radicular pain in a rat model of non-compressive lumbar intervertebral disc herniation,and the mechanism is related to inhibiting activation of astrocytes in the spinal dorsal horns.

Suplementos nutricionales en el deterioro cognitivo y la enfermedad de Alzheimer: revisión de la literatura / Dietary supplements in cognitive impairment and Alzheimer's disease: a literature review

RESUMEN OBJETIVOS: Evaluar los efectos del consumo de ácidos grasos omega 3 en forma de suplementos, complementos o alimentos sobre la función cognitiva de los adultos. MÉTODOS: Se realizó una revisión de la literatura en las bases de datos Medline y Embase, buscando ensayos clínicos, estudios observacionales, revisiones sistemáticas y estudios experimentales que relacionaran los ácidos grasos omega 3 con función cognitiva y Alzheimer. RESULTADOS: La mayoría de los estudios relacionó la suplementación de cápsulas con omega 3, el consumo de pescado u otros alimentos con contenido de omega 3, con resultados en pruebas de función cognitiva, desenlace de enfermedad o imágenes diagnósticas, encontrando en general efectos benéficos, que parecen ser mayores en personas sanas y con mejor función cognitiva de base. Hubo diferencias en los resultados encontrados en los ensayos clínicos y revisiones sistemáticas, que podrían atribuirse a la variabilidad en las dosis de la suplementación, el tiempo de seguimiento y la manera en que se midió la función y el deterioro cognitivo. CONCLUSIÓN: El consumo de ácidos grasos omega 3 en forma de suplementos, complementos o alimentos ricos en estos como el pescado parece tener efectos benéficos en la función cognitiva de las personas adultas.

SUMMARY OBJECTIVES: To evaluate the effects of omega 3 fatty acids consumption in the form of dietary supplement, complement or food-products presentation on adult cognitive function. METHODS: A literature review in two databases (Medline and Embase) was undertaken, searching for clinical trials, observational studies, systematic reviews and experimental studies concerning omega-3 fatty acids and their relation with cognitive function and Alzheimer's disease. RESULTS: Most studies linked supplementation with omega-3 capsules and consumption of fish and other omega-3 containing foods with results in cognitive function testing, outcomes in diseases or diagnostic imaging and found beneficial effects, which seem to be stronger in healthier persons with better cognitive function at baseline. There were differences in the results found in clinical trials and systematic reviews, which could be attributable to the variability in the supplementation dose, the length of follow-up and the methods used to assess cognitive function and decline. CONCLUSION: The use of omega-3 fatty acids in supplement, complement or food-products presentation seems to have beneficial effects in the cognitive function of healthy adults.

Combination therapy with butyrate and docosahexaenoic acid for keloid fibrogenesis: an in vitro study

Abstract: Background: A single, effective therapeutic regimen for keloids has not been established yet, and the development of novel therapeutic approaches is expected. Butyrate, a short-chain fatty acid, and docosahexaenoic acid (DHA), a ω-3 polyunsaturated fatty acid, play multiple anti-inflammatory and anticancer roles via their respective mechanisms of action. Objective: In this study, we evaluated the antifibrogenic effects of their single and combined use on keloid fibroblasts. Methods: Keloid fibroblasts were treated with butyrate (0-16 mM) and/or DHA (0-100 µM) for 48 or 96 h. Results: Butyrate inhibited cell proliferation, and α-smooth muscle actin (α-SMA) and type III collagen expressions, with inhibition of the transforming growth factor (TGF)-β1 and TGF-β type I receptor expressions and increased prostaglandin E2 with upregulation of cyclooxygenase-1 expression with induction of histone acetylation. DHA inhibited α-SMA, type III collagen, and TGF-β type I receptor expressions. Then, the butyrate/DHA combination augmented the antifibrogenic effects, resulting in additional inhibition of α-SMA, type I and III collagen expressions, with strong disruption of stress fiber and apoptosis induction. Moreover, the butyrate/DHA combination inhibited the cyclooxygenase-2 expression, suggesting stronger anti-inflammatory effect than each monotherapy. Study limitations: Activation in keloid tissue is affected not only by fibroblasts but also by epithelial cells and immune cells. Evaluation of the effects by butyrate and DHA in these cells or in an in vivo study is required. Conclusion: This study demonstrated that butyrate and docosahexaenoic acid have antifibrogenic effects on keloid fibroblasts and that these may exert therapeutic effects for keloid.

Effects of saturated and unsaturated fatty acids on proliferation and autophagy of lung cancer cells / 解放军医学杂志

Objective To investigate the effects of saturated fatty acids and unsaturated fatty acids on proliferation and autophagy of human lung cancer cells. Methods The lung cancer cells A549 were treated with stearic acid (saturated fatty acid) and doconexent (DHA, unsaturated fatty acid), respectively, in concentrations of 0, 30, 60, 120 and 240μmol/L. MTT test and cell clone formation assay were performed to detect the proliferation of A549 cells. The morphology of A549 autophagy was observed by confocal laser scanning microscopy after A549 cells were treated with stearic acid or DHA for 24 hours. Western blotting assay was used to detect the expression of autophagy-related protein after A549 cells were treated with stearic acid or DHA for 12, 24 and 36 hours, respectively. Results 30-240μmol/L stearic acid or DHA both inhibited the proliferation of A549 cells (P<0.05). Both stearic acid and DHA induced autophagy of A549 cells, meanwhile, down-regulated Phospho-mTOR (ser2481) and up-regulated LC3Ⅱ/LC3Ⅰ of A549 cells (P<0.05). Conclusions Both saturated fatty acid and unsaturated fatty acid can inhibit the proliferation and induce autophagy of lung cancer cells. The mechanisms of autophagy may be related to Phospho-mTOR (ser2481) signaling pathway.

Docosahexaenoic acid inhibits hypoxia-induced pulmonary arterial smooth muscle cells phenotype switching by inhibiting NFATc1 signaling / 中华心血管病杂志

Objective@#To explore the molecular mechanism of docosahexaenoic acid (DHA) on regulating the phenotype switching of hypoxia-induced pulmonary arterial smooth muscle cells (PASMCs).@*Methods@#The PASMCs were isolated from Sprague Dawley rats. PASMCs were divided into five groups: normal control group, hypoxia group (1%O2, 94%N2, 5% CO2 stimulation for 12 hours), hypoxia+ DHA group (10 μmol/L DHA pretreatment followed by 12 hours hypoxia), hypoxia+ DHA+ NFATc1 overexpression group (transfection of the NFATc1 lentivirus for 24 hours, followed by hypoxia stimulation for 12 hours after 10 μmol/L DHA treatment), and hypoxia+ DHA+ siNFATc1 group (transfection the siNFATc1 for 24 hours, followed by hypoxia stimulation for 12 hours after 10 μmol/L DHA treatment). The hypoxia stimulation was achieved by use of a special hypoxia incubator (1%O2, 94%N2, 5%CO2). The expressions of NFATc1 of various groups were determined by qRT-PCR and Western blot. The expression of α-SMA was determined by immunofluorescence staining, qRT-PCR and Western blot. The expression of SM22 was determined by qRT-PCR. The proliferation of PASMC was determined by EDU staining.@*Results@#The mRNA and protein expression levels of NFATc1 were significantly upregulated in hypoxia group compared with the normal control group (P<0.05), while hypoxia-induced upregulation of NFTAc1 could be significantly downregulated by DHA treatment (P<0.05). The α-SMA positive cell number, protein and mRNA levels of α-SMA and the mRNA level of SM22 were significantly lower in the hypoxia group than in normal control group, which could be significantly reversed by DHA, the protective effects could then be abolished by NFATc1 overexpression. Above indices were significantly lower in the hypoxia+ DHA+ siNFATc1 group than in hypoxia+ DHA+ NFATc1 overexpression group (P<0.05). The proliferation of PASMCs was significantly higher in the hypoxia group than in the control group (P<0.05), and which could be significantly reduced by DHA (P<0.05), and the protective effect of DHA could be significantly abolished by overexpression of NFATc1 (P<0.05). The proliferation of PASMCs was significantly lower in the hypoxia+ DHA+ siNFATc1 group than in the hypoxia+ DHA+ overexpression NFATc1 group (P<0.05).@*Conclusion@#DHA could prevent hypoxia-induced PASMCs phenotype switching and proliferation by inhibiting NFATc1 signaling.

Mechanism underlying docosahexaenoic acid-induced regulation of angiopoietin expression in human brain vascular pericytes subjected to oxygen-glucose deprivation and restoration: the relationship with SSeCKS / 中华麻醉学杂志

Objective To evaluate the relationship between the mechanism underlying docosahexaenoic acid (DHA)-induced regulation of angiopoietin expression and Src-suppressed C kinase substrate (SSeCKS) in human brain vascular pericytes (HBVPs) subjected to oxygen-glucose deprivation and restoration (OGD/R).Methods HBVPs were seeded in 96-well or in 6-well plates at a density of 2× 105 cells/ml and divided into 5 groups (n =18 each) using a random number table:control group (group C),OGD/R group,DHA group (group D),SSeCKS gene silencing group (group S) and SSeCKS gene silencing plus DHA group (group SD).The model of OGD/R injury was established as follows:the cells were subjected to O2-glucose deprivation for 24 h in glucose-and serum-free culture medium aerated with 94％ N2-5％ CO2-1％ O2 followed by restoration of O2-glucose supply for 6 h in high-glucose DMEM culture medium in normal atmosphere.DHA was added at 1 h before hypoxia with the final concentration of 40 μmol/L in group D.Small interfering RNA induced SSeCKS gene silencing in S and SD groups.Subsequently,DHA with the final concentration of 40 μmol/L was added at 1 h before hypoxia in group SD.At 6 h of reoxygenation,the cell survival rate was determined by CCK-8 assay,the amount of LDH released was detected using ELISA,and the expression of SSeCKS,angiopoietin-1 (Ang-1) and Ang-2 was detected by Western blot.Results Compared with group C,the cell survival rate was significantly decreased,the amount of LDH released was increased,the expression of SSeCKS and Ang-1 was down-regulated,the expression of Ang-2 was up-regulated,and Ang-1/Ang-2 ratio was decreased in group OGD/R,and the expression of SSeCKS was down-regulated in group S (P＜0.05).Compared with group OGD/R,the cell survival rate was significantly increased,the amount of LDH released was decreased,the expression of SSeCKS and Ang-1 was up-regulated,the expression of Ang-2 was down-regulated,and Ang-1/Ang-2 ratio was increased in group D (P＜O.05),and no significant change was found in the parameters mentioned above in group SD (P＞0.05).Compared with group D,the cell survival rate was significantly decreased,the amount of LDH released was increased,the expression of SSeCKS and Ang-1 was down-regulated,the expression of Ang-2 was up-regulated,and Ang-1/Ang-2 ratio was decreased in group SD (P＜0.05).Conclusion The mechanism by which DHA increases the ratio of Ang-1/Ang-2 may be totally related to up-regulation of SSeCKS expression in HBVPs subjected to OGD/R.

Effects of docosahexenoic acid on large conductance Ca+-activated K+ channels in retinal smooth muscle cells / 中华眼底病杂志

Objective To investigate the effects ofdocosahexenoic acid (DHA) on large conductance Ca2+-activated K+ (BK) channels in normal retinal artery smooth muscle cells (RASMCs).Methods Cultured human RASMCs (6 th-8 th generations) were used to patch clamp experiment.The open probabihties (NP0) in BK channels with different concentrations (0.0,1.0,3.0,5.0,7.5,10.0 μmol/L) of DHA were recorded by patch clamp technique in single channel configuration.RASMCs were intervened by different concentrations (0.0,1.0,5.0 μmol/L) of DHA as control group,low and high doses of DHA groups,respectively.The protein expressions of β subunit of BK channels in RASMCs from three groups were measured by Western blot.Results The NP0 of BK channels were 0.044 4±0.001 2,0.081 2±0.004 2,0.209 0±0.006 1,0.310 5±0.005 3,0.465 0±0.007 8 and 0.497 7±0.014 5 with perfusate of 0.0,1.0,3.0,5.0,7.5,10.0 μtmol/L DHA.DHA activated BK channels in a dose-dependent manner (F=2.621,P＜0.05).There was no significant difference in the protein expression of control group,low and high doses of DHA groups (F=1 1.657,P＞0.05).Conclusion DHA can directly activate BK channels,no increasing in subunit expression of BK channels.

Effect of exogenous protectin DX on acute lung injury in septic mice / 中华麻醉学杂志

Objective To investigate the effect of exogenous protectin DX (PDX) on acute lung injury in septic mice.Methods Thirty male C57BL/6 mice,aged 6-8 weeks,weighing 20-25 g,were randomly divided into 3 groups (n =10 each) using a random number table:sham operation group (Sham group),sepsis group (S group) and PDX group.Sepsis was produced by cecum ligation and puncture (CLP) in the mice anesthetized with pentobarbital sodium.At 1 h after CLP,PDX 300 ng was injected intraperitoneally in PDX group,and the equal volume of normal saline was given in Sham and S groups.At 24 h after CLP,the mice were sacrificed,and the broncho-alveolar lavage fluid (BALF) was collected for determination of interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α),IL-6 and IL-10 concentrations,and the lungs were removed for microscopic examination and for determination of the myeloperoxidase (MPO) activity,wet/dry lung weight ratio (W/D ratio) and phosphorylation of nuclear factor-kappa B (NF-κB) p65.Lung injury scores were calculated.Results Compared with Sham group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein and inflammatory factors in BALF were significantly increased in S and PDX groups (P＜0.05).Compared with S group,the lung injury score,MPO activity,W/D ratio,phosphorylation of NF-κB p65,and concentrations of protein,IL-1β,TNF-α and IL-6 in BALF were significantly decreased,and the concentration of IL-10 in BALF was significantly increased in PDX group (P＜0.05).Conclusion Exogenous PDX can alleviate acute lung injury through inhibiting NF-κB activity in the lung tissues of septic mice.

Effects of docosahexaenoic acid on expression of Ang-2 and VEGF in rat brain microvascular endo-thelial cells subjected to oxygen-glucose deprivation / 中华麻醉学杂志

Objective To evaluate the effects of docosahexaenoic acid ( DHA) on the expression of angiotensin?2 ( Ang?2) and vascular endothelial growth factor ( VEGF) in rat brain microvascular endo?thelial cells (BMVECs) subjected to oxygen?glucose deprivation (OGD). Methods Primarily cultured rat BMVECs were divided into 3 groups ( n=18 each) using a random number table: control group ( group C) , OGD group and DHA group. The cells were cultured with glucose?free and serum?free DMEM culture medium in OGD and DHA groups. In group DHA, DHA 40μmol was added, and then the cells were ex?posed to 1%O2?5%CO2?94%N2 in an air?tight incubator. The cells were cultured in the normal glucose and normal oxygen conditions in group C. All the cells were cultured for 24 h. Cell apoptosis was detected using Annexin V∕propidium iodide flow cytometry assay, and the apoptosis rate was calculated. The concentra?tions of Ang?2, VEGF, prostaglandin E2 ( PGE2 ) and prostacyclin ( PGI2 ) in the supernatant of the cul?ture medium were determined by enzyme?linked immunosorbent assay. The expression of Ang?2 mRNA and VEGF mRNA in cells was detected by real?time polymerase chain reaction. The expression of cyclooxygen?ase?2 ( COX?2) protein in cells was detected by Western blot. Results Compared with group C, the ap? optosis rate and concentrations of Ang?2, VEGF, PGE2 and PGI2 in the supernatant were significantly in?creased, and the expression of Ang?2 mRNA, VEGF mRNA and COX?2 protein was significantly up?regu?lated in OGD and DHA groups (P<0.05). Compared with group OGD, the apoptosis rate and concentra?tions of Ang?2, VEGF, PGE2 and PGI2 in the supernatant were significantly decreased, and the expression of Ang?2 mRNA, VEGF mRNA and COX?2 protein was significantly down?regulated in group DHA ( P<0.05) . Conclusion DHA can inhibit the expression of Ang?2 and VEGF in rat brain BMVECs subjected to OGD and reduce cell apoptosis, and down?regulated expression of COX?2 protein is involved in the mecha?nism.

Effect of resolvin D1 on focal cerebral ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of resolvin D1 on focal cerebral ischemia?reperfusion ( I∕R) injury in rats. Methods One hundred and twenty adult male Sprague?Dawley rats, aged 7 weeks, weighing 260-280 g, were randomly divided into 5 groups ( n=24 each) using a random number table:sham operation group (group S), group I∕R, low?dose resolvin D1 group (group LRD), medium?dose resolvin D1 group ( group MRD) , and high?dose resolvin D1 group ( group HRD) . Focal cerebral I∕R was induced by right middle cerebral artery occlusion using a nylon thread inserted into internal carotid artery and advanced cranially until resistance was met. The occlusion was maintained for 2 h followed by 24 h reperfusion. In LRD, MRD and HRD groups, 0.03, 0.10, 0.30 nmol resolvin D1 5 μl was injected into the lateral cerebral ventricle at the beginning of reperfusion, respectively. Neurological deficits were evaluated at 24 h of reperfusion and scored. The rats were then sacrificed, and their brains were removed for determination of infarct volume (by TTC staining), cerebral water content, Evans blue content and expression of matrix metalloproteinase?9 ( MMP?9) in the ischemic cortex. Results Compared with group S, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly increased, and the expression of MMP?9 was up?regulated in the other 4 groups. Compared with group I∕R, the neurological deficit scores, cerebral infarct volume, and cerebral water and Evans blue content were significantly decreased, and the expression of MMP?9 was down?regulated in group MRD and group HRD, and no significant change was found in the parameters mentioned above in group LRD. Conclusion Resolvin D1 can attenuate focal cerebral I∕R injury in rats, and down?regulation of MMP?9 expression and decrease in permeability of blood?brain barrier may be involved in the mechanism.

Effect of docosahexaenoic acid on hepatic ischemia-reperfusion injury in rats / 中华麻醉学杂志

Objective To evaluate the effect of docosahexaenoic acid (DHA) on hepatic ischemia-reperfusion (I/R) injury in rats.Methods Fifteen male Sprague-Dawley rats, aged 8-10 weeks, weighing 250-300 g, were randomly divided into 3 groups (n =5 each) using a random number table: sham operation group (group S), hepatic I/R group (group I/R) , and group DHA.Hepatic I/R was induced by clamping the hepatic pedicle supplying the left and middle lobes of the liver for 60 min, followed by 24 h reperfusion in anesthetized rats.DHA 4 mg/kg was injected intravenously at 30 min before ischemia and 10 min of reperfusion in group DHA.The equal volume of solvent was given instead in S and I/R groups.Blood samples were taken from the inferior vena cava at 24 h of reperfusion for determination of serum alanine aminotransferase (ALT), and aspartate aminotransferase (AST) activities, and resolvin D1 concentrations.The rats were then sacrificed, and the livers were removed for determination of myeloperoxidase (MPO) activity (by spectrophotometry), and interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) mRNA expression (by quantitative real-time reverse transcriptase polymerase chain reaction).The livers were cut into sections which were stained with haematoxylin and eosin, and examined under light microscope.Results Compared to group S, the serum ALT and AST activities, serum resolvin D1 concentrations, and MPO activity, and IL-6 and TNF-α mRNA expression in liver tissues were significantly increased in I/R and DHA groups (P＜0.05).Compared to group Ⅰ/R, the serum resolvin 1D1 concentrations, and MPO activity and TNF-α mRNA expression in liver tissues were significantly decreased (P＜0.05) , and no significant difference was found in the serum ALT and AST activities in group DHA (P＞0.05).There was no significant difference in pathological changes of the liver between group DHA and group I/R.Conclusion DHA can attenuate inflammatory responses during hepatic I/R, but it is not sufficient to mitigate liver injury in rats.

Perfil de incorporação de ácidos graxos em membranas de eritrócitos de recém-nascidos prematuros recebendo nutrição parenteral com diferentes emulsões lipídicas / Profile of fatty acids incorporation in erythrocyte membrane of premature newborns who received parenteral nutrition with different lipid emulsions

Introdução: Devido a diversos fatores, recém-nascidos prematuros, em sua maioria, necessitam de nutrição parenteral e uma fonte lipídica que possua um equilíbrio entre os variados tipos de ácidos graxos. SMOFlipid® 20%, uma nova emulsão lipídica pode ser mais adequada para esse equilíbrio. Objetivo: Avaliar o perfil de incorporação de ácidos graxos em eritrócitos de prematuros recebendo essa nova emulsão lipídica, comparada com outra emulsão baseada em óleo de soja. Métodos: Em um ensaio clinico controlado randomizado duplo cego avaliou-se 47 recém-nascidos pré-termo que receberam nutrição parenteral SMOFlipid® 20% (n=25) ou LIPOVENOS® MCT 20% (n=22). Foram avaliados parâmetros laboratoriais, clínicos, demográficos e o perfil de incorporação de ácidos graxos na membrana de eritrócitos. Resultados: Os parâmetros clínicos e demográficos como peso, perímetro cefálico, comprimento, idade gestacional e índice de Apgar não diferiram entre os grupos. Os valores de triglicerídeos e da lipoproteína de muito baixa densidade (VLDL) foram estatisticamente maiores no grupo SMOFLIPID® 20%. Níveis de Aspartato aminotransferase (AST) foram menores em ambos os grupos e os níveis de bilirrubina total e frações não tiveram diferenças. A emulsão SMOFlipid® 20% aumentou os níveis dos ácidos docosa-hexaenoico DHA (C 22:6 w3) e Eicosapentaenoico EPA (C 20:5 w3) na membrana dos eritrócitos. Conclusões: Neste grupo de recém-nascidos pré-termos, essa nova emulsão lipídica, além de mostrar segurança, contribuiu para uma mudança benéfica no perfil de incorporação de ácidos graxos nas membranas celulares, principalmente DHA e EPA.

Introduction: Due to several factors, premature newborn infants, in most cases, require parenteral nutrition and a lipid source with balance among the different types of fatty acids. SMOFlipid® 20%, a new lipid emulsion may be more appropriate for this balance. Objectives: To evaluate the profile of fatty acids incorporation in erythrocytes of premature newborn infants receiving this new lipid emulsion compared with an emulsion based on soybean oil. Methods: In a randomized, controlled, double-blind clinical trial, 47 preterm newborn who received parenteral nutrition SMOFlipid® 20% (n=25) or Lipovenos MCT® 20% (n=22) were evaluated. Laboratorial, clinical and demographic parameters and the profile of incorporation of fatty acids in the erythrocyte membrane were evaluated. Results: The clinical and demographic parameters such as weight, head circumference, length, gestational age, and Apgar scores did not differ between the groups. The values of triglycerides and lipoprotein of very low density (VLDL) were statistically higher in the SMOFlipid® 20% group. Levels of aspartate aminotransferase (AST) were lower in both groups and levels of total bilirubin and fractions had no differences. The SMOFlipid® 20% emulsion increased the levels of the docosahexaenoic acid (DHA) and eicosapentaenoic (EPA) acid in the erythrocytes membrane. Conclusions: In this group of preterm newborn infants, this new lipid emulsion, besides showing security, contributed to a beneficial change in the incorporation profile of fatty acids cell membranes, especially DHA and EPA.

Suplementação de ácidos graxos ômega-3, estado nutricional e qualidade de vida de pacientes com câncer gastrintestinal: estudo duplo-cego, randomizado e placebo controlado / Omega-3 fatty acid supplementation, nutritional statusand quality of life in patients with gastrointestinal cancer:double-blind, placebo-controlled, randomized study

Introdução: a caquexia do câncer é caracterizada pela perda ponderal, imunossupressão e está associada a pior prognóstico e qualidade de vida. Objetivos: avaliar o efeito da suplementação de ω-3 sobre o estado nutricional, capacidade funcional e qualidade de vida de pacientes com câncer gastrintestinal. Métodos: o grupo placebo (P) (n=10) recebeusete cápsulas de 1.000 mg de óleo de soja e o grupo suplemento (S) (n=11) sete cápsulas de 1.000 mg de óleo de peixe e linhaça contendo 214,3 mg de ácido eicosapentaenoico e 113,5 mg de docosahexaenoico, diariamente, por 14 dias. Foram avaliados peso, composição corporal, marcadores inflamatórios e imunológicos, capacidade funcional e qualidade de vida. Resultados: a média de variação de peso do grupo P antes e depois do tratamento foi de -0,44 ± 2,7 kg e do grupo S foi de 0,07 ± 1,4 kg, sem diferença estatística. A média de IMC da amostra foi de 20,5 ± 3,4 kg/m2. Houve significativa redução dos níveis séricos de proteínas totais (p=0,005) e albumina (p=0,011) para o grupo P; aumento dos níveis de proteína C reativa (PCR) (p=0,005) e redução da contagem total de linfócitos (p=0,037). Verificou-se aumento dos níveis séricos da transferrina do grupo S (p=0,010), bem como redução dos níveis de PCR (p=0,033) e da cortisolemia (p=0,020). Encontrou-se aumento para a Escala de Performance de Karnofsky (p=0,020) no grupo S. Não foram encontradas diferenças para status funcional, sintomas e saúde global. Conclusões: o presente estudo encontrou resultados que dão suporte à suplementação de ω-3 em Oncologia. No entanto, são necessárias mais investigações associando os ω-3 a outras estratégias terapêuticas.

Introduction: Cancer cachexia is characterized by weight loss, immunosuppression and is associated with worse prognosis and quality of life. Objectives: To evaluate the effect of ω-3 supplementation on nutritional status, functional capacity and quality of life of patients withgastrointestinal cancer. Methods: the placebo group (P) (n = 10) received seven 1,000 mg capsules of soybean oil and the supplement group (S) (n = 11) seven 1,000 mg capsules of fish oil and flaxseed containing 214.3 mg of eicosapentaenoic acid and 113.5 mg of docosahexaenoicacid daily for 14 days. We evaluated weight, body composition, inflammatory and immunological markers, functional capacity and quality of life. Results: The average weight variation of the P group before and after treatment was -0.44 ± 2.7 kg and of S group was 0.07 ± 1.4 kg, with no statistical difference. The average BMI of the sample was 20.5 ± 3.4 kg / m 2. There was a significant reduction of total serum protein (p = 0.005) and albumin (p = 0.011) in the P group; and an increase in levels of C-reactive protein (CRP) (p = 0.005) and decrease in total lymphocyte count (p = 0.037). An increase in serum transferdiagnósrin (p = 0.010) as well as a reduction in levels of CRP (p = 0.033) and cortisol (p = 0.020) were found in the S group. We found an increase for the Karnofsky Performance Scale (p = 0.020) in group S. No differences were foundfor functional status, symptoms, and overall health. Conclusions: The present study supports the supplementation of ω-3 in Oncology. However, more research is needed involving ω-3 and other therapeutic strategies.

Supplementation with the omega-3 docosahexaenoic acid: influence on the lipid composition and fatty acid profile of human milk / Suplementação com ácido graxo ômega-3 docosahexaenoico: influência sobre a composição lipídica e perfil de ácidos graxos no leite humano

OBJECTIVE: This study assessed the impact of supplementing the diet of women during pregnancy and lactation with fish oil containing the omega-3 fatty acid docosahexaenoic acid, and its influence on the composition of human milk. METHODS: The sample comprised 60 women aged 18 to 38 years with appropriate dietary pattern, all of them healthy and nonsmokers. The intervention consisted of a daily supplementation with fish oil capsules that corresponded to a daily intake of 315mg of docosahexaenoic acid and 80mg of eicosapentaenoic acid during the third trimester of pregnancy and the first three months postpartum. The total fat content and fatty acid profile of their milk were determined by creamatocrit and gas chromatography. Descriptive statistics were used for data analysis and the significance level was set at p<0.05. RESULTS: There was no statistical difference between the fat contents of the study (fish oil capsules) and control (capsules containing corn starch as filler) groups. However, the milk of women taking fish oil contained higher docosahexaenoic and eicosapentaenoic acid levels 30 and 60 days after delivery. These results demonstrate that high omega-3 intake can influence its concentration in human milk. CONCLUSIONS: Given the importance of docosahexaenoic acid in the neonatal period, it is appropriate for pregnant and breastfeeding women to supplement on long-chain polyunsaturated fatty acids, which may be done by adding fish oil to the regular diet.

OBJETIVO: Este estudo teve como objetivo avaliar o impacto da suplementação na dieta de gestantes e de lactantes com ácidos graxos ômega-3 docosahexaenoico, sob a forma de óleo de peixe, e sua influência na composição do leite humano. MÉTODOS: A amostra foi constituída de 60 gestantes, com idade entre 18 e 38 anos, saudáveis, com padrão alimentar adequado e não fumantes. A intervenção consistiu na suplementação da dieta com cápsulas de óleo de peixe, totalizando um consumo diário de 315mg de ácido docosahexaenoico e 80mg de ácido eicosapentaenoico, no período entre o terceiro trimestre de gravidez e o terceiro mês após o parto. O teor de lipídeos totais e do perfil de ácidos graxos foi determinado pelos métodos de crematócrito e de cromatografia gasosa. Para a análise dos dados foi utilizada estatística descritiva e nível de significância de p<0,05. RESULTADOS: Entre o grupo sujeito à dieta suplementada (cápsulas de óleo de peixe) e o grupo controle (cápsulas contendo amido de milho como excipiente), não se constatou diferença estatística quanto aos valores totais de lipídeos. Entretanto, no leite das mães do primeiro grupo, a suplementação com óleo de peixe mostrou teores mais elevados na concentração dos ácidos docosahexaenoico e eicosapentaenoico, nos tempos 30 e 60 dias, demonstrando que um maior consumo de ômega-3 pode influenciar na sua concentração no leite humano. CONCLUSÃO: Considerando a importância do ácido docosahexaenoico no período neonatal, é adequado incrementar com ácidos graxos poliinsaturados de cadeia longa a alimentação de gestantes e de lactantes, o que pode ocorrer pela suplementação da dieta com óleo de peixe.

Effects of omega-3 fatty acids on regulatory T cells in hematologic neoplasms

The development of leukemia and lymphomas is related to the increase in inflammatory process modulators. These, in turn, have divergent actions on the neoplastic process. Populations of T cells have different roles in the neoplastic environment; while interferon-gamma positive T cells have antitumor activity, the FoxP3+interleukin-10 positive population present a pro-tumor activity. Simultaneously, the inflammatory process promotes the mobilization of fatty acids from the cell membrane to produce lipid mediators, which also participate of the inflammatory response. Eicosapentaenoic (EPA) and docosahexaenoic (DHA) omega-3 fatty acids, when incorporated in the plasmatic membrane, decrease the arachidonic acid (AA) metabolism and the production of eicosanoids derived from it. Thus, an alternative family of lipid mediators are produced that are often less inflammatory than those produced from arachidonic acid. Fatty acids can also influence the production of peptide mediators such as cytokines, and the expression of transcription factors, which can determine the production patterns of eicosanoids and cytokines as well as cell differentiation. Due to these properties, the objective of this literature review was to investigate studies published over the last 15 years on the effects of using omega-3 fatty acids on inflammatory markers in leukemia and lymphomas.