Papel inmunomodulador de la vitamina D y los ácidos grasos poliinsaturados omega-3 en trastornos autoinmunes: Revisión de la Literatura / Immunomodulatory role of vitamin D and omega-3 polyunsaturated fatty acids in autoinmune disorders: Literature Review

Los trastornos autoinmunes representan una familia de al menos 80 condiciones diferentes que surgen de una respuesta aberrante del sistema inmunológico resultando finalmente en la destrucción de tejidos y órganos específicos del cuerpo. Es importante destacar que durante las últimas tres décadas los estudios epidemiológicos han proporcionado evidencia de un aumento constante en la incidencia y prevalencia de trastornos autoinmunes. En los últimos años, varios estudios han demostrado que la vitamina D y los ácidos grasos poliinsaturados (AGPs) omega-3 ejercen propiedades inmunomoduladoras y antiinflamatorias sinérgicas que pueden aprovecharse positivamente para la prevención y el tratamiento de trastornos autoinmunes. En este sentido, el reciente ensayo clínico denominado VITAL (ensayo de vitamina D y omega 3); un estudio a gran escala, aleatorizado, doble ciego, controlado con placebo encontró que la suplementación conjunta de vitamina D y AGPs omega-3 (VIDOM) puede reducir la incidencia de enfermedades autoinmunes. En esta revisión de la literatura, resumimos los mecanismos moleculares detrás de las propiedades inmunomoduladoras y antiinflamatorias de la vitamina D y los AGPs omega-3, así como la posible interacción bidireccional entre el metabolismo de la vitamina D y el metabolismo de los AGPs omega-3 que justifica la co- suplementación VIDOM en trastornos autoinmunes(AU)

Autoimmune disorders represent a family of at least 80 different conditions that arise from an aberrant immune system response, which ultimately results in the destruction of specific body tissues and organs. It is important to highlight that during the last three decades epidemiological studies have provided evidence of a steady increase in the incidence and prevalence of autoimmune disorders. In recent years, several studies have shown that vitamin D and omega-3 polyunsaturated fatty acids (PUFAs) exert synergistic immunomodulatory and anti-inflammatory properties that can be positively harnessed for the prevention and treatment of autoimmune disorders. In this sense, the recent clinical trial called VITAL (Vitamin D and Omega 3 trial) - a large, randomized, double-blind, placebo- controlled study - found that co-supplementation of vitamin D and omega-3 PUFAs (VIDOM) can reduce the incidence of autoimmune diseases. In this literature review, we summarize the molecular mechanisms behind the immunomodulatory and anti-inflammatory properties of vitamin D and omega-3 PUFAs, as well as the possible bidirectional interaction between vitamin D metabolism and omega-3 PUFA metabolism that justifies VIDOM co- supplementation in autoimmune disorders(AU)

Fish Oil Improves Dysbiosis of Host-microbial Interaction and Maintains Remission in Colitis Mice / 中国生物化学与分子生物学报

n-3 polyunsaturated fatty acids (PUFAs) play an active role in controlling the progression of ulcerative colitis (UC), but its mechanism is not very clear. In this study, we compared the effects of fish oil (the main component is n-3 PUFAs) in the mouse model with acute and chronic colitis induced by dextran sulfate sodium (DSS). Male C57BL/6J mice were randomly divided into six groups, and each group had ten mice. The alleviating effect of fish oil on chronic colitis was significantly better than acute colitis as indicated by the following analysis: the weight loss of mice (P < 0. 05), decreased disease activity index (DAI) score (P<0. 05), colonic edema, colon length index and histopathological score (P < 0. 05), and serum pro-inflammatory factor levels like IL-1β, TNF-α, and IL-6 (P < 0. 01). Moreover, fish oil promoted the level of serum anti-inflammatory factor IL-10 (P<0. 05). The treatment of fish oil increased the n-3 PUFA concentration in the intestinal epithelium of mice (P < 0. 01), especially EPA (P<0. 05). 16S rRNA sequencing of feces revealed that fish oil significantly increased the relative abundance of butyrate-producing flora (Clostridiales) and probiotics (Bifidobacteriales) in the feces of the maintained remission model group, reduce the proportion of aerobic, parthenogenic anaerobic and pathogenic, and improved the disorder of glycan biosynthesis and metabolism and oxidative phosphorylation (P<0. 05). Compared with the induced remission fish oil group, fish oil treatment led to an elevated expression of mechanical barrier and energy metabolism pathway proteins in the maintained remission fish oil group. Our results showed that fish oil exerted a more potent inhibitory effect in the remission mice model, which may be related to effectively strengthening the mechanical barrier, improving the composition and function of intestinal microbiota and concentration of butyric acids and improving dysbiosis of host-microbial interaction.

The immunoregulatory effect of co-3 polyunsaturated fatty acids on lymphocyte in cGVH mice / 中国药理学通报

Aim To investigate the effect of dietary intake of o)-3 poly unsaturated fatty acids ( u>-3 PUFAs) on the immune function of chronic graft versus host disease (cGVH) lupus model mice.Methods A single intraperitoneal injection of bml2 mice lymphocytes was used to establish a cGVH mouse model.On the day of modeling, 90% cd-3 PUFAs and 97% EPA were given by gavage for 14 days.The immune indexes of mice were evaluated by flow cytometry, and the serum total J J J ∗ IgG levels were measured by ELISA.Results Compared with control group, cGVH group significantly down-regulated Treg subsets, and up-regulated the Tfh , GC B and plasma subsets in the lupus mice.Comparer] with model control group, u>-3 PUFAs could significantly elevate Treg subsets, and decrease TFH, (X] B, and plasma subsets; serum total IgG levels in the 97% EPA group were significantly reduced.Conclusion In the cGVH lupus mouse model, co-3 PUFAs can suppress some immune functions by increasing Treg cells, reducing TFH, GC B, plasma cells and inhibiting the secretion of IgG.Such immunomodulatory effect provides new sights into the development of a potentially novel treatment modality for cGVH.

Effects of ω-3 Polyunsaturated Fatty Acids on Biophysical Properties and Migration of Dendritic Cells / 医用生物力学

Objective From the perspective of biophysics and immunology, the effects of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) on biophysical characteristics, cytoskeleton and migration ability of mouse derived dendritic cells (DCs) were analyzed, so as to explore the effect of ω-3 polyunsaturated fatty acids (ω-3 PUFAs) on immune function of DCs and its potential mechanism. Methods The bone marrow-derived monocytes from C57BL/6J mice were isolated and induced to differentiate into immature dendritic cells (imDCs) by 20 ng/mL recombinant murine granulocyte-macrophage colony-stimulating factor (rmGM-CSF) and 10 ng/mL recombinant mouse interleukin-4 (rmIL-4), After 6 days, 100 ng/mL lipopolysaccharide was added to induce mature dendritic cells (mDCs). Further the morphological observation and positive rate of CD11c in imDCs and mDCs were analyzed, Then at different concentrations of EPA and DHA (0-60 μmol/L), the cell viability and apoptosis of DCs were detected by cell counting kit-8 (CCK-8) kit and flow cytometry. After the optimal concentration of EPA and DHA were determined, the changes of the membrane fluidity, electrophoretic mobility (EPM) and osmotic fragility of DCs were separately detected by the fluorescence polarization, cell electrophoresis and concentration gradient. The expression of filamentous actin (F-actin) was detected by the immunofluorescence. Finally, the migration ability of DCs was detected by the Transwell system. Results The positive rate of CD11c in DCs was about 80%. The viability of DCs decreased in a dose-dependent manner under the action of EPA and DHA of different concentrations, which didn’t induce the apoptosis of DCs. Under the action of 50 μmol/L EPA and DHA, the osmotic fragility and EPM of DCs significantly decreased, and the membrane fluidity significantly increased. The expression of F-actin in DCs obviously increased, and the migration rate of cells obviously decreased. Conclusions ω-3 PUFAs may affect the cytoskeleton structure and biophysical characteristics of DCs, inhibit the migration, and then affect its immune function.

Potentials of Immunonutrition in Wound Healing: A Review (Potensi Imunonutrisi dalam Penyembuhan Luka: Tinjauan) / Jurnal Sains Kesihatan Malaysia

@#A delayed wound healing process can lead to detrimental complications in chronic wound patients such as tissue necrosis and systemic infections. Application of immunonutrition (IN) in experimental animal models and chronic wound patients has shown promising and improved wound healing processes. IN restores the supply of essential nutrients that are critical for cell growth and tissue repair in the wounded subjects. Several commonly found nutrients in IN formulations include polyunsaturated fatty acids (PUFAs), essential amino acids, trace elements such as zinc and vitamins. Recently, some studies suggested the use of traditionally used herbs like curcumin in IN recipes due to its efficient wound healing properties. The roles and functions of IN in wound healing encompass recruitment of white blood cells, platelets and fibroblasts into the wounded area during the coagulation and inflammation phases, enhancement of fibroblast proliferation, collagen synthesis and neovascularization in the proliferation phase; and lastly, regulation of tissue re-epithelization for wound closure and recovery. In this review, the roles and functions of individual nutrients were deliberately discussed alongside their mechanisms of action in wound healing. This aims to provide a more holistic insight into the potentials of those nutrients when used as part of IN for major wound patients. Despite its remarkable effects in wound healing, several criteria should be considered in an IN formulation: the type and severity of wounds, administration timing and mode of administration, and concoction of immune-boosting nutrients in order to ensure the optimal wound healing effects.

Construction of transgenic mice with Δ15 Des enzyme activity by using a PiggyBac transposon / 生物工程学报

Essential fatty acids are those that could not be synthesized by the body itself but crucial for health and life. Studies have shown that ω-3 fatty acids may facilitate human physiological functions. Mammals lack ω-3 desaturase gene, and the Δ15 fatty acid desaturase (Δ15 Des) from Caenorhabditis elegans can transform the ω-6 polyunsaturated fatty acids (PUFAs) into ω-3 PUFAs. Transgenic mice expressing Δ15 Des enzyme activity was constructed by using a PiggyBac transposon (PB). Homozygous transgenic mice with stable inheritance was bred in a short time, with a positive rate of 35.1% achieved. The mice were fed with 6% ω-6 PUFAs and the changes of fatty acids in mice were detected by gas chromatography (GC). The expression level of Δ15 Des in mice was detected by quantitative PCR (qPCR) and Western blotting (WB). qPCR and GC analysis revealed that the percentage of positive mice harboring the active gene was 61.53%. Compared with traditional methods, the transformation efficiency and activity of Δ15 Des were significantly improved, and homozygotes showed higher activity than that of heterozygotes. This further verified the efficient transduction efficiency of the PiggyBac transposon system.

Acción de flavonoides sobre la conversión de ácidos grasos poliinsaturados de cadena larga a partir de ácidos grasos esenciales / Action of flavonoids on conversion of long chain polyunsaturated fatty acids from essential fatty acids

RESUMEN Estudios epidemiológicos y clínicos han reportado múltiples beneficios a partir de la ingesta de ácidos grasos poliinsaturados de cadena larga n-3 (AGPI-CL n-3) EPA (ácido eicosapentaenoico) y DHA (ácido docosahexaenoico), sin embargo, la sobreexplotación de los recursos marinos limita su disponibilidad actual y futura. El ácido alfa-linolénico (ALA) es precursor metabólico de AGPI-CL n-3, por tanto su consumo es una alternativa a considerarse. No obstante, la conversión de ALA hacia EPA y DHA no es eficiente. Por otra parte, antioxidantes como los flavonoides incrementan la concentración sérica y tisular de AGPI-CL n-3, aunque los mecanismos subyacentes no están completamente dilucidados. Se explora la acción de los AGPI y flavonoides sobre el metabolismo de los AGPI-CL n-3, al modular factores de transcripción como los proliferadores de peroxisomas alfa (PPAR-α), la proteína de unión a los elementos regulatorios de esteroles (SREBP-1) y la expresión génica de las enzimas ácido graso desaturasas delta 5 (Δ5) y delta 6 (Δ6). También se recogen otras hipótesis que explicarían el incremento de AGPI n-3, como la acción antioxidante ejercida por los flavonoides y sus metabolitos.

ABSTRACT Epidemiological and clinical studies have reported multiple benefits from the intake of Long Chain Polyunsaturated Fatty Acids n-3 (LC-PUFA n-3), EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid); however, overexploitation of marine sources limits current and future availability. The alpha-linolenic acid (ALA) is a metabolic precursor of PUFAs n-3-LC, therefore its consumption is an alternative to be considered. However, the conversion of ALA to EPA and DHA is not efficient. On other hand, antioxidants such as flavonoids increase serum and tissue concentration of PUFA LC n-3, although the underlying mechanisms are not fully elucidated. The effect of PUFAs and flavonoids on metabolism PUFAs n-3 LC. to modulate transcription factors such as peroxisome proliferators alpha receptor (PPAR-α), the sterol regulatory element-binding protein, (SREBP 1) and genic expression of fatty acid desaturase enzymes delta 5 (Δ5) and delta 6 (Δ6) was explored. Other hypotheses that could explain the increase of n-3 PUFAs were also included such as antioxidant action, exerted by flavonoids and their metabolites.

Effect of ω-3PUFAs on cognitive deficit in rats with schizophrenia / 中华行为医学与脑科学杂志

Objective To investigate the antagonistic effect of ω-3PUFAs on cognitive impairment in MK-801-induced schizophrenia (SZ) rats and its mechanism.Methods Rat model of schizophrenia was induced by MK-801.Morris water maze was used to detect the change of cognitive function in rats.The number of neonatal neurons in hippocampus was detected by Brdu staining.CREB,p-CREB,BDNF,TrkB and p-TrkB levels were detected by Weston Blot.Results MK-801 induced schizophrenia-like cognitive impairment (the escape latency in the water maze test was (6.51±3.10)s for Ctr group,(15.27±6.20)s for Mod group;acrossing times was (4.63±1.06) times for Ctr group,(2.00±1.15) times for Mod group),reduced the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area,Mod/Ctr was 0.656±0.066) and impaired the CREB/BDNF/TrkB pathway (the relative level of gray value,Mod/Ctr:CREB was 0.393±0.065,p-CREB was 0.591±0.015,BDNF was 0.716±0.115,TrkB was 0.787±0.029,p-TrkB was 0.586±0.013).ω-3PUFAs improved the CREB/BDNF/TrkB pathway activity by increasing CREB and TrKB level and their phosphorylation (the relative level of gray value,Pre/Ctr:CREB was 1.139±0.111,p-CREB was 0.845±0.243,BDNF was 0.864±0.133,TrkB was 0.916±0.022,p-TrkB was 0.952±0.047),and then recovered the number of neonatal neurons in hippocampus (the relative level of neonatal neuron number per unit area,Pre/ Ctr was 1.183±0.101),thereby reduced the cognitive dysfunction in schizophrenia rats(the escape latency in the water maze was (7.44±4.55)s for Pre;acrossing times was (3.86±1.68) times for Pre).Conclusion ω-3PUFAs can relieve the MK-801-induced schizophrenia-like cognitive impairment.

Effect of dietary n-3 Polyunsaturated Fatty Acids on Bony Remodeling during Eruptive Tooth Movement

The aim of this study was to investigate the effect of n-3 polyunsaturated fatty acids (PUFAs) on eruptive movement during tooth development. Sprague-Dawley (SD) rat pups were randomly divided into two groups; control group and experimental group. The experimental group was administered daily with n-3 PUFA by intraperitoneal (IP) injection. After 10 days postpartum, rat pups were sacrificed to evaluate the effect of n-3 PUFA on eruptive tooth movement. Histological analyses were by hematoxylin-eosin (H&E) staining. Tartrate-resistant acid phosphatase (TRAP) assay was performed to compare the osteoclast distribution in the bone matrix above the developing molar teeth. Incisor teeth eruptions were noticeably observed in IP group, as compared to control group. Rat pups in IP group showed faster tooth eruption on day 8 after birth. Through histological analyses, IP group showed thinner bone matrix and more osteoclasts above the 1st molar teeth, as compared to control group. TRAP assay showed significantly stronger stained pattern that the osteoclast above the 1st molar teeth in IP group, as compared to control group. The results suggested that n-3 PUFA could affect osteoclastic activity involved in bony remodeling during eruptive tooth movement.

Effects of ω-3 polyunsaturated fatty acids on the proliferation of human gastric cancer cell line AGS / 西安交通大学学报(医学版)

ABSTRACT:Objective To investigate the effects of ω-3 polyunsaturated fatty acids on the proliferation of human gastric cancer cell line AGS and the possible mechanisms.Methods Human gastric cancer line AGS and human microvascular epithelial cell HMEC-1 were treated with different concentrations of docosdhexaenoic acid (DHA)and eicosapentaenoic acid (EPA).The inhibition of cell proliferation was evaluated by MTT assay and cell morphology.Flow cytometry was used to detect the cell cycle change.The expressions of mitochondrial respiratory membrane protein complex Ⅰ,Ⅱ and V were analyzed with Western blot.Results DHA and EPA could markedly inhibit the proliferation of AGS in significant time-dependent and concentration-dependent manners (P 0.05).Conclusion ω-3 PUFAs can selectively inhibit the growth and proliferation of human gastric cancer cell line AGS.These effects may be as-sociated with arresting cell cycle in G0/G1 phase and inhibiting the energy metabolism of AGS cells.

Association between fish and shellfish, and omega-3 PUFAs intake and CVD risk factors in middle-aged female patients with type 2 diabetes

BACKGROUND/OBJECTIVES: This study was performed to investigate the association between the dietary intake of fish and shellfish, and omega-3 polyunsaturated fatty acids (PUFAs) and cardiovascular disease (CVD) risk factors in the middle-aged Korean female patients with Type 2 diabetes (T2D). SUBJECTS/METHODS: A cross-sectional analysis was performed with 356 female patients (means age: 55.5 years), who were recruited from the Huh's Diabetes Clinic in Seoul, Korea between 2005 and 2011. The dietary intake was assessed by a validated semi-quantitative food frequency questionnaire and analyzed using the Computer Aided Nutritional Analysis program (CAN-Pro) version 4.0 software. RESULTS: In a multiple regression analysis after the adjustment for confounding factors such as age, BMI, duration of diagnosed T2D, alcohol consumption, fiber intake, sodium intake, and total energy intake, fish and shellfish intake of the subjects was negatively associated with triglyceride and pulse wave velocity (PWV). Omega-3 PUFAs intake was negatively associated with triglyceride, systolic blood pressures, diastolic blood pressures, and PWV. The multiple logistic regression analysis with the covariates showed a significant inverse relationship between the omega-3 PUFAs consumption and prevalence of hypertriglyceridemia [OR (95% CI) for greater than the median compared to less than the median: 0.395 (0.207-0.753)]. CONCLUSIONS: These results suggest that the consumption of fish and shellfish, good sources of omega-3 PUFAs, may reduce the risk factors for CVD in the middle-aged female patients with T2D.

Nutritional support with ω-3 polyunsaturated fatty acids in patients undergoing hepatectomy / 国际外科学杂志

Objective By comparing the therapeutic effects of different nutrition support,to elementarily evaluate the protocol of nutrition support with ω-3 polyunsaturated fatty acids in patients undergoing hepatectomy.Methods Retrospective and comparative analysis was applied.From January 2009 to January 2011,82 patients undergoing liver resection were selected from Nanjing Drum Tower Hospital and divided into three groups according to different nutrition supporting protocol:total parenteral nutrition group (23,TPN for short),combined enteral nutrition group (30,EN for short),ω-3 PUFAs group (29).TPN group was given total parenteral nutrition.EN group was given both parenteral and enteral nutrition.ω-3 PUFAs group was given parenteral nutrition,enteral nutrition and ω-3 PUFAs.By comparing the general situation,the incidence of post-operation complications and index of liver function,the effect of different nutrition supporting plans could be comprehensively evaluated.Results (1) None patients from any groups had severe complications such as bile leakage and hemobilia.Slight complications included ascites and pleural effusion.No difference is of significance in statistics science.(2) Compared with TPN group,patients from EN and ω-3 PUFAs group had shorter defecating time and post-surgery hospital stay,the difference is of significance in statistics science (P =0.001,t =4.624; P =0.001,t =5.019).There was no significant difference between EN and ω-3 PUFAs group (P ＞ 0.05).(3) For patients received operation with major hepatectomy (≥4 segments),ALT in ω-3 PUFAs group was lower than EN group in the 3rd and 5th day after operation (P=0.024,t =2.432; P=0.042,t =2.144).(4) For patients with cirrhosis,TB in ω-3 PUFAs group was lower than EN group in the 3rd and 5th day after operation (P =0.032,t =2.202; P =0.035,t =2.183).Conclusions It is beneficial to use nutritional support in patients received hepatectomy.For patients received major hepatectomy and patients with cirrhosis,nutrition support with ω-3 PUFAs had better protective effects.

Effects of ?-3 polyunsaturated fatty acids on bone biomechanics in ovariectomized rats / 肠外与肠内营养

Objective:To explore the benefit effects of ?-3 polyunsaturated fatty acids on bone biomechanics in ovariectomized(OVX) rats.Methods: 60 virgin female Sprague-Dawley rats were randomized by the stratified weight method into 6 groups: ① Sham group:deionized water 2 mL/d;②OVX group:deionized water 2 mL/d;③E2 group: OVX +17?-ethinylestradiol 0.1 mg/(kg?d);④ A group: OVX+?-3 PUFAs 75 mg/(kg?d);⑤B group: OVX+?-3 PUFAs 150 mg/(kg?d);⑥ C group: OVX+?-3 PUFAs 300 mg/(kg?d).Each group had 10 rats.After feeding for 90 days,the rats were killed and femur were separated.The maximum load,maximum deformation,elastic load,elastic deformation and energy absorption were measured from three point bending test.Bone wet weights were measured.Result: The femur biomechanics markers of OVX group decreased obviously,while that of all medicated group increased obviously(P