Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 11.054
Filter
1.
Lipids Health Dis ; 23(1): 214, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982376

ABSTRACT

Omega-3 polyunsaturated fatty acids (n-3 PUFAs), mainly including α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), possess antioxidant properties and play a crucial role in growth and development. However, the combined effects of ALA, EPA, and DHA at different concentrations have rarely been reported. This work explored the effects of EPA, ALA, and DHA on the viability and antioxidant capacity of mouse hepatocytes, with the objective of enhancing the antioxidant capacity. Within the appropriate concentration range, cell viability and the activity of glutathione S-transferase, superoxide dismutase, and catalase were increased, while the oxidation products of malondialdehyde and the level of intracellular reactive oxygen species were obviously reduced. Thus, oxidative stress was relieved, and cellular antioxidant levels were improved. Finally, response surface optimization was carried out for EPA, ALA, and DHA, and the model was established. The antioxidant capacity of the cells was highest at EPA, ALA, and DHA concentrations of 145.46, 405.05, and 551.52 µM, respectively. These findings lay the foundation for further exploration of the interactive mechanisms of n-3 PUFAs in the body, as well as their applications in nutraceutical food.


Subject(s)
Antioxidants , Cell Survival , Docosahexaenoic Acids , Eicosapentaenoic Acid , Fatty Acids, Omega-3 , Hepatocytes , Oxidative Stress , Reactive Oxygen Species , Superoxide Dismutase , Animals , Mice , Hepatocytes/metabolism , Hepatocytes/drug effects , Antioxidants/pharmacology , Antioxidants/metabolism , Oxidative Stress/drug effects , Fatty Acids, Omega-3/pharmacology , Eicosapentaenoic Acid/pharmacology , Docosahexaenoic Acids/pharmacology , Reactive Oxygen Species/metabolism , Cell Survival/drug effects , Superoxide Dismutase/metabolism , Catalase/metabolism , Malondialdehyde/metabolism , alpha-Linolenic Acid/pharmacology , Glutathione Transferase/metabolism
2.
Int J Mol Sci ; 25(13)2024 Jun 28.
Article in English | MEDLINE | ID: mdl-39000257

ABSTRACT

Lipid mediators from fatty acid oxidation have been shown to be associated with the severity of Krabbe disease (KD), a disorder linked to mutations in the galactosylceramidase (GALC) gene. This study aims to investigate the effects of n-3 polyunsaturated fatty acid (PUFA) supplementation on KD traits and fatty acid metabolism using Twitcher (Tw) animals as a natural model for KD. Wild-type (Wt), heterozygous (Ht), and affected Tw animals were treated orally with 36 mg n-3 PUFAs/kg body weight/day from 10 to 35 days of life. The end product of PUFA peroxidation (8-isoprostane), the lipid mediator involved in the resolution of inflammatory exudates (resolvin D1), and the total amount of n-3 PUFAs were analyzed in the brains of mice. In Tw mice, supplementation with n-3 PUFAs delayed the manifestation of disease symptoms (p < 0.0001), and in the bran, decreased 8-isoprostane amounts (p < 0.0001), increased resolvin D1 levels (p < 0.005) and increased quantity of total n-3 PUFAs (p < 0.05). Furthermore, total brain n-3 PUFA levels were associated with disease severity (r = -0.562, p = 0.0001), resolvin D1 (r = 0.712, p < 0.0001), and 8-isoprostane brain levels (r = -0.690, p < 0.0001). For the first time in a natural model of KD, brain levels of n-3 PUFAs are shown to determine disease severity and to be involved in the peroxidation of brain PUFAs as well as in the production of pro-resolving lipid mediators. It is also shown that dietary supplementation with n-3 PUFAs leads to a slowing of the phenotypic presentation of the disease and restoration of lipid mediator production.


Subject(s)
Brain , Dietary Supplements , Disease Models, Animal , Fatty Acids, Omega-3 , Leukodystrophy, Globoid Cell , Animals , Mice , Fatty Acids, Omega-3/metabolism , Fatty Acids, Omega-3/pharmacology , Fatty Acids, Omega-3/administration & dosage , Brain/metabolism , Brain/drug effects , Leukodystrophy, Globoid Cell/diet therapy , Leukodystrophy, Globoid Cell/metabolism , Leukodystrophy, Globoid Cell/drug therapy , Leukodystrophy, Globoid Cell/genetics , Phenotype , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/metabolism , Lipid Metabolism/drug effects , Dinoprost/analogs & derivatives , Dinoprost/metabolism , Male
3.
Nutrients ; 16(13)2024 Jun 27.
Article in English | MEDLINE | ID: mdl-38999781

ABSTRACT

BACKGROUND: Epidemiological studies have shown that fatty acids, especially polyunsaturated fatty acids (PUFAs), influence colorectal carcinogenesis. Colon polyps, particularly those identified as precancerous, are a frequently encountered phenomenon associated with PUFAs. However, the results are inconsistent. Therefore, we investigated the effect of PUFAs on colon polyps in individuals of European ancestry. METHODS: Single nucleotide polymorphisms correlating with PUFAs and colon polyps were derived from extensive genome-wide association studies, encompassing a discovery cohort of 135,006 samples and a corresponding validation set with 114,999 samples. Causality was assessed by employing a range of techniques, such as inverse variance weighted (IVW), weighted median, MR-Egger, and simple and weighted modes. The analysis was complemented with sensitivity checks using leave-one-out and heterogeneity evaluation through MR-IVW and Cochran's Q. RESULTS: A thorough analysis was performed to examine the causal effects of PUFAs on the development of colon polyps. The findings indicated that levels of Omega-3 fatty acids (OR = 1.0014, 95% CI 1.0004-1.0024, p = 0.004), the ratio of Docosahexaenoic acid (DHA)/total fatty acids (FAs) (DHA/totalFA; OR = 1.0015, 95% CI 1.0002-1.0028, p = 0.023), and the ratio of Omega-3/totalFA (Omega-3/totalFA; OR = 1.0013, 95% CI 1.0003-1.0022, p = 0.010) were identified as biomarkers associated with an increased risk of colon polyps. Conversely, the ratio of Omega-6/Omega-3 (OR = 0.9986, 95% CI 0.9976-0.9995, p = 0.003) and the ratio of Linoleic acid (LA)/totalFA (LA/totalFA; OR = 0.9981, 95% CI 0.9962-0.9999, p = 0.044) were negatively associated with susceptibility to colon polyps. The MR-Egger and MR-IVW analysis revealed that pleiotropy and heterogeneity did not significantly impact the outcomes. CONCLUSION: This study has uncovered a possible adverse effect of PUFAs, notably Omega-3, on the formation of colon polyps. Elevated Omega-3 levels were correlated with a heightened risk of colon polyps.


Subject(s)
Colonic Polyps , Fatty Acids, Unsaturated , Genome-Wide Association Study , Mendelian Randomization Analysis , Polymorphism, Single Nucleotide , Humans , Colonic Polyps/genetics , Fatty Acids, Omega-3 , Risk Factors , Male , White People/genetics , Female , Docosahexaenoic Acids
4.
Nutrients ; 16(13)2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38999828

ABSTRACT

This study aimed to investigate a synergistic anti-inflammatory effect of a citrus flavonoid nobiletin and docosahexaenoic acid (DHA), one of n-3 long-chain polyunsaturated fatty acids, in combination. Simultaneous treatment with nobiletin and DHA synergistically inhibited nitric oxide production (combination index < 0.9) by mouse macrophage-like RAW 264.7 cells stimulated with lipopolysaccharide (LPS) without cytotoxicity. On the other hand, the inhibitory effect of nobiletin and DHA in combination on proinflammatory cytokine production was not synergistic. Neither nobiletin nor DHA affected the phagocytotic activity of RAW 264.7 cells stimulated with LPS. Immunoblot analysis revealed that the inhibition potency of DHA on the phosphorylation of ERK and p38 and nuclear translocation of NF-κB is markedly enhanced by simultaneously treating with nobiletin, which may lead to the synergistic anti-inflammatory effect. Overall, our findings show the potential of the synergistic anti-inflammatory effect of nobiletin and DHA in combination.


Subject(s)
Anti-Inflammatory Agents , Docosahexaenoic Acids , Drug Synergism , Flavones , Lipopolysaccharides , Macrophages , Nitric Oxide , Animals , Mice , Flavones/pharmacology , Lipopolysaccharides/pharmacology , RAW 264.7 Cells , Anti-Inflammatory Agents/pharmacology , Docosahexaenoic Acids/pharmacology , Nitric Oxide/metabolism , Macrophages/drug effects , Macrophages/metabolism , NF-kappa B/metabolism , Phosphorylation/drug effects , Phagocytosis/drug effects , Cytokines/metabolism , p38 Mitogen-Activated Protein Kinases/metabolism
5.
Nutrients ; 16(13)2024 Jul 05.
Article in English | MEDLINE | ID: mdl-38999896

ABSTRACT

BACKGROUND: During pregnancy, the demand for omega-3 fatty acids, notably docosahexaenoic acid (DHA), escalates for both maternal and foetal health. Insufficient levels can lead to complications and can affect foetal development. This study investigated omega-3 status and its relation to dietary intake in pregnant Latvian women, along with its impact on gestational duration and newborn birth weight. METHODS: The study comprised 250 pregnant and postpartum women with a mean age of 31.6 ± 4.8 years. Nutrition and omega-3 supplementation data were collected through a questionnaire covering 199 food items and 12 supplements. Fatty acids in erythrocyte membrane phospholipids were analysed via gas chromatography with flame ionization detection. RESULTS: The median omega-3 fatty acid intake, including eicosapentaenoic acid (EPA) and DHA from diet and supplements, was 0.370 g/day, which is deemed sufficient. However, the median weekly fish intake (126.0 g) and daily nut/seed intake (7.4 g) were insufficient. The median omega-3 supplement intake was 1.0 g/day. No correlation between omega-3 supplement intake and the omega-3 index was observed. There was a weak correlation between the DHA intake from fish and the omega-3 index (r = 0.126, p = 0.047), while a significant correlation between the total EPA and DHA intake from various sources and the omega-3 index was noted (r = 0.163, p = 0.01). Most women (61.6%) had an omega-3 index < 4%, while 34.8% had an index between 4 and 8%, and only 3.6% had an index > 8%. Notably, significant differences in EPA levels and the omega-3 index were found among respondents with differing infant birth weights (p < 0.05). CONCLUSIONS: The omega-3 intake during pregnancy adheres to the established guidelines, although fish consumption remains insufficient. A preconception evaluation of the omega-3 index is advocated to optimize prenatal intake. The indications suggest potential correlations between EPA levels, the omega-3 index, and infant birth weight.


Subject(s)
Birth Weight , Dietary Supplements , Fatty Acids, Omega-3 , Humans , Female , Pregnancy , Fatty Acids, Omega-3/administration & dosage , Adult , Infant, Newborn , Gestational Age , Docosahexaenoic Acids/administration & dosage , Maternal Nutritional Physiological Phenomena , Diet , Eicosapentaenoic Acid/administration & dosage , Nutritional Status , Young Adult
6.
Int J Mol Sci ; 25(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38999927

ABSTRACT

Docosahexaenoic acid (DHA, C22:6 ω3) may be involved in various neuroprotective mechanisms that could prevent Alzheimer's disease (AD). Its influence has still been little explored regarding the dysfunction of the endolysosomal pathway, known as an early key event in the physiopathological continuum triggering AD. This dysfunction could result from the accumulation of degradation products of the precursor protein of AD, in particular the C99 fragment, capable of interacting with endosomal proteins and thus contributing to altering this pathway from the early stages of AD. This study aims to evaluate whether neuroprotection mediated by DHA can also preserve the endolysosomal function. AD-typical endolysosomal abnormalities were recorded in differentiated human SH-SY5Y neuroblastoma cells expressing the Swedish form of human amyloid precursor protein. This altered phenotype included endosome enlargement, the reduced secretion of exosomes, and a higher level of apoptosis, which confirmed the relevance of the cellular model chosen for studying the associated deleterious mechanisms. Second, neuroprotection mediated by DHA was associated with a reduced interaction of C99 with the Rab5 GTPase, lower endosome size, restored exosome production, and reduced neuronal apoptosis. Our data reveal that DHA may influence protein localization and interactions in the neuronal membrane environment, thereby correcting the dysfunction of endocytosis and vesicular trafficking associated with AD.


Subject(s)
Alzheimer Disease , Docosahexaenoic Acids , Endosomes , Lysosomes , Neurons , rab5 GTP-Binding Proteins , Humans , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/metabolism , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , rab5 GTP-Binding Proteins/metabolism , Endosomes/metabolism , Neurons/metabolism , Neurons/pathology , Neurons/drug effects , Lysosomes/metabolism , Cell Line, Tumor , Amyloid beta-Protein Precursor/metabolism , Apoptosis , Neuroprotective Agents/pharmacology , Cell Survival/drug effects
7.
Nat Commun ; 15(1): 5571, 2024 Jul 02.
Article in English | MEDLINE | ID: mdl-38956041

ABSTRACT

Statin drugs lower blood cholesterol levels for cardiovascular disease prevention. Women are more likely than men to experience adverse statin effects, particularly new-onset diabetes (NOD) and muscle weakness. Here we find that impaired glucose homeostasis and muscle weakness in statin-treated female mice are associated with reduced levels of the omega-3 fatty acid, docosahexaenoic acid (DHA), impaired redox tone, and reduced mitochondrial respiration. Statin adverse effects are prevented in females by administering fish oil as a source of DHA, by reducing dosage of the X chromosome or the Kdm5c gene, which escapes X chromosome inactivation and is normally expressed at higher levels in females than males. As seen in female mice, we find that women experience more severe reductions than men in DHA levels after statin administration, and that DHA levels are inversely correlated with glucose levels. Furthermore, induced pluripotent stem cells from women who developed NOD exhibit impaired mitochondrial function when treated with statin, whereas cells from men do not. These studies identify X chromosome dosage as a genetic risk factor for statin adverse effects and suggest DHA supplementation as a preventive co-therapy.


Subject(s)
Docosahexaenoic Acids , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Mitochondria , X Chromosome , Animals , Female , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Male , Mice , Mitochondria/drug effects , Mitochondria/metabolism , Humans , X Chromosome/genetics , Docosahexaenoic Acids/pharmacology , Induced Pluripotent Stem Cells/metabolism , Induced Pluripotent Stem Cells/drug effects , Gene Dosage , Mice, Inbred C57BL , Blood Glucose/metabolism , Blood Glucose/drug effects , Glucose/metabolism , Diabetes Mellitus/genetics , Diabetes Mellitus/chemically induced , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism
8.
Trop Anim Health Prod ; 56(6): 190, 2024 Jun 29.
Article in English | MEDLINE | ID: mdl-38949740

ABSTRACT

This study aimed to evaluate and analyze the effects of a flushing diet containing Docosahexaenoic acid (DHA) and Eicosapentaenoic acid (EPA) from Lemuru (Sardinella sp) fish oil on the reproductive performance parameters of Garut ewes. Forty (n = 40) primiparous Garut ewes aged 12-14 months with an average body weight of 28.92 ± 4.94 kg were assigned into four experimental treatment groups. The experimental diets contained roughage: concentrate (30:70%) designated as control concentrate (CNT), flushing concentrate with 6% palm oil (PO), flushing concentrate with 3% palm oil mixed with 3% lemuru oil as DHA and EPA sources (PFO), and flushing concentrate with the addition of 6% lemuru oil (FO). Treatment animals were fed two weeks before and after conception and parturition (8 weeks of total flushing treatment). The addition of fish oil at either 3% (PFO) or 6% (FO) resulted in significantly higher reproductive performance of ewes by increasing the litter size, as reflected by the birth of multiple kids (P < 0.05) compared to CNT and PO. Adding fish oil (PFO and FO) also maintains gestation, resulting in increased lamb yield, especially in the FO treatment, which yields the highest lamb yield (0% single lamb birth). The lamb male ratio was also higher with fish oil supplementation (PFO and PO) (P < 0.05). This research revealed a positive effect of 6% Lemuru oil on decreasing embryo loss and increasing the proportion of twin births. These findings thus support the hypothesis that ration flushing with double the required DHA and EPA from 6% Lemuru fish oil (FO) resulted in significantly higher reproductive performance in Garut sheep.


Subject(s)
Animal Feed , Docosahexaenoic Acids , Eicosapentaenoic Acid , Fish Oils , Animals , Female , Eicosapentaenoic Acid/administration & dosage , Eicosapentaenoic Acid/pharmacology , Eicosapentaenoic Acid/analysis , Docosahexaenoic Acids/administration & dosage , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/pharmacology , Fish Oils/administration & dosage , Animal Feed/analysis , Dietary Supplements/analysis , Reproduction/drug effects , Diet/veterinary , Sheep, Domestic/physiology , Pregnancy
9.
PLoS One ; 19(7): e0307552, 2024.
Article in English | MEDLINE | ID: mdl-39028744

ABSTRACT

In Japan, stocked chum salmon (Oncorhynchus keta) fry may have become the perfect prey for non-native brown trout (Salmo trutta), which are popular targets of anglers. If this is the case, fry stocking which is intended to boost commercial fishing may be helping to sustain the populations of an invasive predator. We used dietary and biochemical analyses to examine whether brown trout quickly restore their nutritional status following wintertime declines by preying upon chum salmon fry that are stocked in spring. We targeted six rivers in Hokkaido, Japan, three with fry stocking and three without. Changes in brown trout condition factor, triglyceride contents in muscle and serum, serum insulin-like growth factor-1 (IGF-1; an indicator of short-term growth), and docosahexaenoic acid (DHA; an essential fatty acid abundant in fish) content in muscle were examined between before stocking and during the stocking period in the six rivers. Dietary analysis showed that brown trout preyed on fry during the stocking period in all stocked rivers. Their nutritional status tended to be higher during the stocking period than before stocking in stocked rivers, but not in unstocked rivers. These results suggest that the massive stocking of chum salmon fry provides brown trout with the perfect prey to quickly restore their nutritional status and fuel increased growth; this may therefore be a controversial issue among stakeholders.


Subject(s)
Oncorhynchus keta , Trout , Animals , Japan , Insulin-Like Growth Factor I/metabolism , Insulin-Like Growth Factor I/analysis , Fisheries , Triglycerides/blood , Triglycerides/metabolism , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/analysis , Rivers , Predatory Behavior , Seasons
10.
J Biosci Bioeng ; 138(2): 105-110, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38825559

ABSTRACT

Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid (EPA; C20:5n-3) and docosahexaenoic acid (DHA; C22:6n-3) are widely used as additives in fish feed in the aquaculture sector. To date, the supply of omega-3 PUFAs have heavily depended upon fish oil production. As the need for omega-3 PUFAs supply for the growing population increases, a more sustainable approach is required to keep up with the demand. The oleaginous diatom Fistulifera solaris is known to synthesize EPA with the highest level among autotrophically cultured microalgae, however, this species does not accumulate significant amounts of DHA, which, in some cases, is required in aquaculture rather than EPA. This is likely due to the lack of expression of essential enzymes namely Δ5 elongase (Δ5ELO) and Δ4 desaturase. In this study, we identified endogenous Δ5ELO genes in F. solaris and introduced recombinant expression cassettes harboring Δ5ELO into F. solaris through bacterial conjugation. As a result, it managed to induce the synthesis of docosapentaenoic acid (DPA; C22:5n-3), a direct precursor of DHA. This study paves the way for expanding our understanding of the omega-3 PUFAs pathway using endogenous genes in the oleaginous diatom.


Subject(s)
Diatoms , Docosahexaenoic Acids , Eicosapentaenoic Acid , Fatty Acids, Omega-3 , Diatoms/metabolism , Diatoms/genetics , Fatty Acids, Omega-3/metabolism , Eicosapentaenoic Acid/metabolism , Eicosapentaenoic Acid/biosynthesis , Docosahexaenoic Acids/metabolism , Docosahexaenoic Acids/biosynthesis , Fatty Acid Desaturases/metabolism , Fatty Acid Desaturases/genetics , Genetic Engineering , Fatty Acid Elongases/metabolism , Fatty Acid Elongases/genetics , Microalgae/metabolism , Microalgae/genetics , Aquaculture
11.
BMC Pediatr ; 24(1): 384, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849784

ABSTRACT

BACKGROUND: Preterm born infants are at risk for brain injury and subsequent developmental delay. Treatment options are limited, but optimizing postnatal nutrition may improve brain- and neurodevelopment in these infants. In pre-clinical animal models, combined supplementation of docosahexaenoic acid (DHA), choline, and uridine-5-monophosphate (UMP) have shown to support neuronal membrane formation. In two randomized controlled pilot trials, supplementation with the investigational product was associated with clinically meaningful improvements in cognitive, attention, and language scores. The present study aims to assess the effect of a similar nutritional intervention on brain development and subsequent neurodevelopmental outcome in infants born very and extremely preterm. METHODS: This is a randomized, placebo-controlled, double-blinded, parallel-group, multi-center trial. A total of 130 infants, born at less than 30 weeks of gestation, will be randomized to receive a test or control product between term-equivalent age and 12 months corrected age (CA). The test product is a nutrient blend containing DHA, choline, and UMP amongst others. The control product contains only fractions of the active components. Both products are isocaloric powder supplements which can be added to milk and solid feeds. The primary outcome parameter is white matter integrity at three months CA, assessed using diffusion-tensor imaging (DTI) on MRI scanning. Secondary outcome parameters include volumetric brain development, cortical thickness, cortical folding, the metabolic and biochemical status of the brain, and product safety. Additionally, language, cognitive, motor, and behavioral development will be assessed at 12 and 24 months CA, using the Bayley Scales of Infant Development III and digital questionnaires (Dutch version of the Communicative Development Inventories (N-CDI), Ages and Stages Questionnaire 4 (ASQ-4), and Parent Report of Children's Abilities - Revised (PARCA-R)). DISCUSSION: The investigated nutritional intervention is hypothesized to promote brain development and subsequent neurodevelopmental outcome in preterm born infants who have an inherent risk of developmental delay. Moreover, this innovative study may give rise to new treatment possibilities and improvements in routine clinical care. TRIAL REGISTRATION: WHO International Clinical Trials Registry: NL-OMON56181 (registration assigned October 28, 2021).


Subject(s)
Brain , Choline , Dietary Supplements , Docosahexaenoic Acids , Uridine Monophosphate , Humans , Brain/growth & development , Brain/diagnostic imaging , Infant, Newborn , Double-Blind Method , Docosahexaenoic Acids/administration & dosage , Infant , Child Development , Infant, Extremely Premature/growth & development , Infant, Premature/growth & development , Randomized Controlled Trials as Topic
12.
Nutrients ; 16(11)2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38892670

ABSTRACT

Tumor cells are characterized by a delicate balance between elevated oxidative stress and enhanced antioxidant capacity. This intricate equilibrium, maintained within a threshold known as redox homeostasis, offers a unique perspective for cancer treatment by modulating reactive oxygen species (ROS) levels beyond cellular tolerability, thereby disrupting this balance. However, currently used chemotherapy drugs require larger doses to increase ROS levels beyond the redox homeostasis threshold, which may cause serious side effects. How to disrupt redox homeostasis in cancer cells more effectively remains a challenge. In this study, we found that sodium selenite and docosahexaenoic acid (DHA), a polyunsaturated fatty acid extracted from marine fish, synergistically induced cytotoxic effects in colorectal cancer (CRC) cells. Physiological doses of DHA simultaneously upregulated oxidation and antioxidant levels within the threshold range without affecting cell viability. However, it rendered the cells more susceptible to reaching the upper limit of the threshold of redox homeostasis, facilitating the elevation of ROS levels beyond the threshold by combining with low doses of sodium selenite, thereby disrupting redox homeostasis and inducing MAPK-mediated paraptosis. This study highlights the synergistic anticancer effects of sodium selenite and DHA, which induce paraptosis by disrupting redox homeostasis in tumor cells. These findings offer a novel strategy for more targeted and less toxic cancer therapies for colorectal cancer treatment.


Subject(s)
Colorectal Neoplasms , Docosahexaenoic Acids , Homeostasis , MAP Kinase Signaling System , Oxidation-Reduction , Reactive Oxygen Species , Sodium Selenite , Docosahexaenoic Acids/pharmacology , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/metabolism , Sodium Selenite/pharmacology , Humans , Oxidation-Reduction/drug effects , Homeostasis/drug effects , Reactive Oxygen Species/metabolism , MAP Kinase Signaling System/drug effects , Cell Line, Tumor , Oxidative Stress/drug effects , Cell Survival/drug effects , Antioxidants/pharmacology , Drug Synergism , Antineoplastic Agents/pharmacology , Paraptosis
13.
Molecules ; 29(11)2024 May 21.
Article in English | MEDLINE | ID: mdl-38893305

ABSTRACT

There has been an increase in interest in the application of ω-3 PUFAs, especially EPA and DHA, in the development of various food products owing to their myriad health benefits. However, most fish oils do not contain more than 30% combined levels of EPA and DHA. In this study, through the urea complexation procedure, the production of EPA and DHA concentrate in their free fatty acids (FFAs) form was achieved from an enzymatic oil extracted from common kilka (Clupeonella cultriventris caspia). To gain the maximum value of EPA and DHA, the response surface methodology (RSM), which is an effective tool to categorize the level of independent variables onto the responses of an experimental process, was also used. Different variables including the urea-fatty acids (FAs) ratio (in the range of 2-6, w/w), the temperature of crystallization (in the range of -24-8 °C), and the time of crystallization (in the range of 8-40 h) were investigated by response surface methodology (RSM) for maximizing the EPA and DHA contents. Following the model validation, the levels of the variables at which the maximum desirability function (0.907 score) was obtained for response variables were 5:1 (urea-FAs ratio), -9 °C (the temperature of crystallization), and 24 h (the time of crystallization). Under these optimal conditions, increases of 2.2 and 4.4 times in the EPA and DHA concentrations were observed, respectively, and an increase in the concentrations of EPA and DHA from 5.39 and 13.32% in the crude oil to 12.07 and 58.36% in the ω-3 PUFA concentrates were observed, respectively. These findings indicate that the urea complexation process is efficient at optimizated conditions.


Subject(s)
Fatty Acids, Omega-3 , Fish Oils , Urea , Urea/chemistry , Fatty Acids, Omega-3/chemistry , Fish Oils/chemistry , Docosahexaenoic Acids/chemistry , Docosahexaenoic Acids/analysis , Eicosapentaenoic Acid/chemistry , Eicosapentaenoic Acid/analysis , Animals , Crystallization
14.
Mar Drugs ; 22(6)2024 Jun 19.
Article in English | MEDLINE | ID: mdl-38921596

ABSTRACT

Omega-3 fatty acids are in high demand due to their efficacy in treating hypertriglyceridemia and preventing cardiovascular diseases. However, the growth of the industry is hampered by low purity and insufficient productivity. This study aims to develop an efficient RP-MPLC purification method for omega-3 fatty acid ethyl esters with high purity and capacity. The results indicate that the AQ-C18 featuring polar end-capped silanol groups outperformed C18 and others in retention time and impurity separation. By injecting pure fish oil esters with a volume equivalent to a 1.25% bed volume on an AQ-C18 MPLC column using a binary isocratic methanol-water (90:10, v:v) mobile phase at 30 mL/min, optimal omega-3 fatty acid ethyl esters were obtained, with the notable purity of 90.34% and a recovery rate of 74.30%. The total content of EPA and DHA produced increased from 67.91% to 85.27%, meeting the acceptance criteria of no less than 84% set by the 2020 edition of the Pharmacopoeia of the People's Republic of China. In contrast, RP-MPLC significantly enhanced the production efficiency per unit output compared to RP-HPLC. This study demonstrates a pioneering approach to producing omega-3 fatty acid ethyl esters with high purity and of greater quantity using AQ-C18 RP-MPLC, showing this method's significant potential for use in industrial-scale manufacturing.


Subject(s)
Chromatography, Reverse-Phase , Esters , Fatty Acids, Omega-3 , Fish Oils , Fatty Acids, Omega-3/chemistry , Fatty Acids, Omega-3/isolation & purification , Esters/chemistry , Esters/isolation & purification , Fish Oils/chemistry , Chromatography, Reverse-Phase/methods , Chromatography, High Pressure Liquid/methods , Docosahexaenoic Acids/chemistry , Docosahexaenoic Acids/isolation & purification , Eicosapentaenoic Acid/chemistry , Eicosapentaenoic Acid/isolation & purification
15.
Math Biosci ; 374: 109228, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38851528

ABSTRACT

Chronic pain is a major cause of disability and suffering in osteoarthritis (OA) patients. Endogenous specialised pro-resolving molecules (SPMs) curtail pro-inflammatory responses. One of the SPM intermediate oxylipins, 17-hydroxydocasahexaenoic acid (17-HDHA, a metabolite of docosahexaenoic acid (DHA)), is significantly associated with OA pain. The aim of this multidisciplinary work is to develop a mathematical model to describe the contributions of enzymatic pathways (and the genes that encode them) to the metabolism of DHA by monocytes and to the levels of the down-stream metabolites, 17-HDHA and 14-hydroxydocasahexaenoic acid (14-HDHA), motivated by novel clinical data from a study involving 30 participants with OA. The data include measurements of oxylipin levels, mRNA levels, measures of OA severity and self-reported pain scores. We propose a system of ordinary differential equations to characterise associations between the different datasets, in order to determine the homeostatic concentrations of DHA, 17-HDHA and 14-HDHA, dependent upon the gene expression of the associated metabolic enzymes. Using parameter-fitting methods, local sensitivity and uncertainty analysis, the model is shown to fit well qualitatively to experimental data. The model suggests that up-regulation of some ALOX genes may lead to the down-regulation of 17-HDHA and that dosing with 17-HDHA increases the production of resolvins, which helps to down-regulate the inflammatory response. More generally, we explore the challenges and limitations of modelling real data, in particular individual variability, and also discuss the value of gathering additional experimental data motivated by the modelling insights.


Subject(s)
Docosahexaenoic Acids , Monocytes , Osteoarthritis , Docosahexaenoic Acids/metabolism , Humans , Osteoarthritis/metabolism , Monocytes/metabolism , Models, Biological , Pain/metabolism
16.
Cells ; 13(11)2024 May 28.
Article in English | MEDLINE | ID: mdl-38891064

ABSTRACT

Periodontal disease is characterized by inflammation and bone loss. Central to its pathogenesis is the dysregulated inflammatory response, complicating regenerative therapies. Mesenchymal stem cells (MSCs) hold significant promise in tissue repair and regeneration. This study investigated the effects of specialized pro-resolving mediators (SPMs), Resolvin E1 (RvE1) and Maresin 1 (MaR1), on the osteogenic differentiation of human bone marrow-derived MSCs under inflammatory conditions. The stem cells were treated with SPMs in the presence of lipopolysaccharide (LPS) to simulate an inflammatory environment. Osteogenic differentiation was assessed through alkaline phosphatase activity and alizarin red staining. Proteomic analysis was conducted to characterize the protein expression profile changes, focusing on proteins related to osteogenesis and osteoclastogenesis. Treatment with RvE1 and MaR1, both individually and in combination, significantly enhanced calcified deposit formation. Proteomic analysis revealed the differential expression of proteins associated with osteogenesis and osteoclastogenesis, highlighting the modulatory impact of SPMs on bone metabolism. RvE1 and MaR1 promote osteogenic differentiation of hBMMSCs in an inflammatory environment, with their combined application yielding synergistic effects. This study provides insights into the therapeutic potential of SPMs in enhancing bone regeneration, suggesting a promising avenue for developing regenerative therapies for periodontal disease and other conditions characterized by inflammation-induced bone loss.


Subject(s)
Cell Differentiation , Docosahexaenoic Acids , Eicosapentaenoic Acid , Inflammation , Mesenchymal Stem Cells , Osteogenesis , Osteogenesis/drug effects , Humans , Eicosapentaenoic Acid/pharmacology , Eicosapentaenoic Acid/analogs & derivatives , Docosahexaenoic Acids/pharmacology , Mesenchymal Stem Cells/metabolism , Mesenchymal Stem Cells/drug effects , Cell Differentiation/drug effects , Inflammation/pathology , Proteomics , Bone Marrow Cells/metabolism , Bone Marrow Cells/drug effects , Bone Marrow Cells/cytology , Lipopolysaccharides/pharmacology
17.
J Agric Food Chem ; 72(27): 15311-15320, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38943596

ABSTRACT

Omega-3 long-chain polyunsaturated fatty acids (LCPUFA) play critical roles in human development and health. Their intake is often effectively estimated solely based on seafood consumption, though the high intake of terrestrial animal-based foods with minor amounts of LCPUFA may be significant. Covalent adduct chemical ionization (CACI) tandem mass spectrometry is one approach for de novo structural and quantitative analysis of minor unsaturated fatty acids (FA), for which standards are unavailable. Here, CACI-MS and MS/MS are used to identify and quantify minor omega-3 LCPUFA of terrestrial animal foods based on the application of measured response factors (RFs) to various FA. American mean intakes of pork, beef, chicken, and eggs contribute 20, 27, 45, and 71 mg/day of docosahexaenoic acid (DHA), respectively. The estimated intake of omega-3 DHA, eicosapentaenoic acid, and docosapentaenoic acid from nonseafood sources is significant, at 164, 103, and 330 mg/day, greater than most existing estimates of omega-3 LCPUFA intake.


Subject(s)
Chickens , Eggs , Fatty Acids, Omega-3 , Animals , Fatty Acids, Omega-3/analysis , Fatty Acids, Omega-3/chemistry , Eggs/analysis , Humans , United States , Cattle , Swine , Meat/analysis , Tandem Mass Spectrometry/methods , Mass Spectrometry/methods , Docosahexaenoic Acids/analysis , Docosahexaenoic Acids/chemistry
18.
Nutrients ; 16(12)2024 Jun 16.
Article in English | MEDLINE | ID: mdl-38931250

ABSTRACT

Fatty acids (FAs) are an essential component of the erythrocyte membrane, and nutrition and physical exercise are two variables that affect their structure and function. The aim of this study was to evaluate the erythrocyte profile in a group of high-level endurance runners, as well as the changes in different FAs, throughout a sports season in relation to the training performed. A total of 21 high-level male endurance runners (23 ± 4 years; height: 1.76 ± 0.05) were evaluated at four different times throughout a sports season. The athletes had at least 5 years of previous experience and participated in national and international competitions. The determination of the different FAs was carried out by gas chromatography. The runners exhibited low concentrations of docosahexaenoic acid (DHA) and omega-3 index (IND ω-3), as well as high values of stearic acid (SA), palmitic acid (PA), and arachidonic acid (AA), compared to the values of reference throughout the study. In conclusion, training modifies the erythrocyte FA profile in high-level endurance runners, reducing the concentrations of polyunsaturated fatty acids (PUFAs) such as DHA and AA and increasing the concentrations of saturated fatty acids (SFAs) such as SA and the PA. High-level endurance runners should pay special attention to the intake of PUFAs ω-3 in their diet or consider supplementation during training periods to avoid deficiency.


Subject(s)
Athletes , Erythrocytes , Fatty Acids , Physical Endurance , Running , Humans , Male , Running/physiology , Erythrocytes/metabolism , Erythrocytes/chemistry , Fatty Acids/blood , Physical Endurance/physiology , Adult , Young Adult , Athletes/statistics & numerical data , Docosahexaenoic Acids/blood , Fatty Acids, Omega-3/blood , Arachidonic Acid/blood , Seasons , Palmitic Acid/blood
19.
Int Immunopharmacol ; 136: 112316, 2024 Jul 30.
Article in English | MEDLINE | ID: mdl-38823183

ABSTRACT

The objective of this study was to investigate the neuroimmune mechanisms implicated in the enhancement of gastrointestinal function through the administration of oral DHA. Mast cell-deficient mice (KitW-sh) and C57BL/6 mice were used to establish postoperative ileus (POI) models. To further validate our findings, we conducted noncontact coculture experiments involving dorsal root ganglion (DRG) cells, bone marrow-derived mast cells (BMMCs) and T84 cells. Furthermore, the results obtained from investigations conducted on animals and cells were subsequently validated through clinical trials. The administration of oral DHA had ameliorative effects on intestinal barrier injury and postoperative ileus. In a mechanistic manner, the anti-inflammatory effect of DHA was achieved through the activation of transient receptor potential ankyrin 1 (TRPA1) on DRG cells, resulting in the stabilization of mast cells and increasing interleukin 10 (IL-10) secretion in mast cells. Furthermore, the activation of the pro-repair WNT1-inducible signaling protein 1 (WISP-1) signaling pathways by mast cell-derived IL-10 resulted in an enhancement of the intestinal barrier integrity. The current study demonstrated that the neuroimmune interaction between mast cells and nerves played a crucial role in the process of oral DHA improving the intestinal barrier integrity of POI, which further triggered the activation of CREB/WISP-1 signaling in intestinal mucosal cells.


Subject(s)
Docosahexaenoic Acids , Ileus , Interleukin-10 , Intestinal Mucosa , Mast Cells , Mice, Inbred C57BL , Postoperative Complications , TRPA1 Cation Channel , Animals , Mast Cells/drug effects , Mast Cells/immunology , Docosahexaenoic Acids/pharmacology , Docosahexaenoic Acids/therapeutic use , TRPA1 Cation Channel/metabolism , Mice , Ileus/drug therapy , Ileus/immunology , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/immunology , Intestinal Mucosa/pathology , Intestinal Mucosa/metabolism , Male , Interleukin-10/metabolism , Postoperative Complications/drug therapy , Postoperative Complications/immunology , Ganglia, Spinal/metabolism , Ganglia, Spinal/drug effects , Disease Models, Animal , Coculture Techniques , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
20.
Nat Commun ; 15(1): 4711, 2024 Jun 03.
Article in English | MEDLINE | ID: mdl-38830841

ABSTRACT

The fetal development of organs and functions is vulnerable to perturbation by maternal inflammation which may increase susceptibility to disorders after birth. Because it is not well understood how the placenta and fetus respond to acute lung- inflammation, we characterize the response to maternal pulmonary lipopolysaccharide exposure across 24 h in maternal and fetal organs using multi-omics, imaging and integrative analyses. Unlike maternal organs, which mount strong inflammatory immune responses, the placenta upregulates immuno-modulatory genes, in particular the IL-6 signaling suppressor Socs3. Similarly, we observe no immune response in the fetal liver, which instead displays metabolic changes, including increases in lipids containing docosahexaenoic acid, crucial for fetal brain development. The maternal liver and plasma display similar metabolic alterations, potentially increasing bioavailability of docosahexaenoic acid for the mother and fetus. Thus, our integrated temporal analysis shows that systemic inflammation in the mother leads to a metabolic perturbation in the fetus.


Subject(s)
Fetus , Lipopolysaccharides , Liver , Lung , Placenta , Female , Pregnancy , Placenta/metabolism , Placenta/immunology , Animals , Fetus/immunology , Fetus/metabolism , Lung/immunology , Lung/metabolism , Liver/metabolism , Liver/immunology , Docosahexaenoic Acids/metabolism , Suppressor of Cytokine Signaling 3 Protein/metabolism , Suppressor of Cytokine Signaling 3 Protein/genetics , Mice , Inflammation/immunology , Inflammation/metabolism , Mice, Inbred C57BL , Adaptation, Physiological/immunology , Fetal Development/immunology , Maternal-Fetal Exchange/immunology , Interleukin-6/metabolism , Interleukin-6/immunology
SELECTION OF CITATIONS
SEARCH DETAIL