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Frontiers in Public Health 2022This study aimed to investigate the association of α-linolenic acid (ALA; 18:3 ω-3) dietary intake with very short sleep duration (<5 h) in adults based on the CDC's...
OBJECTIVES
This study aimed to investigate the association of α-linolenic acid (ALA; 18:3 ω-3) dietary intake with very short sleep duration (<5 h) in adults based on the CDC's National Health and Nutrition Examination Survey data.
METHODS
Multinomial logistic regression was used to explore the association of ALA intake with very short sleep. To make the estimation more robust, bootstrap methods of 1,000 replications were performed. Rolling window method was used to investigate the trend of the odds ratios of very short sleep with age. A Kruskal-Wallis test was applied to estimate the differences in the ORs of very short sleep between genders and different age groups.
RESULTS
Compared with the first tertile, the ORs of very short sleep and the corresponding 95% CIs for the second and the third tertile of dietary ALA intake in males were 0.618 (0.612, 0.624) and 0.544 (0.538, 0.551), respectively, and in females were 0.575 (0.612, 0.624) and 0.432 (0.427, 0.437). In most cases, the differences between different ages were more significant than those between different sexes. Men's very short sleep odds ratios for the second tertile of ALA intake increased linearly with age before 60.
CONCLUSIONS
The risk of a very short sleep duration was negatively related to the dietary intake of ALA. The effect of ALA on very short sleep is significantly different among groups of different genders and ages.
Topics: Adult; Diet; Eating; Female; Humans; Male; Nutrition Surveys; Sleep; alpha-Linolenic Acid
PubMed: 36062128
DOI: 10.3389/fpubh.2022.986424 -
International Journal of Biological... Jan 2021Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau....
Alzheimer's disease is characterized by important patho-proteins, which being composed of Amyloid-β plaques and intracellular neurofibrillary tangles of Tau. Intrinsically disordered protein tau has several interacting partners, which are necessary for its normal functioning. Tau has been shown to interact with various proteins, nucleic acid, and lipids. α-Linolenic acid (ALA) a plant-based omega-3 fatty acid has been studied for its role as neuroprotective and beneficial fatty acid in the brain. In this study, we are focusing on the ability of ALA to induce spontaneous assembly in tau protein. ALA inhibited the Tau aggregation as indicated by reduced ThS fluorescence kinetics, which indicates no aggregation of Tau. Similarly, SDS-PAGE analysis supported that ALA exposure inhibited the aggregation as no higher-order tau species were observed. Along with its ability to impede the aggregation of Tau, ALA also maintains a native random coiled structure, which was estimated by CD spectroscopy. Finally, TEM analysis showed that the formation of Tau fibrils was found to be discouraged by ALA. Hence, conclusion of the study suggested that ALA profoundly inhibited aggregation of Tau and maintained it's the random-coil structure.
Topics: Humans; Protein Conformation; Protein Multimerization; Protein Unfolding; alpha-Linolenic Acid; tau Proteins
PubMed: 33130263
DOI: 10.1016/j.ijbiomac.2020.10.226 -
Molecules (Basel, Switzerland) Sep 2022α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In...
α-Linolenic acid (ALA) is a natural essential fatty acid widely found in plant seed oils and beans, which shows positive anti-inflammatory and antiallergic effects. In our previous study, ALA was proven to bind tightly to the seven protein targets closely associated with allergic rhinitis (AR) by molecular docking, which indicates that ALA may have a potential role in the treatment of AR. A mouse model of AR induced by ovalbumin (OVA) was adopted in this study to explore the therapeutical effect and potential mechanism of ALA in treating AR. Results demonstrated that ALA remarkably relieved the nasal symptoms, reduced the OVA-sIgE level in the serum, relieved the histopathological injuries, and downregulated the mRNA expression levels of IL-6 and IL-1β in the nasal mucosa. ALA also remarkably moderated the imbalance of Th1/Th2 cells, increased the mRNA expression levels of T-bet and STAT1, and reduced GATA3 and STAT6. ALA was proven to have a substantial therapeutic effect on mice with AR, and the underlying mechanism was likely to be the regulation of Th1/Th2 imbalance through the JAK/T-bet/STAT1 and JAK/GATA3/STAT6 pathways. This study provides a specific experimental basis for the clinical use and drug development of ALA in the treatment of AR.
Topics: Animals; Anti-Allergic Agents; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Inflammation; Interleukin-6; Mice; Mice, Inbred BALB C; Molecular Docking Simulation; Nasal Mucosa; Ovalbumin; Plant Oils; RNA, Messenger; Rhinitis, Allergic; Th2 Cells; alpha-Linolenic Acid
PubMed: 36144628
DOI: 10.3390/molecules27185893 -
Journal of Nanoscience and... Feb 2021Micro RNA-146 (miR-146) is involved in mediating many innate and adaptive immune and inflammatory responses in the body. It is associated with a variety of systemic...
Micro RNA-146 (miR-146) is involved in mediating many innate and adaptive immune and inflammatory responses in the body. It is associated with a variety of systemic inflammation or autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and type 2 diabetes. In recent years, microRNAs (miRNAs) and nanotechnology have become research hotspots in cardiovascular pathology. The close relationship between host miRNAs and has gradually been discovered by scientists, which may provide new directions for the treatment and prevention of viral myocarditis. At the same time, recent studies have also found that nano--linolenic acid and its metabolites can inhibit the production of inflammatory cytokines such as TNF- and IL-17; At the same time, they also have anti-lipid peroxidation effects. Therefore, in order to further explore the role of miR-146 and nano--linolenic acid in the occurrence and development of viral myocarditis, in this study, a mouse model of viral myocarditis was used to establish a VMC mouse model using . Intervention with different doses of nano--linolenic acid, the control group was injected with the same amount of sodium chloride buffer, and the changes in cardiac function and inflammation indexes were compared to evaluate the role in the pathogenesis of viral myocarditis. The results showed that this study suggested that serum miR-146 concentration in viral myocarditis mice is increased and is positively correlated with serum IL-17 and TNF- concentrations. This suggest that miR-146 in the circulation may be involved in the pathogenesis of viral myocarditis through IL-17 and TNF-, providing a theoretical basis for the role of miR-146 in viral myocarditis, but its specific mechanism of action needs to be further studied. At the same time, the research in this experiment showed that nano--linolenic acid significantly improves the survival rate of CVB3 infected mice and reduces myocardial damage. And with the increase of the dosage of nano--linolenic acid, the effect is more significant, showing a significant dose-effect relationship.
Topics: Animals; Diabetes Mellitus, Type 2; Enterovirus B, Human; Mice; Mice, Inbred BALB C; MicroRNAs; Myocarditis; Myocardium; alpha-Linolenic Acid
PubMed: 33183485
DOI: 10.1166/jnn.2021.18645 -
Advances in Nutrition (Bethesda, Md.) Nov 2023Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia,... (Meta-Analysis)
Meta-Analysis Review
Effect of Alpha-Linolenic Acid Supplementation on Cardiovascular Disease Risk Profile in Individuals with Obesity or Overweight: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Overweight and obesity are highly prevalent worldwide and are associated with cardiovascular disease (CVD) risk factors, including systematic inflammation, dyslipidemia, and hypertension. Alpha-linolenic acid (ALA) is a plant-based essential polyunsaturated fatty acid associated with reduced CVD risks. This systematic review and meta-analysis aimed to investigate the effects of supplementation with ALA compared with the placebo on CVD risk factors in people with obesity or overweight (International Prospective Register of Systematic Reviews Registration No. CRD42023429563). This review included studies with adults using oral supplementation or food or combined interventions containing vegetable sources of ALA. All studies were randomly assigned trials with parallel or crossover designs. The Cochrane Collaboration tool was used for assessing the risk of bias (Version 1). PubMed, Web of Science, Embase, and Cochrane library databases were searched from inception to April 2023. Nineteen eligible randomized controlled trials, including 1183 participants, were included in the meta-analysis. Compared with placebo, dietary ALA supplementation significantly reduced C-reactive protein concentration (standardized mean difference [SMD] = -0.38 mg/L; 95% confidence interval [CI]: -0.72, -0.04), tumor necrosis factor-α concentration (SMD = -0.45 pg/mL; 95% CI: -0.73, -0.17), triglyceride in serum (SMD = -4.41 mg/dL; 95% CI: -5.99, -2.82), and systolic blood pressure (SMD = -0.37 mm Hg; 95% CI: -0.66, -0.08); but led to a significant increase in low-density lipoprotein cholesterol concentrations (SMD = 1.32 mg/dL; 95% CI: 0.05, 2.59). ALA supplementation had no significant effect on interleukin-6, diastolic blood pressure, total cholesterol, or high-density lipoprotein cholesterol (all P ≥ 0.05). Subgroup analysis revealed that ALA supplementation at a dose of ≥3 g/d from flaxseed and flaxseed oil had a more prominent effect on improving CVD risk profiles, particularly where the intervention duration was ≥12 wk and where the baseline CVD profile was poor.
Topics: Adult; Humans; Cardiovascular Diseases; alpha-Linolenic Acid; Overweight; Randomized Controlled Trials as Topic; Cholesterol, HDL; Obesity; Dietary Supplements
PubMed: 37778442
DOI: 10.1016/j.advnut.2023.09.010 -
Nutrients Jan 2022The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated...
The retina requires docosahexaenoic acid (DHA) for optimal function. Alpha-linolenic acid (ALA) and DHA are dietary sources of retinal DHA. This research investigated optimizing retinal DHA using dietary ALA. Previous research identified 19% DHA in retinal phospholipids was associated with optimal retinal function in guinea pigs. Pregnant guinea pigs were fed dietary ALA from 2.8% to 17.3% of diet fatty acids, at a constant level of linoleic acid (LA) of 18% for the last one third of gestation and retinal DHA levels were assessed in 3-week-old offspring maintained on the same diets as their mothers. Retinal DHA increased in a linear fashion with the maximum on the diet with LA:ALA of 1:1. Feeding diets with LA:ALA of 1:1 during pregnancy and assessing retinal DHA in 3-week-old offspring was associated with optimized retinal DHA levels. We speculate that the current intakes of ALA in human diets, especially in relation to LA intakes, are inadequate to support high DHA levels in the retina.
Topics: Animal Nutritional Physiological Phenomena; Animals; Animals, Newborn; Diet; Dietary Fats; Docosahexaenoic Acids; Female; Guinea Pigs; Linoleic Acid; Maternal Nutritional Physiological Phenomena; Phospholipids; Pregnancy; Retina; alpha-Linolenic Acid
PubMed: 35057481
DOI: 10.3390/nu14020301 -
Experimental Biology and Medicine... Apr 2023Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy,...
Hyperexcitability is a major mechanism implicated in several neuropsychiatric disorders, such as organophosphate-induced status epilepticus (SE), primary epilepsy, stroke, spinal cord injury, traumatic brain injury, schizophrenia, and autism spectrum disorders. Underlying mechanisms are diverse, but a functional impairment and loss of GABAergic inhibitory neurons are common features in many of these disorders. While novel therapies abound to correct for the loss of GABAergic inhibitory neurons, it has been difficult at best to improve the activities of daily living for the majority of patients. Alpha-linolenic acid (ALA) is an essential omega-3 polyunsaturated fatty acid found in plants. ALA exerts pleiotropic effects in the brain that attenuate injury in chronic and acute brain disease models. However, the effect of ALA on GABAergic neurotransmission in hyperexcitable brain regions involved in neuropsychiatric disorders, such as the basolateral amygdala (BLA) and CA1 subfield of the hippocampus, is unknown. Administration of a single dose of ALA (1500 nmol/kg) subcutaneously increased the charge transfer of inhibitory postsynaptic potential currents mediated by GABA receptors in pyramidal neurons by 52% in the BLA and by 92% in the CA1 compared to vehicle animals a day later. Similar results were obtained in pyramidal neurons from the BLA and CA1 when ALA was bath-applied in slices from naïve animals. Importantly, pretreatment with the high-affinity, selective TrkB inhibitor, k252, completely abolished the ALA-induced increase in GABAergic neurotransmission in the BLA and CA1, suggesting a brain-derived neurotrophic factor (BDNF)-mediated mechanism. Addition of mature BDNF (20 ng/mL) significantly increased GABA receptor inhibitory activity in the BLA and CA1 pyramidal neurons similar to the results obtained with ALA. ALA may be an effective treatment for neuropsychiatric disorders where hyperexcitability is a major feature.
Topics: Rats; Humans; Animals; Basolateral Nuclear Complex; alpha-Linolenic Acid; Brain-Derived Neurotrophic Factor; Rats, Sprague-Dawley; Activities of Daily Living; Synaptic Transmission; Receptors, GABA-A
PubMed: 37208920
DOI: 10.1177/15353702231165010 -
Cell Adhesion & Migration Dec 2021Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques...
Microglia, the resident immune cells, were found to be activated to inflammatory phenotype in Alzheimer's disease (AD). The extracellular burden of amyloid-β plaques and Tau seed fabricate the activation of microglia. The seeding effect of extracellular Tau species is an emerging aspect to study about Tauopathies in AD. Tau seeds enhance the propagation of disease along with its contribution to microglia-mediated inflammation. The excessive neuroinflammation cumulatively hampers phagocytic function of microglia reducing the clearance of extracellular protein aggregates. Omega-3 fatty acids, especially docosahexaenoic acid and eicosapentaenoic acid, are recognized to induce anti-inflammatory phenotype of microglia. In addition to increased cytokine production, omega-3 fatty acids enhance phagocytic receptors expression in microglia. In this study, we have observed the phagocytosis of extracellular Tau in the presence of α-linolenic acid (ALA). The increased phagocytosis of extracellular Tau monomer and aggregates have been observed upon ALA exposure to microglia cells. After internalization, the degradation status of Tau has been studied with early and late endosomal markers Rab5 and Rab7. Further, the lysosome-mediated degradation of internalized Tau was studied with LAMP-2A, a lysosome marker. The enhanced migratory ability in the presence of ALA could be beneficial for microglia to access the target and clear it. The increased migration of microglia was found to induce the microtubule-organizing center repolarization. The data indicate that the dietary fatty acids ALA could significantly enhance phagocytosis and intracellular degradation of internalized Tau. Our results suggest that microglia could be influenced to reduce extracellular Tau seed with dietary fatty acids.
Topics: Alzheimer Disease; Humans; Microglia; Neuroinflammatory Diseases; Phagocytosis; alpha-Linolenic Acid; tau Proteins
PubMed: 33724164
DOI: 10.1080/19336918.2021.1898727 -
International Journal of Food Sciences... May 2021Consumption of omega-3 fatty acids, including the precursor α-linolenic acid (ALA) is often sub-optimal and not in line with international guidelines. Supplementation...
Consumption of omega-3 fatty acids, including the precursor α-linolenic acid (ALA) is often sub-optimal and not in line with international guidelines. Supplementation is debatable, but some individuals, e.g., pre-diabetic, low-grade inflammation, cardiometabolic yet otherwise healthy subjects, might benefit from supra-physiological omega-3 intake, particularly to lessen inflammation. We explored the feasibility of a large clinical trial by performing a pilot study to evaluate adherence, palatability, and self-reported side effects of ALA administration in a group of volunteers. We enrolled 12 individuals with borderline dyslipidemia or overweight, treated with dietary advice according to international guidelines and who had insufficient intakes of essential fatty acids. Subjects were followed for nutritional counselling and were matched with appropriate controls. Patients were administered 6 g/day of ALA, for two months. We report the absence of side effects. such as fishy aftertaste and gastrointestinal distress, in addition to a slight decrease of C-reactive protein concentrations (Identifier: ISRCTN13118704).
Topics: Adult; Aged; Blood Pressure; C-Reactive Protein; Diet; Dietary Supplements; Fatty Acids, Essential; Feasibility Studies; Female; Heart; Humans; Inflammation; Male; Middle Aged; Overweight; Patient Compliance; Pilot Projects; alpha-Linolenic Acid
PubMed: 32746658
DOI: 10.1080/09637486.2020.1802581 -
International Journal of Nanomedicine 2021Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility....
PURPOSE
Small molecule modified antitumor drug conjugate nanoparticles have the advantages of high drug loading, simple synthesis and preparation, and better biocompatibility. Due to the large demand for exogenous α-linolenic acid (ALA) by tumor cells, we synthesized α-linolenic acid-paclitaxel conjugate (ALA-PTX) and prepared α-linolenic acid-paclitaxel conjugate nanoparticles (ALA-PTX NPs), in order to obtain better tumor cellular uptake and antitumor activity in vitro and in vivo.
METHODS
We synthesized and characterized ALA-PTX, and then prepared and characterized ALA-PTX NPs. The cellular uptake, uptake pathways, intracellular behavior, in vitro and in vivo antitumor activity of ALA-PTX NPs were evaluated.
RESULTS
The size of ALA-PTX NPs was approximately 110.7±1.7 nm. The drug loading was approximately 90% (w/w) with CrEL-free and organic solvent-free characteristics. The cellular uptake of ALA-PTX NPs was significantly higher than that of PTX injection by MCF-7, MCF-7/ADR and HepG2 cells. In these three cell lines, the cellular uptake of ALA-PTX NPs at 6h was approximately 1.5-2.6 times higher than that of PTX injection. ALA-PTX NPs were ingested through clathrin-mediated endocytosis, then transferred to lysosomes, and could dissolve in cells to play an antitumor activity. The in vitro and in vivo antitumor activity of ALA-PTX NPs was confirmed in MCF-7/ADR and HepG2 cell models and tumor-bearing nude mouse models.
CONCLUSION
ALA-PTX NPs developed in our study could provide a new method for the preparation of nano-delivery systems suitable for antitumor therapy that could increase tumor cellular uptake and enhance antitumor activity.
Topics: Animals; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Cell Line, Tumor; Endocytosis; Mice; Nanoparticles; Paclitaxel; alpha-Linolenic Acid
PubMed: 34737564
DOI: 10.2147/IJN.S331578