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Journal of Virology Nov 2023Porcine epidemic diarrhea caused by porcine coronaviruses remains a major threat to the global swine industry. Fatty acids are extensively involved in the whole life of...
Porcine epidemic diarrhea caused by porcine coronaviruses remains a major threat to the global swine industry. Fatty acids are extensively involved in the whole life of the virus. In this study, we found that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) significantly reduced the viral load of porcine epidemic diarrhea virus (PEDV), transmissible gastroenteritis virus (TGEV), and porcine delta coronavirus (PDCoV) and acted on the replication of the viruses rather than attachment and entry. We further confirmed that DHA and EPA inhibited PEDV replication by alleviating the endoplasmic reticulum stress. Meanwhile, DHA and EPA alleviate PEDV-induced inflammation and reactive oxygen species (ROS) levels and enhance the cellular antioxidant capacity. These data indicate that DHA and EPA have antiviral effects on porcine coronaviruses and provide a molecular basis for the development of new fatty acid-based therapies to control porcine coronavirus infection and transmission.
Topics: Animals; Coronavirus; Coronavirus Infections; Docosahexaenoic Acids; Eicosapentaenoic Acid; Porcine epidemic diarrhea virus; Swine; Swine Diseases; Transmissible gastroenteritis virus; Virus Replication; Endoplasmic Reticulum Stress
PubMed: 37843366
DOI: 10.1128/jvi.01209-23 -
Biomolecules Aug 2023Sepsis is triggered by microbial infection, injury, or even major surgery. Both innate and adaptive immune systems are involved in its pathogenesis. Cytoplasmic presence... (Review)
Review
Sepsis is triggered by microbial infection, injury, or even major surgery. Both innate and adaptive immune systems are involved in its pathogenesis. Cytoplasmic presence of DNA or RNA of the invading organisms or damaged nuclear material (in the form of micronucleus in the cytoplasm) in the host cell need to be eliminated by various nucleases; failure to do so leads to the triggering of inflammation by the cellular cGAS-STING system, which induces the release of IL-6, TNF-α, and IFNs. These cytokines activate phospholipase A2 (PLA2), leading to the release of polyunsaturated fatty acids (PUFAs), gamma-linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), which form precursors to various pro- and anti-inflammatory eicosanoids. On the other hand, corticosteroids inhibit PLA2 activity and, thus, suppress the release of GLA, AA, EPA, and DHA. PUFAs and their metabolites have a negative regulatory action on the cGAS-STING pathway and, thus, suppress the inflammatory process and initiate inflammation resolution. Pro-inflammatory cytokines and corticosteroids (corticosteroids > IL-6, TNF-α) suppress desaturases, which results in decreased formation of GLA, AA, and other PUFAs from the dietary essential fatty acids (EFAs). A deficiency of GLA, AA, EPA, and DHA results in decreased production of anti-inflammatory eicosanoids and failure to suppress the cGAS-STING system. This results in the continuation of the inflammatory process. Thus, altered concentrations of PUFAs and their metabolites, and failure to suppress the cGAS-STING system at an appropriate time, leads to the onset of sepsis. Similar abnormalities are also seen in radiation-induced inflammation. These results imply that timely administration of GLA, AA, EPA, and DHA, in combination with corticosteroids and anti-IL-6 and anti-TNF-α antibodies, may be of benefit in mitigating radiation-induced damage and sepsis.
Topics: Humans; Tumor Necrosis Factor-alpha; Interleukin-6; Tumor Necrosis Factor Inhibitors; Inflammation; Fatty Acids, Unsaturated; Eicosanoids; Eicosapentaenoic Acid; Arachidonic Acid; Cytokines; Docosahexaenoic Acids; Anti-Inflammatory Agents; Sepsis
PubMed: 37759732
DOI: 10.3390/biom13091332 -
Prostaglandins & Other Lipid Mediators Dec 2023Evidence for the biosynthetic pathways of the specialized pro-resolving mediator (SPM) protectin D1 (PD1) and its biochemical further local metabolism were presented... (Review)
Review
Evidence for the biosynthetic pathways of the specialized pro-resolving mediator (SPM) protectin D1 (PD1) and its biochemical further local metabolism were presented during the 8th European Workshop on Lipid Mediators, organized June 29th-July 1st, 2022, in Stockholm, Sweden. Herein, we provide an extended and detailed discussion of these topics. PD1, one of 43 SPMs reported so far, exhibits very potent pro-resolution and anti-inflammatory bioactions. Many research groups worldwide have confirmed these and other interesting bioactions. The protectins constitute, together with the lipoxins, resolvins, and maresins, the four individual SPM families, which have received a great interest in basic biomedical research and drug discovery efforts.
Topics: Humans; CD59 Antigens; Biosynthetic Pathways; Anti-Inflammatory Agents; Eicosanoids; Lipoxins; Docosahexaenoic Acids; Inflammation; Inflammation Mediators
PubMed: 37806439
DOI: 10.1016/j.prostaglandins.2023.106787 -
Archives of Microbiology Aug 2023Omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA), are essential polyunsaturated fatty acids with... (Review)
Review
Omega-3 fatty acids, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and α-linolenic acid (ALA), are essential polyunsaturated fatty acids with diverse health benefits. The limited conversion of dietary DHA necessitates its consumption as food supplements. Omega-3 fatty acids possess anti-arrhythmic and anti-inflammatory capabilities, contributing to cardiovascular health. Additionally, DHA consumption is linked to improved vision, brain, and memory development. Furthermore, omega-3 fatty acids offer protection against various health conditions, such as celiac disease, Alzheimer's, hypertension, thrombosis, heart diseases, depression, diabetes, and certain cancers. Fish oil from pelagic cold-water fish remains the primary source of omega-3 fatty acids, but the global population burden creates a demand-supply gap. Thus, researchers have explored alternative sources, including microbial systems, for omega-3 production. Microbial sources, particularly oleaginous actinomycetes, microalgae like Nannochloropsis and among microbial systems, Thraustochytrids stand out as they can store up to 50% of their dry weight in lipids. The microbial production of omega-3 fatty acids is a potential solution to meet the global demand, as these microorganisms can utilize various carbon sources, including organic waste. The biosynthesis of omega-3 fatty acids involves both aerobic and anaerobic pathways, with bacterial polyketide and PKS-like PUFA synthase as essential enzymatic complexes. Optimization of physicochemical parameters, such as carbon and nitrogen sources, pH, temperature, and salinity, plays a crucial role in maximizing DHA production in microbial systems. Overall, microbial sources hold significant promise in meeting the global demand for omega-3 fatty acids, offering an efficient and sustainable solution for enhancing human health.
Topics: Humans; Docosahexaenoic Acids; Biosynthetic Pathways; Fatty Acids, Omega-3; Actinobacteria; Carbon
PubMed: 37642791
DOI: 10.1007/s00203-023-03666-x -
Mayo Clinic Proceedings Apr 2024To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the associations of docosahexaenoic acid (DHA), a marine omega-3 fatty acid, with long-term all-cause mortality, cardiovascular (CV) mortality, and cancer mortality.
PATIENTS AND METHODS
We analyzed data from UK Biobank, which included 117,702 subjects with baseline plasma DHA levels and 12.7 years of follow-up between April 2007 and December 2021. Associations with risk for mortality endpoints were analyzed categorically by quintile of DHA plasma levels.
RESULTS
Comparing the lowest to highest quintiles of circulating levels of DHA, there was 21% lower risk of all-cause mortality (HR, 0.79; 95% CI, 0.74 to 0.85; P<.0001). In a secondary analysis, we merged the UK Biobank findings with those from a recent FORCE (Fatty Acid and Outcome Research Consortium) meta-analysis that included 17 prospective cohort studies and 42,702 individuals examining DHA and mortality associations. The cumulative sample population included 160,404 individuals and 24,342 deaths during a median of 14 years of follow-up. After multivariable adjustment for relevant risk factors comparing the lowest to the highest quintiles of DHA, there was 17% lower risk of all-cause mortality (95% CI, 0.79 to 0.87; P<.0001), 21% lower risk for CV disease mortality (95% CI, 0.73 to 0.87; P<.001), 17% lower risk for cancer mortality (95% CI, 0.77 to 0.89; P<.0001), and 15% lower risk for all other mortality (95% CI, 0.79 to 0.91; P<.001).
CONCLUSION
Higher DHA levels were associated with significant risk reductions in all-cause mortality, as well as reduced risks for deaths due to CV disease, cancer, and all other causes. The findings strengthen the hypothesis that DHA, a marine-sourced omega-3, may support CV health and lifespan.
Topics: Humans; Docosahexaenoic Acids; Cause of Death; Eicosapentaenoic Acid; Prospective Studies; Fatty Acids, Omega-3; Cardiovascular Diseases; Risk Factors; Neoplasms
PubMed: 38506781
DOI: 10.1016/j.mayocp.2023.11.026 -
Prostaglandins & Other Lipid Mediators Aug 2023Stroke and dementia are global leading causes of neurological disability and death. The pathology of these diseases is interrelated and they share common, modifiable... (Review)
Review
Stroke and dementia are global leading causes of neurological disability and death. The pathology of these diseases is interrelated and they share common, modifiable risk factors. It is suggested that docosahexaenoic acid (DHA) prevents neurological and vascular disorders induced by ischemic stroke and also prevent dementia. The purpose of this study was to review the potential preventative role of DHA against ischemic stroke-induced vascular dementia and Alzheimer's disease. In this review, I analyzed studies on stroke-induced dementia from the PubMed, ScienceDirect, and Web of Science databases as well as studies on the effects of DHA on stroke-induced dementia. As per the results of interventional studies, DHA intake can potentially ameliorate dementia and cognitive function. In particular, DHA derived from foods such as fish oil enters the blood and then migrates to the brain by binding to fatty acid binding protein 5 that is present in cerebral vascular endothelial cells. At this point, the esterified form of DHA produced by lysophosphatidylcholine is preferentially absorbed into the brain instead of free DHA. DHA accumulates in nerve cell membrane and is involved in the prevention of dementia. The antioxidative and anti-inflammatory properties of DHA and DHA metabolites as well as their ability to decrease amyloid beta (Aβ) 42 production were implicated in the improvement of cognitive function. The antioxidant effect of DHA, the inhibition of neuronal cell death by Aβ peptide, improvement in learning ability, and enhancement of synaptic plasticity may contribute to the prevention of dementia induced by ischemic stroke.
Topics: Humans; Alzheimer Disease; Docosahexaenoic Acids; Amyloid beta-Peptides; Dementia, Vascular; Ischemic Stroke; Endothelial Cells; Antioxidants; Stroke
PubMed: 37028469
DOI: 10.1016/j.prostaglandins.2023.106733 -
Atherosclerosis Dec 2023We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of... (Randomized Controlled Trial)
Randomized Controlled Trial
Eicosapentaenoic and docosahexaenoic acid supplementation and coronary artery calcium progression in patients with coronary artery disease: A secondary analysis of a randomized trial.
BACKGROUND AND AIMS
We previously reported that an omega-3 fatty acid index ≥4% with high-dose eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) prevented progression of noncalcified plaque. Higher coronary artery calcium (CAC) scores and progression of CAC are associated with increased cardiovascular events and mortality. We examined the effect of EPA + DHA on CAC score.
METHODS
A total of 242 patients with coronary artery disease (CAD) on statin therapy were randomized to 1.86 g EPA and 1.5 g DHA daily or none (control) for 30 months. The CAC score was measured at baseline and 30-months with non-contrast, cardiac computed tomography.
RESULTS
Both EPA + DHA and control groups had significant progression in CAC scores over 30 months (median change:183.5 vs 221.0, respectively, p < 0.001) despite a 13.6% reduction in triglyceride level with EPA + DHA. No significant difference was observed between groups for the total group, by baseline CAC scores of <100, 100-399, 400-999 and ≥1000 or quartiles of achieved levels of EPA, DHA and the omega-3 fatty acid index. Similar rates of CAC progression were noted in those on high-intensity statin compared to low- and moderate-intensity statin.
CONCLUSIONS
EPA and DHA added to statin resulted in similar CAC progression over 30 months regardless of baseline CAC categories, statin intensity and achieved levels of EPA, DHA and the omega-3 fatty acid index.
Topics: Humans; Coronary Artery Disease; Docosahexaenoic Acids; Calcium; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Calcium, Dietary; Dietary Supplements
PubMed: 38056242
DOI: 10.1016/j.atherosclerosis.2023.117388 -
Clinical Nutrition (Edinburgh, Scotland) Sep 2023Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
Recent randomized clinical trials have raised concerns regarding potential off target adverse effects from supplementation of n-3 polyunsaturated fatty acids (PUFA) on atrial fibrillation (AF) risk. We aimed to assess risk and potential mediators of AF and 'micro-AF' from n-3 PUFA in post-myocardial infarction (MI) patients.
METHODS
In the OMEMI trial, 70-82 y. o. patients with a recent MI were randomized to 1.8 g/day of eicosapentaenoic-/docosahexaenoic acid (EPA/DHA) or placebo (corn oil) for two years. New-onset AF and 'micro-AF' was recorded by clinical detection and by screening with Zenicor thumb-ECG (adjudicated by blinded investigators). Serum EPA and DHA were measured at baseline and study end.
RESULTS
At baseline, 759 of 1014 (75%) patients had no AF history. These patients were aged 75 ± 4 years and 71% were male. During follow-up, 43 patients developed new-onset AF (39 clinically-detected and 4 by thumb-ECG screening). In addition, 27 patients had episodes of micro-AF, yielding a total of 70 patients with new-onset AF or 'micro-AF'. In the n-3 PUFA group 46 (11.9%) had AF/'micro-AF' (28 AF, 18 'micro-AF') and in the placebo group 24 (6.5%) had AF/micro-AF (15 AF, 9 micro-AF); HR 1.90 (95%CI 1.16-3.11), P = 0.011. Changes in serum EPA (but not DHA) mediated the effect from n-3 PUFA on AF risk, explaining 65% of the association.
CONCLUSION
Supplementation of n-3 PUFA post MI increases the risk of 'micro-AF' and AF, and increases in EPA seems to be an important mediator of the treatment effect from n-3 PUFA on the risk of AF.
STUDY REGISTRATION
OMEMI Study; ClinicalTrails.gov identifier: NCT0184194.
Topics: Humans; Male; Female; Fatty Acids, Omega-3; Atrial Fibrillation; Dietary Supplements; Eicosapentaenoic Acid; Myocardial Infarction; Docosahexaenoic Acids
PubMed: 37515843
DOI: 10.1016/j.clnu.2023.07.002 -
Life Sciences Aug 2023Rheumatoid arthritis is an autoimmune disease which induces chronic inflammation and increases the risk for sarcopenia and metabolic abnormalities. Nutritional...
AIMS
Rheumatoid arthritis is an autoimmune disease which induces chronic inflammation and increases the risk for sarcopenia and metabolic abnormalities. Nutritional strategies using omega 3 polyunsaturated fatty acids could be proposed to alleviate inflammation and improve the maintenance of lean mass. Independently, pharmacological agents targeting key molecular regulators of the pathology such as TNF alpha could be proposed, but multiple therapies are frequently necessary increasing the risk for toxicity and adverse effects. The aim of the present study was to explore if the combination of an anti-TNF therapy (Etanercept) with dietary supplementation with omega 3 PUFA could prevent pain and metabolic effects of RA.
MATERIALS AND METHODS
RA was induced using collagen-induced arthritis (CIA) in rats to explore of supplementation with docosahexaenoic acid, treatment with etanercept or their association could alleviate symptoms of RA (pain, dysmobility), sarcopenia and metabolic alterations.
KEY FINDINGS
We observed that Etanercept had major benefits on pain and RA scoring index. However, DHA could reduce the impact on body composition and metabolic alterations.
SIGNIFICANCE
This study revealed for the first time that nutritional supplementation with omega 3 fatty acid could reduce some symptoms of rheumatoid arthritis and be an effective preventive treatment in patients who do not need pharmacological therapy, but no sign of synergy with an anti-TNF agent was observed.
Topics: Rats; Animals; Etanercept; Docosahexaenoic Acids; Arthritis, Experimental; Sarcopenia; Tumor Necrosis Factor Inhibitors; Arthritis, Rheumatoid; Fatty Acids, Omega-3; Inflammation; Pain
PubMed: 37270172
DOI: 10.1016/j.lfs.2023.121826 -
The Journal of Nutritional Biochemistry Oct 2023Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary...
Ferroptosis due to polyunsaturated fatty acid (PUFA) peroxidation has been implicated in the pathogenesis of acute kidney injury (AKI), suggesting the risk of dietary intake of PUFA for people susceptible to AKI. Clinically, however, in addition to ferroptosis, other mechanisms also contribute to different types of AKI such as inflammation associated necroptosis and pyroptosis. Therefore, the role of PUFA, especially ω3 PUFA which is a common food supplement, in various AKIs deserves further evaluation. In this study, rhabdomyolysis- and folic acid-induced AKI (Rha-AKI and FA-AKI) were established in mice fed with different fatty acids Histology of kidney, blood urea nitrogen and creatinine, lipid peroxidation, and inflammatory factors were examined. Results showed that these two types of AKIs had diametrically different pathogenesis indicated by that ferrostatin-1 (Fer-1), a lipid antioxidant, can attenuate FA-AKI rather than Rha-AKI. Further, dietary DHA (provided by fish oil) reduced tubular injury and renal lesion by inhibiting peroxidation and inflammation in mice with Rha-AKI while increasing cell death, tissue damage, peroxidation and inflammation in mice with FA-AKI. In human renal tubular epithelial cell line HK-2, MTT assay and DHE staining showed that both myoglobin and ferroptosis inducers can cause cell death and oxidative stress. Ferroptosis inducer-induced cell death was promoted by DHA, while such result was not observed in myoglobin-induced cell death when adding DHA. This study illustrates that the mechanisms of AKI might be either ferroptosis dependent or -independent and the deterioration effect of dietary DHA depends on whether ferroptosis is involved.
Topics: Humans; Mice; Animals; Docosahexaenoic Acids; Myoglobin; Acute Kidney Injury; Fatty Acids, Omega-3; Fatty Acids, Unsaturated; Inflammation
PubMed: 37490984
DOI: 10.1016/j.jnutbio.2023.109418