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The Journal of Allergy and Clinical... Nov 2023Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D, and low levels of prostaglandin E. Further,...
BACKGROUND
Aspirin-exacerbated respiratory disease (AERD) is associated with high levels of cysteinyl leukotrienes, prostaglandin D, and low levels of prostaglandin E. Further, 15-hydroxyeicosatetraenoic acid (15-HETE) levels may have predictive value in therapeutic outcomes of aspirin desensitization. Accumulation of nasal group 2 innate lymphoid cells (ILC2s) has been demonstrated during COX-1 inhibition in AERD, although the relationships between tissue ILC2 accumulation, reaction symptom severity, and novel lipid biomarkers are unknown.
OBJECTIVE
We sought to determine whether novel lipid mediators are predictive of nasal ILC2 accumulation and symptom scores during COX-1 inhibitor challenge in patients with AERD.
METHODS
Blood and nasal scraping samples from patients with AERD were collected at baseline and COX-1 inhibitor reaction and then processed for flow cytometry for nasal ILC2s and serum for lipidomic analysis.
RESULTS
Eight patients with AERD who were undergoing aspirin desensitization were recruited. Of the 161 eicosanoids tested, 42 serum mediators were detected. Baseline levels of 15-HETE were negatively correlated with the change in numbers of airway ILC2s (r = -0.6667; P = .0428). Docosahexaenoic acid epoxygenase metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) was positively correlated with both changes in airway ILC2s (r = 0.7143; P = .0305) and clinical symptom scores (r = 0.5000; P = .0081).
CONCLUSION
Low levels of baseline 15-HETE predicted a greater accumulation of airway ILC2s in patients with AERD who were receiving COX-1 inhibition. Further, increases in the cytochrome P pathway metabolite 19,20-dihydroxy-4Z,7Z,10Z,13Z,16Z-docosapentaenoic acid (19,20-diHDPA) were associated with increased symptoms and nasal ILC2 accumulation. Future studies to assess how these mediators might control ILC2s may improve the understanding of AERD pathogenesis.
Topics: Humans; Immunity, Innate; Lymphocytes; Asthma, Aspirin-Induced; Hydroxyeicosatetraenoic Acids; Cyclooxygenase Inhibitors; Sinusitis; Nasal Mucosa; Prostaglandins; Eicosanoids; Aspirin; Nasal Polyps
PubMed: 37543185
DOI: 10.1016/j.jaci.2023.06.028 -
Progress in Lipid Research Jul 2023This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA... (Review)
Review
This review is about the role of arachidonic acid (ArA) in foetal and early growth and development. In 1975 and '76, we reported the preferential incorporation of ArA into the developing brain of rat pups, its conservation as a principal component in the brains of 32 mammalian species and the high proportion delivered by the human placenta for foetal nutrition, compared to its parent linoleic acid (LA). ArA is quantitatively the principal acyl component of membrane lipids from foetal red cells, mononuclear cells, astrocytes, endothelium, and placenta. Functionally, we present evidence that ArA, but not DHA, relaxes the foetal mesenteric arteries. The placenta biomagnifies ArA, doubling the proportion of the maternal level in cord blood. The proportions of ArA and its allies (di-homo-gamma-linolenic acid (DGLA), adrenic acid and ω6 docosapentaenoic acid) are similar or higher than the total of ω3 fatty acids in human milk, maintaining the abundant supply to the developing infant. Despite the evidence of the importance of ArA, the European Food Standard Agency, in 2014 rejected the joint FAO and WHO recommendation on the inclusion of ArA in infant formula, although they recommended DHA. The almost universal dominance of ArA in the membrane phosphoglycerides during human organogenesis and prenatal growth suggests that the importance of ArA and its allies in reproductive biology needs to be re-evaluated urgently.
Topics: Pregnancy; Female; Humans; Animals; Rats; Arachidonic Acid; Docosahexaenoic Acids; Linoleic Acid; Infant Formula; Glycerophospholipids; Mammals
PubMed: 36746351
DOI: 10.1016/j.plipres.2023.101222 -
Frontiers in Endocrinology 2023The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
OBJECTIVE
The purpose of this study was to investigate the association between serum polyunsaturated fatty acids (PUFAs) and bone mineral density (BMD).
METHODS
We performed a cross-sectional study based on data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. The weighted multiple linear regression model was utilized to determine the association between serum PUFAs and BMD. Further smoothed curve fitting and threshold effect analysis were conducted. Finally, we performed a subgroup analysis.
RESULTS
In total, 1979 participants aged 20-59 years were enrolled. After adjusting for all covariates, we found that serum docosapentaenoic acid (DPA) was positively associated with head BMD (β = 0.0015, 95% Cl: 0.0004, 0.0026, P = 0.008296) and lumbar spine BMD (β = 0.0005, 95% Cl: 0.0000, 0.0010, P = 0.036093), and serum eicosadienoic acid (EDA) was negatively associated with thoracic spine BMD (β = -0.0008, 95% Cl: -0.0016, -0.0000, P = 0.045355). Smoothed curve fitting revealed a nonlinear positive association between serum DPA and lumbar spine BMD. Threshold effect analysis indicated that the threshold of serum DPA was 81.4 µmol/L. Subgroup analysis revealed a positive correlation between serum DPA and head BMD in the subgroup aged 50-59 years (β = 0.0025, 95% Cl: 0.0002, 0.0049, P = 0.035249) and females (β = 0.0026, 95% Cl: 0.0008, 0.0044, P = 0.005005). There was a positive relationship between serum DPA and lumbar spine BMD in females (β = 0.0008, 95% Cl: 0.0001, 0.0015, P = 0.017900) and a negative association between serum EDA and thoracic spine BMD in the subgroup aged 30-39 years (β = -0.0016, 95% Cl: -0.0031, -0.0001, P = 0.041331), males (β = -0.0012, 95% Cl: -0.0023, -0.0001, P = 0.039364) and other races (β = -0.0021, 95% Cl: -0.0037, -0.0006, P = 0.008059).
CONCLUSION
This study demonstrated a linear positive relationship between serum DPA and head BMD, a nonlinear positive association between serum DPA and lumbar spine BMD, and a linear negative correlation between serum EDA and thoracic spine BMD in US adults.
Topics: Male; Female; Humans; Adult; Bone Density; Nutrition Surveys; Absorptiometry, Photon; Cross-Sectional Studies; Fatty Acids, Unsaturated; Lumbar Vertebrae
PubMed: 38047106
DOI: 10.3389/fendo.2023.1266329 -
Nutrients Apr 2024Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for...
Colorectal cancer (CRC), a major global health concern, may be influenced by dietary protein digestibility impacting gut microbiota and metabolites, which is crucial for cancer therapy effectiveness. This study explored the effects of a casein protein diet (CTL) versus a free amino acid (FAA)-based diet on CRC progression, gut microbiota, and metabolites using carcinogen-induced (AOM/DSS) and spontaneous genetically induced ( mice) CRC mouse models. Comprehensive approaches including 16s rRNA gene sequencing, transcriptomics, metabolomics, and immunohistochemistry were utilized. We found that the FAA significantly attenuated CRC progression, evidenced by reduced colonic shortening and histopathological alterations compared to the CTL diet. Notably, the FAA enriched beneficial gut bacteria like and and reversed CRC-associated dysbiosis. Metabolomic analysis highlighted an increase in ornithine cycle metabolites and specific fatty acids, such as Docosapentaenoic acid (DPA), in FAA-fed mice. Transcriptomic analysis revealed that FAA up-regulated Egl-9 family hypoxia inducible factor 3 (Egln 3) and downregulated several cancer-associated pathways including Hippo, mTOR, and Wnt signaling. Additionally, DPA was found to significantly induce EGLN 3 expression in CRC cell lines. These results suggest that FAA modulate gut microbial composition, enhance protective metabolites, improve gut barrier functions, and inhibit carcinogenic pathways.
Topics: Animals; Mice; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Carcinogenesis; Cell Transformation, Neoplastic; Carcinogens; Amino Acids; Colorectal Neoplasms
PubMed: 38613073
DOI: 10.3390/nu16071040 -
PloS One 2023Omega-3 has been extensively studied for its cardiovascular disease (CVD) benefits. However, the results of this evidence are inconsistent. Therefore, in this study,...
BACKGROUND
Omega-3 has been extensively studied for its cardiovascular disease (CVD) benefits. However, the results of this evidence are inconsistent. Therefore, in this study, dietary omega-3 intake was investigated further in relation to coronary heart disease (CHD) risk among U.S. adults.
METHODS
We used data from the National Health and Nutrition Examination Survey (NHANES) database for people ages 20 years and older between 1999 and 2018 to conduct a cross-sectional survey. The Medical Condition Questionnaire (MCQ) was used to determine CHD status. We measured dietary omega-3 intake using two 24-hour dietary recall interviews. Multivariate logistic regression and subgroup analysis were used to explore the correlation between dietary omega-3 intake and CHD. The dose-response relationship between the two was analyzed with a restricted cubic spline (RCS).
RESULTS
31,184 study subjects were included, of whom 1,604 (5.14%) were patients with CHD. By quintile (Q) of dietary omega-3 intake, after adjusting for all confounding factors, compared with Q1, when total dietary omega-3, alpha-linolenic acid (ALA), docosapentaenoic acid (DPA), eicosatetraenoic acid (ETA), eicosapentaenoic acid (EPA), and docosahexenoic acid (DHA) intake reached Q5, the odds ratio (95% confidence interval, CI) of CHD were 0.76 (0.60, 0.96), 0.73 (0.57, 0.94), 0.70 (0.54, 0.92), 0.66 (0.50, 0.85), 0.84 (0.69, 1.02), and 0.83 (0.64, 1.07), respectively, while EPA and DHA were not significantly associated with the disease (Trend p > 0.05). Intake of omega-3 and CHD were linearly related (P for nonlinear = 0.603). No significant interactions were found within subgroups except for the age group (P for interaction = 0.001). Sensitivity analysis and multivariate logistic regression results are generally in agreement.
CONCLUSIONS
Total dietary omega-3, ALA, DPA, and ETA intake were negatively associated with CHD risk. In contrast, EPA and DHA had no significant correlation with CHD.
Topics: Adult; Humans; United States; Nutrition Surveys; Docosahexaenoic Acids; Cross-Sectional Studies; Fatty Acids, Omega-3; Eicosapentaenoic Acid; Coronary Disease
PubMed: 38117698
DOI: 10.1371/journal.pone.0294861 -
Biomolecules Sep 2023Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid...
Psoriasis is a skin disease characterized by epidermal hyperplasia and an inappropriate activation of the adaptive immunity. A dysregulation of the skin's lipid mediators is reported in the disease with a predominance of the inflammatory cascade derived from n-6 polyunsaturated fatty acids (n-6 PUFAs). Bioactive lipid mediators derived from arachidonic acid (AA) are involved in the inflammatory functions of T cells in psoriasis, whereas n-3 PUFAs' derivatives are anti-inflammatory metabolites. Here, we sought to evaluate the influence of a supplementation of the culture media with eicosapentaenoic acid (EPA) on the lipid profile of a psoriatic skin model produced with polarized T cells. Healthy and psoriatic skin substitutes were produced following the auto-assembly technique. Psoriatic skin substitutes produced with or without T cells presented increased epidermal and dermal linolenic acid (LA) and AA levels. N-6 PUFA lipid mediators were strongly measured in psoriatic substitutes, namely, 13-hydroxyoctadecadienoic acid (13-HODE), prostaglandin E (PGE) and 12-hydroxyeicosatetraenoic acid (12-HETE). The added EPA elevated the amounts of EPA, n-3 docosapentaenoic acid (DPA) and docosahexaenoic acid (DHA) in the epidermal and dermal phospholipids. The EPA supplementation balanced the production of epidermal lipid mediators, with an increase in prostaglandin E (PGE), 12-hydroxyeicosapentaenoic acid (12-HEPE) and -eicosapentaenoyl-ethanolamine (EPEA) levels. These findings show that EPA modulates the lipid composition of psoriatic skin substitutes by encouraging the return to a cutaneous homeostatic state.
Topics: Humans; Eicosapentaenoic Acid; T-Lymphocytes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Eicosanoids; Arachidonic Acid; Skin Diseases; Psoriasis; Dinoprostone
PubMed: 37759812
DOI: 10.3390/biom13091413 -
Frontiers in Immunology 2023Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a...
Activation of pancreatic stellate cells (PSCs) to cancer-associated fibroblasts (CAFs) is responsible for the extensive desmoplastic reaction observed in PDAC stroma: a key driver of pancreatic ductal adenocarcinoma (PDAC) chemoresistance leading to poor prognosis. Specialized pro-resolving mediators (SPMs) are prime modulators of inflammation and its resolution, traditionally thought to be produced by immune cells. Using liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based lipid mediator profiling PSCs as well as primary human CAFs express enzymes and receptors to produce and respond to SPMs. Human PSC/CAF SPM secretion profile can be modulated by rendering these cells activated [transforming growth factor beta (TGF-β)] or quiescent [all- retinoic acid (ATRA)]. ATRA-induced nuclear translocation of arachidonate-15-lipoxygenase (ALOX15) was linked to increased production of n-3 docosapentaenoic acid-derived Resolvin D5 (RvD5), among other SPMs. Inhibition of RvD5 formation increases cancer cell invasion, whereas addback of this molecule reduced activated PSC-mediated cancer cell invasion. We also observed that circulating concentrations of RvD5 levels were decreased in peripheral blood of metastatic PDAC patients when compared with those measured in plasma of non-metastatic PDAC patients. Together, these findings indicate that RvD5 may regulate cancer-stroma cross-talk and invasion.
Topics: Humans; Arachidonate 15-Lipoxygenase; Pancreatic Stellate Cells; Chromatography, Liquid; Tandem Mass Spectrometry; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Tretinoin; Neoplasm Invasiveness
PubMed: 38035115
DOI: 10.3389/fimmu.2023.1248547 -
Journal of Atherosclerosis and... Aug 2023To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii,...
AIM
To identify the most differentiated serum lipids, especially concerning particle size and fractions, between Japanese living in Japan and Japanese-Americans in Hawaii, in the absence of possible genetic confounders, and cross-sectionally examine the associated modifiable lifestyle factors.
METHODS
Overall, 1,241 (aged 40-59 years) Japanese living in Japan and Japanese-Americans in Hawaii were included. We quantified 130 serum lipid profiles (VLDL 1-5, IDL, LDL 1-6, high-density lipoprotein [HDL] 1-4, and their subfractions) using Bruker's H-nuclear magnetic resonance spectrometer for the primary outcome. Modifiable lifestyle factors included body mass index (BMI), physical activity, alcohol and smoking habits, and 70 nutrient parameters. We evaluated the different lipids between the groups using partial least squares-discriminant analysis and association between extracted lipids and lifestyle factors using multivariable linear regression analysis.
RESULTS
Concentrations of HDL4, HDL with the smallest particle size, were lower in Japanese than in Japanese-Americans of both sexes. Higher fish-derived omega-3 fatty acid intake and lower alcohol intake were associated with lower HDL4 concentrations. A 1% higher kcal intake of total omega-3 fatty acids was associated with a 9.8-mg/dL lower HDL4. Fish-derived docosapentaenoic acid, eicosapentaenoic acid, and docosahexaenoic acid intake were inversely associated with HDL4 concentration. There was no relationship between country, sex, age, or BMI.
CONCLUSIONS
Japanese and Japanese-Americans can be differentiated based on HDL4 concentration. High fish intake among the Japanese may contribute to their lower HDL4 concentration. Thus, HDL particle size may be an important clinical marker for coronary artery diseases or a fish consumption biomarker.
Topics: Animals; Female; Humans; Male; Asian; Fatty Acids, Omega-3; Lipoproteins, HDL; Lipoproteins, LDL; Smoking; Adult; Middle Aged; Hawaii; East Asian People; Japan; Health Status
PubMed: 36328528
DOI: 10.5551/jat.63762 -
The Chinese Journal of Physiology 2023Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0%...
Regular moderate physical exercise is beneficial for the cardiovascular system. Our prior study has demonstrated a long-term moderate exercise (4-week of 60-min 74.0% V̇O treadmill running) is optimal in protecting from exhaustive exercise-induced cardiac ischemic injury. This study is aimed to investigate the effect of long-term moderate exercise on myocardial metabolome in rats. Thirteen male Sprague-Dawley rats were randomly assigned into the control group (C) and the long-term moderate exercise group (E). The targeted metabolomics of the myocardium was analyzed by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system. Results showed that the metabolites categories of bile acids (BAs), fatty acids (FAs), and phenylpropanoic acids were significantly decreased. The biosynthesis of unsaturated FAs pathway was significantly downregulated. The altered metabolites in the E Group included decreased FAs (pentadecanoic acid, 10Z-heptadecenoic acid, dihomo-gamma-linolenic acid, docosahexaenoic acid, docosapentaenoic acid, and 10Z-nonadecenoic acid), decreased BAs (chenodeoxycholic acid and beta-muricholic acid), decreased organic acids (glycolic acid and 2-hydroxyglutaric acid), decreased carbohydrate (N-acetylneuraminic acid, Neu5Ac), decreased amino acids (α-aminobutyric acid and norvaline), decreased phenylpropanoic acids (hydroxyphenyllactic acid), and benzoic acids (4-hydroxybenzoic acid and phthalic acid). The results indicated that long-term moderate exercise has promoted lipids utilization in myocardium while exerted little influence on carbohydrate metabolism and diminished many detrimental metabolites. Notably, decrease of myocardial carbohydrate Neu5Ac after long-term moderate exercise might predict a prospective metabolomics biomarker for cardioprotection. This research has displayed the effect of long-term moderate exercise on myocardial metabolomic profiling in rats and indicated some promising metabolites which can be applied for exercise benefits in future.
Topics: Rats; Male; Animals; Rats, Sprague-Dawley; Chromatography, Liquid; Prospective Studies; Tandem Mass Spectrometry; Metabolome; Myocardium; Carbohydrates
PubMed: 38149568
DOI: 10.4103/cjop.CJOP-D-23-00126 -
BMC Musculoskeletal Disorders May 2024Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and...
BACKGROUND
Synovitis, characterized by inflammation of the synovial membrane, is commonly induced by meniscus tears. However, significant differences in inflammatory responses and the key inflammatory mediators of synovium induced by different types of meniscal tears remain unclear.
METHODS
Magnetic resonance imaging (MRI) was employed to identify the type of meniscus tear, and the quantification of synovial inflammation was assessed through H&E staining assay. Transcription and expression levels of IL-1β and IL-6 were evaluated using bioinformatics, ELISA, RT-qPCR, and IHC of CD68 staining assays. The therapeutic potential of Docosapentaenoic Acid (DPA) was determined through network pharmacology, ELISA, and RT-qPCR assays. The safety of DPA was assessed using colony formation and EdU staining assays.
RESULTS
The results indicate that both IL-1β and IL-6 play pivotal roles in synovitis pathogenesis, with distinct expression levels across various subtypes. Among tested meniscus tears, oblique tear and bucket handle tear induced the most severe inflammation, followed by radial tear and longitudinal tear, while horizontal tear resulted in the least inflammation. Furthermore, in synovial inflammation induced by specific meniscus tears, the anterior medial tissues exhibited significantly higher local inflammation than the anterior lateral and suprapatellar regions, highlighting the clinical relevance and practical guidance of anterior medial tissues' inflammatory levels. Additionally, we identified the essential omega-3 fatty acid DPA as a potential therapeutic agent for synovitis, demonstrating efficacy in blocking the transcription and expression of IL-1β and IL-6 with minimal side effects.
CONCLUSION
These findings provide valuable insights into the nuanced nature of synovial inflammation induced by various meniscal tear classifications and contribute to the development of new adjunctive therapeutic agents in the management of synovitis.
Topics: Tibial Meniscus Injuries; Synovitis; Magnetic Resonance Imaging; Synovial Membrane; Humans; Fatty Acids, Unsaturated; Male; Interleukin-1beta; Animals; Interleukin-6; Female; Menisci, Tibial; Mice; Disease Models, Animal
PubMed: 38734632
DOI: 10.1186/s12891-024-07491-1