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Frontiers in Immunology 2024To explore the influence of serum metabolites on the risk of psoriasis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To explore the influence of serum metabolites on the risk of psoriasis.
METHODS
In the initial stage, we applied Mendelian randomization to evaluate the association between 1,400 serum metabolites and the risk of psoriasis. Causal effects were primarily assessed through the Inverse-Variance Weighted method and Wald Ratio's odds ratios, and 95% confidence intervals. False Discovery Rate was used for multiple comparison corrections. Sensitivity analyses were conducted using Cochran's Q Test, MR-PRESSO. MR-Steiger Test was employed to check for reverse causality. In the validation stage, we sought other sources of psoriasis GWAS data to verify the initial results and used meta-analysis to combine the effect sizes to obtain robust causal relationships. In addition, we also conducted metabolic pathway enrichment analysis on known metabolites that have a causal relationship with the risk of psoriasis in both stages.
RESULTS
In the initial stage, we identified 112 metabolites causally associated with psoriasis, including 32 metabolite ratios and 80 metabolites (69 known and 11 unknown). In the validation stage, 24 metabolites (16 known, 1 unknown, and 7 metabolite ratios) were confirmed to have a causal relationship with psoriasis onset. Meta-analysis results showed that the overall effect of combined metabolites was consistent with the main analysis in direction and robust in the causal relationship with psoriasis onset. Of the 16 known metabolites, most were attributed to lipid metabolism, with 5 as risk factors and 8 as protective factors for psoriasis. Peptidic metabolite Gamma-glutamylvaline levels had a negative causal relationship with psoriasis, while exogenous metabolite Catechol sulfate levels and amino acid 3-methylglutaconate levels had a positive causal relationship with the disease onset. The metabolites associated with psoriasis risk in the two stages are mainly enriched in the following metabolic pathways: Glutathione metabolism, Alpha Linolenic Acid and Linoleic Acid Metabolism, Biosynthesis of unsaturated fatty acids, Arachidonic acid metabolism, Glycerophospholipid metabolism.
CONCLUSION
Circulating metabolites may have a potential causal relationship with psoriasis risk, and targeting specific metabolites may benefit psoriasis diagnosis, disease assessment, and treatment.
Topics: Humans; Mendelian Randomization Analysis; Causality; Risk Factors; Protective Factors; Psoriasis
PubMed: 38529280
DOI: 10.3389/fimmu.2024.1343301 -
Foods (Basel, Switzerland) Oct 2023The synthesis of tea fatty acids plays a crucial role in determining the oil content of tea seeds and selecting tea tree varieties suitable for harvesting both leaves...
The synthesis of tea fatty acids plays a crucial role in determining the oil content of tea seeds and selecting tea tree varieties suitable for harvesting both leaves and fruits. However, there is limited research on fatty acid synthesis in tea trees, and the precise mechanisms influencing tea seed oil content remain elusive. To reveal the fatty acid biosynthesis mechanism, we conducted a photosynthetic characteristic and targeted metabolomics analysis in comparison between Jincha 2 and Wuniuzao cultivars. Our findings revealed that Jincha 2 exhibited significantly higher net photosynthetic rates (Pn), stomatal conductance (Gs), and transpiration rate (Tr) compared with Wuniuzao, indicating the superior photosynthetic capabilities of Jincha 2. Totally, we identified 94 metabolites with significant changes, including key hormone regulators such as gibberellin A1 (GA1) and indole 3-acetic acid (IAA). Additionally, linolenic acid, methyl dihydrojasmonate, and methylthiobutyric acid, precursors required for fatty acid synthesis, were significantly more abundant in Jincha 2 compared with Wuniuzao. In summary, our research suggests that photosynthetic rates and metabolites contribute to the increased yield, fatty acid synthesis, and oil content observed in Jincha 2 when compared with Wuniuzao.
PubMed: 37893714
DOI: 10.3390/foods12203821 -
Clinical and Experimental Medicine Nov 2023Idiopathic inflammatory myopathy (IIM) are heterogeneous autoimmune diseases that primarily affect the proximal muscles. IIM subtypes include dermatomyositis (DM),...
Idiopathic inflammatory myopathy (IIM) are heterogeneous autoimmune diseases that primarily affect the proximal muscles. IIM subtypes include dermatomyositis (DM), polymyositis (PM), and anti-synthetase syndrome (ASS). Metabolic disturbances may cause irreversible structural damage to muscle fibers in patients with IIM. However, the metabolite profile of patients with different IIM subtypes remains elusive. To investigate metabolic alterations and identify patients with different IIM subtypes, we comprehensively profiled plasma metabolomics of 46 DM, 13 PM, 12 ASS patients, and 30 healthy controls (HCs) using UHPLC-Q Exactive HF mass spectrometer. Multiple statistical analyses and random forest were used to discover differential metabolites and potential biomarkers. We found that tryptophan metabolism, phenylalanine and tyrosine metabolism, fatty acid biosynthesis, beta-oxidation of very long chain fatty acids, alpha-linolenic acid and linoleic acid metabolism, steroidogenesis, bile acid biosynthesis, purine metabolism, and caffeine metabolism are all enriched in the DM, PM, and ASS groups. We also found that different subtypes of IIM have their unique metabolic pathways. We constructed three models (five metabolites) to identify DM, PM, ASS from HC in the discovery and validation sets. Five to seven metabolites can distinguish DM from PM, DM from ASS, and PM from ASS. A panel of seven metabolites can identify anti-melanoma differentiation-associated gene 5 positive (MDA5 +) DM with high accuracy in the discovery and validation sets. Our results provide potential biomarkers for diagnosing different subtypes of IIM and a better understanding of the underlying mechanisms of IIM.
Topics: Humans; Dermatomyositis; Myositis; Polymyositis; Autoimmune Diseases; Biomarkers
PubMed: 37103652
DOI: 10.1007/s10238-023-01073-6 -
Nutrients Aug 2023The microbiota gut-brain axis (mGBA) is an important contributor to mental health and neurological and mood disorders. Lipopolysaccharides (LPS) are endotoxins that are...
The microbiota gut-brain axis (mGBA) is an important contributor to mental health and neurological and mood disorders. Lipopolysaccharides (LPS) are endotoxins that are components of Gram-negative bacteria cell walls and have been widely shown to induce both systemic and neuro-inflammation. Flaxseed () is an oilseed rich in fibre, n3-poly-unsaturated fatty acid (alpha-linolenic acid (ALA)), and lignan, secoisolariciresinol diglucoside, which all can induce beneficial effects across varying aspects of the mGBA. The objective of this study was to determine the potential for dietary supplementation with flaxseed or flaxseed oil to attenuate LPS-induced inflammation through modulation of the mGBA. In this study, 72 5-week-old male C57Bl/6 mice were fed one of three isocaloric diets for 3 weeks: (1) AIN-93G basal diet (BD), (2) BD + 10% flaxseed (FS), or (3) BD + 4% FS oil (FO). Mice were then injected with LPS (1 mg/kg i.p) or saline ( = 12/group) and samples were collected 24 h post-injection. Dietary supplementation with FS, but not FO, partially attenuated LPS-induced systemic (serum TNF-α and IL-10) and neuro-inflammation (hippocampal and/or medial prefrontal cortex IL-10, TNF-α, IL-1β mRNA expression), but had no effect on sickness and nest-building behaviours. FS-fed mice had enhanced fecal microbial diversity with increased relative abundance of beneficial microbial groups (i.e., Lachnospiraceae, , Coriobacteriaceae), reduced , and increased production of short-chain fatty acids (SCFAs), which may play a role in its anti-inflammatory response. Overall, this study highlights the potential for flaxseed to attenuate LPS-induced inflammation, in part through modulation of the intestinal microbiota, an effect which may not be solely driven by its ALA-rich oil component.
Topics: Male; Animals; Mice; Flax; Linseed Oil; Lipopolysaccharides; Interleukin-10; Brain-Gut Axis; Tumor Necrosis Factor-alpha; Gastrointestinal Microbiome; Diet
PubMed: 37630732
DOI: 10.3390/nu15163542 -
Foods (Basel, Switzerland) Nov 2023This research elaborates the process of enriching table eggs with n-3 polyunsaturated fatty acids (n-3 PUFA) and presents the effect of such enriched eggs on human...
This research elaborates the process of enriching table eggs with n-3 polyunsaturated fatty acids (n-3 PUFA) and presents the effect of such enriched eggs on human health. The experiment was performed on 480 TETRA SL laying hens divided into three groups. Feeding mixtures contained 5% of oils (K = soybean oil, P1 = 3.5% linseed oil + 1.5% fish oil, P2 = 3% linseed oil + 2% fish oil). Referring to the content of α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), eggs of P1 and P2 groups were significantly richer in n-3 PUFA than eggs of the control group ( = 0.001). Atherogenic (AI), thrombogenic (TI), and hypo/hypercholesterolemic (HHI) indexes of egg yolks were more favourable in enriched eggs than in conventional eggs. Fatty acid profiles in the blood of examinees that consumed conventional and enriched eggs (treatments K and P1, respectively) differed significantly in total saturated fatty acids (ΣSFA) ( = 0.041) and in the content of ALA ( = 0.010). The consumption of n-3 PUFA-enriched eggs lowered the Σn-6 PUFA/Σn-3 PUFA ratio in the examinees' blood serum (27%) and had a favourable effect on some blood biochemical indicators. This research confirmed the assumption that the use of a combination of fish and linseed oil in mixtures for laying hens in an amount of up to 5% will increase the content of omega-3 in table eggs, but it was not confirmed that the consumption of these eggs in a short period of time (21 days) has a positive effect on human health.
PubMed: 38231614
DOI: 10.3390/foods12234202 -
Food Chemistry: X Oct 2023The n6/n3 ratios improved meat quality of terrestrial animals, but alpha-linolenic acid/linoleic acid (ALA/LNA) ratios were rarely studied in aquatic animals. In this...
The n6/n3 ratios improved meat quality of terrestrial animals, but alpha-linolenic acid/linoleic acid (ALA/LNA) ratios were rarely studied in aquatic animals. In this study, sub-adult grass carp were fed diets fed diets containing six varying ALA/LNA ratios (0.03, 0.47, 0.92, 1.33, 1.69, and 2.15) for 9 weeks and the total value of n3 + n6 (1.98) was kept constant for all six treatments. The results indicated optimal ALA/LNA ratio improved growth performance, changed fatty acid composition in grass carp muscle, and promoted glucose metabolism. Additionally, optimal ALA/LNA ratio improved chemical attributes by increasing crude protein and lipid contents, and technological attributes by increasing pH value and shear force in grass carp muscle. The signaling pathways related to fatty acid metabolism and glucose metabolism (LXRα/SREBP-1, PPARα, PPARγ, AMPK) might be responsible for these changes. Dietary optimal ALA/LNA ratio based on PWG, UFA and glucose contents was 1.03, 0.88 and 0.92, respectively.
PubMed: 37384144
DOI: 10.1016/j.fochx.2023.100752 -
World Journal of Diabetes May 2024The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes...
BACKGROUND
The understanding of bile acid (BA) and unsaturated fatty acid (UFA) profiles, as well as their dysregulation, remains elusive in individuals with type 2 diabetes mellitus (T2DM) coexisting with non-alcoholic fatty liver disease (NAFLD). Investigating these metabolites could offer valuable insights into the pathophy-siology of NAFLD in T2DM.
AIM
To identify potential metabolite biomarkers capable of distinguishing between NAFLD and T2DM.
METHODS
A training model was developed involving 399 participants, comprising 113 healthy controls (HCs), 134 individuals with T2DM without NAFLD, and 152 individuals with T2DM and NAFLD. External validation encompassed 172 participants. NAFLD patients were divided based on liver fibrosis scores. The analytical approach employed univariate testing, orthogonal partial least squares-discriminant analysis, logistic regression, receiver operating characteristic curve analysis, and decision curve analysis to pinpoint and assess the diagnostic value of serum biomarkers.
RESULTS
Compared to HCs, both T2DM and NAFLD groups exhibited diminished levels of specific BAs. In UFAs, particular acids exhibited a positive correlation with NAFLD risk in T2DM, while the ω-6:ω-3 UFA ratio demonstrated a negative correlation. Levels of α-linolenic acid and γ-linolenic acid were linked to significant liver fibrosis in NAFLD. The validation cohort substantiated the predictive efficacy of these biomarkers for assessing NAFLD risk in T2DM patients.
CONCLUSION
This study underscores the connection between altered BA and UFA profiles and the presence of NAFLD in individuals with T2DM, proposing their potential as biomarkers in the pathogenesis of NAFLD.
PubMed: 38766436
DOI: 10.4239/wjd.v15.i5.898 -
Molecules (Basel, Switzerland) Aug 2023Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and...
Structural Studies of Monounsaturated and ω-3 Polyunsaturated Free Fatty Acids in Solution with the Combined Use οf NMR and DFT Calculations-Comparison with the Liquid State.
Molecular structures, in chloroform and DMSO solution, of the free fatty acids (FFAs) caproleic acid, oleic acid, α-linolenic acid, eicosapentanoic acid (EPA) and docosahexaenoic acid (DHA) are reported with the combined use of NMR and DFT calculations. Variable temperature and concentration chemical shifts of the COOH protons, transient 1D NOE experiments and DFT calculations demonstrate the major contribution of low molecular weight aggregates of dimerized fatty acids through intermolecular hydrogen bond interactions of the carboxylic groups, with parallel and antiparallel interdigitated structures even at the low concentration of 20 mM in CDCl. For the dimeric DHA, a structural model of an intermolecular hydrogen bond through carboxylic groups and an intermolecular hydrogen bond between the carboxylic group of one molecule and the ω-3 double bond of a second molecule is shown to play a role. In DMSO-d solution, NMR and DFT studies show that the carboxylic groups form strong intermolecular hydrogen bond interactions with a single discrete solvation molecule of DMSO. These solvation species form parallel and antiparallel interdigitated structures of low molecular weight, as in chloroform solution. This structural motif, therefore, is an intrinsic property of the FFAs, which is not strongly affected by the length and degree of unsaturation of the chain and the hydrogen bond ability of the solvent.
PubMed: 37630396
DOI: 10.3390/molecules28166144 -
Frontiers in Microbiology 2023Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia....
BACKGROUND
Inhaled oxygen is the first-line therapeutic approach for maintaining tissue oxygenation in critically ill patients, but usually exposes patients to damaging hyperoxia. Hyperoxia adversely increases the oxygen tension in the gut lumen which harbors the trillions of microorganisms playing an important role in host metabolism and immunity. Nevertheless, the effects of hyperoxia on gut microbiome and metabolome remain unclear, and metagenomic and metabolomics analysis were performed in this mouse study.
METHODS
C57BL/6 mice were randomly divided into a control (CON) group exposed to room air with fractional inspired oxygen (FiO) of 21% and a hyperoxia (OXY) group exposed to FiO of 80% for 7 days, respectively. Fecal pellets were collected on day 7 and subjected to metagenomic sequencing. Another experiment with the same design was performed to explore the impact of hyperoxia on gut and serum metabolome. Fecal pellets and blood were collected and high-performance liquid chromatography with mass spectrometric analysis was carried out.
RESULTS
At the phylum level, hyperoxia increased the ratio of ( = 0.049). At the species level, hyperoxia reduced the abundance of ( = 0.007), ( = 0.010), and ( = 0.011) . Linear discriminant analysis effect size (LEfSe) revealed that and , both belonging to , were the marker microbes of the CON group, while was the marker microbes of the OXY group. Metagenomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Carbohydrate-Active enZYmes (CAZy) revealed that hyperoxia provoked disturbances in carbohydrate and lipid metabolism. Fecal metabolomics analysis showed hyperoxia reduced 11-dehydro Thromboxane B2-d4 biosynthesis ( = 1.10 × 10). Hyperoxia blunted fecal linoleic acid metabolism ( = 0.008) and alpha-linolenic acid metabolism ( = 0.014). We showed that 1-docosanoyl-glycer-3-phosphate ( = 1.58 × 10) was the most significant differential serum metabolite inhibited by hyperoxia. In addition, hyperoxia suppressed serum hypoxia-inducible factor-1 (HIF-1, = 0.007) and glucagon signaling pathways ( = 0.007).
CONCLUSION
Hyperoxia leads to gut dysbiosis by eliminating beneficial and oxygen strictly intolerant with genomic dysfunction of carbohydrate and lipid metabolism. In addition, hyperoxia suppresses unsaturated fatty acid metabolism in the gut and inhibits the HIF-1 and glucagon signaling pathways in the serum.
PubMed: 37840730
DOI: 10.3389/fmicb.2023.1197970 -
Heliyon Nov 2023The presented study examines the chemical composition and antioxidant activity of the petroleum ether fraction of (PEF-RO), which was obtained via 75 % ethanol...
The presented study examines the chemical composition and antioxidant activity of the petroleum ether fraction of (PEF-RO), which was obtained via 75 % ethanol extraction followed by petroleum ether extraction. The obtained fractions were analyzed by gas chromatography-mass spectrometry (GC-MS). The antioxidant activity of PEF-RO was investigated using various assays, including 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulfonate (ABTS) free radical scavenging, and ferric reducing antioxidant power (FRAP) method. A total of 82 chemical components were successfully identified, totaling 10.06 % of PEF-RO content. The identified components consisted of 24 hydrocarbons, 14 ketones, 16 alcohols, 4 phenols, 14 esters, and 10 other compounds. Notably, verbenone (2.4377 %), vitamin A (0.6854 %), -geraniol (0.5998 %), linolenic acid (0.5713 %), and 1,8-eucalyptol (0.5323 %) were the most abundant compounds, and there are many trace components in PEF-RO. PEF-RO's IC values of DPPH and ABTS free radical scavenging were determined as 0.36 mg/mL and 0.19 mg/mL, respectively. FRAP-method was employed to measure the total antioxidant energy of PEF-RO, which displayed good antioxidant activity. The obtained data provides the foundation for the comprehensive development and utilization of .
PubMed: 37942163
DOI: 10.1016/j.heliyon.2023.e21316