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Introduction: Multiple system atrophy (MSA) is a rapidly progressing neurodegenerative disorder. Although diverse biomarkers have been established for Parkinson's disease (PD), no widely accepted markers have been identified in MSA. Pyruvate and lactate are the end-product of glycolysis and crucial for brain metabolism. However, their correlation with MSA remains unclear. Moreover, it is elusive how lifestyles modify these metabolites. Methods: To investigate the correlation and diagnostic value of plasma pyruvate and lactate levels in MSA and PD. Moreover, we explored how lifestyle-related metabolites interact with these metabolites in determining the disease risk. We assayed the 3 metabolites in pyruvate/lactate and 6 in the tea/coffee metabolic pathways by targeted mass spectrometry and evaluate their interactions and performance in diagnosis and differentiation between MSA and PD. Results: We found that 7 metabolites were significantly different between MSA, PD and healthy controls (HCs). Particularly, pyruvate was increased in PD while significantly decreased in MSA patients. Moreover, the tea/coffee metabolites were negatively associated with the pyruvate level in HCs, but not in MSA and PD patients. Using machine-learning models, we showed that the combination of pyruvate and tea/coffee metabolites diagnosed MSA (AUC = 0.878) and PD (AUC = 0.833) with good performance. Additionally, pyruvate had good performance in distinguishing MSA from PD (AUC = 0.860), and the differentiation increased (AUC = 0.922) when combined with theanine and 1,3-dimethyluric acid. Conclusions: This study demonstrates that pyruvate correlates reversely with MSA and PD, and may play distinct roles in their pathogenesis, which can be modified by lifestyle-related tea/coffee metabolites.
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Introduction: Pneumoconiosis emerges as the most critical and prevalent occupational disease in China at present, according to research. Studies indicate that pneumoconiosis may indeed impact the body's phospholipid metabolism. Methods: In this study, serum samples were taken from 46 paired participants, which included patients with pneumoconiosis and dust-exposed workers. We employed ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) technology in targeted lipidomics to investigate serum target phospholipids. Initially, a pilot study was conducted with a selection of 24 pneumoconiosis patients and 24 dust-exposed workers, using both univariate and multivariate statistical analyses to preliminarily identify significant differences in phospholipids. Subsequent to this, the remaining subjects were engaged in a validation study, wherein receiver operating characteristic (ROC) analysis was performed to further substantiate the screening potency of potential lipid biomarkers for pneumoconiosis. Results: The pilot study revealed significantly reduced serum levels of 16â¶0 lysophosphatidylcholines (Lyso PC), 18â¶0-18â¶1 phosphatidylglycerol (PG), 18â¶0-18â¶1 phosphatidylethanolamine (PE), 18â¶0 PE, and 18â¶1 lysophosphatidylethanolamineï¼Lyso PE) in the case group in comparison to the control group. Additionally, 18â¶0 PE, 18â¶0-18â¶1 PE, and 18â¶1 Lyso PE emerged as significant phospholipids with superior diagnostic values [area under the curve (AUC)>0.7]. A diagnostic model was established, built on 16â¶0 PC and 18â¶0 PE (AUC>0.8). In the ROC analyses of validation studies, the 18â¶0-18â¶1 PE and this diagnostic model demonstrated excellent screening efficiency (AUC>0.7). Discussion: A significant divergence in phospholipid metabolism has been observed between pneumoconiosis patients and dust-exposed workers. The 18â¶0-18â¶1 PE present in serum could potentially function as a lipid biomarker for pneumoconiosis. Additionally, diagnostic models were developed relying on 16â¶0 PC and 18â¶0 PE, proving to have superior screening efficiency.
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OBJECTIVE: Welding fume exposure is inevitable of welding workers and poses a severe hazard to their health since welding is a necessary industrial process. Thus, preclinical diagnostic symptoms of worker exposure are of great importance. The aim of this study was to screen serum differential metabolites of welding fume exposure based on UPLC-QTOF-MS/MS. METHODS: In 2019, 49 participants were recruited at a machinery manufacturing factory. The non-target metabolomics technique was used to clarify serum metabolic signatures in people exposed to welding fume. Differential metabolites were screened by OPLS-DA analysis and Student's t-test. The receiver operating characteristic curve evaluated the discriminatory power of differential metabolites. And the correlations between differential metabolites and metal concentrations in urine and whole blood were analyzed utilizing Pearson correlation analysis. RESULTS: Thirty metabolites were increased significantly, and 5 metabolites were decreased. The differential metabolites are mainly enriched in the metabolism of arachidonic acid, glycero phospholipid, linoleic acid, and thiamine. These results observed that lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol(PGF1α/16:0) had a tremendous anticipating power with relatively increased AUC values (AUC > 0.9), and they also presented a significant correlation of Mo concentrations in whole blood and Cu concentrations in urine, respectively. CONCLUSION: The serum metabolism was changed significantly after exposure to welding fume. Lysophosphatidylcholine (20:1/0:0) and phosphatidylglycerol (PGF1α/16:0) may be a potential biological mediator and biomarker for laborers exposure to welding fume.
Subject(s)
Air Pollutants, Occupational , Occupational Exposure , Welding , Humans , Air Pollutants, Occupational/analysis , Lysophosphatidylcholines/analysis , Tandem Mass Spectrometry , Occupational Exposure/adverse effects , Occupational Exposure/analysis , Metabolome , Inhalation Exposure/analysisABSTRACT
Parabens are endocrine-disrupting chemicals (EDCs) that have estrogen-like activities and may cause male reproductive disorders. Here, we developed a method for the simultaneous determination of four parabens (MeP, EtP, n-PrP, n-BuP) and two metabolites (4-HB and 3,4-DHB) in human seminal plasma by UPLC-MS/MS. The method was used to analyze 144 seminal plasma samples from Chinese males. MeP, EtP, n-PrP, and 4-HB were the dominant compounds. MeP, EtP, and n-PrP were significantly correlated to each other. In addition, 4-HB was significantly correlated to MeP, EtP, n-PrP, and 3,4-DHB, respectively. The results provide direct evidence that parabens and their metabolites are widely distributed in the male reproductive system. The study presents the paraben metabolites levels in human seminal plasma for the first time.
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BACKGROUND AND AIMS: Carotid atherosclerosis is an important cause of ischemic stroke. Lipids play a key role in the progression of atherosclerosis. To date, the spatial lipid profile of carotid atherosclerotic plaques related to histology has not been systematically investigated. METHODS: Carotid atherosclerosis samples from 12 patients were obtained and classified into four classical pathological stages (preatheroma, atheroma, fibroatheroma and complicated lesion) by histological staining. Desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) was used to investigate the lipid profile of carotid atherosclerosis, and correlated it with histological information. Bioinformatics technology was used to process MSI data among different pathological stages of atherosclerosis lesions. RESULTS: A total of 55 lipids (26 throughout cross-section regions [TCSRs], 13 in lipid-rich regions [LRRs], and 16 in collagen-rich regions [CRRs]) were initially identified in carotid plaque from one patient. Subsequently, 32 of 55 lipids (12 in TCSRs, eight in LRRs, and 12 in CRRs) were further screened in 11 patients. Pathway enrichment analysis showed that multiple metabolic pathways, such as fat digestion and absorption, cholesterol metabolism, lipid and atherosclerosis, were enriched in TCSRs; sphingolipid signaling pathway, necroptosis pathway were enriched in LRRs; and glycerophospholipid metabolism, ether lipid metabolism pathway were mainly enriched in CRRs. CONCLUSIONS: This study comprehensively showed the spatial lipid metabolism footprint in human carotid atherosclerotic plaques. The lipid profiles and related metabolism pathways in three regions of plaque with disease progression were different markedly, suggesting that the different metabolic mechanisms in these regions of carotid plaque may be critical in atherosclerosis progression.
Subject(s)
Atherosclerosis , Carotid Artery Diseases , Plaque, Atherosclerotic , Humans , Plaque, Atherosclerotic/pathology , Carotid Artery Diseases/pathology , Atherosclerosis/pathology , Carotid Arteries/pathology , Lipids/chemistryABSTRACT
BACKGROUND: The diagnosis of cerebral thrombosis origin is challenging and remains unclear. This study aims to identify thrombosis due to cardioembolism (CE) and large artery atherosclerosis (LAA) from a new perspective of distinct metabolites. METHODS: Distinct metabolites between 26 CE and 22 LAA origin thrombi, which were extracted after successful mechanical thrombectomy in patients with acute ischemic stroke in the anterior circulation, were analyzed with a ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) system. Enriched metabolic pathways related to the metabolites were identified. Least absolute shrinkage selection operator regression analyses and a filtering method were used to select potential predictors. Furthermore, four machine learning classifiers, including decision tree, logistic regression, random forest (RF), and k means unsupervised classification model, were used to evaluate the predictive ability of the selected metabolites. RESULTS: UPLC-QTOF-MS analysis revealed that levels of 88 and 55 metabolites were elevated in LAA and CE thrombi, respectively. Kyoto Encyclopedia of Genes and Genomes analysis revealed a significant difference between the pathways enriched in the two types of thrombi. Six metabolites (diglyceride (DG, 18:3/24:0), DG (22:0/24:0), phytosphingosine, galabiosylceramide (18:1/24:1), triglyceride (15:0/16:1/o-18:0), and glucosylceramide (18:1/24:0)) were finally selected to build a predictive model. The predictive RF model was confirmed to be the best, with a satisfactory stability and prediction capacity (area under the curve=0.889). CONCLUSIONS: Six metabolites as potential predictors for distinguishing between cerebral thrombi of CE and LAA origin were identified. The results are useful for understanding the pathogenesis and for secondary stroke prevention.
Subject(s)
Atherosclerosis , Ischemic Stroke , Stroke , Thrombosis , Humans , Ischemic Stroke/complications , Atherosclerosis/complications , Atherosclerosis/diagnosis , Stroke/complications , Thrombosis/complications , Arteries/pathologyABSTRACT
In this work, untargeted lipidomics was employed to analyze the effects of coal dust exposure on serum metabolite profiles. Furthermore, the potential of differential metabolites as novel biomarkers for diagnosis was investigated by binary logistic classification model. Nineteen differential metabolites were found among the three groups. The compounds were enriched in pathways associated with linoleic acid metabolism and pyrimidine metabolism. Fifty-three differential metabolites were found in coal dust-exposed people and CWP patients, and they were mainly enriched in glycerophospholipid metabolism. Three differential metabolites were correlated with lung function values. The diagnostic model, composed of lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0), showed strong discrimination ability between dust-exposed people and CWP patients. The sensitivity, specificity, and AUC values of the model were 0.869, 0.600, and 0.750, respectively. The results suggest that coal worker's pneumoconiosis causes abnormal lipid metabolism in the body. A diagnostic model may aid current CWP diagnostic methods, and lysoPI (16:0/0:0), bilirubin, and lysoPC (24:1/0:0) can be used as potential CWP biomarkers. Further study is warranted to validate the findings in larger populations.
Subject(s)
Anthracosis , Coal Mining , Pneumoconiosis , Humans , Pneumoconiosis/complications , Pneumoconiosis/diagnosis , Lipidomics , Anthracosis/complications , Coal , Dust , Biomarkers , BilirubinABSTRACT
Acer truncatum Bunge seed oil (ASO) is rich in ω-9 (53.93%) and ω-6 (30.7%) fatty acids (FAs) and characterized by 3-7% nervonic acid (NA, C24:1ω-9). Evidence suggests that ω-9 FAs such as NA participate in processes of cognitive improvement; however, their mechanism remains ambiguous. In this study, we investigated the effect of ASO on rat memory and the change in lipid profiling and underlying metabolism. After ASO was administrated to rats for one, three and seven days, their capacity for learning and memory significantly increased via the MWM test. Lipid profiling showed alterations in a wide range of metabolic features after ASO was administrated to the rats, in which sphingolipids (SP) in the serum and glycerophospholipids (GP) in the brain were regulated significantly. The changes in the fatty acids in the serum and brain showed the synergetic effects of NA, EA, OA and DHA, where NA, EA and OA exhibited similar change trends. The enrichment analysis based on KEGG indicated that ASO supplementation evoked the pathways of neurotrophin signaling, glycerophospholipid metabolism and sphingolipid metabolism, which are related to memory and cognition improvement. Among the metabolites with different molecular forms, the biomarkers with C24:1ω-9 chains exhibited a positive correlation with others both in the serum SP and brain GP. These results suggest the synergistic effects of ω-9 FAs and that their conversion into each other may result in enhanced cognition in rats ingesting Acer truncatum Bunge seed oil.
Subject(s)
Acer , Fatty Acids, Essential/pharmacology , Fatty Acids, Monounsaturated/pharmacology , Lipid Metabolism/drug effects , Plant Oils/pharmacology , Animals , Cognition/drug effects , Diet , Disease Models, Animal , Maze Learning/drug effects , Random Allocation , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND AND PURPOSE: Radiotherapy is a standard treatment for head and neck tumors that significantly increases patients' long-term survival rates. However, late cerebrovascular complications, especially carotid artery stenosis (CAS), have gained increasing attention. Investigation of biomarkers of radiation-induced CAS may help to elucidate the mechanism by which radiation induces damage to blood vessels and identify possible preventive measures against such damage. MATERIALS AND METHODS: In this study, we used lipidomics strategy to characterize the lipids present in 8 radiation-induced carotid plaques (RICPs) and 12 atherosclerotic carotid plaques (ASCPs). We also used desorption electrospray ionization-mass spectrometry imaging (DESI-MSI) to map the spatial distribution of the screened lipids from 2 RICPs samples and 2 ASCPs samples. RESULTS: The results showed that 31 metabolites in RICPs were significantly higher than that in ASCPs, 24 of which were triglycerides (TGs). We used four machine learning models to select potential indicators from the 31 metabolites. Six TGs [TG(17:2/17:2/18:0), TG(17:1/17:2/18:0), TG(17:0/17:2/18:0), TG(17:2/17:2/20:0), TG(17:1/17:2/20:0), TG(15:0/22:0/22:2)] were found to be the potential markers for distinguishing RICPs and ASCPs (AUC = 0.83). The DESI-MSI results suggested that the 6 TGs were localized in the collagen fiber regions and confirmed the differences of these TGs between the two kinds of plaques. CONCLUSIONS: The 6 TGs primarily localized in the collagen fiber regions of plaques are likely to be potential indicators for the differentiation of RICPs from ASCPs which may have implications in the mechanisms and possible preventive measures against RICPs.
Subject(s)
Lipids , Spectrometry, Mass, Electrospray Ionization , Collagen , Humans , Lipids/analysis , Spectrometry, Mass, Electrospray Ionization/methodsABSTRACT
Hexavalent chromium (Cr(VI)) compound is considered as a common environmental and occupational pollutant due to widespread application in industry and agriculture. Cr(VI) as a carcinogen poses a serious threat to human health and the underlying mechanisms need further investigation. Previous studies had demonstrated the characteristic expression profiling after Cr(VI) treatment in vitro and in vivo at the levels of gene and protein. The comprehensive metabolic signatures were also conducive to discover potential biomarkers for effects assessment of Cr(VI) toxicity. In the current study, Ultra-performance liquid chromatography coupled with mass spectrometry (UPLC-MS) non-targeted metabolomics was applied to analyze serum metabolic changes in 77 chromate exposure workers and 62 controls. Thirteen metabolites were found significantly decreased and 41 metabolites were increased, which were involved in arginine and proline metabolism, and glycerophospholipid metabolism by bioinformatic analysis. Furthermore, there were significant negative correlations between blood Cr level and Arginine, PC(18:2/24:4) and PC(14:0/16:0), subgroup analyses indicated that these correlations were observed in male-only subgroups, and were not found among chromate workers and controls separately. Diet could be a potential confounder which was not controlled rigorously in this study. These findings provided preliminary clues to investigate the underlying mechanisms of Cr(VI)-induced toxicity and were required to be further verified in future researches.
Subject(s)
Chromium/adverse effects , Metabolome/drug effects , Metabolomics , Occupational Exposure/adverse effects , Proteome/drug effects , Proteomics , Adult , Arginine/blood , Biomarkers/blood , Case-Control Studies , Chromatography, Liquid , Computational Biology , Female , Humans , Lipidomics , Male , Middle Aged , Occupational Health , Phosphatidylcholines/blood , Spectrometry, Mass, Electrospray IonizationABSTRACT
The adverse effects of parabens raise concerns about their extensive use as preservatives in consumer products, especially in cosmetics. Until now, their distribution and excretion in humans have attracted little attention. Here, we quantified various agents including, for the first time, methyl-; ethyl-; n-propyl-; n-butyl-, and i-butylparaben (MeP, EtP, PrP, n-BuP, i-BuP); methyl- and ethyl-protocatechuate (OH-MeP and OH-EtP); hydroxybenzoic acid (4-HB); and 3,4-dihydroxybenzoic acid (3,4-DHB) in urine, serum, and seminal plasma samples from 50 healthy Chinese men in Beijing, China. Urine paraben concentrations were 1-2 orders of magnitudes higher than those in serum and seminal plasma. MeP and PrP were predominant and correlated with each other in the urine, serum, and seminal plasma. In urine, we observed a significant correlation between MeP and OH-MeP; EtP and OH-EtP; and 4-HB and 3,4-DHB concentrations. All these results provide new information on parabens as biomarkers for the assessment of exposure.
Subject(s)
Parabens , Semen , Adult , Beijing , China , Correlation of Data , Environmental Exposure/analysis , Humans , Male , Parabens/analysis , Semen/chemistryABSTRACT
A sensitive, high-throughput method was established for the simultaneous determination of 12 antiepileptics in serum by ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The antiepileptics were gabapentin, lamotrigine, pregabalin, lacosamide, levetiracetam, topiramate, oxcarbazepine, clonazepam, sodium valproate, carbamazepine, phenobarbital and phenytoin sodium. Phenacetin and chlorzoxazone were used as internal standards. The antiepileptics and internal standards were extracted from serum by protein precipitation using acetonitrile as the precipitant. Chromatographic separation was achieved on an ACQUITY UPLC BEH C18 column with a gradient mobile phase comprising 10 mmol/L ammonium formate aqueous solution and methanol (containing 10 mmol/L ammonium formate) at a flow rate of 0.4 mL/min. Detection was performed in multiple reaction monitoring mode with ion mode switching. The results showed good linear trends in their respective concentration ranges and the correlation coefficients (r2) were greater than 0.992. The spiked recoveries of the 12 antiepileptics in serum were 90.80%-114.0% at the three spiked levels. The intra-assay (n=6) and inter-assay (n=3) precisions were less than 13.2% and 14.8%, respectively. The method has high specificity and sensitivity, and it can be used for clinical blood concentration monitoring and pharmacokinetic studies of the 12 antiepileptics.