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1.
Heliyon ; 10(5): e26588, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38434286

RESUMO

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.

2.
Prostaglandins Other Lipid Mediat ; 171: 106816, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38302009

RESUMO

Coal workers' pneumoconiosis (CWP) is one of the most common inhalation occupational diseases. It is no effective treatment methods. Early diagnosis of CWP could reduce mortality. Lipid mediators (LMs) as key mediators in the generation and resolution of inflammation, are natural biomarkers for diagnosis inflammatory disease, such as CWP. The UHPLC-MRM technique was used to detect LMs in urine. The metabolic network of LMs in CWP and CT group samples was comprehensively analyzed. Screening for major difference compounds between the two groups. Aimed to contribute to the early diagnosis and treatment of CWP. Urinary levels of 13-OxoODE, 9-OxoODE, and 9,10-EpOME were significantly higher in the CWP group compared with the CT group (P < 0.05). In the model group, the area under the receiver operating characteristic (ROC) for 9-OxoODE,13-OxoODE,9,10-EpOME was 84.4%, 73.3%, and 80.9%, respectively. In the validation group, the area under the ROC was 87.0%, 88.8%, and 68.8% for 9-OxoODE,13-OxoODE,9,10-EpOME, respectively. According to the logistic regression model, the area under the ROC was 80.4% in the model group and 86.7% in the validation group. 13-OxoODE,9-OxoODE,9,10-EpOME could be used as biomarkers for early diagnosis. Significant abnormalities of LOX and CYP450 enzyme pathways were seen in CWP organisms. Changes in the CYP450 enzyme pathway may be associated with PAHs.


Assuntos
Antracose , Humanos , Antracose/diagnóstico , Inflamação , Biomarcadores
3.
Commun Biol ; 6(1): 1001, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37783835

RESUMO

Hypoxic-ischemic encephalopathy (HIE) at high-altitudes leads to neonatal mortality and long-term neurological complications without effective treatment. Acer truncatum Bunge Seed extract (ASO) is reported to have effect on cognitive improvement, but its molecular mechanisms on HIE are unclear. In this study, ASO administration contributed to reduced neuronal cell edema and improved motor ability in HIE rats at a simulated 4500-meter altitude. Transcriptomics and WGCNA analysis showed genes associated with lipid biosynthesis, redox homeostasis, neuronal growth, and synaptic plasticity regulated in the ASO group. Targeted and untargeted-lipidomics revealed decreased free fatty acids and increased phospholipids with favorable ω-3/ω-6/ω-9 fatty acid ratios, as well as reduced oxidized glycerophospholipids (OxGPs) in the ASO group. Combining multi-omics analysis demonstrated FA to FA-CoA, phospholipids metabolism, and lipid peroxidation were regulated by ASO treatment. Our results illuminated preliminary metabolism mechanism of ASO ingesting in rats, implying ASO administration as potential intervention strategy for HIE under high-altitude.


Assuntos
Acer , Hipóxia-Isquemia Encefálica , Ratos , Animais , Neuroproteção , Altitude , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/prevenção & controle , Hipóxia-Isquemia Encefálica/complicações , Multiômica , Extratos Vegetais/farmacologia , Isquemia
4.
China CDC Wkly ; 5(38): 849-855, 2023 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-37814648

RESUMO

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 16∶0 lysophosphatidylcholines (Lyso PC), 18∶0-18∶1 phosphatidylglycerol (PG), 18∶0-18∶1 phosphatidylethanolamine (PE), 18∶0 PE, and 18∶1 lysophosphatidylethanolamine(Lyso PE) in the case group in comparison to the control group. Additionally, 18∶0 PE, 18∶0-18∶1 PE, and 18∶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 16∶0 PC and 18∶0 PE (AUC>0.8). In the ROC analyses of validation studies, the 18∶0-18∶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 18∶0-18∶1 PE present in serum could potentially function as a lipid biomarker for pneumoconiosis. Additionally, diagnostic models were developed relying on 16∶0 PC and 18∶0 PE, proving to have superior screening efficiency.

5.
Ecotoxicol Environ Saf ; 262: 115343, 2023 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-37562173

RESUMO

Allergic rhinitis (AR) and adenoid hypertrophy (AH) are common nasal diseases in children. Studies have shown that heavy metals are environmental risk factors for nasal diseases, and the pathogenic mechanisms may be related to dysregulation of nasal mucosal microbiota. However, it is unclear how heavy metal exposure relates to the nasal mucosal microbiota in nasal diseases. Therefore, we explored serum metal exposure levels and nasal mucosal microbiota composition in children with different nasal disease, and further studied the potential correlation between metal exposure and disease-related taxa. There were 64 children recruited for this study. The 23 metals concentrations in serum were measured by inductively coupled plasma mass spectrometry, and nasal mucosal bacteria was identified by 16S rRNA sequencing. Nasal diseases (AR and AH) in children were associated with alterations in the abundance and diversity of the nasal mucosal microbiota. The nasal microbiota of children with AR showed lower diversity, while the microbiota of children with AH showed higher diversity. Linear discriminant analysis Effect Size showed 108 differentially abundant taxa between AR and control groups, 35 differentially abundant taxa among large adenoid, moderate adenoid and small adenoid groups. The serum zinc concentration was negatively correlated with Pielou's eveness index and Simpson's Index in children classified by adenoid size. The spearman correlation analysis showed that multiple disease-related taxa were closely associated with metal concentrations in serum. Our findings may support a link between metal exposure and the diversity and composition of nasal bacteria in children with nasal disease, which present new evidence for the effects of metals on children health.

6.
Food Funct ; 14(14): 6610-6623, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37395364

RESUMO

Hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of acute neonatal death and chronic neurological damage, and severe HIE can have secondary sequelae such as cognitive impairment and cerebral palsy, for which effective interventions are lacking. In this study, we found that continuous 30-day intake of Acer truncatum Bunge seed oil (ASO) reduced brain damage and improved cognitive ability in HIE rats. Using lipidomic strategies, we observed that HIE rats had decreased unsaturated fatty acids and increased lysophospholipids in the brain. However, after 30 days of ASO treatment, phospholipids, plasmalogens, and unsaturated fatty acids increased, while lysophospholipids and oxidized glycerophospholipids decreased in both serum and the brain. Enrichment analysis showed that ASO intake mainly affected sphingolipid metabolism, fat digestion and absorption, glycerolipid metabolism and glycerophospholipid metabolic pathways in serum and the brain. Cluster, correlation, and confirmatory factor analyses showed that cognitive improvement after ASO administration was attributed to increased essential phospholipids and ω3/6/9 fatty acids, coupled with decreased oxidized glycerophospholipids in HIE rats. Our findings indicate that ASO has the potential to be developed as an effective food supplement for ischemic hypoxic newborns.


Assuntos
Acer , Hipóxia-Isquemia Encefálica , Ratos , Animais , Hipóxia-Isquemia Encefálica/tratamento farmacológico , Hipóxia-Isquemia Encefálica/metabolismo , Lipidômica , Cognição , Glicerofosfolipídeos , Óleos de Plantas/farmacologia
7.
Int Arch Occup Environ Health ; 96(7): 1029-1037, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37243737

RESUMO

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.


Assuntos
Poluentes Ocupacionais do Ar , Exposição Ocupacional , Soldagem , Humanos , Poluentes Ocupacionais do Ar/análise , Lisofosfatidilcolinas/análise , Espectrometria de Massas em Tandem , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Metaboloma , Exposição por Inalação/análise
8.
Anal Sci ; 39(7): 1163-1170, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37231185

RESUMO

Potassium ion (K+) plays an important role in the maintenance of cellular biological process for human health. Thus, the detection of K+ is very important. Here, based on the interaction between thiamonomethinecyanine dye and G-quadruplex formation sequence (PW17), K+ detection spectrum was characterized by UV-Vis spectrometry. The single-stranded sequence of PW17 can fold into G-quadruplex in the presence of K+. PW17 can induce a dimer-to-monomer transition of the absorption spectrum of cyanine dyes. This method shows high specificity against some other alkali cations, even at high concentrations of Na+. Further, this detection strategy can realize the detection of K+ in tap water.


Assuntos
DNA , Quadruplex G , Humanos , DNA/genética , DNA/química , Análise Espectral , Corantes Fluorescentes/química , Potássio/análise
9.
Toxicon ; 226: 107067, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36871921

RESUMO

Approximately 70%∼90% of mushroom poisoning deaths are caused by the class of mushroom toxins known as amatoxins. However, the rapid elimination of amatoxins from plasma within 48 h after mushroom ingestion limits the practical value of plasma amatoxin analysis as a diagnostic indicator of Amanita mushroom poisoning. To increase the positive detection rate and extend the detection window of amatoxin poisoning, we developed a new method to detect protein-bound α-amanitin based on the hypothesis that RNAP II-bound α-amanitin released from the tissue into the plasma could be degraded by trypsin hydrolysis and then detected by conventional liquid chromatography-mass spectrometry (LC‒MS). Toxicokinetic studies on mice intraperitoneally injected with 0.33 mg/kg α-amanitin were conducted to obtain and compare the concentration trends, detection rates, and detection windows of both free α-amanitin and protein-bound α-amanitin. By comparing detection results with and without trypsin hydrolysis in the liver and plasma of α-amanitin-poisoned mice, we verified the credibility of this method and the existence of protein-bound α-amanitin in plasma. Under the optimized trypsin hydrolysis conditions, we obtained a time-dependent trend of protein-bound α-amanitin in mouse plasma at 1-12 days postexposure. In contrast to the short detection window (0-4 h) of free α-amanitin in mouse plasma, the detection window of protein-bound α-amanitin was extended to 10 days postexposure, with a total detection rate of 53.33%, ranging from the limit of detection to 23.94 µg/L. In conclusion, protein-bound α-amanitin had a higher positive detection rate and a longer detection window than free α-amanitin in mice.


Assuntos
Alfa-Amanitina , Intoxicação Alimentar por Cogumelos , Animais , Camundongos , Intoxicação Alimentar por Cogumelos/diagnóstico , Tripsina/metabolismo , Amanitinas/química , Cromatografia Líquida , Amanita/química
10.
Toxics ; 11(2)2023 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-36851005

RESUMO

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.

11.
Atherosclerosis ; 364: 20-28, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36459728

RESUMO

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.


Assuntos
Aterosclerose , Doenças das Artérias Carótidas , Placa Aterosclerótica , Humanos , Placa Aterosclerótica/patologia , Doenças das Artérias Carótidas/patologia , Aterosclerose/patologia , Artérias Carótidas/patologia , Lipídeos/química
12.
J Neurointerv Surg ; 15(7): 701-707, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35654581

RESUMO

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.


Assuntos
Aterosclerose , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , AVC Isquêmico/complicações , Aterosclerose/complicações , Aterosclerose/diagnóstico , Acidente Vascular Cerebral/complicações , Trombose/complicações , Artérias/patologia
13.
Artigo em Inglês | MEDLINE | ID: mdl-36554689

RESUMO

Long-term inhalation of welding fume at high exposure can cause welder's pneumoconiosis, and metals in welding dust are associated with respiratory dysfunction. This cross-sectional study, which contains 384 Chinese male workers who were or had been working in a container factory, aimed to assess the potential risk of haemal and urinary metal content in welder's pneumoconiosis. Further, we investigated their effects on lung function parameters. Metal content and lung function were measured using inductively coupled plasma-mass spectrometry (ICP-MS) and spirometer, respectively. The concentration and metal content of respirable dust as well as total dust were collected at this container factory. Lung function of cases with welder's pneumoconiosis was significantly worse, as indicated by lower values of FVC, FVC% predicted, FEV1, FEV1% predicted, MEF25% predicted, and MMEF% predicted (p < 0.05). Results of logistic regression models showed that haemal Cr and Zn were risk factors of welder's pneumoconiosis (OR = 4.98, 95%CI: 1.73-21.20, p = 0.009 for Cr; OR = 5.23, 95%CI: 1.56-41.08, p = 0.033 for Zn) after adjusted with age, BMI, working years, welding dust exposure years, and smoking status. Multiple linear regression models showed that several metals (haemal Cd and Pb; urinary Cd and Fe) were significantly associated with different lung function indices in the welder's pneumoconiosis group. Compared to non-welders, welders were exposed to considerably higher levels of respirable dust, total dust, and six kinds of metals (p < 0.05). In conclusion, haemal Cr and Zn are positively related to welder's pneumoconiosis. Meanwhile, Cd and Pb might worsen lung function in welder's pneumoconiosis.


Assuntos
Exposição Ocupacional , Pneumoconiose , Soldagem , Masculino , Humanos , Estudos Transversais , Pulmão , Cádmio/análise , Chumbo/análise , Pneumoconiose/epidemiologia , Poeira/análise , China , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise
14.
Wei Sheng Yan Jiu ; 51(5): 803-807, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36222044

RESUMO

OBJECTIVE: To develop the certified reference material in freeze-dried human urine. METHODS: Normal human urine was collected, mixed and filtered as a matrix, then the urine was prepared by adding standard, mixing, sub-packaging, and freeze-drying; After the homogeneity and stability were tested by inductively coupled plasma mass spectrometer, the urine were determined by two methods in seven independent laboratories and the uncertainty of the certified reference material was evaluated. RESULTS: The minimum sample intake of the developed certified reference material was 0.50 mL, and the homogeneity was good. The freeze-dried material was stable for 12 months at ≤4 ℃, and the reference material was stable at 4 ℃ after reconstitution for the 7 d. The standard value and uncertainty of the two levels were(16.0±1.0) µg/L and(30.7±2.1) µg/L(k=2), respectively. CONCLUSION: The certified reference material of chromium in freeze-dried human urine in this research met the national certified reference material requirements and could be used for the quality control of the detection of chromium in laboratory human urine.


Assuntos
Cromo , Liofilização , Humanos , Espectrometria de Massas/métodos , Controle de Qualidade , Padrões de Referência
15.
Environ Sci Pollut Res Int ; 29(56): 85444-85453, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35796929

RESUMO

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.


Assuntos
Antracose , Minas de Carvão , Pneumoconiose , Humanos , Pneumoconiose/complicações , Pneumoconiose/diagnóstico , Lipidômica , Antracose/complicações , Carvão Mineral , Poeira , Biomarcadores , Bilirrubina
16.
Arch Toxicol ; 96(6): 1751-1766, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35384471

RESUMO

Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. We conducted dose-effect and time-effect studies in mice that were intraperitoneally injected with 0.33-0.66 mg/kg α-amanitin to establish a poisoning model. The liver/body weight ratio, serological indices, and pathology were evaluated to characterize the liver injury. In the time-effect study, the liver transcriptome was analyzed to explore the mRNA changes resulting from RNAP II inhibition and the underlying pathways associated with recovery. Based on the two animal studies, we established a poisoning model with three sequential liver states: early injury, regulation, and recovery. The mRNA changes reflected by the differentially expressed genes (DEGs) in the transcriptome could be used to illustrate the inhibition of RNAP II by α-amanitin. DEGs at four key time points were well matched with the three liver states, including 8-h downregulated genes in the early injury state, 16-h and 72-h upregulated genes in the regulation state, and 96-h upregulated/downregulated genes in the recovery state. By clustering analysis, the mTOR signaling pathway was screened out as the most promising potential pathway promoting recovery. The results of our investigations of the pathways and events downstream of the mTOR pathway indicated that the activation of mTOR probably contributes crucially to liver regeneration, which could be a promising basis for drug development.


Assuntos
Agaricales , Alfa-Amanitina , Fígado , Intoxicação Alimentar por Cogumelos , Transcriptoma , Alfa-Amanitina/intoxicação , Animais , Perfilação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Intoxicação Alimentar por Cogumelos/metabolismo , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo
17.
Food Funct ; 13(5): 2475-2490, 2022 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-35147628

RESUMO

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.


Assuntos
Acer , Ácidos Graxos Essenciais/farmacologia , Ácidos Graxos Monoinsaturados/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Óleos de Plantas/farmacologia , Animais , Cognição/efeitos dos fármacos , Dieta , Modelos Animais de Doenças , Aprendizagem em Labirinto/efeitos dos fármacos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
18.
Radiother Oncol ; 167: 25-33, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34902371

RESUMO

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.


Assuntos
Lipídeos , Espectrometria de Massas por Ionização por Electrospray , Colágeno , Humanos , Lipídeos/análise , Espectrometria de Massas por Ionização por Electrospray/métodos
19.
Toxicol Lett ; 349: 92-100, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34153407

RESUMO

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.


Assuntos
Cromo/efeitos adversos , Metaboloma/efeitos dos fármacos , Metabolômica , Exposição Ocupacional/efeitos adversos , Proteoma/efeitos dos fármacos , Proteômica , Adulto , Arginina/sangue , Biomarcadores/sangue , Estudos de Casos e Controles , Cromatografia Líquida , Biologia Computacional , Feminino , Humanos , Lipidômica , Masculino , Pessoa de Meia-Idade , Saúde Ocupacional , Fosfatidilcolinas/sangue , Espectrometria de Massas por Ionização por Electrospray
20.
Environ Sci Pollut Res Int ; 28(30): 41120-41126, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33774781

RESUMO

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.


Assuntos
Parabenos , Sêmen , Adulto , Pequim , China , Correlação de Dados , Exposição Ambiental/análise , Humanos , Masculino , Parabenos/análise , Sêmen/química
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