SCIENCE OF THE TOTAL ENVIRONMENT
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2024
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IF 8.2
Chanlin Fang,Yundong Yu,Shanshan Di,Xinquan Wang,Yuanxiang Jin
The tire antioxidant 6PPD has garnered extensive attention due to its widespread presence in the environment and the harmful effects of its transformation products on aquatic organisms. 6PPD has been detected in airborne dust, and it can enter mammals through inhalation exposure. While the toxic effects of 6PPD exposure have been reported in mammals, its effects on hepatic metabolism still remain poorly understood. Here, we collected the serum and liver samples at 1, 6, and 72 h following a single oral exposure of 100 mg/kg body weight (bw) 6PPD, respectively. We also investigated changes in serum and hepatic physiological indicators and metabolites, correspondingly. Results indicated that single time oral exposure a high dose of 6PPD did not significantly affect the physiological indexes of rats within a short time frame. However, untargeted metabolomics analysis of the metabolites in the liver at 1, 6, and 72 h revealed that the number of differential expression metabolites gradually increased over time and the most affected substances were lipids and lipid-like molecules. Interestingly, the KEGG pathway enrichment analysis indicated that 6PPD disrupted the riboflavin metabolism, leading to a significant decrease in FMN levels at all time points. In addition, the hepatic glucose metabolism was significantly affected at 6 and 72 h after oral administration. Taken together, short-term exposure to 6PPD disturbed lipid and riboflavin metabolism and gradually affected glucose metabolism in the liver of rats. These findings revealed the impacts of 6PPD on the hepatic metabolism in animals, and also offered some important insights into its toxicology and health risk.
研究领域:
毒理学
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环境科学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL CHROMATOGRAPHY
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2017
·Vol. 31
·期 9
·e3956
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IF 1.613
Yan Li,Gaotong Lin,Bingbao Chen,Jing Zhang,Lingtian Wang,Zixia Li,Yungang Cao,Congcong Wen,Xuezhi Yang,Gaozhong Cao,Xianqin Wang,Guoquan Cao
We developed a serum metabolomic method by gas chromatography–mass spectrometry (GC–MS) to evaluate the effect of alprazolam in rats. The GC–MS with HP-5MS (0.25 μm × 30 m × 0.25 mm) mass was conducted in electron impact ionization (EI) mode with electron energy of 70 eV, and full-scan mode with m / z 50–550. The rats were randomly divided to four groups, three alprazolam-treated groups and a control group. The alprazolam-treated rats were given 5, 10 or 20 mg/kg (low, medium, high) of alprazolam by intragastric administration each day for 14 days. The serum samples were corrected on the seventh and fourteenth days for metabolomic study. The blood was collected for biochemical tests. Then liver and brain were rapidly isolated and immersed for pathological study. Compared with the control group, on the seventh and fourteen days, the levels of d -glucose, 9,12-octadecadienoic acid, butanoic acid, l -proline, d -mannose and malic acid had changed, indicating that alprazolam induced energy metabolism, fatty acid metabolism and amino acid metabolism perturbations in rats. There was no significant difference for alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, urea and uric acid between controls and alprazolam groups. According to the pathological results, alprazolam is not hepatotoxic. Metabolomics could distinguish different alprazolam doses in rats.
研究领域:
药理学
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代谢组学
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毒理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PROTEOME RESEARCH
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2024
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IF 3.8
Yuqing Zhang,Hui Zhao,Jinhui Zhao,Wangjie Lv,Xueni Jia,Xin Lu,Xinjie Zhao,Guowang Xu
The co-occurrence of multiple chronic metabolic diseases is highly prevalent, posing a huge health threat. Clarifying the metabolic associations between them, as well as identifying metabolites which allow discrimination between diseases, will provide new biological insights into their co-occurrence. Herein, we utilized targeted serum metabolomics and lipidomics covering over 700 metabolites to characterize metabolic alterations and associations related to seven chronic metabolic diseases (obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, fatty liver) from 1626 participants. We identified 454 metabolites were shared among at least two chronic metabolic diseases, accounting for 73.3% of all 619 significant metabolite–disease associations. We found amino acids, lactic acid, 2-hydroxybutyric acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity across multiple chronic metabolic diseases. Many carnitines were specifically associated with hyperuricemia. The hypercholesterolemia group showed obvious lipid metabolism disorder. Using logistic regression models, we further identified distinguished metabolites of seven chronic metabolic diseases, which exhibited satisfactory area under curve (AUC) values ranging from 0.848 to 1 in discovery and validation sets. Overall, quantitative metabolome and lipidome data sets revealed widespread and interconnected metabolic disorders among seven chronic metabolic diseases. The distinguished metabolites are useful for diagnosing chronic metabolic diseases and provide a reference value for further clinical intervention and management based on metabolomics strategy.
研究领域:
医学
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生物化学
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代谢研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
INFLAMMATION
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2024
·
IF 4.5
Cai Lu-Qiong,Li Xiu-Chun,Wang Yang-Yue,Chen Yu-Xin,Zhu Xia-Yan,Zuo Zi-Yi,Si-Ma Yi-Qun,Lin Yi-Nuo,Li Xiao-Kun,Huang Xiao-Ying
Aging is a physiological condition accomplished with persistent low-grade inflammation and metabolic disorders. FGF21 has been reported to act as a potent longevity determinant, involving inflammatory response and energy metabolism. In this study, we engineered aging FGF21 knockout mice of 36–40 weeks and observed that FGF21 deficiency manifests a spontaneous inflammatory response of lung and abnormal accumulation of lipids in liver. On one hand, inflamed state in lungs and increased circulating inflammatory cytokines were found in FGF21 knockout mice of 36–40 weeks. To evaluate the ability of FGF21 to suppress inflammation, a subsequent study found that FGF21 knockout aggravated LPS-induced pulmonary exudation and inflammatory infiltration in mice, while exogenous administration of FGF21 reversed these malignant phenotypes by enhancing microvascular endothelial junction. On the other hand, FGF21 knockout induces fatty liver in aging mice, characterized by excessive accumulation of triglycerides within hepatocytes. Further quantitative metabolomics and lipidomics analysis revealed perturbed metabolic profile in liver lacking FGF21, including disrupted glucose and lipids metabolism, glycerophospholipid metabolism, and amino acid metabolism. Taken together, this investigation reveals the protective role of FGF21 during aging by weakening the inflammatory response and balancing energy metabolism.
研究领域:
衰老
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分子生物学
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免疫学
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代谢
✓ 已验证
DOI
PubMed
高影响因子
Chinese Journal of Natural Medicines
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2018
·
IF 1.991
Hao QIAN,Fang-Jun YU,Dan-Yi LU,Bao-Jian WU,Xing-Wang ZHANG,Huan WANG,Zhi-Guo MA
Poliumoside is representative of phenylethanoid glycosides, which are widely found in many plants. Poliumoside is also regarded as the main active component of Callicarpa kwangtungensis Chun (CK), though its oral bioavailability in rat is extremely low (0.69%) and its in vivo and in vitro metabolism has not yet been systematically investigated. In the present study, an ultra performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC/Q-TOF-MS) method was employed to identify the metabolites and investigate the metabolic pathways of poliumoside in rat after oral administration 1.5 g·kg –1 of poliumoside. As a result, a total of 34 metabolites (30 from urine, 17 from plasma, and 4 from bile) and 9 possible metabolic pathways (rearrangment, reduction, hydration, hydrolyzation, dehydration, methylation, hydroxylation, acetylation, and sulfation) were proposed in vivo . The main metabolite, acteoside, was quantified after incubated with rat intestinal bacteria in vitro . In conclusion, the present study systematically explored the metabolites of poliumoside in vivo and in vitro , proposing metabolic pathways that may be significant for further metabolic studies of poliumoside.
研究领域:
药理学
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分析化学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICAL AND ENVIRONMENTAL SCIENCES
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2020
·
IF 2.656
Yu Meng WANG,Wei Yi WANG,Li Yan SUN,Qiang LI,Zhi Jun ZHAO,Jian HU,Rong Yu ZHANG,Li Hua WANG
Objective To explore potential serum biomarkers of children with Kashin-Beck Disease (KBD) and the metabolic pathways to which the biomarkers belong. Methods A two-stage metabolomic study was employed. The discovery cohort included 56 patients, 51 internal controls, and 50 external controls. The metabolites were determined by HPLC-(Q-TOF)-MS and confirmed by Human Metabolome Databases (HMDB) and Metlin databases. MetaboAnalyst 3.0 and the Kyoto Encyclopedia of Genes and Genomes (KEGG) database were used to analyze the metabolic pathways of the candidate metabolites. The use of HPLC-(Q-TRAP)-MS enabled quantitative detection of the target metabolites which were chosen using the discovery study and verified in another independent verification cohort of 31 patients, 41 internal controls, and 50 external controls. Results Eight candidate metabolites were identified out in the discovery study, namely kynurenic acid, N-α-acetylarginine, 6-hydroxymelatonin, sphinganine, ceramide, sphingosine-1P, spermidine, and glycine. These metabolites exist in sphingolipid, glutathione, and tryptophan metabolic pathways. In the second-stage study, five candidate metabolites were validated, including kynurenic acid, N-α-acetylarginine, sphinganine, spermidine, and sphingosine-1P. Except for spermidine, all substances exhibited low expression in the case group compared with the external control group, and the difference in levels of sphinganine, spermidine, and sphingosine-1P was statistically significant. Conclusion The direction of change of levels of sphinganine, spermidine, and sphingosine-1P in the two-stage study cohorts was completely consistent, and the differences were statistically significant. Therefore, these substances can be used as potential biomarkers of KBD. Furthermore, these results raise the possibility that sphingolipid metabolic pathways may be closely related to KBD.
研究领域:
医学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Toxics
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2024
·Vol. 12
·期 4
·288
·
IF 3.9
Kun Zhou,Miaomiao Tang,Wei Zhang,Yanling Chen,Yusheng Guan,Rui Huang,Jiawei Duan,Zibo Liu,Xiaoming Ji,Yingtong Jiang,Yanhui Hu,Xiaoling Zhang,Jingjing Zhou,Minjian Chen
The increasing use of molybdate has raised concerns about its potential toxicity in humans. However, the potential toxicity of molybdate under the current level of human exposure remains largely unknown. Endogenous metabolic alterations that are caused in humans by environmental exposure to pollutants are associated with the occurrence and progression of many diseases. This study exposed eight-week-old male C57 mice to sodium molybdate at doses relevant to humans (0.01 and 1 mg/kg/day) for eight weeks. Inductively coupled plasma mass spectrometry (ICP-MS) and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS) were utilized to assess changes in urine element levels and serum metabolites in mice, respectively. A total of 838 subjects from the NHANES 2017–2018 population database were also included in our study to verify the associations between molybdenum and cadmium found in mice. Analysis of the metabolome in mice revealed that four metabolites in blood serum exhibited significant changes, including 5-aminolevulinic acid, glycolic acid, l-acetylcarnitine, and 2,3-dihydroxypropyl octanoate. Analysis of the elementome revealed a significant increase in urine levels of cadmium after molybdate exposure in mice. Notably, molybdenum also showed a positive correlation with cadmium in humans from the NHANES database. Further analysis identified a positive correlation between cadmium and 2,3-dihydroxypropyl octanoate in mice. In conclusion, these findings suggest that molybdate exposure disrupted amino acid and lipid metabolism, which may be partially mediated by molybdate-altered cadmium levels. The integration of elementome and metabolome data provides sensitive information on molybdate-induced metabolic disorders and associated toxicities at levels relevant to human exposure.
研究领域:
环境科学
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毒理学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
SCIENTIA HORTICULTURAE
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2022
·
IF 4.342
Xiaoya Tao,Qiong Wu,Suqing Huang,Beiwei Zhu,Feng Chen,Bin Liu,Luyun Cai,Linchun Mao,Zisheng Luo,Li Li,Tiejin Ying
Primary metabolites play crucial roles during fruit development and ripening. Phytohormone abscisic acid (ABA) has been reported to regulate postharvest tomato fruit ripening. However, knowledge about ABA in regulating primary metabolism in tomato fruit is obscure. In the present research, cherry tomato fruit were infiltrated with 1.0 mM ABA or deionized water under vacuum, and kept in darkness for 15 d. The changes of the relative contents of sugars, organic acids, and amino acids, as well as the expression levels of key genes involved in sugar and organic acid metabolisms, were analyzed. Results showed exogenous ABA accelerated tomato fruit ripening, accompanying with the enhanced changes of fruit color and firmness, the higher levels of respiration rate and ethylene production. Meanwhile, exogenous ABA enhanced the relative levels of some primary metabolites, such as glucose, lyxose and fructose; citric acid, citramalic acid, ascorbic acid and gluconic acid; also serine, pyroglutamic acid, GABA, glutamic acid, aspartic acid, asparagine and glutamine (1.69-3.25 folds). Furthermore, exogenous ABA stimulated the expression levels of most key genes (such as SPSs, SPP2, TIV1, Lins, SUSs, PPCs, MDH and CS ) (log 2 fold change ranged from 1.06 to 3.64). Results indicate ABA is systematically involved in the regulation of primary metabolism, which may provide valuable information for exploring technical means to improve tomato taste and flavor.
研究领域:
植物生理学
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园艺学
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食品科学
✓ 已验证
产品关联
DOI
高影响因子
ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY
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2019
·
IF 4.527
Zhi Tang,Yunxiu Li,Yousheng Jiang,Jinquan Cheng,Shunqing Xu,Jianqing Zhang
Polybrominated diphenyl ethers (PBDEs) as potential neurotoxicants in environment may possess hazards to human health. Previous studies have reported that PBDEs exposure could induce oxidative stress and disturb mitochondrial functions in mammalian cells. However, the toxicological mechanism remains to be clarified. In this work, the neurotoxic effect and underlying mechanism of 2,2′,4,4′-tetrabromodiphenyl ether (BDE-47) was investigated by using human neuroblastoma SK-N-SH cells as an effective model. A liquid chromatography-mass spectrometry (LC-MS)-based metabolomics approach combined with cell viability assay was applied to elucidate the metabolic perturbations and relevant toxicological pathways upon BDE-47 exposure. Our results shown that the SK-N-SH cell viability decreased in a dose-dependent manner after exposure to BDE-47 at 24 h within the concentration range of 5–250 μM, and an IC 50 value of 88.8 μM was obtained. Based on the dose-response curve and cell morphological observation, the 5 and 10 μM BDE-47 doses (equal to IC 5 and IC 10 , respectively) were used for metabolomics study to capture the sensitive metabolic response following BDE-47 exposure. After BDE-47 treatment, nine metabolites were identified as potential biomarkers, and the most disturbed metabolic pathways were mainly involved in alanine , aspartate and glutamate metabolism, glutathione metabolism, tyrosine and phenylalanine metabolism, and pyrimidine metabolism, which imply that metabolic changes related to neurotransmitters , oxidative stress, and nucleotide-mediated signal transduction systems were the sensitive pathways mostly influenced. Our findings reported here may provide potential neurotoxic effect biomarkers and prompt deep understanding of the molecular and metabolic mechanisms triggered by BDE-47 exposure.
研究领域:
毒理学
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细胞生物学
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代谢组学
✓ 已验证
DOI
PubMed
高影响因子
International Journal of Clinical and Experimental Medicine
·
2015
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IF 1.277
Meiling Zhang,Shihui Bao,Feiou Lin,Yingying Lin,Lijing Zhang,Mengzhi Xu,Xueli Huang,Congcong Wen,Lufeng Hu,Guanyang Lin
This study aimed to evaluate the effect of Datura stramonium on rats by examining the differences in urine and serum metabolites between Datura stramonium groups and control group. SIMCA-P+12.0.1.0 software was used for partial least-squares discriminant analysis (PLS-DA) to screen for the differential metabolites. Fifteen metabolites in urine including malonic acid, pentanedioic acid, D-xylose, D-ribose, xylulose, azelaic acid, threitol, glycine, butanoic acid, D-mannose, D-gluconic acid, galactonic acid, myo-inositol, octadecanoic acid, pseudouridine and ten metabolites in serum including alanine, butanedioic acid, L-methionine, propanedioic acid, hexadecanoic acid, D-fructose, tetradecanoic acid, D-glucose, D-galactose, oleic acid were selected as the characteristic metabolites. The PLS-DA scores plot indicated that serum and urine metabolites have a variety of changes among low dose group, high dose group and control group. These metabolites were related with amino metabolism, lipid metabolism and energy metabolism. The result reflected the relationship between metabolites in rat fluid and Datura stramonium spectra. Potential differences in metabolites and metabolic pathway analysis showed that the establishment of urine and serum metabolomics methods for further evaluating drug has great significance.
研究领域:
药理学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Virology Journal
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2023
·Vol. 20
·期 1
·1-18
·
IF 4.8
Cai Haiqing,Yang Xia,Yang Yunyun,Feng Yi,Wen Anlin,Yang Ying,Wen Ming,Ou Deyuan
IntroductionDuck enteritis virus (DEV) mainly causes infectious diseases characterized by intestinal haemorrhage, inflammation and parenchymal organ degeneration in ducks and other poultry. However, the mechanism by which it causes intestinal damage in ducks is not well understood. Metabolomics can provide an in-depth understanding of the full complexity of the disease.Methods In this study, 24 clinically healthy green-shell ducks (weight 1.5 kg ± 20 g) were randomly divided into 2 groups (experimental group, 18; control group, 6). The experimental group was intramuscularly injected with 0.2 mL of DEV virus in solution (TCID50 3.16 × 108 PFU/mL), and the control group was injected with 0.2 mL of sterile normal saline. Duck duodenum and ileum tissue samples were collected at 66 h, 90 h and 114 h post-injection (12 h of fasting before killing), and metabolomics analysis of duck duodenum and ileum tissues at the three time points (66, 90, 114 h) was performed by liquid chromatography–mass spectrometry (LC–MS) to screen for and analyse the potential differentiated metabolites and related signalling pathways.Results Screening was performed in the positive/negative mode (Pos: Positive ion mode; the ionization of substances at the ion source with positive ions such as H+, NH4+, Na+ and K+; Neg: Negative ion mode; the ionization of substances at the ion source with negative ions such as Cl−, OAc−), and compound abundance was compared to that in the control group. The total number of differentially abundant compounds in the duodenum at 66 h, 90 h and 114 h of DEV infection gradually increased, and metabolites such as cytidine, 2′-deoxyriboside and 4-guanidinobutyric acid were differentially abundant metabolites common to all three time periods. The metabolic pathways related to inflammatory response and immune response were tryptophan acid metabolism, cysteine-methionine metabolism, histidine metabolism and other amino acid metabolism and fat metabolism. Among them, the metabolic pathways with more differentially abundant metabolites were amino acid biosynthesis, cysteine and methionine metabolism, tryptophan metabolism, unsaturated fatty acid biosynthesis and purine metabolism, and the metabolic pathways with more enrichment factors were the IgA-related intestinal immune network pathway and lysosome pathway. Compared with the control group, there were 16 differentially abundant metabolites in the ileum tissue of DEV-infected ducks at 66 h of infection, 52 at 90 h of infection, and 40 at 14 h of infection with TD114. The metabolic pathways with more enriched differentially abundant metabolites were pyrimidine metabolism, tyrosine metabolism, phenylalanine metabolism and tryptophan biosynthesis. The metabolic pathways with the most enrichment factors were the mTOR signalling pathway, ferroptosis pathway, tryptophan metabolism pathway and caffeine metabolism pathway.Conclusion Comparative analysis showed that the number of differentially abundant metabolites in the duodenum and ileum differed to some extent after DEV infection, with significantly more differentially abundant metabolites in duodenal tissues and fewer in ileal tissues; after DEV infection, the highest number of differentially abundant metabolites was obtained at 114 h of DEV infection, followed by the second highest at 90 h of infection and the lowest at 66 h of infection. The common differentially abundant metabolites in duodenal and ileal tissues were prostaglandins, arachidonic acid, and arachidonic ethanolamine. The main metabolic pathways in the duodenum were the IgA-associated intestinal immune network pathway and the lysosomal pathway, and the metabolic pathways with more enriched factors in the ileum were the mTOR signalling pathway, the ferroptosis pathway, and the tryptophan metabolism pathway.
研究领域:
兽医学
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分子生物学
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免疫学
✓ 已验证
DOI
PubMed
高影响因子
PeerJ
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2023
·
IF 2.7
Xinxin Lin,Shiqi He,Suyu Wu,Tianwen Zhang,Sisi Gong,Tang Minjie,Yao Gao
Osteoarthritis (OA) is the most common joint disease in the world, characterized by pain and loss of joint function, which has led to a serious reduction in the quality of patients’ lives. In this work, ultrahigh performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-QToF/MS) in conjunction with multivariate pattern recognition methods and an univariate statistical analysis scheme were applied to explore the serum metabolic signatures within OA group ( n = 31), HC (healthy controls) group ( n = 57) and non-OA group ( n = 19) for early diagnosis and differential diagnosis of OA. Based on logistic regression analysis and receiver operating characteristic (ROC) curve analysis, seven metabolites, including phosphatidylcholine (18:0/22:6), p-cresol sulfate and so on, were identified as critical metabolites for the diagnosis of OA and HC and yielded an area under the curve (AUC) of 0.978. The other panel of unknown m/z 239.091, phosphatidylcholine (18:0/18:0) and phenylalanine were found to distinguish OA from non-OA and achieved an AUC of 0.888. These potential biomarkers are mainly involved in lipid metabolism, glucose metabolism and amino acid metabolism. It is expected to reveal new insight into OA pathogenesis from changed metabolic pathways.
研究领域:
医学
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代谢组学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）