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Geographical Factor Influences the Metabolite Distribution of House Edible Bird's Nests in Malaysia.Frontiers in Nutrition 2021Edible Bird's Nest (EBN) is famously consumed as a food tonic for its high nutritional values with numerous recuperative and therapeutic properties. EBN is majority...
Edible Bird's Nest (EBN) is famously consumed as a food tonic for its high nutritional values with numerous recuperative and therapeutic properties. EBN is majority exploited from swiftlet houses but the differences in terms of metabolite distribution between the production site of house EBN is not yet fully understood. Therefore, this study was designed to identify the metabolite distribution and to determine the relationship pattern for the metabolite distribution of house EBNs from different locations in Malaysia. The differences of metabolite distribution in house EBN were studied by collecting the samples from 13 states in Malaysia. An extraction method of eHMG was acquired to extract the metabolites of EBN and was subjected to non-targeted metabolite profiling liquid chromatography-mass spectrometry (LC-MS). Unsupervised multivariate analysis and Venn diagram were used to explore the relationship pattern among the house EBNs in Malaysia. The geographical distribution surrounded the swiftlet house was investigated to understand its influences on the metabolite distribution. The hierarchical clustering analysis (HCA) combined with correlation coefficient revealed the differences between the house EBNs in Malaysia with four main clusters formation. The metabolites distribution among these clusters was unique with their varied combination of geographical distribution. Cluster 1 grouped EBNs from Selangor, Melaka, Negeri Sembilan, Terengganu which geographically distributed with major oil palm field in township; Cluster 2 included Perak and Sarawak with high distribution of oil palm in higher altitude; Cluster 3 included Perlis, Kelantan, Kedah, Penang from lowland of paddy field in village mostly and Cluster 4 grouped Sabah, Pahang, Johor which are majorly distributed with undeveloped hills. The metabolites which drove each cluster formation have happened in a group instead of individual key metabolite. The major metabolites that characterised Cluster 1 were fatty acids, while the rest of the clusters were peptides and secondary metabolites. The metabolite profiling conducted in this study was able to discriminate the Malaysian house EBNs based on metabolites distribution. The factor that most inferences the differences of house EBNs were the geographical distribution, in which geographical distribution affects the distribution of insect and the diet of swiftlet.
PubMed: 34262923
DOI: 10.3389/fnut.2021.658634 -
Metabolites Apr 2021Plant roots are composed of many differentiated tissue types, with each tissue exhibiting differential quantitative and qualitative accumulation of metabolites. The...
Plant roots are composed of many differentiated tissue types, with each tissue exhibiting differential quantitative and qualitative accumulation of metabolites. The large-scale nontargeted metabolite profiles of these differentiated tissues are complex, which complicates the interpretation and development of hypotheses relative to the biological roles of differentially localized metabolites. Thus, we created a data visualization tool to aid in the visualization and understanding of differential metabolite accumulations in roots. This was achieved through the development of the Metabolite Atlas based upon an adaptation of the Arabidopsis Electronic Fluorescent Pictograph (eFP) Browser. roots were dissected into border cells, root cap, elongation zone, mature root, and root secretions. Each tissue was then analyzed by UHPLC-QTOF-MS and GC-Q-MS. Data were uploaded into a MySQL database and displayed in the Metabolite Atlas. The data revealed unique differential spatial localization of many metabolites, some of which are discussed here. Ultimately, the Metabolite Atlas compiles metabolite data into a singular, useful, and publicly available web-based tool that enables the visualization and understanding of differential metabolite accumulation and spatial localization.
PubMed: 33924579
DOI: 10.3390/metabo11040238 -
Clinical Drug Investigation Aug 2023Tolebrutinib is a covalent inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are thought to be...
BACKGROUND AND OBJECTIVE
Tolebrutinib is a covalent inhibitor of Bruton's tyrosine kinase, an enzyme expressed in B lymphocytes and myeloid cells including microglia, which are thought to be major drivers of inflammation in multiple sclerosis. This excretion balance and metabolism study evaluated the metabolite profile of tolebrutinib in healthy male volunteers.
METHODS
Six healthy volunteers received a 60-mg oral dose of [C]-tolebrutinib, and metabolite profiling of C-labeled metabolites was performed using a combination of liquid chromatography, mass spectrometry, and radioactivity assay methods.
RESULTS
Tolebrutinib was rapidly and completely absorbed from the gastrointestinal tract, followed by rapid and extensive metabolism. Excretion via feces was the major elimination pathway of the administered radioactivity (78%). Tolebrutinib was highly metabolized, with 19 metabolites identified in human plasma. Phase 1 biotransformations were primarily responsible for the circulating metabolites in plasma. Seven metabolites that achieved exposure in plasma similar to or higher than the parent compound were characterized biochemically for inhibition of Bruton's tyrosine kinase activity. Metabolite M8 exceeded the exposure threshold of 10% (18%) of the total radioactivity but had little if any pharmacological activity. Metabolite M2 (4% of circulating radioactivity) retained the ability to irreversibly and potently inhibit Bruton's tyrosine kinase in vitro, similar to the parent compound. Tolebrutinib and metabolite M2 had short (3.5-h) half-lives but durable pharmacodynamic effects as expected for an irreversible antagonist.
CONCLUSIONS
Tolebrutinib was extensively metabolized to multiple metabolites. The hydroxylated metabolite M2 demonstrated similar inhibitory potency toward Bruton's tyrosine kinase as the parent compound. Both tolebrutinib and metabolite M2 likely contributed to pharmacological activity in vivo.
Topics: Humans; Male; Agammaglobulinaemia Tyrosine Kinase; Administration, Oral; Feces; Protein Kinase Inhibitors; Chromatography, Liquid
PubMed: 37642857
DOI: 10.1007/s40261-023-01296-1 -
Addictive Behaviors Reports Dec 2022Self-report and nicotine detection are methods to measure smoking exposure and can both lead to misclassification. It is important to highlight discrepancies between...
INTRODUCTION
Self-report and nicotine detection are methods to measure smoking exposure and can both lead to misclassification. It is important to highlight discrepancies between these two methods in the context of epidemiological research.
OBJECTIVE
The aim of this cross-sectional study is to assess the agreements between self-reported smoking status and nicotine metabolite detection.
METHODS
Data of 599 participants from the Netherlands Epidemiology of Obesity study were used to compare serum metabolite levels of five nicotine metabolites (cotinine, hydroxy-cotinine, cotinine -Oxide, norcotinine, 3-hydroxy-cotinine-glucuronide) between self-reported never smokers (n = 245), former smokers (n = 283) and current smokers (n = 71). We assessed whether metabolites were absent or present and used logistic regression to discriminate between current and never smokers based on nicotine metabolite information. A classification tree was derived to classify individuals into current smokers and non/former smokers based on metabolite information.
RESULTS
In 94% of the self-reported current smokers, at least one metabolite was present, versus in 19% of the former smokers and in 10% of the never smokers. In none of the never smokers, cotinine--oxide, 3-hydroxy-cotinine--glucorinide or norcotinine was present, while at least one of these metabolites was detected in 68% of the self-reported current smokers. The classification tree classified 95% of the participants in accordance to their self-reported smoking status. All self-reported smokers who were classified as non-smokers according to the metabolite profile, had reported to be occasional smokers.
CONCLUSION
The agreement between self-reported smoking status and metabolite information was high. This indicates that self-reported smoking status is generally reliable.
PubMed: 36187563
DOI: 10.1016/j.abrep.2022.100457 -
Basic & Clinical Pharmacology &... Feb 2008Most of the developmental effects that populations experience are believed to be linked with their exposure scenario and/or their susceptibility to these exposures. In... (Review)
Review
Most of the developmental effects that populations experience are believed to be linked with their exposure scenario and/or their susceptibility to these exposures. In environmental public health, most studies have focused on exposures to environmental chemicals but certainly other environmental factors and susceptibility factors must be considered. Our laboratory assesses exposure to environmental chemicals by measuring the chemical, its metabolite(s) or chemical adduct(s) in a biological matrix taken from members of the populations of interest (via biomonitoring). To help interpret data from the many uses of biomonitoring and for other purposes in public health, we have determined, and made public, data on the concentrations of environmental chemicals in the general population of the USA. Exposures at critical time periods of development to many of these chemicals have been linked with adverse developmental effects. In this paper, we examine this linkage using several chemicals as examples and providing biomonitoring information for these chemicals in the US population as a whole but also at various life stages.
Topics: Animals; Centers for Disease Control and Prevention, U.S.; Embryonic Development; Environmental Monitoring; Environmental Pollutants; Female; Fetal Development; Human Development; Humans; Maternal-Fetal Exchange; Pregnancy; United States
PubMed: 18226062
DOI: 10.1111/j.1742-7843.2007.00185.x -
The Plant Journal : For Cell and... Apr 2012Single-cell analysis is a promising method for understanding not only cellular physiology but also biological mechanisms of multicellular organisms. Although neighboring... (Review)
Review
Single-cell analysis is a promising method for understanding not only cellular physiology but also biological mechanisms of multicellular organisms. Although neighboring cells in multicellular organisms originate from the same genomic information, different circumstances around cells or epigenetic differences have different influences on each cell, leading to differing expression of genes, and thus differing levels and dynamics of metabolites, in single cells. However, single-cell analysis is a tough challenge, even with recent technologies, because of the small size of single cells. Unlike genes, metabolites cannot be amplified, and therefore metabolite analysis is another issue. To analyze such a tiny quantity of metabolites in a single cell, various techniques have been tried and developed. Especially in mass spectrometry, marked improvements in both detection sensitivity and ionization techniques have opened up the challenge for the analysis of metabolites in single cells. In this review, we discuss the method for metabolite detection at the level of single cells and recent advancements in technology.
Topics: Mass Spectrometry; Metabolomics; Plant Cells; Plants; Single-Cell Analysis
PubMed: 22449041
DOI: 10.1111/j.1365-313X.2012.04967.x -
Metabolites May 2020Metabolomics is increasingly important for biomedical research, but large-scale metabolite identification in untargeted metabolomics is still challenging. Here, we...
Metabolomics is increasingly important for biomedical research, but large-scale metabolite identification in untargeted metabolomics is still challenging. Here, we present Jumbo Mass spectrometry-based Program of Metabolomics (JUMPm) software, a streamlined software tool for identifying potential metabolite formulas and structures in mass spectrometry. During database search, the false discovery rate is evaluated by a target-decoy strategy, where the decoys are produced by breaking the octet rule of chemistry. We illustrated the utility of JUMPm by detecting metabolite formulas and structures from liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analyses of unlabeled and stable-isotope labeled yeast samples. We also benchmarked the performance of JUMPm by analyzing a mixed sample from a commercially available metabolite library in both hydrophilic and hydrophobic LC-MS/MS. These analyses confirm that metabolite identification can be significantly improved by estimating the element composition in formulas using stable isotope labeling, or by introducing LC retention time during a spectral library search, which are incorporated into JUMPm functions. Finally, we compared the performance of JUMPm and two commonly used programs, Compound Discoverer 3.1 and MZmine 2, with respect to putative metabolite identifications. Our results indicate that JUMPm is an effective tool for metabolite identification of both unlabeled and labeled data in untargeted metabolomics.
PubMed: 32408578
DOI: 10.3390/metabo10050190 -
BMC Genomics Aug 2023The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease,...
BACKGROUND
The natural products, metabolites, of gut microbes are crucial effect factors on diseases. Comprehensive identification and annotation of relationships among disease, metabolites, and microbes can provide efficient and targeted solutions towards understanding the mechanism of complex disease and development of new markers and drugs.
RESULTS
We developed Gut Microbial Metabolite Association with Disease (GMMAD), a manually curated database of associations among human diseases, gut microbes, and metabolites of gut microbes. Here, this initial release (i) contains 3,836 disease-microbe associations and 879,263 microbe-metabolite associations, which were extracted from literatures and available resources and then experienced our manual curation; (ii) defines an association strength score and a confidence score. With these two scores, GMMAD predicted 220,690 disease-metabolite associations, where the metabolites all belong to the gut microbes. We think that the positive effective (with both scores higher than suggested thresholds) associations will help identify disease marker and understand the pathogenic mechanism from the sense of gut microbes. The negative effective associations would be taken as biomarkers and have the potential as drug candidates. Literature proofs supported our proposal with experimental consistence; (iii) provides a user-friendly web interface that allows users to browse, search, and download information on associations among diseases, metabolites, and microbes. The resource is freely available at http://guolab.whu.edu.cn/GMMAD .
CONCLUSIONS
As the online-available unique resource for gut microbial metabolite-disease associations, GMMAD is helpful for researchers to explore mechanisms of disease- metabolite-microbe and screen the drug and marker candidates for different diseases.
Topics: Humans; Gastrointestinal Microbiome; Biological Products; Databases, Factual; Levamisole
PubMed: 37620754
DOI: 10.1186/s12864-023-09599-5 -
International Journal of Tryptophan... 2022Tryptophan is the precursor of kynurenine pathway (KP) metabolites which regulate immune tolerance, energy metabolism, and vascular tone. Since these processes are... (Review)
Review
INTRODUCTION
Tryptophan is the precursor of kynurenine pathway (KP) metabolites which regulate immune tolerance, energy metabolism, and vascular tone. Since these processes are important during pregnancy, changes in KP metabolite concentrations may play a role in the pathophysiology of pregnancy complications. We hypothesize that KP metabolites can serve as novel biomarkers and preventive therapeutic targets. This review aimed to provide more insight into associations between KP metabolite concentrations in maternal and fetal blood, and in the placenta, and adverse maternal pregnancy and fetal outcomes.
METHODS
A systematic search was performed on 18 February 2022 comprising all KP metabolites, and keywords related to maternal pregnancy and fetal outcomes. English-written human studies measuring KP metabolite(s) in maternal or fetal blood or in the placenta in relation to pregnancy complications, were included. Methodological quality was assessed using the ErasmusAGE quality score (QS) (range: 0-10). A meta-analysis of the mean maternal tryptophan and kynurenine concentrations in uncomplicated pregnancies was conducted.
RESULTS
Of the 6262 unique records, 37 were included (median QS = 5). Tryptophan was investigated in most studies, followed by kynurenine, predominantly in maternal blood (n = 28/37), and in the second and third trimester of pregnancy (n = 29/37). Compared to uncomplicated pregnancies, decreased tryptophan in maternal blood was associated with an increased prevalence of depression, gestational diabetes mellitus, fetal growth restriction, spontaneous abortion, and preterm birth. Elevated tryptophan was only observed in women with pregnancy-induced hypertension compared to normotensive pregnant women. In women with preeclampsia, only kynurenic acid was altered; elevated in the first trimester of pregnancy, and positively associated with proteinuria in the third trimester of pregnancy.
CONCLUSIONS
KP metabolite concentrations were altered in a variety of maternal pregnancy and fetal complications. This review implies that physiological pregnancy requires a tight balance of KP metabolites, and that disturbances in either direction are associated with adverse maternal pregnancy and fetal outcomes.
PubMed: 36467775
DOI: 10.1177/11786469221135545 -
Journal of Animal Science Oct 2022The objective was to test the hypothesis that supplementation of diets for gestating sows with 25-hydroxycholecalciferol (25-OH-D3) or 1-hydroxycholecalciferol (1-OH-D3)...
Effects of 25-hydroxycholecalciferol (25-OH-D3) and 1-hydroxycholecalciferol (1-OH-D3) on serum bone biomarkers and calcium and phosphorus balance and concentrations of energy in diets without or with microbial phytase fed to sows in late gestation.
The objective was to test the hypothesis that supplementation of diets for gestating sows with 25-hydroxycholecalciferol (25-OH-D3) or 1-hydroxycholecalciferol (1-OH-D3) affects serum biomarkers for bone and increases Ca and P balance and the apparent total tract digestibility (ATTD) of gross energy (GE), and the concentrations of digestible energy (DE) and metabolizable energy (ME) in diets without or with microbial phytase. Sixty multiparous sows were allotted to 1 of 6 diets. Diets were formulated using a 3 × 2 factorial with 3 inclusions of supplemental vitamin D metabolite (no metabolite, 25-OH-D3, or 1-OH-D3) and 2 inclusion levels of microbial phytase (0 or 1,000 units). Sows were housed individually in metabolism crates and feces and urine were collected quantitatively. Results indicated that there was no difference in the ATTD of dry matter (DM) and GE and concentration of DE among the 3 diets containing microbial phytase, but the ATTD of DM and GE and concentration of DE was greater (P < 0.05) in diets containing 1-OH-D3 compared with the diet without a vitamin D metabolite if phytase was not used (interaction; P < 0.05). In diets without microbial phytase, ME was greater in diets containing either one of the 2 vitamin D metabolites than in the diet without a vitamin D metabolite, but among diets with microbial phytase, the ME of the 1-OH-D3 diet was less than of the 25-OH-D3 diet (interaction; P < 0.05). No effect of microbial phytase on concentrations of DE and ME was observed. There was no interaction between supplementation of microbial phytase and vitamin D metabolites for Ca and P balances, and regardless of metabolite supplementation, use of microbial phytase increased (P < 0.05) the ATTD and retention of Ca and P. Regardless of dietary phytase, the ATTD and retention of Ca and P increased (P < 0.05) for sows fed a diet containing one of the vitamin D metabolites compared with sows fed the diet without a vitamin D metabolite. Serum biomarkers for bone resorption or bone tissue synthesis were not affected by experimental diets. In conclusion, the ATTD of DM and GE, concentrations of DE and ME, and Ca and P balance in phytase-free diets fed to sows in late gestation were increased by supplementation with 1-OH-D3 or 25-OH-D3, but no differences between the 2 vitamin D metabolites were observed. Supplementation of diets with microbial phytase increased Ca and P balance, but did not affect DE and ME of diets.
Topics: Pregnancy; Animals; Female; 6-Phytase; Calcium; Calcifediol; Phosphorus; Phosphorus, Dietary; Digestion; Animal Feed; Gastrointestinal Tract; Calcium, Dietary; Diet; Biomarkers; Bone and Bones
PubMed: 36074541
DOI: 10.1093/jas/skac299