PubMed

Sci Total Environ. 2023 Jan 30:161890. doi: 10.1016/j.scitotenv.2023.161890. Online ahead of print.ABSTRACTAs non-conventional wastewater treatment, vegetation filters make the most of the natural attenuation processes that occur in soil to remove contaminants, while providing several environmental benefits. However, this practice may introduce contaminants of emerging concern (CECs) and their transformation products (TPs) into the environment. A potential improvement to the system was tested using column experiments containing soil (S) and soil amended with woodchips (SW) or biochar (SB) irrigated with synthetic wastewater that included 11 selected CECs. This study evaluated: i) known CECs attenuation and ii) unknown metabolites formation. Known CECs attenuation was assessed by total mass balance by considering both water and soil media. An untargeted metabolomic strategy was developed to assess the formation of unknown metabolites and to identify them in water samples. The results indicated that SB enhanced CECs attenuation and led to the formation of fewer metabolites. Sorption and biodegradation processes were favored by the bigger surface area of particles in SB column, especially for compounds with negative charges. Incorporating woodchips into soil shortened retention times in the column, which reduced attenuation phenomena and resulted in the formation of significantly more metabolites. Incomplete biodegradation reactions, fostered by shorter retention times in SW column could mainly explain these results.PMID:36731565 | DOI:10.1016/j.scitotenv.2023.161890

Sci Total Environ. 2023 Jan 30:161541. doi: 10.1016/j.scitotenv.2023.161541. Online ahead of print.ABSTRACTImidacloprid, a widely used neonicotinoid insecticide, poses a significant threat to aquatic ecosystems. Behavior is a functional indicator of the net sensory, motor, and integrative processes of the nervous system and is presumed to be more sensitive in detecting toxicity. In the present study, we investigated the behavioral effects of imidacloprid at the level of environmental concentrations (1, 10 and 100 μg/L) for a constant exposure to zebrafish adults, and performed the integrated transcriptomic and metabolomic analysis to analyze the molecular mechanism underlying behavioral effects of imidacloprid. Our results show that imidacloprid exposure significantly induce behavioral disruptions characterized by anxiety, depression, and reduced physiological function including exploratory, decision, social interaction and locomotor activity. Integrated transcriptomic and metabolomic analysis indicate that the disruption of circadian rhythm, metabolic imbalance of arginine and proline, and neurotransmitter disorder are the underlying molecular mechanisms of behavioral impairment induced by imidacloprid. The "gene-metabolite-disease" network consisted by 11 metabolites and 15 genes is associated human disease Alzheimer's disease (AD) and schizophrenia. Our results confirm the behavioral impairment induced by imidacloprid at environmental concentrations for constant exposure. The identified genes and metabolites can be used not only to illustrate the underlying mechanisms, but also can be developed as biomarkers in determining the ecological risk of imidacloprid to aquatic organisms even Homo sapiens.PMID:36731560 | DOI:10.1016/j.scitotenv.2023.161541

Phytomedicine. 2023 Jan 20;111:154628. doi: 10.1016/j.phymed.2022.154628. Online ahead of print.ABSTRACTBACKGROUND: Depression affects not only the central nervous system, but also the peripheral system. Xiaoyaosan (XYS), a classical traditional Chinese medicine (TCM) prescription, exhibits definite anti-depression effects demonstrated both clinically and experimentally. However, its compatibility has not been entirely revealed due partly to the complex compositions of herbs contained.AIM: Based on the strategy of "Efficacy Group", this study aimed to reveal the compatibility of XYS from the perspective of "gut-liver-kidney" axis.METHODS: Firstly, XYS was divided into two efficacy groups, i.e. Shugan (SG) and Jianpi (JP) groups. Classic behaviors of rats were measured to confirm the anti-depression effects of XYS and its two efficacy groups. On top of this, gut microbiota analysis and kidney metabolomics were performed by 16S rRNA sequencing and 1H NMR, respectively.RESULTS: We found that XYS and its efficacy groups significantly regulated the abnormalities of behaviors and kidney metabolism of depressed rats, as well as intestinal disorders, but to different degrees. The regulatory effects of XYS and its efficacy groups on behaviors and kidney metabolomics of depressed rats had the same order, i.e. XYS > SG > JP, while the order of regulating gut microbiota was XYS > JP > SG. Both XYS and its efficacy groups significantly ameliorated gut microbiota disturbed, especially significant modulation of Peptostreptococcaceae. XYS significantly regulated nine kidney metabolites, while SG and JP regulated four and five differential metabolites, respectively, indicating that the two efficacy groups synergistically exhibited anti-depression effects, consequently contributing to the overall anti-depression effects of XYS.CONCLUSION: The current findings not only innovatively demonstrate the anti-depression effects and compatibility of XYS from the perspective of "gut-liver-kidney" axis, comprehensively using "Efficacy Group" strategy, macro behavioristics, metabolome and microbiome, and also provide a new perspective, strategy, and methodology for studying complex diseases and the compatibility of TCMs.PMID:36731299 | DOI:10.1016/j.phymed.2022.154628

J Pharm Biomed Anal. 2023 Jan 18;226:115246. doi: 10.1016/j.jpba.2023.115246. Online ahead of print.ABSTRACTEr-Miao-Wan formula (EMW), composed of Phellodendri Chinensis Cortex and Atractylodis Rhizoma, is widely used in the treatment of hyperuricemia (HUA), gout, and related complications as a classic compound formula. However, its mechanisms for the treatment of HUA still need to be further systematically investigated. The study aimed to perform modern analytical techniques to elucidate the mechanisms of EMW in improving the symptoms of HUA from the perspective of metabolomics. We used a high-fructose diet to establish a rat model of HUA to evaluate the effects of EMW on improving HUA. Next, we established a targeted metabolomics analysis method to quantitatively analyze purine metabolites in plasma by using ultra-high-performance liquid chromatography with ultraviolet and triple quadrupole mass spectrometry (UHPLC-UV-QQQ MS), and combined with plasma non-targeted metabolomics analysis by using ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q/TOF MS) to clarify the potential mechanisms of EMW to improve HUA. Oral administration of EMW could significantly increase the urinary uric acid and decrease the serum uric acid, and exhibited a remarkable effect on improving HUA. Plasma targeted metabolomics analysis showed that six purine metabolites related to HUA, including uric acid, hypoxanthine, xanthine, deoxyadenosine, deoxyguanosine, and deoxyinosine, were changed in the EMW-treated group. Further, principal component analysis (PCA) and partial least squares discrimination analysis (PLS-DA) showed that the mechanism of EMW interfering with purine metabolic pathway in the rats with HUA could be different from that of allopurinol. On the basis of plasma non-targeted metabolomics, PCA and orthogonal partial least squares discriminant analysis (OPLA-DA) screened and identified 23 potential biomarkers in the rats with HUA, and 11 biomarkers showed a trend of reversion after the intervention of EMW. The pathway analysis suggested that EMW might have therapeutic effects on the rats with HUA via the metabolic pathways including phenylalanine metabolism, glycerophospholipid metabolism, and tryptophan metabolism. In this study, a plasma targeted metabolomics method that can simultaneously quantify nine purine metabolites in rats with HUA was established for the first time, which can be used to study diseases closely related to HUA. In addition, we further explored the overall effect of EMW on HUA in combination with the metabonomic method established by non-targeted metabolomics, which was helpful to solve the defect that the pharmacological mechanism caused by multi-components and multi-targets of traditional Chinese medicine was difficult to explain scientifically and comprehensively. In summary, EMW could effectively alleviate the symptoms of high-fructose-induced HUA, and the study provided a reference for the potential therapeutic mechanism of EMW.PMID:36731256 | DOI:10.1016/j.jpba.2023.115246

Clin J Sport Med. 2022 Oct 10. doi: 10.1097/JSM.0000000000001074. Online ahead of print.ABSTRACTOBJECTIVE: Recombinant human erythropoietin (rHuEpo) is prohibited by the World Anti-Doping Agency but remains the drug of choice for many cheating athletes wishing to evade detection using current methods. The aim of this study was to identify a robust metabolomics signature of rHuEpo using an untargeted approach in blood (plasma and serum) and urine.DESIGN: Longitudinal study.SETTING: University of Glasgow.PARTICIPANTS: Eighteen male participants regularly engaged in predominantly endurance-based activities, such as running, cycling, swimming, triathlon, and team sports, were recruited.INTERVENTIONS: Each participant received 50 IU·kg-1 body mass of rHuEpo subcutaneously every 2 days for 4 weeks. Samples were collected at baseline, during rHuEpo administration (over 4 weeks) and after rHuEpo administration (week 7-10). The samples were analyzed using hydrophilic interaction liquid chromatography mass spectrometry.MAIN OUTCOME MEASURES: Significant metabolic signatures of rHuEpo administration were identified in all biofluids tested in this study.RESULTS: Regarding metabolomics data, 488 plasma metabolites, 694 serum metabolites, and 1628 urinary metabolites were identified. Reproducible signatures of rHuEpo administration across all biofluids included alterations of pyrimidine metabolism (orotate and dihydroorotate) and acyl-carnitines (palmitoyl-carnitine and elaidic carnitine), metabolic pathways that are associated with erythropoiesis or erythrocyte membrane function, respectively.CONCLUSIONS: Preliminary metabolic signatures of rHuEpo administration were identified. Future studies will be required to validate these encouraging results in independent cohorts and with orthogonal techniques, such as integration of our data with signatures derived from other "omics" analyses of rHuEpo administration (eg, transcriptomics).PMID:36731031 | DOI:10.1097/JSM.0000000000001074

Curr Opin Infect Dis. 2022 Dec 9. doi: 10.1097/QCO.0000000000000893. Online ahead of print.ABSTRACTPURPOSE OF REVIEW: There are an estimated 374 million new sexually transmitted infections (STIs) worldwide every year. Our review article examines the current evidence of how STI acquisition, transmission, and pathogenesis is impacted upon by the genital microbiota, with a focus on epidemiological, biochemical, and immunological features.RECENT FINDINGS: At least in women, a genital microbiota dominated by lactobacilli has long been considered optimal for reproductive health, while depletion of lactobacilli may lead to a genital microenvironment dominated by anaerobic pathogens, which can manifest clinically as bacterial vaginosis. Recent research efforts have characterized genital microbiota composition in greater resolution, sometimes at species-level, using proteomics, metabolomics, and deep sequencing. This has enhanced our understanding of how specific microbiota members influence acquisition or clinical manifestation of STI pathogen infection. Other advances include a steady, though still slow, increase in the number of studies that sought to determine the genital (penile or urethral) microbiota of males and how it may impact that of their female partners' genital microbiota and risk of STI acquisition. Altogether, these data enabled us to explore the concept that genital microbiota may be sexually transmitted and influence pathogenesis and clinical presentation of other STI.SUMMARY: With STI infection rates increasing worldwide, it is important now more than ever to find novel STI prevention strategies. Understanding if and how the genital microbiota is a modifiable risk factor for STI transmission, acquisition, and clinical manifestation may prove to be an important strategy in our efforts to curb morbidity in at risk populations.PMID:36729748 | DOI:10.1097/QCO.0000000000000893

Chembiochem. 2023 Feb 2. doi: 10.1002/cbic.202200757. Online ahead of print.ABSTRACTStreptomyces coelicolor is a prolific producer of natural products and serves as a model organism for their study. It produces several pigmented antibiotics, the most well-studied of which are the actinorhodins. We utilized a combination of liquid chromatography-mass spectrometry (LC-MS) and computational tools used for annotating the detected species (e.g., spectral matching, in silico predictors, molecular networking) to identify putative new actinorhodin analogs. These studies led to the discovery of the first trimeric benzoisochromanequinone, θ-actinorhodin (1). Further metabolomics analysis revealed that the relative amounts of shunt products produced were similar between the two growth conditions explored. This suggests that while substantially different products were being produced, the biosynthetic gene clusters were similarly active. Overall, this work describes the discovery of the first trimeric benzoisochromanequinone and explores the biosynthetic processes that may lead to its production via metabolomics analysis of relevant intermediates.PMID:36729633 | DOI:10.1002/cbic.202200757

J Pediatr Gastroenterol Nutr. 2022 Dec 27. doi: 10.1097/MPG.0000000000003693. Online ahead of print.ABSTRACTBACKGROUND/OBJECTIVES: Eosinophilic esophagitis (EoE) is an inflammatory disease of unclear etiology. The aim of this study was to use untargeted plasma metabolomics to identify metabolic pathway alterations associated with EoE to better understand the pathophysiology.METHODS: This prospective, case-control study included 72 children, aged 1-17 years, undergoing clinically indicated upper endoscopy (14 diagnosed with EoE and 58 controls). Fasting plasma samples were analyzed for metabolomics by high-resolution dual-chromatography mass spectrometry. Analysis was performed on sex-matched groups at a 2:1 ratio. Significant differences among the plasma metabolite features between children with and without EoE were determined using multivariate regression analysis and were annotated with a network-based algorithm. Subsequent pathway enrichment analysis was performed.RESULTS: Patients with EoE had a higher proportion of atopic disease (85.7% vs. 50% p-value p=0.019) and any allergies (100% vs. 57.1% p-value=0.0005). Analysis of the dual chromatography features resulted in a total of 918 metabolites that differentiated EoE and controls. Glycerophospholipid metabolism was significantly enriched with the greatest number of differentiating metabolites and overall pathway enrichment (p < 0.01). Multiple amino and fatty acid pathways including linoleic acid were also enriched, as well as pyridoxine metabolism (p<0.01).CONCLUSIONS: In this pilot study, we found differences in metabolites involved in glycerophospholipid and inflammation pathways in pediatric patients with EoE using untargeted metabolomics, as well as overlap with amino acid metabolome alterations found in atopic disease.PMID:36728821 | DOI:10.1097/MPG.0000000000003693

Anal Chem. 2023 Feb 2. doi: 10.1021/acs.analchem.2c03323. Online ahead of print.ABSTRACTTwo-dimensional (2D) 1H-13C heteronuclear single quantum coherence (HSQC) has been increasingly applied to metabolomics studies because it can greatly improve the resolving capability compared with one-dimensional (1D) 1H NMR. However, preprocessing methods such as peak matching and alignment tools for 2D NMR-based metabolomics have lagged behind similar methods for 1D 1H NMR-based metabolomics. Correct matching and alignment of 2D NMR spectral features across multiple samples are particularly important for subsequent multivariate data analysis. Considering different intensity dynamic ranges of a variety of metabolites and the chemical shift variation across the spectra of multiple samples, here, we developed an efficient peak matching and alignment algorithm for 2D 1H-13C HSQC-based metabolomics, called global intensity-guided peak matching and alignment (GIPMA). In GIPMA, peaks identified in all spectra are pooled together and sorted by intensity. Chemical shift of a stronger peak is regarded to be more accurate and reliable than that of a weaker peak. The strongest undesignated peak is chosen as the reference of a new cluster if it is not located within the chemical shift tolerance of any existing peak cluster (PC), or otherwise it is matched to an existing PC and the aligned chemical shift of the PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the cluster. Setting an optimum chemical shift tolerance (Δδo) is critical for the peak matching and alignment across multiple samples. GIPMA dynamically searches for and intelligently selects the Δδo for peak matching to maximize the number of valid peak clusters (vPC), that is, spectral features, among multiple samples. By GIPMA, fully automatic peakwise matching and alignment do not require any spectrum as initial reference, while the chemical shift of each PC is updated as the intensity-weighted average of the chemical shifts of all peaks in the same PC, which is warranted to be statistically more accurate. Accurate chemical shifts for each representative spectral feature will facilitate subsequent peak assignment and are essential for correct metabolite identification and result interpretation. The proposed method was demonstrated successfully on the spectra of six model mixtures consisting of seven typical metabolites, yielding correct matching of all known spectral features. The performance of GIPMA was also demonstrated on 2D 1H-13C HSQC spectra of 87 real extracts of 29 samples of five Dendrobium species. Hierarchical cluster analysis (HCA) and principal component analysis (PCA) of the 87 matched and aligned spectra by GIPMA generates correct classification of the 29 samples into five groups. In summary, the proposed algorithm of GIPMA provided a practical peak matching and alignment method to facilitate 2D NMR-based metabolomics studies.PMID:36728684 | DOI:10.1021/acs.analchem.2c03323

J Agric Food Chem. 2023 Feb 2. doi: 10.1021/acs.jafc.2c06821. Online ahead of print.ABSTRACTFu brick tea theabrownin (FBTB) is a kind of biomacromolecule produced by oxidative polymerization of tea polyphenols. Although a variety of diseases can be alleviated by TB, its ability to treat ulcerative colitis (UC) is still worth exploring. A dextran sulfate sodium (DSS)-induced chronic UC mouse model was designed to first explore the alleviatory effect of FBTB on UC and its underlying mechanism by the sequencing of fecal 16S rRNA genes, metabolomics, and fecal microbiota transplantation (FMT). Administration of FBTB at 400 mg/kg bw in DSS-damaged mice could effectively reduce colonic damage and inflammation and improve colonic antioxidant capacity to relieve the UC-caused symptoms. FBTB could correct the disrupted gut microbiota caused by UC and contribute to the proliferation of Lactobacillus and Parasutterella. FMT in combination with antibiotic treatment showed that FBTB could elevate the levels of microbial tryptophan metabolites, including indole-3-acetaldehyde (IAld) and indole-3-acetic acid (IAA), by selectively promoting the growth of Lactobacillus. Importantly, FBTB-elevated IAld and IAA could activate aromatic hydrocarbon receptors (AhRs) and enhance interleukin-22 production to repair the intestinal barrier. These findings demonstrated that FBTB alleviated UC mainly by targeting the gut microbiota involved in the AhR pathway for prophylactic and therapeutic treatment of UC.PMID:36728562 | DOI:10.1021/acs.jafc.2c06821

Appl Environ Microbiol. 2023 Feb 2:e0201622. doi: 10.1128/aem.02016-22. Online ahead of print.ABSTRACTSulfoquinovose (SQ) is a major metabolite in the global sulfur cycle produced by nearly all photosynthetic organisms. One of the major pathways involved in the catabolism of SQ in bacteria such as Escherichia coli is a variant of the glycolytic Embden-Meyerhof-Parnas (EMP) pathway termed the sulfoglycolytic EMP (sulfo-EMP) pathway, which leads to the consumption of three of the six carbons of SQ and the excretion of 2,3-dihydroxypropanesulfonate (DHPS). Comparative metabolite profiling of aerobically glucose (Glc)-grown and SQ-grown E. coli cells was undertaken to identify the metabolic consequences of the switch from glycolysis to sulfoglycolysis. Sulfoglycolysis was associated with the diversion of triose phosphates (triose-P) to synthesize sugar phosphates (gluconeogenesis) and an unexpected accumulation of trehalose and glycogen storage carbohydrates. Sulfoglycolysis was also associated with global changes in central carbon metabolism, as indicated by the changes in the levels of intermediates in the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway (PPP), polyamine metabolism, pyrimidine metabolism, and many amino acid metabolic pathways. Upon entry into stationary phase and the depletion of SQ, E. coli cells utilize their glycogen, indicating a reversal of metabolic fluxes to allow glycolytic metabolism. IMPORTANCE The sulfosugar sulfoquinovose is estimated to be produced on a scale of 10 billion metric tons per annum, making it a major organosulfur species in the biosulfur cycle. The microbial degradation of sulfoquinovose through sulfoglycolysis allows the utilization of its carbon content and contributes to the biomineralization of its sulfur. However, the metabolic consequences of microbial growth on sulfoquinovose are unclear. We use metabolomics to identify the metabolic adaptations that Escherichia coli undergoes when grown on sulfoquinovose versus glucose. This revealed the increased flux into storage carbohydrates through gluconeogenesis and the reduced flux of carbon into the TCA cycle and downstream metabolism. These changes are relieved upon entry into stationary phase and reversion to glycolytic metabolism. This work provides new insights into the metabolic consequences of microbial growth on an abundant sulfosugar.PMID:36728421 | DOI:10.1128/aem.02016-22

Ther Drug Monit. 2023 Jan 10. doi: 10.1097/FTD.0000000000001063. Online ahead of print.ABSTRACTBACKGROUND: The cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, palbociclib, ribociclib, and abemaciclib, are standard-of-care agents for patients with hormone receptor-positive human epidermal growth factor receptor 2-negative metastatic breast cancer. In support of therapeutic drug monitoring and clinical pharmacokinetic studies, a liquid chromatography coupled with tandem mass spectrometry assay for the simultaneous quantitation of CDK4/6 inhibitors and the major active metabolite M2 of abemaciclib in human plasma has been developed.METHODS: Analytes were extracted from 50 μL of human plasma by precipitating proteins with methanol and then collecting the supernatant. Reversed-phase high-performance liquid chromatography was performed for analyte separation using a biphasic gradient at a flow rate of 0.25-0.5 mL/min. The total run time was 9.5 minutes. The analytes were detected using MS/MS with electrospray ionization operating in positive ion mode.RESULTS: Validation according to the US Food and Drug Administration's guidance showed that the new assay produced accurate (94.7%-107%) and precise (within-run: 1.2%-8.2%; between-run: 0.6%-7.5%) measurements of all analytes over a concentration range of 5-2000 ng/mL. Overall, analyte recoveries were consistent (mean values: 110%-129%). The analytes were also stable in human plasma and the final extract under various storage conditions. Finally, the clinical applicability of the assay was confirmed by quantitation of all analytes in plasma samples obtained from patients treated with CDK4/6 inhibitors. Reproducibility of the measured analyte concentrations in study samples was confirmed successfully by incurred sample reanalysis.CONCLUSIONS: A sensitive liquid chromatography coupled with tandem mass spectrometry method to measure CDK4/6 inhibitors was developed and validated according to the Food and Drug Administration criteria. Quantitation of all analytes in clinical plasma samples confirmed that the assay is suitable for therapeutic drug monitoring and clinical pharmacokinetic studies of CDK4/6 inhibitors.PMID:36728357 | DOI:10.1097/FTD.0000000000001063

J Cell Physiol. 2023 Feb 2. doi: 10.1002/jcp.30953. Online ahead of print.ABSTRACTA common adverse response to the clinical use of glucocorticoids (GCs) is elevated intraocular pressure (IOP) which is a major risk factor for glaucoma. Elevated IOP arises due to impaired outflow of aqueous humor (AH) through the trabecular meshwork (TM). Although GC-induced changes in actin cytoskeletal dynamics, contractile characteristics, and cell adhesive interactions of TM cells are believed to influence AH outflow and IOP, the molecular mechanisms mediating changes in these cellular characteristics are poorly understood. Our studies focused on evaluating changes in the cytoskeletal and cytoskeletal-associated protein (cytoskeletome) profile of human TM cells treated with dexamethasone (Dex) using label-free mass spectrometric quantification, identified elevated levels of specific proteins known to regulate actin stress fiber formation, contraction, actin networks crosslinking, cell adhesion, and Wnt signaling, including LIMCH1, ArgBP2, CNN3, ITGBL1, CTGF, palladin, FAT1, DIAPH2, EPHA4, SIPA1L1, and GPC4. Several of these proteins colocalized with the actin cytoskeleton and underwent alterations in distribution profile in TM cells treated with Dex, and an inhibitor of Abl/Src kinases. Wnt/Planar Cell Polarity (PCP) signaling agonists-Wnt5a and 5b were detected prominently in the cytoskeletome fraction of TM cells, and studies using siRNA to suppress expression of glypican-4 (GPC4), a known modulator of the Wnt/PCP pathway revealed that GPC4 deficiency impairs Dex induced actin stress fiber formation, and activation of c-Jun N-terminal Kinase (JNK) and Rho kinase. Additionally, while Dex augmented, GPC4 deficiency suppressed the formation of actin stress fibers in TM cells in the presence of Dex and Wnt5a. Taken together, these results identify the GPC4-dependent Wnt/PCP signaling pathway as one of the crucial upstream regulators of Dex induced actin cytoskeletal reorganization and cell adhesion in TM cells, opening an opportunity to target the GPC4/Wnt/PCP pathway for treatment of ocular hypertension in glaucoma.PMID:36727620 | DOI:10.1002/jcp.30953

Arterioscler Thromb Vasc Biol. 2023 Feb 2. doi: 10.1161/ATVBAHA.122.318871. Online ahead of print.ABSTRACTBACKGROUND: Acute myocardial infarction (AMI) is a leading cause of death and disability. Diabetes is an important risk factor and a common comorbidity in AMI patients. The higher mortality risk of diabetes-AMI relative to nondiabetes-AMI indicates a need for specific treatment to improve clinical outcome. However, the global metabolic dysregulation of AMI complicated with diabetes is still unclear. We aim to systematically interrogate changes in the metabolic microenvironment immediate to AMI episodes in the absence or presence of diabetes.METHODS: In this work, quantitative metabolomics was used to investigate plasma metabolic differences between diabetes-AMI (n=59) and nondiabetes-AMI (n=59) patients. A diverse array of perturbed metabolic pathways involving carbohydrate metabolism, lipid metabolism, glycolysis, tricarboxylic acid cycle, and amino acid metabolism emerged.RESULTS: In all, our omics-oriented approach defined a metabolic signature of afflicted mitochondrial function aggravated by concurrent diabetes in AMI patients. In particular, our analyses uncovered N-lactoyl-phenylalanine and lysophosphatidylcholines as key functional metabolites that skewed the metabolic picture of diabetes-AMI relative to nondiabetes-AMI. N-lactoyl-phenylalanine was strongly associated with metabolic indicators reflective of mitochondrial overload and negatively correlated with HbA1c specifically in hyperglycemic AMI, suggestive of its central role in glucose utilization and mitochondrial energy production instrumental to the clinical outcome of diabetes-AMI. Reductions in lysophosphatidylcholines, which were negatively correlated with blood glucose and inflammatory markers, might further compromise glucose expenditure and aggravate inflammation leading to poorer prognosis in diabetes-AMI.CONCLUSIONS: As circulating metabolite levels are amenable to therapeutic intervention, such shifts in metabolic signatures provide new clues and potential therapeutic targets specific to the treatment of diabetes-AMI.PMID:36727520 | DOI:10.1161/ATVBAHA.122.318871

Arterioscler Thromb Vasc Biol. 2023 Feb 2. doi: 10.1161/ATVBAHA.122.318334. Online ahead of print.ABSTRACTDespite devastating clinical sequelae of calcific aortic valve disease that range from left ventricular remodeling to arrhythmias, heart failure, and early death, the molecular insights into disease initiation and progression are limited and pharmacotherapies remain unavailable. The pathobiology of calcific aortic valve disease is complex and comprehensive studies are challenging valvular calcification is heterogeneous and occurs preferentially on the aortic surface, along a fibrocalcific spectrum. Here, we review efforts to study (epi-)genomic, transcriptomic, proteomic, and metabolomic aspects of aortic valve calcification in combination with network medicine-/systems biology-based strategies to integrate multilayered omics datasets and prioritize druggable targets for experimental validation studies. Ultimately, such holistic approach efforts may open therapeutic avenues that go beyond invasive and costly valve replacement therapy.PMID:36727519 | DOI:10.1161/ATVBAHA.122.318334

J Appl Toxicol. 2023 Feb 1. doi: 10.1002/jat.4440. Online ahead of print.ABSTRACTIn recent years, chromium (Cr) has been found to induce neurotoxicity. However, the underlying mechanism remains unclear. This study aimed to investigate the effects of chromium exposure on the metabolome and microbiome that may contribute to neurotoxicity in juvenile zebrafish. Zebrafish embryos were exposed to 1mg/L Cr (III) and 1mg/L Cr (VI) for seven days, respectively. Swimming distance and locomotor behavior was decreased, and acetylcholinesterase activity was reduced in Cr-exposed groups. Total cholesterol levels were decreased in Cr-exposed groups. The differential-expressed metabolites due to Cr exposure were mainly enriched in primary bile acid biosynthesis, which indicated that Cr exposure may promote cholesterol conversion. The abundance of Bacteroidetes decreased and the abundance of Actinomycetes increased in Cr- exposed groups, as compared to that in the control group. At the genus level, the abundance of Acinetobacter, Acidophorax, Mycobacterium, Aeromonas, Hydrophagophaga and Brevundimonas increased, whereas Chryseobacterium, Pseudomonas, Delftia and Ancylobacter decreased in the Cr-exposed groups. Analysis of the correlation between gut microbiota and bile acid metabolites showed that changes of gut microbial community due to Cr exposure may be related to secondary bile acid metabolism. Collectively, chromium exposure may disturb cholesterol metabolism, including primary bile acid and microbiota-related secondary bile acid metabolism. This study provides potential mechanism of the effects of chromium on neurotoxicity based on modulation of metabolome and gut microbiota diversity, which needs further verification.PMID:36727205 | DOI:10.1002/jat.4440

Front Nutr. 2023 Jan 16;9:1065188. doi: 10.3389/fnut.2022.1065188. eCollection 2022.ABSTRACTINTRODUCTION: Metabolic flexibility (MetF) is the capacity of an organism to oxidate substrate according to substrate availability or demand. The mismatch of substrate availability and oxidation may cause ectopic fat accumulation in the muscle and the liver. The objectives of the study are to examine the effect of 12 weeks of combined exercise on hepatic fat reduction and investigate metabolites related to MetF before and after the high-fat diet between individuals with NAFLD and healthy control with an active lifestyle.METHODS: This study is an open-label, single-center trial randomized controlled clinical study plus a cross-sectional comparison between individuals with NAFLD and healthy control. Individuals with NAFLD were allocated into two groups receiving resistance training (RT) combined with high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT). Anthropometric indicators, clinical blood markers about glucose, lipid metabolism, and hepatic fat content (HFC) were assessed before and after the intervention. The metabolomics was also used to investigate the discrepant metabolites and mechanisms related to MetF.DISCUSSION: Metabolic flexibility reflects the capacity of an organism to switch the oxidation substrates flexibly, which is associated with ectopic fat accumulation. Our study aimed to explore the discrepant metabolites related to MetF before and after a high-fat diet between individuals with NAFLD and healthy control. In addition, the study also examined the effectiveness of RT combined with HIIT or MICT on hepatic fat reduction and quantificationally analyzed the metabolites related to MetF before and after the intervention. Our results provided a perspective on fatty liver-associated metabolic inactivity.TRIAL REGISTRATION: ClinicalTrials.gov: ChiCTR2200055110; Registered 31 December 2021, http://www.chictr.org.cn/index.aspx.PMID:36726820 | PMC:PMC9884837 | DOI:10.3389/fnut.2022.1065188

Front Nutr. 2023 Jan 16;9:1092846. doi: 10.3389/fnut.2022.1092846. eCollection 2022.ABSTRACTINTRODUCTION: Esports is a category of competitive video games that, in many aspects, may be similar to traditional sports; however, the gut microbiota composition of players has not been yet studied.MATERIALS AND METHODS: Here, we investigated the composition and function of the gut microbiota, as well as short chain fatty acids (SCFAs), and amino acids, in a group of 109 well-characterized Polish male esports players. The results were compared with two reference groups: 25 endurance athletes and 36 healthy students of physical education. DNA and metabolites isolated from fecal samples were analyzed using shotgun metagenomic sequencing and mass spectrometry, respectively. Physical activity and nutritional measures were evaluated by questionnaire.RESULTS: Although anthropometric, physical activity and nutritional measures differentiated esports players from students, there were no differences in bacterial diversity, the Bacteroidetes/Firmicutes ratio, the composition of enterotype clusters, metagenome functional content, or SCFA concentrations. However, there were significant differences between esports players and students with respect to nine bacterial species and nine amino acids. By contrast, all of the above-mentioned measures differentiated professional athletes from esports players and students, with 45 bacteria differentiating professional athletes from the former and 31 from the latter. The only species differentiating all three experimental groups was Parabacteroides distasonis, showing the lowest and highest abundance in esports players and athletes, respectively.CONCLUSION: Our study confirms the marked impact of intense exercise training on gut microbial structure and function. Differences in lifestyle and dietary habits between esports players and physical education students appear to not have a major effect on the gut microbiota.PMID:36726816 | PMC:PMC9884692 | DOI:10.3389/fnut.2022.1092846

Front Nutr. 2023 Jan 16;9:1070223. doi: 10.3389/fnut.2022.1070223. eCollection 2022.ABSTRACTINTRODUCTION: Recent evidence supports a role for the gut microbe-metabolites in longevity. However, the phenomenon of hypertension is more common in the longevity area and whether hypertension is associated with longevity remains unclear. Here, we hypothesize that the levels of gut microbiota, SCFAs, and urine metabolites were different between hypertension elderly and hypertension longevity.METHODS: We recruited 46 elderly volunteers from Donglan County, Guangxi, and 32 were selected and included in the experiment. The subjects with hypertension were divided into two groups according to age, Hypertension Elderly (HTE, aged 70.5 ± 8.59, n = 19) and Hypertension Longevity (HTL, aged 100 ± 5.72, n = 13). The gut microbiota, SCFAs, and urine metabolites were determined by three-generation 16S rRNA full-length sequencing, GC-MS, and 1H-NMR, respectively.RESULTS: Compared with the HTL group, the HTE group had higher levels of hypertension-related genera Klebsiella and Streptococcus, while having lower levels of the SCFA-producing genera Bacteroides, Faecalibacterium, and Alistipes. Based on LEFse analysis, Klebsiella pneumoniae, Lactobacillus gasseri, Streptococcus salivarius, Ruminococcus, Actinomyces, Rikenellaceae, f_Saccharimonadaceae, Clostridium perfringens, and Bacteroids, Faecalibacterium prausnitzii, Parabacteroides, Alistipes were biomarkers that showed significant differences between the groups. In addition, the microbial pathways associated with K. pneumoniae and E. coli may promote hypertension, while A. muciniphila may play a role in reversing the development of hypertension in long-lived elderly. Metabolomics revealed that HTL contained a lower concentration of fecal acetate and propionate than HTE, while it contained a higher concentration of serum acetate and urine acetate. Furthermore, their immune cells exhibited no significant changes in SCFAs receptors.CONCLUSION: Although long-lived elderly have extremely high systolic blood pressure, their unique gut microbiota composition and efficient acetate absorption in the colon may offset the damages caused by hypertension and maintain healthy homeostasis.PMID:36726815 | PMC:PMC9884688 | DOI:10.3389/fnut.2022.1070223

Front Nutr. 2023 Jan 16;10:1114880. doi: 10.3389/fnut.2023.1114880. eCollection 2023.ABSTRACTINTRODUCTION: Huangjiu is an important Chinese alcoholic beverage, usually prepared from rice. Although its unique flavor improves with prolonged storage in traditional pottery jars, knowledge of the aging mechanism, necessary for commercialization of an optimum product, remains unclear.METHODS: Here, volatile aroma compounds from forced aged samples exposed to different temperatures and oxygen treatments were measured by GC/MS. After retention time alignment and normalization, the peak vectors were compared over storage time using Pearson's correlation, and a correlation network was established. Marker compounds, representative of traditionally aged Huangjiu, were then monitored and compared to similar compounds in the forced aged product.RESULTS AND DISCUSSION: Correlation network analysis revealed the following: Temperature had little effect on most aroma compounds; alcohols, acids, and esters all increased with increasing dissolved oxygen, while polyphenols, lactones, and ketones were readily oxidized; aldehydes (e.g., furfural and benzaldehyde) were highly dependent on both temperature and dissolved oxygen. Dynamic changes in the targeted aging-markers showed that a higher initial oxygen concentration intensified the "aging-aroma" of Huangjiu in the early and middle stages of storage. Consequently, careful control of oxygen supplementation and storage temperature could be beneficial in controlling the desirable flavor of Huangjiu in the artificially aged product.PMID:36726696 | PMC:PMC9884831 | DOI:10.3389/fnut.2023.1114880