PubMed

Metabolomics. 2024 Jul 29;20(4):88. doi: 10.1007/s11306-024-02145-8.ABSTRACTINTRODUCTION: Food intake biomarkers are used to estimate dietary exposure; however, selecting a single biomarker to evaluate a specific dietary component is difficult due to the overlap of diverse compounds from different foods. Therefore, combining two or more biomarkers can increase the sensitivity and specificity of food intake estimates.OBJECTIVE: This study aimed to evaluate the ability of metabolite panels to distinguish between self-reported fruit consumers and non-consumers among participants in the Longitudinal Study of Adult Health.MATERIALS AND METHODS: A total of 93 healthy adults of both sexes were selected from the Longitudinal Study of Adult Health. A 24-h dietary recall was obtained using the computer-assisted 24-h food recall GloboDiet software, and 24-h urine samples were collected from each participant. Metabolites were identified in urine using liquid chromatography coupled with high-resolution mass spectrometry by comparing their exact mass and fragmentation patterns using free-access databases. Multivariate receiver operating characteristic curve (ROC) analysis and partial least squares discriminant analysis were used to verify the ability of the metabolite combination to classify daily and non-daily fruit consumers. Fruit intake was identified using a 24 h dietary recall (24 h-DR).RESULTS: Bananas, grapes, and oranges are included in the summary. The panel of biomarkers exhibited an area under the curve (AUC) > 0.6 (Orange AUC = 0.665; Grape AUC = 0.622; Bananas AUC = 0.602; All fruits AUC = 0.679; Citrus AUC = 0.693) and variable importance projection score > 1.0, and these were useful for assessing the sensitivity and predictability of food intake in our population.CONCLUSION: A panel of metabolites was able to classify self-reported fruit consumers with strong predictive power and high specificity and sensitivity values except for banana and total fruit intake.PMID:39073486 | DOI:10.1007/s11306-024-02145-8

Mol Omics. 2024 Jul 29. doi: 10.1039/d4mo00015c. Online ahead of print.ABSTRACTLiquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) untargeted metabolomics has become the gold standard for the profiling of low-molecular-weight compounds. Recently, this discipline has raised great interest in forensic sciences, especially in the field of toxicology and for post-mortem interval estimation. The current study aims at evaluating three extraction protocols and two LC-MS/MS assays run in both positive and negative modes, to identify the most suitable method to conduct post-mortem metabolomic profiling of bone tissue. A fragment of the anterior tibia of a 82 years-old male sampled from a human taphonomy facility was powdered via freeze-milling. The powdered sub-samples were extracted in five replicates per protocol. Methods tested were (I) a biphasic chloroform-methanol-water protocol, (II) a single phase methanol-water protocol, and (III) a single phase methanol-acetonitrile-water protocol. LC-MS/MS analyses were carried out via high performance liquid chromatography, either on hydrophilic interaction (HILIC) or on reversed-phase (C18) columns in both positive and negative ionisation modes, coupled with a Q-TOF mass spectrometer. Results suggest that the highest consistency between replicates and quality control samples was obtained with the single phase extractions (i.e., methanol-acetonitrile-water), whilst the ideal combination of instrumental set up HILIC chromatography in positive ionisation mode and of C18 chromatography in negative ionisation mode. For the purpose of forensic investigations, a combination of a single phase extraction and the two aforementioned chromatographic and mass spectrometry modes could represent an ideal set up for obtaining bone metabolomic profiles from taphonomically altered bones.PMID:39073399 | DOI:10.1039/d4mo00015c

Angew Chem Int Ed Engl. 2024 Jul 29:e202409220. doi: 10.1002/anie.202409220. Online ahead of print.ABSTRACTProtein homeostasis in bacteria is regulated by proteases such as the tetradecameric caseinolytic protease P (ClpP). Although substrates of ClpP have been successfully deciphered in genetically engineered cells, methods which directly trap processed proteins within native cells remain elusive. Here, we introduce an in situ trapping strategy which utilizes trifunctional probes that bind to the active site serine of ClpP and capture adjacent substrates with an attached photocrosslinking moiety. After enrichment using an alkyne handle, substrate deconvolution by mass spectrometry (MS) is performed. We show that our two traps bind substoichiometrically to ClpP, retain protease activity, exhibit unprecedented selectivity for Staphylococcus aureus ClpP in living cells and capture numerous known and novel substrates. The exemplary validation of trapped hits using a targeted proteomics approach confirmed the fidelity of this technology. In conclusion, we provide a novel chemical platform suited for the discovery of serine protease substrates beyond genetic engineering.PMID:39073273 | DOI:10.1002/anie.202409220

Parasite Immunol. 2024 Jul;46(7):e13056. doi: 10.1111/pim.13056.ABSTRACTCo-evolutionary adaptation of hookworms with their mammalian hosts has been selected for immunoregulatory excretory/secretory (E/S) products. However, it is not known whether, or if so, how host immunological status impacts the secreted profile of hematophagous adult worms. This study interrogated the impact of host Signal transducer and activator of transcription 6 (STAT6) expression during the experimental evolution of hookworms through the sequential passage of the life cycle in either STAT6 deficient or WT C57BL/6 mice. Proteomic analysis of E/S products by LC-MS showed increased abundance of 15 proteins, including myosin-3, related to muscle function, and aconitate hydratase, related to iron homeostasis. However, most E/S proteins (174 of 337 unique identities) were decreased, including those in the Ancylostoma-secreted protein (ASP) category, and metallopeptidases. Several identified proteins are established immune-modulators such as fatty acid-binding protein homologue, cystatin, and acetylcholinesterase. Enrichment analysis of InterPro functional categories showed down-regulation of Cysteine-rich secretory proteins, Antigen 5, and Pathogenesis-related 1 proteins (CAP), Astacin-like metallopeptidase, Glycoside hydrolase, and Transthyretin-like protein groups in STAT6 KO-adapted worms. Taken together, these data indicate that in an environment lacking Type 2 immunity, hookworms alter their secretome by reducing immune evasion proteins- and increasing locomotor- and feeding-associated proteins.PMID:39073185 | DOI:10.1111/pim.13056

CNS Neurosci Ther. 2024 Jul;30(7):e14887. doi: 10.1111/cns.14887.ABSTRACTAIMS: Neuroinflammation is a recognized contributor to cognitive disorders like Alzheimer's disease, with ferroptosis emerging as a novel mechanism underlying cognitive dysfunction associated with neuroinflammation. Insulin, pivotal in the central nervous system, holds promise for cognitive function enhancement. This study aimed to establish a cognitive impairment model through intracerebroventricular injection of lipopolysaccharide (LPS) and explore the impact of intracerebroventricular insulin injection on cognitive function in mice.METHODS: We employed diverse experimental techniques, including animal behavior testing, molecular assays, targeted metabolomics, nuclear medicine, and electron microscopy, to assess neurodegenerative changes, brain insulin resistance (IR), glucose uptake and metabolism, and ferroptosis. The model of cognitive impairment was induced via intracerebroventricular injection of LPS, followed by intracerebroventricular administration of insulin to evaluate its effects.RESULTS: Insulin treatment effectively mitigated LPS-induced cognitive decline and safeguarded against neuronal degeneration. Furthermore, insulin alleviated LPS-induced insulin resistance, enhanced glucose uptake in the hippocampus, and promoted the Pentose Phosphate Pathway (PPP) and nicotinamide adenine dinucleotide phosphate (NADPH) production. Additionally, insulin activated the glutathione (GSH)-glutathione peroxidase 4 (GPX4) pathway, reducing lipid peroxidation, and mitochondrial damage characteristic of LPS-induced ferroptosis in the hippocampus.CONCLUSION: Our findings underscore the therapeutic potential of insulin in alleviating LPS-induced cognitive impairment and ferroptosis by modulating glucose metabolism. This study offers a promising avenue for future interventions targeting cognitive decline.PMID:39073013 | DOI:10.1111/cns.14887

Phytochem Anal. 2024 Jul 28. doi: 10.1002/pca.3428. Online ahead of print.ABSTRACTINTRODUCTION: Stemona tuberosa Lour. (ST) is a significant traditional Chinese medicine (TCM) renowned for its antitussive and insecticidal properties. ST is commonly subjected to processing in clinical practice before being utilized as a medicinal substance. Currently, the customary technique for processing ST is honey-fried. Nevertheless, the specific variations in chemical constituents of ST before and after honey-fried remain unclear.OBJECTIVE: This work aimed to analyze the variations in chemical constituents of ST before and after honey-fried and to study the distribution of differential markers in the roots.METHODS: UPLC-Orbitrap Fusion MS combined with molecular network analysis was used to analyze the metabolome of ST and honey-fried ST (HST) and to screen the differential metabolites by multivariate statistical analysis. Spatial metabolomics was applied to study the distribution of differential metabolites by desorption electrospray ionization mass spectrometry imaging (DESI-MSI).RESULTS: The ST and HST exhibited notable disparities, with 56 and 61 chemical constituents found from each, respectively. After processing, the types of alkaloids decreased, and 12 differential metabolites were screened from the common compounds. The notable component variations were epibisdehydro-tuberostemonine J, neostenine, tuberostemonine, croomine, neotuberostemonine, and so forth. MSI visualized the spatial distribution of differential metabolites.CONCLUSIONS: Our research provided a rapid and effective visualization method for the identification and spatial distribution of metabolites in ST. Compared with the traditional method, this method offered more convincing data supporting the processing mechanism investigations of Stemona tuberosa from a macroscopic perspective.PMID:39072901 | DOI:10.1002/pca.3428

Eur J Neurosci. 2024 Jul 28. doi: 10.1111/ejn.16482. Online ahead of print.ABSTRACTBoth clinical diagnosis and neuropathological diagnosis are commonly used in literature to categorize individuals as Alzheimer's disease (AD) or non-AD in omics analyses. Whether these diagnostic strategies result in distinct profiles of molecular abnormalities is poorly understood. Here, we analysed one of the most commonly used AD omics datasets in the literature from the Religious Orders Study and Memory and Aging Project (ROSMAP) cohort and compared the two diagnosis strategies using brain transcriptome and metabolome by grouping individuals as non-AD and AD according to clinical or neuropathological diagnosis separately. Differentially expressed genes, associated pathways related with AD hallmarks and AD-related genes showed that the categorization based on neuropathological diagnosis more accurately reflects the disease state at the molecular level than the categorization based on clinical diagnosis. We further identified consensus biomarker candidates between the two diagnosis strategies such as 5-hydroxylysine, sphingomyelin and 1-myristoyl-2-palmitoyl-GPC as metabolite biomarkers and sphingolipid metabolism as a pathway biomarker, which could be robust AD biomarkers since they are independent of diagnosis strategies. We also used consensus AD and consensus non-AD individuals between the two diagnostic strategies to train a machine-learning based model, which we used to classify the individuals who were cognitively normal but diagnosed as AD based on neuropathological diagnosis (asymptomatic AD individuals). The majority of these individuals were classified as consensus AD patients for both omics data types. Our study provides a detailed characterization of both diagnostic strategies in terms of the association of the corresponding multi-omics profiles with AD.PMID:39072881 | DOI:10.1111/ejn.16482

Br J Pharmacol. 2024 Jul 27. doi: 10.1111/bph.16469. Online ahead of print.ABSTRACTBACKGROUND AND PURPOSE: Acute pancreatitis (AP) is associated with acinar cell death and inflammatory responses. Ferroptosis is characterized by an overwhelming lipid peroxidation downstream of metabolic dysfunction, in which NADPH-related redox systems have been recognized as the mainstay in ferroptosis control. Nevertheless, it remains unknown how ferroptosis is regulated in AP and whether we can target it to restrict AP development.EXPERIMENTAL APPROACH: Metabolomics were applied to explore changes in metabolic pathways in pancreatic acinar cells (PACs) in AP. Using wild-type and Ptf1aCreERT2/+IDH2fl/fl mice, AP was induced by caerulein and sodium taurocholate (NaT). IDH2 overexpressing adenovirus was constructed for infection of PACs. Mice or PACs were pretreated with inhibitors of FSP1 or glutathione reductase. Pancreatitis severity, acinar cell injury, mitochondrial morphological changes and pancreatic lipid peroxidation were analysed.KEY RESULTS: Unsaturated fatty acid biosynthesis and the tricarboxylic acid cycle pathways were significantly altered in PACs during AP. Inhibition of ferroptosis reduced mitochondrial damage, lipid peroxidation and the severity of AP. During AP, the NADPH abundance and IDH2 expression were decreased. Acinar cell-specific deletion of IDH2 exacerbated acinar cell ferroptosis and pancreatic injury. Pharmacological inhibition of NADPH-dependent GSH/GPX4 and FSP1/CoQ10 pathways abolished the protective effect of IDH2 overexpression on ferroptosis in acinar cells. CoQ10 supplementation attenuated experimental pancreatitis via inhibiting acinar cell ferroptosis.CONCLUSION AND IMPLICATIONS: We identified the IDH2-NADPH pathway as a novel regulator in protecting against AP via restricting acinar cell ferroptosis. Targeting the pathway and its downstream may shed light on AP treatment.PMID:39072736 | DOI:10.1111/bph.16469

Appl Environ Microbiol. 2024 Jul 29:e0036024. doi: 10.1128/aem.00360-24. Online ahead of print.ABSTRACTCandida albicans, an opportunistic oral pathogen, synergizes with Staphylococcus aureus, allowing bacteria to co-invade and systemically disseminate within the host. Studying human-microbe interactions creates the need for a universal culture medium that supports fungal, bacterial, and human cell culturing, while allowing sensitive analytical approaches such as OMICs and chromatography techniques. In this study, we established a fully defined, customizable adaptation of Dulbecco's modified Eagle medium (DMEM), allowing multi-kingdom culturing of S. aureus, C. albicans, and human oral cell lines, whereas minimal version of DMEM (mDMEM) did not support growth of S. aureus, and neither did supplementation with dextrose, MEM non-essential amino acids, pyruvate, and Glutamax. This new medium composition, designated as "mDMEM-DMP," promoted growth of all tested S. aureus strains. Addition of 25 mM 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid (HEPES) further improved growth, while higher concentrations did not improve growth any further. Higher concentrations of HEPES did result in prolonged stabilization of medium pH. mDMEM-DMP promoted (hyphal) C. albicans monoculturing and co-culturing on both solid and semi-solid surfaces. In contrast to S. aureus, addition of HEPES reduced C. albicans maximum culture optical density (OD). Finally, only buffered mDMEM-DMP (100 mM HEPES) was successful in maintaining the metabolic activity of human oral Ca9-22 and HO1N1 cell lines for 24 hours. Altogether, our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.IMPORTANCE: Interaction between microbes and the host are in the center of interest both in disease and in health. In order to study the interactions between microbes of different kingdoms and the host, alternative media are required. Synthetic media are useful as they allow addition of specific components. In addition, well-defined media are required if high-resolution analyses such as metabolomics and proteomics are desired. We describe the development of a synthetic medium to study the interactions between C. albicans, S. aureus, and human oral epithelial cells. Our findings show that mDMEM-DMP is a versatile and potent culture medium for both microbial and human cell culturing, providing a customizable platform to study human as well as microbial molecular physiology and putative interactions.PMID:39072650 | DOI:10.1128/aem.00360-24

Virulence. 2024 Dec;15(1):2384563. doi: 10.1080/21505594.2024.2384563. Epub 2024 Jul 29.ABSTRACTPhenuiviruses are a class of segmented negative-sense single-stranded RNA viruses, typically consisting of three RNA segments that encode four distinct proteins. The emergence of pathogenic phenuivirus strains, such as Rift Valley fever phlebovirus (RVFV) in sub-Saharan Africa, Severe Fever with Thrombocytopenia Syndrome Virus (SFTSV) in East and Southeast Asia, and Heartland Virus (HRTV) in the United States has presented considerable challenges to global public health in recent years. The innate immune system plays a crucial role as the initial defense mechanism of the host against invading pathogens. In addition to continued research aimed at elucidating the epidemiological characteristics of phenuivirus, significant advancements have been made in investigating its viral virulence factors (glycoprotein, non-structural protein, and nucleoprotein) and potential host-pathogen interactions. Specifically, efforts have focused on understanding mechanisms of viral immune evasion, viral assembly and egress, and host immune networks involving immune cells, programmed cell death, inflammation, nucleic acid receptors, etc. Furthermore, a plethora of technological advancements, including metagenomics, metabolomics, single-cell transcriptomics, proteomics, gene editing, monoclonal antibodies, and vaccines, have been utilized to further our understanding of phenuivirus pathogenesis and host immune responses. Hence, this review aims to provide a comprehensive overview of the current understanding of the mechanisms of host recognition, viral immune evasion, and potential therapeutic approaches during human pathogenic phenuivirus infections focusing particularly on RVFV and SFTSV.PMID:39072499 | DOI:10.1080/21505594.2024.2384563

ACS Chem Neurosci. 2024 Jul 29. doi: 10.1021/acschemneuro.4c00199. Online ahead of print.ABSTRACTIn an era when population aging is increasing the burden of neurodegenerative conditions, deciphering the mechanisms underlying brain senescence is more important than ever. Here, we present a spatial metabolomics analysis of age-induced neurochemical alterations in the mouse brain using negative ionization mode mass spectrometry imaging. The age-dependent effects of the acetylcholinesterase inhibitor tacrine were simultaneously examined. For ultrahigh mass resolution analysis, we utilized a Fourier-transform ion cyclotron resonance spectrometer. To complement this, a trapped ion mobility spectrometry time-of-flight analyzer provided high speed and lateral resolution. The chosen approach facilitated the detection and identification of a wide range of metabolites, from amino acids to sphingolipids. We reported significant, age-dependent alterations in brain lipids which were most evident for sulfatides and lysophosphatidic acids. Sulfatide species, which are mainly localized to white matter, either increased or decreased with age, depending on the carbon chain length and hydroxylation stage. Lysophosphatidic acids were found to decrease with age in the detailed cortical and hippocampal subregions. An age-dependent increase in the glutamine/glutamate ratio, an indicator of glia-neuron interconnection and neurotoxicity, was detected after tacrine administration. The presented metabolic mapping approach was able to provide visualizations of the lipid signaling and neurotransmission alterations induced by early aging and can thus be beneficial to further elucidating age-related neurochemical pathways.PMID:39072364 | DOI:10.1021/acschemneuro.4c00199

Front Immunol. 2024 Jul 12;15:1414476. doi: 10.3389/fimmu.2024.1414476. eCollection 2024.ABSTRACTThe early and accurate identification of predictive biomarkers for antiviral treatment efficacy remains a significant clinical challenge, particularly in the management of chronic hepatitis B (CHB). This study aimed to assess whether the plasma metabolome could reliably predict the success of antiviral therapy in CHB patients. We conducted a retrospective analysis on 56 treatment-naive CHB patients at the First Affiliated Hospital of Zhejiang University from December 2013 to March 2016. Patients who underwent a 48-week treatment regimen of entecavir (ETV) and interferon-alpha (IFN-α) were randomly assigned to either a discovery cohort (n=29) or a validation cohort (n=27). Based on the outcome of the treatment, patients were classified as HBeAg seroconversion group (High responders, Hrp) or the non-remission group (Low responder, Lrp). Our methodology involved an untargeted analysis of the amine/phenol and carboxylic acid submetabolomes in the CHB patients under treatment, utilizing chemical isotope labeling (CIL) techniques with liquid chromatography-mass spectrometry (LC-MS). Several metabolites were identified as having significant diagnostic potential for distinguishing Hrp from Lrp, with areas under the receiver operating characteristic curve (AUC) exceeding those typical clinical indicators. Notably, four metabolites, namely 2-methyl-3-ketovaleric acid, 2-ketohexanoic acid, 6-oxo-1,4,5,6-tetrahydronicotinic acid, and α-ketoisovaleric acid, demonstrated exceptionally high sensitivity and specificity in both cohorts, nearing 100%. In contrast, the clinical indicators, including HBcAb, log(HBsAg), and HBeAb, demonstrated lower and inconsistent sensitivity and specificity between the discovery and validation cohorts. Using HBcAb as a marker, the sensitivity was 87.5% with 76.9% specificity in the discovery cohort; however, the sensitivity dropped to 46.7% with 91.7% specificity in the validation cohort. Using log(HBsAg), the sensitivity was 84.6% with 69.2% specificity in the discovery cohort, compared to 85.7% sensitivity and 83.3% specificity in the validation cohort. For HBeAb, the separation of Hrp and Lrp had a sensitivity of 87.5% with 69.2% specificity in the discovery cohort, while the validation cohort showed 86.7% sensitivity and 91.7% specificity.PMID:39072321 | PMC:PMC11272971 | DOI:10.3389/fimmu.2024.1414476

Chin Herb Med. 2024 Jan 29;16(3):435-448. doi: 10.1016/j.chmed.2023.10.004. eCollection 2024 Jul.ABSTRACTOBJECTIVE: Lilium brownii var. viridulum (LB) and L. lancifolium (LL) are the main sources of medicinal lily (Lilii Bulbus, Baihe in Chinese) in China. However, the functional components of these two species responsible for the treatment efficacy are yet not clear. In order to explore the therapeutic material basis of Lilii Bulbus, we selected L. davidii var. willmottiae (LD) only used for food as the control group to analyze the differences between LD and the other two (LB and LL).METHODS: Metabolome and transcriptome were carried out to investigate the differences of active components in LD vs LB and LD vs LL. Data of metabolome and transcriptome was analysed using various analysis methods, such as principal component analysis (PCA), hierarchical cluster analysis (HCA), and so on. Differentially expressed genes (DEGs) were enriched through KEGG and GO enrichment analysis.RESULTS: The PCA and HCA of the metabolome indicated the metabolites were clearly separated and varied greatly in LL and LB contrasted with LD. There were 318 significantly differential metabolites (SDMs) in LD vs LB group and 298 SDMs in LD vs LL group. Compared with LD group, the significant up-regulation of steroidal saponins and steroidal alkaloids were detected both in LB and LL groups, especially in LB group. The HCA of transcriptome indicated that there was significant difference in LB vs LD group, while the difference between LL and LD varied slightly. Additionally, 47 540 DEGs in LD vs LB group and 18 958 DEGs in LD vs LL group were identified. Notably, CYP450s involving in the biosynthesis of steroidal saponins and steroidal alkaloids were detected, and comparing with LD, CYP724, CYP710A, and CYP734A1 in LB and CYP90B in LL were all up-regulated.CONCLUSION: This study suggested that steroidal saponins and steroidal alkaloids maybe the representative functional components of Lilii Bulbus, which can provide new insights for Lilii Bulbus used in the research and development of classic famous formula.PMID:39072198 | PMC:PMC11283230 | DOI:10.1016/j.chmed.2023.10.004

medRxiv [Preprint]. 2024 Jul 21:2024.07.19.24310722. doi: 10.1101/2024.07.19.24310722.ABSTRACTImmigrants from less industrialized countries who are living in the U.S. often bear an elevated risk of multiple disease due to the adoption of a U.S. lifestyle. Blood metabolome holds valuable information on environmental exposure and the pathogenesis of chronic diseases, offering insights into the link between environmental factors and disease burden. Analyzing 634 serum metabolites from 7,114 Hispanics (1,141 U.S.-born, 5,973 foreign-born) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we identified profound blood metabolic shift during acculturation. Machine learning highlighted the prominent role of non-genetic factors, especially food and gut microbiota, in these changes. Immigration-related metabolites correlated with plant-based foods and beneficial gut bacteria for foreign-born Hispanics, and with meat-based or processed food and unfavorable gut bacteria for U.S.-born Hispanics. Cardiometabolic traits, liver, and kidney function exhibited a link with immigration-related metabolic changes, which were also linked to increased risk of diabetes, severe obesity, chronic kidney disease, and asthma.HIGHLIGHTS: A substantial proportion of identified blood metabolites differ between U.S.-born and foreign-born Hispanics/Latinos in the U.S.Food and gut microbiota are the major modifiable contributors to blood metabolomic difference between U.S.-born and foreign-born Hispanics/Latinos.U.S. nativity related metabolites collectively correlate with a spectrum of clinical traits and chronic diseases.PMID:39072018 | PMC:PMC11275661 | DOI:10.1101/2024.07.19.24310722

Mol Clin Oncol. 2024 Jul 9;21(3):62. doi: 10.3892/mco.2024.2760. eCollection 2024 Sep.ABSTRACTVolumetric-modulated arc therapy (VMAT) is a radiotherapy technique used to treat patients with localized prostate cancer, which is frequently associated with acute adverse events (AEs) that can affect subsequent treatment. Notably, the radiation dose of VMAT can be tailored to each patient. In the present study, a retrospective analysis was performed to predict acute AEs in response to a therapeutic high radiation dose rate based on urinary metabolomic molecules, which are easily collected as noninvasive biosamples. Urine samples from 11 patients with prostate cancer who were treated with VMAT (76 Gy/38 fractions) were collected. The study found that seven patients (~64%) exhibited genitourinary toxicity (Grade 1) and four patients had no AEs. A total of 630 urinary metabolites were then analyzed using a mass spectrometer (QTRAP6500+; AB SCIEX), and 234 relevant molecules for biological and clinical applications were extracted from the absolute quantified metabolite values using the MetaboINDICATOR tool. In the Grade 1 acute AE group, there was a significant negative correlation (rs=-0.297, P<0.05) between the number of VMAT fractions and total phospholipase A2 activity in the urine. Additionally, patients with Grade 1 AEs exhibited a decrease in PC aa C40:1, a phospholipid. These findings suggested that specific lipids found in urinary metabolites may serve as predictive biomarkers for acute AEs in response to external radiotherapy.PMID:39071973 | PMC:PMC11273245 | DOI:10.3892/mco.2024.2760

Food Chem X. 2024 Mar 31;23:101331. doi: 10.1016/j.fochx.2024.101331. eCollection 2024 Oct 30.ABSTRACTTo investigate the correlation between the difference of secondary metabolites and the disease-resistance activity of different varieties of Congou black tea. Among a total of 657 secondary metabolites identified, 183 metabolites had anti-disease activity, 113 were key active ingredients in traditional Chinese medicine (TCM), 73.22% had multiple anti-disease activities, and all were mainly flavonoids and phenolic acids. The main enriched metabolic pathways were phenylpropanoid biosynthesis, biosynthesis of secondary metabolites, flavonoid biosynthesis, and metabolic pathways. Flavonoid and phenolic acid secondary metabolites were more correlated with anti-disease activity and key active TCM ingredients. Conclusion: The types of JGY and Q601 Congou black tea of the relative contents show large differences in secondary metabolites. Flavonoid and phenolic acid secondary metabolites were identified as the primary factors contributing to the variation in secondary metabolites among different varieties of Congou black tea. These compounds also exhibited a stronger correlation with disease resistance activity.PMID:39071939 | PMC:PMC11282962 | DOI:10.1016/j.fochx.2024.101331

Food Chem X. 2024 Jul 2;23:101610. doi: 10.1016/j.fochx.2024.101610. eCollection 2024 Oct 30.ABSTRACTDietary fiber targets the regulation of the intestinal flora and thus affects host health, however, the complex relationship between these factors lacks direct evidence. In this study, the regulatory effects of Konjac glucomannan (KGM) on key metabolites of host intestinal flora were examined by using in vitro fermentation. The results showed that KGM could be utilized by the intestinal flora, which inhibited the relative abundance of Paeniclostridium, Lachnoclostridium, Phascolarctobacterium, and Bacteroides and enriched the relative abundance of Desulfovibrio, Sutterella, etc. Fermentation is accompanied by the production of short-chain acids, including acetic and propionic acids. Metabolomics revealed that KGM significantly promoted amino acid metabolism, lipid metabolism, and the biosynthesis of other secondary metabolites. Correlation analysis results showed that the increase of panose and N-(1-carboxy-3-carboxanilidopropyl) alanylproline content was positively correlated with the relative abundance of Megamonas. These results provide evidence that KGM affects host health by regulating gut microbiota and its metabolites.PMID:39071938 | PMC:PMC11282934 | DOI:10.1016/j.fochx.2024.101610

Food Chem X. 2024 Jun 27;23:101595. doi: 10.1016/j.fochx.2024.101595. eCollection 2024 Oct 30.ABSTRACTThe harvest date is a crucial factor in determining tea quality. For Lu'an Guapian (LAGP) tea, Grain Rain period (GRP) represents a pivotal phase in the transformation of tea quality. The sensory evaluation, computer vision and E-tongue revealed that the liquor color score, B and G values of tea infusion were increased during GRP, while the astringency, bitterness intensities and the R value of the tea infusion were decreased. Consequently, the tea infusion exhibited a greener hue and the taste became appropriate during GRP. Non-targeted metabolomics revealed that the majority of amino acids and derivatives was reduced during GRP. Furthermore, flavonoids, in particular flavonol glycosides, exhibited considerable variation during GRP. Finally, nine metabolites were identified as markers for quality transformation during GRP by PLS and Random Forest. This study investigated the quality of LAGP teas during GRP and filled the gap in the variation of LAGP tea quality during GRP.PMID:39071934 | PMC:PMC11283131 | DOI:10.1016/j.fochx.2024.101595

Food Chem X. 2024 Jul 2;23:101607. doi: 10.1016/j.fochx.2024.101607. eCollection 2024 Oct 30.ABSTRACTTwo untargeted metabolomics approaches (LC-HRMS and 1H NMR) were combined to classify Amarone wines based on grape withering time and yeast strain. The study employed a multi-omics data integration approach, combining unsupervised data exploration (MCIA) and supervised statistical analysis (sPLS-DA). The results revealed that the multi-omics pseudo-eigenvalue space highlighted a limited correlation between the datasets (RV-score = 16.4%), suggesting the complementarity of the assays. Furthermore, the sPLS-DA models correctly classified wine samples according to both withering time and yeast strains, providing a much broader characterization of wine metabolome with respect to what was obtained from the individual techniques. Significant variations were notably observed in the accumulation of amino acids, monosaccharides, and polyphenolic compounds throughout the withering process, with a lower error rate in sample classification (7.52%). In conclusion, this strategy demonstrated a high capability to integrate large omics datasets and identify key metabolites able to discriminate wine samples based on their characteristics.PMID:39071933 | PMC:PMC11279979 | DOI:10.1016/j.fochx.2024.101607

Food Chem X. 2024 Jun 26;23:101600. doi: 10.1016/j.fochx.2024.101600. eCollection 2024 Oct 30.ABSTRACTSignificant differences exist in aroma and taste of different grades of large-leaf black tea. In this study, sensory histology combined with metabolomics were used to investigate the sensory characteristics and phytochemical profiles of different grades of Huangpu black tea (HPBT). Sensory evaluation showed that high grade HPBT had high intensity of pekoe, fresh aroma and umami, with aroma and taste scores declining with decreasing grades. 173 non-volatiles were identified, of which 23 marker metabolites could be used as discrimination of different grades HPBT taste. In addition, 154 volatile compounds were identified in the different grades of HPBT, with 15 compounds as key odorants for distinguishing the aroma of different grades of HPBT. Furthermore, correlation analysis revealed that linalool, geraniol and nonanal contributed to the aroma quality score of HPBT. This study will provide a more comprehensive understanding for processing, quality evaluation and grade evaluation system of large-leaf black tea.PMID:39071923 | PMC:PMC11283085 | DOI:10.1016/j.fochx.2024.101600