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The high-fat diet would lead to excessive fat storage in the liver to form metabolic dysfunction-associated steatotic liver disease (MASLD), and the trend is burgeoning. The aim of the study is to investigate the effects of chlorogenic acid (CGA) on metabolites and gut microorganisms in MASLD mice induced by a high-fat diet. In comparison to the HF group, the TC (total cholesterol), TG (total triglycerides), LDL-C (low-density lipoprotein cholesterol), AST (aspartate aminotransferase) and ALT (alanine transaminase) levels were reduced after CGA supplement. CGA led to an increase in l-phenylalanine, l-tryptophan levels, and promoted fatty acid degradation. CGA increased the abundance of the Muribaculaceae, Bacteroides and Parabacteroides. Changes in these microbes were significantly associated with the liver metabolites level and lipid profile level. These data suggest important roles for CGA regulating the gut microbiota, liver and caecum content metabolites, and TG-, TC- and LDL-C lowering function. [ABSTRACT FROM AUTHOR]

Growing consumer concern about foodborne disease outbreaks and health risks associated with chemical additives has propelled the usage of essential oils (EOs) as novel food additives, but are limited by instability. In this regard, a series of EOs nano/micro-capsules have been widely used to enhance their stability and improve food quality. However, classical food quality assessment methods are insufficient to fully characterize the effects of encapsulated EOs on food properties, including physical, biochemical, organoleptic, and microbial changes. Recently, the rapid development of high-throughput sequencing is accelerating the application of metabolomics in food safety and quality analysis. This review seeks to present the most recent achievements in the application of non-targeted metabolomics to identify and quantify the overall metabolite profile associated with food quality, which can guide the development of emerging food preservation technologies. The scientific findings confirm that metabolomics opens up exciting prospects for biomarker screening in food preservation and contributes to an in-depth understanding of the mechanisms of action (MoA) of EOs. Future research should focus on constructing food quality assessment criteria based on multi-omics technologies, which will drive the standardization and commercialization of EOs for food industry applications. [ABSTRACT FROM AUTHOR]

SUMMARY: The grapevine industry is of high economic importance in several countries worldwide. Its growing market demand led to an acceleration of the entire production processes, implying increasing use of water resources at the expense of environmental water balance and the hydrological cycle. Furthermore, in recent decades climate change and the consequent expansion of drought have further compromised water availability, making current agricultural systems even more fragile from ecological and economical perspectives. Consequently, farmers' income and welfare are increasingly unpredictable and unstable. Therefore, it is urgent to improve the resilience of vineyards, and of agro‐ecosystems in general, by developing sustainable and environmentally friendly farming practices by more rational biological and natural resources use. The PRIMA project PROSIT addresses these challenges by characterizing and harnessing grapevine‐associated microbiota to propose innovative and sustainable agronomic practices. PROSIT aims to determine the efficacy of natural microbiomes transferred from grapevines adapted to arid climate to commonly cultivated grapevine cultivars. In doing so it will test those natural microbiome effects on drought tolerance. This multidisciplinary project will utilize in vitro culture techniques, bioimaging, microbiological tests, metabolomics, metabarcoding and epigenetic analyses. These will be combined to shed light on molecular mechanisms triggered in plants by microbial associations upon water stress. To this end it is hoped that the project will serve as a blueprint not only for studies uncovering the microbiome role in drought stress in a wide range of species, but also for analyzing its effect on a wide range of stresses commonly encountered in modern agricultural systems. Significance Statement: This Perspective Review manuscript focuses on innovative and sustainable solutions to drought stress in viticulture, representing the core research of the "Plant Microbiome in Sustainable Viticulture (PROSIT)" project funded by the PRIMA Foundation with the support of the Horizon 2020 Program. [ABSTRACT FROM AUTHOR]

Due to high-density farming methods and poor farming environments, freshwater fish often have poor muscle texture and a fishy odor before marketing, which impacts consumer acceptance. Short-term low-salinity seawater treatment of freshwater fish before marketing has been found to improve the quality of the fish, but the mechanisms underlying this phenomenon have not yet been revealed. In this study, metabolomics technique was used based on gas chromatography-mass spectrometry (GC–MS) and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to screen different metabolites and predict potential metabolic pathways after treatment with low-salinity seawater. The results showed that 3838 metabolites were presented in all of the carp samples, while 62 and 64 differential metabolites were found in the comparative groups (FW, SW, and CK represented freshwater, seawater and non-transient group, respectively). Additionally, 25 and 26 metabolic pathways were enriched from these groups. Glutaric acid, PC, and creatinine might be potential biomarkers. Seawater aquaculture significantly altered the lipid metabolism, nucleotide metabolism, and amino acid metabolism of carp, enhancing its freshness and having a significant impact on its quality. This study provided insights into the metabolic changes in carp under different rearing conditions and also served as a theoretical basis for salinity treatment before freshwater fish are brought to the market. [ABSTRACT FROM AUTHOR]

Key message: Integrated omics analyses outline the cellular and metabolic events of hemp plants in response to salt stress and highlight several photosynthesis and energy metabolism related pathways as key regulatory points. Soil salinity affects many physiological processes of plants and leads to crop yield losses worldwide. For hemp, a crop that is valued for multiple aspects, such as its medical compounds, fibre, and seed, a comprehensive understanding of its salt stress responses is a prerequisite for resistance breeding and tailoring its agronomic performance to suit certain industrial applications. Here, we first observed the phenotype of salt-stressed hemp plants and found that under NaCl treatment, hemp plants displayed pronounced growth defects, as indicated by the significantly reduced average height, number of leaves, and chlorophyll content. Next, we conducted comparative proteomics and metabolomics to dissect the complex salt-stress response mechanisms. A total of 314 proteins and 649 metabolites were identified to be differentially behaving upon NaCl treatment. Functional classification and enrichment analysis unravelled that many differential proteins were proteases associated with photosynthesis. Through metabolic pathway enrichment, several energy-related pathways were found to be altered, such as the biosynthesis and degradation of branched-chain amino acids, and our network analysis showed that many ribosomal proteins were involved in these metabolic adaptations. Taken together, for hemp plants, influences on chloroplast function probably represent a major toxic effect of salinity, and modulating several energy-producing pathways possibly through translational regulation is presumably a key protective mechanism against the negative impacts. Our data and analyses provide insights into our understanding of hemp’s stress biology and may lay a foundation for future functional genomics studies. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is a severe hazard to human health. Since pathogenesis of UC is still unclear, current therapy for UC treatment is far from optimal. Isoxanthohumol (IXN), a prenylflavonoid from hops and beer, possesses anti-microbial, anti-oxidant, anti-inflammatory, and anti-angiogenic properties. However, the potential effects of IXN on the alleviation of colitis and the action of the mechanism is rarely studied. Here, we found that administration of IXN (60 mg/kg/day, gavage) significantly attenuated dextran sodium sulfate (DSS)-induced colitis, evidenced by reduced DAI scores and histological improvements, as well as suppressed the pro-inflammatory Th17/Th1 cells but promoted the anti-inflammatory Treg cells. Mechanically, oral IXN regulated T cell development, including inhibiting CD4+ T cell proliferation, promoting apoptosis, and regulating Treg/Th17 balance. Furthermore, IXN relieved colitis by restoring gut microbiota disorder and increasing gut microbiota diversity, which was manifested by maintaining the ratio of Firmicutes/Bacteroidetes balance, promoting abundance of Bacteroidetes and Ruminococcus, and suppressing abundance of proteobacteria. At the same time, the untargeted metabolic analysis of serum samples showed that IXN promoted the upregulation of D-(+)-mannose and L-threonine and regulated pyruvate metabolic pathway. Collectively, our findings revealed that IXN could be applied as a functional food component and served as a therapeutic agent for the treatment of UC. Model of IXN ameliorated DSS-induced colitis via regulating T cell development and restoring gut microbiota. Oral IXN could effectively alleviate DSS-induced colitis. Mechanically, IXN restored gut microbiota disorder, increased gut microbiota diversity, altered serum metabolic profile, and regulated Treg/Th17 balance. [ABSTRACT FROM AUTHOR]

Exposure to wildfire smoke is associated with both acute and chronic cardiopulmonary illnesses, which are of special concern for wildland firefighters who experience repeated exposure to wood smoke. It is necessary to better understand the underlying pathophysiology by which wood smoke exposure increases pulmonary disease burdens in this population. We hypothesize that wood smoke exposure produces pulmonary dysfunction, lung inflammation, and gene expression profiles associated with future pulmonary complications. Male Long-Evans rats were intermittently exposed to smoldering eucalyptus wood smoke at 2 concentrations, low (11.0 ± 1.89 mg/m3) and high (23.7 ± 0.077 mg/m3), over a 2-week period. Whole-body plethysmography was measured intermittently throughout. Lung tissue and lavage fluid were collected 24 h after the final exposure for transcriptomics and metabolomics. Increasing smoke exposure upregulated neutrophils and select cytokines in the bronchoalveolar lavage fluid. In total, 3446 genes were differentially expressed in the lungs of rats in the high smoke exposure and only 1 gene in the low smoke exposure (Cd151). Genes altered in the high smoke group reflected changes to the Eukaryotic Initiation Factor 2 stress and oxidative stress responses, which mirrored metabolomics analyses. xMWAS-integrated analysis revealed that smoke exposure significantly altered pathways associated with oxidative stress, lung morphogenesis, and tumor proliferation pathways. These results indicate that intermittent, 2-week exposure to eucalyptus wood smoke leads to transcriptomic and metabolic changes in the lung that may predict future lung disease development. Collectively, these findings provide insight into cellular signaling pathways that may contribute to the chronic pulmonary conditions observed in wildland firefighters. [ABSTRACT FROM AUTHOR]

Dietary methionine restriction (MR) is associated with a spectrum of health‐promoting benefits. Being conducive to prevention of chronic diseases and extension of life span, MR can activate integrated responses at metabolic, transcriptional, and physiological levels. However, how the mitochondria of MR influence metabolic phenotypes remains elusive. Here, we provide a summary of cellular functions of methionine metabolism and an overview of the current understanding of effector mechanisms of MR, with a focus on the aspect of mitochondria‐mediated responses. We propose that mitochondria can sense and respond to MR through a modulatory role of lipoylation, a mitochondrial protein modification sensitized by MR. [ABSTRACT FROM AUTHOR]

Introduction: Fighter pilots must support the effects of many stressors, including physical and psychological exertion, circadian disturbance, jet lag, and environmental stress. Despite the rigorous selection of military pilots, those factors predispose to failures in physiological compensatory mechanisms and metabolic flexibility. Objectives: We compared through NMR-based metabolomics the metabolic profile of Brazilian F5 fighter pilots with different flight experiences vs. the control group of non-pilots. We hypothesized that combat pilots have metabolic flexibility associated with combat flight time. Methods: We evaluated for the first time 34 Brazilian fighter pilots from Santa Cruz Air Base (Rio de Janeiro, RJ) allocated into three groups: pilots with lower total accumulated flight experience < 1,100 h (PC1, n = 7); pilots with higher total accumulated flight experience ≥ 1,100 h (PC2, n = 6); military non-pilots (CONT, n = 21). Data collection included anthropometric measurements, total blood count, lipidogram, markers of oxidative stress, and serum NMR-based metabolomics. Results: In comparison with controls (p < 0.05), pilots exhibited decreased levels of white blood cells (−13%), neutrophils (−15%), lymphocytes (−20%), alfa-glucose (−13%), lactate (−26%), glutamine (−11%), histidine (−20%), and tyrosine (−11%), but higher isobutyrate (+ 10%) concentrations. Significant correlations were found between lactate vs. amino acids in CONT (r = 0.55–0.68, p < 0.001), and vs. glutamine in PC2 (r = 0.94, p = 0.01). Conclusion: Fighter pilots with lower experience showed a dysregulation in immune-metabolic function in comparison with controls, which seemed to be counteracted by the accumulation of flight hours. Those findings might have implications for the health preservation and operational training of fighter pilots. [ABSTRACT FROM AUTHOR]

Introduction: IgA vasculitis diagnosis relies primarily on clinical features and is confirmed by pathological findings. To date, there is no reliable noninvasive diagnostic biomarker. Objective: We aimed to explore the baseline serum metabolome of adult patients with IgA vasculitis to identify potential diagnostic biomarkers. Methods: We performed a study comparing the serum metabolome of patients with IgA vasculitis to that of patients with inflammatory condition, namely spondyloarthritis. Serum analyses were performed by high-performance liquid chromatography-mass spectrometry. Results: Fifty-five patients with IgA vasculitis and 77 controls with spondyloarthritis (age- and sex-matched) were included in this study. The median age of IgA vasculitis patients was 53 years. Two-thirds of patients were female (n = 32). At the time of vasculitis diagnosis, 100% of patients had skin involvement and 69% presented with glomerulonephritis (n = 38). Joint and digestive involvement were observed in 56% (n = 31) and 42% (n = 23) of patients. Four discriminative metabolites between the two groups were identified: 1-methyladenosine, L-glutamic acid, serotonin, and thymidine. The multivariate model built from the serum metabolomes of patients with IgA vasculitis and spondyloarthritis revealed an accuracy > 90%. As this model was significant according to the permutation test (p < 0.01), independent validation showed an excellent predictive value of the test set: sensitivity 98%; specificity 98%, positive predictive value 97% and negative predictive value 98%. Conclusion: To our knowledge, this study is the first to use the metabolomic approach for diagnostic purposes in adult IgA vasculitis, highlighting a specific diagnostic metabolome signature. [ABSTRACT FROM AUTHOR]

Introduction: Bio stimulants are substances and/or microorganisms that are used to improve plant growth and crop yields by modulating physiological processes and metabolism of plants. While research has primarily focused on the broad effects of bio stimulants in crops, understanding their cellular and molecular influences in plants, using metabolomic analysis, could elucidate their effectiveness and offer possibilities for fine-tuning their application. One such bio stimulant containing galacturonic acid as elicitor is used in agriculture to improve wheat vigor and strengthen resistance to lodging. Objective: However, whether a metabolic response is evolved by plants treated with this bio stimulant and the manner in which the latter might regulate plant metabolism have not been studied. Method: Therefore, the present study used 1H-NMR and LC–MS to assess changes in primary and secondary metabolites in the roots, stems, and leaves of wheat (Triticum aestivum) treated with the bio stimulant. Orthogonal partial least squares discriminant analysis effectively distinguished between treated and control samples, confirming a metabolic response to treatment in the roots, stems, and leaves of wheat. Results: Fold-change analysis indicated that treatment with the bio stimulation solution appeared to increase the levels of hydroxycinnamic acid amides, lignin, and flavonoid metabolism in different plant parts, potentially promoting root growth, implantation, and developmental cell wall maturation and lignification. Conclusion: These results demonstrate how non-targeted metabolomic approaches can be utilized to investigate and monitor the effects of new agroecological solutions based on systemic responses. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of type 2 diabetes has surged to epidemic proportions and despite treatment administration/adherence, some individuals experience poorly controlled diabetes. While existing literature explores metabolic changes in type 2 diabetes, understanding metabolic derangement in poorly controlled cases remains limited. Objective: This investigation aimed to characterize the urine metabolome of poorly controlled type 2 diabetes in a South African cohort. Method: Using an untargeted proton nuclear magnetic resonance metabolomics approach, urine samples from 15 poorly controlled type 2 diabetes patients and 25 healthy controls were analyzed and statistically compared to identify differentiating metabolites. Results: The poorly controlled type 2 diabetes patients were characterized by elevated concentrations of various metabolites associated with changes to the macro-fuel pathways (including carbohydrate metabolism, ketogenesis, proteolysis, and the tricarboxylic acid cycle), autophagy and/or apoptosis, an uncontrolled diet, and kidney and liver damage. Conclusion: These results indicate that inhibited cellular glucose uptake in poorly controlled type 2 diabetes significantly affects energy-producing pathways, leading to apoptosis and/or autophagy, ultimately contributing to kidney and mild liver damage. The study also suggests poor dietary compliance as a cause of the patient's uncontrolled glycemic state. Collectively these findings offer a first-time comprehensive overview of urine metabolic changes in poorly controlled type 2 diabetes and its association with secondary diseases, offering potential insights for more targeted treatment strategies to prevent disease progression, treatment efficacy, and diet/treatment compliance. [ABSTRACT FROM AUTHOR]

Introduction: Preeclampsia (PreE) remains a major source of maternal and newborn complications. Prenatal prediction of these complications could significantly improve pregnancy management. Objectives: Using metabolomic analysis we investigated the prenatal prediction of maternal and newborn complications in early and late PreE and investigated the pathogenesis of such complications. Methods: Serum samples from 76 cases of PreE (36 early-onset and 40 late-onset), and 40 unaffected controls were collected. Direct Injection Liquid Chromatography–Mass Spectrometry combined with Nuclear Magnetic Resonance (NMR) spectroscopy was performed. Logistic regression analysis was used to generate models for prediction of adverse maternal and neonatal outcomes in patients with PreE. Metabolite set enrichment analysis (MSEA) was used to identify the most dysregulated metabolites and pathways in PreE. Results: Forty-three metabolites were significantly altered (p < 0.05) in PreE cases with maternal complications and 162 metabolites were altered in PreE cases with newborn adverse outcomes. The top metabolite prediction model achieved an area under the receiver operating characteristic curve (AUC) = 0.806 (0.660–0.952) for predicting adverse maternal outcomes in early-onset PreE, while the AUC for late-onset PreE was 0.843 (0.712–0.974). For the prediction of adverse newborn outcomes, regression models achieved an AUC = 0.828 (0.674–0.982) in early-onset PreE and 0.911 (0.828–0.994) in late-onset PreE. Profound alterations of lipid metabolism were associated with adverse outcomes. Conclusion: Prenatal metabolomic markers achieved robust prediction, superior to conventional markers for the prediction of adverse maternal and newborn outcomes in patients with PreE. We report for the first-time the prediction and metabolomic basis of adverse maternal and newborn outcomes in patients with PreE. [ABSTRACT FROM AUTHOR]

Introduction: The world is experiencing exponential growth in communication, especially wireless communication. Wireless connectivity has recently become a part of everyone's daily life. Recent developments in low-cost, low-power, and miniature devices contribute to a significant rise in radiofrequency-electromagnetic field (RF-EM) radiation exposure in our environment, raising concern over its effect on biological systems. The inconsistent and conflicting research results make it difficult to draw definite conclusions about how RF-EM radiation affects living things. Objectives: This study identified two micro-environments based on their level of exposure to cellular RF-EM radiation, one with significantly less exposure and another with very high exposure to RF-EM radiation. Emphasis is given to studying the metabolites in the urine samples of humans naturally exposed to these two different microenvironments to understand short-term metabolic dysregulations. Methods: Untargeted 1H NMR spectroscopy was employed for metabolomics analyses to identify dysregulated metabolites. A total of 60 subjects were recruited with 5 ml urine samples each. These subjects were divided into two groups: one highly exposed to RF-EM (n = 30) and the other consisting of low-exposure populations (n = 30). Results: The study found that the twenty-nine metabolites were dysregulated. Among them, 19 were downregulated, and 10 were upregulated. In particular, Glyoxylate and dicarboxylate and the TCA cycle metabolism pathway have been perturbed. The dysregulated metabolites were validated using the ROC curve analysis. Conclusion: Untargeted urine metabolomics was conducted to identify dysregulated metabolites linked to RF-EM radiation exposure. Preliminary findings suggest a connection between oxidative stress and gut microbiota imbalance. However, further research is needed to validate these biomarkers and understand the effects of RF-EM radiation on human health. Further research is needed with a diverse population. [ABSTRACT FROM AUTHOR]

Introduction: Changes in skin phenotypic characteristics are based on skin tissue. The study of the metabolic changes in skin tissue can help understand the causes of skin diseases and identify effective therapeutic interventions. Objectives: We aimed to establish and optimize a non-targeted skin metabolome extraction system for skin tissue metabolomics with high metabolite coverage, recovery, and reproducibility using gas chromatography/mass spectrometry. Methods: The metabolites in skin tissues were extracted using eleven different extraction systems, which were designed using reagents with different polarities based on sequential solid-liquid extraction employing a two-step strategy and analyzed using gas chromatograph/mass spectrometry. The extraction efficiency of diverse solvents was evaluated by coefficient of variation (CV), multivariate analysis, metabolites coverage, and relative peak area analysis. Results: We identified 119 metabolites and the metabolite profiles differed significantly between the eleven extraction systems. Metabolites with high abundances in the organic extraction systems, followed by aqueous extraction, were involved in the biosynthesis of unsaturated fatty acids, while metabolites with high abundances in the aqueous extraction systems, followed by organic extraction, were involved in amino sugar and nucleotide sugar metabolism, and glycerolipid metabolism. MeOH/chloroform-H2O and MeOH/H2O-chloroform were the extraction systems that yielded the highest number of metabolites, while MeOH/acetonitrile (ACN)-H2O and ACN/H2O-IPA exhibited superior metabolite recoveries. Conclusion: Our results demonstrated that our research facilitates the selection of an appropriate metabolite extraction approach based on the experimental purpose for the metabolomics study of skin tissue. [ABSTRACT FROM AUTHOR]

Introduction: Thyroid cancer incidence rate has increased substantially worldwide in recent years. Fine needle aspiration biopsy (FNAB) is currently the golden standard of thyroid cancer diagnosis, which however, is invasive and costly. In contrast, breath analysis is a non-invasive, safe and simple sampling method combined with a promising metabolomics approach, which is suitable for early cancer diagnosis in high volume population. Objectives: This study aims to achieve a more comprehensive and definitive exhaled breath metabolism profile in papillary thyroid cancer patients (PTCs). Methods: We studied both end-tidal and mixed expiratory breath, solid-phase microextraction gas chromatography coupled with high resolution mass spectrometry (SPME-GC-HRMS) was used to analyze the breath samples. Multivariate combined univariate analysis was applied to identify potential breath biomarkers. Results: The biomarkers identified in end-tidal and mixed expiratory breath mainly included alkanes, olefins, enols, enones, esters, aromatic compounds, and fluorine and chlorine containing organic compounds. The area under the curve (AUC) values of combined biomarkers were 0.974 (sensitivity: 96.1%, specificity: 90.2%) and 0.909 (sensitivity: 98.0%, specificity: 74.5%), respectively, for the end-tidal and mixed expiratory breath, indicating of reliability of the sampling and analysis method Conclusion: This work not only successfully established a standard metabolomic approach for early diagnosis of PTC, but also revealed the necessity of using both the two breath types for comprehensive analysis of the biomarkers. [ABSTRACT FROM AUTHOR]

Objectives: Although colorectal cancer (CRC) is the leading cause of cancer-related morbidity and mortality, current diagnostic tests for early-stage CRC and colorectal adenoma (CRA) are suboptimal. Therefore, there is an urgent need to explore less invasive screening procedures for CRC and CRA diagnosis. Methods: Untargeted gas chromatography–mass spectrometry (GC-MS) metabolic profiling approach was applied to identify candidate metabolites. We performed metabolomics profiling on plasma samples from 412 subjects including 200 CRC patients, 160 CRA patients and 52 normal controls (NC). Among these patients, 45 CRC patients, 152 CRA patients and 50 normal controls had their fecal samples tested simultaneously. Results: Differential metabolites were screened in the adenoma-carcinoma sequence. Three diagnostic models were further developed to identify cancer group, cancer stage, and cancer microsatellite status using those significant metabolites. The three-metabolite-only classifiers used to distinguish the cancer group always keeps the area under the receiver operating characteristic curve (AUC) greater than 0.7. The AUC performance of the classifiers applied to discriminate CRC stage is generally greater than 0.8, and the classifiers used to distinguish microsatellite status of CRC is greater than 0.9. Conclusion: This finding highlights potential early-driver metabolites in CRA and early-stage CRC. We also find potential metabolic markers for discriminating the microsatellite state of CRC. Our study and diagnostic model have potential applications for non-invasive CRC and CRA detection. [ABSTRACT FROM AUTHOR]

Metabolomic epidemiology studies are complex and require a broad array of domain expertise. Although many metabolite-phenotype associations have been identified; to date, few findings have been translated to the clinic. Bridging this gap requires understanding of both the underlying biology of these associations and their potential clinical implications, necessitating an interdisciplinary team approach. To address this need in metabolomic epidemiology, a workshop was held at Metabolomics 2023 in Niagara Falls, Ontario, Canada that highlighted the domain expertise needed to effectively conduct these studies -- biochemistry, clinical science, epidemiology, and assay development for biomarker validation -- and emphasized the role of interdisciplinary teams to move findings towards clinical translation. [ABSTRACT FROM AUTHOR]

Introduction: Aspalathus linearis (commonly known as rooibos) is endemic to the Cape Floristic Region of South Africa and is a popular herbal drink and skin phytotherapeutic ingredient, with health benefits derived primarily from its unique phenolic content. Several, seemingly habitat-specific ecotypes from the Cederberg (Western Cape) and Northern Cape have morphological, ecological, genetic and biochemical differences. Objectives and methods: Despite the commercial popularity of the cultivated variety, the uncultivated ecotypes are largely understudied. To address gaps in knowledge about the biochemical constituency, ultra-performance liquid chromatography-mass spectrometry analysis of fifteen populations was performed, enabling high-throughput metabolomic fingerprinting of 50% (v/v) methanolic extracts. Antioxidant screening of selected populations was performed via three assays and antimicrobial activity on two microbial species was assessed. The metabolomic results were corroborated with total phenolic and flavonoid screening of the extracts. Results and discussion: Site-specific chemical lineages of rooibos ecotypes were confirmed via multivariate data analyses. Important features identified via PLS-DA disclosed higher relative abundances of certain tentative metabolites (e.g., rutin, aspalathin and apiin) present in the Dobbelaarskop, Blomfontein, Welbedacht and Eselbank sites, in comparison to other locations. Several unknown novel metabolites (e.g., m/z 155.0369, 231.0513, 443.1197, 695.2883) are responsible for metabolomic separation of the populations, four of which showed higher amounts of key metabolites and were thus selected for bioactivity analysis. The Welbedacht and Eselbank site 2 populations consistently displayed higher antioxidant activities, with 2,2-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) radical scavenging activities of 679.894 ± 3.427 µmol Trolox/g dry matter and 635.066 ± 5.140 µmol Trolox/g dry matter, respectively, in correlation with a high number of phenolic and flavonoid compounds. The contribution of the individual metabolites to the pharmacological effectiveness of rooibos remains unknown and as such, further structural elucidation and phytopharmacological testing is thus urgently needed. [ABSTRACT FROM AUTHOR]

Introduction: Two main approaches (organ culture and hypothermia) for the preservation and storage of human donor corneas are globally adopted for corneal preservation before the transplant. Hypothermia is a hypothermic storage which slows down cellular metabolism while organ culture, a corneal culture performed at 28–37 °C, maintains an active corneal metabolism. Researchers, till now, have just studied the impact of organ culture on human cornea after manipulating and disrupting tissues. Objectives: The aim of the current work was to optimize an analytical procedure which can be useful for discovering biomarkers capable of predicting tissue health status. For the first time, this research proposed a preliminary metabolomics study on medium for organ culture without manipulating and disrupting the valuable human tissues which could be still used for transplantation. Methods: In particular, the present research proposed a method for investigating changes in the medium, over a storage period of 20 days, in presence and absence of a human donor cornea. An untargeted metabolomics approach using UHPLC-QTOF was developed to deeply investigate the differences on metabolites and metabolic pathways and the influence of the presence of the cornea inside the medium. Results: Differences in the expression of some compounds emerged from this preliminary metabolomics approach, in particular in medium maintained for 10 and 20 days in presence but also in the absence of cornea. A total of 173 metabolites have been annotated and 36 pathways were enriched by pathway analysis. Conclusion: The results revealed a valuable untargeted metabolomics approach which can be applied in organ culture metabolomics. [ABSTRACT FROM AUTHOR]

We conducted a comprehensive metabolomic analysis of plasma samples obtained from pregnant women who displayed varying post-vaccination antibody titers after receiving mRNA-1273-SARS-CoV-2 vaccines. The study involved 62 pregnant women, all of whom had been vaccinated after reaching 24 weeks of gestation. To quantify post-vaccination plasma antibody titers, we employed binding antibody units (BAU) in accordance with the World Health Organization International Standard. Subsequently, we classified the study participants into three distinct BAU/mL categories: those with high titers (above 2000), medium titers (ranging from 1000 to 2000), and low titers (below 1000). Plasma metabolomic profiling was conducted using 1H nuclear magnetic resonance spectroscopy, and the obtained data were correlated with the categorized antibody titers. Notably, in pregnant women exhibiting elevated anti-SARS-CoV-2 antibody titers, reduced plasma concentrations of acetate and urea were observed. A significant negative correlation between these compounds and antibody titers was also evident. An analysis of metabolomics pathways revealed significant inverse associations between antibody titers and four distinct amino acid metabolic pathways: (1) biosynthesis of phenylalanine, tyrosine, and tryptophan; (2) biosynthesis of valine, leucine, and isoleucine; (3) phenylalanine metabolism; and (4) degradation of valine, leucine, and isoleucine. Additionally, an association between the synthesis and degradation pathways of ketone bodies was evident. In conclusion, we identified different metabolic pathways that underlie the diverse humoral responses triggered by COVID-19 mRNA vaccines during pregnancy. Our data hold significant implications for refining COVID-19 vaccination approaches in expectant mothers. Key messages: Anti-SARS-CoV-2 antibody titers decline as the number of days since COVID-19 vaccination increases. Anti-SARS-CoV-2 antibody titers are inversely associated with acetate, a microbial-derived metabolite, and urea. Amino acid metabolism is significantly associated with SARS-CoV-2 antibody titers. [ABSTRACT FROM AUTHOR]

Baijiu (a Chinese liquor), one of the six world-renowned distilled liquors, is popular among consumers, and Saccharomyces cerevisiae plays the most important role. However, the diversity and metabolic differences of S. cerevisiae Baijiu yeasts remain unclear. Here, we first studied S. cerevisiae strains isolated from fermentative agents and then analyzed the environmental tolerance and metabolomic differences among different S. cerevisiae strains. The 29 S. cerevisiae strains were classified into 14 genotypes based on DNA fingerprints. Environmental tolerance analysis revealed differences among yeasts. A total of 88 classes of 854 secondary metabolites were detected via liquid chromatography coupled with tandem mass spectrometry (LC‒MS/MS), 15 of which accounted for more than 1%, and carboxylic acids and their derivatives accounted for the highest percentage (20.73%), followed by benzene and substituted derivatives (12.76%). Both OPLS-DA and differentially abundant metabolite analysis revealed that the metabolites of the 14 S. cerevisiae genotypes were significantly different, and the differentially abundant metabolites l-erythrulose, 5(s)-HpETE, kaempferide, and cellobiose were obtained. Metabolic pathway analysis revealed that the metabolism of glycine, serine, and threonine differed significantly (p < 0.05). These results revealed the phenotypic diversity of industrial Baijiu yeasts and provided additional options for the utilization of S. cerevisiae yeasts in the brewing industry. [ABSTRACT FROM AUTHOR]

Background: Dietary intake influences gut microbiome composition, which in turn may be associated with colorectal cancer (CRC). Associations of the gut microbiome with colorectal carcinogenesis may be mediated through bacterially regulated, metabolically active metabolites, including trimethylamine N‐oxide (TMAO) and its precursors, choline, L‐carnitine, and betaine. Methods: Prospective associations of circulating TMAO and its precursors with CRC risk were investigated. TMAO, choline, betaine, and L‐carnitine were measured in baseline serum samples from 761 incident CRC cases and 1:1 individually matched controls in the prospective Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort using targeted fully quantitative liquid chromatography tandem mass spectrometry panels. Prospective associations of the metabolites with CRC risk, using multivariable conditional logistic regression, were measured. Associations of a priori–selected dietary exposures with the four metabolites were also investigated. Results: TMAO and its precursors were not associated with CRC risk overall, but TMAO and choline were positively associated with higher risk for distal CRC (continuous ORQ90 vs. Q10 [95% CI] = 1.90 [CI, 1.24–2.92; p =.003] and 1.26 [1.17–1.36; p <.0001], respectively). Conversely, choline was inversely associated with rectal cancer (ORQ90 vs. Q10 [95% CI] = 0.77 [0.76–0.79; p <.001]). Red meat, which was previously associated with CRC risk in the Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial Cohort , was positively associated with TMAO (Spearman rho = 0.10; p =.0003). Conclusions: Serum TMAO and choline may be associated with higher risk of distal CRC, and red meat may be positively associated with serum TMAO. These findings provide insight into a potential microbially mediated mechanism underlying CRC etiology. In a prospective study among men and women in the United States, we measured circulating trimethylamine N‐oxide (TMAO), choline, betaine, and L‐carnitine and found that TMAO and choline were positively associated with distal colon cancers. Our findings support future studies into underlying mechanisms and potential TMAO‐targeted interventions to mitigate colorectal cancer risk. [ABSTRACT FROM AUTHOR]

Background: There is limited understanding of alteration of gut microbiota and metabolome in children with sepsis/septic shock. Methods: In this prospective observational study carried out in a pediatric intensive care unit of a tertiary care center from 2020 to 2022, patients aged <17 years with sepsis/septic shock and healthy children (HC) were enrolled. We characterized the gut bacterial compositions by metagenome sequencing and metabolomes by untargeted gas chromatography-mass spectrometry. The primary outcome was to compare the gut microbiota and metabolome of children with sepsis/septic shock with that of HC. The Firmicutes / Bacteroidetes (F/B) ratio was compared between children with sepsis/septic shock and HC. Key secondary outcomes were to evaluate association of factors associated with a low F/B ratio in children with sepsis/septic shock. Results: A total of 40 children (63% boys) (15 children with sepsis and septic shock and 10 healthy children) with a median (IQR) age of 5.5 (1.5, 10) years were enrolled. In the fecal microbiota, the α-diversity index including Shannon and Simpson indices of the sepsis/septic shock groups was significantly lower than that of the HC. The samples lacked beneficial Bifidobacterium spp. and were dominated by Bacteroides, Enterobacteriaceae, and Enterococcaceae. There was reduction in short-chain fatty acids (SCFAs) in patients with sepsis/septic shock as compared to healthy children. A lower F/B ratio (≤1.57) of the gut microbiota discriminated well between children with sepsis/septic shock and HC. Factors associated with lower F/B ratio were male gender, clinical GI dysfunction, elevated inflammatory markers, and higher organ failure scores. Conclusion: There were significant alterations in the gut microbiota and metabolome in children with sepsis/septic shock as compared to healthy children. Larger study is needed to confirm these exploratory findings and develop potential therapeutic targets that will improve outcomes in children with sepsis/septic shock. [ABSTRACT FROM AUTHOR]

Zabrotes subfasciatus (Boheman) is one of the main pests of storage beans, affecting common bean (Phaseolus vulgaris L.) in tropical world regions. The aim of this study was to evaluate antixenosis of two P. vulgaris genotypes to Z. subfasciatus and the emission of volatile compounds from seeds of these genotypes. Antixenosis in adults and oviposition was evaluated using the obligate antibiosis test, on 'G11051' and 'ICA Pijao' genotypes of common bean to Z. subfasciatus. The volatile compounds of their seeds related to antixenosis were also evaluated. The number of adult insects away from seeds, the percentage of eggs in seeds and the container and the number of total eggs were counted. The presence of volatile compounds was determined by headspace solid-phase microextraction coupled with gas chromatography–mass spectrometry (HS-SPME-GC-MS). Genotype 'G11051' showed higher adult antixenosis (80% non-preference) and antixenosis by oviposition on their seeds than 'ICA Pijao' genotype which showed only 11% repellency. Significant statistical differences were found in the volatile compounds detected. 'G11051' showed 65 compounds and 22 specific to this genotype, while in 'ICA Pijao', 53 compounds were detected, eight of which were specific to this genotype. Of these, dimethyl disulfide, limonene, (E)-2-hexenal and hexanal showed known antixenotic activity. [ABSTRACT FROM AUTHOR]

Summary: Legumes are vital food sources in global diets, especially in developing nations, offering affordability, nutrition, and sustainability. Legumes are rich bioactive compounds as well as in macro‐ and micro‐nutrients and help combat protein‐energy malnutrition. Fermentation is a food processing technique that enhances nutritional content, digestibility and overall composition, rendering fermented legumes like dawadawa, natto, tempeh, and kinema dietary sources worldwide. This simple process leads to significant perturbations in the numerous metabolites contained in legumes and subsequent fermented products. Such metabolites including bioactive constituents, vitamins, minerals, volatile compounds, lipids, amino acids, among others contribute to the flavour, aroma, nutritional value and health beneficial properties of fermented legume products. Modifications in these complex constituents might be somewhat challenging to investigate and understand thus necessitating a robust technique such as metabolomics. Metabolomics as an analytical approach can elucidate how fermentation alters the composition of fermented legumes revealing compositional changes, nutritional enhancements, and impacts of fermentation conditions and microbial metabolism. This review emphasises fermented legumes' dietary importance, the transformative role of fermentation, and the effectiveness of metabolomics in unravelling complex biochemical changes during legume fermentation, providing insights into nutritional, sensory and safety aspects of fermented legumes. [ABSTRACT FROM AUTHOR]

Summary: Edible Mushrooms boast a diverse array of biomolecules with exceptional nutritional and bioactive benefits for humans. This study conducted metabolomic and nutritional analyses, aiming to identify potential bioactive metabolites in Tricholoma mesoamericanum from Pinus forests in Veracruz, Mexico. These mushrooms exhibited high carbohydrate and protein contents, coupled with a significant anti‐oxidant capacity. Metabolomic analysis identified 181 different compounds, with terpenoids, fatty acids, glycerophospholipids, and sphingolipids as the most enriched compound classes detected in T. mesoamericanum. Some compounds presented a positive correlation, while others demonstrated negative correlations with anti‐oxidant activity, ash, carbohydrate, fat, and protein contents. Notably, 39 of these compounds have previously demonstrated medicinal properties in other mushroom species, suggesting potential health benefits for humans. This study presents the first combined nutritional and metabolomic analysis of T. mesoamericanum, highlighting its value and underscoring the importance of sustainable management and further research to explore its bioactive potential, as unveiled in this investigation. [ABSTRACT FROM AUTHOR]

Summary: The field of metabolomics has undergone substantial growth, particularly in its application to cereals and their derived products. This comprehensive analytical technique offers insights into the complex and dynamic metabolic profiles of cereals and their derivatives, thereby contributing to a deeper understanding of the composition, quality, and nutritional aspects of these. Various techniques such as mass spectrometry (MS), chromatography coupled with MS, and nuclear magnetic resonance (NMR) were employed to explore the diverse range of metabolites present in cereals. Studies have focused on different aspects that alter the metabolic profile of cereals and their derived products. The present article elucidates the impact of factors such as genotype, growing conditions, and processing methods on the metabolite composition of cereals. Additionally, it has facilitated the identification of bioactive compounds with potential health benefits, contributing to the development of functional foods. Metabolomics approaches enabled the detection of different phenolics, and other essential metabolites in cereals and their derived products, and their modulatory effects on human health. The advances in metabolomics are considered as a powerful tool for developing innovative and healthier cereal‐based products. [ABSTRACT FROM AUTHOR]

Summary: The antagonistic roles of ethylene and auxin are well established, although the exact role of auxin in ripening regulation remains unclear. A metabolomic approach can be a strategy to understand the role of this phytohormone in improving tomato quality. This study used metabolomic approaches to investigate how the interaction between ethylene and auxin affects tomato fruit nutritional and sensorial quality, with a particular emphasis on aroma metabolites. Tomato (Solanum lycopersicum cv. Micro‐Tom) fruits were randomly grouped according to treatment with ethylene (ETHY), auxin (IAA), or both (ETHY + IAA) phytohormones. Fruits without treatment were grouped in CTRL. Ethylene and auxin treatments affected carbohydrates (fructose, sucrose, and glucose), organic acids (citric and malic acids), and amino acids (valine, asparagine, and GABA), with the main volatile organic compounds precursors positively impacting ETHY + IAA aroma compounds. In conclusion, the comparison of metabolome profiles suggests that auxin regulation may overlap the ethylene regulatory system. Furthermore, tomato fruits treated with both phytohormones maintained metabolic profiles similar to those of untreated fruits in delayed ripening conditions, besides the improved tomato aroma. [ABSTRACT FROM AUTHOR]

Summary: In today's consumer landscape, the health benefits of preserved foods, particularly pickled and salted mustard greens, are gaining recognition on a global scale. To compare health‐promoting compounds between fresh and preserved mustard greens, a comprehensive assessment using proximate composition analysis and untargeted metabolomics was conducted. The sub‐metabolome data revealed distinct profiles for each type of mustard greens, clearly seen in their separation through principal component analysis. The metabolite profiling identified 37 metabolites with significant differences (P‐value < 0.05, −log10 P‐value > 4). Fresh mustard greens were found to be rich in 16 identified metabolites, including sulfonic acids, purines, oxepanes, monosaccharides, fatty acids, amino acids and tripeptides, offering antioxidants, gut enhancers and immune boosters. In contrast, pickled mustard greens exhibited an abundance of 20 identified metabolites in the classes of flavonoids, amino acids and dipeptides, providing antioxidant properties. Salted mustard greens, on the other hand, primarily showcased a high level of uridine diphosphate glucose (a pyrimidine class metabolite), supporting glycoconjugate synthesis among all samples. This study highlights the prominent presence of various classes of metabolites associated with health‐benefit compounds in fresh and preserved mustard greens. These insights contribute to the evaluation of health benefits in the food industry when choosing between pickled and salted preservation methods. [ABSTRACT FROM AUTHOR]

Summary: Fruit is a crucial component of our diet, and breeding to produce nutrient‐rich cultivars necessitates a thorough examination of their metabolite composition. Fruit contains hundreds of different chemicals, including both primary and secondary (or specialised) metabolites. The structural diversity of health promoting and sensory attributes imparting metabolites and their complex interactions during fruit growth and developments were uncovered by high‐throughput metabolomics. Both targeted and non‐targeted metabolomics approach are used for the comprehensive analysis of small molecules from various complex matrices, addressing genetic, environment effect, metabolic programming, etc. With advances of mass spectrometer (MS), targeted metabolomics with non‐targeted metabolomics, MS‐based fingerprinting, profiling or imaging strategies and pseudo‐targeted are being employed to elucidate novel bioactive compounds. The exemplary reports cover a wide range of fruit metabolic implications, addressing the impact of processing on fruit flavour quality, the identification of sensory and nutraceutical biomarkers in fruits, metabolic alterations in fruits during post‐harvesting and future prospects. The examination of metabolomics profiles of multiple fruit species is anticipated to be benefitted for the expansion of fruits in terms of nutritional and health benefits aspects in the upcoming years. [ABSTRACT FROM AUTHOR]

Summary: Fermentation of yellow maize using different inocula yields mahewu products with varying compositions. Comprehensive analysis of the metabolites influencing distinctive characteristics of mahewu from sorghum malt (YMSM); wheat (YMW), malted millet (YMMM) and malted yellow maize (YMYM) inocula was investigated using an untargeted gas chromatography high‐resolution time‐of‐flight mass spectrometry (GC‐HRTOF‐MS)‐based metabolomics. Metabolites in mahewu from different inocula included phenols, fatty acid methyl ester (FAME), benzenes, amides, amines, cyclic compounds, fatty acid ethyl esters (FAEEs), esters, ketones and vitamins which differentiated metabolites identified in raw yellow maize (RYM). Principal component analysis (PCA) showed that the mahewu and related inocula were distinguished across PC1 and PC2. The OPLS‐DA result further intensifies the significant (P ≤ 0.05) metabolite causing variations among samples. This study serves as the first report into the metabolome of yellow maize mahewu from different inocula, serving as a foundation for the quality control of mahewu products for further research. [ABSTRACT FROM AUTHOR]

Summary: Soybean (Glycine max L. Merr.) is a major crop worldwide, providing essential dietary proteins and edible oils for agriculture, food, animal feed and biofuel industries. However, its limited genetic variation makes it vulnerable to harsh environmental conditions, and its chemical diversity was strongly reduced after long domestication. Wild soybean (Glycine soja Sieb. et Zucc.), the ancestor of the G. max, possesses a high level of genetic diversity and thus present a precious reservoir for improving cultivated soybean. Characterising metabolomes of different G. soja accessions is crucial in exploring metabolite accumulation patterns for developing metabolic breeding strategies. This study successfully revealed the metabolomes of sixty‐four seed lines of G. soja collected throughout Japan by a widely targeted metabolomics approach, therefore, providing a good source of information for further studies to induce the production of bioactive compounds and the defence mechanism to stress. [ABSTRACT FROM AUTHOR]

Post‐weaning diarrhea in pigs is a considerable challenge in the pig farming industry due to its effect on animal welfare and production costs, as well as the large volume of antibiotics, which are used to treat diarrhea in pigs after weaning. Previous studies have revealed loci on SSC6 and SSC13 associated with susceptibility to specific diarrhea causing pathogens. This study aimed to identify new genetic loci for resistance to diarrhea based on phenotypic data. In depth clinical characterization of diarrhea was performed in 257 pigs belonging to two herds during the first 14 days post weaning. The daily diarrhea assessments were used for the classification of pigs into case and control groups. Pigs were assigned to case and control groups based only on the incidence of diarrhea in the second week of the study in order to differentiate between differences in etiology. Genome‐wide association studies and metabolomics association analysis were performed in order to identify new biological determinants for diarrhea susceptibility. With the present work, we revealed a new locus for diarrhea resistance on SSC16. Furthermore, studies of metabolomics in the same pigs revealed one metabolite associated with diarrhea. [ABSTRACT FROM AUTHOR]

Day respiration (Rd) is the metabolic, nonphotorespiratory process by which illuminated leaves liberate CO2 during photosynthesis. Rd is used routinely in photosynthetic models and is thus critical for calculations. However, metabolic details associated with Rd are poorly known, and this can be problematic to predict how Rd changes with environmental conditions and relates to night respiration. It is often assumed that day respiratory CO2 release just reflects 'ordinary' catabolism (glycolysis and Krebs 'cycle'). Here, we carried out a pulse‐chase experiment, whereby a 13CO2 pulse in the light was followed by a chase period in darkness and then in the light. We took advantage of nontargeted, isotope‐assisted metabolomics to determine non‐'ordinary' metabolism, detect carbon remobilisation and compare light and dark 13C utilisation. We found that several concurrent metabolic pathways ('ordinary' catabolism, oxidative pentose phosphates pathway, amino acid production, nucleotide biosynthesis and secondary metabolism) took place in the light and participated in net CO2 efflux associated with day respiration. Flux reconstruction from metabolomics leads to an underestimation of Rd, further suggesting the contribution of a variety of CO2‐evolving processes. Also, the cornerstone of the Krebs 'cycle', citrate, is synthetised de novo from photosynthates mostly in darkness, and remobilised or synthesised from stored material in the light. Collectively, our data provides direct evidence that leaf day respiration (i) involves several CO2‐producing reactions and (ii) is fed by different carbon sources, including stored carbon disconnected from current photosynthates. Summary statement: Day respiration (Rd) is the metabolic, nonphotorespiratory process by which illuminated leaves liberate CO2 during photosynthesis. It is often assumed that day respiratory CO2 release just reflects 'ordinary' catabolism (glycolysis and Krebs 'cycle'). Using isotope pulse‐chase, we show that leaf day respiration involves several CO2‐producing reactions and is fed by different carbon sources, including stored carbon disconnected from current photosynthates. [ABSTRACT FROM AUTHOR]

Objectives: To identify and internally validate metabolites predictive of spontaneous preterm birth (sPTB) using multiple machine learning methods and sequential maternal serum samples, and to predict spontaneous early term birth (sETB) using these metabolites. Design: Case–cohort design within a prospective cohort study. Setting: Cambridge, UK. Population or sample: A total of 399 Pregnancy Outcome Prediction study participants, including 98 cases of sPTB. Methods: An untargeted metabolomic analysis of maternal serum samples at 12, 20, 28 and 36 weeks of gestation was performed. We applied six supervised machine learning methods and a weighted Cox model to measurements at 28 weeks of gestation and sPTB, followed by feature selection. We used logistic regression with elastic net penalty, followed by best subset selection, to reduce the number of predictive metabolites further. We applied coefficients from the chosen models to measurements from different gestational ages to predict sPTB and sETB. Main outcome measures: sPTB and sETB. Results: We identified 47 metabolites, mostly lipids, as important predictors of sPTB by two or more methods and 22 were identified by three or more methods. The best 4‐predictor model had an optimism‐corrected area under the receiver operating characteristics curve (AUC) of 0.703 at 28 weeks of gestation. The model also predicted sPTB in 12‐week samples (0.606, 95% CI 0.544–0.667) and 20‐week samples (0.657, 95% CI 0.597–0.717) and it predicted sETB in 36‐week samples (0.727, 95% CI 0.606–0.849). A lysolipid, 1‐palmitoleoyl‐GPE (16:1)*, was the strongest predictor of sPTB at 12 weeks of gestation (0.609, 95% CI 0.548–0.670), 20 weeks (0.630, 95% CI 0.569–0.690) and 28 weeks (0.660, 95% CI 0.599–0.722), and of sETB at 36 weeks (0.739, 95% CI 0.618–0.860). Conclusions: We identified and internally validated maternal serum metabolites predictive of sPTB. A lysolipid, 1‐palmitoleoyl‐GPE (16:1)*, is a novel predictor of sPTB and sETB. Further validation in external populations is required. [ABSTRACT FROM AUTHOR]

The incidence of calcium oxalate (CaOx) urolithiasis between men and women is considerably different. However, the full-scale metabolic changes between genders with CaOx urolithiasis have not been reported. The metabolic profiles in 112 urine samples obtained from 61 males and 51 females diagnosed with CaOx stones were characterized using electrospray ionization-mass spectrometry (ESI-MS). Univariate, multivariate, and bioinformatic analyses were employed to reveal the differential metabolites and perturbed metabolic pathways between genders. In total, 30 dysregulated metabolites were identified as differential metabolites between males and females with CaOx urolithiasis. The primary metabolic pathways were caffeine metabolism, metabolic pathways, and biosynthesis of amino acids. Furthermore, 10 potential metabolites which were mostly contributed to separating the males and female were selected using feature weight calculation. These compounds included creatinine, 3-methylhistidine, n-acetylneuraminic acid, decanoyl-l-carnitine, cortisone, nicotine, 1-methyluric acid, androsterone sulfate, citramalic acid, and 1,7-dimethylxanthine. Finally, a subset of the differential metabolites was identified by receiver operating characteristic (ROC) curve analysis, including creatinine, 3-methylhistidine, n-acetylneuraminic acid, decanoyl-l-carnitine, and 1-methyluric acid (area under the curve = 0.924, 0.844, 0.846, 0.814, 0.814). These metabolites had higher risks in the CaOx stone formation of males than females. The study showed that there were a group of differential metabolites between the males and females with CaOx stones. A subset of these compounds was more closely and positively related to renal stone formation in males than females. Moreover, these metabolites may be the cause of the differences in the incidence of CaOx urolithiasis between genders. [ABSTRACT FROM AUTHOR]

Various substances within the aqueous humor (AH) can directly or indirectly impact intraocular tissues associated with intraocular pressure (IOP), a critical factor in glaucoma development. This study aims to investigate individual changes in these AH substances and the interactions among altered components through a multi‐omics approach. LC/MS analysis was conducted on AH samples from patients with exfoliation syndrome (XFS, n = 5), exfoliation glaucoma (XFG, n = 4), primary open‐angle glaucoma (POAG, n = 11), and cataracts (control group, n = 7). Subsequently, differentially expressed proteins and metabolites among groups, alterations in their network interactions, and their biological functions were examined. Both data‐independent acquisition and data‐dependent acquisition methods were employed to analyze the AH proteome and metabolome, and the results were integrated for a comprehensive analysis. In the proteomics analysis, proteins upregulated in both the XFG and POAG groups were associated with lipid metabolism, complement activation, and extracellular matrix regulation. Metabolomic analysis highlighted significant changes in amino acids related to antioxidant processes in the glaucoma groups. Notably, VTN, APOA1, C6, and L‐phenylalanine exhibited significant alterations in the glaucoma groups. Integration of individual omics analyses demonstrated that substances associated with inflammation and lipid metabolism, altered in the glaucoma groups, showed robust interactions within a complex network involving PLG, APOA1, and L‐phenylalanine or C3, APOD, and L‐valine. These findings offer valuable insights into the molecular mechanisms governing IOP regulation and may contribute to the development of new biomarkers for managing glaucoma. [ABSTRACT FROM AUTHOR]

Pulmonary hypertension (PH) is regarded as cardiovascular disease with an extremely poor prognosis, primarily due to irreversible vascular remodeling. Despite decades of research progress, the absence of definitive curative therapies remains a critical challenge, leading to high mortality rates. Recent studies have shown that serious metabolic disorders generally exist in PH animal models and patients of PH, which may be the cause or results of the disease. It is imperative for future research to identify critical biomarkers of metabolic dysfunction in PH pathophysiology and to uncover metabolic targets that could enhance diagnostic and therapeutic strategies. Metabolomics offers a powerful tool for the comprehensive qualitative and quantitative analysis of metabolites within specific organisms or cells. On the basis of the findings of the metabolomics research on PH, this review summarizes the latest research progress on metabolic pathways involved in processes such as amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in the context of PH. [ABSTRACT FROM AUTHOR]

Background: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. Methods: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. Results: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). Conclusions: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention. [ABSTRACT FROM AUTHOR]

Circadian clock function declines with ageing, which can aggravate ageing‐related diseases such as type 2 diabetes and neurodegenerative disorders. Understanding age‐related changes in the circadian system at a systemic level can contribute to the development of strategies to promote healthy ageing. The goal of this study was to investigate the impact of ageing on 24‐h rhythms in amine metabolites across four tissues in young (2 months of age) and old (22–25 months of age) mice using a targeted metabolomics approach. Liver, plasma, the suprachiasmatic nucleus (SCN; the location of the central circadian clock in the hypothalamus) and the paraventricular nucleus (PVN; a downstream target of the SCN) were collected from young and old mice every 4 h during a 24‐h period (n = 6–7 mice per group). Differential rhythmicity analysis revealed that ageing impacts 24‐h rhythms in the amine metabolome in a tissue‐specific manner. Most profound changes were observed in the liver, in which rhythmicity was lost in 60% of the metabolites in aged mice. Furthermore, we found strong correlations in metabolite levels between the liver and plasma and between the SCN and the PVN in young mice. These correlations were almost completely abolished in old mice. These results indicate that ageing is accompanied by a severe loss of the circadian coordination between tissues and by disturbed rhythmicity of metabolic processes. The tissue‐specific impact of ageing may help to differentiate mechanisms of ageing‐related disorders in the brain versus peripheral tissues and thereby contribute to the development of potential therapies for these disorders. [ABSTRACT FROM AUTHOR]

\n Localized pantothenic acid deficiencies have been observed in several neurodegenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease dementia (PDD), and Huntington’s disease (HD), indicating downstream energetic pathway perturbations. However, no studies have yet been performed to see whether such deficiencies occur across the dementia with Lewy bodies (DLB) brain, or what the pattern of such dysregulation may be.Firstly, this study aimed to quantify pantothenic acid levels across ten regions of the brain in order to determine the localization of any pantothenic acid dysregulation in DLB. Secondly, the localization of pantothenic acid alterations was compared to that previously in AD, PDD, and HD brains.Pantothenic acid levels were determined in 20 individuals with DLB and 19 controls by ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) across ten brain regions. Case–control differences were determined by nonparametric Mann–Whitney U test, with the calculation of S-values, risk ratios, E-values, and effect sizes. The results were compared with those previously obtained in DLB, AD, and HD.Pantothenic acid levels were significantly decreased in six of the ten investigated brain regions: the pons, substantia nigra, motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. This level of pantothenic acid dysregulation is most similar to that of the AD brain, in which pantothenic acid is also decreased in the motor cortex, middle temporal gyrus, primary visual cortex, and hippocampus. DLB appears to differ from other neurodegenerative diseases in being the only of the four to not show pantothenic acid dysregulation in the cerebellum.Pantothenic acid deficiency appears to be a shared mechanism of several neurodegenerative diseases, although differences in the localization of this dysregulation may contribute to the differing clinical pathways observed in these conditions.Decreases in a molecule called pantothenic acid (also known as vitamin B5) have been observed in several areas of the brain in multiple dementia disease, including Alzheimer’s disease, Parkinson’s disease dementia, and Huntington’s disease. However, it is unknown whether such changes also occur in another dementia disease, dementia with Lewy bodies, which shows many of the same symptoms and molecular changes as these conditions. As such, this study was performed in order to determine if and where changes in pantothenic acid occur throughout the dementia with Lewy bodies brain. Using a methodology called liquid chromatography–mass spectrometry, which is able to measure pantothenic acid levels in a highly precise manner in brain tissues, we found that several regions of the dementia with Lewy bodies brain show decreases in pantothenic acid, including some involved in movement such as the substantia nigra and motor cortex, as well as regions associated with cognition and memory such as the hippocampus—looking most similar to the pattern of changes already seen in Alzheimer’s disease. It is possible that these changes contribute to the progression of dementia with Lewy bodies; however, further studies need to be performed to determine at what point these changes happen during the disease and how they may contribute to the development of symptoms. [ABSTRACT FROM AUTHOR]

Hypercholesterolemia (HC) induces, propagates and exacerbates cardiovascular diseases via various mechanisms that are yet not properly understood. Extracellular vesicles (EVs) are involved in the pathomechanism of these diseases. To understand how circulating or cardiac-derived EVs could affect myocardial functions, we analyzed the metabolomic profile of circulating EVs, and we performed an in-depth analysis of cardiomyocyte (CM)-derived EVs in HC. Circulating EVs were isolated with Vezics technology from male Wistar rats fed with high-cholesterol or control chow. AC16 human CMs were treated with Remembrane HC supplement and EVs were isolated from cell culture supernatant. The biophysical properties and the protein composition of CM EVs were analyzed. THP1-ASC-GFP cells were treated with CM EVs, and monocyte activation was measured. HC diet reduced the amount of certain phosphatidylcholines in circulating EVs, independently of their plasma level. HC treatment significantly increased EV secretion of CMs and greatly modified CM EV proteome, enriching several proteins involved in tissue remodeling. Regardless of the treatment, CM EVs did not induce the activation of THP1 monocytes. In conclusion, HC strongly affects the metabolome of circulating EVs and dysregulates CM EVs, which might contribute to HC-induced cardiac derangements. [ABSTRACT FROM AUTHOR]

A research model combining a disease and syndrome can provide new ideas for the treatment of ischemic stroke. In the field of traditional Chinese medicine, blood stasis and toxin (BST) syndrome is considered an important syndrome seen in patients with ischemic stroke (IS). However, the biological basis of IS-BST syndrome is currently not well understood. Therefore, this study aimed to explore the biological mechanism of IS-BST syndrome. This study is divided into two parts: (1) establishment of an animal model of ischemic stroke disease and an animal model of BST syndrome in ischemic stroke; (2) use of omics methods to identify differentially expressed genes and metabolites in the models. We used middle cerebral artery occlusion (MCAO) surgery to establish the disease model, and utilized carrageenan combined with active dry yeast and MCAO surgery to construct the IS-BST syndrome model. Next, we used transcriptomics and metabolomics methods to explore the differential genes and metabolites in the disease model and IS-BST syndrome model. It is found that the IS-BST syndrome model exhibited more prominent characteristics of IS disease and syndrome features. Both the disease model and the IS-BST syndrome model share some common biological processes, such as thrombus formation, inflammatory response, purine metabolism, sphingolipid metabolism, and so on. Results of the "gene–metabolite" network revealed that the IS-BST syndrome model exhibited more pronounced features of complement-coagulation cascade reactions and amino acid metabolism disorders. Additionally, the "F2 (thrombin)–NMDAR/glutamate" pathway was coupled with the formation process of the blood stasis and toxin syndrome. This study reveals the intricate mechanism of IS-BST syndrome, offering a successful model for investigating the combination of disease and syndrome. [ABSTRACT FROM AUTHOR]

Corydalis yanhusuo W.T. Wang is a traditional herb. Benzylisoquinoline alkaloids (BIAs) are the main pharmacological active ingredients that play an important role in sedation, relieving pain, promoting blood circulation, and inhibiting cancer cells. However, there are few studies on the biosynthetic pathway of benzylisoquinoline alkaloids in Corydalis yanhusuo, especially on some specific components, such as tetrahydropalmatine. We carried out widely targeted metabolome and transcriptomic analyses to construct the biosynthetic pathway of benzylisoquinoline alkaloids and identified candidate genes. In this study, 702 metabolites were detected, including 216 alkaloids. Protoberberine-type and aporphine-type alkaloids are the main chemical components in C. yanhusuo bulbs. Key genes for benzylisoquinoline alkaloids biosynthesis, including 6-OMT, CNMT, NMCH, BBE, SOMT1, CFS, SPS, STOX, MSH, TNMT and P6H, were successfully identified. There was no significant difference in the content of benzylisoquinoline alkaloids and the expression level of genes between the two suborgans (mother-bulb and son-bulb). The expression levels of BIA genes in the expansion stage (MB-A and SB-A) were significantly higher than those in the maturity stage (MB-C and SB-C), and the content of benzylisoquinoline alkaloids was consistent with the pattern of gene regulation. Five complete single genes were likely to encode the functional enzyme of CoOMT, which participated in tetrahydropalmatine biosynthesis in C. yanhusuo bulbs. These studies provide a strong theoretical basis for the subsequent development of metabolic engineering of benzylisoquinoline alkaloids (especially tetrahydropalmatine) of C. yanhusuo. [ABSTRACT FROM AUTHOR]

Lithified layers of complex microbial mats known as microbialites are ubiquitous in the fossil record, and modern forms are increasingly identified globally. A key challenge to developing an understanding of microbialite formation and environmental role is how to investigate complex and diverse communities in situ. We selected living, layered microbialites (stromatolites) in a peritidal environment near Schoenmakerskop, Eastern Cape, South Africa to conduct a spatial survey mapping the composition and small molecule production of the microbial communities from environmental samples. Substrate core samples were collected from nine sampling stations ranging from the upper point of the freshwater inflow to the lower marine interface where tidal overtopping takes place. Substrate cores provided material for parallel analyses of microbial community diversity by 16S rRNA gene amplicon sequencing and metabolomics using LC–MS2. Species and metabolite diversities were correlated, and prominent specialized metabolites were targeted for preliminary characterization. A new series of cyclic hexadepsipeptides, named ibhayipeptolides, was most abundant in substrate cores of submerged microbialites. These results demonstrate the detection and identification of metabolites from mass-limited environmental samples and contribute knowledge about microbialite chemistry and biology, which facilitates future targeted studies of specialized metabolite function and biosynthesis. [ABSTRACT FROM AUTHOR]

The popular leafy vegetable lettuce (Lactuca sativa L.) is susceptible to cold stress during the growing season, which slows growth rate, causes leaf yellowing and necrosis, and reduced yield and quality. In this study, transcriptomic and metabolomic analyses of two cold-resistant lettuce cultivars (GWAS-W42 and F11) and two cold-sensitive lettuce cultivars (S13K079 and S15K058) were performed to identify the mechanisms involved in the cold response of lettuce. Overall, transcriptome analysis identified 605 differentially expressed genes (DEGs), including significant enrichment of genes involved in the flavonoid and flavonol (CHS, CHI, F3H, FLS, CYP75B1, HCT, etc.) biosynthetic pathways related to oxidation–reduction and catalytic activity. Untargeted metabolomic analysis identified fifteen flavonoid metabolites and 28 other metabolites potentially involved in the response to cold stress; genistein, quercitrin, quercetin derivatives, kaempferol derivatives, luteolin derivatives, apigenin and their derivatives accumulate at higher levels in cold-resistant cultivars. Moreover, MYBs, bHLHs, WRKYs and Dofs also play positive role in the low temperature response, which affected the expression of structural genes contributing to the variation of metabolites between the resistant and sensitive. These results provide valuable evidence that the metabolites and genes involved in the flavonoid biosynthetic pathway play important roles in the response of lettuce to cold stress. [ABSTRACT FROM AUTHOR]

Currently, there has been a growing interest in fermented foods and plant-based beverages (PBBs) by the consumers because of the benefits they provide to human health or due to restrictions in the diet associated to some pathologies or personal choices. Nuclear magnetic resonance (NMR) is a versatile technique that presents many advantages for the identification and quantification of metabolites in food with a variety of one- and two-dimensional experiments. This review delves into the current applications of NMR in the fields of fermented foods and PBBs. The interest from researchers in the analysis of fermented foods by NMR in the recent literature mainly focused on three main sub-areas: characterization of exopolysaccharides (EPS) and their functional, and rheological properties; metabolomics to find discriminant markers during and after the process of fermentation for the optimization of the productive process or development of products; and characterization of traditional and novel foods. However, the area of plant-based beverages studies by NMR presented a remarkable literature gap. The opportunities for future investigations concerning food authentication, traceability, and functional food development, among others, are presented. [ABSTRACT FROM AUTHOR]

High-altitude cerebral edema (HACE) is a severe neurological condition that can occur at high altitudes. It is characterized by the accumulation of fluid in the brain, leading to a range of symptoms, including severe headache, confusion, loss of coordination, and even coma and death. Exosomes play a crucial role in intercellular communication, and their contents have been found to change in various diseases. This study analyzed the metabolomic characteristics of blood exosomes from HACE patients compared to those from healthy controls (HCs) with the aim of identifying specific metabolites or metabolic pathways associated with the development of HACE conditions. A total of 21 HACE patients and 21 healthy controls were recruited for this study. Comprehensive metabolomic profiling of the serum exosome samples was conducted using ultraperformance liquid chromatography–tandem mass spectrometry (UPLC‒MS/MS). Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed to identify the metabolic pathways affected in HACE patients. Twenty-six metabolites, including (+)-camphoric acid, choline, adenosine, adenosine 5′-monophosphate, deoxyguanosine 5′-monophosphate, guanosine, and hypoxanthine-9-β-D-arabinofuranoside, among others, exhibited significant changes in expression in HACE patients compared to HCs. Additionally, these differentially abundant metabolites were confirmed to be potential biomarkers for HACE. KEGG pathway enrichment analysis revealed several pathways that significantly affect energy metabolism regulation (such as purine metabolism, thermogenesis, and nucleotide metabolism), estrogen-related pathways (the estrogen signaling pathway, GnRH signaling pathway, and GnRH pathway), cyclic nucleotide signaling pathways (the cGMP-PKG signaling pathway and cAMP signaling pathway), and hormone synthesis and secretion pathways (renin secretion, parathyroid hormone synthesis, secretion and action, and aldosterone synthesis and secretion). In patients with HACE, adenosine, guanosine, and hypoxanthine-9-β-D-arabinofuranoside were negatively correlated with height. Deoxyguanosine 5′-monophosphate is negatively correlated with weight and BMI. Additionally, LPE (18:2/0:0) and pregnanetriol were positively correlated with age. This study identified potential biomarkers for HACE and provided valuable insights into the underlying metabolic mechanisms of this disease. These findings may lead to potential targets for early diagnosis and therapeutic intervention in HACE patients. [ABSTRACT FROM AUTHOR]

The past decades have marked the rise of metabolomics and lipidomics as the -omics sciences which reflect the most phenotypes in living systems. Mass spectrometry–based approaches are acknowledged for both quantification and identification of molecular signatures, the latter relying primarily on fragmentation spectra interpretation. However, the high structural diversity of biological small molecules poses a considerable challenge in compound annotation. Feature-based molecular networking (FBMN) combined with database searches currently sets the gold standard for annotation of large datasets. Nevertheless, FBMN is usually based on collision-induced dissociation (CID) data, which may lead to unsatisfying information. The use of alternative fragmentation methods, such as electron-activated dissociation (EAD), is undergoing a re-evaluation for the annotation of small molecules, as it gives access to additional fragmentation routes. In this study, we apply the performances of data-dependent acquisition mass spectrometry (DDA-MS) under CID and EAD fragmentation along with FBMN construction, to perform extensive compound annotation in the crude extracts of the freshwater sentinel organism Gammarus fossarum. We discuss the analytical aspects of the use of the two fragmentation modes, perform a general comparison of the information delivered, and compare the CID and EAD fragmentation pathways for specific classes of compounds, including previously unstudied species. In addition, we discuss the potential use of FBMN constructed with EAD fragmentation spectra to improve lipid annotation, compared to the classic CID-based networks. Our approach has enabled higher confidence annotations and finer structure characterization of 823 features, including both metabolites and lipids detected in G. fossarum extracts. [ABSTRACT FROM AUTHOR]