PubMed

Metabolites. 2025 Feb 11;15(2):119. doi: 10.3390/metabo15020119.ABSTRACTBackground/Objectives: Bupleuri Radix is a plant in the Apiaceae family Bupleurum Chinense DC. or Bupleurum scorzonerifolium Willd. root. The dissimilarities in the metabolite profiles of plants directly correlate with the disparities in their clinical efficacy. Methods: Therefore, the wild Bupleurum Chinense DC. (YBC) and wild Bupleurum scorzonerifolium Willd. (YNC) were used as research materials. They were analyzed using the UPLC-MS/MS and the similarities and differences were uncovered based on differential metabolites. Results: Our results proved that the differences in clinical efficacy between YBC and YNC may be attributed to their distinct metabolite profiles, as follows: (1) a total of 12 classes of 2059 metabolites were identified in the roots, with phenolic acids, terpenoids, and flavonoids being the most abundant metabolic products, with 2026 shared components between the two, 2045 in YBC, and 2040 in YNC; (2) a total of 718 differential metabolites were identified, accounting for 35.44% of the shared metabolites. Among them, YBC had 452 metabolites with higher content relative to YNC, representing 62.95%, and 266 components with lower content, representing 37.05%; (3) the KEEG enrichment analysis results show that the differential metabolic pathways are flavone and flavonol biosynthesis, linoleic acid metabolism, arachidonic acid metabolism, sesquiterpenoid and triterpenoid biosynthesis, and linolenic acid metabolism. Conclusions: These new findings will serve as a foundation for further study of the BR biosynthetic pathway and offer insights into the practical use of traditional Chinese medicine in clinical settings.PMID:39997744 | DOI:10.3390/metabo15020119

Metabolites. 2025 Feb 11;15(2):116. doi: 10.3390/metabo15020116.ABSTRACTBACKGROUND: The postmortem diagnosis of fatal hypothermia presents a considerable challenge in forensic medicine. Metabolomics, a powerful tool reflecting comprehensive changes in endogenous metabolites, offers significant potential for exploring disease mechanisms and identifying diagnostic markers.METHODS: In this study, we employed ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) to perform a non-targeted metabolomic analysis of liver, stomach, spleen, and musculus gastrocnemius tissues from mice subjected to fatal hypothermia.RESULT: A substantial number of differential metabolites were identified in each tissue: 1601 in the liver, 420 in the stomach, 732 in the spleen, and 668 in the gastrocnemius muscle. The most significantly altered metabolites were as follows: magnoflorine (liver, upregulated, ranked first in fold-change), gibberellic acid (stomach, downregulated, ranked first in fold-change), nitrofurantoin (spleen, upregulated, ranked first in fold-change), and isoreserpin (gastrocnemius muscle, downregulated, ranked first in fold-change). Glycerophospholipid metabolism exhibited notable enrichment in all tissues (spleen: second, liver: tenth, stomach: eleventh, gastrocnemius muscle: twenty-first), as did tryptophan metabolism (spleen: thirteenth, liver: eighth, stomach: third, gastrocnemius muscle: seventeenth).CONCLUSIONS: Our findings provide insights into the metabolic perturbations associated with fatal hypothermia in different tissues and lay a foundation for the identification of potential tissue biomarkers for forensic diagnosis.PMID:39997741 | DOI:10.3390/metabo15020116

Metabolites. 2025 Feb 10;15(2):111. doi: 10.3390/metabo15020111.ABSTRACTBACKGROUND: The role of the indoor microbiome in sick building syndrome (SBS) is well-recognized, yet prior studies have been limited to single-center analyses, limiting a broader understanding and applicability of their findings.METHODS: We conducted a multicenter indoor microbiome and metabolome investigation for SBS, involving 1139 middle school students across three regions in Malaysia (Johor Bahru, Terengganu, and Penang). Using high-throughput amplicon sequencing and untargeted LC-MS, indoor microbiome and metabolites were characterized from classroom dust samples.RESULTS: The study found that the prevalence of SBS symptoms was high across all three centers (51.0% to 54.6%). Environmental characteristics, including indoor NO2 and CO2 concentrations and total weight of indoor dust, were positively associated with SBS (p < 0.01, linear regression). Curtobacterium in Terengganu was negatively associated with SBS, and Clostridium perfringens in Johor Bahru was positively associated with SBS (p < 0.01, FDR < 0.05). Whereas all identified fungal taxa, including an uncharacterized uc_f_Auriculariaceae_sp., Duportella kuehneroides, and Wallemia mellicola, were positively associated with SBS (p < 0.01, FDR < 0.05) in Johor Bahru and Terengganu. Mediation analysis revealed that the adverse health effects of NO2 on SBS were partially mediated by the increased abundance of uc_f_Auriculariaceae_sp. (p < 0.05, total effect mediated 51.40%). Additionally, potential protective metabolites (S-adenosylmethionine, N-acetylserotonin, sphinganine, 4-hydroxy-2-quinolone, and (2E,4Z,8E)-Colneleic acid) were mainly derived from environmental microorganisms, conferring protective effects against nasal symptoms and tiredness. In contrast, synthetic chemicals were associated with higher SBS symptoms, inducing eye and nasal symptoms.CONCLUSIONS: This study emphasizes both the significance of fostering a balanced indoor microbiome/metabolite and the necessity to reduce exposure to deleterious substances, providing new insights for future targeted intervention strategies.PMID:39997738 | DOI:10.3390/metabo15020111

Metabolites. 2025 Feb 10;15(2):113. doi: 10.3390/metabo15020113.ABSTRACTBackground: As a major food crop, maize is highly susceptible to pathogenic bacteria, which greatly reduces its yield and quality. Metabolomics reveals physiological and biochemical changes in organisms and aids in analyzing metabolic changes caused by various factors. Methods: This study utilized metabolomics to examine maize's metabolic changes after NCLB infestation, aiming to uncover related pathways and potential biomarkers. The metabolite measurements were performed during the maize silking stage. Results: PCA showed an obvious dispersion between the treated and untreated groups. OPLS-DA identified 1274 differential metabolites, with 242 being downregulated (mainly phenolics and esters) and 1032 upregulated (primarily organic acids, amino acids, sugars, and derivatives). KEGG annotation revealed 50 affected metabolic pathways, and the biosynthesis of secondary metab-olites and amino acids was significantly enriched. Conclusions: We hypothesized that metabolic pathways related to sugar metabolism, proline metabolism, and jasmonic acid synthesis are associated with NCLB susceptibility. These findings provide critical insights into the metabolic responses of maize to biotic stress, offering a theoretical basis for future research on plant resistance mechanisms.PMID:39997737 | DOI:10.3390/metabo15020113

Metabolites. 2025 Feb 10;15(2):112. doi: 10.3390/metabo15020112.ABSTRACTOsteoarthritis (OA) and rheumatoid arthritis (RA) are joint diseases that share similar clinical features but have different etiologies, making a differential diagnosis particularly challenging. Background/Objectives: Utilizing advanced machine learning (ML) techniques on metabolomic data, this study aimed to identify key metabolites in synovial fluid (SF) that could aid in distinguishing between OA and RA. Methods: Metabolite data from the MetaboLights database (MTBLS564), analyzed using nuclear magnetic resonance (NMR), were processed using normalization, a principal component analysis (PCA), and a partial least squares discriminant analysis (PLS-DA) to reveal prominent clustering. Results: Decision forests and random forest classifiers, optimized using genetic algorithms (GAs), highlighted a selection of a few metabolites-primarily glutamine, pyruvate, and proline-with significant discriminative power. A Shapley additive explanations (SHAP) analysis confirmed these metabolites to be pivotal predictors, offering a streamlined approach for clinical diagnostics. Conclusions: Our findings suggest that a minimal set of key metabolites can effectively be relied upon to distinguish between OA and RA, supported by an optimized ML model achieving high accuracy. This workflow could streamline diagnostic efficiency and enhance clinical decision-making in rheumatology.PMID:39997736 | DOI:10.3390/metabo15020112

Metabolites. 2025 Feb 8;15(2):110. doi: 10.3390/metabo15020110.ABSTRACTBackground/Objectives: Lipids are an important component of human nutrition. Conventional milk is obtained from animals, and dairy milk is consumed by many people worldwide. Recently, milk consumers have been increasingly shifting towards plant-based milk options. The aim of the study was the qualitative identification of lipid metabolites in animal- and plant-based milk, the identification and comparison of the fatty acids (FAs) of milk, and the qualitative identification of the lipid groups among the milk varieties. Methods: Milk samples were obtained from local grocery stores. Lipids were extracted using a modified Folch method and analyzed using nuclear magnetic resonance (NMR) metabolomics. Gas and liquid chromatography mass spectrometry methods (GC-MS and LC-MS) were used to identify the FAs and lipid groups. Lipid weights were compared and the NMR profiles of the lipids analyzed by multivariate statistical analysis. Principal component analysis was performed for the milk lipids obtained from the animal, and plant milk varieties. Results: Clustering of NMR data showed two main clusters: cow/almond/cashew and goat/soy/coconut. GC-MS analysis of the methylated fatty acids (FAs) showed the presence of 12:0, 14:0, 16:0, 16:1, 17:0, 18:0, 18:1, 18:2, 20:1, and 20:2 in all milk types, while FAs 19:0 and 20:4 were observed only in the dairy milk. LC-MS data showed common masses that may indicate the presence of mono- and diacyl glycerols and several lysophospholipids among the different types of milk. Conclusions: This study shows the advantage of using NMR, GC-MS, and LC-MS to differentiate the lipids among different milk types and compare them on one platform.PMID:39997734 | DOI:10.3390/metabo15020110

Metabolites. 2025 Feb 7;15(2):107. doi: 10.3390/metabo15020107.ABSTRACTBackground/Objectives: The germination process initiates an active process of secondary metabolism, which produces a series of secondary metabolites, including flavonoids. Methods: A metabolomics and transcriptomics analysis was conducted on maize grains germinated at three different stages. Results: A total of 374 metabolites were detected in maize grains. From the raw maize grain to various stages of germination, 3 anthocyanins, 61 flavones, 12 flavonols, 13 flavanones, and 6 isoflavones were identified, respectively. An integrated omics analysis discovered that a total of 16 flavonoid metabolites were mapped to 4 KEGG pathways, which were associated with 40 related genes. This indicates that germination has significant benefits in improving the nutritional function of corn kernels. Conclusions: In summary, the findings of this study provide valuable insights into flavonoid metabolites and related genes, demonstrating the profound impact of germination treatment on the nutritional and functional aspects of maize grains.PMID:39997732 | DOI:10.3390/metabo15020107

Metabolites. 2025 Feb 7;15(2):106. doi: 10.3390/metabo15020106.ABSTRACTBackground: Metabolomics serves as a very useful tool for elucidating disease mechanisms and identifying biomarkers. Establishing reference intervals (RIs) of metabolites in a healthy population is crucial to the application of metabolomics in life sciences and clinics. Methods: We enrolled 615 healthy Chinese adults aged between 21 and 85 years. Their health status was ascertained through clinical examinations, biochemical parameters, and medical history. Targeted metabolomics and lipidomics analyses were applied to quantify 705 metabolites and lipids in the serum, establishing RIs and investigating the effect of sex and age on the metabolome and lipidome. Results: This study is the first large-scale effort in China to establish RIs for metabolites in the apparently healthy population. We found that most of the sex-related metabolites, including amino acids, acyl-carnitines and triacylglycerols, had higher concentrations in males, while the other sex-related lipids showed higher concentrations in females. Most of the age-related metabolites increased with age, including those associated with protein synthesis, nitric oxide synthesis, energy metabolism, and lipid metabolism. Conclusions: This study gives the reference intervals of the healthy Chinese metabolome and lipidome and their relationship with sex and age, which facilitates life sciences and precision medicine, especially for disease research and biomarker discovery.PMID:39997731 | DOI:10.3390/metabo15020106

Metabolites. 2025 Feb 6;15(2):102. doi: 10.3390/metabo15020102.ABSTRACTBackground:Citrus Exocortis Viroid (CEVd) is a non-coding RNA pathogen capable of infecting a wide range of plant species, despite its lack of protein-coding ability. Viroid infections induce significant alterations in various physiological and biochemical processes, particularly impacting plant metabolism. This study shows the metabolic changes upon viroid infection in tomato plants (Solanum lycopersicum var. 'MoneyMaker') exhibiting altered levels of salicylic acid (SA), a key signal molecule involved in the plant defence against this pathogen. Methods: Transgenic RNAi_S5H lines, which have the salicylic acid 5-hydroxylase gene silenced to promote SA accumulation, and NahG lines, which overexpress a salicylate hydroxylase to degrade SA into catechol and prevent its accumulation, were used to establish different SA levels in plants, resulting in varying degrees of resistance to viroid infection. The analysis was performed by using gas chromatography-mass spectrometry (GC-MS) to explore the role of volatile organic compounds (VOCs) in plant immunity against this pathogen. Results: Our results revealed distinct volatile profiles associated with plant immunity, where RNAi_S5H-resistant plants showed significantly enhanced production of monoterpenoids upon viroid infection. Moreover, viroid-susceptible NahG plants emitted a broad range of VOCs, whilst viroid-tolerant RNAi_S5H plants exhibited less variation in VOC emission. Conclusions: This study demonstrates that SA levels significantly influence metabolic responses and immunity in tomato plants infected by CEVd. The identification of differential emitted VOCs upon CEVd infection could allow the development of biomarkers for disease or strategies for disease control.PMID:39997727 | DOI:10.3390/metabo15020102

Metabolites. 2025 Feb 6;15(2):101. doi: 10.3390/metabo15020101.ABSTRACTBackground/Objectives: Determining appropriate cellular objectives is crucial for the system-scale modeling of biological networks for metabolic engineering, cellular reprogramming, and drug discovery applications. The mathematical representation of metabolic objectives can describe how cells manage limited resources to achieve biological goals within mechanistic and environmental constraints. While rapidly proliferating cells like tumors are often assumed to prioritize biomass production, mammalian cell types can exhibit objectives beyond growth, such as supporting tissue functions, developmental processes, and redox homeostasis. Methods: This review addresses the challenge of determining metabolic objectives and trade-offs from multiomics data. Results: Recent advances in single-cell omics, metabolic modeling, and machine/deep learning methods have enabled the inference of cellular objectives at both the transcriptomic and metabolic levels, bridging gene expression patterns with metabolic phenotypes. Conclusions: These in silico models provide insights into how cells adapt to changing environments, drug treatments, and genetic manipulations. We further explore the potential application of incorporating cellular objectives into personalized medicine, drug discovery, tissue engineering, and systems biology.PMID:39997726 | DOI:10.3390/metabo15020101

Metabolites. 2025 Feb 5;15(2):98. doi: 10.3390/metabo15020098.ABSTRACTBackground:Semiliquidambar cathayensis Chang is an extremely valuable and endangered medicinal plant. To investigate the exploitation and rational utilization of S. cathayensis, this study conducted metabolomics analysis of the leaves and bark of artificially cultivated S. cathayensis at different developmental stages. Methods: These metabolites were detected and identified by Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry (UPLC-MS/MS) technology, and then univariate statistical analyses, multivariate pattern analyses, and pathway analyses were carried out. Results: As a result, a total of 801 metabolites were detected in S. cathayensis; differential metabolites in leaves at different developmental stages were mainly enriched in pathways related to flavonoids, whereas differential metabolites in bark at different developmental stages were mainly aromatic compounds, amino acids, and flavonoids, among others. This study revealed that young leaves are ideal for use in treating rheumatism, regulating blood pressure, and lowering blood glucose, while old leaves are better suited for skincare products and extracting materials to prevent neurodegenerative diseases and support women's ovarian health. As for bark, four-year-old S. cathayensis bark is optimal for extracting myricetin. If the pharmaceutical, chemical, food, and industrial fields require extensive extraction of L-phenylalanine, trans-3-hydroxycinnamate, and 4-hydroxyphenylacetate, and if the medical field needs to extract anti-allergy, liver protection, and anti-coagulant ingredients, the two-year-old S. cathayensis bark is the best choice. Conclusions: Thus, this study established a solid theoretical framework for the rational, effective, and sustainable utilization of S. cathayensis leaves and bark.PMID:39997723 | DOI:10.3390/metabo15020098

Metabolites. 2025 Feb 5;15(2):97. doi: 10.3390/metabo15020097.ABSTRACTBackground/Objectives: Petroleum contamination in soil exerts toxic effects on earthworms (Eisenia fetida) through non-polar narcotic mechanisms. However, the specific toxicities of individual petroleum components remain insufficiently understood. Methods: This study investigates the effects of four petroleum components-saturated hydrocarbons, aromatic hydrocarbons, resins, and asphaltenes-on earthworms in artificially contaminated soil, utilizing a combination of biochemical biomarker analysis and metabolomics to uncover the underlying molecular mechanisms. Results: The results revealed that aromatic hydrocarbons are the most toxic fraction, with EC50 concentrations significantly lower than those of other petroleum fractions. All tested fractions triggered notable metabolic disturbances and immune responses in earthworms after 7 days of exposure, as evidenced by significant changes in metabolite abundance within critical pathways such as arginine synthesis, a-linolenic acid metabolism, and the pentose phosphate pathway. According to the KEGG pathway analysis, saturated hydrocarbon fractions induced marked changes in glycerophospholipid metabolism, and arginine and proline metabolism pathways, contributing to the stabilization of the protein structure and membrane integrity. Aromatic hydrocarbon fractions disrupted the arachidonic acid metabolic pathway, leading to increased myotube production and enhanced immune defense mechanisms. The TCA cycle and riboflavin metabolic pathway were significantly altered during exposure to the colloidal fraction, affecting energy production and cellular respiration. The asphaltene fraction significantly impacted glycolysis, accelerating energy cycling to meet stress-induced increases in energy demands. Conclusions: Aromatic hydrocarbons accounted for the highest level of toxicity among the four components in petroleum-contaminated soils. However, the contributions of other fractions to overall toxicity should not be ignored, as each fraction uniquely affects key metabolic pathways and biological functions. These findings emphasize the importance of monitoring metabolic perturbations caused by petroleum components in non-target organisms such as earthworms. They also reveal the specificity of the toxic metabolic effects of different petroleum components on earthworms.PMID:39997722 | DOI:10.3390/metabo15020097

Metabolites. 2025 Feb 4;15(2):96. doi: 10.3390/metabo15020096.ABSTRACTBACKGROUND: Cigarette smoking is a leading cause of preventable mortality, largely due to the absence of effective, non-invasive biomarkers for early disease detection. Profiling serum metabolomics to identify metabolic changes holds the potential to accelerate the detection process and identify individuals at risk of developing smoking-related diseases.OBJECTIVES: This study investigated the biochemical and metabolomic changes induced by nicotine exposure, with a focus on disruptions in amino acid, lipid, and carbohydrate metabolism.METHODS: Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed to observe significant disruptions in lipid and amino acid metabolism, along with alterations in key metabolic pathways. A total of 400 smokers and 100 non-smokers were included to evaluate the biomarkers related to insulin resistance, blood lipid profile, inflammation, and kidney and liver function.RESULTS: The results demonstrated significantly elevated (p < 0.05) levels of glycemic markers in smokers, including fasting blood glucose; glycated hemoglobin (HbA1c); and inflammatory markers such as interleukin-6 (IL-6) and C-reactive protein (CRP). Smokers also exhibited dyslipidemia, with increased total cholesterol (154.888 ± 35.565) and LDL levels (117.545 ± 24.138). Impaired liver and kidney function was evident, with significantly higher levels (p < 0.05) of AST, ALP, ALT, blood urea nitrogen, and creatinine in smokers. A total of 930 metabolites were identified, of which 343 exhibited significant alterations (p < 0.05) in smokers compared to non-smokers. Among these, 116 metabolites were upregulated, and 127 were downregulated. Metabolomic pathway analysis revealed eight significant pathways. The study also identified three lipid metabolites specific to smokers and seven unique to non-smokers. Through LC-MS/MS, fragments of phenylalanine, tryptophan, valine, histidine, carnitine, and sphinganine were detected. Several lipidomic changes associated with insulin resistance and cardiovascular complications were observed. Cadmium (Cd) levels were higher in smokers than non-smokers (1.264 ppb vs. 0.624 ppb) and showed a strong negative correlation (R2 = 0.8061, p-value = 0.015) with serum zinc (Zn), likely due to Cd displacing Zn in proteins and causing nephrotoxicity through accumulation.CONCLUSIONS: This study highlights the distinct metabolic disruptions caused by smoking that could serve as potential biomarkers for the early detection of metabolic diseases. It emphasizes the importance of metabolomics in identifying systemic indicators of smoking-related health issues, providing new opportunities for preventive and therapeutic interventions.PMID:39997721 | DOI:10.3390/metabo15020096

Metabolites. 2025 Feb 4;15(2):95. doi: 10.3390/metabo15020095.ABSTRACTBACKGROUND: Oxycodone has an elevated abuse liability profile compared to other prescription opioid medications. However, many human and rodent metabolomics studies have not been specifically focused on oxycodone.OBJECTIVES: Investigating metabolomics changes associated with oxycodone exposure can provide insights into biochemical mechanisms of the addiction cycle and prognosis prediction.METHODS: Plasma samples from 16 rats at pre-exposure and intoxication time points were profiled on the Metabolon platform. A total of 941 metabolites were characterized. We employed a k-Nearest Neighbor imputation to impute metabolites with low levels of missingness and binarized metabolites with moderate levels of missingness, respectively.RESULTS: Of the 136 binarized metabolites, 6 showed differential abundance (FDR < 0.05), including 5 that were present at pre-exposure but absent at intoxication (e.g., adenine), while linoleamide (18:2n6) exhibited the opposite behavior. Among the 798 metabolites with low levels of missingness, 364 showed significant changes between pre-exposure and intoxication (FDR < 0.01), including succinate, oleamide, and sarcosine. We identified four pathways, including tryptophan metabolism, that were nominally enriched among the metabolites that change with oxycodone exposure (p < 0.05). Furthermore, we identified several metabolites that showed nominal correlations with the Addiction Index (composite of oxycodone behaviors): 17 at pre-exposure and 8 at intoxication. In addition, the changes in abundance between pre-exposure and intoxication time points of 9 metabolites were nominally correlated with the Addiction Index, including sphingomyelins, methylhistidines, and glycerols.CONCLUSIONS: In summary, not only were we able to capture oxy-induced changes in metabolic pathways using easily accessible blood samples, but we also demonstrated the potential of blood metabolomics to better understand addiction liability.PMID:39997720 | DOI:10.3390/metabo15020095

Metabolites. 2025 Feb 3;15(2):93. doi: 10.3390/metabo15020093.ABSTRACTBACKGROUND: Alzheimer's disease is a central nervous system degenerative disease closely related to age with a complex pathogenesis. As a natural medicinal plant, forest-grown ginseng (GSF) contains abundant ginsenosides and offers significant neuroprotective effects.METHODS: In this study, we comprehensively investigated the effect of GSF on the cell viability of PC12 cells in an AD model alongside metabolic changes in the serum and brains of mice, combined with an efficacy evaluation of PC12 cells in vitro and UHPLC-MS-based metabolomics in vivo. The goal of this study is to clarify the potential mechanism of GSF in treating AD.RESULTS: The PC12 cell results showed that GSF can promote the proliferation of PC12 cells, reduce the content of IL-8, increase the activity of SOD, and alleviate the inflammation and oxidative stress induced by Aβ25~35. The immunohistochemical results for the mouse brain tissue also showed that GSF could reduce the inflammatory response of mouse brain tissue by reducing the overexpression of IBa1. AD was alleviated by reducing Aβ protein deposition in the mouse brain tissue. An untargeted metabolomics analysis was performed using UHPLC-Q-Exactive MS and principal component analysis (PCA) to identify the differentially expressed metabolites in the serum and brain tissue of AD mice after treatment. Twenty and seventeen different metabolites were identified in the serum and brain tissue, respectively. The pathway enrichment analysis of differential metabolites showed that GSF could treat AD by up-regulating succinic acid semialdehyde, carbamoyl phosphate, Sphingosine 1-phosphate, L-cystathionine, 2-ketobutyric acid, Vanillylmandelic acid, and D-Ribose to regulate sphingomyelin metabolism, the synthesis and metabolism of neurotransmitters and precursors, and energy metabolism.CONCLUSIONS: GSF can reduce neuroinflammation and alleviate Alzheimer's disease by regulating the metabolic disorders of amino acids, sphingolipids, unsaturated fatty acids, and arachidonic acid in mice serum and brain tissue metabolites. These results suggest a link between metabolite imbalance and AD, and reveal the basis for the mechanism of ginsenosides in AD treatment.PMID:39997718 | DOI:10.3390/metabo15020093

Metabolites. 2025 Feb 2;15(2):88. doi: 10.3390/metabo15020088.ABSTRACTBACKGROUND: Epidemiological studies using metabolomics often encounter challenges due to metabolite profiles being influenced by multiple modifiable behavioral factors, including regular exercise, smoking, drinking, and weight control. This study aimed to identify modifiable behavioral factors reflected in metabolites by clustering subjects based on their metabolite profiles. Networks of metabolites were constructed to visualize their relationships and the differences between clustering groups.METHODS: Sixty-four healthy men were included in this study. Information on regular exercise, smoking, and drinking was collected by questionnaires, and body mass index (BMI), an indicator of weight control, was calculated based on measured height and weight. Through targeted metabolomics, the concentrations of 149 metabolites were quantified. Subjects were clustered using the k-means method based on metabolite composition. Correlation-based networks were constructed for each cluster using Cytoscape software, followed by network analysis.RESULTS: The subjects were divided into two clusters, with BMI identified as a distinguishing feature. Four lyso-phosphatidylcholines (PCs), six diacyl-PCs, and one acyl-alkyl-PC were positively associated with BMI. In the constructed network, acyl-alkyl-PCs exhibited the highest degrees, suggesting their central role in BMI-associated metabolic pathways.CONCLUSIONS: These findings suggest that metabolites can reflect behavioral factors, with BMI exerting a significant influence on metabolite profiles, particularly through its associations with phosphatidylcholines.PMID:39997714 | DOI:10.3390/metabo15020088

Metabolites. 2025 Feb 1;15(2):86. doi: 10.3390/metabo15020086.ABSTRACTINTRODUCTION AND OBJECTIVE: This literature review aims to provide an overview of the progress in metabolomic assessment in animal and cell models and in humans with diabetic neuropathy (DN).METHODS: Metabolomics has emerged as an important approach for investigating, identifying, and describing biomarkers related to DN. None has yet been validated for use in clinical practice.RESULTS: DN induced significant alterations in energy metabolism and carbohydrates, lipids, amino acids, peptides, and proteins. Several treatments for DN, evaluated using metabolomics, were proved to have promising results.CONCLUSIONS: The ideal metabolite or set of metabolites that could be used as biomarkers should identify patients with diabetes prone to develop DN or those prone to progress to severe forms of sensory loss, associated with risk of ulcerations and amputation. Another potential use of a metabolite might be as an indicator of treatment response in clinical trials using agents with potential disease-modifying properties.PMID:39997711 | DOI:10.3390/metabo15020086

Metabolites. 2025 Feb 1;15(2):84. doi: 10.3390/metabo15020084.ABSTRACTBackground/Objectives: Although malaria is one of the oldest known human diseases, it continues to be a major global health challenge. According to UNICEF, the global malaria mortality rate exceeded 600,000 annually in 2022, which includes more than 1000 children dying each day. This study aimed to investigate the comprehensive chemical profile and biological activities, particularly the antimalarial activity, of Lycium shawii (Awsaj), a shrub traditionally used in the Arabian Peninsula, Middle East, India, and Africa to treat a myriad of ailments. Methods: Crude extracts of L. shawii were prepared using water, ethanol, methanol, and acetone. Nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) were utilized to perform untargeted metabolomics to maximize metabolite detection and tentatively identify bioactive phytochemicals. The total phenolic content (TPC) was measured for each extract, and bioassays were conducted to evaluate their antimalarial, antibacterial, and anti-inflammatory activities, particularly those of the water extract, which is the traditional method of consumption in Arabian folk medicine. Results: A total of 148 metabolites were detected, 45 of which were classified as phytochemicals. The bioassays revealed that the water extract that is traditionally used showed promising antimalarial potential by significantly inhibiting β-hematin formation in vitro at 1 mg/mL (with an absorbance of 0.140 ± 0.027). This is likely due to the rich presence of quinoline in the aqueous extract among several other bioactive phytochemicals, such as phenylpropanoids, alkaloids, flavonoids, and benzenoids. However, their anti-inflammatory and antibacterial activities were found to be weak, with only a minor inhibition of nitric oxide (NO) production in LPS-induced RAW 264.7 cells at a concentration of 500 µg/mL and weak antibacterial effects against pathogens like P. aeruginosa, MRSA, A. baumannii, and K. pneumoniae with an MIC of 500 μg/mL. The results also revealed that the methanolic extract had the highest TPC at 26.265 ± 0.005 mg GAE/g. Conclusions: The findings support the traditional medicinal use of L. shawii and highlight its potential as a source of novel therapeutic compounds, particularly for treating malaria. This study encourages further research to isolate and develop effective plant-based anti-malarial agents.PMID:39997709 | DOI:10.3390/metabo15020084

Metabolites. 2025 Jan 30;15(2):81. doi: 10.3390/metabo15020081.ABSTRACTBackground/Objectives: The 'Xinli No. 7' pear is a new pear variety with the advantages of early ripening, high quality, high storage resistance, and a long shelf life. Peel color is an important appearance-related trait and an important indicator of fruit quality and commercial value. Methods: In this study, we investigated the polyphenol compound biosynthesis metabolic pathway in the fruit pericarp of 'Xinli No. 7' pear using metabolomic and transcriptomic approaches, and qRT-PCR was used for the relative expression analysis of 21 DEGs associated with flavonoid biosynthesis. Results: A total of 128 phenolic compounds were identified, along with 1850 differently expressed genes (DEGs) in peels of different colors. Caftaric acid, apigenin, astragalin, phlorizin, prunin, taxifolin, rutin, naringenin, and their derivatives were abundant in the peel of 'Xinli No. 7' pear. An integrated analysis of transcriptomic and metabolomic data revealed that one PGT1, one LAR, two ANS, three 4CL, one CHS, one DFR, and one CHI gene involved in flavonoid biosynthesis exhibited markedly different expression levels in the fruit pericarp of 'Xinli No. 7' pear. Metabolic profiling of pear skin led to the identification of polyphenol substances involved in the flavonoid biosynthetic process and revealed 16 flavonoid compounds with high accumulation in pear fruit with red skin (PR). Notably, MYBs (25), bHLHs (18), WRKYs (15), NACs (15), ERFs (15), and MADs (2) may also contribute to the accumulation of flavonoid metabolites and the biosynthesis of anthocyanins in the peel of 'Xinli No. 7'. Conclusions: Therefore, our results demonstrate the key role of phenolic compounds and candidate transcription factors involved in the peel color formation of 'Xinli No. 7' pear fruit.PMID:39997706 | DOI:10.3390/metabo15020081

Metabolites. 2025 Jan 26;15(2):76. doi: 10.3390/metabo15020076.ABSTRACTBackground: Elevated choline kinase alpha (ChoK) levels are observed in most solid tumors, including glioblastomas (GBM), and ChoK inhibitors have demonstrated limited efficacy in GBM models. Given that hypoxia is associated with resistance to GBM therapy, we hypothesized that tumor hypoxia could be responsible for the limited response. Therefore, we evaluated the effects of hypoxia on the function of JAS239, a potent ChoK inhibitor in four GBM cell lines. Methods: Rodent (F98 and 9L) and human (U-87 MG and U-251 MG) GBM cell lines were subjected to 72 h of hypoxic conditioning and treated with JAS239 for 24 h. NMR metabolomic measurements and analyses were performed to evaluate the signaling pathways involved. In addition, cell proliferation, cell cycle progression, and cell invasion parameters were measured in 2D cell monolayers as well as in 3D cell spheroids, with or without JAS239 treatment, in normoxic or hypoxic cells to assess the effect of hypoxia on JAS239 function. Results: Hypoxia and JAS239 treatment led to significant changes in the cellular metabolic pathways, specifically the phospholipid and glycolytic pathways, associated with a reduction in cell proliferation via induced cell cycle arrest. Interestingly, JAS239 also impaired GBM invasion. However, effects from JAS239 were variable depending on the cell line, reflecting the inherent heterogeneity of GBMs. Conclusions: Our findings indicate that JAS239 and hypoxia can deregulate cellular metabolism, inhibit cell proliferation, and alter cell invasion. These results may be useful for designing new therapeutic strategies based on ChoK inhibition, which can act on multiple pro-tumorigenic features.PMID:39997701 | DOI:10.3390/metabo15020076