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Metabolites
Volume 15
Issue 8
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Metabolites, Volume 15, Issue 8 (August 2025) – 70 articles

Cover Story (view full-size image): Urinary small extracellular vesicles provide a new source of biomarkers for chronic kidney disease of unknown etiology (CKDu), a disease that is prevalent among young male agricultural workers who toil in hot, humid areas around the world. A limited set of workers provided two urine samples on the same day, at the beginning and end of the workday. Isolated small extracellular vesicles from workers who had early symptoms of kidney disease, as determined by KODIGO standards, contained altered expression of two inflammation-associated surface proteins, CD25 and CD45. In addition, 21 lipids, including several bioactive lipids, e.g., DAG, LPC, LPE, PI, and PE(O), distinguished these workers from those without kidney impairment. The approach used by this pilot study should be further evaluated with a larger population. View this paper
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15 pages, 1327 KiB  
Article
Tentative Identification of Chemical Constituents in Liuwei Dihuang Pills Based on UPLC-Orbitrap-MS
by Lanxiang Yang, Min Tao, Rongping Tao, Mingzhu Cao and Rui Wang
Metabolites 2025, 15(8), 561; https://doi.org/10.3390/metabo15080561 - 21 Aug 2025
Abstract
Background: Liuwei Dihuang Pills, a classic traditional Chinese medicine formula, has been widely used in clinical practice for its multiple pharmacological effects. However, the systematic characterization and identification of its chemical constituents, especially the aqueous decoction, remain insufficient, which hinders in-depth research on [...] Read more.
Background: Liuwei Dihuang Pills, a classic traditional Chinese medicine formula, has been widely used in clinical practice for its multiple pharmacological effects. However, the systematic characterization and identification of its chemical constituents, especially the aqueous decoction, remain insufficient, which hinders in-depth research on its pharmacodynamic material basis. Thus, there is an urgent need for a comprehensive analysis of its chemical components using advanced analytical techniques. Methods: After screening chromatographic columns, the ACQUITY UPLC™ HSS T3 column (100 mm × 2.1 mm, 1.8 μm) was selected. The column temperature was set to 40 °C, and the mobile phase consisted of 0.1% formic acid in water (A) and 0.1% formic acid in acetonitrile (B). A gradient elution program was adopted, and the separation was completed within 20 min. Ultra-high performance liquid chromatography–Orbitrap mass spectrometry (UPLC-Orbitrap-MS) combined with a self-established information database was used for the analysis. Results: A total of 80 compounds were tentatively identified, including 13 monoterpenoids, 6 phenolic acids, 16 iridoids, 11 flavonoids, 25 triterpenoids, and 9 other types. Triterpenoids are mainly derived from Poria cocos and Alisma orientale; iridoids are mainly from Rehmannia glutinosa; monoterpenoids are mainly from Moutan Cortex; and flavonoids are mainly from Dioscorea opposita. Among them, monoterpenoids, iridoids, and triterpenoids are important pharmacodynamic components. The cleavage pathways of typical compounds (such as pachymic acid, catalpol, oxidized paeoniflorin, and puerarin) are clear, and their mass spectral fragment characteristics are consistent with the literature reports. Conclusions: Through UPLC-Orbitrap-MS technology and systematic optimization of conditions, this study significantly improved the coverage of chemical component identification in Liuwei Dihuang Pills, providing a comprehensive reference for the research on its pharmacodynamic substances. However, challenges remain in the identification of trace components and isomers. In the future, analytical methods will be further improved by combining technologies such as ion mobility mass spectrometry or multi-dimensional liquid chromatography. Full article
(This article belongs to the Special Issue Analysis of Specialized Metabolites in Natural Products)
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12 pages, 821 KiB  
Article
Antiparasitic Effect of Polyphenols and Terpenes from Natural Products Against Trypanosoma cruzi and Leishmania mexicana
by Diana V. Navarrete-Carriola, Gildardo Rivera, Eyra Ortiz-Pérez, Alma D. Paz-González, Ana Verónica Martínez-Vázquez, Laura Victoria Aquino-González, Liliana Argueta-Figueroa, Michael P. Doyle and Adriana Moreno-Rodríguez
Metabolites 2025, 15(8), 560; https://doi.org/10.3390/metabo15080560 - 21 Aug 2025
Viewed by 29
Abstract
Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic [...] Read more.
Background: Worldwide, the number of cases of parasitic diseases has been increasing; however, available treatments have variable adverse effects and low efficacy, mainly in Neglected Tropical Diseases such as Chagas disease and Leishmaniasis. Therefore, the development of new and more effective antiparasitic drugs is important. Natural products are the source of secondary metabolites with different biological activities, such as antibacterial, anticancer, anti-inflammatory, and antiparasitic. Objectives: In this work, secondary metabolites (phenols and terpenes) from natural products were selected to be evaluated against the epimastigotes of NINOA and A1 strains of Trypanosoma cruzi and the promastigotes of M379 strain and FCQEPS native isolate of Leishmania mexicana. Additionally, their cytotoxicity and selectivity index were determined. Methods: Eighteen secondary metabolites were evaluated in vitro against T. cruzi epimastigotes and L. mexicana promastigotes; additionally, their cytotoxicity on the J774.2 macrophage cell line was determined. Results: The compounds l-(-)-menthol (14, IC50 = 24.52 µM) and β-citronellol (11, IC50 = 21.54 µM) had higher trypanocidal activity than the reference drug (benznidazole) against NINOA and A1 strains of T. cruzi, respectively. On the other hand, para-anisyl alcohol (4, IC50 = 34.89 µM) had higher leishmanicidal activity than the reference drug (glucantime®) against M379 and the FCQEPS native isolate of L. mexicana. Finally, in silico, the determination of their pharmacokinetic and toxicological properties showed that they are promising candidates for oral and topical uses. Conclusions: This study opens the possibility of using secondary metabolites as scaffolds for access to the development of new molecules for the treatment of parasite diseases. Full article
(This article belongs to the Special Issue Advances in Secondary Metabolites: Phytochemical Analysis and Bioactivity Assays)
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18 pages, 1585 KiB  
Article
Modeling the Sensory Characteristics of Japanese Sake Using the Sake Metabolome Analysis Method
by Takuji Kobayashi, Yuko Komatsu-Hata, Ryota Saito, Hisashi Yazawa, Masayuki Takahashi, Ken Oda and Kazuhiro Iwashita
Metabolites 2025, 15(8), 559; https://doi.org/10.3390/metabo15080559 - 20 Aug 2025
Viewed by 145
Abstract
Background/Objectives: The components of food and beverages are important elements that determine their palatability. Although the components of sake, a traditional Japanese alcoholic beverage, have been studied for many years, their correlation with sensory characteristics is unclear. Methods: We investigate the correlation with [...] Read more.
Background/Objectives: The components of food and beverages are important elements that determine their palatability. Although the components of sake, a traditional Japanese alcoholic beverage, have been studied for many years, their correlation with sensory characteristics is unclear. Methods: We investigate the correlation with the sake metabolome analysis method developed by our group using ultra-high-performance liquid chromatography quadrupole time-of-flight mass spectrometry. We constructed orthogonal projections to latent structure models to predict sensory evaluation data obtained through the quantitative descriptive analysis method from the sake metabolome data. Results: For two years of study, 8 sensory evaluation models of the 2016 brewing year and 11 sensory evaluation models of the 2017 brewing year, including color, ethyl hexanoate, Hine-ka, Nama hine-ka, ethyl acetate, grainy/sweet aroma, sweetness, sourness, body, astringency, harsh taste/acrid taste, aftertaste, and overall quality, demonstrated a predictive performance with Q2 > 0.5. Liquid chromatography-based analytical data indicated that it is possible to predict not only taste but also aroma. Additionally, the generalization performance of the prediction models for sensory evaluation attributes common to both years was verified. Conclusions: These results provide a new option for explaining the sensory characteristics of sake from its components and contribute to a deeper understanding of them. Full article
(This article belongs to the Special Issue Advances in Food Sciences: Metabolomics to Unravel the Complexity of Food Metabolites)
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13 pages, 2522 KiB  
Article
Metabolomic Variation in Sugarcane Maturation Under a Temperate Climate
by Yasuhiro Date, Chiaki Ishikawa and Hiroshi Ono
Metabolites 2025, 15(8), 558; https://doi.org/10.3390/metabo15080558 - 20 Aug 2025
Viewed by 188
Abstract
Background: Metabolomics is a powerful tool used for the evaluation of sugarcane components which are key factors influencing its response to biotic and abiotic stresses. However, little is known about the compositional variability and diversity of the sugarcane juice metabolome under practical field [...] Read more.
Background: Metabolomics is a powerful tool used for the evaluation of sugarcane components which are key factors influencing its response to biotic and abiotic stresses. However, little is known about the compositional variability and diversity of the sugarcane juice metabolome under practical field conditions in temperate climates. Methods: In this study, we characterized metabolomic differences and variability in sugarcane juice components during the maturation stage of nine cultivars grown in a temperate climate in Japan using a nuclear magnetic resonance-based metabolomics approach, aiming to provide insights into genotype-dependent adaptability to environmental and climate changes. Results: Principal component analysis revealed distinct metabolic profiles based on cultivar and maturation level. Notably, sucrose levels increased from September to December accompanied by decreased glucose and fructose levels across all cultivars. Early-maturing cultivars had high sucrose content even with shorter growing periods, suggesting particular advantages for sugar production in temperate climates. Additionally, 4-aminobutyric acid accumulated in all cultivars as maturation progressed. On the other hand, trans-aconitic acid, choline, and branched-chain amino acids showed cultivar-dependent trends. In one example, choline concentrations increased significantly in specific cultivars during maturation. Conclusions: These findings support a deeper understanding of metabolic adaptation and may aid in identifying cultivars better suited to environmental fluctuations. Full article
(This article belongs to the Special Issue Metabolomic Technology in Quality and Safety of Agricultural Products and Foods)
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16 pages, 2557 KiB  
Article
Differential Impacts of Environmentally Relevant Microplastics on Gut Barrier Integrity in Mice Fed High-Fat Diet Versus Normal Chow Diet
by Huixia Niu, Ying Yang, Yuting Zhou, Xue Ma, Zhehao Ding, Manjin Xu, Lizhi Wu, Xueqing Li, Mingluan Xing, Qin Zhang, Hao Chen, Xiongwei Tao, Zhe Mo, Zhijian Chen, Pengcheng Tu and Xiaoming Lou
Metabolites 2025, 15(8), 557; https://doi.org/10.3390/metabo15080557 - 20 Aug 2025
Viewed by 218
Abstract
Background: Despite escalating global pollution from microplastics (MPs) and the concurrent surge in high-fat food consumption, the health impacts of MP exposure on individuals under different dietary patterns remain poorly understood. Methods: This study investigated the differential effects of environmentally relevant concentrations of [...] Read more.
Background: Despite escalating global pollution from microplastics (MPs) and the concurrent surge in high-fat food consumption, the health impacts of MP exposure on individuals under different dietary patterns remain poorly understood. Methods: This study investigated the differential effects of environmentally relevant concentrations of polystyrene microplastics (5 μm, 8 mg/kg) on gut barrier function in mice fed either a normal chow diet (CD) or a high-fat diet (HFD). Results: Key findings revealed that, in HFD-fed mice, MP exposure significantly reduced (p < 0.05) the transcriptional levels of genes encoding the tight junction proteins (ZO-1, Occludin, and Claudin-1), as well as the mucin protein Muc-2, accompanied by decreased protein expression levels of these markers in both colonic and ileal tissues. In contrast, no significant differences were observed in CD-fed mice exposed to MPs. Analysis of the gut microbiota and measurement of short-chain fatty acid (SCFA) metabolites showed that MPs induced significant alterations in the composition and diversity indices of the gut microbiota, along with a marked decrease (p < 0.05) in the levels of the characteristic metabolite butyrate in HFD-fed mice. Conversely, butyrate levels remained unchanged in CD-fed mice following MP exposure. Quantitative PCR (qPCR) and immunofluorescence staining of colonic tissues demonstrated that MP exposure significantly downregulated (p < 0.05) both the transcription and protein expression of peroxisome proliferator-activated receptor γ (PPARγ) in HFD-fed mice. Again, no significant changes were detected in CD-fed mice. Conclusions: These results collectively indicate that the impact of microplastics on the intestinal barrier differs significantly between mice fed normal and high-fat diets. The gut microbiota and its metabolites, particularly butyrate, may play a critical role, possibly through modulating PPARγ signaling. This study contributes valuable insights into understanding the toxicity profiles of microplastics and establishing crucial links between dietary patterns and the health effects of emerging pollutants. Full article
(This article belongs to the Special Issue Effects of Environmental Exposure on Host and Microbial Metabolism)
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12 pages, 436 KiB  
Article
Effects of IGF1 rs6214 Polymorphism and Milk Consumption on Serum Levels of IGF-1 and GH and Body Composition
by Julio Cesar Grijalva-Avila, Ignacio Villanueva-Fierro, Sandra Consuelo Martínez-Estrada, Gerardo Grijalva-Avila, Alonso Gándara-Mireles, Gildardo Rivera, Antonio Loera-Castañeda, Horacio Almanza-Reyes, Leslie Patrón-Romero and Verónica Loera-Castañeda
Metabolites 2025, 15(8), 556; https://doi.org/10.3390/metabo15080556 - 20 Aug 2025
Viewed by 248
Abstract
Milk and dairy are rich in insulin-like growth factor 1 (IGF-1), a protein secreted through the action of growth hormone (GH) and implicated in growth and metabolism. Objective: This study aimed to investigate the roles of milk intake and body composition and identify [...] Read more.
Milk and dairy are rich in insulin-like growth factor 1 (IGF-1), a protein secreted through the action of growth hormone (GH) and implicated in growth and metabolism. Objective: This study aimed to investigate the roles of milk intake and body composition and identify the presence of the single nucleotide variant (SNV) rs6214 in the insulin-like growth factor 1 gene (IGF1) and its effects on the serum IGF-1 and GH levels and body composition. Methods: We analyzed 110 volunteers with and without a history of milk intake. Through a case–control study with one hundred ten healthy volunteers, serum IGF-1 and GH levels were measured using the ELISA technique, the body composition was determined with bio-electrical impedance equipment, genotyping of the rs6214 SNV was carried out using real-time PCR, and a dietary questionnaire was administered to assess milk intake, with or without consumption. Results: The results showed that the highest levels of IGF-1 were found in people who regularly consumed milk, along with a lower body mass index (BMI) and percentage of fat. A lower BMI and fat percentage were associated with higher levels of IGF-1, lean mass, and SNV presence. Lower levels of BMI and percentages of subcutaneous and visceral fat were found in regular milk consumers. Conclusions: Our study suggests that dairy intake and the IGF1 gene rs6214 SNV are associated with higher levels of IGF-1, high levels of lean mass, a low BMI, a low % fat, and low visceral fat. Full article
(This article belongs to the Special Issue Functional Foods and Natural Bioactive Compounds: Strategies to Face Metabolic Syndrome and Related Non-Communicable Diseases)
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16 pages, 3032 KiB  
Article
Non-Targeted Metabolomics Analysis of Metabolic Differences Between Different Concentrations of Protein Diets in the Longest Dorsal Muscle of Tibetan Pigs
by Feifan Zhang, Jinhui Liang, Hongliang Zhang, Mengqi Duan, Dong Yang, Chamba Yangzom and Peng Shang
Metabolites 2025, 15(8), 555; https://doi.org/10.3390/metabo15080555 - 19 Aug 2025
Viewed by 148
Abstract
Background/Objectives: The aim of this study was to explore the effects of diets with different protein levels on the metabolite composition and metabolic pathways of the longest dorsal muscle of Tibetan pigs, in order to provide a metabolic basis for optimizing the nutritional [...] Read more.
Background/Objectives: The aim of this study was to explore the effects of diets with different protein levels on the metabolite composition and metabolic pathways of the longest dorsal muscle of Tibetan pigs, in order to provide a metabolic basis for optimizing the nutritional regulation strategy of Tibetan pigs. Methods: A total of 32 healthy 180-day-old depopulated male Tibetan pigs were randomly divided into four groups and fed diets with protein levels of 10%, 12%, 14%, and 16%, respectively, with a feeding cycle of 8 weeks. The longest dorsal muscle samples were collected, and their metabolic profiles were systematically analyzed by LC-MS non-targeted metabolomics. Results: The TIC plots of the quality control samples were highly overlapped, indicating a stable instrumental detection process and good consistency of sample processing. Principal component analysis and orthogonal partial least squares discriminant analysis revealed significant metabolic differences between groups with different protein levels. A total of multiple differential metabolites was obtained based on VIP value and p-value screening, and Venn diagram analysis revealed a total of 11 metabolites among the three comparative groups, suggesting that they may have key roles in the protein regulation process. Volcano plots further clarified the number and trend of significantly up- and down-regulated metabolites in each group. KEGG pathway enrichment analysis showed that, with the elevation of protein level, the metabolic pathway response showed a tendency of expanding from basal energy metabolism to the complex network of amino acid synthesis, steroidogenesis, endocrine signaling, and detoxification pathways, especially in the high-protein-treated group. Conclusions: The study showed that different protein intake levels could significantly regulate the metabolites and key metabolic pathways in the longest muscle of Tibetan pigs, which provided theoretical support for the scientific formulation of a protein supply program to optimize the quality and growth performance of Tibetan pork. Full article
(This article belongs to the Section Animal Metabolism)
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26 pages, 3880 KiB  
Review
Review of Biological Activities of Some Rare Oils from Amazonian Plants
by Luana Merckling-Almeida da Silva, Nicolas Merckling, Enrico Bigi, Katiane Cunha de Melo and Iuliana Popa
Metabolites 2025, 15(8), 554; https://doi.org/10.3390/metabo15080554 - 19 Aug 2025
Viewed by 264
Abstract
Background/Objectives: A great biodiversity of compounds from Brazilian medicinal plants are considered to be a promising source for biological activities in the cosmetics and pharmaceuticals sectors. Lipids and mainly fatty acids from Brazilian medicinal plants and their bioactive components are promising ingredients with [...] Read more.
Background/Objectives: A great biodiversity of compounds from Brazilian medicinal plants are considered to be a promising source for biological activities in the cosmetics and pharmaceuticals sectors. Lipids and mainly fatty acids from Brazilian medicinal plants and their bioactive components are promising ingredients with proven diverse biological activities. To undertake a review of some rare oils of Brazilian medicinal plants with corroborated biological activities, we selected data from the scientific literature reporting the efficacy of plants used in folk medicine as antioxidant, anti-inflammatory or other types of activity of their oil phases extracts and isolated fatty acids. Methods: A search of the literature was undertaken by using the following web tools: Web of Science, SciFinder, Pub-Med and ScienceDirect. The terms “biological activity”, “anti-inflammatory”, “açai oil, andiroba oil, bacuri butter, buriti oil, cupuaçu butter and pracaxi oil”, and “free fatty acids” and “Amazonian plant oils” were used as keywords in the search engines. The Tropicos and Reflora websites were used to verify the origin of the plants, and only native plants from Brazil were included in this review. Only the publications reporting the use of well-accepted scientific protocols to corroborate the potential biological activities of rare oils of Amazonian plants were considered. Results: We selected 6 Brazilian medicinal plant oils extracts (acai, andiroba, bacuri, buriti, cupuaçu, pracaxi) with multiple biological activities. The observations were presented as a function of the oil origin and the most important biological activities were detailed. Conclusions: The collected data on the rare oils from Amazonian plants, in the form of crude extract and/or isolated compounds, showed significant biological activities involving different mechanisms of action, indicating that these oils could be an important source of lipids with biological activity. Full article
(This article belongs to the Topic From Plant to Pharmacology: Understanding the Metabolism of Natural Products)
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15 pages, 621 KiB  
Review
Aldosterone and Cardiovascular Risk Across the Lifespan
by Roshan A. Ananda, Trevor A. Mori and Jun Yang
Metabolites 2025, 15(8), 553; https://doi.org/10.3390/metabo15080553 - 17 Aug 2025
Viewed by 310
Abstract
Aldosterone excess, particularly in the context of primary aldosteronism, is associated with adverse cardiovascular outcomes. Historically considered a condition of resistant hypertension with hypokalaemia, patients with primary aldosteronism often experienced prolonged diagnostic delay with significant end-organ damage involving the renal, cardiovascular, and central [...] Read more.
Aldosterone excess, particularly in the context of primary aldosteronism, is associated with adverse cardiovascular outcomes. Historically considered a condition of resistant hypertension with hypokalaemia, patients with primary aldosteronism often experienced prolonged diagnostic delay with significant end-organ damage involving the renal, cardiovascular, and central nervous systems at diagnosis. Emerging research has revealed a wide spectrum of renin-independent aldosteronism, ranging from subclinical disease with normal or mildly elevated BP to overt disease marked by resistant hypertension and cardiovascular complications. Subclinical forms of primary aldosteronism have been identified across all age groups, and it is increasingly linked to early signs of adverse cardiac remodelling, even in young adults. Notably, adverse cardiac remodelling was independent of blood pressure. Furthermore, primary aldosteronism confers excess cardiovascular morbidity and mortality compared to blood-pressure-matched essential hypertension. Importantly, these risks can be mitigated through timely diagnosis and treatment with mineralocorticoid receptor antagonists. In this narrative review, we explore the cardiovascular consequences of aldosterone excess, discuss the pathophysiological mechanisms underlying cardiac remodelling, and examine the implications of renin-independent aldosteronism for cardiovascular risk across the lifespan. Full article
(This article belongs to the Special Issue Adrenal Neuroendocrine System and Cardiometabolic Health)
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15 pages, 1218 KiB  
Article
Choline Metabolism to the Proatherogenic Metabolite Trimethylamine Occurs Primarily in the Distal Colon Microbiome In Vitro
by Anthony M. Buckley, Sarah Zaidan, Michael G. Sweet, Duncan J. Ewin, Juanita G. Ratliff, Aliyah Alkazemi, William Davis Birch, Ashley M. McAmis and Andrew P. Neilson
Metabolites 2025, 15(8), 552; https://doi.org/10.3390/metabo15080552 - 16 Aug 2025
Viewed by 233
Abstract
Background/Objectives: Gut microbial metabolism of choline and related quaternary amines to trimethylamine (TMA) is the first step in the production of trimethylamine N-oxide (TMAO), a circulating metabolite that contributes to the development of atherosclerosis and other forms of cardiovascular disease (CVD). No data [...] Read more.
Background/Objectives: Gut microbial metabolism of choline and related quaternary amines to trimethylamine (TMA) is the first step in the production of trimethylamine N-oxide (TMAO), a circulating metabolite that contributes to the development of atherosclerosis and other forms of cardiovascular disease (CVD). No data exist on regional differences in TMA production within the colon due to difficulties studying gut regions in vivo. A better understanding of TMA production by gut microbiota is needed to develop strategies to limit TMA production in the gut and TMAO levels in circulation with the goal of reducing CVD risk. Methods: We employed our novel three-compartment MiGut in vitro model, which establishes three distinct microbial ecologies mimicking the proximal, mid, and distal colon, to study conversion of choline to TMA by human gut microbiota using isotopically labelled substrate. Results: Choline-d9 was almost completely converted to TMA-d9 in vessels 2–3 (mimicking the mid and distal colon) within 6–8 h, but little conversion occurred in vessel 1 (mimicking the proximal colon). Abundance of cutC, part of the cutC/D gene cluster responsible for choline conversion to TMA, was highest in vessel 1 vs. 2–3, suggesting that its expression or activity may be suppressed in the proximal colon. Another possibility is that the viability/activity of bacteria expressing cutC could be suppressed in the same region. Conclusions: This novel finding suggests that while bacteria capable of converting choline to TMA exist throughout the colon, their activity may be different in distinct colon regions. The regional specificity of TMA production, if confirmed in vivo, has implications for both basic microbial ecology related to CVD and the development of strategies to control TMA and TMAO production, with the goal of lowering CVD risk. These findings warrant further study in vitro and in vivo. Full article
(This article belongs to the Section Nutrition and Metabolism)
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13 pages, 1384 KiB  
Article
Metabolomics Network Analysis of Various Genotypes Associated with Schizophrenia Gene Variant
by Hema Sekhar Reddy Rajula, Cristina Piras, Karolina Krystyna Kopeć, Antonio Noto, Martina Spada, Katia Lilliu, Mirko Manchia, Michele Mussap, Luigi Atzori and Vassilios Fanos
Metabolites 2025, 15(8), 551; https://doi.org/10.3390/metabo15080551 - 15 Aug 2025
Viewed by 232
Abstract
Background: This study investigates metabolic perturbations in serum samples associated with different genotypes (AA, AC, and CC) of the schizophrenia susceptibility gene NOS1AP-rs12742393. Methods: Publicly available datasets acquired using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–QTOFMS) were analyzed by employing network and enrichment [...] Read more.
Background: This study investigates metabolic perturbations in serum samples associated with different genotypes (AA, AC, and CC) of the schizophrenia susceptibility gene NOS1AP-rs12742393. Methods: Publicly available datasets acquired using ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UPLC–QTOFMS) were analyzed by employing network and enrichment approaches. Results: Key metabolites, including tryptophan, 2-aminobutyric acid, palmitic acid, and 5-hydroxytryptophan, were strongly linked to metabolic networks in genotypes AA-AC and AA. Enrichment analysis was conducted to identify metabolite sets differentially distributed across these genotypes, with a particular focus on genotype AA. Conclusions: The findings suggest that NOS1AP-rs12742393 contributes to complex metabolic alterations involving amino acids, organic compounds, fatty acids, and cholic acids. Moreover, serum metabolome analysis demonstrates sufficient sensitivity and specificity to provide insights into NOS1AP-rs12742393 genotype-associated metabolic profiles, supporting a network-based approach to understanding schizophrenia susceptibility. Full article
(This article belongs to the Special Issue Risk Prediction and Novel Biomarker Discovery of Chronic Diseases by Advanced Methodologies in Lipidomics and Metabolomics)
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12 pages, 505 KiB  
Article
Postprandial Cardiometabolic Parameters in Older Adults with Normal-Weight Obesity: A Cross-Sectional Pilot Study
by Dhanya O. Pathangi, Alexis R. Quirk, Jenna K. Schifferer, Sarah E. Fruit, Morgan E. Higgins, Emily R. Wolf, Cindy E. Tsotsoros, Sam R. Emerson and Bryant H. Keirns
Metabolites 2025, 15(8), 550; https://doi.org/10.3390/metabo15080550 - 15 Aug 2025
Viewed by 242
Abstract
Background/Objectives: Normal-weight obesity describes those with a normal body mass index (BMI) and high body fat percent. Older adults with normal-weight obesity (NWO-O) are at increased risk for cardiovascular disease (CVD), but underlying mechanisms remain unclear. This pilot study examined whether NWO-O had [...] Read more.
Background/Objectives: Normal-weight obesity describes those with a normal body mass index (BMI) and high body fat percent. Older adults with normal-weight obesity (NWO-O) are at increased risk for cardiovascular disease (CVD), but underlying mechanisms remain unclear. This pilot study examined whether NWO-O had an unfavorable cardiometabolic response to acute high-fat meal intake compared to normal BMI, low body fat percent individuals that were both older (NWL-O) and younger (NWL-Y). Methods: Participants (N = 29) with a normal BMI were grouped as follows: NWL-Y (18–35 years, low body fat percent; n = 12), NWL-O (≥60 years, low body fat percent; n = 9), and NWO-O (≥60 years, high body fat percent; n = 8). All participants completed an abbreviated fat tolerance test (75 g fat). Fasting and 4 h blood samples were collected to measure lipids (triglycerides and high-density lipoprotein cholesterol [HDL-C]), biomarkers of intestinal permeability (lipopolysaccharide binding protein [LBP] and soluble cluster of differentiation [sCD14]), and the inflammatory marker interleukin (IL)-6. Results: NWO-O had higher percent, absolute, and trunk fat compared to NWL-Y and NWL-O (p’s ≤ 0.01). Conversely, percent lean mass was lower in NWO-O versus both NWL groups (p’s ≤ 0.01). NWO-O had higher fasting triglycerides than NWL-Y (p < 0.05), but all groups were in the clinically normal range on average (≤107 mg/dL). However, NWO-O had higher 4 h triglycerides (239.4 ± 101.0 mg/dL) compared to NWL-Y and NWL-O (p < 0.01), consistent with an adverse response. The absolute change in triglycerides was higher in NWO-O relative to NWL-Y (p < 0.01), but not compared to NWL-O (p = 0.06). Fasting IL-6 was higher in NWO-O relative to NWL-Y (p < 0.05). Fasting and 4 h sCD14 were similarly higher in NWL-O and NWO-O versus NWL-Y (p’s < 0.01). Conclusions: NWO-O had an exaggerated postprandial triglyceride response compared to younger and similar-aged NWL individuals, which could reflect hepatic very low-density lipoprotein overproduction or impaired triglyceride clearance. Future work should continue to investigate the role of postprandial dyslipidemia in NWO-O’s reported CVD risk. Full article
(This article belongs to the Special Issue Impact of Macronutrients on Metabolism)
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18 pages, 814 KiB  
Article
Dual Impact of Iron Deficiency and Antibiotics on Host Metabolism: A Tissue-Level Analysis
by Shannon Shoff, Sydney Thomas, Peng Ji, Mariana Parenti and Carolyn M. Slupsky
Metabolites 2025, 15(8), 549; https://doi.org/10.3390/metabo15080549 - 14 Aug 2025
Viewed by 314
Abstract
Background/Objectives: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and [...] Read more.
Background/Objectives: Iron deficiency (ID) is a common nutritional deficiency in infancy and early childhood associated with increased risk of infection and increased likelihood of receiving antibiotic intervention. In the context of ID, antibiotics have been shown to exaggerate the growth impairments and negative impacts on metabolic health of ID itself. The objective of this research was to assess the tissue-level impact of antibiotics when provided during ID. Methods: ID was induced in piglets by withholding an iron dextran shot shortly after birth, and iron deficiency was maintained after weaning by providing an iron-deficient diet starting on postnatal day (PD) 25. Half of the ID piglets received a 3-day antibiotic course (ID + Abx) consisting of spectinomycin and gentamicin from PD34-36. The kidney, liver, skeletal muscle, and hippocampal metabolomes, as well as activity of proteins in the mTOR signaling pathway, were assessed on PD43. Results: While ID had minimal impacts on the liver, kidney, and skeletal muscle metabolomes, ID + Abx impaired energy metabolism and increased ketosis and oxidative stress in peripheral tissues. Hippocampal metabolites involved in neurotransmitter synthesis pathways were affected by ID and ID + Abx to a greater extent. Additionally, the activities of several proteins in the mTOR pathway were upregulated in the hippocampi of ID + Abx piglets compared to both ID and control piglets. Abx provided to iron-sufficient piglets had minimal effects on tissue metabolomes and did not alter the activity of proteins in the mTOR pathway. Conclusions: These results highlight that antibiotic treatment in ID alters metabolism in peripheral tissues and the developing hippocampus beyond those induced by ID alone. Considering that infants and children are develop rapidly, the combination of ID and antibiotics may have lasting impacts on neurodevelopment and cognition. Full article
(This article belongs to the Section Nutrition and Metabolism)
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17 pages, 11905 KiB  
Article
Metabolomic Profiling Reveals the Effects of Cu-Ag Nanoparticles on Tomato Bacterial Wilt
by Weimin Ning, Lei Jiang, Mei Yang, Tianhao Lei, Chan Liu, Fei Zhao, Pan Shu and Yong Liu
Metabolites 2025, 15(8), 548; https://doi.org/10.3390/metabo15080548 - 13 Aug 2025
Viewed by 304
Abstract
Background: The bacterial wilt of tomatoes, caused by Ralstonia solanacearum, is a soil-borne plant disease that causes substantial agricultural economic losses. Various nanoparticles have been utilized as antibacterial agents to mitigate pathogenic destructiveness and improve crop yields. However, there is a lack [...] Read more.
Background: The bacterial wilt of tomatoes, caused by Ralstonia solanacearum, is a soil-borne plant disease that causes substantial agricultural economic losses. Various nanoparticles have been utilized as antibacterial agents to mitigate pathogenic destructiveness and improve crop yields. However, there is a lack of in-depth research on how nanoparticles affect tomato metabolite levels to regulate the bacterial wilt of tomatoes. Methods: In this study, healthy and bacterial wilt-infected tomatoes were treated with Cu-Ag nanoparticles, and a metabolomics analysis was carried out. Results: The results showed that Cu-Ag nanoparticles had a significant prevention and control effect on the bacterial wilt of tomatoes. Metabolomic analysis revealed that the nanoparticles could significantly up-regulate the expression levels of terpenol lipids, organic acids, and organic oxygen compounds in diseased tomatoes, and enhance key metabolic pathways such as amino acid metabolism, carbohydrate metabolism, secondary metabolite metabolism, and lipid metabolism. These identified metabolites and pathways could regulate plant growth and defense against pathogens. Correlation analysis between the tomato microbiome and metabolites showed that most endophytic microorganisms and rhizospheric bacteria were positively correlated with fatty acyls groups and organic oxygen compounds. Conclusions: This study reveals that Cu-Ag nanoparticles can actively regulate the bacterial wilt of tomatoes by up-regulating the levels of lipid metabolism and organic oxygen compounds, providing an important theoretical basis for the application of nanoparticles in agriculture. Full article
(This article belongs to the Special Issue Metabolomics and Plant Defence, 2nd Edition)
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11 pages, 1192 KiB  
Article
Comparative Study Between the Short-Term Effects of Replacement Therapy with Liquid and Tablet Formulations of Levothyroxine on Insulin Resistance Markers in Recently Thyroidectomized Female Patients
by Francesco Baratta, Federica Moscucci, Raffaella Bocale, Carmine Savoia, Nicholas Cocomello, Ilaria Lospinuso, Evaristo Ettorre, Giovambattista Desideri and Alfredo Pontecorvi
Metabolites 2025, 15(8), 547; https://doi.org/10.3390/metabo15080547 - 13 Aug 2025
Viewed by 310
Abstract
Background/Objectives: Levothyroxine (L-T4) replacement therapy is essential following total thyroidectomy. While liquid L-T4 formulations exhibit superior pharmacokinetic properties compared to tablets, their specific metabolic impact—particularly on insulin resistance—remains unclear. The aim of this study was to compare the short-term effects of liquid [...] Read more.
Background/Objectives: Levothyroxine (L-T4) replacement therapy is essential following total thyroidectomy. While liquid L-T4 formulations exhibit superior pharmacokinetic properties compared to tablets, their specific metabolic impact—particularly on insulin resistance—remains unclear. The aim of this study was to compare the short-term effects of liquid versus tablet L-T4 replacement therapy on insulin resistance indices in recently thyroidectomized women and to identify baseline predictors of metabolic response. Methods: A post hoc analysis included 130 women randomized to receive either liquid or tablet L-T4 after total thyroidectomy. Metabolic parameters—including the homeostatic model assessment for insulin resistance (HOMA-IR), triglycerides-glucose (TyG) index, and triglycerides-to-HDL cholesterol (TG/HDL-C) ratio—were assessed at baseline and after two months. Results: Both L-T4 formulations significantly improved insulin resistance indices over two months. Liquid L-T4 induced a more pronounced reduction in HOMA-IR (treatment effect p = 0.022) and fasting insulin levels (treatment effect p = 0.017) compared to the tablet formulation. No significant between-group differences were observed for TyG index or TG/HDL-C ratio. Changes in insulin resistance markers were independent of body mass index variations and were predicted by baseline metabolic parameters including insulin, glucose, and lipid levels. Conclusions: L-T4 replacement therapy improves insulin resistance markers shortly after thyroidectomy, with the liquid formulation exerting a greater effect on hepatic insulin sensitivity. These findings support the individualized selection of L-T4 formulations to optimize both endocrine and metabolic outcomes post-thyroidectomy. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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20 pages, 1864 KiB  
Article
Serum Metabolomic Signatures in Nonhuman Primates Treated with a Countermeasure and Exposed to Partial- or Total-Body Radiation
by Alana D. Carpenter, Yaoxiang Li, Benjamin E. Packer, Oluseyi O. Fatanmi, Stephen Y. Wise, Sarah A. Petrus, Martin Hauer-Jensen, Amrita K. Cheema and Vijay K. Singh
Metabolites 2025, 15(8), 546; https://doi.org/10.3390/metabo15080546 - 12 Aug 2025
Viewed by 277
Abstract
Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing [...] Read more.
Background: Irradiation-induced injury is a common fallout of radiological/nuclear accidents or therapeutic exposures to high doses of radiation at high dose rates. Currently, there are no prophylactic drugs available to mitigate radiation injury as a result of exposure to lethal doses of ionizing radiation. Gamma-tocotrienol (GT3) of vitamin E is a promising radioprotector under advanced development which has been tested for efficacy in both murine and nonhuman primate (NHP) models. Previously, we have demonstrated that GT3 has radioprotective efficacy in intestinal epithelial and crypt cells, and restores transcriptomic changes in NHPs with a supralethal dose of 12 Gy total-body irradiation (TBI). Methods: In this study, we evaluated the effect of 12 Gy partial-body irradiation (PBI) or TBI on metabolomic changes in serum samples and the extent to which GT3 was able to modulate these irradiation-induced changes. A total of 32 nonhuman primates were used for this study, and blood sample were collected 3 days (d) prior to irradiation, and 4 hours (h), 8 h, 12 h, 1 d, 2, and 6 d post-irradiation. Results: Our results demonstrate that exposure to a supralethal dose of radiation induces a complex range of metabolomic shifts with similar degrees of dysregulation in both partial- and total-body irradiated animals. The C21-steroid hormone biosynthesis and metabolism pathway was significantly dysregulated in both PBI and TBI groups, with minimal protection afforded by GT3 administration. Conclusions: GT3 offered a differential response in terms of protected metabolites and pathways in either group that was most effective at the early post-irradiation time points. Full article
(This article belongs to the Section Advances in Metabolomics)
4 pages, 147 KiB  
Editorial
Salivary Fingerprint in the Metabolomics Era: Potential and Challenges
by Tatiana Kelly da Silva Fidalgo and Ana Paula Valente
Metabolites 2025, 15(8), 545; https://doi.org/10.3390/metabo15080545 - 12 Aug 2025
Viewed by 247
Abstract
In recent years, the field of metabolomics has significantly advanced our understanding of human health and disease by providing a comprehensive snapshot of metabolic alterations [...] Full article
(This article belongs to the Special Issue Salivary Fingerprint in Metabolomics Era: Potential and Challenges)
2 pages, 136 KiB  
Retraction
RETRACTED: El-Garawani et al. In Vitro Induction of Apoptosis in Isolated Acute Myeloid Leukemia Cells: The Role of Anastatica hierochuntica Methanolic Extract. Metabolites 2022, 12, 878
by Islam M. El-Garawani, Amira S. Abd El-Gaber, Noura A. Algamdi, Aamer Saeed, Chao Zhao, Omar M. Khattab, Mohamed F. AlAjmi, Zhiming Guo, Shaden A. M. Khalifa and Hesham R. El-Seedi
Metabolites 2025, 15(8), 544; https://doi.org/10.3390/metabo15080544 - 12 Aug 2025
Viewed by 239
Abstract
The journal Metabolites retracts the article “In Vitro Induction of Apoptosis in Isolated Acute Myeloid Leukemia Cells: The Role of Anastatica hierochuntica Methanolic Extract” [...] Full article
16 pages, 1520 KiB  
Article
Preoperative Tyrosine Levels as Predictive Biomarkers for Excessive Fat-Free Mass Loss Following Laparoscopic Sleeve Gastrectomy in Patients with Morbid Obesity
by Inyoung Lee, Eunhye Seo, Yeongkeun Kwon, Chang Min Lee, Nam Hoon Kim, Jong-Han Kim, Sung Il Choi and Sungsoo Park
Metabolites 2025, 15(8), 543; https://doi.org/10.3390/metabo15080543 - 11 Aug 2025
Viewed by 363
Abstract
Background/Objectives: Fat-free mass (FFM) loss after metabolic and bariatric surgery (MBS) is associated with adverse long-term outcomes, including osteoporosis. Identifying biomarkers that predict excessive FFM loss can improve perioperative patient management and postoperative risk stratification. This study investigated whether preoperative amino acid [...] Read more.
Background/Objectives: Fat-free mass (FFM) loss after metabolic and bariatric surgery (MBS) is associated with adverse long-term outcomes, including osteoporosis. Identifying biomarkers that predict excessive FFM loss can improve perioperative patient management and postoperative risk stratification. This study investigated whether preoperative amino acid metabolite (AAM) levels could predict excessive FFM loss after laparoscopic sleeve gastrectomy (LSG). Methods: Forty patients with morbid obesity who underwent LSG between 2019 and 2020 were retrospectively analyzed. Based on the FFM loss to body weight loss ratio (%FFML/BWL) at 3 months postoperatively, patients were categorized into excessive (>25%) and non-excessive (≤25%) FFM loss groups. Anthropometric measurements and serum sampling were performed preoperatively and at 3, 6, and 12 months postoperatively. AAM profiles were collected before surgery. Statistical analyses, including logistic regression and receiver operating characteristic curves, were performed. Results: Twenty-five patients showed excessive FFM loss 3 months after surgery. They had significantly lower preoperative tyrosine (Tyr) levels (p = 0.025). Logistic regression revealed that higher Tyr levels were significantly associated with lower odds of being male, suggesting a potential protective effect (odds ratio (OR) =0.019, p = 0.010). Tyr profiling demonstrated acceptable predictive performance (area under the curve =0.715, p = 0.025). Despite nonsignificant p-values, trends showed lower FFM and muscle mass and higher fat mass in the excessive FFM loss group throughout follow-up. Conclusions: Preoperative Tyr profiling may help identify patients at risk for excessive FFM loss. These findings support prioritizing metabolic health alongside total weight loss in the evaluation of MBS outcomes. Full article
(This article belongs to the Special Issue Exploring Pathological Mechanisms in Obesity, Diabetes, and Metabolic Syndrome)
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16 pages, 1716 KiB  
Article
Flavonoids and Sesquiterpene Lactones from Lychnophora ericoides (Arnica-Do-Cerrado) and Their In Vitro Effects on Multiple Myeloma and Acute Myeloid Leukemia
by Calisto Moreno Cardenas, Ren Ove Kratzert, Sofie Hanifle, Elida Cleyse Gomes da Mata Kanzaki, Isamu Kanzaki, Brigitte Kircher and Serhat Sezai Çiçek
Metabolites 2025, 15(8), 542; https://doi.org/10.3390/metabo15080542 - 9 Aug 2025
Viewed by 324
Abstract
Objectives: Multiple myeloma and acute myeloid leukemia are severe forms of blood cancer, which lack effective therapies for treatment. In our search for new chemical lead structures from nature, we were investigating the Brazilian medicinal plant arnica-do-cerrado (Lychnophora ericoides). Methods: Repeated [...] Read more.
Objectives: Multiple myeloma and acute myeloid leukemia are severe forms of blood cancer, which lack effective therapies for treatment. In our search for new chemical lead structures from nature, we were investigating the Brazilian medicinal plant arnica-do-cerrado (Lychnophora ericoides). Methods: Repeated chromatography led to the isolation of four flavonoids and three sesquiterpenoids, which were evaluated for their cytostatic and cytotoxic properties against HL-60, MOLM-13, AMO-1, and KMS-12 PE cancer cells as well as the non-malignant HS-5 cell line. Results: Whereas the isolated flavonoids displayed only moderate activity, the three sesquiterpene lactones goyazensolide, centratherin, and lychnopholide exhibited pronounced effects against all four tested cell lines. Goyazensolide was the most effective compound, inhibiting proliferation and metabolic activity with IC50 values between 1.0 and 1.6 µM, as well as 1.0 to 2.0 µM, respectively. Centratherin and lychnopholide were somewhat less active but showed higher selectivity towards malignant cell lines, which was most pronounced for MOLM-13 cells. Conclusion: The results of this study revealed interesting natural products that will be further evaluated for their potential as new lead compounds for the treatment of acute myeloid leukemia and multiple myeloma. Full article
(This article belongs to the Special Issue Effects of Secondary Plant Metabolites on Human Health)
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14 pages, 2274 KiB  
Article
Molybdenum-Induced Oxidative and Inflammatory Injury and Metabolic Pathway Disruption in Goat Pancreas
by Longfei Li, Yang Ran and Xiaoyun Shen
Metabolites 2025, 15(8), 541; https://doi.org/10.3390/metabo15080541 - 9 Aug 2025
Viewed by 279
Abstract
Background: Molybdenum (Mo) is an essential trace element for animals, but too much intake can cause adverse effects. Due to the metabolic characteristics of goats and other ruminants, they are more susceptible to the cumulative effects of Mo toxicity. A high Mo [...] Read more.
Background: Molybdenum (Mo) is an essential trace element for animals, but too much intake can cause adverse effects. Due to the metabolic characteristics of goats and other ruminants, they are more susceptible to the cumulative effects of Mo toxicity. A high Mo intake can cause multi-organ toxicity in ruminants, but the mechanism of damage to the pancreas is still unclear. The aim of this study was to systematically analyze the key regulatory pathways of pancreatic injury induced by Mo in goats using a metabolomics approach. Methods: Twenty male Yudong Black goats (22.34 ± 1.87 kg, six months) were randomly divided into a control group (fed a basal diet) and the Mo group (fed a basal diet supplemented with 50 mg·kg−1 Na2MoO4·2H2O). After 60 days of continuous feeding, their pancreatic tissues were collected and the mineral elements, antioxidant capacity, and inflammatory factors were examined. Untargeted metabolomics based on HILIC UHPLC-Q-EXACTIVE MS was used to analyze changes in metabolites. The core regulatory mechanisms were revealed by KEGG enrichment analysis. Results: The results demonstrated that goats in the Mo group showed obvious clinical signs, such as lethargy, loss of appetite, and unsteady gait. The pancreatic tissue of goats in the Mo group exhibited significantly elevated levels of Mo and copper, accompanied by a marked reduction in antioxidant capacity and concurrent increases in inflammatory cytokine levels. Between the Mo group and control group, 167 differentially expressed metabolites were identified. KEGG enrichment analysis showed that it disrupted multiple metabolic pathways, including glycine, serine, and threonine metabolism, cysteine and methionine metabolism, and butanoate metabolism. Conclusions: This study mainly revealed, at the metabolomics level, that Mo exposure would disrupt the metabolic pathways related to antioxidant capacity in goat pancreata. It provides new insights into the molecular mechanisms of Mo-induced pancreatic injury in goats. Full article
(This article belongs to the Section Animal Metabolism)
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20 pages, 1995 KiB  
Systematic Review
MALDI-TOF MS Biomarkers for Methicillin-Resistant Staphylococcus aureus Detection: A Systematic Review
by Pedro Santos, Irina Alho and Edna Ribeiro
Metabolites 2025, 15(8), 540; https://doi.org/10.3390/metabo15080540 - 8 Aug 2025
Viewed by 386
Abstract
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant challenge in healthcare. Conventional and molecular techniques used for MRSA identification are either time-consuming or costly. Alternatively, Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) offers a rapid method for microbial identification and has [...] Read more.
Background/Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) infections remain a significant challenge in healthcare. Conventional and molecular techniques used for MRSA identification are either time-consuming or costly. Alternatively, Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry (MALDI-TOF MS) offers a rapid method for microbial identification and has the potential to detect biomarkers that distinguish methicillin resistance in S. aureus isolates. The aim of this study was to identify methicillin-resistant discriminative biomarkers for S. aureus obtained using MALDI-TOF MS. Methods: A systematic review was conducted by searching databases such as PubMed and Web of Science for studies that focused on MRSA detection with biomarkers by MALDI-TOF MS, including all relevant studies published up to July 2024. The review protocol was registered in PROSPERO registry. Results: A total of 15 studies were selected for analysis. Data were extracted on study location, sample size, MALDI-TOF MS analyzer, sample preparation, methicillin resistance and sensitivity biomarkers, and the use of Artificial Intelligence (AI) models. Notably, PSM-mec and delta toxin were frequently reported as informative biomarkers, detectable at 2414 ± 2 Da and 3006 ± 2 Da, respectively. Additionally, eight studies used AI models to identify specific biomarkers differentiating methicillin-resistant and methicillin-sensitive strains, based on differences in peak intensities or the exclusive presence of certain peaks. Moreover, two studies employed detection of MRSA in low concentrations from biological samples and others employed an optimized matrix solution for improved analysis. Conclusions: Overall, MALDI-TOF MS is not only a powerful tool for the identification of bacterial isolates but also shows strong potential for rapid, cost-effective detection of methicillin resistance in S. aureus through biomarker analysis. Given that it is already implemented in several clinical laboratories, this approach could be adopted without significant additional cost. Full article
(This article belongs to the Special Issue Novel Approaches for Metabolomics in Drugs and Biomarkers Discovery: 2nd Edition)
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27 pages, 1703 KiB  
Review
Spatially Resolved Plant Metabolomics
by Ronald J. Myers, Jr., Zachary M. Tretter, Abigail G. Daffron, Eric X. Fritschi, William Thives Santos, Maiya L. Foster, Matthew Klotz, Kristin M. Stafford, Christina Kasch, Thomas J. Taylor, Lillian C. Tellefson, Tyler Hartman, Dru Hackler, Preston Stephen and Lloyd W. Sumner
Metabolites 2025, 15(8), 539; https://doi.org/10.3390/metabo15080539 - 8 Aug 2025
Viewed by 485
Abstract
Research and innovation in metabolomics tools to measure metabolite accumulation within plants have led to important discoveries with respect to the improvement of plant stress tolerance, development, and crop yield. Traditional metabolomics analyses have commonly utilized gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, [...] Read more.
Research and innovation in metabolomics tools to measure metabolite accumulation within plants have led to important discoveries with respect to the improvement of plant stress tolerance, development, and crop yield. Traditional metabolomics analyses have commonly utilized gas chromatography–mass spectrometry and liquid chromatography–mass spectrometry, but these methods are often performed without regard for the spatial locations of metabolites within tissues. Methods for mass spectral imaging (MSI) have recently been developed to detect and spatially resolve metabolite accumulation and are rapidly being adopted on a wider scale. Since 2010, the number of publications incorporating mass spectral imaging has grown from approximately 80 articles to over 378 on a yearly basis, constituting an increase of at least 350% during this time frame. Spatially resolved metabolite accumulation data provides unique insights into the function and regulation of plant biochemical pathways. Mass spectral imaging is commonly paired with desorption ionization technologies, including matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI), to generate accurate, spatially resolved metabolomics data from prepared tissue segments. Here, we describe the most recent advancements in sample preparation methods, mass spectral imaging technologies, and data processing tools that have been developed to address the limits of MSI technology. Additionally, we summarize recent applications of MSI technologies in plant metabolomics and discuss potential avenues for future research advancements within the plant biology community through the use of these technologies. Full article
(This article belongs to the Special Issue Mass Spectrometry Imaging and Spatial Metabolomics)
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2 pages, 132 KiB  
Correction
Correction: Lloyd et al. Chemical Diversity of UK-Grown Tea Explored Using Metabolomics and Machine Learning. Metabolites 2025, 15, 52
by Amanda J. Lloyd, Alina Warren-Walker, Jasen Finch, Jo Harper, Kathryn Bennet, Alison Watson, Laura Lyons, Pilar Martinez Martin, Thomas Wilson and Manfred Beckmann
Metabolites 2025, 15(8), 538; https://doi.org/10.3390/metabo15080538 - 8 Aug 2025
Viewed by 210
Abstract
There was a provenance issue with the seed varieties in the original publication [...] Full article
11 pages, 330 KiB  
Article
Triglyceride–Glucose Index and New-Onset Type 2 Diabetes Mellitus in Middle-Aged Men
by Lanfranco D’Elia, Domenico Rendina, Roberto Iacone, Pasquale Strazzullo and Ferruccio Galletti
Metabolites 2025, 15(8), 537; https://doi.org/10.3390/metabo15080537 - 8 Aug 2025
Viewed by 353
Abstract
Background: Type 2 diabetes mellitus (T2DM) is a major contributor to cardiovascular disease worldwide, with insulin resistance (IR) being a central pathophysiological mechanism. The triglyceride–glucose (TyG) index, derived from routine fasting measures, has emerged as a simple yet reliable proxy for IR and [...] Read more.
Background: Type 2 diabetes mellitus (T2DM) is a major contributor to cardiovascular disease worldwide, with insulin resistance (IR) being a central pathophysiological mechanism. The triglyceride–glucose (TyG) index, derived from routine fasting measures, has emerged as a simple yet reliable proxy for IR and is increasingly recognised for its prognostic value in metabolic disorders. Despite growing interest, longitudinal evidence on TyG and incident T2DM, especially within European cohorts, remains limited and inconsistent. Therefore, we aimed to estimate the predictive role of TyG on the development of T2DM in an 8-year follow-up observation of a sample of adult men. Methods: We analysed data from 789 adult men without baseline T2DM, enrolled in the Olivetti Heart Study. Receiver operating characteristic curve analysis was used to determine the optimal TyG threshold for predicting new-onset T2DM. Results: Baseline TyG exhibited a strong, linear association with the subsequent development of T2DM. A TyG value above 4.88 was associated with an approximately twofold increase in risk, both before and after adjustment for confounding factors. Conclusions: The principal findings of this study indicate a significant predictive value of the TyG index in the development of new-onset T2DM. These observations suggest that the TyG index may serve as a low-cost, simple, and non-invasive tool for early cardio-metabolic risk assessment. Full article
(This article belongs to the Section Endocrinology and Clinical Metabolic Research)
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15 pages, 2691 KiB  
Review
SGLT2 Inhibitors: Multifaceted Therapeutic Agents in Cardiometabolic and Renal Diseases
by Ana Checa-Ros, Owahabanun-Joshua Okojie and Luis D’Marco
Metabolites 2025, 15(8), 536; https://doi.org/10.3390/metabo15080536 - 7 Aug 2025
Viewed by 362
Abstract
Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce [...] Read more.
Background: Sodium–glucose cotransporter-2 inhibitors (SGLT2is), initially developed as antihyperglycemic agents, have emerged as multifunctional therapeutics with profound cardiorenal and metabolic benefits. Their unique insulin-independent mechanism, targeting renal glucose reabsorption, distinguishes them from conventional antidiabetic drugs. Mechanisms and Clinical Evidence: SGLT2is induce glycosuria, reduce hyperglycemia, and promote weight loss through increased caloric excretion. Beyond glycemic control, they modulate tubuloglomerular feedback, attenuate glomerular hyperfiltration, and exert systemic effects via natriuresis, ketone utilization, and anti-inflammatory pathways. Landmark trials (DAPA-HF, EMPEROR-Reduced, CREDENCE, DAPA-CKD) demonstrate robust reductions in heart failure (HF) hospitalizations, cardiovascular mortality, and chronic kidney disease (CKD) progression, irrespective of diabetes status. Adipose Tissue and Metabolic Effects: SGLT2is mitigate obesity-associated adiposopathy by shifting macrophage polarization (M1 to M2), reducing proinflammatory cytokines (TNF-α, IL-6), and enhancing adipose tissue browning (UCP1 upregulation) and mitochondrial biogenesis (via PGC-1α/PPARα). Modest weight loss (~2–4 kg) occurs, though compensatory hyperphagia may limit long-term effects. Emerging Applications: Potential roles in non-alcoholic fatty liver disease (NAFLD), polycystic ovary syndrome (PCOS), and neurodegenerative disorders are under investigation, driven by pleiotropic effects on metabolism and inflammation. Conclusions: SGLT2is represent a paradigm shift in managing T2DM, HF, and CKD, with expanding implications for metabolic syndrome. Future research should address interindividual variability, combination therapies, and non-glycemic indications to optimize their therapeutic potential. Full article
(This article belongs to the Special Issue Metabolic Modulators in Cardiovascular Disease Management)
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12 pages, 264 KiB  
Article
Discriminative Capacity of Visceral Adiposity and Triglyceride Glucose-Waist Circumference Indices for Metabolic Syndrome in Spanish Adolescents: A Cross-Sectional Study
by Ángel Fernández-Aparicio, Miriam Mohatar-Barba, Javier S. Perona, Jacqueline Schmidt-RioValle, Carmen Flores Navarro-Pérez and Emilio González-Jiménez
Metabolites 2025, 15(8), 535; https://doi.org/10.3390/metabo15080535 - 7 Aug 2025
Viewed by 336
Abstract
Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and [...] Read more.
Background/Objectives: Adolescence is a critical period for the early detection of metabolic syndrome (MetS), a condition that increases the risk of cardiometabolic diseases in adulthood. Timely identification of at-risk adolescents enables targeted prevention strategies. This study aimed to analyze the discriminative capacity and accuracy of six biochemical and/or anthropometric indices related to lipid metabolism and adiposity for the early detection of MetS in a sample of Spanish adolescents. Methods: A cross-sectional study carried out according to the STROBE guidelines. A sample of 981 adolescents aged 11–16 years old were randomly recruited from schools in Southeastern Spain. The presence or absence of MetS was determined according to the International Diabetes Federation criteria. The following biochemical and/or anthropometric indices were evaluated: triglyceride glucose index, visceral adiposity index, logarithm children’s lipid accumulation product, triglyceride glucose-body mass index, triglyceride glucose-waist circumference, and triglyceride glucose-waist-to-hip ratio. Results: The triglyceride glucose-waist-to-hip ratio and triglyceride glucose-body mass index parameters were the strongest indicators associated with MetS in boys and girls, respectively, after adjusting for several factors. Moreover, all evaluated indices showed optimal AUC values, with the visceral adiposity index and triglyceride glucose-waist circumference index exhibiting the highest discriminative capacity in both genders. Conclusions: The evaluated biochemical and anthropometric indices—particularly visceral adiposity index and triglyceride-glucose-waist circumference—show promise as accessible biomarkers for identifying adolescents at metabolic risk. These indices may serve as practical tools in preventive health strategies aimed at improving metabolic health by screening adolescents at risk of MetS, thereby helping to reduce the future burden of non-communicable diseases. Full article
(This article belongs to the Special Issue Effects of Diet on Metabolic Health of Obese People)
18 pages, 2516 KiB  
Article
Joint Metabolomics and Transcriptomics Reveal Rewired Glycerophospholipid and Arginine Metabolism as Components of BRCA1-Induced Metabolic Reprogramming in Breast Cancer Cells
by Thomas Lucaora and Daniel Morvan
Metabolites 2025, 15(8), 534; https://doi.org/10.3390/metabo15080534 - 7 Aug 2025
Viewed by 398
Abstract
Background/Objectives: The breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene whose mutations are associated with increased susceptibility to develop breast or ovarian cancer. BRCA1 mainly exerts its protective effects through DNA double-strand break repair. Although not itself [...] Read more.
Background/Objectives: The breast cancer susceptibility gene 1 (BRCA1) is a tumor suppressor gene whose mutations are associated with increased susceptibility to develop breast or ovarian cancer. BRCA1 mainly exerts its protective effects through DNA double-strand break repair. Although not itself a transcriptional factor, BRCA1, through its multiple protein interaction domains, exerts transcriptional coregulation. In addition, BRCA1 expression alters cellular metabolism including inhibition of de novo fatty acid synthesis, changes in cellular bioenergetics, and activation of antioxidant defenses. Some of these actions may contribute to its global oncosuppressive effects. However, the breadth of metabolic pathways reprogrammed by BRCA1 is not fully elucidated. Methods: Breast cancer cells expressing BRCA1 were investigated by multiplatform metabolomics, metabolism-related transcriptomics, and joint metabolomics/transcriptomics data processing techniques, namely two-way orthogonal partial least squares and pathway analysis. Results: Joint analyses revealed the most important metabolites, genes, and pathways of metabolic reprogramming in BRCA1-expressing breast cancer cells. The breadth of metabolic reprogramming included fatty acid synthesis, bioenergetics, HIF-1 signaling pathway, antioxidation, nucleic acid synthesis, and other pathways. Among them, rewiring of glycerophospholipid (including phosphatidylcholine, -serine and -inositol) metabolism and increased arginine metabolism have not been reported yet. Conclusions: Rewired glycerophospholipid and arginine metabolism were identified as components of BRCA1-induced metabolic reprogramming in breast cancer cells. The study helps to identify metabolites that are candidate biomarkers of the BRCA1 genotype and metabolic pathways that can be exploited in targeted therapies. Full article
(This article belongs to the Section Cell Metabolism)
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31 pages, 3977 KiB  
Article
Exploring the Cytokinin Profile of Doliocarpus dentatus (Aubl.) Standl. From Guyana and Its Relationship with Secondary Metabolites: Insights into Potential Therapeutic Benefits
by Ewart A. Smith, Ainsely Lewis, Erin N. Morrison, Kimberly Molina-Bean, Suresh S. Narine and R. J. Neil Emery
Metabolites 2025, 15(8), 533; https://doi.org/10.3390/metabo15080533 - 6 Aug 2025
Viewed by 520
Abstract
Background/Objectives: Possessing red and white ecotypes, and utilized in traditional Guyanese medicine, Doliocarpus dentatus’ red ecotype is preferred locally for its purported superior therapeutic efficacy. Although therapeutic metabolites were detected in D. dentatus previously, phytohormones remain largely unexplored, until now. Cytokinins, [...] Read more.
Background/Objectives: Possessing red and white ecotypes, and utilized in traditional Guyanese medicine, Doliocarpus dentatus’ red ecotype is preferred locally for its purported superior therapeutic efficacy. Although therapeutic metabolites were detected in D. dentatus previously, phytohormones remain largely unexplored, until now. Cytokinins, phytohormones responsible for plant cell division, growth and differentiation, are gaining traction for their therapeutic potential in human health. This study screened and quantified endogenous cytokinins and correlated detected cytokinins with selected secondary metabolites. Methods: Liquid chromatography–mass spectrometry was used to acquire phytohormone and metabolite data. Bioinformatics tools were used to assess untargeted metabolomics datasets via statistical and pathway analyses, and chemical groupings of putative metabolites. Results: In total, 20 of the 35 phytohormones were detected and quantified in both ecotypes, with the red ecotype displaying higher free base and glucoside cytokinin concentrations and exhibited 6.2 times the total CK content when compared to the white ecotype. Pathway analysis revealed flavonoid and monoterpenoid biosynthesis in red and white ecotypes, respectively. Positive correlations between specific cytokinins and alkaloids, and between trans-Zeatin and isopentenyladenosine riboside with phenolic compounds were observed. Conclusions: These results suggest that the red ecotype’s elevated cytokinin levels coupled with flavonoid biosynthesis enrichment support its preference in Guyanese traditional medicine. Full article
(This article belongs to the Section Plant Metabolism)
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Correction
Correction: Mahnashi et al. In-Vitro, In-Vivo, Molecular Docking and ADMET Studies of 2-Substituted 3,7-Dihydroxy-4H-chromen-4-one for Oxidative Stress, Inflammation and Alzheimer’s Disease. Metabolites 2022, 12, 1055
by Mater H. Mahnashi, Mohammed Abdulrahman Alshahrani, Mohammed H. Nahari, Syed Shams ul Hassan, Muhammad Saeed Jan, Muhammad Ayaz, Farhat Ullah, Osama M. Alshehri, Mohammad Ali Alshehri, Umer Rashid and Abdul Sadiq
Metabolites 2025, 15(8), 532; https://doi.org/10.3390/metabo15080532 - 6 Aug 2025
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Abstract
There was an error in the original publication [...] Full article
(This article belongs to the Special Issue Identification and Therapeutic Properties of Secondary Metabolites of Medicinal Plants)
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