Metabolites[JOURNAL]
Sun
200 papers
Screening and Stratification Utility of GDF-15 and FGF-21 in Individuals Evaluated for Suspected Mitochondrial Disease: A Malaysian Cohort Study.
Omar A, Abg Kamaludin DP, Mohamed WAS … +6 more , Nordin FDA, Mohamed R, Razali BH, Ismail I, Hock NL, Jalil JA
Metabolites · 2026 May · PMID 42346354 · Full text
: Early detection of mitochondrial disorders remains challenging due to phenotypic heterogeneity and limited access to definitive molecular diagnostics. Circulating biomarkers such as growth differentiation factor-15 (GD...
: Early detection of mitochondrial disorders remains challenging due to phenotypic heterogeneity and limited access to definitive molecular diagnostics. Circulating biomarkers such as growth differentiation factor-15 (GDF-15) and fibroblast growth factor-21 (FGF-21) have emerged as potential adjunct indicators. This study evaluated the screening and stratification utility of GDF-15 and FGF-21 in individuals assessed for suspected mitochondrial disease. : Archived biological specimens collected between 2016 and 2017 were analysed from 221 individuals stratified into clinically high-risk, screen-positive non-high-risk, post-mortem unexplained death and healthy controls groups. Plasma and fibroblast lysate concentrations of GDF-15 and FGF-21 were quantified using enzyme-linked immunosorbent assays. Biomarker performance was assessed using receiver operating characteristic (ROC) analysis, comparative group analysis and correlation testing across clinically defined referral groups. : Both biomarkers were significantly elevated in clinically high-risk and screen-positive individuals compared with controls. GDF-15 demonstrated better discriminatory performance than FGF-21, with an area under the curve (AUC) of 0.7187 ± 0.0556 versus 0.6301 ± 0.0603. At a threshold of 300 pg/mL, GDF-15 demonstrated high sensitivity with moderate specificity for differentiation between clinically defined high-risk individuals and controls. Correlation analysis showed weak associations between GDF-15 and lactate and ammonia, while FGF-21 correlated modestly with glucose and alkaline phosphatase. A moderate positive correlation was observed between GDF-15 and FGF-21 across the overall cohort. : GDF-15 and, to a lesser extent, FGF-21 may support early screening and stratification of individuals evaluated for suspected mitochondrial disease and assist in prioritising cases for further diagnostic evaluation.
Transcriptomic and Metabolomic Insights into the Enhanced Quality of Seedlings in Sugar-Free Versus Conventional Tissue Culture Systems.
Kang C, Lin T, Wang H … +7 more , Wang Y, Wu D, Duan W, Zhang Z, Zhang C, Chen X, Chen F
Metabolites · 2026 May · PMID 42346353 · Full text
, a high-value medicinal orchid, faces significant challenges in quality standardization during large-scale tissue culture due to a lack of understanding of the underlying molecular mechanisms. This study aimed to compar...
, a high-value medicinal orchid, faces significant challenges in quality standardization during large-scale tissue culture due to a lack of understanding of the underlying molecular mechanisms. This study aimed to compare "Jianlan No.2" plantlets cultured under a conventional tissue culture system (CK) and a sugar-free tissue culture system (TD), to elucidate the phenotypic and molecular basis for quality improvement. A systematic comparison was conducted. Phenotypic traits of plantlets from both systems were measured. Integrated transcriptomic (RNA sequencing) and untargeted metabolomic analyses were employed to identify the molecular differences at the gene expression and metabolite accumulation levels. TD-grown seedlings exhibited significantly superior growth characteristics, including greater plant height, higher rooting rate, and improved transplant survival. Transcriptomic analysis identified 416 differentially expressed genes (DEGs) (44 upregulated, 372 downregulated in TD), which were significantly enriched in pathways related to cell wall organization, apoplast, and photosynthesis. Sixteen key genes were pinpointed as closely associated with seedling growth and metabolic regulation. Metabolomic profiling revealed 502 differentially accumulated metabolites (DAMs), with significant perturbations primarily in phenylpropanoid biosynthesis and terpenoid metabolism. The sugar-free tissue culture system enhances seedling quality by coordinately modulating photosynthetic capacity, carbon metabolism, and the biosynthesis of key secondary metabolites. These findings provide a crucial molecular foundation for optimizing tissue culture protocols and advancing the standardized, high-quality cultivation of this valuable medicinal plant.
Humanin Restores Metabolic Hormone Homeostasis of Leptin, Ghrelin, Irisin and Asprosin in Streptozotocin-Induced Diabetic Mice.
Bulut F, Adam M, Ozgen A … +1 more , Ozcan M
Metabolites · 2026 May · PMID 42346352 · Full text
: Diabetes mellitus is closely associated with mitochondrial dysfunction, which disrupts cellular energy metabolism and perturbs hormonal homeostasis. Humanin (HN), a 24-amino acid peptide encoded within the mitochondria...
: Diabetes mellitus is closely associated with mitochondrial dysfunction, which disrupts cellular energy metabolism and perturbs hormonal homeostasis. Humanin (HN), a 24-amino acid peptide encoded within the mitochondrial genome, has attracted considerable attention due to its cytoprotective and metabolic regulatory properties. Despite its recognized biological potential, the role of HN in coordinating key metabolic hormone networks under diabetic conditions remains poorly understood. This study aimed to investigate the integrative effects of repeated humanin administration on key metabolic hormones leptin, ghrelin, irisin, and asprosin and its potential role in restoring hormonal homeostasis in a streptozotocin (STZ)-induced diabetic mouse model. : Forty male mice were randomly assigned to four groups ( = 10 for each group): control, HN (4 mg/kg/day), STZ (150 mg/kg), and STZ + HN. Humanin was administered intraperitoneally for 15 consecutive days. Serum levels of leptin, asprosin, irisin, and ghrelin were measured using enzyme-linked immunosorbent assay (ELISA), and data were analyzed using one-way ANOVA followed by Tukey's post hoc test. : STZ-induced diabetes markedly disrupted metabolic hormone balance, as indicated by decreased leptin and irisin levels and increased asprosin concentrations. Repeated HN treatment effectively restored leptin levels and suppressed asprosin concentrations, while irisin levels showed a relative increase compared to the STZ animals. In addition, ghrelin levels were significantly elevated in HN-treated diabetic mice compared to untreated STZ animals. : These findings indicate that humanin exerts an integrative, multi-hormonal regulatory effect, supporting the restoration of metabolic and endocrine homeostasis under diabetic conditions.
Probiotics After Metabolic and Bariatric Surgery: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Ezzi MY
Metabolites · 2026 May · PMID 42346351 · Full text
Patients undergoing metabolic and bariatric surgery (MBS) are at risk of micronutrient deficiencies and gut dysbiosis. Probiotics (such as Lactobacillus, Bifidobacterium) have been proposed as adjunct therapy to optimize...
Patients undergoing metabolic and bariatric surgery (MBS) are at risk of micronutrient deficiencies and gut dysbiosis. Probiotics (such as Lactobacillus, Bifidobacterium) have been proposed as adjunct therapy to optimize postoperative outcomes. This review aimed to evaluate the effect of postoperative probiotic supplementation on anthropometric, metabolic, inflammatory, and micronutrient outcomes in MBS patients. : Nine electronic databases were systematically searched, including PubMed, Web of Science, Cochrane Library, Google Scholar, Popline, Global Health Library, Virtual Health Library, New York Academy of Medicine, and OpenGrey, from inception through October 2024. Only randomized controlled trials (RCTs) were included. The Cochrane Collaboration risk-off-bias tool was used for quality assessment. Meta-analyses were performed using Comprehensive Meta-Analysis software version 2. Fixed-effects or random-effects models based on heterogeneity (I threshold: 50%) were applied. Mean differences (MD) and 95% confidence intervals (CI) were calculated for all continuous variables. : Thirteen RCTs encompassing 666 patients (probiotics group: n = 344; control group: n = 322) were included. Incomplete outcome data represented the most prevalent high-risk domain (23%). Probiotic supplementation was associated with significantly improved serum vitamin D (MD: 25.32 nmol/L, 95% CI: 6.96-43.67, = 0.007) and vitamin B12 levels (MD: 39.36 pg/mL, 95% CI: 1.88-76.84, = 0.04). No statistically significant differences were observed in anthropometric outcomes (%EWL, BMI, weight, or waist circumference), lipid profile, glycemic indices, or inflammatory markers (TNF-α, IL-6, CRP). : Postoperative probiotic supplementation may significantly improve vitamin D and B12 levels in patients undergoing MBS, suggesting a supportive role in mitigating micronutrient deficiencies. However, these findings should be interpreted with caution due to substantial heterogeneity across studies. Probiotics did not significantly affect weight loss, metabolic parameters, or inflammatory markers. Clinicians may consider probiotics as an adjunct strategy to support micronutrient status in at-risk postoperative patients. Large-scale, strain-specific trials incorporating standardized dietary control and microbiome profiling are warranted.
Acute Capillary Plasma Biomarker, Neuromuscular, and Perceptual Responses to Standardised Soccer Match Play in Elite Players: A Descriptive Study of Asynchronous Multi-Domain Recovery.
Du L, Xiao J, Li C … +7 more , Liu S, Jiang Y, Dou Y, Zhao H, Zhong W, Zhao K, Liu C
Metabolites · 2026 May · PMID 42346350 · Full text
BACKGROUND: Soccer match play induces substantial mechanical, metabolic, inflammatory, and neuromuscular stress, yet post-match monitoring in applied settings often relies on isolated markers, venous sampling, or limited...
BACKGROUND: Soccer match play induces substantial mechanical, metabolic, inflammatory, and neuromuscular stress, yet post-match monitoring in applied settings often relies on isolated markers, venous sampling, or limited time points. This observational repeated-measures study aimed to describe whether capillary-derived biomarkers, neuromuscular performance, and perceptual measures showed asynchronous recovery during the first 48 h after a standardised soccer match in elite players. METHODS: Twenty-two elite male outfield soccer players completed a standardised 90 min match. Capillary blood biomarkers, countermovement jump (CMJ), 20 m sprint performance, maximal voluntary contraction (MVC), and delayed onset muscle soreness (DOMS) were assessed before the match, immediately post-match, and at 24 and 48 h post-match. Time effects were analysed using repeated-measures mixed-effects models, and associations between biochemical and functional responses were examined descriptively. RESULTS: Match play induced clear but domain-specific disturbances. IL-6 and cortisol rose rapidly immediately post-match, whereas hsCRP, CK, LDH, myoglobin, and DOMS showed delayed peaks during early recovery. CK, LDH, myoglobin, and soreness remained above baseline at 48 h. CMJ and sprint performance were impaired after the match but largely recovered by 48 h, whereas MVC showed its greatest decrement at 24 h. Exploratory associations indicated that larger muscle damage responses tended to co-occur with greater strength and jump decrements and higher soreness, but these analyses were not causal. CONCLUSIONS: Recovery after a standardised elite soccer match was multidimensional and non-synchronous across physiological, neuromuscular, and perceptual domains. A capillary-based, multi-domain assessment strategy may provide a feasible descriptive perspective for field-based observation of post-match fatigue.
Metabolomics Analysis of Aged Garlic Extract for the Identification of Novel Compounds.
Nakamoto M, Nishimura T, Ohtani M … +1 more , Matsutomo T
Metabolites · 2026 May · PMID 42346349 · Full text
BACKGROUND/OBJECTIVES: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory...
BACKGROUND/OBJECTIVES: Aged garlic extract (AGE), produced by aging raw garlic in an aqueous ethanol solution for over 10 months, exhibits multiple pharmacological activities, including antioxidant and anti-inflammatory effects. However, because AGE has a complex composition and many constituents remain insufficiently characterized, the chemical basis underlying its broad activities is not fully understood. This study aimed to investigate these previously overlooked compounds in AGE to better understand its chemical complexity. METHODS: AGE was fractionated using bioactivity assays to select target fractions for detailed chemical analysis. Metabolomics profiling was performed using liquid chromatography-mass spectrometry (LC-MS). Compounds were tentatively identified through database matching, fragmentation pattern analysis, and comparison with authentic standards. RESULTS: Thirteen compounds not previously reported in AGE were tentatively identified. Citric acid was present at high levels. Citrulline and galacturonic acid were detected in AGE but not in raw garlic, suggesting that they are formed during the aging process. Trigonelline was detected and tentatively identified in the AGE sample used in this study. The remaining compounds included choline, 5-oxoproline, malic acid, gluconic acid, adenine, succinic acid, mucic acid, pipecolinic acid, and caffeic acid. These compounds may contribute to the diverse biological activities of AGE. CONCLUSIONS: These findings expand the chemical characterization of AGE and provide a foundation for understanding its broad pharmacological activities. They may also support future studies on functional food development and the health benefits of AGE.
Integrating Sensory Evaluation and Metabolomics to Reveal the Metabolic Basis of Taste and Flesh Color in Melon ( L.).
Zhou Y, Li B, He W … +9 more , Liu F, Fan Y, Du J, Cui X, Lian W, Shen Q, Wang Y, Zhao Z, Wang C
Metabolites · 2026 May · PMID 42346348 · Full text
: The sensory quality of melon ( L.) is determined by the complex interplay of metabolites within the fruit. However, the underlying metabolic mechanisms based on consumer sensory experience remain underexplored. : Senso...
: The sensory quality of melon ( L.) is determined by the complex interplay of metabolites within the fruit. However, the underlying metabolic mechanisms based on consumer sensory experience remain underexplored. : Sensory evaluation was conducted on twelve melon cultivars, recording flesh color and quantitatively scoring acidity, sweetness, firmness, and aroma intensity. Based on the sensory results, eight cultivars were selected to establish two contrasting groups: sweet-type vs. acidic-type and orange-fleshed vs. green-fleshed. Untargeted metabolomics (UPLC-QTOF-MS) was then performed to analyze the samples, and differential metabolites were screened using OPLS-DA combined with univariate analysis. : Pathway enrichment analysis revealed that the key distinction between sweet and acidic taste profiles was associated with the specific accumulation of citric acid within the tricarboxylic acid (TCA) cycle in the acidic-type group. Regarding flesh color, the orange-fleshed group was enriched with carotenoid derivatives like β-citraurinene and the oxidized tocopherol product α-tocopherolquinone, whereas the green-fleshed group mainly accumulated phytol, a chlorophyll degradation product, along with more abundant terpenoids. : By integrating sensory phenotyping with metabolomic analysis, this study identified key differential metabolites and candidate pathways associated with taste and color in melon, providing metabolic insights and data resources for quality evaluation and regulation.
Bile Acids and the Gut-X Axis: TCM-Mediated Systemic Protection and Therapeutic Opportunities for Multi-Organ Diseases.
He J, Qin L, Sun X
Metabolites · 2026 May · PMID 42346347 · Full text
The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut-X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptor...
The gut microbiota regulates host physiology and drives extraintestinal diseases through the gut-X axis. Bile acids (BAs) function as key mediators of this interorgan crosstalk by activating nuclear and membrane receptors (FXR, TGR5, PXR, VDR). Traditional Chinese Medicine (TCM) demonstrates efficacy across multiple organ systems through multi-component formulations. This narrative review synthesizes evidence from preclinical and clinical studies supporting that TCM exerts systemic protection via strategic modulation of the microbiota-BA-host receptor axis, which functions as a core regulatory circuit within a larger network of microbial metabolites. Mechanistically, representative TCM formulas remodel gut microbial ecology and reinforce intestinal barrier integrity, leading to optimized BA profiles. These favorable BA signatures engage tissue-specific receptor signaling to resolve inflammation, mitigate fibrosis, and restore metabolic homeostasis across the gut-heart, gut-kidney, gut-liver, gut-bone, and gut-endocrine axes. Support for this causal relationship is provided by microbiota depletion, fecal transplantation, and multi-omics studies, collectively suggesting that TCM's benefits are microbiota-dependent and at least partially BA-mediated. Moreover, context-dependent modulation of BA receptors, such as differential regulation of FXR, enables TCM to achieve pathology-specific outcomes. Current evidence is derived predominantly from preclinical models, and clinical data remain lacking. Nonetheless, the microbiota-BA-organ axis thus provides a potential framework for understanding TCM's systemic actions and establishes a molecular basis for developing microbiome-informed precision therapeutics. Future directions include patient stratification and precision intervention design inspired by TCM's ecological modulation strategies.
Enhanced Synthesis of Polyphenols and Terpenes by UV-A Irradiation in Leaves.
Li S, Zhang Z, Yang L … +3 more , Wang H, Gu H, Liu J
Metabolites · 2026 May · PMID 42346346 · Full text
Secondary metabolites not only constitute the material basis for plant responses to multiple environmental stresses but are also extensively utilized in the pharmaceutical industry. In the present work, we investigated...
Secondary metabolites not only constitute the material basis for plant responses to multiple environmental stresses but are also extensively utilized in the pharmaceutical industry. In the present work, we investigated the metabolic response of to UV-A irradiation through transcriptomic and metabolomic analyses. After 16 h of UV-A treatment with an intensity of 2.5 μmol m s and 8 h of dark cultivation, a total of 4343 differentially expressed genes were identified, most of which were associated with fatty acid metabolism, biosynthesis of secondary metabolites, and ribosome. Of the 1959 metabolites detected in samples exposed to a 16/8 h UV-A/dark cycle for 6 days, a total of 223 differentially accumulated metabolites were identified and classified into 12 subgroups, with phenolic acids and flavonoids representing the largest subgroups. Comprehensive analyses indicated that polyphenols and terpenes play critical roles in the adaptation of to UV-A irradiation. The phytohormone methyl jasmonate was identified as a key regulator of the enhanced synthesis of these secondary metabolites, through activation of transcription factors from the MYB and bHLH families. This study deepens our understanding of secondary metabolic regulation in response to UV-A stress and provides a simple and reliable method to promote the accumulation of specific secondary metabolites in species.
Untargeted Metabolomics and Metabolite-Gene Network Analysis Predict NF-κB Inhibition in Artemisian B-Treated Triple-Negative Breast Cancer Cells.
Shan S, Hu Z, Xue G … +4 more , Yao P, Du P, Gan R, Wang J
Metabolites · 2026 May · PMID 42346345 · Full text
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived...
Triple-negative breast cancer (TNBC) remains a formidable clinical challenge due to the scarcity of targeted therapies and profound metabolic heterogeneity. Although Artemisian B, a dimeric sesquiterpene lactone derived from Artemisia argyi, exhibits potent antiproliferative activity, its comprehensive metabolic footprint and the translation of these perturbations into downstream signaling regulation remain poorly characterized. To address this gap, we employed an integrative analytical framework combining untargeted metabolomics, topology-guided metabolite-gene network mapping, and parallel experimental validation in MDA-MB-231 cells. This workflow systematically profiled cellular phenotypes, global metabolic reprogramming, and key signaling nodes, enabling the prioritization of high-confidence mechanistic links between metabolic alterations and signal transduction. Artemisian B dose-dependently suppressed TNBC cell viability (IC = 12.12 μM) and triggered mitochondrial apoptosis, characterized by Bax upregulation, Bcl-2 downregulation, and caspase-9/3 activation. Untargeted metabolomics identified 129 significantly altered metabolites, reflecting extensive dysregulation across lipid peroxidation, bioenergetics, and nucleotide metabolism. Topological analysis of the metabolite-gene network identified the NF-κB pathway as a highly interconnected hub within this perturbed landscape. Parallel experimental validation corroborated this prediction, demonstrating that Artemisian B consistently suppressed the phosphorylation of IKKα/β, IκBα, and p65, while markedly attenuating p65 nuclear translocation. Artemisian B induces TNBC apoptosis through extensive metabolic reprogramming coupled with concurrent inhibition of NF-κB signaling. By seamlessly integrating untargeted metabolomics with network topology, our framework not only successfully bridges metabolic perturbations with signaling outcomes but also establishes a versatile, dual-perspective strategy applicable to both biochemical reaction networks and signal transduction pathways. This approach provides a robust predictive paradigm for decoding the multi-target pharmacological mechanisms of natural products.
Lean Mass and Musculoskeletal Preservation in GLP-1-Based Obesity Treatment: Nutrition, Exercise, Supplementation, and Monitoring Strategies.
Šantić R, Martinović L, Pavlović N … +5 more , Rušić D, Kumrić M, Martinović D, Tičinović Kurir T, Božić J
Metabolites · 2026 May · PMID 42346344 · Full text
GLP-1-based obesity pharmacotherapy has shifted clinical attention from the magnitude of weight loss to the quality of weight loss. This review evaluates whether body composition changes during treatment with GLP-1-based...
GLP-1-based obesity pharmacotherapy has shifted clinical attention from the magnitude of weight loss to the quality of weight loss. This review evaluates whether body composition changes during treatment with GLP-1-based agents represent clinically meaningful muscle loss and identifies nutrition, supplementation, exercise, and monitoring strategies that may help preserve lean mass, function, bone health, and nutritional adequacy. A comprehensive narrative review was performed using focused searches of PubMed, publisher-hosted journal platforms, and reference lists of key primary studies and recent evidence syntheses through March and May 2026. Evidence was organized around body composition, muscle quality and function, dietary protein and micronutrient adequacy, exercise, supplementation, bioelectrical impedance analysis, imaging, and emerging biomarkers. Semaglutide and tirzepatide preferentially reduce fat mass, including visceral and ectopic adiposity, while producing smaller but consistent reductions in lean mass or lean soft tissue. However, DXA-derived lean mass and BIA-derived fat-free mass are not equivalent to skeletal muscle, and lean tissue loss does not necessarily indicate impaired strength or physical performance. The most defensible supportive care model combines food-first nutritional counseling, adequate protein intake, structured resistance exercise, management of gastrointestinal adverse effects, and risk-based monitoring of micronutrient inadequacy. Protein supplementation and nutritionally complete meal replacements may be useful when intake is insufficient, whereas creatine, essential amino acids or leucine, beta-hydroxy-beta-methylbutyrate, fiber, probiotics, omega-3 fatty acids, and multi-ingredient products remain adjunctive options supported mainly by indirect or phenotype-specific evidence. Future GLP-1 trials and clinical care should move beyond body weight and total lean mass toward integrated assessment of muscle quantity, muscle quality, function, bone, and nutritional adequacy, and standardized BIA-based clinical monitoring where advanced imaging is not feasible.
Plasma Lipidomic Remodeling in Behçet's Disease Reveals Alterations Associated with Vascular Involvement.
Koçak E, Yücel Ç, Kablan SE … +4 more , Sertoğlu E, Özgürtaş T, Nemutlu E, Omma A
Metabolites · 2026 May · PMID 42346343 · Full text
: Behçet's disease (BD) is a chronic multisystem inflammatory disorder in which vascular involvement represents a major cause of morbidity and mortality. However, the molecular mechanisms underlying vascular involvement...
: Behçet's disease (BD) is a chronic multisystem inflammatory disorder in which vascular involvement represents a major cause of morbidity and mortality. However, the molecular mechanisms underlying vascular involvement remain poorly understood. Lipidomics offers a powerful approach to investigate disease-associated metabolic alterations at the lipid level. : Plasma lipidomic profiles were analyzed in 48 patients with BD, including 18 with vascular involvement, and 40 age- and sex-matched healthy controls. Lipids were extracted using a chloroform-methanol-based protocol and analyzed by LC-qTOF-MS. Data processing and lipid annotation were performed using MS-DIAL. Multivariate and univariate statistical analyses, together with class-based KEGG pathway mapping, were applied to evaluate lipidomic alterations. : Principal component analysis demonstrated a clear separation between BD patients and healthy controls, indicating extensive lipidomic remodeling. BD was associated with significant alterations in phosphatidylcholines, sphingomyelins, diacylglycerols, and triacylglycerols, reflecting coordinated changes in membrane structure, lipid-mediated signaling, and energy metabolism. Pathway analysis further supported the involvement of glycerophospholipid, glycerolipid, and phosphatidylinositol-related metabolic pathways. Comparison between BD patients with and without vascular involvement revealed no major global lipidomic shift; however, specific lipid species showed consistent alterations. Two phosphatidylcholine species (PC 33:2 and ether-linked PC 31:4e) were decreased, whereas one triacylglycerol species (TAG 58:2) was increased in patients with vascular involvement. : These findings suggest that BD is characterized by coordinated lipidomic reprogramming involving membrane remodeling, inflammatory signaling, and metabolic adaptation. Vascular involvement appears to be associated with subtle, lipid-specific alterations rather than a global lipidomic shift, highlighting potential molecular features of disease progression.
Multiple Reaction Monitoring (MRM)-Based Targeted Kidney Metabolite Profiling of a Mouse Model of Hyperuricemia.
Li H, Tang T, Zhang Q … +7 more , Song T, Zhao Z, Zhu L, Chen Q, Zhang H, Zhang Y, Kong J
Metabolites · 2026 May · PMID 42346342 · Full text
Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underl...
Chronic urate nephropathy (CUN), also referred to as gouty nephropathy, represents a severe renal disease primarily precipitated by long-term hyperuricemia (HUA) and gout. However, the precise molecular mechanisms underlying its pathogenesis remain poorly understood. The present study was designed to explore these mechanisms from the perspective of targeted metabolomics. The HUA mice constructed by urate oxidase (Uox) gene knockout (KO) and their corresponding wild-type controls were employed for the present study. Serum clinical biochemical parameters were determined, and renal histopathological changes were evaluated using hematoxylin-eosin (HE) staining and Masson's trichrome staining. A targeted metabolomic strategy based on multiple reaction monitoring (MRM) was utilized to profile the renal metabolic landscape of Uox-KO mice, and potential metabolic biomarkers for CUN were identified via multivariate data analysis. Clinical biochemical analysis revealed a significant elevation in serum uric acid, creatinine, and urea nitrogen levels in Uox-KO mice compared with control mice. Histopathological observations confirmed a typical CUN phenotype in Uox-KO mice, characterized by renal tubular vacuolar degeneration and dilatation, desquamation of tubular epithelial cells into the lumen, neutrophil infiltration, glomerular crowding, and renal interstitial fibrosis. Metabolomic analysis identified a total of 291 differentially regulated metabolites in Uox-KO mice relative to control animals. These perturbed metabolites were involved in multiple key biochemical pathways, including amino acid biosynthesis, ABC transporter signaling pathway, purine metabolism, aminoacyl-tRNA biosynthesis, protein digestion and absorption, glycerophospholipid metabolism, and serotonergic synaptic transmission. Notably, pathological parameters, including biochemical measurements and histological observations, were significantly correlated with key differential metabolites associated with CUN progression. Furthermore, eleven differential metabolites (pyroglutamic acid, fructose, riboflavin, dimethyl-L-arginine, glucaric acid, indoxyl sulfate, palmitoylethanolamide, trimethylamine N-oxide, 3-hydroxyanthranilic acid, spermidine, and hippuric acid) were identified as potential metabolic biomarkers for the diagnosis and prognosis of CUN. These findings illustrate that targeted tissue metabolomic analysis constitutes a powerful tool for deciphering the molecular mechanisms of diseases, thus offering novel insights into the pathogenesis of CUN.
Integrating Metabolomics and Gut Microbiota to Reveal the Therapeutic Effect of Flos Against Respiratory Syncytial Virus.
Wang Y, Gao Y, Liang Y … +2 more , Zhao B, Liu L
Metabolites · 2026 May · PMID 42346341 · Full text
: This study aimed to investigate the therapeutic effects and potential mechanisms of Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut mi...
: This study aimed to investigate the therapeutic effects and potential mechanisms of Flos (Jinyinhua, JYH) against respiratory syncytial virus (RSV)-induced pneumonia by integrating lung tissue metabolomics with gut microbiota analysis. : An RSV-infected mouse model was established through intranasal inoculation. Lung pathological changes, viral RNA levels, lung index, and inflammatory cytokine levels were evaluated. Untargeted metabolomics and 16S rRNA gene amplicon sequencing were performed to characterize JYH-mediated alterations in pulmonary metabolites and the gut microbiota. Spearman correlation analysis was conducted to assess associations between differentially abundant bacterial genera and significantly altered metabolites. : JYH alleviated RSV-induced pulmonary histopathological injury, reduced viral RNA levels, decreased lung index and interleukin-6 (IL-6) levels, and increased interferon-γ (IFN-γ) levels. Metabolomic profiling identified 46 differential metabolites, among which 26 showed a reversal trend following JYH administration. These metabolites were mainly enriched in pathways associated with the synaptic vesicle cycle, lysosomal function, and Forkhead box O (FoxO) signaling. Gut microbiota analysis showed that JYH increased microbial richness and diversity, whereas KEGG-based functional prediction indicated that the differentially abundant taxa were primarily involved in amino acid, carbohydrate, and nucleotide metabolism. Moreover, correlation analysis revealed significant associations between key bacterial genera, including , , and , and differential metabolites such as pyridoxamine, uridine monophosphate (UMP), and argininosuccinic acid. : JYH may protect against RSV-induced pneumonia by restoring pulmonary metabolic homeostasis and modulating gut microbiota composition. These findings provide new insights into metabolite-microbiota interactions underlying the anti-RSV activity of JYH.
Impact of Oil Spill Stress on Amino Acid Abundance in .
Xue D, Su H, Yu J … +3 more , Yang X, Li N, Chen S
Metabolites · 2026 May · PMID 42346340 · Full text
: Oil spills have dramatically increased, causing significant damage and pollution to marine ecosystems. The entry of petroleum hydrocarbons into the ocean may lead to the occurrence of harmful algal blooms (HABs). The a...
: Oil spills have dramatically increased, causing significant damage and pollution to marine ecosystems. The entry of petroleum hydrocarbons into the ocean may lead to the occurrence of harmful algal blooms (HABs). The amino acid changes in harmful algae after oil spills remain unclear. : In order to study the effect of oil spills on the amino acid mechanism of typical causative species, the composition and relative abundance of amino acids in were investigated under different water accommodated fractions (WAFs) of 180# fuel oil. : Random forest prediction of polycyclic aromatic hydrocarbon toxicity to microalgae identified pyrene, benzo[k]fluoranthene, and fluoranthene as significant contributors. A total of 16 species of amino acids were detected in , among which alanine, proline, aspartic acid, cysteine, lysine, and histidine were the predominant ones. As the concentration of the WAF increased, alanine abundance decreased significantly, indicating that the WAF disrupted the metabolic balance of alanine, with the degree of interference being positively correlated with exposure concentration. With the increase in culture time, the abundance of cysteine increased at 1%, 3%, and 5% WAFs, whereas the cysteine increased and then decreased at 7% and 10% WAFs. The abundance of aspartic acid and lysine showed no obvious pattern with culture time under WAF stress. Significant increases in the abundance of proline and histidine were observed in the WAF treatments. : This study investigated the impact of oil spill pressure on the amino acid content of harmful algae, providing a scientific basis for understanding the potential impact of oil spills on the occurrence of HABs.
Metabolic Responses of Grapevine Leaves to Grapevine Leafroll-Associated Virus 3 Infection.
Tomaz I, Preiner D, Buljević N … +1 more , Vončina D
Metabolites · 2026 May · PMID 42346339 · Full text
: Grapevine leafroll-associated virus 3 (GLRaV-3) is a severe phloem-limited grapevine virus, meaning it is restricted to sugar-transporting vascular tissue, which helps explain its strong effects on leaf physiology and...
: Grapevine leafroll-associated virus 3 (GLRaV-3) is a severe phloem-limited grapevine virus, meaning it is restricted to sugar-transporting vascular tissue, which helps explain its strong effects on leaf physiology and carbon transport. However, its impact on leaf oxidative status, phenolic composition, and volatile organic compounds (VOCs) remains insufficiently characterized. : Virus-free and GLRaV-3-infected grapevine leaves were analyzed for photosynthetic pigments, oxidative stress markers, phenolic compounds, and VOCs using spectrophotometric assays, HPLC-DAD/FLD, and SPME-Arrow-GC/MS. Data were evaluated using one-way ANOVA, multiple testing correction, principal component analysis (PCA), and exploratory partial least squares-discriminant analysis (PLS-DA). : GLRaV-3-infected leaves showed lower chlorophyll a (576.75 vs. 657.85 mg 100 g DW), chlorophyll b (282.96 vs. 314.05 mg 100 g DW), and total carotenoids (125.89 vs. 154.65 mg 100 g DW), but higher malondialdehyde (11.91 vs. 8.73 nmol g DW), HO (0.36 vs. 0.25 μmol g DW), and proline (8.83 vs. 7.98 μmol g DW). Phenolic profiling showed increased levels of several flavonols and hydroxycinnamic acids, including kaempferol-3-O-glucuronide (2.81-fold), myricetin-3-O-glucoside (1.75-fold), quercetin-3-O-glucuronide (1.48-fold), and caffeic acid (1.30-fold). VOC profiling revealed higher relative abundances of several green leaf volatile-related compounds and methyl salicylate, including 1-methoxy-2-propanol (1.85-fold), 1-penten-3-ol (1.58-fold), hexanal (1.42-fold), and methyl salicylate (1.37-fold). PCA summarized treatment-related differences, with the first two components explaining 63.73% of phenolic and 74.09% of VOC variability, while exploratory PLS-DA/VIP analysis further supported the identification of treatment-associated discriminant metabolic features. : GLRaV-3 infection is associated with reduced pigment content, increased oxidative stress markers, and coordinated changes in phenolic and VOC profiles. These metabolite changes provide insight into grapevine responses to viral infection and highlight GLRaV-3-associated metabolic features for future targeted studies of grapevine leafroll disease.
Detection of Nitazenes (2-Benzylbenzimidazoles)-Novel Synthetic Opioids in Coronial Casework in Victoria, Australia.
Scully L, Castle JW, Di Rago M … +5 more , de Boer HH, Schumann J, Crump K, Glowacki L, Gerostamoulos D
Metabolites · 2026 May · PMID 42346338 · Full text
: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to th...
: The 2-benzylbenzimidazoles or nitazenes are an evolving class of highly potent mu-opioid receptor agonists. Nitazenes were originally developed in the late 1950s for pharmaceutical use as analgesics; however, due to their extreme potency and the risk of adverse health outcomes, pharmaceutical research was discontinued. Since 2019, nitazenes have emerged as illicit drugs of abuse, causing significant concern. From 2021, they have been detected in both coronial and clinical casework in Victoria, Australia. This study examined nitazene-related coronial casework in Victoria from 2021 to 2025 to explore the trends and characteristics of nitazene-related deaths. : Relevant cases were identified from the Victorian Institute of Forensic Medicine's (VIFM's) case management system. Data were collated and analysed from all coronial cases where a nitazene was detected by a toxicological analysis between 1 January 2021 and 31 December 2025. Trend comparisons were made with nitazene detections reported in other countries. : Nitazenes were detected in 23 deaths from a total of approximately 33,108 coronial cases admitted to the VIFM for investigation over the time period. The age range was 17-45 years, with a median of 32 and with 87% of the deaths being male. The nitazenes detected were protonitazene ( = 14), metonitazene ( = 5), isotonitazene ( = 2), -pyrrolidino etonitazene ( = 2), -desethyl isotonitazene ( = 1), methylenedioxynitazene ( = 1) and etodesnitazene ( = 1). Two cases contained more than one nitazene; both involved protonitazene, one involved metonitazene, and the other involved -desethyl isotonitazene and methylenedioxynitazene. The timeline of detection of these nitazenes displays similarities with emergence trends in other countries. The nitazene concentrations ranged from 0.1 to 33 ng/mL. Broad polydrug usage was evident in all cases, with other drugs co-detected in the blood including stimulants (particularly, methylamphetamine (48%) and cocaine (44%)) as well as pharmaceutical benzodiazepines (43%) and pharmaceutical opioids (22%), and 13% had 6-monoacetylmorphine detected in either blood or urine. Novel benzodiazepines (39%) were also common, including bromazolam, which was co-detected in 35% of cases. Nineteen deaths were attributed solely to nitazene-related mixed-drug toxicity, while the remaining four cases were attributed to cardiac- and pulmonary-related disease, with polydrug use deemed a contributing factor. : This novel case series adds comprehensive toxicological information to the body of evidence reinforcing the high risk of harm associated with the use of nitazenes. It is imperative that toxicology services continue to monitor for nitazenes to promote community awareness against nitazene-related harm.
Chemical Structure Representation Standardization Is Needed to Generalize Metabolite-Pathway Involvement Prediction Across KEGG, Reactome, and MetaCyc Knowledgebases.
Huckvale ED, Moseley HNB
Metabolites · 2026 May · PMID 42346337 · Full text
: Due to the utility of knowing the pathway involvement of metabolites detected in biological experiments, knowledgebases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and MetaCyc have annotated c...
: Due to the utility of knowing the pathway involvement of metabolites detected in biological experiments, knowledgebases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and MetaCyc have annotated compound entries to specific pathways defined by the knowledgebase. However, these compound-pathway annotations are largely incomplete and are costly to obtain experimentally or curate from published scientific literature. This metabolite-pathway annotation incompleteness problem is amenable to machine learning (ML)-based solutions. But to date, no machine learning model has been trained on all three knowledgebases to maximize its performance and robustness. This may be due to inconsistencies in chemical structure representation that can confuse a model and greatly reduce generalizability. : We constructed a new training dataset with roughly 50,000,000 entries using compound-pathway annotations derived from KEGG, Reactome, and MetaCyc. We trained and tested a multitask classification, graph convolutional neural network-like model that classifies compound involvement with 8056 pathways that have unique pathway representations, based on annotated compound chemical structures represented with chemical substructure features. While the initial dataset contained inconsistencies in chemical structure representations across knowledgebases, we alleviated this issue by standardizing chemical structure representation using InChI (IUPAC International Chemical Identifier) canonicalization. We compared the performance of the non-standardized versus the standardized dataset and quantified their generalizability by comparing training set compounds to their knowledgebase cross-references. : While the non-standardized dataset scored a mean Matthews correlation coefficient (MCC) of 0.8725 ± 0.0064, the standardized dataset scored an MCC of 0.9036 ± 0.0033. When comparing model generalizability, the non-standardized chemical structure representations had a huge 0.2687 drop in mean MCC, while the standardized chemical structure representations only had a 0.0384 drop in mean MCC. : We constructed the largest ML-ready dataset for predicting compound-pathway involvement to date. Next, we constructed, trained, and evaluated the highest performing ML model capable of predicting the highest number of pathway annotations to date. We discovered that standardizing chemical structure representation is an essential step when predicting novel chemical structures.
Mendelian Randomization Analysis of Systemic Iron Status and Risk of Metabolic Dysfunction-Associated Steatotic Liver Disease.
Yue W, Yang Y, Ma J … +4 more , Zhang J, Wang X, Min J, Wang F
Metabolites · 2026 May · PMID 42346336 · Full text
: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global public health crisis, progressing to hepatic cirrhosis and hepatocellular carcinoma. This study investigated the causal role of systemic iron...
: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a global public health crisis, progressing to hepatic cirrhosis and hepatocellular carcinoma. This study investigated the causal role of systemic iron status in MASLD progression. : A two-sample Mendelian randomization (MR) design was implemented, with genetic variants serving as instrumental variables for four core systemic iron biomarkers. Outcome data for hepatic steatosis (8785 cases; 912,105 controls) and hepatic fibrosis/cirrhosis (3798 cases; 904,599 controls) were extracted from the FinnGen and UK Biobank databases. Multiple complementary MR methodologies and three instrumental variable selection strategies were applied to ensure robust causal inference. : Genetically predicted higher serum iron (odds ratio, OR: 1.42, 95% confidence interval, 95% CI: 1.34, 1.50), ferritin (OR: 1.84, 95% CI: 1.55, 2.18), and transferrin saturation (TfSat, OR: 1.24, 95% CI: 1.19, 1.30), together with lower total iron-binding capacity (TIBC, OR: 0.81, 95% CI: 0.77, 0.85), were significantly associated with increased hepatic steatosis risk ( < 0.00625). Similar associations were observed for hepatic fibrosis/cirrhosis: serum iron (OR: 1.66, 95% CI: 1.29, 2.14), ferritin (OR: 2.52, 95% CI: 1.52, 4.18), TfSat (OR: 1.40, 95% CI: 1.19, 1.63), and reduced TIBC (OR: 0.70, 95% CI: 0.60, 0.81). MR-Bayesian model averaging prioritized serum iron (MIP: 0.85, θ^MACE: 0.295; PP: 0.725; θ^λ: 0.344) as the top-ranked factors for steatosis and TIBC (MIP: 0.604, θ^MACE: -0.240; PP: 0.476, θ^λ: -0.358) for fibrosis/cirrhosis. : Elevated systemic iron status causally drives MASLD onset and progression, highlighting iron homeostasis and ferroptosis as potential targets for prevention and clinical management.
Mapping Spatiotemporal Metabolic Perturbations in Alloxan-Induced Diabetic Rat Kidneys Using Spatial Metabolomics and Proteomic Integration.
Lan T, Liu C, Zhang X … +4 more , Zhang X, Liu Y, Shao W, Wang Z
Metabolites · 2026 May · PMID 42346335 · Full text
Diabetic nephropathy (DN) is characterized by complex and region-specific metabolic dysregulation that is not captured by conventional biomarkers. However, the spatiotemporal organization of metabolic alterations across...
Diabetic nephropathy (DN) is characterized by complex and region-specific metabolic dysregulation that is not captured by conventional biomarkers. However, the spatiotemporal organization of metabolic alterations across renal compartments in type 1 diabetes remains poorly understood. In this study, spatial metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was applied to investigate metabolic alterations in kidney tissues from alloxan-induced diabetic rats at 4 and 8 weeks post-induction. Complementary LC-MS/MS metabolite profiling and label-free proteomic analysis were performed to support pathway interpretation. Spatial metabolomics revealed pronounced region- and time-dependent metabolic reprogramming in diabetic kidneys. Early-stage (DN-4w) changes were characterized by elevated glucose and activation of glucose-associated pathways, including the polyol pathway, accompanied by accumulation of acylcarnitines and lipid intermediates, indicating metabolic substrate overload. At later stages (DN-8w), glucose and related metabolites declined, reflecting impaired metabolic capacity and mitochondrial dysfunction. Broad remodeling of lipid metabolism, including glycerophospholipids, fatty acids, and hexosylceramide, was observed, along with dysregulation of amino acid metabolism and redox-related pathways. These alterations exhibited clear regional heterogeneity across renal cortex and medulla, highlighting compartment-specific metabolic vulnerability. This study provides a comprehensive spatial characterization of metabolic perturbations during DN progression, revealing coordinated alterations in glucose utilization, lipid metabolism, and mitochondrial function. The findings demonstrate the value of spatial metabolomics in uncovering region-specific metabolic mechanisms and provide new insights into the pathogenesis of diabetic nephropathy.
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