Metabolites[JOURNAL]
Sun
200 papers
Integrated Metabolomics and Transcriptomics Reveal the Influence of Natural and Cultivation-Managed Habitats on Metabolic Divergence and Flavonoid Enrichment in .
Wang E, Gao W, Wang P … +1 more , Wang X
Metabolites · 2026 Apr · PMID 42188003 · Full text
: Environmental conditions in natural and cultivation-managed habitats strongly influence plant physiology and medicinal quality. However, the molecular mechanisms underlying metabolic differentiation in remain poorly u...
: Environmental conditions in natural and cultivation-managed habitats strongly influence plant physiology and medicinal quality. However, the molecular mechanisms underlying metabolic differentiation in remain poorly understood. This study aimed to elucidate the metabolic and transcriptional differences between wild and cultivated and to identify the regulatory mechanisms driving habitat-associated variation in metabolite profiles. : We applied integrated non-targeted metabolomics and transcriptomics to compare metabolic profiles and gene expression in the leaves and stems of 15-month-old wild and cultivated plants. Gene-metabolite correlation analysis was performed to identify coordinated correlation networks associated with key biosynthetic pathways. : Our analyses revealed clear differences in metabolite composition and transcriptional patterns between habitat types, suggesting distinct strategies of metabolic resource allocation. Wild plants showed significant enrichment of amino acids and other primary metabolites, whereas cultivated plants accumulated higher levels of flavonoids. Gene-metabolite correlation analysis indicated that multiple flavonoid metabolites were closely associated with key structural genes, including , , and , forming a tightly connected correlation network. In addition, several transcription factor families, including MYB, bHLH, WRKY, and AP2/ERF, showed strong correlations with genes involved in the flavonoid pathway, suggesting that flavonoid accumulation in cultivated plants may be associated with coordinated transcriptional control. : Taken together, these findings suggest that habitat conditions are associated with differences in metabolic networks and resource allocation in . This work provides new insight into the metabolic plasticity of this medicinal plant and highlights potential factors associated with molecular mechanisms that may contribute to variation in medicinal quality.
Spatially Resolved Metabolomic Profiling Reveals Progression-Associated Metabolic Reprogramming in Colorectal Liver Metastasis.
Zhu Y, Cai Y, Wang Q … +6 more , Guo H, Xie Q, Xiang Y, Yu S, Wu B, Qiu L
Metabolites · 2026 Apr · PMID 42188002 · Full text
: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity com...
: Colorectal cancer (CRC) is a leading cause of cancer-related mortality, with colorectal liver metastasis (CRLM) being the major determinant of poor prognosis. Tumor metabolic reprogramming and spatial heterogeneity complicate biomarker discovery and clinical management. This study aimed to characterize the spatial metabolomic landscape of CRC and identify progression-associated metabolic alterations and potential metabolic signatures for liver metastasis. : A total of 23 tissue samples were collected from patients with CRC, with and without liver metastasis. Air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to map the spatial metabolite distributions. Region-of-interest analysis guided by histopathology enabled comparative metabolomic profiling across different tissue types. Multivariate statistical analysis, pathway enrichment, and receiver operating characteristic (ROC) curve analyses were performed to identify key metabolic alterations and evaluate potential biomarker performance. : Distinct spatial metabolomic profiles were observed across normal mucosa, primary tumors, liver metastases, and normal liver tissues. In primary colorectal tumors, amino acid, purine, and choline metabolism were significantly upregulated, whereas liver metastases were characterized by elevated levels of triglycerides, diglycerides, cholesteryl esters, and acylcarnitines, indicating enhanced lipid synthesis, incomplete fatty acid oxidation, and/or mitochondrial dysfunction. Progression-associated analyses across tissue types revealed consistently increasing trends in glycerides and acylcarnitines, along with heterogeneous alterations in amino acids and phospholipids. Furthermore, 122 differential metabolites were identified between metastatic and non-metastatic CRC, and a four-lipid panel demonstrated strong discriminatory performance. : This study provides a spatially resolved characterization of metabolic reprogramming during CRC progression and liver metastasis, highlighting lipid and amino acid metabolism as key features and revealing the metabolic signatures of CRLM.
Regulation of Human Renal Transporters by Pregnancy-Related Hormones in Primary Proximal Tubular Epithelial Cells.
Tsang YP, Wang K, Kelly EJ … +2 more , Mao Q, Unadkat JD
Metabolites · 2026 Apr · PMID 42188001 · Full text
: Pregnancy is associated with increased renal secretory clearance of drugs mediated by organic anion transporters (OATs) and organic cation transporter 2 (OCT2). Circulating concentrations of pregnancy-related hormones...
: Pregnancy is associated with increased renal secretory clearance of drugs mediated by organic anion transporters (OATs) and organic cation transporter 2 (OCT2). Circulating concentrations of pregnancy-related hormones (PRHs) increase with gestational age, providing a plausible mechanism for renal OAT and OCT2 regulation. : Using primary human proximal tubular epithelial cells (PTECs), we quantified the effects of PRHs, at trimester-specific concentrations, on the mRNA expression of renal drug transporters (apical and basal) and metabolizing enzymes (DMETs), as well as endocytic receptors. PTECs from three female, premenopausal donors were cultured in an optimized Transwell system that maintains measurable OAT activity. PTECs were then exposed for 72 h to trimester-matched PRH cocktails at physiologic (1×) or supraphysiologic (10×) concentrations, with medium replaced every 24 h. DMET and endocytic receptor mRNA were quantified by RT-qPCR, and uptake activities of OAT1/2/3, OCT2, OAT4, and OCTN1 were measured with selective substrates or substrate-inhibitor pairs. : At 1× PRHs, renal DMET and endocytic receptor mRNA expression was unchanged across trimester-related PRH concentration except for consistent downregulation of PEPT2. Uptake activity for all measured transporters was unchanged. At 10× PRHs, selective changes in mRNA expression of transporters were observed (e.g., induction of OAT1), but these changes did not translate into changes in activity. : Our data argue against PRHs as the main driver of the increase in OAT-mediated drug secretion during pregnancy. Alternative mechanisms (e.g., flow-dependent mechanotransduction and untested hormones [e.g., prolactin, hCG]) should be evaluated to explain gestation-dependent changes in renal secretory clearance of drugs.
Toxicokinetic Studies of the Two Stimulants M-ALPHA and -Methyl-cyclazodone Using In Vitro and In Vivo Tools.
Gampfer TM, Klaes S, Eckstein N … +1 more , Meyer MR
Metabolites · 2026 Apr · PMID 42188000 · Full text
Synthetic stimulants represent the most prevalent subclass on the new psychoactive substances (NPSs) market. However, the toxicokinetic properties of M-ALPHA, a regioisomer of MDMA and -methyl-cyclazodone a pemoline deri...
Synthetic stimulants represent the most prevalent subclass on the new psychoactive substances (NPSs) market. However, the toxicokinetic properties of M-ALPHA, a regioisomer of MDMA and -methyl-cyclazodone a pemoline derivative, are not yet characterized. Therefore, this study investigated the metabolism of both NPSs in pooled liver S9 fraction and rat urine, characterized cytochrome P450 (CYP) kinetics and plasma protein binding (PPB), and assessed the CYP inhibition potential of M-ALPHA, using high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (HPLC-HRMS/MS). Four metabolites of M-ALPHA were detected including one phase I and three phase II metabolites, resulting from demethylenation followed by subsequent methylation or glucuronidation. For -methyl-cyclazodone, one phase I metabolite formed via -demethylation was identified. The primary enzymes involved in M-ALPHA metabolism were CYP2B6 and CYP2D6. Notably, M-ALPHA inhibited these enzymes to a strong or moderate extent, respectively. In contrast, the metabolism of -methyl-cyclazodone was primarily mediated by CYP2A6. PPB studies indicated low-to-moderate binding for both compounds, suggesting that significant protein-binding interactions are unlikely. As M-ALPHA only formed metabolites that overlapped with those of MDMA, differing only by minor retention time shifts, reliable HPLC-HRMS/MS-based identification may be challenging in clinical and forensic toxicology settings as well as doping analysis. Furthermore, drug-drug interactions following polydrug use cannot be excluded for either NPS, particularly when co-ingested with other CYP substrates metabolized by the same isoforms.
Circulating Lipid Traits and Ovarian Cancer Risk: A Systematic Review and Meta-Analysis with Mendelian Randomization Integration.
Marian M, Ardelean A, Rosu M … +9 more , Tarta C, Isaic A, Brebu D, Marian C, Faur IA, Pasca P, Faur IF, Stoian D, Korodi A
Metabolites · 2026 Apr · PMID 42187999 · Full text
: Metabolic dysregulation is increasingly recognized as a contributor to carcinogenesis; however, the role of circulating lipid traits in ovarian cancer remains unclear. : A systematic review and meta-analysis were condu...
: Metabolic dysregulation is increasingly recognized as a contributor to carcinogenesis; however, the role of circulating lipid traits in ovarian cancer remains unclear. : A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines. PubMed, Web of Science, Scopus, and Embase were searched from inception to March 2026. Observational studies evaluating triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and total cholesterol (TC) in relation to ovarian cancer risk were included. Random-effects models were used to pool relative risks (RRs). Robustness was assessed via sensitivity analyses, influence diagnostics, and multiverse analysis. Mendelian randomization (MR) evidence was integrated for causal inference. : Six observational studies were included in the meta-analysis. Elevated triglyceride levels were associated with increased ovarian cancer risk, while HDL-C showed a modest inverse association. LDL-C and total cholesterol were not significantly associated with risk. Sensitivity analyses excluding early follow-up strengthened the triglyceride association. MR analyses supported a potential causal role for triglycerides but not for HDL-C. : Circulating triglycerides may represent a metabolically relevant risk factor for ovarian cancer. Further large-scale prospective and mechanistic studies are warranted.
Atherogenic Index of Plasma Relationship with Cardiovascular Risk Factors and Frailty and Value as Determinant of Mortality in Elderly Patients with Severe Aortic Stenosis.
Mazzone A, Gaggini M, Vassalle C
Metabolites · 2026 Apr · PMID 42187998 · Full text
: Frailty is a common finding in elderly subjects with severe aortic stenosis (AoS) and a strong predictor of mortality and disability after aortic valve surgery. The atherogenic index of plasma (AIP) is related to diffe...
: Frailty is a common finding in elderly subjects with severe aortic stenosis (AoS) and a strong predictor of mortality and disability after aortic valve surgery. The atherogenic index of plasma (AIP) is related to different cardiovascular (CV) risk factors, which in turn are correlated to the progression of frailty as well as of AoS. : to analyze the association of AIP with different CV risk factors and frailty scores and its value as a determinant of mortality in older adults with severe AoS. : The association of AIP with a multidimensional assessment of frailty by using Fried criteria and the following indices; timed up-and-go test (TUG) for gait function; Charlson Index (CI), basic activities of daily living (BADL) and instrumental activities of daily living (IADL) for disability; mini-mental state examination for cognitive function evaluation (MMSE); Geriatric Depression Score for mood disorder (GDS); Mini Nutritional Assessment (MNA) for nutritional status was assessed in 102 elderly AoS patients (33 males; mean age 83 ± 6 yrs). Moreover, the relationship between AIP and demographic, lifestyle, traditional CV risk factors and CV mortality was also evaluated. : Significant relationships between AIP and glycemia and inflammatory parameters (CRP, ESR and fibrinogen) as well as with troponin I were found. Moreover, AIP significantly correlates with CI, BADL, IADL and MNA. However, the Kaplan-Meier analysis did not show any significant difference for survival rates according to AIP intervals of risk, whereas ejection fraction remained the only significant determinant after multivariate adjustment for mortality at the Cox proportional hazard models analysis in this patient population. : Higher AIP is significantly associated with cardiometabolic risk and increased physical dysfunction risk and frailty in AoS pts, evidencing its potential use as a simple biomarker in this clinical setting, although it did not represent a significant determinant for mortality in this population.
A Structured Computational Roadmap for Lipidomics in R: Reproducible Workflows from Raw Data to Functional Insight.
Papatheodorou MP, Vlamos P, Krokidis MG
Metabolites · 2026 Apr · PMID 42187997 · Full text
Lipidomics has emerged as a transformative discipline in biomedical research, providing high-resolution insights into metabolic signaling and disease pathophysiology. The R programming language provides a widely adopted...
Lipidomics has emerged as a transformative discipline in biomedical research, providing high-resolution insights into metabolic signaling and disease pathophysiology. The R programming language provides a widely adopted framework for extensible analysis of complex lipidomic datasets due to its robust biostatistical infrastructure. Herein, we present a comprehensive roadmap for lipidomics in R, structured around a standardized analytical lifecycle: from raw data acquisition and preprocessing to structural annotation, statistical modeling and functional interpretation. We critically contextualize and integrate a curated suite of widely adopted R packages (version 4.3.0), including xcms and MSnbase for feature extraction, LipidMS 3.0 for fragmentation-based identification, and lipidr for quality control and normalization. Furthermore, we demonstrate how advanced tools such as mixOmics and clusterProfiler can be integrated to bridge the gap between differential lipid abundance and systems-level biological insights. Particular emphasis is placed on reproducibility, nomenclature standardization and the emerging role of machine learning in biomarker discovery. By synthesizing these resources into a coherent pipeline, this guide provides a structured reference for researchers. Further discussion addresses methodological pitfalls, statistical assumptions and reproducibility constraints that frequently compromise lipidomics studies. Ultimately, this structured approach facilitates systematic tool selection, accelerating the translation of complex lipidomic signatures into reproducible and clinically meaningful discoveries.
Altered Lipid Metabolism in Psoriatic Arthritis: A Comprehensive Review.
Popova-Belova S, Geneva-Popova M, Stoilova S … +3 more , Popova V, Nikolov G, Nikolov D
Metabolites · 2026 Apr · PMID 42187996 · Full text
Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting both the joints and skin. Beyond musculoskeletal manifestations, patients with PsA frequently exhibit alterations in lipid metabolism, contributing t...
Psoriatic arthritis (PsA) is a chronic inflammatory disorder affecting both the joints and skin. Beyond musculoskeletal manifestations, patients with PsA frequently exhibit alterations in lipid metabolism, contributing to an increased risk of cardiovascular disease. Dyslipidemia in PsA arises from multiple mechanisms, including systemic inflammation, insulin resistance, and imbalances in adipokines such as leptin, adiponectin, and resistin. A structured literature search was conducted in PubMed, Scopus, and Web of Science to identify relevant studies on lipid metabolism in psoriatic arthritis, and the evidence was synthesized narratively. PsA is also commonly associated with obesity and metabolic syndrome, further exacerbating dyslipidemia and cardiovascular risk. Interventions including weight loss, lifestyle modification, and anti-inflammatory treatments have been shown to improve lipid profiles and clinical outcomes. This review provides a comprehensive overview of current knowledge on altered lipid metabolism in PsA, highlighting underlying mechanisms, clinical implications, and therapeutic strategies to reduce cardiovascular risk.
Effects of a Reprometabolic Syndrome-Inducing Eucaloric High-Fat Diet on Insulin Sensitivity, Body Composition, the Lipidome, and the Microbiome.
Schauer IE, Kuhn K, Bradford AP … +6 more , Fought AJ, Frank DN, Kotter CV, Robertson CE, Duffy K, Santoro N
Metabolites · 2026 Apr · PMID 42187995 · Full text
: We previously demonstrated recapitulation of the relative hypogonadotropic hypogonadism of obesity, the Reprometabolic Syndrome (RMS), in women of normal BMI with a one-month high-fat, eucaloric diet (HFD). : Assess ef...
: We previously demonstrated recapitulation of the relative hypogonadotropic hypogonadism of obesity, the Reprometabolic Syndrome (RMS), in women of normal BMI with a one-month high-fat, eucaloric diet (HFD). : Assess effects of HFD on sleep, body composition and lifestyle and metabolic secondary outcomes and correlate insulin sensitivity changes with the RMS. : A total of 18 normally cycling women aged 18-38 with BMI 18-24 kg/m were enrolled for a four-month study including a eucaloric HFD (48% calories from fat) for one menstrual cycle. Activity, sleep, body composition, and the lipidome were measured in all participants. Fecal microbiome was analyzed in the last nine participants, and insulin sensitivity by two-stage hyperinsulinemic euglycemic clamp was measured before and after HFD in 15 participants. : Relative to the pre-diet period, BMI, activity and sleep measures did not change, except for waking after sleep onset (WASO), which appeared to decrease during and post HFD. DXA revealed statistically significant decreases in total percent fat, total fat mass, visceral fat volume, and trunk fat volume. Whole-body insulin sensitivity decreased with the HFD while adipocyte insulin sensitivity was unaffected. Insulin sensitivity changes did not correlate with change in gonadotropins or response to gonadotropin releasing hormone (GnRH). Multiple significant changes in plasma lipids were observed, including increased ceramides and glucosylceramides. Microbiome analysis revealed increased microbial diversity. : A one-month eucaloric HFD that induced RMS in normal-weight, reproductive-aged women also induced whole-body insulin resistance (IR) and multiple lipidomics changes potentially associated with IR. These changes in IR occurred despite overall stable activity, BMI and sleep, but did not correlate with the HPO axis defects. The unexpected decrease in body fat and increase in microbial diversity may be related to specific dietary elements of the HFD.
Correction: Sun et al. Effects of Polysaccharide on Gut Microbiota, the Intestinal Mucosal Barrier, and Inflammation in Diabetic Mice. 2025, , 8.
Sun L, Yuan H, Ma H … +1 more , Wang Y
Metabolites · 2026 Mar · PMID 42042931 · Full text
The authors would like to make the following correction to their published paper [...].
The authors would like to make the following correction to their published paper [...].
Aerobic Exercise Alleviates Oxidative Stress and Inflammation to Attenuate High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice.
Zhang L, Wang W, Zheng F … +6 more , Weng J, Lu Y, Li Q, Li T, Li W, Wang L
Metabolites · 2026 Apr · PMID 42042930 · Full text
: The development of non-alcoholic fatty liver disease (NAFLD) is closely linked to oxidative stress and inflammation. Aerobic exercise has been shown to improve NAFLD, although its underlying mechanisms remain incomplet...
: The development of non-alcoholic fatty liver disease (NAFLD) is closely linked to oxidative stress and inflammation. Aerobic exercise has been shown to improve NAFLD, although its underlying mechanisms remain incompletely understood. This study utilized mice to investigate the role of Sestrin2 in aerobic exercise-induced amelioration of NAFLD. : Random assignment of C57BL/6J and mice yielded four groups: C (control), CE (aerobic exercise), AS ( control), and AE ( aerobic exercise). Aerobic exercise lasting 12 weeks was administered to the CE and AE groups. Serum biomarkers were analyzed by ELISA, liver tissue morphology was assessed via HE and ORO staining, and macrophage polarization was evaluated through immunofluorescence. Additionally, mRNA and protein expression levels were measured by qPCR and Western blot. : Aerobic exercise reduced liver wet weight, lipid accumulation, and steatosis in mice. Aerobic exercise attenuates hepatic oxidative stress, and upregulated the expression of regulation oxidative stress related gene and proteins of Nrf2, HO-1, CAT, and SOD1 in mice. Aerobic exercise promoted a shift in macrophage polarization from the pro-inflammatory M1 phenotype toward the anti-inflammatory M2 phenotype in the liver, and significantly reduced TNF-α and IL-1β levels, accompanied by upregulation of Sestrin2 expression, enhanced AMPK phosphorylation, inhibited mTORC1 in the liver. : These findings suggest that aerobic exercise alleviates oxidative stress and inflammation in NAFLD, with Sestrin2 activation playing a central role.
Quercetin Attenuates Non-Alcoholic Fatty Liver Disease in Association with the Inhibition of Hepatic IL-1β/iNOS and IL-1β/CD45 Axes of Inflammation and Fibrosis Accompanied by Reduced Endogenous Metabolites and Apoptosis.
Alqahtani SA, Alshehri HH, Ashour H … +8 more , Abdallah H, Rashed L, Badi RM, Mohammed MED, Al-Ani B, Alzamil NM, Albawardi A, Aboulhoda BE
Metabolites · 2026 Apr · PMID 42042929 · Full text
BACKGROUND: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide...
BACKGROUND: Liver inflammation and fibrosis are directly associated with non-alcoholic fatty liver disease (NAFLD). Dysregulation of the potent pro-inflammatory cytokine interleukin-1 beta (IL-1β), inducible nitric oxide synthase (iNOS), and tissue leukocyte infiltration (CD45 +ve) are connected with multiorgan injury and fibrosis. We investigated whether the induction of NAFLD can cause dysregulation in the hepatic IL-1β/iNOS and IL-1β/CD45 axes of inflammation and fibrosis, as well as in endogenous metabolites (lipids, glucose, and insulin) and apoptosis, in the presence and absence of the flavonoid quercetin. METHODS: The model group of rats was fed with a high-fat and high-carbohydrate diet (HFCD) for 4 weeks. The protective group of rats was given both quercetin (50 mg/kg) and HFCD for 4 weeks. All rats were sacrificed on day 29. RESULTS: NAFLD was induced in rats as demonstrated by dyslipidemia, hyperglycemia, insulin resistance, liver inflammation, and elevation of liver injury enzymes. NAFLD was also associated with the upregulation of hepatic IL-1β, iNOS, CD45, and apoptosis (p53). Biomarkers of fibrosis (TIMP-1 and α-SMA) were also elevated, and fibrosis was confirmed in the model group by increased collagen deposition and elevated stages of fibrosis score (Stage 1 to 2 of Brunt's NASH classification). All these parameters were significantly ( < 0.01) modulated by quercetin treatment. Additionally, a significant ( < 0.001) correlation between IL-1β and hepatic injury parameters was observed. CONCLUSIONS: These findings suggest a potential association between NAFLD and the IL-1β/iNOS and IL-1β/CD45 axes of liver injury and fibrosis, as well as dyslipidemia, glycemia, and apoptosis, with quercetin exhibiting beneficial hepatic pleiotropic effects.
Comparative Analysis of Two Dietary Saturated Fat Types on Metabolite Profiles Crossing the Blood-Brain Barrier of Poultry Chicks.
Orimaye OE, Omaliko PC, Lichti NI … +2 more , Cooper BR, Fasina YO
Metabolites · 2026 Apr · PMID 42042928 · Full text
The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty ac...
The dorsal raphe nucleus (DRN) produces and distributes serotonin, while the hypothalamus (HYP) uses serotonergic signals to regulate physiological processes in chickens. Coconut oil (COCO), rich in medium-chain fatty acids, is rapidly absorbed without re-esterification. Day-old broilers (Ross 708 male, n = 160) were distributed into two dietary treatments with five replicates of 16 birds each. The birds were fed a corn-soybean meal (SBM) basal diet supplemented with 3% of poultry fat (CON) or coconut oil (COCO). The body-weight gain (BWG), feed intake (FI), and feed conversion ratio (FCR) were recorded over a 3-week period, and the data were subjected to a -test. Untargeted metabolomic analysis by high-performance liquid chromatography (HPLC-MS) was used to evaluate the influence of the type of dietary fat on metabolite profiles in the DRN, HYP, and plasma of broiler chickens. Principal component analysis (PCA) was used to identify unique metabolites, and ANOVA was used to identify the metabolites that were significantly abundant ( < 0.05). The metabolites were then annotated using the KEGG and HMDB databases. Birds in the COCO treatment gained more weight on average (0.8446 kg/bird) than birds in the CON group (0.8132 kg/bird; = 0.0496). Five metabolites associated with multiple significant cellular processes, such as brain function, energy metabolism, and neurotransmission, showed similar differential expression patterns, while two metabolic pathways (butanoate metabolism and alanine, aspartate and glutamate metabolism) were identified. The dietary inclusion of COCO improves BWG in poultry and enhances their overall well-being by modulating metabolite profiles, supporting neurotransmission, and enriching the metabolic pathways essential for growth and brain function.
Critical Role for Malic Enzymes in MYC-Mediated Cellular Adaptation to Glutamine Depletion.
Si Y, Li W, Chen Y … +4 more , Yuan J, Hu C, Liu Y, Li L
Metabolites · 2026 Apr · PMID 42042927 · Full text
MYC-driven tumors exhibit significant glutamine addiction, but the metabolic adaptation mechanisms enabling their survival under glutamine deprivation remain incompletely understood. Malic enzymes catalyze the oxidative...
MYC-driven tumors exhibit significant glutamine addiction, but the metabolic adaptation mechanisms enabling their survival under glutamine deprivation remain incompletely understood. Malic enzymes catalyze the oxidative decarboxylation of malate to pyruvate while generating NADPH, linking central carbon metabolism to redox homeostasis. This study investigates whether and how ME1 and ME2 mediate cell adaptation to glutamine starvation and explores their functional division in relation to p53 status. Using MYC-amplified, p53-mutant (G266E) SF188 glioblastoma cells, we performed siRNA-mediated knockdown, overexpression, and rescue experiments. Cell survival was assessed by trypan blue exclusion and Annexin V/PI staining. ROS levels and NADP/NADPH ratios were measured by DCFH-DA fluorescence and enzymatic assays. Metabolite tracing was conducted using [U-C] glutamine followed by LC-MS. Key findings were validated in additional cell lines including HCT116, U2OS and MDA-MB-231. ME1 and ME2 promote SF188 cell survival under glutamine deprivation, an effect that depends on their catalytic activity but is independent of TCA cycle anaplerosis. ME1 maintains redox balance by generating NADPH, and antioxidant treatment rescues the survival defect caused by ME1 knockdown. In contrast, ME2 does not contribute to redox regulation but stabilizes mutant p53 (G266E) via proteasome inhibition. Both of these pro-survival functions are attenuated upon MYC knockdown, suggesting a dependency on MYC expression. Across all cell lines tested, ME1 and ME2 also promote survival through redox maintenance, although the isoform responsible for antioxidant function differs. ME1 and ME2 support metabolic adaptation to glutamine starvation through distinct, isoform-specific mechanisms that depend on MYC expression and p53 mutation status. These findings suggest malic enzymes as potential therapeutic targets in MYC-driven, p53-mutant tumors.
Selected Brain Metabolites and Mitochondrial DNA Copy Number as Potential Markers of Ongoing Neurodegeneration in Patients with Wolfram Syndrome.
Zmysłowska-Polakowska E, Płoszaj T, Skoczylas S … +7 more , Grzybowska-Adamowicz J, Barańska D, Matera K, Palatyńska-Ulatowska A, Młynarski W, Zmysłowska A, Ciborowski M
Metabolites · 2026 Apr · PMID 42042926 · Full text
: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mel...
: Wolfram syndrome (WFS) is a rare neurodegenerative disease that is genetically determined and inherited in an autosomal recessive manner. Although the first clinical symptom appearing in early childhood is diabetes mellitus, subsequent symptoms are associated with optic nerve atrophy, followed by central nervous system atrophy. : The aim of the study was to analyse magnetic resonance images (MRI) of the brain in combination with single-voxel magnetic resonance spectroscopy (MRS) and to assess the copy number of mitochondrial DNA (mtDNA-CN) in 10 patients with WFS compared with a control group of 17 healthy individuals. : A significant decrease in the amount of selected metabolites was observed in WFS patients compared to controls in all assessed brain regions (pons, cerebellum, white matter, thalamus, and hippocampus). For three metabolites, Glutamate (Glu), Glutamate + Glutamine (Glx) and total N-acetylaspartate (TNAA), significant differences in concentrations were found between the study groups in almost all matrices evaluating specific areas of the brain ( < 0.011), with the exception of a trend toward reduced TNAA in the hippocampus ( = 0.065). In addition, patients with WFS had a significant decrease in the mitochondrial-to-nuclear DNA ratio compared to controls ( < 0.0003). Some metabolites, such as N-acetylaspartate and total N-acetylaspartate, showed strong correlations with specific regions of the visual pathway on MRI scans in patients with WFS. : Selected brain metabolites and mtDNA-CN may become potential markers of WFS, and the results of this study may be used to define indicators for future therapeutic strategies.
Red Blood Cell Distribution Width and Neutrophil-to-Lymphocyte Ratio as Markers of Cardiovascular Disease and Vascular Calcification in Chronic Kidney Disease: A Large Cohort Study.
Zagaliotis A, Roumeliotis A, Roumeliotis S … +11 more , Neofytou IE, Varouktsi G, Leptokaridou-Mourtzila E, Stamou A, Sgouropoulou V, Kocic G, Veljkovic A, Bittner R, Jahnen-Dechent W, Schurgers LJ, Liakopoulos V
Metabolites · 2026 Apr · PMID 42042925 · Full text
BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) in chronic kidney disease (CKD) arises from a multifaceted interplay of pathophysiological processes, including chronic inflammation, oxidative stress (OS), and acceler...
BACKGROUND/OBJECTIVES: Cardiovascular disease (CVD) in chronic kidney disease (CKD) arises from a multifaceted interplay of pathophysiological processes, including chronic inflammation, oxidative stress (OS), and accelerated vascular calcification (VC). Red blood cell distribution width (RDW) and the neutrophil-to-lymphocyte ratio (NLR) have emerged as simple, inexpensive, and readily available hematological indices that may capture these underlying disturbances. As such, they hold promise as accessible biomarkers for stratifying cardiovascular risk in patients with CKD. METHODS: This cross-sectional study enrolled 497 patients, comprising 477 with CKD across all stages and 20 controls. We evaluated the associations of RDW and NLR with both traditional and non-traditional cardiovascular risk factors, as well as with serum calcification propensity (T50). Spearman's correlation and multivariable regression analysis were used to assess these relationships. RESULTS: Both RDW and NLR were significantly elevated in patients with established CVD ( < 0.001 for both) and demonstrated a progressive increase across advancing CKD stages ( < 0.001). RDW and NLR showed positive correlations with age, CVD duration, urea, phosphorus, parathormone, CRP, FG23, and mean carotid intima-media thickness (cIMT), while exhibiting inverse correlations with eGFR, serum albumin, hemoglobin, lipids, antioxidants such as superoxide dismutase, fetuin-A, and T50. Additionally, NLR correlated positively with the duration of hypertension and diabetes, as well as with albuminuria. Quartile analysis revealed a stepwise decline in T50 across increasing categories of RDW and NLR, supporting the link with impaired calcification defense. In multivariable analysis, T50 independently predicted NLR (β = -0.013; = 0.018), whereas total cholesterol (β = -0.011; = 0.019) and cIMT (β = 0.38; = 0.018) emerged as independent determinants of RDW. CONCLUSIONS: RDW and NLR strongly reflect the burden of inflammation, metabolic disturbance, and vascular dysfunction in patients across the CKD spectrum. The consistent associations with impaired calcification defense and with established cardiovascular risk markers underscore the potential value as accessible indicators of cardiovascular vulnerability in CKD. These findings support incorporating RDW and NLR into routine risk assessment and highlight T50 as a mechanistically relevant determinant of hematologic inflammation profiles.
Metabolomic Profiling Reveals Geographical Origin, Tissue-Specific Specialization, and Environmental Plasticity in Secondary Metabolism of .
Li Z, Li J, Hu Y … +6 more , Wu X, Duan X, Kong D, Li X, Cheng J, Wang M
Metabolites · 2026 Apr · PMID 42042924 · Full text
: (), an endangered ornamental and medicinal orchid, displays significant variability in its bioactive compounds depending on geographical and environmental factors. To decipher these influences, we investigated metabol...
: (), an endangered ornamental and medicinal orchid, displays significant variability in its bioactive compounds depending on geographical and environmental factors. To decipher these influences, we investigated metabolic divergence across three cultivars (GN, LS, DX) cultivated in greenhouse and outdoor conditions using untargeted metabolomics. : Metabolites extracted from stem and leaf tissues were analyzed via UHPLC-Q Exactive Orbitrap MS, and the raw data were processed using XCMS for peak alignment and quantification. Differentially abundant metabolites (DAMs) were identified by multivariate statistical analyses including PCA and OPLS-DA. Metabolic pathways were annotated using KEGG, HMDB, and LIPID Maps databases, with enrichment analysis and visualization performed via TBtools II and Hiplot. : Metabolite profiling and multivariate analysis revealed distinct chemotypes. The DX cultivar exhibited anthocyanin enrichment in its stems, correlating with a red pigmentation, while GN accumulated specific amino acid derivatives. Tissue-specific metabolic specialization was evident, with leaves displaying greater flavonoid diversity and stems prioritizing lipid and amino acid metabolism. Outdoor cultivation enhanced flavonoid biosynthesis, whereas greenhouse conditions favored alkaloid accumulation. Functional analysis identified both conserved pathways, like phenylpropanoid biosynthesis, and varietal-specific adaptations in amino acid and secondary metabolism. Notably, alkaloid levels declined sharply during plant defoliation. : Our findings demonstrate that environmental factors and geographical origin synergistically shape the metabolic profiles of . This provides a scientific basis for optimizing cultivation strategies-through targeted environmental adjustments and varietal selection-to enhance the yield of desired bioactive compounds.
Identification of Primary Hyperoxaluria Type III by Gas Chromatography/Mass Spectrometry-Based Urine Metabolomics.
Kuhara T, Ohse M, Fukasawa T … +2 more , Maruyama K, Pitt J
Metabolites · 2026 Apr · PMID 42042923 · Full text
Primary hyperoxaluria type III (PH3) causes kidney stones in children and adults. Gas chromatography/mass spectrometry (GC/MS)-based metabolomics has been applied to study patients with primary hyperoxaluria types I and...
Primary hyperoxaluria type III (PH3) causes kidney stones in children and adults. Gas chromatography/mass spectrometry (GC/MS)-based metabolomics has been applied to study patients with primary hyperoxaluria types I and II, 2,8-dihydroxyadenine lithiasis, and xanthinuria types I to III. This study was performed to verify the usefulness of this technique for the diagnosis of PH3. Specifically, we evaluated an 8-month-old infant with recurrent kidney stones. GC/MS-based metabolomics was performed on spot urine samples using initial urease pretreatment without fractionation. Metabolomics revealed increased levels of 2,4-dihydroxyglutarate and 4-hydroxyglutamate. No simultaneous elevations of these two critical biomarkers were observed in other patients, except for one case of PH3 confirmed by the identification of mutations. A moderate increase in 4-hydroxyglutamate has been observed only in cases of primary hyperammonemia, in which analytes such as orotate, uridine, glutamine, or proline, but not 2,4-dihydroxyglutarate, are biomarkers, thus distinguishing PH3 from primary hyperammonemia. GC/MS-based urine metabolomics enables the rapid screening and chemical diagnosis of PH3 and other congenital anomalies that cause urolithiasis. This technique can also be used to monitor disease progression, as patients with PH3 benefit from long-term follow-up, particularly when transitioning from childhood to adulthood. The timely identification of patients with hereditary urolithiasis is crucial. To address this, a discussion was had about the current diagnostic criteria.
Diagnostic Criteria and Genetic Basis of Polycystic Ovary Syndrome: A Narrative Review.
Cepero-González MLA, Aguilar-Galarza A, Rodríguez-García VM … +2 more , García-Gasca T, Moreno Celis U
Metabolites · 2026 Apr · PMID 42042922 · Full text
This study reviews the main candidate genes involved in the pathophysiology of Polycystic Ovary Syndrome (PCOS). PCOS is a common endocrine-metabolic disorder in women of reproductive age, characterized by menstrual irre...
This study reviews the main candidate genes involved in the pathophysiology of Polycystic Ovary Syndrome (PCOS). PCOS is a common endocrine-metabolic disorder in women of reproductive age, characterized by menstrual irregularity, hyperandrogenism, and polycystic ovarian morphology. It is associated with increased metabolic and cardiovascular risk and is a leading cause of infertility. Although its pathophysiology is not fully understood, alterations in the hypothalamic-pituitary-ovarian axis, insulin metabolism, and steroidogenesis have been described. Polymorphisms in genes encoding hormones, enzymes, and receptors in these pathways contribute to clinical variability and ethnic differences, offering potential for early diagnosis and personalized medicine. This review summarizes key candidate genes related to insulin metabolism (INS, INSR, IRS-1), the hypothalamic-pituitary-ovarian axis (LHβ, LHCGR, FSHR, GnRHR, AMH, AMHR2, KISS1, CAPN10), steroidogenesis (CYP11A, CYP17A1, CYP19A1, CYP21, 17β-HSD, SHBG, AR, STAR), and other clinically relevant mechanisms such as obesity, lipid metabolism (PPARG, VDR, FTO), and follicular development (ACE).
Unveiling the Fragrant Secrets of : Terpenoid Pathways and Floral Scent Dynamics.
Wang S, He S, Yuan C … +5 more , Chen X, Sam HV, Lum WC, Dou Y, Shi R
Metabolites · 2026 Apr · PMID 42042921 · Full text
BACKGROUND/OBJECTIVES: The orchid Paxt., valued for its ornamental and medicinal properties, is widely used in horticulture, medicine, and food industries. METHODS: This study investigated dynamic changes in aroma-activ...
BACKGROUND/OBJECTIVES: The orchid Paxt., valued for its ornamental and medicinal properties, is widely used in horticulture, medicine, and food industries. METHODS: This study investigated dynamic changes in aroma-active volatile organic compounds (VOCs) and associated gene expression in flowers across four developmental stages (bud, half bloom, full bloom, and aging) using headspace solid-phase microextraction, gas chromatography-mass spectrometry, and transcriptome analysis. RESULTS: Floral VOCs, particularly volatile terpenoids and esters, were most abundant at full bloom. Among the 664 VOCs identified, α-hemelene, β-bisabolene, δ-naphthalene, perillyl alcohol, L-perillyl alcohol, terpinen-4-ol, 2-(4-methylphenyl)propan-2-ol, cis-3-hexenyl butyrate, and α-pinene were likely to contribute to floral scent. Terpene biosynthesis pathways played a pivotal role in floral fragrance formation. A comprehensive terpenoid biosynthesis pathway for floral scent was proposed, and eight genes encoding key regulatory enzymes were identified. CONCLUSIONS: These results provide new insights into terpenoid metabolism in Dendrobium and may guide future research on the utilization of floral scent.
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