Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Integrative phenomics, metabolomics, and flavoromics reveal key quality indicators during the formation of flavor and bioactive compounds in Alpinia hainanensis (Zingiberaceae) fruit

Sun, 11/05/2025 - 12:00
Food Chem. 2025 May 7;486:144602. doi: 10.1016/j.foodchem.2025.144602. Online ahead of print.ABSTRACTAlpinia hainanensis seed (AHS) is a traditional spice and medicinal material with limited studies on its flavor and bioactive chemistry. This study integrated anatomical and microstructural analyses, flavor traits, and full-spectrum metabolome profiling using GC-MS and UPLC-MS/MS to characterize AHS quality. A total of 1543 metabolites were identified, with 41 key flavor compounds showing spatiotemporal specificity. Boiled and dried mature AHS exhibited optimal flavor with large dried fruit, dark and heavy seeds, and strong pungency. Different bioactive compounds peaked across 4-10 weeks post-anthesis, indicating stage-specific medicinal potential. Oil cell traits correlated with bioactive compounds of pinocembrin, cardamonin, and 3-carene accumulation, while bitterness correlated with pinocembrin. Postharvest processing enhanced seed pungency and increased peel terpenoids, supporting value-added utilization. Metabolite accumulation was associated with galactose, fatty acid, terpene, and phenylpropanoid pathways. These findings provide a foundation for refining A. hainanensis harvesting, processing, and utilization.PMID:40349519 | DOI:10.1016/j.foodchem.2025.144602

Improvement of semen quality in Longyou Partridge Chicken by dietary N-acetyl-L-glutamic acid and its mechanism study

Sun, 11/05/2025 - 12:00
Poult Sci. 2025 Apr 30;104(8):105234. doi: 10.1016/j.psj.2025.105234. Online ahead of print.ABSTRACTThe aim of the study was to investigate the mechanisms of the N-acetyl-L-glutamic (NAG) diet in improving rooster semen quality after cryopreservation. A total of 60 individually housed chickens were randomly allocated to three groups: a basal diet group (C), a basal diet supplemented with 2 g/kg NAG group (NL), and a basal diet supplemented with 4 g/kg NAG group (NH). Semen quality was evaluated on days 15 and 30, including fresh sperm motility and cryopreservation efficacy. Serum biochemical parameters, hormone levels, immune indices, semen metabolites, and gut microbiota composition were assessed at 30 d. NAG supplementation significantly improved semen quality. At 15 and 30 d, both NL and NH groups showed a significant increase in the total motile sperm ratio (TM) in fresh semen compared to the control (P ≤ 0.05). At 30 d, group NH exhibited significantly higher percentage of sperm in a straight-line trajectory (LIN) in fresh semen than both the C and NL groups. After cryopreservation, the sperm TM and LIN from chickens with NAG dietary for 30 days were significantly better in the NL group compared to C and NH groups (P ≤ 0.05). Metabolomic analysis identified significant upregulation of metabolites, including melatonin and ferulic acid, in cryopreserved semen from NAG-supplemented groups, while 5-hydroxylysine and inosine-1-phosphate were significantly reduced. Serum antioxidant capacity, as measured by glutathione peroxidase (GSH-Px) was significantly higher, while malondialdehyde (MDA) levels lower in NAG groups compared to C (P ≤ 0.05). No significant differences in immune markers or reproductive hormones were observed across groups. Gut microbiota analysis revealed that NAG supplementation enhanced beneficial bacterial populations. In conclusion, NAG supplementation improved sperm motility and cryopreservation outcomes, potentially by increasing the levels of semen melatonin and ferulic acid and reducing the body oxidative stress. And it can improve the overall health level by regulating the gut microbiota through diet. These findings highlight NAG's potential as a dietary supplement to improve semen quality and overall reproductive efficiency in poultry.PMID:40349463 | DOI:10.1016/j.psj.2025.105234

Systematical accumulating and regulating evaluations of leaf functional metabolites in geographically isolated edible medicinal plants of Piper sarmentosum

Sun, 11/05/2025 - 12:00
J Plant Physiol. 2025 May 3;310:154512. doi: 10.1016/j.jplph.2025.154512. Online ahead of print.ABSTRACTThe edible medicinal plant Piper sarmentosum is widely distributed in south China. This study raised a hypothesis of geographically isolated P. sarmentosum plants possessing potential site- or/and plant-dependent accumulating metabolites, expressing genes, and colonizing bacteria. Here, P. sarmentosum plants of Guangzhou City (PG, comparison group) and Hainan Island (PH, control group) were collected for assaying leaf metabolomes (LMs), leaf transcriptomes (LTs), and leaf-assembled bacterial communities (LABCs), respectively. In LMs and LTs, 930 metabolites and 82,606 unigenes were identified with 552 differently accumulated metabolites (DAMs) and 28,177 differently expressed genes (DEGs), respectively. In LABCs, cluster analysis yielded 822 PG-PH-common, 1114 PG-unique, and 203 PH-unique operational taxonomic units (OTUs). In contrast of PH-LMs, the elevated accumulations of alkaloids and lipids and the decreased accumulations of flavonoids and phenolic acids were observed in PG-LMs. Typically, the DAMs and DEGs were co-enriched in two metabolic pathways of phenylpropanoids and flavonoids, visibly displaying the related DEGs, such as chalcone synthase (CHS), chalcone isomerase (CHI) and phenylalanine amino lyase (PAL), with regulating the functional DAMs, such as phenylalanine, tyrosine, p-coumaric acid, and naringenin. Noticeably, these DAMs were also significantly correlated with a number of different types or/and abundances of leaf-assembled bacteria (DTAB) between PG- and PH-LABCs, such as Flavobacterium and Pseudomonas. Therefore, this study clearly elucidated the functional metabolite accumulations and the close relationships with plant mRNA expressions and bacterial colonizations in geographically isolated plants of P. sarmentosum, providing new insight of selectively utilizing leaf food- and medicine-associated metabolites in different habitats of edible medicinal plants.PMID:40349452 | DOI:10.1016/j.jplph.2025.154512

The effects of nitrite stress on metabolites and gene expression in sea Cucumbers (Apostichopus japonicus)

Sun, 11/05/2025 - 12:00
Mar Environ Res. 2025 May 8;209:107203. doi: 10.1016/j.marenvres.2025.107203. Online ahead of print.ABSTRACTChronic nitrite accumulation in intensive aquaculture poses a significant threat to the sustainability of sea cucumbers (Apostichopus japonicus), a key species in marine aquaculture. This study investigated the molecular and metabolic responses of A. japonicus to 21-day nitrite stress (4.88 mg/L) through transcriptomic and metabolomic analyses. At the end of the experiment, the weight gain rate of the Cg group was 11 %, while that of the Nc group was -9 %. Nitrite exposure significantly impaired growth performance of A. japonicus (p < 0.05). Metabolomic profiling identified 36 differential metabolites, revealing activation of the TCA cycle and amino acid metabolism to prioritize energy production and nitrogen reallocation. Transcriptomic data highlighted 226 differentially expressed genes. Notably, Zimp10, a key regulator of TCA cycle activity in echinoderms, was upregulated, while FALDH, a glycolysis-related gene, was downregulated, indicating a shift toward energy-efficient aerobic respiration. Antioxidant capacity was compromised through suppression of glutathione metabolism genes (MGST1, GST), exacerbating oxidative damage. Stress signaling pathways were dynamically regulated. Downregulation of Ras1-X2 suppressed mTOR activity, activating autophagy and mitophagy for cellular repair. Additionally, enrichment of NOD-like receptor pathways and upregulation of vGTPase1-like signaled immune engagement. Prolonged nitrite exposure overwhelmed adaptive mechanisms, leading to physiological decline. These results demonstrate A. japonicus of reliance on metabolic reprogramming and stress signaling to mitigate nitrite toxicity, while highlighting vulnerabilities in antioxidant defenses. The study provides critical insights for optimizing aquaculture environments through targeted management of nitrite exposure and metabolic resilience strategies.PMID:40349400 | DOI:10.1016/j.marenvres.2025.107203

From Multi-Omics to Visualization and Beyond: Bridging Micro and Macro Insights in CAR-T Cell Therapy

Sun, 11/05/2025 - 12:00
Adv Sci (Weinh). 2025 May 11:e2501095. doi: 10.1002/advs.202501095. Online ahead of print.ABSTRACTChimeric antigen receptor T (CAR-T) cell therapies, a cornerstone of immunotherapy, have demonstrated remarkable efficacy in treating hematological malignancies and have more recently expanded into applications for solid tumors and autoimmune diseases. Emerging multidimensional profiling technologies offer promising solutions for enhancing CAR-T efficacy, overcoming resistance, and facilitating the development of novel CAR-T constructs. The integration of genomics, epigenomics, transcriptomics, proteomics, metabolomics, and microbiomics enables a comprehensive understanding of the intrinsic mechanisms underlying CAR-T therapy, while single-cell and spatial omics significantly improve data resolution and analytical depth. Coupled with advances in biomedical engineering, visualization technologies form the foundation for omics data generation by bridging microscopic and macroscopic scales and enabling dynamic, 3D in vivo monitoring of CAR-T behavior. Artificial intelligence (AI) further supports this framework by enabling the analysis of complex, high-dimensional datasets. This review highlights recent advances in the integration of multidimensional omics within CAR-T therapy and explores cutting-edge developments in visualization technologies and AI applications. The full convergence of multi-omics, visualization tools, and AI is poised to deliver transformative insights into the mechanisms governing CAR-T cell therapy.PMID:40349154 | DOI:10.1002/advs.202501095

Mapping the molecular signature of ABA-regulated gene expression in germinating barley embryos

Sat, 10/05/2025 - 12:00
BMC Plant Biol. 2025 May 10;25(1):619. doi: 10.1186/s12870-025-06654-z.ABSTRACTBACKGROUND: Abscisic acid (ABA) regulates key plant processes, including seed germination, dormancy, and abiotic stress responses. While its physiological role in germination is well-documented, the molecular mechanisms are still poorly understood. To address this, we analyzed transcriptomic and metabolomic changes in ABA-treated germinating barley (Hordeum vulgare) embryos. To map ABA-responsive gene expression across embryonic tissues, we employed the Visium Spatial Transcriptomics (10× Genomics). This approach, which remains technically challenging to be applied in plant tissues, enabled the precise localization of gene expression across six embryo regions, offering insights into tissue-specific expression patterns that cannot be resolved by traditional RNA-seq.RESULTS: Transcriptomic analysis indicated that ABA acts primarily as a germination repressor. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses linked ABA-inhibited genes to energy metabolism, lignin biosynthesis, cell wall organization, and photosynthesis, while induced genes were associated with environmental adaptation and phytohormone signaling. Differentially expressed genes (DEGs) correlated with metabolites involved in phytohormone pathways, including gibberellins, jasmonates, brassinosteroids, salicylic acid, auxins, and ABA metabolism. Comparisons with developing seed transcriptomes suggested an ABA-associated gene expression signature in embryos. Spatial transcriptomics technique made possible the precise identification of ABA-induced transcriptional changes within distinct embryonic tissues.CONCLUSIONS: Integrating transcriptomics, metabolomics and spatial transcriptomics defined the molecular signature of ABA-induced modulation of phytohormonal crosstalk, energy metabolism, and tissue-specific gene activity in germinating seeds. The successful use of spatial transcriptomics adds a novel layer of resolution for understanding tissue-specific ABA responses during barley seed germination. These findings offer new insights into the ABA role in seed germination and potential strategies for enhancing crop resilience.PMID:40348990 | DOI:10.1186/s12870-025-06654-z

The plant-beneficial fungus Trichoderma harzianum T22 modulates plant metabolism and negatively affects Nezara viridula

Sat, 10/05/2025 - 12:00
BMC Plant Biol. 2025 May 10;25(1):615. doi: 10.1186/s12870-025-06650-3.ABSTRACTBACKGROUND: Plant-beneficial fungi play an important role in enhancing plant health and resistance against biotic and abiotic stresses. Although extensive research has focused on their role in eliciting plant defences against pathogens, their contribution to induced resistance against herbivorous insects and the underlying mechanisms remain poorly understood. In this study, we used insect bioassays and untargeted metabolomics to investigate the impact of root inoculation of sweet pepper with the plant-beneficial fungus Trichoderma harzianum T22 on direct defence responses against the insect herbivore Nezara viridula.RESULTS: We observed reduced relative growth rate of N. viridula on leaves of fungus-inoculated plants, with no change in mortality. Untargeted metabolomic analyses revealed that inoculation with T. harzianum did not affect the leaf metabolome in the absence of herbivory five weeks after inoculation. However, compared to non-inoculated plants, inoculated plants exhibited significant metabolic alterations in herbivore-damaged leaves following N. viridula feeding, while changes in the metabolic profile of distant leaves were less pronounced. Notably, metabolites involved in the shikimate-phenylpropanoid pathway, known to be involved in plant defence responses, displayed higher accumulation in damaged leaves of inoculated plants compared to non-inoculated plants.CONCLUSION: Our results indicate that root inoculation with T. harzianum T22 affects plant defences against N. viridula, leading to reduced insect performance. Metabolite-level effects were primarily observed in damaged leaves, suggesting that the priming effect mainly results in localized metabolite accumulation at the site of attack. Future research should focus on identifying the detected compounds and determining their role in impairing N. viridula performance.PMID:40348966 | DOI:10.1186/s12870-025-06650-3

A multi-omics dataset of C57 BL/6J mice regulated function by feed with ε-polylysine

Sat, 10/05/2025 - 12:00
Sci Data. 2025 May 10;12(1):771. doi: 10.1038/s41597-025-05103-8.ABSTRACTThe proteomic and metabolomic differences in mice fed ε-polylysine were detected by high-throughput sequencing and screening. The effects of ε-polylysine on the proteome and metabolomics of C57 BL/6 J mice were studied. DIA proteome sequencing and liquid chromatography-mass spectrometry (LC-MS) were used to compare ε-polylysine-modified mouse proteome and metabolome. In this study, we analyzed the regulatory effects of ε-polysine on glycerophospholipid metabolism, glutathione metabolism, and ABC transporters pathways. The sequencing data and LC-MS/MS raw data of samples are stored in MetaboLights and ProteomeXchange databases for efficient reuse and to explore the differences in metabolism and protein expression among mice fed with different levels of ε-polylysine, aiming to screen for critical proteins and differential metabolites in valuable regulatory pathways.PMID:40348754 | DOI:10.1038/s41597-025-05103-8

Antidepressant effect of Radix bupleuri - Radix paeoniae alba herb pair on chronic unpredictable mild stress rats based on cortical metabolomics

Sat, 10/05/2025 - 12:00
BMC Complement Med Ther. 2025 May 10;25(1):168. doi: 10.1186/s12906-025-04898-8.ABSTRACTOBJECTIVE: Depression is a serious mental disorder, and its incidence rate has increased rapidly. Radix Bupleuri (root of Bupleurum chinensis DC. BR)-Radix Paeoniae Alba (root of Paeonia lactiflora Pall. PRA) herb pair has been historically used for treating depression in Traditional Chinese Medicine (TCM) while the mechanisms need to be fully revealed.METHODS: The effects of the BR-PRA herb pair were investigated using a rat model of chronic unpredictable mild stress (CUMS). First, the depressive-like behavior of rats was evaluated by open field test (OFT), elevated plus-maze test (EMP), and forced swimming test (FST). Secondly, histomorphological changes in the CA1 and CA3 regions of the hippocampus were analyzed by hematoxylin-eosin, nissl, and Golgi staining. Ultra high-performance liquid chromatograph tandem quadrupole mass spectrometry (UHPLC-QTRAP-MS/MS) was performed to reveal potential antidepressant mechanisms.RESULTS: Following CUMS exposure, rats displayed depressive-like behavior, and neuronal death in the hippocampal region was observed. Consequently, these abnormal changes were reversed by BR-PRA herb-pair intervention. A total of 26 different metabolites related to depression were identified by metabolomics, mainly involving eleven metabolic pathways of pentose phosphate pathway, purine metabolism, and amino sugar and nucleotide sugar metabolism. BR-PRA herb-pair improved four metabolites, including homocitrulline, N-acetyllysine, corticosterone, and N-acetylglutamate. It also may affect the development of depression by interfering with the hypothalamus-pituitary-adrenal axis (HPA axis), amino acid metabolism related to lysine and glutamate, and modulation of oxidative stress.CONCLUSION: BR-PRA herb-pair alleviated depressive-like behavior in CUMS rats, recovered hippocampus damage, and regulated cerebral cortex metabolism, which may be related to the HPA axis, amino acid metabolism related to lysine and glutamate, and modulation of oxidative stress.CLINICAL TRIAL NUMBER: Not applicable.PMID:40348996 | DOI:10.1186/s12906-025-04898-8

Maternal and umbilical cord plasma purine concentrations after oral carbohydrate loading prior to elective Cesarean delivery under spinal anesthesia: a randomized controlled trial

Sat, 10/05/2025 - 12:00
BMC Pregnancy Childbirth. 2025 May 10;25(1):556. doi: 10.1186/s12884-025-07637-6.ABSTRACTOBJECTIVE: To evaluate the effect of preoperative intake of oral carbohydrates versus standard preoperative fasting prior to elective cesarean delivery on plasma purine levels (hypoxanthine, xanthine, and uric acid) and beta-hydroxybutyrate (β-HB) in mother's blood plasma and umbilical cord blood plasma.METHODS: Prospective randomized clinical trial, performed according to the Declaration of Helsinki, IRB approval (KB-0012/113/19, 13.05.2019). Patients with at term gestation with singleton uncomplicated pregnancies, scheduled for cesarean delivery under spinal anaesthesia were randomized in a 1:1 ratio to Group I (oral carbohydrate drinks (CHO Group, oral carbohydrate drink - 200 mL - 12.5% dextrose in water) 2 h prior to surgery in addition to standard solid fasting (6 h) or Group II which underwent only standard fasting (6 h - solids, 2 h for - liquids, SF Group). Blood samples were collected at 2 h after carbohydrate consumption (maternal) and at umbilical cord clamping (umbilical cord). The primary outcomes - plasma concentrations of hypoxanthine, xanthine, uric acid, in maternal blood and umbilical cord blood were measured using high-performance liquid chromatography. The secondary outcomes were blood pH, and lactate, and butyrate concentration.RESULTS: The study was conducted between August 2019, and March 2020 with 148 patients enrolled (75 CHO group; 73 SF group). Lower concentrations of hypoxanthine (3.87 (3.13-5.18) vs. 4.85 (3.88-6.53)µmol/l, p = 0.00050) and xanthine (0.79 (0.68-0.95) vs. 1.00 (0.88-1.22) µmol/l, < 0.00001) were observed in the maternal blood plasma and umbilical cord blood plasma (10.6 (8.00-16.5) vs. 13.9 (8.53-24.8) µmol/l, p = 0.035 and 1.05 (0.82-1.58) vs. 1.45 (0.94-3.17) µmol/l, p = 0.0035) in patients supplemented with carbohydrates. No difference in β-hydroxybutyrate concentration was noted.CONCLUSIONS: Oral carbohydrate loading prior to cesarean delivery was associated with lower plasma purine levels in maternal and umbilical cord blood. Further work to understand the role of the purinergic pathway and ATP metabolism in maternal and neonatal health may guide interventions such as carbohydrate loading to optimize outcomes.TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04069806 (20190823).PMID:40348958 | DOI:10.1186/s12884-025-07637-6

Multiomics reveals the synergistic response of gut microbiota and spider A. ventricosus to lead and cadmium toxicity

Sat, 10/05/2025 - 12:00
Bull Environ Contam Toxicol. 2025 May 10;114(5):77. doi: 10.1007/s00128-025-04057-2.ABSTRACTThe potential crosstalk between the host and gut microbiota (GM) under heavy metal compound pollution remains unexplored. Herein, using comprehensive analysis of metagenomics, metabolomics, behavioral analysis, and cell morphology to investigate the causal relationship between GM and host responses to cadmium (Cd) and lead (Pb) toxicities. Results indicate that Pb and Cd pollution, alone or together, hinder spider predatory behavior and change the composition and function of GM. Combined exposure reduces protein and exogenous compound metabolism, while single exposure affects energy and lipid metabolism. Gut microbiota helps spider antioxidant activity by increasing glutathione, lipoic acid, and L-cysteine. Oxidative damage, increased Enterobacteriaceae (Salmonella), and lipopolysaccharide (LPS) may harm the midgut barrier. Upregulation of choline and acetylcholine, and downregulation of spermidine, may initiate neurotoxicity. Inhibiting actinomycetes might boost sodium gallate for detoxifying single contaminants. Combined pollution detoxification may involve downregulation of indole synthesis metabolic bacteria, tryptophan, indole metabolites, cytochrome P450 (CYP450), and an increase in Desulfobulbia could remove heavy metals and reduce oxidative stress. Combined pollution has a synergistic effect, making the toxicity of multiple pollutants greater than their individual effects, impacting metal resistance genes (MRGs), and antibiotic resistance ontology (AROs) which used for classifying and describing antibiotic resistance, midgut barrier integrity, oxidative stress, and detoxification. The results help to elucidate the interplay of GM and host's reactions, and aid in monitoring and bioremediation of heavy metal pollution.PMID:40348945 | DOI:10.1007/s00128-025-04057-2

Blood metabolites, protein regulatory networks and their roles in pan-cancer: a mendelian randomisation study

Sat, 10/05/2025 - 12:00
Discov Oncol. 2025 May 10;16(1):721. doi: 10.1007/s12672-025-02522-2.ABSTRACTBACKGROUND: Metabolic dysregulation was closely associated with cancers. However, there is a lack of studies to explore the relationship between blood metabolites, related proteins, and different types of cancer.METHODS: Two-sample Mendelian randomization (MR) analysis was used to assess the causal effects of genetically determined metabolites and metabolite ratios on solid cancers. we analyzed 1400 metabolites/metabolite ratios as exposures and 16 cancers from UK Biobank/FinnGen as outcomes. Protein-metabolite interactions were mapped via MR and visualized with Cytoscape, followed by Gene Ontology enrichment. Clinical validation included metabolomic profiling of 75 breast cancer patients and 20 controls.RESULTS: MR analysis identified 11 metabolites or metabolite ratios causally associated with cancer risk. Moreover, 48 proteins were demonstrated to be involved in the regulation of these metabolites, which are predominantly enriched in 5 significant metabolic pathways in cancers. Clinically, elevated lignoceroylcarnitine (C24) reduced breast cancer risk, while high glucose-to-mannose and alanine-to-asparagine ratios increased risk.CONCLUSIONS: Our study revealed a causal effects of metabolites and its related proteins/pathways on various types of cancers.PMID:40348923 | DOI:10.1007/s12672-025-02522-2

Recommendations for sample selection, collection and preparation for NMR-based metabolomics studies of blood

Sat, 10/05/2025 - 12:00
Metabolomics. 2025 May 10;21(3):66. doi: 10.1007/s11306-025-02259-7.ABSTRACTBACKGROUND: Metabolic profiling of blood metabolites, particularly in plasma and serum, is vital for studying human diseases, human conditions, drug interventions and toxicology. The clinical significance of blood arises from its close ties to all human cells and facile accessibility. However, patient-specific variables such as age, sex, diet, lifestyle and health status, along with pre-analytical conditions (sample handling, storage, etc.), can significantly affect metabolomic measurements in whole blood, plasma, or serum studies. These factors, referred to as confounders, must be mitigated to reveal genuine metabolic changes due to illness or intervention onset.REVIEW OBJECTIVE: This review aims to aid metabolomics researchers in collecting reliable, standardized datasets for NMR-based blood (whole/serum/plasma) metabolomics. The goal is to reduce the impact of confounding factors and enhance inter-laboratory comparability, enabling more meaningful outcomes in metabolomics studies.KEY CONCEPTS: This review outlines the main factors affecting blood metabolite levels and offers practical suggestions for what to measure and expect, how to mitigate confounding factors, how to properly prepare, handle and store blood, plasma and serum biosamples and how to report data in targeted NMR-based metabolomics studies of blood, plasma and serum.PMID:40348843 | DOI:10.1007/s11306-025-02259-7

Fast urine metabolomics for the assessment of Zopiclone effects on insomnia

Sat, 10/05/2025 - 12:00
J Pharmacol Toxicol Methods. 2025 Apr 29:107745. doi: 10.1016/j.vascn.2025.107745. Online ahead of print.ABSTRACTInsomnia is a common symptom of many diseases and is closely associated with neurodegenerative diseases. Zopiclone is one of several clinical hypnotics for treating insomnia. However, some patients are sensitive to this drug treatment, whereas others are not, and the underlying mechanisms remain unclear, causing confusion for making therapeutic regimens and prolong the course of the disease. In present work, we developed a fast urine metabolomics' method for evaluating the sensitivity of insomnia patients to Zopiclone treatment. Firstly, we extracted urine metabolome using methanol-water solutions of different ratios. Secondly, the extracts were either directly injected into LC-MS analysis or dried and resuspended using methanol-water solutions of different concentrations for LC-MS analysis. Then, the total abundance and chromatographic behaviors of urine metabolome from different extraction methods were compared with each other. The optimal extraction method is to mix 50 μl of urine with an equal volume of methanol and 150 μl of water for LC-MS analysis. Finally, the developed method was applied to a metabolomics study of urine from patients with insomnia to evaluate the effectiveness of Zopiclone in treating insomnia. The results showed that there were significant statistical differences in the levels of acylcarnitines, β-hydroxybutyrate (BHB), 4-hydroxybutyric acid (GHB), 3-hydroxyisovaleric acid, citrate, leucine, isoleucine, and valine between the sensitive and insensitive groups treated with Zopiclone. Furthermore, alterations in levels of GHB, valine, and isoleucine were closely correlated with Pittsburgh Sleep Quality Index (PSQI) scores, which may be potential biomarkers for assessing the sensitivity of insomnia patients to Zopiclone treatment, and guiding therapy adjustment.PMID:40348733 | DOI:10.1016/j.vascn.2025.107745

Links between gut microbiota with specific serum metabolite groups in pregnant women with overweight or obesity

Sat, 10/05/2025 - 12:00
Nutr Metab Cardiovasc Dis. 2025 Apr 16:104095. doi: 10.1016/j.numecd.2025.104095. Online ahead of print.ABSTRACTBACKGROUND AND AIM: Gut microbiota may regulate metabolism but is incompletely characterized in pregnancy. Our objective was to investigate the relations using omics techniques.METHODS AND RESULTS: In a cross-sectional setting, fecal and serum samples of 361 healthy pregnant women with overweight or obesity were analyzed with a combinatorial approach of metagenomics and targeted NMR-based metabolomics, with statistical and machine learning techniques to identify and analyze the extent to which the gut microbiota composition and predicted functions would be reflected in the serum metabolome. We identified five biclusters, each of which consisted of a set of gut microbial species and serum metabolites with correlated abundance profiles. Two of the biclusters included metabolites that have been linked to the cardiovascular health; one was linked with factors known to increase the risk i.e., various sizes of lipoprotein subclasses (VLDL and LDL), subclasses of relative lipoprotein lipid concentrations (VLDL, IDL, and LDL), apolipoprotein B, and an inflammation marker, glycoprotein acetylation. These metabolites were associated with abundances of species such as, Enterocloster bolteae and Ruminococcus gnavus. The second bicluster included metabolites linked with a reduced cardiovascular risk, such as different sizes of HDL (high-density lipoprotein), subclasses for relative lipoprotein lipid concentrations and mean diameter for HDL particles, and fatty acid ratios. These metabolites were associated with abundances of species, such as Bacteroides cellulosilyticus and Alistipes finegoldii. We did not observe any biclusters between predicted pathways and serum metabolites.CONCLUSION: Overall, we identified five biclusters of co-abundant gut bacteria and serum metabolites , of which two were linked to pro-atherogenic and anti-atherogenic properties.TRIAL REGISTRATION: www.CLINICALTRIALS: Gov: NCT01922791.PMID:40348632 | DOI:10.1016/j.numecd.2025.104095

Optimal Approaches to Treating and Preventing Acute and Chronic Pouchitis by Altering Microbial Profiles

Sat, 10/05/2025 - 12:00
Gastroenterol Clin North Am. 2025 Jun;54(2):469-483. doi: 10.1016/j.gtc.2024.12.007. Epub 2025 Jan 9.ABSTRACTPouchitis is the most common complication after restorative proctocolectomy with ileal pouch-anal anastomosis for ulcerative colitis. The authors review the role of the microbiota in both the pathogenesis of pouchitis, primarily via dysbiosis, as well as the resultant treatment strategies focused on correcting dysbiosis among patients with pouchitis. These include the role of antibiotics, probiotics, and potentially metabolomics in both treatment and risk stratification.PMID:40348499 | DOI:10.1016/j.gtc.2024.12.007

Microbial Influences on Irritable Bowel Syndrome

Sat, 10/05/2025 - 12:00
Gastroenterol Clin North Am. 2025 Jun;54(2):351-365. doi: 10.1016/j.gtc.2024.12.003. Epub 2025 Jan 10.ABSTRACTSince the description of postinfection irritable bowel syndrome (IBS), a role for gut microbes in the pathogenesis of IBS has been proposed. Molecular microbiological tools have now been applied to IBS, though data are largely derived from fecal samples with attendant limitations. Metagenomics, metabolomics, and other 'omics facilitate a comprehensive picture of the microbiome and its metabolic activity. Has a microbial signature characteristic of IBS been identified? The answer is no; this should not be a surprise given the heterogeneity of the phenotype and each individual's microbiome profile.PMID:40348492 | DOI:10.1016/j.gtc.2024.12.003

Metabolic profile of urine of albuminuric and non-albuminuric nephropathic diabetic patients suggests TCA-cycle related biomarkers

Sat, 10/05/2025 - 12:00
Diabetes Res Clin Pract. 2025 May 8:112215. doi: 10.1016/j.diabres.2025.112215. Online ahead of print.ABSTRACTAIM: Diabetic kidney disease (DKD) is a common and serious complication of diabetes. Moreover, ∼25 % of DKD patients are non-albuminuric complicating diagnosis. This study aimed to identify potential urinary metabolic biomarkers in healthy and DKD patients, both with (A-DKD) and without albuminuria (NA-DKD).METHODS: We analyzed urine samples from healthy controls (n = 23) and DKD (n = 17) patients. DKD patients were further split into NA-DKD (n = 5) and A-DKD (n = 12). A non-targeted proton nuclear magnetic resonance (1H NMR) metabolomics was used to explore metabolic differences.RESULTS: DKD patients exhibited lower levels of citrate, hypoxanthine, formate, isobutyrate, glycine, phenylacetate, dimethylamine, and valine in urine samples, and higher levels of trans-aconitate, glycolate, and taurine. Citrate presented the strongest negative correlation (r = -0.65,p < 0.0001), followed by hypoxanthine (r = -0.49,p = 0.004), isobutyrate (r = -0.45,p = 0.004) and formate (r = -0.41,p = 0.009). On the other hand, glycolate (r = 0.46,p = 0.003), taurine (r = 0.47,p = 0.007), and trans-aconitate (r = 0.41,p = 0.05) were positively correlated with albuminuria. Glycine was downregulated, and alanine was upregulated in NA-DKD compared to A-DKD. Receiver operating characteristic curve analysis identified citrate, hypoxanthine, and taurine as key predictors for distinguish patients with normal and higher levels of albuminuria.CONCLUSION: Urinary metabolites related to Krebs cycle (TCA) and purine metabolism can potentially serve as a marker to individualize therapeutic choices in DKD, especially for non-albuminuric phenotype.PMID:40348339 | DOI:10.1016/j.diabres.2025.112215

Unraveling mercury-selenium interactions through metabolomics: Impacts on riverside communities in the Amazon

Sat, 10/05/2025 - 12:00
Environ Pollut. 2025 May 8:126398. doi: 10.1016/j.envpol.2025.126398. Online ahead of print.ABSTRACTAmazonian riverside populations face high mercury (Hg) and selenium (Se) exposure through diet and fish-rich consumption. While Hg is a well-known neurotoxin with systemic effects, the impacts of chronic Se exposure and its interaction with Hg in the human body remain insufficiently understood. Consequently, we aimed to elucidate metabolomic changes associated with varying Hg and Se blood levels. This study analyzed 352 blood samples, categorized into five groups based on Hg and Se levels, using nuclear magnetic resonance (NMR) spectroscopy. Partial least squares discriminant analysis (PLS-DA) revealed that elevated Hg exposure resulted in disrupted glucose, lactate, and branched-chain amino acid metabolism due to oxidative stress and energy dysfunction. Remarkably, individuals with high Hg and elevated Se in blood exhibited metabolic profiles closer to the control group, suggesting a protective Se effect. Additionally, proline and glutamine exhibited differential responses to Hg and Se levels. Furthermore, our analysis provided insights into Hg detoxification mechanisms through selenoprotein interactions. These findings highlight the potential of Se to mitigate Hg toxicity and underscore its dietary importance for at-risk populations.PMID:40348267 | DOI:10.1016/j.envpol.2025.126398

MgFe-LDHs/Vallisneria natans combined system for simultaneous elimination of endogenous N and P pollution in eutrophic water: Performance, synergetic mechanism, and metagenomics analysis

Sat, 10/05/2025 - 12:00
Environ Res. 2025 May 8:121798. doi: 10.1016/j.envres.2025.121798. Online ahead of print.ABSTRACTEutrophication is the main factor for the degradation of lake ecosystems. More than exogenous input, endogenous N and P nutrients are responsible for it. Although the P passivation technology with functional materials is common for alleviating endogenous P pollution, will it have the same effect for endogenous N removal? In this study, a novel MgFe-LDHs/Vallisneria natans (V. natans) combined system was established for effective eliminating endogenous N and P simultaneously. During remediation periods, MgFe-LDHs/V. natans combined system with the most obvious improvement for overlying water quality that was reflected by DO, ORP, and SS, and TP, TN, and NH4+-N removal efficiency were up to 99%. In sediments, TP and TN removal rate was approximately 68% and 63%, where the reduction of Org-P and NH4+-N accounted for the majority of it, respectively. Under stimulation of MgFe-LDHs, NH4+-N assimilation in V. natans could be promoted through improving the metabolizing enzymes activity. In turn, V. natans contributed to Org-P mineralization by secreting organic acid, further facilitating IP enrichment on MgFe-LDHs. Additionally, owing to the synergism between V. natans allelopathy and MgFe-LDHs, the symbiotic relationship between microbial communities was much closer and more stable, the expression of functional genes that relate to denitrification, assimilatory nitrate reduction, phosphorylation and organophosphorus mineralization processes were up-regulated prominently. That is, microorganisms acted synergistically were important for endogenous N and P elimination performance. This study proposed a high-efficiency and environmentally friendly materials/plants combined remediation technology for eutrophication, especially those where with much high endogenous N and P loading.PMID:40348264 | DOI:10.1016/j.envres.2025.121798

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