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
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

LC-MS-based untargeted metabolomics reveals benzoic acid as a predictive biomarker for embryo implantation potential

Mon, 07/04/2025 - 12:00
Analyst. 2025 Apr 7. doi: 10.1039/d4an01552e. Online ahead of print.ABSTRACTEvaluating the quality of embryos and implantation potential is a critical determinant of in vitro fertilization and embryo transfer, and it is also one of the main challenges of assisted reproductive technology. A reliable non-invasive method to choose the best candidate with real implantation potential for transfer from two day-3 embryos with equal morphological quality is still lacking clinically. In this article, a sensitive LC-MS method was developed and metabolomic profiling analysis in a 3-day embryo culture medium was performed. Differential metabolites were analysed in two kinds of commercial culture media, and a total of 66 common metabolites were obtained from 106 independent samples in 5 batches. The relationship between changes in key metabolite, benzoic acid, concentration and the embryo implantation result was discovered. This work improved coverage through conditional optimization, enhanced the reliability of omics data through multi-batch validation, and provided a potential biomarker for evaluating the implantation potential of day-3 embryos.PMID:40190166 | DOI:10.1039/d4an01552e

Enhanced Separation of Extracellular Vesicles Using Capillary Isotachophoresis With Spacer Compounds

Mon, 07/04/2025 - 12:00
Electrophoresis. 2025 Apr 6. doi: 10.1002/elps.202400113. Online ahead of print.ABSTRACTExtracellular vesicles (EVs) are pivotal in numerous physiological and pathological processes, such as immune responses, viral pathogenesis, pregnancy, cardiovascular diseases, and cancer progression. Their capacity to influence complex intracellular pathways highlights their therapeutic potential in addressing various conditions, including neurodegenerative diseases and cancer. A novel capillary isotachophoresis (cITP) method was developed for the electrokinetic characterization of pre-isolated EVs. Distinct peaks could be resolved at near-baseline resolution using a novel mixture of spacer ions and laser-induced fluorescence (LIF) detection. The vesicles were effectively separated from the unbound carboxyfluorescein diacetate succinimidyl ester (CFDA-SE) amine-reactive fluorescent stain used to detect them and from residual contaminants. The identity of the peaks shown in the electropherograms was validated via various methods, including incubation with specific antibodies or spiking of putative contaminants, such as proteins and lipoproteins. This report thus provides a detailed proof-of-concept for using cITP-LIF for extracellular vesicle isolation, subtype fractionation, and profiling.PMID:40189777 | DOI:10.1002/elps.202400113

Strengthening the reporting of diet item details in feeding studies measuring the dietary metabolome: The DID-METAB core outcome set statement

Sun, 06/04/2025 - 12:00
Eur J Clin Invest. 2025 Apr 6:e70030. doi: 10.1111/eci.70030. Online ahead of print.NO ABSTRACTPMID:40189732 | DOI:10.1111/eci.70030

Suboptimal pre-anthesis water status mitigates wheat susceptibility to fusarium head blight and triggers specific metabolic responses

Sun, 06/04/2025 - 12:00
Sci Rep. 2025 Apr 6;15(1):11773. doi: 10.1038/s41598-025-96159-4.ABSTRACTThe impact of abiotic challenges on plant physiology reshapes plant-pathogen interactions by modulating the plant immune responses. In wheat, the development of Fusarium Head Blight (FHB) is heavily influenced by environmental conditions, especially during the pre-anthesis stage, just before fungal infection occurs. The early stages of infection are thus likely conditioned by prior environmental changes with consequences on the disease outcome that require further characterization. In this study, we aimed to assess the impact of pre-anthesis water depletion followed by rapid rehydration at inoculation on the expression of FHB-related molecular determinants with emphasis on susceptibility factors and metabolism-related processes. Water depletion altered plant physiology and its effects remained detectable after three days after rehydration, leading to significantly reduced FHB symptoms. Dual-transcriptomics, combined with untargeted metabolomics, revealed two key findings including (i) extensive metabolic changes specific to prior water stress, and (ii) the strong conservation of previously identified candidate susceptibility genes regulation. Considering the combined stress effects, a unique response signature emerged, highlighting that immune responses are strongly interwoven with physiological adjustments. Our findings provide new insights into the trade-offs that plants make under multiple challenges and identify original wheat metabolic determinants that may improve FHB resistance even in suboptimal physiological conditions.PMID:40189612 | DOI:10.1038/s41598-025-96159-4

Gut microbiota contributes to protection against porcine deltacoronavirus infection in piglets by modulating intestinal barrier and microbiome

Sun, 06/04/2025 - 12:00
Microbiome. 2025 Apr 7;13(1):93. doi: 10.1186/s40168-025-02092-z.ABSTRACTBACKGROUND: Gut microbiota plays a critical role in counteracting enteric viral infection. Our previous study demonstrated that infection of porcine deltacoronavirus (PDCoV) disturbs gut microbiota and causes intestinal damage and inflammation in piglets. However, the influence of gut microbiota on PDCoV infection remains unclear.RESULTS: Firstly, the relationship between gut microbiota and disease severity of PDCoV infection was evaluated using 8-day-old and 90-day-old pigs. The composition of gut microbiota was significantly altered in 8-day-old piglets after PDCoV infection, leading to severe diarrhea and intestinal damage. In contrast, PDCoV infection barely affected the 90-day-old pigs. Moreover, the diversity (richness and evenness) of microbiota in 90-day-old pigs was much higher compared to the 8-day-old piglets, suggesting the gut microbiota is possibly associated with the severity of PDCoV infection. Subsequently, transplanting the fecal microbiota from the 90-day-old pigs to the 3-day-old piglets alleviated clinical signs of PDCoV infection, modulated the diversity and composition of gut microbiota, and maintained the physical and chemical barrier of intestines. Additionally, metabolomic analysis revealed that the fecal microbiota transplantation (FMT) treatment upregulated the swine intestinal arginine biosynthesis, FMT significantly inhibited the inflammatory response in piglet intestine by modulating the TLR4/MyD88/NF-κB signaling pathway.CONCLUSIONS: PDCoV infection altered the structure and composition of the gut microbiota in neonatal pigs. FMT treatment mitigated the clinical signs of PDCoV infection in the piglets by modulating the gut microbiota composition and intestinal barrier, downregulating the inflammatory response. The preventive effect of FMT provides novel targets for the development of therapeutics against enteropathogenic coronaviruses. Video Abstract.PMID:40189556 | DOI:10.1186/s40168-025-02092-z

The key metabolic pathway of roots and leaves responses in Arachis hypogaea under Al toxicity stress

Sun, 06/04/2025 - 12:00
BMC Plant Biol. 2025 Apr 7;25(1):439. doi: 10.1186/s12870-025-06460-7.ABSTRACTBACKGROUND: Aluminum (Al) toxicity inhibits plant growth and alters gene expression and metabolite profiles. However, the molecular mechanisms underlying the effects of Al toxicity on peanut plants remain unclear. Transcriptome and metabolome analyses were conducted to investigate the responses of peanut leaves and roots to Al toxicity.RESULTS: Al toxicity significantly inhibited peanut growth, disrupted antioxidant enzyme systems in roots and leaves, and impaired nutrient absorption. Under Al toxicity stress, the content of indole-3-acetic acid-aspartate (IAA-Asp) decreased by 23.94% in leaves but increased by 12.91% in roots. Methyl jasmonate (MeJA) levels in leaves increased dramatically by 2642.86%. Methyl salicylate (MeSA) content in leaves and roots increased significantly by 140.00% and 472.22%, respectively. Conversely, isopentenyl adenosine (IPA) content decreased by 78.95% in leaves and 20.66% in roots. Transcriptome analysis identified 5831 differentially expressed genes (DEGs) in leaves and 6405 DEGs in roots, whereas metabolomics analysis revealed 210 differentially accumulated metabolites (DAMs) in leaves and 240 DAMs in roots. Under Al toxicity stress, both leaves and roots were significantly enriched in the "linoleic acid metabolism" pathway. Genes such as lipoxygenase LOX1-5 and LOX2S were differentially expressed, and metabolites, including linoleic acid and its oxidized derivatives, were differentially accumulated, mitigating oxidative stress.CONCLUSIONS: This study elaborates on the potential complex physiological and molecular mechanisms of peanuts under aluminum toxicity stress, and highlights the importance of linoleic acid metabolism in coping with aluminum toxicity. These findings enhance our understanding of the impact of aluminum toxicity on peanut development and the response of key metabolic pathways, providing potential molecular targets for genetic engineering to improve crop resistance to aluminum stress.PMID:40189501 | DOI:10.1186/s12870-025-06460-7

Pharmacometabolomics: An emerging platform for understanding the pathophysiological processes and therapeutic interventions

Sun, 06/04/2025 - 12:00
Int J Pharm. 2025 Apr 4:125554. doi: 10.1016/j.ijpharm.2025.125554. Online ahead of print.ABSTRACTPharmacometabolomics has emerged as a new subclass of metabolomics, aiming to predict an individual's response to a drug or optimize therapy based on prior information on an individual's metabolic profile. Pharmacometabolomics is being explored in drug discovery, biomarker identification, disease diagnosis, monitoring of disease progression, and therapeutic intervention. The time points-based sample collection is essential to measure the response of individuals to pathophysiological processes and therapeutic interventions. Analytical techniques such as NMR, LC-MS, and GC-MS have been employed to assess a huge number of metabolites present in biological systems. NMR has an advantage over other analytical techniques as it provides a snapshot of tissue and biological fluids, however, it requires higher magnetic fields to achieve better resolution. GC-MS could cover a wide range of metabolites due to high resolution but requires derivatization for certain metabolites. LC-MS is equally competitive and separates a wide range of metabolites with diverse polarities but requires extensive method development. Several platforms have been developed to analyze the analytical data and provide meaningful results via data reduction methods. PCA and PLS-DA are the most common methods for reduction dimensionality through simplified multivariate data modeling. This manuscript brings insights into the overview of pharmacometabolomics experimental design and the application of various analytical techniques and multivariate statistical analysis in the various fields of medical research.PMID:40189169 | DOI:10.1016/j.ijpharm.2025.125554

Serum and urine metabolite correlates of vitamin D supplementation in the Atherosclerosis Risk in Communities (ARIC) Study

Sun, 06/04/2025 - 12:00
Clin Nutr ESPEN. 2025 Apr 4:S2405-4577(25)00263-3. doi: 10.1016/j.clnesp.2025.03.172. Online ahead of print.ABSTRACTBACKGROUND & AIMS: Vitamin D regulates calcium and phosphorus homeostasis, skeletal health, and potentially other aspects of health. There are limitations of existing vitamin D biomarkers. We aimed to discover novel vitamin D biomarkers by investigating serum and urine metabolites associated with vitamin D supplementation.METHODS: We examined cross-sectional associations between vitamin D supplementation and serum and urine metabolites in Atherosclerosis Risk in Communities Study participants at visit 5 (2011-2013). Untargeted metabolomic profiling of serum and spot urine samples was performed by Metabolon, Inc. We analyzed associations between vitamin D supplementation and log2-transformed metabolites using linear regression models adjusted for demographic, lifestyle, and health covariates.RESULTS: Of 5225 participants with serum metabolites analyzed (mean age 76 [SD 5] years, 57% female, 20% Black), 45% reported taking vitamin D supplements. Eighty-two of 933 serum metabolites were associated with vitamin D supplementation (P<0.05/933). Most were lipids (n=36). Of 1565 participants with urine metabolites analyzed, one-third (37%) used vitamin D. Nineteen of 946 urine metabolites were associated with vitamin D supplementation (P<0.05/946). Most were cofactors and vitamins (n=12). After adjusting for other supplement use (multivitamin/mineral, omega-3, B and C vitamins), 5 serum metabolites (pro-hydroxy-pro, pyroglutamine, sulfate, creatine, and 2-hydroxypalmitate) and no urine metabolites were significantly associated with vitamin D supplementation.CONCLUSIONS: Many serum and urine metabolites were associated with vitamin D supplementation. Five serum metabolites remained associated with vitamin D after adjustment for other dietary supplements, including metabolites of bone collagen degradation, glutathione metabolism, and sphingolipid metabolism. These metabolites may reflect physiological activities of vitamin D and, thus, improve assessment of vitamin D adequacy to achieve functional outcomes. These merit further investigation as potential vitamin D biomarkers.PMID:40189143 | DOI:10.1016/j.clnesp.2025.03.172

Toxicological evaluation and metabolic profiling of earthworms (Eisenia fetida) after exposure to microplastics and acetochlor

Sun, 06/04/2025 - 12:00
Environ Res. 2025 Apr 4:121546. doi: 10.1016/j.envres.2025.121546. Online ahead of print.ABSTRACTIn recent years, microplastic (MPs) and pesticide pollution have become prominent issues in the field of soil pollution. This research endeavored to assess the impact of ultraviolet radiation (UV) on the characteristics of microplastics, as well as investigating the toxicological effect on earthworms (Eisenia fetida) when subjected to the dual stressors of microplastics and acetochlor (ACT). This research found that microplastics aged under UV were more prone to wear and tear in the environment, and produced more oxygen-containing functional groups. Chronic exposure experiments were conducted on ACT and aged-MPs. The results revealed that aged-MPs and ACT inhibited earthworm growth, induced oxidative stress, and caused damage to both the body cavity muscles and the intestinal lumen. Compared with individual exposure, combined exposure increased the oxidative products (superoxide dismutase (SOD) and catalase (CAT)) and altered the expression levels of related genes (TCTP and Hsp70) significantly. PE inflicted more significant harm to the earthworm intestinal tissue compared to PBAT. By 1H-NMR metabolomics, the investigation delved into the repercussions of PE and ACT on the metabolic pathways of earthworms. Exposure to ACT and PE can disrupt the stability of intestinal membranes stability, amino acid metabolism, neuronal function, oxidative stress and energy metabolism. Overall, the research revealed that combined exposure of MPs and ACT exacerbated the negative effects on earthworms significantly, and contributed valuable insights to environmental risk assessment of the combined toxicity of microplastics and pesticides.PMID:40189011 | DOI:10.1016/j.envres.2025.121546

The metabolomic signature of childhood trauma

Sun, 06/04/2025 - 12:00
Biol Psychiatry. 2025 Apr 4:S0006-3223(25)01106-0. doi: 10.1016/j.biopsych.2025.03.018. Online ahead of print.ABSTRACTBACKGROUND: Although childhood trauma is an important risk factor for various diseases, biological mechanisms remain insufficiently understood. To deepen this understanding, we investigated the wide-spectrum metabolomic signature of childhood trauma exposure in a large adult cohort.METHODS: Baseline and six-year follow-up data from the Netherlands Study of Depression and Anxiety were used (Nparticipants=2,902, Nobservations=4,800). Childhood trauma exposure was retrospectively assessed with the Childhood Trauma Interview. Plasma metabolite levels were measured with the Metabolon mass spectrometry-based untargeted metabolomics platform at both timepoints. Mixed-effect models evaluated the metabolomics associations of childhood trauma while controlling for sociodemographic, lifestyle, health-related, and technical covariates. We examined the overlap between the metabolomic profiles of childhood trauma and depression. External replication was tested in 308 additional participants.RESULTS: Childhood trauma was associated in a dose-response manner with 18 metabolites. Upregulated metabolites were nominally enriched with compounds involved in fatty acid and branched-chain amino acid metabolism (p=3.91e-02, qFDR>.05) while downregulated metabolites were nominally enriched with corticosteroids (p=2.24e-03, qFDR>.05). Six of the 18 metabolites were linked to childhood trauma but not depression. Findings were partially replicated using an alternative measure for childhood trauma (effect sizes correlation r=0.94) and an external sample (r=0.54).CONCLUSIONS: Childhood trauma was linked in a dose-response manner to a biological signature encompassing a wide array of metabolites. Dysregulations were observed in amino acid and fatty acid metabolism as well as hypothalamic-pituitary-adrenal axis function. Further studies should corroborate these findings and develop early-intervention strategies targeting trauma-related biological mechanisms to prevent cardiometabolic and psychiatric diseases.PMID:40189007 | DOI:10.1016/j.biopsych.2025.03.018

Multi-Omics Analysis Reveals BPF Exposure Causes Hepatic Glucose and Lipid Metabolism Disorder in Rats by Disrupting Energy Homeostasis

Sun, 06/04/2025 - 12:00
Toxicology. 2025 Apr 4:154130. doi: 10.1016/j.tox.2025.154130. Online ahead of print.ABSTRACTBisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the toxicity of BPF to the liver and how it affects glucose metabolism and lipid metabolism is still unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.PMID:40188933 | DOI:10.1016/j.tox.2025.154130

The integrated analysis of transcriptomics and metabolomics reveals the effects of tea polyphenols on lipid metabolism in lion-head geese

Sun, 06/04/2025 - 12:00
Poult Sci. 2025 Mar 1;104(6):104958. doi: 10.1016/j.psj.2025.104958. Online ahead of print.ABSTRACTTea polyphenols are a class of natural plant compounds with potent antioxidant properties, and their critical role in regulating lipid metabolism has been demonstrated in numerous studies. However, systematic research on the effects of tea polyphenols on lipid metabolism in lion-head geese remains limited. In this study, we examined the impact of tea polyphenols on lipid metabolism in geese through an integrative analysis of transcriptomics and metabolomics. A total of 240 healthy male lion-head geese with similar body weights at 1 day of age were randomly allocated into two treatment groups (6 replicates per group, with 20 geese per replicate). The control group received a basal diet, while the experimental group was supplemented with 1000 mg/kg of tea polyphenols (50.4 % catechin purity) in the basal diet for 18 weeks. The results indicated that serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) activities were significantly increased (P < 0.05), while malondialdehyde (MDA) levels were significantly decreased (P < 0.05) in the tea polyphenol group compared to the control group. Additionally, serum triglycerides (TG), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) activities were significantly lower (P < 0.05) in the tea polyphenol group than in the control group. Hepatic transcriptomic analysis further revealed that tea polyphenols significantly modulated the expression of several genes involved in lipid metabolism, including angiopoietin-like 4 (ANGPTL4), which plays a role in regulating lipid homeostasis, as well as glycerophosphodiester phosphodiesterase domain containing 2 (GDPD2), immunoglobulin heavy chain (IGH), proto-oncogene protein c-fos (FOS), and matrix metallopeptidase 1 (MMP1), etc. Serum metabolomic analysis also demonstrated significant alterations in lipid metabolites induced by tea polyphenols, including the downregulation of fatty acyl metabolites such as L-Palmitoylcarnitine and Hexadecanal. Moreover, the combined analysis revealed a strong positive correlation between ANGPTL4 and the organic compounds of steroidal saponins, such as Glucoconvallasaponin B, and negative correlations with glycerophospholipid metabolites, such as LysoPC (P-16:0). The comprehensive analysis suggests that the inclusion of tea polyphenols in the diet enhances the antioxidant capacity of lion-head geese, improves hepatic lipid profiles, and regulates lipid metabolism via modulating lipid metabolism-related genes and metabolites.PMID:40188624 | DOI:10.1016/j.psj.2025.104958

Plasma metabolomics differentiating and predicting prognosis of coronary artery disease patients with distinct nutritional status

Sun, 06/04/2025 - 12:00
Nutr Res. 2025 Jan 15;137:1-13. doi: 10.1016/j.nutres.2025.01.004. Online ahead of print.ABSTRACTThis study investigated the metabolic mechanisms underlying the association between malnutrition and poor prognosis in coronary artery disease (CAD). We hypothesized that specific metabolites associated with nutritional status impact all-cause mortality and Major Adverse Cardiovascular Events in CAD patients. To test this hypothesis, we evaluated the nutritional status of 5182 CAD patients from multiple centers using three nutritional risk screening tools and analyzed the impact on CAD outcomes with restricted cubic splines and Cox regression. Poor nutritional status was found to be linked to increased adverse outcomes. Further analysis using multiple linear regression and mediation analysis identified elevated concentrations of β-pseudouridine and dulcitol, and decreased concentrations of l-tryptophan and LPC (18:2/0:0), among other metabolites, as mediators of this association. Employing Least Absolute Shrinkage and Selection Operator for variable selection, we integrated these metabolites with clinical variables, which significantly improved the predictive accuracy for adverse outcomes. Our results highlight significant metabolic disparities in CAD patients based on nutritional status and provide novel insights into the role of nutrition-associated metabolites in CAD prognosis. These findings suggest that customized nutritional interventions targeting these metabolites could positively influence the progression of CAD.PMID:40188579 | DOI:10.1016/j.nutres.2025.01.004

Protocol for dual metabolomics and proteomics using nanoflow liquid chromatography-tandem mass spectrometry

Sun, 06/04/2025 - 12:00
STAR Protoc. 2025 Apr 5;6(2):103745. doi: 10.1016/j.xpro.2025.103745. Online ahead of print.ABSTRACTNanoflow liquid chromatography-tandem mass spectrometry (nLC-MS) benefits untargeted metabolomics by enhancing sensitivity and integrating proteomics for the same sample. Here, we present a protocol to enable nLC-MS for dual metabolomics and proteomics. We describe steps for solid-phase micro-extraction (SPME)-assisted metabolite cleaning and enrichment, which avoids capillary column blockage. We then detail nLC-MS data acquisition and analysis. This protocol has been applied in diverse specimens including biofluids, cell lines, and tissues. For complete details on the use and execution of this protocol, please refer to Lin et al.1.PMID:40188434 | DOI:10.1016/j.xpro.2025.103745

PGPB-driven bioenrichment and metabolic modulation of Salicornia europaea under marine Aquaponic conditions

Sun, 06/04/2025 - 12:00
World J Microbiol Biotechnol. 2025 Apr 7;41(4):124. doi: 10.1007/s11274-025-04335-5.ABSTRACTThis study analyzed the secondary metabolite profile of Salicornia europaea inoculated with Brevibacterium casei EB3 and Pseudomonas oryzihabitans RL18 in aquaponic systems, exploring the metabolic mechanisms responsible for the observed shifts. Experiments were conducted in both microcosm and pilot-scale aquaponic setups to evaluate how these metabolic shifts vary across different system scales and their potential contributions to the observed increased accumulation of bioactive compounds with antioxidant and antimicrobial properties, including some phenolic acids, such as caffeic acid (154-fold), flavonoids (2.85-fold), and some unsaturated fatty acids, such as oct-3-enoic acid (32-fold). Metabolic profiling revealed shifts in pathways associated with plant growth and stress resilience, such as amino acid and phenolic biosynthesis. Additionally, differences in metabolic responses observed between microcosm and pilot-scale systems underscored the importance of understanding scaling effects. These findings highlight the potential for optimizing aquaponic systems by leveraging microbial-plant interactions to enhance ecological and economic outcomes. This approach offers valuable applications in nutrient recycling, phytopharmaceutical development, and the advancement of saline agriculture within integrated aquaculture frameworks.PMID:40189660 | DOI:10.1007/s11274-025-04335-5

Elucidating molecular lipid perturbations in trigeminal neuralgia using cerebrospinal fluid lipidomics

Sun, 06/04/2025 - 12:00
Sci Rep. 2025 Apr 6;15(1):11777. doi: 10.1038/s41598-025-89755-x.ABSTRACTTrigeminal neuralgia (TN) is a neuropathic facial pain disorder characterized by severe stabbing pain along the trigeminal nerve. While its pathogenesis remains unclear, nerve demyelination and inflammation are likely involved. Current research has primarily focused on various blood-based omics approaches, which do not fully capture the lipid alterations occurring during TN progression in brain. In contrast, our study is the first to investigate cerebrospinal fluid (CSF) lipidomic profiles in TN patients, aiming to elucidate potential disease mechanisms. CSF samples were collected from 22 TN patients and 18 healthy controls, followed by untargeted lipidomic analysis using high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. A pipeline for lipid identification and relative quantification, combined with statistical analysis, revealed 188 lipid species across 21 classes. We found significant upregulation of Cer-NPs, LPCs, PCs, TGs, and OxTGs in TN patients, while stigmasterol hexoside was downregulated. Moderate correlations were observed between lipid species and clinical parameters. These findings highlight considerable CSF lipidome alterations in TN, suggesting roles for nerve demyelination, neuroinflammation, and pain sensitization in its pathogenesis. Our study provides novel insights into lipid targets that may offer therapeutic potential for managing TN.PMID:40189602 | DOI:10.1038/s41598-025-89755-x

Protein associations and protein-metabolite interactions with depressive symptoms and the p-factor

Sun, 06/04/2025 - 12:00
Transl Psychiatry. 2025 Apr 6;15(1):128. doi: 10.1038/s41398-025-03362-y.ABSTRACTDespite increasing mental health problems among young people, few studies have examined associations between plasma proteins and mental health. Interactions between proteins and metabolites in association with mental health problems remain underexplored. In 730 twins, we quantified associations between plasma proteins measured at age 22 with 21 indicators of either depressive symptoms or the p-factor and tested for interactions with metabolites. Symptoms were collected from questionnaires and interviews completed by different raters (e.g., self-report, teachers) through adolescence to young adulthood (12 to 22 years). We found 47 proteins associated with depressive symptoms or the p-factor (FDR < 0.2), 9 being associated with both. Two proteins, contactin-1 and mast/stem cell growth factor receptor kit, positively interacted with valine levels in explaining p-factor variability. Our study demonstrates strong associations between plasma proteins and mental health and provides evidence for proteome-metabolome interactions in explaining higher levels of mental health problems.PMID:40189586 | DOI:10.1038/s41398-025-03362-y

Integrating metabolomics and network pharmacology to investigate Mu Jin Powder prevents ethanol-induced gastric ulcer in rats

Sun, 06/04/2025 - 12:00
J Ethnopharmacol. 2025 Apr 4:119730. doi: 10.1016/j.jep.2025.119730. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Gastric ulcer (GU) is a common multifactorial gastrointestinal disorder, affecting millions of people worldwide. Mu Jin Powder (MJP), a renowned herbal pair, was recorded in Yizong Jinjian by Wu Qian during the Qing dynasty. This combination has been integrated into traditional Chinese medicine (TCM) prescriptions for gastrointestinal diseases, particularly GU, and has demonstrated significant results in modern medicine studies. However, the specific advantages of MJP for GU and its underlying mechanisms remain insufficiently understood, requiring further investigation.AIM OF THE STUDY: To assess the preventive effects of MJP on ethanol-induced gastric mucosal injury and elucidate its underlying mechanisms.MATERIALS AND METHODS: This study was based on ethanol induced SD rat model to elucidate the pharmacological effects of MJP. The chemical components of MJP and the absorbed components in the serum of treated rats were identified by UPLC-Q-TOF-MS. Serum metabolomics and Network pharmacology were applied to investigate the potential mechanisms of MJP against GU, and the mechanistic pathways were verified through PCR and Western blot analyses.RESULTS: In vivo pharmacological experiments demonstrated that MJP significantly reduced ulcer area and improved the histopathological features of gastric tissues. Fifty-three chemical components were determined in MJP, and 18 absorbed components were detected in the serum of treated rats for the first time. Non-targeted serum metabolomics revealed 28 significantly altered differential metabolites, most of which were modulated and normalized by MJP. Comprehensive network pharmacology and metabolomics analyses indicated that MJP exerted anti-GU effects by intervening in 5 key target proteins (PTG2, CHRNA7, CA1, PTG1, CASP3, and AKT1) and regulating differential metabolites. PCR and Western blot analyses suggested that MJP may inhibit the PI3K/Akt/NF-κB pathway to prevent ethanol-induced gastric ulcers.CONCLUSIONS: Mu Jin Powder effectively ameliorates ethanol-induced gastric ulcers in rats, potentially by inhibiting the PI3K/Akt/NF-κB pathway.PMID:40188894 | DOI:10.1016/j.jep.2025.119730

Targeting regulation of nitrate removal and chlorophenol degradation through hydrogen/oxygen switching

Sun, 06/04/2025 - 12:00
Water Res. 2025 Mar 31;281:123581. doi: 10.1016/j.watres.2025.123581. Online ahead of print.ABSTRACTNitrate is a common co-contaminant with 2,4-dichlorophenol (2,4-DCP) in water, presenting a challenge for environmental remediation. Under anaerobic conditions, the ring cleavage of chlorophenol is inefficient, while under aerobic conditions, nitrate removal is hindered. In this study, a microbial consortium capable of hydrogenotrophic denitrification and 2,4-DCP degradation was cultured, aiming to achieve efficient nitrate removal and 2,4-DCP degradation by alternately switching between hydrogen (H2) and oxygen (O2). Under H2 conditions, nitrate removal exceeded 90 %, while under O2 conditions, 2,4-DCP degradation reached 100 %. Under H2 conditions, the abundance of the Nar gene which was involved in nitrate reduction was higher than that under O2 conditions, promoting hydrogenotrophic denitrification. In contrast, under O2 conditions, 2,4-DCP degradation occurred via hydroxylation, ring-cleavage, dechlorination, and mineralization through the TCA cycle. Metagenomic and metabolomic analysis was performed to explore microbial metabolic pathways and potential synergistic mechanisms involved in hydrogenotrophic denitrification and 2,4-DCP biodegradation. In the H2-atmosphere, microbes (Methylobacillus and Chromobacterium), genes (E3.1.1.45 and speG), and metabolites (Cytosine and Uridine) may play a crucial role in hydrogenotrophic denitrification. In the O2-atmosphere, the functional genus of Paracoccus and Aquamicrobium associated with genes (tfdB and tfdC) may contribute to 2,4-DCP and its metabolites 2-Chloromaleylacetate degradation. These findings confirmed the role of functional microbial communities through H2/O2 regulation. This work provides a promising technological reference for treating industrial wastewater containing phenols and nitrogen.PMID:40188788 | DOI:10.1016/j.watres.2025.123581

A dietary pattern promoting gut sulfur metabolism is associated with increased mortality and altered circulating metabolites in low-income American adults

Sun, 06/04/2025 - 12:00
EBioMedicine. 2025 Apr 5;115:105690. doi: 10.1016/j.ebiom.2025.105690. Online ahead of print.ABSTRACTBACKGROUND: Excessive hydrogen sulfide in the gut, generated by sulfur-metabolising bacteria from foods, has been linked to intestinal inflammation and human diseases. We aim to investigate the interplay between diet and sulphur-metabolising bacteria in relation to mortality and circulating metabolites in understudied populations.METHODS: In the Southern Community Cohort Study (SCCS), a prospective cohort of primarily low-income American adults, habitual diets were assessed using a food frequency questionnaire at baseline (2002-2009). A sulfur microbial diet score (SMDS) was developed among 514 Black/African American participants by linking habitual dietary intakes with the abundance of sulfur-metabolising bacteria profiled by faecal shotgun metagenomics. The SMDS was then constructed among all eligible SCCS participants (50,114 Black/African American and 23,923 non-Hispanic White adults), and its associations with mortality outcomes were examined by Cox proportional hazards model and Fine-Grey subdistribution hazard model. The association between SMDS and 1110 circulating metabolites was examined by linear regression among 1688 SCCS participants with untargeted metabolomic profiling of baseline plasma samples.FINDINGS: Over an average 13.9-year follow-up, SMDS was associated with increased all-cause mortality (HR [95% CI] for the highest vs. lowest quartiles: 1.21 [1.15-1.27]) and cardiovascular disease (1.18 [1.08-1.29]), cancer (1.13 [1.02-1.25]), and gastrointestinal cancer-specific (1.22 [1.00-1.49]) mortality among Black/African American participants (all P-trend<0.05). The associations were largely consistent across participant subgroups. Similar results were observed among non-Hispanic White participants. The SMDS was associated with 112 circulating metabolites, which mediated 36.15% of the SMDS-mortality association (P = 0.002).INTERPRETATION: A dietary pattern promoting sulfur-metabolising gut bacteria may contribute to increased total and disease mortality in low-income American adults.FUNDING: This study was funded by the National Institutes of Health, United States, to Vanderbilt University Medical Center, United States, and Anne Potter Wilson Chair endowment to Vanderbilt University, United States.PMID:40188743 | DOI:10.1016/j.ebiom.2025.105690

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