PubMed

FASEB J. 2025 Feb 15;39(3):e70365. doi: 10.1096/fj.202402930R.ABSTRACTExercise impinges on almost all physiological processes at an organismal level and is a potent intervention to treat various diseases. Exercise performance is well established to display diurnal rhythm, peaking during the late active phase. However, the underlying molecular/metabolic factors and mitochondrial energetics that possibly dictate time-of-day exercise capacity remain unknown. Here, we have unraveled the importance of diurnal variation in mitochondrial functions as a determinant of skeletal muscle exercise performance. Our results show that exercise-induced muscle metabolome and mitochondrial energetics are distinct at ZT3 and ZT15. Importantly, we have elucidated key diurnal differences in mitochondrial functions that are well correlated with disparate time-of-day-dependent exercise capacity. Providing causal mechanistic evidence, we illustrate that loss of Sirtuin4 (SIRT4), a well-known mitochondrial regulator, abrogates mitochondrial diurnal variation and consequently abolishes time-of-day-dependent muscle output. Therefore, our findings unequivocally demonstrate the pivotal role of baseline skeletal muscle mitochondrial functions in dictating diurnal exercise capacity.PMID:39902884 | DOI:10.1096/fj.202402930R

Oncoimmunology. 2025 Dec;14(1):2460281. doi: 10.1080/2162402X.2025.2460281. Epub 2025 Feb 4.ABSTRACTThe exploration of therapeutic targets in neuroblastoma (NB), which needs more attempts, can benefit patients with high-risk NB. Based on metabolomic and transcriptomic data in mediastinal NB tissues, we found that the content of long-chain acylcarnitine (LCAC) was increased and positively associated with leptin expression in advanced NB. Leptin over-expression forced naïve CD4+ T cells to differentiate into Treg cells instead of Th17 cells, which benefited from NB cell proliferation, migration, and drug resistance. Mechanically, leptin in NB cells blunted the activity of carnitine palmitoyltransferase 2 (CPT2), the key enzyme for LCAC catabolism, by inhibiting sirtuin 3-mediated CPT2 deacetylation, which depresses oxidative phosphorylation (OXPHOS) for energy supply and increases lactic acid (LA) production from glycolysis to modulate CD4+ T cell differentiation. These findings highlight that excess leptin contributes to lipid metabolism dysfunction in NB cells and subsequently misdirects CD4+ T cell differentiation in tumor micro-environment (TME), indicating that targeting leptin could be a therapeutic strategy for retarding NB progression.PMID:39902867 | DOI:10.1080/2162402X.2025.2460281

Phytopathology. 2025 Feb 4. doi: 10.1094/PHYTO-10-24-0315-R. Online ahead of print.ABSTRACTAllicin exhibits strong inhibitory activity against phytopathogenic fungi; however, its antifungal mechanism remains unclear. This study assessed allicin's inhibitory effects on several phytopathogenic fungi, revealing a half-maximal effective concentration of 125.47 μg/ml against the hyphal growth of Botrytis cinerea. Micromorphological analysis showed that allicin caused abnormalities in the hyphae, including unclear organelle boundaries and organelle dissolution. Integrated transcriptomic, and proteomic, and metabolomic assays indicated that allicin induced differential gene and protein expression, particularly in the plasma membrane, oxidative stress processes, and energy metabolism pathways. Additionally, differentially expressed metabolites were involved in the inhibition of hyphal growth. Biochemical assays demonstrated that allicin inhibited ATP production and damaged hyphal cell membranes. Molecular docking revealed that allicin could bind to dihydrolipoamide dehydrogenase (DLDH), an enzyme rich in cysteine residues, with a binding free energy of -6.322 kcal/mol. Through antimicrobial activity testing of allicin analogues and molecular docking analysis, the active groups of allicin and its interaction with DLDH were identified. This study shows that allicin interferes with energy metabolism, impacts cell membrane and wall integrity by targeting cysteine-containing proteins, and inhibits the proliferation of plant pathogenic fungi. These insights into the antifungal mechanism will provide valuable data for the development and field application of allicin analogues.PMID:39902848 | DOI:10.1094/PHYTO-10-24-0315-R

Toxicol Pathol. 2025 Feb 4:1926233241311269. doi: 10.1177/01926233241311269. Online ahead of print.ABSTRACTMass Spectrometry Imaging (MSI) is a powerful tool to understand molecular pathophysiology and therapeutic and toxicity mechanisms, as well as for patient stratification and precision medicine. MSI, a label-free technique offering detailed spatial information on a large number of molecules in different tissues, encompasses various techniques including Matrix-Assisted Laser Desorption Ionization (MALDI), Desorption Electrospray Ionization (DESI), and Secondary Ion Mass Spectrometry (SIMS) that can be applied in diagnostic and toxicologic pathology. Given the utmost importance of high-quality samples, pathologists play a pivotal role in providing comprehensive pathobiology and histopathology knowledge, as well as information on tissue sampling, orientation, morphology, endogenous biomarkers, and pathogenesis, which are crucial for the correct interpretation of targeted experiments. This article introduces MSI and its fundamentals, and reports on case examples, determining the best suited technology to address research questions. High-level principles and characteristics of the most used modalities for spatial metabolomics, lipidomics and proteomics, sensitivity and specific requirements for sample procurement and preparation are discussed. MSI applications for projects focused on drug metabolism, nonclinical safety assessment, and pharmacokinetics/pharmacodynamics and various diagnostic pathology cases from nonclinical and clinical settings are showcased.PMID:39902784 | DOI:10.1177/01926233241311269

Clin Transl Med. 2025 Feb;15(2):e70159. doi: 10.1002/ctm2.70159.NO ABSTRACTPMID:39902723 | DOI:10.1002/ctm2.70159

Comb Chem High Throughput Screen. 2025 Feb 3. doi: 10.2174/0113862073335304241023153906. Online ahead of print.ABSTRACTBACKGROUND: Diabetes mellitus (DM) is a chronic metabolic disease. The leaves of Dimocarpus longan Lour. (LYY), a well-known traditional Chinese medicine (TCM) with Guangxi national characteristics often used in simple recipes to treat DM has attracted increasing attention. In this study, we investigated the therapeutic effects of LYY in diabetic rats from a metabolomic perspective.METHODS: The type 2 diabetes (T2DM) rat model was induced by a high-sugar and high-fat diet (HSFD) combined with 40 mg/kg streptozotocin (STZ). After oral administration of LYY (10.7 g/kg) for 28 d, their weight, fasted blood glucose (FBG), blood lipid levels, and inflammatory factors were assessed. The feces, urine, and serum samples of the rats were collected, and proton nuclear magnetic resonance (1H-NMR) technology was used to explore the changes in the sample's metabolism spectrum and analyze the relevant targeted metabolic pathways.RESULTS: Compared with the diabetes group, LYY rats significantly delayed the reduction of body weight and decreased the FBG level (P <0.01); the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein-cholesterol (LDL-C), IL-6, and TNF-α in serum significantly reduced (P < 0.05, 0.01), and the level of high-density lipoprotein-cholesterol (HDL-C) significantly increased (P < 0.01). 2 candidate biomarkers were identified from feces samples, and 4 associated metabolic pathways were discovered. 13 potential biomarkers were screened from urine samples, leading to the identification of 16 related metabolic pathways. Similarly, 5 potential biomarkers were screened from serum samples, and 11 related metabolic pathways were found.CONCLUSION: LYY can regulate the metabolic disorder caused by T2DM by regulating amino acid metabolism, amino acid synthesis, and tricarboxylic acid cycle, which provides a specific reference for the clinical treatment of T2DM.PMID:39902541 | DOI:10.2174/0113862073335304241023153906

J Pharm Anal. 2025 Jan;15(1):101116. doi: 10.1016/j.jpha.2024.101116. Epub 2024 Sep 26.ABSTRACTMetabolomics covers a wide range of applications in life sciences, biomedicine, and phytology. Data acquisition (to achieve high coverage and efficiency) and analysis (to pursue good classification) are two key segments involved in metabolomics workflows. Various chemometric approaches utilizing either pattern recognition or machine learning have been employed to separate different groups. However, insufficient feature extraction, inappropriate feature selection, overfitting, or underfitting lead to an insufficient capacity to discriminate plants that are often easily confused. Using two ginseng varieties, namely Panax japonicus (PJ) and Panax japonicus var. major (PJvm), containing the similar ginsenosides, we integrated pseudo-targeted metabolomics and deep neural network (DNN) modeling to achieve accurate species differentiation. A pseudo-targeted metabolomics approach was optimized through data acquisition mode, ion pairs generation, comparison between multiple reaction monitoring (MRM) and scheduled MRM (sMRM), and chromatographic elution gradient. In total, 1980 ion pairs were monitored within 23 min, allowing for the most comprehensive ginseng metabolome analysis. The established DNN model demonstrated excellent classification performance (in terms of accuracy, precision, recall, F1 score, area under the curve, and receiver operating characteristic (ROC)) using the entire metabolome data and feature-selection dataset, exhibiting superior advantages over random forest (RF), support vector machine (SVM), extreme gradient boosting (XGBoost), and multilayer perceptron (MLP). Moreover, DNNs were advantageous for automated feature learning, nonlinear modeling, adaptability, and generalization. This study confirmed practicality of the established strategy for efficient metabolomics data analysis and reliable classification performance even when using small-volume samples. This established approach holds promise for plant metabolomics and is not limited to ginseng.PMID:39902459 | PMC:PMC11788866 | DOI:10.1016/j.jpha.2024.101116

Front Mol Biosci. 2025 Jan 20;11:1520876. doi: 10.3389/fmolb.2024.1520876. eCollection 2024.ABSTRACTINTRODUCTION: Ovarian cancer has been difficult to cure due to acquired or intrinsic resistance and therefore, newer or more effective drugs/approaches are needed for a successful treatment in the clinic. Erastin (ER), a ferroptosis inducer, kills tumor cells by generating and accumulating reactive oxygen species (ROS) within the cell, resulting in an iron-dependent oxidative damage-mediated ferroptotic cell death.METHODS: We have utilized human ovarian cancer cell lines, OVCAR-8 and its adriamycin-selected, multi-drug resistance protein (MDR1)-expressing NCI/ADR-RES, both equally sensitive to ER, to identify metabolic biomarkers of ferroptosis.RESULTS: Our studies showed that ER treatment rapidly depleted cellular glutathione and cysteine and enhanced formation of ophthalamate (OPH) in both cells. Opthalalmate has been proposed to be a biomarker of oxidative stress in cells. Our study also found significant decreases in cellular taurine, a natural antioxidant in cells. Additionally, we found that ER treatment decreased cellular levels of NAD+/NADP+, carnitines and glutamine/glutamate in both cells, suggesting significant oxidative stress, decrease in energy production, and cellular and mitochondrial disfunctions, leading to cell death.CONCLUSION: Our studies identified several potential biomarkers of ER-induced ferroptosis including OPH, taurine, NAD+, NADP+ and glutamate in ovarian cancer cells. Identifying specific metabolic biomarkers that are predictive of whether a cancer is susceptible to ferroptosis will help us devise more successful treatment modalities.PMID:39902375 | PMC:PMC11788483 | DOI:10.3389/fmolb.2024.1520876

Research (Wash D C). 2025 Feb 3;8:0604. doi: 10.34133/research.0604. eCollection 2025.ABSTRACTOsteoarthritis (OA) is the most prevalent joint disease, yet effective disease-modifying OA drugs (DMOADs) remain elusive. Targeting macrophage polarization has emerged as a promising avenue for OA treatment. This study identified skatole through high-throughput screening as an efficient modulator of macrophage polarization. In vivo experiments demonstrated that skatole administration markedly reduced synovitis and cartilage damage in both destabilization of medial meniscus (DMM)-induced OA mice and monosodium iodoacetate (MIA)-induced OA rats. Mechanistically, skatole activated signal transducer and activator of transcription 6 (Stat6) signaling, promoting M2 macrophage polarization, while inhibiting nuclear factor-κB (NFκB) and mitogen-activated protein kinase (MAPK) signaling pathways to suppress M1 polarization. RNA-sequencing analysis, targeted metabolomics, and mitochondrial stress tests further revealed that skatole treatment shifted macrophages toward oxidative phosphorylation for energy production. Additionally, it up-regulated genes associated with glutathione metabolism and reactive oxygen species (ROS) pathways, reducing intracellular ROS production. The CUT&Tag assay results indicated that the downstream transcription factor p65 of NFκB can directly bind to gene loci related to inflammation, oxidative phosphorylation, and glutathione metabolism, thereby modulating gene expression. This regulatory process is inhibited by skatole. At the chondrocyte level, conditional medium from skatole-treated M1 macrophages balanced anabolism and catabolism in mouse chondrocytes and inhibited apoptosis. In IL1β-treated chondrocytes, skatole suppressed inflammation and catabolism without affecting apoptosis or anabolism. Overall, skatole maintains immune microenvironment homeostasis by modulating macrophage polarization in joints and preserves cartilage function by balancing chondrocyte anabolism and catabolism, effectively alleviating OA. These findings suggest skatole's potential as a DMOAD.PMID:39902346 | PMC:PMC11788598 | DOI:10.34133/research.0604

SAGE Open Med. 2024 Nov 8;12:20503121241296701. doi: 10.1177/20503121241296701. eCollection 2024.ABSTRACTBACKGROUND: Patients recovering from COVID-19 often present with impaired health and persisting symptoms such as exercise intolerance ⩾3 months post-infection. Uncertainty remains about long-term recovery. We aimed to review studies examining cardiac function, macro- or microvascular function, blood biomarkers and physical activity in adult patients post-COVID-19 and highlight current knowledge gaps.RESULTS: Using echocardiography, persistent cardiac involvement of the left ventricle was observed in a fraction of patients both hospitalized and non-hospitalized. Ventricular dysfunction was often subclinical but may partly contribute to exercise intolerance post-COVID-19. Endothelial dysfunction was seen on micro- and macrovascular levels using retinal vessel imaging methods and brachial artery flow-mediated dilation, respectively. Studies reporting blood biomarkers of disease-specific impairment and endothelial dysfunction yielded upregulated inflammation, hypercoagulability, organ and endothelial damage up to several months after infection. Omics' scale lipid profiling studies provide preliminary evidence of alterations in several lipid subspecies, mostly during acute COVID-19, which might contribute to subsequent endothelial and cardiometabolic dysfunction. Yet, more robust evidence is warranted. Physical activity may be reduced up to 6 months post-COVID-19. However, studies measuring physical activity more precisely using accelerometry are sparse. Overall, there is growing evidence for long-term multiple organ dysfunction.CONCLUSION: Research combining all the above methods in the search for underlying mechanisms of post-COVID-19 symptoms is mostly missing. Moreover, studies with longer follow-ups (i.e. ⩾18 months) and well-matched control groups are lacking. The findings may aid the development of rehabilitation regimes for post-COVID-19 syndrome.CONDENSED ABSTRACT: This review examined cardiac function, vascular function, blood biomarkers and physical activity in patients post-COVID-19. Evidence suggests long-term dysfunction in multiple organ systems and exercise intolerance due to various factors, including endothelial damage and, in some patients, subclinical ventricular dysfunction. We highlight knowledge gaps for further research to aid post-COVID-19 rehabilitation.PMID:39902344 | PMC:PMC11789121 | DOI:10.1177/20503121241296701

Pract Lab Med. 2025 Jan 16;44:e00454. doi: 10.1016/j.plabm.2025.e00454. eCollection 2025 Apr.ABSTRACTBACKGROUND: FibraChek is a newly developed mass spectrometry (MS) assay kit approved by the National Medical Products Administration (NMPA) of China for quantifying L-tyrosine (Tyr) and taurocholic acid (TCA) in serum, aiding liver fibrosis diagnosis. This study aimed to assess its analytical performance.METHODS: The analytical performance was investigated based on NMPA and CLSI guidelines. Method suitability in the clinical context was tested by analyzing clinical samples from liver fibrosis patients confirmed via liver biopsy.RESULTS: The assay enables simultaneous determination of Tyr and TCA, demonstrating compliance with performance parameters such as linearity, dynamic range, limit of detection (LOD), limit of quantification (LOQ), recovery, repeatability, reproducibility, and stability. It validated a linear range of 20-1000 μmol/L for Tyr and 10.3-618 ng/ml for TCA, maintaining stability after 5 freeze-thaw cycles for 14 months. Components remained stable for up to 7 days at room temperature and 30 days at 2-8 °C. TCA and Tyr were stable for up to 36 months at -20 °C or -80 °C. The method effectively quantified Tyr and TCA in serum from liver fibrosis patients and healthy controls.CONCLUSIONS: This is the first MS-based assay for non-invasive liver fibrosis detection validated for clinical use, providing a rapid and reliable analytical protocol suitable for routine analysis.PMID:39902333 | PMC:PMC11788763 | DOI:10.1016/j.plabm.2025.e00454

Front Genet. 2025 Jan 20;15:1527223. doi: 10.3389/fgene.2024.1527223. eCollection 2024.ABSTRACTPelvic organ prolapse (POP) is a common gynecological disease caused by pathological defects, lesions, or mechanical weakening of the support structures of the pelvic floor. However, its pathogenesis is unclear. Circular RNAs (circRNAs) are covalently closed, endogenous biomolecules, which are thought to play an important role on skeletal muscle development by regulating gene expression. In this study, five pairs of peripheral blood samples from control and POP groups were used for circRNA sequencing analysis to obtain differential expression profiles. A total of 75 differentially expressed circRNAs (DEcircRNAs) were identified (fold change >2.0, P < 0.05). Furthermore, RT-qPCR confirmed that the expression levels of two circRNAs (hsa_circ_0067962 and hsa_circ_0057051) were significantly lower in the POP group. The two validated DEcircRNAs were abundantly involved in the collagen catabolic process. The circRNA-miRNA-mRNA network of two DEcircRNAs comprised nine mRNAs, which indicated that hsa_circ_0067962 and hsa_circ_0057051 may be involved in the pathogenesis of POP by regulating these nine mRNAs.PMID:39902300 | PMC:PMC11788335 | DOI:10.3389/fgene.2024.1527223

Front Plant Sci. 2025 Jan 20;15:1492424. doi: 10.3389/fpls.2024.1492424. eCollection 2024.ABSTRACTThe quality of fresh tea leaves is crucial to the final product, and maintaining microbial stability in tea plantations is essential for optimal plant growth. Unique microbial communities play a critical role in shaping tea flavor and enhancing plant resilience against biotic stressors. Tea production is frequently challenged by pests and diseases, which can compromise both yield and quality. While biotic stress generally has detrimental effects on plants, it also activates defense metabolic pathways, leading to shifts in microbial communities. Microbial biocontrol agents (MBCAs), including entomopathogenic and antagonistic microorganisms, present a promising alternative to synthetic pesticides for mitigating these stresses. In addition to controlling pests and diseases, MBCAs can influence the composition of tea plant microbial communities, potentially enhancing plant health and resilience. However, despite significant advances in laboratory research, the field-level impacts of MBCAs on tea plant microecology remain insufficiently explored. This review provides insights into the interactions among tea plants, insects, and microorganisms, offering strategies to improve pest and disease management in tea plantations.PMID:39902199 | PMC:PMC11788416 | DOI:10.3389/fpls.2024.1492424

Front Pharmacol. 2025 Jan 20;15:1463673. doi: 10.3389/fphar.2024.1463673. eCollection 2024.ABSTRACTINTRODUCTION: Diabetic nephropathy (DN), a major complication of diabetes, presents with poor clinical outcomes and affects patients throughout their lifetime. α-Methyltryptophan (α-MT) is a blocker of the amino acid transporter. SLC6A14 and also an inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1).METHODS: In this study, we employed a nuclear magnetic resonance-based metabolomic approach to investigate the therapeutic effects of α-MT in a db/db mouse model of DN and explore the underlying molecular mechanisms.RESULTS: The results of the study demonstrated that α-MT significantly reduced the urinary excretion of albumin and creatinine, improved kidney function, and decreased renal fibrosis in db/db mice. Metabolomic analyses of kidney tissues and urine samples indicated that db/db mice displayed increased activity of the enzyme IDO1, and alongside pronounced metabolic disturbances. These disturbances are chiefly characterized by alterations in amino acid metabolism, energy production pathways, membrane biochemical features, and nicotinamide metabolism, all of which have been implicated in mTOR signaling and apoptotic pathways.DISCUSSION: Administration of α-MT to db/db mice showed evidence of IDO1 inhibition and rectification of metabolic dysfunctions with concurrent suppression of mTOR signaling and apoptosis. These findings highlight the potential of α-MT as a promising therapeutic agent for diabetic nephropathy.PMID:39902076 | PMC:PMC11788373 | DOI:10.3389/fphar.2024.1463673

Front Immunol. 2025 Jan 20;15:1528222. doi: 10.3389/fimmu.2024.1528222. eCollection 2024.ABSTRACTAcute lung injury (ALI) is a common respiratory disease, Cordycepin has been reported to reduce ALI, which is an effective component in Cordyceps militaris solid medium extract (CMME). Therefore, we aimed to explore the alleviating effect and mechanism of CMME on ALI. This study evaluated the effect of CMME on lipopolysaccharide (LPS)-induced ALI mice by analyzing intestinal flora and metabolomics to explore its potential mechanism. We assessed pulmonary changes, inflammation, oxidative stress, and macrophage and neutrophil activation levels, then we analyzed the gut microbiota through 16S rRNA and analyzed metabolomics profile by UPLC-QTOF/MS. The results showed that CMME treatment improved pulmonary injury, reduced inflammatory factors and oxidative stress levels, and decreased macrophage activation and neutrophil recruitment. The 16S rRNA results revealed that CMME significantly increased gut microbiota richness and diversity and reduced the abundance of Bacteroides compared with Mod group significantly. Metabolic analysis indicated that CMME reversed the levels of differential metabolites and may ameliorate lung injury through purine metabolism, nucleotide metabolism, and bile acid (BA) metabolism, and CMME did reverse the changes of BA metabolites in ALI mice, and BA metabolites were associated with inflammatory factors and intestinal flora. Therefore, CMME may improve lung injury by regulating intestinal flora and correcting metabolic disorders, providing new insights into its mechanism of action.PMID:39902053 | PMC:PMC11788161 | DOI:10.3389/fimmu.2024.1528222

Am J Hypertens. 2025 Feb 4:hpaf015. doi: 10.1093/ajh/hpaf015. Online ahead of print.ABSTRACTBACKGROUND: Pulmonary arterial hypertension (PAH) is a kind of pulmonary vascular lesion characterized by vasoconstriction and reshaping of small pulmonary arteries, ultimately resulting in increased pulmonary artery pressure and pulmonary vascular resistance, and eventually leading to right ventricular failure and death. This study was aimed to construct a platelet-derived growth factor BB (PDGF-BB)-induced rat pulmonary artery smooth muscle cells (PASMCs) model and conduct a combined transcriptomic and metabolomic analysis to identify proliferation-related targets, thereby enhancing understanding of the pathogenesis underlying PAH.METHODS: Rat PASMCs were isolated and cultured in the presence or absence of PDGF-BB for 24 hours. Cells were collected for transcriptomics and metabolomics investigations.RESULTS: A total of 1288 differentially expressed genes (572 up-regulated and 716 down-regulated) were identified in PDGF-BB-treated rat PASMCs compared to control cells. Subsequently, Gene ontology (GO) enrichment analysis revealed that 791 enriched GO terms were significantly enriched in PDGF-BB treated cells. Similarly, 294 differential metabolic pathways were enriched in PDGF-BB treated cells according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, Gene Set Enrichment Analysis (GSEA) were performed on the differentially expressed genes (DEGs). It turned out that 7219 gene sets were more enriched in PDGF-BB treated cells. In addition, a total of 28 secondary differential metabolites were identified in PDGF-BB-treated rat PASMCs compared to control cells (p-value < 0.05 and VIP > 1).CONCLUSIONS: We speculate that Mylk, Pla2g4a, Gucy1b1, Adcy8, Adcy4, Gucy1a2, Col3a1, and Plcb4 are potential targets for the treatment of PAH.PMID:39901736 | DOI:10.1093/ajh/hpaf015

Anim Biosci. 2025 Jan 24. doi: 10.5713/ab.24.0567. Online ahead of print.ABSTRACTOBJECTIVE: Subclinical hypocalcemia induces metabolic stress, which adversely affects the production performance of peripartal dairy goats. This study sought to uncover new aspects of disease prevention and control by applying metabolomics and lipidomics to identify key differences in metabolite expression between affected and healthy animals.METHODS: This study collected plasma samples from 96 primiparous Guanzhong dairy goats with similar body condition scores (2.75 ± 0.15, mean ± standard deviation) on the day of calving, aiming to uncover new aspects of disease prevention and control by applying metabolomics and lipidomics to identify key differences in metabolite expression between affected and healthy animals.RESULTS: The study identified 23 differential metabolites and 30 differentially altered lipids involved in various metabolic pathways, such as phenylalanine and tyrosine metabolism, aminoacyl-tRNA biosynthesis, and glycerophospholipid metabolism. Our research revealed significant differences in the regulation of calcium-related hormones and associated metabolites between subclinical hypocalcemic and healthy dairy goats. Specifically, we found a positive correlation between parathyroid hormone (PTH) and aspartate aminotransferase (AST) in the healthy group, contrasting with a negative correlation observed in the subclinical hypocalcemic group.CONCLUSION: Additionally, phenylalanine and phosphatidylserine were identified as potential biomarkers indicative of subclinical hypocalcemia. These findings offer a novel approach to managing subclinical hypocalcemia in dairy goats, potentially transforming prevention and control strategies in the dairy goat industry.PMID:39901708 | DOI:10.5713/ab.24.0567

J Proteome Res. 2025 Feb 3. doi: 10.1021/acs.jproteome.4c00858. Online ahead of print.ABSTRACTIonizing radiation exposure from a potential nuclear energy plant leak or detonation of a nuclear weapon can cause massive casualties to both warfighters and civilians. RNA, proteins, and metabolite biomarkers in biological specimens like blood and tissue have shown potential to determine radiation dose levels. However, these biomarkers in blood and urine are short-lived, typically detectable within hours or a few days. To address the need for stable, long-term radiation exposure biomarkers, we developed two mass spectrometry-based methods using noninvasive hair samples to identify radiation-exposure biomarkers. Our results show that hippuric acid and 5-methoxy-3-indoleacetate significantly increase after higher (4 gray) doses of gamma irradiation compared to lower (1 and 2 Gy) doses or nonexposed hair samples. While 2-aminooctadec-4-ene-1,3-diol, oleoyl ethanolamide, palmitoylcarnitine, 25-hydroxy vitamin D3, vernolic acid, and azelaic acid significantly increased over time after exposure. Trimethylamine N-oxide (TMAO) was found in higher concentrations in female specimens across all time points. Further validation using a machine learning model suggested that these biomarkers can predict differences in the exposure dose and time point. Our findings highlight the potential of noninvasive hair sample analysis for assessing radiation exposure, offering a viable alternative to address critical public health concerns of unexpected radiation exposure.PMID:39901696 | DOI:10.1021/acs.jproteome.4c00858

Curr Rev Clin Exp Pharmacol. 2025 Jan 31. doi: 10.2174/0127724328332998250118182255. Online ahead of print.ABSTRACTDepression is a prevalent mood disorder with significant public health implications. Despite extensive research, its precise causes remain inadequately understood. Recently, interest has surged in the role of the gut microbiome and its metabolites in the pathophysiology of depression. This review aims to provide a comprehensive overview of the relationship between gut microbiota, its metabolites, and depression while exploring potential mechanisms influencing the efficacy of antidepressant medications. A narrative review methodology was employed, synthesizing recent studies utilizing a multi-omics approach. We examined alterations in gut microbiome composition and metabolite production in individuals diagnosed with depression, discussing the technical tools and methods commonly applied in this research area. The findings indicate that individuals with depression show significant alterations in gut microbiome composition, notably an imbalance in Firmicutes, Bacteroidetes, and Actinobacteria. Changes in metabolite production, including short-chain fatty acids, tryptophan, and bile acids, were also observed. Moreover, the review highlights that antidepressant medications may exert their therapeutic effects by modulating gut microbiota and its metabolites. This review emphasizes the intricate interplay between gut microbiota, its metabolites, and depression, revealing critical insights into the mechanisms underlying antidepressant efficacy. We recommend that future research focus on elucidating these interactions to develop innovative therapeutic strategies, potentially transforming the management of depression through microbiota-targeted approaches.PMID:39901675 | DOI:10.2174/0127724328332998250118182255

J Extracell Vesicles. 2025 Feb;14(2):e70043. doi: 10.1002/jev2.70043.ABSTRACTAlzheimer´s disease (AD) is the most frequent neurodegenerative disorder in the world and is characterised by the loss of memory and other cognitive functions. Metabolic changes associated with AD are important players in the development of the disease. However, the mechanism underlying these changes is still unknown. Extracellular vesicles (EVs) are nano-sized particles that play an important role in regulating pathophysiological processes and are a non-invasive manner to obtain information of the cell that is secreting them. The analysis of brain-derived EVs (bdEVs) will provide new insights in the metabolic processes associated with AD. To characterize bdEVs in AD, we optimised a method to isolate them from tissue of different brain regions, obtaining the highest enrichment in isolations from the temporal cortex. We performed unbiased untargeted metabolomics analysis on post-mortem human temporal cortex tissue and bdEVs from the same region of AD patients and healthy controls. Both, univariate and multivariate statistical analysis were used to determine the metabolites that influence the separation between AD patients and controls. Interestingly, a clear separation between control and AD groups was obtained with bdEVs, which allowed to select 12 relevant features by a validated PLS-DA model. Furthermore, comparison of tissue and bdEVs identified 68 common features. The pathway enrichment analysis of the common metabolites showed that the alanine, aspartate and glutamate pathway and the arginine, phenylalanine, tyrosine pathway were the most significant ones in the separation between the AD patients and controls. The phenylalanine, tyrosine and tryptophan pathway, still had a very high influence in the separation between groups, albeit not significant. Notably, some metabolites were identified for the first time in bdEVs. For example, the N-acetyl aspartic acid (NAA) metabolite present in bdEVs was suitable to differentiate AD patients from healthy controls. Furthermore, the analysis of the hippocampus, midbrain, temporal and entorhinal cortex and their respective bdEVs indicated that the metabolic profiles of different brain areas were distinct and showed some correlation between the metabolome of the tissue and its respective bdEVs. Thus, our study highlights the potential of bdEVs to understand the metabolic fingerprint associated with AD and their potential use as diagnostic and therapeutic targets.PMID:39901643 | DOI:10.1002/jev2.70043