PubMed
Metabolomic characteristics of cord blood from neonates with hyperkalemia after antenatal exposure to ritodrine and magnesium sulfate
Sci Rep. 2025 Jan 16;15(1):2186. doi: 10.1038/s41598-025-85938-8.ABSTRACTIn the management of pregnancy, ritodrine has been used to prevent preterm birth, and magnesium sulfate (MgSO4) has been used to prevent preterm labor and preeclampsia. Neonates born to mothers receiving these medications occasionally show an increase in serum potassium concentration. Recently, an elevated risk of neonatal hyperkalemia has been reported, particularly when ritodrine and MgSO4 are co-administered; however, the underlying mechanisms remain unclear. We conducted a retrospective cohort study of 142 preterm infants born between 24 and 36 weeks of gestation, categorized into groups exposed to antenatal ritodrine, MgSO4, both agents, or neither. In addition, we investigated the association between potassium levels and metabolites in the serum of umbilical cord blood from 33 infants exposed to antenatal ritodrine and MgSO4 using a metabolomic analysis. Our findings revealed a significant elevation in serum potassium concentration associated with metabolomic findings of activation of glycolysis and the derived metabolic routes in preterm neonates exposed to both ritodrine and MgSO4. Our data indicate that the concurrent administration of ritodrine and MgSO4 caused distinctive metabolic alterations, potentially leading to an additional increase in the intracellular potassium concentration in the fetus. Consequently, this mechanism may imply an elevation in serum potassium concentration postnatally through the redistribution of potassium.PMID:39819995 | DOI:10.1038/s41598-025-85938-8
Identification of serum metabolite biomarkers in premature infants with bronchopulmonary dysplasia: protocol for a multicentre prospective observational cohort study
BMJ Open. 2025 Jan 15;15(1):e089064. doi: 10.1136/bmjopen-2024-089064.ABSTRACTINTRODUCTION: Bronchopulmonary dysplasia (BPD) is one of the most common and significant complications of preterm birth. It ultimately leads to a decrease in the quality of life for preterm infants and impacts their long-term health. Early prediction and timely intervention are crucial to halting the development of BPD. This study aims to identify the biomarkers that can predict the early occurrence and development of BPD by screening serum metabolites in preterm infants. This will provide strong support for the early prediction of BPD and targeted interventions in future research.METHODS AND ANALYSIS: This is a prospective, multicentre, open-label, observational cohort study spanning 3 years. It will be conducted in six major neonatal intensive care units in Shenzhen, China, involving preterm infants born at gestational ages <32 weeks. Demographic data and treatment information will be collected prospectively. Serum samples will be collected at five distinct time points: within 24 hours after birth, at 1 week, 2 weeks, 28 days and at 36 weeks postmenstrual age. These samples will undergo analysis using liquid chromatography-tandem mass spectrometry for untargeted metabolomics studies. Participants will be categorised into BPD and non-BPD groups based on their final diagnosis, and metabolite differences between these groups will be analysed. The study aims to enrol 1500 preterm infants with gestational ages <32 weeks over 3 years. A three-step analysis strategy-discovery, validation and clinical testing-will be used to identify and validate the clinical utility of novel biomarkers. Additionally, a nested case-control study will be conducted, matching participants 1:1 with a control group sharing similar BPD risk factors.ETHICS AND DISSEMINATION: Our protocol has been approved by the Medical Ethics Committees of all participating hospitals, including Peking University Shenzhen Hospital, Shenzhen People's Hospital, Shenzhen Baoan Women's and Children's Hospital, Longgang District Maternity and Child Healthcare Hospital, Nanshan Maternity and Child Healthcare Hospital and Shenzhen Luohu People's Hospital. We will disseminate our study results through academic conferences and peer-reviewed public journals.TRIAL REGISTRATION NUMBER: ChiCTR2400081615.PMID:39819932 | DOI:10.1136/bmjopen-2024-089064
Metabolomics identifies plasma biomarkers of localized radiation injury
Sci Rep. 2025 Jan 16;15(1):2166. doi: 10.1038/s41598-025-85717-5.ABSTRACTA radiological accident may result in the development of a local skin radiation injury (LRI) which may evolve, depending on the dose, from dry desquamation to deep ulceration and necrosis through unpredictable inflammatory waves. Therefore, early diagnosis of victims of LRI is crucial for improving medical care efficiency. This preclinical study aims to identify circulating metabolites as biomarkers associated with LRI using a C57BL/6J mouse model of hind limb irradiation. More precisely, two independent mice cohorts were used to conduct a broad-spectrum profiling study followed by a suspect screening analysis performed on plasma metabolites by mass spectrometry. An integrative analysis was conducted through a multi-block sparse partial least square discriminant analysis (sPLS-DA) to establish multi-scale correlations between specific metabolites levels and biological, physiological (injury severity), and functional parameters (skin perfusion). The identified biomarker signature consists in a 6-metabolite panel including putrescine, uracil, 2,3-dihydroxybenzoate, 3-hydroxybenzoate, L-alanine and pyroglutamate, that can discriminate mice according to radiation dose and injury severity. Our results demonstrate relevant molecular signature associated with LRI in mice and support the use of plasma metabolites as suitable molecular biomarkers for LRI prognosis and diagnosis.PMID:39819895 | DOI:10.1038/s41598-025-85717-5
Comprehensive analysis of metabolomics and transcriptomics reveals varied tepal pigmentation across Gloriosa varieties
BMC Plant Biol. 2025 Jan 17;25(1):66. doi: 10.1186/s12870-025-06067-y.ABSTRACTGloriosa L. possesses exceptional ornamental value, with its floral hues exhibiting a wide range of variations. In this study, we employed sophisticated colorimetry, Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS), and transcriptome sequencing to investigate the phenotypic expression of tepal colors, the composition of carotenoids and anthocyanins, and the differential gene expression in four Gloriosa varieties during their full bloom phase. Our findings revealed that the redness of the tepals, indicated by higher a* values, increased with the intensity of the red hue, while lighter colors corresponded to higher L* values. Metabolomic analysis identified 50 carotenoids and 60 anthocyanins. It was observed that carotenoids primarily influence the yellow and orange color of Gloriosa tepals, with β-carotene, lutein, and zeaxanthin being the predominant carotenoids. Anthocyanins serve as the principal coloring agents in the orange, red and purple tepals of Gloriosa. High levels and proportions of cyanidins and pelargonidins are key contributors to the formation of red and purple tepals, while high levels and proportions of peonidins also play a significant role in purple coloration. In contrast, the presence of high levels and proportions of pelargonidins alone is a crucial factor in the formation of orange tepals. Transcriptomic data unearthed 57 and 92 candidate differentially expressed genes (DEGs) belong to carotenoid and anthocyanin biosynthesis pathway, respectively, with PSY, PDS, DFR, and ANS genes considered as critical genes for the differential accumulation of pigments of Gloriosa tepals. Weighted gene co-expression network analysis (WGCNA) revealed significant co-expression patterns between 217 transcription regulatory factors (TFs) and 8 carotenoid biosynthesis genes, and between 194 TFs and 41 anthocyanin biosynthesis genes. qRT-PCR verified the expression patterns of four carotenoid biosynthesis-related genes, eight anthocyanin biosynthesis-related genes, and three transcription regulatory factors. It was found that Cluster-121969.6 (MYB) gene is specifically expressed in the tepals of the four varieties (compared to stems and leaves) and shows a high consistency with the trend of anthocyanin content changes. This research provides new insights into the mechanisms underlying the formation of diverse floral colors in Gloriosa tepals.PMID:39819392 | DOI:10.1186/s12870-025-06067-y
Assays to Enhance Metabolic Phenotyping in the Kidney
Am J Physiol Renal Physiol. 2025 Jan 17. doi: 10.1152/ajprenal.00232.2024. Online ahead of print.ABSTRACTThe kidney is highly metabolically active, and injury induces changes in metabolism that can impact repair and fibrosis progression. Changes in expression of metabolism-related genes and proteins provide valuable data, but functional metabolic assays are critical to confirm changes in metabolic activity. Stable isotope metabolomics are the gold standard, but these involve considerable cost and specialized expertise. Both the Seahorse bioflux assays and substrate oxidation assays in tissues ex vivo are two relatively cost-effective assays for interrogating metabolism. Many institutions have access to Seahorse bioflux analyzers, which can easily and quickly generate data, but guidelines to enhance reproducibility are lacking. We investigate how variables (e.g. primary versus immortalized cells, time in culture) impact the data generated by Seahorse bioflux analyzers. In addition, we show the utility of 3H-palmitate, a new approach for assessing fatty acid oxidation in the kidney, in uninjured and injured kidney cortices. The 3H-palmitate substrate oxidation assays also demonstrate significant sex-dependent and strain-dependent differences in rates of fatty acid oxidation. These data should facilitate metabolic interrogation in the kidney field with enhanced reproducibility.PMID:39819047 | DOI:10.1152/ajprenal.00232.2024
Multi-Omics Assessment of Puff Volume-Mediated Salivary Biomarkers of Metal Exposure and Oxidative Injury Associated with Electronic Nicotine Delivery Systems
Environ Health Perspect. 2025 Jan;133(1):17005. doi: 10.1289/EHP14321. Epub 2025 Jan 16.ABSTRACTBACKGROUND: Since their inception, electronic nicotine delivery systems (ENDS) have gained increasing popularity, sparking a vaping epidemic among adolescents in the US and globally. Several ENDS safety concerns have emerged as device features and formats that contribute to heavy metal exposure and toxicity continue to evolve and outpace regulatory efforts.OBJECTIVES: Our objective was to integrate ENDS emission profiles with salivary proteome and metabolome data to characterize exposure factors that may influence adverse vaping-mediated health outcomes.METHODS: A total of 56 participants (38 exclusive ENDS users and 18 non-ENDS users) were recruited. A subset of 15 exclusive ENDS users completed puffing topography assessments to obtain individual vaping behavior patterns using each participant's ENDS device. Inductively coupled plasma mass spectrometry was used to determine the metal content of emissions (12 ENDS devices) generated using a programmable ENDS aerosol generation system and saliva (15 exclusive ENDS users and 5 non-ENDS users). Saliva samples from 10 exclusive ENDS users and 5 non-ENDS users were analyzed for proteomic, metabolomic, inflammatory, and oxidative stress/damage biomarkers.RESULTS: A linear puff volume-dependent increase in particle emissions and heavy metals was observed in ENDS aerosols and saliva of exclusive ENDS users. Elevated puff volume-dependent levels of salivary cytokines, including tumor necrosis factor-alpha (TNFα), interleukin-1 beta (IL-1β), and IL-6, were observed alongside the oxidative damage indicators malondialdehyde (MDA), superoxide dismutase (SOD), and 8-hydroxy-2'-deoxyguanosine (8-OHdG). Proteome-metabolome network analysis showed a higher risk of potentially developing neurological and respiratory diseases in ENDS users compared with non-ENDS users. Integrated salivary proteome-metabolome-metallome network analysis further demonstrated that heavy metals were associated with proteomic and metabolomic perturbations, with notable alterations in inflammatory response, immune function, and disease-related pathways.DISCUSSION: A significant correlation between heavy metals, cytokines, and oxidative stress markers reveals a potential role of vaping behavior in exposure to metals and changes in markers associated with DNA damage and inflammation. Our study demonstrates the importance of characterizing vaping behavior and puffing topography when examining the human health implications of ENDS use. https://doi.org/10.1289/EHP14321.PMID:39819025 | DOI:10.1289/EHP14321
Phase I trial comparing bile acid and short-chain fatty acid alterations in stool collected from human subjects treated with omadacycline or vancomycin
Antimicrob Agents Chemother. 2025 Jan 17:e0125124. doi: 10.1128/aac.01251-24. Online ahead of print.ABSTRACTOmadacycline, an aminomethylcycline tetracycline, has a low propensity to cause Clostridioides difficile infection (CDI) in clinical trials. Omadacycline exhibited a reduced bactericidal effect compared with vancomycin on key microorganisms implicated in bile acid homeostasis and short-chain fatty acids (SCFAs), key components of CDI pathogenesis. The purpose of this study was to assess bile acid and SCFA changes in stool samples from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers, who were given oral omadacycline or vancomycin for 10 days. Daily stool samples were assessed for bile acids and SCFA concentrations using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Bile acids changed significantly over time for all subjects (P < 0.01 for each bile acid), with vancomycin causing a larger change in the primary bile acids, cholic acid (P < 0.001) and chenodeoxycholic acid (P < 0.001), and a reduced change in the secondary bile acid, lithocholic acid (P < 0.001). The secondary bile acid ursodeoxycholic acid was reduced less by vancomycin than by omadacycline (P < 0.001). All SCFA concentrations were reduced from baseline with a larger effect observed with vancomycin for isobutyric acid (P = 0.0034), propionic acid (P = 0.0012), and acetic acid (P = 0.047). Microbial changes associated with the use of vancomycin versus omadacycline were also associated with changes in bile acid homeostasis and SCFA concentrations. Oral omadacycline produced a distinctive metabolomic profile compared with vancomycin when administered to healthy subjects. The metabolic findings help further our understanding of the lower CDI risk properties of omadacycline and warrant phase 2 investigations using omadacycline as a CDI antibiotic.IMPORTANCE: The purpose of this study was to assess bile acid and SCFA changes in stool samples obtained from healthy volunteers given omadacycline or vancomycin. Stool samples were collected daily from 16 healthy volunteers given a 10-day oral course of omadacycline or vancomycin. Vancomycin caused a larger change in the primary bile acids and SCFA concentrations compared with omadacycline. The metabolic findings help further our understanding of the mechanistic basis for the lower-risk properties of omadacycline causing CDI and warrant phase 2 investigations using omadacycline as a CDI antibiotic.CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT06030219.PMID:39819014 | DOI:10.1128/aac.01251-24
ABCoRT: Retention Time Prediction for Metabolite Identification via Atom-Bond Co-Learning
J Chem Inf Model. 2025 Jan 16. doi: 10.1021/acs.jcim.4c02179. Online ahead of print.ABSTRACTLiquid chromatography retention time (RT) prediction plays a crucial role in metabolite identification, a challenging and essential task in untargeted metabolomics. Accurate molecular representation is vital for reliable RT prediction. To address this, we propose a novel molecular representation learning framework, ABCoRT(Atom-Bond Co-learning for Retention Time prediction), designed for predicting metabolite retention times. Our model transforms molecular graphs into dual hypergraphs, enabling the collaborative updating of atomic and bond information within both molecular graphs and hypergraphs, thereby producing highly informative molecular representations. We evaluated ABCoRT on a large-scale Small Molecule Retention Time (SMRT) data set comprising 80,038 molecules. Our model achieved a mean absolute error (MAE) of 25.75 s and a mean relative error (MRE) of 3.24% after removing nonretained molecules. Additionally, we fine-tuned pretrained ABCoRT models on six additional data sets from PredRet, achieving the lowest MAEs on five of them. Additionally, in metabolite screening conducted on the MetaboBASE and RIKEN_PlaSM data sets from the MassBank of North America, ABCoRT demonstrates its capability to filter out 38.35 and 28.46% of candidate compounds, respectively.PMID:39818945 | DOI:10.1021/acs.jcim.4c02179
<em>Phytophthora alni</em> Infection Reinforces the Defense Reactions in <em>Alnus glutinosa</em> - <em>Frankia</em> Roots to the Detriment of Nodules
Mol Plant Microbe Interact. 2025 Jan 16. doi: 10.1094/MPMI-12-24-0160-R. Online ahead of print.ABSTRACTAlnus glutinosa, able to establish symbiosis with mutualistic bacteria of the genus Frankia, is one of the main species in European riparian environments, where it performs numerous biological and socio-economic functions. However, riparian ecosystems face a growing threat from Phytophthora alni, a highly aggressive waterborne pathogen causing severe dieback in A. glutinosa. To date, the tripartite interaction between the host plant, the symbiont Frankia and the pathogen remains unexplored but is critical for understanding how pathogen-induced stress influences the nodule molecular machinery and so on the host-symbiont metabolism. In the present study, we aimed to explore for the first time how P. alni affects the overall molecular processes of Alnus glutinosa - Frankia nodules, with a special focus on unraveling the spatial expression of defense mechanisms within these tissues. We conducted a laboratory experiment based on P. alni infection of young A. glutinosa seedlings nodulated with Frankia alni ACN14a, non-infected or infected with the pathogen P. alni. Multi-omics analyses were carried out on nodules (N) and associated roots (AR) of the same plant in order to underline the impact on the nodule molecular processes (i.e. N/AR markers) when the host plant is infected compared to non-infected plants. Our results revealed that P. alni infection modified the molecular nodule processes and induced reprograming of defense-related markers by a shift in associated roots to the detriment of nodules. These findings suggest that A. glutinosa reinforces locally its immune responses in roots but moderates this activation in nodule to preserve its Frankia symbiont.PMID:39818942 | DOI:10.1094/MPMI-12-24-0160-R
Combined Analysis of the Leaf Metabolome, Lipidome, and Candidate Gene Function: Insights into Genotypic Variation in Phosphorus Utilization Efficiency in Stylosanthes guianensis
J Agric Food Chem. 2025 Jan 17. doi: 10.1021/acs.jafc.4c06927. Online ahead of print.ABSTRACTStylo (Stylosanthes guianensis) exhibits excellent tolerance to low-phosphate (Pi) availability, but the underlying mechanisms responsible for improving the phosphorus (P) utilization efficiency (PUE) remain unclear. This study employed metabolomics, lipidomics, and gene expression analyses to investigate the differential responses to low-Pi stress between the high-PUE genotype CF047827 and the cultivar Reyan No. 2. Results showed that CF047827 had higher expression levels of membrane lipid remodeling-related genes in its leaves compared to Reyan No. 2 under low-Pi conditions. This was accompanied by greater phospholipid degradation and non-P-containing lipid biosynthesis in the leaves of CF047827. Furthermore, the purple acid phosphatase gene SgPAP27a, which is more highly expressed in the leaves of CF047827 than in Reyan No. 2 under low-Pi conditions, was identified and functionally characterized. Its role in promoting phospholipid degradation and enhancing PUE was confirmed through heterologous expression in Arabidopsis. These findings provide insights and identify potential candidate genes for breeding high-PUE crop cultivars.PMID:39818859 | DOI:10.1021/acs.jafc.4c06927
Sex-Specific Mechanisms of Fluoride-Induced Gonadal Injury: A Multi-Omics Investigation into Reproductive Toxicity and Gut Microbiota Disruption
J Agric Food Chem. 2025 Jan 16. doi: 10.1021/acs.jafc.4c10190. Online ahead of print.ABSTRACTFluoride, a common agricultural additive used to enhance plant resilience and pest control, poses toxicity risks when exposure surpasses safe thresholds, affecting ecosystems and human health. While its reproductive toxicity is recognized, the sex-specific and cross-generational effects remain underexplored. To address this gap, we employed an integrative approach combining transcriptomics (next-generation sequencing (NGS)), bioinformatic network analysis, gut microbiota sequencing, and in vivo functional assays. ICR mice (F0 generation), both male and female, were exposed to fluoride (100 mg/L in drinking water) for 35 days, continuing through gestation and offspring weaning. Our transcriptomic analysis revealed significant upregulation of autophagy (via the PI3K-AKT-mTOR pathway) and oxidative stress-induced mitochondrial dysfunction in gonadal tissue, with more pronounced effects observed in males. Further integrated analyses of transcriptomic and metabolomic data, supported by in vivo experiments, highlighted oxidative stress, mitochondrial dysfunction, and PI3K-AKT-mTOR pathway activation with stronger effects in males. The principal component analysis confirmed sex-specific transcriptome alterations, with males showing more substantial disruption. Additionally, 16S rRNA sequencing identified significant gut dysbiosis, particularly in males, with an increased Firmicutes/Bacteroidetes ratio and higher abundances of Oscillospirales and Anaerovoracaceae. Moreover, our study identified significant correlations between specific gut microbiota (e.g., Firmicutes, Proteobacteria) and autophagy, oxidative stress, and mitochondrial dysfunction pathways, with notable sex-dependent differences. These findings suggest that gut microbiota may play a critical role in modulating fluoride-induced reproductive toxicity, particularly through their effects on oxidative stress and cellular homeostasis. The breakdown of the gut barrier and elevated serum/gonadal lipopolysaccharide (LPS) levels in fluoride-treated mice further established a link between gut dysbiosis and fluoride-induced reproductive toxicity. These findings underscore the importance of considering sex differences in xenobiotic-induced reproductive and developmental toxicity.PMID:39818830 | DOI:10.1021/acs.jafc.4c10190
Development and Validation of a Highly Sensitive Isotope-Coded Equivalent Reporter Ion Assay for the Semi-Quantification of Isocoumarins in Complex Matrices
Anal Chem. 2025 Jan 16. doi: 10.1021/acs.analchem.4c05069. Online ahead of print.ABSTRACTThe accurate quantification of multicomponents using LC-MS is pivotal for ensuring the quality control of herbal medicine, as well as the investigation of their analysis of biological tissue distribution. However, two significant challenges persist: the scarcity of authentic standards and the selection of appropriate internal standards. In this study, we present a highly sensitive isotope-coded equivalent reporter ion assay (iERIA) that combines equivalently quantitative ion and isotope-coded derivatization strategies. This method offers triple functionality: enabling the semidetermination of multiple components using a single standard, introducing stable isotope-labeled internal standards, and enhancing MS detection signals. Using four isocoumarins as a model, namely, 5-carboxylmellein, 5-hydroxymethylmellein, 5-methylmellein, and 5-hydroxymellein, we successfully quantified these compounds across various matrices, including herbal extracts, plasma, urine, and liver tissue. Reporter ions at m/z 170 and 234 generated by the dansulfonyl derivatives of isocoumarins, were subsequently detected for calculating the concentrations of samples based on the equivalent ion method. It is very beneficial for trace detection in biological samples free of any concentration steps, with an increased LOD of 50 times after dansyl chloride derivatization. Additionally, the introduction of stable isotope-labeled internal standards using d6-dansyl chloride mitigated matrix effects and instrument drift, ensuring the accuracy and precision of the semiquantification. This practical UPLC-MS/MS strategy significantly expands the applicability of multicomponent determination, with promising implications in diverse domains such as herbal medicine active ingredient analysis, food function and safety assessment, and metabolomics research.PMID:39818760 | DOI:10.1021/acs.analchem.4c05069
Silica-Activated Redox Signaling Confers Rice with Enhanced Drought Resilience and Grain Yield
ACS Nano. 2025 Jan 16. doi: 10.1021/acsnano.4c14608. Online ahead of print.ABSTRACTUnder a changing climate, enhancing the drought resilience of crops is critical to maintaining agricultural production and reducing food insecurity. Here, we demonstrate that seed priming with amorphous silica (SiO2) nanoparticles (NPs) (20 mg/L) accelerated seed germination speed, increased seedlings vigor, and promoted seedling growth of rice under polyethylene glycol (PEG)-mimicking drought conditions. An orthogonal approach was used to uncover the mechanisms of accelerated seed germination and enhanced drought tolerance, including electron paramagnetic resonance, Fourier transform infrared spectroscopy (FTIR), metabolomics, and transcriptomics. It was revealed that the unique surface chemistry of amorphous silica, characterized by an enrichment of silanol and siloxane groups, can catalyze the production of reactive oxygen species. This, in turn, initiates redox signaling and activates downstream drought-responsive genes. In addition, silica-primed seeds exhibited a significant enrichment of 18 amino acids and 6 sugars compared to those undergoing hydropriming, suggesting the accelerated mobilization of stored energy reserves. The drought-tolerance trait was observed in vegetative tissues of 35 day-old plants, where this tolerance was associated with an accelerated catabolism of amino acids and an enhanced anabolism of antioxidants. A separated field trial showed that SiO2NPs seed priming not only increased rice grain yield by 7.77% (p = 0.051) and 6.48% (p = 0.066), respectively, under normal and drought conditions but also increased the grain amino acid content. These results demonstrate that a simple and cost-effective nanoseed-priming approach can convey life cycle-long drought tolerance while simultaneously increasing rice grain yield and nutrition quality, providing an effective and sustainable strategy to cultivate climate-resilient crops.PMID:39818733 | DOI:10.1021/acsnano.4c14608
12/15-Lipoxygenase-Derived Electrophilic Lipid Modifications in Phagocytic Macrophages
ACS Chem Biol. 2025 Jan 16. doi: 10.1021/acschembio.4c00624. Online ahead of print.ABSTRACTMacrophages remove apoptotic cells via phagocytosis, also known as efferocytosis, during inflammation to maintain tissue homeostasis. This process is accompanied by various metabolic changes in macrophages including the production of lipid metabolites by fatty acid oxygenases. Among these, highly reactive metabolites, called lipid-derived electrophiles (LDEs), modify cysteines and other nucleophilic amino acids in intracellular proteins. However, the landscape and functions of the modifications by these electrophilic metabolites have been poorly characterized. In this study, we used activity-based protein profiling to quantitatively profile the cysteine reactivity landscape and identify the potential targets of endogenous LDE modification during efferocytosis in mouse peritoneal macrophages. Using this methodology, we identified multiple cysteine sites that are highly likely to be modified by LDEs generated by 12/15-lipoxygenase (12/15-LOX), an efferocytosis-related fatty acid oxygenase that is highly expressed in peritoneal macrophages. Among these, actin-depolymerizing protein Cofilin-1 was found to be a target of 12/15-LOX-derived LDEs. In vitro Cofilin-1 activity was attenuated by 12/15-LOX-derived LDEs, and intracellular actin stabilization and efferocytosis were substantially enhanced by the LDE treatment of mouse peritoneal macrophages. These results highlighted the role of intracellular LDE modification during efferocytosis in macrophages.PMID:39818720 | DOI:10.1021/acschembio.4c00624
Fumarate
Trends Endocrinol Metab. 2025 Jan 15:S1043-2760(24)00332-1. doi: 10.1016/j.tem.2024.12.010. Online ahead of print.NO ABSTRACTPMID:39818479 | DOI:10.1016/j.tem.2024.12.010
Urinary biomarkers of preeclampsia: An update
Adv Clin Chem. 2025;124:197-211. doi: 10.1016/bs.acc.2024.11.002. Epub 2024 Nov 22.ABSTRACTPreeclampsia (PE), a pregnancy-related syndrome, has motivated extensive research to understand its pathophysiology and develop early diagnostic methods. 'Omic' technologies, focusing on genes, mRNA, proteins, and metabolites, have revolutionized biological system studies. Urine emerges as an ideal non-invasive specimen for omics analysis, offering accessibility, easy collection, and stability, making it valuable for identifying biomarkers. A comprehensive exploration of urinary omics in preeclampsia is discussed in this review. Proteomic studies identified biomarkers such as SERPINA-1 and uromodulin, showing promise for early diagnosis and severity assessment. Metabolomic analyses revealed alterations in metabolites like glycine and hippurate, providing insights into molecular mechanisms underlying PE. Challenges include methodological inconsistencies and the need for standardized protocols. Urinary omics technologies have significantly advanced our understanding of PE pathophysiology and hold promise for improved diagnosis and management. Biomarkers identified through these approaches offer potential for early detection, severity stratification, and elucidation of underlying mechanisms.PMID:39818437 | DOI:10.1016/bs.acc.2024.11.002
Ion mobility spectrometry and ion mobility-mass spectrometry in clinical chemistry
Adv Clin Chem. 2025;124:123-160. doi: 10.1016/bs.acc.2024.10.003. Epub 2024 Nov 1.ABSTRACTAdvancements in clinical chemistry have major implications in terms of public health, prompting many clinicians to seek out chemical information to aid in diagnoses and treatments. While mass spectrometry (MS) and hyphenated-MS techniques such as LC-MS or tandem MS/MS have long been the analytical methods of choice for many clinical applications, these methods routinely demonstrate difficulty in differentiating between isomeric forms in complex matrices. Consequently, ion mobility spectrometry (IM), which differentiates molecules on the basis of size, shape, and charge, has demonstrated unique advantages in the broad application of stand-alone IM and hyphenated IM instruments towards clinical challenges. Here, we highlight representative IM applications and approaches and describe contemporary commercial offerings of IM technology and how these can be, or are currently being, applied to the field of clinical chemistry.PMID:39818435 | DOI:10.1016/bs.acc.2024.10.003
Shading stress promotes lignin biosynthesis in soybean seed coat and consequently extends seed longevity
Int J Biol Macromol. 2025 Jan 14:139913. doi: 10.1016/j.ijbiomac.2025.139913. Online ahead of print.ABSTRACTThe macromolecular components of the seed coat, particularly lignin, play a critical role in regulating seed viability. In the maize-soybean intercropping (MSI) system, shading stress was reported to enhance the viability of soybean seeds. However, the specific role of seed coat lignin in this process remains poorly understood. In this study, we demonstrated that soybean seed coats derived from the MSI system exhibit significantly higher lignin content and mechanical resistance compared to those from the sole cropping systems. Further investigations with artificial shading treatments revealed a substantial impact on the accumulation of phenylpropanoids in soybean seeds. Notably, shading applied during the reproductive stage resulted in decreased levels of anthocyanins, proanthocyanidins, and isoflavones, while simultaneously increasing lignin content. Moreover, both the mechanical resistance of the seed coats and the seeds' longevity under deteriorative conditions improved significantly compared to the normal light control. Gene expression and metabolomics analyses indicated that shading stress promotes the expression of key genes involved in lignin biosynthesis within the soybean seed coats, increasing the amount of several intermediate metabolites. Taken together, these findings reveal that shading stress in the MSI system promotes the biosynthesis and accumulation of lignin in soybean seed coats and thereby regulating seed longevity.PMID:39818396 | DOI:10.1016/j.ijbiomac.2025.139913
The potential function of chalcone isomerase (CHI) gene on flavonoid accumulation in Amomum tsao-ko fruit by transcriptome and metabolome
Int J Biol Macromol. 2025 Jan 14:139897. doi: 10.1016/j.ijbiomac.2025.139897. Online ahead of print.ABSTRACTFlavonoids are the major medicinally active ingredients that exert potential effects in Amomum tsao-ko. In total, 277 flavonoid metabolites were identified in fresh and dried fruits of three different accessions of A. tsao-ko (Amomum tsao-ko), which could be classified into eight classes with more metabolites classified as flavonol. Furthermore, 193 differential flavonoid metabolites (DFMs) were selected from the six samples (three fresh and dried fruits), the main DFMs identified in the fresh and dried fruits of A. tsao-ko were apigenin and its derivatives, and 11 main DFMs were identified. Upon analyzing the variations in flavonoid content between fresh and dried fruits, our findings indicate that the L accession demonstrate a superior accumulation of flavonoid metabolites in their dried fruits. Combination with transcriptome data, the synthesis of flavone and isoflavone metabolites in fresh fruits of A. tsao-ko may be affected by the changes in the expression of chalcone isomerase genes and regulated by the NAC and AP2 transcription factor. This study provides an important theoretical basis for the functional study of flavonoid synthesis-related genes and transcription factors in A. tsao-ko fruits and for the breeding of these fruits with high flavonoid content.PMID:39818395 | DOI:10.1016/j.ijbiomac.2025.139897
Polysaccharides isolated from Cibotium barometz attenuate chronic inflammatory pain: Molecular chemical structure and role of phenylalanine
Int J Biol Macromol. 2025 Jan 14:139911. doi: 10.1016/j.ijbiomac.2025.139911. Online ahead of print.ABSTRACTThis investigation represents a pioneering effort to examine the therapeutic effects of PCB specifically in the context of CFA-induced mice, as well as to elucidate the underlying mechanisms that facilitate such effects. Our study utilized advanced methodologies, namely high-performance liquid chromatography coupled with mass spectrometry (HPLC-MS)-based metabolomics, alongside comprehensive multivariate data analysis, to identify a distinctive metabolic profile associated with acute inflammation. Through our analyses, we discovered that several potential metabolites were significantly implicated in a variety of critical metabolic pathways. These pathways include glycerophospholipid metabolism, which plays an essential role in maintaining cellular membrane integrity and signaling; the biosynthesis of phenylalanine, tyrosine, and tryptophan, which are vital amino acids involved in numerous physiological processes; phenylalanine metabolism, which is significant for neurotransmitter synthesis; as well as the metabolism of alanine, aspartate, and glutamate, which are crucial for various metabolic functions, including neurotransmission and energy production. The metabolic alterations observed in both serum and spinal cord samples provide invaluable insights into the biochemical changes associated with inflammatory processes, thereby highlighting the potential therapeutic impact of PCB. The findings from this study not only deepen our understanding of the metabolic disturbances that occur during acute inflammation but also offer a solid theoretical foundation for clarifying the specific mechanisms through which PCB exerts its anti-inflammatory effects.PMID:39818377 | DOI:10.1016/j.ijbiomac.2025.139911