PubMed

J Hazard Mater. 2025 Feb 19;489:137675. doi: 10.1016/j.jhazmat.2025.137675. Online ahead of print.ABSTRACTDue to its similarity in hydrophobic properties to perfluorooctanesulfonic acid (PFOS), 6:2 fluorotelomer sulfonic acid (6:2 FTSA) has emerged as a key substitute for PFOS. Its presence in aquatic environments, along with the coexistence of polyethylene terephthalate (PET), may impact the growth of aquatic plants and ecosystem stability. This study explored the changes in antioxidant defense, photosynthetic system, and metabolic responses of water hyacinths (Eichhornia crassipes) under individual and combined exposure conditions. The results indicated that water hyacinth efficiently accumulated 6:2 FTSA, with notably higher accumulation levels in leaves compared to roots, leading to a more pronounced stress response in leaves. The contents of nitrate, nitrite, ammonium, and the activities of nitrogen assimilation enzymes in leaves increased significantly, which in turn boosted the levels of reactive oxygen species (ROS) scavengers such as glutamic acid and glutathione, as well as antioxidant defense enzymes. Meanwhile, leaf photosynthesis was significantly suppressed due to the resource reallocation. This was corroborated by disruptions in the chloroplast thylakoid structure and alterations in chlorophyll fluorescence parameters. Metabolomics analysis further revealed that the contents of monosaccharides and organic acids decreased markedly, whereas amino acid levels increased significantly, suggesting that water hyacinths prioritized antioxidant defense mechanisms at the expense of growth. Additionally, we observed that the phytotoxic effects of 6:2 FTSA were exacerbated in the presence of PET nanoplastics, with the aforementioned indicators exhibiting synergistic effects. This study provides phenotypic, physiological, metabolic, and transcriptional insights into the toxic effects of the coexistence of PET nanoplastics and 6:2 FTSA on water hyacinths, offering toxicological data (e.g., oxidative stress markers and gene expression profiles) for assessing the environmental risks associated with emerging contaminants and proposing management strategies.PMID:39978202 | DOI:10.1016/j.jhazmat.2025.137675

J Hazard Mater. 2025 Feb 16;489:137625. doi: 10.1016/j.jhazmat.2025.137625. Online ahead of print.ABSTRACTPrenatal exposure to vanadium has been associated with reduced birth size, however, the specific molecular mechanism underlying this effect remains largely unexplored. We measured vanadium in maternal plasma during early pregnancy, and characterized metabolomics profiling in cord blood among 1020 mother-infant pairs from the Wuhan Healthy Baby Cohort, China. After adjusting for potential confounders, a 2-fold increase in maternal plasma vanadium concentration was associated with a decrease of 25.1 g (95 % CI: -45.1, -5.1) and 0.429 g/cm (95 % CI -0.758 to -0.101) in birth weight and weight-for-length (WFL), respectively. Of the 423 metabolites detected, 42 metabolites and 10 metabolic pathways were significantly linked to both vanadium and birth size. The effect of vanadium on reduced birth weight and WFL was significantly mediated by 14 metabolites, including 2 hormones (cortisol and corticosterone), 1 amino acid (lysine), and 11 lipids, with a mediating effect range of 7 % to 17 %. In addition, the lysine degradation pathway significantly mediated a 19 % change in the association between vanadium exposure and both lower birth weight and WFL. Higher maternal vanadium exposure was linked to reduced birth size, and the perturbed metabolites and pathways involved in hormones, amino acids, oxidative stress, and lipid peroxidation may explain the mechanism.PMID:39978194 | DOI:10.1016/j.jhazmat.2025.137625

J Hazard Mater. 2025 Feb 14;489:137621. doi: 10.1016/j.jhazmat.2025.137621. Online ahead of print.ABSTRACTCombined pollution with heavy metals and microplastics (MPs) is widespread in farmland soil, and MPs can affect the efficiency and capacity of cadmium (Cd) uptake by hyperaccumulators. However, there is a significant knowledge gap regarding the response of hyperaccumulators under such conditions. This study utilized Solanum nigrum L. (S. nigrum), a well-known Cd hyperaccumulator, to investigate the combined effects of polyethylene microplastics (PE-MPs) and Cd contamination on Cd accumulation in S. nigrum, and to systematically explore the underlying mechanisms. The results demonstrated that high doses of PE-MPs significantly inhibited S. nigrum growth and reduced Cd concentration and accumulation in plants. Meanwhile, the decrement of bioavailable Cd content and the formation of C-H and -COO in rhizosphere soil were observed with the presence of PE-MPs. The simultaneous exposure of PE-MPs and Cd caused the significant increase in the proportions of Proteobacteria and Acidobacteriota, indicating that certain PE-degrading microorganisms may play a pivotal role in aforementioned processes. More importantly, the relative abundance of the genera Pseudolabrys, DEV008, and Flavobacterium was significantly elevated, likely contributing to the response of S. nigrum to combined toxicity. Co-exposure caused a significant downregulation of biosynthetic processes, involving carbohydrates and adenosine. Additionally, the biosynthesis of ABC transporters, phenylpropanoids, flavonoids, and organic acids was also significantly affected. The findings provide a comprehensive understanding of the soil-plants ecosystem under combined pollution and provide valuable information for advancing phytoremediation strategies.PMID:39978192 | DOI:10.1016/j.jhazmat.2025.137621

Spectrochim Acta A Mol Biomol Spectrosc. 2025 Feb 9;333:125883. doi: 10.1016/j.saa.2025.125883. Online ahead of print.ABSTRACTThe blood serum of patients infected by the Hepatitis B virus contains high molecular weight fractions and low molecular weight fractions (LMWF) of biomarker proteins of the disease. The LMWF including the associated peptidome and metabolome, is recognized as a critical molecular population with high potential for research on disease-associated biomarkers. This fraction of biomarkers can be suppressed by HMWF, proteins such as albumin, and immunoglobulins hence difficult to be detected. The purpose of this study is to separate HMWF) and LMWF using 100 kDa centrifugal filtration devices resulting in two parts including residue (HMWF) and filtrate parts (LMWF) of blood serum followed by the analysis of the later part employing surface-enhanced Raman spectroscopy (SERS). This strategy can enhance this optical technique's capability to characterize the biochemical changes caused by the infection of HBV and the diagnosis of the disease. The silver nanoparticles (Ag-NPs) were employed as a SERS substrate to distinguish between filtrate parts of the blood serum of HBV patients and healthy individuals based on their specific SERS peaks. The SERS spectral features associated with the filtrate parts of HBV patients' blood serum are well differentiated from the healthy volunteers. Principle component analysis (PCA) was applied on the SERS spectral data sets of HBV patients and healthy individuals and found extremely beneficial for the classification of their SERS spectral groups. Moreover, partial least square regression analysis (PLSR) has shown excellent performance in the quantitative analysis of the viral load values of the HBV patients using their SERS spectral data sets.PMID:39978181 | DOI:10.1016/j.saa.2025.125883

Ecotoxicol Environ Saf. 2025 Feb 19;292:117932. doi: 10.1016/j.ecoenv.2025.117932. Online ahead of print.ABSTRACTTea plants (Camellia sinensis) tend to accumulate excessive amounts of fluoride (F) compared to other plants. However, the specific mechanisms of F tolerance or detoxification in tea plants remain insufficiently understood. This study employed ultra-high performance liquid chromatography quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) to identify critical metabolites involved in F detoxification across two distinct tea plant cultivars with varying F accumulation capacities. Notably, malic acid and citric acid emerged as key metabolites that differentially accumulated under F-stressed conditions. Weighted gene co-expression network analysis indicated that C. sinensis aluminum (Al)-activated malate transporter genes CsALMT9 and CsALMT14 may be implicated in the response to F stress in C. sinensis. Further investigations revealed that CsALMT14 localized to the plasma membrane and exhibited significant transcriptional induction upon exposure to F toxicity. Moreover, heterologous expression of CsALMT14 enhanced F tolerance by mitigating F accumulation in transgenic yeast and Arabidopsis thaliana. Additionally, silencing of CsALMT14 by antisense oligodeoxynucleotide and virus-induced gene silencing reduced the content of malic acid but increased the accumulation of citric acid in tea plants, which might be attributed to the down-regulated expression of malic acid synthesis- and citric acid degradation-related genes. These findings suggest that CsALMT14 confers tolerance to F toxicity through F efflux and regulation of malic acid and citric acid metabolism-related gene expression, thereby providing a novel strategy for F detoxification in tea plants.PMID:39978103 | DOI:10.1016/j.ecoenv.2025.117932

Ecotoxicol Environ Saf. 2025 Feb 19;292:117891. doi: 10.1016/j.ecoenv.2025.117891. Online ahead of print.ABSTRACTThe placenta is an important organ for fetal growth. Air pollution during pregnancy may cause adverse effects on offsprings via placental dysfunction. However, the metabolites underlie the effects of PM2.5 on placenta have not been well studied. 329 pregnant women were randomly selected from the Shanghai Maternal-Child Pairs Cohort. Gestational PM2.5 exposure levels were assessed using individual air sampling method and satellite-based exposure assessment mode, respectively. Placental weight, length, width and thickness were measured by obstetrician-gynecologist at the time of delivery. Ultra high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was used to quantify metabolites in serum from the first and third trimester. Associations between PM2.5 and placental characteristics were analyzed by generalized estimating equation and multiple linear regression. The exposure-response relationship was plotted using restricted cubic splines (RCS). Based on the meet-in-the-middle approach, the metabolites underlying the effects of PM2.5 on placenta were explored. The associations between placental width (βTrimester2=-0.497, 95 %CI: -0.801, -0.193), (βTrimester3=-0.279, 95 % CI: -0.543, -0.016) and chorionic disk area (βTrimester2=-12.634,95 %CI: -21.698, -3.570), (βTrimester3=-9.113, 95 %CI: -17.113, -1.112) with PM2.5 exposure at the second and third trimester were found. The associations between placental characteristics with PM2.5 exposure assessed by individual air sampling and satellite-based methods were consistent. L-arginine (L-Arg), caprylic acid (CA), tauroursodeoxycholic acid (TUDCA), glycylproline (Gly-Pro), maltotriose (MT) and N-acetylneuramic acid (NANA) intermediate the effect of PM2.5 exposure on placental chorionic disk area in the third trimester. CONCLUSION: The second and third trimesters may be the sensitive windows of placental abnormalities to PM2.5 exposure. Caprylic acid (CA), glycylproline (Gly-Pro), and N-acetylneuramic acid (NANA) play a key role on the effects of PM2.5 exposure on placenta. This study provides potential biomarkers of placental exposure to PM2.5, providing an opportunity for future research as well as detection.PMID:39978100 | DOI:10.1016/j.ecoenv.2025.117891

Food Chem. 2025 Feb 17;476:143431. doi: 10.1016/j.foodchem.2025.143431. Online ahead of print.ABSTRACTLactiplantibacillus plantarum has been well acknowledged to produce exopolysaccharides (EPS) as a defense mechanism against acid stress. However, the complete biosynthetic pathway of EPS in L. plantarum and its impact on the cell growth and primary metabolism were still unclear. To fill these gaps, we carried out phenotypic, proteomic and metabolomics analysis of L. plantarum HMX2 cultured under different acidic conditions. Component and structure analysis showed that the repeating unit of EPS consisted of N-acetylmannosamine, N-acetylglucosamine, galactose, mannoses and glucoses. Multiomics analysis facilitated the curation and entablement of the complete EPS biosynthetic pathway ready for use in genome-scale metabolic models. Furthermore, proteomics and metabolomics data indicated that compared to the pH 6.5 condition, the acid stress at pH 4.5 significantly accelerated glycolysis and EPS biosynthesis processes while reduced the metabolic fluxes through the TCA cycle and the lactic acid fermentation, which suggested a trade-off between primary and secondary metabolism.PMID:39977986 | DOI:10.1016/j.foodchem.2025.143431

Food Chem. 2025 Feb 6;476:143238. doi: 10.1016/j.foodchem.2025.143238. Online ahead of print.ABSTRACTSeabuckthorn fruit oil (SBFO) is recognized for its high nutritional value, yet it remains highly prone to oxidation during storage. The changes in its primary components and micronutrient molecules during storage have not been thoroughly investigated. This study employed untargeted lipidomics and metabolomics to dynamically monitor alterations in lipid composition and metabolites of SBFO over 30 days of accelerated storage. Lipidomics analysis revealed an increase in TGs and oxidized fatty acids, while sphingolipids, glycerophospholipids, and total lipid content showed significant reductions (p < 0.05). After 30 days, metabolomics combined with bioinformatics analysis identified 13 critical pathways, with linoleic acid metabolism consistently associated with SBFO oxidation. Key oxidation products included 9(S)-HpODE, 9,10,13-TriHOME, and 9,10-DHOME. This study provides potential targets for developing endogenous antioxidants in SBFO and offers new perspectives on the oxidation mechanisms of edible oils.PMID:39977978 | DOI:10.1016/j.foodchem.2025.143238

Hum Reprod Update. 2025 Feb 20:dmaf002. doi: 10.1093/humupd/dmaf002. Online ahead of print.ABSTRACTBACKGROUND: Ovarian aging occurs earlier than the aging of many other organs and has a lasting impact on women's overall health and well-being. However, effective interventions to slow ovarian aging remain limited, primarily due to an incomplete understanding of the underlying molecular mechanisms and drug targets. Recent advances in omics data resources, combined with innovative computational tools, are offering deeper insight into the molecular complexities of ovarian aging, paving the way for new opportunities in drug discovery and development.OBJECTIVE AND RATIONALE: This review aims to synthesize the expanding multi-omics data, spanning genome, transcriptome, proteome, metabolome, and microbiome, related to ovarian aging, from both tissue-level and single-cell perspectives. We will specially explore how the analysis of these emerging omics datasets can be leveraged to identify novel drug targets and guide therapeutic strategies for slowing and reversing ovarian aging.SEARCH METHODS: We conducted a comprehensive literature search in the PubMed database using a range of relevant keywords: ovarian aging, age at natural menopause, premature ovarian insufficiency (POI), diminished ovarian reserve (DOR), genomics, transcriptomics, epigenomics, DNA methylation, RNA modification, histone modification, proteomics, metabolomics, lipidomics, microbiome, single-cell, genome-wide association studies (GWAS), whole-exome sequencing, phenome-wide association studies (PheWAS), Mendelian randomization (MR), epigenetic target, drug target, machine learning, artificial intelligence (AI), deep learning, and multi-omics. The search was restricted to English-language articles published up to September 2024.OUTCOMES: Multi-omics studies have uncovered key mechanisms driving ovarian aging, including DNA damage and repair deficiencies, inflammatory and immune responses, mitochondrial dysfunction, and cell death. By integrating multi-omics data, researchers can identify critical regulatory factors and mechanisms across various biological levels, leading to the discovery of potential drug targets. Notable examples include genetic targets such as BRCA2 and TERT, epigenetic targets like Tet and FTO, metabolic targets such as sirtuins and CD38+, protein targets like BIN2 and PDGF-BB, and transcription factors such as FOXP1.WIDER IMPLICATIONS: The advent of cutting-edge omics technologies, especially single-cell technologies and spatial transcriptomics, has provided valuable insights for guiding treatment decisions and has become a powerful tool in drug discovery aimed at mitigating or reversing ovarian aging. As technology advances, the integration of single-cell multi-omics data with AI models holds the potential to more accurately predict candidate drug targets. This convergence offers promising new avenues for personalized medicine and precision therapies, paving the way for tailored interventions in ovarian aging.REGISTRATION NUMBER: Not applicable.PMID:39977580 | DOI:10.1093/humupd/dmaf002

Bioinformatics. 2025 Feb 20:btaf081. doi: 10.1093/bioinformatics/btaf081. Online ahead of print.ABSTRACTMOTIVATION: Untargeted metabolomics involves a large-scale comparison of the fragmentation pattern of a mass spectrum against a database containing known spectra. Given the number of comparisons involved, this step can be time-consuming.RESULTS: In this work, we present a GPU-accelerated cosine similarity implementation for Tandem Mass Spectrometry (MS), with an approximately 1000-fold speedup compared to the MatchMS reference implementation, without any loss of accuracy. This improvement enables repository-scale spectral library matching for compound identification without the need for large compute clusters. This impact extends to any spectral comparison-based methods such as molecular networking approaches and analogue search.AVAILABILITY: All code, results, and notebooks supporting are freely available under the MIT license at https://github.com/pangeAI/simms/.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:39977359 | DOI:10.1093/bioinformatics/btaf081

Geroscience. 2025 Feb 20. doi: 10.1007/s11357-025-01559-z. Online ahead of print.ABSTRACTThere is growing evidence that higher intermuscular fat (IMF) is associated with worse processing speed, measured by the digit symbol substitution test (DSST) in older adults. However, the underlying biological mechanisms are not well understood. Considering that both muscle and the brain are metabolically active organs, we sought to identify metabolites that may explain the IMF-DSST association. We assessed 613 plasma metabolites in 2388 participants from the Health, Aging, and Body Composition Study (mean age ± SD 74.7 ± 2.9 years, 50% men, 63% white), using liquid chromatography-mass spectrometry. We confirmed that higher IMF was associated with worse DSST scores (standardized beta (95% CI) - 0.08 (- 0.12, - 0.03), p < 0.001). Sixty-six metabolites were significantly associated with both IMF and DSST. Four of the 66 metabolites attenuated the association by ≥ 10%: higher levels of adrenic acid (polyunsaturated fatty acid), and lower levels of C20:5 lysophosphatidylcholine (lysophospholipid), 1-methylnicotinamide (vitamin B3-related myokine), and maslinic acid (triterpene) were associated with higher IMF and worse DSST. Together, they explained 41% of the IMF-DSST association. Pathway enrichment analyses identified two significant shared pathways: unsaturated fatty acid metabolism and the citrate (TCA) cycle. This study provides hypothesis-generating evidence that a set of circulating metabolites related to unsaturated fatty acids, energy metabolism, and myokines may partially explain the inverse association of IMF with processing speed. The findings, if further confirmed by independent studies, advance our understanding of molecular pathways underlying muscle-brain crosstalk. Whether the identified metabolites are early predictors of future decline in processing speed should be further investigated.PMID:39976843 | DOI:10.1007/s11357-025-01559-z

Nat Prod Rep. 2025 Feb 20. doi: 10.1039/d4np00064a. Online ahead of print.ABSTRACTCovering: 1982 up to the end of 2024Marine exometabolites (EMs) are small molecules released by marine (micro)organisms into the seawater. Collectively, all of the released EMs contribute to the chemical seascape of a marine ecosystem. Accessing and describing these waterborne molecules are a key focus of various disciplinary fields that aim to study marine biogeochemical cycles, translate the chemical language of the oceans (chemical ecology), or discover new structural entities with biological properties (natural product discovery). Beginning with the semantics of marine exometabolites, this review elucidates the different sampling methods and MS-based metabolomic analyses that are used to describe the chemical composition of seawater of benthic ecosystems. These technical and analytical advances offer promising avenues for describing the structural diversity of marine exometabolites and deciphering their functions in various ecological contexts.PMID:39976689 | DOI:10.1039/d4np00064a

Anal Bioanal Chem. 2025 Feb 20. doi: 10.1007/s00216-025-05785-4. Online ahead of print.ABSTRACTThe spatial metabolic analysis of tumor tissues following neoadjuvant chemotherapy (NAC) is critical for understanding chemotherapy-induced metabolic changes. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) offers a powerful tool for revealing spatially resolved metabolic profiles within tissues. However, necrotic regions in post-NAC tissues are fragile, creating challenges for sample preparation and MALDI MSI analysis. In this study, we introduce an optimized workflow employing conductive tape to stabilize tissue samples during sectioning and MALDI MSI analysis, preserving necrotic areas while maintaining tissue integrity. Using this technique, we successfully mapped metabolic alterations across necrotic and viable regions of post-NAC tumor tissues, providing new insights into metabolic changes that occur after chemotherapy. Our findings establish MALDI MSI as a valuable tool for spatially resolved metabolomics in post-NAC tumor tissues, offering insights into chemotherapy-induced metabolic changes.PMID:39976685 | DOI:10.1007/s00216-025-05785-4

J Virol. 2025 Feb 20:e0228224. doi: 10.1128/jvi.02282-24. Online ahead of print.ABSTRACTCoronaviruses hijack host cell metabolic pathways and resources to support their replication. They induce extensive host endomembrane remodeling to generate viral replication organelles and exploit host membranes for assembly and budding of their enveloped progeny virions. Because of the overall significance of host membranes, we sought to gain insight into the role of host factors involved in lipid metabolism in cells infected with Middle East respiratory syndrome coronavirus (MERS-CoV). We employed a single-cycle infection approach in combination with pharmacological inhibitors, biochemical assays, lipidomics, and light and electron microscopy. Pharmacological inhibition of acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN), key host factors in de novo fatty acid biosynthesis, led to pronounced inhibition of MERS-CoV particle release. Inhibition of ACC led to a profound metabolic switch in Huh7 cells, altering their lipidomic profile and inducing lipolysis. However, despite the extensive changes induced by the ACC inhibitor, the biogenesis of viral replication organelles remained unaffected. Instead, ACC inhibition appeared to affect the trafficking and post-translational modifications of the MERS-CoV envelope proteins. Electron microscopy revealed an accumulation of nucleocapsids in early budding stages, indicating that MERS-CoV assembly is adversely impacted by ACC inhibition. Notably, inhibition of palmitoylation resulted in similar effects, while supplementation of exogenous palmitic acid reversed the compound's inhibitory effects, possibly reflecting a crucial need for palmitoylation of the MERS-CoV spike and envelope proteins for their role in virus particle assembly.IMPORTANCEMiddle East respiratory syndrome coronavirus (MERS-CoV) is the etiological agent of a zoonotic respiratory disease of limited transmissibility between humans. However, MERS-CoV is still considered a high-priority pathogen and is closely monitored by WHO due to its high lethality rate of around 35% of laboratory-confirmed infections. Like other positive-strand RNA viruses, MERS-CoV relies on the host cell's endomembranes to support various stages of its replication cycle. However, in spite of this general reliance of MERS-CoV replication on host cell lipid metabolism, mechanistic insights are still very limited. In our study, we show that pharmacological inhibition of acetyl-CoA carboxylase (ACC), a key enzyme in the host cell's fatty acid biosynthesis pathway, significantly disrupts MERS-CoV particle assembly without exerting a negative effect on the biogenesis of viral replication organelles. Furthermore, our study highlights the potential of ACC as a target for the development of host-directed antiviral therapeutics against coronaviruses.PMID:39976449 | DOI:10.1128/jvi.02282-24

Appl Environ Microbiol. 2025 Feb 20:e0237624. doi: 10.1128/aem.02376-24. Online ahead of print.ABSTRACTThe purpose of this study was to evaluate the combined effects of puerarin (Pue) and insoluble dietary fiber from Hericium erinaceus (HEIDF) on obesity induced by a high-fat diet (HFD) in mice, focusing on their effects on lipid and glucose metabolism, gut microbiota (GM), and serum metabolites. Glucose tolerance, tissue pathology, and serum biochemical levels were conducted to assess the effects of puerarin combined with Hericium Erinaceus insoluble dietary fiber (LH) on glucose and lipid metabolism. 16S rRNA sequencing and untargeted metabonomics were employed to explore the underlying mechanisms. The results showed that the LH group significantly reduced body weight and hepatic and adipose lipid accumulation, and improved glucose tolerance and dyslipidemia compared to the Pue or HEIDF groups alone. Moreover, the LH group exhibited enhanced regulation of GM, including increased microbial diversity, higher abundance of beneficial bacteria such as g__Lactobacillus and g__Bacillus, and a decreased Firmicutes-to-Bacteroidota ratio. In addition, the LH group ameliorated HFD-induced serum metabolite changes and promoted the activation of tryptophan and glycerophospholipid metabolism pathways. The combination of Pue and HEIDF exhibits a synergistic anti-obesity effect by modulating specific GM (g__Lactobacillus and g__Bacillus) and serum metabolites.IMPORTANCEThe combination of HEIDF and Pue holds significant importance in the context of obesity. This synergistic effect not only aids in weight management but may also enhance metabolic health through various mechanisms, including increased satiety and promotion of fat oxidation. Therefore, incorporating these two components into the daily diet could offer effective strategies for the prevention and intervention of obesity and its related diseases.PMID:39976439 | DOI:10.1128/aem.02376-24

Ann Neurol. 2025 Feb 20. doi: 10.1002/ana.27208. Online ahead of print.ABSTRACTOBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by altered metabolome and energy homeostasis, manifesting with body mass index changes and hypermetabolism-both prognostic of disease progression and survival. The cross-sectional ALS metabolome has been characterized, but longitudinal correlations to functional decline are lacking.METHODS: We longitudinally evaluated metabolomes from ALS plasma and terminal postmortem spinal cord and brain motor cortex tissue. We constructed 3 plasma models. A linear mixed effects model correlated all metabolite levels across all timepoints to their corresponding functional scores. An interaction model predicted a longitudinal change in function from baseline metabolites, whereas a progression model identified metabolites linked to a 20% or 50% drop in function. In postmortem samples, differential metabolites in onset versus second spinal cord segments served as a surrogate of disease progression. Mendelian randomization assessed potential causality from metabolites.RESULTS: In plasma, all models primarily selected lipid metabolites and sub-pathways, in addition to amino acids, xenobiotics, and various less frequently selected pathways. Among lipids, fatty acids and sphingomyelins were predominant, along with plasmalogens, phosphatidylcholines, and lysophospholipids. Sex interaction findings were nominal. In the spinal cord, sphingomyelin and long-chain saturated and monounsaturated fatty acids were more abundant in the onset segment tissue, whereas phosphatidylcholines and phosphatidylethanolamines were less abundant. Mendelian randomization suggested that impaired carnitine and short chain acylcarnitine metabolism may be genetically determined in ALS, along with various antioxidant derivatives.INTERPRETATION: Our findings suggest metabolomic changes primarily involving different lipid classes and carnitine metabolism may underscore ALS severity and progression. ANN NEUROL 2025.PMID:39976286 | DOI:10.1002/ana.27208

Psychol Med. 2025 Feb 20;55:e57. doi: 10.1017/S0033291725000339.NO ABSTRACTPMID:39976211 | DOI:10.1017/S0033291725000339

Front Immunol. 2025 Feb 5;16:1502605. doi: 10.3389/fimmu.2025.1502605. eCollection 2025.ABSTRACTUlcerative colitis is a chronic disease that has not well-established etiology. The role of microbial dysregulation in its pathogenesis has been recently highlighted. Overall, microbiome alterations concern the reduction of bacterial abundance and diversity, resulting in gut microbiome imbalance negatively affecting immunological aspects. There is a link between ulcerative colitis and the oral microbiome. The changes of oral microbiome are found at many levels, from gently dysbiotic composition to the presence of the main periodontal microbes. The analysis of oral microbiome can be a part of personalized medicine due to the fact that it is a potential biomarker. Patients with ulcerative colitis may manifest dental symptoms/problems, such as periodontitis (strongly related to the red-complex pathogens-Porphyromonas gingivalis, Tannerella forsythia, Treponema denticola, and bacteria belonging to the other complexes, such as Fusobacterium nucleatum and Aggregatibacter actinomycetecomitans), dental caries, oral ulcerations, leukoplakia, halitosis, and others. Notably, the DMFT (Decayed, Missing, Filled Teeth) index is higher in these patients compared to healthy subjects. According to some data, oral lichen planus (which is a disease with an immunological background) can also be observed in ulcerative colitis patients. It seems that deep understanding of ulcerative colitis in association with oral microbiome, immunology, and dental manifestations may be crucial to provide complex treatment from a dental point of view.PMID:39975550 | PMC:PMC11836005 | DOI:10.3389/fimmu.2025.1502605

bioRxiv [Preprint]. 2025 Feb 5:2025.02.04.636472. doi: 10.1101/2025.02.04.636472.ABSTRACTThe "dark matter" of metabolomics refers to the large number of unidentified features in metabolomic studies, mostly from mass spectrometry (MS) based analysis (deSilva2015; David2021; Giera2024). The topic is pertinent to the analytical coverage of small molecules in biomedical research (Kind2009; Uppal2016), approaches to metabolite annotation (Domingo2018; Chaleckis2019; Metz2025), mapping reaction pathways (Zamboni2015) and the promise of applying metabolomics and exposomics to precision medicine (Wishart2016; Vermeulen2020). The number of unidentified features is not a direct account of number of compounds, as a metabolite can have isotopologues, adducts and fragments that are measured in the same data (Mahieu2017; Wang2019; Li2023a). Giera et al (2024) recently reported that in-source fragments (ISFs) accounted for over 70% of MS/MS features in METLIN, one of the leading spectral databases, suggesting that ISFs could be a significant portion of the "dark matter". Since the reference spectra in METLIN are based on chemical standards, we examine here the LC-MS (liquid chromatography coupled mass spectrometry) metabolomics from biological samples, which are the most relevant in biomedical investigations.PMID:39975275 | PMC:PMC11838597 | DOI:10.1101/2025.02.04.636472

bioRxiv [Preprint]. 2025 Feb 8:2025.02.03.636312. doi: 10.1101/2025.02.03.636312.ABSTRACTNeutrophils are highly abundant innate immune cells that are constantly produced from myeloid progenitors in the bone marrow. Differentiated neutrophils can perform an arsenal of effector functions critical for host defense. This study aims to quantitatively understand neutrophil mitochondrial metabolism throughout differentiation and activation, and to elucidate the impact of mitochondrial metabolism on neutrophil functions. To study metabolic remodeling throughout neutrophil differentiation, murine ER-Hoxb8 myeloid progenitor-derived neutrophils and human induced pluripotent stem cell-derived neutrophils were assessed as models. To study the metabolic remodeling upon neutrophil activation, differentiated ER-Hoxb8 neutrophils and primary human neutrophils were activated with various stimuli, including ionomycin, MSU crystals, and PMA. Characterization of cellular metabolism by isotopic tracing, extracellular flux analysis, metabolomics, and fluorescence-lifetime imaging microscopy revealed dynamic changes in mitochondrial metabolism. As neutrophils mature, mitochondrial metabolism decreases drastically, energy production is fully offloaded from oxidative phosphorylation, and glucose oxidation through TCA cycle is substantially reduced. Nonetheless, mature neutrophils retain the capacity for mitochondrial metabolism. Upon stimulation with certain stimuli, TCA cycle is rapidly activated. Mitochondrial pyruvate carrier inhibitors reduce this re-activation of the TCA cycle and inhibit the release of neutrophil extracellular traps. Mitochondrial metabolism also impacts neutrophil redox status, migration, and apoptosis without significantly changing overall bioenergetics. Together, these results demonstrate that mitochondrial metabolism is dynamically remodeled and plays a significant role in neutrophil function and fate. Furthermore, these findings point to the therapeutic potential of mitochondrial pyruvate carrier inhibitors in a range of conditions where dysregulated neutrophil response drives inflammation and contributes to pathology.PMID:39975244 | PMC:PMC11838513 | DOI:10.1101/2025.02.03.636312