PubMed
Myricetin alleviates high-fat diet-induced atherosclerosis in ApoE<sup>-/-</sup> mice by regulating bile acid metabolism involved in gut microbiota remodeling
Food Funct. 2025 Mar 10. doi: 10.1039/d5fo00374a. Online ahead of print.ABSTRACTAtherosclerosis poses a significant threat to global health. This study aimed to investigate the effects of myricetin (MYR) on high-fat diet (HFD)-induced atherosclerosis in ApoE-/- mice. Our findings demonstrated that MYR treatment significantly reduced the formation of atherosclerotic plaques, particularly at a high dose of 100 mg kg-1 day-1. Additionally, MYR markedly attenuated lipid metabolism disorders in ApoE-/- mice by decreasing body weight, improving serum lipid profiles, and reducing lipid deposition. Analysis of 16S rRNA sequencing revealed that MYR treatment enhanced the abundance of probiotic g_Lachnospiraceae_NK4A136, while it reduced that of obesity-associated genera, including Rikenellaceae_RC9_gut_group and Alistipes. Metabolomic analysis and RT-qPCR tests indicated that MYR upregulated hepatic bile acid biosynthesis, evidenced by increased total bile acid levels and enhanced expression of key enzymes CYP7A1 and CYP8B1, particularly through the classical biosynthetic pathway. Spearman's correlation analysis revealed strong associations between the regulated bile acids and these aforementioned bacteria. Therefore, our results demonstrated that MYR exerts an anti-atherosclerotic effect by modulating the gut-liver axis.PMID:40059779 | DOI:10.1039/d5fo00374a
Dengue Virus and Lipid Metabolism: Unraveling the Interplay for Future Therapeutic Approaches
Emerg Microbes Infect. 2025 Mar 10:2477647. doi: 10.1080/22221751.2025.2477647. Online ahead of print.ABSTRACTIn recent years, Dengue virus (DENV) has continued to pose significant health risks in tropical and subtropical areas worldwide, raising health alerts worldwide. It can cause hyperviremia in humans and can even lead to fatal clinical diseases. The life cycle of DENV is intricately linked to cellular lipids, and the virus selectively utilizes relevant enzymes involved in lipid metabolism to modulate the existing metabolic system in host cells during entry, replication, assembly, and other stages, thereby creating an environment conducive to its complete replication cycle. At present, there is a lack of effective and specific anti-DENV treatment measures. This review summarizes the recently identified lipid metabolism molecules and metabolic related diseases that affect DENV infection, explores the dependence of DENV on lipid metabolism and provides potential targets for the treatment of dengue fever (DF).PMID:40059731 | DOI:10.1080/22221751.2025.2477647
Serum Proteomic and Metabolomic Signatures of High Versus Low Physical Function in Octogenarians
Aging Cell. 2025 Mar 10:e70002. doi: 10.1111/acel.70002. Online ahead of print.ABSTRACTPhysical function declines with aging, yet there is considerable heterogeneity, with some individuals declining very slowly while others experience accelerated functional decline. To gain insight into mechanisms promoting high physical function with aging, we performed proteomics, targeted metabolomics, and targeted kynurenine-focused metabolomic analyses on serum specimens from three groups of octogenarians: High-functioning master athletes (HF, n = 16), healthy normal-functioning non-athletes (NF, n = 12), and lower functioning non-athletes (LF, n = 11). Higher performance status was associated with evidence consistent with: Lower levels of circulating proinflammatory markers, as well as unperturbed tryptophan metabolism, with the normal function of the kynurenic pathway; higher circulating levels of lysophosphatidylcholines that have been previously associated with better mitochondrial oxidative capacity; lower activity of the integrated stress response; lower levels of circulating SASP protein members; and lower levels of proteins that reflect neurodegeneration/denervation. Extending the observations of previous studies focused on the biomarkers of aging that predict poor function, our findings show that many of the same biomarkers associated with poor function exhibit attenuated changes in those who maintain a high function. Because of the cross-sectional nature of this study, results should be interpreted with caution, and bidirectional causality, where physical activity behavior is both a cause and outcome of differences in the biomarker changes, remains a possible interpretation.PMID:40059508 | DOI:10.1111/acel.70002
A Review of Retention Time Alignment Methods and Tools for Proteomics Data
Proteomics. 2025 Mar 9:e202400088. doi: 10.1002/pmic.202400088. Online ahead of print.ABSTRACTMass spectrometry (MS) is widely used in proteomics research in recent years. In practice, MS is often coupled with liquid chromatography or gas chromatography to analyze complex mixtures. Retention time (RT) is a critical feature that distinguishes different components in mixtures. And RT alignment is one of the crucial methods for correlating identical components across different samples. This review provides a broad perspective of RT alignment methods and tools used in proteomics and metabolomics. Firstly, we categorize these methods and tools into four types based on the information they employ, and introduce them, respectively. Subsequently, we present the application of RT alignment in proteomics. We have emphasized that the identification-free strategy might be a potential application of RT alignment. Finally, we summarize the limitations of current methods and discuss the future direction of RT alignment.PMID:40059493 | DOI:10.1002/pmic.202400088
S-Methyl Methanethiosulfonate, the Main Human Metabolite of S-Methyl-L-Cysteine Sulfoxide, Alters Energy Metabolism in Prostate Cancer Cells
Mol Nutr Food Res. 2025 Mar 9:e70008. doi: 10.1002/mnfr.70008. Online ahead of print.ABSTRACTCruciferous and allium vegetables contain the sulfur compound S-methyl-L-cysteine-sulfoxide (SMCSO). Considering SMCSO is found at a higher abundance compared to the glucosinolates, there are limited reports on its effect on health, with the majority of the evidence on the beneficial effects on glucose metabolism in rodent models. In the current study, we investigated the metabolic effects of SMCSO and its metabolite, S-methyl methanethiosulfonate (MMTSO), on prostate cancer metabolism. DU145 prostate cancer cells were cultured in 5.5 mM (basal), 10 mM (intermediate) and 25 mM (high) glucose concentrations in the presence of SMCSO or MMTSO (100 µM). Using Seahorse technology, MMTSO but not SMCSO reduced mitochondrial metabolism, mitochondrial ATP, and the percentage of oxidative phosphorylation and increased the fatty acid dependency of DU145 cells. Transcriptomic and metabolomic analyses observed cellular and energy metabolism pathways and immune response changes. These data show that MMTSO alters several features of energy metabolism in DU145 prostate cancer cells, shifting them towards a non-cancerous phenotype. These data are consistent with the notion that MMTSO may contribute to the beneficial effects of a broccoli-rich diet and metabolic effects of prostate cancer.PMID:40059483 | DOI:10.1002/mnfr.70008
The Restoration of Energy Pathways Indicates the Efficacy of Ketamine Treatment in Depression: A Metabolomic Analysis
CNS Neurosci Ther. 2025 Mar;31(3):e70324. doi: 10.1111/cns.70324.ABSTRACTAIMS: Despite the clinical benefits of ketamine in treating major depressive disorder (MDD), some patients exhibit drug resistance, and the intricate mechanisms underlying this await comprehensive explication. We used metabolomics to find biomarkers for ketamine efficacy and uncover its mechanisms of action.METHODS: The study included 40 MDD patients treated with ketamine in the discovery cohort and 24 patients in the validation cohort. Serum samples from the discovery cohort receiving ketamine were analyzed using ultra performance liquid chromatography-mass spectrometry to study metabolomic changes and identify potential biomarkers. Metabolic alterations were evaluated pre- and post-ketamine treatment. Spearman correlation was applied to examine the relationship between metabolite alterations and depressive symptom changes. In addition, potential biomarkers, particularly thyroxine, were investigated through quantitative measurements in the validation cohort.RESULTS: We found that energy metabolite changes (adenosine triphosphate, adenosine diphosphate [ADP], pyruvate) were different in responders versus non-responders. The magnitude of the ADP shift was strongly correlated with the rate of reduction in Montgomery-Asberg Depression Rating Scale (MADRS) scores (Rho = 0.48, pFDR = 0.018). Additionally, baseline free triiodothyronine (FT3) levels are inversely associated with the rate of MADRS reduction (Rho = -0.645, p = 0.017).CONCLUSIONS: Ketamine ameliorates depressive symptoms by modulating metabolic pathways linked to energy metabolism. Low baseline FT3 levels appear to predict a positive response in MDD patients, suggesting FT3 has potential as a biological marker for clinical ketamine treatment.TRIAL REGISTRATION: ChiCTR-OOC-17012239.PMID:40059071 | DOI:10.1111/cns.70324
Advancing atherosclerosis research: The Power of lipid imaging with MALDI-MSI
Atherosclerosis. 2025 Feb 15:119130. doi: 10.1016/j.atherosclerosis.2025.119130. Online ahead of print.ABSTRACTAtherosclerosis is a chronic inflammatory disease that is one of the leading causes of mortality globally. It is characterized by the formation of atheromatous plaques in the intima layer of larger arteries. The (fibro-)fatty plaques usually develop asymptomatically within the vessel until a serious event such as myocardial infarction or stroke occurs. Lipids play a pivotal role in disease progression, but while the causal role of cholesterol is beyond doubt, the distribution of numerous other lipids within the heterogeneous layers of atherosclerotic plaques, and their biological function remain unclear. A deeper understanding of the pathophysiological progression of the disease for prognostics, diagnostics, treatment, and prevention is of great need. Mass spectrometry imaging (MSI), in particular with matrix-assisted laser desorption/ionization (MALDI) offers an unprecedented untargeted characterization of the physiological microenvironment, unraveling the spatial distribution of numerous biochemical compounds. MALDI-MSI offers an advantageous balance of sample preparation, chemical sensitivity, and spatial resolution, and thus has been established as a key technology in modern biomedical analysis. This review focuses on the analysis of lipids in atherosclerotic lesions with MALDI-MSI, for which the past years showed major developments in the spatial characterization of lipids and their interaction within atherosclerotic plaques. We will cover main contributions with a focus on the recent decade, elaborate possibilities, limitations, main findings, and recent developments from sample handling to instrumentation, and estimate current challenges and potentials of MALDI-MSI with respect to a clinical application.PMID:40059002 | DOI:10.1016/j.atherosclerosis.2025.119130
Monitoring the mitochondrial localization of mycobacterial proteins
Methods Cell Biol. 2025;194:135-149. doi: 10.1016/bs.mcb.2024.10.018. Epub 2024 Nov 18.ABSTRACTMitochondrion apart from being the energy hub of the cell, is also the center of various signaling pathways. During intracellular infection, either bacterial or viral, several pathogen proteins, metabolites, and possibly, lipids interact with the host mitochondria. These interactions allow the pathogens, such as Mtb, to reprogram the host mitochondrial functions, screwing the host immune responses and resulting in the persistence of the bacteria. Therefore, mitochondria offer a critical target organelle for various therapeutic interventions. This chapter deals with methods to demonstrate and establish the mitochondrial localization of Mtb proteins by confocal microscopy and mitochondrial enrichment. Transient transfection of mammalian constructs or infection Mycolicibacterium smegmatis infection could be used to overexpress the candidate Mtb protein in host cells, allowing the study of changes in the mitochondria's composition and function with regard to localization studies, mitochondrial DNA and RNA, proteomics, metabolomics, lipidomics, and bioenergetics.PMID:40058957 | DOI:10.1016/bs.mcb.2024.10.018
A screening system to determine the effect of bacterial metabolites on MAdCAM-1 expression by transformed endothelial sinusoidal cells
Methods Cell Biol. 2025;194:119-133. doi: 10.1016/bs.mcb.2024.01.007. Epub 2024 Feb 26.ABSTRACTMucosal addressin cell adhesion molecule 1 (MAdCAM-1) expression in high endothelial venules is regulated by bacterial metabolites emanating from the gut and the interaction of MAdCAM-1 with α4β7 integrin mediates lymphocyte diapedesis into gut-associated secondary lymphoid tissues. MAdCAM-1 thus controls the abundance of circulating immunosuppressive T cells that can reach malignant tissue and compromise the therapeutic efficacy of anticancer immunotherapy. Here we describe a biosensor-based phenotypic assessment that facilitates the high throughput screening (HTS)-compatible assessment of MAdCAM-1 regulation in response to exposure to bacterial metabolites. This screening routine encompasses high endothelial venule cells expressing green fluorescent protein (GFP) under the control of the MAdCAM-1 promoter combined with robot-assisted bioimaging and a multistep image analysis pipeline. Altogether this system facilitates the discovery of bacterial composites that control anticancer immunity via the sequestration of Th17-specific regulatory T cells (Treg17) in the gut.PMID:40058956 | DOI:10.1016/bs.mcb.2024.01.007
Unraveling molecular mechanisms of 1-deoxynojirimycin and polyphenol biosynthesis in mulberry leaves in response to ultrasound elicitation: An integrated metabolomics and transcriptomics approach
Food Res Int. 2025 Apr;206:116072. doi: 10.1016/j.foodres.2025.116072. Epub 2025 Feb 25.ABSTRACT1-Deoxynojirimycin (1-DNJ) and polyphenols are the primary anti-diabetic components in mulberry leaves (MLs) but their low natural abundance limits their application. To address this, we investigated the impact of ultrasonication (US) on the accumulation of 1-DNJ, total phenolic content (TPC), and total flavonoid content (TFC) in MLs. Under the optimal conditions determined by the Box-Behnken design, 1-DNJ, TPC, and TFC levels increased by 2.10-, 2.66-, and 2.11-fold, respectively. US treatment also changed the surface microstructure and increased electrical conductivity, polyphenolic content, antioxidant capacity, as well as α-glucosidase, α-amylase, and xanthine oxidase inhibitory activities, while inhibiting polyphenol oxidase and peroxidase activities in MLs. Metabolomics and transcriptomics analyses identified 458 differential metabolites (DMs) and 9429 differentially expressed genes (DEGs). These DMs and DEGs are involved in key metabolic pathways for synthesizing 1-DNJ and phenolic compounds. Our findings demonstrated that US treatment boosted the biosynthesis of 1-DNJ and phenolic compounds by upregulating the expression of key enzymes, thereby increasing their contents in MLs. This study demonstrates an innovative strategy for improving bioactive components, particularly 1-DNJ, in MLs, providing the potential to increase the values of MLs in the food and nutraceutical industries.PMID:40058923 | DOI:10.1016/j.foodres.2025.116072
Omics approaches to explore the coffee fermentation microecosystem and its effects on cup quality
Food Res Int. 2025 Apr;206:116035. doi: 10.1016/j.foodres.2025.116035. Epub 2025 Feb 22.ABSTRACTThe cultivation and postharvest processing of coffee constitute the basis of the subsistence and traditional culture for rural family-owned farms, as well as for the economic success of commercial enterprises in many coffee-producing countries worldwide. The quality of the final beverage is determined by a multitude of variables. A key post-harvest factor is the spontaneous fermentation of the coffee beans, conducted directly on the farm, to remove the mucilage that firmly adheres to the beans. The effect of this fermentation step on the aromatic profile of the coffee is not yet sufficiently understood. All of the above have drawn the attention of researchers on the application of various omics approaches to elucidate fermentation processes in more detail. These approaches have been used to study the fermentation of Arabica (Coffea arabica) beans, as this species is economically most important worldwide. It is known that Arabica mild coffee is obtained through the wet method, which involves fermenting depulped coffee beans using various strategies and then washing the fermented coffee with clean water. In contrast, the fermentation of Canephora coffee beans has been much less studied using omics technologies. This review highlights the trends and future research in coffee fermentation based on a scientometric analysis, supplemented by a traditional systematic literature review. It highlights the composition of the coffee fermentation microbiome, as elucidated by metagenomics applications, in light of several factors that can influence its structure. Additionally, it considers the metabolites associated with microbial metabolism that can influence the chemical composition of coffee beans and, consequently, the cup quality. In this way, this review evidences the promising path in understanding microbial functions in coffee fermentation and in particular in the development of microbial inocula and in the refinement of fermentation processes to improve coffee quality.PMID:40058902 | DOI:10.1016/j.foodres.2025.116035
Effects of Lactobacillus curvatus SQ-425 and Staphylococcus simulans 65-4 as starter cultures on sensory characteristics, microbial communities and metabolites in fermented sausage
Food Res Int. 2025 Apr;206:116030. doi: 10.1016/j.foodres.2025.116030. Epub 2025 Feb 22.ABSTRACTMixed starting cultures have been reported to perform better than commonly used single Lactic acid bacteria in meat fermentation. Lactobacillus curvatus SQ-425 and Staphylococcus simulans 65-4 were screened from 67 sausages collected from southwest regions in China to investigate the effects of single and combined inoculation (SF and CMF) on sausages quality, while natural fermentation (NF) was used as a control group. Inoculation of mixed cultures resulted in a continuous decrease in pH during fermentation, an increase in redness values of sausages and the highest sensory score. Inoculation of mixed starter cultures increased the richness of bacterial communities in sausages, but their diversity decreased. The diversity and richness of the fungal community were increased, and spoilage microorganisms such as Shigella and Fusarium were suppressed. The starting cultures did not obviously affect the fatty acid composition of the sausages, but significantly increased the diversity of volatiles, especially aldehydes and alcohols. The generation of unique flavor compounds such as 2-undecenal, p-methoxy benzaldehyde and 3, 5-octadien-2-ol was found in the CMF group. Metabolomics and correlation analyses showed that amino acid metabolism was significantly enhanced in the CMF group, with Aspergillus contributing significantly to amino acid production in the CMF group, in addition to Staphylococcus, Lactobacillus, and Sphingomonas being positively correlated with amino acid metabolites. It is further inferred that the production of amino acids and their derivatives is facilitated by the conversion of fumarate in the TCA cycle into the lysine biosynthetic pathway and the urea cycle.PMID:40058898 | DOI:10.1016/j.foodres.2025.116030
IDENTIFICATION OF THE METABOLOMIC ALTERATIONS ASSOCIATED WITH THE FORMATION OF BISPHENOL-A SULFATE METABOLITE IN HepG2 CELLS
Food Chem Toxicol. 2025 Mar 7:115382. doi: 10.1016/j.fct.2025.115382. Online ahead of print.ABSTRACTThe elucidation of the causal relationship between bisphenol-A (BPA) exposure and hepatoxic outcomes is challenging because of the complexity in both the BPA-derived metabolites formed in the liver and the associated endogenous molecular responses. We performed parallel metabolism experiments with BPA to characterize the BPA sulfate formation and the associated alterations in the metabolome level in HepG2 cells using mass spectrometry-based metabolome wide association study. Briefly, HepG2 cells were exposed for 8 or 24 h to 1 or 10 μM BPA in DMSO or DMSO alone. The levels of BPA sulfate in the cell culture media were quantified, and the sulfation efficiency was about 0.4 % observed for both 1 and 10 μM BPA in HepG2 cells. Targeted metabolomic analyses revealed alterations belonging to forty metabolic pathways following BPA exposure. Featured by the decreasing of estrone sulfate, estrogen metabolism was observed as the top 1 enriched pathway in response to BPA exposure. MWAS suggests that BPA sulfate formation in HepG2 cells resulted in vitamin B6 deficiency and dysregulated vitamin B6-dependent processes, for example, the kynurenine pathway in tryptophan metabolism. These findings collectively provide insights into the linkage between exogenous and endogenous metabolism and the potential initial events in BPA exposure-relevant hepatoxicity.PMID:40058625 | DOI:10.1016/j.fct.2025.115382
Effects of excessive Platycodon grandiflorus root on gut microbiota and host co-metabolism in mice
J Ethnopharmacol. 2025 Mar 7:119577. doi: 10.1016/j.jep.2025.119577. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Platycodon grandiflorus root, is a widely used herb in East Asia for treating respiratory diseases, but research on its oral safety is limited.AIM OF THE STUDY: This study examines the potential adverse gastrointestinal reactions resulting from excessive consumption of Platycodon grandiflorus root (PR) and its effects on gut microbiota and host co-metabolism.MATERIALS AND METHODS: This study evaluated the effects of different doses (1.5, 4.5, and 7.5 g/kg/day) of PR on ICR mice through gavage. Select the 7.5 g/kg/day dosage group and the control group to assess intestinal morphology and conduct histopathological studies. Examine inflammation-related factors and tight junction proteins using WB, qPCR, and ELISA. Additionally, perform 16S rDNA sequencing and metabolomic analyses to evaluate changes in gut microbiota and endogenous metabolites. Finally, the clearance of gut microbiota with antibiotics, the effects of excessive PR on mice were investigated.RESULTS: Excessive intake of PR can lead to mortality in mice, as well as symptoms such as intestinal flatulence and slowed intestinal transit, suggesting the occurrence of chronic intestinal pseudo-obstruction accompanied by endotoxemia. It altered both α-diversity and β-diversity in the gut microbiota of mice, with increased relative abundances of Pseudomonadota, Verrucomicrobiota, Escherichia-Shigella, Akkermansia, Bacteroides, and Klebsiella, closely linked to intestinal obstruction and bacterial overgrowth. Excessive intake of PR also resulted in metabolic disturbances in mice, particularly in the levels of metabolites such as bate-hydroxybutyrate, 5,6-dihydrouracil, uridine, isoleucine, mannitol, bate-alanine, L-cysteine, L-tyrosine, and orotic acid, which may provide insights into the side effects associated with excessive consumption of PR. Clearing the gut microbiota significantly mitigated adverse effects on the intestines and restored metabolite levels.CONCLUSIONS: This study demonstrates that excessive PR induces gut microbiota and metabolic disruption in normal mice, with the overgrowth of Gram-negative bacteria releasing LPS that impair smooth muscle contraction, leading to adverse effects such as chronic intestinal pseudo-obstruction.PMID:40058476 | DOI:10.1016/j.jep.2025.119577
Kai-Xin-San polysaccharides exert therapeutic effects on D-gal and Aβ<sub>25-35</sub>-induced AD rats by regulating gut microbiota and metabolic profile
Int J Biol Macromol. 2025 Mar 7:141850. doi: 10.1016/j.ijbiomac.2025.141850. Online ahead of print.ABSTRACTMetabolic abnormalities and gut microbiota imbalance are intricately linked to the onset and progression of Alzheimer's disease (AD). Kai-Xin-San (KXS) is a traditional herbal formula known for its therapeutic effects on AD. Our previous research indicated that Kai-Xin-San polysaccharide (KXS-P) exhibits a significant therapeutic impact on AD, but the precise mechanisms remain incompletely understood. In this study, untargeted fecal metabolomics and 16S rRNA gene sequencing were used to investigate the potential mechanisms by which KXS-P acts against AD. Key metabolites and gut microbial species were identified using multivariate analysis and a comprehensive examination of intestinal microecology. Our findings revealed that KXS-P improves lipid metabolism in AD rats by modulating a series of lipid molecules and bile acid levels. Additionally, KXS-P regulated gut microbiota composition and restored the symbiotic relationships within the gut microbiome. Notably, the anti-inflammatory effect of KXS-P may be related to its regulation of specific lipotypes levels and the abundance of Romboutsia, Bifidobacterium and Alloprevotella. KXS-P demonstrates the ability to alleviate symptoms of AD rats through multiple mechanisms: ① Improving lipid metabolism and maintaining lipid homeostasis; ② Reducing neuronal and inflammatory damage; ③ Regulating the composition and symbiotic relationships of gut microbiota to preserve intestinal microecological balance.PMID:40058438 | DOI:10.1016/j.ijbiomac.2025.141850
Absolute quantitative lipidomics reveals the disturbance of lipid metabolism induced by oral exposure of titanium dioxide nanoparticles
NanoImpact. 2025 Mar 7:100554. doi: 10.1016/j.impact.2025.100554. Online ahead of print.ABSTRACTThe widespread use of titanium dioxide nanoparticles (TiO2 NPs) as a white pigment in consumer goods increases the possibility of its release into the environment, which poses a great health risk to human beings. Many studies have proved the liver damage caused by TiO2 NPs, but the research about the potential effects of TiO2 NPs on liver lipid metabolism has been limited. Therefore, we selected Sprague-Dawley (SD) rats to explore the effects of long-term exposure to TiO2 NPs on lipid metabolism. Rats were exposed to TiO2 NPs at 0, 2, 10, 50 mg/kg body weight daily for 90 consecutive days. Subsequently, absolute quantitative lipidomics was used to ascertain variation of differential lipid metabolites in rat liver and serum. The results showed that TiO2 NPs (50 mg/kg) changed 22 lipid metabolites such as DAG (18:2/20:5) and TAG (58:10/FA18:2) in rat liver. In the serum, the alteration of 119 lipid metabolites such as DAG (18:0/18:2) were more significant. There was a significant correlation between the different lipid metabolites in liver and serum. At the same time, it was observed that the relative expression levels of oxidative stress-related genes Nrf-2 and Ho-1 changed significantly, and they were closely related to differential metabolites. In conclusion, oral exposure of TiO2 NPs has changed the lipid metabolomics of liver and serum, and the strong induction of oxidative stress may be related to it. TAG and DAG are key metabolites and metabolic pathways in two distinct biological samples, serving as potential indicators of liver injury to a certain extent.PMID:40058412 | DOI:10.1016/j.impact.2025.100554
Intestinal 8 gingerol attenuates TBI-induced neuroinflammation by inhibiting microglia NLRP3 inflammasome activation in a PINK1/Parkin-dependent manner
Phytomedicine. 2025 Feb 26;140:156580. doi: 10.1016/j.phymed.2025.156580. Online ahead of print.ABSTRACTBACKGROUND: traumatic brain injury (TBI) is irreversible brain damage, leading to inflammation and cognitive dysfunction. Microglia involved in the inflammatory response after TBI. The gut microbiota, known as the body's "second brain," regulates neurogenesis and immune responses, but its precise role in regulating TBI remains unclear.PURPOSE: to investigate the effect of gut microbiota and metabolites disorder on TBI injury.STUDY DESIGN: 16SrRNA and metabolomics compared gut microbiota and metabolites in sham group and TBI group, then proved that the differential metabolite 8-gingerol (8G) alleviated the microglia neuroinflammatory response after TBI.METHODS: fecal microbiota transplantation explored the role of dysbiosis in TBI. LC/MS detected the content of 8-gingerol in cecum, blood, and brain. HE, Nissl, Tunel staining and mNSS score evaluated brain injury. Western blot and immunofluorescence detected the expression of inflammasome-related proteins and mitophagy-related proteins in brain tissue and BV2 cells. RNA sequencing analyzed the molecular mechanism of 8-gingerol.RESULT: rats transplanted with TBI feces had worse brain injury and neurological deficits than those with normal feces. 16SrRNA and metabolomics found that TBI caused dysbiosis and decreased 8-gingerol level, leading to severe neuroinflammation. Mechanistically, 8-gingerol inhibited NLRP3 inflammasome by promoting PINK1-Parkin mediated mitophagy in microglia. Inhibition of Parkin, through either small interfering RNA or the inhibitor 3MA reversed the inhibitory effect of 8-gingerol on NLRP3 by blocking mitophagy. BV2 cells transcriptome showed that 8-gingerol significantly increased the expression of autophagy factor Wipi1, and small interfering RNA of Wipi1 abolished the effect of 8-gingerol on promoting mitophagy and the inhibitory effect on NLRP3.CONCLUSION: our findings shed light on the pivotal role of gut microbes in TBI, and identify 8 gingerol as an important anti-inflammatory compound during TBI.PMID:40058316 | DOI:10.1016/j.phymed.2025.156580
A novel framework for industrial pesticide effluent assessment: Integrating chemical screening, multi-endpoint responses and literature-based validation
J Hazard Mater. 2025 Mar 5;490:137830. doi: 10.1016/j.jhazmat.2025.137830. Online ahead of print.ABSTRACTIndustrial pesticide effluents pose substantial risks to aquatic ecosystems, yet comprehensive understanding of their toxicological impacts remains limited. This study presents an integrated approach to evaluate the ecological risks of pesticide manufacturing effluents through chemical screening and multi-endpoints biological responses. Using zebrafish embryos as a model organism, we demonstrated that effluent discharge point (EDP) sample induced 100 % mortality, while diluted samples exhibited significant developmental toxicity, cardiovascular injury, immunosuppression, and behavioral alterations. Non-targeted metabolomics analysis revealed the molecular mechanisms underlying these toxic responses. Through chemical screening and targeted quantification, we identified three predominant azole fungicides - propiconazole (2.11 μg/L), hexaconazole (13.3 μg/L), and tebuconazole (18.66 μg/L) - that exhibited synergistic toxicity. Notably, our innovative meta-analysis framework based on literature data validated the toxicological profiles of detected compounds, providing an efficient alternative to conventional bioassays. This study establishes a comprehensive framework for assessing industrial effluent toxicity and demonstrates the value of integrating chemical analysis with biological responses for environmental risk assessment.PMID:40058200 | DOI:10.1016/j.jhazmat.2025.137830
Taurine supplementation alleviates asthma airway inflammation aggravated by HOCl exposure
J Hazard Mater. 2025 Feb 28;490:137796. doi: 10.1016/j.jhazmat.2025.137796. Online ahead of print.ABSTRACTEnvironmental pollutant exposure has been demonstrated to be associated with the onset and progression of asthma. Hypochlorous acid (HOCl), as an environmental exposure-relevant chlorine-based disinfectant, its role in asthmatic airway inflammation remains unclear. Through administering HOCl in drinking water during early life and the perinatal period, we discovered that early-life HOCl drinking water exposure not only aggravated airway inflammation in asthmatic mice but also that perinatal HOCl drinking water exposure could promote airway inflammation in the offspring of asthmatic mice. By gut microbiota sequencing, it was found that HOCl drinking water exposure could reduce the gut microbiota diversity in asthmatic mice, with the abundances of Lactobacillus, Faecalibaculum, Muribaculum, and [Eubacterium]_ventriosum_group being decreased, while increasing the abundances of Dubosiella and Parabacteroides. Further fecal metabolomics analysis revealed that HOCl drinking water exposure significantly enhanced the arachidonic acid metabolism pathway. And there was a certain correlation between the abundances of the significantly altered bacterial genera and the levels of arachidonic acid metabolites. Finally, treatment with taurine, a HOCl neutralizer, showed that taurine could significantly alleviate the asthma airway inflammation aggravated by HOCl exposure. In summary, these results provide evidence for the exacerbation of asthma airway inflammation by HOCl exposure and confirm that taurine supplementation can serve as a potential therapeutic approach.PMID:40058197 | DOI:10.1016/j.jhazmat.2025.137796
UPLC-MS and multivariate analysis reveal metabolic pathway adaptations to training in professional football players
Talanta. 2025 Mar 4;291:127893. doi: 10.1016/j.talanta.2025.127893. Online ahead of print.ABSTRACTMetabolomics provides direct insights into biological processes by analyzing metabolites. While univariate and multivariate analyses, alongside pathway and functional analysis tools like mummichog, are commonly employed, integrating these results to interpret biological significance remains a challenge, limiting the potential of metabolomic analyses. This study introduces innovative methods to analyze metabolic adaptations in professional football players using a unique UPLC-TOF-MS dataset comprising 93 urinary samples collected over a 10-month football season. Urinary metabolomic profiles were linked to training load data obtained through an electronic performance tracking system. Three approaches combining multivariate analysis with pathway-level insights were developed. PLS regression p-values integrated with functional metabolic analysis identified training load-associated pathways overlooked by univariate methods. Cluster cross-validation enhanced these insights by assessing the contribution of each pathway to the predictive performance, ranking pathways driving the PLS model. Backward feature elimination refined metabolic features most strongly linked to training load, improving the practicality of findings for targeted biomarker validation. Univariate analyses highlighted alterations in Phenylalanine and Histidine metabolisms related to total external load. Multivariate methods identified additional pathways, including Tryptophan, Purine, and Tyrosine metabolisms, as top contributors to the association between metabolic profiles and training load. Results demonstrate that combining multivariate techniques with functional analysis expands understanding of athletes' metabolic responses, offering more comprehensive biomarker discovery beyond the scope of univariate approaches. These findings underscore the value of integrating multivariate strategies with pathway insights to enhance the biological interpretation of metabolomic data.PMID:40058141 | DOI:10.1016/j.talanta.2025.127893