PubMed

Front Immunol. 2025 Feb 14;16:1550500. doi: 10.3389/fimmu.2025.1550500. eCollection 2025.ABSTRACTMacrophages, crucial innate immune cells, defend against pathogens and resolve inflammation, maintaining tissue balance. They perform phagocytosis, present antigens to T cells, and bond innate and adaptive immunity through various activation states. Classical activation is associated with Th1 responses and interferon γ production, while alternative activation, induced by interleukin 4, is characterized by increased endocytosis, reduced secretion of pro-inflammatory cytokines, and roles in immunoregulation and tissue remodeling. Although these represent opposite extremes observed in vitro, the remarkable plasticity of macrophages allows for a wide spectrum of activation phenotypes that are complex to characterize experimentally. While the application of omics techniques has resulted in significant advances in the characterization of macrophage polarization, lipidomic studies have received lesser attention. Beyond their role as structural components and energy sources, lipids function as signaling molecules that regulate macrophage activation and polarization, thereby shaping immune responses. This work reviews the interaction between lipid signaling and macrophage polarization, exploring how lipid metabolism influences macrophage phenotype and function. These insights offer potential therapeutic strategies for immune-mediated diseases and inflammation-related disorders, including inflammaging.PMID:40028333 | PMC:PMC11867965 | DOI:10.3389/fimmu.2025.1550500

Front Immunol. 2025 Feb 14;16:1509114. doi: 10.3389/fimmu.2025.1509114. eCollection 2025.ABSTRACTINTRODUCTION: Ulcerative colitis (UC) is often characterized by dysbiosis of the colonic microbiota and metabolic disturbances, which can lead to liver damage. Patchoulene epoxide (PAO), a tricyclic sesquiterpene derived from the aged essential oil of Pogostemonis Herba, is known for its anti-inflammatory and ulcer-healing properties. However, its dual protective role against UC and liver injury remains largely unexplored. This study aims to elucidate the protective effect and underlying mechanism of PAO against dextran sulfate sodium (DSS)-induced UC and liver injury in mice.METHODS: Colitis and liver injury in mice were induced by adding 3% DSS to their drinking water continuously for 7 days, and PAO at the doses of 20 and 40 mg/kg was administered orally to mice daily from the first day until the experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon and liver tissues were collected for biochemical analyses. Additionally, the fecal microbiome and its metabolites of treated mice were characterized using 16S rRNA amplicon sequencing and metabolomics.RESULTS: PAO significantly reduced the disease activity index and mitigated colonic atrophy in UC mice. It also improved colonic and hepatic pathological changes by safeguarding tight and adherens junctions, and suppressing the generation of pro-inflammatory cytokines and lipopolysaccharide. These beneficial effects were attributed to PAO's capability to regulate the colonic microbiota and metabolic processes. PAO was found to enhance the diversity of the colonic microbiota and to shift the microbial balance in UC mice. Specifically, it restored the microbiota from an Akkermansia-dominated state, characteristic of UC, to a healthier Muribaculaceae-dominated composition. Furthermore, PAO corrected the colon metabolic disturbance in UC mice by modulating the purine metabolism, notably increasing the abundance of deoxyadenosine, adenosine and guanine in UC mice.CONCLUSIONS: The therapeutic effect of PAO on UC and liver injury was mainly attributed to its regulation of colonic microbiota and purine metabolism. These insights emphasize the overall therapeutic benefits of PAO in treating UC and liver injury.PMID:40028318 | PMC:PMC11868103 | DOI:10.3389/fimmu.2025.1509114

Front Cell Infect Microbiol. 2025 Feb 14;15:1523863. doi: 10.3389/fcimb.2025.1523863. eCollection 2025.ABSTRACTThis study aimed to investigate the relationship between gut microbiota composition, fecal metabolites, and postoperative prognosis in patients with extrahepatic cholangiocarcinoma (eCCA). A total of 53 patients with resectable eCCA and 21 healthy volunteers as a control group were included. 16S rRNA gene sequencing and metabolomic analyses revealed significant differences in the gut microbial community structure and altered fecal metabolites profiles between eCCA patients and healthy controls. Univariate and multivariate Cox regression analyses indicated that factors such as preoperative total bilirubin, indirect bilirubin, and specific metabolites were closely associated with overall survival in patients with eCCA post-surgery. The constructed nomogram model further demonstrated the predictive value of these factors, achieving a C-index of 0.718, with calibration curves confirming its strong predictive performance. In conclusion, gut microbiota composition and fecal metabolites play a crucial role in the surgical prognosis of eCCA patients, providing new insights for clinical prognostic assessment.PMID:40028184 | PMC:PMC11868125 | DOI:10.3389/fcimb.2025.1523863

ACS Omega. 2025 Feb 11;10(7):6368-6384. doi: 10.1021/acsomega.4c03407. eCollection 2025 Feb 25.ABSTRACTPentachlorophenol (PCP) is one of the most common chlorophenols utilized in numerous industrial processes, including the production of dyes, pesticides, wood preservatives, disinfectants, antiseptics, and medicines because it has fungicidal and bactericidal characteristics. Previous studies on catfish (Heteropneustes fossilis) revealed that PCP acts as a potent endocrine disruptor and also causes behavioral changes in a concentration-dependent manner. However, the toxicological effects of PCP have not been compared between male and female catfish. The present study aims to investigate the toxic effects of PCP on catfish through histopathological changes, oxidative stress, and serum metabolomics after 60 days of exposure. Chronic exposure to sublethal concentrations of PCP resulted in significant histopathological alterations in the liver and gonad, including leukocyte infiltration, hepatocyte degeneration, follicular layer dissolution, and abnormal sperm distribution. Increased levels of lipid peroxidation and hydrogen peroxide, along with decreased antioxidant enzyme activity, were observed in PCP-exposed groups. A 1H NMR-based metabolomics approach was employed to investigate the toxic effects of PCP on catfish serum, revealing alterations in various metabolites, including amino acids, organic acids, glucose, cholesterol, and neurotransmitters, in a dose-dependent manner. Multivariate partial least-squares discriminant analysis (PLS-DA) identified metabolic changes associated with oxidative stress, disruption in hormone synthesis and reproduction, disturbance in osmoregulation and membrane stabilization, energy metabolism disorder, amino acid metabolism disorder, and neurotransmitter imbalance in PCP-exposed catfish. This study demonstrates the efficacy of metabolomics in elucidating the toxicity and underlying mechanisms of wood preservatives like PCP, providing valuable insights for risk assessment in toxicology research. Overall, these findings contribute to our understanding of the toxicological effects of PCP exposure on aquatic organisms and highlight the potential of histology, oxidative stress, and metabolomics in assessing environmental contaminants' risks.PMID:40028089 | PMC:PMC11866196 | DOI:10.1021/acsomega.4c03407

bioRxiv [Preprint]. 2025 Feb 17:2025.02.13.638125. doi: 10.1101/2025.02.13.638125.ABSTRACTPoor therapeutic index is a principal cause of drug attrition during development. A case in point is L-asparaginase (ASNase), an enzyme-drug approved for treatment of pediatric acute lymphoblastic leukemia (ALL) but too toxic for adults. To elucidate potentially targetable mechanisms for mitigation of ASNase toxicity, we performed multi-omic profiling of the response to sub-toxic and toxic doses of ASNase in mice. We collected whole blood samples longitudinally, processed them to plasma, and extracted metabolites, lipids, and proteins from a single 20-µL plasma sample. We analyzed the extracts using multiple reaction monitoring (MRM) of 500+ water soluble metabolites, 750+ lipids, and 375 peptides on a triple quadrupole LC-MS/MS platform. Metabolites, lipids, and peptides that were modulated in a dose-dependent manner appeared to converge on antioxidation, inflammation, autophagy, and cell death pathways, prompting the hypothesis that inhibiting those pathways might decrease ASNase toxicity while preserving anticancer activity. Overall, we provide here a streamlined, three-in-one LC-MS/MS workflow for targeted metabolomics, lipidomics, and proteomics and demonstrate its ability to generate new insights into mechanisms of drug toxicity.PMID:40027784 | PMC:PMC11870395 | DOI:10.1101/2025.02.13.638125

bioRxiv [Preprint]. 2025 Feb 17:2025.02.13.637433. doi: 10.1101/2025.02.13.637433.ABSTRACTNuclear factor erythroid 2-related factor 2 (NFE2L2/NRF2) is a critical mediator of the cellular oxidative stress response. Aberrant activation of NRF2 is common in lung and upper aerodigestive cancers, where it promotes tumor initiation and progression and confers resistance to chemotherapy, radiation therapy, and immune checkpoint inhibitors. As such, NRF2 therapeutic inhibitors are actively being sought. We previously reported that the antiparasitic drug Pyrimethamine (PYR) inhibits NRF2 in cell lines and in a NRF2-inducible genetically engineered mouse model. Here we design, synthesize, and define structure-activity relationships across a series of 25 PYR-based derivatives to reveal WCDD115 as a 22-fold more potent inhibitor of NRF2 (57nM versus 1.2µM). PYR is known to inhibit plasmodial and human dihydrofolate reductase (DHFR). We found that WCDD115 inhibits hDHFR with 31-fold greater potency than PYR (144nM versus 4.49µM). Metabolomics showed strong similarities between PYR, WCDD115 and methotrexate. Genetic, pharmacological and metabolic epistasis studies reveal that DHFR inactivation is required for NRF2 suppression by WCDD115 and PYR. Global and targeted proteomics revealed overlapping profiles for WCDD115, PYR and methotrexate, including suppression of NRF2 oxidative stress response and activation of TP53 and the DNA damage response. Therefore, PYR and a novel potent derivative WCDD115 are effective, indirect inhibitors of NRF2 and its antioxidant functions. These data underscore the importance of one- carbon metabolism for the NRF2 signaling pathway and support a new therapeutic strategy to suppress NRF2-driven cancer biology.PMID:40027760 | PMC:PMC11870417 | DOI:10.1101/2025.02.13.637433

bioRxiv [Preprint]. 2025 Feb 17:2025.02.12.637912. doi: 10.1101/2025.02.12.637912.ABSTRACTBACKGROUND: Clustering analysis is a foundational step in exploratory data analysis workflows, with dimensionality reduction methods commonly used to visualize multidimensional data in lower-dimensional spaces and infer sample clustering. Principal Component Analysis (PCA) is widely applied in metabolomics but is often suboptimal for clustering visualization. Metabolomics data often require specialized manipulations such as blank removal, quality control adjustments, and data transformations that demand efficient visualization tools. However, the lack of user-friendly tools for clustering without computational expertise presents a challenge for metabolomics researchers. ClusterApp addresses this gap as a web application that performs Principal Coordinate Analysis (PCoA), expanding clustering alternatives in metabolomics. Built on a QIIME 2 Docker image, it enables PCoA computation and Emperor plot visualization. The app supports data input from GNPS, GNPS2, or user-provided spreadsheets. Freely available, ClusterApp can be locally installed as a Docker image or integrated into Jupyter notebooks, offering accessibility and flexibility to diverse users.RESULTS: To demonstrate the data preprocessing techniques available in ClusterApp, we analyzed two Liquid Chromatography coupled to Tandem Mass Spectrometry (LC-MS/MS) metabolomics datasets: one exploring metabolomic differences in mouse tissue samples and another investigating coral life history stages. Among the dissimilarity measures available, the Bray-Curtis measure effectively highlighted key metabolomic variations and patterns across both datasets. Targeted filtering significantly enhanced data reliability by retaining biologically relevant features, 10,617 in the coral dataset and 7,341 in the mouse dataset while eliminating noise. The combination of Total Ion Current (TIC) normalization and auto-scaling improved clustering resolution, revealing distinct separations in tissue types and life stages. ClusterApp's flexible features, such as customizable blank removal and group selection, provided tailored analyses, enhancing visualization and interpretation of metabolomic profiles.CONCLUSION: ClusterApp addresses the need for accessible, dynamic tools for exploratory data analysis in metabolomics. By coupling data transformation capabilities with PCoA on multiple dissimilarity matrices, it provides a versatile solution for clustering analysis. Its web interface and Docker-based deployment offer flexibility, accommodating a wide range of use cases through graphical or programmatic interactions. ClusterApp empowers researchers to uncover meaningful patterns and relationships in metabolomics data without requiring cumbersome data manipulation or advanced bioinformatics expertise.PMID:40027717 | PMC:PMC11870400 | DOI:10.1101/2025.02.12.637912

World J Hepatol. 2025 Feb 27;17(2):101201. doi: 10.4254/wjh.v17.i2.101201.ABSTRACTLiver cancer, particularly hepatocellular carcinoma (HCC), remains a significant global health challenge due to its high mortality rate and late-stage diagnosis. The discovery of reliable biomarkers is crucial for improving early detection and patient outcomes. This review provides a comprehensive overview of current and emerging biomarkers for HCC, including alpha-fetoprotein, des-gamma-carboxy prothrombin, glypican-3, Golgi protein 73, osteopontin, and microRNAs. Despite advancements, the diagnostic limitations of existing biomarkers underscore the urgent need for novel markers that can detect HCC in its early stages. The review emphasizes the importance of integrating multi-omics approaches, combining genomics, proteomics, and metabolomics, to develop more robust biomarker panels. Such integrative methods have the potential to capture the complex molecular landscape of HCC, offering insights into disease mechanisms and identifying targets for personalized therapies. The significance of large-scale validation studies, collaboration between research institutions and clinical settings, and consideration of regulatory pathways for clinical implementation is also discussed. In conclusion, while substantial progress has been made in biomarker discovery, continued research and innovation are essential to address the remaining challenges. The successful translation of these discoveries into clinical practice will require rigorous validation, standardization of protocols, and cross-disciplinary collaboration. By advancing the development and application of novel biomarkers, we can improve the early detection and management of HCC, ultimately enhancing patient survival and quality of life.PMID:40027561 | PMC:PMC11866143 | DOI:10.4254/wjh.v17.i2.101201

Imeta. 2025 Jan 9;4(1):e266. doi: 10.1002/imt2.266. eCollection 2025 Feb.ABSTRACTPolyunsaturated fatty acid-derived oxylipins regulate systemic inflammation and exert cardiovascular effects, yet their role in ST-segment elevation myocardial infarction (STEMI) remains unclear. Herein, we used targeted metabolomics and machine learning algorithms to develop an oxylipin-based risk model to accurately predict recurrent major adverse cardiovascular events (MACE) after STEMI in two independent prospective cohorts with 2 years of follow-up. The in vivo effects of significant oxylipin predictors were explored via a murine myocardial ischemia‒reperfusion model and functional metabolomics. Among the 130 plasma oxylipins detected in discovery cohort (n = 645), patients with and without recurrent MACE exhibited significant differences in a variety of oxylipin subclasses. We constructed an oxylipin-based prediction model that showed powerful performance in predicting recurrent MACE in the discovery cohort (predictive accuracy: 91.5%). The predictive value of the oxylipin marker panel was confirmed in an independent external validation cohort (predictive accuracy: 89.9%; n = 401). Furthermore, we found that the anti-inflammatory/pro-resolving oxylipin (ARO) predictor panel showed better prognostic performance than the pro-inflammatory oxylipin predictor panel in both cohorts. Compared with the treatment of pro-inflammatory oxylipin predictor panel, combined treatment of six ARO predictors, including 14,15 epoxy-eicosatrienoic acid, 14(15)-epoxy-eicosatetraenoic acid, 12,13-epoxy-octadecenoic acid, lipoxin A4, resolving D1, and 6 keto-prostaglandin F1 showed significant cardiac activities and synergistic metabolic actions in myocardial infarction‒reperfusion model mice. We also mechanistically identified an important role of ARO predictors in restraining ceramide/lysophosphatidylcholine synthesis and inhibiting inflammatory responses. Overall, the present study depicted the landscape of oxylipin profiles in the largest panel of STEMI patients worldwide. Our results also highlight the great potential of bioactive oxylipins in prognostic prediction and therapeutics after STEMI.PMID:40027487 | PMC:PMC11865345 | DOI:10.1002/imt2.266

Imeta. 2025 Feb 21;4(1):e70000. doi: 10.1002/imt2.70000. eCollection 2025 Feb.ABSTRACTCholesterol gallstones (CGS) still lack effective noninvasive treatment. The etiology of experimentally proven cholesterol stones remains underexplored. This cross-sectional study aims to comprehensively evaluate potential biomarkers in patients with gallstones and assess the effects of microbiome-targeted interventions in mice. Microbiome taxonomic profiling was conducted on 191 samples via V3-V4 16S rRNA sequencing. Next, 60 samples (30 age- and sex-matched CGS patients and 30 controls) were selected for metagenomic sequencing and fecal metabolite profiling via liquid chromatography-mass spectrometry. Microbiome and metabolite characterizations were performed to identify potential biomarkers for CGS. Eight-week-old male C57BL/6J mice were given a lithogenic diet for 8 weeks to promote gallstone development. The causal relationship was examined through monocolonization in antibiotics-treated mice. The effects of short-chain fatty acids such as sodium butyrate, sodium acetate (NaA), sodium propionate, and fructooligosaccharides (FOS) on lithogenic diet-induced gallstones were investigated in mice. Gut microbiota and metabolites exhibited distinct characteristics, and selected biomarkers demonstrated good diagnostic performance in distinguishing CGS patients from healthy controls. Multi-omics data indicated associations between CGS and pathways involving butanoate and propanoate metabolism, fatty acid biosynthesis and degradation pathways, taurine and hypotaurine metabolism, and glyoxylate and dicarboxylate metabolism. The incidence of gallstones was significantly higher in the Clostridium glycyrrhizinilyticum group compared to the control group in mice. The grade of experimental gallstones in control mice was significantly higher than in mice treated with NaA and FOS. FOS could completely inhibit the formation of gallstones in mice. This study characterized gut microbiome and metabolome alterations in CGS. C. glycyrrhizinilyticum contributed to gallstone formation in mice. Supplementing with FOS could serve as a potential approach for managing CGS by altering the composition and functionality of gut microbiota.PMID:40027485 | PMC:PMC11865347 | DOI:10.1002/imt2.70000

Imeta. 2025 Feb 14;4(1):e272. doi: 10.1002/imt2.272. eCollection 2025 Feb.ABSTRACTThe gut microbiota influences host immunity and metabolism, and changes in its composition and function have been implicated in several non-communicable diseases. Here, comparing germ-free (GF) and specific pathogen-free (SPF) mice using spatial transcriptomics, single-cell RNA sequencing, and targeted bile acid metabolomics across multiple organs, we systematically assessed how the gut microbiota's absence affected organ morphology, immune homeostasis, bile acid, and lipid metabolism. Through integrated analysis, we detect marked aberration in B, myeloid, and T/natural killer cells, altered mucosal zonation and nutrient uptake, and significant shifts in bile acid profiles in feces, liver, and circulation, with the alternate synthesis pathway predominant in GF mice and pronounced changes in bile acid enterohepatic circulation. Particularly, autophagy-driven lipid droplet breakdown in ileum epithelium and the liver's zinc finger and BTB domain-containing protein (ZBTB20)-Lipoprotein lipase (LPL) (ZBTB20-LPL) axis are key to plasma lipid homeostasis in GF mice. Our results unveil the complexity of microbiota-host interactions in the crosstalk between commensal gut bacteria and the host.PMID:40027481 | PMC:PMC11865341 | DOI:10.1002/imt2.272

Imeta. 2025 Feb 17;4(1):e70002. doi: 10.1002/imt2.70002. eCollection 2025 Feb.ABSTRACTThe rapid growth of microbiome research has generated an unprecedented amount of multi-omics data, presenting challenges in data analysis and visualization. To address these issues, we present MicrobiomeStatPlots, a comprehensive platform offering streamlined, reproducible tools for microbiome data analysis and visualization. This platform integrates essential bioinformatics workflows with multi-omics pipelines and provides 82 distinct visualization cases for interpreting microbiome datasets. By incorporating basic tutorials and advanced R-based visualization strategies, MicrobiomeStatPlots enhances accessibility and usability for researchers. Users can customize plots, contribute to the platform's expansion, and access a wealth of bioinformatics knowledge freely on GitHub (https://github.com/YongxinLiu/MicrobiomeStatPlot). Future plans include extending support for metabolomics, viromics, and metatranscriptomics, along with seamless integration of visualization tools into omics workflows. MicrobiomeStatPlots bridges gaps in microbiome data analysis and visualization, paving the way for more efficient, impactful microbiome research.PMID:40027478 | PMC:PMC11865346 | DOI:10.1002/imt2.70002

Curr Res Microb Sci. 2025 Feb 5;8:100358. doi: 10.1016/j.crmicr.2025.100358. eCollection 2025.ABSTRACTBacteroides species are key members of the human gut microbiome and play crucial roles in gut ecology, metabolism, and host-microbe interactions. This study investigated the strain-specific production of neuroactive metabolites by 18 Bacteroidetes (12 Bacteroides, 4 Phocaeicola, and 2 Parabacteroides) using multi-omics approaches. Genomic analysis revealed a significant potential for producing GABA, tryptophan, tyrosine, and histidine metabolism-linked neuroactive compounds. Using untargeted and targeted metabolomics, we identified key neurotransmitter-related or precursor metabolites, including GABA, l-tryptophan, 5-HTP, normelatonin, kynurenic acid, l-tyrosine, and norepinephrine, in a strain- and media-specific manner, with GABA (1-2 mM) being the most abundant. Additionally, extracellular vesicles (EVs) produced by Bacteroides harbor multiple neuroactive metabolites, mainly GABA, and related key enzymes. We used CRISPR/Cas12a-based gene engineering to create a knockout mutant lacking the glutamate decarboxylase gene (gadB) to demonstrate the specific contribution of Bacteroides finegoldii-derived GABA in modulating intestinal homeostasis. Cell-free supernatants from wild-type (WT, GABA+) and ΔgadB (GABA-) provided GABA-independent reinforcement of epithelial membrane integrity in LPS-treated Caco-2/HT29-MTX co-cultures. EVs from WT and ΔgadB attenuated inflammatory immune response of LPS-treated RAW264.7 macrophages, with reduced pro-inflammatory cytokines (IL-1β and IL-6), downregulation of TNF-α, and upregulation of IL-10 and TGF-β. GABA production by B. finegoldii had a limited impact on gut barrier integrity but a significant role in modulating inflammation. This study is the first to demonstrate the presence of a myriad of neuroactive metabolites produced by Bacteroides species in a strain- and media-specific manner in supernatant and EVs, with GABA being the most dominant metabolite and influencing immune responses.PMID:40027450 | PMC:PMC11868947 | DOI:10.1016/j.crmicr.2025.100358

Res Pract Thromb Haemost. 2025 Jan 16;9(1):102681. doi: 10.1016/j.rpth.2025.102681. eCollection 2025 Jan.ABSTRACTBACKGROUND: The timely administration of platelet transfusions is critical for patient survival, and the clinical demand for platelet transfusions has been steadily increasing. However, platelet storage lesions (PSLs) that develop during in vitro preservation exacerbate these shortages. The PSL is significantly influenced by various factors, including temperature, gas composition, and buffering systems. Strategies to mitigate PSLs and improve platelet storage have been actively explored in recent years.OBJECTIVES: This study aimed to investigate whether elevated carbon dioxide (CO2) levels improve platelet quality and functionality during storage.METHODS: Platelet concentrates from 28 donors were stored under control or 3% CO2 conditions at 22 ± 2 °C for up to 7 days. Platelet quality was evaluated through scanning electron microscopy, adhesion, aggregation, clot contraction, activation, apoptosis assays, blood gas, adenosine triphosphate, metabolomics analyses, and in vivo thrombosis and survival tests.RESULTS: Our findings indicate that increasing the CO2 concentration in the storage environment mitigates PSLs and improves platelet quality.CONCLUSION: Our study highlights the potential benefits of utilizing a high CO2 storage environment to improve platelet preservation, offering a promising method to address clinical platelet shortages.PMID:40027443 | PMC:PMC11869954 | DOI:10.1016/j.rpth.2025.102681

Int J Med Sci. 2025 Feb 10;22(5):1124-1137. doi: 10.7150/ijms.104801. eCollection 2025.ABSTRACTBackground: Population aging is increasingly recognized as a major global challenge. Researchers have identified a correlation between aging and immunosenescence, leading to dysfunction of the immune system. As a crucial component of the innate immune system, age-related changes in neutrophils have garnered significant attention from researchers, but the underlying mechanisms remain unclear. This study aims to comprehensively evaluate the senescence status and potential mechanisms of neutrophils, and to identify targets for delaying or even reversing senescence. Methods: Blood routine tests and Luminex Multiplex Cytokine Analysis were employed to assess inflammation levels in mice. Flow cytometry and an agarose chemotaxis model were used to evaluate baseline biological functions and stress responses of neutrophils. Transmission electron microscopy and flow cytometry were utilized to compare mitochondrial ultrastructure and function. Metabolomic analysis was performed to examine metabolic patterns. qPCR, Western blotting, and flow cytometry were used to investigate the potential mechanisms of ceramide intervention on neutrophils. Results: Our findings indicate that aged mice exhibit considerable variability in delayed apoptosis among bone marrow neutrophils, alongside a notable reduction in baseline functionality and stress response capabilities. Metabolomic analysis revealed a marked decrease in ceramide levels within aged neutrophils. In vitro ceramide intervention revitalized neutrophil functionality and partially inhibited delayed apoptosis, facilitating the efficient elimination of senescent neutrophils. The underlying mechanism behind these effects might be attributed to ceramide's modulation of mitochondrial permeability, which in turn influences the activation of the cGAS-STING pathway, as well as its regulatory role in maintaining the equilibrium of pro-apoptotic Bcl-2 protein levels. Conclusions: This investigation proficiently assessed neutrophil senescence in terms of both biological functionalities and intrinsic diversity, while concurrently exploring the feasibility and primary mechanisms through which ceramide intervention impacts neutrophil senescence at the levels of signaling pathways, protein expression, and cellular microarchitecture. These findings provide novel insights into evaluating and potentially intervening in immune senescence, with implications for organismal aging.PMID:40027178 | PMC:PMC11866534 | DOI:10.7150/ijms.104801

Food Chem X. 2025 Jan 25;26:102223. doi: 10.1016/j.fochx.2025.102223. eCollection 2025 Feb.ABSTRACTThere are three types of Daqu produced during the fermentation of Moutai Daqu, which are named as white, yellow and black Daqu. However, in-depth studies for them are lacking. Herein, the high-throughput sequencing and metabolomics techniques were used to analyze the differences in Moutai Daqu. The findings indicated that the predominant microorganisms in yellow and white Daqu were Kroppenstedtia and Bacillus, while Oceanbacillus and Scopulibacillus emerged as the primary microorganisms in black Daqu. Further exploration revealed that white and black Daqu played important roles in the liquefaction and saccharification processes. Besides, the results of metabolomics reveals that yellow and black Daqu exhibit a higher abundance of up-regulated amino acids and fatty acids, which exert a more significant effect on Moutai Baijiu flavor and bioactivity. This study reveals the differences among the three types of Moutai Daqu through comprehensive analysis, which provides technical support for improving the quality of Moutai Daqu.PMID:40027113 | PMC:PMC11872403 | DOI:10.1016/j.fochx.2025.102223

Food Chem X. 2025 Feb 11;26:102230. doi: 10.1016/j.fochx.2025.102230. eCollection 2025 Feb.ABSTRACTKnowledge about the quality of meat obtained from different muscles is crucial for developing high-quality camel meat for commercial use. Metabolomic and proteomic profiles of the longissimus thoracic (LT), semitendinosus (ST), and psoas major (PM) muscles of the bactrian camel, which significantly vary in aspects such as intramuscular fat (IMF) content and shear force, were comprehensively compared to evaluate the impact of these changes on meat quality. Compared with ST and PM muscles, LT muscles had higher IMF content, were more tender, and had a lower shear force. Proteomic analysis unveiled significant differences in metabolic enzymes and binding proteins among different muscles. Based on correlation analysis, 20 key proteins and metabolites closely related to meat quality were screened. Integration of proteomic and metabolomic data highlighted oxidative phosphorylation, TCA cycle, and glycolysis as key distinguishing pathways among different muscles. These results offer effective information for producing high-quality camel meat.PMID:40027112 | PMC:PMC11869849 | DOI:10.1016/j.fochx.2025.102230

Front Cell Dev Biol. 2025 Feb 14;13:1543510. doi: 10.3389/fcell.2025.1543510. eCollection 2025.ABSTRACTINTRODUCTION: Recent research indicated a strong link between the gut microbiota and osteoarthritis. However, the complex interplay between the gut microbiota, serum metabolites, and the progression of osteoarthritis in affected individuals remains largely unexplored. This study aimed to investigate the characteristics of the gut microbiota and serum metabolites in patients with osteoarthritis.METHODS: Participants with either healthy knees or osteoarthritis were enrolled and categorized into healthy control (HC) and osteoarthritis (OA) groups. Fecal and blood samples were collected for 16S rRNA gene sequencing, metabolomic analysis via liquid chromatography-mass spectrometry (LC-MS), and integrated evaluation.RESULTS: The results showed no significant variation in gut microbiota richness and diversity between the two groups. However, the abundance of Bacteroides plebeius and Faecalibacterium prausnitzii was reduced in the OA group, both of which are known for their potential as next-generation probiotics for human health. Metabolomic analysis indicated that serum metabolites, including pyrogallol and 3-hydroxybutyrate (3HB), were significantly lower in the OA group. These metabolites are known to positively impact osteoarthritis progression and other diseases and demonstrated good diagnostic performance for distinguishing osteoarthritis patients from healthy controls. Correlation analysis revealed a positive correlation between Bacteroides plebeius and Faecalibacterium prausnitzii and between pyrogallol and 3HB.DISCUSSION: This study highlighted specific gut microbiota and serum metabolite profiles in osteoarthritis patients, suggesting that the specific changes in bacteria and derived metabolites are closely tied to osteoarthritis progression. This underscores the potential of gut microbiota and serum metabolites as modifiable elements and therapeutic targets for osteoarthritis prevention.PMID:40027098 | PMC:PMC11868077 | DOI:10.3389/fcell.2025.1543510

EClinicalMedicine. 2025 Feb 12;81:103083. doi: 10.1016/j.eclinm.2025.103083. eCollection 2025 Mar.ABSTRACTBACKGROUND: Globally, some 45 million children under five years of age are wasted (low weight-for-height). Although 2023 World Health Organisation guidelines on their care did not aim to identify optimal weight gain, they did mention 5-10 g/kg/day as a target, which is a change from prior guidelines that recommended 10-15 g/kg/day, when inpatient-only care was the norm. We aimed to inform future policy/programming on weight gain targets.METHODS: For this systematic review and meta-analysis, we searched Embase, Global Health and Medline. The final search was on 23/02/2024. Papers were included if they reported weight gain of children aged 6-59 months with severe malnutrition during inpatient (facility-based), outpatient (home-based), and hybrid treatment (initially inpatient and progressing to outpatient treatment). Summary data were extracted, and quality was assessed using a NICE Quality Appraisal Checklist. Our primary outcome was mean rate of weight gain (g/kg/day) during treatment. We conducted random-effects meta-analysis to describe pooled mean weight gain by programme type. Meta-regression investigated potential associations of weight gain with length of stay and programme outcomes. We registered the study on PROSPERO (CRD42023266472).FINDINGS: Our search yielded 3173 papers. We reviewed 321 full texts, identifying 126 eligible papers. Of these, 104 papers, including some 240,650 participants, reported weight gain as g/kg/day and were eligible for meta-analysis. Mean rate of weight gain was 8.8 g/kg/day (95% CI: 7.6, 9.9; I2 = 97.8%) across 18 inpatient programmes, 3.4 g/kg/day (95% CI: 2.0, 4.7; I2 = 99.4%) across 12 hybrid programmes, and 3.9 g/kg/day (95% CI: 3.4, 4.4; I2 = 99.7%) across 60 outpatient programmes. We found inconsistent evidence of an association between slower weight gain and higher mortality: there was weak evidence of association after adjusting for programme type (coefficient = -0.4; 95% CI: -0.7, -0.02; p = 0.04; n = 118 programmes). There was high heterogeneity between studies. Details of weight gain calculation methods varied. We found no evidence for publication bias when accounting for programme type (Egger's test p-value = 0.2).INTERPRETATION: Weight gain in outpatient programmes was markedly slower than in inpatient treatment. Clearer reporting of weight gain and a better understanding of the sequelae of faster/slower recovery is important to set future weight gain targets. Our results set an important baseline for current programmes to benchmark against.FUNDING: Medical Research Council/Global Challenges Research Fund, grant number: MR/V000802/1.PMID:40026833 | PMC:PMC11872456 | DOI:10.1016/j.eclinm.2025.103083

Int J Gen Med. 2025 Feb 25;18:1007-1022. doi: 10.2147/IJGM.S509592. eCollection 2025.ABSTRACTPURPOSE: To explore the mechanism of Zhuyang Tongbian Decoction (ZTD) in treating functional constipation (FC) by observing its effects on intestinal flora composition, the metabolic function of gut microbiota, fecal short-chain fatty acid (SCFA) levels, and serum concentrations of TLR4, NF-κB, TNF-α, and IL-6 in patients with FC.PATIENTS AND METHODS: 40 patients with FC were randomly divided into the control group and the treatment group, 20 cases in each group. And 20 healthy volunteers were recruited during the same period. The control group was administered lactulose, while the treatment group was treated with ZTD. 16s RNA sequencing technology was used to compare the changes in the structure and diversity of the intestinal flora of patients before and after treatment. Changes in the levels of SCFAs in faeces and the levels of TLR4, NF-κB, TNF-α and IL-6 in serum were analysed. Metagenomics sequencing assessed microbiota metabolic functions.RESULTS: The treatment group showed a significant increase in the relative abundance of beneficial bacteria, including Bifidobacterium, Lactobacillus, and Faecalibacterium_prausnitzii (P < 0.05), whereas Desulfobacterota and Ruminococcus were significantly reduced (P < 0.05). Notably, fecal acetic and propionic acid levels were significantly higher in the treatment group (P < 0.05). Serum biomarkers TLR4, NF-κB, TNF-α, and IL-6 decreased significantly (P < 0.05). Metagenomics sequencing showed that Carbohydrate metabolism, Metabolism of cofactors and vitamins, and C5- Branched dibasic acid metabolism were significantly increased in functional abundance (P < 0.05).CONCLUSION: ZTD notably improves intestinal flora composition and gut microbiota metabolic function, regulates SCFA levels, and reduces inflammation markers in FC patients. The strain Faecalibacterium_prausnitzii shows significant potential in regulation of intestinal inflammation and may play a crucial role in the treatment efficacy of ZTD for FC.PMID:40026814 | PMC:PMC11871934 | DOI:10.2147/IJGM.S509592