PubMed

Curr Allergy Asthma Rep. 2025 May 9;25(1):24. doi: 10.1007/s11882-025-01198-6.ABSTRACTPURPOSE OF REVIEW: The aim of our review is to summarize the available literature where metabolomics was used in studies on childhood asthma, and to find metabolites that are diagnostic biomarker candidates in childhood asthma. Moreover, the review also describes studies related to metabo-endotypes and heterogeneity of childhood asthma, severity of the disease, and response to drug treatment.RECENT FINDINGS: Metabolomics has opened up new perspectives in childhood asthma investigation. Based on the available literature, we found nine metabolites that demonstrated the highest diagnostic potential for differentiation between children with asthma and healthy controls: adenine, adenosine, benzoic acid, hypoxanthine, p-cresol, taurocholate, threonine, tyrosine, and 1-methyl nicotinamide. Many of the identified metabolites are closely associated with inflammatory processes responsible for asthma. Metabolomic analysis also contributed to characterizing new asthma endotypes highlighting the heterogeneity of pediatric asthma. Metabolomics can bring about valuable insights, which, when integrated with other omic disciplines, can facilitate the diagnosis and management of childhood asthma and the search for new biomarkers of the disease. Improvements in the detection of asthma in preschool children, including asthma endotypes, will ease application of proper treatment and enable elimination of unnecessary test treatment of corticosteroids in young patients.PMID:40341431 | DOI:10.1007/s11882-025-01198-6

Int J Oncol. 2025 Jun;66(6):45. doi: 10.3892/ijo.2025.5751. Epub 2025 May 9.ABSTRACTOxaliplatin (OXA) is a first‑line chemotherapy agent for hepatocellular carcinoma (HCC); however, its application is hindered by low therapeutic sensitivity and severe adverse effects. Acteoside (ACT) has both antitumor and hepatoprotective properties. Therefore, the present study investigated the mechanisms underlying the synergistic and toxicity‑reducing effects of ACT as an adjuvant to OXA in HCC therapy. Liver cancer cell lines and a xenograft mouse model were treated with ACT and/or OXA. In vitro Cell Counting kit‑8, Transwell invasive assay, wound healing assay, cell cycle and apoptosis detection assays assessed cell viability, migration, invasion, cell cycle progression and apoptosis to evaluate the synergistic effects of the combination therapy. In vivo studies examined tumor growth, cell proliferation, survival time and blood biochemical indices. The effects of ACT on OXA‑induced toxicity were also evaluated. Transcriptomics and metabolomics analyses were integrated to elucidate the mechanisms by which ACT enhances OXA efficacy and mitigates its toxicities. The results revealed that ACT synergized with OXA to inhibit HCC progression both in vivo and in vitro. ACT significantly alleviated OXA‑induced toxicity, particularly neurotoxicity. Mechanistically, phosphatidylinositol signaling system‑associated genes/proteins exerted important roles in the anti‑HCC effects of ACT. Western blotting revealed that ACT‑induced upregulation of INPP4B inhibited the PI3K/AKT signaling pathway, which may underlie its ability to enhance the therapeutic efficacy of OXA and reduce its toxic effects. In conclusion, ACT enhanced efficacy and reduced the toxicity of OXA in the treatment of HCC, potentially via the regulation of INPP4B to inhibit the PI3K/AKT signaling pathway.PMID:40341416 | DOI:10.3892/ijo.2025.5751

Food Funct. 2025 May 9. doi: 10.1039/d5fo00384a. Online ahead of print.ABSTRACTThe increasing incidence and associated metabolic complications pose major challenges in the treatment of hyperlipidaemia. Cinnamon is a food and medicinal resource associated with lipid metabolism, but the mechanism by which its active components, cinnamic acid (CA) and cinnamaldehyde (CM), alleviate hyperlipidaemia remains unclear. Biochemical, pathological, gut microbiota, and metabolomic analyses were performed to investigate the effects of CA and CM on HFD-fed mice and the underlying mechanisms involved. Supplementation with CA and CM reduced body weight, liver, and adipose tissue accumulation in HFD-induced mice; improved glucose and lipid metabolism; and decreased inflammation and oxidative stress levels, with CM showing superior efficacy. Faecal microbiota transplantation confirmed that the therapeutic effect was closely related to core gut bacteria and metabolites. Specifically, CA and CM inhibited the growth of lipid metabolism-related genera (e.g., Turicibacter and Romboutsia) and metabolites (e.g., PC, LysoPCs, prostaglandin E2, and arachidonic acid) while promoting the growth of beneficial genera (e.g., Oscillospiraceae and Colidextribacter) and metabolites (e.g., linoleic acid, phytosphingosine, and stercobilin). Additionally, Spearman's correlation analysis revealed that serum and hepatic lipids, as well as inflammatory factors, were positively correlated with Erysipelatoclostridium, Turicibacter, Eubacterium fissicatena, Enterorhabdus, cervonoyl ethanolamide, and acetoxystachybotrydial acetate, whereas they were negatively correlated with Lachnospiraceae NK4A136, stercobilin, LysoPE (15:0/0:0), and phytosphingosine. In contrast, hepatic oxidative stress markers exhibited the opposite correlation pattern. In conclusion, CA and CM have the potential to regulate the core gut microbiota and metabolites to improve lipid metabolism and decrease related inflammation and oxidative stress levels.PMID:40341264 | DOI:10.1039/d5fo00384a

Nat Cancer. 2025 May 8. doi: 10.1038/s43018-025-00946-x. Online ahead of print.ABSTRACTCell therapy with tumor-infiltrating lymphocytes (TILs) has yielded durable responses for multiple cancer types, but the causes of therapeutic resistance remain largely unknown. Here multidimensional analysis was performed on time-serial tumor and blood in a lung cancer TIL therapy trial. Using T cell receptor sequencing on both functionally expanded T cells and neoantigen-loaded tetramer-sorted T cells, we identified tumor antigen-specific T cell receptors. We then mapped clones into individual transcriptomes and found that tumor-reactive clonotypes expressed a dysfunctional program and lacked stem-like features among patients who lacked clinical benefit. Tracking tumor-reactive clonotypes over time, decay of antigen-reactive peripheral T cell clonotypes was associated with the emergence of progressive disease. Further, subclonal neoantigens previously targeted by infused T cells were subsequently absent within tumors at progression, suggesting potential adaptive resistance. Our findings suggest that targeting clonal antigens and circumventing dysfunctional states may be important for conferring clinical responses to TIL therapy.PMID:40341231 | DOI:10.1038/s43018-025-00946-x

Sci Rep. 2025 May 8;15(1):16140. doi: 10.1038/s41598-025-01020-3.ABSTRACTBiogenic synthesized cobalt nanoparticles (NPs), dose optimization toxicity, and metabolic studies of Zea mays are very important before their application in the field. Here, we investigate the morphological, biochemical, and metabolic response of summer maize (Zea mays) against bulk cobalt chloride and Withania-assisted bioengineered cobalt NPs. It was found that cobalt chloride as bulk and concentration of 100 mg/L NPs inhibits growth via significant changes their metabolic and biochemical molecules. While biogenic assisted with Withania, cobalt NPs with concentrations of 50 and 100 mg/L have shown a significant increase in shoot length by 15% and 9% respectively. Root length was found to be decreased at 25 mg/L and 50 mg/L as compared to control. Fresh and dry weight was found to be increased at 25 mg/L and 50 mg/L. However, chlorophyll contents seemed to decline at 25 mg/L and increased at 50 mg/L. Carbohydrate content was found to be decreased at 50 mg/L and 25 mg/L by 76% and 70% respectively. Starch content was found to be increased at 25 mg/L and 50 mg/L by 28% and 33% respectively. Nitrate content was found to be decreased at 50 mg/L by 17%. However, higher tested concentrations showed a very much decrease in these compounds. Results displayed that a small quantity of cobalt oxide nanoparticles had a stimulatory impact on the seedling development while a higher quantity encouraged an inhibitory effect. 100 mg/L also showed an increase in activities when comparison was done against control. At 25 mg/L all activities were found to be maximum. This increased level suggests that the congregation of these secondary metabolites generates an oxidative response in plants when exposed to Cobalt oxide nanoparticles and cobalt chloride. However, further mechanistic research should be adopted as our experimental findings ruled out the generalized phytotoxicity of plants.PMID:40341178 | DOI:10.1038/s41598-025-01020-3

JMIR Res Protoc. 2025 May 8;14:e67570. doi: 10.2196/67570.ABSTRACTBACKGROUND: Weight loss is a cornerstone of obesity treatment and diabetes mellitus type 2 (T2D) prevention, but its implementation in clinical practice is limited by its perceived burden and variability in response. Personalizing interventions to increase their success rate is an unmet clinical need.OBJECTIVE: Identification of predictive factors associated with successful weight loss after sequential exercise in women with obesity.METHODS: The study will consist of a 2-stage analytical approach, including a predictive validation study and a 2:1 randomized cross-over controlled trial. Women aged 25-45 years with obesity (BMI>30) will be included in the study. The intervention will consist of a progressive protocol of aerobic exercise on a treadmill and a bicycle ergometer. We will measure weight loss in terms of fat mass (FM) and fat-free mass (FFM), metabolic flexibility (MetFlex) as ΔRQ (change in respiratory quotient (VCO2/VO2) between basal and insulin-stimulated state during glucose clamp), insulin sensitivity, glucose tolerance, hemoglobin A1c, microbiome composition, and metabolomic signatures.RESULTS: Recruitment for the trial began in January 2024. A total of 12 participants were enrolled and randomized. Among them 6 participants have completed the first phase of the A-arm and 6 participants have completed the control period of the B-arm and their intervention is ongoing. Recruitment is ongoing. We expect the preliminary data from this study to be completed in 2026.CONCLUSIONS: This intervention will investigate whether whole body and gut MetFlex can be further explored and used as ex ante predictors of successful weight loss following exercise intervention, providing proof of concept and paving the way for personalized lifestyle interventions.TRIAL REGISTRATION: ClinicalTrials.gov NCT06329349; https://clinicaltrials.gov/study/NCT06329349.INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/67570.PMID:40340957 | DOI:10.2196/67570

BMC Psychiatry. 2025 May 8;25(1):467. doi: 10.1186/s12888-025-06802-7.ABSTRACTBACKGROUND: Antipsychotic medications are crucial for alleviating symptoms of schizophrenia (SCZ). However, treatment responses vary across individuals, and few reliable biomarkers currently exist to predict the clinical outcome. Therefore, we aim to identify potential lipid markers for treatment outcomes in patients with first-episode SCZ.METHODS: Pre-treatment serum samples were obtained from 95 participants who underwent an 8-week treatment regimen with antipsychotic drugs. Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to acquire serum lipidomic profiles, correlating them with treatment responses at 8 weeks to identify potential lipid signatures. The antipsychotic treatment response was quantified using the percentage change on the Positive and Negative Syndrome Scale (PANSS) scale.RESULTS: By combining LASSO regression and Random Forest regression, we identified 8 positively associated and 2 negatively associated baseline lipids related to the PANSS reduction rate. In the further analysis of logistic regression, we identified three candidate lipids, PC (18:2e_19:0), PE (53:7), and TG (16:2e_19:0_20:5), which could together distinguish poor and good responders, with an AUC of 0.805 (95% CI, 0.715-0.894).CONCLUSIONS: Our findings suggest that this set of lipid biomarkers may have the potential to predict the outcome of antipsychotic drug treatment. Further validation and larger studies are needed to evaluate their potential for clinical applications.CLINICAL TRIAL NUMBER: Not applicable.PMID:40340899 | DOI:10.1186/s12888-025-06802-7

BMC Genomics. 2025 May 8;26(1):456. doi: 10.1186/s12864-025-11618-6.ABSTRACTBACKGROUND: Asian water buffaloes (Bubalus bubalis) in the Yangtze River Basin of China are the important meat provider for local residents because of its outstanding body size. Several previous studies have highlighted their genetic basis of growth characteristics, but the crucial genes regulating growth traits via multi-layer omics are still rarely investigated.RESULTS: We conducted a comprehensive multi-omics analysis integrating blood and muscle transcriptome, plasma metabolome, rumen fluid metagenome, and genome of Haizi water buffaloes. Of note, ribosomal protein L26 (RPL26) located in the evolutionary selection regions associated with body sizes is the top differentially expressed gene (DEG) in both blood and muscle tissues. Further metabolomics and metagenomics identified growth-related molecular biomarkers (myristicin and Bacteroidales) and microbiological composition (Bacteroides and Prevotella). Leveraging cattle quantitative trait loci (QTLs) and genotype-tissue expression (CattleGTEx) databases, we found the significant correlations of QTL_180979 on RPL26 and two identified cis-eQTLs in muscle tissue in the upstream of RPL26 with weight gain. The follow-up cell assay validations confirmed the regulation roles of RPL26 in cell cycle, apoptosis, and differentiation, where the low RPL26 expressions enhanced the antiapoptotic ability and promoted the differentiation of myoblasts into myotubes markedly.CONCLUSIONS: Our study illustrates RPL26 roles in regulating growth traits via both integrated multi-omics analysis and functional validations that suggests the further applications of RPL26 for growth trait selection of water buffaloes.PMID:40340823 | DOI:10.1186/s12864-025-11618-6

J Headache Pain. 2025 May 8;26(1):108. doi: 10.1186/s10194-025-02024-0.ABSTRACTBACKGROUND: Trigeminal activation and sensitisation involved in chronic inflammatory orofacial pain share several similarities with headaches, including migraine. Therefore, understanding the pathophysiological mechanisms is important to determine novel therapies, in which animal models are crucial. Here we aimed to identify key mediators, mechanisms and networks using unbiased multi-omic approaches in a rat orofacial inflammatory pain model.METHODS: Complete Freund's Adjuvant (CFA, 50 µl, 1 mg/mL) was injected into the right whisker pad of male Wistar rats (n = 5-11/group), mechanonociceptive threshold was measured by von Frey filaments. Plasma concentrations of metabolites were measured both by targeted (MxP Quant 500 kit) and untargeted mass spectrometry methods on day 3 when maximal facial allodynia developed. Next-generation sequencing of the trigeminal ganglia (TG) was performed, furthermore, transcriptomic and plasma metabolomic data were analysed together.RESULTS: Plasma carnosine, serotonin and fatty acid levels significantly increased, while tryptophan, kynurenine, tyrosine, phenylalanine, asparagine, glycerolipids, and sphingolipids decreased in response to orofacial inflammation. CFA upregulated the Cxcr3 chemokine receptor and downregulated GNRHR in the TG. Bioinformatic analysis revealed altered amino acid metabolism and fatty acid beta-oxidation involved in mitochondrial energy production, neuroinflammation and immune responses.CONCLUSIONS: Integrated joint pathway analysis of metabolomic and transcriptomic data provides a useful approach to determine pathophysiological mechanisms of trigeminal sensitization and identify novel drug targets for orofacial pain and headaches.PMID:40340645 | DOI:10.1186/s10194-025-02024-0

BMC Genomics. 2025 May 8;26(1):457. doi: 10.1186/s12864-025-11650-6.ABSTRACTBACKGROUND: Fat metabolism plays an important role in animal health and economic benefits. However, the changes in gene expression and metabolites during fat metabolism have not been systematically studied in bovine.RESULTS: This study integrates transcriptomic and metabolomic strategies to delineate the metabolic and gene expression profiles during the adipogenesis of bovine preadipocytes in four different stages. Totally, we identified 328 differentially expressed metabolites (DEMs) and 5257 differentially expressed genes (DEGs) during adipogenesis. Functional enrichment of both DEMs and DEGs highlighted the important roles of fatty acid metabolic pathways. By integrating transcriptomic and metabolomic data, we identified key genes potentially regulating fatty acid metabolism, including FADS2, ACOT7 and ACOT2. We further applied comparison for the functional differences between two FADS2 isoforms (FADS2-T0 and FADS2-T2). The results proved that the lipid metabolism regulated by FADS2-2 has changed due to the loss of 46 amino acids with a transmembrane domain, which finally altering its promoting effect on bovine fat deposition.CONCLUSIONS: In summary, our research provides important resources and key candidate genes for a systematic understanding of the changes in gene expression and lipid metabolism during the process of fat deposition.PMID:40340639 | DOI:10.1186/s12864-025-11650-6

Gut Microbes. 2025 Dec;17(1):2502138. doi: 10.1080/19490976.2025.2502138. Epub 2025 May 8.ABSTRACTColorectal cancer (CRC) is one of the most prevalent cancers worldwide, with high incidence and mortality rates. An increasing body of research suggests that obesity is a significant risk factor for the development of CRC. Moreover, recent findings have highlighted the close association between the gut microbiota and both obesity and CRC. Despite this, the specific mechanisms by which the gut microbiota influences obesity and CRC remain unclear. This study aims to explore the role of the gut bacterium Fusobacterium mortiferum and its metabolite 5-aminovaleric acid (5-AVA) in the development of obesity and CRC. Our study found that the metabolite 5-aminovaleric acid produced by Fusobacterium mortiferum significantly inhibits the expression of the tumor suppressor DKK2. This inhibition leads to enhanced proliferation of CRC cells. Furthermore, we discovered that Fusobacterium mortiferum and 5-AVA can activate the Wnt/β-catenin signaling pathway by inhibiting DKK2, thereby promoting tumor growth. This finding was validated in CRC mouse models and in vitro experiments. Additional mechanistic studies revealed that 5-AVA interacts with the demethylase KDM6B, affecting the demethylation process of DKK2 and subsequently activating the Wnt/β-catenin signaling pathway. Our study retrospectively collected fecal samples from patients who underwent gastrointestinal endoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University over the past five years. Participants were stratified into a healthy control group and an adenoma group based on the outcomes of their colonoscopies. Following this, we conducted metagenomic analysis to identify differential bacteria, and based on the results, we performed bacterial cultivation and metabolomic profiling. The roles of the targeted bacteria and their metabolites were further validated through animal models and cellular assays, employing techniques such as Western Blot, qPCR, immunohistochemistry, molecular docking simulations, and gene overexpression studies. This study uncovers the potential carcinogenic effects of Fusobacterium mortiferum and 5-AVA in the development of obesity and CRC. Our research emphasizes the complex interplay between the gut microbiota and host metabolism and suggests new directions for future research to explore how modulation of the gut microbiota could prevent and treat CRC.PMID:40340623 | DOI:10.1080/19490976.2025.2502138

BMC Cancer. 2025 May 8;25(1):844. doi: 10.1186/s12885-025-14253-2.ABSTRACTBACKGROUND: Increasing pulmonary nodule presentations in lung adenocarcinoma patients reveal diagnostic limitations of CT-based invasiveness assessment. The critical unmet need lies in developing non-invasive biomarkers differentiating invasive adenocarcinoma from premalignant lesions and benign nodules, while characterizing metabolic trajectory from health to metastatic disease.METHODS: Untargeted metabolomics analyzed plasma samples from 102 subjects stratified into four cohorts: confirmed adenocarcinoma (n = 35), benign nodules (n = 22), precursor lesions (n = 24), and healthy controls (n = 21). Multivariate analysis identified discriminative metabolites for constructing an infiltration prediction model.RESULTS: Three diagnostic groups exhibited distinct metabolic profiles. Hexaethylene glycol, tetraethylene glycol, and Met-Thr showed stage-dependent concentration gradients. Progressive malignancy correlated with elevated levels of 41 metabolites. An eight-metabolite panel achieved AUC 0.933 (0.873-0.994) in distinguishing precursors from early malignancies, sustained through internal validation (AUC 0.934, 0.905-0.966).CONCLUSIONS: Met-Thr depletion inversely correlates with malignancy progression, while eight-metabolite signatures demonstrate diagnostic potential for preoperative infiltration assessment in nodular adenocarcinoma.PMID:40340585 | DOI:10.1186/s12885-025-14253-2

Ann Med. 2025 Dec;57(1):2499700. doi: 10.1080/07853890.2025.2499700. Epub 2025 May 8.ABSTRACTBACKGROUND: Xanthoceras sorbifolia Bunge oil (XSBO) has garnered significant interest from researchers due to its distinctive anti-Alzheimer's disease (AD) properties. However, the underlying molecular mechanism remain unclear. This study aims to investigate the potential mechanisms by which XSBO may exert therapeutic effects on AD by employing a combination of network pharmacology analysis and experimental validation.METHODS: The chemical composition and absorbed compounds of XSBO were identified using GC-MS and LC-MS. Network pharmacology analysis was performed using various computational tools to identify hub genes and construct compound-target-pathway networks. Subsequently, both in vitro and in vivo experiments were conducted to confirm the mechanisms by which XSBO may treat AD.RESULTS: The results identified 43 active compounds in XSBO, targeting a total of 223 genes, of which 191 were associated with AD. Network analysis indicated that the active constituents in XSBO, such as 9,12-octadecadienoic acid, linoelaidic acid and 11-octadecenoic acid, interact with targets including MAPK1, MAPK3, AKT1, RXRA, RXRB, PPARD and PPARA to modulate inflammation-related signalling pathways and the sphingolipid signalling pathway. In vitro investigations corroborated that XSBO can significantly influence the viability of Aβ25-35-induced SH-SY5Y cells via the MAPK pathway.CONCLUSIONS: This study demonstrated that XSBO has the potential to mitigate inflammation network disorders through the MAPK pathway and to restore sphingolipid metabolite levels in AD rats, thereby laying a groundwork for future studies.PMID:40340504 | DOI:10.1080/07853890.2025.2499700

mSphere. 2025 May 9:e0059024. doi: 10.1128/msphere.00590-24. Online ahead of print.ABSTRACTPatients with Parkinson's disease (PD) with probable rapid eye movement sleep behavior disorder (RBD) (PD-RBD), a specific subtype of PD, are characterized by the presence of more severe motor and non-motor symptoms. This study aimed to elucidate the characteristics and interactions of gut microbiota and plasma metabolic characteristics of PD-RBD, thus screening for the disease mechanisms. A total of 100 PD patients, 50 healthy controls (HCs) and 16 probable idiopathic RBD (iRBD) patients were collected. There were 33 PD-RBD and 67 patients without probable RBD (PD-nRBD) in PD patients. DNA extraction, PCR amplification, and high-throughput sequencing were used for intestinal microbiota analysis, and ultra-high liquid chromatography tandem mass spectrometry was used for metabolome analysis. Spearman analysis was applied to investigate the correlation of fecal microbiota and plasma metabolome. Our findings revealed Lactobacillaceae (P = 0.017), Christensenellaceae (P = 0.017), Fusobacteriaceae (P = 0.018), Lactobacillus (P = 0.035), Christensenellaceae R-7 group (P = 0.035), and Fusobacterium (P = 0.035) were significantly different in PD-RBD, PD-nRBD, and HC. Moreover, the differential metabolites identified in both PD-nRBD and PD-RBD were 3-hydroxy-2-methylpyridine-4,5-dicarboxylate (VIP = 5.802) and 3-methoxy-4-hydroxyphenylglycol sulfate (VIP = 5.732). Furthermore, our analysis revealed that 3-methoxy-4-hydroxyphenylglycol sulfate showed a positive correlation with Lactobacillus (r = 0.197, P = 0.049). Finally, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. We managed to show that the differential microbiota, differential metabolites, and their interactions in PD-RBD compared to PD-nRBD and HC. This furthers our understanding of disease pathogenesis, and offers fresh perspectives on its detection and treatment.IMPORTANCE: There are currently fewer investigations on the intestinal microbiota and metabolites of probable rapid eye movement sleep behavior disorder (PD-RBD) and idiopathic RBD (iRBD). Our findings indicate that PD-RBD exhibits an increase in Christensenellaceae and 3-methoxy-4-hydroxyphenethyleneglycol sulfate, and that iRBD exhibits a similar trend. This suggests that the PD prodromal stage may have seen this alteration. Furthermore, functional analysis indicated that these distinctive microbiota and metabolites were primarily associated with phenylalanine metabolism and vitamin B6 metabolism. Basic experiments and multi-center, large-cohort clinical researches are worth conducting to confirm this, since they may offer insights for treating individuals with PD-RBD.PMID:40340433 | DOI:10.1128/msphere.00590-24

J Am Soc Mass Spectrom. 2025 May 9. doi: 10.1021/jasms.5c00009. Online ahead of print.ABSTRACTEarly recognition of septic shock is crucial for improving clinical management and patient outcomes, especially in the emergency department (ED). This study conducted serum metabolomic profiling on ED patients diagnosed with septic shock (n = 32) and those without septic shock (n = 92) using a high-resolution mass spectrometer. By implementing a supervised machine learning algorithm, a prediction model based on a panel of metabolites achieved an accuracy of 87.8%. Notably, when employed on a low-resolution instrument, the model maintained its predictive performance with an accuracy of 84.2%. These results demonstrate the potential of metabolite-based algorithms to identify patients at high risk of septic shock. Our proposed workflow aims to optimize risk assessment and streamline clinical management processes in the ED, holding promise as an efficient routine test to promote timely intensive interventions and reduce septic shock mortality.PMID:40340384 | DOI:10.1021/jasms.5c00009

Mol Ther. 2025 May 7:S1525-0016(25)00374-0. doi: 10.1016/j.ymthe.2025.05.004. Online ahead of print.ABSTRACTThis study aims to investigate key microscopic regions involved in colorectal cancer liver metastasis (CRLM), focusing on the crucial role of cancer-associated fibroblasts (CAFs) in promoting tumor progression and providing molecular and metabolism-level insights for its diagnosis and treatment using multi-omics. We followed 12 fresh surgical samples from 2 untreated CRLM patients. Among these, 4 samples were used for spatial transcriptomics (ST), 4 for spatial metabolomics, and 4 for single-cell RNA sequencing (scRNA-seq). Additionally, 92 frozen tissue samples from 40 patients were collected. 7 patients were used for immunofluorescence and RT-qPCR, while 33 patients were used for untargeted metabolomics. ST revealed that the spatial regions of CRLM consists of 7 major components, with fibroblast-dominated regions being the most prominent. These regions are characterized by diverse cell-cell interactions and immunosuppressive, and tumor growth-promoting environments. scRNA-seq identified that SPP1+ fibroblasts interact with CD44+ tumor cells, as confirmed through immunofluorescence. Spatial metabolomics revealed suberic acid and tetraethylene glycol as specific metabolic components of this structure, which was further validated by untargeted metabolomics. In conclusion, a SPP1+fibroblast-rich spatial region with metabolic reprogramming capabilities and immunosuppressive properties was identified in CRLM, which potentially facilitates metastatic outgrowth through interactions with tumor cells.PMID:40340245 | DOI:10.1016/j.ymthe.2025.05.004

Atherosclerosis. 2025 May 5:119218. doi: 10.1016/j.atherosclerosis.2025.119218. Online ahead of print.ABSTRACTThere is striking evidence that a high lipoprotein(a) [Lp(a)] concentration is a strong, independent, and causal cardiovascular risk factor. However, Lp(a) testing rates are very low (1 %-2 %) despite the fact that 1 in 5 individuals have elevated Lp(a) concentrations. The Brussels International Declaration on Lp(a) Testing and Management was co-created by the Lp(a) International Task Force and global leaders at the Lp(a) Global Summit, held in Brussels, Belgium, on March 24-25, 2025. The event, organized by FH Europe Foundation, brought together scientific experts, people with the lived experience of elevated Lp(a) and policy makers from the European Institutions and World Health Organization. The World Heart Federation, Global Heart Hub, and European Alliance for Cardiovascular Health and scientific organizations such as European Atherosclerosis Society, and International Atherosclerosis Society were formal partners. The Summit was hosted by a Member of the European Parliament, Romana Jerković, and held under the patronage of the Polish presidency of the Council of the European Union. The Declaration calls for 1) integration of Lp(a) testing and management into Global, European and National Cardiovascular Health Plans; 2) appropriate investment, policy and programmes in targeting Lp(a) testing and management based on a recent study demonstrating the substantial overall cost-saving to health systems across the globe; 3) political commitment to mandate systematic Lp(a) testing at least once during a person's lifetime, ideally at an early age, with full reimbursement; 4) incorporation of Lp(a) test results in the context of a person's cardiovascular risk assessment, with development of personalised cardiovascular health roadmaps as needed, without fear of discrimination; 5) investment in public and healthcare professional education to increase awareness of Lp(a) and its impact on cardiovascular health.PMID:40340180 | DOI:10.1016/j.atherosclerosis.2025.119218

Int J Biol Macromol. 2025 May 6:143981. doi: 10.1016/j.ijbiomac.2025.143981. Online ahead of print.ABSTRACTThis study explored the immunomodulatory effects of Rehmanniae Radix Praeparata polysaccharides (RP) on LPS-induced immune activation. RP, characterized as a heteropolysaccharide (6.34 kDa and 4.63 kDa) rich in galactose and glucose, was administered to LPS-challenged BALB/c mice at 25 mg/kg and 50 mg/kg doses. Results showed RP significantly reduced pro-inflammatory cytokines (TNF-α, IL-6), lowered oxidative stress (MDA), and boosted antioxidant enzymes (SOD, GSH-Px). It restored splenic structure, mitigated apoptosis, and suppressed the TNF-α/NF-κB/IL-6 pathway. Metabolomics linked RP to sphingolipid metabolism, while gut microbiota analysis revealed increased beneficial bacteria and elevated SCFAs. Transcriptomics confirmed RP's immune regulation via TNF signaling. These findings demonstrate RP's potential in alleviating immune overactivation by modulating inflammation, gut microbiota, and SCFA production, suggesting therapeutic promise for immune-related diseases.PMID:40339850 | DOI:10.1016/j.ijbiomac.2025.143981

J Affect Disord. 2025 May 6:S0165-0327(25)00761-X. doi: 10.1016/j.jad.2025.05.005. Online ahead of print.ABSTRACTBACKGROUND: Depression is a complex and prevalent mental disorder. Numerous studies have reported there were significant metabolomic and proteomic changes in hippocampus of depressed patients. However, few researches have systematically integrated these two omics data to identify key molecular mechanisms underlying depression.METHODS: Based on the data of Protein and Metabolite Network of Depression Database (ProMENDA), we integrate the significantly altered metabolites and proteins of hippocampus in animal models of depression. Pathway analysis was performed using IPA software to explore biological functional disturbance underlying these molecules. Finally, animal model construction, molecular biology experiments, and lentiviral transfection in vitro for gene knockout were performed to verify potential pathways.RESULTS: A total of 682 altered metabolites and 2300 altered proteins were retrieved. Pathway enrichment analysis identified 394 significantly enriched pathways, with the sirtuin signaling mediated authophagy being of particular interest. Further biological validations revealed the decrease of Sirt1, the autophagy-related genes, and autophagy markers in hippocampus of both mouse and Macaca fascicularis models of depression. Lastly, Sirt1 knockdown in primary neurons inhibited autophagy.CONCLUSION: This study expanded our understanding of multi-omics alterations in the hippocampus of depression by revealing that Sirt1 may mediate neuronal autophagy in the hippocampus of animal models of depression, which could further contribute to the pathophysiology of depression.PMID:40339719 | DOI:10.1016/j.jad.2025.05.005

Appetite. 2025 May 6:108048. doi: 10.1016/j.appet.2025.108048. Online ahead of print.ABSTRACTThere is a growing interest in the characterization of eating behavior traits that impact an individual's nutritional status and susceptibility to developing diet-related chronic diseases. This report explored the relationship of cognitive restraint (CR), disinhibition (DI), and hunger (H) with food preference, motivations of food choice, and dietary intake in adults with specific attention to potential sex differences among relationships. Eating behavior was measured in 329 adults from the USDA Nutritional Phenotyping Study using validated questionnaires, and dietary intakes were measured by 24-hour diet recalls. CR was positively associated with food choices motivated by weight control, while DI was negatively associated with relative preference and implicit wanting of high-fat, sweet foods (HFSw). Using cluster analysis, the variance in clusters that encompassed vegetable intake and diet quality scores for males were explained by BMI, total body fat, age, and eating behaviors such as CR, H, wanting of HFSw, and food choice motivations related to health, natural content of foods and weight concerns. In female participants, the variance in vegetable intake and diet quality were explained by age, BMI, body composition, and food choice motivations related to health, natural content, as well as price and convenience. Our data suggests the associations between eating behavior traits, food preference, food choice motivators, and dietary intake/quality differ between males and females. Understanding these sex-specific relationship can aid clinicians in developing targeted strategies for counseling clients towards more healthful dietary patterns.PMID:40339649 | DOI:10.1016/j.appet.2025.108048