PubMed

Metabolomics. 2025 Mar 27;21(2):44. doi: 10.1007/s11306-025-02246-y.ABSTRACTINTRODUCTION: The suboptimal function of transplanted kidney can lead to imbalances in processes controlled by the kidneys, necessitating long-term monitoring of the graft's function and viability. Given the kidneys' high metabolic activity, a metabolomics approach is well-suited for tracking changes in post-transplant patients and holds significant potential for monitoring graft function.OBJECTIVES: Examination of the response of urinary creatinine levels to (i) serum creatinine levels and (ii) allograft function during periods of impaired kidney function in post-transplant patients.METHODS: We analyzed morning and 24-h urine samples from 55 patients who underwent primary kidney transplantation and were uniformly treated with immunosuppressants, with an average follow-up of 50 months post-surgery. We assessed the relative levels of urinary metabolites detectable by NMR spectroscopy and investigated correlations between these metabolite levels and renal function.RESULTS: We observed rather unexpected independence of urinary creatinine levels on levels of serum creatinine as well as on allograft function expressed by eGFR (estimated glomerular filtration rate). This observation allowed a very good agreement of outcomes from raw and creatinine-normalized data, consistent for both morning urine samples and 24-h urine collections. The urinary levels of citrate and acetone were detected to be sensitive to allograft function, and the urinary levels of metabolites in combination showed promising prediction for kidney function, on the level of p-value: for 24 h pooled urine: 4.6 × 10-12 and morning urine: 5.36 × 10-9. We discussed the data also in the light of metabolic changes in blood plasma.CONCLUSION: We support the opinion of critical assessment of renal creatinine clearance when judging the filtration function of the allograft. As the next, urinary metabolomics can serve as an easily available supplement to prediction for allograft function in patients after kidney transplantation.PMID:40146357 | DOI:10.1007/s11306-025-02246-y

Food Funct. 2025 Mar 27. doi: 10.1039/d4fo04761c. Online ahead of print.ABSTRACTMaternal diets during pregnancy and lactation are critical determinants that regulate the metabolic homeostasis in offspring. Our previous research demonstrated that maternal genistein (GEN) intervention ameliorated the dysregulation of glucolipid metabolism induced by intrauterine overnutrition in adult offspring, accompanied by changes in the composition of gut microbiota; however, the underlying mechanisms remain unclear. Here, we used a maternal overnutrition model induced by excess energy intake before and throughout pregnancy and lactation, with maternal GEN administered during the same period. The female offspring were raised on a standard chow diet until sacrificed at 24 weeks. The mRNA levels of browning markers were quantified in inguinal subcutaneous adipose tissues, followed by methylation analysis via the MassArray method. Cecal contents were collected for untargeted metabolomic analysis and a target quantitative analysis of methionine cycle metabolites. Spearman correlation analyses were used to assess whether cecal metabolites are involved in the methylation of browning-related genes and influence their expression. The results showed that maternal GEN supplementation reversed the downregulation of browning markers caused by perinatal high-fat diets in adult female offspring, consistent with a reduction in their methylation levels. Subsequently, we also found that maternal GEN consumption altered cecal metabolite profiles in offspring, promoting the production of bile acids, potent regulators of glucolipid metabolism, and reducing metabolites involved in the methionine cycle, key methyl donors for the methylation process. Furthermore, the abundances of these metabolites were significantly correlated with the methylation and expression levels of browning markers. Overall, this discovery suggested that maternal GEN intake decreased the methylation level of browning markers and induced browning in white adipose tissue of offspring, which correlated with alterations in cecal metabolites. We provide a novel theoretical basis for GEN as a promising nutritional supplement to break the vicious cycle of maternal metabolic disturbances being transmitted to offspring.PMID:40146209 | DOI:10.1039/d4fo04761c

J Invest Dermatol. 2025 Mar 27:S0022-202X(25)00129-0. doi: 10.1016/j.jid.2025.02.012. Online ahead of print.ABSTRACTAcne vulgaris, a prevalent chronic inflammatory disease of the pilosebaceous unit, continues to present with a complex pathogenesis that is not fully understood. The advent of high-throughput sequencing technologies has revolutionized biomedical research, enabling the comprehensive use of multiomics analyses to study diseases with intricate mechanisms, such as acne. This review summarizes the progress in genomics, epigenomics, transcriptomics, proteomics, and metabolomics research on acne. By providing a comprehensive overview, we aim to enhance our understanding of acne pathogenesis and identify potential therapeutic targets that could inspire the prevention and treatment of acne.PMID:40146096 | DOI:10.1016/j.jid.2025.02.012

Oral Dis. 2025 Mar 27. doi: 10.1111/odi.15328. Online ahead of print.ABSTRACTOBJECTIVES: Primary Sjögren's disease (SjD) is a slow-progressing autoimmune disease that affects salivary and lacrimal glands, causing dry eyes (xerophthalmia) and dry mouth (xerostomia). Diagnosing SjD involves clinical, serological, and histological assessments, but reliable biomarkers are lacking.METHODS: This study analyzed the metabolic and proteomic profiles of 19 female SjD patients (based on ACR-EULAR criteria) compared to 20 healthy individuals. Saliva and blood samples were analyzed using mass spectrometry and chromatography. Proteomic analysis was performed with the nanoElute nanoflow system coupled to a timsTof-Pro mass spectrometer, and metabolic profiling with a GC-TOF/MS Pegasus HT.RESULTS: Statistical tests identified significant differences in metabolites and proteins between SjD patients and controls. Metabolome analysis revealed changes in amino acid synthesis, purine and lipid metabolism, and exposure to external compounds. Proteomic analysis indicated immune-related proteins and inflammatory lipid metabolism. GNAI2, B2MG, NGAL, SLUR2, HS90, SODC, and A2GL emerged as potential biomarkers for SjD.CONCLUSION: This study demonstrates the potential of high-performance techniques in identifying biomarkers for SjD diagnosis and prognosis. Data are available via ProteomeXchange (PXD055629).PMID:40145347 | DOI:10.1111/odi.15328

Alzheimers Dement. 2025 Mar;21(3):e70081. doi: 10.1002/alz.70081.ABSTRACTINTRODUCTION: Polypharmacy is common among older adults and people with dementia. Multi-medication therapy poses risks of harm but also targets comorbidities and risk factors associated with dementia, offering therapeutic potential.METHODS: We evaluated the effects of two polypharmacy regimens and monotherapies on male and female AppNL-G-F knock-in mice. We assessed functional, emotional, and cognitive outcomes;amyloid pathology; and serum metabolomics profiles.RESULTS: A combination of metoprolol, simvastatin, aspirin, paracetamol, and citalopram improved memory, reduced amyloid burden and neuroinflammation, and modulated AD-associated metabolomic signatures in male mice, with negligible effects in female mice. Substituting two cardiovascular drugs impacted emotional domains but worsened memory, predominantly in female mice. In males, monotherapies could not explain the combination effects, suggesting drug synergy, whereas in female mice, certain monotherapy effects were lost when combined.DISCUSSION: This study uncovers the sex-specific effects of polypharmacy in an AD model, identifying mechanisms and biomarkers that can guide gender-specific use of medicines in dementia prevention and management.HIGHLIGHTS: Two polypharmacy combinations show sex-specific effects on AD pathology and serum metabolomic profiles. Metoprolol+simvastatin+aspirin+paracetamol+citalopram improves memory and amyloid pathology in male mice. Replacing metoprolol and simvastatin with enalapril and atorvastatin eliminates benefits in male mice and impairs memory in female mice. Selected monotherapies produce sex-specific effects but only partially explain the outcomes of the combinations. Metabolomic pathways in serum indicate possible mechanisms and biomarkers for evaluating the effectiveness and safety of personalized therapies in aging and dementia.PMID:40145346 | DOI:10.1002/alz.70081

Front Pharmacol. 2025 Mar 12;16:1542143. doi: 10.3389/fphar.2025.1542143. eCollection 2025.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease, characterized by hepatic lipid accumulation. The Fufangduzhong formula (FFDZ) is a traditional Chinese medicine (TCM) formulation composed of Eucommia ulmoides Oliv., Leonurus artemisia (Lour.) S. Y. Hu, Prunella vulgaris Linn, Uncariarhynchophylla (Miq.) Miq. ex Havil., and Scutellaria baicalensis Georgi. It has demonstrated hepatoprotective effects and the ability to reduce lipid accumulation. However, its mechanisms against NAFLD remain unclear.METHODS: UPLC-MS/MS was used to identify FFDZ metabolites. C57BL/6J mice were fed a high-fat diet (HFD) supplemented with or without FFDZ (HFD+L, 0.45 g/kg/d; HFD+H, 0.9 g/kg/d) for 12 weeks. Biochemical indicators and histopathological observations were utilized to assess the extent of metabolic homeostasis disorder and hepatic steatosis. An analysis of differentially expressed genes and regulated signaling pathways was conducted using hepatic transcriptomics. Metabolomics analysis was performed to investigate the significantly changed endogenous metabolites associated with NAFLD in mice serum using UPLC-Q-TOF/MS. Western blot was employed to detect proteins involved in the lipid metabolism-related signaling pathways. Oleic acid-induced hepatic steatosis was used to examine the lipid-lowering effect of FFDZ-containing serum in vitro.RESULTS: A total of eight active metabolites were identified from the FFDZ formula and FFDZ-containing serum through UPLC-MS/MS analysis. FFDZ reduced body weight, liver weight, and levels of inflammatory cytokines, and it ameliorated hepatic steatosis, serum lipid profiles, insulin sensitivity, and glucose tolerance in mice with HFD-induced NAFLD. Transcriptomics revealed that FFDZ modulated the lipid metabolism-related pathways, including the PPAR signaling pathway, Fatty acid metabolism, and AMPK signaling pathway. Meanwhile, Western blot analysis indicated that FFDZ downregulated the expression of lipid synthesis-related proteins (Srebp-1c, Acly, Scd-1, Fasn, Acaca, and Cd36) and upregulated the fatty acid oxidation-related proteins (p-Ampk, Ppar-α, and Cpt-1). Furthermore, metabolomics identified FFDZ-mediated reversal of phospholipid dysregulation (PC, PE, LPC, LPE). Additionally, FFDZ-containing serum remarkedly reduced OA-induced lipid accumulation in HepG2 cells.CONCLUSION: The present results demonstrate that FFDZ exerts anti-NAFLD effects by enhancing glucose tolerance and insulin sensitivity, as well as regulating the Ampk signaling pathway to ameliorate lipid metabolism disorder, lipotoxicity, hepatic steatosis, and inflammatory responses.PMID:40144651 | PMC:PMC11936930 | DOI:10.3389/fphar.2025.1542143

iScience. 2025 Feb 17;28(3):112015. doi: 10.1016/j.isci.2025.112015. eCollection 2025 Mar 21.ABSTRACTPancreatic β cells exist in low and high insulin gene activity states that are dynamic on a scale of hours to days. Here, we used live 3D imaging, mass spectrometry proteomics, and targeted perturbations of β cell signaling to comprehensively investigate Ins2(GFP)HIGH and Ins2(GFP)LOW β cell states. We identified the two Ins2 gene activity states in intact isolated islets and showed that cells in the same state were more likely to be nearer to each other. We report the proteomes of pure β cells to a depth of 5555 proteins and show that β cells with high Ins2 gene activity had reduced β cell immaturity factors, as well as increased translation. We identified activators of cAMP signaling (GLP1, IBMX) as powerful drivers of Ins2(GFP)LOW to Ins2(GFP)HIGH transitions. Okadaic acid and cyclosporine A had the opposite effects. This study provides new insight into the proteomic profiles and regulation of β cell states.PMID:40144638 | PMC:PMC11938086 | DOI:10.1016/j.isci.2025.112015

Front Nutr. 2025 Mar 12;12:1544713. doi: 10.3389/fnut.2025.1544713. eCollection 2025.ABSTRACTBACKGROUND: Globally, master's and doctoral students, especially pregraduate students, are under great pressure. Probiotics are emerging as a promising intervention to improve mental health via gut-brain axis.OBJECTIVE: The aim of this study was to explore the impact of Lacticaseibacillus paracasei K56 supplementation on perceived stress among pregraduate students.METHODS: We conducted a double-blind, randomized, placebo-controlled trial in 120 healthy master's and doctoral students who faced graduation. Participants were randomly assigned to either probiotics (containing Lacticaseibacillus paracasei K56 6 × 1010 CFU / d) or placebo group for 2 weeks intervention. The main outcome was perceived stress assessed using Cohen's Perceived Stress Scale-10 (PSS-10). The secondary outcomes were stress, depression, and anxiety assessed by Depression, Anxiety and Stress Scales (DASS), gastrointestinal symptoms, and sleep evaluated by corresponding scales. These outcomes were assessed at baseline, 1, and 2 weeks. Pre- and post-treatment serum biomarkers, gut microbiota composition and metabolites were also detected.RESULTS: There was no difference in changes of PSS-10 scores from baseline to 2 weeks between the K56 groups and the placebo [mean (standard error): -1.68 (0.48) vs. -0.39 (0.46), p = 0.055]. Furthermore, the K56 group exhibited superior reductions in both stress [-2.15 (0.38) vs. -0.96 (0.49), p = 0.035] and anxiety symptoms [-1.54 (0.32) vs. 0.53 (0.43), p = 0.003] via DASS compared with the placebo group. Additionally, those receiving K56 also experienced improved sleep quality (p = 0.010) and elevated levels of serotonin (5-HT) (p = 0.038) compare to placebo group. Moreover, taking probiotics K56 could modulate the pressure-induced changes in gut microbiota composition, particularly by increasing the beneficial bacteria (Lacticaseibacillus and Lacticaseibacillus paracasei), while suppressing suspected pathogenic bacteria (Shieglla and Escherichia_coli). Metabolomic analysis revealed an increased in metabolites, especially butyric acid in the K56 group (p = 0.035). Notably, there was a significant negative correlation between relative abundance of lactobacillus and stress-related symptoms, whereas butyric acid showed a significant positive correlation with lactobacillus abundance level.CONCLUSION: This study suggested the potential benefits of K56 supplementation in alleviating stress and significant effect in reducing anxiety and insomnia among master's and doctoral students, which may be attributed to K56-induced changes in microbial composition and butanoate metabolism.CLINICAL TRIAL REGISTRATION: Chictr.org.cn, identifier ChiCTR2300078447.PMID:40144570 | PMC:PMC11936786 | DOI:10.3389/fnut.2025.1544713

Front Vet Sci. 2025 Mar 12;12:1486406. doi: 10.3389/fvets.2025.1486406. eCollection 2025.ABSTRACTINTRODUCTION: Donkey milk demonstrates closer compositional resemblance to human milk compared to bovine milk, positioning it as an optimal nutritional substitute for infants with cow's milk allergy. Furthermore, its rich profile of bioactive compounds suggests potential immunomodulatory properties. This study systematically investigated the effects of donkey milk supplementation on murine immune function and gut microbiome dynamics, thereby providing mechanistic insights to support its clinical development in functional food applications.METHODS: Following daily intragastric administration of 10 mL/kg of body weight of donkey milk (DM) or distilled water (DW) to the mice for 28 consecutive days, liver tissues were harvested for immunological profiling, with concurrent collection of blood samples for plasma metabolomic analysis and fecal specimens for gut microbiome characterization. Subsequently, the modulatory effects of donkey milk supplementation on immune parameters, intestinal microbiota composition, and plasma metabolic profiles were systematically evaluated.RESULTS: Immunity analysis revealed that intragastric administration of DM raised the levels of IL-6 and TNF-α cytokines in mouse liver. In addition, DM modulated the composition of both the murine gut microbiome and plasma metabolites. One-hundred and forty-five differentially-produced metabolites were identified, most prominently nicotinamide, L-valine, and β-estradiol, that are primarily associated with valine, leucine, and isoleucine biosynthesis and degradation, nicotinate and nicotinamide metabolism, and unsaturated fatty acid biosynthesis. Alterations at phylum, genus, and species levels were evident in the fecal microbiota of mice after intragastric administration of DM. In particular, an increased abundance of the Lactobacillus bacterium was observed. Correlation analysis of differential metabolites and microbiomes indicated a correspondence between Falsiroseomonas and Salipiger species and the antioxidant coenzyme Q that has the potential to activate the immune system.CONCLUSION: The data collectively suggest that DM may adjust the murine gut microbiome and plasma metabolites thereby potentially improving immunity in mice.PMID:40144527 | PMC:PMC11938429 | DOI:10.3389/fvets.2025.1486406

Front Bioeng Biotechnol. 2025 Mar 10;13:1533661. doi: 10.3389/fbioe.2025.1533661. eCollection 2025.ABSTRACTINTRODUCTION: Stress from high light exposure and overexpression of β-carotene ketolase can have significant effects on the synthesis of carotenoids in Chlamydomonas reinhardtii. As a promising platform for carotenoid production, C. reinhardtii needs further research and technological innovation to address challenges, such as environmental interference, exogenous gene expression, and metabolic regulation, to achieve efficient and sustainable production of carotenoids.METHODS: Appropriate β-carotene ketolase were selected from different organisms and subjected for codon optimization based on the preferences of the nuclear genome of C. reinhardtii. After designation, including intron insertion and chloroplast transit peptide, expression vectors were constructed and used for nuclear transformation of C. reinhardtii CC849 by bead milling method. Subsequently, DNA-PCR and RT-PCR were used to identify positive transformants grown with antibiotic stress, LC-MS/MS and metabolic analysis were performed to evaluate the products of transformants.RESULTS: In this study, carotenoid metabolism regulation in C. reinhardtii was investigated in a time-dependent manner through high light exposure and heterologous expression of β-carotene ketolase. The results suggested that the stress from high light exposure (500 μmol/m2/s) negatively regulated the accumulation of β-carotene; positively induced the accumulation of zeaxanthin, echinenone, and canthaxanthin; and continuously promoted accumulation of zeaxanthin and canthaxanthin in C. reinhardtii. Metabolomics analysis suggested that high light exposure stress promoted biosynthesis of carotenoids, improved the intermediates associated with the astaxanthin synthesis pathway, and promoted conversion of β-carotene to downstream substances. Several strategies were implemented to improve canthaxanthin production in C. reinhardtii to achieve overexpression of β-carotene ketolase genes from different sources, including strong promoters, insertion introns, and chloroplast conduction peptides. It was found that β-carotene, echinenone, and canthaxanthin were all significantly increased in the transformed C. reinhardtii overexpressing β-carotene ketolase. Among these, the highest canthaxanthin content was found in pH124-CrtO, which was seven times that observed in the wild type. Moreover, the metabolomics analysis of carotenoids showed promotion of the abscisic acid and astaxanthin pathways in the transformed C. reinhardtii.DISCUSSION: The results of this study provide a new scheme for manipulating the metabolism of carotenoids and promoting the synthesis of high-value carotenoids in C. reinhardtii.PMID:40144396 | PMC:PMC11938120 | DOI:10.3389/fbioe.2025.1533661

Front Endocrinol (Lausanne). 2025 Mar 12;16:1551100. doi: 10.3389/fendo.2025.1551100. eCollection 2025.ABSTRACTThe intricate relationship between bile acid metabolism and skeletal muscle function has emerged as a crucial area of research in metabolic health. This review synthesizes current evidence highlighting the fundamental role of bile acids as key signaling molecules in muscle homeostasis and their therapeutic potential in muscle-related disorders. Recent advances in molecular biology and metabolomics have revealed that bile acids, beyond their classical role in lipid absorption, function as essential regulators of muscle mass and function through multiple signaling pathways, particularly via the nuclear receptor FXR and membrane receptor TGR5. Clinical studies have demonstrated significant associations between altered bile acid profiles and muscle wasting conditions, while experimental evidence has elucidated the underlying mechanisms linking bile acid signaling to muscle protein synthesis, energy metabolism, and regeneration capacity. We critically examine the emerging therapeutic strategies targeting bile acid pathways, including receptor-specific agonists, microbiome modulators, and personalized interventions based on individual bile acid profiles. Additionally, we discuss novel diagnostic approaches utilizing bile acid-based biomarkers and their potential in early detection and monitoring of muscle disorders. This review also addresses current challenges in standardization and clinical translation while highlighting promising future directions in this rapidly evolving field. Understanding the bile acid-muscle axis may provide new opportunities for developing targeted therapies for age-related muscle loss and metabolic diseases.PMID:40144297 | PMC:PMC11936799 | DOI:10.3389/fendo.2025.1551100

Front Microbiol. 2025 Mar 12;16:1553922. doi: 10.3389/fmicb.2025.1553922. eCollection 2025.ABSTRACTINTRODUCTION: Soil microbiome transplantation is a promising technique for enhancing plant holobiont response to abiotic and biotic stresses. However, the rapid assessment of microbiome-plant functional integration in short-term experiments remains a challenge.METHODS: This study investigates the potential of three evergreen sclerophyll species, Pistacia lentiscus (PL), Rosmarinus officinalis (RO), and Juniperus phoenicea (JP), to serve as a reservoir for microbial communities able to confer enhanced tolerance to drought in Salvia officinalis cultivated under water shortage, by analyzing biomass production, plant phenotype, plant ecophysiological responses, and leaf metabolome.RESULTS: Our results showed that the inoculation with the three rhizomicrobiomes did not enhance total plant biomass, while it significantly influenced plant architecture, ecophysiology, and metabolic responses. The inoculation with the JP rhizomicrobiome led to a significant increase in root biomass, resulting in smaller leaves and a higher leaf number. These morphological changes suggest improved water acquisition and thermoregulation strategies. Furthermore, distinct stomatal conductance patterns were observed in plants inoculated with microbiomes from PJ and PL, indicating altered responses to drought stress. The metabolome analysis demonstrated that rhizomicrobiome transplantation significantly influenced the leaf metabolome of S. officinalis. All three rhizomicrobiomes promoted the accumulation of phenolic compounds, terpenoids, and alkaloids, known to play crucial roles in plant defense and stress response. Five molecules (genkwanin, beta-ionone, sumatrol, beta-peltatin-A-methyl ester, and cinnamoyl-beta-D-glucoside) were commonly accumulated in leaves of inoculated sage, independently of the microbiome. Furthermore, unique metabolic alterations were observed depending on the specific inoculated rhizomicrobiome, highlighting the specialized nature of plant-microbe interactions and the possible use of these specific molecules as biomarkers to monitor the recruitment of beneficial microorganisms.DISCUSSION: This study provides compelling evidence that microbiome transplantation can induce phenotypic and metabolic changes in recipient plants, potentially enhancing their resilience to water scarcity. Our findings emphasize the importance of considering multiple factors, including biomass, physiology, and metabolomics, when evaluating the effectiveness of microbiome engineering for improving plant stress tolerance.PMID:40143859 | PMC:PMC11937098 | DOI:10.3389/fmicb.2025.1553922

Front Microbiol. 2025 Mar 12;16:1548427. doi: 10.3389/fmicb.2025.1548427. eCollection 2025.ABSTRACTBACKGROUND: Massa Medicata Fermentata (MMF) is a traditional medicinal/edible fermented product; however, comprehensive research on the fermentation process from a microscopic perspective remains limited. In this study, we aimed to investigate the dynamic changes and correlations of physicochemical properties, microbial communities, and metabolite profiles in different fermentation stages (0, 48, 72, and 96 h) of MMF.METHODS: Standard analytical tests, microbiome sequencing, broad-target metabolism, mixed standard-based mass spectrometry, and fine structure analysis were integrated to elucidate fluctuations in physicochemical, microbial, and metabolic levels during MMF fermentation.RESULTS: During the fermentation process, bacterial diversity generally shows an increasing trend, whereas fungal diversity generally shows a decreasing trend. Revealing that the differentially abundant metabolites were primarily categorized into lipids, amino acids and derivatives, phenolic acids, organic acids, flavonoids, lignans and coumarins, nucleotides and derivatives, and alkaloids. Structural equation modeling and correlation analysis indicated that two species of bacteria (Bacillus velezensis, Bacillus safensis) and four species of fungi (Apiotrichum montevideense, Geotrichum bryndzae, f_Dipodascaceae, Saccharomycopsis fibuligera) showed significant positive correlations with five types of differential metabolites, including lipids, flavonoids, phenolic acids, lignans and coumarins, and organic acids. These differential metabolites are essential components responsible for the therapeutic effects of MMF, particularly those that reach peak concentrations at 72 h of fermentation.CONCLUSION: These findings are expected to provide a reference for developing strategies to strengthen the quality of MMF and promote its modern application.PMID:40143856 | PMC:PMC11936943 | DOI:10.3389/fmicb.2025.1548427

Int J Epidemiol. 2025 Feb 16;54(2):dyaf026. doi: 10.1093/ije/dyaf026.ABSTRACTBACKGROUND: This is the first large-scale longitudinal study of children that describes the temporal trajectories of an extensive collection of metabolic measures that are relevant for lifelong cardiometabolic risk. We also provide a comprehensive picture on how metabolism develops into mature adult sex-specific phenotypes.METHODS: Children born in 1962-92 were recruited by three European studies (n = 20 377 eligible). Biochemical data for ages 0-26 years were available for n = 14 958 participants (n = 8385 with metabolomics). Age associations for 168 metabolic measures (6 physiological traits, 6 clinical biomarkers, and 156 serum metabolomics measures) were determined by using curvilinear regression. Puberty effects were calculated by using logistic regression of biological sex for pre- and post-pubertal age strata.RESULTS: Age-specific concentrations were reported for all measures. Nonlinear age associations were typical, including insulin (R2 = 20.7% ±0.6% variance explained ±SE), glycerol (13.3% ±1.3%), glycoprotein acetyls (40.3% ±1.5%), and branched-chain amino acids (19.5% ±1.6%). Apolipoprotein B was not associated with age (0.7% ±0.4%). Multivariate modeling indicated that boys diverged from girls metabolically during ages 13-17 years. Puberty effects were observed for large high-density lipoprotein cholesterol (P = 8.5 × 10-288), leucine (P < 2.3 × 10-308), glutamine (P < 2.3 × 10-308), albumin (P = 1.7 × 10-161), docosahexaenoic acid (P = 5.2 × 10-50), and sphingomyelin (P = 4.4 × 10-90).CONCLUSION: Novel associations between emerging cardiometabolic risk factors, such as amino acids and glycoprotein acetyls, and growth and puberty were observed. Conversely, apolipoprotein B was stable, which favors its utility for early assessments of lifetime cardiovascular risk.PMID:40143821 | DOI:10.1093/ije/dyaf026

Food Funct. 2025 Mar 27. doi: 10.1039/d4fo06059h. Online ahead of print.ABSTRACTCisplatin (CIS) is a commonly used antitumor drug in clinics, but its application is limited due to hepatotoxicity, nephrotoxicity and gastrointestinal toxicity. In recent years, a large number of studies have shown that the imbalance of intestinal flora is one of the important factors in the malignant development of diseases. Therefore, improving organ function by regulating intestinal flora may be an important strategy to prevent the side effects of chemotherapy drugs. Lycopene (LYC) is found in a wide range of red foods and has antioxidant, anti-inflammatory and immune-enhancing effects. So the purpose of this study was to explore its effect on hepatointestinal injury caused by chemotherapy drugs. The results of this study showed that CIS could significantly restore body weight, diet, water intake, and AST, ALT and other physiological and biochemical indexes of rats. HE staining, projective electron microscopy and TUNEL results showed that LYC alleviated morphological and ultrastructural damage of the liver and intestine. Then, ELISA results showed that LYC can reduce cell apoptosis by increasing the antioxidant capacity and reducing inflammatory response. Secondly, 16sRNA and metabolome results showed that LYC enriched beneficial bacteria (Firmicutes and Proteobacteria), reduced harmful bacteria (E. coli, etc.), enhanced metabolic pathway changes such as taurine and hypotaurine metabolism, and alleviated organ damage caused by CIS. Finally, network pharmacology, molecular docking and immunohistochemistry showed that LYC could reduce CIS induced hepatocyte inflammation and apoptosis by activating the PI3K/AKT pathway. In summary, LYC alleviates the toxic side effects of chemotherapy drugs by regulating the PI3K/AKT pathway and the intestinal microbiota-metabolite-liver axis.PMID:40143795 | DOI:10.1039/d4fo06059h

J Periodontal Res. 2025 Mar 26. doi: 10.1111/jre.13400. Online ahead of print.ABSTRACTAIMS: Poor accuracy of diagnostic and prognostic tools prevents the prediction of peri-implant disease stability or progression. We analyzed metabolites from peri-implant crevicular fluid (PICF) samples from healthy and diseased implants to identify those diagnostic of health and peri-implant disease and predictive of peri-implant bone loss over time.METHODS: Clinical, radiographic examinations and PICF samples were collected from 59 healthy implants, 33 implants with peri-implantitis, and 38 implants with peri-implant mucositis in 71 subjects. A subset of implants was evaluated at 6, 12, 18, and 24 months. Over time, all initially healthy implants remained stable (Group B, N = 28), whereas 6 initially diseased implants continued to lose bone and 8 did not (Group C). PICF metabolites were measured using proton-nuclear magnetic resonance (1H-NMR) 2-dimensional Total Correlation Spectroscopy. PCA and PLS-DA tested the cross-sectional clustering and importance of each metabolite, while the AUC summarized the accuracy of predicting radiographic bone changes ≥ 1 mm at 6-month intervals.RESULTS: At baseline, the Cadaverine/Lysine and Putrescine/Lysine signatures diagnosed peri-implantitis (AUC = 0.76 and 0.70; p < 0.000) with good accuracy, while alpha-ketoglutarate diagnosed implant health (AUC = 0.706; p = 0.002). Combining metabolites increased diagnostic accuracy (AUCCadaverine/Lysine+Methionine = 0.81; p < 0.01). Proline and 1-3-diaminopropane predicted future bone loss (AUCProline = 0.917 and AUC1-3-diaminopropane = 0.854). ANOVA post hoc analysis established that biotin and propionate levels were higher in Group C compared to Groups A and B (p < 0.001; AUCbiotin = 0.889; AUCpropionate = 0.87). Valine levels were higher in Groups A and C compared to Group B (p = 0.002; AUC = 0.841).CONCLUSIONS: 1H-NMR 2-dimensional spectroscopy identified PICF metabolites diagnostic of peri-implantitis with high accuracy. Despite the small number of affected implants, metabolite signatures that predict future bone loss in peri-implantitis appear to be different from those diagnostic of peri-implantitis.PMID:40143571 | DOI:10.1111/jre.13400

Immun Inflamm Dis. 2025 Mar;13(3):e70183. doi: 10.1002/iid3.70183.ABSTRACTOBJECTIVE: Despite growing interest in the gut microbiota and blood metabolome in patients with ankylosing spondylitis (AS), its role remains poorly understood. Here, we investigate how microbial and metabolic alterations contribute to AS.METHODS: Fecal microbiome data from 40 AS patients were compared with those from 40 healthy controls (HCs) using 16S ribosomal RNA (rRNA) gene sequencing. The plasma metabolic profiles were analyzed and integrated with the microbiota data to identify biological characteristics specific to AS.RESULTS: AS patients showed significant enrichment of specific genera, including Megamonas, Elusimicrobium, Dysgonomonas, Ruminococcus_gauvreauii_group, and unclassified_Prevotellaceae. Pathways with the most differentially expressed metabolites included bile secretion; neomycin, kanamycin, and gentamicin biosynthesis; and arachidonic acid metabolism. Positive correlations between Megamonas and Elusimicrobium and metabolites such as piribedil, l-cystathionine, and crocetin dialdehyde suggested microbial enrichment in AS patients.CONCLUSIONS: A disrupted gut microbiota and altered metabolites are present in AS patients. Integrating microbiome and metabolomic data reveals significant disruptions in AS patients, improving our understanding of its pathogenesis.PMID:40143557 | DOI:10.1002/iid3.70183

Pharmaceuticals (Basel). 2025 Mar 12;18(3):398. doi: 10.3390/ph18030398.ABSTRACTBackground and Objectives: Diabetic hepatopathy, characterized by hepatic hypoxia and metabolic dysregulation, has a rising global incidence and prevalence, with limited effective treatments. Hepatic hypoxia activates hypoxia-inducible factor-1 alpha (HIF-1α), regulating sphingolipid metabolism and elevating ceramide, a key factor in insulin resistance. Puerarin (Pue), a flavonoid derived from Pueraria lobata, exhibits therapeutic effects in diabetes, but its effects on hypoxia-related hepatic metabolism are unclear. This study investigates Pue's mechanisms in modulating hepatic metabolism, focusing on HIF-1α and sphingolipid metabolism. Methods: Using bioinformatics and molecular docking, HIF-1α was identified as a key target in diabetic liver disease, confirmed via drug affinity responsive target stability. In vitro experiments utilized insulin-resistant HepG2 cells to assess glucose intake and HIF-1α expression. In vivo, type 2 diabetes mellitus (T2DM) was induced in mice using a high-fat diet and streptozotocin injections. Pue administration was evaluated for its effects on fasting blood glucose, oral glucose tolerance, and hepatoprotective effects. Liver metabolomics and qPCR/Western blot analyses were conducted to assess metabolic pathways. Results: Pue increased glucose uptake in HepG2 cells and bound HIF-1α. Pue reduced HIF-1α expression in HepG2 cells, an effect attenuated by the HIF-1α stabilizer DMOG. Pue improved fasting blood glucose, oral glucose tolerance, and hepatoprotective effects in T2DM mice, which DMOG reversed. Metabolomics revealed that Pue modulates sphingolipid metabolism, decreasing ceramide content. qPCR and Western blot results confirmed that Pue dramatically decreases HIF-1α and SPTLC2 expression. Conclusions: Pue improves diabetic hepatopathy by reducing ceramide expression through the HIF-1α/SPTLC2 pathway, offering a novel therapeutic strategy for diabetes management.PMID:40143173 | DOI:10.3390/ph18030398

Pharmaceuticals (Basel). 2025 Feb 21;18(3):299. doi: 10.3390/ph18030299.ABSTRACTBackground: This is a comparative metabolomic study of the medicinal plant Dryopteris fragrans (L.) Schott from the family Dryopteridaceae Herter (or Aspidiaceae Mett. ex Frank) growing under cold pole conditions in the Oymyakon region of the Republic of Sakha (Yakutia). Methods: The aerial parts of D. fragrans were subjected to extraction using supercritical CO2 extraction and maceration methods. Several experimental conditions were investigated, including a pressure range of 50-300 bar and a temperature range of 31-60 °C. A 1% volume of ethanol was used as a co-solvent in the liquid phase of the extraction. Results: The most effective D. fragrans extraction conditions were 200 Bar pressure and a temperature of 55 °C. Tandem mass spectrometry was used to detect the target analytes. A total of 141 bioactive compounds (86 compounds from the polyphenol group and 55 compounds from other chemical groups) were tentatively identified in extracts of aerial parts of D. fragrans. Among these, thirty chemical constituents from the polyphenol group were identified for the first time. Other compound classes that were newly identified in D. fragrans include naphthoquinones (5,8-dihydroxy-6-methyl-2,3-dihydro-1,4-naphthoquinone, 1,8-dihydroxy-anthraquinone, 1,4,8-trihydroxyanthraquinone, chrysophanol, etc.), diterpenoids (tanshinone IIa, cryptotanshinone, isocryptotanshinone II, tanshinone IIb, etc.), polysaccharides, triterpenoids, and sesquiterpenes. Conclusions: These results highlight that D. fragrans is rich in bioactive compounds and put forward several newly detected compounds for further investigation.PMID:40143079 | DOI:10.3390/ph18030299

J Clin Med. 2025 Mar 17;14(6):2040. doi: 10.3390/jcm14062040.ABSTRACTOncologists increasingly recognize the microbiome as an important facilitator of health as well as a contributor to disease, including, specifically, cancer. Our knowledge of the etiologies, mechanisms, and modulation of microbiome states that ameliorate or promote cancer continues to evolve. The progressive refinement and adoption of "omic" technologies (genomics, transcriptomics, proteomics, and metabolomics) and utilization of advanced computational methods accelerate this evolution. The academic cancer center network, with its immediate access to extensive, multidisciplinary expertise and scientific resources, has the potential to catalyze microbiome research. Here, we review our current understanding of the role of the gut microbiome in cancer prevention, predisposition, and response to therapy. We underscore the promise of operationalizing the academic cancer center network to uncover the structure and function of the gut microbiome; we highlight the unique microbiome-related expert resources available at the City of Hope of Comprehensive Cancer Center as an example of the potential of team science to achieve novel scientific and clinical discovery.PMID:40142848 | DOI:10.3390/jcm14062040