PubMed

J Clin Endocrinol Metab. 2025 May 13:dgaf285. doi: 10.1210/clinem/dgaf285. Online ahead of print.ABSTRACTCONTEXT: Insulin Resistance (IR) contributes to the pathogenesis of type 2 diabetes mellitus (T2DM) and is a risk factor for cardiovascular and neurodegenerative diseases. Amino acid and lipid metabolomic biomarkers associate with future T2DM risk in several epidemiological cohorts. Whether these biomarkers can accurately detect changes in IR status following treatment is unclear.OBJECTIVE: Herein we evaluated the performance of clinical and metabolomic biomarker models to forecast altered IR, following lifestyle-based interventions.DESIGN: We evaluated the performance of two distinct insulin assay types (high-sensitivity ELISA and Immunoassay) and built IR diagnostic models using cross-sectional clinical and metabolomic data. These models were utilised to stratify IR status in pre-intervention fasting samples, from three independent cohorts (META-PREDICT (M-P, n=179), STRRIDE-AT/RT (S-2, n=116) and STRRIDE-PD (S-PD, n=149)). Linear and Bayesian projective prediction strategies were used to evaluate models for fasting insulin and HOMA2-IR and change in fasting insulin with treatment.RESULTS: Both insulin assays accurately quantified international standard insulin (R2>0.99), yet agreement for fasting insulin was less congruent (R2=0.65). A mean treatment effect on fasting insulin was only detectable using an ELISA. Clinical-metabolomic models were statistically related to fasting insulin (R2 0.33-0.39) but with modest capacity to classify IR at a clinically relevant HOMA2-IR threshold. Furthermore, no model predicted treatment responses in any cohort.CONCLUSION: We demonstrate that the choice of insulin assay is critical when quantifying the influence of treatment on fasting insulin, while none of the clinical-metabolomic biomarkers, identified in cross-sectional studies, are suitable for monitoring longitudinally changes in IR status.PMID:40359244 | DOI:10.1210/clinem/dgaf285

J Clin Invest. 2025 May 13:e180826. doi: 10.1172/JCI180826. Online ahead of print.ABSTRACTAccumulating evidence implicates the gut microbiome (GMB) in the pathogenesis and progression of Alzheimer's disease (AD). We recently showed that the GMB regulates reactive astrocytosis and Aβ plaque accumulation in male APPPS1-21 AD model mice. Yet, the mechanism(s) by which GMB perturbation alters reactive astrocytosis in a manner that reduces Aβ deposition remain unknown. Here, we performed metabolomics on plasma from mice treated with antibiotics (abx) and identified a significant increase in plasma propionate, a gut-derived short chain fatty acid, only in male mice. Administration of sodium propionate reduced reactive astrocytosis and Aβ plaques in APPPS1-21 mice, phenocopying the abx-induced phenotype. Astrocyte-specific RNA sequencing on abx and propionate treated mice showed reduced expression of pro-inflammatory and increased expression of neurotrophic genes. Next, we performed flow cytometry experiments where we found abx and propionate decreased peripheral RAR-related orphan receptor-γ (Rorγt)+ CD4+ (Th17) cells and IL-17 secretion, which positively correlated with reactive astrocytosis. Lastly, using an IL-17 monoclonal antibody to deplete IL-17, we found that propionate reduces reactive astrocytosis and Aβ plaques in an IL-17-dependent manner. Together, these results suggest that gut-derived propionate regulates reactive astrocytosis and Aβ amyloidosis by decreasing peripheral Th17 cells and IL-17 release. Thus, propionate treatment or strategies boosting propionate production may represent novel therapeutic strategies for AD.PMID:40359034 | DOI:10.1172/JCI180826

J Biochem Mol Toxicol. 2025 May;39(5):e70291. doi: 10.1002/jbt.70291.ABSTRACTOBJECTIVE: To assess the effects of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) on mitochondrial damage and metabolic disorders induced by acute and chronic hypoxia in mouse kidneys.METHOD: Comprehensive analyses were conducted, including histopathology, mitochondrial morphology analysis, biochemical assessments, transcriptomics and metabolomics.RESULTS: The results revealed that hUC-MSCs significantly improved renal mitochondrial integrity and maintained mitochondrial dynamic balance under both acute and chronic hypoxia. This improvement was achieved by upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator-1 alpha, which ultimately enhanced mitochondrial function. Furthermore, hUC-MSCs reprogrammed renal metabolic disorders, particularly improvements in urea and purine metabolic dysfunction, increased fatty acid oxidation and amelioration of lipid metabolic disorders.CONCLUSION: These findings suggest that hUC-MSCs could be part of a promising strategy for enhancing renal health and metabolic stability in individuals exposed to high altitudes or other hypoxic environments, highlighting their potential therapeutic value in addressing hypoxia-induced mitochondrial damage and renal metabolic disorders.PMID:40358967 | DOI:10.1002/jbt.70291

Nat Prod Res. 2025 May 13:1-12. doi: 10.1080/14786419.2025.2503011. Online ahead of print.ABSTRACTCurculigo orchioides Gaertn. is a traditional medicinal plant widely used in Asia. However, it is often collected from the wild without replanting efforts. Additionally to its slow growth, its availability is further threatened by natural disasters and land-use shifting, putting its future supply at risk. This work aimed to obtain an efficient method for callus initiation and plant multiplication, investigate whether propagules produce secondary metabolites found in the mother plant. Combinations of plant growth regulators were used to initiate callus and/or shoots from leaf explants, and UHPLC-Q-Orbitrap HRMS identified metabolites. The explants cultured on MS medium supplemented with a combination of BAP (5 mg L-1) and IBA (3 mg L-1) initiated callus and regenerated plantlets. Through LC-HRMS analysis, several compounds with pharmacological effects were found in the in vitro propagules. In callus and plantlet leaves, 24 and 27 compounds were identified respectively, dominated by phenolics. Principal component analysis and hierarchical cluster discriminated the metabolites in the propagules and mother plant organs. The essential compounds, (1S,2R)-O-methylnyasicoside, curculigoside B, orcinol glucoside, 2,4-dichloro-5-methoxy-3-methylphenol were determined in callus at a higher concentration than in the mother plant. Conclusively, in vitro propagules of C. orchioides is a valuable alternative source of bioactive compounds.PMID:40358421 | DOI:10.1080/14786419.2025.2503011

J Am Soc Mass Spectrom. 2025 May 13. doi: 10.1021/jasms.4c00418. Online ahead of print.ABSTRACTCoffee is characterized by a complex chemical matrix that significantly influences its organoleptic properties and market value. This complexity is driven by factors such as botanical species, geographical origin, cultivation conditions, and post-harvest processing methods. Metabolomic studies aim to elucidate how these factors impact the biosynthesis of metabolites that contribute to the sensory qualities of high-quality coffee. Among various analytical techniques, liquid chromatography-mass spectrometry (LC-MS) is particularly effective for separating, identifying, and quantifying these compounds. Most metabolomic studies employ high-resolution mass spectrometry (HRMS) for its superior mass accuracy (<1 ppm), whereas the interpretation of low-resolution data requires additional effort, often relying on literature references and proposed fragmentation mechanisms. In this study, we applied LC-ESI(±)LTQ MSn to comprehensively profile coffee metabolites, identifying 60 compounds, including polar compounds and their isomers such as chlorogenic acids, carbohydrates, amino acids, alkaloids, glycosylated diterpenes, and flavonoids. Fragmentation mechanisms were proposed and discussed. The results demonstrate the effectiveness of LC-ESI(±)LTQ MSn in a detailed metabolomic analysis, providing a robust platform for future research in coffee metabolomics.PMID:40358368 | DOI:10.1021/jasms.4c00418

Cells. 2025 Apr 25;14(9):638. doi: 10.3390/cells14090638.ABSTRACTInherited metabolic disorders (IMDs) are genetic disorders that occur in as many as 1:2500 births worldwide. Nevertheless, they are quite rare individually and even more rare is the co-occurrence of two IMDs in one individual. To better understand the metabolic cross-talk between glycosylation changes and deficient energy metabolism, and its potential effect on outcomes, we evaluated patient fibroblasts with likely pathogenic variants in PGM1 and pathogenic variants in NDUFA13 derived from a patient who passed away at 16 years of age. The patient presented with characteristic of PGM1-CDG including bifid uvula, muscle involvement, abnormal glycosylation in blood, and elevated liver transaminases. In addition, hearing loss, seizures, elevated plasma and CSF lactate and a Leigh-like MRI brain pattern were present, which are commonly associated with Leigh syndrome. PGM1-CDG has been reported in about 70 individuals, while NDUFA13 deficiency has so far only been reported in 13 patients. As abundant energy is essential for glycosylation, and both PGM1 and NDUFA13 are linked to energy metabolism, we sought to better understand the underlying biochemical cause of the patient's clinical presentation. To do so, we performed extensive investigations including tracer metabolomics, lipidomics and enzymatic studies on the patient's fibroblasts. We found a profound depletion of UDP-hexoses, consistent with PGM1-CDG. Complex I enzyme activity and mitochondrial function were also impaired, corroborating complex I deficiency and Leigh syndrome. Further, lipidomics analysis showed similarities with both PGM1-CDG and OXPHOS-deficient patients. Based on our results, the patient was diagnosed with both PGM1-CDG and Leigh syndrome. In summary, we present the first case of combined CDG and Leigh syndrome, caused by (likely) pathogenic variants in PGM1 and NDUFA13, and underline the importance of considering the synergistic effects of multiple disease-causing variants in patients with complex clinical presentation, leading to the patient's early demise.PMID:40358162 | DOI:10.3390/cells14090638

Cells. 2025 Apr 22;14(9):626. doi: 10.3390/cells14090626.ABSTRACTOvarian carcinoma is a gynecological cancer with poor long-term survival rates when detected at advanced disease stages. Early symptoms are non-specific, and currently, there are no adequate strategies to identify this disease at an early stage when much higher survival rates can be expected. Ovarian carcinoma is a heterogeneous disease, with various histotypes originating from different cells and tissues, and is characterized by distinct somatic mutations, progression profiles, and treatment responses. Our study presents a targeted metabolomics approach, characterizing seven different ovarian (cancer-) cell lines according to their extracellular, intracellular, and RNA-derived modified nucleoside profiles. Moreover, these data were correlated with transcriptomics data to elucidate the underlying mechanisms. Modified nucleosides are excreted in higher amounts in cancer cell lines due to their altered DNA/RNA metabolism. This study shows that seven different ovarian cancer cell lines, representing different molecular subtypes, can be discriminated according to their specific nucleoside pattern. We suggest modified nucleosides as strong biomarker candidates for ovarian cancer with the potential for subtype-specific discrimination. Extracellular modified nucleosides have the highest potential in the distinguishing of cell lines between control cell lines and themselves, and represent the closest to a desirable, non-invasive biomarker, since they accumulate in blood and urine.PMID:40358150 | DOI:10.3390/cells14090626

Liver Int. 2025 Jun;45(6):e70128. doi: 10.1111/liv.70128.ABSTRACTBACKGROUND AND AIMS: Alcohol-related liver disease (ALD) is a major cause of mortality and disability-adjusted life years. It is not fully understood why a small proportion of patients develop progressive forms of ALD (e.g., fibrosis and cirrhosis). Differences in the metabolic processes could be behind the individual progression of ALD. Our aim was to examine differences in serum metabolome between patients with nonprogressive ALD and patients with an early form of progressive ALD.METHODS: The study had three study groups: progressive ALD (alcohol-related steatohepatitis or early-stage fibrosis, n = 50), nonprogressive ALD (simple steatosis, n = 50) and healthy controls (n = 32). Both ALD groups took part in a voluntary alcohol rehabilitation programme. A nontargeted metabolomics analysis and targeted analysis of short-chain fatty acids were done to the serum samples taken on the day of admission.RESULTS: We found 111 significantly (p < 0.0005) altered identified metabolites between the study groups. Our main finding was that levels of glycine-conjugated bile acids (Cohen's d = 0.90-0.91), glutamic acid (d = 1.01), 7-methylguanine (d = 0.77) and several phosphatidylcholines (d = 0.61-0.85) were elevated in the progressive ALD group in comparison to the nonprogressive ALD group. Glycine-conjugated bile acids, glutamic acid and 7-methylguanine also positively correlated with increased levels of aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transferase, cell death biomarker M65 and liver stiffness.CONCLUSIONS: Our results indicate that the enterohepatic cycle of glycine-conjugated bile acids, as well as lipid and energy metabolism, is altered in early forms of progressive ALD. These metabolic processes could be a target for preventing the progression of ALD.PMID:40358071 | DOI:10.1111/liv.70128

J Exp Bot. 2025 May 13:eraf201. doi: 10.1093/jxb/eraf201. Online ahead of print.ABSTRACTThe rice (Oryza sativa L.) α/β hydrolase D14 LIKE (D14L), a paralog of the strigolactone receptor D14, is essential for the establishment of arbuscular mycorrhizal (AM) symbiosis and responses to karrikins, smoke-derived compounds that regulate several developmental processes. It is supposed that D14L is the receptor for a yet unidentified endogenous growth regulator. Herein, we determined the effects of disrupting the D14L on rice growth and metabolism. Our results revealed that the D14L loss of function altered rice architecture, leading to a significant increase in root growth and mesocotyl elongation, while hindering shoot growth, and a notable decrease in the number of tillers, especially under phosphate limiting conditions. Furthermore, d14l mutants exhibited significant reduction in the total grain yield. Metabolomics analysis revealed a notable shift of key metabolites, such as carbohydrates and amino acids involved in energy production and growth, from shoots to roots. This redistribution likely reflects an adaptive strategy to enhance nutrient acquisition and increase root biomass, albeit at the cost of shoot growth and productivity. Our findings highlight the pivotal role of D14L in regulating the root-to-shoot growth ratio and in coordinating the metabolism and allocation of resources across the rice plant.PMID:40357891 | DOI:10.1093/jxb/eraf201

Phytother Res. 2025 May 13. doi: 10.1002/ptr.8520. Online ahead of print.ABSTRACTHigh fat diet (HFD) is closely linked to demyelination and cognitive deficiency. Previously, we reported that the covalent binding and downregulation of heterogeneous nuclear ribonucleoprotein A1 (HnRNPA1) were responsible for the effectiveness of celastrol against high fat diet (HFD) induced obesity. However, little is known about cognitive functions. This study aimed to evaluate the effectiveness and mechanism of celastrol on cognitive functions and demyelination in HFD mice. In HFD mice, the anti-cognitive dysfunction and anti-demyelination effects of celastrol and HnRNPA1-shRNA were evaluated by Morris water maze and luxol-fast-blue staining. Then, the common biological pathway of celastrol and HnRNPA1-shRNA was clarified by the transcriptomic and metabolomic analyses of amygdala tissue and verified in the amygdala and in cultured MO3.13 cells. Celastrol and HnRNPA1-shRNA alleviated cognitive impairments and amygdala demyelination in HFD mice. By transcriptome analysis, genes co-regulated by celastrol and HnRNPA1-shRNA were focused on the myelin generating cells-oligodendrocyte. Celastrol and HnRNPA1-shRNA alleviated oligodendrocyte differentiation disorder and myelin loss induced by HFD. Association analysis of metabolome and transcriptome indicated that the enhanced central transport and inhibited inactivation of thyroxine may underlie celastrol and HnRNPA1-shRNA mediated regulation of oligodendrocyte. In MO3.13 cells, celastrol mediated downregulation of HnRNPA1. In addition, the pro-maturation effects of celastrol and HnRNPA1-shRNA were confirmed by the downregulation of Dio3 and O1, as well as the upregulation of MBP. Through HnRNPA1-thyroxine axis, celastrol protects against HFD-induced demyelination and cognitive deficits.PMID:40357843 | DOI:10.1002/ptr.8520

Front Endocrinol (Lausanne). 2025 Apr 28;16:1427656. doi: 10.3389/fendo.2025.1427656. eCollection 2025.ABSTRACTBACKGROUND: Rosacea is a common chronic inflammatory skin disease. Limited studies reported the association between plasma lipidome and rosacea.METHODS: We employed a two-sample Mendelian randomization (MR) study to assess the causality between plasma lipidome and rosacea. Plasma lipidome association genome-wide association study (GWAS) data were collected. The inverse variance weighted (IVW) method was utilized as the principal method in our Mendelian randomization (MR) study; we also used the MR-Egger, weighted median, simple mode, and weighted mode methods. The MR-Egger intercept test, Cochran's Q test, MR-Pleiotropy RESidual Sum and Outlier (MR-PRESSO), and leave-one-out analysis were conducted to identify heterogeneity and pleiotropy.RESULTS: A total of 179 lipid species were analyzed; among them, five lipid species were closely related to rosacea. Two species of sterol ester [sterol ester (27:1/22:6) and sterol ester (27:1/15:0)], two species of phosphatidylethanolamine [phosphatidylethanolamine (O-18:2_20:4) and phosphatidylethanolamine (18:0_20:4)], and one species of sphingomyelin [sphingomyelin (d34:0)] were causally associated with rosacea (P < 0.05). All of them play protective roles in patients with rosacea. No heterogeneity or pleiotropy was observed.CONCLUSION: This study provided new evidence of the relationship between plasma lipidome and rosacea. Our MR suggested that five lipid species play protective roles in rosacea progression. These could be novel and effective ways to treat rosacea.PMID:40357208 | PMC:PMC12066300 | DOI:10.3389/fendo.2025.1427656

Food Res Int. 2025 Jun;211:116517. doi: 10.1016/j.foodres.2025.116517. Epub 2025 Apr 22.ABSTRACTIn this study, a semi-quantitative lipidomics approach was utilized to comprehensively delineate the alterations in the lipid profiles of sheep milk before and after fermentation. A total of 887 lipids were identified in both raw sheep milk (RM) and fermented sheep milk (FM), which could be systematically classified into 30 subclasses, with triglycerides, phosphatidylethanolamines, and phosphatidylcholines emerging as the predominant lipid types in both sample groups. In total, 91 significantly different lipids (SDLs) were selected between RM and FM. Compared to RM, 33 SDLs were up-regulated in FM, while 58 SDLs were down-regulated. Furthermore, based on fold change (FC) values, phosphatidylserines (PS (18:1_20:2) and PS (16:0_20:0)) and lysophosphatidylethanolamines (LPE (18:1/0:0) and LPE (0:0/16:0)) were selected as potential biomarkers for distinguishing between RM and FM. Further analysis revealed that 91 SDLs were involved in 39 metabolic pathways, with glycerophospholipid metabolism identified as the most crucial among them. These results provided comprehensive lipidomics data on sheep milk and its fermented milk, which are invaluable for investigations into the nutritional health benefits and flavor characteristics of fermented milk.PMID:40356153 | DOI:10.1016/j.foodres.2025.116517

J Sci Food Agric. 2025 May 13. doi: 10.1002/jsfa.14366. Online ahead of print.ABSTRACTBACKGROUND: Cocoa bean shell (CBS) extracts have emerged as a promising source of antimicrobial compounds. However, the bioactive compounds responsible for their antimicrobial activity have not been studied sufficiently. This study analyzed the antimicrobial properties of 12 extracts from fermented and non-fermented CBS, employing solvent and steam distillation extraction techniques to maximize bioactive diversity. The extracts were assessed against selected bacteria and fungi, including the 'ESKAPE' pathogens.RESULTS: The CBS solvent and steam distillation extracts (except for ethyl acetate-fermented CBS) were found to exhibit antimicrobial activity against Streptococcus mutans with minimum inhibitory concentrations (MICs) as low as 0.0625 mg mL-1, whereas both fermented and non-fermented steam distillation CBS extracts were found to be active against Candida albicans with MICs at 1 mg mL-1. Overall, steam distillation extracts possessed enhanced antimicrobial activity in comparison with solvent extracts of CBS. Fermented CBS extracts were found to possess better antimicrobial activity than non-fermented CBS extracts. Metabolomics analysis identified theobromine (TB) and tetramethylpyrazine (TMP) as molecules that contributed to antimicrobial activity against S. mutans. Results showed that caffeine (CAF), TB and TMP were active against S. mutans and Acinetobacter baumannii, whereas CAF and TB were active against C. albicans. Significant synergistic effects of CAF, TB, and TMP with ciprofloxacin (CIP) were observed against Klebsiella aerogenes.CONCLUSION: These findings highlight the significant potential of bioactive compounds present in CBS for use in the development of sustainable antimicrobial agents. These naturally occurring compounds, including CAF, TB, and TMP, exhibited notable antimicrobial properties, which could also be harnessed to enhance the activity of commonly used antibiotics such as ciprofloxacin. Future studies could focus on determining the mode of action of these bioactive molecules. © 2025 The Author(s). Journal of the Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.PMID:40357655 | DOI:10.1002/jsfa.14366

Front Cell Infect Microbiol. 2025 Apr 28;15:1513270. doi: 10.3389/fcimb.2025.1513270. eCollection 2025.ABSTRACTLung cancer is a significant health concern that poses a considerable threat to human health and quality of life. In order to enhance the prognosis of patients with lung cancer, we conducted a combined analysis of 16S rDNA gene sequencing of alveolar lavage fluid and LC-MS metabolomics research, with the objective of identifying biomarkers in patients with early-stage lung cancer presenting as SPN. A comparison of the benign nodule group and the early-stage lung cancer patients revealed that the phylum-level Bacteroidetes and the genus-level Chryseobacterium and Delftia were more abundant in the latter group. Additionally, the Fusobacteriales might serve as a predictive marker for the diagnosis of early-stage lung cancer. In the context of metabolomics, the early-stage lung cancer was found to be characterised by elevated levels of specific metabolites, including Alternariol, dTMP, Oxymatrine, Gedunin, PC 36:4. Conversely, reductions in other metabolites, such as LPC O-24:0, PC 18:2_18:3, PC 19:2_19:2, Cholecalciferol and T-2 Triol, were also observed. Correlation analyses demonstrated that alveolar lavage microorganisms were closely associated with differential metabolites. Specifically, reductions in Cholecalciferol were associated with a variety of high-abundance flora and involved in vitamin digestion and absorption pathways. Furthermore, reductions in cholecalciferol may serve as a robust predictor of early-stage lung cancer. These findings provide new predictive biomarkers for early-stage lung cancer manifested by SPN, which is clinically important and requires further study of the potential mechanisms of action and function of the targets.PMID:40357400 | PMC:PMC12066597 | DOI:10.3389/fcimb.2025.1513270

Front Genet. 2025 Apr 28;16:1587854. doi: 10.3389/fgene.2025.1587854. eCollection 2025.ABSTRACTThe hypoxia-ischemia (H-I) diseases share some common mechanisms which may help to delay the diseases' processing. However, the shared features are still unclear due to the lack of large scale high-quality multi - omics data that specifically target the same disease, population, and tissues/cells. In this study, we developed a novel risk assessment method to analyze four H-I diseases including eclampsia/preeclampsia (PE), pulmonary arterial hypertension (PAH), high-altitude polycythemia (HAPC), and ischemic stroke (IS). A combined new evaluation score was designed to integrate evaluation information from genomics, transcriptomics, proteomics, and metabolomics in previous researches. Genes were then divided into different groups according to their risk assessment score. The most significant group (direct biomarkers) contained genes with direct evidence of association to H-I disease: PIEZO2 and HPGD (shared), TSIX and SAA1 (PAH - specific), GSTM1, DNTT, and IGKC (HAPC - specific), LEP, SERPINA3, and ARHGEF4 (PE - specific), CD3D, ITK, and RPL18A (IS - specific). The groups 'Intermediate crucial biomarkers' contained genes played important roles in H-I disease related biological processes: CXCL8 (shared), HBG2, GRIN2A, and FGFBP1 (PAH - specific), FAM111B (HAPC - specific), C12orf39 and SLAMF1 (PE - specific). The genes lacking disease-association evidence but with similar characteristics with the above two groups were considered as 'potential minor-effect biomarkers': are SRRM2 - AS1 (shared), ATP8A1 (PAH - specific), RXFP1 and HJURP (HAPC - specific), HIST1H1T (PE - specific). With the development of biological experiments, these intermediate crucial and potential minor-effect biomarkers may be proved to be direct biomarkers in the future. Therefore, these biomarkers may serve as an entry point for subsequent research and are of great significance.PMID:40357364 | PMC:PMC12066567 | DOI:10.3389/fgene.2025.1587854

Front Med (Lausanne). 2025 Apr 28;12:1489100. doi: 10.3389/fmed.2025.1489100. eCollection 2025.ABSTRACTINTRODUCTION: The intricate pathogenesis of renal fibrosis necessitates identifying biomarkers at various stages to facilitate targeted therapeutic interventions, which would enhance patient survival rates and significantly improve prognosis.METHODS: We investigated the changes in gut microbiota and serum metabolites during the early, middle, and late stages of renal fibrosis in rats using 16S rDNA sequencing and UPLC-QTOF/MS-based metabolomics.RESULTS: We identified 5, 21, and 14 potential gut microbial markers and 19, 23, and 31 potential metabolic markers in the MOD1, MOD2, and MOD4 groups, respectively. Bifidobacterium was identified as a shared microbial marker between the MOD1 and MOD2 groups; Prevotellaceae_NK3B31_group and Bacteroides were identified as shared microbial markers between the MOD2 and MOD4 groups. The pathways of arachidonic acid metabolism and retinol metabolism were found to play a significant role in the modulation of renal fibrosis at 1, 2, and 4 weeks. Notably, the metabolic biomarkers 8,9-EET and 5(S)-HPETE within these pathways emerged as critical determinants influencing renal fibrosis.DISCUSSION: Our findings demonstrated that the severity of renal fibrosis is associated with dysbiosis of the gut microbiota and alterations in serum metabolites.PMID:40357302 | PMC:PMC12068064 | DOI:10.3389/fmed.2025.1489100

Front Vet Sci. 2025 Apr 28;12:1541257. doi: 10.3389/fvets.2025.1541257. eCollection 2025.ABSTRACTINTRODUCTION: MSTN is a well-studied inhibitor of skeletal muscle development, but its mechanism of affecting gut metabolites and the functions it exerts through this pathway are still unclear. This study aims to reveal how MSTN affects the metabolism process by regulating gut metabolites.METHODS: Combined analysis of jejunal contents metabolome and jejunal tissue transcriptome was used to compare the differences in intestinal metabolites and intestinal tissue gene expression between MSTN mutant and wild-type bovines.RESULTS: Metabolomic analysis identified that compared to wild-type bovine, the abundance of 304 metabolites were significantly changed in MSTN mutant cattle including 142 upregulated and 162 downregulated. Transcriptome results showed that the expression level of 1541 genes were influenced by MSTN disruption, including 536 upregulated genes and 1005 downregulated genes, which were categorized into 311 KEGG signaling pathways, primarily related to disease and metabolism. Correlation analysis results suggested a notable cross-regulation between the transcript levels of some specific genes in jejunal tissues and the abundance of jejunal metabolites, represented by fatty metabolites and genes associated with fatty acid degradation, synthesis and elongation.DISCUSSION: Collectively, the result of this study indicated that MSTN gene mutation led to alterations in gut microbial metabolites by increasing the abundance of beneficial monounsaturated fatty acids (MUFAs) such as oleic acid, then to promote fatty acid degradation while inhibiting its synthesis by regulating the expression levels of relevant genes. These results provide a foundation for understanding the effects of MSTN gene mutations on gut metabolites and its certain functions that MSTN regulated via gut metabolites.PMID:40357198 | PMC:PMC12066744 | DOI:10.3389/fvets.2025.1541257

Adv Redox Res. 2025 Mar;14:100122. doi: 10.1016/j.arres.2025.100122. Epub 2025 Feb 11.ABSTRACTBACKGROUND: Cigarettes and electronic cigarettes generate many redox-active materials which could impact children's health through second-hand exposures. High-resolution metabolomics methods enable use of non-targeted mass spectrometry of plasma to test for redox consequences of second-hand exposures.OBJECTIVES: Our objectives were to test for oxidative stress metabolites and altered metabolic pathways associated with second-hand exposure to redox-active flavorants and flavorant metabolites in plasma of infants and children.METHODS: Untargeted plasma metabolomics data for infants and children in a population known to include individuals with second-hand exposures to cigarettes and electronic cigarettes were analyzed for cotinine and metabolites of flavorants. A metabolome-wide association study (MWAS) was performed separately for cotinine and menthol glucuronide, derived from the redox-active flavorant, menthol. Pathway enrichment analysis was used to identify metabolic pathways, and xMWAS was used to detect metabolic communities associated with flavorant metabolites.RESULTS: Menthol glucuronide was one of several flavorant metabolites positively correlated with cotinine. MWAS and pathway enrichment analysis revealed that some pathways associated with both menthol glucuronide and cotinine, while others only associated with menthol glucuronide, including sphingolipid, glycerophospholipid, antioxidant, N-glycan and mitochondrial energy metabolism. 4-hydroxynonenal and other oxidized lipids positively correlated with menthol glucuronide.DISCUSSION: The results show that flavorants from second-hand electronic cigarette and cigarette exposures in infants and children are associated with changes in redox metabolism which are known to associate with human lung diseases.PMID:40357186 | PMC:PMC12068848 | DOI:10.1016/j.arres.2025.100122

Front Plant Sci. 2025 Apr 28;16:1489918. doi: 10.3389/fpls.2025.1489918. eCollection 2025.ABSTRACTINTRODUCTION: Lilium cernuum, a fragrant purple-red wild lily endemic to Northeast Asia, represents both ecological significance (as a key protected species) and horticultural value. While its white variant (L. cernuum var. album) exhibits distinct flower color and fragrance traits, the molecular mechanisms underlying these variations remain poorly understood. Previous studies attributed the low anthocyanin content in the white variant to LcMYB12 downregulation, yet comprehensive analyses of associated genes and metabolic pathways are lacking.METHODS: This study employed integrated transcriptomics, metabolomics, and volatile metabolomics to systematically compare L. cernuum and its white variant. We analyzed differential gene expression in the phenylpropanoid and flavonoid biosynthesis pathways, quantified anthocyanin/flavonoid metabolites, and assessed volatile organic compound profiles.RESULTS: The white variant showed significant reductions in flavonoids (catechin, epicatechin) and anthocyanins (cyanidin, pelargonidin, peonidin), linked to the downregulation of 58 genes in the flavonoid pathway-including PAL, C4H, 4CL, and UFGT. Critically, UFGT suppression disrupted anthocyanin glycosylation, promoting degradation and vacuolar accumulation failure. Concurrently, phenylpropanoid pathway inhibition reduced p-coumaric acid synthesis, diminishing downstream anthocyanins and volatile compounds (eugenol/methyleugenol).DISCUSSION: Our multi-omics approach reveals that flower color loss in L. cernuum var. album results from synergistic effects of transcriptional regulation and metabolic flux redirection. The UFGT-mediated glycosylation defect provides a novel explanation for anthocyanin instability in white petals. These findings complement prior genetic studies and establish a framework for targeted breeding of ornamental traits in Lilium species.PMID:40357149 | PMC:PMC12066478 | DOI:10.3389/fpls.2025.1489918

Front Pharmacol. 2025 Apr 28;16:1482323. doi: 10.3389/fphar.2025.1482323. eCollection 2025.ABSTRACTINTRODUCTION: Phlomoides rotata (Benth. ex Hook.f.) Mathiesen (syn. Lamiophlomis rotata (Benth. ex Hook.f.) Kudô) (P. rotate) is a traditional Tibetan medicine known for its hemostatic, analgesic, and anti-inflammatory effects, as well as its high content of 8-O-Acetyl Shanzhiside methyl ester (8-OaS). Clinical and experimental studies have reported gastrointestinal side effects, such as diarrhea, loose stools, even to black stools, associated with P. rotata. Given the bitter taste characteristic, laxative and antipyretic effects of iridoid glycosides, this study aims to investigate the antipyretic and anti-inflammatory effects of 8-OaS (the primary iridoid glycosides of P. rotate) on yeast-induced pyrexia in rats. Additionally, the role 8-OaS in modulating the intestinal flora composition and metabolome profile is explored.METHODS: The pyretic rat model was established by injected subcutaneously with 20% dry yeast suspension. Serum, hypothalamic tissues and colon content were collected for the assessment of relevant indicators. The peripheral inflammatory factors and central thermoregulatory mediators were assessed using enzyme-linked immunosorbent assay (ELISA). The expressions of mRNA and protein in hypothalamic tissue were evaluated through polymerase chain reaction (PCR), immunohistochemistry, and western blotting. 16S rDNA sequencing and LC-MS/MS were performed to determine the alteration and correlation of the intestinal flora and neurotransmitters in the colonic contents and hypothalamus.RESULTS AND DISCUSSION: Results show that 8-OaS treatment reduced pyrogenic cytokines (such as IL-6, IL-1β), and down-regulated the level of central thermoregulatory mediators (PGE2), via multiply involved in TLR4/NF-κB and HSP70/NF-κB signaling pathways. Crucially, 8-OaS treatment significantly reduced the relative abundance of Alistipes (P < 0.01), Odoribacter (P < 0.05) and Alistipes_finegoldii (P < 0.05) in the intestinal flora. The correlation analysis demonstrated that 8-OaS treatment significantly correlated with the increasing on the abundance of Alistipes and levels of 5-hydroxytryptamine (P < 0.01), and tryptamine (P < 0.01). Our findings indicate that 8-OaS exhibits significant antipyretic and anti-inflammatory properties, potentially mediated by intestinal flora and metabolites of neurotransmitters. The results of this study may help to elucidate the antipyretic and anti-inflammatory mechanism of 8-OaS based on intestinal flora and metabolomics analysis.PMID:40356990 | PMC:PMC12066650 | DOI:10.3389/fphar.2025.1482323