PubMed

Int J Mol Sci. 2025 Mar 25;26(7):2970. doi: 10.3390/ijms26072970.ABSTRACTChaga (Inonotus obliquus) is an increasingly used natural product in botanical dietary supplements, valued for its bioactive compounds. However, inconsistent standardized analytical methods raise concerns over product authenticity, mislabeling, and quality control. This study employs a multi-analytical approach to differentiate wildcrafted chaga canker from North American chaga dietary supplements, particularly those containing mycelia fermented grain products. High-Performance Thin-Layer Chromatography (HPTLC), Liquid Chromatography with Evaporative Light Scattering Detection (LC-ELSD) or Photo/Diode Array Detection (LC-PDA/DAD), Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry (LC-QToF-MS), Nuclear Magnetic Resonance (NMR) spectroscopy, UV-Vis spectrophotometry, and iodine-starch assays were used to evaluate key markers, including triterpenoids, polysaccharides, and melanin. Whole chaga canker contained triterpenoids (inotodiol, trametenolic acid) and phenolics, like osmundacetone, while melanin absorbance at 500 nm differentiated it from fermented grain products. β-Glucan quantification and iodine-starch assays confirmed starch-rich composition in fermented grains and its absence in authentic chaga canker. NMR fingerprinting and LC-QToF-MS metabolomics demonstrated stark compositional deviations between wildcrafted chaga canker, I. obliquus mycelium, and fermented grain products. By integrating complementary techniques, we establish a framework that can reliably distinguish genuine chaga canker from misrepresented products, ensuring consumer safety and fostering trust in the functional mushroom, canker, and mycelium markets.PMID:40243601 | DOI:10.3390/ijms26072970

Int J Mol Sci. 2025 Mar 21;26(7):2856. doi: 10.3390/ijms26072856.ABSTRACTIn recent years, there have been many studies on the response of plants to heavy metal stress, but the metabolic changes in bryophytes, pioneer plants quickly responding to environmental changes, under exogenous cadmium (Cd) stress have yet to be explored. In this indoor experiment, the responses in the metabolome of bryophyte Tortella tortuosa (Hedw.) Limpr. to different Cd exposure levels (0 (CK), 5 (T1), and 10 (T2) mg·L-1) were analyzed. The results showed that the number of differentially accumulated metabolites (DAMs) secreted by T. tortuosa increased with the increase in the Cd concentration, and the biosynthesis of cofactors, D-Amino acid metabolism, Arginine biosynthesis, ATP-binding cassette transporters (ABC transporters), and biosynthesis of alkaloids derived from shikimate pathway were the main pathways enriched by DAMs. The relative abundances of malic acid, N-Formylkynurenine, L-Glutamine, L-Histidine, LL-2,6-Diaminopimelic acid, and fusaric acid in the T2 treatment increased by 16.06%, 62.51%, 14.51%, 11.92%, 21.37%, and 35.79%, respectively (p < 0.05), compared with those of the CK, and the correlation analysis results showed that the above DAMs were closely related to the changes in plant antioxidant enzyme activity and Cd concentration. These results indicate that the secretion of amino acid (N-Formylkynurenine, L-Histidine) and organic acids (isocitric acid, LL-2,6-Diaminopimelic acid, malic acid) through the metabolic pathways, including biosynthesis of amino acids, biosynthesis of cofactors, glyoxylate and dicarboxylate metabolism, and ABC transporters, is the metabolic mechanism of T. tortuosa to resist exogenous Cd stress. This study will provide a reference for the monitoring and remediation of heavy metal pollution.PMID:40243446 | DOI:10.3390/ijms26072856

Int J Mol Sci. 2025 Mar 21;26(7):2862. doi: 10.3390/ijms26072862.ABSTRACTChronic kidney disease (CKD) has become one of the most rapidly advancing diseases of the century, contributing significantly to increased mortality and morbidity. Metabolomics presents a promising approach to understanding CKD pathogenesis and identifying novel biomarkers for early diagnosis. This study evaluated serum and urine metabolomic profiles in CKD patients with declining glomerular filtration rates (eGFR). Using targeted metabolomics, we quantified seven potential metabolites in blood and urine samples from 20 healthy individuals and 99 CKD patients staged by eGFR according to the KDIGO guidelines. The analysis was conducted using ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry. The metabolites investigated included L-phenylalanine, L-methionine, arginine, indoxyl sulfate, kynurenic acid, and L-acetylcarnitine. Quantitative assessments were performed using pure standards and validated through methods such as the limit of detection (LOD) and limit of quantification (LOQ). The findings identified potential biomarkers for early CKD diagnosis: in serum, L-phenylalanine, L-methionine, arginine, kynurenic acid, and indoxyl sulfate, while L-acetylcarnitine was significant in urine. These biomarkers could provide valuable insights into CKD progression and support in developing more effective diagnostic tools for early intervention.PMID:40243426 | DOI:10.3390/ijms26072862

Int J Mol Sci. 2025 Mar 21;26(7):2843. doi: 10.3390/ijms26072843.ABSTRACTThe heat shock response (HSR) is a conserved cellular mechanism critical for adaptation to environmental and physiological stressors, with broad implications for cell survival, immune responses, and cancer biology. While the HSR has been extensively studied at the proteomic and transcriptomic levels, the role of lipid metabolism and membrane reorganization remains underexplored. Here, we integrate mass spectrometry-based lipidomics with RNA sequencing to characterize global lipidomic and transcriptomic changes in HeLa cells exposed to three conditions: control, heat shock (HS), and HS with eight hours of recovery. Heat shock-induced extensive lipid remodeling, including significant increases in fatty acids, glycerophospholipids, and sphingolipids, with partial normalization during recovery. Transcriptomic analysis identified over 2700 upregulated and 2300 downregulated genes under heat shock, with GO enrichment suggesting potential transcriptional contributions to lipid metabolism. However, transcriptional changes alone did not fully explain the observed lipidomic shifts, suggesting additional layers of regulation. Joint pathway analysis revealed enrichment in glycerophospholipid and sphingolipid metabolism, while network analysis identified lipid transport regulators (STAB2, APOB), stress-linked metabolic nodes (KNG1), and persistent sphingolipid enrichment during recovery. These findings provide a comprehensive framework for understanding lipid-mediated mechanisms of the HSR and highlight the importance of multi-omics integration in stress adaptation and disease biology.PMID:40243420 | DOI:10.3390/ijms26072843

Int J Mol Sci. 2025 Mar 21;26(7):2841. doi: 10.3390/ijms26072841.ABSTRACTPerilla frutescens (Perilla) has great potential for utilization in food and medicine due to the abundance of secondary metabolites, especially phenolic compounds. However, the molecular mechanism underlying phenolic compound synthesis in perilla remains poorly understood. By targeted metabolome analysis, we found nine differentially accumulated metabolites among QS2, QS6, and QO7 leaves and nine unique metabolites which only exist in QS6. Furthermore, transcriptome analysis showed the differential expression genes (DEGs) were significantly enriched into phenylpropanoid- and flavonoid-related pathways. Moreover, the integrated transcriptome and metabolome analyses indicated 14 candidates highly correlated with phenolic compound biosynthesis. In addition, phenylpropanoid- and flavonoid-biosynthesis-related DEGs, including one PAL, one CYP73A, one 4CL, two CHI, two F3H, one FLS, three CHS, two CYP75B1, one ANS, and two DFR, were isolated. The results in this study provide useful information for the metabolic regulation of phenolic compounds and serve as essential gene resources for future breeding programs.PMID:40243409 | DOI:10.3390/ijms26072841

Int J Rheum Dis. 2025 Apr;28(4):e70206. doi: 10.1111/1756-185X.70206.ABSTRACTOBJECTIVE: Macrophages, as participants of innate and cellular immunity, play an important role in RA disease. However, whether Saussurea involucrata injection (SII) can regulate the polarization of macrophages and influence the development of RA remains unclear.METHOD: The cells of M0, M1, M1SII, M2, and M2SII groups were analyzed by transcriptome and untargeted metabolic sequencing. Differentially expressed mRNAs(DE-mRNAs), and differential metabolites were screened. GO and KEGG enrichment analysis of DE-mRNAs and differential metabolites was performed.RESULTS: We first screened 3836 DE-mRNAs and 100 metabolites in the M0 and M1 groups. A total of 4588 DE-mRNAs and 30 metabolites were screened in the M1 and M2 groups. Besides, a total of 1529 DE-mRNAs and 38 metabolites were screened in the M1 and M1SII groups. DE-mRNAs enriched GO and KEGG entries between M0 and M1 groups showed TNF signaling pathway, ECM-receptor interaction and PI3K-Akt signaling pathway, etc. The pathways of differentially enriched metabolites include Tryptophan metabolism, Secondary bile acid biosynthesis, etc. DE-mRNAs enriched GO and KEGG entries between M1 and M2 groups showed positive regulation of cell adhesion, JAK-STAT signaling pathway, and Chemokine signaling pathways. Differential metabolites are enriched in Metabolic pathways, Bile secretion, and Tryptophan metabolism. DE-mRNAs enriched GO and KEGG entries between M1 and M1 SII groups include cell adhesion molecule binding, ECM-receptor interaction and PI3K-Akt signaling pathway. Differential metabolite enrichment pathways include Neuroactive ligand-receptor interaction and dicarboxylate metabolism, etc. CONCLUSION: Through transcriptome and untargeted metabolomics sequencing analysis, we found that the mechanism of action of SII in the treatment of RA disease may be related to the regulation of macrophages. Importantly, it was found that the TGF-β signaling pathway, PI3K-Akt signaling pathway, Glyoxylate and dicarboxylate metabolism may be closely related to SII regulation of M1 macrophages for RA treatment.PMID:40243382 | DOI:10.1111/1756-185X.70206

United European Gastroenterol J. 2025 Apr 17. doi: 10.1002/ueg2.70025. Online ahead of print.ABSTRACTBACKGROUND: Chronic pancreatitis is a risk factor for pancreatic cancer. Autoimmune pancreatitis is a unique form of chronic pancreatitis that is primarily characterized by its immune mediate etiology, clinically resembling pancreatic cancer, yet uniquely responsive to steroid treatment.OBJECTIVE: Early and accurate diagnosis of autoimmune pancreatitis is vital for effective treatment and patient prognosis, for which new diagnostic tools are urgently required. Gut microbiota dysbiosis has been identified to correlate with the development of pancreatic diseases, which provides new opportunities for the discovery of disease biomarkers.METHODS: We utilized a mass spectrometric global metabolomics investigation of patient autoimmune pancreatitis and chronic pancreatitis fecal samples, investigating microbiome, dietary and human metabolism.RESULTS: We discovered a series of newly identified metabolic signatures between both patient groups including enterolactone, 4-guanidinobutanoic acid, and methylthioadenosine sulfoxide. Additionally, the analysis revealed significant differences in several metabolic pathways such as fatty acids, alkaloids, amino acids and peptides.CONCLUSION: Our observations provide novel insights into important metabolic human pathways and microbiome-derived metabolites to distinguish autoimmune pancreatitis from chronic pancreatitis. These findings reveal systemic metabolic responses and the identified metabolites may be developed into potential biomarkers for future diagnosis to distinguish between autoimmune pancreatitis and chronic pancreatitis.PMID:40243134 | DOI:10.1002/ueg2.70025

J Psychopharmacol. 2025 Apr 17:2698811251332838. doi: 10.1177/02698811251332838. Online ahead of print.ABSTRACTBACKGROUND: The amino acid L-alanine, has been shown to be elevated in biofluids during major depression but its relevance remains unexplored.AIM: We have investigated the effects of repeated L-alanine administration on emotional behaviours and central gene expression in mice.METHODS: Mice received a daily, 2-week intraperitoneal injection of either saline or L-alanine at 100 or 200 mg/kg and were exposed to the open field, light-dark box and forced swim test. The expression of L-alanine transporters (asc-1, ASCT2), glycine receptor subunits (GlyRs), NMDA receptor subunits (GluNs) mRNAs were measured, together with western blots of the signalling protein mammalian target of rapamycin (mTOR). Since L-alanine modulates glucose homeostasis, peripheral and central metabolomes were evaluated with 1H-NMR.RESULTS: L-alanine administration at 100 mg/kg, but not at 200 mg/kg, to both male and female mice increased latency to float and reduced floating time in the forced swim test, but had no effect on anxious behaviour in the open field and light-dark box tests. There was a significant reduction in mRNAs encoding asc-1 and ASCT2 and GluN2B in the hippocampus of mice following 100 mg/kg L-alanine only. On western blots, hippocampal GluN2B immunoreactivity was reduced, but mTOR signalling was increased in the 100 mg/kg L-alanine group. 1H-NMR revealed gender-specific changes in the forebrain, plasma and liver metabolomes only at 200 mg/kg of L-alanine.CONCLUSIONS: Our data suggest that L-alanine may have antidepressant-like effect that may involve the modulation of glutamate neurotransmission independently of metabolism. In major depression, therefore, elevated L-alanine may be a homeostatic response to pathophysiological processes, though this will require further investigation.PMID:40242990 | DOI:10.1177/02698811251332838

Int J Mol Med. 2025 Jun;55(6):92. doi: 10.3892/ijmm.2025.5533. Epub 2025 Apr 17.ABSTRACTOsteosarcoma, the most prevalent primary bone malignancy in children and adolescents, poses significant challenges due to its aggressive nature and propensity for metastasis. Despite advances in treatment, survival rates for high‑risk patients remain unsatisfactory, underscoring the urgent need for innovative approaches. This review explores the vital role of multi‑omics‑integrating genomics, transcriptomics, proteomics and metabolomics‑in unraveling the complex biological landscapes of osteosarcoma. By providing comprehensive insights into tumor heterogeneity, signaling pathways and metabolic reprogramming, multi‑omics facilitates the identification of novel biomarkers and therapeutic targets. The objective of the present study was to highlight the transformative potential of multi‑omics in enhancing the understanding and management of osteosarcoma, ultimately paving the way for personalized treatment strategies and improved patient outcomes. Through this synthesis, the study calls for a concerted effort to integrate multi‑omics into clinical practice, fostering a more precise approach to osteosarcoma care.PMID:40242955 | DOI:10.3892/ijmm.2025.5533

JID Innov. 2025 Mar 8;5(3):100361. doi: 10.1016/j.xjidi.2025.100361. eCollection 2025 May.ABSTRACTAtopic dermatitis (AD) is an inflammatory skin disease characterized by chronic pruritic eczema with an estimated prevalence of 10% in adults and 50% of them suffering from moderate-to-severe manifestations. Dupilumab, an IL-4/IL-13 inhibitor, is approved for treating moderate-to-severe AD. However, dupilumab-associated ocular surface disease (DAOSD) emerges in up to 60% of dupilumab-treated patients, constituting a major AD-specific adverse event. DAOSD pathogenesis has not been fully understood yet. To elucidate the metabolic changes occurring after dupilumab treatment in patients with AD, we focused in this prospective single-center cohort study particularly on patients who developed DAOSD. In total, 20 patients with AD underwent dupilumab therapy, with 6 developing DAOSD. Plasma and serum samples were collected at baseline, 4 and 16 weeks after treatment initiation, and during the conjunctivitis episode. In addition, 10 age- and sex-matched healthy controls were sampled solely at baseline. High-resolution mass spectrometry was employed for metabolomic and lipidomic analysis of all blood samples. Targeted metabolomics and lipidomic with multivariate analysis unveiled significant metabolic and lipidic disparities (such as increased activity of benzoic acid, tyrosine and indole metabolism, and others) between AD patients with and those without DAOSD. Metabolomics and lipidomic analysis further deepen our comprehension of DAOSD pathogenesis.PMID:40242789 | PMC:PMC12002936 | DOI:10.1016/j.xjidi.2025.100361

Front Immunol. 2025 Apr 2;16:1545976. doi: 10.3389/fimmu.2025.1545976. eCollection 2025.ABSTRACTBACKGROUND: Unlike lung adenocarcinoma, patients with advanced squamous carcinoma exhibit a low proportion of driver gene positivity, with fewer effective treatment strategies available. Chemoimmunotherapy has now become the standard first-line treatment for individuals diagnosed with advanced lung squamous carcinoma. Serum metabolomics holds significant potential for application in predicting responses to chemoimmunotherapy and is capable of identifying and validating potential biomarkers. The aim of our study was to establish a model that can predict the prognosis of chemoimmunotherapy in patients with advanced lung squamous cell carcinoma, integrating metabolomics with machine learning techniques.METHODS: We collected 79 serum samples from patients with advanced lung squamous cell carcinoma before receiving combined immunotherapy and performed untargeted metabolomics analysis. Patients were divided into non-response (NR) and response (R) groups according to overall survival (OS), and prognostic models were constructed and validated using different machine learning methods. The patients were further categorized into high-risk and low-risk groups based on the median risk score, to assess the model's predictive performance.RESULTS: There were significant differences in metabolites and metabolic pathways between NR and R groups, and 117 differential metabolites were preliminarily screened (p < 0.05, VIP > 1). Further, least absolute shrinkage and selection operator (LASSO) and random forest (RF) were used to identify metabolites, and then their common metabolites were used as the best biomarkers to build a prediction model containing 8 differential metabolites. Based on these biomarkers, RF, support vector machine (SVM) and logistic regression were used to randomly divide patients into training and validation sets in a 7:3 ratio, respectively. We found that the RF method resulted in area under curves (AUCs) of 0.973 and 0.944 for the training and validation sets, respectively, with the best predictive performance. Subsequently, both OS and progression-free survival (PFS) were notably reduced in the high-risk group when contrasted with the low-risk group.CONCLUSIONS: We developed a model containing 8 metabolites based on metabolomics and machine learning that may predict survival outcomes in patients with advanced lung squamous cell carcinoma undergoing chemoimmunotherapy, helping to more accurately assess efficacy and prognosis in clinical practice.PMID:40242771 | PMC:PMC12000773 | DOI:10.3389/fimmu.2025.1545976

Front Genet. 2025 Apr 2;16:1528935. doi: 10.3389/fgene.2025.1528935. eCollection 2025.ABSTRACTHigh-altitude polycythemia (HAPC) represents a pathological escalation of the physiological erythrocytosis induced by chronic hypoxia exposure. While moderate erythroid expansion enhances oxygen delivery, HAPC manifests as hematologic disorder characterized by hemoglobin thresholds (≥21 g/dL males; ≥19 g/dL females) and multi-organ complications including microcirculatory thrombosis, right ventricular hypertrophy, and uric acid dysmetabolism. This review critically evaluates the continuum between adaptive and maladaptive polycythemia through multiscale analysis of erythrocyte biology. We integrate genomic predisposition patterns, bone marrow erythroid kinetic studies, and peripheral erythrocyte pathophenotypes revealed by multi-omics profiling (iron-redox proteome, hypoxia-metabolome crosstalk). Current diagnostic limitations are highlighted, particularly the oversimplification of hemoglobin cutoffs that neglect transitional dynamics in erythrocyte turnover. By reconstructing the erythroid life cycle-from hypoxia-sensitive progenitor commitment to senescent cell clearance-we propose a phase transition model where cumulative epigenetic-metabolic derangements overcome homeostatic buffers, triggering pathological erythroid amplification. These insights reframe HAPC as a systems biology failure of erythroid adaptation, informing predictive biomarkers and targeted interventions to preserve hematological homeostasis in hypoxic environments.PMID:40242475 | PMC:PMC12000012 | DOI:10.3389/fgene.2025.1528935

Eco Environ Health. 2025 Mar 3;4(2):100140. doi: 10.1016/j.eehl.2025.100140. eCollection 2025 Jun.ABSTRACTEvaluating the plant risk of soil pollution by plant physiological indices usually requires a long cycle and has significant uncertainty. In this study, oxidative potential (OP) of the in situ heavy metal contaminated soils was measured by the dithiothreitol method. The oxidative stress response of the model plant ryegrass (Lolium perenne L.) induced by heavy metal contaminated soil was evaluated by the biomarkers, including superoxide dismutase and total antioxidant capacity. The comprehensive biomarker response index has a significant exponential correlation with the OP of soil (r ​= ​0.923, p ​< ​0.01) in ryegrass. Metabolomics analysis also showed a significant relationship of the metabolic effect level index of amino acids and sugars with OP. Random forest was selected from four machine learning models to screen the metabolites most relevant to OP, and Shapley additive explanations analysis was used to explain the contribution and the influence direction of the features on the model. Based on the selected 20 metabolites, the metabolic pathways most related to OP in plants, including alkaloid synthesis and amino acids metabolism, were identified. Compared to the plant physiological indices, OP is a more stable and faster indicator for the plant risk assessment of heavy metals contaminated soil.PMID:40242345 | PMC:PMC12002993 | DOI:10.1016/j.eehl.2025.100140

Comput Struct Biotechnol J. 2025 Apr 3;27:1440-1448. doi: 10.1016/j.csbj.2025.04.004. eCollection 2025.ABSTRACTThe generation of omics data sets has become an important approach in modern pharmacological and toxicological research as it can provide mechanistic and quantitative information on a large scale. Analyses of these data frequently revealed a non-linear dose-response relationship underscoring the importance of the modeling process to infer biological exposure limits. A number of tools have been developed for dose-response modeling and various thresholds have been defined as a quantitative representation of the effect of a substance, such as effective concentrations or benchmark doses (BMD). Here we present DoseRider an easy-to-use web application and a companion R package for linear and non-linear dose-response modeling and assessment of BMD at the level of biological pathways or signatures using generalized mixed effect models. This approach allows to analyze custom or provided multi-omics data such as RNA sequencing or metabolomics data and its annotation of a collection of pathways and gene sets from various species. Moreover, we introduce the concept of the trend change doses (TCDs) as a numerical descriptor of effects derived from complex dose-response curves. The usability of DoseRider was demonstrated by analyses of RNA sequencing data of bisphenol AF (BPAF) treatment of a human breast cancer cell line (MCF-7) at 8 different concentrations using gene sets for chemical and genetic perturbations (MSigDB). The BMD for BPAF and a set of genes upregulated by estrogen in breast cancer was 0.2 µM (95 %-CI 0.1-0.5 µM) and the lowest TCD (TCD1) was 0.003 µM (95 %-CI 0.0006-0.01 µM). The comprehensive presentation of the results underlines the suitability of the system for pharmacogenomics, toxicogenomics, and applications beyond.PMID:40242291 | PMC:PMC12001094 | DOI:10.1016/j.csbj.2025.04.004

Front Oncol. 2025 Apr 2;15:1548146. doi: 10.3389/fonc.2025.1548146. eCollection 2025.ABSTRACTBACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare and highly aggressive form of non-Hodgkin lymphoma, primarily confined to the central nervous system. In recent years, growing evidence has indicated that dysbiosis of the gut microbiota is closely associated with the development of various malignancies. This study aims to systematically explore the potential role of gut microbiota and their metabolic pathways in the pathogenesis of PCNSL by integrating metagenomic and metabolomic approaches.MATERIALS AND METHODS: A total of 33 PCNSL patients and 32 healthy controls were enrolled in this study, and fecal samples were collected from each participant. The fecal samples were analyzed using metagenomic and metabolomic techniques, followed by KEGG pathway enrichment analysis to investigate the biological pathways enriched by the differential gut microbiota and metabolites.RESULTS: Significant differences were observed in the composition of gut microbiota and metabolites between PCNSL patients and healthy controls. In the gut microbiota of PCNSL patients, the abundance of the phylum Proteobacteria was markedly increased, while the Firmicutes/Bacteroidetes (F/B) ratio was significantly elevated. Metabolomic analysis revealed that the abundance of oleamide was significantly reduced in the PCNSL group, while the relative abundance of deoxycholic acid was significantly elevated. KEGG pathway analysis indicated that the differential gut microbiota and metabolites were primarily involved in key metabolic pathways such as nitrogen metabolism, phenylalanine metabolism, purine metabolism, and pyrimidine metabolism, with these pathways being more active in PCNSL patients.CONCLUSION: This study is the first to systematically investigate the differences in gut microbiota and their metabolites between PCNSL patients and healthy individuals, highlighting the potential role of gut microbiota alterations in the pathogenesis of PCNSL.PMID:40242244 | PMC:PMC12000031 | DOI:10.3389/fonc.2025.1548146

Gastro Hep Adv. 2024 Dec 31;4(4):100606. doi: 10.1016/j.gastha.2024.100606. eCollection 2025.ABSTRACTBACKGROUND AND AIMS: The Mediterranean diet pattern (MDP) is associated with health-associated gut microbes and metabolites. However, the impact of the MDP on the fecal metabolome in ulcerative colitis (UC) remains unclear. We characterized the fecal metabolome of patients with UC with high adherence to the MDP compared to the Canadian habitual diet (CHD). Furthermore, we explored potential differences in the fecal metabolome between dietary responders and nonresponders to the MDP.METHODS: Utilizing untargeted metabolomics on a subset of fecal samples obtained from a randomized controlled trial, adult patients with quiescent UC underwent a 12-week intervention following either the MDP (n = 8) or CHD (n = 8). Liquid chromatography-tandem mass spectrometry was employed to profile endogenous fecal metabolites, while 16S amplicon sequencing was utilized to profile the fecal microbiota.RESULTS: A total of 701 human metabolites were detected, with 35 exhibiting significant differential expression between the MDP and CHD groups. Noteworthy, folate biosynthesis, sphingolipid biosynthesis, and steroid biosynthesis were identified as major pathways affected. Moreover, microbial analysis showed that individuals with increased levels of the class Bacteroidia (Bacteroides vulgatus [B. vulgatus], B. uniformis, and B. acidifaciens) in their stool at baseline were more likely to respond to the MDP.CONCLUSION: High adherence to an MDP is associated with beneficial metabolite changes associated with reducing inflammation in UC. In addition, fiber-degrading microbes abundant before dietary intervention played a role in the responsiveness to the MDP. This work lays the groundwork for developing a metabolic signature associated with the MDP to develop personalized nutrition strategies for UC prevention and treatment. ClinicalTrials.gov Number: NCT03053713.PMID:40242173 | PMC:PMC12001123 | DOI:10.1016/j.gastha.2024.100606

Front Cell Infect Microbiol. 2025 Apr 2;15:1541289. doi: 10.3389/fcimb.2025.1541289. eCollection 2025.ABSTRACTBACKGROUND: Clinically, Qing-Re-Hua-Shi Decoction (QRHSD) has been clinically used to treat ulcerative colitis (UC) with satisfactory outcomes and minimal side effects. However, its molecular mechanisms remain unclear.PURPOSE: This study investigates the effects of QRHSD on DSS-induced colitis in mice, employing multi-omics analyses, including RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology analysis.METHODS: The chemical composition of QRHSD was analyzed using quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). A UC mice model was induced by 3% DSS for 7 days. The effects and mechanisms of QRHSD on UC were evaluated via hematoxylin and eosin, immunofluorescence assay, flow cytometry, western blot, RNA-seq transcriptomics, 16S rRNA microbiomics, non-targeted metabolomics, and network pharmacology. Correlation analyses and validation experiments explored links between transcriptomic, microbiome, metabolomic profiles, and UC-related clinical indices.RESULTS: UPLC-Q-TOF/MS identified 55 compounds in QRHSD. QRHSD significantly reduced clinical activity, histological changes, and inflammatory factors in UC mice, regulated Th17/Treg balance, and enhanced intestinal barrier integrity. 16S rRNA analysis showed that QRHSD altered gut microbiota composition, increasing beneficial bacteria (e.g., Lactobacillus) and decreasing harmful bacteria (e.g., Morganella). Non-targeted metabolomics revealed 507 metabolites associated with UC amelioration, enriched in pathways like bile secretion, ABC transporters, and amino acid biosynthesis. RNA-seq analysis, network pharmacology, and experimental verification showed that QRHSD significantly regulated key signaling pathways, including PI3K/AKT, NF-κB, and MAPK signaling pathways. Finally, correlation analysis highlighted connections among UC-related clinical factors, gut microbiota, and metabolites.CONCLUSION: QRHSD could modulate the gut microbiota, metabolic homeostasis, and multiple signal pathways in the treatment of DSS-induced UC, revealing the mechanism of traditional Chinese medicine therapy for UC.PMID:40242025 | PMC:PMC11999956 | DOI:10.3389/fcimb.2025.1541289

Front Plant Sci. 2025 Apr 2;16:1478061. doi: 10.3389/fpls.2025.1478061. eCollection 2025.ABSTRACTINTRODUCTION: Tetrastigma hemsleyanum Diels et Gilg is a medicinal plant known for its diverse pharmacological effects, including anti-inflammatory, anti-tumor, anti-hepatocellular carcinoma, and antipyretic activities. To explore the medicinal components from different parts of the plant and to fully utilize T. hemsleyanum, this study investigated the mechanisms underlying the differential accumulation of metabolites in its tuberous roots, fibrous roots, and leaves.METHODS: This study employed a combination of metabolomics and transcriptomics to analyze the metabolic profiles of T. hemsleyanum. Using LC-MS/MS technology in positive ion mode, metabolites were identified and quantified in the tuberous roots, fibrous roots, and leaves. Key metabolic pathways were analyzed to understand the spatial distribution of bioactive compounds.RESULTS: A total of 65 metabolites were identified in the tuberous roots, 203 in the fibrous roots, and 235 in the leaves. The main compounds identified included flavonoids, alkaloids, terpenoids, glycosides, ketones, and amino acids and their derivatives. Flavonoids, glycosides, alkaloids, and terpenoids were strongly accumulated in the tuberous roots, while flavonoid alcohols, glycosides, alkaloids, and terpenoids were predominant in the leaves and fibrous roots. The phenylpropanoid biosynthesis pathway and isoflavonoid biosynthesis were found to play a major role in the pharmacological effects of T. hemsleyanum. The glucosinolate pathway and ABC transporters were also identified as key contributors to tissue-specific metabolic accumulation.DISCUSSION: These results elucidate the molecular mechanisms behind the differential accumulation of metabolites in different parts of T. hemsleyanum. The findings provide important insights into the spatial distribution of its bioactive components and their biosynthetic pathways, offering a foundation for further development and utilization of this medicinal plant.PMID:40241824 | PMC:PMC12000079 | DOI:10.3389/fpls.2025.1478061

Front Vet Sci. 2025 Apr 2;12:1554771. doi: 10.3389/fvets.2025.1554771. eCollection 2025.ABSTRACTPreservation of sperm significantly contributes to the advancement of assisted reproductive technologies, genetic conservation and improvement efforts, and precision breeding of livestock. This review distills knowledge from the existing information and emerging patterns in the field of buck sperm cryopreservation. The primary focus is on the challenges and opportunities associated with improving extender formulations and freezing techniques in order to enhance the vitality of sperm after thawing and to increase the potential for conception. This review assesses the efficacy and limitations of conventional extenders derived from egg yolk or soybean lecithin, and the adverse impacts of seminal plasma enzymes on sperm quality during the processes of chilling and cryopreservation. Significant progress has been made in the fields of molecular biology namely lipidomics, proteomics, metabolomics, DNA methylation providing valuable knowledge regarding the unique reactions of sperm to cryopreservation. The utilization of the "omics" technologies has shown intricate molecular transformation that occur in sperm during freezing and thawing. Moreover, detection of molecular biomarkers that indicate the quality of sperm and their ability to withstand freezing provides opportunities to choose the best sperm samples for cryopreservation. This, in turn, enhances the results of artificial insemination and genetic conservation endeavors. This review emphasizes the necessity for adopting a comprehensive approach that combines molecular and cellular knowledge with practical methods in the field of sperm cryopreservation to ensure production of goats as major food animals in the global scale.PMID:40241808 | PMC:PMC12001040 | DOI:10.3389/fvets.2025.1554771

Food Chem X. 2025 Mar 28;27:102424. doi: 10.1016/j.fochx.2025.102424. eCollection 2025 Apr.ABSTRACTRipened Pu-erh tea (RPT) is renowned for its distinctive flavor and health benefits. However, its complex fermentation process poses challenges in ensuring consistency in production. This study investigated RPT flavor formation through sensory evaluation, multi-omics analysis, and multivariate statistical approaches. By day 24, the tea exhibited a reddish-brown infusion and a mellow, thick taste (MT_RPT), achieving the highest sensory score (94.0, P < 0.05). Sixteen flavor-related chemical components exhibited significant changes (P < 0.05). The contents of free amino acids, L-theanine, tea polyphenols, flavonoids, catechins, and thearubigins decreased. In contrast, the contents of total soluble sugars, caffeine, theobromine, epicatechin, and theabrownins (TBs) increased, reaching 74.1 mg/g, 65.38 mg/g, 3.13 mg/g, 3.33 mg/g, and 134.84 mg/g, respectively. Additionally, 33 nonvolatile metabolites (e.g., pelargonidin 3-O-glucoside, dihydroisorhamnetin, and puerarin) were significantly correlated with MT_RPT flavor (VIP > 1, |r| ≥ 0.8, P < 0.05) and influenced by key functional microbes, including Pantoea, Aspergillus, Brachybacterium, and Staphylococcus. By day 30, the infusion darkened, and sensory scores declined (81.4, P < 0.05), attributed to the dominance of Brevibacterium. This microbial shift reduced water-soluble pectin, free amino acids, and 11 metabolites while increasing TBs and theophylline (219.33 mg/g and 0.09 mg/g, respectively). Therefore, TBs were identified as a crucial indicator of optimal fermentation. Moreover, redundancy analysis indicated that the tea pile's central temperature, moisture content, and pH were essential fermentation parameters (P < 0.05). These findings deepen our understanding of MT_RPT flavor development mechanisms and provide valuable insights into precise fermentation control.PMID:40241696 | PMC:PMC12002954 | DOI:10.1016/j.fochx.2025.102424