PubMed

Molecules. 2025 Feb 17;30(4):923. doi: 10.3390/molecules30040923.ABSTRACTAstragali Radix (AR), a traditional food and medicinal herb used for thousands of years, is widely recognized for its role in enhancing immunity, particularly when combined with adjuvant chemotherapy. The two primary types of AR available in the market are imitation wild AR (grown for seven years) and cultivated AR (grown for two years). However, whether differences exist in their immune-enhancing effects and chemical constituents remains unclear. In this study, a comparative analysis was performed to evaluate the immune activity and chemical composition of cultivated and imitation wild AR. Immune activity was assessed through in vivo animal studies, while metabolomic analysis was used to characterize their chemical profiles. The results demonstrate that AR possesses significant antitumor and immune-enhancing activities, with imitation wild AR showing superior efficacy compared with cultivated AR. Following 16 days of daily AR treatment, both the thymus and spleen coefficients were significantly increased, effectively reversing the immune dysfunction induced by cyclophosphamide (CTX). Moreover, the administration of AR showed no significant toxicity, as evidenced by the stable liver and kidney function indicators, including ALT, UREA, and CRE levels. To investigate chemical differences, a customized chemotaxonomic-based in-house library containing 215 compounds was developed and integrated with the Progenesis QI informatics platform for metabolite annotation. Using multivariate analysis, 48 constituents were identified in total: 46 unique to the imitation wild AR and 45 specific to the cultivated AR. The correlation between chemical constituents and the pharmacological effects of AR was evaluated. Based on orthogonal partial least-squares discriminant analysis (OPLS-DA) and S-plot analysis, five potential biomarkers were identified, including Calycosin-7-glucoside, Rhamnocitrin-3-O-β-D-glucopyranoside, Ononin, 3,5-Dicaffeoylquinic acid, and Acetylastragaloside I. These biomarkers likely account for the differences in immune-enhancing effects between the two AR types. This study provides a scientific foundation for the rational use of Astragali Radix.PMID:40005233 | DOI:10.3390/molecules30040923

Molecules. 2025 Feb 12;30(4):850. doi: 10.3390/molecules30040850.ABSTRACTNowadays, the diagnosis of Parkinson's disease (PD) remains essentially clinical, based on the subjective observations of clinicians. In addition, misdiagnosis with other neuro disorders, such as Alzheimer's (AD), can occur. Herein, an untargeted lipidomic analysis of 75 plasma samples was performed to identify lipid species capable of discriminating between these two neuro groups. Therefore, PLS-DA and OPLS-DA analysis revealed significant differences in patient profiles in the sphingolipid and glycerophospholipid categories. As a result, a putative lipid biomarker panel was developed, which included HexCer (40:1; O2) and PC (O-32:0), with an area under the receiver operating characteristic curve (AUC) > 80, respectively. This panel was effective in discriminating between diseased and healthy subjects, but most importantly, it could discriminate between two neurodegenerative disorders that can present similar symptoms, namely PD and AD. Together, these findings suggest that the dysregulated metabolism of lipids plays a critical role in AD and PD pathology and may represent a valuable clinical tool for their diagnosis. Thus, further targeted studies are encouraged to better understand the underlying mechanisms of PD and confirm the diagnostic potency of the identified lipid metabolites.PMID:40005161 | DOI:10.3390/molecules30040850

Molecules. 2025 Feb 10;30(4):821. doi: 10.3390/molecules30040821.ABSTRACTNatural matrices have historically been a cornerstone in drug discovery, offering a rich source of structurally diverse and biologically active compounds. However, research on natural products often faces significant challenges due to the complexity of natural matrices, such as urine, and the limitations of bioactivity assessment assays. To ensure reliable insights, it is crucial to optimize experimental conditions to reveal the bioactive potential of samples, thereby improving the validity of statistical analyses. Approaches in metabolomics further strengthen this process by identifying and focusing on the most promising compounds within natural matrices, enhancing the precision of bioactive metabolite prioritization. In this study, we assessed the bioactivity of 17 dromedary urine samples on human renal cells under serum-reduced conditions (1%FBS) in order to minimize possible FBS-derived interfering factors. Using viability assays and Annexin V/PI staining, we found that the tumor renal cell lines Caki-1 and RCC-Shaw were more sensitive to the cytotoxic effects of the small molecules present in dromedary urine compared to non-tumor HK-2 cells. Employing NMR metabolomics analysis combined with detected in vitro activity, our statistical model highlights the presence of bioactive compounds in dromedary urine, such as azelaic acid and phenylacetyl glycine, underscoring its potential as a sustainable source of bioactive molecules within the framework of green chemistry and circular economy initiatives.PMID:40005133 | DOI:10.3390/molecules30040821

Molecules. 2025 Feb 8;30(4):782. doi: 10.3390/molecules30040782.ABSTRACTAccurate quantification of indoxyl sulfate (IndS) and p-cresyl sulfate (pCS) is essential for understanding their role in chronic kidney disease (CKD) progression and for developing strategies to mitigate their harmful effects, including cardiovascular morbidity and renal fibrosis. Advances in liquid chromatography-high-resolution mass spectrometry (LC-HRMS) enable the integration of powerful diagnostic tools into clinical laboratories. Along with accurate quantification, precise mass measurements allow for untargeted compound identification.METHODS: An LC-HRMS was validated for quantifying IndS and pCS in human serum, following EMA guidelines. The method involved protein precipitation with methanol, micro-LC for chromatographic separation, and detection based on accurate mass, with simultaneous high-resolution full-scan acquisition. Clinical samples from patients with varying degrees of renal insufficiency and samples obtained before and after hemodiafiltration were analyzed.RESULTS: The method demonstrated acceptable linearity, precision, and accuracy. The measurement range for both analytes was from 100 to 40,000 ng/mL. Serum levels of IndS and pCS correlated with decreased renal function. After hemodiafiltration, there was a significant reduction of IndS (50%) and pCS (43%). Simultaneous untargeted analysis allowed to identify metabolites significantly underexpressed after hemodiafiltration.CONCLUSIONS: An accurate LC-HRMS method was validated for the quantification of IndS and pCS serum levels in patients with CKD, providing insights into toxin dynamics and enabling untargeted metabolic evaluation.PMID:40005095 | DOI:10.3390/molecules30040782

Molecules. 2025 Feb 7;30(4):779. doi: 10.3390/molecules30040779.ABSTRACTThe rapid and accurate annotation of the complex compounds and metabolites in natural products remains a significant challenge. In this study, we developed an integrated strategy to efficiently and accurately profile both the prototypes and metabolites of natural products in vivo. And this was achieved by establishing a gypenosides constituent database and utilizing R programming language to combine sample selection, virtual metabolite database construction, polygon mass defect filtering, and Kendrick mass defect filtering. In addition, the annotation strategy was successfully applied to identify the prototypes and metabolites of gypenosides in mice serum. As a case study, gypenoside LXXV was used to validate the feasibility of this approach. The results demonstrated 36 prototypes and 108 metabolites were annotated from the serum by the established annotation strategy. The prototype and eight metabolites of gypenoside LXXV were further confirmed, indicating that the proposed strategy is available. This study provides a novel approach for the rapid and accurate identification of prototypes and metabolites of natural products and offers new insights into the metabolic processes of gypenosides in vivo.PMID:40005091 | DOI:10.3390/molecules30040779

Molecules. 2025 Feb 7;30(4):772. doi: 10.3390/molecules30040772.ABSTRACTPeperomia campylotropa (Piperaceae) is a species with a traditional Mexican gastroprotective use that has never-before been studied using metabolomics. This study explores the ethnobotanical use of the species, aiming to define the gastroprotective effect of the aqueous extract and characterize its secondary metabolites by UHPLC-MS analysis. To validate its use, we botanically identified the species re-collected in the Municipality of Buenavista de Cuéllar, Guerrero, Mexico. We conducted interviews to provide evidence of the traditional details of its consumption and knowledge. Subsequently, qualitative phytochemical tests were performed to elucidate the possible secondary metabolites, which were also characterized under UHPLC-MS analysis and analyzed according to their primary type and retention times. Indomethacin (IND)- and ethanol (EtOH)-induced gastric damage models in Wistar rats were used for pharmacological evaluation, considering the ulceration index and gastroprotection percentage. Along with the participation in the mechanism of action of nitric oxide (NO), sulfhydryl (-SH) groups and prostaglandins (PG) were elucidated by Wistar rats pretreated with N(ω)-nitro-L-arginine methyl ester (L-NAME), N-Ethylmaleimide (NEM), and IND, respectively. Acute intragastric toxicity was also estimated in NIH female mice. Ninety people were interviewed, revealing the traditional knowledge of P. campylotropa as food and medicine for stomach diseases, including irritation and indigestion. The presence of phenolic compounds (48%), N-containing compounds (22%), glycosides (21%), terpenoids (7%), and lactones (4%) were verified by preliminary phytochemical analysis and by UHPLC-MS in which 162 secondary metabolites were characterized. Besides that, the aqueous extract at 62.5, 125, and 250 mg/kg of body weight (b.w.) decreased the ulcerative index, showing gastroprotection percentages between 60 and 80%, similar to that of omeprazole. Furthermore, -SH group participation in its activity was established. All this evidence supports the gastroprotective activity of P. campylotropa for the first time and contributes to understanding its secondary metabolite content.PMID:40005084 | DOI:10.3390/molecules30040772

Molecules. 2025 Feb 7;30(4):770. doi: 10.3390/molecules30040770.ABSTRACTBACKGROUND/OBJECTIVES: This study explores the metabolic adaptations and quality differences between wild and farmed gilthead seabream (Sparus aurata), with a particular focus on lipid composition and metabolite profiles. These differences are examined in the context of varying environmental conditions, feeding regimes, and post-harvest processes. High-resolution magic-angle-spinning nuclear magnetic resonance (HR-MAS NMR) spectroscopy was employed to perform the metabolomic analysis.RESULTS: Farmed seabream exhibited higher lipid content and PUFA levels (e.g., DHA and EPA) due to aquaculture diets, while wild seabream showed lower lipid concentrations and elevated levels of polar metabolites. Metabolic trade-offs in wild seabream reflected greater physical activity and environmental adaptation. The K-value indicated faster spoilage in farmed seabream, particularly from Greece, linked to handling conditions. HR-MAS provided precise, reproducible results, allowing direct quantification of key metabolites without altering sample integrity.METHODS: HR-MAS NMR was employed to analyze muscle tissue from wild and farmed seabream (produced in Spain and imported from Greece), providing high-resolution spectra without requiring sample extraction. Metabolite quantification included polyunsaturated fatty acids (PUFAs), creatine, taurine, lactate, and trimethylamine N-oxide (TMAO). Freshness was monitored using the K-value index, calculated from ATP derivative levels in samples stored at 4 °C.CONCLUSIONS: The study highlights the influence of diet and environment on the metabolic profiles of seabream. HR-MAS NMR emerges as a robust method for metabolomic studies and freshness assessment. Findings emphasize the potential for dietary adjustments to optimize aquaculture practices and fish quality while underscoring the importance of sustainable production strategies. Further research into lipid metabolism genes and environmental factors is recommended to deepen understanding of these adaptations.PMID:40005081 | DOI:10.3390/molecules30040770

Nutrients. 2025 Feb 18;17(4):724. doi: 10.3390/nu17040724.ABSTRACTBackground/Objectives: Long-term spaceflight in a microgravity environment frequently results in gastrointestinal dysfunction, presenting substantial challenges to astronauts' health. Hericium erinaceus, a plant recognized for its dual use as food and medicine, contains a key functional component called Hericium erinaceus polysaccharide (HEP), which is purported to promote gastrointestinal health. This study aims to investigate the protective effects of HEP against gastrointestinal disturbances induced by simulated weightlessness and to elucidate its regulatory mechanisms. Methods: Sprague Dawley rats subjected to a tail suspension model were administered either a standard diet or a diet supplemented with 0.125% HEP over a period of 4 weeks (the intake of HEP is approximately 157.5 mg/kg bw/d, n = 8), metagenomics and targeted metabolomics to investigate the effects of HEP on gastrointestinal hormone secretion disorders, gut microbiota dysbiosis, and intestinal barrier damage induced by simulated weightlessness. Results: Dietary supplementation with HEP was observed to significantly alleviate weightlessness-induced gastrointestinal hormone disruptions, enhancing motility and intestinal barrier function while reducing inflammation. In addition, HEP improved gut microbiota by boosting beneficial bacteria as Oscillibacter sp.1-3, Firmicutes bacterium ASF500, and Lactobacillus reuteri, while reducing harmful bacteria like Escherichia coli and Mucispirillum schaedleri at the species level. Furthermore, HEP altered the serum metabolic profile of the rats, reducing inflammation by upregulating the tryptophan metabolism pathway and enhancing the production of short-chain fatty acids. Conclusions: HEP effectively protects against gastrointestinal dysfunction induced by simulated weightlessness by regulating hormone secretion and maintaining intestinal homeostasis.PMID:40005052 | DOI:10.3390/nu17040724

Nutrients. 2025 Feb 18;17(4):720. doi: 10.3390/nu17040720.ABSTRACTBACKGROUND/OBJECTIVES: Acute alcohol consumption can cause intestinal dysfunction, whereas L-theanine (LTA) has shown the potential to support intestinal health. We explored L-theanine's ability to protect against acute alcohol-induced injury.METHODS: Male C57BL/6 mice were administered LTA for 28 d and then underwent acute alcohol intestinal injury modeling for 8 days.RESULTS: The results revealed that LTA ameliorated alcohol-induced pathological damage in the duodenum and gut permeability, improved secretory immunoglobulin A (SIgA) content, and reduced oxidative stress, inflammatory markers, and serum lipopolysaccharide (LPS) content in mice. Furthermore, LTA restored the composition of the intestinal flora, increasing the abundance of Alloprevotella, Candidatus_Saccharimonas, Muribaculum, and Prevotellaceae_UCG-001. Additionally, LTA increased beneficial metabolites, such as oxyglutaric acid and L-ascorbic acid, in the HIF-1 pathway within the enrichment pathway. Further investigation into the HIF-1 signaling pathway identified up-regulation of claudin-1, HIF-1α, occludin, and ZO-1, and down-regulation of TLR4, PHD2, p65 NF-κB, TNF-α, and IFN-γ mRNA and protein levels.CONCLUSIONS: These results suggest that LTA may enhance the intestinal barrier by activating the HIF-1 signaling pathway to regulate the TLR4/NF-κB/HIF-1α axis, thereby reducing acute alcoholic intestinal injury.PMID:40005048 | DOI:10.3390/nu17040720

Nutrients. 2025 Feb 11;17(4):640. doi: 10.3390/nu17040640.ABSTRACTPurpose: Ketone bodies could be useful biomarkers in multiple sclerosis (MS) because the pathophysiological processes underlying MS disease progression induce metabolic stress. The purpose was to assess the relationships of ketone bodies with biomarkers of metabolic, inflammatory, and oxidative stress in MS. Methods: Blood samples and neurological assessments were obtained from 153 healthy controls (HC), 187 relapsing-remitting (RRMS), and 91 progressive MS (PMS) patients. AcAc, BHB, and acetone were measured using proton nuclear magnetic resonance spectroscopy. Indices of inflammatory vulnerability (IVX), metabolic malnutrition (MMX), and metabolic vulnerability (MVX) were computed from the NMR profiles. Cholesterol, apolipoprotein, lipid peroxidation, and antioxidant profiles were obtained. Regression analysis adjusted for age, sex, body mass index, and HC, RRMS, or PMS disease status. Results: AcAc and BHB levels were greater in MS compared to HC. BHB and ketone bodies were positively associated with disability on the MS Severity Scale and ambulation time. BHB was positively associated with IVX, MMX, and MVX. AcAc was positively associated with MMX and negatively associated with IVX and MVX. Total ketone body concentration was positively associated with MMX and MVX. BHB and AcAc levels were negatively associated with the amino acids alanine, valine, and leucine. Conclusions: Ketone bodies are associated with inflammatory vulnerability, metabolic vulnerability, and ambulatory disability measures in MS.PMID:40004969 | DOI:10.3390/nu17040640

Genes (Basel). 2025 Feb 15;16(2):224. doi: 10.3390/genes16020224.ABSTRACTPURPOSE: Horse racing may cause stress-induced physiological changes and tissue damage in horses, but the changes in miRNA expression, protein expression, and metabolic substances in the plasma exosomes of the Yili horse after racing are still unclear. This study detected miRNA, protein expression, and metabolic substances in the plasma exosomes of Yili horses before and after competition, providing new insights for post-race recovery and care of Yili horses.METHOD: Eight three-year-old Yili horses that had undergone training were selected as the research subjects, with four horses that had not competed as the control group and four horses that had participated in the competition for half an hour as the training group. Extract whole blood and separate plasma from two groups of horses, and then extract plasma exosomes; MiRNAs, proteins, and metabolites in extracellular vesicles were detected and analyzed using miRNAomics, proteomics, and metabolomics. P Result: After the competition, the levels of miRNAs related to the cytoplasm and nucleus in Yili horse plasma exosomes increased, and miRNAs related to the transcription and transcriptional regulation of biological processes significantly increased. The levels of proteins related to the cytoplasm and nucleus also increased, and the levels of proteins related to cell signaling function increased, carbohydrates and their metabolites were significantly reduced.CONCLUSIONS: The competition process causes significant changes in the miRNA, proteomics, and metabolomics of plasma exosomes in the Yili horses, which are mainly related to metabolic regulation.PMID:40004554 | DOI:10.3390/genes16020224

Genes (Basel). 2025 Feb 4;16(2):197. doi: 10.3390/genes16020197.ABSTRACTOBJECTIVES: Training is essential for enhancing equine athletic performance, but the genetic mechanisms that regulate athletic performance are unknown. Therefore, this paper aims to identify candidate genes and metabolic pathways for the effects of training on equine athletic performance through multi-omics analyses.METHODS: The experiment selected 12 untrained trot-type Yili horses, which underwent a 12-week professional training program. Blood samples were collected at rest before training (BT) and after training (AT). Based on their race performance, whole blood and serum samples from 4 horses were chosen for transcriptomic and metabolomic analyses.RESULTS: The race performance of the horses is dramatically improved in the AT period compared to the BT (p < 0.01) period. The transcriptome analysis identified a total of 57 differentially expressed genes, which were significantly enriched in pathways related to circadian entrainment, steroid hormone biosynthesis, chemokine signaling, and cholinergic synapses (p < 0.05). Additionally, metabolomic analysis revealed 121 differentially identified metabolites, primarily enriched in metabolic pathways such as histidine metabolism, purine metabolism, and the PI3K-Akt signaling pathway. The integration of transcriptomic and metabolomic analyses uncovered five shared pathways, and further combined pathway analyses identified eight differentially expressed genes that correlate with 19 differentially identified metabolites.CONCLUSIONS: The current findings will contribute to establishing a theoretical framework for investigating the molecular mechanisms of genes associated with the impact of training on equine athletic performance. Additionally, these results will serve as a foundation for enhancing the athletic capabilities of trot-type Yili horses.PMID:40004526 | DOI:10.3390/genes16020197

Nat Neurosci. 2025 Feb 25. doi: 10.1038/s41593-025-01889-3. Online ahead of print.ABSTRACTHere we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid species containing polyunsaturated fatty acids (PUFAs). Feeding C9 ALS/FTD flies PUFAs yielded a modest increase in survival. However, increasing PUFA levels specifically in neurons of C9 ALS/FTD flies, by overexpressing fatty acid desaturase enzymes, led to a substantial extension of lifespan. Neuronal overexpression of fatty acid desaturases also suppressed stressor-induced neuronal death in iPS cell neurons of patients with both C9 and TDP-43 ALS/FTD. These data implicate neuronal fatty acid saturation in the pathogenesis of ALS/FTD and suggest that interventions to increase neuronal PUFA levels may be beneficial.PMID:40000803 | DOI:10.1038/s41593-025-01889-3

Sci Rep. 2025 Feb 25;15(1):6718. doi: 10.1038/s41598-025-90858-8.ABSTRACTSepsis, characterized as a severe systemic inflammatory response syndrome, typically originates from an exaggerated immune response to infection that gives rise to organ dysfunction. Serving as one of the predominant causes of death among critically ill patients, it's pressing to acquire an in-depth understanding of its intricate pathological mechanisms to strengthen diagnostic and therapeutic strategies. By integrating genomic, transcriptomic, proteomic, and metabolomic data across multiple biological levels, multi-omics research analysis has emerged as a crucial tool for unveiling the complex interactions within biological systems and unraveling disease mechanisms in recent years. Samples were collected from 23 cases of sepsis patients and 10 healthy volunteers from January 2019 to December 2020. The protein components in the samples were explored by independent data acquisition (DIA) analysis method, while Circular RNA (circRNA) categories were usually identified by RNA sequencing (RNA-seq) technology. Subsequent to the above steps, data quality monitoring was performed by employing software, and unqualified sequences were excluded, and conditions were set for differential expression network analysis (protein group and circRNA group were separately used log2 |FC|≥ 1 and log2 |FC|≥ 2, P < 0.050). Gene Ontology (GO) enrichment analysis and gene set enrichment analysis (GSEA) analysis were performed on common differentially expressed proteins, followed by protein-protein interaction between common differentially expressed genes and cytoscape software enrichment analysis, and subsequently its association with associated diseases (Disease Ontology (DO)) was investigated in an all-round manner. Afterwards, the distribution distinction of common differentially expressed genes in sepsis group and healthy volunteer group was displayed by heat map after Meta-analysis. Subsequent to the above procedures, pivotal targets with noticeable survival curve distinctions in two states were screened out after Meta-analysis. At last, their potential value was verified by in vitro cell experiment, which provided reference for further discussion of the diagnostic value and prognostic effect of target gene. A total of 174 DEPs and 308 DEcircRNAs were identified in the proteomics analysis, while a total of 12 common differentially expressed genes were identified after joint analysis. The protein-protein interaction (PPI) network suggested the degree of interaction between the dissimilar genes, and the heat map demonstrated their specific distribution in distinct groups. Through enrichment analysis, these proteins predominantly participated in a sequence of crucial processes such as intracellular material synthesis and secretion, changes in inflammatory receptors and immune inflammatory response. The meta-analysis identified that S100P is highly expressed in sepsis. As illustrated by the ROC curve, this gene has high clinical diagnostic value, and utimately confirmed its expression in sepsis through in vitro cell experiments. In these two groups of healthy people and septic patients, S100P demonstrated a more obvious trend of differential expression; Cell experiments also proved its value in diagnosis and prognosis judgment in sepsis; As a result, they may become diagnostic and prognostic markers for sepsis in clinical practice.PMID:40000745 | DOI:10.1038/s41598-025-90858-8

Sci Rep. 2025 Feb 26;15(1):6845. doi: 10.1038/s41598-025-91444-8.ABSTRACTColorectal cancer (CRC) can evolve from colorectal adenomas, which can be further classified into non-advanced adenomas (NAAs) and advanced adenomas (AAs) based on their clinical characteristics. Their prognoses are vastly different, with patients with NAAs having significantly lower recurrence and CRC-related mortality rates than those with AA or CRC. Although serum metabolomics has shown promise for the early diagnosis of CRC, the differences in serum metabolite composition between NAA and AA still need to be further elucidated. This study aimed to explore the mechanism of CRC occurrence and development based on the unique serum metabolic fingerprints of different stages of CRC and to discover a new non-invasive diagnostic method based on serum metabolomics. A clinical CRC progression cohort containing healthy control (NC; n = 40), NAA (n = 40), AA (n = 40), and CRC (n = 22) groups was constructed, and untargeted metabolomic analysis based on liquid chromatography/mass spectrometry was performed to analyze the serum metabolite characteristics of each group. A semi-quantitative analysis of intergroup metabolite differences was conducted, focusing on specific metabolites that differed in the NAA and AA groups. Finally, variable metabolites were selected based on least absolute shrinkage and selection operator (LASSO) regression analysis, and receiver operating characteristic curves were plotted to evaluate the efficacy of the serum metabolite-based diagnostic model in distinguishing NC/NAA populations from AA/CRC populations. Metabolomic analysis revealed significant differences in the composition of metabolites in the NC and NAA groups compared to the CRC group, whereas the serum metabolites of the AA group were similar to those of the CRC group. The levels of 33 metabolites were significantly different in the serum of AA/CRC patients compared to that of NAA patients, and their functions included glycerophospholipid, sphingolipid, and caffeine metabolism. LASSO regression analysis identified 57 differential metabolite variables between the NC/NAA and AA/CRC groups. The diagnostic model constructed using the random forest algorithm had the best discrimination effect, with areas under the curve of 1.000 (95% confidence interval [CI] 1.000-1.000) and 0.685 (95% CI 0.540-0.830) for the training and testing sets, respectively. The composition of serum metabolites is specific to the different stages of CRC development. The serum metabolite composition of patients with AAs was similar to that of patients with CRC. Auxiliary diagnostic measures based on serum metabolites have the potential to guide the follow-up and treatment of patients with adenoma.PMID:40000732 | DOI:10.1038/s41598-025-91444-8

Autophagy. 2025 Feb 25. doi: 10.1080/15548627.2025.2471736. Online ahead of print.ABSTRACTThe activation of STING1 can lead to the production and secretion of cytokines, initiating antitumor immunity. Here, we screened an ion channel ligand library and identified tetrandrine, a bis-benzylisoquinoline alkaloid, as an immunological adjuvant that enhances antitumor immunity by preventing the autophagic degradation of the STING1 protein. This tetrandrine effect is independent of its known function as a calcium or potassium channel blocker. Instead, tetrandrine inhibits lysosomal function, impairing cathepsin maturation, and autophagic degradation. Proteomic analysis of lysosomes identified TAX1BP1 as a novel autophagic receptor for the proteolysis of STING1. TAX1BP1 recognizes STING1 through the physical interaction of its coiled-coil domain with the cyclic dinucleotide binding domain of STING1. Systematic mutation of lysine (K) residues revealed that K63-ubiquitination of STING1 at the K224 site ignites TAX1BP1-dependent STING1 degradation. Combined treatment with tetrandrine and STING1 agonists promotes antitumor immunity by converting "cold" pancreatic cancers into "hot" tumors. This process is associated with enhanced cytokine release and increased infiltration of cytotoxic T-cells into the tumor microenvironment. The antitumor immunity mediated by tetrandrine and STING1 agonists is limited by neutralizing antibodies to the type I interferon receptor or CD8+ T cells. Thus, these findings establish a potential immunotherapeutic strategy against pancreatic cancer by preventing the autophagic degradation of STING1.PMID:40000606 | DOI:10.1080/15548627.2025.2471736

J Proteome Res. 2025 Feb 25. doi: 10.1021/acs.jproteome.4c00806. Online ahead of print.ABSTRACTMeningioma, the most prevalent brain tumor, poses significant challenges due to its unclear transition from low-grade to aggressive forms, with limited knowledge about grade-specific markers. We have utilized vibrational spectroscopic techniques such as ATR-FTIR and Raman spectroscopy, alongside LC-MS/MS-based mass spectrometry to understand the systemic cues and evaluate them for clinical practice. The acquired Raman and ATR-FTIR spectra of 46 meningioma patients (27 low-grade and 19 high-grade) and 8 healthy individuals revealed 98.15% and 83.33% accuracy based on PC-LDA. The grade classification revealed an accuracy of around 70%, implying the presence of subtypes and transition phases. The observed alterations corresponded to lipids, nucleic acids, and proteins. Further, the LC-MS/MS-based study identified different derivatives of cholines, indoles, lipids, sphingosine, tryptophan, and their respective metabolic pathways as contributors in tumorigenesis and progression. Further, PRM-based targeted validation and feature selection was carried out on 43 meningioma patients and 17 healthy controls. Glycochenodeoxycholic acid, indole-3-acetic acid, trans-3-indoleacrylic acid, glycodeoxycholic acid, 5α-dihydrotestosteroneglucornide, and glycocholic acid segregated meningioma samples with an accuracy of around 90% while features like indole-3-acetic acid, stercobilin, sphingosine-1-phosphate, deoxycholic acid, and citric acid could classify grades with around 70% accuracy. These findings suggest that further validation across larger cohorts could enhance its usage in clinical settings.PMID:40000599 | DOI:10.1021/acs.jproteome.4c00806

Rice (N Y). 2025 Feb 25;18(1):9. doi: 10.1186/s12284-025-00762-y.ABSTRACTThe jasmonate ZIM-domain (JAZ) proteins, known as inhibitors in the jasmonic acid (JA) pathway, have been reported to play a protective role against abiotic stress in plants. Nevertheless, the specific role of JAZ proteins in rice seedlings under alkaline stress remains unexplored. In this study, we mainly focus on OsJAZ10, investigating the physiological response mechanism and metabolic regulation on rice seedlings challenged by alkaline stress. Our results revealed that the antioxidant enzyme activity and osmotic adjustment ability of the OsJAZ10 overexpression lines were less affected by alkaline stress compared to WT (Wild-type) line. Metabolomic analysis demonstrated a significant accumulation of organic acids, including citrate and DL-malate, as well as amino acids such as DL-serine, DL-glutamine, threonine, glycine, and L-glutamate, in the OsJAZ10 overexpression plants in response to alkaline stress. Besides, OsJAZ10 was also involved in pantothenate and CoA biosynthesis, carbon fixation, and C5-branched dibasic acid metabolism in response to alkaline stress. Finally, OsJAZ10 was found to negatively regulated the biosynthesis and signaling of jasmonic acid pathway by repressing JA-responsive genes. Overall, this research elucidates the role of OsJAZ10 in conferring enhanced tolerance to alkaline stress in rice, providing valuable insights for the development of stress-tolerant rice varieties.PMID:40000553 | DOI:10.1186/s12284-025-00762-y

Planta. 2025 Feb 26;261(4):67. doi: 10.1007/s00425-025-04648-7.ABSTRACTWe describe the biological importance of proteins secreted in plants under different conditions and biological processes, the secretion mechanisms, methodologies for obtaining and identifying these proteins, and future perspectives. Molecule secretion inside and outside the cell is relevant to all areas of plant biology. Protein secretion, in particular, has intriguing possibilities due to the different secretion pathways that the cell uses to send biochemical messages. The secretion of proteins-secretomes-into extracellular space in response to different stimuli or stress situations, in vitro or in planta conditions, has been studied in plants and plant tissues. Proteomics has allowed the quantitative and qualitative analysis of this process and the measurement of proteins associated with the cellular development of different tissues. This has provided the means of evaluating a more precise biochemical state of the cells and the changes that occur during their growth. With the development of new techniques in proteomics, such as mass spectrometry, sequencing, and bioinformatics, it is now possible to elucidate the main proteins secreted, with all their posttranslational modifications, in different plant species and under different specific conditions. This review presents the different pathways of protein secretion in plants, highlighting the well-known importance of signal peptides. The advances and disadvantages of in planta and in vitro systems used for proteomic purposes are discussed. The principal proteomic techniques to better understand the biological function of the secretome are summarized.PMID:40000454 | DOI:10.1007/s00425-025-04648-7

Trends Biochem Sci. 2025 Feb 24:S0968-0004(25)00025-8. doi: 10.1016/j.tibs.2025.01.010. Online ahead of print.ABSTRACTElucidating plant biosynthetic pathways is key to advancing a sustainable bioeconomy by enabling access to complex natural products through synthetic biology. Despite progress from genomic, transcriptomic, and metabolomic approaches, much multiomics data remain underutilized. This review highlights state-of-the-art multiomics strategies for discovering plant biosynthetic pathways, addressing challenges in data acquisition and interpretation with emerging computational tools. We propose an integrated workflow combining molecular networking, reaction pair analysis, and gene expression patterns to enhance data utilization. Additionally, artificial intelligence (AI)-driven approaches promise to revolutionize pathway discovery by streamlining data analysis and validation. Integrating multiomics data, chemical insights, and advanced algorithms can accelerate understanding of plant metabolism and bioengineering valuable natural products efficiently.PMID:40000312 | DOI:10.1016/j.tibs.2025.01.010