PubMed

Neuro Oncol. 2025 Mar 6:noaf059. doi: 10.1093/neuonc/noaf059. Online ahead of print.ABSTRACTBACKGROUND: Primary central nervous system lymphoma (PCNSL) treatment relies on a high-dose methotrexate based chemotherapy (HD-MTX-based CT) regimen; however, whether there is a specific microbiota composition association with treatment response and clinical outcomes remains incompletely understood.METHODS: We conducted a prospective study of PCNSL patients, included in the clinical trial NCT02313389 and the ancillary study NCT04253496 from 2020 to 2023, where patients were treated with first line HD-MTX-based polychemotherapy without a consolidation treatment. Stool (n=52), cerebrospinal fluid (CSF, n=52), and plasma samples (n=35) were collected before and/or after therapy initiation to perform metagenomic, flow cytometry, and metabolomic analyses. Plasma metabolomic data of 90 patients also included in the BLOCAGE clinical trial was subsequently used as a validation cohort.RESULTS: Unsupervised clustering of microbial data identified two distinct gut microbial communities, differing in Parabacteroides distasonis abundance, which correlated with progression-free survival and overall survival in both uni- and multivariate analyses. Higher P. distasonis levels were linked to increased plasma betaine/valine metabolites and enhanced CD8 T cell infiltration in the CSF, suggesting a connection between gut microbiota and immune regulation. Stratifying the validation cohort by betaine/valine content confirmed these clinical associations.CONCLUSIONS: Our findings suggest that gut microbiome communities modulate clinical outcomes in PCNSL patients undergoing standard treatment. Moreover, after future validation in external cohorts, the quantification of Parabacteroides distasonis could potentially provide a basis for patient stratification and guide personalized therapeutic strategies in the near future.PMID:40048707 | DOI:10.1093/neuonc/noaf059

Anal Chem. 2025 Mar 6. doi: 10.1021/acs.analchem.4c06477. Online ahead of print.ABSTRACTMetabolite analysis is essential for understanding the biochemical processes and pathways that sustain life, providing insights into the complex interactions within cellular systems and clinical examinations. This review explores recent applications of nuclear magnetic resonance (NMR) spectroscopy in metabolite studies. Various methods enhancing analytical accuracy for metabolome profiling and metabolic pathway studies, including spectral simplification techniques, quantitative NMR, high-resolution MAS NMR, and isotopic labeling, are discussed. The application of NMR in in situ and in vivo studies is also covered, highlighting in-cell NMR and in vivo MRS techniques. Last but not least, we discuss recent advancements in NMR hyperpolarization, with a focus on dynamic nuclear polarization (DNP), chemically induced dynamic nuclear polarization (CIDNP), para-hydrogen-induced polarization (PHIP), and signal amplification by reversible exchange (SABRE). These advancements offer significant potential for enhancing the sensitivity and accuracy of metabolite studies and are expected to further deepen the study and understanding of metabolites and metabolic pathways.PMID:40048643 | DOI:10.1021/acs.analchem.4c06477

J Agric Food Chem. 2025 Mar 6. doi: 10.1021/acs.jafc.5c00868. Online ahead of print.ABSTRACTCold argon plasma (CAP) effectively modifies casein (CN) structures by cleaving peptide chains and altering allergenic epitopes. This study assessed the allergenicity of CAP-treated CN in KU812 cells and BALB/c mouse models, supported by a multiomics approach integrating 16S rDNA sequencing, serum metabolomics, and jejunal transcriptomics. CAP treatment reduced CN allergenicity, evidenced by decreased KU812 cell degranulation, alleviated allergic responses in mice, and a Th1/Th2 balance shift toward Th1 dominance. Furthermore, CAP-treated CN restored the gut microbiota equilibrium, increasing the number of beneficial bacteria. Multiomics analysis highlighted its impact on lipid metabolism pathways, with Zbp1 and Hbb-bt identified as potential regulators of allergic responses. These findings underscore the potential of cold argon plasma as an innovative strategy to reduce food allergenicity through multifaceted physiological mechanisms, offering promising therapeutic applications in food allergy management.PMID:40048467 | DOI:10.1021/acs.jafc.5c00868

Proc Natl Acad Sci U S A. 2025 Mar 11;122(10):e2423767122. doi: 10.1073/pnas.2423767122. Epub 2025 Mar 6.ABSTRACTRecent physical binding screens suggest that protein-metabolite interactions are more extensive than previously recognized. To elucidate the functional relevance of these interactions, we developed a mass spectrometry-based screening method for higher throughput in vitro enzyme assays. By systematically quantifying the effects of 79 metabolites on the activity of 20 central Escherichia coli enzymes, we not only assess functional relevance but also gauge the depth of the current understanding of regulatory interactions within one of the best-characterized networks. Our identification of 50 inhibitors and 14 activators not only expands the range of known input signals but also uncovers novel regulatory logic. For instance, we observed that AMP inhibits malic enzyme to safeguard the cyclic operation of the tricarboxylic acid cycle, and erythrose-4-phosphate inhibits 6-phosphogluconate dehydrogenase to redirect flux from the pentose phosphate pathway into the Entner-Doudoroff pathway. Discrepancies between our standardized assays and existing database entries suggest that many previously reported interactions might occur only under specific, often nonphysiological conditions. Our dataset represents a systematically determined functional protein-metabolite interaction network, establishing a baseline for allosteric regulation in central metabolism. These results enhance our understanding of the regulatory logic governing metabolic processes and underscore its significance in cellular adaptation and growth.PMID:40048276 | DOI:10.1073/pnas.2423767122

J Biomol NMR. 2025 Mar 6. doi: 10.1007/s10858-025-00462-1. Online ahead of print.ABSTRACTThe use of Escherichia coli for recombinant protein production is a cornerstone in structural biology, particularly for nuclear magnetic resonance (NMR) spectroscopy studies. Understanding the metabolic behavior of E. coli under different carbon sources is critical for optimizing isotope labeling strategies, which are essential for protein structure determination by NMR. Recent advancements, such as mixed pyruvate labeling, have enabled improved backbone resonance assignment in large proteins, making selective isotopic labeling strategies more important than ever for NMR studies. In this study, we aimed to investigate the metabolic adaptations of E. coli when grown on pyruvate as the sole carbon source, a common condition used to achieve selective labeling for NMR spectroscopy. Using NMR-based metabolomics, we tracked key metabolic shifts throughout the culture process to better understand how pyruvate metabolism affects protein production and isotopic labeling. Our results reveal that pyruvate is rapidly depleted before IPTG induction, while acetate and lactate accumulate due to overflow metabolism. These byproducts persist after induction, indicating that pyruvate is diverted into waste pathways, which limits its efficient use in isotope incorporation. This metabolic inefficiency presents a challenge for isotopic labeling protocols that rely on pyruvate as a carbon source for NMR studies. Our results highlight the need to fine-tune pyruvate supplementation to improve metabolic efficiency and isotopic labeling, making this study directly relevant to optimizing protocols for NMR studies involving protein structure determination. These insights provide valuable guidance for enhancing the quality and yield of isotopically labeled proteins in NMR spectroscopy.PMID:40048033 | DOI:10.1007/s10858-025-00462-1

Metabolomics. 2025 Mar 6;21(2):38. doi: 10.1007/s11306-025-02234-2.NO ABSTRACTPMID:40048010 | DOI:10.1007/s11306-025-02234-2

Metabolomics. 2025 Mar 6;21(2):37. doi: 10.1007/s11306-024-02198-9.ABSTRACTINTRODUCTION: Firefighters face regular exposure to known and probable human carcinogens, such as polycyclic aromatic hydrocarbons (PAHs), benzene, and formaldehyde, leading to an increased risk of various cancers compared to the general population. Hispanic and black firefighters are at increased risk of additional cancers not elevated in non-Hispanic white firefighters, yet biological pathways underlying these differences are unknown.OBJECTIVES: The study objectives were to evaluate differences in the urinary metabolome between Hispanic and non-Hispanic firefighters, pre-and post-fireground exposure.METHODS: To investigate the metabolic patterns, we employed a comprehensive metabolomics pipeline that leveraged liquid chromatography coupled with high-resolution mass spectrometry. We applied linear mixed effects regression to identify the differential metabolites at an FDR < 0.05 among 19 Hispanic and 81 non-Hispanic firefighters. We also performed overrepresentation analysis using Mummichog to identify enriched pathways at FDR < 0.05.RESULTS: Out of 175 features in HILIC(-) mode and 1847 features in RP(+) mode, we found 26 and 276 differential urinary features, respectively, when comparing Hispanic and non-Hispanic firefighters. We noted pathway enrichment in tryptophan and galactose metabolism. However, post-exposure, we did not observe differences in the metabolomic response by ethnicity despite differing fireground exposures.CONCLUSION: Dysregulation in the tryptophan and galactose pathway is an important contributor to cancer risks and may explain the increased cancer risk among Hispanic firefighters.PMID:40048004 | DOI:10.1007/s11306-024-02198-9

ACS Nano. 2025 Mar 6. doi: 10.1021/acsnano.5c00325. Online ahead of print.ABSTRACTInflammatory bowel disease (IBD) compromises the intestinal barrier and disrupts gut microbiota, impacting liver function via the gut-liver axis, which in turn influences the intestinal microbiota through lipid metabolites exacerbating IBD. This study introduced a probiotic-based treatment using Lactobacillus acidophilus encapsulated in tungsten ion-loaded mesoporous polydopamine (LA@WMPDA) to ameliorate colitis and balance enterohepatic homeostasis. After oral administration, the encapsulation could protect Lactobacillus acidophilus, scavenge reactive oxygen/nitrogen species, and the released tungsten ions would inhibit abnormal Enterobacteriaceae growth during colitis, consequently restoring the intestinal barrier and regulating the gut microbiota. Nontargeted metabolomics and transcriptomics analyses showed increased short-chain fatty acids and indole derivatives, and decreased hepatic lipid metabolism. Pathways associated with immune response, cell migration and death, and response to bacterium showed significant down-regulation in the colon and liver transcriptome analysis. Thus, this study provided a pioneered paradigm for IBD treatment and highlighted the regulation of liver-related metabolic functions via the gut-liver axis.PMID:40047584 | DOI:10.1021/acsnano.5c00325

J Food Sci. 2025 Mar;90(3):e70106. doi: 10.1111/1750-3841.70106.ABSTRACTColitis, a troublesome inflammatory disease that significantly impacts daily life, has garnered considerable attention in recent times. Protolysates play a crucial role in the treatment of colitis, and the intestines and ovum of Cucumaria frondosa represent a readily available source of these hydrolysates. However, the effects of C. frondosa intestines and ovum hydrolysates (CFHs) on colitis have not been thoroughly investigated. We initially examined the molecular weight distribution of CFHs and found that the fraction of molecules with a weight less than 1000 Da accounted for 86.98%, indicating that the hydrolysis primarily produced oligopeptides. Subsequently, we employed a dextran sulfate sodium-induced experimental colitis model to assess the therapeutic potential of CFHs. The findings indicated that preventive administration of CFHs dramatically attenuated the pathological manifestations associated with colitis in mice, including weight loss, colon shortening, and tissue damage. Furthermore, CFHs suppressed the secretion of pro-inflammatory cytokines IL-6, TNF-α, and IL-1β, as well as MPO in colon tissue. Metagenomic sequencing demonstrated that CFHs could restore balance to the dysregulated gut microbiota by reinforcing Bacteroidota and suppressing Verrucomicrobia populations, impacting various microbial functions. Metabolomic analyses further revealed that CFHs exhibited a more efficacious modulatory effect on DSS-induced metabolic abnormalities, including amino acid biosynthesis, linoleic acid metabolism, and dopaminergic synapses. In conclusion, CFHs showed promise in alleviating colitis, laying the groundwork for the development and application of CFHs as functional food for colitis relief.PMID:40047330 | DOI:10.1111/1750-3841.70106

J Sci Food Agric. 2025 Mar 6. doi: 10.1002/jsfa.14203. Online ahead of print.ABSTRACTBACKGROUND: Jujube (Zizyphus jujuba), belonging to the Rhamnaceae, contains various bioactive components including flavonoids and polysaccharides. In our previous study, jujube quality was improved by application of nano-selenium (Nano-Se) and melatonin; however, little research has been conducted on the induced molecular mechanisms. Zizyphus jujuba cv. Huizao was used as experimental materials to compare and analyze the transcriptomics and metabolomics mechanisms.RESULTS: Compared with the control, 305, 422, and 240 metabolites and 24, 281, and 44 genes were significantly changed at the metabolic and transcriptional levels in Nano-Se, melatonin, and Nano-Se with melatonin treatments, respectively. The metabolomics indicated that the differentially expressed metabolites were involved in phenylpropanoid biosynthesis, fructose, and mannose metabolic pathways. The Nano-Se with melatonin treatment group increased the contents of glucose and total Se by 1.8 and 5.4 times, respectively. Transcriptomics showed that differentially expressed genes of Nano-Se and melatonin treatment were mainly enriched in phenylpropanoid biosynthesis, pentose, and glucuronate interconversions pathways. In addition, several transcription factors from the NAC, WRKY, MYB, and WRKY families were identified in melatonin versus control and melatonin versus Nano-Se. Furthermore, combined transcriptomic and metabolomic analysis showed that phenylpropanoid biosynthesis, starch and sucrose metabolism, the mutual conversion pathway of pentose, and glucuronate interconversions were the vital pathways in response to Nano-Se and melatonin treatment.CONCLUSION: Overall, these results provide new insights into jujube response to Nano-Se and melatonin, and improve our understanding of the jujube molecular mechanisms induced by Nano-Se and melatonin. © 2025 Society of Chemical Industry.PMID:40047252 | DOI:10.1002/jsfa.14203

Front Plant Sci. 2025 Feb 19;16:1497732. doi: 10.3389/fpls.2025.1497732. eCollection 2025.ABSTRACTWheat stem sawfly (WSS) causes devastating yield loss in both common bread wheat (Triticum aestivum L.) and durum wheat (Triticum turgidum L. var durum) in the North American Great Plains. The early stem solidness phenotype confers solid stems early in plant development coinciding with the flight period of WSS and provides protection to plants during the critical oviposition period. With this phenotype, pith is lost as the plant develops, which may allow for enhanced biological control of surviving larvae by braconid parasitoids Bracon cephi (Gahan) and Bracon lissogaster Muesebeck, as well as having additional potential yield benefits from utilizing reabsorbed pith components. Here, we use an untargeted transcriptomics and metabolomics approach to explore the mechanisms related to the early stem solidness phenotype in three cultivars of spring wheat and two cultivars of durum wheat in addition to three near- isogenic pairs of spring wheat and two near- isogenic pairs of durum wheat. We identified effects of growth stage and allele on expression of metabolites and transcripts associated with stem solidness, development of cell walls and programmed cell death. A caffeic acid methylesterase and pectin methylesterase were upregulated in hollow stemmed Reeder and lines with the 3BLa allele, which likely influences lignin subunit proportions as well as the production of volatile semiochemicals that impact the behavior of adult WSS. TaVPE3cB, a gene associated with programmed cell death and thickening of cell walls, also had increased expression in hollow stemmed lines and is likely partially responsible for the hollow stemmed phenotype observed. Growth stage and allele also affected the expression of transcripts and metabolites involved in the phenylpropanoid pathway, carbohydrate and glycoside biosynthesis and lipid biosynthesis, implicating the involvement of these pathways in resistance and plant response to infestation by WSS.PMID:40046948 | PMC:PMC11880032 | DOI:10.3389/fpls.2025.1497732

Front Pharmacol. 2025 Feb 19;16:1520439. doi: 10.3389/fphar.2025.1520439. eCollection 2025.ABSTRACTBACKGROUND: Diabetes mellitus (DM) is a metabolic disease with high morbidity, which significantly affects human life and health expenditures. Previous studies have demonstrated that artemether (ATM) has anti-diabetes and anti-inflammation activities, but its mechanism has not been fully elucidated. This research aimed to elucidate the impact of ATM on glucolipid metabolism in a type 2 diabetes mellitus (T2DM) model db/db mice and what kind of role the gut microbiota played, and explored the underlying mechanisms involved.METHODS: C57BL/KsJ-db/db mice were treated with 80 and 160 mg/kg of ATM for 8 weeks, with metformin as a positive control.RESULTS: ATM treatment (160 mg/kg) observably ameliorated insulin resistance (IR), hyperglycemia, hyperlipemia and pathological injury in the liver and pancreas. In addition, ATM significantly decreased the expression of TNF-α, IL-1β, IL-6, NF-κB and IL-17A, and significantly increased the level of IL-10 in diabetic mice. 16S rRNA sequencing and targeted GC-MS metabolomics result indicated that ATM restored gut microbiota dysbiosis based on increasing beneficial bacteria Lactobacillus and reducing pathogenic bacteria Helicobacter and Prevotella leading to the accumulation of propionic and valeric acids and the reduction of lipopolysaccharides (LPS) release, intestinal inflammation and intestinal barrier damage. Network pharmacology and metabolomics identified the AMPK/mTOR pathway as the main signaling involved in ATM improves glucolipid metabolism and inflammation in T2DM. Western blotting results revealed that ATM suppressed the phosphorylation of mTOR, P38, P65, IKBα and IRS1 whlie increased the levels of p-AMPK, TLR4, and occludin in mice liver and colon.CONCLUSION: Taken together, ATM may modulate the composition of gut microbiota, increasing the abundance of Lactobacillus, which in turn elevates the levels of SCFAs. The elevation of SCFAs, especially propionic acid, may activate the AMPK/mTOR pathway, leading to a decrease in the levels of TNF-α, IL-1β, IL-6, NF-κB, and IL-17A, while increasing the levels of IL-10, thereby alleviating the inflammatory state and improving glucolipid metabolic disorder in T2DM. These findings laid a theoretical foundation for the clinical application of ATM in T2DM.PMID:40046742 | PMC:PMC11879814 | DOI:10.3389/fphar.2025.1520439

BMJ Oncol. 2024 Nov 13;3(1):e000472. doi: 10.1136/bmjonc-2024-000472. eCollection 2024.ABSTRACTOBJECTIVE: Osteosarcoma is the most common primary bone sarcoma. About 50% of patients develop metastatic disease and their 5-year survival lingers at around 20%-30%. T cell checkpoint blockade immunotherapies have revolutionised cancer treatment in the last decade, but their impact remains limited in osteosarcoma.METHODS AND ANALYSIS: In order to reveal potentially novel immunotherapeutic strategies for advanced osteosarcoma, we conducted an immunogenomic characterisation of a unique sample set comprising 30 osteosarcoma samples from seven patients, collected throughout disease progression. We performed RNA-sequencing and imaging mass cytometry analysis on these samples to reveal the immunological landscape during osteosarcoma progression.RESULTS: Transcriptional and phenotypical hallmarks of cytotoxic T cell-driven anticancer immunity were enriched in metastatic lesions as compared with primary tumours. Spatial analysis showed T cells infiltrating central regions of osteosarcoma metastases, indicating the absence of an immune excluded environment. In parallel, we found a pronounced increase in the expression of cancer testis antigens, particularly melanoma antigen family A (MAGEA)-related antigens, in osteosarcoma metastases, which was validated in an independent cohort (N=91). In addition, we demonstrated the presentation of MAGE-derived peptides in three out of four osteosarcoma cell lines.CONCLUSION: These findings indicate a concurrent augmentation of cytotoxic antitumour immune responses and expression of MAGEA antigens from primary to metastatic osteosarcoma. This observation suggests the exploration of MAGEA antigens as potential targets for immunotherapy in the treatment of advanced osteosarcoma.PMID:40046246 | PMC:PMC11880787 | DOI:10.1136/bmjonc-2024-000472

Front Cell Dev Biol. 2025 Feb 19;13:1490231. doi: 10.3389/fcell.2025.1490231. eCollection 2025.ABSTRACTStudies have shown that histidine 179A and 183A (H179, 183A) of the ZNF32 protein exhibit point-like nuclear speckles, but the causes of such speckle formation and their effects on breast cancer cells remain unknown. In this study, we prepared breast cancer cells containing ZNF32 H179, 183A, H179A, and H183A and observed nuclear speckles in all three cell types. Transcriptome analysis showed that these nuclear speckles may be related to changes in the activities of the cell growth factor and RNA polymerase II transcription factor. Comprehensive transcriptomics and metabolomics analyses showed that the formation of ZNF32 nuclear speckles was accompanied by changes in choline metabolism. Both in vivo and in vitro experiments suggested that ZNF32 H179A and H183A but not H179, 183A could promote breast cancer cell proliferations. We then explored and verified the differentially expressed genes through RNA-seq and RT-qPCR to explain the different proliferation abilities of these mutations. The dual luciferase reporter gene assay confirmed that ZNF32 H179A and H183A could transcriptionally activate ISY1-RAB43 and UPK3BL1 while inhibiting the transcription of SNX22; this is attributable to the fact that these mutations cause different zinc finger structure changes in ZNF32. The present study deepens the understanding of ZNF32 mutations with respect to nuclear speckle formation and their roles in the proliferation of breast cancer cells.PMID:40046230 | PMC:PMC11880268 | DOI:10.3389/fcell.2025.1490231

Front Immunol. 2025 Feb 19;16:1522346. doi: 10.3389/fimmu.2025.1522346. eCollection 2025.ABSTRACTThe establishment of placentation and maternal-fetal tolerance are important determinants of a successful pregnancy. Tacrolimus, also known as FK506, is a calcineurin inhibitor that has often been used for pregnant women after solid organ transplantation. Previous therapeutic interventions have shown the benefits of using the immuno-suppressive agent FK506 in improving clinical pregnancy and live birth rates and reducing the risk of spontaneous miscarriage. However, the mechanism(s) by which FK506 is involved in these processes have not been fully elucidated. To further characterize its function in early pregnancy, we explored the effect of FK506 on the human-derived first trimester extravillous trophoblast cells (HTR8/SVneo cells) and found that FK506 promoted invasion, tube formation and proliferation, but inhibited apoptosis of HTR8/SVneo cells. Based on the integrated metabolomics and transcriptomics analyses, the present study provided the cellular and molecular cues evidently showing that FK506 had positive effects on the placentation and maternal-fetal tolerance through modulating FASN-CEACAM1 pathway. The spontaneous-abortion-prone model gave further evidence that FK506 exerted a protective effect on pregnancy by regulating the FASN-CEACAM1 axis. These findings might provide a new fundamental mechanism and promising potential of low-dose FK506 in preventing pregnancy loss.PMID:40046057 | PMC:PMC11879939 | DOI:10.3389/fimmu.2025.1522346

Hortic Res. 2024 Dec 16;12(4):uhae350. doi: 10.1093/hr/uhae350. eCollection 2025 Apr.ABSTRACTStrawberry fruits, known for their excellent taste and potential health benefits, are particularly valued for their rich content of hydrolyzable tannins (HTs). These compounds play key roles in regulating growth and development. However, the molecular mechanisms underlying HT synthesis in plants remains poorly elucidated. In this study, based on a correlation analysis between the transcriptome and metabolome of HTs, galloyl glucosyltransferase (UGT84A22), serine carboxypeptidase-like acyltransferases (SCPL-ATs), and carboxylesterases (CXEs) were screened. Furthermore, in vitro enzymatic assays confirmed that FaSCPL3-1 acted as a hydrolyzable tannins synthase (HTS), catalyzing the continuous galloylation of glucose to form simple gallotannins (GTs). Additionally, FaCXE1/FaCXE3/FaCXE7 catalyzed the degalloylation of simple GTs and ellagitannins (ETs), and FaUGT84A22 catalyzed the glycosylation of gallic acid (GA) to produce 1-O-β-glucogallin (βG), a galloyl donor. Moreover, in FvSCPL3-1-RNAi transgenic strawberry plants, the contents of simple GT and some ET compounds were reduced, whereas, in FaCXE7 overexpressing strawberry plants, these compounds were increased. These enzymes constituted a biosynthetic pathway of galloyl derivatives, termed the "galloylation-degalloylation cycle" (G-DG cycle). Notably, the overexpression of FaCXE7 in strawberry plants not only promoted HT synthesis but also interfered with plant growth and development by reducing lignin biosynthesis. These findings offer new insights into the mechanisms of HT accumulation in plants, contributing to improving the quality of berry fruits quality and enhancing plant resistance.PMID:40046039 | PMC:PMC11879120 | DOI:10.1093/hr/uhae350

Front Microbiol. 2025 Feb 19;15:1481111. doi: 10.3389/fmicb.2024.1481111. eCollection 2024.ABSTRACTINTRODUCTION: Xierezhuyubuxu decoction (XRZYBXD) is prepared by adding and reducing the Dahuang Zhechong Pill, which is a traditional Chinese medicinal formula in "The Synopsis of Prescriptions of the Golden Chamber". XRZYBXD has previously been reported to have good efficacy in treating Hepatocellular carcinoma (HCC) in clinical and basic research. However, its underlying mechanism in treating HCC has not been fully elucidated. The aim of the study is to investigate the pro-pyroptosis effect of XRZYBXD in HCC and the role of gut microbiota in this process.METHODS: Firstly, we executed comprehensive analyses of XRZYBXD on pyroptosis, intestinal flora, microbial metabolites and intestinal barrier function using TUNEL, IHC, ELISA, WB, Q-PCR, 16S rRNA sequencing, and untargeted metabolomics in a H22 tumor-bearing mice model. Further, through rescue experiment of antibiotics-induced microbiota depletion and fecal microbial transplantation (FMT) experiment, the mechanism of XRZYBXD promoting pyroptosis of HCC by improving intestinal flora was verified.RESULTS: We found that XRZYBXD medium and high dose significantly inhibited the growth of tumor and induced pyroptosis of hepatoma cells. They also modified intestinal ecological disorders by expansion of the abundance of beneficial bacteria (such as Akkermansia muciniphila and Parabacteroides distasonis) and reduction of the abundance of harmful bacteria (such as Barnesiella intestinihominis). Accordingly, microbiota metabolites and intestinal barrier function were also significantly improved by XRZYBXD.DISCUSSION: Further, elimination of gut microbiota by antibiotics weakened the efficacy of XRZYBXD, and FMT with feces from the XRZYBXD high dose group achieved similar therapeutic efficacy as XRZYBXD. In brief, XRZYBXD promote pyroptosis of hepatoma cells via adjusting intestinal dysbiosis.PMID:40046008 | PMC:PMC11880294 | DOI:10.3389/fmicb.2024.1481111

Curr Eye Res. 2025 Mar 6:1-11. doi: 10.1080/02713683.2025.2472369. Online ahead of print.ABSTRACTPURPOSE: The primary aim of this article was to investigate differences in the metabolomic profile of tear fluid obtained from pre-operative cataract patients, with or without dry eye disease. The objective was to look for metabolomic signatures that might discriminate between the two groups.METHODS: A total of 222 patients were enrolled in the study. Eighty-one were randomly selected for metabolomic analysis from both dry eye positive and dry eye negative groups, categorized prior to cataract surgery. Tear film was collected using Schirmer-1 strips and analyzed using an optimized method developed for low-volume Schirmer samples and allowing for repeated analyses, including other -omics approaches at a later stage. Metabolomic data were collected using a global liquid chromatography-mass spectrometry method. Samples were compared using principal component analysis and volcano plots to look for overall global differences as well as group-specific metabolic signatures.RESULTS: All samples were analyzed with a high number of features identified. No group-specific clustering was observed in principal component analysis for the dry eye positive or dry eye negative groups. However, volcano plots revealed that a majority of the metabolomic features had lower concentration in the dry eye positive group compared to the dry eye negative group. Four of these features had a Log2-fold change ≤ -1 and p value ≤.05. These warrant further study.CONCLUSION: Although no overall global difference was observed on the principal component analysis plots, a general trend of lower metabolite concentrations in the dry eye disease group was shown. Moreover, several metabolites of interest were discovered with significantly different signal intensities between the groups. These metabolites may aid future diagnostics and serve as possible biomarkers and therapeutic targets for dry eye disease in pre-operative cataract patients.PMID:40045865 | DOI:10.1080/02713683.2025.2472369

Phytother Res. 2025 Mar 5. doi: 10.1002/ptr.8466. Online ahead of print.ABSTRACTAngelica dahurica radix (ADR), the root of the botanical family Apiaceae (genus Angelica, species Angelica dahurica (Hoffm.)), has been used to treat colitis in clinical practice. The immunomodulatory effects of ADR are attributed to its polysaccharides (RP). However, its mechanism of action has not been elucidated. In this study, RP's structure was determined through nuclear magnetic resonance analysis. Dextran sulfate sodium-induced colitis in mice was utilized to assess the therapeutic efficacy of RP, while experiments involving fecal microbiota transplantation (FMT) and antibiotic treatment were performed to investigate the contribution of gut microbiota to RP's protective function. Non-targeted metabolomics was utilized to identify potential targets for elucidating the underlying mechanisms. RP is likely composed of (→4)-α-D-Glcp-(1→ and →4)-α-D-Galp-(1→). It effectively alleviated DSS-induced colitis by restoring the balance of the gut microbial community, a finding validated through FMT and antibiotic intervention experiments. Imidazole propionate (ImP) emerged as a potential target for RP's efficacy in treating colitis, which inhibits the activation of peroxisome proliferator-activated receptor gamma (PPAR-γ). Our findings suggest that RP may confer protection against colitis by activating the PPAR-γ signaling pathway through alleviating the constraint imposed by ImP.PMID:40045660 | DOI:10.1002/ptr.8466

Se Pu. 2025 Mar;43(3):289-294. doi: 10.3724/SP.J.1123.2024.04025.ABSTRACT"Admiring the lofty mountains, one realizes their own lack of talent." To further promote the implementation of new curriculum standards, a comprehensive instrumental analysis experiment was designed. Metabolomics, an emerging technology developed after genomics and proteomics, is an important part of systems biology. This study aims to explore the applications of metabolomics in the fields of environment and health. Sample pretreatment technology and detection methods for separating and enriching gallium were chosen through a literature review and group discussion. Students then experimentally analyzed the changes in metabolite content in cells cultured with metal-anticancer gallium drugs, which helped them understand the widespread application of metabolomics in the fields of environment and health. Additionally, material characterization was conducted using X-ray photoelectron spectroscopy (XPS) and thermogravimetric analysis (TG), and the gallium metal in metabolites was qualitatively and quantitatively analyzed using inductively coupled plasma mass spectrometry (ICP-MS). During discussions of this experiment, the teacher guided students in using large-scale instruments to solve problems comprehensively, fostering a research-based teaching approach to build a solid foundation for conducting efficient instrument analysis and comprehensive experiments within the classroom in future.PMID:40045652 | DOI:10.3724/SP.J.1123.2024.04025