PubMed

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

Se Pu. 2025 Mar;43(3):207-219. doi: 10.3724/SP.J.1123.2024.04003.ABSTRACTGlutamine synthetase (GS), the only enzyme responsible for de novo glutamine synthesis, plays a significant role in cancer progression. As an example of the consequences of GS mutations, the R324C variant causes congenital glutamine deficiency, which results in brain abnormalities and neonatal death. However, the influence of GS-deficient mutations on cancer cells remains relatively unexplored. In this study, we investigated the effects of GS and GS-deficient mutations, including R324C and previously unreported K241R, which serve as models for GS inactivation. This study provided intriguing insights into the intricate relationship between GS mutations and cancer cell metabolism. Our findings strongly support recent studies that suggest GS deletion leads to the suppression of diverse signaling cascades associated with glutamine metabolism under glutamine-stripping conditions. The affected processes include DNA synthesis, the citric acid cycle, and reactive oxygen species (ROS) detoxification. This suppression originates from the inherent inability of cells to autonomously synthesize glutamine under glutamine-depleted conditions. As a key source of reduced nitrogen, glutamine is crucial for the formation of purine and pyrimidine bases, which are essential building blocks for DNA synthesis. Furthermore, the citric acid cycle is inhibited by the absence of negatively charged glutamate within the mitochondrial matrix, particularly when glutamine is scarce. This deficiency decreases the flux of α-ketoglutarate (α-KG), a principal driver of the citric acid cycle. Intermediate metabolites of the citric acid cycle directly or indirectly contribute to the generation of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, a core component of redox homeostasis. Using the GS_R324C and GS_K241R mutants, we conducted an integrative transcriptomics and metabolomics analysis. The GS mutants with reduced activity activated multiple amino acid biosynthesis pathways, including arginine-proline, glycine-serine-threonine, and alanine-aspartate-glutamate metabolism. This intriguing behavior led us to hypothesize that despite hindrance of the citric acid cycle, abundant intracellular glutamate is redirected through alternative processes, including transamination. Simultaneously, key metabolic enzymes in the amino acid synthesis pathways, such as glutamic-oxaloacetic transaminase 1 (GOT1), glutamic-pyruvic transaminase 2 (GPT2), pyrroline-5-carboxylate reductase 1 (PYCR1), and phosphoserine aminotransferase 1 (PSAT1), exhibited increased mRNA levels. Additionally, GS deficiency appeared to upregulate the expression of glutamine transporters SLC38A2 and SLC1A5. Thus, restricting extracellular amino acids, such as glutamine, induces a stress response while promoting transcription or translation by a select group of genes, thereby facilitating cellular adaptation. However, similar to GS_WT, both GS_R324C and GS_K241R were modulated by glutamine treatment. Among GS-activity-dependent behaviors, the increased expression of numerous aminoacyl-tRNA synthetases (ARSs), which are critical for aminoacyl-tRNA biosynthesis, remains poorly understood. Most ARS-encoding genes are transcriptionally induced by activating transcription factor 4 (ATF4), the expression of which increases under oxidative stress, endoplasmic reticulum stress, hypoxia, and amino acid limitation. In GS-deficient cells, the increased expression of ATF4 was accompanied by pronounced stress caused by glutamine starvation. Thus, ARS upregulation may predominantly arise from increased ATF4 expression in GS-deficient cells. Additionally, transcriptomic analysis revealed the differential expression of specific genes, regardless of GS activity, suggesting that GS is involved in various processes other than glutamine synthesis, including angiogenesis. Although our omics study was limited to H1299 cells, in subsequent experiments, we validated our findings using additional cell lines, including Hepa1-6 and LN-229. To attain a more comprehensive understanding of the impact of the newly identified GS_K241R mutant, our investigation should be extended to various cell types and mouse models. In summary, we identified and investigated GS-deficient mutations in cancer cells and conducted an integrative transcriptomics-metabolomics analysis with comparisons to wild-type GS. This comprehensive approach provided crucial insights into the intricate pathways modulated by GS activity. Our findings advance the understanding of how GS functions in the context of reprogrammed cellular metabolism, particularly during glutamine deprivation. The altered metabolism triggered by elevated glutamate levels arising from GS mutations highlights the remarkable plasticity of cancer cell metabolism. Notably, considering the increasing research focus on GS as a potential therapeutic target in various cancer types, the findings of this study could provide innovative perspectives for drug development and the formulation of clinical treatment strategies.PMID:40045642 | DOI:10.3724/SP.J.1123.2024.04003

Anim Biosci. 2025 Feb 27. doi: 10.5713/ab.24.0628. Online ahead of print.ABSTRACTOBJECTIVE: The aim of this study is to investigate the dynamic changes of plasma bile acids (BA) and their associations with physiological metabolisms and fecal microbiome in transitional dairy cows.METHODS: Twenty multiparous dairy cows were selected, the blood and fecal samples were collected at d -21, -7, +7, and +21 relative to calving. The targeted metabolome and 16s rDNA gene sequencing were applied to detect BA profiles and fecal microbial composition, respectively.RESULTS: Totally, 32 BA species including 9 primary BAs (PBA) and 23 secondary BAs (SBA) were identified. Most of the PBAs (7 out to 9) and SBAs (15 out to 23) exhibited significant increases postpartum compared to prepartum. Notably, ursodeoxycholic acid, taurocholic acid and 7-ketodeoxycholic acid showed higher importance. Correlation analysis showed the BAs concentrations positively correlated with the concentrations of aspartate aminotransferase, total antioxidant capacity, and glutathione peroxidase, but negatively correlated with the concentrations of triglyceride significantly. A decline in bacterial alpha diversity in postpartum and significantly different β-diversity were observed. Additionally, 30 significant different genera were identified over the transition period. Among these, six and eleven biomarkers such as Alistipes and Ruminococcaceae_UCG_014 were identified at +7d and +21d, respectively. Furthermore, the abundances of choloylglycine hydrolase and 7-alpha-hydroxysteroid dehydrogenase involved in SBA biosynthesis were significantly higher postpartum as determined by PICRUSt2 analysis over the transition period.CONCLUSION: These findings underscore a significant surge in the demand for BAs for postpartum dairy cows and highlight the potential impact of BAs on bovine health. By shedding light on these metabolic dynamics, our study offers valuable insights into strategies for optimizing the nutrition and well-being of perinatal dairy cows.PMID:40045625 | DOI:10.5713/ab.24.0628

Aging Cell. 2025 Mar 5:e70037. doi: 10.1111/acel.70037. Online ahead of print.ABSTRACTNicotinamide adenine dinucleotide kinase (NADK) is essential to the generation of nicotinamide adenine dinucleotide phosphate (NADP(H)), an important metabolic coupling factor involved in glucose-stimulated insulin secretion. In the present study, we showed that the expression of Nadk and Nadk2 transcripts and NADP(H) content were lower in islets of 80-week-old (aged) mice than those of 8-week-old (young) mice. This was associated with diminished oral glucose tolerance of old mice and the glucose-stimulated insulin secretion (GSIS) response of islets. Knockdown (KD) of Nadk or Nadk2 gene expression in NIT-1 cells impaired glucose-stimulated insulin secretion. Metabolomic analysis revealed that Nadk KD specifically affected purine metabolism in glucose-stimulated cells. The levels of 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) were higher in KD cells than in the non-targeting control (NTC) cells. Phosphorylation of AMP-activated protein kinase (AMPK) was elevated in glucose-treated KD cells compared to that of NTC cells. Increased AICAR level and AMPKα phosphorylation were observed in the glucose-stimulated islets of the aged mice. Genetic and pharmacological inhibition of AMPK promoted glucose-stimulated insulin release by KD cells and the aged mouse islets. It is likely that NADK is modulatory to AMPK activation in pancreatic β-cells and to their GSIS response. Enhanced AICAR formation in KD cells was accompanied by significantly increased conversion from inosine monophosphate (IMP) in a tetrahydrofolate (THF)-dependent manner. Folate supplementation augmented the GSIS response of KD cells and aged mouse islets. Taken together, these findings suggest that the aging-associated decline in NADK expression may underlie the reduced insulin secretory capacity of pancreatic β-cells.PMID:40045495 | DOI:10.1111/acel.70037

Gut Microbes. 2025 Dec;17(1):2474143. doi: 10.1080/19490976.2025.2474143. Epub 2025 Mar 5.ABSTRACTThe interplay between bile acids (BAs) and metabolic diseases has gained importance in recent years, with a variety of studies investigating their relationship with diverging results. Therefore, in the present study we performed a detailed analysis of BA metabolism in 492 subjects with different metabolic phenotypes. Besides microbiomics and metabolomics this investigation included in silico analysis of community metabolism to examine metabolic interchange between different microbes as well as microbes and the human host. Our findings revealed distinct changes in the BA profiles of patients with diabetes and prediabetes, whereas obesity alone had no influence on circulating BAs. Impaired glycemic control led to increased circulating BAs, a shift toward more secondary BAs, and an increase in the ratio of glycine to taurine-conjugated BAs. Additional analyses revealed that the ratio of glycine to taurine conjugation demonstrated variations between the single BAs, cholic acid (CA), chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), regardless of the metabolic status, with CA having a higher fraction of taurine conjugation. Furthermore, we found that microbiome alterations are associated with BAs, independent of diabetes or obesity. Analysis of microbial community metabolism revealed differential relative pathway abundance in relation to diabetes, particularly those related to membrane and polyamine synthesis. Increased bacterial cross-feeding of polyamines, galactose, and D-arabinose also coincided with an increase in BA. Notably, our serum metabolome analysis mirrored several of the previously in silico predicted exchanged metabolites, especially amino acid metabolism. Therefore, targeting BA metabolism may be a future approach for the treatment of metabolic diseases, especially prediabetes and type 2 diabetes.PMID:40045464 | DOI:10.1080/19490976.2025.2474143

BMC Cancer. 2025 Mar 5;25(1):402. doi: 10.1186/s12885-025-13820-x.ABSTRACTBACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is among the most aggressive malignancies, underscoring the need for early diagnosis to improve patient outcomes. Tumor-derived exosomes, which can be non-invasively obtained and reflect the metabolic state of tumors in real-time, are under increasing investigation for their diagnostic potential. Herein we analyzed metabolite differences in exosomes, serum, and tissues from patients with HNSCC to identify potential diagnostic biomarkers of clinical relevance.METHODS: Non-targeted metabolomics based on liquid chromatography-mass spectrometry was employed to quantify metabolites in exosome, serum, and tissue samples from 11 patients with HNSCC and six patients without cancer. The metabolic profiles of HNSCC were analyzed through univariate and multivariate statistical methods, differential metabolite analysis, and pathway enrichment analysis.RESULTS: We identified three differential metabolites in exosomes, 45 in serum, and 33 in tissues. Notably, patients with HNSCC exhibited significant disruptions in protein and amino acid metabolism. Spermine was exclusively detected in exosomes and tissues from patients with HNSCC. We hypothesize that spermine is extracellularly secreted by malignant cells via exosomes and subsequently enters the bloodstream. Moreover, spermine synthase was highly expressed in HNSCC tissues. Knocking down spermine synthase markedly impaired HNSCC cell proliferation and migration.CONCLUSIONS: This study provides a preliminarily characterization of the metabolic profile of HNSCC and highlights spermine and its synthetic pathways as potential diagnostic and therapeutic targets. Future studies are warranted to elucidate the mechanism of action of spermine in HNSCC and explore its utility in early diagnosis and therapeutic development.PMID:40045286 | DOI:10.1186/s12885-025-13820-x

Nat Metab. 2025 Mar 5. doi: 10.1038/s42255-025-01245-6. Online ahead of print.ABSTRACTPreclinical studies have shown that asparagine deprivation enhances T cell antitumour responses. Here we apply compassionate use of L-asparaginase, usually employed to treat blood malignancies, on patients with recurrent metastatic nasopharyngeal carcinoma. The use of L-asparaginase notably enhances immune-checkpoint blockade therapy in patients by strengthening CD8+T cell fitness. Our study shows that this combination is a promising avenue for clinical application and provides further mechanistic insight into how asparagine restriction rewires T cell metabolism.PMID:40045118 | DOI:10.1038/s42255-025-01245-6

Planta. 2025 Mar 5;261(4):79. doi: 10.1007/s00425-025-04646-9.ABSTRACTOmics approaches provide comprehensive insights into plant arsenic stress responses, setting the stage for engineering arsenic-tolerant crops. Understanding arsenic (As) toxicity in plants is crucial for environmental and agricultural sustainability, considering the implications of As in impacting soil productivity and environmental health. Although some articles already examined the detailed molecular mechanisms behind As toxicity and tolerance, a comprehensive review of recent omics advancements in studying plant responses to As exposure is needed. The present review highlights the valuable contribution of omics approaches (genomics, transcriptomics, proteomics, and metabolomics) to characterize the intricate response to As overall, which could empower As-tolerant plant development. Genomic techniques, such as QTL mapping, GWAS, RAPD, and SSH, hold the potential to provide valuable insights into the genetic diversity and expression patterns associated with the plant response to As stress, highlighting also the power of new advanced technology such as CRISPR-Cas9. Transcriptomics approaches (e.g., microarrays and RNA sequencing) revealed gene expression patterns in plants under As stress, emphasizing the role of sulfur metabolism in As tolerance. Proteomics, using 2-DE combined with MALDI-ToF MS or ESI-MS/MS, offers insights into the stress-inducible proteins and their involvement in As toxicity mitigation, while iTRAQ-based proteomics enabled an understanding of cultivar-specific responses under high As concentration. Metabolomics, with LC-MS, GC-MS, (U)HPLC, and NMR, elucidated small molecule alterations and complex metabolic activities occurring under As plant exposure. Compendium of data and evidence-related tools offers a foundation for advancing As-tolerant plant development and promoting environmental and agricultural resilience.PMID:40044842 | DOI:10.1007/s00425-025-04646-9

Sci Rep. 2025 Mar 5;15(1):7763. doi: 10.1038/s41598-025-91039-3.ABSTRACTSeed dormancy is a common physiological phenomenon during storage which has a great impact on timely germination of seeds. An in-depth analysis of the physiological and molecular mechanisms of perilla seed dormancy release is of great significance for cultivating high-vigor perilla varieties. We used gibberellin A3-soaked seeds (GA), natural dormancy-release seeds (CK) and water-soaked seeds (WA) to study the changes in the transcriptome and metabolome of dormancy release. The germination test revealed that the optimum concentration of gibberellin A3 for releasing dormancy from perilla seeds was 200 mg/L. The results revealed that plant hormone signal transduction, starch and sucrose metabolism and citric acid cycle were significantly enriched metabolic pathways closely related to seed dormancy release. Perilla seeds release their dormancy by enhancing the expression of GID1, PIF3, SnRK2, IAA, ARR-A, GH3, MKK4_5, otsB, GN1_2_3, glgC, WAXY, inhibiting the expression of DELLA, PP2C, glga, bglX, and GN4, and regulating the content of gibberellin A4, abscisic acid, auxin, sucrose, maltose, trehalose, and α-D-glucose 1-phosphate. Auxin plays an important role in breaking perilla seed dormancy and promoting seed germination. The energy required for breaking seed dormancy and germination of perilla seeds is mainly provided through sucrose metabolism. Citric acid cycle (TCA cycle) is the main energy supply transformation pathway for seed germination.PMID:40044827 | DOI:10.1038/s41598-025-91039-3

Nat Commun. 2025 Mar 5;16(1):2213. doi: 10.1038/s41467-025-57675-z.NO ABSTRACTPMID:40044695 | DOI:10.1038/s41467-025-57675-z

Nat Commun. 2025 Mar 5;16(1):2215. doi: 10.1038/s41467-025-57674-0.NO ABSTRACTPMID:40044665 | DOI:10.1038/s41467-025-57674-0

Cell Prolif. 2025 Mar 5:e70014. doi: 10.1111/cpr.70014. Online ahead of print.ABSTRACTMaternal age has been reported to impair oocyte quality. However, the molecular mechanisms underlying the age-related decrease in oocyte competence remain poorly understood. Cumulus cells establish direct contact with the oocyte through gap junctions, facilitating the provision of crucial nutrients necessary for oocyte development. In this study, we obtained the proteomic and metabolomic profiles of cumulus cells from both young and old mice. We found that fatty acid beta-oxidation and nucleotide metabolism, markedly active in aged cumulus cells, may serve as a compensatory mechanism for energy provision. Tryptophan undergoes two principal metabolic pathways, including the serotonin (5-HT) synthesis and kynurenine catabolism. Notably, we discovered that kynurenine catabolism is reduced in aged cumulus cells compared to young cells, whereas 5-HT synthesis exhibited a significant decrease. Furthermore, the supplement of 5-HT during cumulus-oocyte complexes (COCs) culture significantly ameliorated the metabolic dysfunction and meiotic defects in old oocytes. In sum, our data provide a comprehensive multiple omics resource, offering potential insights for improving oocyte quality and promoting fertility in aged females.PMID:40044606 | DOI:10.1111/cpr.70014

J Affect Disord. 2025 Mar 3:S0165-0327(25)00325-8. doi: 10.1016/j.jad.2025.02.109. Online ahead of print.ABSTRACTBACKGROUND: Major depressive disorder (MDD) involves molecular alterations and pathway dysregulation. Metabolic interconnections are crucial for normal functioning, yet current analysis focuses on individual pathways or biomarkers, overlooking intricate metabolic biomarker interactions.METHODS: Plasma metabolomic data from 182,053 UK Biobank participants [9425 MDD, and 172,628 healthy controls (HC)] were used to construct metabolic correlation networks through bootstrap inference analysis (bootstrap step size: 1000, 3000, 5000, 7000, 9000; n = 1000 times/size). Differential core metabolic network signatures between MDD and HC were identified by machine learning, followed by metabolic pathway analysis. Various deep learning and machine learning models were employed to differentiate MDD from HC groups using the identified network features and baseline characteristics.RESULTS: The MDD metabolic network showed marked reorganization, with a sparser and more streamlined network structure compared to controls (p < 0.05 for both Vnet-edge and Vnet-node). Analysis of the core network in MDD revealed four key altered pathways, with linoleic acid metabolism being the most influential (p < 0.01, impact = 0.29). An extreme gradient boosting model combining network signatures and baseline features achieved 73 % accuracy, and an AUROC of 0.82 in differentiating MDD from HC groups.CONCLUSIONS: This large-scale, metabolomic connectome analysis revealed consistent dysregulated metabolic network features in MDD, providing a robust and distinguishable framework compared to controls. The MDD network exhibits distinct connectivity patterns, particularly within linoleic acid metabolism. Integrating metabolomics as networks, rather than isolated markers, offers a promising approach for elucidating MDD pathophysiology and identifying diagnostic biomarkers.PMID:40044084 | DOI:10.1016/j.jad.2025.02.109