PubMed

BMC Genomics. 2025 May 16;26(1):494. doi: 10.1186/s12864-025-11664-0.ABSTRACTBACKGROUND: The cytochrome P450 superfamily comprises a large group of enzymes crucial for the biosynthesis and metabolism of diverse endogenous and exogenous secondary metabolites in plants. Chrysanthemum, an ornamental genus with considerable medicinal value, is one of the most economically important floricultural crops in the world. The characteristics and functions of CYP450 genes in Chrysanthemum species, however, remain largely unknown.RESULTS: In this study, we identified 371 CYP450 genes in the Chrysanthemum indicum genome, and categorized them into 8 clans and 44 families through phylogenetic analysis. Gene duplication analysis revealed 111 genes in 47 tandem duplicated clusters and 28 genes in 15 syntenic blocks, suggesting that extensive duplication events may account for the rapid expansion of CiCYP450 superfamily. Additionally, extensive variations in gene structure, motif composition, and cis-regulatory element likely enhance the functional diversity of CiCYP450 proteins. Volatile metabolomic analysis detected a total of 53 distinct volatile organic compounds across the leaves, stems, and roots of C. indicum, with 19 and 16 compounds being exclusive to leaves and stems, respectively. Transcriptomic analysis identified 248 expressed CiCYP450 genes, with 31, 40, and 88 specifically or preferentially expressed in leaves, stems, and roots, respectively. Further correlation analyses between gene expression levels and compound contents highlighted 36 candidate CiCYP450 genes potentially responsible for the biosynthesis of 47 volatile organic compounds.CONCLUSIONS: The genome-wide analyses of cytochrome P450 superfamily offers essential genomic resources for functional studies of CiCYP450 genes, and is significant for the molecular breeding of Chrysanthemum.PMID:40375135 | DOI:10.1186/s12864-025-11664-0

Nat Struct Mol Biol. 2025 May 15. doi: 10.1038/s41594-025-01554-0. Online ahead of print.ABSTRACTDeciphering the processes through which cancer cells overcome stress, escape a repressive microenvironment and metastasize remains a challenge. Autophagy has been demonstrated to regulate cancer metastasis and C-terminal binding protein (CtBP) has been previously implicated in promoting metastasis in breast cancer. Here we identify the formation of a complex between CtBP and tripartite-motif-containing protein 28 (TRIM28) in the nucleus. Interestingly, this complex regulates the stability of both proteins, as the removal of either partner leads to degradation of the other. Furthermore, the stability of this complex in the nucleus inhibits autophagy through two independent mechanisms. Firstly, the formation of the complex sequesters TRIM28 in the nucleus, preventing its involvement in and its degradation through autophagy. Secondly, this complex participates in the suppression of PTEN expression and leads to inhibition of Unc-51-like kinase 1-mediated autophagy through activation of the protein kinase B-mammalian target of rapamycin pathway. Using mammary gland-specific CtBP-knockout mice, we demonstrate that repression of autophagy by the CtBP-TRIM28 complex modulates luminal duct formation. In breast cancer models, CtBP-TRIM28-dependent inhibition of cellular autophagy also promotes malignant metastasis. Therefore, our study reveals similarities between the mechanisms driving tumor progression and those involved in normal mammary gland development, potentially helping to pave the way toward targeted intervention in breast cancer metastasis.PMID:40374929 | DOI:10.1038/s41594-025-01554-0

Commun Biol. 2025 May 15;8(1):755. doi: 10.1038/s42003-025-08182-w.ABSTRACTThe nutrient exchange between corals and their symbiotic microalgae (Symbiodiniaceae) is vital for coral survival. Disruptions in this mutualistic relationship, often due to stress-induced dysbiosis, contribute significantly to coral mortality and reef decline globally. Dysbiosis is associated with substantial shifts in various metabolites, notably a rise in inositol, a sugar alcohol, though its role in coral-algae interactions remains unclear. Using a cnidarian model, we identify Symbiodiniaceae as the main source of inositol, with myo- and scyllo-inositol being the dominant forms under normal conditions. During heat stress, scyllo-inositol levels increase by 1.8 times in symbiotic hosts, and up to 26 times in cultured Symbiodiniaceae (Breviolum minutum). Meanwhile, myo-inositol decreases in host tissues but doubles within Symbiodiniaceae, indicating altered nutrient-sharing or stress signalling. In contrast, no changes are observed in aposymbiotic cnidarians (without Symbiodiniaceae). Additionally, inhibiting inositol production and transport in symbiotic tissues disrupts metabolite profiles, mimicking effects seen under heat stress, suggesting that inositol transport is crucial for maintaining metabolic balance and nutrient exchange. These findings reveal that disruptions in inositol dynamics play a critical role in stress responses, offering insights into dysbiosis mechanisms driving coral reef crises.PMID:40374873 | DOI:10.1038/s42003-025-08182-w

Sci Rep. 2025 May 15;15(1):16921. doi: 10.1038/s41598-025-90304-9.ABSTRACTNature has been considered an interesting source of secondary bioactive compounds. Plants and their associated endophytes are common sources for these active constituents. Our study demonstrates the metabolomics profiling of the ethyl acetate extracts of three endophytic fungi associated with rosemary roots (Cladosporium spp., Alternaria spp. and Talaromyces spp.) in addition to the in vitro evaluation of the antitrypanosomal potential. The results revealed the presence of 47 metabolites from different chemical classes such as terpenes, phenolics, alkaloids, polyketides, macrolides, and others. Furthermore, the extracts of Cladosporium, Alternaria and Talaromyces exhibited potential inhibitory effects against T. brucei with IC50 values of 1.3, 3.2 and 3.5 µg/mL, respectively. Supporting the study, the identified compounds were docked against two proteins: Rhodesain in complex with a macrolactam inhibitor and ornithine decarboxylase in complex with a c-terminal fragment of antizyme. The docking simulations showed that most of the identified compounds have moderate to comparable docking score (S = - 3.82 to - 6.10 kcal/mol) within rhodesain active site. In addition, they showed weak to moderate docking scores (- 2.33 to - 5.9 kcal/mol) with a differential docking profile within ornithine decarboxylase active site. According to these findings, fungal endophytes associated with rosemary roots can be considered as a promising source of antitrypanosomal bioactive metabolites.PMID:40374861 | DOI:10.1038/s41598-025-90304-9

Metabolomics. 2025 May 15;21(3):67. doi: 10.1007/s11306-025-02267-7.ABSTRACTBACKGROUND: Neurodegenerative disorders are a group of debilitating diseases affecting the central nervous system, and are characterized by the progressive loss of neurons, leading to declines in cognitive function, movement, and overall quality of life. While the exact causes remain elusive, it's believed that a combination of genetic, environmental, and lifestyle factors contribute to their development. Metabolites, the end products of cellular processes, reflect the physiological state of an organism. By analysing these molecules, researchers can gain a deeper understanding of the underlying metabolic changes associated with neurodegenerative disorders.AIM OF REVIEW: This review aims to explore the possibilities between metabolites and their association with neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), Parkinson's disease (PD), Multiple sclerosis (MS) and Huntington's disease (HD).KEY SCIENTIFIC CONCEPTS OF REVIEW: Metabolomic studies could potentially illuminate altered biochemical pathways, facilitating earlier detection and treatment of these conditions. Metabolomic investigations have revealed the role of oxidative stress, alterations in glucose and fat metabolism, mitochondrial dysfunction, apoptosis, glutamate excitotoxicity and alterations in myelin composition in neurodegenerative disorders. The common metabolic biomarkers identified includes glutamate, taurine, uric acid, branched chain amino acids, acylcarnitine, creatinine, choline, with some more amino acids and lipids. Metabolomics offers valuable insights into disease mechanisms and potential therapeutic targets by identifying biochemical and metabolic alterations, but still there are several aspects to be explored for accurate mapping of metabolites with specific pathway involved in the disease.PMID:40374790 | DOI:10.1007/s11306-025-02267-7

Sci Rep. 2025 May 15;15(1):16981. doi: 10.1038/s41598-025-00312-y.ABSTRACTPeople who visit high-altitude for research and development work, pilgrimage, recreational purposes and deployments are exposed to different environmental conditions such as low temperature and atmospheric pressure, leading to hypoxia, high radiation, dry air, and non-availability of fresh food and vegetables. These environmental stressors have significant physiological effects on the human body. Among these challenges, hypobaric hypoxia at high-altitude affects aerobic metabolism and thereby reduces the supply of metabolic energy. Metabolic alterations may further lead to extreme environment related maladaptation as evidenced by alterations in the levels of metabolites and metabolic pathways. To investigate the variation in the metabolite profile, urine samples were collected from 16 individuals at baseline (BL, 210 m) and high-altitude (HA, 4200 m). Untargeted urinary metabolic profiling was performed by liquid chromatography-mass spectrometry (LC-MS) in conjunction with statistical analysis. Univariate and multivariate statistical analyses revealed 33 differentially abundant metabolites based on fold change, VIP score and p value. These distinct metabolites were primarily associated with pathways related to phenylalanine, tyrosine and tryptophan biosynthesis; metabolism of phenylalanine, biotin, tyrosine, cysteine and methionine along with alanine, aspartate and glutamate metabolism. Thes pathways are also linked with pentose and glucuronate interconversions, citrate cycle, vitamin B6 and porphyrin metabolism. Furthermore, receiver operating characteristic curve analysis detected five metabolites namely, 2-Tetrahydrothiopheneacetic acid, 1-Benzyl-7,8-dimethoxy-3-phenyl-3H-pyrazolo [3,4-c] isoquinoline, Abietin, 4,4'-Thiobis-2-butanone, and Hydroxyisovaleroyl carnitine with high range of sensitivity and specificity. In summary, this longitudinal study demonstrated novel metabolic variations in humans exposed to high-altitude, utilising the potential of LC-MS based metabolomics. Thus, the present findings shed light on the impact of hypoxic exposure on metabolic adaptation and provide a better understanding about the pathophysiological mechanisms underlying high-altitude illnesses correlated to tissue hypoxia.PMID:40374771 | DOI:10.1038/s41598-025-00312-y

Sci Rep. 2025 May 15;15(1):16959. doi: 10.1038/s41598-025-01343-1.ABSTRACTPropolis has significant hepatoprotective effects, but the active components, targets, and mechanisms have not been fully elucidated. Here, we integrated network pharmacology, serum metabolomics, and 16 S rRNA sequencing to disclose the hepatoprotective effects of Chinese propolis (CP) by lipopolysaccharide (LPS)-induced acute liver injury (ALI) in mice. The core active ingredients of CP against ALI, including quercetin, luteolin, and kaempferol, can bind stably to pro-inflammatory factors such as TNF-α, IL-6, IL-1β, and IFN-γ. CP and its active ingredient quercetin obviously alleviated LPS-induced ALI in mice and downregulated the levels of pro-inflammatory genes (Tnf-α, Il-1β, Il-6, Mcp-1, Ifn-γ, and Cox-2) while increasing the protein expression levels of the antioxidant factors Nrf2 and HO-1. Untargeted serum metabolomics analysis indicated that CP and quercetin ameliorated LPS-induced metabolic disorders mainly by modulating the ascorbate and aldarate metabolisms. 16 S rRNA sequencing demonstrated that CP and quercetin modulated the gut microbiota, augmenting the relative abundance of anti-inflammatory bacteria like Lactobacillus and Dubosiella and diminishing the pro-inflammatory bacteria like Alistipes. Spearman correlation analysis revealed that there existed significant correlations among inflammatory factors, gut microbiota, and differential metabolites of serum after propolis pretreatment. Our research indicated that propolis effectively alleviated pathological damage in LPS-induced ALI mice mainly through partially restoring the ecology of gut flora and metabolic disorders to reduce inflammation.PMID:40374745 | DOI:10.1038/s41598-025-01343-1

Sci Rep. 2025 May 15;15(1):16897. doi: 10.1038/s41598-025-01705-9.ABSTRACTMetformin reduces the incidence of breast cancer in patients with obesity and type 2 diabetes. However, our knowledge of the effects of metformin on breast cancer recurrence is limited. Within the randomized double-blind placebo-controlled phase II trial MetBreCS, we examined changes in breast tissue from breast cancer survivors with BMI > 25 kg/m2 after treatment with metformin. To identify metformin-regulated signaling pathways, we integrated the transcriptomic, metabolomic and steroid hormone profiles using bivariate and functional analyses. We identified MS4A1, HBA2, MT-RNR1, MT-RNR2, EGFL6 and FDCSP expression to be differentially expressed in breast tissues from metformin-treated postmenopausal women. The integration of transcriptomic and metabolomic profiles revealed down-regulation of immune response genes associated with reduced levels of arginine and citrulline in the metformin-treated group. The integration of transcriptomic and steroid hormone profiles showed an enrichment of steroid hormone biosynthesis and metabolism pathways with highly negatively correlated CYP11A1 and CYP1B1 expression in breast tissue from postmenopausal metformin-treated women. Our results indicate that postmenopausal breast cancer survivors treated with metformin have specific changes in breast tissue gene expression that may prevent the development of new tumors.Trial registration: MetBreCs trial is registered at European Union Clinical Trials Register (EudraCT Protocol # 2015-001001-14) on 07/10/2015.PMID:40374694 | DOI:10.1038/s41598-025-01705-9

Nat Commun. 2025 May 15;16(1):4509. doi: 10.1038/s41467-025-59163-w.ABSTRACTKidney disease, the ninth leading cause of death in the United States, suffers from poor diagnostic efficiency (10%). Traditional biopsies use molecular reagents to enhance diagnostic power but are limited by overlapping spatial and chromatic signals, product quality variability, and additional processing. To address these challenges without disrupting routine diagnostics, we implement label-free imaging modalities-stimulated Raman scattering (SRS), second harmonic generation (SHG), and two-photon fluorescence (TPF)-within a single setup. We identify morphological, lipidomic, and metabolic biomarkers in control and diabetic kidney samples at subcellular resolution. Label-free Stimulated Raman Histology (SRH) reveals distinct collagen morphology, mesangial-glomerular volumes, lipid saturation, redox status, and lipid-protein concentrations previously unrecognized in kidney diseases. Using the same tissue section enhances diagnostic value without compromising limited tissue. These multimodal biomarkers broadly deepen the understanding of kidney disease progression by integrating lipidomic, fibrotic, and metabolic data.PMID:40374604 | DOI:10.1038/s41467-025-59163-w

J Microbiol Biotechnol. 2025 May 15;35:e2501026. doi: 10.4014/jmb.2501.01026.ABSTRACTMetabolic profiling is a valuable tool for elucidating the biochemical pathways and key metabolites involved in the health benefits associated with microbial fermentation. In this study, we investigated the metabolic changes occurring during the fermentation of lettuce leaves by Bacillus subtilis, a widely studied bacterium known for its diverse metabolic capabilities. Through non-targeted metabolic profiling, we identified and characterized metabolites that may contribute to the beneficial effects of fermented lettuce. Using gas chromatography-mass spectrometry (GC/MS), we identified 54 metabolites in the fermented lettuce samples. Additionally, we elucidated the alterations in metabolite profiles during the bioconversion of lettuce using B. subtilis. Notably, 11,14-eicosadienoic acid, 13-docosenoic acid, and oleic acid were either produced or enriched during bioconversion, were identified as potential contributors to the enhanced nutritional and bioactive properties of fermented lettuce. This study underscores the potential of metabolic profiling to uncover the metabolic pathways and specific metabolites associated with health benefits in fermented foods. These findings pave the way for developing functional foods with improved nutritional value and bioactivity.PMID:40374527 | DOI:10.4014/jmb.2501.01026

Sci Bull (Beijing). 2025 Apr 29:S2095-9273(25)00466-9. doi: 10.1016/j.scib.2025.04.062. Online ahead of print.NO ABSTRACTPMID:40374473 | DOI:10.1016/j.scib.2025.04.062

Am J Chin Med. 2025;53(3):889-908. doi: 10.1142/S0192415X25500338.ABSTRACTIt is crucial to prevent and treat liver fibrosis in patients with chronic liver disease. Dihydromyricetin (DMY) is a natural flavonoid compound from traditional Chinese medicine, known to alleviate chronic liver injury. However, its role in regulating inflammatory responses through gut microbiota and metabolic changes remains unclear. In this study, a mouse model of liver fibrosis was induced with carbon tetrachloride (CCl4), and DMY was administered via gavage. Histopathology, immunohistochemistry, Reverse Transcription Polymerase Chain Reaction (RT-PCR), 16S rRNA sequencing, and untargeted metabolomics were employed to evaluate DMY's pharmacological effects on CCl4-induced liver fibrosis and explore its underlying mechanisms. Our results show that DMY reduced the aspartate transaminase (AST) and alanine transaminase (ALT) serum levels in liver fibrosis model mice, and lowered the mRNA expression of pro-inflammatory cytokines and fibrosis markers. Additionally, DMY restored the richness and diversity of the gut microbiota, with several microbiota taxa significantly correlating with inflammatory markers. Metabolomic analysis of serum and liver tissue revealed that DMY significantly altered the liver metabolite disturbances induced by CCl4. Pearson correlation analysis demonstrated a strong relationship between microbial composition and liver metabolites. These results suggest that DMY alleviates liver fibrosis in mice by reshaping the gut microbiota and host metabolism, thereby improving the inflammatory response.PMID:40374379 | DOI:10.1142/S0192415X25500338

Am J Chin Med. 2025;53(3):833-862. doi: 10.1142/S0192415X25500314.ABSTRACTEmerging evidence suggests that changes in the composition of the gut microbiota may play an important role in the pathogenesis of Parkinson's disease (PD). Paeonia lactiflora Pall., a traditional Chinese medicinal herb belonging to the genus Paeonia, is commonly used in Chinese medicinal practice for the treatment of PD. However, the specific mechanisms of its action remain poorly understood. This study aimed to further determine the neuroprotective properties of Paeonia lactiflora Pall. water extract (PWE) in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD model, and to investigate its potential implications for the pathogenesis of PD. A PD mouse model was established via the intraperitoneal administration of MPTP, followed by the assessment of motor function using behavioral tests. Western blotting and histopathological analysis were used to measure the levels of dopaminergic (DAergic) neurodegeneration-related factors in the midbrain (containing the substantia nigra (SN)) and striatum. 16S rRNA gene sequencing and metabolomic analysis were applied to identify differences in the gut microbiota and metabolites, respectively. Our results indicate that PWE effectively protects against MPTP-induced motor deficits, loss of DAergic neurons, blood-brain barrier (BBB) damage, and neuroinflammation in PD. The protective effects of PWE against PD are mediated through modulation of the gut microbiota, specifically by an increase in the abundance of the genus Dubosiella. In this study, we selected D. newyorkensis as a representative strain of the genus, and determined its therapeutic effects in an MPTP-induced PD mouse model. Our preliminary findings suggest that the neuroprotective effects of D. newyorkensis may be related to the production of serum indoleacetic acid.PMID:40374370 | DOI:10.1142/S0192415X25500314

Anal Chim Acta. 2025 Jul 8;1358:344098. doi: 10.1016/j.aca.2025.344098. Epub 2025 Apr 19.ABSTRACTBACKGROUND: Mass Spectrometry Imaging (MSI) is a label-free imaging technique used in spatial metabolomics to explore the distribution of various metabolites within biological tissues. Spatial segmentation plays a crucial role in the biochemical interpretation of MSI data, yet the inherent complexity of the data-characterized by large size, high dimensionality, and spectral nonlinearity-poses significant analytical challenges in MSI segmentation. Although deep learning approaches based on convolutional neural networks (CNNs) have shown considerable success in spatial segmentation for biomedical imaging, they often struggle to capture the comprehensive structural information of MSI data.RESULTS: We propose SagMSI, an unsupervised graph convolution network (GCN)-based segmentation strategy that combines spatial-aware graph construction of MSI data with a GCN module within a deep neural network. This approach enables flexible, effective, and precise spatial segmentation. We applied SagMSI to both simulated data and various MSI experimental datasets and compared its performance against three commonly used segmentation methods, including t-SNE + k-means, a pipeline implemented by the R package Cardinal, and a CNN-based segmentation method. Visual comparisons with histological images and quantitative evaluations using the silhouette coefficient and adjusted rand index demonstrate that SagMSI excels in segmenting complex tissues, revealing detailed sub-structures, and delineating distinct boundaries of sub-organs with minimal noise interference. The integration of graph-based neural networks with spatially structural information offers deeper insights into spatial omics.SIGNIFICANCE: The MSI data is modelled by graph structure so as to incorporate the biomolecular profiling and spatial adjacency within neighboring pixels. The GCN framework generates meaningful pixel representations by learning local and global contextual information through the graph-based structure, thus enabling precise segmentation of MSI. The approach demonstrated high flexibility, robustness to noise, and applicability in exploring complex tissue structures and identifying marker ions associated with microregions.PMID:40374250 | DOI:10.1016/j.aca.2025.344098

Am J Clin Nutr. 2025 May 13:S0002-9165(25)00259-X. doi: 10.1016/j.ajcnut.2025.04.036. Online ahead of print.ABSTRACTThe Mediterranean Diet Pyramid was officially published in the American Journal of Clinical Nutrition in 1995. Since then, our understanding of the role of the Mediterranean diet (MedDiet) and its role in reducing risk of chronic diseases has grown substantially. The aim of this article is to provide a narrative review of the historical context of the MedDiet and its environmental impact, summarize health-related evidence from the past three decades, and explore its practical applications and cultural adaptations. A large body of evidence from prospective cohort studies, randomized controlled trials, and mechanistic studies consistently supports the benefits of the MedDiet for the prevention of chronic diseases, particularly cardiometabolic diseases and improving healthy aging. Growing evidence demonstrates that the MedDiet promotes favorable changes in circulating metabolites and gut microbiome composition, providing novel insights into biological mechanisms underlying its health benefits and informing the development of precision nutrition strategies. The MedDiet aligns with the principles of the Planetary Health Diet recommended by the EAT-Lancet Commission, which aims to promote both human health and environmental sustainability. The development of the MedDiet pyramid 30 years ago inspired the creation of the Asian, African, and Latin American Heritage Diet Pyramids. Despite robust evidence, further studies are needed to evaluate the long-term effectiveness and adaptability of the MedDiet across diverse populations, cultural settings, and food environments.PMID:40374164 | DOI:10.1016/j.ajcnut.2025.04.036

Clin Res Hepatol Gastroenterol. 2025 May 13:102613. doi: 10.1016/j.clinre.2025.102613. Online ahead of print.ABSTRACTColorectal cancer (CRC) exhibits significant heterogeneity across different colonic subsites, which vary in embryological origin, microbiome, metabolome, and molecular profiles, affecting tumorigenesis, treatment response, and prognosis. We emphasize the importance of this subsite heterogeneity to advance precision medicine in CRC. Colorectal cancer (CRC) is a major public health crisis worldwide, with significant morbidity and mortality. Despite its prevalence, the majority of clinical and basic research studies have historically simplified CRC into broad categories such as right-sided colon cancer, left-sided colon cancer, and rectal cancer [1]. This oversimplification overlooks the critical differences among the distinct colonic subsites: cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, and sigmoid colon [2,3]. Each of these subsites exhibits unique embryological origins, vascular supply, neural innervation, and microbial colonization, which drive spatially defined heterogeneity in tumorigenesis, treatment response, and survival [4]. This commentary calls for a paradigm shift in CRC research, advocating for a molecular-clinicopathological framework that recognizes the distinct characteristics of each colonic subsites.PMID:40374162 | DOI:10.1016/j.clinre.2025.102613

Cell Signal. 2025 May 13:111865. doi: 10.1016/j.cellsig.2025.111865. Online ahead of print.ABSTRACTChoroidal neovascularization (CNV) is one of the main causes of visual loss. Endothelial cell metabolic reprogramming is an important mechanism in regulating pathological neovascularization. However, how endothelial cell metabolic reprogramming is regulated in CNV is not yet clear. In this study, we constructed CNV mouse model by laser injury and in vitro cell model by hypoxia-induced mouse brain microvascular endothelial cells (BMECs). We identified glucose transporter Sodium-Dependent Glucose Transporter 1 (SGLT1) regulating endothelial cell metabolic reprogramming by siRNA transfection and metabolomics analysis. Mechanistically, we manifested the TCTTTGTCTG and ATTGCCTC sequences in the sglt1 promoter was targeted by SRY-box transcription factor 3 (SOX3). Furtherly, the function of SOX3 was induced by its Ser97 site combining with CDC-like kinase 2 (CLK2). Our results show that the CLK2-SOX3 combination targets sglt1, thereby inducing metabolic reprogramming of endothelial cells and promoting CNV.PMID:40373839 | DOI:10.1016/j.cellsig.2025.111865

Magn Reson Imaging. 2025 May 13:110421. doi: 10.1016/j.mri.2025.110421. Online ahead of print.ABSTRACTCeliac disease (CeD) is a chronic small intestinal autoimmune disease initiated by dietary gluten in genetically predisposed individuals. Till date, the only effective treatment for CeD is the gluten-free diet (GFD). However, not all patients achieve full histological recovery despite GFD. Thus, it is crucial to assess the treatment response and improvement in the villous architecture following GFD. Therefore, present study investigated the potential of NMR-based metabolomics for identifying non-invasive biomarkers for assessing treatment response. Comprehensive metabolic profiling of 120 biological samples comprising of small intestinal mucosal biopsies, blood plasmas and urines collected at two time points (before and after 6-8 months of GFD) from CeD patients (n = 20) was carried out using proton NMR spectroscopy. The levels of arginine glutamate, and glutamine were significantly reduced in both intestinal mucosa and blood plasma of CeD patients after GFD compared to their baseline values. These amino acids play an important role in intestinal energy metabolism, and alleviating inflammation, thereby contributing to healing mechanisms of small intestinal mucosa, following GFD. A logistic regression statistical model based on the combination of the above three blood plasma metabolites demonstrated AUC of 0.980, Youden index 0.900 with a sensitivity and a specificity of 90 % and 100 % for monitoring treatment response in CeD patients after GFD. The study revealed a panel of non-invasive plasma biomarkers (arginine, glutamate and glutamine) which may serve as surrogates of mucosal healing and treatment response in CeD patients, however, the findings need to be validated in a large cohort of patients.PMID:40373836 | DOI:10.1016/j.mri.2025.110421

Plant Sci. 2025 May 13:112556. doi: 10.1016/j.plantsci.2025.112556. Online ahead of print.ABSTRACTLonicera macranthoides is a vital medicinal herb frequently used in Chinese traditional medicine. Chlorogenic acid (CGA) and luteoloside are the most crucial bioactive pharmaceutical ingredients in L. macranthoides. Although CGA and luteoloside biosynthetic pathway and structural genes appeared to be extensively elucidated, the transcriptional regulation has yet to be unveiled. Here, integration of transcriptome and metabolome revealed a R2R3-MYB transcription factor LmMYB111 positively correlated with CGA concentration, which shares close homology with AtMYB111 and acts as a transcriptional activator. Overexpressing LmMYB111 in tobacco and Lonicera resulted in enhanced production of CGA and luteoloside. RNA-Seq demonstrated that overexpression of LmMYB111 dramatically upregulated CGA and luteoloside biosynthetic genes, including 10 PALs, 3 C4Hs, 7 4CLs, 4 HCT/HQTs, 3 CHSs and 5 CHIs. DNA Affinity Purification sequencing (DAP-Seq) revealed the binding motifs of LmMYB111 and 1135 downstream targets, including structural genes e.g. PAL1/PAL4s, C4H, 4CL2, CHI, and DFR as well as several transcription factors (TFs), e.g. MYB3/MYB4, bHLH62/TT8, BEL1, SCL15/SCL32 and ERF3.The electrophoretic mobility shift assay (EMSA) together with dual-luciferase reporter system (DLR) further proved that LmMYB111 bound to and activated proLmMYB4, proLmPAL1, proLm4CL2, proLmCHI and proLmDFR, therefore facilitating hyperaccumulation of CGA, luteoloside and other phenolics. These findings shed light on the participation of LmMYB111 in CGA and luteoloside biosynthetic regulatory networks in L. macranthoides mediated by controlling the expression of structural genes and TFs, which will contribute to elevate phenolics production by genetic engineering.PMID:40373830 | DOI:10.1016/j.plantsci.2025.112556

Food Chem. 2025 May 8;487:144675. doi: 10.1016/j.foodchem.2025.144675. Online ahead of print.ABSTRACTThis study investigates the digestibility, antioxidant capacity, total phenolic content (TPC) and the release of different metabolites from blended animal (camel and goat) and plant (oat, quinoa, almond) milks upon simulated infant static in vitro digestion. The study indicated that blending produced intermediate protein digestibility alongside enhanced release of bioactive compounds, heightened antioxidant potential, and richer metabolite diversity. Notably, camel-quinoa and goat-quinoa blends stood out for their elevated phenolic levels, robust antioxidant activity, and well-rounded post-digestion metabolite composition, whereas camel-almond exhibited a uniquely balanced amino acid and sugar profile. Metabolomic analysis further revealed that blended milk samples demonstrated higher capacities to activate pathways associated with amino acid biosynthesis and carbohydrate metabolism, suggesting their potential to address nutritional gaps in single-source formulations by creating nutritionally optimized infant formulas. While initial findings are encouraging, further research is crucial to meticulously refine these milk blends as base ingredients, ensuring optimal infant health.PMID:40373722 | DOI:10.1016/j.foodchem.2025.144675