PubMed

Am J Transl Res. 2025 Jan 15;17(1):87-103. doi: 10.62347/MBJY3014. eCollection 2025.ABSTRACTOBJECTIVE: To explore the therapeutic effects of Zhuyang Tongbian Decoction (ZTD) on vasoactive intestinal peptide (VIP) and 5-hydroxytryptamine receptor (5-HTR) in colon tissues, intestinal flora, and fecal metabolites in mice with functional constipation (FC).METHODS: A total of 36 BALB/c mice were divided into six groups: control, model, positive (Cisapride), and ZTD groups with three dosages (1.5 g/mL, 3 g/mL, and 6 g/mL). All mice, except those in the control group, were induced with FC by gavage using the compound diphenoxylate. After establishing the model, each group received the respective treatments by gavage for two weeks. The laxative effect was evaluated by comparing changes in body weight, fecal weight, fecal water content, and the percentage of carbon powder propulsion in the small intestine. Immunohistochemistry was used to assess the distribution and expression of VIP and 5-HTR in proximal colon tissues. Additionally, 16S rRNA sequencing and liquid chromatography with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) non-targeted metabolomics analysis were used to examine the effects of ZTD on intestinal flora composition and metabolites in FC mice.RESULTS: ZTD treatment not only alleviated FC symptoms but also increased the number of VIP and 5-HTR-positive cells in colon tissues. Furthermore, ZTD improved the diversity and abundance of intestinal flora, significantly increasing the relative abundance of Prevotellaceae, Bacteroidales_S24-7_group, Ruminococcaceae, and Roseburia while reducing the abundance of Proteobacteria, Desulfovibrionaceae, Rikenellaceae, Porphyromonadaceae, and Erysipelotrichaceae. In terms of metabolites, ZTD significantly elevated the levels of deoxyadenosine and adenine, while significantly lowering the levels of L-leucine, L-threonine, succinate, tyramine, L-tyrosine, and dopamine.CONCLUSIONS: This study provides a theoretical basis for the treatment of FC with ZTD. ZTD increased levels of the intestinal neurotransmitters VIP and 5-HTR and promoted the colonization of beneficial bacteria, including the dominant butyric acid-producing bacterium Roseburia. Additionally, ZTD reduced fecal dopamine levels, indicating its value as a therapeutic approach for FC.PMID:39959240 | PMC:PMC11826166 | DOI:10.62347/MBJY3014

Front Microbiol. 2025 Jan 31;16:1522036. doi: 10.3389/fmicb.2025.1522036. eCollection 2025.ABSTRACTBifidobacterium species are essential members of the human gut microbiota, playing crucial roles in host health. Variations in the metabolic functions of different Bifidobacterium strains can have distinct health effects, making it essential to understand their metabolic characteristics for the development of targeted probiotic formulations. In this study, we cultivated four selected Bifidobacterium strains from three species: Bifidobacterium animalis subsp. lactis BB-69, Bbm-19, Bifidobacterium brevis BX-18, and Bifidobacterium longum subsp. infantis B8762. We conducted an untargeted comparative metabolomic analysis to investigate the intracellular metabolic profile and functional activities of these strains. A total of 1,340 metabolites were identified, revealing significant variations in their metabolomic profiles. Notably, Bifidobacterium animalis subsp. lactis Bbm-19 showed higher activity in amino acid biosynthesis, while Bifidobacterium animalis subsp. lactis BB-69 exhibited increased activity in secondary bile acid biosynthesis and alpha-linolenic acid metabolism. Bifidobacterium longum subsp. infantis B8762 demonstrated enhanced activity in polycyclic aromatic hydrocarbon degradation, vitamin digestion and absorption, and galactose metabolism. Bifidobacterium breve BX-18 was more active in tryptophan metabolism and pentose and glucuronate interconversions. Targeted analyses of specific metabolites further revealed strain-specific metabolic pathways. This study systematically elucidates the metabolic profile differences among the four investigated Bifidobacterium strains at the untargeted metabolomic level, providing valuable insights into their metabolic characteristics and potential applications in probiotic development.PMID:39959161 | PMC:PMC11826312 | DOI:10.3389/fmicb.2025.1522036

Drug Des Devel Ther. 2025 Feb 10;19:911-929. doi: 10.2147/DDDT.S490900. eCollection 2025.ABSTRACTBACKGROUND: Danggui-Shaoyao-San (DSS) is a traditional Chinese medicine prescription with a history of nearly 2000 years, originally widely used for gynecological diseases, and in recent years research has found that DSS also has a good therapeutic effect on Alzheimer's disease (AD).PURPOSE: The objective is to investigate the metabolic components of the DSS in the blood and the potential mechanisms for AD.MATERIALS AND METHODS: Liquid chromatography‒mass spectrometry (LC-MS) combined with gas chromatography‒mass spectrometry (GC-MS) based non-targeted metabolomics were used to conduct in-depth research. Serum Pharmacology was used to analyze potential mechanisms of DSS for AD. C57BL/6J mice and Hippocampal neuronal cell line (HT-22) were used to prepare the AD model. Enzyme linked immunosorbent assay (Elisa), quantitative polymerase chain reaction (q-PCR), Morris water maze,Western blot (WB), Immunohistochemical and Immunofluorescence were used to study the effect of DSS on AD. Flow cytometry and Cell Counting Kit-8 (CCK-8) reveal the effect of DSS serum on HT-22 proliferation and apoptosis.RESULTS: A total of 57 metabolic components were screened in DSS serum. Serum Pharmacology revealed that the calcium signaling pathway and cAMP/PKA/CREB pathway may be a potential mechanism through which DSS treated AD. DSS can reduce aberrant phosphorylation of Tau and modulates cAMP/PKA/CREB pathway to improve cognition and apoptosis in AD mice. DSS serum can increase the cell viability of HT-22 and reduce apoptosis mainly by alleviating mitochondrial calcium overloading.CONCLUSION: DSS can modulate the calcium signaling pathway and enhance the cAMP/PKA/CREB signaling pathway to ameliorate Tau aberrant phosphorylation, cognitive deficits and neuronal apoptosis after AD.PMID:39959122 | PMC:PMC11827505 | DOI:10.2147/DDDT.S490900

Food Chem X. 2025 Jan 24;25:102213. doi: 10.1016/j.fochx.2025.102213. eCollection 2025 Jan.ABSTRACTVolatile metabolomics was used to analyze volatile organic compounds in celery (Apium graveolens L. cv. Dayehuang) leaves and petioles under ultraviolet (UV) radiation. Results indicated that celery encompassed 328 terpenes, 299 esters, 178 heterocyclic compounds, and 166 ketones. The additional UV radiation altered ester and heterocyclic compound in celery leaves and changed terpenoids, aldehyde, and ester in celery petiole. The content of volatile organic compounds in leaves and petiole of celery under UV radiation was significantly higher than that grown without UV radiation. The content of 40 compounds with green, floral, woody, sweet, citrus, and fruity aromas have significantly altered in celery petioles. In addition, 24 compounds were significantly altered in celery leaves, including woody and sweet. Our study provides a valuable insight into the influences of UV radiation on different parts of celery flavor, and offers a possible way to alter the flavor quality of celery.PMID:39958648 | PMC:PMC11830285 | DOI:10.1016/j.fochx.2025.102213

Front Plant Sci. 2025 Jan 31;15:1526321. doi: 10.3389/fpls.2024.1526321. eCollection 2024.ABSTRACTSesamum indicum, a highly esteemed oil crop, has exhibited remarkable value and potential in diverse areas encompassing the economy, food industry, and health. We have observed that there are small protrusions on the leaves of the indehiscent capsule material G1358. No obvious difference was detected on overall auxin content between the leaves of G1358 and LZ1 from metabolomic analysis. However, auxin levels at the base of G1358 leaves were notably higher than in LZ1, suggesting a correlation between the small protrusions at the base and polar auxin transport (PAT). PAT is essential for regulating growth and development across different plant tissues. PAT primarily relies on three families of transporter proteins: ABCB, PIN, and AUX/LAX. However, the ABCB, PIN, and AUX/LAX protein families in Sesamum indicum have not been systematically characterized. Herein, we identified 21 SiABCBs, 11 SiPINs, and 5 SiLAXs in S. indicum. Our analysis indicated that tandem duplications have facilitated the expansion of SiLAX, SiPIN, and SiABCB gene families, which have undergone purifying selection throughout their evolutionary history. Transcriptome screening and RT-qPCR analysis revealed that SiABCB3, SiABCB6, and SiPIN10 positively regulate PAT, whereas SiABCB7 and SiABCB9 negatively regulate PAT in G1358. These regulatory interactions contribute to the formation of small protrusions in G1358 leaves and enhance the rate of photosynthesis. Our findings provide a theoretical foundation for understanding PAT genes and their roles in the environmental adaptation of sesame.PMID:39958584 | PMC:PMC11825473 | DOI:10.3389/fpls.2024.1526321

Front Plant Sci. 2025 Jan 31;15:1496504. doi: 10.3389/fpls.2024.1496504. eCollection 2024.ABSTRACTINTRODUCTION: The color of Clausena lansium L. Skeels cv. Jixin fruit peel is brown (BP), while the mutant cv. Zijin had purple fruit peels (PP). The coloration of the peels was attributed to significant differences in chlorophyll, carotenoid, and anthocyanin content between BP and PP.METHODS: This study investigates the biosynthetic metabolic activities in the brown and purple peels of Clausena lansium L. Skeels using metabolomics and transcriptomics. It aims to identify metabolic pathways and differentially expressed genes related to flavonoids and anthocyanins biosynthesis.RESULTS: The PP (purple peel) has higher levels of a-carotene and b-carotene but lower levels of chlorophyll a, chlorophyll b, and lutein compared to BP. Zeaxanthin was absent from both peels, suggesting that the b-carotene hydroxylase enzyme is not active. Both peels contain delphinidin-based (Dp) and cyanidin-based (Cy) anthocyanins, but not pelargonidin-based (Pg). The total anthocyanin content and the Dp/Cy ratio are higher in PP than in BP. The delphinidin, cyanidin, and mallow derivatives in the PP were significantly higher than in the BP. The increase of total anthocyanin content and Dp/Cy ratio may be the main reason for the peel color changing from brown to purple. The significant increase of F3H expression in purple peels suggested a higher efficiency of catalyzing the conversion of naringenin into dihydroflavonols in the PP, leading to the higher content of total anthocyanin. Despite the significant increase of FLS expression in PP, the contents of kaempferol, quercetin, and myricetin significantly decreased, suggesting that the increase of FLS expression did not lead to an increase in flavonol biosynthesis.DISCUSSION: The competition between F3'H and F3'5'H may determine the ratio of Dp/Cy, the higher levels of F3'H, F3'5'H, and UFGT expression, lead to the increase accumulation of total anthocyanin and Dp/Cy in PP. The deficiency of Pg in both peels resulted from the substrate specificity of the DFR enzyme. The research also describes the transition in color from BP to PP and details of the biosynthetic pathways for carotenoids and anthocyanins, elucidating the molecular processes underlying anthocyanin production.PMID:39958581 | PMC:PMC11825772 | DOI:10.3389/fpls.2024.1496504

Food Sci Biotechnol. 2024 Sep 2;34(3):815-827. doi: 10.1007/s10068-024-01693-y. eCollection 2025 Feb.ABSTRACTPacific oysters (Crassostrea gigas) are globally renowned shellfish. In South Korea, oysters are commonly packaged with filling water in polyethylene bags. Previous studies have proposed various freshness and quality parameters for oysters, including pH, volatile basic nitrogen content, glycogen content, and viable cell count. We aimed to identify the objective indicators of oyster freshness during storage and distribution using metabolomic analysis and multivariate statistical techniques. Packaged oyster samples were analyzed for metabolites using gas chromatography-mass-spectrometry during 9-days storage at 5 °C or 15 °C. Additionally, the pH, turbidity, and soluble protein content of the filling water were measured. Multivariate statistical analyses, including principal component analysis, partial least squares discriminant analysis, and orthogonal projections to latent structure-discriminant analysis revealed statistically significant results, demonstrating metabolite clustering based on storage duration. In conclusion, this study introduced crucial freshness indicators for stored or distributed oysters by utilizing metabolomic analysis and multivariate statistical techniques.SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10068-024-01693-y.PMID:39958182 | PMC:PMC11822166 | DOI:10.1007/s10068-024-01693-y

Liver Res. 2022 Dec 1;6(4):251-257. doi: 10.1016/j.livres.2022.11.007. eCollection 2022 Dec.ABSTRACTBACKGROUND AND AIMS: The herbal supplement Gancao, also known as licorice, belongs to the genus Glycyrrhiza and has been used worldwide for its hepatoprotective effect. Recent studies have raised concerns about potential herb-drug interactions associated with Gancao via pregnane X receptor (PXR)-mediated induction of hepatic cytochrome P450 3A4 (CYP3A4). The current work aimed to determine the phytochemicals in Gancao that activate PXR and induce CYP3A4.METHODS: DPX2 cells were used for cell-based PXR reporter assays. The phytochemicals in Gancao extract were identified using a metabolomics approach. The effects of PXR activators identified from in vitro studies were further investigated in PXR- and CYP3A4-humanized mouse models.RESULTS: Gancao was verified to be a PXR-activating herb. Two major phytochemicals in Gancao, glycyrrhizin (GZ) and glycyrrhetinic acid (GA), did not activate PXR in the cell-based reporter assays. However, glabridin was shown to activate PXR in a dose-dependent manner. In vivo studies confirmed that GZ is not a PXR activator and glabridin is a weak PXR activator. Although GA did not active PXR in vitro, it induced CYP3A4 expression in a PXR-dependent manner in the PXR- and CYP3A4-humanized mice.CONCLUSIONS: GZ is not a PXR activator. GA could not activate PXR in cell-based reporter assays but it could activate PXR in vivo. Glabridin is a weak PXR activator. This work provides novel insights into the underlying mechanisms of Gancao-related herb-drug interactions via PXR.PMID:39957905 | PMC:PMC11791855 | DOI:10.1016/j.livres.2022.11.007

J Pharm Anal. 2025 Feb;15(2):101101. doi: 10.1016/j.jpha.2024.101101. Epub 2024 Sep 16.ABSTRACTNatural products (NPs) have historically been a fundamental source for drug discovery. Yet the complex nature of NPs presents substantial challenges in pinpointing bioactive constituents, and corresponding targets. In the present study, an innovative natural product virtual screening-interaction-phenotype (NP-VIP) strategy that integrates virtual screening, chemical proteomics, and metabolomics to identify and validate the bioactive targets of NPs. This approach reduces false positive results and enhances the efficiency of target identification. Salvia miltiorrhiza (SM), a herb with recognized therapeutic potential against ischemic stroke (IS), was used to illustrate the workflow. Utilizing virtual screening, chemical proteomics, and metabolomics, potential therapeutic targets for SM in the IS treatment were identified, totaling 29, 100, and 78, respectively. Further analysis via the NP-VIP strategy highlighted five high-confidence targets, including poly [ADP-ribose] polymerase 1 (PARP1), signal transducer and activator of transcription 3 (STAT3), amyloid precursor protein (APP), glutamate-ammonia ligase (GLUL), and glutamate decarboxylase 67 (GAD67). These targets were subsequently validated and found to play critical roles in the neuroprotective effects of SM. The study not only underscores the importance of SM in treating IS but also sets a precedent for NP research, proposing a comprehensive approach that could be adapted for broader pharmacological explorations.PMID:39957901 | PMC:PMC11830376 | DOI:10.1016/j.jpha.2024.101101

Environ Sci Technol Lett. 2025 Jan 24;12(2):166-174. doi: 10.1021/acs.estlett.4c01003. eCollection 2025 Feb 11.ABSTRACTFinding relevant chemicals in the vast (known) chemical space is a major challenge for environmental and exposomics studies leveraging nontarget high resolution mass spectrometry (NT-HRMS) methods. Chemical databases now contain hundreds of millions of chemicals, yet many are not relevant. This article details an extensive collaborative, open science effort to provide a dynamic collection of chemicals for environmental, metabolomics, and exposomics research, along with supporting information about their relevance to assist researchers in the interpretation of candidate hits. The PubChemLite for Exposomics collection is compiled from ten annotation categories within PubChem, enhanced with patent, literature and annotation counts, predicted partition coefficient (logP) values, as well as predicted collision cross section (CCS) values using CCSbase. Monthly versions are archived on Zenodo under a CC-BY license, supporting reproducible research, and a new interface has been developed, including historical trends of patent and literature data, for researchers to browse the collection. This article details how PubChemLite can support researchers in environmental and exposomics studies, describes efforts to increase the availability of experimental CCS values, and explores known limitations and potential for future developments. The data and code behind these efforts are openly available. PubChemLite can be browsed at https://pubchemlite.lcsb.uni.lu.PMID:39957787 | PMC:PMC11823450 | DOI:10.1021/acs.estlett.4c01003

Nat Prod Res. 2025 Feb 17:1-8. doi: 10.1080/14786419.2025.2463702. Online ahead of print.ABSTRACTArgan oil is widely used as an active ingredient of dermo-cosmetic products. Its high demand has led to an increase adulteration with varying amounts of inexpensive herbal oils. The quality control of argan oil is one of the most important issues for pharmaceutical companies. In this study,1H-NMR-based metabolomics study was used as a fast and non-destructive technique to detect adulteration. Argan seeds and oil were purchased from pharmacies and stores. The results showed that pure argan oil doesn't contain α-linolenic acid, while it is present in varying amounts in most herbal oils. A number of argan oils that were purchased from the market or pharmacies, despite the manufacturer's claim that the argan oil is 100% pure with no additives in the final product, had impurities especially in aromatic regions. This is the first attempt to demonstrate that the 1H-NMR-based metabolomics study can successfully apply to detect argan oil adulteration.PMID:39957565 | DOI:10.1080/14786419.2025.2463702

Animal Model Exp Med. 2025 Feb 17. doi: 10.1002/ame2.12569. Online ahead of print.ABSTRACTBACKGROUND: Cannabidiol (CBD) has numerous therapeutic properties, and is used to treat neurological conditions, such as neuroinflammation. However, the optimal dose of CBD to penetrate the brain requires further investigation. The primary aim of this study was to use a mouse model and the intrabuccal route for CBD administration to determine the optimal dose at which CBD can penetrate the brain. The secondary aim was to determine whether sex is a confounding factor.METHODS: Thirty adult Kramnik mice, divided equally into three groups, were administered CBD oil intrabuccally at three doses-10, 20, and 30 mg/kg, euthanized 6 h later, and whole brain, urine, and blood samples were collected. Liquid chromatography with tandem mass spectrometry was used to analyze the collected samples.RESULTS: CBD and its three metabolites-7-carboxy cannabidiol (7-COOH-CBD), 7-hydroxy cannabidiol (7-OH-CBD) and 6-hydroxy cannabidiol (6-OH-CBD), were identified and quantified in all samples. The 10 and 20 mg/kg doses of CBD produced similar results in the brain, but the group given the 10 mg/kg dose had the least variation. The 30 mg/kg dose yielded the highest abundance of CBD and its metabolites in all samples, but also the greatest variation. Sex only became a confounding factor at 30 mg/kg.CONCLUSIONS: This study shows that the intrabuccal route of CBD administration is reliable and the 10 mg/kg dose of CBD is recommended in mice because there were good CBD metabolite concentrations in all samples, with the least variation among the doses, and sex was not a confounder at 10 mg/kg.PMID:39957386 | DOI:10.1002/ame2.12569

Physiol Rep. 2025 Feb;13(4):e70249. doi: 10.14814/phy2.70249.ABSTRACTTubulointerstitial fibrosis is a characteristic hallmark of chronic kidney disease (CKD). Metabolic perturbations in cellular energy metabolism contribute to the pathogenesis of CKD, but the chemical contributors remain unclear. The aim of this investigation was to use two dimensional 1H-nuclear magnetic resonance (2D-COSY) metabolomics to identify the chemical changes of kidney fibrogenesis. An in vitro transforming growth factor-β1 (TGF-β1)-induced model of kidney fibrogenesis with human kidney-2 (HK-2) proximal tubular epithelial cells (PTEC) was used. The model was validated by assaying for various pro-fibrotic molecules, using quantitative PCR and Western blotting. 2D-COSY was performed on treated cells. Morphological and functional changes characteristic of tubulointerstitial fibrosis were confirmed in the model; expression of fibronectin, collagen type IV, smooth muscle actin, oxidative stress enzymes increased (p < 0.05). NMR metabolomics provided evidence of altered metabolite signatures associated with glycolysis and glutamine metabolism, with decreased myo-inositol and choline, and metabolites of the oxidative phase of the pentose phosphate pathway with increased glucose and glucuronic acid. The altered PTEC cellular metabolism likely supports the rapid fibrogenic energy demands. These results, using 2D-COSY metabolomics, support development of a biomarker panel of fibrosis detectable using clinical magnetic resonance spectroscopy to diagnose and manage CKD.PMID:39957082 | DOI:10.14814/phy2.70249

Expert Rev Proteomics. 2025 Feb 16. doi: 10.1080/14789450.2025.2468300. Online ahead of print.ABSTRACTINTRODUCTION: Rare diseases (RDs) are a heterogeneous group of diseases recognized as a relevant global health priority but posing aspects of complexity such as: geographical scattering of affected individuals, improper/late diagnosis, limited awareness, difficult surveillance and monitoring, limited understanding of natural history, and lack of treatment. Usually, RDs have a pediatric onset and are life-long, multisystemic, and associated with a poor prognosis.AREAS COVERED: In this work, we review how high-throughput omics technologies such as genomics, transcriptomics, proteomics, metabolomics, epigenomics, and other well-established omics, which are increasingly more affordable and efficient, can be applied to the study of RDs promoting diagnosis, understanding of pathological mechanisms, biomarker discovery and identification of treatments.EXPERT OPINION: RDs, despite their challenges, offer a niche where collaborative efforts and personalized treatment strategies might be feasible using omics technologies. Specialized consortia fostering multidisciplinary collaboration, data sharing, and the development of biobanks and registries can be built; multi-omics approaches, including so far less exploited omics technologies, along with the implementation of AI tools can be undertaken to deepen our understanding of RDs, driving biomarker discovery and clinical interventions. Nevertheless, technical, ethical, legal and societal issues must be clearly defined and addressed.PMID:39956998 | DOI:10.1080/14789450.2025.2468300

Gut Microbes. 2025 Dec;17(1):2467235. doi: 10.1080/19490976.2025.2467235. Epub 2025 Feb 16.ABSTRACTThe gut microbiota-derived metabolite indole-3-propionic acid (IPA) plays an important role in maintaining intestinal mucosal homeostasis, while the molecular mechanisms underlying IPA regulation on mucosal CD4+ T cell functions in inflammatory bowel disease (IBD) remain elusive. Here we investigated the roles of IPA in modulating mucosal CD4+ T cells and its therapeutic potential in treatment of human IBD. Leveraging metabolomics and microbial community analyses, we observed that the levels of IPA-producing microbiota (e.g. Peptostreptococcus, Clostridium, and Fournierella) and IPA were decreased, while the IPA-consuming microbiota (e.g. Parabacteroides, Erysipelatoclostridium, and Lachnoclostridium) were increased in the feces of IBD patients than those in healthy donors. Dextran sulfate sodium (DSS)-induced acute colitis and CD45RBhighCD4+ T cell transfer-induced chronic colitis models were then established in mice and treated orally with IPA to study its role in intestinal mucosal inflammation in vivo. We found that oral administration of IPA attenuated mucosal inflammation in both acute and chronic colitis models in mice, as characterized by increased body weight, and reduced levels of pro-inflammatory cytokines (e.g. TNF-α, IFN-γ, and IL-17A) and histological scores in the colon. We further utilized RNA sequencing, molecular docking simulations, and surface plasmon resonance analyses and identified that IPA exerts its biological effects by interacting with heat shock protein 70 (HSP70), leading to inducing Th1/Th17 cell apoptosis. Consistently, ectopic expression of HSP70 in CD4+ T cells conferred resistance to IPA-induced Th1/Th17 cell apoptosis. Therefore, these findings identify a previously unrecognized pathway by which IPA modulates intestinal inflammation and provide a promising avenue for the treatment of IBD.PMID:39956891 | DOI:10.1080/19490976.2025.2467235

Commun Biol. 2025 Feb 16;8(1):248. doi: 10.1038/s42003-025-07728-2.ABSTRACTMedium-chain alkanes have strong ecological impacts on marine ecosystems due to their persistence, toxicity, and ability to travel long distances. Microbial degradation is the dominant and ultimate removal process for n-alkanes in the deep ocean, where high hydrostatic pressure (HHP) regulates microbial activity. To gain insight into the impact of hydrostatic pressure (HP) on n-alkane degradation, we applied the deep-ocean experimental simulation to culture Alcanivorax xenomutans A28, a novel piezotolerant bacterium strain from trench sediment, with n-C16 as the sole carbon source under different HPs (0.1, 40, and 80 MPa). Activity analysis demonstrated that HHP stimulated the n-C16 complete mineralization ratio. Transcriptomic and metabolomic analyses showed that HHP induced the intracellular oxidative stress and accelerated the tricarboxylic acid (TCA) cycle. These results indicate a shift of n-alkanes biodegradation pattern regulated by HP, elucidating the fate and ecological risk of n-alkanes in the deep ocean.PMID:39956881 | DOI:10.1038/s42003-025-07728-2

Physiol Plant. 2025 Jan-Feb;177(1):e70119. doi: 10.1111/ppl.70119.ABSTRACTThe cell cycle is predominantly controlled by Cyclins/Cyclin-Dependent Kinases (Cyc/CDK) complexes, which phosphorylate targets involved in cellular proliferation. Evidence suggests that Cyc/CDK targets extend beyond traditional proteins and include enzymes that regulate the central carbon metabolism. Maize embryo axes rapidly internalize and metabolize glucose. After 24 h of imbibition in glucose-rich media, axes exhibited increased length and weight, with more pronounced effects at 72 h. This morphology enhancement was impaired when RO-3306, a specific CDK inhibitor, was added. The protein profile of maize embryo extracts at 18 and 24 h indicated altered phosphorylation patterns following CDK activity inhibition. Metabolomic analysis at 24 h of imbibition revealed that maize embryos without sugar in the media, with or without RO-3306, had a decreased sugar and amino acid content. Conversely, axes exposed to glucose demonstrated increased conversion into various mono and di-saccharides such as fructose, mannitol, galactose, and maltose but not sucrose. This pattern was reversed upon the addition of RO-3306. Glucose promoted the accumulation of amino acids such as cysteine, valine, leucine, and intermediates of the tricarboxylic acid (TCA) cycle, such as malate and citrate. The CDK inhibitor redirected the glucose metabolism toward increased serine levels, followed by other amino acids like phenylalanine, valine, and leucine. Additionally, TCA cycle intermediates and sterols significantly decreased. Overall, these results contribute to understanding the role of CDK in maize morphogenesis during germination and underscore its impact on modulating various central carbon pathways, including glycolysis, amino acid catabolism/anabolism, TCA cycle, and sterols biosynthesis.PMID:39956791 | DOI:10.1111/ppl.70119

Physiol Plant. 2025 Jan-Feb;177(1):e70117. doi: 10.1111/ppl.70117.ABSTRACTSoil alkalization is a global ecological problem that constrains food security and sustainable socio-economic development. As a wild relative of soybean, wild soybean (Glycine soja) exhibits strong salt and alkali stress resistance and its cotyledons play a key role during the emergence (VE) stage. This study aimed to compare variations in growth parameters, cotyledon ultrastructure, photosynthetic physiology, mineral ion and metabolite contents, and gene expression in two ecotypes of wild soybean to elucidate the regulatory mechanisms underlying alkali stress resistance in salt-tolerant wild soybean cotyledons during the VE stage. The results showed that salt-tolerant wild soybean cotyledons exhibited relatively stable growth parameters, dense and orderly chloroplast structure, high photosynthetic rates, as well as high K+ and Ca2+ contents under alkali stress. Metabolomics, transcriptomics, and weighted gene co-expression network analyses revealed that salt-tolerant wild soybean cotyledons adapted to alkali stress during the VE stage by enhancing photosynthetic carbon assimilation pathways, increasing methionine and proline biosynthesis, and enhancing gamma-aminobutyric acid biosynthesis, thereby maintaining a stable carbon and nitrogen balance. In addition, upregulation of the expression of ICL, MS, and ACO2 led to the accumulation of various organic acids, such as pyruvic, aconitic, succinic, oxalic, malic, and fumaric acids, thereby promoting the synthesis of organic acid metabolism modules. This study provides novel insights into the key metabolic modules by which wild soybeans resist alkali stress.PMID:39956781 | DOI:10.1111/ppl.70117

Trends Mol Med. 2025 Feb 15:S1471-4914(25)00016-4. doi: 10.1016/j.molmed.2025.01.016. Online ahead of print.ABSTRACTMetabolomics has emerged as a transformative tool in precision oncology, with substantial potential for advancing biomarker discovery, monitoring treatment responses, and aiding drug development. Integrating artificial intelligence (AI) into metabolomics optimizes data acquisition and analysis, facilitating the interpretation of complex metabolic networks and enabling more effective multiomics integration. In this opinion, we explore recent advances in the application of metabolomics within precision oncology, emphasizing the unique advantages that AI-driven metabolomics offers. We propose that AI not only complements but also amplifies the potential of current platforms, accelerating research progress and ultimately improving patient outcomes. Finally, we discuss the opportunities and challenges involved in translating AI-driven metabolomics into clinical practice for precision oncology.PMID:39956738 | DOI:10.1016/j.molmed.2025.01.016

J Cyst Fibros. 2025 Feb 15:S1569-1993(25)00055-4. doi: 10.1016/j.jcf.2025.02.003. Online ahead of print.ABSTRACTBACKGROUND: In individuals with cystic fibrosis (CF), respiratory viral infections frequently result in hospitalization and have been linked to secondary bacterial infection and colonization, highlighting viral infections as possible contributors to CF lung disease progression. We hypothesized that expression of antiviral host defense genes is dysregulated in CF airway epithelia.METHODS: We infected primary CF and Non-CF airway epithelia with respiratory syncytial virus (RSV) and characterized their responses at 12 hr, 24 hr, 48 hr, 72 hr, and 120 hr post infection (hpi) by RNA sequencing (RNAseq).RESULTS: Our analysis revealed strikingly different gene expression profiles for the CF and Non-CF epithelia over the course of the infection. While both CF and Non-CF cells exhibited an early signature for interferon signaling and antiviral defense pathways, this response was relatively exaggerated and sustained in CF epithelia. We also observed, in both genotypes, a transient downregulation of cilia-associated genes and loss of ciliary activity by 72 hpi. Interestingly, recovery of cilia activity was delayed in the CF epithelia.CONCLUSIONS: These findings further our understanding of innate immune dysfunction in the CF airway epithelium and suggest that virus-induced cilia injury may further compromise host defenses in CF airways.PMID:39956716 | DOI:10.1016/j.jcf.2025.02.003