PubMed
Withaferin A maintained microbiome and metabolome features in A53T transgenic mice via multi-omics integrated analysis
Phytomedicine. 2025 Apr 2;141:156725. doi: 10.1016/j.phymed.2025.156725. Online ahead of print.ABSTRACTBACKGROUND: Withaferin A (WFA), a naturally occurring compound, has shown promise as a therapeutic agent for Parkinson's disease (PD), a neurodegenerative disorder associated with motor and gastrointestinal dysfunctions. However, its effects on gut microbiota metabolism remain poorly understood.PURPOSE: This study aimed to elucidate the neuroprotective mechanisms of WFA in a PD mouse model by investigating its regulation of gut microbiota composition, metabolic pathways, and correlations with brain spatial metabolomics.METHODS: Human SNCA-transgenic (A53T) mice were treated with WFA and evaluated using behavioral tests, immunohistochemistry, Western blot, and ELISA to assess motor/cognitive functions and PD-related pathology. Gut microbiota composition was analyzed via 16S rRNA sequencing, while untargeted fecal metabolomics and brain spatial metabolomics were employed to identify metabolic alterations.RESULTS: WFA significantly improved motor performance, alleviated cognitive deficits, restored intestinal barrier integrity, and reduced neuroinflammation. It elevated the abundance of anti-inflammatory gut bacteria (e.g., Bifidobacterium, Dubosiella, Akkermansia) and reversed 55 fecal metabolites linked to sphingolipid metabolism, serotonergic synapses, and neuroactive ligand- receptor interactions. Spatial metabolomics revealed WFA's regulation of sphingolipid signaling pathways, including sphingosine kinase (Sphk1), ceramidase, sphingosine 1-phosphate receptor (S1PR5), and endocannabinoid receptor CB2 expression. Correlation analysis indicated a link between brain metabolite content and gut microbiota abundance.CONCLUSION: Our findings highlight a potential mechanism of WFA that repairs neurons by modulating the sphingolipid signaling pathway within the microbiota-gut-brain axis.PMID:40220427 | DOI:10.1016/j.phymed.2025.156725
Scutellaria baicalensis Extracts Restrict Intestinal Epithelial Cell Ferroptosis by Regulating Lipid Peroxidation and GPX4/ACSL4 in Colitis
Phytomedicine. 2025 Mar 31;141:156708. doi: 10.1016/j.phymed.2025.156708. Online ahead of print.ABSTRACTBACKGROUND: Ferroptosis in colonic epithelial cells has been implicated in the development of ulcerative colitis (UC) and the accompanying gut leakage. Scutellaria baicalensis Georgi (Scu) is widely used herb medicine for alleviating UC.PURPOSE: We aimed to clarify the therapeutic effect of Scu on UC by inhibiting intestinal epithelial cell ferroptosis and explore its regulatory mechanisms on lipid peroxidation and the GPX4/ACSL4 pathways.METHODS: UPLC-Q-TOF/MS was employed to analyze chemicals in the herbal extract and the colonic exposure of prototypes in Scu-treated mice. Additionally, the main compounds were quantified using HPLC-UV. The ameliorative effects of Scu were comprehensively explored in a UC mouse model established by feeding with dextran sulfate sodium (DSS). HPLC-MS based metabolomic studies were conducted to identify the differential metabolites in colon tissues from Scu or vehicle treated UC mice. Network pharmacology was conducted for target prediction and potential pathway analysis. In conjunction with these bioinformatic analyses, we performed RT-qPCR, immunofluorescence, immunohistochemistry and immunoblotting to elucidate the regulatory mechanisms of Scu on ferroptosis-related pathways in both in vivo and in vitro models.RESULTS: 78 chemical constituents in Scu were characterized, with 42 detected in the colonic tissues of Scu-treated mice. Scu could alleviate UC related symptoms in mice, including increased colon length and decreased pathological score. Furthermore, Scu inhibited pro-inflammatory cytokines and mediators, while improving gut barrier function by increasing the expression of ZO-1 and Occludin at both mRNA and protein levels. Based on metabolomic studies, a total of 71 differential metabolites exhibited a reversal trend following Scu administration. These findings, combined with results from network pharmacology, suggest that arachidonic acid (AA) metabolism and ferroptosis may serve as potential pathways for Scu intervention in UC. Further experiments indicated that the amelioratory actions of Scu on ferroptosis partially contributed to its modulation on lipid peroxidation and its regulatory influence on the GPX4/ASCL4 axis to ameliorate UC. When AA was administered at the same time as concurrently with Scu, the regulatory effects of Scu on ferroptosis, GPX4/ASCL4 axis, and its protective effects against UC were significantly reduced. Moreover, the inhibitory effect of Scu on ferroptosis was weakened when we knocked down GPX4 or overexpressed ACSL4 in vitro.CONCLUSION: The ameliorative effect of Scu in UC is closely related to the regulation of lipid peroxidation and GPX4/ASCL4 mediated intestinal epithelial ferroptosis.PMID:40220415 | DOI:10.1016/j.phymed.2025.156708
Higenamine protects against doxorubicin-induced heart failure by attenuating ferroptosis via modulating the Nrf2/GPX4 signaling pathway
Phytomedicine. 2025 Mar 24;141:156670. doi: 10.1016/j.phymed.2025.156670. Online ahead of print.ABSTRACTBACKGROUND: Higenamine (HG), a benzylisoquinoline alkaloid in Aconiti Lateralis Radix Praeparata (ALRP), has cardioprotective effects. Prior research indicated its potential anti-heart failure (HF) function, yet the molecular mechanism remained elusive.PURPOSE: This study aimed to explore the underlying mechanism of HG against doxorubicin (DOX)-induced HF via an integrated approach involving gut microbiota, untargeted metabolomics, network pharmacology, and molecular biology.METHODS: DOX was employed to induce HF in rats and H9c2 cardiomyocytes injury models. Cardiac injury was assessed using hemodynamic indices, cardiac injury biomarkers, and oxidative stress markers. Cell counting kit-8 (CCK-8) method and high-content analysis were used to investigate the effects of HG on the cell proliferation, morphology and mitochondrial function of H9c2 cardiomyocytes. 16S rDNA sequencing analysis, untargeted metabolomics, and network pharmacology were performed to identify the multi-target and multi-pathway mechanisms of HG in treating HF. Furthermore, reverse transcription quantitative polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western Blotting was used to investigate its intervention on the nuclear factor erythroid 2-related factor 2 (Nrf2)/glutathione peroxidase 4 (GPX4) ferroptosis pathway.RESULTS: HG alleviated DOX-mediated myocardial injury by enhancing cardiac and mitochondrial function, reducing oxidative stress levels, and promoting cell proliferation. Effects of HG on changes in the gut microbiota of rats is characterized by a low abundance of Firmicutes and Proteobacteria, along with a high abundance of Bacteroidetes and Actinobacteria, indicating an improvement in DOX-induced dysbiosis. Untargeted metabolomics combined with network pharmacology showed that HG exerted anti-HF effects by regulating eight metabolites, eight pathways, and interacting with ferroptosis-related targets. Molecular biology studies revealed its cardioprotective effects via regulating the Nrf2/GPX4 ferroptosis pathway.CONCLUSION: HG could inhibit ferroptosis and protect against HF by regulating the Nrf2/GPX4-mediated "mitochondrial-ferroptosis" pathway, offering a potential treatment strategy for HF.PMID:40220414 | DOI:10.1016/j.phymed.2025.156670
Cardioprotective effects of the jiming formula on myocardial metabolism in Mice with myocardial infarction via the AMPK/SIRT1/PGC-1α pathway
Phytomedicine. 2025 Apr 7;141:156727. doi: 10.1016/j.phymed.2025.156727. Online ahead of print.ABSTRACTBACKGROUND: Cardiac dysfunction continues to represent a major global health burden, significantly impacting both disease prevalence and survival rates across populations. Mitochondrial dysfunction is a severe pathological characteristic of heart failure. Altered energy metabolism is intimately linked to the advancement and outcome of heart failure, and regulating myocardial energy metabolism has become an attractive treatment strategy for managing heart failure. Jiming formula (JMF), different from traditional Chinese medicine commonly used for heart protection, has been suggested to be effective in treating heart failure in experiments and clinical practice.PURPOSE: This study integrated targeted metabolomics and transcriptomics to investigate the cardioprotective effects of JMF against myocardial infarction (MI) and the underlying molecular mechanism in mice.METHODS: We first prepared a UHPLC-QTRAP-MS/MS method for analyzing JMF components. The cardioprotective effects of JMF in MI model mice were further identified using echocardiography, hematoxylin and eosin (HE) staining, Masson staining, Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, wheat germ agglutinin (WGA) staining and DHE staining. Differential gene expression in the hearts of the mice was detected using transcriptomics technology, and the cardiac metabolites were further quantified using LC‒ESI‒MS/MS. Network pharmacology was established to predict the cardioprotective components of JMF. Mitochondrial morphology and function in MI mice were evaluated using transmission electron microscopy and ATP assays. Finally, Western blotting and immunofluorescence were used to investigate the protective effects of JMF on the AMPK/SIRT 1/PGC-1 α signaling pathway.RESULTS: A total of 191 and 40 components were identified in the JMF aqueous extract and rat plasma, respectively, indicating the quality of JMF. JMF improved survival rates and cardiac dysfunction in MI model mice in a quantitative manner and reduced adverse remodeling and mitochondrial damage. JMF protected cardiomyocytes from apoptosis and hypertrophy. Transcriptomic analysis revealed that JMF improved the mitochondrial tricarboxylic acid cycle (TCA cycle) in MI mice. Network pharmacology predicted that euodiae fructus may be the herb contributing the most to the effects of JMF. Targeted metabolomics analysis subsequently revealed that JMF treatment improved the substrate content in various pathways of glucose metabolism. JMF also improved poor metabolic remodeling in cardiomyocytes and enhanced glucose aerobic oxidation and ATP production. Enzyme assays revealed that JMF treatment increased the activity of key glycolytic enzymes and mitochondrial respiratory complexes I and IV. Furthermore, JMF activated the AMPK/SIRT1/PGC-1 α signaling pathway, resulting in the upregulation of GLUT4, PKM2, CPT1A and PPARα protein levels while reducing GLUT1 protein levels.CONCLUSION: This research offers a novel perspective for treating MI using JMF. The underlying mechanism may involve the activation of the AMPK/SIRT1/PGC-1α signaling pathway and an increase in the aerobic respiration capacity of mitochondria. These findings provide valuable information regarding the pharmacological effects and mechanisms of JMF. In addition, this study provides a foundation for the application of euodiae fructus in the field of heart disease treatment.PMID:40220403 | DOI:10.1016/j.phymed.2025.156727
Polystyrene microplastics impair brown and beige adipocyte function via the gut microbiota-adipose tissue crosstalk in high-fat diet mice
J Hazard Mater. 2025 Apr 8;492:138225. doi: 10.1016/j.jhazmat.2025.138225. Online ahead of print.ABSTRACTBACKGROUND: Microplastics (MPs) are pervasive in the environment and food. The potential health hazards of this emerging pollutant have raised significant concerns in recent years. However, the underlying mechanism by which MPs have any impact on brown and beige adipocytes in the context of obesity is yet to be investigated.METHODS: The C57BL/6 J mice were randomly assigned to the HFD and HFD+MPs group for 12 weeks of exposure to explore the differences in brown and beige adipocyte function. The gut microbiota analysis, fecal microbiota transplantation and metabolomic profiling were carried out to further determine its potential mechanism.RESULTS: The present work demonstrated that high-fat diet mice accumulate lipids and have reduced energy expenditure after three months of oral administration of MPs. In addition to escalating intestinal dysbiosis, exposing HFD mice to MPs induces thermogenic dysfunction in inguinal white adipose tissue and brown adipose tissue. Following the fecal microbiota transplantation, the accumulation of lipids and dysfunction in energy expenditure within the microbiota of recipient mice further elucidated the inhibitory effect of MPs.CONCLUSIONS: Our results suggest that MPs induced the thermogenic dysfunction of BAT and iWAT by affecting gut microbiota composition. The present study highlights the mechanisms by which MPs produce thermogenic dysfunction in BAT and iWAT and disruption in the gastrointestinal microbiota.PMID:40220396 | DOI:10.1016/j.jhazmat.2025.138225
Integrated breath volatolomics and metabolomics analyses reveals novel biomarker panels for the diagnosis of chronic obstructive pulmonary disease
Talanta. 2025 Mar 24;293:128013. doi: 10.1016/j.talanta.2025.128013. Online ahead of print.ABSTRACTChronic obstructive pulmonary disease (COPD) represents a major public health challenge, underscoring the need for reliable diagnostic biomarkers. Breath analysis has emerged as a rapid, convenient, and non-invasive diagnostic approach for various diseases. This study aimed to identify potential breath biomarkers associated with COPD using mass spectrometry and bioinformatic analysis. Breath volatile organic compounds (VOCs) and exhaled breath condensate (EBC) were collected from 75 participants, including COPD patients and healthy controls (HC). Untargeted volatolomics and metabolomics analyses identified 150 VOCs and 436 metabolites. Differentially expressed VOCs and metabolites between the COPD and HC groups were identified. LASSO logistic classification models were constructed and optimized based on differentially expressed VOCs, metabolites, and their combined data. The optimized diagnostic model, incorporating 4 VOCs and 3 metabolites, achieved superior performance with an area under the curve (AUC) of 0.97, sensitivity of 0.86, specificity of 0.89, and an accuracy of 0.88 in distinguishing COPD patients from healthy individuals. This study highlights the potential of breath analysis as a non-invasive approach for point-of-care COPD diagnosis and identifies a robust panel of VOCs and metabolites for this purpose. Further research is needed to investigate the underlying mechanisms of these biomarkers and to develop highly specific biosensors for non-invasive breath diagnosis of COPD.PMID:40220378 | DOI:10.1016/j.talanta.2025.128013
Developing Light-Emitting Plants (LEPs) with SrAl<sub>2</sub>O<sub>4</sub>: Eu<sup>2+</sup>, Dy<sup>3+</sup> by Using Pressure Infiltration, Optimal Conditions for Glowing and Plant Stress Response
Chem Biodivers. 2025 Apr 12:e202500071. doi: 10.1002/cbdv.202500071. Online ahead of print.ABSTRACTDeveloping light-emitting plants (LEPs) using SrAl2O4 has been working for the past few years because SrAl2O4 is a phosphorescent material with long-lasting and bright glowing properties. The six plant species (Episcia cupreata, Tabebuia argentea, Syngonium hybrid, Mimusops elengi, Schefflera arboricola, and Pilea cadierei) were infused with SrAl2O4, which has a particle size of 2.7 µm. The E. cupreata exhibited the highest phosphorescence (a relative phosphorescence value of 36.93) compared to other plant species. The optimal pressure to infuse SrAl2O4 into the plant is 7 × 104 N/m2 exposed for 60 min while 17.5 g/L SrAl2O4 is the best concentration. After infusion, the plants did not show physical abnormalities. However, the amount of MDA and antioxidants in plants was increased. Based on metabolomics analysis, SrAl2O4 might stress plants, but plants might be able to respond by producing antioxidant compounds. Therefore, using SrAl2O4 to LEPs did not kill the plants and provided high light output.PMID:40220350 | DOI:10.1002/cbdv.202500071
Metabolic Profiling of Activated T Lymphocytes Using Single-Cell Energetic Metabolism by Profiling Translation Inhibition (SCENITH)
Methods Mol Biol. 2025;2904:259-271. doi: 10.1007/978-1-0716-4414-0_18.ABSTRACTMetabolic reprogramming is increasingly recognized as a fundamental aspect of T cell activation, influencing the differentiation, proliferation, and effector functions of lymphocytes. Measuring and screening the metabolic states of activated T cells provide insights into the dynamic interplay between cellular metabolism and immune function. In the following chapter, we provide a simple protocol based on the publication of Argüello et al. [1] to analyze the metabolic state of activated T cells at the single-cell level using standard flow cytometry.PMID:40220239 | DOI:10.1007/978-1-0716-4414-0_18
Metabolic Screening of T Lymphocytes During Activation via SEAHORSE Extracellular Flux (XF) Analysis
Methods Mol Biol. 2025;2904:243-258. doi: 10.1007/978-1-0716-4414-0_17.ABSTRACTUpon activation, T cells undergo a profound reconfiguration of their metabolic profile, transitioning from a quiescent to a metabolically active state characterized by an increase in both aerobic glycolysis and mitochondrial respiration. Seahorse extracellular flux (XF) analysis is a powerful method for measuring the changes in fundamental metabolic pathways in real-time, including aerobic glycolysis and mitochondrial respiration of live T cells. This method allows a precise determination of mitochondrial performance and lactate secretion, which is measured as oxygen consumption rate (OCR) and glycolytic proton efflux rate (ECAR), respectively. By dynamically monitoring these metabolic changes, Seahorse XF analysis provides comprehensive insights into the metabolic dynamics of (activated) T cells across diverse experimental conditions or treatments.PMID:40220238 | DOI:10.1007/978-1-0716-4414-0_17
Metabolic and morphometric analysis of allometric and total liver growth in Post-Hatch chickens
Metabolomics. 2025 Apr 12;21(3):52. doi: 10.1007/s11306-025-02250-2.ABSTRACTINTRODUCTION: This study examines metabolic and morphometric changes in chicken liver metabolism during the post-hatch growth period (days 4-20). During this period, liver metabolism transitions from using yolk-derived lipids to feed derived carbohydrates and proteins. The period also encompasses distinct growth phases with implications for metabolic impacts on total and allometric (proportional) growth.OBJECTIVES: Identify shifts in metabolites and pathways that occur during the change in nutrients and relate these to patterns of total and allometric liver growth.METHODS: Liver samples were collected every other day between days 4-20 and analyzed using metabolomic and morphometric approaches to relate metabolic changes to growth. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to identify trends in the data. Cross-validation ANOVA, and network analyses were applied to evaluate metabolic changes across the time periods.RESULTS: Three liver growth periods were defined. Period A (days 4-8) exploited stored nutrients to support rapid growth. Period B (days 10-14) was transitional as stored nutrients were depleted and feed became the major metabolic driver. By period C (days 16-20) the liver is fully dependent on feed. Positive allometric growth occurs predominantly during period A while the organ continues to grow throughout the entire time.CONCLUSIONS: Metabolic pathways exhibit distinct networks as nutrient resources change over the early post-hatch period. These findings provide a framework for understanding how nutrient-driven metabolism influences liver scaling and functional maturation.PMID:40220201 | DOI:10.1007/s11306-025-02250-2
Increased ZNF83 is a potential prognostic biomarker and regulates oxidative stress-induced ferroptosis in clear cell renal cell carcinoma
J Mol Med (Berl). 2025 Apr 12. doi: 10.1007/s00109-025-02543-y. Online ahead of print.ABSTRACTWhile zinc finger proteins (ZFPs) are known to be crucial in various cellular activities such as gene expression regulation and energy metabolism, their specific roles in tumor progression are not well-documented. This study focuses on Zinc Finger Protein 83 (ZNF83) to explore its impact on clear cell renal cell carcinoma (ccRCC) and assess its viability as a prognostic biomarker. Public datasets were utilized to analyze ZNF83's expression and functions in ccRCC systematically. Further, in vitro and in vivo experiments were conducted to delve deeper into ZNF83's functional role. Techniques like electron microscopy for mitochondrial morphology and ROS level quantification were used to assess ferroptosis. RNA sequencing and metabolomic mass spectrometry were employed to understand ZNF83's role in oxidative stress modulation and ferroptosis resistance. Our findings demonstrated that ZNF83 overexpression significantly enhanced tumor cell survival and proliferation, while ZNF83 knockout suppressed these processes. Under oxidative stress or upon treatment with ferroptosis inducers, ZNF83 expression was markedly upregulated, and the protein predominantly localized to the cell nucleus. Notably, ZNF83 overexpression conferred resistance to ferroptosis, promoting tumor cell survival under ferroptosis-inducing conditions. Conversely, ZNF83 knockout sensitized cells to ferroptosis, increasing tumor cell death. RNA-seq and metabolomic analyses revealed that ZNF83 is intricately involved in the regulation of NRF2, a master regulator of the antioxidant response, and associated signaling pathways. ZNF83 represents a key ferroptosis regulator in ccRCC, serving as both a promising prognostic biomarker and therapeutic target. Targeting ZNF83 may improve treatment strategies for ccRCC patients. KEY MESSAGES: ZNF83 as a crucial regulator of tumor cell survival and proliferation in renal cancer, a novel discovery in the context of renal cancer progression. ZNF83 overexpression confers resistance to ferroptosis, enhancing tumor cell survival under oxidative stress or ferroptosis-inducing conditions. Utilizing both RNA sequencing and metabolomic mass spectrometry, we provide comprehensive insights into the molecular pathways, particularly NRF2-related, regulated by ZNF83 in ccRCC. ZNF83's potential as a novel prognostic biomarker for ccRCC is proposed, offering a new avenue for personalized treatment strategies and improving treatment outcomes for patients.PMID:40220129 | DOI:10.1007/s00109-025-02543-y
Integrated Proteomics and Metabolomics Analyses Reveal Molecular Mechanism of Cardiac Resynchronization Therapy Against Cardiac Fibrosis and Ventricular Arrhythmias
Cardiovasc Toxicol. 2025 Apr 12. doi: 10.1007/s12012-025-09988-0. Online ahead of print.ABSTRACTIt is widely accepted that cardiac resynchronization therapy (CRT) implantation has anti-arrhythmias effect, though few studies observed a pro-arrhythmias effect in non-responders. Left ventricular reverse remodeling (LVRR) is associated with the inhibitory effect of CRT on ventricular arrhythmias (VAs). Cardiac fibrosis is an important factor that influences LVRR. This study aimed to determine the effects of CRT on VAs, LVRR and cardiac fibrosis, and uncover the underlying mechanism. Eleven dogs underwent rapid right ventricular pacing (RVP) for 4 weeks to develop heart failure, and then were randomly divided into a RVP group (n = 5; RVP for another 4 weeks) and a CRT group (n = 6; biventricular pacing for 4 weeks). Another five dogs were in the control group. Compared with the RVP group, CRT prevented the deterioration in systolic dysfunction and cardiac fibrosis. Ventricular fibrillation threshold was decreased by RVP, which was reversed by CRT, indicating an anti-arrhythmic effect of CRT. Proteomics analysis of myocardia from the dogs showed significant alterations in fibrosis-related signaling pathways by CRT. Metabolomics analysis revealed a metabolic reprogramming of the failure heart conferred by CRT. Integrated analysis of the proteomics and metabolomics identified eukaryotic translation initiation factor 4E (eIF4E)-binding protein 1 (4EBP1) as the key mediator of CRT. 4EBP1 was downregulated in myocardia from the dogs in the RVP group, which was rescued by CRT. Moreover, overexpression of 4EBP1 diminished transform growth factor (TGF)-β1-induced human CFBs proliferation and synthesis of collagens. CRT regulates fibrosis-related signaling pathways and induces metabolic reprogramming to against cardiac fibrosis and subsequent VAs, potentially through the upregulation of 4EBP1.PMID:40220080 | DOI:10.1007/s12012-025-09988-0
Adopting ambient ionization mass spectrometry into bioanalytical laboratories
Bioanalysis. 2025 Apr 12:1-5. doi: 10.1080/17576180.2025.2490462. Online ahead of print.NO ABSTRACTPMID:40219911 | DOI:10.1080/17576180.2025.2490462
Guard cell-specific glycine decarboxylase manipulation affects Arabidopsis photosynthesis, growth and stomatal behavior
New Phytol. 2025 Apr 11. doi: 10.1111/nph.70124. Online ahead of print.ABSTRACTPhotorespiration is a mandatory metabolic repair shunt of carbon fixation by the Calvin-Benson cycle in oxygenic phototrophs. Its extent depends mainly on the CO2 : O2 ratio in chloroplasts, which is regulated via stomatal movements. Despite a comprehensive understanding of the role of photorespiration in mesophyll cells, its role in guard cells (GC) is unknown. Therefore, a key enzyme of photorespiration, glycine decarboxylase (GDC), was specifically manipulated by varying glycine decarboxylase H-protein (GDC-H) expression in Arabidopsis GC. Multiple approaches were used to analyze the transgenic lines growth, their gas exchange and Chl fluorescence, alongside metabolomics and microscopic approaches. We observed a positive correlation of GC GDC-H expression with growth, photosynthesis and carbohydrate biosynthesis, suggesting photorespiration is involved in stomatal regulation. Gas exchange measurements support this view, as optimized GC photorespiration improved plant acclimation toward conditions requiring a high photorespiratory capacity. Microscopic analysis revealed that altered photorespiratory flux also affected GC starch accumulation patterns, eventually serving as an underlying mechanism for altered stomatal behavior. Collectively, our data suggest photorespiration is involved in the regulatory circuit that coordinates stomatal movements with CO2 availability. Thus, the manipulation of photorespiration in GC has the potential to engineer crops maintaining growth and photosynthesis under future climates.PMID:40219652 | DOI:10.1111/nph.70124
The Targeted Metabolomic Signatures of Phytohormones in Leaves of Mulberry (Morus alba L.) Are Crucial for Regrowth and Specifically Modulated by the Differential Stubble Lengths
Plants (Basel). 2025 Apr 5;14(7):1126. doi: 10.3390/plants14071126.ABSTRACTVegetative propagation of mulberry (Morus alba L.) via sapling methods, due to the ability to exponentially multiply lateral buds on stem cuttings to enhance rapid shoot formation, is crucial for sericulture industries. The sprouting of mulberry using stubbles is an emerging method for rapid and mass production of mulberry leaves, but the growth mechanisms associated with its use remain obscure. This study is the first to report how the differential stubble lengths from mulberry plants alter and modulate phytohormones and the associated mechanisms. This study seeks to evaluate the growth mechanisms by elucidating the phytohormone signature modulation in response to differential stubble lengths of 0 cm, 5 cm, 10 cm, 20 cm, and a control via targeted metabolomics analysis in mulberry leaves. The results consistently show that the use of differential stubble lengths of mulberry promoted growth, the number of buds, aboveground biomass, and branch and leaf weights by improving the net photosynthesis, transpiration rate, stomatal conductance, and intercellular CO2 relative to the control. The differential stubble lengths not only caused contrasting responses in the contents of plant hormones, including salicylic acid (SA), abscisic acid (ABA), indole-3-acetic acid (IAA), jasmonic acid (JA), and gibberellin (GA), but also modulated higher elemental contents relative to the control. The results further reveal significant and positive correlations between the phytohormones and all growth, biomass, and photosynthetic parameters, highlighting the role of phytohormones in the sprouting and rejuvenation of mulberry stubbles. Meanwhile, the targeted metabolomics analysis identified a total of 11 differentially accumulated phytohormones in response to the differential stubble lengths, which were significantly implicated and enriched in three major pathways, including the biosynthesis of plant hormones (ko01070), metabolic pathways (ko01100), and the plant hormone signal transduction pathway (ko04575). The use of stubbles for rapid leaf production in mulberry plants is of great importance to improve early sprouting and cutting survival, as well as shortening growth and rooting time, and is highly recommended for the sericulture industries.PMID:40219194 | DOI:10.3390/plants14071126
Integrated Transcriptomics and Metabolomics Reveal Key Genes and Metabolic Pathway in Flower and Fruit Color Formation of Cerasus humilis (Bge.) Sok
Plants (Basel). 2025 Apr 2;14(7):1103. doi: 10.3390/plants14071103.ABSTRACTAnthocyanins play a pivotal role in determining the color diversity in the flowers and fruits of Cerasus humilis (Bge.) Sok. This study performed a metabolomic analysis of the flowers and fruits of two varieties differing in pigmentation phenotypes ('Jinou 1' and 'Nongda 5'), and the results indicated that the cyanidin, pelargonidin, paeonidin, and delphinidin were the main substances serving as the primary pigments contributing to their striking chromatic divergence between two varieties. Transcriptome profiling revealed that several key structural genes (ChCHS1, ChDFR, ChF3H, and ChF3'H) in the anthocyanin biosynthesis pathway exhibited significantly elevated expression levels in 'Jinou 1' compared to 'Nongda 5'. Further metabolomic and transcriptomic correlation analyses identified that ChMYB9 and ChMYB12 exhibited strong positive associations with anthocyanin pathway metabolites in both floral and fruit tissues. Notably, ChMYB9 displayed the strongest correlation with the metabolite profiles, suggesting it may serve as a core regulatory component of the anthocyanin biosynthesis. This research provides new insights into the regulatory mechanisms of anthocyanin biosynthesis in C. humilis.PMID:40219170 | DOI:10.3390/plants14071103
Jasmonic Acid-Mediated Antioxidant Defense Confers Chilling Tolerance in Okra (<em>Abelmoschus esculentus</em> L.)
Plants (Basel). 2025 Apr 2;14(7):1100. doi: 10.3390/plants14071100.ABSTRACTChilling stress inhibits the growth of okra (Abelmoschus esculentus L.), reduces its overall agricultural yield, and deteriorates fruit quality. Therefore, it is crucial to elucidate the mechanism through which okra plants respond to chilling stress. This study investigates the molecular mechanisms of chilling tolerance by comparing the transcriptome and metabolome of chilling-tolerant (Ae182) and chilling-sensitive (Ae171) okra varieties. We found that Ae182 exhibits higher antioxidant enzyme activities, including SOD, POD, CAT, and APX, suggesting it mitigates oxidative stress more effectively than Ae171. Metabolomics analysis revealed that Ae182 produces higher levels of jasmonic acid (JA) and JA-isoleucine (JA-Ile) under chilling stress, potentially activating genes that alleviate oxidative damage. Additionally, integrated analyses identified key transcription factors, such as AP2, BHLH, and MYB, associated with JA and chilling stress. These findings provide candidate genes for further research on chilling resistance in okra.PMID:40219168 | DOI:10.3390/plants14071100
Exploring Alternative Splicing in Response to Salinity: A Tissue-Level Comparative Analysis Using <em>Arabidopsis thaliana</em> Public Transcriptomic Data
Plants (Basel). 2025 Mar 30;14(7):1064. doi: 10.3390/plants14071064.ABSTRACTIncreased soil salinity is a major threat to global agriculture and food security, caused mainly by anthropogenic activities and changing climatic cycles. Plants responses to salinity involve multiple regulatory layers, from transcriptome reprogramming to proteomic and metabolomic changes. Alternative splicing (AS) plays a role in coordinating the response to salinity, yet its extent, tissue, and condition specificity, remain poorly understood aspects. In this study, we used 52 publicly available RNA-seq datasets of salinity treatment to identify differential alternative splicing (DAS) events and genes participating in the response to this stimulus. Our findings reveal that either independently or coordinately, AS can regulate up to 20% of the transcriptome detected in Arabidopsis, with treatment intensity being the most determining factor. Moreover, we show that AS regulation was highly tissue-specific, with roots displaying strong AS-mediated stress responses. Furthermore, cross-stress comparisons showed that roots have a core set of AS-regulated genes associated with stress response and development, with functionally distinct sets of genes when comparing salt with other stresses, while also conserving a relevant condition-specific response. We demonstrate the need to integrate AS analysis to better understand plant adaptation mechanisms and highlight the key role of AS in salinity responses, revealing shared AS regulation between salt, heat, and drought responses.PMID:40219132 | DOI:10.3390/plants14071064
Nutraceutical Profile Characterization in Apricot (<em>Prunus armeniaca</em> L.) Fruits
Plants (Basel). 2025 Mar 22;14(7):1000. doi: 10.3390/plants14071000.ABSTRACTThis study characterizes the metabolomic profiles of three reference apricot cultivars ('Bergeron', 'Currot', and 'Goldrich') using 1H NMR spectroscopy and untargeted UPLC-QToF MS/MS to support plant breeding by correlating metabolomic data with fruit phenotyping. The primary objective was to identify and quantify the key metabolites influencing fruit quality from a nutraceutical perspective. The analysis revealed significant differences in primary and secondary metabolites among the cultivars. 'Bergeron' and 'Goldrich' exhibited higher concentrations of organic acids (109 mg/g malate in 'Bergeron' and 202 mg/g citrate in 'Goldrich'), flavonoids such as epicatechin (0.44 mg/g and 0.79 mg/g, respectively), and sucrose (464 mg/g and 546 mg/g), contributing to their acidity-to-sugar balance. Conversely, 'Currot' showed higher levels of amino acids (24.44 mg/g asparagine) and sugars, particularly fructose and glucose (79 mg/g and 180 mg/g), enhancing its characteristic sweetness. These findings suggest that metabolomic profiling can provide valuable insights into the biochemical pathways underlying apricot quality traits, aiding in the selection of cultivars with desirable characteristics. The integration of phenotyping data with 1H NMR and UPLC-QToF MS/MS offers a comprehensive approach to understanding apricot metabolomic diversity, crucial for breeding high-quality, nutritionally enriched fruits that meet market demands.PMID:40219068 | DOI:10.3390/plants14071000
Integrated Physiological, Transcriptomic, and Metabolomic Analysis Reveals Mechanism Underlying the Serendipita indica-Enhanced Drought Tolerance in Tea Plants
Plants (Basel). 2025 Mar 21;14(7):989. doi: 10.3390/plants14070989.ABSTRACTDrought stress significantly impairs the output of tea plants and the quality of tea products. Although Serendipita indica has demonstrated the ability to enhance drought tolerance in host plants, its impact on tea plants (Camellia sinensis) experiencing drought stress is unknown. This study assessed the response of tea plants by inoculating S. indica under drought conditions. Phenotypic and physiological analyses demonstrated that S. indica mitigated drought damage in tea plants by regulating osmotic equilibrium and antioxidant enzyme activity. Metabolome analysis showed that S. indica promoted the accumulation of flavonoid metabolites, including naringin, (-)-epiafzelechin, naringenin chalcone, and dihydromyricetin, while inhibiting the content of amino acids and derivatives, such as homoarginine, L-arginine, N6-acetyl-L-lysine, and N-palmitoylglycine, during water deficit. The expression patterns of S. indica-stimulated genes were investigated using transcriptome analysis. S. indica-induced drought-responsive genes involved in osmotic regulation, antioxidant protection, transcription factors, and signaling were identified and recognized as possibly significant in S. indica-mediated drought tolerance in tea plants. Particularly, the flavonoid biosynthesis pathway was identified from the metabolomic and transcriptomic analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Moreover, flavonoid biosynthesis-related genes were identified. S. indica-inoculation significantly upregulated the expression of cinnamate 4-hydroxylase (C4H), chalcone synthase (CHS), flavanone 3-hydroxylase (F3H), dihydroflavonol 4-reductase (DFR), anthocyanidin reductase (ANR), and leucoanthocyanidin reductase (LAR) genes compared to uninoculated plants subjected to water stress. Consequently, we concluded that S. indica inoculation primarily alleviates drought stress in tea plants by modulating the flavonoid biosynthesis pathway. These results will provide insights into the mechanisms of S. indica-enhanced drought tolerance in tea plants and establish a solid foundation for its application as a microbial agent in the management of drought in tea plants cultivation.PMID:40219054 | DOI:10.3390/plants14070989