PubMed

Food Chem. 2025 Apr 9;483:144255. doi: 10.1016/j.foodchem.2025.144255. Online ahead of print.ABSTRACTThe modern emphasis on food quality, nutritional value, and health benefits has increased demand for nutrient-rich foods. Incorporating functional foods with enhanced nutritional profiles into diets is becoming a key strategy in addressing chronic and acute diseases. In this study, a pot experiment was conducted on the 'Kashi Ratna' cultivar of Capsicum annuum L. under salinity levels of 50 and 100 mM as compared to control (0 mM). UHPLC-HRMS untargeted quantitative metabolomic profiling revealed a significant increase in bioactive compounds such as amino acids, vitamins, fatty acids, alkaloids, capsaicinoids, terpenoids and phenolics under salinity stress. While 50 mM led to higher accumulation of metabolites, but the overall impact of 100 mM salinity was higher, affecting more metabolites. Our findings highlight the potential for utilizing salinity-affected lands as a sustainable and cost-effective solution for enhancing nutritional quality of foods particularly in the context of Global Climate Change.PMID:40220443 | DOI:10.1016/j.foodchem.2025.144255

Food Chem. 2025 Apr 9;483:144298. doi: 10.1016/j.foodchem.2025.144298. Online ahead of print.ABSTRACTWaterless transportation at low temperatures is ideal for many live aquatic organisms. Urechis unicinctus, which boasts unique taste and nutritional characteristics, is well-suited for this transportation method; however, the impacts of transportation duration on U. unicinctus physiology have not been determined. In this study, we determine the optimal duration of low-temperature waterless live transport for U. unicinctus according to physiology, behaviour, nutrition, and taste changes. We determined an optimal transport duration of 48 h, with longer durations inducing oxidative stress, metabolic disorders, lipid degeneration, and tissue damage; increased levels of harmful metabolites, such as ethyl oleate; and decreased levels of beneficial substances, such as fatty alcohols. These changes exacerbated oxidative stress and caused weight loss, nutrient depletion, and reduced sensory quality. By elucidating the molecular mechanisms underlying rapid degradation during U. unicinctus transport, this study has implications for mitigating transport-related quality losses and optimising live seafood transport.PMID:40220437 | DOI:10.1016/j.foodchem.2025.144298

Food Chem. 2025 Apr 3;483:144060. doi: 10.1016/j.foodchem.2025.144060. Online ahead of print.ABSTRACTEdible seedlings are known for their nutritional value and potential health benefits; however, only a limited number of species are currently utilized. To explore new resources, we performed comprehensive metabolite profiling of adzuki bean (Vigna angularis) seedlings using eight cultivars. Through LC-MS/MS fingerprint analysis combined with principal component analysis, significant metabolic changes were revealed in day 11 seedlings, leading to the identification of sixteen compounds including a new coumestan glycoside. Further LC-MS/MS analysis identified 133 metabolites, which were validated by molecular networking. Using fold change and orthogonal partial least squares discriminant analysis, we found that the metabolite changes effectively distinguished between different growth states and cultivars, with flavonoids, and saponins being predominantly observed on days 7-11. Notably, high levels of bacterial neuraminidase metabolites were detected in ARR cultivar at day 7 and in YDC cultivar during days 9-11, suggesting the potential of adzuki bean seedlings as a functional food.PMID:40220434 | DOI:10.1016/j.foodchem.2025.144060

Phytomedicine. 2025 Mar 28;141:156706. doi: 10.1016/j.phymed.2025.156706. Online ahead of print.ABSTRACTBACKGROUND: Shugan Yiyang capsule (SGYY), a commonly used traditional Chinese medicine formulation, is primarily indicated for the treatment of erectile dysfunction, yet existing studies on the therapeutic effects on male infertility (MI) are insufficient and the specific mechanisms remain poorly understood. Given the close relationship between MI, sperm quality, and erectile function, this study aims to investigate the role of SGYY in the restoration of MI and explore the underlying mechanisms.METHODS: The efficacy of SGYY is comprehensively evaluated through pharmacodynamic, metabolomic, and network pharmacology. Sperm parameters, reproductive hormones, sexual behavior, neural enzymes, oxidative stress markers, pro-inflammatory cytokines, and testicular histopathology are measured to reveal the restorative effects of MI. Furthermore, urine and serum metabolomics, along with network pharmacology and surface plasmon resonance, are employed to explore the molecular mechanisms and predict core targets.RESULTS: SGYY significantly improved overall health parameters, including body weight, water intake, urine output, food consumption, and spontaneous activity. Specifically, SGYY prominently recovered sexual behavior, ameliorated sperm quality, increased mitochondrial membrane potential, normalized reproductive hormones, upregulated endothelial nitric oxide synthase, attenuated oxidative stress markers, and pro-inflammatory cytokines, and repaired testicular pathological damage. Metabolomic analysis identified 47 candidate biomarkers, among which SGYY significantly modulated 39 potential biomarkers, encompassing 8 main metabolic pathways such as histidine metabolism, cysteine and methionine metabolism, propanoate metabolism, and taurine and hypotaurine metabolism. Additionally, network pharmacology predicted 8 core targets, comprising HSP90AA1, ESR1, MAPK1, CASP3, IL6, TNF, BCL2, and MAPK8.CONCLUSION: SGYY improves sperm quality and erectile function by regulating oxidative stress, energy metabolism, and neurological function, thereby exerting a restorative effect on MI, as evidenced by the modulation of 8 main metabolic pathways, 39 potential biomarkers, and 8 core targets. Pharmacodynamic provides foundational validation, metabolomic uncovers intrinsic metabolic changes, and network pharmacology predicts therapeutic targets, with findings from the 'Pharmaco-Metabo-Net' tripartite correlation analysis providing a solid theoretical strategy and scientific evidence to support the clinical application of SGYY in restoring MI.PMID:40220430 | DOI:10.1016/j.phymed.2025.156706

Phytomedicine. 2025 Mar 24;141:156680. doi: 10.1016/j.phymed.2025.156680. Online ahead of print.ABSTRACTBACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent metabolic disorder characterized by liver lipid accumulation and insulin resistance. However, effective therapeutic drugs for NAFLD are currently unavailable. Stevia rebaudiana root polysaccharides (SRRP) are inulin-type polysaccharides known for their hypoglycemic properties. Despite this, the effects of SRRP on improving NAFLD and the underlying mechanisms remain poorly understood.PURPOSE: This study aims to evaluate the potential of SRRP in alleviating NAFLD and to explore its mechanisms of action.METHODS: NAFLD was induced in male C57BL/6 J mice through high-fat diet (HFD) feeding, with subsequent SRRP administration over 8 weeks. Comprehensive assessments included serum biochemical profiling, hepatic histopathological examination, and proinflammatory enzyme activity quantification. Mechanistic investigations employed tripartite analytical approaches: gut microbiota analysis via 16S rRNA sequencing, hepatic metabolomic profiling and bile acid profiling, and validation of transport protein expression through Western blot (WB) techniques.RESULTS: SRRP administration significantly alleviated NAFLD through reduced serum lipid concentrations, ameliorated inflammatory responses and oxidative stress, and decreased hepatic lipid deposition mechanistically, SRRP improved the structure of the gut microbiota by enhancing the proliferation of beneficial bacterial, including Lactobacillales and Bifidobacteriales, which subsequently elevated circulating Cholic acid (CA) and Chenodeoxycholic acid (CDCA), and improved hepatic lipid metabolites. Notably, KEGG from metabolomics indicated that the linoleic acid pathway might be associated with the improvement in hepatic lipid metabolite levels by SRRP. In Western blot analysis, SRRP significantly upregulated hepatic ACSL1 and FADS2 in NAFLD mice, demonstrating that the alleviation of NAFLD by SRRP may be achieved through the reduction of hepatic lipid accumulation.CONCLUSIONS: SRRP exerts effects on improving NAFLD by modulating the gut microbiota, hepatic metabolites, bile acid levels, and the expression of ACSL1 and FADS2 proteins, providing more scientific evidence and support for the improvement of NAFLD by SRRP.PMID:40220428 | DOI:10.1016/j.phymed.2025.156680

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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