PubMed

J Ethnopharmacol. 2025 Apr 16:119809. doi: 10.1016/j.jep.2025.119809. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Qiong-Yu-Gao (QYG) is a classical formula that shows protective effects against cisplatin-induced acute kidney injury (AKI). Recent evidence indicates that iridoid glycosides and ginsenosides are the main active substances of QYG. In the production of modern Chinese medicine preparations, ethanol precipitation is a commonly applied but not fully verified refining process.AIM OF STUDY: Pharmacokinetic profiling approaches were used for evaluating the rationality of ethanol precipitation process in the production of modern QYG preparations.MATERIALS AND METHODS: Ethanol precipitation was used to prepare the glycoside-rich fraction (QYG-GS). UPLC-TQ-MS/MS methods were established for quantification of iridoid glycosides and ginsenosides of QYG in plasma and fecal samples. The pharmacokinetic profiles of major glycosides were characterized and compared after oral administration of QYG and QYG-GS in both normal and cisplatin-induced AKI rats.RESULTS: Using the validated quantitative methods, 6 glycosides were determined in plasma samples, and 14 glycosides were determined in fecal samples. More significant pharmacokinetic differences were observed in AKI rats than in normal rats. The ethanol precipitation process significantly increased the Cmax and AUC0-t of catalpol, rehmannioside D, melittoside, leonuride and ginsenoside Rb1, and decreased the T1/2 and MRT0-t values, indicating the increased absorption and accelerated elimination. Additionally, ethanol precipitation significantly decreased the fecal contents of above compounds, but increased the fecal contents of compound K.CONCLUSIONS: UPLC-TQ-MS methods were developed and validated for quantification and comparison of QYG glycosides in biological samples. The ethanol precipitation process significantly altered the pharmacokinetic profiles of major active glycosides in QYG, especially in AKI rats. The findings could provide a helpful reference for selection of ethanol precipitation process in the production of modern QYG preparations.PMID:40250636 | DOI:10.1016/j.jep.2025.119809

J Dairy Sci. 2025 Apr 16:S0022-0302(25)00244-9. doi: 10.3168/jds.2024-26066. Online ahead of print.ABSTRACTLameness, defined as an impaired gait, impacts cow welfare and performance, compromising future health and production, and increasing culling risk. Untargeted milk lipidomics, together with the use of machine learning methods, have shown promise in identifying potential biomarkers for the early detection of lameness, before the development of visible clinical lameness. Prediction of early lameness would allow for the earlier implementation of management and treatment strategies, ultimately reducing the negative consequences. This study aimed to evaluate the predictive accuracy of differences in the milk metabolome and identify milk lipid biomarkers for early lameness detection in first-lactation dairy cows. Untargeted lipidomics and machine learning approaches were used to evaluate the differences in the milk metabolomic profiles in samples collected from heifers during the transition period (before lameness) and at the time of first lameness onset. A total of 56 milk samples from 32 cows (16 lame, 16 control) were analyzed by liquid chromatography-high-resolution mass spectrometry after calving (before lameness) and at lameness onset. Elastic net regression achieved 83% accuracy in predicting lameness from samples collected after calving and 100% accuracy at the time of lameness. A total of 10 mass ions selected by different statistical methods showed potential to be considered predictors of lameness. Pathway analysis revealed significant dysregulation of retinol metabolism after calving in cows that go on to develop lameness in that lactation. This study demonstrated potential for using milk lipidomics for early lameness detection. This, in turn, provides insights into lameness pathogenesis, furthering our understanding of lameness, with the ultimate goal of developing interventions to improve dairy cow welfare and farm productivity.PMID:40250603 | DOI:10.3168/jds.2024-26066

J Nutr. 2025 Apr 16:S0022-3166(25)00227-5. doi: 10.1016/j.tjnut.2025.04.017. Online ahead of print.ABSTRACTBreakthroughs in metabolomics technology have revealed the direct regulatory role of metabolites in physiology and disease. Recent data have highlighted the bioactive metabolites involved in the etiology and prevention, and treatment of metabolic diseases such as obesity, nonalcoholic fatty liver disease (NAFLD), type 2 diabetes mellitus (T2DM), and atherosclerosis. Numerous studies reveal that endogenous metabolites biosynthesized by host organisms or gut microflora regulate metabolic responses and disorders. Lipids, amino acids, and bile acids (BAs), as endogenous metabolic modulators, regulate energy metabolism, insulin sensitivity, and immune response through multiple pathways, such as insulin signaling cascade, chemical modifications, and metabolite-macromolecule interactions. Furthermore, the gut microbial metabolites short-chain fatty acids (SCFAs), as signaling regulators have a variety of beneficial impacts in regulating energy metabolic homeostasis. In this review, we will summarize information about the roles of bioactive metabolites in the pathogenesis of many metabolic diseases. Furthermore, we discuss the potential value of metabolites in the promising preventive and therapeutic perspectives of human metabolic diseases.PMID:40250565 | DOI:10.1016/j.tjnut.2025.04.017

Microbes Infect. 2025 Apr 16:105504. doi: 10.1016/j.micinf.2025.105504. Online ahead of print.ABSTRACTRecurrent vulvovaginal candidiasis (RVVC) takes a toll not only on women's reproductive system but also on patients' life quality. The pathogenesis is still not fully understood. This study sought to explore metabolic profile of vaginal discharge from RVVC patients using non-targeted metabolomics and investigate potential bioactive functions of metabolites. The metabolic spectrum of RVVC patients was remarkably distinguished from healthy control and VVC patients. 324 metabolites with significant difference were detected in RVVC compared with control group, of which 239 were upregulated and 85 were downregulated. Moreover, compared with VVC, RVVC had a total of 67 significantly different metabolites including 43 upregulated metabolites and 24 downregulated metabolites. KEGG pathway analysis showed that Glycerophospholipid (GPL) metabolic pathway and PPAR signaling pathway were significantly changed in RVVC and the metabolites enriched into GPL metabolic pathway including LysoPC(18:1(11Z)), LysoPC(20:3(5Z,8Z,11Z)), PC(16:0/20:2(11Z,14Z)), PC(18:1(11Z)/18:1(9Z)) and PE(22:2(13Z,16Z)/18:3(9Z,12Z,15Z)) were significantly changed in RVVC patients and of high AUC values. In addition, the highest increased LysoPS(18:1(9Z)/0:0) in RVVC was demonstrated to not only inhibit the proliferation and migration of vaginal epithelial cells but also promote apoptosis. Molecular docking which showed strongly bind between LysoPS(18:1(9Z)/0:0) and PPAR-γ lead to a hypothesis that LysoPS(18:1(9Z)/0:0) may have an influence on RVVC through PPAR signaling pathway. Our findings provide new perspectives in understanding the pathogenesis of RVVC.PMID:40250525 | DOI:10.1016/j.micinf.2025.105504

Food Chem Toxicol. 2025 Apr 16:115457. doi: 10.1016/j.fct.2025.115457. Online ahead of print.ABSTRACTThe liver is considered a target organ for the accumulation and toxic effects of nanomaterials exposed to the body, especially after oral exposure, but the key toxic pathways have not been fully defined. This study focused on the hepatotoxicity of titanium dioxide nanoparticles (TiO2 NPs) in vivo and in vitro, and tried to identify key toxic pathways using the concept of systems biology and multi-omics methods. In vivo, protein and metabolomic sequencing were performed on the liver of SD rats (0, 50 mg/kg, 90 days), and 386 differential proteins and 29 differential metabolites were screened out, respectively, and the joint analysis found that they were significantly enriched in alanine, aspartate and glutamate metabolism, and butanoate metabolism. In vitro, exposure to TiO2 NPs could induce cytotoxicity and omics changes at different molecular levels in human hepatocellular carcinoma cells. Single omic analysis showed that differentially expressed proteins and metabolites were 80 and 222, respectively. The enriched pathways related to steroid biosynthesis, cholesterol metabolism at the combine levels of proteome and metabolome. KEGG enrichment analysis showed that PI3K-Akt signaling pathway and PPAR signaling pathway were both significantly affected in vitro and in vivo. Through multi-omics analysis, this work offered fresh perspectives and avenues for research on the toxicity mechanism of TiO2 NPs.PMID:40250523 | DOI:10.1016/j.fct.2025.115457

Cell. 2025 Apr 17;188(8):2043-2062. doi: 10.1016/j.cell.2025.03.011.ABSTRACTMajor progress has been made in elucidating the molecular, cellular, and supracellular mechanisms underlying aging. This has spurred the birth of geroscience, which aims to identify actionable hallmarks of aging. Aging can be viewed as a process that is promoted by overactivation of gerogenes, i.e., genes and molecular pathways that favor biological aging, and alternatively slowed down by gerosuppressors, much as cancers are caused by the activation of oncogenes and prevented by tumor suppressors. Such gerogenes and gerosuppressors are often associated with age-related diseases in human population studies but also offer targets for modeling age-related diseases in animal models and treating or preventing such diseases in humans. Gerogenes and gerosuppressors interact with environmental, behavioral, and psychological risk factors to determine the heterogeneous trajectory of biological aging and disease manifestation. New molecular profiling technologies enable the characterization of gerogenic and gerosuppressive pathways, which serve as biomarkers of aging, hence inaugurating the era of precision geromedicine. It is anticipated that, pending results from randomized clinical trials and regulatory approval, gerotherapeutics will be tailored to each person based on their genetic profile, high-dimensional omics-based biomarkers of aging, clinical and digital biomarkers of aging, psychosocial profile, and past or present exposures.PMID:40250404 | DOI:10.1016/j.cell.2025.03.011

Int J Food Microbiol. 2025 Apr 4;436:111186. doi: 10.1016/j.ijfoodmicro.2025.111186. Online ahead of print.ABSTRACTThis study aims to address the problems of strong bitterness, astringency, and inferior taste in Pu'er tea made from young tea trees. First, four strains of Eurotium cristatum were isolated and screened by the static suspension isolation method using tea infusion as the culture medium and identified through morphological and molecular analysis. One of the strains was selected for the solid - state fermentation of raw Pu'er tea, Pu'er black tea, and Pu'er green tea. The fermentation conditions were optimized via response - surface experimental design. The results showed that the optimized fermentation time, temperature, and relative humidity for the three types of tea were 10 days, 30 °C, 45 %; 5 days, 30 °C, 40 %; and 10 days, 35 °C, 40 % respectively. Sensory evaluation indicated that after fermentation, the color of the tea leaves and tea soup deepened. And the freshness of raw Pu'er tea and green Pu'er tea decreased, while a subtle moldy aroma aroma was introduced after fermentation. The astringency and bitterness were effectively reduced. Chemical analysis revealed that, except for the stable caffeine level, the levels of components such as tea polyphenols and catechins changed significantly. Correlation analysis demonstrated a strong correlation between the color, aroma, and taste of the tea and the contents of various chemical components. GC - MS analysis identified 370 volatile compounds, 262 of which showed differences before and after fermentation. In conclusion, solid - state fermentation with E.cristatum can affect the chemical composition of the three types of tea, improve their taste and flavor, and offer a new approach for enhancing the quality of tea from young tea trees.PMID:40250220 | DOI:10.1016/j.ijfoodmicro.2025.111186

Phytomedicine. 2025 Apr 11;142:156753. doi: 10.1016/j.phymed.2025.156753. Online ahead of print.ABSTRACTBACKGROUND: Gelsenicine, the most toxic constituent of Gelsemium elegans Benth., is known for its diverse pharmacological activities alongside potent neurotoxicity, frequently leading to poisoning incidents following mistaken ingestion. However, its molecular mechanisms remain largely unexplored.PURPOSE: This study aimed to elucidate the key mechanistic network underlying gelsenicine-induced neurotoxicity by employing a comprehensive strategy that integrated metabolomics, network toxicology, molecular docking, and experimental validation.METHODS: Acute oral toxicity tests were conducted in C57BL/6J mice to assess toxic symptoms, determine the median lethal dose (LD50), and evaluate histopathological changes. Untargeted metabolomics was performed to identify differential metabolites and associated pathways in serum, hippocampus (HIP), and medulla oblongata (MO). Integration of network toxicology pinpointed core targets and pathways, which were further validated through molecular docking and RT-qPCR. A core "compound-target-metabolite-pathway" network involved in gelsenicine-induced neurotoxicity was established.RESULTS: Gelsenicine exhibited an oral LD50 of approximately 1.82 mg/kg and induced neurotoxic damage in the HIP and MO. Two untargeted metabolomic approaches detected a broad range of metabolites, revealing that gelsenicine markedly altered the metabolic profiles of serum, HIP, and MO. Network toxicology analysis identified 187 key targets associated with gelsenicine neurotoxicity. Integrated analyses with the predicted targets of differential metabolites indicated that gelsenicine primarily interferes with the energy metabolism network centered on the malate-aspartate shuttle (MAS), affecting pathways such as carbon metabolism, amino acid metabolism, TCA cycle, and PPAR signaling pathway. Malate, glutamate, and aspartate were identified as core metabolites and potential biomarkers of gelsenicine poisoning. RT-qPCR validation revealed that gelsenicine interfered with the expression of core targets, including GLUD1, MDH, GOT and ME, all of which exhibited good binding energy with gelsenicine.CONCLUSION: This study unveiled a novel mechanistic insight into gelsenicine-induced neurotoxicity, demonstrating its capacity to perturb multiple energy metabolism pathways associated with MAS. These findings could enhance the theoretical understanding of gelsenicine's neurotoxic effects and highlight potential applications in clinical diagnosis and forensic identification.PMID:40250031 | DOI:10.1016/j.phymed.2025.156753

J Am Soc Mass Spectrom. 2025 Apr 18. doi: 10.1021/jasms.5c00038. Online ahead of print.ABSTRACTMany existing mass spectral libraries focus on human or microbially derived molecules. Few plant-specific MS2 databases exist, making annotation of botanical samples difficult. To fill this gap in mass spectrometry data availability, the Library Enabling Annotation of Botanical Natural Products (LEAFBot) was constructed. Using a flow injection mass spectrometry method that allowed for rapid throughput data collection, the MS2 spectra of >300 pure botanical secondary metabolites were experimentally measured and complied into a single library housed in the Global Natural Products Social Molecular Networking (GNPS) spectral database. Of these compounds, over 20% were not present in the existing GNPS database, and 11% were not present in any of three main mass spectral databases (GNPS, Metlin, and MassBank). Additionally, LEAFBot contains a wider range of adducts compared to other plant-based mass spectral libraries, enabling more effective annotation of unknown features. The LEAFBot database represents a new resource to the mass spectrometry and metabolomics community seeking to characterize plant-based samples. The possibility of searching against a taxonomically specific library decreases the likelihood of false positives in database searches, and the ease of adding new spectra, following procedures outlined herein, will enable community-lead expansion of the database.PMID:40249845 | DOI:10.1021/jasms.5c00038

Sci Adv. 2025 Apr 18;11(16):eadu4637. doi: 10.1126/sciadv.adu4637. Epub 2025 Apr 18.ABSTRACTIsoprene, emitted by some plants, deters insect herbivory. However, the associated biochemical and physiological responses that confer herbivory resistance remain unknown. We used engineered isoprene-emitting (IE) and non-emitting (NE) control tobacco plants to interpret isoprene-mediated defense against herbivory in plants. Hornworm larvae raised on IE plants exhibited stunted growth compared to those raised on NE plants. Worms preferred to feed on NE rather than IE leaves, indicating deterrent effects of isoprene on insect feeding. Worm feeding induced a greater increase in jasmonic acid (JA), a crucial hormone for insect resistance, in IE leaves compared to that in NE leaves. Assimilation rates were stably maintained in IE plants, suggesting a protective role of isoprene in preserving photosynthetic efficiency during insect herbivory. Wound-induced increase in isoprene emission correlated with the elevation of key metabolites of the isoprene biosynthesis pathway. Our results highlight JA-priming functions of isoprene and provide insights into isoprene-mediated defense against insect herbivory.PMID:40249816 | DOI:10.1126/sciadv.adu4637

Sci Adv. 2025 Apr 18;11(16):eadu1240. doi: 10.1126/sciadv.adu1240. Epub 2025 Apr 18.ABSTRACTLight and CO2 assimilation activate the target of rapamycin (TOR) kinase in photosynthetic cells, but how these signals are transmitted to TOR is unknown. Using the green alga Chlamydomonas reinhardtii as a model system, we identified dihydroxyacetone phosphate (DHAP) as the key metabolite regulating TOR in response to carbon and light cues. Metabolomic analyses of synchronized cells revealed that DHAP levels change more than any other metabolite between dark- and light-grown cells and that the addition of the DHAP precursor, dihydroxyacetone (DHA), was sufficient to activate TOR in the dark. We also demonstrated that TOR was insensitive to light or inorganic carbon but not to exogenous DHA in a Chlamydomonas mutant defective in the export of DHAP from the chloroplast. Our results provide a metabolic basis for the mode of TOR control by light and inorganic carbon and indicate that cytoplasmic DHAP is an important metabolic regulator of TOR.PMID:40249806 | DOI:10.1126/sciadv.adu1240

Sci Adv. 2025 Apr 18;11(16):eadq0334. doi: 10.1126/sciadv.adq0334. Epub 2025 Apr 18.ABSTRACTElevated hexosamine biosynthesis fuels tumor growth by facilitating protein and lipid glycosylation. But which enzyme in this pathway is better to serve as an antitumor target remains unclear. Here, we revealed that targeting GFAT1, the rate-limiting enzyme in hexosamine synthesis, exhibits limited inhibitory effects on glioblastoma (GBM), the most lethal brain tumor. This outcome is due to the compensation of NAGK-mediated hexosamine salvage pathway. Unexpectedly, inhibiting PGM3, which controls the flux of both de novo hexosamine synthesis and salvage pathways, down-regulates the expression of other enzymes in this pathway and suppresses SREBP-1, a critical lipogenic transcription factor, effectively inhibiting GBM growth. Unexpectedly, SREBP-1 transcriptionally up-regulates the expression of hexosamine synthesis enzymes, while inhibition of these enzymes in turn down-regulates SREBP-1 activation via reducing N-glycosylation of its transporter, SCAP. Our study identified PGM3 as a promising target for treating GBM. Its inhibition disrupts the SREBP-1 activation-hexosamine synthesis positive feedback regulation to effectively eliminate GBM cells.PMID:40249802 | DOI:10.1126/sciadv.adq0334

Anal Bioanal Chem. 2025 Apr 18. doi: 10.1007/s00216-025-05847-7. Online ahead of print.ABSTRACTMetabolite annotation is a critical step in discovery metabolomics, but remains a significant challenge. In this study, the accuracy of metabolite annotation was systematically evaluated by leveraging the proposed strategies for simulation of tandem mass spectrometry (MS/MS) data from high-resolution mass spectrometry (HRMS) and then construction of a large-scale virtual database. Furthermore, various similarity scoring methods were comprehensively compared to assess the performance for annotation. First, three key characteristics that are essential for simulating MS/MS spectra to closely resemble experimental data were identified: (i) the number of mass-to-charge ratio (m/z) features, (ii) the differences between neighboring m/z values, and (iii) the intensity distribution of MS/MS features. These factors were employed to generate representative MS/MS spectra for subsequent study. A meticulously designed virtual MS/MS database was constructed to facilitate accurate annotation assessment, which covered over 100,000 metabolites with diverse structural similarities and differences. To evaluate annotation quality, two simulation strategies on the basis of strong and weak data inference were respectively proposed to replicate MS/MS spectra for unknown metabolites. These simulated spectra were then compared with the virtual database, which provided insights into the expected variations in experimental MS/MS data. Furthermore, eight similarity evaluation methods, including entropy similarity (ES) and weighted dot product (W/DP) algorithms, were rigorously evaluated for their effectiveness in metabolite annotation. The results revealed that some methods, such as ES, exhibited strong resistance to interference and broad adaptability across different MS/MS patterns, whereas others selectively yielded reliable outcomes under specific conditions. This study provided a systematic framework for quality evaluation in metabolite annotation and offered strategies to mitigate false-positive identifications. The findings held great significance for advancing metabolomics research and further improving annotation reliability in complex biological samples.PMID:40249542 | DOI:10.1007/s00216-025-05847-7

World J Urol. 2025 Apr 18;43(1):233. doi: 10.1007/s00345-025-05628-y.ABSTRACTPURPOSE: To identify biomarkers for diagnosis and classification of interstitial cystitis/bladder pain syndrome (IC/BPS) by urinary lipidomics coupled with machine learning.METHODS: Urine samples from 138 patients with IC/BPS, including 116 with Hunner lesion (HL) and 22 with no HL, and 71 controls were assessed by lipid chromatography-tandem mass spectrometry. Single and paired lipid analyses of differentially expressed lipids in each group were conducted to assess their diagnostic ability. Machine learning models were constructed based on the identified urinary lipids and patient demographic data, and a five-fold cross-validation method was applied for internal validation. Levels of urinary lipids were adjusted to account for urinary creatinine levels.RESULTS: A total of 218 urinary lipids were identified. Single lipid analysis revealed that urinary levels of C24 ceramide and LPC (14:0) distinguished HL and no HL, with an area under the receiver operating characteristics curve of 0.792 and 0.656, respectively. Paired lipid analysis revealed that summed urinary levels of C24 ceramide and LPI (18:3), and subtraction of PG (36:5) from PC (38:2) distinguished HL and no HL even more accurately, with an area under the curve of 0.805 and 0.752, respectively. A machine learning model distinguished HL and no HL, with the highest area under the curve being 0.873 and 0.750, respectively. Limitations include the opaque black box nature of machine learning techniques.CONCLUSIONS: Urinary levels of C24 ceramide, along with those of C24 ceramide plus LPI (18:3), could be potential biomarkers for HL. Machine learning-coupled urinary lipidomics may play an important role in the next-generation AI- driven diagnostic systems for IC/BPS.PMID:40249505 | DOI:10.1007/s00345-025-05628-y

Methods Mol Biol. 2025;2913:247-249. doi: 10.1007/978-1-0716-4458-4_23.ABSTRACTAll biological samples are potentially infectious, requiring vaccination and protective equipment for laboratory personnel. The risk classification of pathogenic microorganisms, including the yellow fever virus (YFV), is based on potential risks to individuals, communities, and the environment. Countries have their own classification systems, with Brazil previously following global standards until 1995. YFV is classified as a Risk Group 3 pathogen by the WHO, necessitating handling in Biosafety Level 3 (BSL3) laboratories. Personnel must be vaccinated against YFV at least 10 days prior to contact, as there have been cases of occupationally acquired infections among healthcare and laboratory workers.PMID:40249442 | DOI:10.1007/978-1-0716-4458-4_23

Methods Mol Biol. 2025;2913:183-191. doi: 10.1007/978-1-0716-4458-4_16.ABSTRACTThe yellow fever virus (YF), belonging to the Flaviviridae family, has an RNA genome of 10,862 nucleotides and continues to cause significant epidemics in Africa and South America despite an effective vaccine. Timely laboratory identification is essential for emergency immunization campaigns, but delays often lead to unconfirmed outbreaks. The presence of other diseases with similar symptoms complicates differential diagnosis, particularly in endemic regions, and the recent resurgence of YF activity has renewed interest in this arboviral disease. Genomic DNA (gDNA) and plasmids with cloned target sequences serve as standards in quantitative PCR, requiring specific calculations to determine their masses relative to target nucleic acid copy numbers.PMID:40249435 | DOI:10.1007/978-1-0716-4458-4_16

Methods Mol Biol. 2025;2913:39-50. doi: 10.1007/978-1-0716-4458-4_4.ABSTRACTQuantitative RT-PCR (qPCR) provides a rapid, specific, and sensitive method for the determination of yellow fever viral load and presents many advantages including quantitative measurement, low contamination rate, and easy standardization. Here it is presented a semi-automatic RNA extraction followed by one-step PCR reaction. Genome copies were quantified by plasmid standard curve designed to NS5 region. This method provides a specific, rapid, and sensitive diagnosis to yellow fever virus (YFV).PMID:40249423 | DOI:10.1007/978-1-0716-4458-4_4

Methods Mol Biol. 2025;2913:19-27. doi: 10.1007/978-1-0716-4458-4_2.ABSTRACTYellow fever (YF) is an arbovirus caused by a flavivirus. In 90% of cases, it has a benign course with few symptoms. However, a few cases evolve with a moderate or severe form of high mortality. The severe disease usually starts with minor symptoms, with a period of apparent improvement that progresses to toxemia. Yellow fever liver failure is characterized by jaundice, albuminuria, and bleeding. Very high levels of bilirubin and aminotransferases appear to be associated with a worse prognosis. Treatment is usually nonspecific, based on clinical support for complications. However, recently, studies have emerged showing the possibility of YF treatment with Sofosbuvir and plasmapheresis. The use of acetylsalicylic acid, paracetamol, and anti-inflammatory drugs should be avoided.PMID:40249421 | DOI:10.1007/978-1-0716-4458-4_2

Cardiovasc Res. 2025 Apr 18:cvaf069. doi: 10.1093/cvr/cvaf069. Online ahead of print.ABSTRACTAIMS: Adult mammalian cardiomyocytes have limited regenerative potential, and after myocardial infarction (MI), injured cardiac tissue is replaced with fibrotic scar. In contrast, the neonatal mouse heart possesses a regenerative capacity governed by cardiomyocyte proliferation; however, a metabolic switch from glycolysis to fatty acid oxidation during postnatal development results in loss of this regenerative capacity. Interestingly, a sarcomere isoform switch also takes place during postnatal development where slow skeletal troponin I (ssTnI) is replaced with cardiac troponin I (cTnI). It remains unclear whether there is an interplay between sarcomere isoform switching, cardiac metabolism, and regeneration.METHODS AND RESULTS: In this study, we employ proteomics, metabolomics and lipidomics, transgenic mice, MI models, and histological analysis to delineate the molecular and sarcomeric transitions that occur during cardiac maturation and regeneration. First, we utilize integrated quantitative bottom-up and top-down proteomics to comprehensively define the proteomic and sarcomeric landscape during postnatal heart maturation. By employing a cardiomyocyte-specific ssTnI transgenic mouse model, we discovered that ssTnI overexpression increased cardiomyocyte proliferation and the cardiac regenerative capacity of the postnatal heart following MI compared to control mice by histological analysis. Our global proteomic analysis of ssTnI transgenic mice following MI reveals that ssTnI overexpression induces a significant shift in the cardiac proteomic landscape. Additionally, our lipidomic analysis demonstrated a significant upregulation of lipid species in the transgenic mice. This proteomic shift is characterized by an upregulation of key proteins involved in glycolytic metabolism.CONCLUSIONS: Collectively, our data suggest that the postnatal TnI isoform switch may play a role in the metabolic shift from glycolysis to fatty acid oxidation during postnatal maturation. This underscores the significance of a sarcomere-metabolism axis during cardiomyocyte proliferation and heart regeneration.PMID:40249109 | DOI:10.1093/cvr/cvaf069

Plant J. 2025 Apr;122(1):e70160. doi: 10.1111/tpj.70160.ABSTRACTWillows can alleviate soil salinisation while generating sustainable feedstock for biorefinery, yet the metabolomic adaptations underlying their tolerance remain poorly understood. Salix miyabeana was treated with two environmentally abundant salts, NaCl and Na2SO4, in a 12-week pot trial. Willows tolerated salts across all treatments (up to 9.1 dS m-1 soil ECe), maintaining biomass while selectively partitioning ions, confining Na+ to roots and accumulating Cl- and SO 4 2 - $$ {\mathrm{SO}}_4^{2-} $$ in the canopy and adapting to osmotic stress via reduced stomatal conductance. Untargeted metabolomics captured >5000 putative compounds, including 278 core willow metabolome compounds constitutively produced across organs. Across all treatments, salinity drove widespread metabolic reprogramming, altering 28% of the overall metabolome, with organ-tailored strategies. Comparing salt forms at equimolar sodium, shared differentially abundant metabolites were limited to 3% of the metabolome, representing the generalised salinity response, predominantly in roots. Anion-specific metabolomic responses were extensive. NaCl reduced carbohydrates and tricarboxylic acid cycle intermediates, suggesting potential carbon and energy resource pressure, and accumulated root structuring compounds, antioxidant flavonoids, and fatty acids. Na2SO4 salinity triggered accumulation of sulphur-containing larger peptides, suggesting excess sulphate incorporation leverages ion toxicity to produce specialised salt-tolerance-associated metabolites. This high-depth picture of the willow metabolome underscores the importance of capturing plant adaptations to salt stress at organ scale and considering ion-specific contributions to soil salinity.PMID:40249060 | DOI:10.1111/tpj.70160