Metabolites[JOURNAL]
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200 papers
Temperature-Dependent Modulation of Cardiac Metabolism, Post-Injury Survival and Regenerative Rate in Axolotls.
Dittrich A, Andersson SA, Alstrup AKO … +5 more , Sørensen PL, Simonsen MIT, Arildsen MH, Aabling RR, Lauridsen H
Metabolites · 2026 Jun · PMID 42346394 · Full text
: Cardiac regenerative ability varies in vertebrates. Adult mammals cannot mount a regenerative response, while fetal mammals and some salamanders and teleosts fully regenerate the heart after a cryoinjury mimicking a my...
: Cardiac regenerative ability varies in vertebrates. Adult mammals cannot mount a regenerative response, while fetal mammals and some salamanders and teleosts fully regenerate the heart after a cryoinjury mimicking a myocardial infarction. This contrast is suggested to be regulated in part by metabolism, with high regenerative capacity correlating with a comparatively lower mass-specific metabolic rate, ectothermy rather than endothermy and a metabolic phenotype favoring glycolysis in cardiac muscle. : In this physiological study on axolotl salamanders, we altered the housing temperatures from the standard 20 °C to 10 °C, 25 °C and 30 °C and assayed key metabolic parameters as well as cardiac function, survival and regenerative capacity. : Our study demonstrated that while axolotls could be housed at temperatures ranging from 10 °C to 30 °C in an uninjured state, signs of a pathological response involving cardiac and metabolic insufficiency and mortality, especially after cryoinjury, increased progressively with increasing temperatures. We observed several metabolic effects, including differences in oxygen consumption, plasma metabolites and cardiac function. Cardiac regeneration after cryoinjury progressed as expected with only a small remaining injury after 60 days at the standard housing temperature of 20 °C. Regeneration was highly reduced in a reversible manner at 10 °C while regenerative rate was not affected at 25 °C. At 30 °C, cardiac regeneration could not be evaluated as the majority of animals (five out of six) did not survive the injury, likely reflecting insufficient cardiac reserve capacity to simultaneously sustain thermal metabolic effects and support tissue repair. : The ectothermic axolotl undergoes several metabolic changes when exposed to different housing temperatures, with heart regeneration showing a narrower permissive temperature range than survival of the axolotl in an uninjured state.
High-Intensity Interval Training Attenuates Hepatic Fibrosis by Remodeling Lactate Metabolism in MASLD.
Chen X, Su J, Huang W … +2 more , Li Y, Zhang J
Metabolites · 2026 Jun · PMID 42346393 · Full text
: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global metabolic disorder. As a non-pharmacological intervention, the effects of high-intensity interval training (HIIT) on MASLD and it...
: Metabolic dysfunction-associated steatotic liver disease (MASLD) has emerged as a global metabolic disorder. As a non-pharmacological intervention, the effects of high-intensity interval training (HIIT) on MASLD and its molecular mechanisms remain poorly understood. This study aimed to investigate whether HIIT could ameliorate high-fat diet (HFD)-induced liver fibrosis by recalibrating the intrahepatic lactate metabolic axis. An HFD-induced murine MASLD model combined with HIIT intervention was utilized to evaluate the therapeutic efficacy and underlying mechanisms. Hepatosomatic indices, histological architecture and fibrosis severity were examined. Lactate concentrations within the systemic circulation and hepatic parenchyma, alongside comprehensive lipid profiles, were measured. The expressions of genes and proteins involved in hepatic lactate metabolism were delineated via qPCR and Western blotting. The 8-week HIIT intervention effectively improved liver lipid accumulation, hepatocellular injury, and oxidative stress caused by a high-fat diet. Fibrotic expansion and suppressed hepatic stellate cell activation were restricted markedly, as evidenced by the downregulation of collagen type I alpha 1 chain and alpha-smooth muscle actin(α-SMA). HIIT reversed the HFD-induced accumulation of lactate in both systemic circulation and liver tissues, which was found to positively correlate with hepatic α-SMA. Mechanistically, HIIT regulated the expression of the lactate metabolism-related proteins lactate dehydrogenase A and monocarboxylate transporter 1, while selectively enhancing the expression of the gluconeogenic enzymes. Our findings indicate that HIIT effectively ameliorated MASLD and associated hepatic fibrosis by remodeling the hepatic lactate metabolic axis, specifically through the suppression of lactate production and the enhancement of its clearance. These results indicate that targeting lactate homeostasis might be a promising therapeutic strategy for MASLD.
Practical Workflow for Building Local Mass Spectral Libraries for Untargeted Metabolomics.
Myhre TN, Hansen T, Lutchyn T … +2 more , Mardal M, Vasskog T
Metabolites · 2026 Jun · PMID 42346392 · Full text
: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation...
: Metabolite identification and annotation remain major bottlenecks in untargeted metabolomics because mass spectral features often lack sufficient specificity. High-confidence annotation requires experimental validation using authentic standards analyzed under matched chromatographic and ionization conditions, providing greater reliability than in silico predictions or database matching alone. This study aimed to develop a practical and scalable workflow for constructing a high-quality mass spectral library using a commercially available analytical standards kit. : A total of 603 metabolites from the MSMLS kit were organized into 42 mixtures, each containing approximately 15 compounds. Mixture design was based on molecular mass and distribution coefficient values, specifically logD at pH 3.1, with a minimum logD spacing of 0.15 to improve chromatographic separation and reduce co-elution. This strategy was used to minimize the total number of injections while maintaining spectral quality. The resulting spectra were evaluated against online spectral resources and in silico fragmentation predictions. A preliminary proof-of-concept analysis was also performed using human serum samples. : Using this workflow, 471 metabolites, corresponding to approximately 78% of the standards, were successfully detected and incorporated into the spectral library. Comparison with online resources and in silico fragmentation predictions demonstrated improved spectral quality and reliability. The proof-of-concept serum analysis enabled identification of endogenous metabolites using the constructed library. In addition, the robustness and applicability of the workflow were further supported by a method validation study using metabolites derived from this library. : This workflow provides a scalable strategy for constructing mass spectral libraries that balances spectral quality with analytical throughput. By using rational mixture design and authentic standards analyzed under matched experimental conditions, the approach enables substantial metabolite coverage while maintaining data reliability and minimizing experimental effort.
Multi-Targeted Intervention of and Its Bioactive Constituents Against Metabolic Syndrome: From Molecular Mechanisms and Gut Microbiota Modulation to Clinical Translation.
Cheng F, Lv C, Yi Y … +6 more , Wang D, Wang W, Li T, Zhou R, Li Q, Qin S
Metabolites · 2026 Jun · PMID 42346391 · Full text
Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects....
Metabolic syndrome (MetS) is a pressing global health challenge comprising obesity, hyperglycemia, hypertension, and hyperlipidemia. Conventional polypharmacy often presents long-term compliance issues and side effects. Oliv., a traditional medicinal and edible plant rich in iridoids, lignans, flavonoids, and polysaccharides, has emerged as a promising natural intervention. This review aims to systematically summarize the bioavailability and multifaceted pharmacological mechanisms of and its bioactive components in alleviating MetS. We comprehensively reviewed the recent in vitro and in vivo literature to map the functional evidence, specific signaling pathways, and gut microbiota-host interactions associated with extracts and its key phytochemicals (e.g., asperuloside) against various metabolic dysfunctions. Current evidence indicates that operates through a "multi-component, multi-target, and multi-pathway" paradigm. For hyperlipidemia and obesity, it activates hepatic lipid metabolism (PPARα/CPT1A, FXR/CYP7A1) and mitigates oxidative stress (Nrf2/ARE). Furthermore, it dose-dependently reshapes the gut microbiota by enriching beneficial bacteria like Akkermansia and increasing butyrate production, exerting profound gut-liver axis regulation. It also ameliorates hypertension by activating the ACE2-Ang-(1-7)-Mas axis, improves insulin resistance via the AMPK/PI3K/Akt cascade, and manages hyperuricemia by modulating XOD and renal transporters. Notably, the low oral bioavailability of its glycosides highlights the crucial role of gut microbial hydrolysis in its efficacy. : holds substantial therapeutic potential as a multi-target natural supplement for MetS. However, future translational applications necessitate large-scale randomized clinical trials, multi-omics studies to further clarify host-microbiome interactions, and the development of standardized formulations to ensure clinical efficacy.
Exploring the Health Effects of Phytoestrogens.
Kraus V, Birková A, Majerníková M … +1 more , Čižmárová B
Metabolites · 2026 Jun · PMID 42346390 · Full text
BACKGROUND/OBJECTIVES: Phytoestrogens are secondary plant metabolites produced via the phenylpropanoid pathway. They include a broad spectrum of chemical compounds, such as phenolics, flavonoids, isoflavones, coumestans,...
BACKGROUND/OBJECTIVES: Phytoestrogens are secondary plant metabolites produced via the phenylpropanoid pathway. They include a broad spectrum of chemical compounds, such as phenolics, flavonoids, isoflavones, coumestans, lignans, and others. Their chemical structures resemble those of estradiol, and they exhibit biological effects similar to those of human estrogens, influencing many physiological processes throughout life in both men and women-including the timing and progression of puberty. METHODS: The literature search included databases such as PubMed, Scopus, Web of Science, and Google Scholar with the use of specific keywords. Studies were considered eligible if they reported original findings from observational studies (cohort, case-control, and cross-sectional) or from experimental studies. RESULTS: Phytoestrogens can modulate estrogenic activity and interact with a variety of biological pathways. These compounds may play a role in human development and pubertal processes, contribute to overall health, and potentially help alleviate menopausal symptoms and reduce the risk of certain cancers. CONCLUSIONS: Phytoestrogens have numerous positive effects on the human body across various stages of life. Their overall impact and potency, however, seem to be influenced by factors such as intake level, individual genetic variability, and the specific phytoestrogen class consumed.
Functional Role of AveC Residues Ser138 and Ala139 for Avermectin and Doramectin Biosynthesis in .
Li Z, Zhang L, Li X … +2 more , Li M, Xia H
Metabolites · 2026 Jun · PMID 42346389 · Full text
Doramectin (CHC-B1) is an excellent antiparasitic drug produced by feeding cyclohexanecarboxylic acid (CHC) to mutants. AveC, a bifunctional enzyme encoded by (), catalyzes the stereospecific spiroketalization and sele...
Doramectin (CHC-B1) is an excellent antiparasitic drug produced by feeding cyclohexanecarboxylic acid (CHC) to mutants. AveC, a bifunctional enzyme encoded by (), catalyzes the stereospecific spiroketalization and selective dehydration of dihydroxy ketone polyketide intermediates and modulates both the yield and the proportion of avermectin/doramectin in . In our previous work, we constructed a strain harboring a synthetic gene encoding ten amino acid mutations, which produced nearly pure doramectin. However, the doramectin yield achieved only approximately 60% of the total doramectin and CHC-B2 output observed in the parental strain. To investigate the roles of Ser138 and Ala139 of AveC in the biosynthesis of doramectin and avermectin, site-directed mutagenesis was performed at both sites. The production and proportion of avermectin and doramectin were determined using high-performance liquid chromatography (HPLC). AlphaFold2-based molecular docking simulations were used to interpret the results. Among the tested mutants, S138G, S138T, and A139H exhibited the highest doramectin production, achieving 143.87%, 151.22%, and 153.36% of the control level, respectively. Unfortunately, almost none of the tested mutants showed a positive effect on avermectin production. Molecular docking simulations revealed distinct affinities of these mutants for the dihydroxy ketone polyketide intermediate, both with and without a cyclohexyl group. Notably, all three mutants displayed larger substrate-binding cavity volumes compared with the wild-type enzyme, which likely facilitates doramectin synthesis by effectively accommodating the cyclohexyl moiety. Docking results further indicated that Ser138 and Ala139 are positioned within the binding cavity but probably do not directly participate in the dehydration activity. These findings suggest that optimizing cavity size through residue substitutions can enhance substrate specificity for doramectin production while preserving catalytic functionality.
Elabela in Lipid-Related Cardiometabolic Dysfunction: A Critical Narrative Review.
Chęcińska-Maciejewska Z, Pruszyńska-Oszmałek E, Kołodziejski P … +2 more , Ciborek A, Krauss H
Metabolites · 2026 Jun · PMID 42346388 · Full text
Elabela (ELA/APELA/Toddler) is an endogenous peptide ligand of the apelin receptor APLNR (also known as APJ) and, together with apelin, forms the apelinergic signalling system. Its role in embryonic development, the card...
Elabela (ELA/APELA/Toddler) is an endogenous peptide ligand of the apelin receptor APLNR (also known as APJ) and, together with apelin, forms the apelinergic signalling system. Its role in embryonic development, the cardiovascular system, the kidneys and the endothelium is becoming increasingly well characterised, whilst its function in metabolic regulation remains unresolved. Elabela activates pathways essential for metabolic homeostasis-PI3K/Akt, AMPK-related pathways, redox regulation, inflammatory control and pro-survival cascades-but no study has shown that it directly regulates adipocyte lipid metabolism. This narrative review categorises the evidence at the receptor, organ, immunometabolic and intra-adipocyte levels, and also considers the adipose tissue microenvironment as a distinct level of potential relevance. The available data support a role for Elabela as a candidate mediator of lipid-related metabolic dysfunction-via anti-inflammatory, antioxidant and tissue-protective mechanisms-with macrophage lipid metabolism representing the most informative immunometabolic interface. Human studies remain scarce, heterogeneous and limited by a lack of standardisation in assay methods and the unresolved specificity of isoforms. Elabela should therefore be regarded as a candidate indirect modulator of metabolic homeostasis and a candidate biomarker of cardiometabolic stress or adaptation-not as a confirmed direct regulator of adipocyte lipid metabolism.
Exogenous Melatonin Alleviates NaCl-Induced Salinity Stress in Forage Pea ( L.): Concentration Optimization and Genotype-Specific Responses.
Okcu M, Okcu Z, Kaya F … +1 more , Haliloglu K
Metabolites · 2026 Jun · PMID 42346387 · Full text
: Soil salinity is a major constraint on legume productivity worldwide, threatening forage pea ( L.) cultivation in semiarid regions. This study evaluated the effect of exogenous melatonin in attenuating NaCl-induced sal...
: Soil salinity is a major constraint on legume productivity worldwide, threatening forage pea ( L.) cultivation in semiarid regions. This study evaluated the effect of exogenous melatonin in attenuating NaCl-induced salinity stress across diverse forage pea genotypes. : A three-factor factorial experiment was conducted under greenhouse conditions, testing three NaCl levels (0, 100 and 200 mM) and four melatonin concentrations (0, 100, 150 and 200 µM) across 13 genotypes with three replications (468 pots). Nine vegetative traits were measured and analyzed by factorial ANOVA and Tukey's HSD test. : Increasing NaCl from 0 to 200 mM reduced plant height by ~28% and node number by ~32%. Application of 100 µM melatonin under 100 mM NaCl reduced canopy temperature from 28.1 °C to 23.7 °C and restored SPAD values from 21.7 to 26.5 under 200 mM NaCl. By contrast, 200 µM melatonin under severe salinity paradoxically suppressed SPAD to 8.9 and reduced root length. Emirbey and Kirazlí showed the greatest vegetative growth, while Özkaynak exhibited the highest chlorophyll content. : 100 µM melatonin emerged as the optimal concentration for alleviating moderate salt stress in forage pea, and genotype selection is critical when deploying melatonin as a biostimulant under saline conditions. Direct measurement of biomass, yield, and forage quality under field conditions remains an essential next step before agronomic deployment.
Comparative Analysis of Components and Biological Activities in Different Parts of Blume.
Zhang Y, Zhang H, Meng X … +3 more , Zhang Y, Wang D, Chen J
Metabolites · 2026 Jun · PMID 42346386 · Full text
Blume (GE) is a widely used plant with both medicinal and edible properties. Besides the underground tubers, its above-ground parts also have certain medicinal potential. However, most of these resources are frequently d...
Blume (GE) is a widely used plant with both medicinal and edible properties. Besides the underground tubers, its above-ground parts also have certain medicinal potential. However, most of these resources are frequently discarded during production and processing. The differences in chemical composition and bioactivity among different parts of GE remain unclear. In this research, the non-targeted metabolomics method was used to detect the metabolites in the stem (ST), capsule shell (CS), seed (SE), arrow end (AE), middle end (ME), and navel end (NE) of GE. Differential metabolites were screened by multivariate statistical analysis. The pathway enrichment analysis of differential metabolites was carried out by the Kyoto Encyclopedia of Genes and Genomes (KEGG) platform. The antioxidant and -glucosidase inhibitory activities of extracts from six different parts of GE were determined in vitro, followed by correlation analysis between biological activities and key metabolites. Metabolites in different parts of GE were significantly different, including lipids, organic acids, organoheterocyclic compounds, phenylpropanoids, benzenoids, and organic oxygen compounds. The characteristics of metabolites in the underground and above-ground parts of GE were clearly distinct. The contents of lipids, organoheterocyclic compounds, and organic acids were the highest in SE, SE and CS, ST, and AE, respectively. The KEGG pathway enrichment analysis preliminarily suggested that the differences in metabolites from different parts of GE might be related to the arginine biosynthesis pathway, which involves seven metabolites, including -glutamic acid, -arginine, -ornithine, and -aspartate. Compared with the tuber (the conventional medicinal part), ST and CS exhibited excellent antioxidant properties and inhibitory activity against -glucosidase. Correlation analysis indicated that -arginine and -aspartate were positively correlated with the biological activity of GE and may be components preliminarily associated with its difference in activity. This study provided preliminary comparative evidence for the metabolite characteristics from different parts of GE, thereby facilitating the further development and utilization of its above-ground resources.
Relationship Between Calcium and Gut Microbial Composition and Metabolic Pathways in Children with Autism.
Li J, Xu X, Wang H … +3 more , Gao R, Li B, You X
Metabolites · 2026 Jun · PMID 42346385 · Full text
Trace elements may influence autism spectrum disorder (ASD) severity through interactions with the gut microbiota and microbial metabolic functions, but calcium-related evidence remains limited. This cross-sectional stud...
Trace elements may influence autism spectrum disorder (ASD) severity through interactions with the gut microbiota and microbial metabolic functions, but calcium-related evidence remains limited. This cross-sectional study examined associations among hair calcium, gut microbial taxa, metabolic pathways, and behavioral phenotypes in children with ASD. We analyzed 183 children with ASD who had behavioral assessments, hair calcium measurements, and fecal shotgun metagenomic sequencing data. Participants in the lowest and highest calcium quartiles were first compared to characterize group-level microbiome differences. Full-sample analyses then tested associations among continuous hair calcium, microbial taxa, metabolic pathways, and behavioral measures after covariate adjustment. Benjamini-Hochberg false discovery rate correction was applied for multiple testing. Hair calcium was positively associated with CARS, ATEC-Total, ATEC-1, and ATEC-3 scores, with the strongest associations involving ATEC-1 and ATEC-3. Alpha and beta diversity did not differ significantly between calcium quartile groups, but group-based microbiome analyses identified 63 differential species and 22 differential MetaCyc pathways. Full-sample integrated analyses connected calcium-associated microbial taxa, metabolic pathways, and ASD behavioral measures. Hair calcium was associated with ASD behavioral severity, selected gut microbial species, and microbial metabolic pathways. These findings support an association framework connecting longer-term calcium-related mineral profiles, gut microbial functional potential, and behavioral phenotypes, providing a basis for future longitudinal and multi-omics studies.
Metabolomic Signatures of Commercial Ready-to-Drink Beverages by Dual-Mode Untargeted LC-MS/MS.
Blaženović I, Bresnahan K, Wang S
Metabolites · 2026 Jun · PMID 42346384 · Full text
The rapid expansion of functional ready-to-drink (RTD) beverages-formulated with prebiotic fibers, botanical extracts, and reduced sugar-has outpaced systematic characterization of their small-molecule composition. We a...
The rapid expansion of functional ready-to-drink (RTD) beverages-formulated with prebiotic fibers, botanical extracts, and reduced sugar-has outpaced systematic characterization of their small-molecule composition. We applied dual-mode untargeted high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS), integrating hydrophilic interaction (HILIC) and reversed-phase C18 separations, to profile five commercial RTD beverages spanning distinct formulation categories: Coca-Cola, Poppi Orange, OLIPOP Cream Soda, Pure Leaf Unsweetened Black Tea, and BeePop™ Peach + Orange Blossom Honey. Across all products, 478 compounds were structurally annotated at Metabolomics Standards Initiative (MSI) Levels 1 and 2, of which 42 matched compounds with reported bioactivity in a curated literature-based reference database. Seventeen compounds-including the NAD+ precursor trigonelline and multiple B vitamins-were detected across all five products. The number and diversity of compounds with reported bioactivity varied substantially by product and correlated with botanical ingredient complexity. This work presents a qualitative molecular survey of the RTD beverage category using standardized, dual-mode untargeted metabolomics, providing a reference dataset for future targeted quantitation studies.
Metabolomic Evidence for Bee-Driven Detoxification, Nutritional Remodeling, and Geographic Homogenization in Rapeseed Floral Products.
Gao WM, Xiong CM, Li JJ … +1 more , Lu L
Metabolites · 2026 Jun · PMID 42346383 · Full text
Rapeseed ( L.)-derived pollen, pollen-containing anther, bee pollen, and honey are natural health products with both nutritional and functional value. Bee processing plays a key role in the dynamic transformation process...
Rapeseed ( L.)-derived pollen, pollen-containing anther, bee pollen, and honey are natural health products with both nutritional and functional value. Bee processing plays a key role in the dynamic transformation process of bee product formation. Existing research has mostly focused on static analyses of single product types and has not systematically elucidated the hierarchical differences in metabolites from plant pollen to bee products, the remodeling mechanism during bee processing, or the impact of geographical origin and agricultural practices on product metabolic profiles. These research gaps limit the precise development and quality control of rapeseed-derived bee products. This study employed UPLC-MS/MS-based untargeted metabolomics to analyze differential metabolites among rapeseed pollen, pollen-containing anther, bee pollen, and honey and elucidated functional differences via KEGG pathway enrichment analysis. A total of 1308 metabolites were identified, primarily consisting of active components such as flavonoids and terpenoids. Origin-related differences caused by agricultural practices and companion plants were significant in raw pollen but were markedly attenuated by bee processing. Bee pollen showed increased levels of phospholipids and sugars along with reduced toxic substances, forming a safer and more balanced nutritional profile, making it suitable as a nutritional supplement. Honey was highly enriched in monosaccharides and disaccharides, combining flavor with functionality, and is suitable for the development of energy foods. Bee processing actively reshapes the pollen metabolome, attenuates geographical origin differences in raw materials, and enhances the safety and nutritional balance of bee products.
Advances in UDP-Glycosyltransferases from Medicinal Plants: Discovery, Catalytic Mechanism, Engineering and Biosynthetic Application.
Li B, Yao Q, Li C … +4 more , Li J, Xiang Q, Wang Z, Lu W
Metabolites · 2026 Jun · PMID 42346382 · Full text
Glycosylation is a critical structural modification that shapes the pharmacological properties of bioactive ingredients from Traditional Chinese Medicine (TCM), and UDP-glycosyltransferases (UGTs) are the core rate-limit...
Glycosylation is a critical structural modification that shapes the pharmacological properties of bioactive ingredients from Traditional Chinese Medicine (TCM), and UDP-glycosyltransferases (UGTs) are the core rate-limiting biocatalysts mediating this process. Traditional plant extraction methods are constrained by resource scarcity, long growth cycles, low target content and high environmental costs, which cannot meet the large-scale industrial demand for high-value medicinal glycosides. This review systematically outlines the latest global advances in medicinal plant UGT research, covering family classification and physiological functions, multi-omics and AI-assisted gene mining, molecular basis of substrate recognition and catalytic specificity, protein engineering for performance optimization, and the construction of full-spectrum biomanufacturing systems including in vitro multi-enzyme cascades, microbial cell factories and plant suspension cell cultures. We further discuss the core challenges of industrial scale-up, regulatory compliance and clinical translation, as well as the significant economic and technical advantages of synthetic biology-based UGT biomanufacturing platforms. This work provides a complete technical framework for the engineering application of medicinal plant UGTs, to support the green and scalable production of rare natural therapeutic glycosides.
Phytohormonal Regulation of Plant Responses to Major Abiotic Stresses: From Signaling Pathways to Hormonal Crosstalk.
Mehrabi SS, Sabokdast M, Dedicova B
Metabolites · 2026 Jun · PMID 42346381 · Full text
Plants are constantly exposed to diverse abiotic stresses, including drought, salinity, and extreme temperatures, which severely limit growth, development, and crop productivity. These stresses disrupt physiological, bio...
Plants are constantly exposed to diverse abiotic stresses, including drought, salinity, and extreme temperatures, which severely limit growth, development, and crop productivity. These stresses disrupt physiological, biochemical, and molecular processes, leading to reduced photosynthesis, altered water and ion homeostasis, and accumulation of reactive oxygen species (ROS). Plants have evolved sophisticated sensing and signaling mechanisms to perceive these stresses, with phytohormones playing central roles in mediating adaptive responses. Key hormones, including abscisic acid (ABA), salicylic acid (SA), jasmonates (JAs), gibberellins (GAs), auxin (IAA), ethylene (ET), melatonin, and strigolactones (SLs), regulate stress tolerance by controlling stomatal behavior, root architecture, antioxidant systems, osmolyte accumulation, and stress-responsive gene expression. Importantly, these hormones operate within an intricate network of crosstalk, integrating multiple signaling pathways to balance growth and stress adaptation. Interactions among ABA, GA, JA, SA, auxin, ET, SLs, and melatonin enable plants to coordinate transcriptional regulation, protein phosphorylation, and ROS signaling, optimizing survival under fluctuating environmental conditions. Understanding the molecular mechanisms underlying hormonal crosstalk and their roles in abiotic stress tolerance provides valuable insights for developing resilient crops in the face of climate change.
A Chrono-Metabolic Approach to Mental Health: Current Perspectives on Circadian Rhythms, Gut Microbiota, and Microbial Metabolites in Mood Disorders.
Marano G, Acanfora M, Conci L … +6 more , Traversi G, Mazza O, Capristo E, Gaetani E, Franceschini G, Mazza M
Metabolites · 2026 Jun · PMID 42346380 · Full text
Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal align...
Growing evidence indicates that the gut microbiota is not a static ecosystem but a rhythmic metabolic organ whose oscillatory activity is tightly coordinated with host circadian biology. Disruption of this temporal alignment, through irregular diet, sleep disturbance, shift work, or social jet lag, may profoundly alter microbial composition and the production of neuroactive metabolites. These alterations have emerged as potential contributors to the pathophysiology of mood disorders. This review introduces the concept of chrono-metabolic psychiatry, a framework integrating circadian rhythms, gut microbiota dynamics, and host metabolic signaling in the development and course of depressive and bipolar disorders. In this framework, the term "chrono-metabolic" refers to the integration of biological timing, host metabolic regulation, and microbiota-derived metabolic signaling. Chrono-metabolic psychiatry therefore shifts the focus from static dysbiosis or neurotransmitter imbalance alone to the time-dependent interactions among circadian misalignment, microbial rhythmicity, immune regulation, metabolite production, and affective instability. Diurnal fluctuations in short-chain fatty acids, tryptophan-kynurenine metabolites, bile acids, and microbial-derived neurotransmitters interact with clock gene regulation, hypothalamic-pituitary-adrenal axis activity, neuroinflammation, and synaptic plasticity. Chrono-disruption may represent a transdiagnostic vulnerability factor and may confirm the bidirectional relationship between mood instability and microbiota rhythmicity. Emerging therapeutic implications, including chrono-nutrition, time-restricted feeding, targeted probiotic administration ("chronobiotics"), and the microbiota-modulating effects of psychotropic medications are discussed. By shifting from a compositional to a temporal-metabolic perspective, this model highlights the importance of microbial oscillations rather than static dysbiosis alone. Integrating circadian biology into microbiota research may enable metabolomic stratification and pave the way for precision psychiatry approaches grounded in host-microbe metabolic crosstalk. Future longitudinal and time-resolved multi-omics studies are needed to validate this framework and to translate it into clinically actionable interventions.
Nervonic Acid Prevents HFD-Induced Metabolic Dysfunction and Is Associated with Gut Microbiota Remodeling.
Jiang CY, Huang ZL, Liu JL … +5 more , Cen SR, Lu RM, Wei CB, Meng HY, Xu QJ
Metabolites · 2026 Jun · PMID 42346379 · Full text
BACKGROUND: Obesity is closely associated with gut microbiota dysbiosis. Nervonic acid (NA; (15Z)-15-tetracosenoic acid) is a bioactive fatty acid with reported metabolic effects. This study aimed to investigate the asso...
BACKGROUND: Obesity is closely associated with gut microbiota dysbiosis. Nervonic acid (NA; (15Z)-15-tetracosenoic acid) is a bioactive fatty acid with reported metabolic effects. This study aimed to investigate the associations between NA administration, gut microbiota composition changes, and host metabolic phenotypes in high-fat diet (HFD)-fed mice. METHODS: C57BL/6J mice were fed an HFD for 12 weeks and concurrently administered NA at doses of 20, 40, and 60 mg/(kg·d) by gavage. Metabolic parameters, histopathological changes, and fecal microbiota composition (via 16S rRNA gene sequencing) were evaluated. RESULTS: NA administration was associated with significantly attenuated HFD-induced increases in body weight and adipose tissue mass, as well as marked reductions in serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol (all < 0.05). Hepatic steatosis and adipose tissue inflammation were also attenuated. 16S rRNA gene sequencing revealed that NA was associated with the counteraction of HFD-induced gut microbiota dysbiosis, including alterations in α-diversity and community structure. NA was associated with higher relative abundances of taxa such as , , , , , and and lower relative abundances of , , and . Within-group correlation analyses showed that genera with higher relative abundances were inversely associated with lipid parameters and adiposity, whereas genera with lower relative abundances correlated positively with these metabolic indicators. CONCLUSIONS: NA administration was associated with bidirectional changes in gut microbiota composition-the enrichment of certain taxa and the suppression of others-concomitant with the amelioration of HFD-induced metabolic dysfunction. These findings indicate correlations between NA, gut microbiota alterations, and improved metabolic phenotypes; however, causality remains to be established.
Systems-Level Proteomic and Biochemical Profiling of Plasma from Captive Indian Star Tortoise with Reactome Pathway Enrichment Analysis.
Đuričić D, Miljković J, Severin K … +2 more , Prišćan D, Šmit I
Metabolites · 2026 Jun · PMID 42346378 · Full text
The Indian star tortoise () is a protected species for which physiological and molecular health indicators remain poorly characterized. This study aimed to monitor and analyze plasma proteome profiles and biochemical par...
The Indian star tortoise () is a protected species for which physiological and molecular health indicators remain poorly characterized. This study aimed to monitor and analyze plasma proteome profiles and biochemical parameters in captive adult Indian star tortoises and to identify potential diagnostic biomarkers. Plasma samples from nine clinically healthy adult Indian star tortoises (four males and five females) maintained in captivity were subjected to biochemical profiling and proteomic analysis. Sex-related differences in biochemical parameters were evaluated, and differentially expressed proteins were mapped to Reactome pathways to identify significantly enriched biological processes. Plasma biochemical profiling established baseline reference values, indicating stable hepatic and metabolic function in captive tortoises. Creatinine and urea concentrations were significantly higher in females than in males ( < 0.05), suggesting sex-related differences in protein metabolism or renal function. No significant sex-related differences were observed in hepatic enzymes (ALP, ALT, AST, and GGT), muscle-associated enzymes (CK and LDH), glucose, cholesterol, triglycerides, total proteins, albumin, or electrolyte concentrations (Na, K, Ca, Mg, Cl, P, and Fe). Proteomic analysis identified 12 differentially expressed proteins, including nine upregulated and three downregulated proteins. Functional pathway analysis revealed 90 significantly enriched Reactome pathways (FDR < 0.05). Upregulated proteins were primarily associated with cytoskeletal organization (KRT75, KRT5, and KRT17), lipid transport and remodeling (APOB), coagulation (F10), extracellular transport (TTR), immune response (WFDC3), transmembrane signaling (KCP), and gamete interaction (ZAN). Downregulated proteins (C7, SERPING1, and PZP) were linked to complement activation and acute-phase response pathways. Captive Indian star tortoises exhibited increased cytoskeletal remodeling and coagulation activity together with reduced complement activation. These findings provide novel insights into the plasma proteome of this species and identify candidate biomarkers that may support future health assessment, physiological monitoring, and diagnostic applications in Indian star tortoises.
Plasma Metabolite Profiles of Exercising American Foxhound Dogs Fed Different Diets.
Martini SE, de Godoy MRC, Beloshapka AN … +2 more , Buff PR, Swanson KS
Metabolites · 2026 Jun · PMID 42346377 · Full text
Canine athletes have a higher energy requirement and are more susceptible to nutrient depletion, electrolyte imbalance, and metabolic stress than sedentary pets. The objective of this study was to characterize the plasma...
Canine athletes have a higher energy requirement and are more susceptible to nutrient depletion, electrolyte imbalance, and metabolic stress than sedentary pets. The objective of this study was to characterize the plasma metabolome of American Foxhound dogs following a bout of unstructured exercise. Thirty-nine adult American Foxhound dogs (32 intact males, 7 spayed females; age: 6.2 ± 3.1 yr; BW: 36.3 ± 5.3 kg) were allotted to a standard performance diet (CTRL) or NUTRO Natural Choice Adult High Endurance Formula (TEST). After 80 d in the study, blood samples were collected prior to (0 h), and 3 h and 25 h post-exercise (average: 17.7 km run over 2-3 h). Plasma samples of the 10 top performers of each treatment group were analyzed for untargeted metabolite profiling. Of the 566 named metabolites identified, >200 and >185 metabolites were impacted ( < 0.05) by exercise and diet, respectively. Principal component analysis indicated distinct clustering by diet. Random forest analysis highlighted several metabolites having a high degree of predictive accuracy based on diet and exercise, with most related to amino acid, lipid, xenobiotic, and cofactor and vitamin metabolism. Relating to exercise, glycolytic end-products and citric acid cycle intermediates were increased at 3 h post-exercise. Similarly, tocopherols and omega-3 polyunsaturated fatty acids were higher in dogs fed TEST than those fed CTRL during recovery, indicating a lower oxidative stress and anti-inflammatory response. Overall, the data suggest a protective effect (lower susceptibility to oxidative stress and muscle fatigue) of feeding a nutrient-fortified diet for dogs undergoing unstructured exercise.
Editorial: Advances in Food Metabolomics for Functional Food Development and Analysis.
Martinez-Martin MJP, Lloyd AJ
Metabolites · 2026 Jun · PMID 42346376 · Full text
The increasing global demand for healthier diets and functional foods has positioned food metabolomics at the forefront of nutritional science and food innovation [...].
The increasing global demand for healthier diets and functional foods has positioned food metabolomics at the forefront of nutritional science and food innovation [...].
Dual Actions of Butyrate on Immunoepithelial Remodeling in Ex Vivo Intestinal Biopsies from Patients with Inflammatory Bowel Disease.
Troisi S, Pane C, Masi L … +12 more , Biamonte F, Scannone D, Cappa Spina A, Di Mattia M, Emoli V, Capobianco I, Distante S, Rondinone B, Petito V, Gasbarrini A, Lopetuso LR, Scaldaferri F
Metabolites · 2026 Jun · PMID 42346375 · Full text
Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the d...
Butyrate, a microbiota-derived short-chain fatty acid, plays a central role in intestinal homeostasis, yet its concentration-dependent effects on human inflamed mucosa remain poorly defined. This study investigates the dose-dependent impact of butyrate on inflammatory signaling and epithelial architecture in ex vivo intestinal biopsies from patients with inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Intestinal biopsies from six IBD patients (four UC, two CD) were cultured ex vivo for 24 h with calcium butyrate (5, 10, 100 mM). Cytokine secretion was analyzed by multiplex immunoassay, total protein release was quantified, and glandular morphology was assessed by stereological analysis. Butyrate was associated with a dose-dependent reduction in pro-inflammatory cytokines-including TNF-α, IFN-γ, IL-6, and IL-17-in both inflamed and non-inflamed tissue. Non-linear responses were observed for specific mediators, such as IP-10, which displayed a biphasic pattern in inflamed UC biopsies. Notably, UC and CD biopsies exhibited distinct response profiles: UC samples showed marked cytokine modulation, including reduction in IL-15, whereas CD samples, evaluated at 5 and 10 mM, showed limited modulation across conditions. A trend toward reduced total protein secretion was observed in diseased UC biopsies following butyrate exposure. Stereological analysis revealed preservation of glandular area at 5 mM, reduction at 10 mM, and extensive tissue disruption at 100 mM precluding structural evaluation. In this pilot study, butyrate exerts dose-dependent and disease-specific effects in human IBD mucosa within a narrow therapeutic window. These exploratory findings suggest that dose-optimized strategies for butyrate-based interventions may be particularly relevant in UC, although larger confirmatory studies are needed.
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