PubMed

Environ Pollut. 2025 Mar 14:126057. doi: 10.1016/j.envpol.2025.126057. Online ahead of print.ABSTRACTThis letter acknowledges the valuable contribution of the authors' study, which investigates the associations between long-term air pollution exposure and plasma metabolites in two sub-cohorts of the Rotterdam Study. The use of advanced metabolomics techniques and land use regression models for exposure assessment is praised for strengthening the study's methodology. The identification of enriched metabolic pathways, such as steroid hormone biosynthesis and pyrimidine metabolism, provides key insights into how air pollution affects biological systems. However, the letter highlights the limitation of the study's cross-sectional design, which hinders causal inference, and suggests that longitudinal studies would offer more definitive conclusions. The mention of "unannotated metabolites" is noted as an intriguing yet underexplored aspect, and further discussion of confounding factors such as diet and socioeconomic status is encouraged. Overall, the letter offers constructive feedback while recognizing the study's important contribution to the field.PMID:40090451 | DOI:10.1016/j.envpol.2025.126057

Mol Cell Neurosci. 2025 Mar 14:104003. doi: 10.1016/j.mcn.2025.104003. Online ahead of print.ABSTRACTTraumatic brain injury (TBI) induces complex cellular and molecular changes, challenging recovery and therapeutic development. Although molecular pathways have been implicated in TBI pathology, the cellular specificity of these mechanisms remains underexplored. Here, we investigate the role of endothelial cell (EC) EphA4, a receptor tyrosine kinase receptor involved in axonal guidance, in modulating cell-specific transcriptomic changes within the damaged cerebral cortex. Utilizing single-cell RNA sequencing (scRNA-seq) in an experimental TBI model, we mapped transcriptional changes across various cell types, with a focus on astrocytes and ECs. Our analysis reveals that EC-specific knockout (KO) of EphA4 triggers significant alterations in astrocyte gene expression and shifts predominate subclusters. We identified six distinct astrocyte clusters (C0-C5) in the damaged cortex including as C0-Mobp/Plp1+; C1-Slc1a3/Clu+; C2-Hbb-bs/Hba-a1/Ndrg2+; C3-GFAP/Lcn2+; C4-Gli3/Mertk+, and C5-Cox8a+. We validate a new Sox9+ cluster expressing Mertk and Gas, which mediates efferocytosis to facilitate apoptotic cell clearance and anti-inflammatory responses. Transcriptomic and CellChat analyses of EC-KO cells highlights upregulation of neuroprotective pathways, including increased amyloid precursor protein (APP) and Gas6. Key pathways predicted to be modulated in astrocytes from EC-KO mice include oxidative phosphorylation and FOXO signaling, mitochondrial dysfunction and ephrin B signaling. Concurrently, metabolic and signaling pathways in endothelial cells-such as ceramide and sphingosine phosphate metabolism and NGF-stimulated transcription-indicate an adaptive response to a metabolically demanding post-injury hypoxic environment. These findings elucidate potential interplay between astrocytic and endothelial responses as well as transcriptional networks underlying cortical tissue damage.PMID:40090391 | DOI:10.1016/j.mcn.2025.104003

Environ Pollut. 2025 Mar 14;372:126069. doi: 10.1016/j.envpol.2025.126069. Online ahead of print.ABSTRACTPentachlorophenol (PCP) is a pervasive endocrine-disrupting compound present in the environment. Limited research has explored the effects of PCP exposure on gestational diabetes mellitus (GDM), particularly the metabolites-related mechanism. Our study seeks to characterize the interrelationships between PCP exposure, plasma metabolomic markers, and GDM, aiming to elucidate the metabolomic profile mediating PCP-GDM relationship. From a prospective cohort in Changzhou, China, a nested case-control study was conducted, involving 154 GDM cases and 308 controls. We collected fasting blood samples before 16 weeks of gestation and determined PCP levels by UPLC-MS/MS. Plasma metabolomic markers were identified using untargeted metabolomics. Multivariate logistic regression and mediation analysis were used to examine the relationships among PCP exposure, metabolomic markers, and GDM. Using the Mann-Whitney U test, we found that serum PCP levels were significantly higher in GDM cases (median: 0.43 ng/mL, IQR: 0.28-0.77) compared to controls (median: 0.38 ng/mL, IQR: 0.24-0.64; P = 0.041). In the fully adjusted model, which additionally accounted for dietary patterns, the OR (95 %CI) values for GDM across tertiles of serum PCP were 1 (reference), 1.24 (0.73, 2.11), and 2.17 (1.28, 3.68), respectively, indicating a potential dose-response relationship (P trend = 0.004). Furthermore, 152 differential metabolites were identified between groups (FDR <0.05), implicating 4 metabolic pathways: "Nitrogen metabolism", "Alanine, aspartate and glutamate metabolism", "Glycerophospholipid metabolism", and "Pyrimidine metabolism" (FDR <0.1). Mediation analysis revealed that 5 metabolomic markers (such as N-Acetylalanine and 4-Acetamidobutyric acid) significantly mediated the association between PCP and GDM (FDR <0.05), with mediated proportions ranging from 0.15 to 0.31. Together, pregnant women in Eastern China exhibit widespread PCP exposure, with serum PCP levels positively associated with GDM risk. PCP exposure-related metabolomic changes may partially mediate the link between PCP and GDM.PMID:40090288 | DOI:10.1016/j.envpol.2025.126069

Int J Biol Macromol. 2025 Mar 15;307(Pt 2):142127. doi: 10.1016/j.ijbiomac.2025.142127. Online ahead of print.ABSTRACTPhytophthora nicotianae is a highly destructive soil-borne plant pathogen that leads to significant economic losses in agriculture. Chitooligosaccharides (COS) are popular biostimulant which can promote plant growth and responses to biotic and abiotic stresses. However, the role of COS in resisting the black-shank disease (BSD, caused by P. nicotianae) through regulating plant root exudates and rhizosphere microecology remains unclear. An integrative analysis, based on the transcriptome analysis, root exudate metabolome, and biochemical tests, revealed the secretion of more sugar-related differential metabolites and differential gene expressions expressed under COS treatment during the disease resistance response. Furthermore, increased accumulation of trehalose and trehalose 6-phosphate as well as increased activity of trehalose 6-phosphate synthase was observed under COS treatment after inoculation with P. nicotianae. Additionally, sucrose and glucose, which positively regulate resistance to plant diseases, also exhibited elevated levels. Beneficial microorganisms, such as Bacillus were enriched in the rhizosphere soil during COS treatment. The isolated Bacillus velezensis T-2 strain exerted inhibitory activity on P. nicotianae, which was enhanced by the presence of trehalose. This multi-omics study of transcriptome, metabolome, and microbiomics revealed that COS enhances resistance to tobacco BSD by regulating sugar homeostasis and recruiting beneficial microorganisms.PMID:40090279 | DOI:10.1016/j.ijbiomac.2025.142127

Theriogenology. 2025 Mar 12;239:117389. doi: 10.1016/j.theriogenology.2025.117389. Online ahead of print.ABSTRACT5-Aminolevulinic acid (5-ALA) is a crucial metabolic intermediate that affect mitochondrial function in somatic cells. However, the mechanisms by which 5-ALA regulates boar reproductive performance remain unclear. The effect of dietary supplementation of 5-ALA on boar semen quality and reproductive performance were investigated in this study. Forty-five boars were randomly assigned to a control group and four 5-ALA-treatment groups (125, 250, 500, and 1000 mg/kg/d). After nine weeks of treatment, serum and semen samples were collected from the boars for analysis. Results showed that the supplementation of 5-ALA to boar diet significantly (p < 0.05) increased semen volume, total sperm count, and sperm motility while reducing the proportion of abnormality (p < 0.05). Specifically, 250 mg/kg/d 5-ALA treatment significantly (p < 0.05) reduced sperm DNA oxidative damage and elevated serum testosterone levels. Metabolomic analysis revealed that 250 mg/kg/d 5-ALA supplementation significantly increased (p < 0.05) the levels of tricarboxylic acid (TCA) cycle intermediates such as malate and isocitrate, while significantly (p < 0.05) reducing harmful metabolites such as N-acetyl phenylalanine that negatively impact sperm quality and fertility. Notably, 250 mg/kg/d 5-ALA supplementation upregulated the protein levels of mitochondrial oxidative phosphorylation (OXPHOS) complex subunits (NDUFB8, SDHB, UQCRC2, MTCO2, and ATP5A1) and improved sperm mitochondrial membrane potential, adenosine triphosphate (ATP) levels, and complex IV activity (p < 0.05). Regarding reproductive performance, compared to the control, the percentage of piglets born alive increased by 2.97 %, the farrowing rate improved by 10.59 %, and the occurrence of mummified fetuses decreased by 1.07 % in the 5-ALA-treated groups (p < 0.05). Additionally, 250 mg/kg/d 5-ALA had a long-term beneficial advantage on boar semen quality parameters. Accordingly, dietary supplementation of 5-ALA, specifically, 250 mg/kg/d 5-ALA improved boar semen quality by enhancing seminal plasma metabolome, sperm mitochondrial function and overall reproductive performance.PMID:40090234 | DOI:10.1016/j.theriogenology.2025.117389

Chemosphere. 2025 Mar 15;377:144302. doi: 10.1016/j.chemosphere.2025.144302. Online ahead of print.ABSTRACTPrymnesium parvum is one of the main contributors to harmful algal blooms, mainly because of its ability to produce prymnesin, a toxin involved in marine specie deaths occurring in these events. At the same time, scientific works are reporting the existence of microalgae-derived extracellular vesicles in different microalgal strains, which as in other species participate in different cellular processes and intra- and intercellular communication. Now, knowing that each of the toxic Prymnesium parvum strains produce one of the three known types of prymnesin, strains PPSR01, SAG 18.97 and UTEX-2797 (that produce the C-type, B-type and A-type prymnesins, respectively) were selected to investigate the proteome of their extracellular vesicles and to elucidate their cellular functions under normal, nitrogen deficient and phosphorus deficient growth conditions. It was observed that although extracellular vesicle size and morphology did not vary significantly between strains, their proteins showed more differences among strains than among treatments. Nonetheless, it was determined that the extracellular vesicles were involved in metabolic processes, compound synthesis, gene expression and cell growth mechanisms. Additionally, significant changes among strains were found in the vesicular proteomes when these were grown in nitrogen-deficient media, whereas phosphorus deficiency only caused changes in the UTEX-2797 strain. Through metabolomic analysis, the extracellular vesicles derived from this last strain were found to transport prymnesin. Together, these findings highlight the role of microalgae-derived extracellular vesicles in the environmental stress response in P. parvum and their impact in algal blooms.PMID:40090203 | DOI:10.1016/j.chemosphere.2025.144302

Ecotoxicol Environ Saf. 2025 Mar 15;293:118034. doi: 10.1016/j.ecoenv.2025.118034. Online ahead of print.ABSTRACTIn saline alkaline soils, microplastics inevitably form a combined stress with NaCl to limit crop growth, but the molecular mechanisms of their toxic effects remain vague and inadequate. We analyzed the molecular mechanisms underlying the response of maize seedlings to single or combined stresses of MPs and NaCl by means of combined metabolomic and transcriptomic analyses. MPs and NaCl single or combined stresses reduced plant fresh weight by 36.78 %, 50.65 % and 73.97 %, respectively. Analyses showed 2476 differentially expressed genes (DEGs) and 809 differential metabolites (DMs) for MPs, 2306 DEGs and 901 DMs for NaCl, and 2706 DEGs and 938 DMs for the combined stresses, compared to CK. Single or combined stresses mainly altered amino acid synthesis and phenylpropane biosynthetic metabolic pathways. Stress up-regulated glutamine synthetase (glnA), alanine transaminase (ALT), aspartate aminotransferase (ASP), ornithine carbamoyl transferase (argF), and glycine hydroxymethyl transferase (SHM) genes expression and promotes glutamine, 2-oxoglutarate, glutamate, fumarate, arginine, aspartate, L-isoleucine, L-valine, and serine synthesis. NaCl stimulated phenylpropanoid biosynthesis (tyrosine, 4-coumarate, and ferulate), whereas MPs decreased it. In addition, both individual or combined NaCl and MPs stress increased the expression of cinnamyl-alcohol dehydrogenase (CAD) and cinnamoyl-CoA reductase (CCR) to promote sinapaldehyde synthesis. Our study provides a molecular perspective on the response of crops, such as maize, to individual or combined NaCl and MPs stress.PMID:40090167 | DOI:10.1016/j.ecoenv.2025.118034

Ecotoxicol Environ Saf. 2025 Mar 15;293:118038. doi: 10.1016/j.ecoenv.2025.118038. Online ahead of print.ABSTRACTArsenic (As) is an environmental toxicant and human carcinogen, long-term exposure to As can lead to varying degrees of liver injury. In this study, the liver injury model of As poisoned Sprague-Dawley (SD) rats was established, and the potential mechanism was investigated by metabonomics and ionomics. A total of 164 differential expressed metabolites (DEMs) were identified between the As poisoned group and the control group, which mainly involved in nicotinate and nicotinamide metabolism, steroid hormone biosynthesis, taurine and hypotaurine metabolism, and porphyrin metabolism. The levels of 10 ions were significantly increased in As poisoned group, including As, bismuth (Bi), cadmium (Cd), mercury (Hg), manganese (Mn), rubidium (Rb), antimony (Sb), strontium (Sr), uranium(U), and zinc (Zn), in contrast, the levels of lead (Pb) and thallium (TI) were significantly decreased. Spearman correlation analysis showed that As, Cd, Hg and Pb were negatively correlated with androstenedione, protoporphyrinogen IX and estriol, whereas As and Mn was positively correlated with progesterone (PROG), Cd was positively correlated with NAD+ and 3-Sulfino-L-alanine. There are sex differences in changes in metabolites and ions levels. Male and female rats shared 60 DEMs and 2 pathways (steroid hormone biosynthesis and porphyrin metabolism pathway). The levels of As, Cd, Hg, and Sr were significantly changed in both male and female rats. In both female and male rats, As was positively correlated with PROG, and Cd was positively correlated with coproporphyrin III. The results of this study provide new insights to elucidate the mechanism of As-induced liver injury in rats.PMID:40090166 | DOI:10.1016/j.ecoenv.2025.118038

Int Immunopharmacol. 2025 Mar 15;152:114418. doi: 10.1016/j.intimp.2025.114418. Online ahead of print.ABSTRACTIn this study, we employed a reductionist (yet not simplistic) approach utilizing the established invertebrate model system of the pond snail, Lymnaea stagnalis, to investigate the behavioral and molecular effects of systemic administration of lipopolysaccharide (LPS)-a bacterial endotoxin-on the snails' central ring ganglia. Snails received injections of either a low dose (2.5 μg) or a high dose (25 μg) of LPS, and their behavioral and molecular responses were assessed at 2, 6, and 24 h post-injection. With the high dose, snails exhibited a significant increase in homeostatic aerial respiration lasting for at least 24 h, consistent with a sickness-like state induced by the immune challenge. Additionally, we found that when administered 2, 6, or 24 h before operant conditioning training, the high dose of LPS, impaired memory formation. To further explore the underlying molecular mechanisms, we examined the transcriptional effects of the two doses of LPS in the snails' central ring ganglia. Our analysis showed a dose- and time-dependent upregulation of immune and stress-related genes, including key enzymes involved in the kynurenine pathway (KP), toll-like receptor 4 (TLR4), and heat shock protein 70 (HSP70). Metabolomic analysis suggested that the high LPS dose shifted KP metabolism toward the production of neurotoxic metabolites within the ganglia, indicating a LPS-induced neuroinflammatory state. Together, our findings provide valuable insight into the conserved mechanisms of neuroinflammation in this invertebrate model, offering a simplified yet effective tool to further explore the molecular interactions between the immune and central nervous systems.PMID:40090086 | DOI:10.1016/j.intimp.2025.114418

Plant Physiol Biochem. 2025 Mar 7;222:109765. doi: 10.1016/j.plaphy.2025.109765. Online ahead of print.ABSTRACTA complex interplay of environmental factors profoundly influences plant cellular metabolism, with gaseous exchange serving as a fundamental physiological process critical to growth and survival. While well-characterized in natural environments, the role of gaseous exchange in plant in-vitro culture remains underexplored. Plant in-vitro culture offers a versatile platform for studying metabolism, where metabolic networks are highly flexible and sensitive to environmental factors. Despite advancements in understanding these dynamics, there has been relatively little investigation into how gaseous exchange within tissue culture systems affects cellular metabolism. In the present study, we investigated the effects of gaseous exchange on plant growth and metabolism by comparing traditional Parafilm- and micropore-tape-based cultures designed to facilitate different levels of gaseous exchange. A comprehensive metabolomics approach using liquid chromatography-high-resolution mass spectrometry and gas chromatography-mass spectrometry was employed to delineate the metabolic changes in Arabidopsis under Parafilm- and micropore-tape-sealed culture conditions at two and three weeks of growth. Metabolic profiling identified increased levels of oxidized glutathione, arginine, ornithine, and aspartic acid, and decreased levels of TCA cycle intermediates and phenylpropanoid metabolites, indicating that restricted gas exchange alters the redox status and reprograms primary and secondary metabolism. This reprogramming affected amino acid metabolism, arginine metabolism, energy metabolism, as well as phenylpropanoid and flavonoid biosynthetic pathways. Restricted gaseous exchange in Parafilm-wrapped cultures also led to altered accumulation of several essential macro- and microelements in Arabidopsis seedlings. The present study demonstrated that restricted gaseous exchange inhibits plant growth and disrupts metabolism.PMID:40090077 | DOI:10.1016/j.plaphy.2025.109765

Plant Physiol Biochem. 2025 Mar 10;222:109740. doi: 10.1016/j.plaphy.2025.109740. Online ahead of print.ABSTRACTLow temperature (LT) acclimation in winter wheat (Triticum aestivum L.) was related to developmental regulation of transcriptome and metabolome for balancing growth and responses. In this study, six wheat lines from the F8 generation, derived from crosses between spring wheat (Pishtaz) and winter wheat (Claire) with distinct growth habits (based on the Vrn-1 loci) were planted under field conditions. The final leaf number (FLN) and double ridge (DR) formation showed that genotypes without vernalization requirement, including Pishtaz parent, and lines 8041 and 8044 transitioned rapidly into the reproductive stage. They also had lower LT tolerance, antioxidants activity and abscisic acid (ABA) content among genotypes. In these genotypes, cytokinin (CK) and gibberellin (GA3) contents and expression levels of gibberellin 20 oxidase (GA20ox) and gibberellin 3 oxidase (GA3ox) genes, were more active than other genotypes. Facultative lines 8020 and 8025 had higher antioxidants activity and lower hydrogen peroxide (H2O2) and malondialdehyde (MDA) contents compared to spring types. Winter genotypes, including Claire parent, lines 8011 and 8015 had a strong vernalization requirement resulted in prolonged vegetative phase, accompanied by increased LT tolerance, antioxidants activity and expression of ABA biosynthetic genes, confirming that the duration of the vegetative phase plays a key role in determining wheat's winter survival capacity. Higher LT tolerance was effectively related to retarded reproductive phase, minimized redox damages through co-regulating phytohormone-metabolites under developmental periods in winter wheat.PMID:40090075 | DOI:10.1016/j.plaphy.2025.109740

Plant Physiol Biochem. 2025 Mar 12;222:109784. doi: 10.1016/j.plaphy.2025.109784. Online ahead of print.ABSTRACTAs an eco-friendly vineyard floor management, mulching can effectively control weeds, preserve soil moisture, reduce irrigation requirements, and modify the grapevine microclimate. However, its impact on the grapevine microclimate, as well as the variation in grape and wine flavonoids across different growth stages under mulching conditions remains insufficiently studied. Therefore, in the vineyard of a semi-arid region, the whole-field mulching (M) of black geotextile mulch was applied to Vitis vinifera Marselan grapevines from anthesis and removed at three phenological stages. The grape and wine flavonoids during the growing season were evaluated through HPLC-MS, and the transcriptomic data was analyzed in three vintages (2015-2017). Results showed that mulching weakened over 30°% of reflected light, and especially light with longer wavelengths. Mulching helped to reduce water evaporation and lead to higher soil water content. As for berry composition, M slightly decreased the berry weight and accelerated sugar accumulation when mulch removal. Controlled grapes presented higher flavonols at harvest while mulch removal around veraison enhanced the accumulation of anthocyanins. The reflected photosynthetic active radiation, cluster temperature, and soil moisture played important roles in flavonoid regulation. Key genes including VviFLS1, VviLAR1, and VviANR, as well as MYB transcription factors MYBF1, MYBA1, and MYB3 are responsible for flavonoid regulation. M slightly affected the wine flavor profile but improved the wine's appearance. In conclusion, M effectively suppresses weed growth and modifies grapevine microclimate in semi-arid climates, mulch removal around veraison favored the accumulation of grape flavonoids.PMID:40090072 | DOI:10.1016/j.plaphy.2025.109784

Plant Physiol Biochem. 2025 Mar 11;222:109777. doi: 10.1016/j.plaphy.2025.109777. Online ahead of print.ABSTRACTNanotechnology has shown great potential to improve agricultural production and increase crop tolerance to abiotic stresses, including saline-alkaline environments. This study focuses on the biological mechanism of biocompatible iron-doped carbon dots (Fe-C-dots) nanozyme biosynthesized from artemisinin extract to alleviate saline-alkaline stress in wheat (Triticum aestivum L.). Particularly, Fe-C-dots with two types of natural enzyme mimicking properties, target reactive oxygen species (ROS) to assuage oxidative damage and to enhance the antioxidant capacity of enzyme-activated systems. Exogenous application of Fe-C-dots (50 mg/L) significantly promoted wheat growth and increased photosynthetic pigment content and photosynthetic efficiency. At the molecular level, Fe-C-dots treatment activated the nitrogen metabolism pathway of roots, up-regulated the expression of related genes OsNRT2.1, OsGS1, and NADH-GOGAT, and promoted the accumulation of nitrogen in wheat. Transcriptomics and metabolomics analyses reveal that Fe-C-dots triggered metabolic and transcriptional reprogramming in wheat seedlings. Besides, Fe-C-dots activated stress signaling and defense-related pathways, such as plant hormone signal transduction, MAPK, and photosynthesis signaling pathways, the cutin, suberin, wax, flavonoids, and phenolic acids biosynthesis. Importantly, compared to the control group, the application of Fe-C-dots under saline-alkaline stress increased the net photosynthetic rate (Pn) and transpiration rate (Tr) in wheat shoots by 77.5 %, and 78.6 %, respectively. These findings suggested that Fe-C-dots can improve root nitrogen metabolism and stem photosynthesis of wheat, as well as the synthesis of related stress-resistant compounds to cope with the damage of saline-alkaline stress on wheat growth. However, further studies are needed to explore the effectiveness of Fe-C-dots in wheat yield and quality evaluation.PMID:40090071 | DOI:10.1016/j.plaphy.2025.109777

Phytomedicine. 2025 Mar 7;140:156609. doi: 10.1016/j.phymed.2025.156609. Online ahead of print.ABSTRACTBACKGROUND: Burns are a common and serious health issue, with severe burn-induced acute kidney injury (AKI) being a major factor contributing to poor recovery and increased mortality in patients. Theabrownins (TBs), bioactive compounds formed during tea leaf fermentation, have shown promising effects on reducing inflammation, combating oxidative stress, and enhancing metabolic function. However, the roles and mechanisms of TBs in burn-induced kidney injury are still not fully understood.METHODS: The dorsal skin of 3-month-old mice was exposed to hot water for 10 s to induce burn-related renal injury. The mice were then orally administered TBs (40 mg/kg and 400 mg/kg). After 24 h of treatment, the mice were sacrificed for tissue collection. Transcriptomic and metabolomic analyses were performed to identify the pathways modulated by TBs. Metabolomics revealed TB-associated renal metabolites, such as guanidinoacetic acid (GAA) and fumaric acid (FA). Renal tubular epithelial (HK2) cells pretreated with GAA and FA were exposed to hydrogen peroxide (H2O2), cisplatin (CDDP) and erastin to establish a cell injury model. Changes in the levels of relevant molecules were assessed using quantitative RT-PCR, Western blotting, and fluorescence staining.RESULTS: TB treatment significantly increased the survival rate and reduced kidney injury in mice with burn injury. Multiomics analyses and molecular experimental validation revealed that TB treatment downregulated the inflammation, apoptosis, and ferroptosis pathways in the kidneys of mice with burn injury and increased the levels of the renal metabolites GAA and FA. Cellular experiments confirmed that GAA and FA alleviated H2O2-, CDDP- and erastin-induced renal tubular epithelial cell injury by inhibiting apoptosis and ferroptosis.CONCLUSIONS: Burns induce inflammation and kidney damage by upregulating the apoptosis and ferroptosis pathways in renal tissue. TBs alleviate burn-induced renal apoptosis and ferroptosis by increasing the levels of GAA and FA in the kidneys, thereby ameliorating kidney damage. This study innovatively and systematically evaluated the ability of TBs to ameliorate burn-induced kidney injury and, for the first time, identified the potential mechanism by which TBs ameliorate burn-induced kidney damage by increasing the levels of the metabolites GAA and FA in the kidneys.PMID:40090045 | DOI:10.1016/j.phymed.2025.156609

Tree Physiol. 2025 Mar 16:tpaf032. doi: 10.1093/treephys/tpaf032. Online ahead of print.ABSTRACTEfforts to protect germplasm resources of Fraxinus hupehensis (Oleaceae), an endangered species endemic to Dahong Mountain, Hubei Province, China, are facing difficulties due to the deep dormancy of its seeds. To elucidate the molecular regulatory networks underlying dormancy release, an integrated investigation combining physiological profiling with transcriptomic and metabolomic analyses was performed on seeds of F. hupehensis during six critical germination stages. A decrease was observed in the contents of soluble sugar, soluble starch, and crude fat as the germination process progressed, with glycolysis, the tricarboxylic acid cycle, and the pentose phosphate pathways providing energy. Plant hormones such as abscisic acid and gibberellin 4 exerted coordinated regulatory effects throughout this process. Differentially expressed genes and metabolites were detected in metabolic pathways including sugar metabolism, respiratory metabolism, protein synthesis and degradation along with lipid metabolism. Notably, structural hub genes and metabolites in metabolic pathways of starch and sucrose, respiratory, phenylalanine, and linoleic acid played crucial regulatory roles in seed germination. Furthermore, hub transcription factors within the AP2/ERF, bHLH, and MYB families were identified by Weighted Gene Correlation Network Analysis. This study unveiled the regulatory mechanisms of primary metabolic hub pathways during seed germination, providing a theoretical foundation for the breeding and conservation of F. hupehensis and other endangered plant species.PMID:40089902 | DOI:10.1093/treephys/tpaf032

Microbiome. 2025 Mar 15;13(1):74. doi: 10.1186/s40168-025-02069-y.NO ABSTRACTPMID:40089763 | DOI:10.1186/s40168-025-02069-y

Cancer Cell Int. 2025 Mar 15;25(1):97. doi: 10.1186/s12935-025-03727-9.ABSTRACTBACKGROUND: Schisandrin B (Sch B) is an active component in Schisandra chinensis exerting anti-cancer effect, but the mechanism is obscure. This study was designed to explore the mechanism of Sch B against colorectal cancer (CRC).METHOD: Apparent experiments including cell proliferation, transwell, colony formation, etc. were carried out to assess the anti-cancer effect of Sch B to CRC cell lines, and the RNA-seq was performed prior to bioinformatics analysis to explore the key transcriptome alterations, furthermore, an untargeted metabolomics was carried out to profile the metabolic alterations after the treatment with Sch B and an integrated analysis and experiment validation were completed based on RNA-seq and metabolomics to find the critical mechanism.RESULT: The Sch B showed obviously inhibitory effect to cell proliferation, invasion and migration of CRC cell lines with a IC50 value at 75 µM. The RNA-seq and bioinformatics analysis found the ERK/MAPK pathway has been significantly suppressed by the Sch B treatment, while the chemokine, CXCL2, could activate the ERK pathway when binding to its receptor CXCR2. The metabolomics revealed the metabolic profile of CRC cell was remarkably influenced by the Sch B, focusing on the arginine and proline metabolism, ubiquinone, etc. Importantly, the integrated analysis found the DUSP11 connected the ERK pathway and the metabolisms, may mediate the anti-cancer effect of Sch B.CONCLUSION: Sch B showed obviously anti-cancer effect to the CRC through inhibiting CXCL2/ERK/DUSP11 axis, but more experiments are needed to figure out the target of Sch B and validate this mechanism in vivo.PMID:40089741 | DOI:10.1186/s12935-025-03727-9

BMC Plant Biol. 2025 Mar 15;25(1):340. doi: 10.1186/s12870-025-06333-z.ABSTRACTBACKGROUND: Common bean (Phaseolus vulgaris L.) is a thermophilic crop, and exposure to cold stress can significantly impact their yield and quality. To elucidate the impact of cold stress on cold-tolerant 'Wei Yuan' (WY) and cold-sensitive 'Bai Bu Lao' (BBL) of common bean, the mechanism of cold tolerance was studied by physiological and biochemical and multi-omics analysis.RESULTS: In this study, lower relative conductivity and higher malondialdehyde content after cold stress endowed 'WY' seedlings with cold tolerance. A total of 11,837 differentially expressed genes (DEGs) and 923 differential metabolites (DEMs) were identified by transcriptome and metabolomics analysis. Joint analysis showed that under cold stress, DEGs and DEMs in common beans are extensively engaged in sugar, amino acid and isoflavonoid biosynthesis, flavone and flavonol biosynthesis, and plant hormone signal translation, especially related to isoflavone biosynthesis. In addition, it was also found that bHLH and MYB family transcription factors may be involved in the cold signal transduction of common bean.CONCLUSIONS: The above results will provide a theoretical basis for the cold tolerance mechanism of common beans and provide help for the screening of cold-tolerant resources of common beans.CLINICAL TRIAL NUMBER: Not applicable.PMID:40089684 | DOI:10.1186/s12870-025-06333-z

BMC Plant Biol. 2025 Mar 15;25(1):335. doi: 10.1186/s12870-025-06300-8.ABSTRACTBACKGROUND: Salt stress is considered to be one of the major abiotic stresses influencing rice growth and productivity. To improve rice crop productivity in saline soils, it is essential to choose a suitable variety for mitigating salt stress and gain a deep understanding of the underlying mechanisms. The current study explored the salt tolerance mechanism of wild rice 'HD96-1 (salt resistive)' and conventional rice 'IR29 (salt sensitive)' by evaluating morph-physiological, transcriptomic, and metabolomic approaches.RESULTS: Physiological data indicated that HD96-1 had higher chlorophyll content, higher photosynthetic efficiency, more stable Na+/K+, less H₂O₂, and lower electrolyte leakage under salt stress compared with IR29. Transcriptomic and metabolomic data showed that the expression of NHXs in IR29 was significantly down-regulated under salt stress, leading to a large accumulation of Na⁺ in the cytoplasm, and that the expression of CHLH, PORA, and PORB was significantly down-regulated, inhibiting chlorophyll synthesis. HD96-1 maintained the balance of Na⁺ and K⁺ by increasing the expression of NHX4, and there was no significant change in the expression of genes related to chlorophyll synthesis, which made HD96-1 more resistant to salt stress than IR29. In addition, HD96-1 inhibited the excessive synthesis of hydrogen peroxide (H₂O₂) and alleviated oxidative damage by significantly down-regulating the expression of ACX4 under salt stress. HD96-1 promoted the accumulation of isoleucine by up-regulating genes of branched-chain amino acid aminotransferase 2 and branched-chain amino acid aminotransferase 4 and might promote the synthesis of raffinose and stachyose by up-regulating the expression of the gene for galactitol synthase 2, which, in turn, maintained a stable osmotic pressure and relieved osmotic stress. We also found that IR29 and HD96-1 alleviated the inhibition of photosynthesis by salt stress by down-regulating the expression of light-harvesting chromophore protein complex (LHCH II)-related genes and reducing the excessive accumulation of glucose metabolites, respectively. In addition, HD96-1 enhances salt tolerance by regulating C2H2 and bHLH153 transcription factors.CONCLUSION: Under salt stress, HD96-1 maintained ionic balance and photosynthetic efficiency by up-regulating the expression of NHX4 gene and reducing the overaccumulation of glucose metabolites, respectively, and mitigated osmotic stress and oxidative stress by down-regulating the expression of ACX4 and promoting the accumulation of isoleucine, respectively, thereby enhancing the adaptability to salt stress. IR29 maintained photosynthetic efficiency under salt stress by down-regulating the expression of light-harvesting chromophore protein complex (LHCH II)-related genes, thereby enhancing adaptation to salt stress.PMID:40089670 | DOI:10.1186/s12870-025-06300-8

Klin Onkol. 2025;38(1):38-44. doi: 10.48095/ccko202538.ABSTRACTBACKGROUND: The search for effective biomarkers for ovarian cancer (OC) early diagnosis is an urgent task of modern oncogynecology. Metabolic profiling by ultra-high performance liquid chromatography and mass spectrometry (UHPLC-MS) provides information on the totality of all low molecular weight metabolites of patient's biological fluids sample, reflecting the processes occurring in the body. The aim of the study was to research blood plasma and urine metabolomic profile of patients with serous ovarian adenocarcinoma by UHPLC-MS.MATERIAL AND METHODS: To perform metabolomic analysis, 60 blood plasma samples and 60 urine samples of patients diagnosed with serous ovarian carcinoma and 20 samples of apparently healthy volunteers were taken. Chromatographic separation was performed on a Vanquish Flex UHPLC System chromatograph (Thermo Scientific, Germany). Mass spectrometric analysis was performed on an Orbitrap Exploris 480 (Thermo Scientific, Germany) equipped with an electrospray ionization source. Bioinformatic analysis was performed using Compound Discoverer Software (Thermo Fisher Scientific, USA), statistical data analysis was performed in the Python programming language using the SciPy library.RESULTS: Using UHPLC-MS, 1,049 metabolites of various classes were identified in blood plasma. In patients with OC, 8 metabolites had a significantly lower concentration (P &lt; 0.01) compared with conditionally healthy donors, while the content of 19 compounds, on the contrary, increased (P &lt; 0.01). During the metabolomic profiling of urine samples, 417 metabolites were identified: 12 compounds had a significantly lower concentration compared to apparently healthy individuals, the content of 14 compounds increased (P &lt; 0.01). In patients with ovary serous adenocarcinoma, a significant change in the metabolome of blood plasma and urine was found, expressed in abnormal concentrations of lipids and their derivatives, fatty acids and their derivatives, acylcarnitines, phospholipids, amino acids and their derivatives, derivatives of nitrogenous bases and steroids. At the same time, kynurenine, myristic acid, lysophosphatidylcholine and L-octanoylcarnitine are the most promising markers of this disease.CONCLUSION: The revealed changes in the metabolome can become the basis for improving approaches to the diagnosis of serous ovarian adenocarcinoma.PMID:40088435 | DOI:10.48095/ccko202538