PubMed

Physiol Plant. 2025 Mar-Apr;177(2):e70142. doi: 10.1111/ppl.70142.ABSTRACTPhotorespiration is an essential metabolic repair process in oxygenic photosynthesis, as it detoxifies Rubisco's inhibitory oxygenase byproduct, 2-phosphoglycolate (2-PG). It has been demonstrated that improving endogenous photorespiration in C3 plants through enzyme overexpression can enhance photosynthesis and promote plant growth. However, the potential impact of improved photorespiration in leaves on heterotrophic roots remained unexplored. To address this, we conducted a metabolome analysis of Arabidopsis leaves and roots using transgenic lines with enhanced glycine decarboxylase (GDC) activity, achieved by overexpressing the mitochondrial lipoamide dehydrogenase (mtLPD1) subunit. In the leaves, mtLPD1 overexpression primarily resulted in reduced steady-state levels of intermediates associated with photorespiration, the tricarboxylic acid (TCA) cycle, and soluble sugars, while intermediates related to nitrogen metabolism were elevated. In roots, where mtLPD1 expression was unchanged, we observed contrasting accumulation patterns in the transgenic lines compared to the wildtype, including increased levels of photorespiratory and TCA-cycle intermediates. Notably, we also detected elevated amounts of soluble sugars, nitrate, and starch. Phloem exudate analysis revealed altered metabolite profiles in the overexpressors, particularly with respect to photorespiratory intermediates linked to the GDC reaction, as well as soluble sugars and metabolites involved in cellular redox homeostasis. This suggested an increased transport of these metabolites from shoots to roots, thereby altering sink organ metabolism. In summary, we hypothesize that optimizing photorespiration enhances photosynthesis, which leads to an increased export of carbon surplus to heterotrophic tissues. Thus, improving photorespiration may hold potential for increasing yields in beet- and tuber-forming plants.PMID:40032651 | DOI:10.1111/ppl.70142

J Cell Mol Med. 2025 Mar;29(5):e70451. doi: 10.1111/jcmm.70451.ABSTRACTTo investigate the impact of growth hormone (GH) on branched-chain amino acids (BCAAs) catabolism in males with hypopituitarism, we measured the concentration of amino acids in 133 males with hypopituitarism and 90 age-matched healthy controls using untargeted metabolome. A rat model of hypopituitarism was established through hypophysectomy, followed by recombinant human GH (rhGH) intervention. Targeted metabolomics and label-free quantitative phosphoproteomics were utilised to assess amino acid levels in rats and explore the mechanisms of GH's effect on BCAA catabolism. Hypopituitarism exhibited elevated concentrations of BCAAs, which correlated positively with triglyceride, fasting insulin and HOMA-IR. The BCAAs were significantly elevated following hypophysectomy and were substantially reduced upon rhGH intervention. Phosphorylation proteomics analysis in liver tissues revealed that differentially expressed phosphoproteins (DEPPs) after GH treatment were predominantly involved in 'RNA metabolic process', 'Diseases of signal transduction by growth factor receptors' and 'BCAAs degradation'. Notably, 12 proteins in the BCAA degradation pathway showed altered phosphorylation without whole protein changes. Importantly, the expression or phosphorylation modification of BCKDH, BCATs and MuRF1 were restored through rhGH intervention. Hypopituitarism exhibits elevated levels of circulating BCAAs. The increased circulating BCAAs in hypopituitarism may result from enhanced MuRF1-mediated muscle proteolysis, which greatly exceeds the BCAA degradation capacity. This study provides valuable insights into the effects of GH on BCAA catabolism at the scale of the proteomics level.PMID:40032645 | DOI:10.1111/jcmm.70451

Gut. 2025 Mar 3:gutjnl-2024-333297. doi: 10.1136/gutjnl-2024-333297. Online ahead of print.ABSTRACTBACKGROUND: 24-Nor-ursodeoxycholic acid (NorUDCA) is a novel therapeutic bile acid for treating immune-mediated cholestatic liver diseases, such as primary sclerosing cholangitis (PSC).OBJECTIVE: Since PSC strongly associates with T helper-type-like 17 (TH17)-mediated intestinal inflammation, we explored NorUDCA's immunomodulatory potential on TH17 cells.DESIGN: NorUDCA's impact on TH17 differentiation was assessed using a CD4+TNaive adoptive transfer mouse model, and on intraepithelial TH17 pathogenicity and transdifferentiation using an αCD3 stimulation model combined with interleukin-17A-fate-mapping. Mechanistic studies used molecular and multiomics approaches, flow cytometry and metabolic assays with pathogenic (p) TH17. Pathogenicity of pTH17 exposed to NorUDCA in vitro was evaluated following adoptive transfer in intestinal tissues or the central nervous system (CNS). Key findings were validated in an αCD3-stimulated humanised NSG mouse model reconstituted with peripheral blood mononuclear cells from patients with PSC.RESULTS: NorUDCA suppressed TH17 effector function and enriched regulatory T cell (Treg) abundance upon CD4+TNaive cell transfer. NorUDCA mitigated intraepithelial TH17 pathogenicity and decreased the generation of proinflammatory 'TH1-like-TH17' cells, and enhanced TH17 transdifferentiation into Treg and Tr1 (regulatory type 1) cells in the αCD3-model. In vivo ablation revealed that Treg induction is crucial for NorUDCA's anti-inflammatory effect on TH17 pathogenicity. Mechanistically, NorUDCA restrained pTH17 effector function and simultaneously promoted functional Treg formation in vitro, by attenuating a glutamine-mTORC1-glycolysis signalling axis. Exposure of pTH17 to NorUDCA dampened their pathogenicity and expansion in the intestine or CNS upon transfer. NorUDCA's impact on TH17 inflammation was corroborated in the humanised NSG mouse model.CONCLUSION: NorUDCA restricts TH17 inflammation in multiple mouse models, potentiating future clinical applications for treating TH17-mediated intestinal diseases and beyond.PMID:40032499 | DOI:10.1136/gutjnl-2024-333297

Food Res Int. 2025 Mar;205:115981. doi: 10.1016/j.foodres.2025.115981. Epub 2025 Feb 13.ABSTRACTChitosan (CTS) is a natural polysaccharide derived from the deacetylation of chitin. Chitosan-based coatings are widely used for the preservation of hardy kiwifruits. However, the effect of chitosan-based coating on fruit flavor during ripening is rarely reported. In this study, the postharvest qualities of hardy kiwifruits were investigated using chitosan coating and chitosan-silica nanoparticle coating (CTS-SiNPs) during storage at 25°C and 4°C. Physicochemical analyses showed that chitosan coating extended the shelf-life by delaying ripening and maintaining higher quality than uncoated fruits, and CTS-SiNPs treatment showed a superior preservation effect compared to CTS treatment. Untargeted metabolomics analysis based on HS-SPME-GC-MS was used to comprehensively evaluate the volatile profiles of hardy kiwifruits during postharvest storage. The metabolomics analysis showed that two chitosan coating treatments greatly delayed the accumulation of most volatiles while delaying the ripening process, and the differential volatiles were mostly involved in the terpenoids biosynthesis pathway. Notably, most green leaf volatiles (C6/C9 aldehydes, esters and alcohols) and methyl salicylate were up-regulated in the CTS-SiNPs coating groups. In addition, odor activity value (OAV) was used to characterize the key aroma-active compounds and odor profiles. A total of 32 compounds were identified as key aroma-active compounds (OAV ≥ 1) in hardy kiwifruits. The odor profile evaluation showed that the CTS-SiNPs coating treatment enhanced the intensity of the "herbal" odor, while reducing the intensity of "sweet" and "floral" odors in hardy kiwifruits at the eating-ripe stage.PMID:40032473 | DOI:10.1016/j.foodres.2025.115981

Food Res Int. 2025 Mar;205:115978. doi: 10.1016/j.foodres.2025.115978. Epub 2025 Feb 18.ABSTRACTThe market for flavour superior quality cacao provides significant economic and non-economic benefits to farmers. Flavor precursor metabolites, formed during various post-harvest stages, are crucial for developing superior sensory attributes. However, identifying these metabolites and understanding how climate variations and post-harvest practices influence them remains a challenge. This study investigates how the fermentation methodology applied and climate conditions in different zones of the cacao beans producing region of Arauca - Colombia, influence the metabolomic profile of cacao beans and their flavour precursor metabolites. Untargeted metabolomic analysis was performed by UHPLC-ESI-Orbitrap-MS on cacao beans fermented for 0, 24, 48, 72, 96, and 120 h from 9 production zones. The PLS-DA model highlighted that the metabolomics fingerprint changes through fermentation time. Among the most discriminant metabolites, 18 oligopeptides, sucrose, glucose, fructose, flavanols, and acids were tentatively identified. The chemometric analysis showed that fermentation time has a significant impact on the metabolomic profile of cacao beans, while agroclimatic conditions had a minor influence. Metabolomic analyses defined 96 h as the optimal fermentation time to maximize the amount of aroma precursors. Metabolomic analyses identified 96 h as the optimal fermentation time to maximize the amount of aroma precursors across all 9 cacao production zones evaluated. This study underscores the central role of fermentation in shaping flavor precursors, and contributes to the development of new approaches for cacao processing based on the tracking of biochemical and functional compounds (quality biomarkers).PMID:40032472 | DOI:10.1016/j.foodres.2025.115978

Food Res Int. 2025 Mar;205:116010. doi: 10.1016/j.foodres.2025.116010. Epub 2025 Feb 13.ABSTRACTCraft beers have encountered a steady rise in popularity over the years, as these artisanal beers produced by microbreweries have responded to consumer preferences for added novelty in such beverages. With this gain in appeal and interest for the beverage, craft beers have also become a growing industry in many parts of the world, and the same can be said for research within the field. This also extends to the chemistry of craft beers, where one method of exploration involves that of metabolomics, appropriately addressing the multi-faceted aspects of craft beer development and chemistry. Alongside advances in metabolomics in general beer and brewing research, the field also mirrors potential in growth. This review touches on relevant aspects of the beer industry and brewing process as preliminaries for discussions on advances in the field of beer metabolomics, leading to the application of metabolomics in pursuit of studying craft beers; future directions, challenges, and opportunities are also presented.PMID:40032445 | DOI:10.1016/j.foodres.2025.116010

Harmful Algae. 2025 Mar;143:102808. doi: 10.1016/j.hal.2025.102808. Epub 2025 Feb 6.ABSTRACTThe species Karlodinium armiger occasionally co-occurs with Karlodinium veneficum during harmful algal blooms. The only toxin of this species described so far is karmitoxin, a highly ichthyotoxic compound very similar to the karlotoxins produced by K. veneficum. However, information on K. armiger is limited and based on a single Mediterranean strain (K-0668), with few studies investigating its toxicity. Given the high intraspecific variability known in K. veneficum, it was a significant achievement when two additional strains of K. armiger (MD-D6 and MD-D7) were isolated from the Labrador Sea in 2017, enabling comparative studies within this species. The toxicity of these three strains was assessed using the fish gill cell line RTgill-W1 and the cryptophyte Rhodomonas salina. An untargeted metabolomics approach using high-resolution tandem mass spectrometry, along with a computational workflow, provided insights into the metabolomic differences between the strains. Despite being cultivated under identical conditions, the metabolomic profiles and toxicological properties were distinct, even between MD-D6 and MD-D7, which were isolated from the same water sample. While MD-D7 did not exhibit significant toxicity, MD-D6 showed high toxicity and lytic potential, similar to K-0668. Interestingly, karmitoxin was only detected in K-0668, and neither karlotoxins nor any known analogs were detected in any strain. Within this comprehensive workflow, some molecules were found in MD-D6 that share the same chemical space as karmitoxin, making them interesting targets for further research. In conclusion, this study evaluated the toxicological and metabolic variability in three different strains of K. armiger and identified some putative toxin candidates in MD-D6.PMID:40032440 | DOI:10.1016/j.hal.2025.102808

Gene. 2025 Mar 1:149383. doi: 10.1016/j.gene.2025.149383. Online ahead of print.ABSTRACTBACKGROUND: Vitiligo is a prevalent autoimmune skin disorder characterized by progressive depigmented patches of the skin and/or mucosa. Lately, extensive research has been investigating molecular pathogenesis underlying vitiligo, epidermal-immune cell crosstalk, structural aberrations in cellular skin components and immune cell metabolism derangements. Glucose transporter-1 (GLUT-1) has recently proved to be increased in proinflammatory conditions and autoimmune diseases. GLUT-1 expression is upregulated in rheumatoid arthritis, systemic lupus erythematosus, psoriasis and chronic spongiotic dermatitis.OBJECTIVE: To investigate GLUT-1 expression in vitiligo.SUBJECTS AND METHODS: The study included 30 vitiligo patients "vitiligo vulgaris" and 30 healthy individuals. Biopsies of the patients' lesional vitiligo skin and the control group's normal skin were obtained. They were all tested for GLUT-1 mRNA expression using real-time polymerase chain reaction (RT-PCR) and GLUT-1 antibody expression using immunohistochemistry (IHC). Hematoxylin and eosin (H&E) staining for the specimens was additionally done for histopathological assessment.RESULTS: GLUT-1 expression was upregulated in lesional skin of vitiligo patients compared to normal control skin (P-value < 0.001). Also, lesional specimens from stable disease showed more GLUT-1 expression than active disease but without a significant difference (P-value = 0.283). There was no significant correlation between the proposed vitiligo histological scoring system and vitiligo signs of the disease activity score.CONCLUSION: GLUT-1 could play a crucial role in vitiligo disease onset, persistence and progression, through keratinocyte-melanocyte-fibroblast-immune cell crosstalk, being the initially deranged metabolic pathway for all these cells giving an insight into vitiligo metabolomics.PMID:40032057 | DOI:10.1016/j.gene.2025.149383

Nan Fang Yi Ke Da Xue Xue Bao. 2025 Feb 20;45(2):347-358. doi: 10.12122/j.issn.1673-4254.2025.02.16.ABSTRACTOBJECTIVES: To explore the bioactive components in Jiawei Xiaoyao Pills (JWXYP) and their mechanisms for alleviating depression-like behaviors.METHODS: The active compounds, key targets, and pathways of JWXYP were identified using TCMSP and TCMIP databases. Thirty-six SD rats were randomized equally into 6 groups including a control group and 5 chronic unpredictable mild stress (CUMS)-induced depression groups. After modeling, the 5 model groups were treated with daily gavage of normal saline, 1.8 mg/kg fluoxetine hydrochloride (positive control drug), or JWXYP at 1.44, 2.88, and 4.32 g/kg. The depression-like behaviors of the rats were evaluated using behavioral tests, and pathological changes in the liver and hippocampus were examined with HE staining. The biochemical indicators in the serum and brain tissues were detected using ELISA. Serum metabolomics analysis was performed to identify the differential metabolites using OPLS-DA, and gut microbiota changes were analyzed using 16S rDNA sequencing.RESULTS: Network pharmacology revealed that menthone and paeonol in JWXYP were capable of penetrating the blood-brain barrier to regulate inflammatory pathways and protect the nervous system. In the rat models subjected to CUMS, treatment with JWXYP significantly improved body weight loss, sucrose preference and open field activities, reduced liver inflammation, alleviated structural changes in the hippocampal neurons, decreased serum levels of TNF‑α, IL-1β, IL-6 and LBP, and increased 5-HT and VIP concentrations in the serum and brain tissue, and these effects were the most pronounced in the high-dose group. Metabolomics analysis showed changes in such metabolites as indole-3-acetamide and acetyl-L-carnitine in JWXYP-treated rats, involving the pathways for bile acid biosynthesis and amino acid metabolism. 16S rDNA analysis demonstrated increased gut microbiota diversity and increased abundance of Lactobacillus species in JWXYP-treated rats.CONCLUSIONS: JWXYP alleviates depression-like symptoms in rats by regulating the neurotransmitters, inhibiting inflammation and oxidation, and modulating gut microbiota.PMID:40031979 | DOI:10.12122/j.issn.1673-4254.2025.02.16

Nan Fang Yi Ke Da Xue Xue Bao. 2025 Feb 20;45(2):331-339. doi: 10.12122/j.issn.1673-4254.2025.02.14.ABSTRACTOBJECTIVES: To explore the mechanism of Lacticaseibacillus paracasei E6 for improving vinorelbine-induced immunosuppression in zebrafish.METHODS: The intestinal colonization of L. paracasei E6 labeled by fluorescein isothiocyanate (FITC) in zebrafish was observed under fluorescence microscope. In a zebrafish model of vinorelbine-induced immunosuppression, the immunomodulatory activity of L. paracasei E6 was assessed by analyzing macrophage and neutrophil counts in the caudal hematopoietic tissue (CHT), the number of T-lymphocyte, and the expressions of interleukin-12 (IL-12) and interferon-γ (IFN-γ). The contents of short-chain fatty acids (SCFAs) in L. paracasei E6 fermentation supernatant and the metabolites of L. paracasei E6 in zebrafish were detected by LC-MS/MS-based targeted metabolomics. The immunomodulatory effects of the SCFAs including sodium acetate, sodium propionate and sodium butyrate were evaluated in the zebrafish model of immunosuppression.RESULTS: After inoculation, green fluorescence of FITC-labeled L. paracasei E6 was clearly observed in the intestinal ball, midgut and posterior gut regions of zebrafish. In the immunocompromised zebrafish model, L. paracasei E6 significantly alleviated the reduction of macrophage and neutrophil counts in the CHT, increased the fluorescence intensity of T-lymphocytes, and promoted the expressions of IL-12 and IFN-γ. Compared with MRS medium, L. paracasei E6 fermentation supernatant showed significantly higher levels of acetic acid, propionic acid and butyric acid, which were also detected in immunocompromised zebrafish following treatment with L. paracasei E6. Treatment of the zebrafish model with sodium acetate and sodium propionate significantly increased macrophage and neutrophil counts in the CHT and effectively inhibited vinorelbine-induced reduction of thymus T cells.CONCLUSIONS: L. paracasei E6 can improve vinorelbine-induced immunosuppression in zebrafish through its SCFA metabolites acetic acid and propionic acid.PMID:40031977 | DOI:10.12122/j.issn.1673-4254.2025.02.14

Food Chem. 2025 Feb 24;477:143580. doi: 10.1016/j.foodchem.2025.143580. Online ahead of print.ABSTRACTCamellia sinensis var. assamica cultivars 'Zijuan' (ZJ, characterized by high anthocyanin content) and 'Mengku large-leaf' (LL, with high content of catechins) are widely consumed in China. Therefore, when processed into green, white, and black teas, differences in composition and biological activities should be detectable. The aim of this work was to explore these potential differences. To achieve that, in vitro bioactivity assays and metabolomics combined with correlation and ridge analyses were applied. Metabolomics revealed that the concentrations of theasinensins, anthocyanins, and amino acids in ZJ teas were higher than those in LL teas. Compared with green and white teas, black teas had higher concentrations of Amadori rearrangement products and theaflavins. Bioactivity assays showed ZJ teas had stronger bioactivity than LL teas. Catechins, procyanidins, and flavone glycosides were identified as key contributors to bioactivity differences rather than anthocyanins. These results suggested that ZJ was more suitable for making functional tea beverages.PMID:40031135 | DOI:10.1016/j.foodchem.2025.143580

Plant Physiol Biochem. 2025 Feb 26;222:109716. doi: 10.1016/j.plaphy.2025.109716. Online ahead of print.ABSTRACTDrought stress severely limits the growth and productivity of sweet cherry (Prunus avium L.). Dark septate endophytes (DSEs) are a group of root-associated fungi known to enhance plant stress tolerance. This study aimed to explore the role of DSE fungus S16 in improving drought tolerance in sweet cherry seedlings and to reveal the underlying molecular and microbial mechanisms through a multi-omics approach. Physiological analysis showed that S16 inoculation improved plant growth, increased relative water content, photosynthetic rate, and antioxidant enzyme activities, while reducing ion leakage and oxidative damage under drought conditions. Metabolomic and transcriptomic analyses identified key metabolic pathways, particularly flavonoid and phenylpropanoid biosynthesis, as being significantly activated, with upregulation of genes such as PAL, 4CL and CHS, and increased accumulation of metabolites like cinnamic acid (CA) and flavonoid derivatives. Exogenous application of CA at 0.5 mM further enhanced drought resistance by reducing reactive oxygen species (ROS) levels, increasing proline accumulation, and boosting antioxidant enzyme activities. Rhizosphere microbiota analysis revealed that S16 symbiosis and CA treatment under drought conditions increased the abundance of beneficial bacteria, such as members of Sphingomonas, Stenotrophobacter and Parcubacteria, while promoting the dominance of Humicola and Fusarium fungi. These findings provide multi-omics evidence for the role of S16 in enhancing drought tolerance in sweet cherry, offering a theoretical basis for the application of DSE fungi in sustainable fruit tree production.PMID:40031102 | DOI:10.1016/j.plaphy.2025.109716

PLoS One. 2025 Mar 3;20(3):e0315999. doi: 10.1371/journal.pone.0315999. eCollection 2025.ABSTRACTPoor penetration of many anti-tuberculosis (TB) antibiotics into the central nervous system (CNS) is thought to be a major driver of morbidity and mortality in TB meningitis (TBM). While the amount of a particular drug that crosses into the cerebrospinal fluid (CSF) varies from person to person, little is known about the host factors associated with interindividual differences in CSF concentrations of anti-TB drugs. In patients diagnosed with TBM from the country of Georgia (n = 17), we investigate the association between CSF concentrations of anti-TB antibiotics and multiple host factors including serum drug concentrations and CSF concentrations of metabolites and cytokines. We found > 2-fold differences in CSF concentrations of anti-TB antibiotics from person to person for all drugs tested including cycloserine, ethambutol, imipenem, isoniazid, levofloxacin, linezolid, moxifloxacin, pyrazinamide, and rifampin. While serum drug concentrations explained over 30% of the variation in CSF drug concentrations for cycloserine, isoniazid, linezolid, and pyrazinamide (adjusted R2 ≥ 0.3, p < 0.001 for all), there was no significant association between serum concentrations of imipenem and ethambutol and their respective CSF concentrations. CSF concentrations of carnitines were significantly associated with concentrations of ethambutol and imipenem (q < 0.05), and imipenem was the only antibiotic significantly associated with CSF cytokine concentrations. These results indicate that there is high interindividual variability in CSF drug concentrations in patients treated for TBM, which is only partially explained by differences in serum drug concentrations. With the exception of imipenem, there was no association between CSF drug concentrations and concentrations of cytokines and chemokines.PMID:40029856 | DOI:10.1371/journal.pone.0315999

Gut Microbes. 2025 Dec;17(1):2474256. doi: 10.1080/19490976.2025.2474256. Epub 2025 Mar 3.ABSTRACTAtopic dermatitis (AD) is a globally prevalent chronic inflammatory skin disorder. Its pathogenesis remains incompletely understood, resulting in considerable therapeutic challenges. Recent studies have highlighted the significance of the interaction between AD and gut microbiome. In this study, we investigated the effects of probiotic-derived extracellular vesicles on AD. Initially, we isolated and characterized extracellular vesicles from Limosilactobacillus fermentum SLAM 216 (LF216EV) and characterized their composition through multi-omics analysis. Gene ontology (GO) and pathway analysis classified LF216EV proteins into biological processes, molecular functions, and cellular components. Importantly, specific abundance in linoleic, oleic, palmitic, sebacic, and stearic acids indicating upregulated fatty acid metabolism were observed by metabolomic analysis. Furthermore, featured lipid profiling including AcylGlcADG and ceramide were observed in LF216EV. Importantly, in an atopic dermatitis-like cell model induced by TNFα/IFNγ, LF216EV significantly modulated the expression of immune regulatory genes (TSLP, TNFα, IL-6, IL-1β, and MDC), indicating its potential functionality in atopic dermatitis. LF216EV alleviated AD-like phenotypes, such as redness, scaling/dryness, and excoriation, induced by DNCB. Histopathological analysis revealed that LF216EV decreased epidermal thickness and mast cell infiltration in the dermis. Furthermore, LF216EV administration reduced mouse scratching and depression-related behaviors, with a faster onset than the classical treatment with dexamethasone. In the quantitative real-time polymerase chain reaction (qRT-PCR) analysis, we observed a significant increase in the expression levels of htrb2c, sert, and tph-1, genes associated with serotonin, in the skin and gut of the LF216EV-treated group, along with a significant increase in the total serum serotonin levels. Gut microbiome analysis of the LF216EV-treated group revealed an altered gut microbiota profile. Correlation analysis revealed that the genera Limosilactobacillus and Desulfovibrio were associated with differences in the intestinal metabolites, including serotonin. Our findings demonstrate that LF216EV mitigates AD-like symptoms by promoting serotonin synthesis through the modulation of gut microbiota and metabolome composition.PMID:40028723 | DOI:10.1080/19490976.2025.2474256

Plant J. 2025 Mar;121(5):e70040. doi: 10.1111/tpj.70040.ABSTRACTCamellia sinensis is an industrial crop characterized by specific secondary metabolites, which provide numerous benefits to human health. Previous researches reveal that the secondary metabolism of tea plants is significantly affected by various environmental factors, especially light intensity. However, the epigenetic mechanism underlying these high light-induced changes remains systematic research. In this study, physiological analysis suggested that increased photosynthetic product was rapidly converted into other organic compounds in adaptation to high light. The metabolite landscape by widely targeted metabolome revealed 219 differentially accumulated metabolites (DAMs) in high light, with substantial upregulated DAMs accumulated in 'amino acids and derivatives' and 'alkaloids'. The landscape of nine crucial histone modifications showed the distribution diversity in the genome and the complex relationship with gene expression. Integrated analysis of stomatal development, metabolome, epigenome, and transcriptome indicated that the dynamics of histone modifications (H3K4ac, H3K4me3, H3K9ac, H3K9me2, H3K27ac, and H3K27me3) on gene regions were closely related to the expression of regulatory genes in stomatal development and enzyme genes in secondary metabolic pathways, leading to stomatal density and metabolite changes in high light. Furthermore, H3K27ac and H3K27me3 were identified as key histone modifications, regulating critical genes under high light, including CsEPFL9, CsYODAb, CsF3'Hb, CsCHSc, CsANRa, CsDFRb-2, CsAlaDC, CsAAP1, CsGGT2, CsXMPP, Cs7-NMT, CsPORC, and CsPSY. These results suggest the pivotal role of histone modifications in the high light-induced stomatal density and secondary metabolite changes of tea plants.PMID:40028698 | DOI:10.1111/tpj.70040

Cancer Med. 2025 Mar;14(5):e70707. doi: 10.1002/cam4.70707.ABSTRACTAIM: The tumor microenvironment (TME) of non-small cell lung cancer (NSCLC) is highly heterogeneous and is involved in tumorigenesis and resistance to therapy. Among the cells of the TME, endothelial cells are associated with the latter processes through endothelial-to-mesenchymal transition (EndMT). During EndMT, endothelial cells (ECs) progressively lose their endothelial phenotype in favor of a mesenchymal phenotype, which favors the production of cancer-associated fibroblasts (CAFs). Our study aimed to investigate the consequences of exposure to different lung tumor secretomes on EC phenotype and plasticity.MATERIALS AND METHODS: Conditioned media (CM) were prepared from the tumor cell lines A549, H1755, H23, H1437, and H1975. Proliferation and migration of ECs treated with these CMs were assessed by Cyquant and Incucyte technologies, respectively. The angiogenic capacity of ECs was assessed by following tubulogenesis on Matrigel. Phenotypic changes in treated ECs were detected by flow cytometry. Morphological analysis of actin fibers was performed by immunohistochemistry, while proteomic analysis by mass spectrometry was used to identify the protein content of secretomes.RESULTS: A change of the endothelial phenotype was found when human umbilical vein endothelial cells (HUVECs) were treated with different CMs. This phenotypic change was associated with a morphological change, an increase in both stress fiber expression and spontaneous migration. Furthermore, an increase in mesenchymal markers (α-SMA and CD44) confirmed the phenotypic changes. However, the secretomes did not modify the rate of double-labeled cells (vWF+/α-SMA+ or CD31+/CD44+). Proteomic analysis identified potential targets involved in the EndMT with therapeutic relevance.CONCLUSION: Taken together, these data suggest that CMs can induce partial EndMT.PMID:40028673 | DOI:10.1002/cam4.70707

Heliyon. 2025 Feb 5;11(4):e42461. doi: 10.1016/j.heliyon.2025.e42461. eCollection 2025 Feb 28.ABSTRACTBACKGROUND: The chromatographic measurement of polar molecules is often surprisingly complicated. On the one hand, the standard experiments use C18 columns, which is usually unsuitable. On the other hand, these types of molecules can behave vastly differently despite their similarities. Thus, finding the right chromatographic conditions is challenging. HILIC can be an obvious choice, but C18 is still used with suitable analytes. Comparing the two methods would be advantageous, but a numerical comparison can be problematic. Thus, a simple comparing and ranking system is needed and put to use to find the best method for the separation of polar basic molecules.RESULTS: In this paper, nine columns with different stationary phases, from reversed-phase to hydrophilic interaction, are compared and ranked in gradient elution. The effect of pH was also considered. The measurements were repeated in acidic, near-to-neutral, and basic conditions. A straightforward system is developed to rank different stationary phases. Its foundation was peak shapes and resolutions. Every measurement condition with all the columns on the available pHs is evaluated by each property. The testing solution consisted of ten components, which aimed to cover a wide range of polar basic molecules. The comparison also focuses on these analytes. We highlighted which analyte is adaptable to different methods or which needed exclusive conditions. The resulting best column with the optimal conditions is presented and proven highly efficient for their separation.SIGNIFICANCE: A straightforward comparison and ranking system is developed to test multiple chromatographic columns with different stationary phases, from reversed-phase to hydrophilic interaction in gradient elution, seeking the best method for separating polar basic molecules. Nine columns were compared in multiple conditions. The best setup resulting in the competition is presented in detail, which can be applied to a wide range of analytes.PMID:40028593 | PMC:PMC11867270 | DOI:10.1016/j.heliyon.2025.e42461

Front Immunol. 2025 Feb 14;16:1550500. doi: 10.3389/fimmu.2025.1550500. eCollection 2025.ABSTRACTMacrophages, crucial innate immune cells, defend against pathogens and resolve inflammation, maintaining tissue balance. They perform phagocytosis, present antigens to T cells, and bond innate and adaptive immunity through various activation states. Classical activation is associated with Th1 responses and interferon γ production, while alternative activation, induced by interleukin 4, is characterized by increased endocytosis, reduced secretion of pro-inflammatory cytokines, and roles in immunoregulation and tissue remodeling. Although these represent opposite extremes observed in vitro, the remarkable plasticity of macrophages allows for a wide spectrum of activation phenotypes that are complex to characterize experimentally. While the application of omics techniques has resulted in significant advances in the characterization of macrophage polarization, lipidomic studies have received lesser attention. Beyond their role as structural components and energy sources, lipids function as signaling molecules that regulate macrophage activation and polarization, thereby shaping immune responses. This work reviews the interaction between lipid signaling and macrophage polarization, exploring how lipid metabolism influences macrophage phenotype and function. These insights offer potential therapeutic strategies for immune-mediated diseases and inflammation-related disorders, including inflammaging.PMID:40028333 | PMC:PMC11867965 | DOI:10.3389/fimmu.2025.1550500

Front Immunol. 2025 Feb 14;16:1509114. doi: 10.3389/fimmu.2025.1509114. eCollection 2025.ABSTRACTINTRODUCTION: Ulcerative colitis (UC) is often characterized by dysbiosis of the colonic microbiota and metabolic disturbances, which can lead to liver damage. Patchoulene epoxide (PAO), a tricyclic sesquiterpene derived from the aged essential oil of Pogostemonis Herba, is known for its anti-inflammatory and ulcer-healing properties. However, its dual protective role against UC and liver injury remains largely unexplored. This study aims to elucidate the protective effect and underlying mechanism of PAO against dextran sulfate sodium (DSS)-induced UC and liver injury in mice.METHODS: Colitis and liver injury in mice were induced by adding 3% DSS to their drinking water continuously for 7 days, and PAO at the doses of 20 and 40 mg/kg was administered orally to mice daily from the first day until the experimental endpoint. Stool consistency scores, blood stool scores, and body weights were recorded weekly. Disease activity index (DAI) was determined before necropsy, where colon and liver tissues were collected for biochemical analyses. Additionally, the fecal microbiome and its metabolites of treated mice were characterized using 16S rRNA amplicon sequencing and metabolomics.RESULTS: PAO significantly reduced the disease activity index and mitigated colonic atrophy in UC mice. It also improved colonic and hepatic pathological changes by safeguarding tight and adherens junctions, and suppressing the generation of pro-inflammatory cytokines and lipopolysaccharide. These beneficial effects were attributed to PAO's capability to regulate the colonic microbiota and metabolic processes. PAO was found to enhance the diversity of the colonic microbiota and to shift the microbial balance in UC mice. Specifically, it restored the microbiota from an Akkermansia-dominated state, characteristic of UC, to a healthier Muribaculaceae-dominated composition. Furthermore, PAO corrected the colon metabolic disturbance in UC mice by modulating the purine metabolism, notably increasing the abundance of deoxyadenosine, adenosine and guanine in UC mice.CONCLUSIONS: The therapeutic effect of PAO on UC and liver injury was mainly attributed to its regulation of colonic microbiota and purine metabolism. These insights emphasize the overall therapeutic benefits of PAO in treating UC and liver injury.PMID:40028318 | PMC:PMC11868103 | DOI:10.3389/fimmu.2025.1509114

Front Cell Infect Microbiol. 2025 Feb 14;15:1523863. doi: 10.3389/fcimb.2025.1523863. eCollection 2025.ABSTRACTThis study aimed to investigate the relationship between gut microbiota composition, fecal metabolites, and postoperative prognosis in patients with extrahepatic cholangiocarcinoma (eCCA). A total of 53 patients with resectable eCCA and 21 healthy volunteers as a control group were included. 16S rRNA gene sequencing and metabolomic analyses revealed significant differences in the gut microbial community structure and altered fecal metabolites profiles between eCCA patients and healthy controls. Univariate and multivariate Cox regression analyses indicated that factors such as preoperative total bilirubin, indirect bilirubin, and specific metabolites were closely associated with overall survival in patients with eCCA post-surgery. The constructed nomogram model further demonstrated the predictive value of these factors, achieving a C-index of 0.718, with calibration curves confirming its strong predictive performance. In conclusion, gut microbiota composition and fecal metabolites play a crucial role in the surgical prognosis of eCCA patients, providing new insights for clinical prognostic assessment.PMID:40028184 | PMC:PMC11868125 | DOI:10.3389/fcimb.2025.1523863