PubMed

Cell Mol Immunol. 2025 Mar 4. doi: 10.1038/s41423-025-01262-1. Online ahead of print.ABSTRACTAutologous T-cell therapies show limited efficacy in chronic lymphocytic leukemia (CLL), where acquired immune dysfunction prevails. In CLL, disturbed mitochondrial metabolism has been linked to defective T-cell activation and proliferation. Recent research suggests that lipid metabolism regulates mitochondrial function and differentiation in T cells, yet its role in CLL remains unexplored. This comprehensive study compares T-cell lipid metabolism in CLL patients and healthy donors, revealing critical dependence on exogenous cholesterol for human T-cell expansion following TCR-mediated activation. Using multi-omics and functional assays, we found that T cells present in viably frozen samples of patients with CLL (CLL T cells) showed impaired adaptation to cholesterol deprivation and inadequate upregulation of key lipid metabolism transcription factors. CLL T cells exhibited altered lipid storage, with increased triacylglycerols and decreased cholesterol, and inefficient fatty acid oxidation (FAO). Functional consequences of reduced FAO in T cells were studied using samples from patients with inherent FAO disorders. Reduced FAO was associated with lower T-cell activation but did not affect proliferation. This implicates low cholesterol levels as a primary factor limiting T-cell proliferation in CLL. CLL T cells displayed fewer and less clustered lipid rafts, potentially explaining the impaired immune synapse formation observed in these patients. Our findings highlight significant disruptions in lipid metabolism as drivers of functional deficiencies in CLL T cells, underscoring the pivotal role of cholesterol in T-cell proliferation. This study suggests that modulating cholesterol metabolism could enhance T-cell function in CLL, presenting novel immunotherapeutic approaches to improve outcome in this challenging disease.PMID:40033083 | DOI:10.1038/s41423-025-01262-1

Commun Med (Lond). 2025 Mar 3;5(1):44. doi: 10.1038/s43856-025-00755-4.ABSTRACTBACKGROUND: Through a retrospective analysis of existing FDG PET-MRI images, we recently demonstrated that metformin increases the accumulation of FDG in the intestinal lumen, suggesting that metformin stimulates glucose excretion into the intestine. However, the details of this phenomenon remain unclear. We here investigate the detailed dynamics of intestinal glucose excretion, including the rate of excretion and the metabolism of excreted glucose, in both the presence and absence of metformin.METHODS: We quantified intestinal glucose excretion using newly developed FDG PET-MRI-based bioimaging in individuals with type 2 diabetes, both treated and untreated with metformin. The metabolism of excreted glucose was analyzed through mass spectrometry of fecal samples from mice intravenously injected with 13C-labeled glucose.RESULTS: Continuous FDG PET/MRI image taking reveals that FDG is initially observed in the jejunum, suggesting its involvement in FDG excretion. Metformin-treated individuals excrete a significant amount of glucose (~1.65 g h-1 per body) into the intestinal lumen. In individuals not receiving metformin, a certain amount of glucose (~0.41 g h-1per body) is also excreted into the intestinal lumen, indicating its physiological importance. Intravenous injection of 13C-labeled glucose in mice increases the content of 13C in short-chain fatty acids (SCFAs) extracted from feces, and metformin increased the incorporation of 13C into SCFAs.CONCLUSIONS: A previously unrecognized, substantial flux of glucose from the circulation to the intestinal lumen exists, which likely contributes to the symbiosis between gut microbiota and the host. This flux represents a potential target of metformin's action in humans.PMID:40033038 | DOI:10.1038/s43856-025-00755-4

Sci Rep. 2025 Mar 3;15(1):7416. doi: 10.1038/s41598-025-91798-z.ABSTRACTThe clinical application of randomly patterned skin flaps is often limited by their length-to-width ratio, which can negatively impact their viability. This study aims to investigate the effect of ginsenoside Rb1 on the survival of random skin flaps and explores the underlying mechanisms using metabonomic approaches. Sprague-Dawley rats were assigned to a control group, an ischemia-reperfusion (I/R) group, and a ginsenoside Rb1 treatment group. The serum and middle flap tissue of the rats were collected for 1H-NMR spectroscopy detection and computer pattern recognition analysis. Ten days post-surgery, the survival rate of dorsal flaps in Rb1 group (61.06 ± 3.71) % was significantly higher than in I/R group (50.46 ± 1.41)%. Analyses of 1H-NMR spectrum 24 h post-surgery demonstrated increased lipid content in the serum of I/R group. In contrast, serum samples from the Rb1 group exhibited significantly higher levels of glutamate, creatine and fumarate, while lactate, choline/phosphocholine, N-acetylglycoprotein and allantoin were decreased. The contents of ATP/ADP/AMP of glutamine, citrate, tauric acid, and fumarate in flap tissue were increased while those of lactate, acetate and acetoacetate were significantly decreased. These findings suggest that ginsenoside Rb1 may enhance the survival of random skin flaps, potentially providing protective benefits in clinical applications.PMID:40033034 | DOI:10.1038/s41598-025-91798-z

Nat Metab. 2025 Mar 3. doi: 10.1038/s42255-025-01230-z. Online ahead of print.ABSTRACTDespite the high prevalence of neurodevelopmental disorders, the influence of maternal diet during pregnancy on child neurodevelopment remains understudied. Here we show that a western dietary pattern during pregnancy is associated with child neurodevelopmental disorders. We analyse self-reported maternal dietary patterns at 24 weeks of pregnancy and clinically evaluated neurodevelopmental disorders at 10 years of age in the COPSAC2010 cohort (n = 508). We find significant associations with attention-deficit hyperactivity disorder (ADHD) and autism diagnoses. We validate the ADHD findings in three large, independent mother-child cohorts (n = 59,725, n = 656 and n = 348) through self-reported dietary modelling, maternal blood metabolomics and foetal blood metabolomics. Metabolome analyses identify 15 mediating metabolites in pregnancy that improve ADHD prediction. Longitudinal blood metabolome analyses, incorporating five time points per cohort in two independent cohorts, reveal that associations between western dietary pattern metabolite scores and neurodevelopmental outcomes are consistently significant in early-mid-pregnancy. These findings highlight the potential for targeted prenatal dietary interventions to prevent neurodevelopmental disorders and emphasise the importance of early intervention.PMID:40033007 | DOI:10.1038/s42255-025-01230-z

Sci Rep. 2025 Mar 3;15(1):7507. doi: 10.1038/s41598-025-91965-2.ABSTRACTCOVID-19 infection has revealed significant effects on the human blood metabolome and lipoproteome, which have been coherently observed in different cohorts worldwide and across the various waves of SARS-CoV-2 pandemic. As one of the main clinical manifestations of COVID-19 is a severe acute respiratory illness, it is pertinent to explore whether this metabolic/lipoproteomic disturbance is associated with the respiratory symptoms. To this purpose we are here reporting comparative1H NMR analyses of the plasma of 252 COVID-19 patients and of patients with non-COVID-19 interstitial (24 individuals) or lobar (21 individuals) pneumonia, all matched by age, gender and disease severity. The analysis is based on 24 metabolites and 114 lipoprotein parameters. Several common traits are observed among the three groups, albeit with some peculiar features characteristic of each group. The main differences were observed between the lobar cases and all the others.PMID:40032933 | DOI:10.1038/s41598-025-91965-2

Sci Rep. 2025 Mar 3;15(1):7462. doi: 10.1038/s41598-025-87614-3.ABSTRACTLiver regeneration is a complex process crucial for recovery after partial hepatectomy (PH) or ex-vivo liver resection and autotransplantation (ELRA). This study aimed to explore the molecular mechanisms involved in liver regeneration by analyzing peripheral blood samples from three patients with alveolar echinococcosis undergoing PH and ELRA. Peripheral blood samples were collected from three patients undergoing PH and three patients undergoing ELRA at three time points: pre-operation, postoperative day 1, and postoperative day 5, as well as three healthy controls. Transcriptomic analysis was performed to identify differentially expressed genes (DEGs) using RNA sequencing, while metabolomic analysis was conducted using untargeted liquid chromatography-mass spectrometry (LC-MS). Key findings were validated through real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. Transcriptomic analysis revealed 3574 DEGs on post-operative day 1 compared to pre-operation in the ELRA group, and 3269 DEGs on post-operative day 5 compared to day 1. In the PH group, 1619 DEGs were identified on post-operative day 1 compared to pre-operation, and 896 DEGs were found on post-operative day 5 compared to day 1. Among these, 36 common genes were shared between both groups, primarily enriched in metabolic pathways. Integration of common genes, co-expression network analysis and Mfuzz clustering identified KLF14 as a gene correlated with liver regeneration processes, with its association with the PI3K-AKT pathway. Metabolomic analysis highlighted differentially expressed metabolites associated with lipid, amino acid, and energy metabolism. This study provides new insights into the molecular regulation of liver regeneration, identifying KLF14 and associated metabolic processes. These findings offer potential therapeutic targets for enhancing liver repair.PMID:40032908 | DOI:10.1038/s41598-025-87614-3

Sci Rep. 2025 Mar 3;15(1):7437. doi: 10.1038/s41598-025-89601-0.ABSTRACTHypertensive nephropathy (HN), caused by long-term poorly controlled hypertension, is the second common cause of end-stage renal disease after diabetes mellitus, but the pathogenesis of HN is unclear. The purpose of this study was to identify the biological pathways involved in the progression of HN and bile acid (BA)-related biomarkers, and to analyze the role of bile acids in HN. Download gene microarray data from Gene Expression Omnibus. Differentially expressed genes (DEGs) associated with HN were identified, and then DEGs were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis. A protein-protein interaction (PPI) network was established using DEGs to identify BA-related hub genes in combination with bile acid identical targets. An animal model of early hypertensive nephropathy was established using SHR and the concentrations of 39 bile acids were measured quantitatively in the renal cortex to screen for significantly different concentrations and to analyze the correlation between bile acid concentrations and blood pressure. A total of 398 DEGs were screened. The results of enrichment analysis identified multiple biological pathways associated with hypertension, nephropathy and bile acids. Combining PPI network and bile acid-related targets, three BA-related hub genes (APOE, ALB, SERPINA1) were identified. Quantitative analysis of bile acids revealed significant differences in the concentrations of seven bile acids (DCA, CDCA, UDCA, UCA, CA, TDCA, TCDCA). The concentrations of these bile acids showed a positive correlation with blood pressure values in SHR, with CA, DCA and TDCA showing a stronger correlation and specificity with blood pressure in SHR. Three BA-related hub genes (APOE, ALB, SERPINA1) may be involved in the early stages of HN. The concentrations of multiple bile acids were significantly elevated in the early stages of HN, with CA, DCA and TDCA being more correlated and specific with blood pressure and having higher diagnostic value. These BA-related hub genes and BAs may be involved in disease progression in the early stages of HN.PMID:40032896 | DOI:10.1038/s41598-025-89601-0

Transl Psychiatry. 2025 Mar 4;15(1):72. doi: 10.1038/s41398-025-03286-7.ABSTRACTThe heterogeneity of Major Depressive Disorder (MDD) has been increasingly recognized, challenging traditional symptom-based diagnostics and the development of mechanism-targeted therapies. This study aims to identify neuroimaging-based MDD subtypes and dissect their predominant biological characteristics using multi-omics data. A total of 807 participants were included in this study, comprising 327 individuals with MDD and 480 healthy controls (HC). The amplitude of low-frequency fluctuations (ALFF), a functional neuroimaging feature, was extracted for each participant and used to identify MDD subtypes through machine learning clustering. Multi-omics data, including profiles of genetic, epigenetics, metabolomics, and pro-inflammatory cytokines, were obtained. Comparative analyses of multi-omics data were conducted between each MDD subtype and HC to explore the molecular underpinnings involved in each subtype. We identified three neuroimaging-based MDD subtypes, each characterized by unique ALFF pattern alterations compared to HC. Multi-omics analysis showed a strong genetic predisposition for Subtype 1, primarily enriched in neuronal development and synaptic regulation pathways. This subtype also exhibited the most severe depressive symptoms and cognitive decline compared to the other subtypes. Subtype 2 is characterized by immuno-inflammation dysregulation, supported by elevated IL-1 beta levels, altered epigenetic inflammatory measures, and differential metabolites correlated with IL-1 beta levels. No significant biological markers were identified for Subtype 3. Our results identify neuroimaging-based MDD subtypes and delineate the distinct biological features of each subtype. This provides a proof of concept for mechanism-targeted therapy in MDD, highlighting the importance of personalized treatment approaches based on neurobiological and molecular profiles.PMID:40032862 | DOI:10.1038/s41398-025-03286-7

Nat Commun. 2025 Mar 3;16(1):2135. doi: 10.1038/s41467-025-57405-5.ABSTRACTMembrane contact sites between organelles are critical for the transfer of biomolecules. Lipid droplets store fatty acids and form contacts with mitochondria, which regulate fatty acid oxidation and adenosine triphosphate production. Protein compartmentalization at lipid droplet-mitochondria contact sites and their effects on biological processes are poorly described. Using proximity-dependent biotinylation methods, we identify 71 proteins at lipid droplet-mitochondria contact sites, including a multimeric complex containing extended synaptotagmin (ESYT) 1, ESYT2, and VAMP Associated Protein B and C (VAPB). High resolution imaging confirms localization of this complex at the interface of lipid droplet-mitochondria-endoplasmic reticulum where it likely transfers fatty acids to enable β-oxidation. Deletion of ESYT1, ESYT2 or VAPB limits lipid droplet-derived fatty acid oxidation, resulting in depletion of tricarboxylic acid cycle metabolites, remodeling of the cellular lipidome, and induction of lipotoxic stress. These findings were recapitulated in Esyt1 and Esyt2 deficient mice. Our study uncovers a fundamental mechanism that is required for lipid droplet-derived fatty acid oxidation and cellular lipid homeostasis, with implications for metabolic diseases and survival.PMID:40032835 | DOI:10.1038/s41467-025-57405-5

World J Microbiol Biotechnol. 2025 Mar 4;41(3):93. doi: 10.1007/s11274-025-04310-0.ABSTRACTThis study examined the impact of co-culturing Chlorella saccharophila (UTEX247) with Exiguobacterium sp. strain AMK1 on carotenoid production under nitrate-depleted conditions and 3% CO₂ supplementation. The co-culture significantly enhanced the productivity of lutein (238.31 µg.L⁻¹d⁻¹), zeaxanthin (220.72 µg.L⁻¹d⁻¹), violaxanthin (185.42 µg.L⁻¹d⁻¹), and antheraxanthin (84.07 µg.L⁻¹d⁻¹). Compared to nitrate-repleted mono-cultures, these carotenoids increased by 3.54-fold, 4.81-fold, 12.28-fold, and 9.34-fold, respectively. The violaxanthin cycle, activated by CO₂ supplementation, resulted in higher zeaxanthin production, verified through HPLC analysis. Metabolic profiling highlighted a notable rise in sucrose, an algal-specific metabolite, in the co-culture, reflecting enhanced carbon metabolism and carotenoid synthesis. Conversely, trehalose levels were significantly higher in the bacterial mono-culture (297.77 µg.mL⁻¹) than in the co-culture (88.84 µg.mL⁻¹), showing a 1.68-fold reduction as confirmed by GC-MS/MS. This suggests trehalose as a stress marker, with its reduction indicating mutualistic interactions between algal and bacterial. Overall, the co-culture strategy emerges as a promising approach to activate unexpressed pathways, generate novel metabolites, and enhance yields of valuable carotenoids like lutein and zeaxanthin. This aligns with the principles of a circular bioeconomy, leveraging bacterial biofertilizers, valorizing CO₂, and minimizing chemical dependency, thus offering potential for biorefinery applications.PMID:40032712 | DOI:10.1007/s11274-025-04310-0

Semin Immunopathol. 2025 Mar 4;47(1):19. doi: 10.1007/s00281-025-01046-9.ABSTRACTUnderstanding the role of the gut microbiota in the pathogenesis of inflammatory bowel diseases (IBD) has been an area of intense research over the past decades. Patients with IBD exhibit alterations in their microbial composition compared to healthy controls. However, studies focusing solely on taxonomic analyses have struggled to deliver replicable findings across cohorts regarding which microbial species drive the distinct patterns in IBD. The focus of research has therefore shifted to studying the functionality of gut microbes, especially by investigating their effector molecules involved in the immunomodulatory functions of the microbiota, namely metabolites. Metabolic profiles are altered in IBD, and several metabolites have been shown to play a causative role in shaping immune functions in animal models. Therefore, understanding the complex communication between the microbiota, metabolites, and the host bears great potential to unlock new biomarkers for diagnosis, disease course and therapy response as well as novel therapeutic options in the treatment of IBD. In this review, we primarily focus on promising classes of metabolites which are thought to exert beneficial effects and are generally decreased in IBD. Though results from human trials are promising, they have not so far provided a large-scale break-through in IBD-therapy improvement. We therefore propose tailored personalized supplementation of microbiota and metabolites based on multi-omics analysis which accounts for the individual microbial and metabolic profiles in IBD patients rather than one-size-fits-all approaches.PMID:40032666 | DOI:10.1007/s00281-025-01046-9

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