PubMed

Cancer Chemother Pharmacol. 2025 Jan 24;95(1):29. doi: 10.1007/s00280-025-04752-1.ABSTRACTPURPOSE: A comprehensive analysis of metabolites (metabolomics) has been proposed as a new strategy for analyzing liquid biopsies and has been applied to identify biomarkers predicting clinical responses or adverse events associated with specific treatments. Here, we aimed to identify metabolites associated with bortezomib (Btz)-related toxicities and response to treatment in newly diagnosed multiple myeloma (MM).METHODS: Fifty-four plasma samples from transplant-ineligible MM patients enrolled in a randomized phase II study comparing two less-intensive regimens of melphalan, prednisolone and Btz (MPB) were subjected to the lipidomic profiling analysis. The amount of each lipid metabolite in plasma obtained prior to MPB therapy was compared to toxicity grades and responses to MPB therapy.RESULTS: High levels of 7 phospholipids (4 lysophosphatidylcholines and 3 phosphatidylcholines) were observed in cases with Btz-induced ≥ grade 2 peripheral neuropathy (BiPN) (n = 11). In addition, low levels of 3 fatty acids (FAs)-FA (18:2), FA (18:1), and FA (22:6)-were observed in patients who developed severe skin disorders ≥ grade 2 (n = 10). No metabolite significantly associated with treatment response was identified.CONCLUSION: We conclude that levels of specific plasma lipid metabolites are associated with the severity of BiPN and skin disorders in patients with MM. These metabolites may serve as candidate biomarkers to predict Btz-induced toxicity in patients with MM before initiating Btz-containing therapy.PMID:39853402 | DOI:10.1007/s00280-025-04752-1

J Exp Med. 2025 Mar 3;222(3):e20230647. doi: 10.1084/jem.20230647. Epub 2025 Jan 24.ABSTRACTLysosomal stress due to the accumulation of nucleic acids (NAs) activates endosomal TLRs in macrophages. Here, we show that lysosomal RNA stress, caused by the lack of RNase T2, induces macrophage accumulation in multiple organs such as the spleen and liver through TLR13 activation by microbiota-derived ribosomal RNAs. TLR13 triggered emergency myelopoiesis, increasing the number of myeloid progenitors in the bone marrow and spleen. Splenic macrophages continued to proliferate and mature into macrophages expressing the anti-inflammatory cytokine IL-10. In the liver, TLR13 activated monocytes/macrophages to proliferate and mature into monocyte-derived KCs (moKCs), in which, the liver X receptor (LXR) was activated. In accumulated moKCs, tissue clearance genes such as MerTK, AXL, and apoptosis inhibitor of macrophage (AIM) were highly expressed, while TLR-dependent production of proinflammatory cytokines was impaired. Consequently, Rnaset2-/- mice were resistant to acute liver injuries elicited by acetaminophen (APAP) and LPS with D-galactosamine. These findings suggest that TLR13 activated by lysosomal RNA stress promotes the replenishment of tissue-protective Kupffer cells.PMID:39853307 | DOI:10.1084/jem.20230647

Toxics. 2025 Jan 20;13(1):65. doi: 10.3390/toxics13010065.ABSTRACTResidues of the pesticides chlorfenapyr (CFP) and emamectin benzoate (EMB) often coexist in the environment and can be accumulated in the body. To understand the impact of these two chemicals on health, we investigated their effect on the kidneys. In this study, rats were treated with CFP and/or EMB at low/medium/high doses of 1/3/9 mg/kg/day and 0.2/0.6/1.8 mg/kg/day, respectively, via oral gavage for 60 days. Kidneys and serum samples were collected and serum biochemistry and kidney histopathological changes were analyzed and examined. Kidney metabolome alterations were analyzed by using gas chromatography-mass spectrometry. The results showed that combined exposure to CFP and EMB elevated BUN levels and induced pathological damage, which presented as thinner renal tubular epithelial cells, an abnormal glomerular morphology, and an increased fibrotic area. CFP and/or EMB disrupted glutathione metabolism and carbohydrate metabolism, resulting in the alteration of kidney metabolomes and inducing oxidative stress in the cells of kidney tissues. In addition, CFP decreased ATP content and inhibited pyruvate PDH activity in the kidneys. These findings suggest that long-term exposure to CFP and EMB at environmentally relevant levels induce alterations in the renal metabolome, oxidative stress, and an insufficient energy supply, which may contribute to renal histopathological damage.PMID:39853063 | DOI:10.3390/toxics13010065

Toxics. 2025 Jan 17;13(1):64. doi: 10.3390/toxics13010064.ABSTRACT2,6-Dichloro-1,4-benzoquinone (2,6-DCBQ) is an emerging chlorinated disinfection byproduct (DBP) in bodies of water. However, this compound poses an unknown toxic effect on cyanobacteria. In this study, the toxicological mechanisms of 2,6-DCBQ in Microcystis aeruginosa (M. aeruginosa) were investigated through physiological and nontargeted metabolomic assessments. The results show that 2,6-DCBQ inhibited the growth of M. aeruginosa, reduced its photosynthetic pigment and protein contents, increased the levels of reactive oxygen species, damaged the antioxidant defense system, and aggravated the cytomembrane. Meanwhile, 2,6-DCBQ stimulated the production and release of microcystin-LR (MC-LR) and altered the transcripts of genes associated with its synthesis (mcyA, mcyD) and transport (mcyH). In addition, nontargeted metabolomics of M. aeruginosa cells exposed to 0.1 mg/L 2,6-DCBQ identified 208 differential metabolites belonging to 10 metabolic pathways and revealed the considerable interference caused by 2,6-DCBQ among ABC transporters, the two-component system, and folate biosynthesis. This study deepens the understanding of the physiological and nontargeted metabolomic responses of M. aeruginosa exposed to 2,6-DCBQ, offers insights into the toxic effect of 2,6-DCBQ on M. aeruginosa, and provides a theoretical basis for the ecological risk assessment of emerging DBPs in accordance with water quality criteria.PMID:39853062 | DOI:10.3390/toxics13010064

Toxins (Basel). 2025 Jan 11;17(1):33. doi: 10.3390/toxins17010033.ABSTRACTFusarium fungi are widespread pathogens of food crops, primarily associated with the formation of mycotoxins. Therefore, effective mitigation strategies for these toxicogenic microorganisms are required. In this study, the potential of pulsed electric field (PEF) as an advanced technology of increasing use in the food processing industry was investigated to minimize the viability of Fusarium pathogens and to characterize the PEF-induced changes at the metabolomic level. Spores of four Fusarium species (Fusarium culmorum, Fusarium graminearum, Fusarium poae, and Fusarium sporotrichioides) were treated with PEF and cultured on potato dextrose agar (PDA) plates. The viability of the Fusarium species was assessed by counting the colony-forming units, and changes in the mycotoxin content and metabolomic fingerprints were evaluated by using UHPLC-HRMS/MS instrumental analysis. For metabolomic data processing and compound identification, the MS-DIAL (v. 4.80)-MS-CleanR-MS-Finder (v. 3.52) software platform was used. As we found out, both fungal viability and the ability to produce mycotoxins significantly decreased after the PEF treatment for all of the species tested. The metabolomes of the treated and untreated fungi showed statistically significant differences, and PEF-associated biomarkers from the classes oxidized fatty acid derivatives, cyclic hexapeptides, macrolides, pyranocoumarins, carbazoles, and guanidines were identified.PMID:39852986 | DOI:10.3390/toxins17010033

J Cell Biol. 2025 Apr 7;224(4):e202406099. doi: 10.1083/jcb.202406099. Epub 2025 Jan 24.ABSTRACTArginylation is the posttranslational addition of arginine to a protein by arginyltransferase-1 (ATE1). Previous studies have found that ATE1 targets multiple cytoskeletal proteins, and Ate1 deletion causes cytoskeletal defects, including reduced cell motility and adhesion. Some of these defects have been linked to actin arginylation, but the role of other arginylated cytoskeletal proteins has not been studied. Here, we characterize tubulin arginylation and its role in the microtubule cytoskeleton. We identify ATE1-dependent arginylation of ⍺-tubulin at E77. Ate1-/- cells and cells overexpressing non-arginylatable ⍺-tubulinE77A both show a reduced microtubule growth rate and increased microtubule stability. Additionally, they show an increase in the fraction of the stabilizing protein MAP1S associated with microtubules, suggesting that E77 arginylation directly regulates MAP1S binding. Knockdown of Map1s is sufficient to rescue microtubule growth rate and stability to wild-type levels. Together, these results demonstrate a new type of tubulin regulation by posttranslational arginylation, which modulates microtubule growth rate and stability through the microtubule-associated protein, MAP1S.PMID:39852692 | DOI:10.1083/jcb.202406099

Anal Chem. 2025 Jan 24. doi: 10.1021/acs.analchem.4c05823. Online ahead of print.ABSTRACTUrea is an important biomarker for diagnosing various kidney and liver disorders. However, many existing methods rely on invasive blood sampling, which can potentially harm patients. Saliva has been recently recognized as a noninvasive and easily collectible alternative to blood for urea quantification. Electrochemical urea detection in saliva remains limited, with catalytic materials typically applied to the electrode surface via drop casting. This results in a random distribution of materials and potential aggregation on the electrode, which inevitably hinders the efficient mass transport of analytes, reducing both detection sensitivity and the utilization of catalytic materials. In this work, a silver nanoparticle (AgNP)-integrated microdisc array electrode chip was fabricated through the in situ growth of AgNPs on polydopamine (PDA) arrays, which were patterned using the microcontact printing (μCP) technique on an indium tin oxide (ITO) glassy substrate. The resulting AgNP microdisc array chip sensor exhibited much higher sensitivity toward urea sensing and greater material utilization as compared to traditional drop-cast electrodes, due to the enhanced mass transfer. Furthermore, the chip sensors demonstrated superior selectivity when challenged with potential interferences. More importantly, reliable urea quantification was achieved in clinical saliva samples from nephritis patients. These results indicate that the current sensor presents great opportunities for developing a noninvasive and sensitive liquid biopsy platform for urea determination in clinical diagnosis applications.PMID:39852680 | DOI:10.1021/acs.analchem.4c05823

Mar Drugs. 2025 Jan 20;23(1):49. doi: 10.3390/md23010049.ABSTRACTNeuroinflammation and neuronal cell death are leading causes of death in the elderly and underlie various neurodegenerative diseases. These diseases involve complex pathophysiological mechanisms, including inflammatory responses, oxidative stress, and ferroptosis. Compounds derived from deep-sea fungi exhibit low toxicity and potent neuroprotective effects, offering a promising source for drug development. In this study, we isolated 44 natural products from deep-sea-derived fungi and identified isobisvertinol (17) as a compound with anti-inflammatory and ferroptosis-inhibiting effects. Using LPS-induced microglial inflammation and RSL3-induced neuronal ferroptosis models, we found that 17 targets TLR4 to provide neuroprotection. Molecular docking studies revealed that 17 inhibits TLR4 activation by occupying the hydrophobic pocket at the TLR4-MD2 binding site. Additionally, 17 suppresses TLR4, reducing p38 MAPK phosphorylation, and inhibits ferroptosis by decreasing lipid peroxidation and modulating mitochondrial membrane potential. Metabolomic analysis showed that 17 rescues alterations in multiple metabolic pathways induced by RSL3 and increases levels of antioxidant metabolites, including glutamine, glutamate, and glutathione. In summary, our results indicate that isobisvertinol (17) targets TLR4 in neural cells to reduce inflammation and inhibit p38 MAPK phosphorylation, while regulating metabolic pathways, mainly GSH synthesis, to provide antioxidant effects and prevent ferroptosis in neurons.PMID:39852551 | DOI:10.3390/md23010049

Mar Drugs. 2025 Jan 14;23(1):40. doi: 10.3390/md23010040.ABSTRACTThe optimization of bioactive compound extraction from Fucus vesiculosus using ultrasound-assisted extraction (UAE) via sonotrode was investigated to maximize phenolic recovery and antioxidant activity while promoting a sustainable process. Optimal conditions (40% v/v ethanol in water, 38 min, 36% amplitude) were selected to maximize phenolic recovery while considering environmental and energy sustainability by optimizing extraction efficiency and minimizing solvent and energy usage. HPLC-ESI-QTOF-MS analysis tentatively identified 25 phenolic compounds, including sulfated phenolic acids, phlorotannins, flavonoids, and halophenols, with some reported for the first time in F. vesiculosus, underscoring the complexity of this alga's metabolome. The antioxidant activity of the optimized extract was evaluated through FRAP (143.7 µmol TE/g), DPPH (EC50 105.6 µg/mL), and TEAC (189.1 µmol Trolox/g) assays. The optimized process highlights F. vesiculosus as a valuable source of natural antioxidants, with potential applications in biotechnology, cosmetics, and food industries.PMID:39852542 | DOI:10.3390/md23010040

Mar Drugs. 2024 Dec 28;23(1):10. doi: 10.3390/md23010010.ABSTRACTThe waters around the western Antarctic Peninsula are experiencing fast warming due to global change, being among the most affected regions on the planet. This polar area is home to a large and rich community of benthic marine invertebrates, such as sponges, tunicates, corals, and many other animals. Among the sponges, the bright yellow Dendrilla antarctica is commonly known for using secondary diterpenoids as a defensive mechanism against local potential predators. From the dichloromethane extract of sponge samples from Deception Island collected in January 2023, we isolated a novel derivative with an unusual β-lactone diterpene skeleton here named dendrillolactone (1), along with seven previously described diterpenes, including deceptionin (2), a gracilane norditerpene (3), cadlinolide C (4), a glaciolane norditerpene (5), membranolide (6), aplysulphurin (7), and tetrahydroaplysulphurine-1 (8). Here, we also report our studies on the changes in the chemical arsenal of this sponge by slow temperature increase in aquaria experiments. Despite being a species capable of inhabiting volcanically active areas, with frequent water temperature fluctuations due to the existing fumaroles, the results show that diterpenes such as deceptionin, cadlinolide C, membranolide, and tetrahydroaplysulphurin-1 seem to be susceptible to the temperature increase, resulting in a trend to higher concentrations. However, temperatures above 4 °C severely affected sponge metabolism, causing its death much earlier than expected. Further research on the roles of these natural products in D. antarctica and their relationship to the sponge's resilience to environmental changes should help to better understand the defensive mechanisms of Antarctic marine benthos in the context of global change.PMID:39852512 | DOI:10.3390/md23010010

J Fungi (Basel). 2025 Jan 19;11(1):78. doi: 10.3390/jof11010078.ABSTRACTFloccularia luteovirens (F. luteovirens) has garnered increasing attention as an ingredient in both the pharmaceutical and food industries. Depending on the drying method, the accumulation of metabolites can greatly affect the quality. This research employed an untargeted metabolomics (LC-MS/MS) strategy to elucidate the similarities and differences in the morphological characteristics, microstructure, antioxidant capacity, and metabolic profiles of F. luteovirens subjected to three distinct drying methods: natural air-drying (YG), oven-drying (HG), and vacuum freeze-drying (DG). Our findings indicated that the color of F. luteovirens samples dried using the YG and HG methods was yellow-brown, exhibiting a high degree of browning, whereas the samples processed by the DG method displayed a golden-yellow hue and a desirable fullness. Regarding microstructure, the F. luteovirens samples from the YG and HG methods exhibited small and unevenly distributed pores, in contrast to the samples from the DG method, which were structurally intact and characterized by large inter-tissue pores. The antioxidant activity exhibited by F. luteovirens samples, which were processed using the DG method, was found to be significantly superior compared to the antioxidant activity of samples dried using two other methods. A correlation analysis indicated a significant link between antioxidant capacity and lipid as well as lipid-like molecules. Metabolomic analysis identified 1617 metabolites across 15 superclasses, with lipids, lipid-like molecules, organic acids and derivatives, and organic heterocyclic compounds being the predominant metabolites in F. luteovirens. Furthermore, KEGG enrichment analysis highlighted 20 pathways, indicating that the metabolism of amino acids could be significantly involved in the metabolic processes linked to the drying of F. luteovirens. This research clarifies how different drying techniques impact the metabolites or metabolic pathways of F. luteovirens, identifying the mechanisms that influence its quality and providing a reference for optimizing its processing and storage.PMID:39852497 | DOI:10.3390/jof11010078

J Fungi (Basel). 2025 Jan 13;11(1):57. doi: 10.3390/jof11010057.ABSTRACTGanoderma lucidum is a traditional Chinese medicinal fungus, and ganoderma triterpenoids (GTs) are one of the main bioactive compounds. These compounds have various pharmacological functions, including anti-tumor, antioxidant, anti-inflammatory, liver-protective, and immune-regulating effects. However, the manner in which they accumulate, and their biosynthesis mechanisms remain unclear. To screen for the genes that are involved in the biosynthetic pathway of GTs, this study analyzed the differential metabolites and differentially expressed genes (DEGs) among different growth stages of G. lucidum, including the primordia (P), the matured fruiting body (FM), and the post-spore fruiting bodies (FP) using targeted metabolomics and transcriptomics analysis, respectively. The results showed that a total of 699 components were detected, including lignans, terpenoids, amino acids and derivatives, and phenolic acids, among others. Among them, a total of 112 types of triterpenes were detected. Compared with the primordia, there were eight differential metabolites of triterpenoids, with three decreasing and five increasing in the FM stage. A comparison between the FM stage and the FP stage revealed that there were 13 differential metabolites of triterpenoids. A transcriptomics analysis showed that there were 371 DEGs in the P_vs_FM group, including 171 down-regulated genes and 200 up-regulated genes. In the FM_vs_FP group, 2567 DEGs were identified, with 1278 down-regulated genes and 1289 up-regulated genes. Through targeted metabolomics and transcriptome correlation analysis, six TFs and two CYP450s were significantly associated with four triterpenoid components. The results showed that these TFs and CYP450s were positively or negatively correlated with the four triterpenoid components. In addition, interestingly, some flavonoids and phenolic compounds, which have been reported in plants, were also detected in G. lucidum, indicating that it has the potential to be engineered into a strain capable of synthesizing flavonoid compounds. This study provides useful information about key genes involved in GT biosynthesis, but further exploration and in-depth research are needed to better understand the functions of these genes.PMID:39852476 | DOI:10.3390/jof11010057

J Fungi (Basel). 2025 Jan 9;11(1):51. doi: 10.3390/jof11010051.ABSTRACTOphiocordyceps sinensis is a fungus that is cultured through fermentation from wild Chinese cordyceps. While studies have examined its metabolites, the evaluation of its antioxidant capacity remains to be conducted. The antioxidant results of O. sinensis indicate that the ferric ion-reducing antioxidant power (FRAP), antioxidant capacity (2.74 ± 0.12 μmol Trolox/g), 2,2-diphenyl-1-picrylhydrazyl (DPPH•) free radical scavenging rate (60.21 ± 0.51%), and the hydroxyl free radical scavenging rate (91.83 ± 0.68%) reached a maximum on day 30. Using LC-MS/MS to measure the metabolites on D24, D30, and D36, we found that the majority of the differential accumulated metabolites (DAMs) primarily accumulate in lipids, organoheterocyclic compounds, and organic acids and their derivatives. Notably, the DAMs exhibiting high peaks include acetylcarnitine, glutathione, linoleic acid, and L-propionylcarnitine, among others. The transcriptome analysis results indicate that the differentially expressed genes (DEGs) exhibiting high expression peaks on D30 primarily included lnaA, af470, and ZEB1; high expression peaks on D24 comprised SPBC29A3.09c and YBT1; high expression peaks on D36 included dtxS1, PA1538, and katG. The combined analysis revealed significant and extremely significant positive and negative correlations between all the DAMs and DEGs. The primary enriched pathways (p < 0.05) included glutathione metabolism, tryptophan metabolism, carbon metabolism, biosynthesis of secondary metabolites, and phenylalanine metabolism. The metabolic pathway map revealed that the DAMs and DEGs influencing the antioxidant activity of O. sinensis were significantly up-regulated on D30 but down-regulated on D36. The correlation analysis suggests that an increase in the content of DEGs and DAMs promotes an increase in the levels of enzyme and non-enzyme substances, ultimately enhancing the antioxidant capacity of O. sinensis. These findings serve as a reference of how DAMs and DEGs affect the antioxidant activity of O. sinensis. This may contribute to the enhanced development and application of O. sinensis.PMID:39852470 | DOI:10.3390/jof11010051

J Fungi (Basel). 2024 Dec 31;11(1):21. doi: 10.3390/jof11010021.ABSTRACTThe basidiomycete Crucibulum laeve strain LE-BIN1700 (Agaricales, Nidulariaceae) is able to grow on agar media supplemented with individual components of lignocellulose such as lignin, cellulose, xylan, xyloglucan, arabinoxylan, starch and pectin, and also to effectively destroy and digest birch, alder and pine sawdust. C. laeve produces a unique repertoire of proteins for the saccharification of the plant biomass, including predominantly oxidative enzymes such as laccases (family AA1_1 CAZymes), GMC oxidoreductases (family AA3_2 CAZymes), FAD-oligosaccharide oxidase (family AA7 CAZymes) and lytic polysaccharide monooxygenases (family LPMO X325), as well as accompanying acetyl esterases and loosenine-like expansins. Metabolomic analysis revealed that, specifically, monosaccharides and carboxylic acids were the key low molecular metabolites in the C. laeve culture liquids in the experimental conditions. The proportion of monosaccharides and polyols in the total pool of identified compounds increased on the sawdust-containing media. Multiple copies of the family AA1_1, AA3_2, AA7 and LPMOs CAZyme genes, as well as eight genes encoding proteins of the YvrE superfamily (COG3386), which includes sugar lactone lactonases, were predicted in the C. laeve genome. According to metabolic pathway analysis, the litter saprotroph C. laeve can catabolize D-gluconic and D-galacturonic acids, and possibly other aldonic acids, which seems to confer certain ecological advantages.PMID:39852439 | DOI:10.3390/jof11010021

J Fungi (Basel). 2024 Dec 28;11(1):14. doi: 10.3390/jof11010014.ABSTRACTPenicillium expansum is a ubiquitous pathogenic fungus that causes blue mold decay of apple fruit postharvest, and another member of the genus, Penicillium chrysogenum, is a well-studied saprophyte valued for antibiotic and small molecule production. While these two fungi have been investigated individually, a recent discovery revealed that P. chrysogenum can block P. expansum-mediated decay of apple fruit. To shed light on this observation, we conducted a comparative genomic, transcriptomic, and metabolomic study of two P. chrysogenum (404 and 413) and two P. expansum (Pe21 and R19) isolates. Global transcriptional and metabolomic outputs were disparate between the species, nearly identical for P. chrysogenum isolates, and different between P. expansum isolates. Further, the two P. chrysogenum genomes revealed secondary metabolite gene clusters that varied widely from P. expansum. This included the absence of an intact patulin gene cluster in P. chrysogenum, which corroborates the metabolomic data regarding its inability to produce patulin. Additionally, a core subset of P. expansum virulence gene homologues were identified in P. chrysogenum and were similarly transcriptionally regulated in vitro. Molecules with varying biological activities, and phytohormone-like compounds were detected for the first time in P. expansum while antibiotics like penicillin G and other biologically active molecules were discovered in P. chrysogenum culture supernatants. Our findings provide a solid omics-based foundation of small molecule production in these two fungal species with implications in postharvest context and expand the current knowledge of the Penicillium-derived chemical repertoire for broader fundamental and practical applications.PMID:39852433 | DOI:10.3390/jof11010014

J Fungi (Basel). 2024 Dec 24;11(1):3. doi: 10.3390/jof11010003.ABSTRACTNatural compounds derived from microorganisms, especially those with antioxidant and anticancer properties, are gaining attention for their potential applications in biomedical, cosmetic, and food industries. Marine fungi, such as Asteromyces cruciatus, are particularly promising due to their ability to produce bioactive metabolites through the degradation of marine algal polysaccharides. This study investigates the metabolic diversity of A. cruciatus grown on different carbon sources: glucose, Durvillaea spp., and Macrocystis pyrifera. Crude extracts of fungal biomass were analyzed for total phenolic content (TPC), antioxidant capacity (TAC), toxicity, and phenolic compound identification using ultra-high-performance liquid chromatography coupled with high-resolution electrospray ionization mass spectrometry (UHPLC-MS/MS). The analysis revealed the presence of anthraquinone compounds, including emodin (0.36 ± 0.08 mg/g DW biomass) and citrereosein in glucose medium and citrereosein and endocrocin in M. pyrifera medium. No such compounds were detected in Durvillaea spp. medium. The glucose-grown extract exhibited the highest TPC (3.09 ± 0.04 mg GAE/g DW) and TAC (39.70 ± 1.0 µmol TEq/g biomass). Additionally, no detrimental effects were observed on a neuronal cell line. These findings highlight the influence of carbon sources on the production of bioactive metabolites and their functional properties, providing valuable insights into the biotechnological potential of A. cruciatus.PMID:39852423 | DOI:10.3390/jof11010003

Metabolites. 2025 Jan 20;15(1):66. doi: 10.3390/metabo15010066.ABSTRACTIntroduction: This study aimed to capture the early metabolic changes before osteoporosis occurs and identify metabolomic biomarkers at the osteopenia stage for the early prevention of osteoporosis. Materials and Methods: Metabolomic data were generated from normal, osteopenia, and osteoporosis groups with 320 participants recruited from the Nicheng community in Shanghai. We conducted individual edge network analysis (iENA) combined with a random forest to detect metabolomic biomarkers for the early warning of osteoporosis. Weighted Gene Co-Expression Network Analysis (WGCNA) and mediation analysis were used to explore the clinical impacts of metabolomic biomarkers. Results: Visual separations of the metabolic profiles were observed between three bone mineral density (BMD) groups in both genders. According to the iENA approach, several metabolites had significant abundance and association changes in osteopenia participants, confirming that osteopenia is a critical stage in the development of osteoporosis. Metabolites were further selected to identify osteopenia (nine metabolites in females; eight metabolites in males), and their ability to discriminate osteopenia was improved significantly compared to traditional bone turnover markers (BTMs) (female AUC = 0.717, 95% CI 0.547-0.882, versus BTMs: p = 0.036; male AUC = 0.801, 95% CI 0.636-0.966, versus BTMs: p = 0.007). The roles of the identified key metabolites were involved in the association between total fat-free mass (TFFM) and osteopenia in females. Conclusion: Osteopenia was identified as a tipping point during the development of osteoporosis with metabolomic characteristics. A few metabolites were identified as candidate early-warning biomarkers by machine learning analysis, which could indicate bone loss and provide new prevention guidance for osteoporosis.PMID:39852408 | DOI:10.3390/metabo15010066

Metabolites. 2025 Jan 20;15(1):65. doi: 10.3390/metabo15010065.ABSTRACTBACKGROUND: Postoperative ileus (POI) is a common postoperative clinical complication that significantly affects postoperative rehabilitation and quality of life in patients and can even produce secondary complications, leading to serious consequences. External treatment using Shenhuang Plaster (SHP) (Shenque acupoint administration) has definite effects and unique advantages in the prevention and treatment of POI, but its mechanism is not completely clear. In this study, we investigated the therapeutic mechanism behind the effect of Shenhuang Plaster applied to the Shenque acupoint on gastrointestinal motility in POI mice based on metabolomics.MATERIALS AND METHODS: C57BL/6 mice were divided into three groups: blank control (Ctrl), model (POI), and intervention (POI + SHP) groups. SHP treatment was started 3 days before modeling. We employed several behavioral tests and gastrointestinal transit function measurements and performed qRT-PCR analysis, 16S rRNA gene sequencing, and metabolomics analysis on serum metabolites.RESULTS: We found that SHP could reduce the mRNA expression of inflammatory mediators in the smooth muscle tissue of the small intestine, regulate the structure and function of the intestinal microbiota, and modulate serum phenylalanine, carnitine, and glutamic acid levels.CONCLUSIONS: POI mice had obvious intestinal flora disorders and metabolic disorders of amino acids and their derivatives, and there was a significant correlation between differential flora and differential metabolites. SHP could effectively regulate the concentration of intestinal flora and serum metabolites and the metabolic pathway related to amino acids in vivo and, ultimately, achieve a therapeutic purpose in POI. In this study, it was found, for the first time, that applying SHP to the Shenque acupoint could effectively regulate the serum metabolites of phenylalanine, carnitine, and glutamate, and improve postoperative intestinal motile disturbance through association with the intestinal flora.PMID:39852407 | DOI:10.3390/metabo15010065

Metabolites. 2025 Jan 16;15(1):62. doi: 10.3390/metabo15010062.ABSTRACTBlood microsampling (BμS) has recently emerged as an interesting approach in the analysis of endogenous metabolites but also in metabolomics applications. Their non-invasive way of use and the simplified logistics that they offer renders these technologies highly attractive in large-scale studies, especially the novel quantitative microsampling approaches such as VAMs or qDBS. Objectives: Herein, we investigate the potential of BµS devices compared to the conventional plasma samples used in global untargeted mass spectrometry-based metabolomics of blood. Methods: Two novel quantitative devices, namely, Mitra, Capitainer, and the widely used Whatman cards, were selected for comparison with plasma. Venous blood was collected from 10 healthy, overnight-fasted individuals and loaded on the devices; plasma was also collected from the same venous blood. An extraction solvent optimization study was first performed on the three devices before the main study, which compared the global metabolic profiles of the four extracts (three BµS devices and plasma). Analysis was conducted using reverse phase LC-TOF MS in positive mode. Results: BµS devices, especially Mitra and Capitainer, provided equal or even superior information on the metabolic profiling of human blood based on the number and intensity of features and the precision and stability of some annotated metabolites compared to plasma. Despite their rich metabolic profiles, BµS did not capture metabolites associated with biological differentiation of sexes. Conclusions: Overall, our results suggest that a more in-depth investigation of the acquired information is needed for each specific application, as a metabolite-dependent trend was obvious.PMID:39852404 | DOI:10.3390/metabo15010062

Metabolites. 2025 Jan 16;15(1):58. doi: 10.3390/metabo15010058.ABSTRACTBACKGROUND/OBJECTIVES: The transition from a non-lactating to a lactating state is a critical period for lipid metabolism in dairy cows. Danggui Buxue Tang (DBT), stimulating energy metabolism, ameliorates diseases related to lipid metabolism disorders and is expected to be an effective supplement for alleviating excessive lipid mobilisation in periparturient dairy cows. This study aimed to investigate the effects of supplemental DBT on serum biochemical indices, faecal microbial communities, and plasma metabolites in dairy cows.METHODS: Thirty cows were randomly divided into three groups: H-DBT group, L-DBT group, and control group. DBT administration was started on the day of calving and continued once daily for seven days. Faecal and blood samples were collected on calving day, 7 days after calving, and 14 days after calving. The levels of serum biochemical indices were measured at three time points in the three groups using commercial kits. Cows in the H-DBT group and control group were selected for metabolome and 16S rRNA amplicon sequencing.RESULTS: Our research shows that, in dairy cows 7 days postpartum, DBT significantly reduced serum 3-hydroxybutyric acid (BHB) concentrations and the number of cows with BHB concentrations ≥ 1 mmol/L. Additionally, DBT increased serum total cholesterol contents at both 7 and 14 days postpartum. Analysis of the microbiota community showed that DBT modulated the composition and structure of the hindgut microbiota. Metabolomic analysis revealed decreased plasma acetylcarnitine, 2-hydroxybutyric acid, and BHB levels 7 days postpartum, whereas the TCA cycle was enhanced. At 14 days postpartum, DBT altered the plasma bile acid profile, especially glycine-conjugated bile acids, including GCDCA, GUDCA, and GDCA. Correlation analyses showed that the relative abundances of Bacillus, Solibacillus, Dorea, and Romboutsia were strongly correlated with the differential metabolites, which is crucial for the beneficial effects of DBT.CONCLUSIONS: DBT improves energy status and lipid metabolism in postpartum dairy cows by modulating hindgut microbiota and serum lipid metabolites.PMID:39852401 | DOI:10.3390/metabo15010058