PubMed

Phytomedicine. 2025 Mar 18;141:156660. doi: 10.1016/j.phymed.2025.156660. Online ahead of print.ABSTRACTBACKGROUND: Vogt-Koyanagi-Harada (VKH) is a multisystemic autoimmune disorder characterized by bilateral panuveitis frequently accompanied by neurologic manifestations. While metabolic dysregulation is increasingly recognized in the context of autoimmune diseases, the role of specific metabolites in VKH disease remains unexplored.METHODS: Non-targeted and targeted metabolomics analysis, phospho-antibody array, proteome microarray, surface plasmon resonance, and molecular simulation were used to identify molecular target of OA.RESULTS: We investigated metabolic profile of VKH disease and found that oleic acid (OA) was enriched in this disease. A series of functional assays showed that OA could exacerbate experimental autoimmune uveitis (EAU) in association with increased frequency of Th1 and Th17 cells and decreased proportion of Treg cells in vitro. However, the specific molecular target of OA remains elusive. Through proteome microarrays, molecular simulations and surface plasmon resonance assays, Ornithine decarboxylase 1 (ODC1) was identified as target protein of OA. OA could bind to ODC1, increase ODC1 protein expression in both a time- and concentration-dependent manner and promote subsequently putrescine production. Phospho-antibody array analysis revealed that OA inhibited phosphorylation of STAT5A (Y694) in CD4+T cells, leading to imbalance of Th1/Th17 and Treg cells and decreased transcription of IL-10. OA upregulated ODC1 protein and putrescine levels through binding to LYS-78, inhibited phosphorylation of STAT5A protein and subsequently decreased binding of STAT5A at IL-10 promoter.CONCLUSION: These results reveals that OA could be a crucial metabolite for modulation of CD4+T cell differentiation and that ODC1-mediated phosphorylation and transcriptional activity of STAT5A contributes to development of VKH disease progression, highlighting ODC1 as a novel therapeutic target in VKH disease.PMID:40203473 | DOI:10.1016/j.phymed.2025.156660

PLoS One. 2025 Apr 9;20(4):e0321649. doi: 10.1371/journal.pone.0321649. eCollection 2025.ABSTRACTThis study aims to utilize metabolomics to elucidate the key metabolites and metabolic pathways contributing to the quality differences among the grains of 'hongyingzi' (hyz) sorghum and four other varieties naming 'jinuoliang' (Jinl), 'jinnuoliang' (Jinnl), 'lunuohong' (lnh) and 'liaoza 19' (lz19). By analyzing the metabolomics data of the five sorghum varieties, we identified a total of 384 differentially accumulated metabolites (DAMs). Among these, flavonoids, phenolic acids and lipid compounds were the most abundant, exhibiting varying degrees of upregulation and downregulation. Compared to the four cultivars, the hyz sorghum differently exhibited 78, 40, 59 and 63 flavonoids; 29, 54, 30 and 30 phenolic acids; and 9, 27, 26 and 20 lipids, respectively. Multiple comparisons among the five sorghum varieties also identified 38 common DAMs, and the flavonoid pathway is particularly significant in KEGG enrichment. Additionally, as a high tannin content variety, correlation analysis revealed in sorghum that ellagic acid-4-O-glucoside plays a central role in tannin synthesis. These findings would highlight significant differences in the metabolomic profiles between hyz and the control varieties, providing valuable insights for the exploration of key genes involved in flavonoid metabolism and biosynthesis pathways in sorghum seeds.PMID:40202990 | DOI:10.1371/journal.pone.0321649

Invest Ophthalmol Vis Sci. 2025 Apr 1;66(4):21. doi: 10.1167/iovs.66.4.21.ABSTRACTPURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease, and studies have implicated the role of gut microbiota in its pathogenesis. However, characterization of microbiome dysbiosis and associated microbial-derived metabolomic profiles across AMD stages remains unknown. In this pilot study, we explored how gut microbiome composition and gut-derived metabolites differ in AMD.METHODS: Our pilot study analyzed fasted stool samples that were collected from 22 patients at a tertiary academic center. Subjects were classified as control, intermediate AMD, or advanced AMD based on clinical presentation. 16S rRNA amplicon sequencing and standard chromatography-mass spectrometry methods were used to identify bacterial taxonomy composition and abundance of short-chain fatty acids (SCFAs) and bile acids (BAs), respectively. Genetic testing was used to investigate the frequency of 14 high-risk single nucleotide polymorphisms (SNPs) associated with AMD in the AMD cohort.RESULTS: Forty-three differentially abundant genera were present among the control, intermediate, and advanced groups. Taxa with known roles in immunologic pathways, such as Desulfovibrionales (q = 0.10) and Terrisporobacter (q = 1.16e-03), were in greater abundance in advanced AMD patients compared to intermediate. Advanced AMD patients had decreased abundance of 12 SCFAs, including acetate (P = 0.002), butyrate (P = 0.04), and propionate (P = 0.01), along with 12 BAs, including taurocholic acid (P = 0.02) and tauroursodeoxycholic acid (P = 0.04). Frequencies of high-risk SNPs were not significantly different between the intermediate and advanced AMD groups.CONCLUSIONS: This pilot study identifies distinct gut microbiome compositions and metabolomic profiles associated with AMD and its stages, providing preliminary evidence of a potential link between gut microbiota and AMD pathogenesis. To validate these findings and elucidate the underlying mechanisms, future research with larger cohorts and more comprehensive sampling is strongly recommended.PMID:40202735 | DOI:10.1167/iovs.66.4.21

Naunyn Schmiedebergs Arch Pharmacol. 2025 Apr 9. doi: 10.1007/s00210-025-04069-z. Online ahead of print.ABSTRACTRecent research has highlighted the complex relationship between gut microbiota, metabolic pathways, and nonalcoholic fatty liver disease (NAFLD) progression. Gut dysbiosis, commonly observed in NAFLD patients, impairs intestinal permeability, leading to the translocation of bacterial products like lipopolysaccharides, short-chain fatty acids, and ethanol to the liver. These microbiome-associated mechanisms contribute to intestinal and hepatic inflammation, potentially advancing NAFLD to NASH. Dietary habits, particularly those rich in saturated fats and fructose, can modify the microbiome composition, leading to dysbiosis and fatty liver development. Metabolomic approaches have identified unique profiles in NASH patients, with specific metabolites like ethanol linked to disease progression. While bariatric surgery has shown promise in preventing NAFLD progression, the role of gut microbiome and metabolites in this improvement remains to be proven. Understanding these microbiome-related pathways may provide new diagnostic and therapeutic targets for NAFLD and NASH. A comprehensive review of current literature was conducted using multiple medical research databases, including PubMed, Scopus, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov, ScienceDirect, Medline, ProQuest, and Google Scholar. The review focused on studies that examine the relationship between gut microbiota composition, metabolic pathways, and NAFLD progression. Key areas of interest included microbial dysbiosis, endotoxin production, and the influence of diet on gut microbiota. The analysis revealed that gut dysbiosis contributes to NAFLD through several mechanisms, diet significantly influences gut microbiota composition, which in turn affects liver function through the gut-liver axis. High-fat diets can lead to dysbiosis, altering microbial metabolic activities and promoting liver inflammation. Specifically, gut microbiota-mediated generation of saturated fatty acids, such as palmitic acid, can activate liver macrophages and increase TNF-α expression, contributing to NASH development. Different dietary components, including cholesterol, fiber, fat, and carbohydrates, can modulate the gut microbiome and influence NAFLD progression. This gut-liver axis plays a crucial role in maintaining immune homeostasis, with the liver responding to gut-derived bacteria by activating innate and adaptive immune responses. Microbial metabolites, such as bile acids, tryptophan catabolites, and branched-chain amino acids, regulate adipose tissue and intestinal homeostasis, contributing to NASH pathogenesis. Additionally, the microbiome of NASH patients shows an elevated capacity for alcohol production, suggesting similarities between alcoholic steatohepatitis and NASH. These findings indicate that targeting the gut microbiota may be a promising approach for NASH treatment and prevention. Recent research highlights the potential of targeting gut microbiota for managing nonalcoholic fatty liver disease (NAFLD). The gut-liver axis plays a crucial role in NAFLD pathophysiology, with dysbiosis contributing to disease progression. Various therapeutic approaches aimed at modulating gut microbiota have shown promise, including probiotics, prebiotics, synbiotics, fecal microbiota transplantation, and dietary interventions. Probiotics have demonstrated efficacy in human randomized controlled trials, while other interventions require further investigation in clinical settings. These microbiota-targeted therapies may improve NAFLD outcomes through multiple mechanisms, such as reducing inflammation and enhancing metabolic function. Although lifestyle modifications remain the primary recommendation for NAFLD management, microbiota-focused interventions offer a promising alternative for patients struggling to achieve weight loss targets.PMID:40202676 | DOI:10.1007/s00210-025-04069-z

Methods Mol Biol. 2025;2897:627-636. doi: 10.1007/978-1-0716-4406-5_42.ABSTRACTThe metabolites present in seminal plasma are products of several functions in spermatozoa, such as energy production, motility, protection, pH control, and regulation of metabolic activity, among others. The use of metabolomics tools to search for biomarkers in human and animal andrology has grown in recent years and has proven to be highly efficient. With the present technique, it was possible to identify more than 1286 molecules in seminal plasma and more than 1393 molecules in boars' sperm.PMID:40202665 | DOI:10.1007/978-1-0716-4406-5_42

Hepatology. 2025 Apr 9. doi: 10.1097/HEP.0000000000001335. Online ahead of print.ABSTRACTCollagen is the main cargo of the secretory pathway, contributing to hepatic fibrogenesis due to extensive accumulation of extracellular matrix. An excess of collagen deposition is a characteristic feature of several chronic liver diseases. Collagen overproduction imposes pressure on the secretory pathway, altering endoplasmic reticulum (ER) proteostasis. Here we investigated the possible contribution of the unfolded protein response UPR, the main adaptive pathway that monitors and adjusts protein production capacity at the ER, to collagen biogenesis and liver disease. Genetic ablation of the ER stress sensor IRE1 in the liver using conditional knockout mice reduced liver damage and collagen deposition in models of fibrosis, steatosis, and acute hepatotoxicity. Proteomic profiling identified the prolyl 4-hydroxylase (P4HB, also known as PDIA1) as a major IRE1-regulated gene, a critical factor involved in collagen maturation. Cell culture studies demonstrated that IRE1 deficiency results in collagen retention at the ER, reducing its secretion, and this phenotype is rescued by P4HB/PDIA1 overexpression. Analyses of human MASH samples revealed a positive correlation between IRE1 signaling and P4HB/PDIA1 expression as well as the severity of the disease. Altogether, our results establish a role of the IRE1/P4HB axis in the regulation of collagen production and support its implication in the pathogenesis of liver fibrosis.PMID:40202514 | DOI:10.1097/HEP.0000000000001335

Aging (Albany NY). 2025 Apr 7;17. doi: 10.18632/aging.206237. Online ahead of print.ABSTRACTSulfur amino acid restriction (SAAR), lowering the dietary concentration of sulfur amino acids methionine and cysteine, induces strong anti-obesity effects in rodents. Due to difficulties in formulating the SAAR diet for human consumption, its translation is challenging. Since our previous studies suggest a mechanistic role for low glutathione (GSH) in SAAR-induced anti-obesity effects, we investigated if the pharmacological lowering of GSH recapitulates the lean phenotype in mice on a sulfur amino acid-replete diet. Male obese C57BL6/NTac mice were fed high-fat diets with 0.86% methionine (CD), 0.12% methionine (SAAR), SAAR diet supplemented with a GSH biosynthetic precursor, N-acetylcysteine in water (NAC), and CD supplemented with a GSH biosynthetic inhibitor, DL-buthionine-(S, R)-sulfoximine in water (BSO). The SAAR diet lowered hepatic GSH but increased Nrf2, Phgdh, and serine. These molecular changes culminated in lower hepatic lipid droplet frequency, epididymal fat depot weights, and body fat mass; NAC reversed all these changes. BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver. Metabolomics data indicate that BSO and the SAAR diet induce similar changes in the kidney. Unaltered plasma aspartate and alanine transaminases and cystatin-C indicate that long-term continuous administration of BSO is safe. Data demonstrate that BSO recapitulates the SAAR-induced anti-obesity effects and that GSH plays a mechanistic role. BSO dose-response studies in animals and pilot studies in humans to combat obesity are highly warranted.PMID:40202448 | DOI:10.18632/aging.206237

mSystems. 2025 Apr 9:e0025625. doi: 10.1128/msystems.00256-25. Online ahead of print.ABSTRACTMycobacterium tuberculosis has developed a wide array of response mechanisms to various stress factors. Usnic acid has been demonstrated to be a potent antimycobacterial agent that induces stress responses and growth inhibition in many mycobacterial species. Previous studies have shown that it alters the expression of stress-responsive sigma factors, as well as the metabolites and lipid profile in M. tuberculosis H37Ra. This study was designed to examine potential differences in the strain-specific susceptibility of the virulent H37Rv strain to usnic acid. By combining lipidomic and transcriptomic analyses, we uncovered the impact of usnic acid on bacterial metabolism. The observed downregulation of key lipid classes suggested reduced metabolic activity. The simultaneous elevation of mycobactins-siderophores used by members of the genus Mycobacterium to transport free extracellular iron ions into the cytoplasm-indicated the involvement of iron in the stress response generated by usnic acid. The repressed tricarboxylic acid (TCA) cycle and oxidative phosphorylation were compensated by the upregulation of alternative energy production pathways, such as cytochrome P450 and the ferredoxin reductase system. This indicates that mycobacteria may switch to alternative electron transport mechanisms under usnic acid stress using iron-sulfur clusters to generate energy. From a therapeutic perspective, the study highlights iron metabolism as an essential drug target in mycobacteria. Simultaneously, the results confirm the strain-specific metabolic response of sister strains against the same stressing agent.IMPORTANCE: A previous study on the influence of usnic acid on the avirulent H37Ra strain revealed that the early bacterial response was associated with redox homeostasis, lipid synthesis, and nucleic acid repair. The response of bacteria to antimicrobials is specific to each species and strain. Given the genetic and phenotypic differences between the avirulent H37Ra strain and the virulent H37Rv strain, we combined lipidomics and global transcriptomics to uncover the mechanism of action of usnic acid against H37Rv. The study identified strain-specific differences between the virulent H37Rv and avirulent H37Ra. The H37Ra strain exhibited increased metabolic activity, while the H37Rv strain showed a reduction in basic metabolic processes and activated alternative iron-dependent energy production. These differences highlight the varying susceptibility of sister strains within the same species to the same antibacterial agent.PMID:40202336 | DOI:10.1128/msystems.00256-25

Mol Omics. 2025 Apr 9. doi: 10.1039/d4mo00205a. Online ahead of print.ABSTRACTThe increasing exposure to nanoparticles raises a concern over their toxicity. Incidentally, reactive oxygen species (ROS) are produced as a result of the nanoparticle's physicochemical characteristics and interactions with intracellular elements, primarily enzymes, leading to oxidative stress. In this context, the extent of oxidative stress resulting from the toxicity of titanium dioxide nanoparticles (TiO2-NPs) on the cardiovascular system has not yet been thoroughly investigated. Initially, the gel/label-free proteomics (nLC-HRMS/MS) method was used to examine human serum protein interaction and corona composition. Furthermore, different oxidative stress assays (superoxide, total ROS, mitochondrial ROS, and lipid peroxidation) and cell stress assays (apoptosis, ER stress, mitochondrial dysfunction, autophagy, and hypertrophy) were performed in conjunction with endothelial (rat aortic cells) and cardiomyoblast (H9c2) cell cultures. In addition, expression studies (RT-qPCR and immunofluorescence), kinase signalling, and siRNA-mediated gene knockout (NOX2 and XO) studies were conducted. Alongside, in ovo effects on the heart's antioxidant enzymes (SOD and CAT) and metabolomic pathways (1H NMR) confirmed the involvement of oxidative stress in cardiotoxicity. The present results demonstrate a dose-dependent increase in cytotoxicity via the activation of caspase 3 and 9. The dose-dependent increase and its synergistic relationship with cardiovascular stress signalling (ET-1 and Ang-II) highlight the significant role of oxidative stress in nanoparticle toxicity. In summary, this study expands our understanding of the precise health risks associated with human exposure by establishing a connection between the role of the redox system and molecular stress pathways in TiO2-NPs-induced cardiotoxicity.PMID:40202160 | DOI:10.1039/d4mo00205a

CNS Neurosci Ther. 2025 Apr;31(4):e70349. doi: 10.1111/cns.70349.ABSTRACTBACKGROUND: Alzheimer's disease (AD) constitutes a devastating neurodegenerative disorder, manifested by amyloid-β aggregation, phosphorylated tau accumulation, and progressive cognitive deterioration. Current therapeutic interventions remain predominantly symptomatic, underscoring the urgency for more efficacious treatment strategies.PURPOSE: This study elucidated the therapeutic potential of Sanshen San (SSS), a traditional Chinese herbal formula encompassing Polygala Radix, Pini Radix in Poria, and Acori Tatarinowii Rhizoma, on cognitive function and AD pathology.METHODS: We implemented both acute Aβ1-42-injected mice and 5xFAD transgenic mouse models. The therapeutic efficacy of SSS was assessed through behavioral paradigms including Y-maze, Novel Object Recognition, and Morris Water Maze. Molecular mechanisms were delineated utilizing RNA sequencing, metabolomics analysis, immunofluorescence staining, Golgi-Cox staining, transmission electron microscopy, and Western blotting.RESULTS: Chemical analysis unveiled 10 principal bioactive compounds in SSS. The formula substantially ameliorated cognitive performance in both Aβ1-42-injected and 5xFAD mouse models, attenuated Aβ plaque burden, and augmented microglial phagocytosis. SSS safeguarded synaptic integrity, enhanced mitochondrial function, and facilitated autophagy. Transcriptomic and metabolomic analyses demonstrated that SSS predominantly operates by reinstating synaptic transmission and neurotransmitter function, particularly in the dopaminergic system.CONCLUSION: SSS efficaciously mitigates AD pathology through potentiating synaptic function, optimizing mitochondrial homeostasis, and restoring neurotransmitter balance, exemplifying a promising multi-target therapeutic strategy for the treatment of AD.PMID:40202070 | DOI:10.1111/cns.70349

Front Plant Sci. 2025 Mar 25;16:1509193. doi: 10.3389/fpls.2025.1509193. eCollection 2025.ABSTRACTINTRODUCTION: Plant height is an important agronomic trait that not only affects crop yield but is also related to crop resistance to abiotic and biotic stresses.METHODS: In this study, we analyzed the differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) between Brazilian banana and local dwarf banana (Df19) through transcriptomics and metabolomics, and combined morphological differences and endogenous hormone content to analyze and discuss themolecular mechanisms controlling banana height.RESULTS: Sequencing data showed that a total of 2851 DEGs and 1037 DAMs were detected between Brazilian banana and local dwarf banana (Df19). The main differential biological pathways of DEGs involve plant hormone signaling transduction, Cutin, suberin and wax biosynthesis, phenylpropanoid biosynthesis, mitogen-activated protein kinase (MAPK) signaling pathway in plants, amino sugar and nucleotide sugar metabolism, etc. DAMs were mainly enriched in ATP binding cassette (ABC) transporters, amino and nucleotide sugar metabolism, glycerophospholipid metabolism, lysine degradation, and phenylalanine metabolism.DISCUSSION: Our analysis results indicate that banana plant height is the result of the synergistic effects of hormones such as abscisic acid (ABA), gibberellic acid (GA3), indole-3-acetic acid (IAA), jasmonic acid (JA), brassinosteroids (BR) and other plant hormones related to growth. In addition, transcription factors and ABC transporters may also play important regulatory roles in regulating the height of banana plants.PMID:40201783 | PMC:PMC11975952 | DOI:10.3389/fpls.2025.1509193

Front Plant Sci. 2025 Mar 25;16:1533187. doi: 10.3389/fpls.2025.1533187. eCollection 2025.ABSTRACTMacadamia integrifolia, a perennial evergreen crop valued for its nutritious nuts, also exhibits a diverse range of inflorescence colors that possess both ornamental and biological significance. Despite the economic importance of macadamia, the molecular mechanisms regulating flower coloration remain understudied. This study employed a combination of metabolomic and biochemical approaches to analyze metabolites present in inflorescences from 11 Macadamia cultivars, representing distinct color phenotypes. A total of 787 metabolites were identified through the use of ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), the majority of which were phenolic acids, flavonoids, and flavonols. Principal component analysis and clustering yielded a classification of the samples into three major flower color groups. The differential metabolites were found to be enriched in pathways such as flavonoid, flavonol, and phenylpropanoid biosynthesis, which have been demonstrated to be key contributors to color variation. Moreover, weighted gene co-expression network analysis (WGCNA) identified metabolite modules that were strongly associated with specific flower colors. This revealed that key compounds, including kaempferol, quercetin derivatives, and anthocyanins, were the primary drivers of pigmentation. This study provides a comprehensive framework for understanding the genetic, biochemical, and environmental factors influencing macadamia flower color. These findings contribute to the theoretical understanding of macadamia reproductive biology and have practical implications for molecular breeding, ornamental enhancement, and optimizing pollinator attraction to improve crop yield and ecological sustainability.PMID:40201779 | PMC:PMC11975671 | DOI:10.3389/fpls.2025.1533187

ISME Commun. 2025 Mar 22;5(1):ycaf050. doi: 10.1093/ismeco/ycaf050. eCollection 2025 Jan.ABSTRACTThe human gut microbiota plays a vital role in maintaining host health by acting as a barrier against pathogens, supporting the immune system, and metabolizing complex carbon sources into beneficial compounds such as short-chain fatty acids. Brilliant blue E-133 (BB), is a common food dye that is not absorbed or metabolized by the body, leading to substantial exposure of the gut microbiota. Despite this, its effects on the microbiota are not well-documented. In this study, we cultivated the Simplified Human Microbiota Model (SIHUMIx) in a three-stage in vitro approach (stabilization, exposure, and recovery). Using metaproteomic and metabolomic approaches, we observed significant shifts in microbial composition, including an increase in the relative abundance of Bacteroides thetaiotaomicron and a decrease in beneficial species such as Bifidobacterium longum and Clostridium butyricum. We observed lower protein abundance in energy metabolism, metabolic end products, and particularly lactate and butyrate. Disturbance in key metabolic pathways related to energy production, stress response, and amino acid metabolism were also observed, with some pathways affected independently of bacterial abundance. These functional changes persisted during the recovery phase, indicating that the microbiota did not fully return to its pre-exposure state. Our findings suggest that BB has a lasting impact on gut microbiota structure and function, raising concerns about its widespread use in the food industry. This study underscores the need for further research into the long-term effects of food colorants on the gut microbiota and their potential health implications.PMID:40201425 | PMC:PMC11977461 | DOI:10.1093/ismeco/ycaf050

Front Mol Biosci. 2025 Mar 25;12:1518873. doi: 10.3389/fmolb.2025.1518873. eCollection 2025.ABSTRACTINTRODUCTION: The bioactive compound 3,5-DiCQA, derived from Duhaldea nervosa, has been traditionally utilized in folk remedies for bone fractures and osteoporosis. However, its therapeutic mechanisms remain unclear.METHODS: We employed UHPLC-Q Exactive Orbitrap MS-based cell metabolomics to investigate the molecular mechanisms of 3,5-DiCQA in MC3T3-E1 cells. Cell proliferation was assessed via MTT assay, differentiation by alkaline phosphatase (ALP) activity, and mineralization through alizarin red staining and cetylpyridinium chloride quantification. Metabolomic profiling compared drug-treated and control groups.RESULTS: Results from MTT assays demonstrated that 3,5-DiCQA significantly promoted cell proliferation at 100 μM. Alkaline phosphatase (ALP) assays and alizarin red staining revealed enhanced osteoblast differentiation and mineralization, respectively. Calcification deposition was significantly increased in the calcified stained cells by cetylpyridinium chloride quantization, indicating that 3,5-DiCQA can promote the mineralization of MC3T3-E1 cells. Metabolomic analysis identified key metabolic changes, including the downregulation of phytosphingosine and upregulation of sphinganine and citric acid.DISCUSSION: These findings suggest that 3,5-DiCQA promotes osteoblast proliferation, differentiation and mineralization through pathways such as sphingolipid metabolism, arginine and proline metabolism, mucin type O-glycan biosynthesis and the citrate cycle (TCA cycle). This study provides insights into the therapeutic potential of 3,5-DiCQA for osteoporosis and highlights the utility of metabolomics in elucidating traditional Chinese medicine (TCM).PMID:40201241 | PMC:PMC11975594 | DOI:10.3389/fmolb.2025.1518873

Front Immunol. 2025 Mar 25;16:1483764. doi: 10.3389/fimmu.2025.1483764. eCollection 2025.ABSTRACTMyalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex chronic disease of which the underlying (molecular) mechanisms are mostly unknown. An estimated 0.89% of the global population is affected by ME/CFS. Most patients experience a multitude of symptoms that severely affect their lives. These symptoms include post-exertional malaise, chronic fatigue, sleep disorder, impaired cognitive functions, flu-like symptoms, and chronic immune activation. Therapy focusses on symptom management, as there are no drugs available. Approximately 60% of patients develop ME/CFS following an acute infection. Such a preceding infection may induce a state of trained immunity; defined as acquired, nonspecific, immunological memory of innate immune cells. Trained immune cells undergo long term epigenetic reprogramming, which leads to changes in chromatin accessibility, metabolism, and results in a hyperresponsive phenotype. Initially, trained immunity has only been demonstrated in peripheral blood monocytes and macrophages. However, more recent findings indicate that hematopoietic stem cells in the bone marrow are required for long-term persistence of trained immunity. While trained immunity is beneficial to combat infections, a disproportionate response may cause disease. We hypothesize that pronounced hyperresponsiveness of innate immune cells to stimuli could account for the aberrant activation of various immune pathways, thereby contributing to the pathophysiology of ME/CFS. In this mini review, we elaborate on the concept of trained immunity as a factor involved in the pathogenesis of ME/CFS by presenting evidence from other post-infectious diseases with symptoms that closely resemble those of ME/CFS.PMID:40201181 | PMC:PMC11975576 | DOI:10.3389/fimmu.2025.1483764

Int J Nanomedicine. 2025 Apr 4;20:4123-4144. doi: 10.2147/IJN.S500159. eCollection 2025.ABSTRACTPURPOSE: Schwann cell-derived extracellular vesicles (SCEVs) have demonstrated favorable effects in spinal cord, peripheral nerve, and brain injuries. Herein, a scalable, standardized, and efficient isolation methodology of SCEVs obtaining a high yield with a consistent composition as measured by proteomic, lipidomic, and miRNA analysis of their content is described for future clinical use.METHODS: Human Schwann cells were obtained ethically from nine donors and cultured in a defined growth medium optimized for proliferation. At confluency, the culture was replenished with an isolation medium for 48 hours, then collected and centrifuged sequentially at low and ultra-high speeds to collect purified EVs. The EVs were characterized with mass spectrometry to identify and quantify proteins, lipidomic analysis to assess lipid composition, and next-generation sequencing to confirm miRNA profiles. Each batch of EVs was assessed to ensure their therapeutic potential in promoting neurite outgrowth and cell survival.RESULTS: High yields of SCEVs were consistently obtained with similar comprehensive molecular profiles across samples, indicating the reproducibility and reliability of the isolation method. Bioactivity to increase neurite process growth was confirmed in vitro. The predominance of triacylglycerol and phosphatidylcholine suggested its role in cellular membrane dynamics essential for axon regeneration and inflammation mitigation. Of the 2517 identified proteins, 136 were closely related to nervous system repair and regeneration. A total of 732 miRNAs were cataloged, with the top 30 miRNAs potentially contributing to axon growth, neuroprotection, myelination, angiogenesis, the attenuation of neuroinflammation, and key signaling pathways such as VEGFA-VEGFR2 and PI3K-Akt signaling, which are crucial for nervous system repair.CONCLUSION: The study establishes a robust framework for SCEV isolation and their comprehensive characterization, which is consistent with their therapeutic potential in neurological applications. This work provides a valuable proteomic, lipidomic, and miRNA dataset to inform future advancements in applying SCEV to the experimental treatment of neurological injuries and diseases.PMID:40201152 | PMC:PMC11977562 | DOI:10.2147/IJN.S500159

Front Psychiatry. 2025 Mar 25;16:1499361. doi: 10.3389/fpsyt.2025.1499361. eCollection 2025.ABSTRACTBACKGROUND: Insomnia is the most prevalent sleep disorder worldwide. Electroacupuncture is effective in improving sleep quality, daytime fatigue status, and anxiety and depression in patients with insomnia, and this study aimed to investigate the metabolic pathways and their possible mechanisms in response to the efficacy of electroacupuncture in the treatment of insomnia.METHODS: A single-center, double-blind, clinical trial was the study's design. For this study, a total of 99 participants were enrolled, and they will be split into two groups: one for insomnia and the other for health. There are 33 healthy people in the healthy group and 66 insomnia patients in the insomnia group. Acupuncture treatment will be administered to the intervention group three times a week for four weeks, for a total of twelve treatments, and will be followed up for 3 months. A combination of UPLC-Q/TOF-MS and UPLC-QQQ-MS/MS was used to qualitatively and quantitatively examine the serum of 99 participants. The Pittsburgh Sleep Quality Index (PSQI) and serum metabolomics provided the primary findings. The Insomnia Severity Index (ISI), Hyperarousal Scale (HAS), Fatigue Feverity Scale (FSS), Hamilton Depression Scale (HAMD), Hamilton Anxiety Scale (HAMA), Sleep Diary and The Montreal Cognitive Assessment (MoCA) were the secondary outcomes. For the insomnia group, serum will be collected at baseline, at the end of treatment, and the scale will be collected at baseline, after 4 weeks of treatment, and at 3 months of follow-up. For the healthy group, serum will be collected at baseline.DISCUSSION: This study aimed to assess the modulatory effects of electroacupuncture on relevant metabolic markers using serum metabolomics, to explore the potential mechanisms and relevant metabolic pathways of electroacupuncture for the treatment of insomnia, and to provide strong scientific evidence for the treatment of insomnia by electroacupuncture.TRIAL REGISTRATION: ChiCTR2400085660 (China Clinical Trial Registry, http://www.chictr.org.cn, registered on June 14, 2024).PMID:40201058 | PMC:PMC11975891 | DOI:10.3389/fpsyt.2025.1499361

J Res Med Sci. 2025 Jan 30;30:4. doi: 10.4103/jrms.jrms_840_22. eCollection 2025.ABSTRACTBACKGROUND: Cardiotoxicity from chemotherapy may result in cardiomyopathy and heart failure. Clinicians can use the evaluation of cardiotoxicity-specific biomarkers, such as microRNA, as a tool for the early detection of cardiotoxicity. The study's objective was to assess miR-146a levels as a potential biomarker for the detection of cardiotoxicity brought on by chemotherapy in patients with breast cancer.MATERIALS AND METHODS: Using quantitative reverse transcription-polymerase chain reaction, the levels of miR-146a were assessed in the blood of 37 breast cancer patients receiving anthracyclines without cardiotoxicity and 33 breast cancer patients experiencing cardiotoxicity brought on by chemotherapy after chemotherapy. Left ventricular ejection fraction (LVEF) ≥50% was used to define heart failure by echocardiography.RESULTS: MiR-146a did not show any significant difference in expression between these two study groups (P = 0.48, t-test). The expression level of miR-146a was not significantly associated with LVEF, age, and body mass index (P > 0.05), according to Pearson correlation.CONCLUSION: MiR-146a may be a diagnostic or prognostic biomarker for cardiotoxicity brought on by chemotherapy, even though there was no discernible difference in the expression level of miR-146a between the control group and the breast cancer patients who were experiencing this side effect of chemotherapy. Therefore, miR-146a expression needs to be examined in a sizable cohort of breast cancer patients who are experiencing cardiotoxicity brought on by chemotherapy.PMID:40200966 | PMC:PMC11974593 | DOI:10.4103/jrms.jrms_840_22

J Agric Food Chem. 2025 Apr 9. doi: 10.1021/acs.jafc.5c03048. Online ahead of print.ABSTRACTDrought stress significantly limits crop productivity and poses a critical threat to global food security. Silica nanoparticles (SiO2NPs) have shown a potential to mitigate drought stress, but the role of the nanostructure on overall efficacy remains unclear. This study evaluated solid (SSiO2NPs), porous (PSiO2NPs), and hollow (HSiO2NPs) SiO2NPs for their effects on drought-stressed tomatoes (Solanum lycopersicum L.). Silicic acid release rates followed the order: HSiO2NPs > PSiO2NPs > SSiO2NPs > Bulk-SiO2. Compared to untreated controls, foliar application of PSiO2NPs and HSiO2NPs under drought stress significantly improved shoot Si concentrations and plants' dry weight. These treatments also enhanced antioxidant enzyme activities (catalase, peroxidase, and superoxide dismutase) and phytohormone-targeted metabolome levels (jasmonic acid, salicylic acid, and auxin), contributing to greater drought tolerance. Conversely, SSiO2NPs, silicic acid, and Bulk-SiO2 had minimal impact on plant dry weight or physiological responses. These results highlight the importance of nanoparticles architecture in alleviating drought stress and promoting sustainable agriculture.PMID:40200726 | DOI:10.1021/acs.jafc.5c03048

J Vet Pharmacol Ther. 2025 Apr 8. doi: 10.1111/jvp.13510. Online ahead of print.ABSTRACTIsavuconazole, a triazole antifungal used in humans for invasive fungal infections, may be effective for treating canine fungal infections, although data on its use in dogs is limited. This study aimed to determine the pharmacokinetics and safety of a single dose of isavuconazole in dogs, administered both intravenously and orally. Six healthy dogs received 186 mg isavuconazonium sulfate in a crossover design, with blood samples collected over 28 days and an 8-week washout period. Plasma isavuconazole and isavuconazonium concentrations were measured by liquid chromatography/mass spectrometry, and pharmacokinetic parameters were determined by non-compartmental analysis. Isavuconazole was well tolerated, with key findings including intravenous clearance at 350 ± 112 mL/kg/h, volume of distribution at steady state at 9.8 ± 4.5 L/kg, and a terminal half-life of 90 ± 44 h. For oral administration, the maximum concentration was 0.60 ± 0.27 μg/mL, time to maximum concentration was 6.73 ± 2.45 h, terminal half-life was 125 ± 80 h, and the area under the curve was 7.44 ± 2.39 μg h/mL. Oral bioavailability was 81.4% ± 12.8%. These results suggest isavuconazole has a long half-life in dogs and is well absorbed orally when administered in the fasted state. Further studies are warranted to establish a therapeutic regimen in dogs.PMID:40200720 | DOI:10.1111/jvp.13510