PubMed

J Orthop Translat. 2025 Jan 22;51:37-50. doi: 10.1016/j.jot.2024.12.008. eCollection 2025 Mar.ABSTRACTBACKGROUND: Fresh osteochondral allografts (OCAs) contain numerous immunogenic components in the subchondral bone (SB). Whether high-speed centrifugation (HSC) reduces immune rejection by removing bone marrow elements (BMEs), compared to methods without HSC, remains unknown. This study aimed to validate the efficacy and safety of HSC in reducing immune rejection by removing allogeneic BMEs.METHODS: OCAs were obtained from the femoral condyles of the stifle joint in 18 pigs. Gross observations, histological staining, weight measurements, and DNA extraction were performed to assess the effects of centrifugation speed and duration on BMEs removal in OCAs. The effect of HSC on OCAs preservation was determined in vitro using microbiological testing, live/dead cell staining, and histological staining. Moreover, the co-culture effect of RAW264.7 cells and OCAs with or without HSC in vitro was evaluated using enzyme-linked immunosorbent assay (ELISA), histological staining, and immunohistochemical staining. The transplantation effect of OCAs with or without HSC was examined in vivo using a subcutaneous mouse model. Finally, the residues in the centrifuge tubes were analysed using ELISA, haematoxylin and eosin (HE) staining, and metabolomic analysis.RESULTS: Centrifugal speeds of 12000 rpm for 1 min were sufficient to reduce BMEs by over 90 %. HSC had a protective effect on chondrocytes and the extracellular matrix during the in vitro preservation of OCAs. In addition, OCAs using the HSC method exhibited reduced recognition by the host immune system compared with OCAs without HSC, thereby reducing immune rejection. Lipids were the most abundant and difficult-to-remove antigenic components and are the most likely to affect host macrophage polarisation, playing an important role in immune rejection.CONCLUSION: Our study demonstrated that HSC method significantly reduces immune rejection by removing BMEs from OCAs.THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Our study demonstrated that HSC is a simple, efficient, and safe physical method for removing antigenic components from OCAs, effectively reducing immune rejection and highlighting its clinical potential.PMID:39906333 | PMC:PMC11791335 | DOI:10.1016/j.jot.2024.12.008

Front Vet Sci. 2025 Jan 21;12:1527284. doi: 10.3389/fvets.2025.1527284. eCollection 2025.ABSTRACTCottonseed meal is a promising alternative to soybean meal in poultry feed, but concerns over free gossypol limit its use. Although the general toxicity of free gossypol is well-known, its specific effects on the liver-the primary site where it accumulates-are less thoroughly studied, particularly at the molecular level. This study investigated the hepatotoxic effects of gossypol acetate (GA) on goslings through a comprehensive analysis combining morphology, transcriptomics, and metabolomics. Forty-eight 7-day-old male goslings with similar body weight (BW) were randomly assigned to two groups: a control group, receiving a saline solution (0.9%, 2.5 mL/kg BW), and a GA-treated group, administered GA at 50 mg/kg BW orally for 14 days. Histological analysis revealed signs of liver damage, including granular degeneration, hepatocyte enlargement, necrosis, and mitochondrial injury. Transcriptomic analysis identified 1,137 differentially expressed genes, with 702 upregulated and 435 downregulated. Key affected pathways included carbon metabolism, glycolysis/gluconeogenesis, pyruvate metabolism, propanoate metabolism, TCA cycle, fatty acid degradation, primary bile acid biosynthesis, tryptophan metabolism, cysteine and methionine metabolism, focal adhesion, and the PPAR signaling pathway. Metabolomic analysis revealed 109 differential metabolites, 82 upregulated and 27 downregulated, implicating disruptions in linoleic acid metabolism, arachidonic acid metabolism, cAMP signaling, and serotonergic synapse pathways. Overall, GA-induced hepatotoxicity involves impaired energy production, disrupted lipid metabolism, and abnormal liver focal adhesion, leading to liver cell dysfunction. These findings highlight the vulnerability of mitochondria and critical metabolic pathways, providing insights into the molecular mechanisms of GA toxicity and guiding future studies on mitigating GA-induced liver damage in goslings.PMID:39906302 | PMC:PMC11792171 | DOI:10.3389/fvets.2025.1527284

Front Plant Sci. 2025 Jan 21;15:1483538. doi: 10.3389/fpls.2024.1483538. eCollection 2024.ABSTRACTAstragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao (AMM) is an important medicinal plant that is used for both medicine and food. It is widely used in Asia and South Asia. It is normally cultivated by transplanting the annual rhizomes. Understanding the dormancy of underground buds of AMM is essential for its harvest and transplantation. Despite thorough research on bud dormancy in perennial woody plants, perennial herbs, and especially medicinal plants, such as AMM, have rarely been studied. We analyzed the transcriptome and non-targeted metabolome of dormant buds stage-by-stage to investigate the regulatory mechanism of the transition from endo- to ecodormancy. A total of 1,069 differentially accumulated metabolites (DAMs) participated in amino acid and carbohydrate metabolism. Transcriptome analysis revealed 16,832 differentially expressed genes (DEGs). Functional enrichment analysis indicated that carbohydrate metabolism, hormone signaling pathways, and amino acid metabolism contributed to the transition from endo- to ecodormancy. Starch and sucrose metabolism and hormone signaling pathways were mainly analyzed in the transition between different dormancy states. During the transition from endo- to ecodormancy, the highest content of indole-3-acetic acid (IAA) and the highest number of DEGs enriched in the IAA signaling pathway demonstrated that IAA may play a key role in this process. We obtained candidate genes through co-expression network analysis, such as BGL, GN, glgC, and glgB, which are involved in starch and sucrose metabolism. The transcription factors MYB, ERF, bHLH, zinc finger, and MADS-box may regulate the genes involved in hormone signal transduction and starch and sucrose metabolism, which are critical for regulating the transition from endo- to ecodormancy in AMM buds. In summary, these results provide insights into the novel regulatory mechanism of the transition of endo- to ecodormancy in underground buds of AMM and offer new analytical strategies for breaking dormancy in advance and shortening breeding time.PMID:39906223 | PMC:PMC11790638 | DOI:10.3389/fpls.2024.1483538

Anal Chem. 2025 Feb 5. doi: 10.1021/acs.analchem.4c05530. Online ahead of print.ABSTRACT1H NMR spectroscopy has enabled the quantitative profiling of metabolites in various biofluids, emerging as a possible diagnostic tool for metabolic disorders and other diseases. To boost the signal-to-noise ratio and detect proton resonances near the water signal, current 1H NMR experiments require solvent suppression schemes (e.g., presaturation, jump-and-return, WATERGATE, excitation sculpting, etc.). Unfortunately, these techniques affect the quantitative assessment of analytes containing exchangeable protons. To address this issue, we introduce two new one-dimensional (1D) 1H NMR techniques that eliminate the water signal, preserving the intensities of exchangeable protons. Using GENETICS-AI, a software that combines an evolutionary algorithm and artificial intelligence, we tailored new water irradiation devoid (WADE) pulses and optimized the 1D 1H NOESY sequence for metabolomic analysis. When applied to human urine samples, kidney tissue extract, and plasma, the WADE technique allowed for accurate measurement of typical metabolites and direct quantification of urea, which is usually challenging to measure using standard NMR experiments. We anticipate that these new NMR techniques will significantly improve the accuracy and reliability of metabolite quantitative assessment for a wide range of biological fluids.PMID:39905912 | DOI:10.1021/acs.analchem.4c05530

Small. 2025 Feb 5:e2410638. doi: 10.1002/smll.202410638. Online ahead of print.ABSTRACTThe development of matrices has shown great potential for fluid metabolic analysis in disease detection. However, single-fluid metabolomic analysis has been recognized as insufficient to fully capture the complexities of diseases such as liver disease, which limits detection accuracy. To this end, the hollow dodecahedral nanocages-based analytical tool is developed, featuring four-high characteristics of speed, throughput, efficiency, and patient compliance, to enhance extraction of multifluid metabolic profiles. The cross-referencing of these profiles among different liver diseases, including hepatocellular carcinoma (HCC), chronic liver disease (CLD), and healthy controls, enhances the diagnosis of liver diseases, particularly achieving near-perfect discrimination for HCC with an AUC value of 0.990, significantly outperforming any single fluid analysis. Additionally, the dynamic changes in expression levels of the key biomarkers throughout disease progression are explored, providing insights into their temporal evolution, and highlighting their role in monitoring disease status. This work highlights that multifluid metabolic analysis can comprehensively and sensitively reflect the disease status, enabling precise identification of complex diseases and facilitating personalized treatment.PMID:39905898 | DOI:10.1002/smll.202410638

Clin Mol Hepatol. 2025 Feb 5. doi: 10.3350/cmh.2024.0694. Online ahead of print.ABSTRACTBACKGROUND: Hepatitis B virus (HBV) hijacks host cell metabolism, especially host glutamine metabolism, to support its replication. Glutamate dehydrogenase 1 (GDH1), a mitochondrial enzyme crucial for glutamine metabolism, can interact with histone demethylases to regulate gene expression through histone methylation. However, the mechanisms underlying GDH1-mediated glutamine metabolism reprogramming and the roles of key metabolites during HBV infection remain unclear.METHODS: Transcriptomic and metabolomic analyses of HBV-infected cell were performed. Both HBV-infected cells and humanized liver chimeric mice were used to elucidate the effect of glutamine metabolism on HBV.RESULTS: HBV infection leads to the abnormal activation of glutamine metabolism, including upregulation of key enzymes and metabolites involved in glutamine metabolism. The viral core protein (HBc) mediates the translocation of GDH1 into the nucleus, where GDH1 activates covalently closed circular DNA (cccDNA) transcription by converting glutamate to α-ketoglutarate (αKG). Mechanistically, the promoting effect of GDH1-derived αKG on cccDNA transcription is independent of its conventional role. Rather, αKG directly interacts with the lysine-specific demethylase KDM4A and enhances KDM4A demethylase activity to regulate αKG-dependent histone demethylation, controlling cccDNA transcription.CONCLUSIONS: Our findings highlight the importance of glutamine metabolism in HBV transcription and suggest that glutamine deprivation is a potential strategy for silencing cccDNA transcription.PMID:39905842 | DOI:10.3350/cmh.2024.0694

J Cell Biochem. 2025 Feb;126(2):e70002. doi: 10.1002/jcb.70002.ABSTRACTGlioblastoma multiforme (GBM), a highly heterogeneous CNS tumor known for its highest incidence rates and poor prognosis has shown limited success in the therapies due to hypoxia-driving immune-suppression in the tumor microenvironment (TME). Emerging evidence highlights the involvement of tumor cell-derived exosomes in tumor-associated microglia polarization via transfer of exosomal onco-proteins and miRNAs. Although the regulatory role of long noncoding RNAs (lncRNAs) in immune signaling are known, its mechanism in microglial polarization via exosomes in GBM still remains poorly understood. In our study, we found that in comparison to the normoxic GBM-derived exosomes lncRNA H19 was significantly upregulated in hypoxic GBM-derived exosomes. Hypoxic GBM-derived exosomes and secretome (conditioned media) caused the reduction in the % phagocytosis of microglia as compared with the control group. Moreover, GBM secretome caused increase in the M2-specific genes (IL10, STAT-3, CD163, CD206) in microglia indicating its polarization to the protumorigenic (M2) phenotype. LncRNA H19 knocked down GBM-secretome treatment in microglia further reduced the STAT-3 expression indicating H19 mediated signaling. Overall, our results suggest the involvement of hypoxic exosomes and lncRNA H19 in microglial polarization and H19 as a potential target.PMID:39905831 | DOI:10.1002/jcb.70002

Mol Cancer. 2025 Feb 4;24(1):43. doi: 10.1186/s12943-025-02242-9.ABSTRACTThe diagnosis and treatment of non-small cell lung cancer in clinical settings face serious challenges, particularly due to the lack of integration between the two processes, which limit real-time adjustments in treatment plans based on the patient's condition and drive-up treatment costs. Here, we present a multifunctional pH-sensitive core-shell nanoparticle containing quercetin (QCT), termed AHA@MnP/QCT NPs, designed for the simultaneous diagnosis and treatment of non-small cell lung cancer. Mechanistic studies indicated that QCT and Mn2+ exhibited excellent peroxidase-like (POD-like) activity, catalysing the conversion of endogenous hydrogen peroxide into highly toxic hydroxyl radicals through a Fenton-like reaction, depleting glutathione (GSH), promoting reactive oxygen species (ROS) generation in mitochondria and endoplasmic reticulum, and inducing ferroptosis. Additionally, Mn2+ could activate the cGAS-STING signalling pathway and promote the maturation of dendritic cells and infiltration of activated T cells, thus inducing tumor immunogenic cell death (ICD). Furthermore, it exhibited effective T2-weighted MRI enhancement for tumor imaging, making them valuable for clinical diagnosis. In vitro and in vivo experiments demonstrated that AHA@MnP/QCT NPs enabled non-invasive imaging and tumor treatment, which presented a one-stone-for-two-birds strategy for combining tumor diagnosis and treatment, with broad potential for clinical application in non-small cell lung cancer therapy.PMID:39905491 | DOI:10.1186/s12943-025-02242-9

Microbiome. 2025 Feb 4;13(1):36. doi: 10.1186/s40168-024-02011-8.ABSTRACTBACKGROUND: Disorder in bile acid (BA) metabolism is known to be an important factor contributing to diarrhea. However, the pathogenesis of BA disorder-induced diarrhea remains unclear.METHODS: The colonic BA pool and microbiota between health piglets and BA disorder-induced diarrheal piglets were compared. Fecal microbiota transplantation and various cell experiments further indicated that chenodeoxycholic acid (CDCA) metabolic disorder produced CDCA-3β-glucuronide, which is the main cause of BA disorder diarrhea. Non-targeted metabolomics uncovered the inhibition of the BA glucuronidation by Lactobacillus reuteri (L. reuteri) is through deriving indole-3-carbinol (I3C). In vitro, important gene involved in the reduction of BA disorder induced-diarrhea were screened by RNA transcriptomics sequencing, and activation pathway of FXR-SIRT1-LKB1 to alleviate BA disorder diarrhea and P53-mediated apoptosis were proposed in vitro by multifarious siRNA interference, CO-IP, immunofluorescence, and so on, which mechanism was also verified in a variety of mouse models.RESULTS: Here, we reveal for the first time that core microbiota derived I3C represses gut epithelium glucuronidation, particularly 3β-glucuronic CDCA production, which reaction is mediated by host UDP glucuronosyltransferase family 1 member A4 (UGT1A4) and necessary of BA disorder induced diarrhea. Mechanistically, L. reuteri derived I3C activates aryl hydrocarbon receptor to decrease UGT1A4 transcription and CDCA-3β-glucuronide content, thereby upregulating FXR-SIRT1-LKB1 signal. LKB1 binds with P53 based on protein interaction, ultimately resists to apoptosis and diarrhea. Moreover, I3C assists CDCA to attain the ameliorative effects of FXR activation in BA disorder diarrhea, through reversion of abnormal metabolism pathway, improving the outcomes of CDCA supplement.CONCLUSION: These findings uncover the crucial interplay between gut epithelial cells and microbes, highlighting UGT1A4-mediated conversion of CDCA-3β-glucuronide as a key target for ameliorating BA disorder-induced diarrhea. Video Abstract.PMID:39905483 | DOI:10.1186/s40168-024-02011-8

Microb Cell Fact. 2025 Feb 4;24(1):36. doi: 10.1186/s12934-025-02657-5.ABSTRACTAcetic acid, a by-product of cytidine synthesis, competes for carbon flux from central metabolism, which may be directed either to the tricarboxylic acid (TCA) cycle for cytidine synthesis or to overflow metabolites, such as acetic acid. In Escherichia coli, the acetic acid synthesis pathway, regulated by the poxB and pta genes, facilitates carbon consumption during cytidine production. To mitigate carbon source loss, the CRISPR-Cas9 gene-editing technique was employed to knock out the poxB and pta genes in E. coli, generating the engineered strains K12ΔpoxB and K12ΔpoxBΔpta. After 39 h of fermentation in 500 mL shake flasks, the cytidine yields of strains K12ΔpoxB and K12ΔpoxBΔpta were 1.91 ± 0.04 g/L and 18.28 ± 0.22 g/L, respectively. Disruption of the poxB and pta genes resulted in reduced acetic acid production and glucose consumption. Transcriptomic and metabolomic analyses revealed that impairing the acetic acid metabolic pathway in E. coli effectively redirected carbon flux toward cytidine biosynthesis, yielding a 5.26-fold reduction in acetate metabolism and an 11.56-fold increase in cytidine production. These findings provide novel insights into the influence of the acetate metabolic pathway on cytidine biosynthesis in E. coli.PMID:39905471 | DOI:10.1186/s12934-025-02657-5

J Transl Med. 2025 Feb 4;23(1):149. doi: 10.1186/s12967-025-06146-6.ABSTRACTBACKGROUND: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a disease of unknown aetiology characterised by symptoms of post-exertional malaise (PEM) and fatigue leading to substantial impairment in functioning. Other key symptoms include cognitive impairment and unrefreshing sleep, with many experiencing pain. To date there is no complete understanding of the triggering pathomechanisms of disease, and no quantitative biomarker available with sufficient sensitivity, specificity, and adoptability to provide conclusive diagnosis. Clinicians thus eliminate differential diagnoses, and rely on subjective, unspecific, and disputed clinical diagnostic criteria-a process that often takes years with patients being misdiagnosed and receiving inappropriate and sometimes detrimental care. Without a quantitative biomarker, trivialisation, scepticism, marginalisation, and misunderstanding of ME/CFS continues despite the significant disability for many. One in four individuals are bed-bound for long periods of time, others have difficulties maintaining a job/attending school, incurring individual income losses of thousands, while few participate in social activities.MAIN BODY: Recent studies have reported promising quantifiable differences in the biochemical and electrophysiological properties of blood cells, which separate ME/CFS and non-ME/CFS participants with high sensitivities and specificities-demonstrating potential development of an accessible and relatively non-invasive diagnostic biomarker. This includes profiling immune cells using Raman spectroscopy, measuring the electrical impedance of blood samples during hyperosmotic challenge using a nano-electronic assay, use of metabolomic assays, and certain techniques which assess mitochondrial dysfunction. However, for clinical application, the specificity of these biomarkers to ME/CFS needs to be explored in more disease controls, and their practicality/logistics considered. Differences in cytokine profiles in ME/CFS are also well documented, but finding a consistent, stable, and replicable cytokine profile may not be possible. Increasing evidence demonstrates acetylcholine receptor and transient receptor potential ion channel dysfunction in ME/CFS, though how these findings could translate to a diagnostic biomarker are yet to be explored.CONCLUSION: Different biochemical and electrophysiological properties which differentiate ME/CFS have been identified across studies, holding promise as potential blood-based quantitative diagnostic biomarkers for ME/CFS. However, further research is required to determine their specificity to ME/CFS and adoptability for clinical use.PMID:39905423 | DOI:10.1186/s12967-025-06146-6

BMC Pulm Med. 2025 Feb 4;25(1):60. doi: 10.1186/s12890-025-03519-x.ABSTRACTBACKGROUND: Aspiration pneumonia (AP) is a type of lung inflammation caused by the aspiration of food, oropharyngeal secretions, or gastric contents. This condition is particularly common in older adults and individuals with impaired swallowing or consciousness. While the diagnosis of AP relies on clinical history, swallowing assessments, and imaging, these methods have significant limitations, often leading to underdiagnosis or misdiagnosis. Reliable biomarkers for AP diagnosis are lacking, making early detection and treatment challenging.METHODS: Nineteen patients diagnosed with pneumonia were included in this study, divided into two groups: AP (n = 10) and non-AP (n = 9). Biological fluid samples, including bronchoalveolar lavage fluid (BALF), saliva, serum, sputum, and urine, were analyzed using non-targeted liquid chromatography with tandem mass spectrometry (LC-MS/MS). Differential metabolites were identified using fold change analysis, statistical significance, and receiver operating characteristic (ROC) curve analysis to evaluate their diagnostic potential. Spearman correlation was used to examine the relationship between selected metabolites and clinical parameters.RESULTS: Significant metabolic differences were found between AP and non-AP patients, with many different metabolites identified across biological fluids. Dehydroepiandrosterone sulfate (DHEAS), Androstenediol-3-sulfate (ADIOLS), and beta-muricholic acid were identified as key biomarkers through fold change analysis and ROC curve analysis, showing consistent increasing or decreasing trends in BALF, sputum, and serum samples. DHEAS was found to be negatively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II) (r = - 0.619, p = 0.005) in BALF sample. The area under curve (AUC) values showed that these molecules could serve as effective biomarkers for AP.CONCLUSIONS: This study identifies DHEAS, ADIOLS and beta-muricholic acid as promising biomarkers for AP, with the potential to improve early diagnosis and treatment. These findings underscore the clinical value of metabolomics in developing diagnostic tools for AP, facilitating better clinical management and patient outcomes. Further research is required to validate these biomarkers in larger cohorts and explore their mechanistic roles in AP pathophysiology.PMID:39905415 | DOI:10.1186/s12890-025-03519-x

Breast Cancer Res. 2025 Feb 4;27(1):18. doi: 10.1186/s13058-025-01970-6.ABSTRACTBACKGROUND: Mammographic breast density (MBD), a strong predictor of breast cancer, is highly influenced by body mass index (BMI) in childhood and early adulthood, but the mechanisms underlying these associations are not fully understood. Our goal is to identify biomarkers that mediate the associations of BMI at ages 10 and 18 with MBD in premenopausal women.METHODS: This study consists of 705 premenopausal women who had their screening mammogram at Washington University in St. Louis, MO, and provided a fasting blood sample. Our comprehensive metabolomic and lipidomic profiling yielded complete data for 828 metabolites and 857 lipid species after imputation. We used Volpara to determine volumetric measures of MBD. We performed high dimensional mediation analysis using the HIMA R package, adjusted for confounders, to determine whether lipid species and metabolites mediate the associations of BMI at 10 and 18 with MBD. We applied a false discovery rate (FDR) p-value < 0.1.RESULTS: Four metabolites (glutamate, β-cryptoxanthin, cortolone glucuronide (1), phytanate) significantly mediated the association of BMI at 10 with volumetric percent density (VPD), and two (glutamate, β-cryptoxanthin) mediated the association of BMI at 18 with VPD. Glutamate was the strongest mediator across time points. Glutamate mediated 6.7% (FDR p-value = 0.06) and 9.3% (FDR p-value = 0.008) of the association between BMI at age 10 and 18, respectively. Four lipid species (CER(18:0), LCER(14:0), LPC(18:1), PC(18:1/18:1)), mediated the association of BMI at 10 with VPD, while five lipid species (CER(18:0), LCER(14:0), PC(18:1/18:1), TAG56:5-FA22:5, TAG52:2-FA16:0) mediated the association of BMI at 18 with VPD. The strongest mediator was PC(18:1/18:1), which mediated 9.7%, (FDR-p = 0.009) and 7.7%, (FDR-p = 0.04) of the association of BMI at age 10 and 18 with VPD, respectively.CONCLUSIONS: Metabolites in amino acid, lipid, cofactor/vitamin, and xenobiotic super-pathways as well as lipid species across the phospholipid, neutral complex lipid and sphingolipid super-pathways mediated the associations of BMI in early-life and MBD in premenopausal women. This study offers insight into the biological mechanisms underlying the link between early-life adiposity and MBD, which can support future research into breast cancer prevention.PMID:39905412 | DOI:10.1186/s13058-025-01970-6

BMC Complement Med Ther. 2025 Feb 4;25(1):43. doi: 10.1186/s12906-025-04786-1.ABSTRACTBACKGROUND: Honey has been successfully used in wound care and cosmetics because of its effective biological properties, including antibacterial, antioxidant, and anti-inflammatory activities. Polyphenols, particularly phenolic acids, are key honey components responsible for these beneficial effects. In recent years, there has been a growing demand for natural, ecologically friendly, and biodegradable products in the modern cosmetics and wound care market. This study aimed to identify and quantify phenolic acids in four Polish honey samples of different botanical origins (heather, buckwheat, linden and rapeseed) and to assess for the first time the permeation of the identified phenolic acids through the skin and their accumulation after the application of pure honey samples, as well as honey-based hydrogel and emulsion formulations.METHODS: The honey samples' antioxidant activity and total phenolic content were determined using the DPPH and ABTS assays and the Folin-Ciocalteu method, respectively. Phenolic acids and volatile compounds were identified and quantified in honey samples using the HPLC-UV and GC-MS method, respectively. The biocompatibility of the honey samples was evaluated using a murine fibroblast cell line (L929). A Franz-type vertical diffusion cell with porcine skin was used to assess phenolic acid's permeation and skin accumulation from different honey-based pharmaceutical formulations. The biodegradability of the prepared formulations was also characterised.RESULTS: Gallic acid, 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, coumaric acid, and 3-hydroxybenzoic acid were identified and quantified in the honey samples. Heather honey exhibited significantly higher antioxidant activity and total polyphenol content than the other honey samples. Heather, linden and buckwheat honey samples significantly decreased cell viability at concentrations of 5% and 2.5%, while rapeseed honey sample markedly reduced fibroblast viability only at 5%. Among the tested formulations - pure honey, hydrogel, and emulsion - higher skin permeation and accumulation rates of phenolic acids were observed with the prepared honey-based hydrogels than with the pure honeys and emulsions. Additionally, the prepared formulations were classified as partially biodegradable.CONCLUSIONS: The obtained results confirmed the effectiveness of two pharmaceutical formulations in the form of a hydrogel or emulsion containing honey after applied topically. The inclusion of honey in the vehicle, in particular hydrogel increased the penetration of phenolic acids through the skin.PMID:39905375 | DOI:10.1186/s12906-025-04786-1

BMC Plant Biol. 2025 Feb 4;25(1):145. doi: 10.1186/s12870-025-06176-8.ABSTRACTBACKGROUND: Dendrobium nobile Lindl belongs to the genus Dendrobium of the orchid family and is a valuable herbal medicine. Drought stress severely affects the growth of D. nobile Lindl; however, the specific regulatory mechanisms have not yet been elucidated.RESULTS: In the present study, we conducted a combined transcriptome and metabolome analysis of D. nobile Lindl stems under different drought stress conditions. Global transcriptomic changes were detected in Dendrobium under different drought stress conditions. KEGG enrichment analysis showed that the DEGs were enriched in plant hormone signal transduction; cutin, suberin, and wax biosynthesis; starch and sucrose metabolism; and the biosynthesis of various plant secondary metabolites. The differentially abundant metabolites (DAMs) detected using STEM analysis were enriched in pathways associated with glucosinolate biosynthesis and cyanoamino acid metabolism. We constructed a regulatory network for the drought tolerance of Dendrobium by weighted gene co-expression analysis.CONCLUSIONS: The results showed that arginine and proline metabolism, glucosinolate biosynthesis and tyrosine metabolism pathways participated in regulating drought stress in D. nobile Lindl. Our study provides a theoretical basis for studying the drought resistance mechanisms in Dendrobium.PMID:39905284 | DOI:10.1186/s12870-025-06176-8

Nat Biotechnol. 2025 Feb 4. doi: 10.1038/s41587-025-02554-7. Online ahead of print.ABSTRACTHere we report a method, smol-seq (small-molecule sequencing), using structure-switching aptamers (SSAs) and DNA sequencing to quantify metabolites. In smol-seq, each SSA detects a single target molecule and releases a unique DNA barcode on target binding. Sequencing the released barcodes can, thus, read out metabolite levels. We show that SSAs are highly specific and can be multiplexed to detect multiple targets in parallel, bringing the power of DNA sequencing to metabolomics.PMID:39905266 | DOI:10.1038/s41587-025-02554-7

Nat Biotechnol. 2025 Feb 4. doi: 10.1038/s41587-024-02551-2. Online ahead of print.ABSTRACTTumors exhibit an increased ability to obtain and metabolize nutrients. Here, we implant engineered adipocytes that outcompete tumors for nutrients and show that they can substantially reduce cancer progression, a technology termed adipose manipulation transplantation (AMT). Adipocytes engineered to use increased amounts of glucose and fatty acids by upregulating UCP1 were placed alongside cancer cells or xenografts, leading to significant cancer suppression. Transplanting modulated adipose organoids in pancreatic or breast cancer genetic mouse models suppressed their growth and decreased angiogenesis and hypoxia. Co-culturing patient-derived engineered adipocytes with tumor organoids from dissected human breast cancers significantly suppressed cancer progression and proliferation. In addition, cancer growth was impaired by inducing engineered adipose organoids to outcompete tumors using tetracycline or placing them in an integrated cell-scaffold delivery platform and implanting them next to the tumor. Finally, we show that upregulating UPP1 in adipose organoids can outcompete a uridine-dependent pancreatic ductal adenocarcinoma for uridine and suppress its growth, demonstrating the potential customization of AMT.PMID:39905264 | DOI:10.1038/s41587-024-02551-2

Sci Rep. 2025 Feb 4;15(1):4159. doi: 10.1038/s41598-025-88485-4.ABSTRACTGestational Diabetes Mellitus (GDM) is an emerging maternal health problem with increasing incidences. The lack of complete understanding of its pathophysiological mechanisms and novel regulatory biomarkers makes early diagnosis difficult. High-throughput RNA sequencing and computational bioinformatics analyses were conducted to identify novel hub genes, and their regulatory mechanisms were validated through qRT-PCR, western blot, and siRNA-mediated knockdown studies. Intermediate metabolites and circulatory levels of amino acids in the serum of GDM patients and healthy controls were measured. Transcriptomic studies identified SNW1 as the most sensitive and specific biomarker, significantly up-regulated in GDM (fold change = 1.09; p < 0.001). Metabolomic studies indicated significantly elevated gluconeogenesis in GDM, evidenced by decreased levels of alanine and increased levels of pyruvate and glucose compared to controls. siRNA-mediated knockdown of SNW1 in PANC1 cells resulted in significant down-regulation of alanine aminotransferase (ALT/GPT) and insulin receptor substrate (IRS1), while glucose transporters (GLUT2/GLUT4) and insulin (INS) were significantly up-regulated at both mRNA and protein levels. This study identified SNW1 as a novel insulin-resistant gene that induces hyperglycemia by elevating gluconeogenesis and decreasing glucose uptake. SNW1 may be considered a potential therapeutic target with clinical utility for the management of GDM.PMID:39905161 | DOI:10.1038/s41598-025-88485-4

Nat Commun. 2025 Feb 4;16(1):1347. doi: 10.1038/s41467-025-56646-8.ABSTRACTIon suppression is a major problem in mass spectrometry (MS)-based metabolomics; it can dramatically decrease measurement accuracy, precision, and sensitivity. Here we report a method, the IROA TruQuant Workflow, that uses a stable isotope-labeled internal standard (IROA-IS) library plus companion algorithms to: 1) measure and correct for ion suppression, and 2) perform Dual MSTUS normalization of MS metabolomic data. We evaluate the method across ion chromatography (IC), hydrophilic interaction liquid chromatography (HILIC), and reversed-phase liquid chromatography (RPLC)-MS systems in both positive and negative ionization modes, with clean and unclean ion sources, and across different biological matrices. Across the broad range of conditions tested, all detected metabolites exhibit ion suppression ranging from 1% to >90% and coefficients of variation ranging from 1% to 20%, but the Workflow and companion algorithms are highly effective at nulling out that suppression and error. To demonstrate a routine application of the Workflow, we employ the Workflow to study ovarian cancer cell response to the enzyme-drug L-asparaginase (ASNase). The IROA-normalized data reveal significant alterations in peptide metabolism, which have not been reported previously. Overall, the Workflow corrects ion suppression across diverse analytical conditions and produces robust normalization of non-targeted metabolomic data.PMID:39905052 | DOI:10.1038/s41467-025-56646-8

Sci Rep. 2025 Feb 4;15(1):4236. doi: 10.1038/s41598-024-80492-1.ABSTRACTDiabetic nephropathy (DN) is one of the major causes of end-stage renal disease. This study aimed to explore the internal relationship between metabolic processes and autoimmune responses in patients with DN via untargeted metabolomics and Olink proteomics. The serum of 10 patients who were diagnosed with DN and 10 healthy individuals via untargeted metabolomics and Olink proteomics. Animal models were used to validate the characterized genes. Correlation analysis of major differentially abundant metabolites and differentially expressed proteins revealed that SIRT2 might be a key hub linking energy metabolism and innate immune responses. KEGG enrichment analysis showed that HIF-1 signaling pathway and renal cell carcinoma pathway were co-enriched pathways in energy metabolism and inflammatory response. VEGFA plays a vital role in these two signaling pathways. The ability of SIRT2 to regulate VEGFA expression has been demonstrated. In vivo experiments revealed that SIRT2, VEGFA, and HIF-1α were highly expressed in the kidneys of mice with diabetic nephropathy. In conclusion, our study combines metabolomics and proteomics to provide valuable insights into the synergistic roles of metabolic disorders and inflammatory responses in DN. The data suggest that SIRT2 may be a key target affecting these processes.PMID:39905044 | DOI:10.1038/s41598-024-80492-1