PubMed

JPEN J Parenter Enteral Nutr. 2025 Feb 17. doi: 10.1002/jpen.2728. Online ahead of print.ABSTRACTBACKGROUND: Malnutrition or risk of malnutrition is present in about one-third of patients admitted to Western hospitals and is identified by either screening for malnutrition or further nutrition assessment. To date, there are no commonly accepted biomarkers of malnutrition, which could expedite screening efforts, ease diagnosis, and hasten treatment. We aimed to investigate whether metabolomics could identify markers associated with malnutrition in hospitalized patients and performed a retrospective metabolomic cohort study in this patients' group.METHODS: The study population included adult patients hospitalized in a medical unit. Malnutrition was identified by the second step of the Global Leadership Initiative on Malnutrition criteria independently of the outcome of the screening step (nutritional risk screening 2002). Amino acids were determined by targeted metabolomics using gas chromatography-tandem mass spectrometry and liquid chromatography-tandem mass spectrometry. Logistic regression analyses with Benjamini-Hochberg procedure to reduce false discovery rate were used to identify biomarkers associated with malnutrition.RESULTS: In total, 218 patients were included in the final analysis, with 62 patients having a diagnosis of malnutrition. In crude analyses, 11 metabolites were associated with malnutrition, but further adjustment attenuated the associations. After multiple adjustment, neopterin and cystatin C were positively associated with malnutrition, whereas His, Cys, and kynurenine to tryptophan ratio were negatively associated.CONCLUSION: The observed associations require confirmation in a replication cohort before they can be recommended as biomarkers of malnutrition.PMID:39961686 | DOI:10.1002/jpen.2728

Int J Biol Macromol. 2025 Feb 15:141129. doi: 10.1016/j.ijbiomac.2025.141129. Online ahead of print.ABSTRACTIn the process of aging, adverse changes such as weakened intestinal barrier function, increased chronic inflammation, and decreased gut microbiota diversity often occur. We explored the protective effects of Oat β-glucan (BG) on the gut homeostasis of naturally aging mice. The study shows that daily intervention with 400 mg/kg BG effectively modulates the intestinal mucosal structure, mechanical barrier function [Zonula occludens-1 (ZO-1), occludin, and claudin], and anti-inflammatory [Tumor Necrosis Factor-α (TNF-α), Interleukin-6 (IL-6), and IL-1β], as well as antioxidant responses in aging mice. Spearman correlation analyses showed that BG supplementation increased acetate levels by 1.8-fold, propionate levels by 2.5-fold, and butyrate-derived GABA levels by 2.5-fold. Additionally, BG supplementation improved the gut microbiota, increasing the abundance of beneficial bacteria like Bacteroidota, Prevotellaceae, Coprobacillaceae, and Faecalibacterium. These microbes metabolize BG to produce short-chain fatty acids (SCFAs), activating butanoate and propanoate metabolic pathways to maintain intestinal homeostasis. In conclusion, this study identifies the therapeutic effects of BG in regulating intestinal barrier homeostasis and gut microbiota, providing new insights for nutritional intervention strategies in the elderly.PMID:39961571 | DOI:10.1016/j.ijbiomac.2025.141129

Int J Biol Macromol. 2025 Feb 15:141149. doi: 10.1016/j.ijbiomac.2025.141149. Online ahead of print.ABSTRACTPrevious studies found that sodium alginate (SA) was protective against several liver diseases. However, the effect of SA on drug-induced liver injury is not clear. This study investigated the effect and mechanism of SA on isoniazid (INH)-induced liver injury in mice. Twenty-one male BALB/c mice were randomly divided into three groups: the control (AIN-93 M diet), the INH (AIN-93 M diet with 0.66 g INH/kg diet) and the SA group (AIN-93 M diet with 0.66 g INH/kg diet and 0.8 g SA/kg diet). After 10 weeks, the liver function indices, histopathological changes, fecal metabolites, and gut microbiota compositions were measured. Compared with the INH group, the SA group had significantly reduced alanine aminotransferase (ALT) and histopathological liver injury. Also, the SA treatment significantly reduced the content of several fecal metabolites including the indole, phenylalanine, and tyrosine derivatives. In addition, the SA treatment significantly increased the content of seven gut bacteria including Dorea, Eubacterium xylanophilum group, and Papillibacter and reduced the content of 11 gut bacteria including Alloprevotella. The changes in fecal metabolites and gut bacteria were associated with those in serum ALT and histopathological liver injury. In conclusion, SA alleviated INH-induced liver injury in mice by modulating fecal metabolites and gut bacteria.PMID:39961567 | DOI:10.1016/j.ijbiomac.2025.141149

Bioresour Technol. 2025 Feb 15:132243. doi: 10.1016/j.biortech.2025.132243. Online ahead of print.ABSTRACTNanoscale zero-valent iron (nZVI)-mediated anaerobic digestion commonly focuses on electron transfer between syntrophic bacteria, neglecting intracellular energy conservation strategies and amino acid metabolism. In this study, F420H2 dehydrogenase abundance increased by 5.1 %, 27.0 % and 31.5 % at 10 30 and 50 mM nZVI dosing, respectively, enabling an efficient transmembrane proton-coupled electron transfer mode. Electron bifurcation (EB) enzymes involved in methanogenesis responded differently to nZVI, with HdrA2B2C2 initially increasing at 10 mM and decreasing at 30 and 50 mM, while MvhADG-HdrABC was completely down-regulated. Metabolomics further demonstrated that nZVI reduced riboflavin and flavin mononucleotide content, which is detrimental to the EB. Instead, an alternative measure to maintain electron flow and energy conservation under high nZVI exposure is high expression of ndh and F-type or V/A-type ATPase genes. Additionally, enhancing C1-unit carrier expression through amino acid metabolism regulation emerged as a key strategy. This study provides new perspectives on nZVI-mediated anaerobic digestion.PMID:39961521 | DOI:10.1016/j.biortech.2025.132243

J Ethnopharmacol. 2025 Feb 15:119493. doi: 10.1016/j.jep.2025.119493. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Xiangshao Sanjie Oral Liquid (XSSJ) is a traditional Chinese medicine formulation used clinically for the treatment of mammary gland hyperplasia (MGH), yet its mechanism remains obscure.AIM OF THE STUDY: The purpose of this study was to explore the therapeutic mechanism of XSSJ on MGH using a comprehensive strategy of plasma metabolomics and network pharmacology.MATERIALS AND METHODS: The rat model of MGH was established, and the multiple indicators were employed for efficacy evaluation. Then, a metabolomics strategy was established to find plasma metabolites and metabolic pathways that may be important in inducing MGH. In addition, UPLC-Q-TOF-MS and network pharmacological analysis were used to identify the prototype compounds of XSSJ in rat plasma and target genes that may cause the effect. Finally, the results were integrated and verified by RT-qPCR and Western Blot (WB).RESULTS: XSSJ has a therapeutic effect on MGH. 29 differential metabolites of XSSJ in the treatment of MGH were identified by metabolomics. After administration of XSSJ, 16 prototype compounds were found in the rat plasma, which were associated with 179 potential therapeutic targets. Comprehensive analysis revealed that XSSJ reversed the mRNA expression of EGFR, ESR1, AKT1, SRC and PTPN11 in MGH rats. In addition, different doses of XSSJ inhibited the expression of p-PI3K and p-AKT proteins.CONCLUSION: This study combined metabolomics and network pharmacology to reveal the regulatory effect of XSSJ on MGH through PI3K/AKT pathway, which provided further support for the clinical application of XSSJ.PMID:39961425 | DOI:10.1016/j.jep.2025.119493

J Ethnopharmacol. 2025 Feb 15:119498. doi: 10.1016/j.jep.2025.119498. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) Danggui Buxue Decoction (DBD) was initially recorded in Nei Wai Shang Bian Huo Lun. Known for its immune regulatory and hematopoietic effects, DBD improved the quality of life in non-small-cell lung cancer (NSCLC) patients. Previous research confirmed that DBD can alleviate gemcitabine (GEM) induced myelosuppression. However, the specific metabolic mechanisms underlying this action remain unclear.AIM OF THE STUDY: The aim of our study was to explore the metabolic mechanism of DBD against GEM-induced myelosuppression using non-targeted metabolomics and network pharmacology. Additionally, we aimed to validate our findings through enzyme linked immunosorbent assays (ELISA) and western blot (WB).MATERIALS AND METHODS: Initially, a GEM-induced myelosuppression model in mice was established by administering GEM (100 mg/kg) twice. Serum, bone marrow nucleated cells (BMNCs) and thymus samples were collected at different time points. Ultra-high-performance liquid chromatography coupled with Q Exactive Orbitrap mass spectrometry (UHPLC-QE-MS/MS) was employed based on non-targeted metabolomics and network pharmacology was conducted to identify the key compounds, core targets and pathways that mediate the effects of DBD. Furthermore, the targets identified through metabolic and network pharmacology were jointly analyzed to select crucial metabolism pathways. Finally, our findings were experimentally validated using ELISA and WB.RESULTS: The results revealed 116 differential metabolites as metabolic biomarkers of DBD in the treatment of GEM-induced myelosuppression. Among these, pathway analysis was conducted on 32 distinct metabolites with KEGG ID, which were subsequently linked to a joint pathway involving 115 targets of DBD-related disease in the PPI network. Pyrimidine synthesis and histidine (HIS) metabolism were identified as the most critical metabolic pathways for DBD in treating GEM-induced myelosuppression. DBD was found to enhance adenosine production through CD73 and additionally regulate TNF-α IL-8 and IL-10.CONCLUSION: In summary, pyrimidine synthesis, HIS metabolism, CD73 and inflammatory factors play significant roles in DBD's alleviation of GEM-induced myelosuppression. In this study, a comprehensive strategy of multi-tissues and multi-time point metabolomics, network pharmacology and pharmacological experiments was used to further illuminate the complex mechanisms of DBD against GEM-induced myelosuppression.PMID:39961424 | DOI:10.1016/j.jep.2025.119498

J Ethnopharmacol. 2025 Feb 15:119503. doi: 10.1016/j.jep.2025.119503. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: As a typical Traditional Chinese Medicine (TCM) couplet medicine, Arum Ternatum Thunb. (Pinellia ternata (Thunb.) Makino, known as Banxia in Chinese) and Citrus Reticulata (pericarps of Citrus reticulata Blanco, known as Chenpi in Chinese) has been widely used in clinical practice for their properties of drying dampness, resolving phlegm, relieving oppression and masses. According to the TCM theories, the imbalance in fluid metabolism could lead to the accumulation of the excess dampness and phlegm, resulting in the pathological phenotype as 'damp-phlegm syndrome'. It can further lead to polycystic ovary syndrome (PCOS) when this accumulation of the excess fluid presents in uterus, affecting women's fertility and endocrine function. Recent studies have indicated that Banxia-Chenpi herbal pair (BXCP) exhibits significant therapeutic effects on damp-phlegm syndrome, yet the precise mechanisms underlying its anti-PCOS actions remain to be fully elucidated.AIM OF THE STUDY: The objective was to investigate the signaling pathway involved in steroid biosynthesis, particularly the cytochrome P450 family 17, subfamily A, member 1 (CYP17A1), and to evaluate the effects and mechanisms of BXCP in ameliorating PCOS through both in vivo and in vitro experiments.MATERIALS AND METHODS: A systematic evaluation was conducted to assess BXCP's effects on serum biochemical indicators and ovarian tissue pathology in a PCOS rat model (induced by high-fat diet + letrozole) and a DHT-induced human granulosa cells (KGN) model. Core targets were screened using absorbed components analysis, bioinformatics, metabolomics, and network analysis. RT-qPCR and Western blot techniques were employed to confirm the expression of CYP17A1 and related signaling molecule expression during BXCP's amelioration of PCOS, both in vivo and in vitro.RESULTS: BXCP significantly ameliorated PCOS in vivo by mitigating weight gain, regulating estrus cycles, and normalizing sex hormone levels in rats. It upregulated metabolites related to steroid biosynthesis, including cortolone and progesterone, with CYP19A1, AKR1C3, and HSD17B1 as key regulators of CYP17A1. The main BXCP components, Naringenin and Nobiletin, increased CYP17A1 and CYP19A1 protein expression while decreased AKR1C3 and HSD17B1.CONCLUSION: In conclusion, BXCP ameliorates PCOS by activating the CYP17A1-centered steroid biosynthesis pathway. These findings provide new insights into BXCP's clinical potentials in the management of patients with PCOS, highlighting the importance of TCM in modern medicine.PMID:39961422 | DOI:10.1016/j.jep.2025.119503

Mol Cell Endocrinol. 2025 Feb 15:112491. doi: 10.1016/j.mce.2025.112491. Online ahead of print.ABSTRACTThe management of shock in critical care must transition from a predominantly hemodynamic approach to one that comprehensively addresses the biological intricacies of this complex multisystemic syndrome. A thorough understanding of the metabolic mechanisms involved in shock is pivotal for precise patient phenotyping and accurate risk stratification. Metabolomics, an emerging "-omics" approach, offers a powerful tool for unraveling the molecular underpinnings of shock. By analyzing the metabolic pathways within the cardiovascular system, metabolomics can elucidate the diverse mechanisms leading to circulatory insufficiency. This approach holds significant promise for identifying clinically actionable diagnostic and prognostic biomarkers, which can enhance individualized patient management and potentially prevent the progression to multi-organ failure. Improved insight into the metabolic alterations in shock may pave the way for novel therapeutic strategies and more targeted treatments, ultimately improving patient outcomes in critical care settings. This work provides a comprehensive overview of metabolomic investigations in shock, focusing on septic shock and the main metabolic pathways involved in cardiac and vascular dysfunction.PMID:39961415 | DOI:10.1016/j.mce.2025.112491

Mol Metab. 2025 Feb 15:102113. doi: 10.1016/j.molmet.2025.102113. Online ahead of print.ABSTRACTOBJECTIVE: Increased expression of glutaminase (GLS) has been found to correlate with more aggressive disease and poorer prognosis in patients with several types of cancer, including breast, lung, and pancreatic cancer. G9a histone methyltransferase inhibitors may have anticancer activity. The present study assessed whether BIX01294 (BIX), a G9a histone methyltransferase inhibitor, can inhibit glutaminase (GLS) in pancreatic ductal adenocarcinoma (PDAC) cells.METHODS: The effects of BIX on mitochondrial metabolism in PDAC cells were evaluated by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS) metabolomic analysis. To assess the impact of BIX on glutathione dynamics, real-time changes in glutathione levels were monitored by FreSHtracer-based GSH assays.RESULTS: BIX significantly inhibited the growth of PDAC cells, both in vitro and in vivo, and robustly induced apoptotic cell death. BIX significantly increased the cellular NADP+/NADPH ratio and decreased the ratio of reduced-to-oxidized glutathione (GSH:GSSG). In addition, BIX decreased GSH levels and increased ROS levels. N-acetyl-L-cysteine (NAC) supplementation dramatically rescued PDAC cells from BIX-induced apoptosis. Furthermore, BIX inhibited the transcription of GLS by inhibiting Jumonji-domain histone demethylases but not G9a histone methyltransferase. One Jumonji-domain histone demethylase, KDM6B, epigenetically regulated GLS expression by binding to the GLS gene promoter.CONCLUSIONS: Collectively, these findings suggest that BIX could be a potent therapeutic agent in patients with PDAC through its inhibition of GLS-mediated cellular redox balance.PMID:39961401 | DOI:10.1016/j.molmet.2025.102113

Comp Biochem Physiol Part D Genomics Proteomics. 2025 Feb 9;54:101441. doi: 10.1016/j.cbd.2025.101441. Online ahead of print.ABSTRACTGreater amberjack (Seriola dumerili) has a significant value in the global aquaculture industry because of its adaptive traits and rapid growth rate. However, the unsynchronized growth of greater amberjack poses challenges in its cultivation, and the molecular mechanisms underlying it remain unclear. In the current study, greater amberjack individuals showing growth differences were collected and subjected to transcriptomics and metabolomics analyses. Metabolomics analysis revealed 164 and 206 significantly different metabolites (SDMs) in the positive ion mode (POS) and negative ion mode (NEG) of liquid chromatography-tandem mass spectrometry (LC-MS/MS), respectively (VIP > 1 and P < 0.05). Transcriptomics analysis confirmed 534 differentially expressed genes (DEGs), with |log2FC| > 1 and false discovery rate (FDR) < 0.05. A total of 87 enriched pathways were identified by integrated metabolomics and transcriptomics analyses and exhibited that fast-growing group (FG) hold enhanced digestive and anabolic capacities, superior glycine synthesis capability, strong feeding behavior, and high skeletal biomineralization activity, while the slow-growing group (SG) consumed additional energy to cope with environmental stress, and growth was hindered during the generation of immune responses. These results revealed the underlying molecular mechanisms of unsynchronized growth in S. dumerili, and promoted the selection process for growth traits.PMID:39961181 | DOI:10.1016/j.cbd.2025.101441

Poult Sci. 2025 Feb 7;104(3):104884. doi: 10.1016/j.psj.2025.104884. Online ahead of print.ABSTRACTThe development of pre-recruitment follicles plays a critical role in determining egg-laying performance in poultry. This study combines proteomic and metabolomic analyses to explore changes in proteins and metabolites, to elucidate key regulatory mechanism involved in chicken pre-recruitment follicular development. Histological examination revealed a significant increase in yolk deposition in small yellow follicles (SYF) compared to small white follicles (SWF). Metabolomics analysis identified significantly enriched differential metabolites (DMs) between SWF and SYF in pathways such as Lysosome, Ferroptosis, Biosynthesis of unsaturated fatty acids, and Tryptophan metabolism. Particularly, Adenosine-5'-Diphosphate (ADP) was downregulated during follicular recruitment and was significantly enriched in the lysosome pathway. Proteomic analyses revealed that differentially expressed proteins (DEPs) in SWF and SYF were enriched in pathways including Lysosome, Glutathione metabolism, Cholesterol metabolism, Arginine and proline metabolism, and amino acid biosynthesis. Among these DEPs, NAD-dependent protein deacetylase sirtuin 5 (SIRT5) was significantly upregulated, while lysosomal-associated membrane protein 1 (LAMP1) was down-regulated during the development of pre-recruitment follicles. SIRT5 was linked to the negative regulation of reactive oxygen species metabolism, whereas LAMP1 was associated with lysosome and autophagy pathways. Further validation experiments demonstrated high expression of SIRT5 in SYF, particularly in granulosa cells (GCs). Silencing SIRT5 in GCs resulted in increased ROS production and upregulated expression of autophagy-related proteins LC3Ⅱ and Beclin1, as well as lysosome markers LAMP1. Conversely, lipid droplet deposition and p62 expression were suppressed. inhibited. Taken together, these findings suggest that SIRT5 upregulation promotes the development of pre-recruitment follicles by inhibiting the autophagy-lysosome pathway in chicken GCs.PMID:39961169 | DOI:10.1016/j.psj.2025.104884

Appl Biochem Biotechnol. 2025 Feb 17. doi: 10.1007/s12010-025-05199-z. Online ahead of print.ABSTRACTThe tree bean (Parkia timoriana (DC). Merr) is an underutilized legume and is abundantly found in Southeast Asia. It is valued for its nutritious pods and cultivated for food and timber. Despite of the presence of several nutrients, the regulatory networks involved in secondary metabolite biosynthesis in the tree bean remain largely unexplored. Recent studies have highlighted that consumption of its pods provides numerous health benefits, including antioxidant, α-glucosidase inhibitory, antibacterial, antidiabetic, and insecticidal activities. To elucidate the biosynthesis of specific metabolites in this plant, a comparative metabolite and transcriptomic analysis of the leaf and root tissues of P. timoriana was carried out. The study revealed that P. timoriana leaf and root tissues contain varying levels of phenolics, flavonoids, and terpenoids. 1H nuclear magnetic resonance (1H NMR) analysis identified 16 significant metabolites in the leaf and root tissues, including sugars, amino acids, and organic acids. L-dihydroxyphenylalanine (L-DOPA), an amino acid derivative and precursor to dopamine, was detected for the first time in the seeds. Additionally, the presence of pinitol in P. timoriana was also confirmed. De novo RNA-sequence analysis identified differentially expressed genes (DEGs) in both the tissues. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis identified pathways associated with shikimate pathway, such as phenylpropanoid and flavonoid biosynthesis. MapMan pathway analysis revealed a high number of transcripts related to phenylalanine, tryptophan, tyrosine, and condensed tannin biosynthesis. The research conducted identified secondary metabolites in P. timoriana, and their probable biosynthetic pathway which can be used for medicinal and nutritional purposes.PMID:39960613 | DOI:10.1007/s12010-025-05199-z

Food Funct. 2025 Feb 17. doi: 10.1039/d4fo05625f. Online ahead of print.ABSTRACTGermination and fermentation are effective ways to improve polyphenol contents in whole grains; however, their mechanisms await clear explanation. This study aimed to elucidate the mechanisms underlying the release and transformation of polyphenols during germination and fermentation with L. plantarum. Results showed that the phenolic content significantly increased after germination and fermentation. Dynamic changes of carbohydrate-hydrolyzing enzymes and structural characteristics detected by FTIR, X-ray diffraction, and CLSM indicated that the destruction of hemicellulose and the secretion of xylanase were crucial for releasing polyphenols. Targeted metabolomics revealed that a total of 73 polyphenols and their catabolites were identified. Differential metabolites between millets (M) and germinated millets (GM), as well as between GM and germinated-fermented millets (FGM), were revealed. Quantitative analysis of differential metabolites combined with KEGG pathways showed that the contents of cinnamic acid, caffeic acid, ferulic acid, and sinapic acid significantly increased after germination, likely associated with phenylpropanoid biosynthesis. However, these polyphenols markedly decreased after fermentation. The contents of 3,4-dihydroxybenzoic acid, 2,5-dihydroxybenzoic acid, and 4-hydroxyphenylethanol significantly increased after fermentation, suggesting associations with phenylalanine, tyrosine, and tryptophan biosynthesis and tyrosine metabolism. Our results demonstrated the enhancement of polyphenol contents via the combination of germination and fermentation and the related mechanisms during these processes, which provides valuable insights for the utilization of cereals in the food industry.PMID:39960291 | DOI:10.1039/d4fo05625f

Angew Chem Int Ed Engl. 2025 Feb 17:e202408701. doi: 10.1002/anie.202408701. Online ahead of print.ABSTRACTPhotoaffinity labeling is a widely used methodology for interrogating small molecule-protein interactions. However, these applications are limited by the few photo-cross-linkers that typically modify the affinity and the binding mode of the original ligand. Here, we report the development of new target agnostic photoaffinity warheads, sulfohydrazones that form a reactive carbene upon UV irradiation. Careful optimization of the reaction conditions allowed us to effectively label five different amino acid residues in proteins. Our approach turned biologically relevant hydrazones and sulfohydrazones to intrinsically irreversible covalent binders without structural modifications by photoactivation as demonstrated on monoamine oxidase A (MAO-A) enzyme and STAT5b (Signal transducer and activator of transcription 5b) transcription factor. Sulfohydrazones are readily accessible by transforming the corresponding carbonyl group of a ligand or a suitable tag that extends the application domain of the method for any ligands exemplified by conditional labelling of the acetylcholine esterase enzyme and the oncogenic mutant of GTP-ase KRasG12D.PMID:39960219 | DOI:10.1002/anie.202408701

J Agric Food Chem. 2025 Feb 17. doi: 10.1021/acs.jafc.4c11335. Online ahead of print.ABSTRACTBiflavonoids, a distinctive subclass of plant flavonoids, have a unique dimerized structure and possess a range of biological activities. The clinical applications of biflavonoids in human health have been impeded by challenges related to bioavailability and hydrophilicity. In contrast, biflavonoid glycosides, which demonstrate enhanced pharmacodynamic and pharmacokinetic properties compared to their aglycones, are notably limited in availability. In this work, we developed a robust enzymatic system to biosynthesize biflavonoid glycosides using O-glycosyltransferase UGT74AN2 and sucrose synthase AtSuSy. This innovative system exhibited remarkable substrate promiscuity successfully, glycosylating 10 structurally diverse biflavonoids. Through purification and structural characterization, we identified four biflavonoid monoglycosides (1a, 2a, 4a, and 5a) as well as two diglycosides (1b and 3b). All synthesized products showed a significant increase in water solubility compared to their aglycones, with enhancements ranging from 20- to 980-fold. Furthermore, compound 1a demonstrated significantly enhanced antiproliferative activity against PC-3 cells compared to its corresponding aglycones. Metabolomic and transcriptomic analyses showed that the increased antitumor activity of 1a may be attributed to changes in the expression levels of various drug transporters, particularly within the ABC, PDE, and ATPase gene families. While compound 1 elevated the mRNA levels of several ABC transporters and ATPases, 1a did not induce these effects, highlighting a distinct mode of action. This study established an efficient enzymatic approach for the biosynthesis of biflavonoid glycosides and underscored their potential as valuable small molecules for drug discovery.PMID:39960015 | DOI:10.1021/acs.jafc.4c11335

Front Endocrinol (Lausanne). 2025 Jan 27;16:1514010. doi: 10.3389/fendo.2025.1514010. eCollection 2025.ABSTRACTBACKGROUND: Asthenozoospermia is a common cause of male infertility. Studies have shown that sperm quality and motility are affected by the gut-testis axis that can regulate testicular metabolism and function through the gut microbiota and its metabolites. Acupuncture is an important modality of complementary and alternative medicine. It can improve sperm motility, but it remains unclear whether acupuncture can enhance sperm vitality by influencing the gut-testis axis.METHODS: In this study, sperm quality, testicular pathology, and serum hormone levels were assessed using a cyclophosphamide-induced mouse model. Real-time PCR, a western blot analysis, and immunofluorescence techniques were used to assess the effects of acupuncture on the gut barrier and blood-testis barrier functions. In addition, gut microbiome and metabolomics were used to study the impact of acupuncture on the gut microbiota structure, serum, and testicular metabolites in asthenozoospermic mice. Further validation was obtained by performing a fecal microbiota transplantation (FMT).RESULTS: Acupuncture improved the sperm quality; ameliorated testicular pathology; increased serum testosterone (T), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) levels; and repaired gut and blood-testis barrier damage in asthenozoospermic mice. The abundances of Bacteroidota, Firmicutes, Faecalibaculum, and Dubosiella were associated with sperm motility, as shown by a gut microbiome analysis. Serum metabolomics revealed that differentially expressed metabolites (DEMs), such as cytosine and N-oleyl-leucine, were closely related to sperm motility. Testicular metabolomics analysis revealed DEMs, such as 5-fluorouridine and 1-acetylimidazole, were also associated with sperm motility. Furthermore, reproductive function improvements in asthenozoospermic mice through acupuncture were achieved via an FMT.CONCLUSION: Acupuncture may alleviate asthenozoospermia symptoms by modulating the gut-testis axis and repairing the gut-testis barrier.PMID:39959619 | PMC:PMC11827431 | DOI:10.3389/fendo.2025.1514010

Int J Yoga. 2024 Sep-Dec;17(3):163-174. doi: 10.4103/ijoy.ijoy_178_24. Epub 2024 Dec 14.ABSTRACTOBJECTIVE: Diabetes management remains challenging despite advancements in therapeutics, with many subjects developing complications. Yoga has been shown to aid diabetes management. This study investigates the impact of yoga therapy on diabetes progression, utilizing proteomics and metabolomics analyses to explore underlying molecular mechanisms.METHODOLOGY: A 3-month longitudinal study involving healthy subjects with prediabetes and diabetes was conducted. Blood glucose, glycated hemoglobin (HbA1c), lipid profile, and malondialdehyde (MDA) levels were measured before and after the yoga intervention.RESULTS AND CONCLUSION: Healthy subjects showed no significant changes in blood glucose, lipid profile, HbA1c, or MDA levels. However, subjects with prediabetes and diabetes experienced positive changes, with decreases in HbA1c and MDA levels. Proteomics and metabolomics analyses provided insights into the molecular mechanisms by which yoga attenuates diabetes progression in subjects with prediabetes and diabetes. This study is a pioneering effort to understand the molecular basis of yoga's beneficial effects on diabetes management.PMID:39959515 | PMC:PMC11823562 | DOI:10.4103/ijoy.ijoy_178_24

Front Cell Neurosci. 2025 Jan 31;19:1542164. doi: 10.3389/fncel.2025.1542164. eCollection 2025.ABSTRACTAge-related hearing loss (ARHL) is a complex condition with genetic, aging, and environmental influences. Sirtuins, particularly SIRT1, are NAD-dependent protein deacetylases critical to aging and stress responses. SIRT1 is modulated by nicotinamide N-methyltransferase (NNMT) and its product, N1-methylnicotinamide (MNAM), which influence ARHL progression. While SIRT1 is protective under certain conditions, its overexpression may paradoxically exacerbate hearing loss. This study examines MNAM supplementation's impact on SIRT1 expression and ARHL in low-fat diet (LFD)-fed B6 and CBA mice. Mice were divided into LFD and LFD + MNAM groups and evaluated for auditory function, cochlear morphology, metabolic profiles, and SIRT1 expression at 3, 6, and 12 months of age. MNAM supplementation accelerated ARHL in both strains, with B6 mice showing more pronounced and earlier disease progression. Auditory brainstem response (ABR) thresholds were significantly elevated, and distortion-product otoacoustic emissions (DPOAE) indicated outer hair cell dysfunction. Cochlear histology revealed reduced hair cell and spiral ganglion cell counts, as well as decreased Na+/K+-ATPase α1 expression and endocochlear potential. MNAM increased SIRT1 protein levels in the cochlea without altering Sirt1 mRNA, suggesting post-transcriptional regulation. Metabolomic analysis revealed disrupted mitochondrial and oxidative pathways, including fatty acid oxidation and gluconeogenesis. Tricarboxylic acid (TCA) cycle dysregulation was evident, particularly in B6 mice, with elevated pyruvate, fumarate, and lactate levels. Despite similar metabolic trends in CBA mice, their slower aging profiles mitigated ARHL progression. These results suggest that while moderate SIRT1 expression protects against ARHL, overexpression disrupts metabolic homeostasis, accelerating cochlear aging and dysfunction. The dual role of SIRT1 emphasizes the need for precise modulation of its expression for effective therapeutic interventions. Future research should explore mechanisms underlying SIRT1-induced cochlear damage and strategies to maintain balanced SIRT1 expression. This study highlights MNAM's detrimental effects on ARHL, underscoring its significance for developing targeted approaches to delay ARHL onset and preserve auditory function.PMID:39959464 | PMC:PMC11825784 | DOI:10.3389/fncel.2025.1542164

Front Pharmacol. 2025 Jan 31;16:1449639. doi: 10.3389/fphar.2025.1449639. eCollection 2025.ABSTRACTSpatial metabolomics is an emerging technology that integrates mass spectrometry imaging (MSI) with metabolomics, offering a novel visual perspective for traditional metabolomics analysis. This technology enables in-depth analysis in three dimensions: qualitative, quantitative, and localization of metabolites. Spatial metabolomics precisely reflects the characteristics of metabolic network changes in metabolites within entire tissues or specific micro-regions. It provides a detailed understanding of the pharmacodynamic material basis and mechanisms of action. These capabilities suggest that spatial metabolomics can offer significant technical support for studying the complex pathophysiology of mental disorders. Although the mechanisms underlying mental disorders have been reviewed multiple times, this paper provides a comprehensive comparison between traditional metabolomics and spatial metabolomics. It also summarizes the latest progress and challenges of applying spatial metabolomics to the study of mental disorders and traditional Chinese medicine.PMID:39959419 | PMC:PMC11825820 | DOI:10.3389/fphar.2025.1449639

Front Plant Sci. 2025 Jan 31;16:1544500. doi: 10.3389/fpls.2025.1544500. eCollection 2025.ABSTRACTThe acidic taste of Mei fruit (Prunus mume) is a major contributor to its quality, but its formation mechanism remains unclear. Here, we unraveled the networks of organic acid and flavonoid metabolism in two Mei fruit. The results showed that the differentially expressed genes were mainly concentrated in the processes of carbohydrate derivative binding, carboxylic acid, and organic acid metabolism. While the differentially accumulated metabolites were mainly associated with flavone and flavonol biosynthesis and amino acid and carbon metabolism. Moreover, we identified key metabolites, such as citric and succinic acids, which may be central to the development of acidity in Mei fruit, and determined that they are under the regulatory influence of specific genes, including galactinol-sucrose-galactosyltransferase 5, mitogen-activated protein kinase kinase kinase NPK1-like, glutamate receptor, and chalcone isomerase. Furthermore, transcription factors ERF027, bHLH92, bHLH35, and WRKY23 were identified as potential pivotal regulators within these networks. These results provide new insights into the metabolic regulation of acidity and flavonoid in Mei fruit.PMID:39959350 | PMC:PMC11825340 | DOI:10.3389/fpls.2025.1544500