PubMed

Cureus. 2025 Jan 9;17(1):r156. doi: 10.7759/cureus.r156. eCollection 2025 Jan.ABSTRACT[This retracts the article DOI: 10.7759/cureus.74161.].PMID:39791019 | PMC:PMC11717357 | DOI:10.7759/cureus.r156

Front Endocrinol (Lausanne). 2024 Dec 26;15:1464171. doi: 10.3389/fendo.2024.1464171. eCollection 2024.ABSTRACTINTRODUCTION: It is well acknowledged that lipids assume a critical role in oocyte maturation and early embryonic metabolism, this study aimed to evaluate the relationship between the lipid composition of plasma and follicular fluid (FF), and the consequences of embryonic development. This study compared the lipidomic profiles of paired plasma and FF samples obtained from sixty-five Chinese women who underwent assisted reproductive technology (ART) treatments.METHODS: Non-targeted lipidomics analysis.RESULT: Results not only indicated similarities in lipid composition between these biofluids, but also revealed a number of unique differences. The biomatrix distinction was found to be primarily driven by lipids belonging to the lysophosphatidylcholines (LPC), phosphatidylethanolamines (PE), ether PE, and triglyceride (TG) classes. In addition, specific species from these subclasses were discovered to be correlated with embryo development outcomes during ART. Notably, the composition of the fatty acyl chains appeared to play a crucial role in these associations. Furthermore, thirteen plasma lipid variables were identified, represented by Phosphatidylcholine 18:014:0 and PE P-18:020:1, which correlated with successful blastocyst formation (BF).DISCUSSION: The present study demonstrated that FF has a distinctive lipid composition, setting it apart from plasma; and the association observed with embryonic development underscored an important role of lipid composition in the healthy development of oocytes.PMID:39790287 | PMC:PMC11712041 | DOI:10.3389/fendo.2024.1464171

J Cancer Prev. 2024 Dec 30;29(4):105-112. doi: 10.15430/JCP.24.015.ABSTRACTGiven the evolutionary nature of tumor complexities and heterogeneity, the early diagnosis of cancer encounters various challenges. Complexities at the level of metabolite reprogramming are compelling in the background of invasiveness, metastasis, drug- and radiation-induced metabolic alterations, immunotherapy-influenced changes, and pro-tumor niche including microbiome. Therefore, it is crucial to examine both current and future obstacles associated with early cancer detection specifically in the context of tumor metabolite biomarkers at preclinical and clinical levels. In conclusion, the significance of tumor metabolite biomarkers must be aligned with a comprehensive approach to achbieve diagnosis and prognosis of cancer patients by securing solutions to formidable challenges.PMID:39790219 | PMC:PMC11706722 | DOI:10.15430/JCP.24.015

Anal Chem. 2025 Jan 9. doi: 10.1021/acs.analchem.4c04442. Online ahead of print.ABSTRACTThe development of multitargeted drugs is urgent for ischemic stroke. TRPV1 and TRPM8 are important targets of ischemic stroke. Previous drug candidate screening has identified that muscone, l-borneol, and ferulic acid may target TRPV1 and TRPM8 for ischemic stroke. However, the mechanisms of these drug candidates on targets were ill-informed. Therefore, firstly, a tongue-tissue biosensor was constructed. It explored the activation or inhibition mechanisms of drug candidates targeting TRPV1 and TRPM8 in a near-physiological environment. It was found that muscone could specifically inhibit TRPM8 and selectively activate TRPV1, while l-borneol exhibited the opposite effect. It suggested a synergistic network between these two drug candidates. Furthermore, more selective protein biosensors were developed to delve deeper into the synergistic mechanisms. A strong synergistic effect of muscone and l-borneol was proved. Molecular docking revealed that the synergistic effect was caused by different action sites, respectively. Subsequently, the synergistic effect of muscone and l-borneol was further confirmed by hypoxic nerve injury models of Caenorhabditis elegans (C. elegans) and antithrombus and anti-ischemic models of zebrafish. Ultimately, through nontargeted metabolomics, it was found that muscone and l-borneol mainly regulated Ca2+ concentration and energy metabolism by pathways such as purine and amino acid metabolisms. In conclusion, this research identified critical targets and synergistic drug candidates for multitarget neuroprotection of ischemic stroke. In addition, it has systemically demonstrated the feasibility of the integration of tissue/protein biosensors and metabolomics for the research and development of multitarget drugs. Compared to other screening and validation methods for drugs and targets, the biosensors we developed not only achieved higher sensitivity and specificity in complex physiological environments, ensuring a wider detection range, but also greatly saved biological samples. Simultaneously, they could be extended to other complex systems, such as biomarker screening in clinical samples and exosomes isolated from stem cells.PMID:39789730 | DOI:10.1021/acs.analchem.4c04442

BMC Plant Biol. 2025 Jan 10;25(1):38. doi: 10.1186/s12870-024-05984-8.ABSTRACTBACKGROUND: Perilla frutescens (L.) Britt. (Lamiaceae) leaves are essential culinary and medicinal herbs, native to East Asian countries. Three types of Perilla leaves, including green, green/purple and purple, are mainly found, and the leaf color is a critical attribute for consumer preferences. However, the extent of diversity and variability of metabolites in Perilla leaves of different colors remain elusive. Thus, in this study, we applied LC-QqQ-MS (liquid chromatography triple quadrupole tandem mass spectrometry)-based widely targeted metabolic profiling to investigate variation in the metabolite profiles of green (PF1), green/purple (PF2) and purple (PF3) Perilla leaves.RESULTS: We qualitatively and quantitatively identified a total of 1239 metabolites in Perilla leaves of different colors. Amino acids and derivatives (15.50%), flavonoids (14.77%), phenolic acids (12.19%), lipids (9.60%), carbohydrates and derivatives (8.47%), organic acids and derivatives (7.99%), nucleotides and derivatives (7.99%), and terpenoids (5.25%) were the major classes of metabolites in perilla leaves. In contrast to green leaves, the principal component analysis and correlation analysis revealed a considerable influence of genotypes for the variation in purple leaves' metabolite profiles. Differentially accumulated metabolites (DAMs) analysis revealed that flavonoids, phenolic acids, and amino acids and derivatives were the major DAMs, and the phenylpropanoid pathway was the most differentially regulated. All DAMs, including four potential metabolic discriminative biomarkers, were screened out. In addition, we revealed the accumulation patterns of bioactive compounds in the leaves of different colors. It was noteworthy that most of the differentially accumulated flavonoids showed a higher relative content in PF3, followed by PF2 and PF1. Glycosylated cyanidins and delphinidins were identified as the key compounds responsible for the purple coloration of leaves. Finally, we found that the variation in glutamate metabolism may be one of the main contributors for variation in metabolite profiles and biological attributes of Perilla leaves of different colors.CONCLUSION: Our results showed that the metabolic processes, mainly phenylpropanoid biosynthesis and amino acid metabolism, are differently regulated in green, green/purple and purple Perilla leaves. Furthermore, they offer valuable data for a comprehensive use of Perilla leaves and exploring gene-metabolites interactions in Perilla leaves.PMID:39789475 | DOI:10.1186/s12870-024-05984-8

Anim Microbiome. 2025 Jan 9;7(1):4. doi: 10.1186/s42523-024-00366-9.ABSTRACTBACKGROUND: Cows that develop metritis experience dysbiosis of their uterine microbiome, where opportunistic pathogens overtake uterine commensals. An effective immune response is critical for maintaining uterine health. Nonetheless, periparturient cows experience immune dysregulation, which seems to be intensified by prepartum over-condition. Herein, Bayesian networks were applied to investigate the directional correlations between prepartum body weight (BW), BW loss, pre- and postpartum systemic immune profiling and plasma metabolome, and postpartum uterine metabolome and microbiome.RESULTS: The Bayesian network analysis showed a positive directional correlation between prepartum BW, prepartum BW loss, and plasma fatty acids at parturition, suggesting that heavier cows were in lower energy balance than lighter cows. There was a positive directional correlation between prepartum BW, prepartum systemic leukocyte death, immune activation, systemic inflammation, and metabolomic changes associated with oxidative stress prepartum and at parturition. Immune activation and systemic inflammation were characterized by increased proportion of circulating polymorphonuclear cells (PMN) prepartum, B-cell activation at parturition, interleukin-8 prepartum and at parturition, and interleukin-1β at parturition. These immune changes together with plasma fatty acids at parturition had a positive directional correlation with PMN extravasation postpartum, which had a positive directional correlation with uterine metabolites associated with tissue damage. These results suggest that excessive PMN migration to the uterus leads to excessive endometrial damage. The aforementioned changes had a positive directional correlation with Fusobacterium, Porphyromonas, and Bacteroides in cows that developed metritis, suggesting that excessive tissue damage may disrupt physical barriers or increase substrate availability for bacterial growth.CONCLUSIONS: This work provides robust mechanistic hypotheses for how prepartum BW may impact peripartum immune and metabolic profiles, which may lead to uterine opportunistic pathogens overgrowth and metritis development.PMID:39789616 | DOI:10.1186/s42523-024-00366-9

BMC Microbiol. 2025 Jan 9;25(1):11. doi: 10.1186/s12866-024-03725-3.ABSTRACTBACKGROUND: Folpet is a nonspecific sulfonamide fungicide widely used to protect crops from mildew. However, the in vivo effects of folpet on glucose metabolism homeostasis, gut microbiota, and abundance of drug resistance genes remain unknown. The purpose of this study was to assess the effects of the pesticide, folpet, on glucose metabolism homeostasis, and folpet-induced changes in the intestinal microbiota and resistance genes in mice.METHODS: Mice were orally administered folpet at 0, 1, 10, and 100 mg/kg body weight/day for 5 weeks. Blood sugar levels in mice were measured after 5 weeks of folpet administration. Metagenomic sequencing and drug resistance gene analyses were performed to explore changes in the abundance of gut microbiota members and drug resistance genes in mice after folpet administration. Correlation analysis was performed using metabolomics to explore the relationship between intestinal microbiota, drug resistance genes, and glucose metabolism.RESULTS: Mice in the folpet group had significantly lower blood glucose levels than those in the control group. The abundance of Atopobium, Libanicoccus, Collinsella, and Parabacteroides in the intestinal microbiota of folpet-treated mice was significantly higher than that in the control group. However, the abundance of Mailhella, Bilophila, Roseburia, and Bacteroides were reduced in folpet-treated mice. Compared with the control group, the abundance of APH6-Ic and AAC6-Ie-APH2-Ia resistance genes in mice treated with folpet significantly increased. The abundance of tetQ, ermE, and BahA resistance genes was significantly reduced after folpet treatment.CONCLUSIONS: Folpet is associated with changes in the abundance of gut microbiota in mice and may also affect the abundance of drug-resistance genes and the regulation of blood glucose levels.PMID:39789436 | DOI:10.1186/s12866-024-03725-3

Cell Mol Biol Lett. 2025 Jan 9;30(1):3. doi: 10.1186/s11658-024-00681-8.ABSTRACTBACKGROUND: Metabolism is error prone. For instance, the reduced forms of the central metabolic cofactors nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH), can be converted into redox-inactive products, NADHX and NADPHX, through enzymatically catalyzed or spontaneous hydration. The metabolite repair enzymes NAXD and NAXE convert these damaged compounds back to the functional NAD(P)H cofactors. Pathogenic loss-of-function variants in NAXE and NAXD lead to development of the neurometabolic disorders progressive, early-onset encephalopathy with brain edema and/or leukoencephalopathy (PEBEL)1 and PEBEL2, respectively.METHODS: To gain insights into the molecular disease mechanisms, we investigated the metabolic impact of NAXD deficiency in human cell models. Control and NAXD-deficient cells were cultivated under different conditions, followed by cell viability and mitochondrial function assays as well as metabolomic analyses without or with stable isotope labeling. Enzymatic assays with purified recombinant proteins were performed to confirm molecular mechanisms suggested by the cell culture experiments.RESULTS: HAP1 NAXD knockout (NAXDko) cells showed growth impairment specifically in a basal medium containing galactose instead of glucose. Surprisingly, the galactose-grown NAXDko cells displayed only subtle signs of mitochondrial impairment, whereas metabolomic analyses revealed a strong inhibition of the cytosolic, de novo serine synthesis pathway in those cells as well as in NAXD patient-derived fibroblasts. We identified inhibition of 3-phosphoglycerate dehydrogenase as the root cause for this metabolic perturbation. The NAD precursor nicotinamide riboside (NR) and inosine exerted beneficial effects on HAP1 cell viability under galactose stress, with more pronounced effects in NAXDko cells. Metabolomic profiling in supplemented cells indicated that NR and inosine act via different mechanisms that at least partially involve the serine synthesis pathway.CONCLUSIONS: Taken together, our study identifies a metabolic vulnerability in NAXD-deficient cells that can be targeted by small molecules such as NR or inosine, opening perspectives in the search for mechanism-based therapeutic interventions in PEBEL disorders.PMID:39789421 | DOI:10.1186/s11658-024-00681-8

Ecotoxicology. 2025 Jan 9. doi: 10.1007/s10646-024-02846-9. Online ahead of print.ABSTRACTMany contaminants from scattered sources constantly endanger streams that flow through heavily inhabited areas, commercial districts, and industrial hubs. The responses of transplanted mussels in streams in active biomonitoring programs will reflect the dynamics of environmental stream conditions. This study evaluated the untargeted metabolomic and proteomic responses and free radical scavenging activities of transplanted mussels Sinanodonta woodiana in the Winongo Stream at three stations (S1, S2, S3) representing different pollution levels: low (S1), high (S2), and moderate (S3). The investigation examined untargeted metabolomic and proteomic responses in the gills and 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) activities in the gills, mantle, and digestive glands. Metabolomic analysis revealed a clear separation between mussel responses from the three stations after 28 days of exposure, with specific metabolites responding to different pollution levels. Proteomic analysis identified β-Actin protein in all stations. The β-Actin protein sequence of unexposed mussels had coverage of 17%, and increased to 23% at S1 on day 28 and 34% at S2 and S3 on day 28. All tissues showed increased DPPH and ABTS activities from day 3 to day 28, mainly in stations S2 and S3. These findings underscore the impact of pollution levels on the metabolomic and proteomic responses of S. woodiana and the importance of these discoveries as early indicators (biomarkers) of long-term aquatic environmental problems. In the face of current environmental challenges, this research raises concerns about the health of water bodies. It underscores the importance of developing robust, standardized, and dependable analytical techniques for monitoring the health of aquatic environments.PMID:39789405 | DOI:10.1007/s10646-024-02846-9

Vet Res Commun. 2025 Jan 10;49(2):70. doi: 10.1007/s11259-024-10620-9.ABSTRACTThis study investigated, for the first time, the alterations in the uterine echotexture and blood flow in cyclic and acyclic (inactive ovary) goats using ultrasonography. The study aimed also to evaluate the metabolomic changes in the plasma of cyclic and acyclic goats. Furthermore, the histopathological approach was applied to the specimens of the uterus to validate the findings of this study. Based on monitoring the estrous cyclicity, goats were assigned into either a cyclic group or an acyclic one (n = 7, each). Ovarian morphometry and hemodynamics were assessed to confirm group assignment. Full ultrasonographic examinations were performed to assess the uterine echotexture by B-mode ultrasonography and uterine hemodynamics by color Doppler ultrasonography in the cyclic group (at days 10-12) and acyclic group. Additionally, blood samples were withdrawn for measuring hormonal concentrations and for metabolomics analysis. Specimens of the uterus were executed for histopathological evaluation in both groups. Results revealed alterations in the uterine hemodynamics and endometrial echotexture. Goats in the cyclic group attained a significantly higher color pixel area of the endometrium compared to those in the acyclic one (P< 0.001). However, the pixel intensity of the endometrium echotexture was significantly (P< 0.05) lower in the cyclic group than in the smooth inactive ovary one. There were significant (P< 0.05) increases in the concentrations of FSH, LH, and inhibin in the cyclic group compared to their concentrations in the acyclic one. Goats in the acyclic group attained noticeable (P< 0.001) lower concentrations of E2 and P4 than in the cyclic goats. The metabolomic results revealed the existence of several up- and down-regulated metabolites among the studied groups. In this investigation, untargeted metabolomic analysis revealed the existence of 5 up-regulated metabolites (ketoleucine, L-fucose, D-glucurono-6,3-lactone, melatonin, and 5-methoxy tryptamine) and 5 down-regulated ones (p-octopamine, 3-hydroxyisovaleric acid, methylmalonic acid, 4-hydroxyphenylpyruvic acid, and cadaverine) in the cyclic group compared to the acyclic one. The enrichment analysis of the significant metabolites showed top pathways that may be involved in these changes, such as fructose and mannose metabolism, valine. Leucine, and isoleucine biosynthesis, linoleic acid metabolism, arginine biosynthesis, and vitamin B6 metabolism based on the KEGG enriched pathway. Altogether, the histopathological assessment showed noticeable changes in the columnar epithelial lining of the endometrial epithelium, endometrial vascularity, and endometrial glands among the studied groups. In conclusion, this study extrapolated the differences between cyclic goats (during the mid-luteal phase) and acyclic ones in terms of hormonal, hemodynamics, echotexture of the uterus, and circulating metabolomics. These findings are very crucial to fully assess the fertility potential in goats.PMID:39789373 | DOI:10.1007/s11259-024-10620-9

Commun Med (Lond). 2025 Jan 9;5(1):12. doi: 10.1038/s43856-024-00703-8.ABSTRACTBACKGROUND: Multiple sulfatase deficiency (MSD) is an exceptionally rare neurodegenerative disorder due to the absence or deficiency of 17 known cellular sulfatases. The activation of all these cellular sulfatases is dependent on the presence of the formylglycine-generating enzyme, which is encoded by the SUMF1 gene. Disease-causing homozygous or compound heterozygous variants in SUMF1 result in MSD. Other than symptomatic treatment, no curative therapy exists as of yet for MSD. Eight out of these 17 sulfatases are primarily localized in the lysosome.METHODS: Two siblings with attenuated MSD underwent hematopoietic cell transplantation (HCT), evaluating the possibility of lysosomal enzymatic cross-correction from the donor cells.RESULTS: There is evidence of correction of currently available biomarkers within 3 months post-HCT. Untargeted metabolomics also shows continued correction of multiple biochemical abnormalities in the post-HCT period. Furthermore, this article also presents the neuropsychological outcomes of these children as well as the results of untargeted metabolomics analysis in this condition.CONCLUSIONS: These data suggest biochemical benefits post-transplant along with slowing of disease progression. Long-term follow-up is necessary to fully evaluate the therapeutic benefit of HCT in MSD.PMID:39789203 | DOI:10.1038/s43856-024-00703-8

Nat Commun. 2025 Jan 9;16(1):551. doi: 10.1038/s41467-024-55800-y.ABSTRACTCompetition among bacteria for carbohydrates is pivotal for colonization resistance (CR). However, the impact of Western-style diets on CR remains unclear. Here we show how the competition between Klebsiella oxytoca and Klebsiella pneumoniae is modulated by consuming one of three Western-style diets characterized by high-starch, high-sucrose, or high-fat/high-sucrose content. In vivo competition experiments in ampicillin-treated mice reveal that K. oxytoca promotes K. pneumoniae decolonization on all dietary backgrounds. However, mice on the high-fat/high-sucrose diet show reduced pathogen clearance. Microbiome analysis reveals that the combination of Western-style diets and ampicillin treatment synergize in microbiome impairment, particularly noticeable in the presence of high dietary fat content. The diet-independent degradation of ampicillin in the gut lumen by K. oxytoca beta-lactamases facilitates rapid commensal outgrowth, which is required for subsequent pathogen clearance. Our findings provide insights into how diet modulates functional microbiome recovery and K. oxytoca-mediated pathogen elimination from the gut.PMID:39789003 | DOI:10.1038/s41467-024-55800-y

Nat Commun. 2025 Jan 9;16(1):541. doi: 10.1038/s41467-024-55605-z.ABSTRACTThe energetic demands of proliferating cells during tumorigenesis require close coordination between the cell cycle and metabolism. While CDK4 is known for its role in cell proliferation, its metabolic function in cancer, particularly in triple-negative breast cancer (TNBC), remains unclear. Our study, using genetic and pharmacological approaches, reveals that CDK4 inactivation only modestly impacts TNBC cell proliferation and tumor formation. Notably, CDK4 depletion or long-term CDK4/6 inhibition confers resistance to apoptosis in TNBC cells. Mechanistically, CDK4 enhances mitochondria-endoplasmic reticulum contact (MERCs) formation, promoting mitochondrial fission and ER-mitochondrial calcium signaling, which are crucial for TNBC metabolic flexibility. Phosphoproteomic analysis identified CDK4's role in regulating PKA activity at MERCs. In this work, we highlight CDK4's role in mitochondrial apoptosis inhibition and suggest that targeting MERCs-associated metabolic shifts could enhance TNBC therapy.PMID:39788939 | DOI:10.1038/s41467-024-55605-z

New Phytol. 2025 Jan 9. doi: 10.1111/nph.20364. Online ahead of print.ABSTRACTIncreasing atmospheric CO2 levels have a variety of effects that can influence plant responses to microbial pathogens. However, these responses are varied, and it is challenging to predict how elevated CO2 (eCO2) will affect a particular plant-pathogen interaction. We investigated how eCO2 may influence disease development and responses to diverse pathogens in the major oilseed crop, soybean. Soybean plants grown in ambient CO2 (aCO2, 419 parts per million (ppm)) or in eCO2 (550 ppm) were challenged with bacterial, viral, fungal, and oomycete pathogens. Disease severity, pathogen growth, gene expression, and molecular plant defense responses were quantified. In eCO2, plants were less susceptible to Pseudomonas syringae pv. glycinea (Psg) but more susceptible to bean pod mottle virus, soybean mosaic virus, and Fusarium virguliforme. Susceptibility to Pythium sylvaticum was unchanged, although a greater loss in biomass occurred in eCO2. Reduced susceptibility to Psg was associated with enhanced defense responses. Increased susceptibility to the viruses was associated with reduced expression of antiviral defenses. This work provides a foundation for understanding how future eCO2 levels may impact molecular responses to pathogen challenges in soybean and demonstrates that microbes infecting both shoots and roots are of potential concern in future climatic conditions.PMID:39788902 | DOI:10.1111/nph.20364

Fitoterapia. 2025 Jan 3:106375. doi: 10.1016/j.fitote.2024.106375. Online ahead of print.NO ABSTRACTPMID:39788796 | DOI:10.1016/j.fitote.2024.106375

Anal Chim Acta. 2025 Jan 22;1336:343491. doi: 10.1016/j.aca.2024.343491. Epub 2024 Nov 27.ABSTRACTBACKGROUND: Untargeted metabolomics requires robust and reliable strategies for data processing to extract relevant information form the underlying raw data. Multiple platforms for data processing are available, but the choice of software tool can have an impact on the analysis. This study provides a comprehensive evaluation of four workflows based on commonly used metabolomics software tools: XCMS, Compound Discoverer, MS-DIAL, and MZmine. These tools were applied to a dataset derived from bovine saliva samples spiked with small polar molecules analyzed by anion exchange chromatography coupled to high resolution mass spectrometry.RESULTS: The analysis revealed significant differences in the number and overlap of detected features, with only approximately 8 % of the features included in all four peak tables. Among the overlapping features, MS-DIAL demonstrated the greatest similarity to manual integration, while XCMS and MZmine also performed well. In contrast, Compound Discoverer had issues to reliably integrate high baseline peaks. This study also explores various post-processing strategies, including missing value imputation, transformation, scaling, and filtering. The assessment of missing values indicated that they primarily originated from low abundance, making imputation with small values the most effective approach. No clear evidence suggested that transformation is necessary for downstream statistical analyses. Auto scaling emerged as the most suitable strategy for data scaling. Low thresholds for blank filtering were found to be the most effective in enhancing data quality. The optimization of filtering thresholds required a careful balance to remove unnecessary information while retaining vital data.SIGNIFICANCE AND NOVELTY: This work provides an overview of commonly applied strategies in untargeted metabolomics analysis, emphasizing the importance of careful workflow selection and optimization. It serves as a resource for refining data processing strategies to achieve accurate and reliable results, while also offering fresh insights into the challenges encountered throughout the untargeted metabolomics processing pipeline.PMID:39788662 | DOI:10.1016/j.aca.2024.343491

J Agric Food Chem. 2025 Jan 9. doi: 10.1021/acs.jafc.4c07689. Online ahead of print.ABSTRACTThe fasting hypoglycemic effect of casein hydrolysate (CH) was investigated in db/db diabetic-like mice using a multiomics integrated analysis of peptidome, transcriptome, and metabolome. Results showed that the oral administration of CH at a dose of 600 mg/kg/day for 4 weeks reduced the fasting blood glucose levels by 14.73 ± 9.77%, alleviated insulin resistance (HOMA-IR index) by 36.91 ± 22.62%, and mitigated hepatic damage in db/db diabetic-like mice. Hepatic differential metabolites after CH treatment were enriched in Glu-related metabolites, which acted as substrates for the TCA cycle, enhancing hepatic glucose consumption. The hepatic transcriptomic results revealed that CH treatment upregulated (p < 0.05) hub gene expressions of pparg and pik3cb, leading to an activation of the PPAR signaling pathway, further improving the insulin/PI3K/AKT signaling pathway. The hub gene expressions were highly correlated with Glu-related metabolites in multiomics integrated analysis. Glx/Glx-containing peptides (Glx represents Glu and Gln) in CH, as a dietary supplement to increase hepatic Glu-related metabolites, might be the key active component responsible for its hypoglycemic effect. Particularly, the supplement of Glx was confirmed to effectively (p < 0.05) enhance glucose consumption in hepatocytes. This provides a basis for the development of CHs as functional food.PMID:39788553 | DOI:10.1021/acs.jafc.4c07689

Exp Hematol. 2025 Jan 7:104710. doi: 10.1016/j.exphem.2025.104710. Online ahead of print.ABSTRACTHematological malignancies encompass a diverse array of subtypes, contributing to substantial heterogeneity that poses challenges in predicting clinical outcomes. Leveraging the capabilities of nuclear magnetic resonance holds substantial promise in the detection of serum biomarkers and individual metabolic alterations in patients. The study involved the analysis of the sera from patients with acute myeloid leukemia, chronic lymphocytic leukemia, and non-Hodgkin lymphoma to investigate the impacted metabolites and their associated pathways. The quantitative 1D 1H nuclear magnetic resonance method was employed to identify alterations. Metabolite annotations were validated using 2D analyses. Discriminating chemometric models and receiver operating characteristic curves were created using the MetaboAnalyst platform. The findings revealed significant alterations in the serum levels of amino acid catabolism products, citrate cycle intermediates, and phospholipids. The acute myeloid leukemia group showed differences in glucogenic amino acids related to the glycolysis pathway, while the chronic lymphocytic leukemia and non-Hodgkin lymphoma groups displayed variances in fumarate and acetate levels linked to the citrate cycle pathway. In the leukemia groups, higher levels of products from the protein degradation pathway were observed. The biomarker panels for each malignancy group exhibited outstanding discrimination from controls. Healthy individuals differed distinctly from patients, indicating commonly observed metabolic adaptation patterns among frequent hematological malignancies. The small cohort study using nuclear magnetic resonance metabolomics in various hematological malignancy subtypes revealed significant changes in serum amino acid and protein degradation end-product levels, suggesting prolonged leukocyte lifespan and increased energy demand.PMID:39788411 | DOI:10.1016/j.exphem.2025.104710

Clin Immunol. 2025 Jan 7:110428. doi: 10.1016/j.clim.2025.110428. Online ahead of print.ABSTRACTEpidemiologic studies have shown a continuous increase in mortality risk associated with overweight, thus highlighting the health risks beginning before the onset of obesity. However, early changes in inflammatory signaling induced by an obesogenic diet remain largely unknown since studies of obesity typically utilize models induced by months of continuous exposure to a high-fat diet. Here, we investigated how short-term overfeeding remodels inflammatory signaling. We developed and characterized a mouse model of overweight induced by seven days of the Western diet enriched in saturated fats and sucrose, compared to the standard, low-fat laboratory diet or a long-term Western diet for 22 weeks. The short-term Western diet caused a median weight gain of 6 %, while the long-term Western diet increased weight by 92 %. Circulating levels of cholesterol, triglycerides, insulin, and leptin were increased by both diets, but only the long-term Western diet caused transaminitis and significant hepatic steatosis. Both models reduced the alpha and beta diversity of the microbiome. Tryptophan metabolism was perturbed by both models; the long-term Western diet also affected histidine and vitamin B6 metabolism. The short-term and long-term Western diets increased expression of TLR4 on peritoneal immune cells and TLR4-driven plasma levels of proinflammatory cytokines comparably, showing one week of the Western diet was sufficient for inducing inflammation typical of chronic obesity. These findings highlight the importance of diet not only in preclinical studies, but also in the clinical care of individuals with inflammatory disorders.PMID:39788355 | DOI:10.1016/j.clim.2025.110428

Biochim Biophys Acta Mol Cell Biol Lipids. 2025 Jan 7:159593. doi: 10.1016/j.bbalip.2025.159593. Online ahead of print.ABSTRACTDHHC-mediated protein-S-palmitoylation is recognized as a distinct and reversible lipid modification, playing a pivotal role in the progression and prevention of multiple diseases, including cancer and neurodegenerative disorders. Over the past decade, growing evidence indicates the crucial role of DHHC2 in preventing tumorigenesis by palmitoylation of various protein substrates. However, a comprehensive understanding of the specific impact of DHHC2 on cancer cell metabolic regulation remains unclear. To investigate the metabolites change by DHHC2, we conducted untargeted metabolomic profiling on the HEK-293 T cell line with DHHC2- Knockdown (DHHC2-KD), DHHC2-Overexpression (DHHC2-OE) and empty vector control (Ctrl) conditions via LC-MS/MS-based analysis. Our dataset revealed the identification of a total of 73 metabolites encompassing all the conditions, with only 22 showing significant differences in univariate analysis. Furthermore, we performed pathway analysis with metabolites having VIP ≥ 0.7, P value ≤0.05, and fold change (FC) > 2 in DHHC2-OE (upregulated) and FC < 0.5 in DHHC2-OE or FC > 2 in DHHC2-KD condition (downregulated). We unveiled significant expression of the pyrimidine metabolism, urea cycle, and aspartate metabolism due to the abundance of onco-metabolites such as glutamine, uridine, and glutamic acid in the DHHC2-KD condition. However, DHHC2 overexpression resulted in a higher expression of metabolites previously reported to be associated with anti-cancer activity, such as betaine and 5'-methylthioadenosine (5'-MTA). Overall, this study sheds light on the changes mediated by DHHC2 in a cancer cell metabolome and suggests avenues for further investigation into other DHHC isoforms and their metabolic aspects.PMID:39788345 | DOI:10.1016/j.bbalip.2025.159593