PubMed

Anal Bioanal Chem. 2025 Feb 22. doi: 10.1007/s00216-025-05794-3. Online ahead of print.ABSTRACTThe challenge of robust and automated glycopeptide quantitation from liquid chromatography-mass spectrometry (LC-MS) data has yet to be adequately addressed by commercial software. Recently, open-source tools like Skyline and LaCyTools have advanced the field of label-free MS1 level quantitation. Yet, important steps late in the data processing workflow remain manual. Because manual data curation is time-consuming and error-prone, it presents a bottleneck, especially in an era of emerging high-throughput methodologies and increasingly complex analyses such as antigen-specific antibody glycosylation. We addressed this gap by developing GlycoDash, an R Shiny-based interactive web application designed to democratize label-free high-throughput glycoproteomics data analysis. The software comes in at a stage where analytes have been identified and quantified, but whole measurement and individual analyte signals of insufficient quality for quantitation remain and reduce the quality of the overall dataset. GlycoDash focuses on these challenges by incorporating several options for measurement and metadata linking, spectral and analyte curation, normalization, and repeatability assessment, and additionally includes glycosylation trait calculation, data visualization, and reporting capabilities that adhere to FAIR principles. The performance and versatility of GlycoDash were demonstrated across antibody glycoproteomics data of increasing complexity, ranging from relatively simple monoclonal antibody glycosylation analysis to a clinical cohort with over a thousand measurements. In a matter of hours, these large, diverse, and complex datasets were curated and explored. High-quality datasets with integrated metadata ready for final analysis and visualization were obtained. Critical aspects of the curation strategy underlying GlycoDash are discussed. GlycoDash effectively automates and streamlines the curation of glycopeptide quantitation data, addressing a critical need for high-throughput glycoproteomics data analysis. Its robust performance across diverse datasets and its comprehensive feature toolbox significantly enhance both research and clinical applications in glycoproteomics.PMID:39985669 | DOI:10.1007/s00216-025-05794-3

Bioinformatics. 2025 Feb 22:btaf077. doi: 10.1093/bioinformatics/btaf077. Online ahead of print.ABSTRACTMOTIVATION: Modeling genome-scale metabolic networks (GEMs) helps understand metabolic fluxes in cells at a specific state under defined environmental conditions or perturbations. Elementary Flux Modes (EFMs) are powerful tools for simplifying complex metabolic networks into smaller, more manageable pathways. However, the enumeration of all EFMs, especially within GEMs, poses significant challenges due to computational complexity. Additionally, traditional EFM approaches often fail to capture essential aspects of metabolism, such as co-factor balancing and by-product generation.The previously developed Minimum Network Enrichment Analysis (MiNEA) method addresses these limitations by enumerating alternative minimal networks for given biomass building blocks and metabolic tasks. MiNEA facilitates a deeper understanding of metabolic task flexibility and context-specific metabolic routes by integrating condition-specific transcriptomics, proteomics, and metabolomics data. This approach offers significant improvements in the analysis of metabolic pathways, providing more comprehensive insights into cellular metabolism.RESULTS: Here, I present MiNEApy, a Python package reimplementation of MiNEA, which computes minimal networks and performs enrichment analysis. I demonstrate the application of MiNEApy on both a small-scale and a genome-scale model of the bacterium E. coli, showcasing its ability to conduct minimal network enrichment analysis using minimal networks and context-specific data.AVAILABILITY: MiNEApy can be accessed at: https://github.com/vpandey-om/mineapy.SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.PMID:39985451 | DOI:10.1093/bioinformatics/btaf077

Adv Sci (Weinh). 2025 Feb 22:e2408769. doi: 10.1002/advs.202408769. Online ahead of print.ABSTRACTAutoantibodies and their post-translational modifications (PTMs) are insightful markers of autoimmune diseases providing diagnostic and prognostic clues, thereby informing clinical decisions. However, current autoantibody analyses focus mostly on IgG1 glycosylation representing only a subpopulation of the actual IgG proteome. Here, by taking rheumatoid arthritis (RA) as prototypic autoimmune disease, we sought to circumvent these shortcomings and illuminate the importance of (auto)antibody proteoforms employing a novel comprehensive mass spectrometry (MS)-based analytical workflow. Profiling of anti-citrullinated protein antibodies (ACPA) IgG and total IgG in paired samples of plasma and synovial fluid revealed a clear distinction of autoantibodies from total IgG and between biofluids. This discrimination relied on comprehensive subclass-specific PTM profiles including previously neglected features such as IgG3 CH3 domain glycosylation, allotype ratios, and non-glycosylated IgG. Intriguingly, specific proteoforms were found to correlate with markers of inflammation and disease accentuating the need of such approaches in clinical investigations and calling for further mechanistic studies to comprehend the role of autoantibody proteoforms in defining autoimmune responses.PMID:39985219 | DOI:10.1002/advs.202408769

FEBS J. 2025 Feb 22. doi: 10.1111/febs.70029. Online ahead of print.ABSTRACTDuchenne muscular dystrophy is a severe neuromuscular wasting disease that is caused by a primary defect in dystrophin protein and involves organism-wide comorbidities such as cardiomyopathy, metabolic and mitochondrial dysfunction, and nonprogressive cognitive impairments. Physiological stress exposure in the mdx mouse model of Duchenne muscular dystrophy results in phenotypic abnormalities that include locomotor inactivity, hypotension, and increased morbidity. Severe and lethal stress susceptibility in mdx mice corresponds to metabolic dysfunction in several coordinated metabolic pathways within dystrophin-deficient skeletal muscle, as well as prolonged elevation in mdx plasma corticosterone levels that extends beyond the wild-type (WT) stress response. Here, we performed a targeted mass spectrometry-based plasma metabolomics screen focused on biological stress pathways in healthy and dystrophin-deficient mdx mice exposed to mild scruff stress. One-third of the stress-relevant metabolites interrogated displayed significant elevation or depletion in mdx plasma after scruff stress and were restored to WT levels by skeletal muscle-specific dystrophin expression. The metabolic pathways of mdx mice altered by scruff stress are associated with regulation of the hypothalamic-pituitary-adrenal axis, locomotor tone, neurocognitive function, redox metabolism, cellular bioenergetics, and protein catabolism. Our data suggest that a mild stress triggers an exaggerated, multi-system metabolic response in mdx mice.PMID:39985215 | DOI:10.1111/febs.70029

Lipids Health Dis. 2025 Feb 21;24(1):61. doi: 10.1186/s12944-024-02425-1.ABSTRACTLipid metabolism is a well-regulated process essential for maintaining cellular functions and energy homeostasis. Dysregulation of lipid metabolism is associated with various conditions, including cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. This review explores the mechanisms underlying lipid metabolism, emphasizing the roles of key lipid species such as triglycerides, phospholipids, sphingolipids, and sterols in cellular physiology and pathophysiology. It also examines the genetic and environmental factors contributing to lipid dysregulation and the challenges of diagnosing and managing lipid-related disorders. Recent advancements in lipid-lowering therapies, including PCSK9 inhibitors, ezetimibe, bempedoic acid, and olpasiran, provide promising treatment options. However, these advancements are accompanied by challenges related to cost, accessibility, and patient adherence. The review highlights the need for personalized medicine approaches to address the interplay between genetics and environmental factors in lipid metabolism. As lipidomics and advanced diagnostic tools continue to progress, a deeper understanding of lipid-related disorders could pave the way for more effective therapeutic strategies.PMID:39984909 | DOI:10.1186/s12944-024-02425-1

BMC Complement Med Ther. 2025 Feb 21;25(1):67. doi: 10.1186/s12906-025-04774-5.ABSTRACTBACKGROUND: Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder with significant metabolic and hormonal dysregulation. Marjoram (Origanum majorana L.), known for its medicinal properties, has potential in managing PCOS through various bioactive compounds.OBJECTIVE: This study aims to evaluate the effects of marjoram on PCOS symptoms using serum pharmacochemistry, network pharmacology, and molecular docking in a DHEA-induced rat model.METHODS: Polycystic Ovary Syndrome (PCOS) was induced in rats using dehydroepiandrosterone (DHEA). Marjoram's therapeutic effects were evaluated by analyzing oxidative stress biomarkers, hormone levels, and ovarian histopathology. Untargeted serum metabolomics, conducted with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC TQD-MS/MS), identified key bioactive compounds. These compounds were then examined through network pharmacology to map their interactions with PCOS-related pathways, with findings validated via molecular docking.RESULTS: Marjoram treatment significantly reduced oxidative stress by decreasing nitric oxide (NO) and increasing total antioxidant capacity (TAC). Hormonal analysis revealed that high-dose marjoram (100 mg/kg) normalized progesterone, estradiol, testosterone and FSH levels. Body weight gain was also reduced with marjoram treatment, especially at the higher dose. Histopathological evaluation showed fewer ovarian cysts and improved follicular structure with marjoram administration. Network pharmacology analysis highlighted the steroid hormone biosynthesis and estrogen signaling pathways as critical targets, with apigenin and oleic acid identified as active compounds. Molecular docking confirmed strong interactions of these compounds with core PCOS-associated proteins, further supporting marjoram's potential in modulating PCOS symptoms.CONCLUSION: This study reveals that marjoram contains a diverse range of active compounds that can modulate crucial biochemical and histological markers related to PCOS. By combining serum pharmacochemistry with network pharmacology, the research highlights marjoram's potential as a natural supplement to help alleviate PCOS symptoms and slow the syndrome's progression. These findings support further investigation into marjoram's role as a complementary therapy for managing PCOS.PMID:39984989 | DOI:10.1186/s12906-025-04774-5

Mol Med. 2025 Feb 21;31(1):76. doi: 10.1186/s10020-025-01129-1.ABSTRACTHydroxy-alpha-sanshool (HAS) has attracted attention because of its various biological activities, such as hypoglycemic, hypolipidemic, and antioxidant activities. In this study, we investigated the effects of HAS on insulin resistance (IR) and its mechanism. HAS reduced fasting blood glucose (FBG), promoted insulin (INS) secretion, significantly decreased levels of interleukin (IL)-1, IL-6, tumor necrosis factor (TNF)-α and monocyte chemoattractant protein-1 (MCP-1), and increased the IL-2 level in serum of IR model mice. HAS regulated the mRNA levels of protein kinase B (Akt), B-cell lymphoma extra-large (Bcl-xL), stearoyl-CoA desaturase-1 (SCD1), nuclear factor kappa B (NF-κB), and eukaryotic translation initiation factor 4E (eIF4E). Additionally, differentially abundant metabolites in IR model mice treated with HAS were involved in these signaling pathways including prion disease, choline metabolism in cancer, regulation of lipolysis in adipocytes and the pentose phosphate pathway and positively regulated betaine abundance. In conclusion, HAS activated the phosphatidylinositol-3 kinase (PI3K)/Akt insulin and NF-κB signaling pathways to maintain glucose homeostasis and regulate IR.PMID:39984861 | DOI:10.1186/s10020-025-01129-1

BMC Plant Biol. 2025 Feb 21;25(1):237. doi: 10.1186/s12870-025-06223-4.ABSTRACTThe phytohormone brassinosteroid (BR) regulate various developmental and physiological processes in plants. However, the function of BR during early seedling development stage in rapeseed is largely unknown. To understand the effects of exogenous BR during early seedling development, the ZS11 and BR-INSENSITIVE (bin2) mutants were treated with BR before seed sowing and seed germination stage under 16/8 hours light/dark cycle. The phenotype results indicated that BR promotes only seedling establishment but not seed germination stage in ZS11, while no function in bin2 mutants. Since BRs play a crucial role in regulation of developmental transition between growth in the dark (skotomorphogenesis) and growth in the light (photomorphogenesis), the ZS11 and bin2 mutants were treated with BR under continuous light and dark. The BR treatment also showed the same functions as 16/8 hours light/dark cycle. To understand the function of BR on expression levels, the differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) between mock- and BR-treated seedlings were explored. A total of 234 significantly DEGs were identified between the mock- and BR-treated groups by transcriptomic analyses. These DEGs were markedly enriched in BR biosynthesis, pentose and glucuronate interconversions and plant hormone signal transduction pathways. Meanwhile, a total of 145 DEMs were identified through metabolomics analyses, with a significant enrichment in lipid substances. Interestingly, some genes and metabolites associated with auxin pathway were identified, which exhibited up-regulation in both DEGs and DEMs after BR treatment. Subsequently, functional enrichment analyses revealed that the majority of DEGs and DEMs were primarily enriched in ascorbate and aldehyde metabolism, arginine and proline metabolism, tryptophan metabolism (the main route for auxin synthesis) and cyanogenic amino acid metabolism. Furthermore, it was found that glutamate was up-regulated in nitrogen metabolism, glyoxylate and dicarboxylate metabolism, and arginine and proline metabolism pathways. These indicated that the glutamate signaling pathway was a key regulatory pathway for exogenous BR to induce seedling establishment. These evidence implied that exogenous BR treatment lead to up-regulation of auxin-related genes expression, then promoted seedling establishment in rapeseed.PMID:39984844 | DOI:10.1186/s12870-025-06223-4

J Appl Microbiol. 2025 Feb 21:lxaf044. doi: 10.1093/jambio/lxaf044. Online ahead of print.ABSTRACTAIMS: To combat health conditions, such as multi-resistant bacterial infections, cancer and metabolic diseases, new drugs need to be urgently found and, in this respect, marine Actinomycetota have a high potential to produce secondary metabolites with pharmacological importance. We aimed to study the cultivable Actinomycetota community associated with a marine sponge from the Portuguese coast, Hymeniacidon perlevis, and investigate the potential of the retrieved isolates to produce compounds with antimicrobial, anticancer and anti-obesity properties.METHODS AND RESULTS: The analysis of the 16S rRNA gene revealed 79 Actinomycetota isolates affiliated with twelve genera - Brachybacterium, Dietzia, Glutamicibacter Gordonia, Micrococcus, Micromonospora, Nocardia, Nocardiopsis, Paenoartrhobacter, Rhodococcus, Streptomyces and Tsukamurella, most of which affiliated with the genus Streptomyces. The screening of antimicrobial activity revealed 13 strains, all belonging to the Streptomyces genus, capable of inhibiting the growth of Candida albicans, Bacillus subtilis or Staphylococcus aureus. Forty-three extracts exhibited cytotoxic activity against at least one tested cell line (HepG2, HCT-116 and hCMEC-D3). Three extracts that were active against the two cancer cell lines tested, did not reduce the viability of the non-cancer endothelial cell line, hCMEC-D3. One Gordonia strain exhibited anti-obesity activity, revealed by its ability to reduce the neutral lipids in zebrafish larvae. Mass spectrometry-based dereplication analysis of active extracts identified several compounds associated with known Actinomycetota natural products. Nonetheless, five clusters contained metabolites that did not match any annotated natural products, suggesting they may represent new bioactive molecules.CONCLUSIONS: This work contributed to increase the knowledge on the diversity and bioactive potential of Actinomycetota associated with H. perlevis.PMID:39984721 | DOI:10.1093/jambio/lxaf044

Trends Endocrinol Metab. 2025 Feb 20:S1043-2760(25)00023-2. doi: 10.1016/j.tem.2025.01.007. Online ahead of print.ABSTRACTPlant-based diets emphasize higher intake of plant foods and are low in animal products. Individuals following plant-based diets have a lower risk of chronic conditions; however, the mechanisms underlying these associations are not completely understood. Omics data have opened opportunities to investigate the mechanistic effect of dietary intake on health outcomes. Here, we review omics analyses of plant-based diets in feeding and observational studies, showing that although metabolomics and proteomics identified candidate biomarkers and distinct pathways modifiable by plant-based diets, current evidence from transcriptomics and methylomics is limited. We also argue that future studies should examine how unhealthful plant-based diets are associated with a higher risk of health outcomes and integrate multiple omics data from feeding studies to provide further mechanistic insights.PMID:39984401 | DOI:10.1016/j.tem.2025.01.007

FEMS Microbiol Ecol. 2025 Feb 21:fiae160. doi: 10.1093/femsec/fiae160. Online ahead of print.ABSTRACTThe microbiome of Saccharina latissima, an important brown macroalgal species in Europe, significantly influences its health, fitness, and pathogens resistance. Yet, comprehensive studies on the diversity and function of microbial communities (bacteria, eukaryotes, and fungi) associated with this species are lacking. Using metabarcoding, we investigated the epimicrobiota of S. latissima and correlated microbial diversity with metabolomic patterns (LC-MS/MS). Specific epibacterial and eukaryotic communities inhabit the S. latissima surface, alongside a core microbiota, while fungal communities show lower and more heterogeneous diversity. Metabolomic analysis revealed a large diversity of mass features, including putatively annotated fatty acids, amino derivatives, amino acids, and naphthofurans. Multiple-factor analysis linked microbial diversity with surface metabolome variations, driven mainly by fungi and bacteria. Two taxa groups were identified: one associated with bacterial consortia and the other with fungal consortia, each correlated with specific metabolites. This study demonstrated a core bacterial and eukaryotic microbiota associated with a core metabolome and highlighted interindividual variations. Annotating the surface metabolome using Natural Products databases suggested numerous metabolites potentially involved in inter-species chemical interactions. Our findings establish a link between microbial community structure and function, identifying two microbial consortia potentially involved in the chemical defense of S. latissima.PMID:39984283 | DOI:10.1093/femsec/fiae160

Anal Chim Acta. 2025 Mar 22;1344:343728. doi: 10.1016/j.aca.2025.343728. Epub 2025 Jan 25.ABSTRACTBACKGROUND: Metabolomics and lipidomics analysis of various biological samples offer insights into potential mechanisms of health and disease development. Tissue samples, compared to other biological samples, are less elucidated due to challenges in sample collection and lack of standardized sample preparation protocols for reproducible tissue homogenization and broad-range metabolite extraction.RESULTS: Pork tissue samples were homogenized with six different solvent mixtures with increasing lipophilicity, followed by metabolites extraction using methanol for polar and methyl-tert-butyl ether (MTBE) in methanol (MeOH) for highly lipophilic compounds. Metabolite profiles of supernatant and homogenate extraction for three extract volumes were compared. Solvent dependent pipette tip blockage was addressed by introduction of a prewetting correction factor for non-polar homogenization solutions and low volume tissue homogenate pipetting. Upset plots were applied for multi-dimensional metabolite extraction efficiency evaluation for 24 different sample preparation conditions. The best-performing homogenization solution was PBS; MeOH (1:1; v/v), combined with a two-step polar metabolite and lipid extraction using MeOH and 75 % MTBE in MeOH employing the tissue homogenate. The optimized experimental conditions were applied on mouse pancreas tissues, providing evidence of varying metabolic pathway activities across different anatomical regions of an organ.SIGNIFICANCE: This study introduces a comprehensive tissue sample preparation and metabolite quantification workflow, covering highly polar to highly lipophilic metabolites using targeted high performance liquid chromatography electrospray ionization triple quadrupole-linear ion trap mass spectrometer (HPLC-ESI-QTRAP-MS/MS) for absolute quantitation of amino acids, organic acids and keto-acids, acyl-carnitines, and phospho-choline lipids.PMID:39984215 | DOI:10.1016/j.aca.2025.343728

Anal Chim Acta. 2025 Mar 22;1344:343727. doi: 10.1016/j.aca.2025.343727. Epub 2025 Jan 25.ABSTRACTBACKGROUND: Simultaneous determination of different natures of analytes is of great significance for saving sample volumes and simplifying analytical procedures. However, sample preparation for the simultaneous extraction of polar and non-polar analytes represents a challenge in sample preparation. Inspired by the successive liquid-phase microextraction (sLPME) method for acidic and basic analytes that we previously developed, we first proposed an efficient successive electromembrane extraction (sEME) system by adjusting the acidity of the donor solution and using binary organic solvents for extraction of polar and non-polar targets from biological samples in this work.RESULTS: We performed a detailed optimization of the sEME system. Here, carnitine (C0) and acylcarnitines were selected as model analytes since the demand increased especially in metabolomics studies. The combination of 2-nonanone and 2-nitrophenylpentyl ether (NPPE) was selected as supported liquid membranes (SLMs), and trichloroacetic acid (TCA) 100 % (v/v) was added to donor solution to adjust the acidity of the donor solution after the first sEME process (sEME-1). The recoveries of the targets in blood and urine were 47%-119% and 54%-118%, respectively. Moreover, the sEME systems were evaluated by liquid chromatography tandem mass spectrometry (LC-MS/MS) from biological samples. The limit of detection (LOD) and limit of quantitation (LOQ) of analytes were 0.03-1.33 ng mL-1 and 0.09-4.42 ng mL-1, respectively.SIGNIFICANCE: sEME enabled the extraction of polar and non-polar analytes from the same sample under optimal extraction conditions for all target analytes, which provided ideas for efficient sEME of exogenous and endogenous analytes from biological samples for forensic, clinical, and epidemiological studies.PMID:39984214 | DOI:10.1016/j.aca.2025.343727

Brain Behav Immun. 2025 Feb 19:S0889-1591(25)00046-7. doi: 10.1016/j.bbi.2025.02.006. Online ahead of print.ABSTRACTThe gut microbiota plays crucial roles in the development and functions of the central nervous system (CNS) as well as in modulation of neurobehavior in heath and disease. The gut brush border enzyme intestinal alkaline phosphatase (IAP) is an important positive regulator of gut microbial homeostasis. In mice, IAP is encoded by Akp3 gene, which is specifically expressed in the duodenum of the small intestine. IAP deficiency alters gut bacterial composition and gut barrier function. Decreased IAP activity has been observed in aging, gut inflammatory diseases, and metabolic disorders. We hypothesized that this enzyme could also play an important role in modulating neurobehavior. We performed deep sequencing of gut bacterial 16S rRNA and found that IAP deficiency changed gut microbiota composition at various taxonomic levels. Using targeted metabolomic analysis, we also found that IAP deficiency resulted in changes of gut bacteria-derived metabolites in serum and brain metabolism. Neurobehavioral analyses revealed that Akp3-/- (IAP knockout) mice had decreased basal nociception thresholds, increased anxiety-like behavior, and reduced locomotor activity. Furthermore, Akp3-/- mice had more pronounced brain microglial phagocytic activity, together with an increase in the activated microglia population. Fecal microbiota transplantation from wildtype to Akp3-/- mice partially improved neurobehavior and reduced brain microglial phagocytic activity in Akp3-/- mice. This study demonstrates that deficiency of the endogenous gut-derived host factor IAP induces behavioral phenotype changes (nociception; motor activity, and anxiety) and affects brain microglia activity. Changes in the gut microbiota induced by knocking down Akp3 contribute to behavioral changes, which is probably mediated by microglia activity modulated by the gut bacteria-derived metabolites.PMID:39984137 | DOI:10.1016/j.bbi.2025.02.006

Int J Biol Macromol. 2025 Feb 19:141288. doi: 10.1016/j.ijbiomac.2025.141288. Online ahead of print.ABSTRACTUlcerative colitis (UC) is characterized by impaired gut barrier, dysregulated immune responses and pronounced gut dysbiosis. Euglena gracilis (EG), rich in β-1,3-glucan (EGP), exhibits immunomodulatory properties, yet its effects on colitis and EGP's role as a core bioactive component are unclear. The aim of this study was to investigate the protective effects of EGP against UC by targeting gut barrier, T-cell immunity and gut microbiota. Results indicated that EG and EGP effectively improved the body weight, colon growth and reduced disease activity index of the DSS-induced mice. Both treatments also significantly suppressed the level of TNF-α and IL-6, restored gut barrier by upregulating ZO-1 and balanced Th17/Treg cells ratio. Microbiota analysis revealed EG and EGP reshaped gut microbiota composition, with an increase in beneficial strains, particularly within the Bacteroidota phylum. Metabolomics linked these changes to enhanced amino acid metabolism. Bacteroides fragilis, a Bacteroidota member, displayed similar anti-colitis bioactivity. In vitro fermentation with fecal samples from UC patients confirmed EGP's role in reshaping gut microbiota, increasing beneficial families such as Clostridiaceae and Lactobacillaceae, while enhancing tryptophan metabolism with anti-inflammatory indoles. These findings identify EGP as the core active component of EG, highlighting its potential in UC prevention through microbiota modulation, gut barrier support and immune regulation.PMID:39984099 | DOI:10.1016/j.ijbiomac.2025.141288

Eur J Pharmacol. 2025 Feb 19:177395. doi: 10.1016/j.ejphar.2025.177395. Online ahead of print.ABSTRACTSolasonine (SS) has been shown to inhibit the proliferation of various malignant tumors, though its effects on lipid metabolism in tumor cells are less understood. This study investigated SS's anti-tumor mechanism in oral squamous cell carcinoma (OSCC) using lipidomics, cell, and animal models. SS inhibited the growth of CAL27 and WSU-HN30 cells and reduced tumor volume in mice. Lipidomic analysis revealed an increase in diglyceride (DG) and a decrease in triglyceride (TG) levels, alongside a reduction in diacylglycerol acyltransferase 1 (DGAT1), key to TG synthesis. SS also induced reactive oxygen species (ROS) production and mitochondrial damage. Molecular docking confirmed SS's interaction with DGAT1, suggesting it prevents DG to TG conversion, inhibiting OSCC proliferation.PMID:39984013 | DOI:10.1016/j.ejphar.2025.177395

Mol Cell Proteomics. 2025 Feb 19:100928. doi: 10.1016/j.mcpro.2025.100928. Online ahead of print.ABSTRACTGlycosylation of immunoglobulin G (IgG) is recognized as a key modulator of cellular effector functions. At the same time, an increasing body of evidence underlines the importance of other antibody isotypes, especially IgA and IgM, in pathophysiological conditions. Therefore, methods to efficiently study the complex interplay between isotypes, subclasses, and glycosylation of antibodies during acute and chronic states of inflammation are needed. As a solution, we present an integrated and comprehensive method combining simultaneous affinity enrichment of IgG, IgA, and IgM with a single measurement, glycopeptide-centered LC-MS analysis of all isotypes which provides protein-specific (isotype and subclass), and site-specific N- and O-glycosylation quantitation. A two-protease approach provided individual peptides for each glycosylation site, allowing unambiguous compositional assignment and relative quantitation of glycoforms on the MS1 level as well as structural confirmation and partial isomer assignment on the MS/MS level. We demonstrate that our methodology can be efficiently applied to large clinical studies revealing differences of antibody glycosylation in woman during and after pregnancy, as well as between healthy donors and patients with rheumatoid arthritis. In addition, this showcased the advantages of our method in comprehensiveness and resolution of isotypes, subclasses, and glycosylation sites as well as its precision and robustness.PMID:39983994 | DOI:10.1016/j.mcpro.2025.100928

Environ Res. 2025 Feb 19:121183. doi: 10.1016/j.envres.2025.121183. Online ahead of print.ABSTRACTClimate change and air pollution pose significant global health threats, including impacts on diabetes risk; however, their long-term effects on insulin resistance (IR), a key determinant in diabetes pathophysiology, remain unclear. This study investigated whether exposure to heatwaves, temperature fluctuations, and warm-season ozone (O3) contributes to or exacerbates IR and explored the potential mediating role of biological aging. The study enrolled 6,901 participants and assessed both traditional and novel IR indicators: estimated glucose disposal rate (eGDR), triglyceride-glucose (TyG) index, triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-c), metabolic score for IR (METS-IR), TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), waist-to-height ratio (WHtR), TyG-WHtR, and lipid accumulation product (LAP). Ordinary least squares regression models were applied to evaluate the long-lasting effects of heatwaves, temperature fluctuation, and warm-season O3 on IR, incorporating Huber-White robust standard errors for model stability. Causal mediation analysis was utilized to investigate the mediating effects of biological aging. We found that exposure to heatwaves and higher concentrations of warm-season O3 was associated with elevated IR levels, with males, smokers, drinkers, and low-income individuals being more vulnerable. Accelerated biological aging (including body age, metabolomic aging rate, etc.) could significant mediate the long-lasting effects of heatwaves and warm-season O3. Our findings suggest that climate change and air pollution could amplify the vulnerability of glucose metabolism, particularly in males, smokers, drinkers, and individuals with low-income. More importantly, our findings reveal the importance of mitigating biological aging to prevent IR in the future, as global diabetes prevalence escalates rapidly.PMID:39983967 | DOI:10.1016/j.envres.2025.121183

Comp Biochem Physiol C Toxicol Pharmacol. 2025 Feb 19:110145. doi: 10.1016/j.cbpc.2025.110145. Online ahead of print.ABSTRACTThe ecological conditions of freshwater aquaculture are deteriorating by degrees in recent years. Consequently, the comprehensive utilization of saline-alkaline water has garnered increasing societal attention. Here, crucian carp (Carassius auratus) were exposed to 20, 40 mmol/L NaHCO3 for 30 days (T, F group). Metabolomic analyses were conducted using UPLC-QTOF/MS, complemented by biochemical and microbiology profiling to elucidate the damage of the saline environment to the intestinal microbial structure, which in turn interfered with the energy metabolism. It was observed that carbonate alkalinity (CA) exposure not only caused intestine oxidative stress but also changed the levels of several digestive enzymes, including α-amylase (AMS), chymotrypsin (CHY), lipase (LPS). Metabolomic analysis identified 22 different metabolites (DEMs) in T group and 77 DEMs in F group. MetaboAnalyst analysis indicated that these metabolites are primarily involved in energy-related pathways, including the citric acid cycle, galactose metabolism, and glycine, serine, and threonine metabolism. Intestinal microbial diversity and community composition were altered under carbonate alkalinity exposure, with increase in Proteobacteria abundance and decline in Firmicutes, abundance alongside enrichment of Sphingomonas. Herein, saline-alkaline stress disrupted the physiological homeostasis of the crucian carp intestine, leading to microbial dysbiosis and energy metabolic imbalance. This study provides a theoretical foundation for understanding the stress response of the crucian carp intestine and the role of the intestinal microbiome in host resilience under adverse environmental conditions.PMID:39983937 | DOI:10.1016/j.cbpc.2025.110145

J Plant Physiol. 2025 Feb 15;306:154453. doi: 10.1016/j.jplph.2025.154453. Online ahead of print.ABSTRACTAn interesting aspect that links the geomagnetic field (GMF) to the evolution of life lies in how plants respond to the reduction of the GMF, also known as hypomagnetic field (HMF). In this work, tomato plants (Solanum lycopersicum cv Microtom) were exposed either to GMF or HMF and were studied during the development of leaves and fruit set. Changes of expression of genes encoding for primary and secondary metabolites, including Reactive Oxygen Species (ROS), proteins, fatty acids, polyphenols, chlorophylls, carotenoids and phytohormones were assessed by qRT-PCR, while the corresponding metabolite levels were quantified by GC-MS and HPLC-MS. Two tomato homologs of the fruit fly magnetoreceptor MagR, Isca-like 1 and erpA 2, were modulated by HMF, as were numerous tomato genes under investigation. In tomato leaves, positive correlations were observed with most of the genes associated with phytohormones production, ROS scavenging and production, and lipid metabolism, whereas an almost reversed trend was found in flowers and fruits. Interestingly, downregulation of Isca-like 1 and erpA 2 was found to correlate with an upregulation of most unripe fruit genes. Exposure to HMF reduced chlorophyll and carotenoid content, decreased photosynthetic efficiency and increased non-photochemical quenching. Auxins, gibberellins, cytokinins, abscisic acid, jasmonic acid and salicylic acid content and the expression of genes related to their metabolism correlated with tomato ISCA modulation. The results here reported suggest that Isca-like 1 and erpA 2 might be important players in tomato magnetoreception.PMID:39983659 | DOI:10.1016/j.jplph.2025.154453