PubMed

Microbiome. 2026 Mar 5. doi: 10.1186/s40168-026-02365-1. Online ahead of print.ABSTRACTBACKGROUND: Stress experienced by newly received cattle is a significant challenge in the beef industry, frequently resulting in weakened immune responses and impaired growth. The rumen microbiota is essential to host health, and its imbalance can exacerbate stress. This study investigates the mechanisms by which creatine pyruvate (CrPyr) mitigates stress in newly received cattle through multi-omics approaches, including metagenomics, metabolomics, in vitro and in vivo experiments, and rumen microbiota transplantation (RMT) in mice.RESULTS: Our results revealed that CrPyr significantly reduces stress-related hormones (cortisol and adrenocorticotropic hormone) and inflammatory markers (IL-6, IL-1β, and TNF-α), and enhanced antioxidant capacity (SOD: 57.38 versus 46.93 U/mL, P < 0.05; GSH-Px: 305.87 versus 217.07 U/mL, P < 0.05; T-AOC: 9.62 versus 7.66 U/mL, P < 0.05). Metagenomic analysis demonstrated that CrPyr increased Prevotella abundance, a key rumen bacterium involved in volatile fatty acid (VFA) production, and enriches metabolic pathways associated with energy metabolism (ATP synthesis, and pyruvate metabolism) and antioxidant defense (glutathione metabolism, FC = 1.08, P < 0.05). In vitro and in vivo experiments, as well as RMT studies in mice, further validate these findings, demonstrating that CrPyr promote VFA synthesis and increased ATP production through the electron transport phosphorylation pathway.CONCLUSIONS: CrPyr modulates the abundance of ruminal Prevotella in transport-stressed cattle to enhance glutathione and VFA metabolism and to accelerate ATP and nucleotide synthesis, thereby alleviating stress in newly received cattle. This multimodal approach established CrPyr as an effective nutritional intervention that improves rumen function and increases livestock productivity. Video Abstract.PMID:41782139 | DOI:10.1186/s40168-026-02365-1

J Nanobiotechnology. 2026 Mar 4. doi: 10.1186/s12951-026-04135-5. Online ahead of print.ABSTRACTBACKGROUND: The pulmonary immune system orchestrates lung homeostasis and protects against environmental insults through coordinated actions of immune and structural cells. Traditional Chinese medicine recognized the functional interaction between the lungs and the large intestine more than 2000 years ago, but direct evidence for this relationship in modern biomedical research remains limited. Although inhaled nanomaterials can induce lung fibrosis, the underlying immune mechanisms and their impact on large intestine remain poorly understood. Here, we integrated spatial transcriptomics, mRNA-seq, metabolomics, microbiome profiling, and validation in vitro to investigate how multi-walled carbon nanotubes (MWCNTs) exposure affects pulmonary immune responses and gut homeostasis in mice.RESULTS: MWCNTs were administered to mice via oropharyngeal aspiration. We integrated spatial transcriptomics, bulk RNA sequencing, serum metabolomics, 16S rRNA microbiome profiling, and macrophage experiments in vitro. This multi-omics approach mapped pulmonary cellular alterations, identified key cell-cell signaling pathways, and examined downstream metabolic and intestinal changes provoked by MWCNTs. The results suggested that inhaled MWCNTs induced distinct spatial reorganization of pulmonary cellular architecture, characterized by macrophage- and fibroblast-enriched clusters associated with localized immune activation. Furthermore, cell-cell communication analysis identified Slamf7-Slamf7 interactions as key drivers of macrophage superactivation evidenced by excessive pro-inflammatory cytokine release. Notably, knockdown of Slamf7 in alveolar macrophages in vitro effectively attenuated the superactivation. The macrophage superactivation altered serum metabolic profiles, particularly in pathways related to energy metabolism and inflammation. Finally, lung injury extended to the distal intestine, where rectal epithelial barrier integrity was compromised, resulting in microbial and metabolic imbalance.CONCLUSION: These findings highlight the hazardous potential of inhaled MWCNTs based on macrophage superactivation induced by Slamf7 in the lung, providing mechanistic evidence for the lung-gut link described in traditional Chinese medicine. Together, our results identify molecular targets to mitigate nanomaterial immunotoxicity and inform the design and using of safer, surface-engineered MWCNTs.PMID:41782027 | DOI:10.1186/s12951-026-04135-5

Microbiome. 2026 Mar 4. doi: 10.1186/s40168-026-02368-y. Online ahead of print.ABSTRACTBACKGROUND: The gut microbiota influences poultry health, nutrition, feed efficiency (FE), and overall productivity. However, the relationship between gut microbes, including bacteria and phages, and FE in ducks remains underexplored. To address this, we integrated cecal 16S amplicon, metagenome, microbiota-derived short-chain fatty acids (SCFAs) profiling, liver transcriptome, and serum metabolome data to illustrate the contribution of the gut microbiome (bacteria and viruses) to duck FE.RESULTS: We reconstructed viral genomes and prokaryotic metagenome-assembled genomes (MAGs) and annotated their genes using comprehensive databases. Prokaryotic hosts of viruses were also predicted to understand virus-host dynamics within the gut ecosystem. Our results revealed that high-FE ducks have higher concentration of propionate and butyrate in cecum compared with low-FE ducks. The metagenome sequencing revealed distinct cecal microbiota profiles between two groups, with increased relative abundance of representative SCFA producers, especially Paraprevotella sp905215575 and Bacteroides sp944322345, and enhanced SCFA-biosynthesis pathways in high-FE ducks. Virome genome assembly identified two phages encoding auxiliary metabolic genes (AMGs) involved in pyruvate metabolism, enhancing nutrient availability for host bacteria to produce SCFAs (e.g., temperate phage-encoded pyruvate phosphate dikinase) or exploiting host central metabolic pathways for viral replication (e.g., lytic phage-encoded formate C-acetyltransferase). Furthermore, these representative SCFA-producing bacteria and phage consortia were associated with serum metabolites (including L-histidine and 4-hydroxydecanedioylcarnitine) linked to duck FE.CONCLUSION: Collectively, these findings provide novel insights into the gut microbial factors regulating FE in ducks, offering potential strategies to optimize poultry nutrition and productivity. Video Abstract.PMID:41782011 | DOI:10.1186/s40168-026-02368-y

J Nanobiotechnology. 2026 Mar 5. doi: 10.1186/s12951-026-04231-6. Online ahead of print.ABSTRACTNano-pesticides represent a significant technology advancement in modern agricultural, offering improved target specificity and reduced chemical load. However, their potential to induce subtle, sub-lethal disturbance in soil microbial function remains poorly resolved and is not adequately capture by conventional indicators such as microbial diversity, abundance, or bulk enzymatic activity. The central novelty of this review lies in proposing post-translational modifications (PTMs) as functional, early-warning biomarkers for nano-pesticide induced microbial stress, providing a molecular resolution that bridges exposure and ecological outcome. This review critically examines the current evidence on nano-pesticides-microbiome interaction and PTM-centric framework to interpret microbial responses at the protein regulation level. We highlight phosphorylation, acetylation, and ubiquitination regulate microbial stress responses, modulating detoxification enzymes, efflux pumps, and cellular signalling pathways under nanoparticle-induced stress. Unlike prior reviews that emphasize toxicity endpoints or gene-level responses, this work integrates metaproteomic evidence demonstrating PTM enrichment within stress-responsive functional protein groups across real environmental datasets, underscoring their relevance as conserved biomarkers of adaptive and maladaptive responses. By integrating metagenomics with metaproteomic and metabolomics, this review illustrates how PTM profiling enables mechanistic insight into microbial adaptation, functional impairment, and resilience under nano-pesticide pressure. Furthermore, we introduce a systems-level perspective that combines PTM data with computational modelling and AI-assisted bioinformatics to predict microbiome shifts and ecological risk, an approach not previously synthesized within the context of nano-pesticide assessment. Collectively, this review bridges nanomaterial design, microbial molecular regulation, and environmental risk evaluation, and proposes PTM-based assessment as a new paradigm for developing microbiome-safe, eco-compatible nano-pesticides and advancing molecular environmental monitoring strategies.PMID:41781966 | DOI:10.1186/s12951-026-04231-6

BMC Psychiatry. 2026 Mar 4. doi: 10.1186/s12888-026-07937-x. Online ahead of print.ABSTRACTBACKGROUND: Obsessive-Compulsive Disorder (OCD) and Trichotillomania (TTM) are classified together as Obsessive-Compulsive and Related Disorders, yet their distinct neurobiological underpinnings remain poorly understood. This study represents the first untargeted metabolomic analysis comparing adolescents with OCD and TTM to identify differential metabolic signatures.METHOD: This cross-sectional study included 62 female adolescents aged 10-18 years: 20 with OCD, 22 with TTM, and 20 healthy controls. Plasma samples were analyzed using liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-Q-TOF/MS). Metabolomic data were processed using MZmine 2.53 and MetaboAnalyst 6.0, with metabolites showing |log₂(fold change)| > 0.585 (corresponding to fold change > 1.5 or < 0.67) and p < 0.05 considered significant.RESULTS: Exploratory principal component analysis showed visual separation of the OCD group from healthy controls, while the TTM group showed partial overlap with controls. In OCD versus controls, linoleic acid (LA) was markedly decreased (FC: 0.02), while trihexosylceramide (FC: 15.48) and 7a,12a-dihydroxy-cholestene-3-one (FC: 4.33) were significantly elevated. TTM showed elevated arachidonic acid (AA) (FC: 9.60) and trihexosylceramide (FC: 13.42), with severely reduced biocytin (FC: 0.01) compared to controls. Direct comparison between disorders revealed LA (FC: 51.39) and AA (FC: 3.55) were higher in TTM versus OCD, while biocytin (FC: 0.10) was lower. These findings suggest that OCD and TTM exhibit distinct patterns of metabolite differences.CONCLUSION: OCD showed reduced LA levels, consistent with potential perturbations in omega-6 metabolism. TTM showed elevated AA levels and reduced biocytin, consistent with previously reported oxidative stress and altered energy metabolism in this disorder. These metabolic differences represent candidate metabolites warranting targeted validation and may provide preliminary insights into distinct neurobiological mechanisms rather than direct clinical applicability.CLINICAL TRIAL NUMBER: Not applicable.PMID:41781889 | DOI:10.1186/s12888-026-07937-x

J Headache Pain. 2026 Mar 4. doi: 10.1186/s10194-026-02315-0. Online ahead of print.NO ABSTRACTPMID:41781872 | DOI:10.1186/s10194-026-02315-0

Nature. 2026 Mar 4. doi: 10.1038/s41586-026-10193-4. Online ahead of print.ABSTRACTFerroptosis, a major mechanism of non-apoptotic programmed cell death, critically regulates the homeostasis and functionality of peripheral CD4+ and CD8+ T cells1-6. Here we demonstrate that in mouse, resistance of T cells to ferroptosis depends critically on the composition of standard rodent diets, and that dietary effects on ferroptosis (DEFs) have a crucial role in regulation of T cell homeostasis and immune responses. DEFs are microbiota-independent and are driven by variations in dietary polyunsaturated and monounsaturated fatty acids (PUFAs and MUFAs) that lead to variations in abundance of lipid species in lymphoid tissues and T cells. Consistently, ferroptosis resistance of human T cells also correlated with plasma lipid profiles across multiple healthy cohorts, exhibiting negative associations with PUFA/MUFA ratios in major lipid classes. DEFs dictate T cell resilience in the absence of the essential lipid peroxide scavenger GPX4 and broadly modulate T cell-dependent humoral immunity and T cell-mediated anti-tumour immunity, including in chimeric antigen receptor T cell therapy. Mechanistically, ACSL4, which preferentially biosynthezises PUFA-containing phospholipids7, is highly expressed in T cells and underpins DEF-mediated regulation of follicular helper T (TFH) cell generation and function. Our findings reveal the physiological significance of lipid metabolism in driving DEFs in immunity and suggest strategies targeting lipid metabolism to enhance vaccine efficacy and T cell-mediated immunotherapy.PMID:41781622 | DOI:10.1038/s41586-026-10193-4

Sci Rep. 2026 Mar 4. doi: 10.1038/s41598-026-42524-w. Online ahead of print.ABSTRACTChicken eggs are one of the most consumed foods worldwide. However, the practice of chicken culling in the poultry industry involves unnecessary animal suffering and finding a way to put an end to this has become a societal priority. One approach that has been propagated as acceptable is based on the selection of female eggs early in the incubation process and the devitalization of the male eggs. It is with this objective in mind that we searched for a biomarker for early gender screening in eggs. Applying an untargeted mass spectrometry approach, we profiled allantoic fluid of different day-old eggs and identified the feature 3-[(2-aminoethyl)sulfanyl]butanoic acid (ASBA) as a strong biomarker for in-ovo gender prediction for day-9 old embryos. In the present work, we describe the identification of ASBA as a new biomarker in allantoic fluid for gender screening and the optimization of a high throughput assay using acoustic droplet ejection-mass spectrometry (ADE-MS). Special attention is given to the optimization of ADE-MS compatible liquid handling and the development of the data processing to ensure a reliable gender prediction. We have been able to accurately determine the gender of day-9 eggs in a cohort of 154 samples with a prediction accuracy of 95.5%, with a throughput of 1800 samples per hour for the prototype, which may vary in production systems.PMID:41781573 | DOI:10.1038/s41598-026-42524-w

J Agric Food Chem. 2026 Mar 4. doi: 10.1021/acs.jafc.5c13677. Online ahead of print.ABSTRACTNuclear magnetic resonance (NMR) spectroscopy is widely adopted for assessing biochemical composition in agriculture. This study evaluated the feasibility of 400 MHz NMR to detect biochemical differences in Hass avocados grown under conventional (N = 101) and regenerative (N = 105) farming practices in Southwestern Australia. Phosphite, associated with Phytophthora root rot management, was a key discriminating feature (area under ROC curve = 0.96), being detected in 90% of conventional avocados (mean: 49 mg/kg) and 6 regenerative samples (mean: 24 mg/kg). To assess translational potential, water extracts of five samples were analyzed using 80 MHz benchtop NMR. Phosphite was detectable below the strictest maximum residue limit (25 mg/kg), demonstrating the potential of NMR as a sustainable and cost-effective solution for monitoring phosphite residues. This proof-of-concept benchtop NMR approach demonstrates analytical feasibility but requires further validation before application in field-based traceability or regulatory contexts, with a potential future relevance to environmental monitoring, sustainable agriculture, and other crop systems.PMID:41780928 | DOI:10.1021/acs.jafc.5c13677

Mol Cell Proteomics. 2026 Mar 2:101548. doi: 10.1016/j.mcpro.2026.101548. Online ahead of print.ABSTRACTOxidative stress triggers redox-sensitive post-translational modifications, notably disulfide bond formation involving cysteine residues. However, these bonds are often overlooked in proteomics due to the routine use of reducing agents. Here, we employed liquid chromatography-mass spectrometry (LC-MS) based metabolomics and non-reducing tandem mass tag (TMT) proteomics to investigate the effects of H2O2 on MDA-MB-231 cells. Metabolomic analysis revealed pathway-specific inhibition of major metabolic pathways including glycolysis, the tricarboxylic acid (TCA) cycle, and nucleotide biosynthesis. Proteomic analysis using the DBond algorithm revealed extensive and isoform-specific disulfide crosslinks across more than 1,000 proteins. These linkages were enriched at redox-sensitive cysteines near basic residues and displayed high isoform specificity. Our findings demonstrate that disulfide bond formation serves as a selective mechanism of redox regulation. This study highlights the utility of non-reducing proteomics in elucidating redox-controlled protein networks and structural dynamics under oxidative stress.PMID:41780889 | DOI:10.1016/j.mcpro.2026.101548

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00194-3. doi: 10.3168/jds.2025-27877. Online ahead of print.ABSTRACTFood allergies are a major challenge in current healthcare. Probiotics and human milk oligosaccharides (HMO) are increasingly being used to address food allergies. However, the role of nonfucosylated neutral oligosaccharides in food allergies remains unclear. Moreover, HMO interact positively with probiotics, but the synergistic effects and underlying mechanisms of their combined action in alleviating food allergies remain poorly understood. Consequently, Bifidobacterium longum ssp. infantis (B. infantis), which exhibits the greatest capacity to use HMO, was chosen for this study. The effects of lacto-N-neotetraose (LNnT), B. infantis, and their combination on allergy was assessed using an ovalbumin (OVA)-induced allergic mouse model. The mechanisms underlying the alleviation of food allergies by LNnT + B. infantis were also investigated through genomics and metabolomics. The results demonstrated that LNnT and B. infantis exerted partial modulatory effects on allergic symptoms, BW, mast cell degranulation, cytokine levels, and immune cell populations in mice. Notably, the simultaneous administration of LNnT and B. infantis significantly outperformed the administration of either LNnT or B. infantis alone, indicating a synergistic effect. Furthermore, LNnT + B. infantis was found to alleviate intestinal injury. Gut microbiota analysis revealed that LNnT + B. infantis reduced the abundance of the allergy-associated bacterium Desulfovibrio and significantly increased the levels of beneficial bacteria, including Lactobacillus, Limosilactobacillus, and Blautia. The LNnT + B. infantis treatment also enhanced steroid hormone biosynthesis, ascorbate and aldarate metabolism, and nucleotide metabolism. Some substances in these pathways are produced by the gut microbiota and are linked to allergy amelioration. In conclusion, LNnT + B. infantis alleviates food allergies by modulating the gut microbiota and its associated metabolic functions in OVA mice.PMID:41780875 | DOI:10.3168/jds.2025-27877

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00185-2. doi: 10.3168/jds.2025-27993. Online ahead of print.ABSTRACTPrebiotics promote the proliferation and colonization of probiotics in the intestine; therefore, synergistic application of probiotics and functional oligosaccharides can confer significant health benefits to the host. This study optimized a complex prebiotic combination that enhanced the growth of Lactobacillus paracasei ProSci-92 by measuring the optical density at 600 nm, pH, and viable cell counts. Through response surface optimization, the optimal ratio was determined to be 1.959% trehalose, 1.029% inulin, and 1.582% fructooligosaccharides. Under these conditions, cell density reached 1.629 ± 0.012, and the viable cell count was (6.5 ± 0.28) × 109 cfu/mL, representing increases of 12.3% and 1.67-fold, respectively, compared with the de Man, Rogosa, and Sharpe agar medium control group. The optimized compound was subsequently applied to fermented milk; its rheological properties, texture characteristics, and viable bacterial counts were analyzed using sucrose as the control. The results show that the compound group coagulated 1 h earlier than did the sucrose control, and exhibited higher elasticity and viscosity coefficients. During the 28-d storage period, the pH decreased gradually (final value: 4.16), titratable acidity remained low (final value: 102°T [degrees of titratable acidity]), viable bacterial count remained above 108 cfu/mL, and water-holding capacity averaged 65.86%. Moreover, both textural attributes and sensory evaluation scores improved significantly. Metabolomic analysis identified 87 differential metabolites between the PC92-Oli (experimental) group and the PC92-Suc (control) group, which were primarily associated with the ABC transport system, AA biosynthesis, and carbon metabolism pathways. The compound oligosaccharide mixture activated specific metabolic pathways in the strain, promoted the synthesis of functional metabolites, inhibited fatty acid production, and accelerated extracellular polysaccharide synthesis. These findings provide a strong scientific basis for enhancing the product development and functional properties of probiotic fermented milk, and offer innovative perspectives and strategies for improving its production and storage characteristics.PMID:41780873 | DOI:10.3168/jds.2025-27993

J Dairy Sci. 2026 Mar 2:S0022-0302(26)00164-5. doi: 10.3168/jds.2025-26902. Online ahead of print.ABSTRACTArtificial reproduction technologies (ART) may exert long-term effects on offspring, which have not yet been addressed in dairy cattle. This longitudinal study examined reproductive outcomes and transgenerational effects of embryo recipients conceived by different ART, including artificial insemination (AI) and embryo transfer (ET) with fresh, frozen, and vitrified embryos. For this purpose, in vitro-produced (IVP) embryos were transferred to synchronized recipients (n = 298 ET from AI, and n = 84 ET from IVP-ET origin). Pregnancy on d 40 and 62, birth to term, and gestation length were recorded. From birth until adulthood, calf morphometry (weight, size, and chest perimeter) was monitored (n = 142 animals), and IGF2 methylation and expression were analyzed in peripheral blood lymphocytes (n = 113 samples). The plasma metabolome on d 0 (n = 179 samples) and d 7 (n = 176 samples) and metabolically regulated pathways were compared between estrus-synchronized recipients born by AI and ET. Data were analyzed with generalized mixed models (parametric) and Kruskal-Wallis test (nonparametric). Pregnancy and birth rates did not differ between AI and ET recipients. However, mothers from ET-born recipients were heavier at calving, and their calves showed transgenerational effects, including higher birth weight, size, gestation length, and daily weight gain compared with those from AI recipients. Only calves born from frozen embryos displayed transient IGF2 hypomethylation on d 30, which disappeared later on. In contrast, IGF2 expression decreased on d 0 and 30 in calves born from cryopreserved embryos, and increased in calves aged 2 to14 mo from vitrified embryos, but did not differ thereafter between any group. Among females >6 mo old, those from frozen embryos and AI were heavier and taller than females from vitrified and fresh embryos. Certain metabolite concentrations on d 0 and d 7 differed among recipient groups, mainly in essential amino acids and 1-carbon-generating units metabolites. Overall metabolic differences (Mahalanobis distance matrix) between females were higher in AI than in ET-cryopreserved females on d 0, and in AI versus ET-fresh females on d 7. These findings suggest that ART induces epigenetic and metabolic variations, potentially influencing nutritional efficiency.PMID:41780859 | DOI:10.3168/jds.2025-26902

Cancer Lett. 2026 Mar 2:218393. doi: 10.1016/j.canlet.2026.218393. Online ahead of print.ABSTRACTHepatocellular carcinoma remains a leading cause of cancer mortality worldwide, with peritumoral microenvironment interactions playing a critical role in disease progression. This multi-omics study employed artificial intelligence-pathology, single-nucleus multi-omics, spatial transcriptomics, and metabolomics to characterize peritumoral ductular reactions. Ductular reaction scores strongly predicted poor clinical outcomes and correlated with cirrhosis severity. We identified three functionally distinct cholangiocyte subpopulations, with Small_duct_type_Cho exhibiting robust fibroblast interactions that promote stromal remodeling. Metabolomic profiling revealed tumor margin enrichment of cholic acid, which induced CD8+ T cell dysfunction via NR1H4-dependent PD1 upregulation. Importantly, NR1H4 inhibition synergized with anti-PD1 therapy in murine models, significantly suppressing tumor growth. These results position ductular reactions as both a prognostic biomarker and therapeutic target, with cholic acid/NR1H4 pathway inhibition representing a promising immunotherapeutic strategy for hepatocellular carcinoma patients.PMID:41780844 | DOI:10.1016/j.canlet.2026.218393

Clin Chim Acta. 2026 Mar 2:120937. doi: 10.1016/j.cca.2026.120937. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is frequently diagnosed at an advanced stage due to tumor heterogeneity and chronic liver damage, which reduce the performance of single biomarkers and complicate the clinical interpretation of laboratory results. The genotoxic diethylnitrosamine (DENA)-induced hepatocarcinogenesis model provides a stage-resolved and experimentally controlled framework associated with genotoxic stress, inflammation, and fibrosis, along with metabolic adaptation in target tissues and circulating biofluids. This review summarizes multi-omics data from DENA models and translational cohorts, encompassing genomics/epigenomics, transcriptomics, proteomics, metabolomics, and glycomics, as well as liquid biopsy analytes, including cell-free DNA, extracellular vesicle cargo, and circulating tumor cell markers. We integrated the dynamics of injury progression to fibrosis and tumor development at the pathway scale, highlighting multi-analyte biomarker sets that improve the differentiation between advanced fibrosis/cirrhosis and early hepatocellular carcinoma (HCC). Additionally, we examined enabling technologies in analytical techniques, including targeted mass spectrometry (MS), PCR-based methods, and clinically scalable glycoprofiling. Notably, we propose a stage-aware biomarker selection paradigm that emphasizes mechanistic consistency, analytical viability, and clinical actionability to facilitate earlier identification and longitudinal tracking. Finally, we discuss the practical implications of multicenter validation and a harmonized study design to enhance reproducibility and expedite clinical translation.PMID:41780833 | DOI:10.1016/j.cca.2026.120937

J Nutr. 2026 Mar 2:101453. doi: 10.1016/j.tjnut.2026.101453. Online ahead of print.ABSTRACTBACKGROUND: Independently, diet and exercise can benefit bone health, but they are seldom studied in combination.OBJECTIVE: We investigated how dietary supplementation with tart cherry (TC) alone and in combination with exercise affects bone, and whether this response differs with age.METHODS: Two cohorts of female C57BL/6 mice (6-wk-old;n=12 mice/group & 60-wk-old;n=14 mice/group) were assigned to diets (Control vs. TC diet) and exercise (with vs. without treadmill running) for 8 wks. Bone microarchitecture, biomechanics, and gene expression of regulators of bone cell differentiation and activity were assessed. Data were analyzed using 2-way ANOVA followed by post-hoc testing. Diet effects on serum untargeted metabolomics were analyzed using unpaired t-tests. For all analyses, alpha=0.05.RESULTS: Diet and exercise differentially affected young and aging mice. Both TC (P<0.0001) and exercise (P<0.05) independently increased femoral trabecular bone in young mice. Although exercise failed to increase cortical parameters, it improved bone strength. In the aging cohort, TC treatment improved cortical thickness (P<0.05) and biomechanical properties of the femur. The effects of TC and exercise were not additive in either cohort. Within the bone of young mice, TC increased (P<0.01) the expression of Bmp2, a regulator of osteoblast differentiation and decreased (P<0.01) matrix metalloproteinases (Mmp8 and Mmp9), involved in bone matrix degradation. In the aging mice, TC increased (P<0.05) regulators of osteoblast differentiation (Osx and Bmp2), and TC and exercise independently increased Col1a1, indicative of osteoblast activity. Metabolomics revealed increases in xenometabolites from TC and the gut microbiota (e.g., hippuric acid, methyltyrosine, and methylgalactoside) in both cohorts, which positively correlated with bone parameters.CONCLUSIONS: We conclude there was no added benefit of combining TC with the running protocol used in this study. TC had a pronounced osteogenic effect in both age groups and metabolomic profiling revealed new potential mechanisms by which its bone effects are mediated.PMID:41780825 | DOI:10.1016/j.tjnut.2026.101453

Microb Pathog. 2026 Mar 2:108417. doi: 10.1016/j.micpath.2026.108417. Online ahead of print.ABSTRACTBoesenbergia rotunda (L.) Mansf. rhizome has been traditionally used to treat abscesses, leukoplakia, and leukorrhea. Candida albicans is a major cause of these incidences and can lead to bloodstream infection. This study aimed to evaluate the effectiveness and mechanisms of B. rotunda extract on susceptibility, biofilm formation, and invasion into human endothelial EA.hy926 cells of bloodstream-isolated C. albicans. Their virulence were determined by microdilution, metabolic activity, lactate dehydrogenase release, and internalization assays. Alterations in biomolecule composition were determined by Fourier-transform infrared microspectroscopy. The metabolomic profiles during host-pathogen interactions were assessed with high-resolution accurate-mass spectrometry. The B. rotunda extract consisted of 15.60% (w/w) pinostrobin and 6.02% (w/w) pinocembrin. All strains of C. albicans were not susceptible to the extract at a concentration of 100 μg/mL. The biofilm formation was inhibited only in C. albicans Isolate03 by the B. rotunda extract with IC50 value of 46.03 μg/mL. However, the ability of Isolate03 and Isolate04, invasive phenotypes, to damage the endothelial EA.hy926 cells was significantly inhibited with IC50 values of 27.39 and 30.81 μg/mL, respectively. The extract markedly altered the invasive phenotype's biomolecule composition and metabolomic profiles. The glycogen and carbohydrate compositions were decreased, whereas protein was increased. Moreover, propanoate and glycerolipid metabolism were dramatically regulated. These results suggest that alterations of biomolecule and metabolism could decrease their virulences because metabolic adaptation involved in pathogenic traits of C. albicans. Therefore, the B. rotunda extract might disrupt biomolecule compositions and metabolic pathways of the isolated C. albicans, thereby reducing biofilm formation and tissue invasion.PMID:41780771 | DOI:10.1016/j.micpath.2026.108417

J Control Release. 2026 Mar 2:114774. doi: 10.1016/j.jconrel.2026.114774. Online ahead of print.ABSTRACTExcessive reactive oxygen species (ROS) accumulation and dysregulated inflammation drive acetaminophen (APAP)-induced acute liver injury (ALI), yet the therapeutic effect of the commonly used clinical drug N-acetylcysteine (NAC) still has certain limitations at present. Here, we engineered a multifunctional nanozyme nanocomposite, MPCNH, by in situ deposition of bimetallic PtCu nanoparticles onto UiO-66 metal-organic frameworks (MOFs), loading NAC, and coating with hyaluronic acid (HA) to enhance biocompatibility. MPCNH exhibited cascade superoxide dismutase (SOD)-like and catalase (CAT)-like catalytic activities, enabling rapid ROS clearance and mitochondrial protection in APAP-challenged hepatocytes. Meanwhile, the delivery of the therapeutic drug NAC was achieved. In vivo, MPCNH lowered serum transaminases, activated the Keap1-Nrf2 antioxidant pathway, shifted macrophages polarization toward an anti-inflammatory M2 phenotype and restored metabolic balance. By integrating catalytic and pharmacological functions, MPCNH offers a synergistic strategy to simultaneously eliminate oxidative stress and regulate inflammation, providing a promising therapeutic platform for oxidative stress-driven liver injury.PMID:41780678 | DOI:10.1016/j.jconrel.2026.114774

J Ethnopharmacol. 2026 Mar 2:121460. doi: 10.1016/j.jep.2026.121460. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Aloperine (ALO), an alkaloid derived from Sophora alopecuroides L., demonstrates therapeutic potential against malignant tumors, while the role of ALO and its molecular mechanisms in ovarian cancer remain unclear.AIM OF THE STUDY: This study aims to systematically investigate the efficacy and molecular mechanisms of ALO against ovarian cancer by integrating network pharmacology and metabolomics.MATERIALS AND METHODS: The anti-tumor effect of ALO on ovarian cancer cells was evaluated using CCK-8, colony formation, cell scratch and transwell invasion assay in vitro. An ovarian cancer xenograft mouse model was used to evaluate the anti-ovarian cancer effect of ALO in vivo. Potential targets of ALO in ovarian cancer were predicted via network pharmacology, and the binding affinity of ALO to the potential targets was analyzed using molecular docking techniques. High-performance liquid chromatography-mass spectrometry (HPLC-MS) was used to identify the different metabolites of ALO and their metabolic pathways in ovarian cancer cells, followed by multi-level integrated analysis of network pharmacology and metabolomics results. Metabolite detection kits, western blotting, and qPCR were employed to validate the involved metabolites and their associated target genes.RESULTS: ALO suppressed the proliferation, migration and invasion of ovarian cancer cells SKOV-3 and ES-2 in a dose dependent manner in vitro. Correspondingly, ALO inhibited the growth of ovarian cancer xenografts in vivo. Network pharmacology and molecular docking analysis revealed Mouse double minute 2 homolog (MDM2), Janus kinase 2 (JAK2), Cyclin-dependent kinase 2 (CDK2), Myeloperoxidase (MPO), Janus kinase 1(JAK1) and Androgen receptor (AR) as the potential targets of ALO in ovarian cancer. While metabolomics analysis showed that ALO increases citrate acid and α-ketoglutarate (α-KG) levels in ovarian cancer cells. The integrated metabolomics, network pharmacology, and molecular docking identified that ALO primarily affects the tricarboxylic acid cycle (TCA cycle) and three hub genes, including MDM2, JAK2, and CDK2. In the experimental validation, ALO treatment increased the levels of key metabolites citrate acid and α-KG in the TCA cycle in ovarian cancer cells, while suppressed the levels of pyruvate and lactate, the primary metabolites of glycolysis, ultimately leading to a reduction in cellular ATP content. Moreover, ALO suppressed the glycolytic protein expression of GLUT1, PKM2 and LDHA in ovarian cancer cells. MDM2, JAK2, and CDK2 were identified as the most promising targets of ALO in ovarian cancer.CONCLUSION: ALO demonstrates anti-ovarian cancer effects both in vitro and in vivo through the enhancement of TCA cycle and reversing of aerobic glycolysis in ovarian cancer cells, providing a robust experimental foundation for future investigation of the potential clinical utility of ALO in ovarian cancer therapy.PMID:41780620 | DOI:10.1016/j.jep.2026.121460

J Lipid Res. 2026 Mar 2:101011. doi: 10.1016/j.jlr.2026.101011. Online ahead of print.ABSTRACTOxylipins are oxidized polyunsaturated fatty acids (PUFA) such as hydroxy-PUFA and epoxy-PUFA. Total oxylipins are commonly analyzed following base hydrolysis as non-esterified oxylipins by means of LC-MS/MS. For that, a standard operation procedure has been developed, which was successfully tested in an international interlaboratory comparison (J. Lipid Res. (2020) 61: 1424-1436). Here, we report the concentrations of total oxylipins in NIST SRM 1950 plasma determined by LC-MS/MS analyses in different labs, which are similar to those in other freshly prepared human plasma samples . Hydroxy-PUFA of the long chain PUFA arachidonic acid (ARA), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) occur between 1 and 75 nmol/L (0.3-24 ng/mL) and linoleic acid (LA)-derived hydroxy-PUFA up to 400 nmol/L (120 ng/mL). The concentration of ARA, DHA- and EPA-derived epoxy-PUFA ranges between 2 and 20 nmol/L (0.6-6 ng/mL) and LA up to 100 nmol/L (32 ng/mL). We also report 70 oxylipins which cannot be detected (∼<0.5 nmol/L; 0.2 ng/mL), such as multiple hydroxylated PUFA, including so-called SPM (exept for 10,17-DiHDHA), and most isoprostanes. If the plasma is prepared or stored inappropriately, oxylipins are formed by autoxidation, leading to artificially high levels of total oxylipins. This is shown for the concentrations in different commercially available plasma pools of unknown origin, being 100-1000 fold higher. The concentrations provided here for NIST SRM 1950 plasma and freshly prepared plasmathus inform which concentration range of total oxylipins should be expected in human plasma from healthy subjects, and increase the utility of NIST SRM 1950 for analytical quality control protocols.PMID:41780594 | DOI:10.1016/j.jlr.2026.101011