PubMed

Plant Cell Environ. 2025 Feb 10. doi: 10.1111/pce.15427. Online ahead of print.ABSTRACTInsect symbiotic microbiota acting as a third-party force of plant-insect interactions, play a significant role in insect hosts tolerance to phytochemical defences. However, it remains unknown whether insect symbiotic bacteria can assist the host in degrading phytochemical defences induced by egg deposition. Plagiodera versicolora is a worldwide forest pest. Our study showed that P. versicolora egg deposition on Populus davidiana × Populus bolleana induced significant changes in the transcriptome and metabolome of leaves. Combined qRT-PCR and LC-MS quantitative analysis of metabolic pathways showed that the contents of chlorogenic acid and rutin were significantly increased upon egg deposition in poplar. Bioassays indicated that the high concentration of chlorogenic acid induced by egg deposition could significantly reduce the performance of germ-free larvae. Six symbiotic bacterial strains with potential ability to degrade chlorogenic acid were isolated and identified. Their degradation products did not affect larval survival either. In vivo inoculation assays showed that four of those symbiotic bacteria could assist in the degradation of high concentration of chlorogenic acid induced by egg deposition and improve the larval survival. Our study provides clear evidence that the insect symbiotic bacteria can mediate the tolerance of herbivorous insects against plant toxins induced by egg deposition.PMID:39925102 | DOI:10.1111/pce.15427

Anal Chem. 2025 Feb 9. doi: 10.1021/acs.analchem.4c06265. Online ahead of print.ABSTRACTOxylipins are bioactive lipid mediators derived from polyunsaturated fatty acids (PUFAs) that play crucial roles in physiological and pathological processes. The analysis and identification of oxylipins are challenging due to the numerous isomeric forms. Ion mobility (IM), which separates ions based on their spatial configuration, combined with liquid chromatography (LC) and mass spectrometry (MS), has been proven effective for separating isomeric compounds. In this study, we developed an extensive oxylipin library containing information on retention time (RT), m/z, and CCS values for 74 oxylipin standards using LC-IM-QTOF-MS in positive and negative ionization modes. The oxylipins in the library were grouped into 15 isomer categories to evaluate the efficacy of IM in isomeric separation. Various adducts were investigated, including protonated, deprotonated, and sodiated forms. The ΔCCS% for more than 1000 isomeric pairs was calculated, revealing that 30% of these exhibited a ΔCCS% greater than 2%. Positive ionization mode demonstrated superior separation capabilities, with 274 isomer pairs achieving baseline separation (ΔCCS% > 4%). Sodium adducts significantly improved isomer separation. With the inclusion of LC separation, only nine oxylipins coeluted, forming six different isomeric pairs. CCS values for the adducts [M+Na]+ and [M+2Na-H]+ separated three of these isomeric pairs. The CCS values were compared to experimental libraries, confirming the high reproducibility of CCS measurements, with average errors below 2%. Applying this library to mouse brain samples, 19 different oxylipins were identified by matching RT, m/z, and CCS values. Coeluting isomers, 9- and 13-HODE, 8- and 12-HETE, and 15-oxo-ETE and 14(15)-EpETrE, were successfully separated and identified using drift time separation.PMID:39924946 | DOI:10.1021/acs.analchem.4c06265

Aging Cell. 2025 Feb 9:e14482. doi: 10.1111/acel.14482. Online ahead of print.ABSTRACTLongevity individuals have lower susceptibility to chronic hypoxia, inflammation, oxidative stress, and aging-related diseases. It has long been speculated that "rejuvenation molecules" exist in their blood to promote extended lifespan. We unexpectedly discovered that longevity individuals exhibit erythrocyte oxygen release function similar to young individuals, whereas most elderly show reduced oxygen release capacity. Untargeted erythrocyte metabolomics profiling revealed that longevity individuals are characterized by youth-like metabolic reprogramming and these metabolites effectively differentiate the longevity from the elderly. Quantification analyses led us to identify multiple novel longevity-related metabolites within erythrocytes including adenosine, sphingosine-1-phosphate (S1P), and glutathione (GSH) related amino acids. Mechanistically, we revealed that increased bisphosphoglycerate mutase (BPGM) and reduced MFSD2B protein levels in the erythrocytes of longevity individuals collaboratively work together to induce elevation of intracellular S1P, promote the release of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) from membrane to the cytosol, and thereby orchestrate glucose metabolic reprogramming toward Rapoport-Luebering Shunt to induce the 2,3-BPG production and trigger oxygen delivery. Furthermore, increased glutamine and glutamate transporter expression coupled with the enhanced intracellular metabolism underlie the elevated GSH production and the higher anti-oxidative stress capacity in the erythrocytes of longevity individuals. As such, longevity individuals displayed less systemic hypoxia-related metabolites and more antioxidative and anti-inflammatory metabolites in the plasma, thereby healthier clinical outcomes including lower inflammation parameters as well as better glucose-lipid metabolism, and liver and kidney function. Overall, we identified that youthful erythrocyte function and metabolism enable longevity individuals to better counteract peripheral tissue hypoxia, inflammation, and oxidative stress, thus maintaining healthspan.PMID:39924931 | DOI:10.1111/acel.14482

Mol Nutr Food Res. 2025 Feb 9:e202401017. doi: 10.1002/mnfr.202401017. Online ahead of print.ABSTRACTHyperuricemia (HUA) is a globally prevalent metabolic disease characterized by excessive production or insufficient excretion of uric acid in the serum. Although several drugs are available for the treatment of HUA, they have been associated with undesirable side effects. Therefore, this study aims to evaluate the therapeutic effects of sunflower head extract (KHE) on HUA in a mouse model and explore its potential mechanisms. All mice were randomly divided into three groups: Normal control (NC, 0.5% CMC-Na), HUA model (MD, yeast extract paste 20 g/kg), and KHE treatment group (KHE, 1 g/kg). Biochemical indicators, the oxidative stress state, and metabolomics were analyzed. KHE reduced the levels of 5-aminoimidazole ribonucleotide, xanthine, hypoxanthine, and uric acid in the serum of mice with HUA but increased the levels of adenine and taurine. KHE decreased the activities of superoxide dismutase (SOD) enzymes, the hepatic hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels, and the serum levels of betaine aldehyde and beta-D-glucosamine. KHE improved oxidative stress levels and mitigated potential damage to the kidneys and joints caused by urate deposition. These findings provide comprehensive evidence supporting the anti-HUA effects and underlying mechanisms of KHE in HUA mice.PMID:39924811 | DOI:10.1002/mnfr.202401017

Oncoimmunology. 2025 Dec;14(1):2457797. doi: 10.1080/2162402X.2025.2457797. Epub 2025 Feb 9.ABSTRACTMetabolic processes are crucial in immune regulation, yet the impact of metabolic heterogeneity on immunological functions remains unclear. Integrating metabolomics into immunology allows the exploration of the interactions of multilayered features in the biological system and the molecular regulatory mechanism of these features. To elucidate such insight in lung squamous cell carcinoma (LUSC), we analyzed 106 LUSC tumor tissues. We performed high-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) to obtain spatial metabolic profiles, and immunohistochemistry to detect tumor-infiltrating T lymphocytes (TILs). Unsupervised k-means clustering and Simpson's diversity index were employed to assess metabolic heterogeneity, identifying five distinct metabolic tumor subpopulations. Our findings revealed that TILs are specifically associated with metabolite distributions, not randomly distributed. Integrating a validation cohort, we found that heterogeneity-correlated metabolites interact with CD8+ TIL-associated genes, affecting survival. High metabolic heterogeneity was linked to worse survival and lower TIL levels. Pathway enrichment analyses highlighted distinct metabolic pathways in each subpopulation and their potential responses to chemotherapy. This study uncovers the significant impact of metabolic heterogeneity on immune functions in LUSC, providing a foundation for tailoring therapeutic strategies.PMID:39924768 | DOI:10.1080/2162402X.2025.2457797

Gut Microbes. 2025 Dec;17(1):2464225. doi: 10.1080/19490976.2025.2464225. Epub 2025 Feb 9.ABSTRACTPolyamines are important gut microbial metabolites known to affect host physiology, yet the mechanisms behind their microbial production remain incompletely understood. In this study, we developed a stable isotope-resolved metabolomic (SIRM) approach to track polyamine biosynthesis in the gut microbiome. Viable microbial cells were extracted from fresh human and mouse feces and incubated anaerobically with [U-13C]-labeled inulin (tracer). Liquid chromatography-high resolution mass spectrometry analysis revealed distinct 13C enrichment profiles for spermidine (SPD) and putrescine (PUT), indicating that the arginine-agmatine-SPD pathway contributes to SPD biosynthesis in addition to the well-known spermidine synthase pathway (PUT aminopropylation). Species differences were observed in the 13C enrichments of polyamines and related metabolites between the human and mouse microbiome. By analyzing the fecal metabolomics and metatranscriptomic data from an inflammatory bowel disease (IBD) cohort, we found significantly higher polyamine levels in IBD patients compared to healthy controls. Further investigations using single-strain SIRM and in silico analyses identified Bacteroides spp. as key contributors to polyamine biosynthesis, harboring essential genes for this process and potentially driving the upregulation of polyamines in IBD. Taken together, this study expands our understanding of polyamine biosynthesis in the gut microbiome and will facilitate the development of precision therapies to target polyamine-associated diseases.PMID:39924644 | DOI:10.1080/19490976.2025.2464225

BMC Plant Biol. 2025 Feb 10;25(1):168. doi: 10.1186/s12870-025-06121-9.ABSTRACTJuglans sigillata Dode is rich in flavonoids, but the low ratio of female to male flower buds limits the development of the J. sigillata industry. While the abundance of flavonoids in J. sigillata is known, whether flavonoids influence female flower bud differentiation has not been reported. In this study, we explored the regulatory mechanisms of gene expression and metabolite accumulation during female flower bud differentiation through integrated transcriptomic and metabolomic analyses. Our findings revealed that flavonoid biosynthesis is a key pathway influencing female flower bud differentiation, with metabolites primarily shifting towards the isoflavonoid, flavone, and flavonol branches. Structural genes such as chalcone synthase, dihydroflavonol 4-reductase, flavonol synthase, and flavonoid 3',5'-hydroxylase were identified as playing crucial regulatory roles. The expression of these genes promoted the accumulation of flavonoids, which in turn influenced female flower bud differentiation by modulating key regulatory genes including Suppressor of Overexpression of Constans1, Constans, Flowering Locus T, and APETALA1. Furthermore, transcription factors (TFs) highly expressed during the physiological differentiation of female flower buds, particularly M-type MADS, WRKY, and MYB, were positively correlated with flavonoid biosynthesis genes, indicating their significant role in the regulation of flavonoid production. These results offer valuable insights into the mechanisms of female flower bud differentiation in J. sigillata and highlight the regulatory role of flavonoids in plant bud differentiation.PMID:39924518 | DOI:10.1186/s12870-025-06121-9

Expert Rev Proteomics. 2025 Feb 9. doi: 10.1080/14789450.2025.2463324. Online ahead of print.ABSTRACTINTRODUCTION: Exogenous Cushing's syndrome is the result of long-term exposure to glucocorticoids, while endogenous Cushing's syndrome occurs due to excessive production of glucocorticoids within the body. Cushing's syndrome remains a diagnostic challenge for the treating physician.Mass spectrometry, with its better resolution, detectability and specificity, paved the way to understanding the cellular and molecular mechanisms involved in the several diseases that facilitated the evolution of biomarkers and personalized medicine, which can be applicable to manage Cushing's syndrome as well.AREAS COVERED: There are only a few reports of mass spectrometry-based metabolomic approaches to endogenous Cushing's syndrome of certain etiologies. However, the application of this approach in the diagnosis of exogenous Cushing has not been explored much. This review attempts to discuss the application of the mass spectrometry-based metabolomic approach in the evaluation of Cushing's syndrome.EXPERT OPINION: Global metabolomics has the potential to discover altered metabolites and associated signaling and metabolic pathways, which may serve as potential biomarkers that would help in developing tools to accelerate precision medicine. Multi-omics approaches will provide innovative solutions to develop molecular tests for multi-molecule panel assays.PMID:39924469 | DOI:10.1080/14789450.2025.2463324

Psychol Med. 2025 Feb 10;55:e30. doi: 10.1017/S0033291724003374.ABSTRACTBACKGROUND: Post-traumatic stress disorder (PTSD) is characterized by severe distress and associated with cardiometabolic diseases. Studies in military and clinical populations suggest that dysregulated metabolomic processes may be a key mechanism. Prior work identified and validated a metabolite-based distress score (MDS) linked with depression and anxiety and subsequent cardiometabolic diseases. Here, we assessed whether PTSD shares metabolic alterations with depression and anxiety and if additional metabolites are related to PTSD.METHODS: We leveraged plasma metabolomics data from three subsamples nested within the Nurses' Health Study II, including 2835 women with 2950 blood samples collected across three time points (1996-2014) and 339 known metabolites assayed by mass spectrometry-based techniques. Trauma and PTSD exposures were assessed in 2008 and characterized as follows: lifetime trauma without PTSD, lifetime PTSD in remission, and persistent PTSD symptoms. Associations between the exposures and the MDS or individual metabolites were estimated within each subsample adjusting for potential confounders and combined in random-effects meta-analyses.RESULTS: Persistent PTSD symptoms were associated with higher levels of the previously developed MDS. Out of 339 metabolites, we identified 29 metabolites (primarily elevated glycerophospholipids and glycerolipids) associated with persistent symptoms (false discovery rate < 0.05; adjusting for technical covariates). No metabolite associations were found with the other PTSD-related exposures.CONCLUSIONS: As the first large-scale, population-based metabolomics analysis of PTSD, our study highlighted shared and distinct metabolic differences linked to PTSD versus depression or anxiety. We identified novel metabolite markers associated with PTSD symptom persistence, suggesting further connections with metabolic dysregulation that may have downstream consequences for health.PMID:39924258 | DOI:10.1017/S0033291724003374

Biomed Environ Sci. 2025 Jan 20;38(1):106-111. doi: 10.3967/bes2024.179.NO ABSTRACTPMID:39924160 | DOI:10.3967/bes2024.179

Cancer Lett. 2025 Feb 7:217537. doi: 10.1016/j.canlet.2025.217537. Online ahead of print.ABSTRACTMetastatic duodenopancreatic neuroendocrine tumors (dpNETs) are the primary cause of mortality among patients with Multiple Endocrine Neoplasia Type 1 (MEN1). Emerging evidence implicates the microbiome and microbial-derived secreted factors in promoting cancer development and progression. In the current study, we report that the circulating microbial-associated uremic toxins trimethylamine N-oxide (TMAO), indoxyl sulfate (IS), cresol sulfate (CS), cresol glucuronide (CG), and phenol sulfate (PS) are elevated in MEN1 patients with metastatic dpNETs. Proteomic- and metabolomic-based analysis of resected dpNET tissues from MEN1 patients also revealed detectable levels of uremic toxins that positively correlated with peptide-based signatures corresponding to Fusobacterium nucleatum, Faecalibacterium prausnitzii, and Klebsiella pneumoniae and negatively correlated with Streptococcus pneumoniae and Streptococcus thermophilus. A microbial-associated uremic toxin panel (MUTP) was developed and, in an independent case-control validation cohort, the panel yielded an area under the receiver operating characteristic curve (AUC) of 0.94 (95% CI: 0.85-1.00) with 67% sensitivity at 95% specificity for identifying MEN1 patients with metastatic dpNETS. Increases in circulating microbial-associated uremic toxins during early stages of neoplasia were also found to be associated with poor overall survival in an Men1fl/flPdx1-CreTg mouse model of MEN1 pancreatic NETs. Our findings suggest that microbial dysbiosis is associated with disease aggressiveness and that increases in circulating microbial-associated uremic toxins may be a prognostic indication for MEN1 individuals who are at risk of having metastatic dpNETs.PMID:39924079 | DOI:10.1016/j.canlet.2025.217537

Mol Cell Proteomics. 2025 Feb 7:100926. doi: 10.1016/j.mcpro.2025.100926. Online ahead of print.ABSTRACTIn eukaryotic organisms, protein kinases regulate diverse protein activities and signaling pathways through phosphorylation of specific protein substrates. Isolating and characterizing kinase substrates is vital for defining downstream signaling pathways. The Kinase Client (KiC) assay is an in vitro synthetic peptide LC-MS/MS phosphorylation assay that has enabled identification of protein substrates (i.e., clients) for various protein kinases. For example, previous use of a 2,100-member (2k) peptide library identified substrates for the extracellular ATP receptor-like kinase, P2K1. Many P2K1 clients were confirmed by additional in vitro and in planta studies, including Integrin-Linked Kinase 4 (ILK4), for which we provide the evidence herein. In addition, we developed a new KiC peptide library containing 8,000 (8k) peptides based on phosphorylation sites primarily from Arabidopsis thaliana datasets. The 8k peptides are enriched for sites with conservation in other angiosperm plants, with the paired goals of representing functionally conserved sites and usefulness for screening kinases from diverse plants. Screening the 8k library with the active P2K1 kinase domain identified 177 phosphopeptides, including calcineurin B-like protein (CBL9) and G protein alpha subunit 1 (GPA1), which functions in cellular calcium signaling. We confirmed that P2K1 directly phosphorylates CBL9 and GPA1 through in vitro kinase assays. This expanded 8k KiC assay will be a useful tool for identifying novel substrates across diverse plant protein kinases, ultimately facilitating the exploration of previously undiscovered signaling pathways.PMID:39923935 | DOI:10.1016/j.mcpro.2025.100926

Cell Mol Gastroenterol Hepatol. 2025 Feb 7:101474. doi: 10.1016/j.jcmgh.2025.101474. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Clostridioides difficile infection (CDI) causes colitis and diarrhea. C. difficile bacterium produces toxins A and B, which cause intestinal inflammation. A metabolomics analysis discovered fecal metabolites with anti-inflammatory effects in CDI. We aimed to identify an anti-CDI metabolite that can inhibit CDI-mediated colitis and prevent recurrence.METHODS: Fresh human colonic tissues and primary human cells were used to determine metabolite effects. Humanized C. difficile-infected HuCD34-NCG mice and antibiotics-treated human gut microbiota-treated (ABX+HGM) hamsters were used to simulate the human environment.RESULTS: High-throughput screening and fecal metabolomics analysis identified anti-inflammatory metabolites. Compared to other tested metabolites, citrulline preserved the mucosal integrity of toxin-exposed fresh human colonic tissues with reduced macrophage inflammatory protein 1 alpha (MIP-1α) and increased interleukin-10 (IL-10) expression. Oral citrulline treatment alleviated cecal inflammation in hamsters infected with C. difficile ribotype 027. This was accomplished by the augmented expression of cecal IL-10 and the diminished level of cecal MIP-1α. Citrulline and vancomycin synergistically prevented recurrence in the infected ABX+HGM hamsters. In C57BL/6J mice infected with C. difficile VPI10463, citrulline ameliorated colitis by reducing colonic Ccl3 mRNA expression. In immunologically humanized HuCD34-NCG mice infected with toxin B-expressing C. difficile ribotype 017, citrulline ameliorated colitis with increased human IL-10 expression in colonic macrophages. Citrulline suppressed MIP-1α secretion and GSK3α/β dephosphorylation in the toxin A-exposed human colonic epithelial cells and promoted IL-10 expression in toxin B-exposed human macrophages and heat shock protein 27 phosphorylation.CONCLUSION: Citrulline exerts anti-inflammatory effects in the intestines against C. difficile toxins and inhibits CDI recurrence in mice and hamsters.PMID:39923847 | DOI:10.1016/j.jcmgh.2025.101474

Food Chem Toxicol. 2025 Feb 7:115314. doi: 10.1016/j.fct.2025.115314. Online ahead of print.ABSTRACTCitrinin (Cit) is a metabolite of Monascus Aspergillus that is known to be nephrotoxic and affects the safety of Monascus products. Here, we investigated the effects of an intervention with bioactive Polygonatum sibiricum polysaccharides (PSPS) on Cit-induced toxic damage in populations with dietary patterns characterized by alcohol consumption. Our results showed that the PSPS intervention significantly increased the levels of intestinal Cit and its metabolite M1. Additionally, the PSPS intervention mitigated intestinal damage, as well as liver and kidney stress, and flora disruption induced by combined exposure to Cit and alcohol. It also promoted the recovery of Lactobacillus abundance. However, there was no significant improvement in hippocampal damage. Metabolomics analysis indicated that the PSPS significantly influenced the metabolic pathways involved in energy metabolism in liver and kidney, such as aspartic acid and tyrosine metabolism. Correlation analysis revealed a significant relationship between the reduction of Cit metabolites and the differential metabolites in the liver and kidney. Our results demonstrated that the PSPS intervention showed promise in improving intestinal flora imbalances, enhancing the barrier function against Cit, alleviating intestinal, liver, and kidney damage, and addressing the metabolic disorders along the gut-liver-kidney axis resulting from the co-exposure to Cit and alcohol.PMID:39923830 | DOI:10.1016/j.fct.2025.115314

Talanta. 2025 Jan 31;287:127646. doi: 10.1016/j.talanta.2025.127646. Online ahead of print.ABSTRACTSolid phase microextraction (SPME), as a sampling/sample preparation technique, offers unique solutions for the most challenging applications, including metabolomics studies of living systems. However, for global metabolomics it is critical to use an SPME sampler facilitating the extraction of both volatiles and nonvolatiles, which at the same time is compatible with thermal and solvent-assisted desorption. As a promising universal coating, recently hydrophilic-lipophilic balanced (HLB) particles immobilized in PTFE have been introduced as a new SPME sampler to provide a wide-range of analyte coverage and compatibility with solvent and thermal desorption. Thus, making it suitable for both gas and liquid chromatography (GC/LC) based applications. However, its potential in metabolomics has not been investigated to date. In this study, HLB/PTFE SPME fibers were prepared, evaluated with selected polar and non-polar metabolites relevant to biological systems, and validated for cell-line studies. The validation proved that these fibers can extract a wide-range of molecules (LogP: 4.2 to 15.6) with acceptable accuracy (≤19% RE%) and repeatability (intra-day ≤17% and inter-day 12% RSD%). The LOQ was determined to vary between 150.0 and 500.0 ng/mL. Upon validation, the fibers were used in a proof-of-concept study for extraction of endometabolome and exometabolome of melanoma B16F10 and lung cancer LL2 cell lines. The metabolome studies showed that HLB/PTFE fibers provide lower coverage, but for some compounds higher extraction efficiency compared to HLB/PAN fibers used in LC-based metabolomics. Fibers also proved suitable for GC-MS analysis, allowing for the detection of 36 volatile organic compounds in the headspace of the cell lines and RPMI medium.PMID:39923666 | DOI:10.1016/j.talanta.2025.127646

Ecotoxicol Environ Saf. 2025 Feb 8;291:117800. doi: 10.1016/j.ecoenv.2025.117800. Online ahead of print.ABSTRACTLong-term exposure to hexavalent chromium [Cr(VI)] has been linked to lung cancer, and cyclooxygenase-2 (COX-2) is a well-known inflammatory factor. However, the role and mechanism of COX-2 in Cr(VI)-induced carcinogenesis are not clear yet. To address this question, we employed a mouse model exposed to Cr(VI) through intranasal instillation of particulate zinc chromate (ZnCrO4) for 12 weeks. Metabolomics and RNA-seq assays revealed enhanced activity of the arachidonic acid (AA)/eicosanoid metabolism pathway in lung tissues from mice exposed to Cr(VI). COX-2, the key enzyme of the AA/eicosanoid pathway, was significantly upregulated in Cr(VI)-exposed lung tissues, as well as in the Cr(VI)-induced transformed (Cr-T) cells compared to parental BEAS-2B (B2B) cells. We then employed multidisciplinary in vitro and in vivo functional assays to characterize the role of COX-2 in Cr(VI)-induced lung cancer. The results indicated that COX-2 functioned as an oncogene to promote the malignant transformation of B2B cells and enhance the proliferation, migration, tumor growth, and angiogenesis of Cr-T cells. Nuclear factor E2-related factor-2 (Nrf2) was identified as a transcription factor for COX-2. Nrf2 was upregulated in response to Cr(VI) exposure and contributed to Cr(VI)-induced lung cancers, in part by upregulating COX-2 expression. Moreover, microRNA-379 (miR-379) was found to target COX-2 to inhibit its expression posttranscriptionally. MiR-379 was downregulated in Cr(VI)-exposed lung tissues and Cr-T cells, and ectopic miR-379 expression reduced Cr-T cell viability and migration, with partial reversal upon COX-2 restoration. In summary, our study revealed the oncogenic role of COX-2 and identified two novel regulatory mechanisms for COX-2 overexpression in Cr(VI)-induced carcinogenesis.PMID:39923569 | DOI:10.1016/j.ecoenv.2025.117800

Ecotoxicol Environ Saf. 2025 Feb 8;291:117837. doi: 10.1016/j.ecoenv.2025.117837. Online ahead of print.ABSTRACTIn this study, we treated tobacco seedlings with 0, 200, 400, and 800 mg/kg Pb2 +, and explored the response mechanism of tobacco under Pb stress through a combination of growth physiology and metabolomics analysis. The physiological results showed that compared with CK, with the increase of Pb concentration, Pb treatment inhibited tobacco growth, reduced the biomass and photosynthetic pigment content of tobacco seedlings, and severely damaged the chloroplast structure. In addition, compared with CK, the pore conductivity and pore density of Pb800 treatment decreased by 45.77 % and 93.55 %, respectively. Pb treatment disrupted the cell membrane system, and Pb800 treatment increased the content of malondialdehyde (MDA) in leaves and roots by 67.65 % and 31.90 %, respectively. Meanwhile, Pb treatment increased the activity of tobacco SOD and POD enzymes. Metabolomics results showed that Pb stress enhanced tryptophan metabolism, glutathione metabolism, alanine, aspartate, and glutamate metabolism, as well as cysteine and methionine metabolism pathways. These results indicate that increasing the content of photosynthetic pigments and hormones, clearing reactive oxygen species by enhancing antioxidant enzyme activity, and improving amino acid metabolism may play an important role in reducing the toxicity of Pb to tobacco.PMID:39923568 | DOI:10.1016/j.ecoenv.2025.117837

Biomaterials. 2025 Feb 3;318:123164. doi: 10.1016/j.biomaterials.2025.123164. Online ahead of print.ABSTRACTPreventing relapse after resection of a primary tumor continues to be an unmet clinical need. Development of adjuvant biomaterials with the capacity to kill residual cancer cells after tumor resection is of clinical importance. Here we developed a library of metallo-alginate hydrogels containing high concentrations of metallic ions such as Ca2+ in combination with Zn2+, Li+, or Mg2+ to disrupt Ca2+ homeostasis in the mitochondria of cancer cells by local hyperthermia. To synergistically kill tumor cells and suppress the growth of rechallenged tumors, we embedded oncogene-silencing nucleic acids (mTOR siRNA) loaded into polymerc nanoparticles (NPs) composed of poly (β-amino esters) in the metallo-alginate hydrogels, targeting cancer cells that activate multi-drug resistance pathways such PI3K/AKT/mTOR. Metabolomic studies showed alterations in the Warburg effect, mitochondrial transport, and the TCA cycle, confirming cancer cell damage. In vivo studies of this targeted therapy in mice demonstrated a sex-dependent effect. Male B16F10-tumor-bearing mice treated with the synergistic therapy showed restrained tumor growth. In contrast, no therapeutic effect was observed in female counterparts. Our results demonstrate that in situ-formed NP-loaded metallo-alginate hydrogels can modulate two distinct immune signaling networks that are relevant for enhancing cancer cell death. On the basis of our findings, this combination therapy emerges as a promising sex-dependent strategy for clinical translation.PMID:39923537 | DOI:10.1016/j.biomaterials.2025.123164

Food Chem. 2025 Feb 5;474:143216. doi: 10.1016/j.foodchem.2025.143216. Online ahead of print.ABSTRACTFermented Amaranth stems is a traditional Chinese fermented vegetable known for its distinctive aroma, produced through natural microbial fermentation. However, the metabolic processes, flavor compounds, and microbial communities involved in its fermentation are not well understood. This study provides a comprehensive analysis using an integrated approach combining flavoromics, untargeted metabolomics, and metagenomics to examine the dynamic changes in metabolites and microbiota during fermentation. A total of 108 volatile organic compounds were identified, with sugar metabolism peaking on the third day of fermentation. The microbial community analysis revealed that key genera such as Pseudomonas, Acinetobacter, Pectobacterium, and Enterobacter play a significant role in flavor formation. The findings offer critical insights into the fermentation mechanisms and the production of flavor compounds, providing a foundation for optimizing fermentation processes and improving the flavor quality of fermented Amaranth stems. This research holds practical significance for enhancing food safety by controlling microbial communities during fermentation.PMID:39923519 | DOI:10.1016/j.foodchem.2025.143216

Phytomedicine. 2025 Feb 2;139:156460. doi: 10.1016/j.phymed.2025.156460. Online ahead of print.ABSTRACTBACKGROUND: Autoimmune hepatitis (AIH) seriously endangers human health. Therefore, it is urgent to find new therapeutic drugs and targets for AIH. In this context, 7-O-α-L-rhamnopyranosyl-kaempferol-3-O-β-D-glucopyranoside (KGR), a flavonoid compound found in Embelia laeta (L.) Mez, has not been evaluated for its efficacy.OBJECTIVE: This study aimed to investigate the therapeutic effect and mechanisms of KGR on AIH.RESEARCH DESIGN: Concanavalin A (Con A) was used to establish a mouse AIH model. Molecular biology methods were used to evaluate the efficacy of KGR and transcriptomics, proteomics, and metabolomics were innovatively combined to revel the mechanism of action of KGR against AIH, which was verified by experiments.RESULTS: Mouse liver sections demonstrated that KGR reduced the degree of degeneration and necrosis in liver cells in mice. Compared with the Con A group, KGR significantly reduced serum aminotransferase levels, inhibited the release of proinflammatory cytokines in the liver tissue, and inhibited oxidative stress (OS) by reducing malondialdehyde level and enhancing superoxide dismutase activity. Finally, multiomics revealed that primary bile acids synthesis and the FXR-TLR4/MYD88/JNK signaling pathway may be the regulatory targets of KGR.CONCLUSION: The study results demonstrated that KGR inhibited OS and inflammatory responses by regulating primary bile acid synthesis and thereby inhibiting the FXR-TLR4/MYD88/JNK signaling pathway, and had a protective effect on Con A-induced AIH.PMID:39923428 | DOI:10.1016/j.phymed.2025.156460