PubMed

Sci Total Environ. 2025 Jan 4;959:178323. doi: 10.1016/j.scitotenv.2024.178323. Online ahead of print.ABSTRACTThe unique properties of per- and polyfluoroalkyl substances (PFAS) have driven their pervasive use in different industrial applications, leading to substantial environmental pollution and raising critical concerns about the long-term impacts on ecosystem and human health. To tackle the global challenge of PFAS contamination, there is an urgent need for sustainable and efficient remediation strategies. Phytoremediation has emerged as a promising eco-friendly approach with the potential to mitigate the spread of these persistent contaminants. However, addressing this complex issue requires interdisciplinary cutting-edge research to develop comprehensive and scalable solutions for effective PFAS management. This review highlights recent advancements in the detection, quantification, and monitoring of PFAS uptake by plants, providing a detailed description of PFAS accumulation in several plant species. Besides, the physiological and molecular responses elicited by these pollutants are described. Leveraging omic technologies, including genomics, transcriptomics, and proteomics, provides unprecedented insights into the plant-PFAS interaction. Novel approaches based on artificial intelligence to predict this interaction and up to date disposal and valorization methods for PFAS-contaminated plant biomass, are discussed here. This review offers an interdisciplinary approach to explore what has been discovered so far about PFAS phytoremediation, covering the entire process from contaminant uptake to sustainable disposal, providing a roadmap for future research.PMID:39756293 | DOI:10.1016/j.scitotenv.2024.178323

Comp Biochem Physiol Part D Genomics Proteomics. 2024 Dec 30;54:101409. doi: 10.1016/j.cbd.2024.101409. Online ahead of print.ABSTRACTThis study investigated the mechanisms by which high salinity conditions stimulate adult Artemia females to produce diapaused cysts. We used a 1H NMR-based metabolomic approach to elucidate the metabolic regulation between ovoviviparity and oviparity in Artemia exposed to different salinities. At a salinity of 80 ppt, 100 % of females produced diapaused cysts, compared to 20 % at 50 ppt. Metabolic profiling revealed significant alterations in a range of metabolites, including 5,6-dihydrouracil, betaine, and malate, in females undergoing oviparity at 80 ppt compared to ovoviviparity at 30 ppt. Multivariate statistical analyses indicated clear separation between the two reproductive strategies. The up-regulated metabolites in oviparity were involved in significant metabolic pathways, such as β-alanine metabolism and the citrate cycle, highlighting substantial metabolic differences between the two reproductive strategies. These identified metabolic pathways might play crucial roles in the maternal response to high salinity, facilitating embryo protection and enhancing the survival and reproductive success of brine shrimp. These findings provide a basis for further research into the molecular mechanisms underlying Artemia adaptation to high salinity environments.PMID:39756218 | DOI:10.1016/j.cbd.2024.101409

Plant Physiol Biochem. 2024 Dec 29;220:109464. doi: 10.1016/j.plaphy.2024.109464. Online ahead of print.ABSTRACTPurslane is a plant with high nutritional content that is mainly produced in the central part of Mexico. The nutritional content of purslane depends on various factors such as climatic and soil conditions, phenology, and fertilization. This article describes the 1H NMR metabolomics profiling of purslane in relation to fertilization at two harvest stages: C1 and C2 (27 and 42 days after emergence). During the first stage, 30 metabolites were identified including free amino acids and organic acids. In the second stage, 35 metabolites were identified, with higher concentrations of carbohydrates and nucleosides being observed. Multivariate analysis revealed differences in the metabolome between harvests C1 and C2. Notably, higher abundances of fructose, galactose, α-glucose, β-glucose, myo-inositol, sucrose, and nucleosides such as adenosine and uridine were observed in C2. Discriminant analysis further demonstrated variations in metabolites among plants treated with different doses of nitrogen, phosphorus, and potassium at the two harvest stages studied. Plants treated with the highest dose of nitrogen (300 kg N ha-1) exhibited maximum levels of metabolites, while low nitrogen-treated plants (0 kg N ha-1) displayed an inverse trend. Amino acids such as alanine, asparagine, GABA, glutamine, histidine, isoleucine, leucine, phenylalanine, proline, threonine, tyrosine, and valine were found to be the most abundant in plants treated with N300. In contrast, untreated plants showed higher levels of citric acid and malic acid. Our results highlight the effectiveness of 1H NMR as a methodology for understanding the role of fertilization and nutrient content in optimizing the crop production of purslane.PMID:39756182 | DOI:10.1016/j.plaphy.2024.109464

Ecotoxicol Environ Saf. 2025 Jan 4;289:117643. doi: 10.1016/j.ecoenv.2024.117643. Online ahead of print.ABSTRACTThe threat posed by light pollution to human health is increasing remarkably. As demand for high-efficiency and bright lighting increases, so does the blue light content from artificial sources. Although animal studies suggested blue light induced depression-like behaviors, human evidence remained limited, and the mechanisms by which blue light affects depression remained elusive. This study aimed to investigate the association between blue light exposure and depression in humans, and explored the underlying mechanisms that driving depression-like behaviors induced by blue light. Our population findings showed that the high-blue-light exposure at night was positively associated with depressive symptoms. Lactic acid was relevant to depression with Mendelian randomization analysis. Moreover, animal studies demonstrated that exposure to blue light during sleep (BLS) induced depression-like behaviors in the animals. Metabolomics and colorimetric analyses revealed elevated levels of lactic acid in the cerebrospinal fluid and lateral habenula (LHb) of rats with depression-like behaviors induced by BLS. The administration of a lactate inhibitor (Oxamate) alleviated these behaviors, along with changes in neuronal excitability, synaptic function, and morphology in the LHb. Overall, our study suggests that excessive exposure to high blue light-content artificial light at night links to increased depressive symptoms, revealing possible molecular mechanisms and prevention strategies, which are crucial for addressing environmentally related mental health issues.PMID:39756180 | DOI:10.1016/j.ecoenv.2024.117643

Theriogenology. 2024 Dec 31;235:19-30. doi: 10.1016/j.theriogenology.2024.12.027. Online ahead of print.ABSTRACTSperm cryopreservation is a complex process involving gene expression, protein synthesis, membrane stability, and metabolic adaptation. However, molecular alterations in sperm cryopreservation and the mechanisms defending against freezing damage remain poorly understood. This study investigates these changes and defense mechanisms using transcriptomics, proteomics, and metabolomics data. During sperm cryopreservation, the expression level of G protein subunit alpha i3 (GNAI3) was significantly downregulated in post-thaw sperm (P < 0.001), while matrix metallopeptidase 9 (MMP9) was upregulated compared to FS groups (P < 0.01). Additionally, interleukin 6 (IL6) expression in the CS group showed an approximate increase (P < 0.05), whereas ribosomal protein S27a (RPS27A) expression decreased markedly (P < 0.05). Other important molecules such as macrophage stimulating 1 receptor (MST1R), hypoxia-inducible factor 1 subunit alpha (HIF1A), fibroblast growth factor 8 (FGF8), CD9 molecule (CD9), peptidase D (PEPD) and terminal nucleotidyltransferase 5B (TENT5B) also exhibited significant changes in expression (P < 0.05). Moreover, the study revealed the regulatory roles of metabolites such as glucose and glutamic acid during sperm cryopreservation. The involvement of catalase (CAT) protein in antioxidant defense was also noted. The interactions among mRNAs, miRNAs, proteins, and metabolites highlight the critical role of the FoxO signaling pathway in modulating responses to freezing. Our study reveals the molecular regulatory mechanisms of sperm during cryopreservation, emphasizing the importance of the FoxO pathway and specific metabolites in response to cryo-injury. These findings provide deeper insights into the complexity of sperm cryobiology and offer practical guidance for optimizing sperm cryopreservation.PMID:39756112 | DOI:10.1016/j.theriogenology.2024.12.027

Food Chem. 2024 Dec 26;471:142634. doi: 10.1016/j.foodchem.2024.142634. Online ahead of print.ABSTRACTSystematic research is still lacking on the content of hydrophilic compounds in Fu Brick Tea (FBT) from major Chinese production regions and their variation patterns during the processing of FBT. This study utilized optimized non-targeted (UHPLC-Q-Exactive Orbitrap-MS) and targeted (UHPLC-QqQ-MS) metabolomics to analyze 73 FBT samples from six regions of China and 30 samples from different stages of FBT processing. 573 and 74 hydrophilic compounds were respectively relatively and absolutely quantified for the first time. Among the 73 FBT samples, alkaloids were the most abundant (26221.76-36701.75 mg/kg), followed by soluble sugars (211372.59-26112.85 mg/kg), organic acids (17014.07-23589.20 mg/kg), amino acids (6664.59-9791.46 mg/kg), nucleotides (1020.33-2175.16 mg/kg), and nucleoside (650.86-1446.26 mg/kg). During the processing of FBT, sugars, acids, nucleotides, and nucleosides increased, while amino acids decreased, and alkaloids slightly increased. This study enhances the understanding of hydrophilic compounds in FBT.PMID:39756097 | DOI:10.1016/j.foodchem.2024.142634

Food Chem. 2024 Dec 31;470:142657. doi: 10.1016/j.foodchem.2024.142657. Online ahead of print.ABSTRACTGiven the widespread industrial and domestic use of probiotic blends based on combinations of lactic acid bacteria (LAB) and yeasts to produce fermented foods or beverages that are supposed to provide health benefits, this study aimed to generate knowledge and concepts on biologically relevant activities, metabolism and metabolic interactions in yeast/LAB communities. For this, the postbiotic capabilities of three probiotic candidates, including two lactic acid bacteria (i.e., Lactococcus lactis subsp. hordniae and Lactococcus lactis subsp. lactis) and the yeast Pichia kudriavzevii, isolated from a traditional home-made kefir, were explored combining an assortment of bioassays with a GC-MS footprint metabolomic strategy. Cell-free supernatants from cultures showed antimicrobial/antioxidant activity and inhibited biofilm formation by Salmonella sp. Several bioactive secondary metabolites (including tyrosol, phenylethyl alcohol, 2,3-butanediol, erythritol, tryptophol, putrescine, cadaverine, 3-phenyllactate, 2-hydroxyisocaproate) were detected which may contribute to the odor and flavour of the fermented products and their effects on human body.PMID:39756085 | DOI:10.1016/j.foodchem.2024.142657

Food Chem. 2024 Dec 27;470:142675. doi: 10.1016/j.foodchem.2024.142675. Online ahead of print.ABSTRACTSalt enhances flavor and salinity in Chinese curing; however, excessive use can pose health risks, while reducing NaCl may harm taste. This study utilized targeted and untargeted metabolomics to investigate the intrinsic molecular mechanisms that drive flavor formation in cured sea bass subjected to salt. Glycine, succinic acid, lactic acid and uridine significantly contributed to the taste profile of the cured sea bass. A total of 668 lipid molecules were annotated in the samples, of which 60 were classified as differential lipids. Non-targeted lipidomic analysis identified phosphatidylcholine and phosphatidylethanolamine as the major flavor precursors, constituting 40.12 % of the total. Elevated salt concentrations significantly enhanced the production and accumulation of key differential volatile flavor components, including 1-octen-3-ol, 2-undecanone and 2-pentylfuran. Thus, salt facilitated the degradation and oxidation of lipids, leading to the formation of key flavor compounds that contribute to the enhancement of the flavor profile of cured sea bass.PMID:39756082 | DOI:10.1016/j.foodchem.2024.142675

Food Chem. 2024 Dec 31;470:142679. doi: 10.1016/j.foodchem.2024.142679. Online ahead of print.ABSTRACTAtemoya fruit deteriorates rapidly during post-harvest storage. A complete understanding of the metabolic mechanisms underlying this process is crucial for developing effective preservation strategies. Metabolomic approaches combined with machine learning offer new opportunities to identify quality-related biomarkers. This study compared atemoya quality stored at 25 °C and 10 °C using untargeted metabolomics integrated with generative adversarial network (GAN) and random forest (RF) analysis. It was found that GAN successfully amplified the metabolomic dataset 10-fold, enabling robust RF-based identification of 20 quality change-related biomarkers. These biomarkers were primarily involved in energy metabolism, reactive oxygen species regulation and primary metabolic pathways including amino acids, lipids and carbohydrates. Low-temperature storage inhibited respiration, preserved cell structure and altered specific glycerophospholipid metabolic pathways. These findings provide molecular insights into low temperature preservation mechanisms and establish a novel framework for metabolomic data analysis in postharvest research.PMID:39756079 | DOI:10.1016/j.foodchem.2024.142679

Food Chem. 2024 Dec 27;470:142627. doi: 10.1016/j.foodchem.2024.142627. Online ahead of print.ABSTRACTThe effect of dehulling and cooking on the in vitro digestibility, and phenolic profiles was evaluated for four Dutch sorghum varieties (HD7 and HD19, Sorghum bicolor; and HD100 and HD101 Sorghum nigricans) bred in the Netherlands. Protein content ranged from 9 to 14 % and grains with black pericarp were more resistant to dehulling. Essential amino acids composition analysis showed that the lysine chemical score (∼0.6) was lower than that required for adults. Phenolic profiling by UHPLC-ESI-QTOF/MS allowed annotaion of 219 phenolic compounds, with flavonoids as the most representative class (91 %). Dehulling and genotype had stronger influence on the phenolic profiles than cooking; however, hydrothermal treatment was essential for the depolymerization of proanthocyanidin dimers and trimers. The combination of dehulling and boiling improved in vitro protein digestibility and increased in vitro bioaccessibility of key phenolic compounds. These processes are effective for developing high-quality sorghum-based products using Dutch varieties.PMID:39756077 | DOI:10.1016/j.foodchem.2024.142627

J Biochem Mol Toxicol. 2025 Jan;39(1):e70116. doi: 10.1002/jbt.70116.ABSTRACTThis study investigates the metabolic disruptions caused by nicotine (NIC) exposure, with a particular focus on amino acid and lipid metabolism, and evaluates resveratrol (RSV) as a potential protective agent. Mice were divided into four groups: control (CON), NIC-exposed, NIC + RSV-treated, and RSV-only. NIC exposure resulted in significant weight loss, elevated glucose levels, altered lipid profiles, and organ damage, particularly in the liver and kidneys. Increased inflammation was evidenced by elevated levels of IL-6 and CRP. In contrast, RSV treatment mitigated these effects by improving lipid profiles, glycemic indices, and reducing inflammatory markers. Histopathological analysis confirmed reduced tissue damage in the NIC + RSV group compared to the NIC-alone group. Metabolomics analysis using LC-MS/MS revealed significant dysregulation in lipid, amino acid, and nucleotide metabolism in NIC-exposed mice. Fold-change analysis identified altered metabolites, including sphingomyelin 36:1;02 (p < 0.001), valine (p < 0.001), triacylglycerol 4:0-18:1 (p < 0.001), and ceramide 32:1;02 (p < 0.001). Amino acids such as arginine, phenylalanine, glutamic acid, tyrosine, and lysine, as well as NIC metabolites like nornicotine and cotinine, were identified, underscoring molecular fragmentation analysis findings. RSV treatment partially restored metabolic balance, highlighting its role as a metabolic modulator. This study underscores the therapeutic potential of RSV in alleviating NIC-induced metabolic dysfunctions by restoring lipid homeostasis and reducing inflammation. Additionally, it emphasizes the importance of RSV in addressing NIC-related metabolic impairments and the need for noninvasive biomarkers for early disease detection.PMID:39756060 | DOI:10.1002/jbt.70116

J Am Soc Mass Spectrom. 2025 Jan 5. doi: 10.1021/jasms.4c00364. Online ahead of print.ABSTRACTReproducibility in untargeted metabolomics data processing remains a significant challenge due to software limitations and the complex series of steps required. To address these issues, we developed Nextflow4MS-DIAL, a reproducible workflow for liquid chromatography-mass spectrometry (LC-MS) metabolomics data processing, validated with publicly available data from MetaboLights (MTBLS733). Nextflow4MS-DIAL automates LC-MS data processing to minimize human errors from manual data handling. The workflow supports software containerization, ensuring computational reproducibility and enabling collaborative research. Nextflow4MS-DIAL is compatible with any Unix-like system and supports multiple job schedulers, offering flexibility and ease of use. The Nextflow4MS-DIAL workflow is available under the permissive MIT license: https://github.com/Nextflow4Metabolomics/nextflow4ms-dial.PMID:39755959 | DOI:10.1021/jasms.4c00364

Sci Rep. 2025 Jan 4;15(1):796. doi: 10.1038/s41598-024-84796-0.ABSTRACTThe presence of high-risk human papillomavirus (HR-HPV) contributes to the development of cervical lesions and cervical cancer. Recent studies suggest that an imbalance in the cervicovaginal microbiota might be a factor in the persistence of HR-HPV infections. In this study, we collected 156 cervicovaginal fluid (CVF) of women with HR-HPV infection, which were divided into three groups (negative for intraepithelial lesions = 78, low/high-grade squamous intraepithelial lesions = 52/26). We performed metabolomics and 16 S rRNA sequencing to identify changes in metabolites and cervicovaginal microbiota among patients with HR-HPV infection and varying grades of cervical lesions. We detected 164 metabolites and 389 flora types in the three groups. Ten CVF metabolites-N-methylalanine, phenylacetaldehyde, succinic acid, 2-3-dihydroxypyridine, DL-p-hydroxylphenyllactic acid, gluconic acid lactone, guanine, glucose-6-phosphate, erythrose, and sucrose showed significant associations with disease severity and distinct separation patterns in HR-HPV-infected patients with LSIL and HSIL, with an area under the curve of 0.928. The most abundant microbial communities in the CVF were Gardnerella. Gardnerella was found to be associated with increased levels of succinic acid, thereby highlighting distinct metabolic profiles. These findings suggest that the development of cervical lesions resulting from persistent HR-HPV infection is associated with significant alterations in systemic metabolism and shifts in the cervicovaginal microbiota, providing valuable insights into the metabolic and microbiota changes linked to disease severity.PMID:39755909 | DOI:10.1038/s41598-024-84796-0

Chin Med. 2025 Jan 4;20(1):6. doi: 10.1186/s13020-024-01052-3.ABSTRACTBACKGROUND: Jianwei Xiaoshi oral liquid (JWXS), a classical traditional prescription comprising various edible medicinal plants, has demonstrated significant efficacy in treating paediatric indigestion. It originates from Jianpi Pill, which is developed in the Ming Dynasty and nourishes the spleen and regulates gastrointestinal function. However, the specific molecular mechanisms involved remain unclear.METHODS: To elucidate the material base of JWXS and its underlying mechanism in treating dyspepsia, the UHPLC-Q-Orbitrap HRMS method and network pharmacology were utilized. This was followed by pharmacological experiments, transcriptomics analyses and gut microbiota studies to further investigate the effects of JWXS on dyspepsia.RESULTS: A total of 105 compounds, mainly flavonoids, alkaloids, organic acids and cyclic peptides, were identified. According to the five principles of generic drug properties, 43 candidate compounds were screened out. Their efficacy was verified through gastric emptying and intestinal propulsion experiments. Transcriptomic analysis revealed that JWXS primarily alleviated dyspepsia symptoms by regulating the secretion of 8 key proteins in the pancreatic secretion pathway. The differences in the gut microbiota, as identified through 16S rRNA and ITS2 sequencing, were subsequently more pronounced than those observed in the bacterial microbiota of the model group. In total, 15 differential bacteria and 16 differential fungi were identified. Targeted metabolomics analysis of SCFAs revealed a significant decrease in valeric acid (VA), acetic acid (AA), and isovaleric acid (IVA) levels in the model group, which were restored to the corresponding levels after the administration of JWXS. Correlation analysis revealed that VA, AA, and IVA were positively correlated with Lactobacillus and Bacteroides, and negatively correlated with Aspergillus and Candida. This further suggested that JWXS might alleviate symptoms of indigestion by regulating the composition of the microbiota, increasing the variety and quantity of beneficial bacteria, reducing fungal contamination, and further increasing the levels of SCFAs in the body.CONCLUSION: JWXS improved functional dyspepsia in immature rats via a mechanism involving the regulation of the secretion of 8 key proteins in the pancreatic secretion pathway and the amelioration of flora disorders.PMID:39755683 | DOI:10.1186/s13020-024-01052-3

J Nanobiotechnology. 2025 Jan 5;23(1):7. doi: 10.1186/s12951-024-03073-4.ABSTRACTSelenium promotes plant growth and improves nutritional quality, and the role of nano-selenium in alfalfa in regulating nutritional quality is unknown. In this study, using the 15N labeling method, it was found that nano-selenium could promote plant nitrogen metabolism and photosynthesis by increasing the light energy capture capacity and the activities of key enzymes of the nitrogen metabolism process, leading to an increase in alfalfa nitrogen accumulation and dry matter content. The transcriptome and metabolome revealed that nano-selenium mainly affected the pathways of 'biosynthesis of amino acids', 'starch and sucrose metabolism', 'pentose and glucuronate interconversions', 'pentose phosphate pathway', and 'flavonoid biosynthesis'. At the early stage of nano-selenium treatment, the nitrogen metabolism, sugar metabolism, and flavonoid metabolism pathways were regulated by modulating the expression of genes such as NR, Nir, GS, GOGAT, E3.1.1.11, adh, CHS, FLS, etc., which increased the amount of L-glutamic, L-histidine, glycerone-P, coniferin, naringenin chalcone, and other beneficial substances, thus promoting the acceleration of nitrogen accumulation by plants. In summary, this study provides a better understanding of the mechanisms by which nano-selenium regulates key nitrogen metabolic pathways in alfalfa.PMID:39755664 | DOI:10.1186/s12951-024-03073-4

Reprod Biol Endocrinol. 2025 Jan 4;23(1):1. doi: 10.1186/s12958-024-01330-7.ABSTRACTBACKGROUND: A didelphic uterus represents a unique and infrequent congenital condition in which a woman possesses two distinct uteri, each with its own cervix. This anomaly arises due to partial or incomplete merging of the Müllerian ducts during the developmental stages in the womb. Accounting for uterine malformations, a didelphic uterus is a relatively rare condition, affecting approximately 0.5-2% of the population and is considered one of the more uncommon types of uterine abnormalities.METHODS: This case report aims to study the physical separation in uterine didelphys and its impact on endometrial microbiome and inflammation, and the patterns of endometrial receptivity observed.RESULTS: Endometrial receptivity analyses revealed a similar receptive state in both uteri, both in the early receptive phase. Differential markers of chronic endometritis, including CD138, and MUM1-positive cells, were observed when comparing endometrial biopsies from both uteri. The right uterus exhibited a higher prevalence of these positive cells. Regarding the microbiome, significant differences were found between the uteri, notably in the right uterus, a clear non-dominance of lactobacilli and the presence of genera such as Staphylococcus, Streptococcus, and Acinetobacter. Additionally, the right uterus presented a less 'favourable' microenvironment, a characteristic that was also reflected in the right cervix; both sites presenting less lactobacilli than the left side samples. A distinct metabolomic signature associated with the physical separation of the uteri contributed to the differences in endometrial milieu.CONCLUSIONS: Our study revealed that physical separation, among other factors in uterus didelphys, affects the endometrial microbiome, metabolome, and inflammatory state, with significant microbiome variation observed between the uteri, although similar endometrial receptivity patterns were noted.PMID:39755646 | DOI:10.1186/s12958-024-01330-7

J Hematol Oncol. 2025 Jan 4;18(1):2. doi: 10.1186/s13045-024-01655-1.ABSTRACTBACKGROUND: Targeting glucose uptake by glucose transporter (GLUT) inhibitors is a therapeutic opportunity, but efforts on GLUT inhibitors have not been successful in the clinic and the underlying mechanism remains unclear. We aim to identify the key metabolic changes responsible for cancer cell survival from glucose limitation and elucidate its mechanism.METHODS: The level of phosphorylated YAP was analyzed with Western blotting and Phos-tag immunoblotting. Glucose limitation-induced metabolic changes were analyzed using targeted metabolomics (600MRM). The anti-cancer role of metabolite was examined using colony formation assay and APCmin/+ mice. Co-immunoprecipitation, LS-MS, qRT-PCR, and immunofluorescence were performed to explore the underlying mechanisms.RESULTS: We found that D-Ribose-5-phosphate (D5P), a product of the pentose phosphate pathway connecting glucose metabolism and nucleotide metabolism, functions as a metabolic checkpoint to activate YAP under glucose limitation to promote cancer cell survival. Mechanistically, in glucose-deprived cancer cells, D5P is decreased, which facilitates the interaction between MYH9 and LATS1, resulting in MYH9-mediated LATS1 aggregation, degradation, and further YAP activation. Interestingly, activated YAP further promotes purine nucleoside phosphorylase (PNP)-mediated breakdown of purine nucleoside to restore D5P in a feedback manner. Importantly, D5P synergistically enhances the tumor-suppressive effect of GLUT inhibitors and inhibits cancer progression in mice.CONCLUSIONS: Our study identifies D5P as a metabolic checkpoint linking glucose limitation stress and YAP activation, indicating that D5P may be a potential anti-cancer metabolite by enhancing glucose limitation sensitivity.PMID:39755622 | DOI:10.1186/s13045-024-01655-1

BMC Oral Health. 2025 Jan 4;25(1):25. doi: 10.1186/s12903-024-05355-7.ABSTRACTBACKGROUND: Streptococcus mutans (S. mutans) contributes to caries. The biofilm formed by S. mutans exhibits greater resistance to drugs and host immune defenses than the planktonic form of the bacteria. The objective of this study was to evaluate the anti-biofilm effect of cordycepin from the perspective of metabolomics.METHODS: The minimum inhibitory concentration (MIC) was determined to evaluate the antimicrobial effect of cordycepin on planktonic S. mutans. The 24-h biofilm was treated with 128 µg/mL of cordycepin for 10 min at the 8- or 20-h time points. Biofilm biomass and metabolism were assessed using crystal violet and MTT assays and cordycepin cytotoxicity was evaluated in human oral keratinocytes (HOK) using CCK-8 assays. The live bacterial rate and the biofilm volume were assessed by confocal laser scanning microscopy. Metabolic changes in the biofilm collected at different times during with cordycepin were analyzed by metabolomics and verified by quantitative real-time PCR.RESULTS: The results showed that treatment with 128 µg/mL cordycepin reduced both the biomass and metabolic activity of the biofilm without killing the bacteria, and cordycepin at this concentration showed good biocompatibility. Metabolomics analysis showed that differentially abundant metabolites following cordycepin treatment were mainly related to purine and nucleotide metabolism. After immediate treatment with cordycepin, genes related to purine and nucleotide metabolism were downregulated, and the levels of various metabolites changed significantly. However, the effect was reversible. After continuing culture for 4 h, the changes in genes and most metabolites were reversed, although the levels of 2'-deoxyadenosine, 2'-deoxyinosine, and adenine remained significantly different.CONCLUSIONS: Cordycepin has the effect of anti-biofilm of S. mutans, mainly related to purine and nucleotide metabolism.PMID:39755609 | DOI:10.1186/s12903-024-05355-7

J Immunother Cancer. 2025 Jan 4;13(1):e009415. doi: 10.1136/jitc-2024-009415.ABSTRACTBACKGROUND: Immune checkpoint inhibitors (ICIs) in combination with antiangiogenic drugs have shown promising outcomes in the third-line and subsequent treatments of patients with microsatellite stable metastatic colorectal cancer (MSS-mCRC). Radiotherapy (RT) may enhance the antitumor effect of immunotherapy. However, the effect of RT exposure on patients receiving ICIs and targeted therapy remains unclear. This study aimed to investigate the association between RT exposure and clinical responses to fruquintinib (a highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor) plus sintilimab (an anti-programmed death 1 antibody; F&S) in previously treated patients with MSS-mCRC and to explore predictive biomarkers.METHODS: In this prospective observational study, patients with mCRC receiving F&S as third-line or subsequent treatment were enrolled. Eligible patients were divided into the RT cohort (RTC) and the non-RT cohort (NRTC) according to their RT history. The primary endpoint was the objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Pretreatment fecal and serum samples were collected for microbiome analysis, metabolome analysis, and immune signatures to identify biomarkers for treatment.RESULTS: A total of 55 patients were included, of which 25 were in the RTC and 30 in the NRTC. Better ORR (28.0% vs 6.7%, p=0.048), DCR (80.0% vs 36.7%, p=0.002), median PFS (6.2 vs 2.7 months, p<0.001), and median OS (14.8 vs 5.9 months, p=0.019) were noted in patients with RTC than those with NRTC. The enrichment of Lactobacillus, Bifidobacterium, and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:3(8Z,11Z,14Z)) in RTC significantly predicted better DCR and PFS, whereas guanosine and interleukin-10 predominated in patients with NRTC were negatively correlated with PFS and OS.CONCLUSIONS: Patients with RT exposure benefited significantly from F&S in the third-line or subsequent treatment for MSS-mCRC. Gut microbiota, metabolites, and cytokines may help predict F&S outcomes for mCRC, which may be helpful in treatment decision-making.TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT05635149.PMID:39755582 | DOI:10.1136/jitc-2024-009415

Environ Pollut. 2025 Jan 2:125634. doi: 10.1016/j.envpol.2025.125634. Online ahead of print.ABSTRACTThe extensive presence of per-/polyfluoroalkyl substances (PFASs) in the environment and their adverse effects on organisms have garnered increasing concern. With the shift of industrial development from legacy to emerging PFASs, expanding the understanding of molecular responses to legacy and emerging PFASs is essential to accurately assess their risks to organisms. Compared with traditional toxicological approaches, omics technologies including transcriptomics, proteomics, metabolomics/lipidomics, and microbiomics allow comprehensive analysis of the molecular changes that occur in organisms after PFAS exposure. This paper comprehensively reviews the insights of omics approaches, especially the multi-omics approach, on the toxic mechanisms of both legacy and emerging PFASs in recent five years, focusing on hepatotoxicity, developmental toxicity, immunotoxicity, reproductive toxicity, neurotoxicity, and the endocrine-disrupting effect. PFASs exert various toxic effects via lipid and amino acid metabolism disruption, perturbations in several cell signal pathways, and binding to nuclear receptors. Notably, integrating multi-omics offers a thorough insight into the mechanisms of toxicity associated with PFASs. The gut microbiota plays an essential regulatory role in the toxic mechanisms of PFAS-induced hepatotoxicity. Finally, further research directions for PFAS toxicology based on omics technologies are prospected.PMID:39755359 | DOI:10.1016/j.envpol.2025.125634