PubMed

Cell Rep. 2025 Jan 28;44(1):115134. doi: 10.1016/j.celrep.2024.115134. Epub 2024 Dec 31.ABSTRACTThe physiological perturbations induced by high-altitude exposure in mountain climbers, manifesting as immunological and metabolic deviations, have been previously reported but are not fully understood. In this study, we obtain multi-omic profiles of climbers' blood samples, including single-cell transcriptomic analysis of 375,722 immune cells, and plasma metabolomics and lipidomics. Longitudinal analysis reveals dynamic immune response profiles, during the acclimatization period, characterized by the downregulation of inflammatory responses in myeloid cell subsets and by the enhancement of immune effector processes in cytotoxic CD8+ T, γδT, and CD16+ natural killer cells. In contrast, during extreme-altitude mountaineering, the activation of inflammatory responses and impairment of immune effector function are observed, concomitant with an increased cellular response to hypoxia and oxidative stress pathways. Furthermore, glycolysis and antioxidant gene expression are upregulated during extreme-altitude mountaineering. Plasma metabolic analysis reveals significant alterations, involving enhanced glutamine and fatty acid metabolism.PMID:39932189 | DOI:10.1016/j.celrep.2024.115134

FASEB J. 2025 Feb 15;39(3):e70355. doi: 10.1096/fj.202402842R.ABSTRACTPulmonary hypertension associated with left heart disease (PH-LHD) represents the most prevalent form of pulmonary hypertension; however, being lacks precise and effective treatment strategies. Recent clinical studies have indicated a positive correlation between the volume of pericardiac adipose tissue (PAT) and the severity of PH-LHD. Nonetheless, there is a paucity of research characterizing PAT phenotypes in PH-LHD disease models. This study aimed to elucidate the gene-level characteristics of PAT in PH-LHD through RNA sequencing and targeted metabolomic analysis of PAT in order to identify potential therapeutic targets for PH-LHD by modulating PAT. This study developed a mouse model of PH-LHD through cardiac overload combined with metabolic syndrome and verified that PAT volume and adipocyte size were significantly increased in PH-LHD mice. We used RNA sequencing to reveal that DEGs in PAT were primarily enriched in fatty acid metabolism pathways. Then, real-time PCR showed no significant differences in the mRNA expression of inflammatory markers or adipocytokines; however, genes of fatty acid synthesis (Fasn, Acaca, and Scd1) and fatty acid decomposition (Ehhadh, Acot4, and Pdk1) significantly changed between the two groups. Consistently, targeted metabolomic analysis showed levels of most types of medium- and long-chain fatty acids substantially reduced in PAT, suggesting that PAT in PH-LHD mice exhibits suppressed fatty acid de novo synthesis and enhanced fatty acid breakdown, resulting in impaired fatty acid storage. These findings highlight the potential of targeting PAT fatty acid synthesis and metabolism pathways as a novel therapeutic approach for PH-LHD.PMID:39932146 | DOI:10.1096/fj.202402842R

Curr Drug Metab. 2025 Feb 7. doi: 10.2174/0113892002360132250122164637. Online ahead of print.ABSTRACTBACKGROUND: Chemotherapy-induced immunosuppression significantly impacts patient's quality of life. Umbelliferone (UMB) is known for its anti-inflammatory, antioxidant, and anti-apoptotic properties, but its effects on cyclophosphamide (CTX)-induced immunosuppression need further study.METHODS: We established a CTX-induced immunosuppressed mouse model and administered varying doses of UMB. Immune function was assessed by evaluating white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios. Serum levels of IL-2, IFN-γ, IgA, IgM, and IgG, along with macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation, were measured. Untargeted metabolomics was used to identify key pathways regulated by UMB, and RT-qPCR and Western blotting were performed to analyze the expression of related enzymes and metabolites.RESULTS: UMB intervention increased white blood cells, lymphocytes, thymus and spleen indices, and CD4+/CD8+ T cell ratios in CTX-immunosuppressed mice. It reversed reduced levels of serum IL-2, IFN-γ, IgA, IgM, and IgG and improved macrophage phagocytic activity, NK cytotoxicity, and lymphocyte proliferation. Key pathways identified by metabolomics included histidine and purine metabolism. UMB improved levels of histamine, L-glutamate, L-aspartate, xanthine, dAMP, deoxyinosine, xanthosine, and cGMP and upregulated HDC, ASPA, and PNP while downregulating XDH, PDE5, ROS, and MDA in spleen tissue. UMB enhanced SOD activity and GSH levels and reduced apoptosis, as indicated by lower TUNEL-positive expression.CONCLUSION: UMB enhanced immune function in CTX-immunosuppressed mice through the regulation of histidine and purine metabolism, exhibiting antioxidant and anti-apoptotic effects. These findings highlight the potential of UMB in mitigating immunosuppression.PMID:39931991 | DOI:10.2174/0113892002360132250122164637

Chem Asian J. 2025 Feb 11:e202401374. doi: 10.1002/asia.202401374. Online ahead of print.ABSTRACTPomacea canaliculata is an invasive species that poses significant threats to agriculture and human health. The development of environmentally friendly molluscicides is crucial for its management. In this study, we synthesized 17 fluoropyridylphenylurea derivatives using a halogen modulation strategy to explore their potential as molluscicides. Compounds L-1 and L-2 demonstrated notable molluscicidal activity, with LC50 values of 1.377 mg/L and 1.001 mg/L, respectively. Among these, L-2 exhibited superior efficacy while causing minimal harm to other aquatic organisms, particularly fish. The molluscicidal mechanism of L-2 was investigated using Tandem Mass Tags (TMT)-labeled quantitative proteomic analysis and non-targeted metabolic analysis. These analyses revealed that L-2 significantly affected the liver metabolism of P. canaliculata by disrupting the transaminase, gluconeogenesis, and glycolysis pathways. This metabolic disruption is likely a contributing factor to the mortality observed in the snails. Our findings suggest that compound L-2 is a promising molluscicide, offering high efficiency and minimal environmental impact. These insights could guide future research and development in molluscicide applications.PMID:39931954 | DOI:10.1002/asia.202401374

Food Funct. 2025 Feb 11. doi: 10.1039/d4fo03049d. Online ahead of print.ABSTRACTCholesterol is an important lipid molecule that affects the gut microbiome upon ingestion. We systematically investigated the effects of cholesterol on the microbiota of the large and small intestines using ex vivo and in vivo models, combining flow cytometry, metabolomics, and metagenomics. The results showed that cholesterol directly causes a loss of bacterial membrane polarity and integrity, as well as a reduction in microbial metabolic activity. Cholesterol directly affected the global metabolism of the large and small intestinal microbiota, including amino acid, carbohydrate, and nucleotide metabolism. Ex vivo and in vivo studies shared similar results, showing that cholesterol increased the abundance of the primary bile acid-metabolizing bacteria Clostridium and Dorea in the large intestinal microbiota, confirming the enrichment effect of cholesterol on these bacteria. In the in vivo model, increased conjugated bile acids in the small intestine and decreased abundance of BSH-containing Bifidobacterium were observed due to cholesterol. Only in vivo models have demonstrated that cholesterol increases phosphatidylcholine levels in both the small and large intestines, which may be related to the effects of cholesterol on host metabolism. The pro-inflammatory capacity of the intestinal microbiota was enhanced by cholesterol, as evidenced by the increased levels of IL-1β and TNF-α in THP-1 cells upon stimulation with cholesterol-treated microbiota. This study comprehensively elucidates the effects of cholesterol on the composition and metabolic functions of the microbiota in both the large and small intestines. It offers a novel perspective on the ways in which cholesterol affects host metabolism via the gut microbiome.PMID:39931947 | DOI:10.1039/d4fo03049d

Front Pharmacol. 2025 Jan 27;16:1485340. doi: 10.3389/fphar.2025.1485340. eCollection 2025.ABSTRACTHua-Feng-Dan is a traditional Chinese medicine used to treat ischemic stroke, but little is known about its therapeutic mechanism. This study explored whether and how the mechanism involves readjustment of gut microbiota. Rats were subjected to middle cerebral artery occlusion as a model of ischemic stroke or to sham surgery, then treated or not with Hua-Feng-Dan. The different groups of animals were compared in terms of neurological score, cerebral infarct volume, brain edema, brain and gut histopathology to assess stroke severity. They were also compared in terms of indices of intestinal barrier permeability, inflammation and oxidative stress, brain metabolites as well as composition of the gut microbiota and their metabolites. Hua-Feng-Dan significantly reduced cerebral infarct volume and brain water content and improved neurological score, ischemic brain histopathology, and gut histopathology. It partially reversed stroke-induced intestinal barrier disruption and leakage, inflammation, dyslipidemia and oxidative stress, as well as the stroke-induced increase in pathogenic gut microbiota (e.g., Escherichia-Shigella, Enterococcus, Clostridium_innocuum_group) and decrease in beneficial microbiota (e.g., Lachnospiraceae, unclassified__f__Lachnospiracea and Ruminococcus_torques_group). The treatment altered levels of 39 and 38 metabolites produced during gut microbial and brain tissue metabolism respectively, mainly of amino acids, nucleosides, short-chain fatty acids, and essential fatty acids. Levels of factors related to inflammation and intestinal barrier permeability correlated positively with relative abundance of Escherichia-Shigella and Clostridium_innocuum_group, and negatively with 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, dihomo-α-linolenic acid, dihomolinoleic acid, and 10-nitrolinoleic acid. Conversely, levels of 4-(glutamylamino) butanoate, 2-hydroxy-3-methylbutyric acid, and 10-nitrolinoleic acid correlated positively with relative abundance of unclassified__f__Lachnospiracea. Our results suggest that Hua-Feng-Dan may mitigate ischemic stroke injury by renormalizing gut microbiota and restoring gut barrier function, gut metabolism, thereby helping to alleviate inflammatory, neurological damage, and brain metabolic disorders.PMID:39931688 | PMC:PMC11808003 | DOI:10.3389/fphar.2025.1485340

Front Pharmacol. 2025 Jan 27;16:1518481. doi: 10.3389/fphar.2025.1518481. eCollection 2025.ABSTRACTINTRODUCTION: Chronic nephrotoxicity caused by CNIs (CICN) manifests clinically as chronic kidney disease (CKD). Astragaloside IV (AS-IV) plays a certain role in the treatment of CKD. This study aimed to verify the ameliorative effects of AS-IV on CICN and further explore the mechanisms underlying the modulation of the "gut-transcriptome-metabolome coexpression network" by AS-IV within the context of the "gut-kidney axis" to improve CICN.METHODS: Five groups of 40 mice were studied: a normal group (N, olive oil), a model group (M, CsA, 30 mg kg--1 d-1), a low-dose AS-IV group (CsA + AS-IV, 30 mg kg-1 d-1 + 10 mg kg-1 d-1), a high-dose AS-IV group (CsA + AS-IV, 30 mg kg-1 d-1 + 20 mg kg-1 d-1), and a valsartan group (CsA + Val, 30 mg kg-1 d-1 + 10 mg kg-1 d-1). The gut microbiota, renal transcriptome, and urine metabolome were separately detected to construct a gut-transcriptome-metabolome coexpression network. The target species, target genes, and target metabolites of AS-IV were evaluated.RESULTS: CsA led to increased proteinuria and a deterioration of kidney function, accompanied by increased inflammation and oxidative stress, whereas AS-IV improved kidney damage. AS-IV inhibited intestinal permeability and disrupted the microbiota structure, increasing the abundance of Lactobacillus reuteri, Bifidobacterium animalis, Ignatzschineria indica, and Blautia glucerasea. Six coexpression pathways related to transcription and metabolism, including the citrate cycle, ascorbate and aldarate metabolism, proximal tubule bicarbonate reclamation, glycolysis/gluconeogenesis, ferroptosis, and drug metabolism-cytochrome P450, were identified. Seven target metabolites of AS-IV were identified in the 6 pathways, including UDP-D-galacturonic acid, 2-phenylethanol glucuronide, dehydroascorbic acid, isopentenyl pyrophosphate, alpha-D-glucose, 3-carboxy-1-hydroxypropylthiamine diphosphate and citalopram aldehyde. Five target genes of AS-IV, Ugt1a2, Ugt1a9, Ugt1a5, Pck1, and Slc7a11, were also identified and predicted by NONMMUT144584.1, MSTRG.30357.1 and ENSMUST00000174821. Lactobacillus reuteri was highly correlated with renal function and the target genes and metabolites of AS-IV. The target genes and metabolites of AS-IV were further validated. AS-IV inhibited intestinal-derived urinary toxins and improved renal tissue apoptosis, lipid accumulation, collagen deposition, and mitochondrial damage.CONCLUSION: AS-IV improved CICN through the coexpression of the gut-transcriptome-metabolome network. The six pathways related to energy metabolism driven by L. reuteri, including the citrate cycle, ascorbate and alderate metabolism, proximal tube bicarbonate metabolism, glycolysis/gluconeogenesis, ferroptosis, drug metabolism-cytochrome P450, are important mechanisms.PMID:39931687 | PMC:PMC11807982 | DOI:10.3389/fphar.2025.1518481

Front Nutr. 2025 Jan 27;12:1518525. doi: 10.3389/fnut.2025.1518525. eCollection 2025.ABSTRACTBACKGROUND: Active dietary flavonoids are a promising resource for novel drug discovery. Sweet potato, a widely cultivated functional crop, is abundant in flavonoids. However, the active ingredients associated with acute myeloid leukemia (AML) treatment and their underlying mechanisms have not been reported to date.OBJECTIVE: This study aims to identify novel drugs against AML from sweet potato by integrating metabolomics analysis, network pharmacology, and experimental validation.METHODS: Firstly, ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to analyze the major constituents in sweet potato. Then, nine active ingredients were selected for validation of their anti-leukemia effects. Subsequently, three of them underwent network pharmacology analyses and in vitro experimental verification. Finally, the anti-leukemia effect of cynaroside was further confirmed through in vivo experimental validation.RESULTS: Firstly, the flavonoid content of stem, leaves, flesh, and peel from 13 sweet potato cultivars was examined. The leaves of Nanshu 017 exhibited the highest flavonoid content of 2.27% dry weight (DW). Then, an extract derived from these leaves was employed for in vitro experiments, demonstrating significant inhibition of AML cell growth. Subsequently, based on the results of metabolomics analysis and network pharmacology, cynaroside, nepitrin, and yuanhuanin were identified as potential antileukemia agents present in sweet potato for the first time; while CASP3, KDR, EGFR, and SRC were recognized as pivotal targets of these three monomers against AML. Finally, the antileukemia effects of cynaroside, nepitrin, and yuanhuanin were confirmed through in vitro and in vivo experimental validation.CONCLUSION: In summary, sweet potato leaves extract possesses an antileukemic effect while cynaroside, nepitrin, and yuanhuanin demonstrate potential as treatments for AML.PMID:39931370 | PMC:PMC11807822 | DOI:10.3389/fnut.2025.1518525

Front Plant Sci. 2025 Jan 27;15:1501966. doi: 10.3389/fpls.2024.1501966. eCollection 2024.ABSTRACTINTRODUCTION: In the present study, the flower of Chinese peony (CPF), major waste by-product of Chinese Herb Radix paeoniae, was comprehensively investigated for the first time.METHODS: A validated UHPLC Orbitrap Mass spectrometry combined a three-levels characterization strategy were used to analyze CPF samples from four representative cultivars. The anti-inflammatory and antioxidant activities were analyzed using RAW264.7 cells, and DPPH, ABTS, FRAP, and ORAC antioxidant assays.RESULTS: A total of 150 chemical components were identified in CPF, among them, more than 50 components were reported from this species for the first time, with potential new chemicals reported. 67 quantified or semi-quantified targeted metabolomics analysis indicated a clear distinction between flower parts and four cultivars. CPF demonstrated significant antioxidant activities and displayed anti-inflammatory effects by reducing nitric oxide, IL-6, and TNF-a release in LPS-induced macrophages. Correlation analysis highlighted a strong positive correlation between total phenolic content and DPPH ABTS, and FRAP antioxidant activities.DISCUSSION: The present study is the first to comprehensively investigate the chemical profile and bioactivities of CPF, which provide insights into further understanding of its health-promoting potential.PMID:39931332 | PMC:PMC11808149 | DOI:10.3389/fpls.2024.1501966

Food Sci Nutr. 2025 Feb 10;13(2):e70004. doi: 10.1002/fsn3.70004. eCollection 2025 Feb.ABSTRACTCoccinia grandis (L.) Voigt (C. grandis), a member of the Cucurbitaceae family, is recognized for its phytochemicals that possess antioxidant and antidiabetic properties, along with a wide array of nutritional and health-promoting benefits. However, a comprehensive investigation of the phytochemical profiles and biologically active constituents in different parts of C. grandis has not yet been reported. Therefore, this study aimed to evaluate the phytochemical constituents of three distinct parts of C. grandis (fruit, leaves, and stem) at the same growth stage. The phytochemicals in C. grandis were identified using UHPLC-HRMS-based untargeted metabolomics, followed by a quantitative analysis of the primary metabolites. The qualitative analysis revealed 60 secondary metabolites, including phenolic compounds (6 hydroxybenzoic acids, 22 hydroxycinnamic acids, 2 coumarins, 1 flavanone, 1 flavanonol, 2 flavones, 22 flavonols, and 2 lignans) and triterpenes (2 cucurbitacins). Furthermore, nine plant hormones and 30 amino acids were successfully identified. The quantitative analysis of 32 types of secondary metabolites indicated that the leaves contained the highest total amounts of flavonoids (501.37 mg/100 g) and hydroxycinnamic acids (1148.23 mg/100 g). Additionally, the analysis of amino acids revealed a total of 20 types, with the leaf extract exhibiting the highest total amounts of both essential and nonessential amino acids, followed by the fruit and stem extracts. In conclusion, the analysis of the primary and secondary metabolite composition and content of various parts of C. grandis demonstrated that the leaf extract replace with had the greatest functionality, suggesting its potential utility in the development of health functional foods.PMID:39931272 | PMC:PMC11808390 | DOI:10.1002/fsn3.70004

Front Aging Neurosci. 2025 Jan 27;17:1530046. doi: 10.3389/fnagi.2025.1530046. eCollection 2025.ABSTRACTBACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder, with mild cognitive impairment (MCI) often serving as its precursor stage. Early intervention at the MCI stage can significantly delay AD onset.METHODS: This study employed untargeted urine metabolomics, with data obtained from the MetaboLights database (MTBLS8662), combined with orthogonal partial least squares-discriminant analysis (OPLS-DA) to examine metabolic differences across different stages of AD progression. A decision tree approach was used to identify key metabolites within significantly enriched pathways. These key metabolites were then utilized to construct and validate an AD progression prediction model.RESULTS: The OPLS-DA model effectively distinguished the metabolic characteristics at different stages. Pathway enrichment analysis revealed that Drug metabolism was significantly enriched across all stages, while Retinol metabolism was particularly prominent during the transition stages. Key metabolites such as Theophylline, Vanillylmandelic Acid (VMA), and Adenosine showed significant differencesdifferencesin the early stages of the disease, whereas 1,7-Dimethyluric Acid, Cystathionine, and Indole exhibited strong predictive value during the MCI to AD transition. These metabolites play a crucial role in monitoring AD progression. Predictive models based on these metabolites demonstrated excellent classification and prediction capabilities.CONCLUSION: This study systematically analyzed the dynamic metabolic differences during the progression of AD and identified key metabolites and pathways as potential biomarkers for early prediction and intervention. Utilizing urinary metabolomics, the findings provide a theoretical basis for monitoring AD progression and contribute to improving prevention and intervention strategies, thereby potentially delaying disease progression.PMID:39931229 | PMC:PMC11807997 | DOI:10.3389/fnagi.2025.1530046

J Inflamm Res. 2025 Feb 6;18:1855-1874. doi: 10.2147/JIR.S500014. eCollection 2025.ABSTRACTPURPOSE: To explore the protective effect and underlying mechanism of Quzhou Aurantii Fructus flavonoids (QAFF) on Ulcerative colitis (UC).METHODS: The constituents of QAFF were accurately determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The therapeutic impacts of QAFF were assessed in dextran sulfate sodium (DSS)-induced UC mice, focusing on the changes in body weight, disease activity index (DAI), colon length, histological assessment of colonic tissues, levels of pro-inflammatory cytokines, and expression of tight junction proteins. Western blotting confirmed key regulatory proteins within the differential signaling pathways, guided by transcriptome analysis. Additionally, the influence of QAFF on the gut microbiome was explored through 16S ribosomal RNA (rRNA) sequencing. The alterations in endogenous metabolites were detected by untargeted metabolomics, and their potential correlation with intestinal flora was then examined utilizing Spearman correlation analysis. Subsequently, the regulation of gut microbiome by QAFF was validated by fecal microbiota transplantation (FMT).RESULTS: Eleven flavonoids, including Naringin and hesperidin, were initially identified from QAFF. In vivo experiments demonstrated that QAFF effectively ameliorated colitis symptoms, reduced IL-6, IL-1β, and TNF-α levels, enhanced intestinal barrier integrity, and downregulated PI3K/AKT pathway activation. Furthermore, QAFF elevated the levels of beneficial bacteria like Lachnospiraceae_NK4A136_group and Alloprevotella and concurrently reduced the pathogenic bacteria such as Escherichia-Shigella, [Eubacterium]_siraeum_group, and Parabacteroides. Metabolomics analysis revealed that 34 endogenous metabolites exhibited significant alterations, predominantly associated with Glycerophospholipid metabolism. These metabolites were significantly correlated with those differential bacteria modulated by QAFF. Lastly, the administration of QAFF via FMT ameliorated the colitis symptoms.CONCLUSION: QAFF could ameliorate inflammatory responses and intestinal barrier dysfunction in DSS-induced UC mice probably by modulating the PI3K/AKT signaling pathway and gut microbiome, offering promising evidence for the therapeutic potential of QAFF in UC treatment.PMID:39931170 | PMC:PMC11809370 | DOI:10.2147/JIR.S500014

Rapid Commun Mass Spectrom. 2025 May 30;39(10):e10007. doi: 10.1002/rcm.10007.ABSTRACTGancao Fuzi decoction (GCFZT) is a traditional Chinese formula, which has been commonly used in clinical practice to treat inflammatory diseases. However, the active substance of GCFZT in the treatment of inflammation is not fully clarified. In this study, we used orthogonal experiments to design different GCFZT formulations, resulting in a total of 16 GCFZT formulations. Subsequently, UPLC-Q-TOF-MS/MS was used to analyze the chemical composition of different formulations, and the anti-inflammatory activity differences of these formulations were evaluated through an LPS-induced RAW264.7 inflammatory cell model. Combined with machine learning algorithms such as PLS-DA and RF, four main active substances in GCFZT were screened. Finally, network pharmacology techniques were used to investigate the potential anti-inflammatory mechanisms of these main active substances, and the results showed that GCFZT mainly regulates the expression of core targets such as ALOX5, NFKB1, and TLR4 through main active substances such as chlorogenic acid, riboflavin, and formononetin, thereby affecting the NF kappa B signaling pathway, the Toll-like receptor signaling pathway, and the Th17 cell differentiation. This study provides a reference for the anti-inflammatory mechanism of GCFZT and a scientific basis for its clinical application.PMID:39930763 | DOI:10.1002/rcm.10007

J Obstet Gynaecol Res. 2025 Feb;51(2):e16229. doi: 10.1111/jog.16229.ABSTRACTBACKGROUND: The pathogenesis of preeclampsia (PE) remains unclear, but the interaction between intestinal flora and PE has been attention in recent studies. Several studies have shown that imbalanced intestinal flora plays an important role in the inducement of PE.PURPOSE: The potential correlation among intestinal flora, metabolites, and fetal growth restriction was explored by integrating data and analyzing neonatal growth. The study is hoped to provide references for subsequent studies.METHODS: A comparison between the intestinal flora of healthy pregnant women and pregnant with PE was conducted using 16S rRNA gene sequencing. Subsequently, the feces, serum and umbilical cord blood collected from healthy pregnant women and those with PE were analyzed using global untargeted metabolomics to identify differences in metabolites.RESULTS: The results showed that Bifidobacterium, Chryseobacterium, Eubacterium, Pravotella and Bacteroides are the core species associated with many metabolites. Normal-birth weight had a negative correlation with the abundance of raclopride, Phe-Gly-O and Lys-Phe-OH showed a positive correlation with Phosphonate and Lys-Gly. Simultaneously, these core metabolites showed a strong correlation with other growth indices (BPD, AC, FL). In summary, the imbalance of intestinal flora in pregnant women may alter the abundance of the core metabolites, thereby affecting the neonatal growth.CONCLUSIONS: A global untargeted metabolomics was performed on the samples including feces, serum, and umbilical cord blood. The integrated multi-omics analysis revealed the interaction among intestinal flora, metabolites and the clinical indices, demonstrating the potential effects of the imbalance of intestinal flora on neonatal growth in the pregnant women with PE.PMID:39930654 | DOI:10.1111/jog.16229

Plant J. 2025 Feb;121(3):e17252. doi: 10.1111/tpj.17252.ABSTRACTGlobal metabolic and transcriptional reprogramming is a common event in plant abiotic stress responses, however, the relevant molecular mechanisms remain largely unknown. Here, we characterized the physiological function and molecular mechanism for the rice UGT706F1. We found that UGT706F1 can be potently induced by high temperature. Its overexpression can markedly enhance the heat tolerance of rice through improving the capacity of scavenging reactive oxygen species, whereas its functional deletion results in heat sensitivity in rice. To investigate the regulatory mechanism of UGT706F1 in response to high temperature, we carried out extensive screening of the in vitro enzymatic activity of UGT706F1 and discovered that UGT706F1 exhibits broad-spectrum activity toward flavonoid compounds. Through targeted flavonoid metabolomics analysis, we further revealed that the overexpression of UGT706F1 elevated the content of diverse flavonoids and flavonoid glycosides in rice. Subsequently, via transcriptome analysis, we found that following heat treatment, the overexpression of UGT706F1 was capable of enhancing the transcriptional activity of those genes including the flavonoid synthases, heat shock factors, heat shock proteins, glutathione S-transferase, and various antioxidant enzymes. Furthermore, we identified an R2R3 MYB-type transcription factor MYB61 and demonstrated that MYB61 could directly bind the promoter of UGT706F1 and activate the transcription of UGT706F1. The overexpression of MYB61 also enhanced the heat tolerance and increased flavonoid glycosides. Overall, this study unveiled a novel pathway of the plant heat tolerance response mediated by MYB61-UGT706F1 module and identified a new UGT player for the metabolic and transcriptional regulation under high-temperature circumstance.PMID:39930614 | DOI:10.1111/tpj.17252

J Exp Clin Cancer Res. 2025 Feb 10;44(1):47. doi: 10.1186/s13046-025-03302-0.ABSTRACTThe focus of cancer immunotherapy has traditionally been on immune cells and tumor cells themselves, often overlooking the tumor secretome. This review provides a comprehensive overview of the intricate relationship between tumor cells and the immune response in cancer progression. It highlights the pivotal role of the tumor secretome - a diverse set of molecules secreted by tumor cells - in significantly influencing immune modulation, promoting immunosuppression, and facilitating tumor survival. In addition to elucidating these complex interactions, this review discusses current clinical trials targeting the tumor secretome and highlights their potential to advance personalized medicine strategies. These trials aim to overcome the challenges of the tumor microenvironment by designing therapies tailored to the secretome profiles of individual cancer patients. In addition, advances in proteomic techniques are highlighted as essential tools for unraveling the complexity of the tumor secretome, paving the way for improved cancer treatment outcomes.PMID:39930476 | DOI:10.1186/s13046-025-03302-0

Adv Exp Med Biol. 2025;1468:207-212. doi: 10.1007/978-3-031-76550-6_34.ABSTRACTDysregulation of lipid metabolism has been linked with risk for age-related retinal diseases including age-related macular degeneration (AMD). However, how dysregulated lipid metabolism contributes to AMD development is unknown. In this study, we evaluated the retinal and plasma lipidomes of a mouse model displaying retinal pigmented epithelium (RPE) pathologies that are observed in AMD including RPE dysmorphia and degeneration. We found that the RPE phenotypes in mice overexpressing transmembrane protein 135 (Tmem135 TG) are correlated with retinal and plasma lipidome changes. While distinct lipid profiles were observed in the retina and plasma of Tmem135 TG mice, a common finding in both retinal and plasma lipidomes was an increase of lipids containing C22:5. This data suggests that accumulation of C22:5-containing lipids may contribute to the development of the RPE pathologies in Tmem135 TG mice.PMID:39930197 | DOI:10.1007/978-3-031-76550-6_34

BMC Plant Biol. 2025 Feb 10;25(1):174. doi: 10.1186/s12870-025-06189-3.ABSTRACTSeagrasses maintain cellular water balance by regulating ion concentrations and accumulating organic osmolytes, enabling them to survive in the fluctuating salinity of intertidal environments. However, the molecular mechanisms underlying seagrass responses to salinity changes remain relatively understudied. To address this, we conducted a multi-omics analysis of Ruppia sinensis under low, moderate, and high salinity conditions to uncover the mechanisms behind its adaptation to salinity fluctuations. Our research revealed that the transition from low to high salinity significantly altered the physiological characteristics of R. sinensis. Simultaneously, the species enhanced its ability to cope with and adapt to salinity fluctuations by increasing antioxidant enzyme activity. Integration of multi-omics data further indicated that under high salinity conditions, R. sinensis synthesizes more flavonoids to bolster its adaptive capacity. Additionally, the phenylpropanoid metabolic pathway appears to play a crucial role in the response of R. sinensis to changes in water salinity.PMID:39930400 | DOI:10.1186/s12870-025-06189-3

BMC Plant Biol. 2025 Feb 11;25(1):178. doi: 10.1186/s12870-025-06154-0.ABSTRACTGlobally, rice bacterial blight disease causes significant yield losses. Metabolomics is a vital tool for understanding this disease by analyzing metabolite levels and pathways involved in resistance and susceptibility. It enables the development of disease-resistant rice varieties and sustainable disease management strategies. This study has focused on the metabolic response to bacterial blight disease in three rice varieties: the near isogenic rice line IRBB27, wild rice (Oryza minuta-CG154:IRGC No. 93259, accession No. EC861737), and the susceptible control IR24. However, detailed metabolomics studies in wild rice remain largely unexplored. So, metabolic analysis with untargeted liquid chromatography mass spectrometry analysis (LC-MS/MS) was performed at various time points, including pre infection and post infection at 12 h and 24 h with Xanthomonas oryzae pv. oryzae (Xoo). In this study, a total of 6067 metabolites were identified. Pre-infection stage of the susceptible, resistant, and wild rice had 675, 660, and 702 identified metabolites, respectively, but these numbers were altered at post-infection stages. Various defense-related metabolites, including amino acids, flavonoids, alkaloids, terpenoids, nucleotide derivatives, organic acids, inorganic compounds, fatty acid and lipid derivatives have been identified. PCA and PLS-DA plots revealed differences in the metabolome among susceptible, resistant, and wild genotypes, suggesting distinct metabolic profiles for each. In this study, we found 149 metabolites were upregulated and 162 downregulated in the wild type (CG154) compared to the susceptible cultivar (IR24). Similarly, 85 metabolites were upregulated and 92 downregulated in the resistant near isogenic line (IRBB27) compared to IR24, while 156 were upregulated and 149 downregulated in CG154 compared to IRBB27. Key metabolites, including flavonoids, terpenoids, and phenolic compounds, showed significantly higher levels (P ≤ 0.01) in resistant varieties. These identified defense metabolites could serve as potential biomarkers for bacterial blight resistance in rice. The findings from this study have important implications for the development of new rice cultivars with tolerance to bacterial blight disease.PMID:39930388 | DOI:10.1186/s12870-025-06154-0

BMC Plant Biol. 2025 Feb 10;25(1):173. doi: 10.1186/s12870-025-06163-z.ABSTRACTBACKGROUND: Chrysanthemum (Chrysanthemum × morifolium) is one of the four major cut flowers worldwide and is valued for ornamental, culinary, and medicinal purposes. Terpenoids are key components of the fragrance of chrysanthemum; they not only serve to repel insect herbivores and promote pollination but also impact the value of the plant. However, the terpene production of chrysanthemum and the regulatory mechanisms involved remain unclear.RESULTS: We used gas chromatography‒mass spectrometry (GC‒MS) to identify 177 compounds, including 106 terpenes, in ten chrysanthemum cultivars. Monoterpene derivatives and sesquiterpenes were the most common. Next, we identified 27 candidate hub genes for terpene production in chrysanthemum via combined transcriptome and metabolome analysis, as well as weighted gene coexpression network analysis. The three terpenes synthesis-related genes were significantly expressed in the disc florets of the different chrysanthemum cultivars. We concluded that the transcription factors TCP8, TCP5, ATHB8, ATHB7, HAT22, TGA1, TGA4, and WHY1 may regulate terpene synthesis.CONCLUSIONS: In this study, we profiled terpenes in chrysanthemum florets and constructed a key terpene-transcription factor network related to terpene synthesis. These findings lay the groundwork for future research into the mechanism of terpene synthesis in chrysanthemum as well as in other plants.PMID:39930381 | DOI:10.1186/s12870-025-06163-z