PubMed

J Ethnopharmacol. 2025 Feb 10:119477. doi: 10.1016/j.jep.2025.119477. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Marsdenia tenacissima dried stems have been used to treat asthma, trachitis, rheumatism, and carbuncles. M. Tenacissima extract is now available in China under the brand name "Xiao Ai Ping" and is commonly used in conjunction with chemotherapy to treat a number of diseases, including liver cancer, gastric cancer, colon cancer, and non-small cell lung cancer.PURPOSE OF THE STUDY: The research focused on the potential mechanisms contributing to the in vivo therapeutic effects on breast cancer using the ethyl acetate portion of M. tenacissima extract (EMTE), demonstrating significant promise in treating lung cancer in our initial experiments.MATERIALS AND METHODS: We examined the impact of EMTE on the growth of breast cancer through experiments on homoplastic breast cancer mice. Moreover, we utilised UPLC-Q-TOF/MS analysis to identify the components of EMTE and anticipate its potential therapeutic targets. Through network pharmacology, we predicted the potential targets and pathways affected by EMTE in relation to breast cancer. Additionally, we analysed the metabolic changes induced by EMTE during its anti-breast cancer effects.RESULTS: The MAPK pathway was identified as the most likely route by which EMTE could influence breast cancer through network pharmacological enrichment of pathways. Research on animals showed that EMTE could successfully inhibit the development of breast tumours in the homoplastic breast cancer mouse model. We observed that EMTE treatment affected the metabolism of breast cancer mice, particularly in the biosynthesis of phenylalanine, tyrosine, tryptophan, linoleic acid metabolism, and pyrimidine metabolism. These metabolic alterations may have contributed to the effects of glycolysis, tumour immune evasion, and pyrimidine de novo synthesis.CONCLUSION: Based on the results of network pharmacological and metabolomic analysis, we postulate that the inhibition of the MAPK/ERK pathway may have played a role in promoting apoptosis in breast cancer cells and confirmed relevant protein expression of the MAPK/ERK signaling pathway with Western blotting in tumour tissue of homoplastic breast cancer mice.PMID:39938764 | DOI:10.1016/j.jep.2025.119477

J Ethnopharmacol. 2025 Feb 10:119474. doi: 10.1016/j.jep.2025.119474. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Li-Chong-Xiao-Zhen granules (LCXZG) has the effect of " activate blood and resolve stasis," " soften hardness and dissipate binds " properties, and was widely used in the clinic for decades to treat uterine fibroids and ovarian cancer (OC), which is called "zheng jia" in traditional Chinese medicine.AIM OF THE STUDY: The aim of this study is to identify the active components of LCXZG and elucidate the mechanism of LCXZG in ovarian cancer by combining network pharmacology, metabolomics and proteomics.MATERIAL AND METHODS: The absorbed compounds in serum of LCXZG was identified by liquid chromatography-mass spectrometry. Network pharmacology was used to predict the active components and target genes of LCXZG. The therapy mechanism of LCXZG on OC were determined by establishing a nude mouse xenograft tumor model and using combined metabolomics and proteomics analysis.RESULTS: A total of 218 absorbed compounds in serum of LCXZG were identified by UPLC-MS. Network pharmacology results showed that lipid and atherosclerosis, chemical carcinoma-receptor activation and PI3K-AKT signaling were potential target pathways of LCXZG in the treatment of OC. Further metabolomics and proteomics studies demonstrated that LCXZG altered glycerophospholipid metabolism in ovarian cancer.CONCLUSIONS: This study demonstrated that most of the active Compound of LCXZG are Paeoniflorin, Sucrose, Amygdalin and Benzoylpaeoniflorin, which may exert their anti-tumor effects by regulating glycerophospholipid metabolism in ovarian cancer.PMID:39938763 | DOI:10.1016/j.jep.2025.119474

Clin Res Hepatol Gastroenterol. 2025 Feb 10:102546. doi: 10.1016/j.clinre.2025.102546. Online ahead of print.ABSTRACTBACKGROUND: Hepatocellular carcinoma (HCC) ranks sixth in incidence and third in mortality among all cancers. Chronic infection by hepatitis B and C viruses are the predominant risk factors for HCC, but other factors related to metabolic disorders including diabetes and obesity are also involved.METHODS: Ten male HCC patients with chronic HBV infection were included in this study. Primary HCC tissues were obtained from all study participants following liver resection. Normal tissues that were simultaneously collected served as the controls and were defined as tissue at least 5 cm from the tumor edge. Tissues were subjected to untargeted metabolomics and transcriptome analyses.RESULTS: We identified 31 and 41 differentially expressed metabolites (DEMs) in positive and negative ion modes, respectively. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that 15 DEMs were enriched in ABC transporters, nine in purine metabolism, eight in central carbon metabolism in cancer, and seven in biosynthesis of amino acids. Regarding the transcriptome analysis, 1,224 significantly upregulated and 887 downregulated RNAs were found. KEGG pathway analysis revealed that the most significantly enriched pathways were metabolic pathways. Integrated analysis showed seven pathways that were highly activated in HCC tissues including PI3K/Akt, ABC transporters, caffeine metabolism, carbon metabolism, biosynthesis of amino acids, arginine biosynthesis, alanine, aspartate, and glutamate metabolism.CONCLUSION: Some DEMs could be biomarkers or therapeutic targets for HCC. Moreover, we found that MAGEB2 was significantly elevated in HCC tissues for the first time, and its association with HCC needs to be explored by functional studies.PMID:39938636 | DOI:10.1016/j.clinre.2025.102546

Biochem Biophys Res Commun. 2025 Feb 8;752:151466. doi: 10.1016/j.bbrc.2025.151466. Online ahead of print.ABSTRACTThe prevalence of metabolic dysfunction-associated steatohepatitis (MASH) is increasing annually, which is a global public health issue. Although clinical trials are lacking, observational studies indicate that bariatric surgery can alleviate the progression of MASH. Here, we performed sleeve gastrectomy (SG) and Sham surgery on 8-week-old mice, and then fed a AMLN diet for 24 weeks to construct a diet-inducted MASH mice model after 4-week post-surgery recovery. Applying a multi-omics approach combining metagenomics, metabolomics, and transcriptomics, we found that SG prevents the development of hepatic steatosis, inflammation, and fibrosis in MASH mice not only by significantly altering the structure of gut microbiota including s_Akkermansia muciniphila, s_Alistiples dispar, g_Helicobacter and s_uc_Oscillospiraceae, but also by modulating the levels of serum metabolites including l-arginine and taurocholic acid (TCA). These results suggest that SG and the alteration of gut microbiota and its related serum metabolites can be served as the effective therapeutic strategies for MASH.PMID:39938449 | DOI:10.1016/j.bbrc.2025.151466

Food Chem. 2025 Feb 4;474:143223. doi: 10.1016/j.foodchem.2025.143223. Online ahead of print.ABSTRACTEffective selenium supplementation strategies are essential for alleviating global selenium deficiency. This study utilized the high‑selenium-tolerant strain Lactiplantibacillus plantarum NML21 to produce selenium-enriched yogurt, successfully converting inorganic Se(IV) into organic selenium, with selenoproteins accounting for 69.52 % of the total selenium content (995.19 ± 68.60 μg/g). Selenium-enriched yogurt exhibited excellent physicochemical properties and antioxidant activity. Volatile flavor analysis identified 36 compounds, with NML21 and SeNML21 significantly enhancing ketone flavors in yogurt, particularly increasing the contents of 2-heptanone and 2,3-pentanedione. Untargeted metabolomics identified 215 non-volatile metabolites, with NML21 and SeNML21 significantly regulating key metabolic pathways, including the phosphotransferase system, ABC transporters, and amino acid biosynthesis, promoting the accumulation of beneficial metabolites. Selenium specifically influenced the biosynthesis pathways of ABC transporters, phenylalanine, tyrosine, and tryptophan. This study demonstrates that NML21 is a promising strain for producing selenium-enriched functional yogurt, offering innovative perspectives for dietary selenium supplementation and functional food development.PMID:39938303 | DOI:10.1016/j.foodchem.2025.143223

Food Chem. 2025 Feb 6;475:143256. doi: 10.1016/j.foodchem.2025.143256. Online ahead of print.ABSTRACTHoney has been recognized for its role in disease prevention through nutritional modulation. In this study, we comprehensively assessed the physicochemical parameters, metabolic profile, antioxidant and anti-inflammatory activities of multifloral honeys produced by Apis cerana cerana in Sansha City (SS), Hainan Province. Metabolomic analysis identified SS honey had multiple bioactive compounds known for antioxidant and anti-inflammatory properties. Compared to A. cerana cerana honey from central regions of Hainan Province, SS honey showed higher levels of TFC (113.80 mg RE/100 g) and TPC (45.86 mg GAE/100 g). Furthermore, SS honey demonstrated greater antioxidant activity, as evidenced by FRAP (1503.16 μmol TE/kg), DPPH IC50 (33.59 mg/mL), and ABTS IC50 (11.03 mg/mL). SS honey significantly reduced the levels of cyclooxygenase-2 (COX-2), interleukin-1β (IL-1β), interleukin-6 (IL-6), inducible nitric oxide synthase (iNOS), and tumor necrosis factor-α (TNF-α) in lipopolysaccharide (LPS)-induced RAW 264.7 cells, along with suppressing the mRNA expression of these inflammatory markers.PMID:39938270 | DOI:10.1016/j.foodchem.2025.143256

Plant Physiol Biochem. 2025 Jan 20;221:109462. doi: 10.1016/j.plaphy.2024.109462. Online ahead of print.ABSTRACTLignification is one of the key factors restricting the postharvest storage quality of fruit and vegetable. In this study, the potential effects of carboxymethyl chitosan (CMCS) on the phenolic compounds, metabolomic, lignin metabolites and related gene expression of okra during postharvest storage were explored. The results showed that CMCS could alleviate the accumulation of H2O2 and O2•- of postharvest okra, maintain the content of phenolic compounds and balance the antioxidant level. Metabolome data analysis showed that the biosynthesis of lignin-related metabolites in CMCS treatment group was down-regulated compared with the control group. The contents of 14 lignin metabolites in okra were further determined by LC-MS/MS, the results showed that CMCS could delay the accumulation of lignin metabolites, such as L-phenylalanine, 4-hydroxycinnamic acid, ferulic acid, coniferyl aldehyde, sinapyl alcohol, caffeyl aldehyde. The results of quantitative real-time PCR (qRT-PCR) showed that CMCS treatment could inhibit the expression of AePAL, AeC4H, AeCAD and AePOD. Collectively, CMCS can delay the lignification of postharvest okra by inhibiting the excessive accumulation of lignin metabolites in the phenylpropanoid pathway, thereby maintaining postharvest quality.PMID:39938161 | DOI:10.1016/j.plaphy.2024.109462

Plant Physiol Biochem. 2025 Feb 1;221:109588. doi: 10.1016/j.plaphy.2025.109588. Online ahead of print.ABSTRACTBoron (B) deficiency and copper (Cu) excess are common problems in citrus orchard soils. Citrus sinensis seedlings were exposed to 25 (B25) or 2.5 (B2.5) μM H3BO3 and 0.5 (Cu0.5) or 350 (Cu350) μM CuCl3 for 24 weeks. Cu350 upregulated 2210 (1012) genes and 482 (341) metabolites and downregulated 3201 (695) genes and 175 (43) metabolites in roots at B2.5 (B25). Further analysis showed that the B-mediated mitigation of Cu toxicity in roots involved the coordination of the following aspects: (a) enhancing the ability to maintain cell wall and plasma membrane stability and function; (b) lowering the impairment of Cu350 to primary and secondary metabolisms and enhancing their adaptability to Cu350; and (c) alleviating Cu350-induced oxidative stress via the coordination of reactive oxygen species (ROS) and methylglyoxal detoxification systems. Cu350 upregulated the abundances of some saccharides, amino acids and derivatives, phospholipids, secondary metabolites, and vitamins, and the expression of several ROS detoxification-related genes in roots of B2.5-treated seedlings (RB2.5), but these adaptive responses did not prevent RB2.5 from Cu-toxicity (oxidative damage). The study identified some genes, metabolites, and metabolic processes/pathways possibly involved in root Cu tolerance. Additionally, the responses of gene expression and metabolite profiling to Cu-B treatments differed between leaves and roots. Therefore, this study provided novel information for B to reduce Cu toxicity in roots and might contribute to the development of soil amendments targeting Cu excess in citrus and other crops.PMID:39938160 | DOI:10.1016/j.plaphy.2025.109588

Plant Physiol Biochem. 2025 Feb 6;221:109604. doi: 10.1016/j.plaphy.2025.109604. Online ahead of print.ABSTRACTJuglans sigillata, an endemic species in China, serves as a vital local economic resource. Aluminum (Al) stress caused by soil acidification can potentially threaten the growth of J. sigillata. This study aimed to elucidate the mechanism of the alleviation of Al stress by silicon (Si) in J. sigillata. The results showed that Si could reduce the Al accumulation of walnut and improve root growth under Al stress. Si also increased peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) activities and soluble sugar and proline contents, reduced malonaldehyde (MDA) and H2O2 contents and the O2- production rate, and maintained the homeostasis of cells. Transcriptome analysis revealed significant up-regulation of genes encoding plant hormones (ABA, IAA, and CTK) and photosystem II components (PsbO, PsbQ, PsbW, and PsbY). Under Al stress conditions, the application of exogenous Si notably enhanced the expression of genes associated with heavy metal transport (CAX, PAA, ABC, HMA, NRAMP, and ZIP). Comprehensive transcriptome and metabolomics analysis showed that Si regulated secondary metabolite metabolism via the phenylalanine, galactose, and tryptophan pathway, altered cell wall composition, increased energy supply, and reduced auxin synthesis in root tip transition zones to alleviate Al toxicity of J. sigillata. In summary, the application of Si significantly alleviated Al-induced damage in J. sigillata.PMID:39938159 | DOI:10.1016/j.plaphy.2025.109604

J Infect Dis. 2025 Feb 12:jiaf072. doi: 10.1093/infdis/jiaf072. Online ahead of print.ABSTRACTBACKGROUND: Accurate diagnosis of community-acquired pneumonia (CAP) can be challenging. Clinical findings are non-specific, and interpretations of chest radiographs have poor inter-rater reliability. Pilot studies demonstrate the potential for metabolomics to identify metabolite concentrations that differentiate children with CAP from those without. The objective of this study was to expand these findings in a large cohort of children with CAP compared with controls.METHODS: Urine was collected from children, 3 months to 12 years old, with emergency department visits for suspected CAP and community-based controls. Nuclear magnetic resonance spectrometry was used to identify and quantify metabolites. A random forest approach developed three models discriminating cases from community-based controls based on: 1) clinical signs and symptoms; 2) metabolites, and 3) the combination of both. The area under the receiver operating characteristic curve (AUC) was computed for each model.RESULTS: Included were 253 cases and 122 controls. The metabolite-only model had similar discriminatory ability as the combination model (AUC: 0.97 and 0.99, respectively). The discriminating metabolites in the metabolite-only model were 2-aminobutyrate, fumarate, hypoxanthine, acetone, leucine, quinolinate, valine, O-acetylcarnitine, citrate and trigonelline. In the combined model, discriminatory clinical factors included receipt of corticosteroids, fever, cough, rapid breathing, decreased oral intake, difficulty breathing, receipt of albuterol, abnormal sleepiness, vomiting and wheezing, and included five additional metabolites compared to the metabolite only model (4-hydroxybenzoate, isoleucine, carnitine, 2-hydroxyisovalerate, betaine, succinate).CONCLUSIONS: Urine metabolite concentrations can accurately discriminate healthy children from children with suspected CAP. Metabolites associated with CAP may overcome limitations of prior diagnostic approaches.PMID:39938055 | DOI:10.1093/infdis/jiaf072

PLoS One. 2025 Feb 12;20(2):e0305065. doi: 10.1371/journal.pone.0305065. eCollection 2025.ABSTRACTViral infections induce major shifts in cellular metabolism elicited by active viral replication and antiviral responses. For the virus, harnessing cellular metabolism and evading changes that limit replication are essential for productive viral replication. In contrast, the cellular response to infection disrupts metabolic pathways to prevent viral replication and promote an antiviral state in the host cell and neighboring bystander cells. This competition between the virus and cell results in measurable shifts in cellular metabolism that differ depending on the virus, cell type, and extracellular environment. The resulting metabolic shifts can be observed and analyzed using global metabolic profiling techniques to identify pathways that are critical for either viral replication or cellular defense. SARS-CoV-2 is a respiratory virus that can exhibit broad tissue tropism and diverse, yet inconsistent, symptomatology. While the factors that determine the presentation and severity of SARS-CoV-2 infection remain unclear, metabolic syndromes are associated with more severe manifestations of SARS-CoV-2 disease. Despite these observations a critical knowledge gap remains between cellular metabolic responses and SARS-CoV-2 infection. Using a well-established untargeted metabolomics analysis workflow, we compared SARS-CoV-2 infection of human lung carcinoma cells. We identified significant changes in metabolic pathways that correlate with either productive or non-productive viral infection. This information is critical for characterizing the factors that contribute to SARS-CoV-2 replication that could be targeted for therapeutic interventions to limit viral disease.PMID:39937842 | DOI:10.1371/journal.pone.0305065

Invest Ophthalmol Vis Sci. 2025 Feb 3;66(2):37. doi: 10.1167/iovs.66.2.37.ABSTRACTPURPOSE: To explore the alterations in metabolites of wet age-related macular degeneration (wAMD) by conducting metabolomics in aqueous humor from patients with wAMD and to assess the potential effects of anti-vascular endothelial growth factor (anti-VEGF) on these metabolites.METHODS: Metabolomic analysis was performed on the aqueous humor of 30 patients with wAMD receiving anti-VEGF treatments and 20 controls, via ultra-high performance liquid chromatography tandem mass spectrometry. The aqueous humor samples collected from untreated patients with wAMD were classified as the pre-wAMD group. Accordingly, the samples collected from patients with wAMD receiving one anti-VEGF treatment were designated as the post-wAMD group. Individuals were further classified into responders and nonresponders according to their reaction to the treatment. Principal component analysis, hierarchical cluster analysis, and the Kyoto Encyclopedia of Genes and Genomes annotation and enrichment analysis, were subsequently performed. Machine learning and receiver operating characteristic curve analyses were used to further analyze potential vital metabolites.RESULTS: Among the 1001 metabolites verified in the aqueous humor, 306 compounds separated patients with pre-wAMD from the control group, whereas 68 metabolites differentiated patients with post-wAMD and patients with pre-wAMD. Enrichment in metabolic pathways was noted in ABC transporters, thiamine metabolism, glycerophospholipid metabolism, mammalian target of rapamycin signaling pathway and tyrosine metabolism, and so on. Machine learning and receiver operating characteristic curves analysis suggested that δ-valerolactam could not only distinguish between patients with wAMD and the control group, but also differentiate between patients with post-wAMD and patients with pre-wAMD. Changes in acylcarnitine were observed in anti-VEGF responders with wAMD.CONCLUSIONS: There were noticeable alterations in the aqueous humor of patients with wAMD involving many metabolites that are associated with ABC transporters, glycerophospholipid metabolism, and the mammalian target of rapamycin signaling pathway. It is possible that δ-valerolactam can be applied as a biomarker in wAMD.PMID:39937494 | DOI:10.1167/iovs.66.2.37

Anal Chem. 2025 Feb 12. doi: 10.1021/acs.analchem.4c05565. Online ahead of print.ABSTRACTSerum endogenous metabolites and coexisting exogenous compounds are closely related to human health. Metabolomics often uses high-resolution mass spectrometry (HRMS), but current exposomics studies typically rely on triple quadrupole tandem mass spectrometry due to lower concentrations in the body. As a result, metabolome-exposome-wide association studies (mEWAS) require a combination of untargeted metabolomics and several targeted exposomics methods to measure more exposures, leading to increased time and sample consumption. In this study, a novel method was proposed by leveraging the advantages of recently introduced Zeno MRMHR technology; it allows for the simultaneous acquisition of the metabolome in HRMS and the exposome in multiple reaction monitoring (MRM) modes in one injection. The signal responses for exogenous compounds in MRM were comparable to those of metabolites in HRMS. This method was rigorously validated, and all exogenous standards had relative standard deviations (RSDs) below 20% for intraday and interday repeatability. Over 90% of metabolic features exhibited RSDs below 20% in these assessments. The method also had a broad quantification range, with lower limits of quantification (LLOQ) from 0.1 to 25 ng/mL and higher limits of quantification (HLOQ) from 2.5 to 1000 ng/mL. This approach was demonstratively applied to a type 2 diabetes mellitus cohort to identify serum risk factors and study the metabolome-exposome association. To our knowledge, this study is the first implementation of a unified method for the simultaneous analysis of endogenous metabolites in the untargeted mode and 210 exogenous compounds in the targeted mode in one injection, offering a novel tool for mEWAS research.PMID:39937451 | DOI:10.1021/acs.analchem.4c05565

Appl Biochem Biotechnol. 2025 Feb 12. doi: 10.1007/s12010-025-05195-3. Online ahead of print.ABSTRACTRegular long-term exercise can benefit the body and reduce the risk of several diseases, such as cardiovascular disease, diabetes, and obesity. However, the proteomic and metabolomic changes, as well as the physiological responses associated with long-term exercise, remain incompletely understood. To investigate the effects of long-term exercise on the human body, 14 subjects with long-term exercise habits and 10 subjects without exercise habits were selected for this study. Morning urine samples were collected and analyzed for untargeted metabolomics and proteomics using liquid chromatography-mass spectrometry. A total of 404 differential metabolites and 394 differential proteins were screened in this research, and the analysis results indicated that long-term exercise may affect energy metabolism, amino acid synthesis and metabolism, nucleotide metabolism, steroid hormone biosynthesis, and the inflammatory response. These findings offer a more comprehensive understanding of the molecular effects of long-term exercise on the human body and provide a basis for future research exploring the underlying mechanisms.PMID:39937413 | DOI:10.1007/s12010-025-05195-3

J Cell Mol Med. 2025 Feb;29(3):e70419. doi: 10.1111/jcmm.70419.ABSTRACTLipotoxicity plays a crucial role in the progression of diabetic kidney disease (DKD), yet the dynamic changes in renal lipid composition from diabetes to early-stage DKD remain unclear. Free fatty acids, lactosylceramides and cardiolipin (CL) were identified as the most significantly altered lipids by quantitatively comparing targeted lipids in the renal cortex of the classic spontaneous diabetic db/db mice using high-coverage targeted lipidomics. Further investigation into the causes and effects of decreased CL, which is a unique mitochondrial phospholipid, was conducted in mitochondria-rich renal proximal tubular cells by using western blotting, real-time PCR, immunohistochemistry and transmission electron microscopy. Reduced expression of cardiolipin synthase, a key enzyme in the CL synthesis pathway, and inhibition of CL-related mitophagy were confirmed under high glucose conditions. In addition, the protective effect of CL-targeted Szeto-Schiller 31 in preserving mitophagy was demonstrated in both in vivo and in vitro studies. These findings provide new insights into the pathogenesis of early-stage DKD from a lipid perspective and offer a theoretical basis for discovering new treatments.PMID:39936909 | DOI:10.1111/jcmm.70419

mSystems. 2025 Feb 12:e0101224. doi: 10.1128/msystems.01012-24. Online ahead of print.ABSTRACTGelatinous zooplankton (GZ) represents an important component of marine food webs, capable of generating massive blooms with severe environmental impact. When these blooms collapse, considerable amounts of organic matter (GZ-OM) either sink to the seafloor or can be introduced into the ocean's interior, promoting bacterial growth and providing a colonizable surface for microbial interactions. We hypothesized that GZ-OM is an overlooked marine hotspot for transmitting antimicrobial resistance genes (ARGs). To test this, we first re-analyzed metagenomes from two previous studies that experimentally evolved marine microbial communities in the presence and absence of OM from Aurelia aurita and Mnemiopsis leidyi recovered from bloom events and thereafter performed additional time-resolved GZ-OM degradation experiments to improve sample size and statistical power of our analysis. We analyzed these communities for composition, ARG, and mobile genetic element (MGE) content. Communities exposed to GZ-OM displayed up to fourfold increased relative ARG and up to 10-fold increased MGE abundance per 16S rRNA gene copy compared to the controls. This pattern was consistent across ARG and MGE classes and independent of the GZ species, indicating that nutrient influx and colonizable surfaces drive these changes. Potential ARG carriers included genera containing potential pathogens raising concerns of ARG transfer to pathogenic strains. Vibrio was pinpointed as a key player associated with elevated ARGs and MGEs. Whole-genome sequencing of a Vibrio isolate revealed the genetic capability for ARG mobilization and transfer. This study establishes the first link between two emerging issues of marine coastal zones, jellyfish blooms and ARG spread, both likely increasing with future ocean change. Hence, jellyfish blooms are a quintessential "One Health" issue where decreasing environmental health directly impacts human health.IMPORTANCEJellyfish blooms are, in the context of human health, often seen as mainly problematic for oceanic bathing. Here we demonstrate that they may also play a critical role as marine environmental hotspots for the transmission of antimicrobial resistance (AMR). This study employed (re-)analyses of microcosm experiments to investigate how particulate organic matter introduced to the ocean from collapsed jellyfish blooms, specifically Aurelia aurita and Mnemiopsis leidyi, can significantly increase the presence of antimicrobial resistance genes and mobile genetic elements in marine microbial communities by up to one order of magnitude. By providing abundant nutrients and surfaces for bacterial colonization, organic matter from these blooms enhances ARG proliferation, including transfer to and mobility in potentially pathogenic bacteria like Vibrio. Understanding this connection highlights the importance of monitoring jellyfish blooms as part of marine health assessments and developing strategies to mitigate the spread of AMR in coastal ecosystems.PMID:39936903 | DOI:10.1128/msystems.01012-24

Physiol Plant. 2025 Jan-Feb;177(1):e70068. doi: 10.1111/ppl.70068.ABSTRACTThe severe scarcity of wild resources of Ardisia crenata Sims (AS) has greatly limited its current clinical and pharmaceutical applications. We aimed to demonstrate the substitutability of stems and leaves for AS roots. In this study, 28 local samples from the Guizhou Province of China were selected for a comprehensive comparison of quality markers, chemical composition and efficacy. HPLC analysis showed that both stems and leaves contained bergenin, the main active ingredient of AS. Metabolomics studies showed that the chemical composition of the three parts was 99% similar. Network pharmacology analysis showed that similar signalling targets including STAT3 and MAPK1, AKT1 and EP300, SRC and TP53, were targeted by three parts. Animal experiments further demonstrated that extracts from the three different parts of the plant relieved the pathological symptoms of acute pharyngitis, and decreased serum inflammatory factors, showing similar efficacy. In sum, these findings strongly proved that stems and leaves can be used as supplements or substitutes for roots, providing a powerful strategy to solve the problem of AS resource shortage and greatly promoting the optimal utilization of AS. The study also anticipated some additional benefits, including the expansion of natural sources of bergenin and the discovery of potential cancer-related targets of AS.PMID:39936472 | DOI:10.1111/ppl.70068

Curr Pharm Des. 2025 Feb 6. doi: 10.2174/0113816128362600250203051056. Online ahead of print.ABSTRACTINTRODUCTION: Atrophic vaginitis (AV) is a common and frequently occurring disease, lacking effective curative measures. Exploring the mechanism of vaginal mucosal homeostasis from the perspective of metabolites has great research prospects.METHODS: We compared the metabolic profiles of vaginal secretions between AV patients and healthy individuals via liquid chromatography-tandem mass spectrometry (LC-MS/MS). We further explored effective and sensitive metabolites and metabolic pathways for senile vaginitis through bioinformatics analysis and experimental verification. Through untargeted metabolomics analysis, we screened 561 differential metabolites in two groups of vaginal secretion samples. These differential metabolites were mainly concentrated in fatty acids/carboxylic acids, glycerophospholipids, organic oxides, steroids, and their derivatives. They were mainly enriched in purine metabolism, diabetic cardiomyopathy generation, and choline metabolism pathways.RESULTS: The receiver operating characteristic analysis showed the metabolites (e.g., guggulsterone, umbelliprenin, and inosinic acid) to have good discrimination ability for the AV group. In addition, we also explored the potential mechanism of action of umbelliprenin at the cellular level.CONCLUSION: This study is expected to provide a new perspective for understanding the relationship between metabolites and the pathogenesis of AV.PMID:39936425 | DOI:10.2174/0113816128362600250203051056

J Coll Physicians Surg Pak. 2025 Feb;35(2):203-208. doi: 10.29271/jcpsp.2025.02.203.ABSTRACTOBJECTIVE: To evaluate the causal relationship between 1,400 metabolites and colorectal and gastric cancer.STUDY DESIGN: Mendelian randomisation study. Place and Duration of the Study: The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, China, from July to August 2024.METHODOLOGY: Metabolite genome-wide association study (GWAS) data and genetic data from the Canadian Longitudinal Study on Aging (CLSA) as well as the expensive FinnGen project, respectively, were sourced. Suitable instrumental variables were chosen based on their association with metabolites at a genome-wide significance level, thus ensuring a high degree of reliability in the causal inferences drawn. Inverse variance weighting (IVW) was used for initial analysis. Sensitivity analyses were conducted using MR Egger regression and weighted median methods to validate findings and assess potential pleiotropy or bias.RESULTS: Metabolites were included in the study of 8,299 individuals. Gastric cancer included 1,307 cases and 287,137 controls; while colorectal cancer included 6,509 cases and 287,137 controls. The research identified sixty-nine metabolites associated with varying degrees of risk enhancement or mitigation. For gastric cancer, a more focused discovery highlighted two metabolites with significant causal links-associated with increased risk as well as a protective effect. Sensitivity analyses confirmed the validity of these findings.CONCLUSION: By elucidating specific metabolites that exert direct causal effects on colorectal and gastric cancer risk, the study marked a significant advancement in the understanding of the metabolic pathways involved in cancer development.KEY WORDS: Mendelian randomisation, Colorectal cancer, Gastric cancer, Metabolites, Genetic variants, Genome-wide association studies, Causal inference.PMID:39936199 | DOI:10.29271/jcpsp.2025.02.203

Front Endocrinol (Lausanne). 2025 Jan 28;16:1487058. doi: 10.3389/fendo.2025.1487058. eCollection 2025.ABSTRACTCONTEXT: As a novel SGLT1 inhibitor, SY-009 has been preliminarily confirmed in a phase Ib clinical study for its ability to reduce postprandial blood glucose in patients with type 2 diabetes mellitus (T2DM). However, the effects of SY-009 on human plasma metabolomics are still unknown.OBJECTIVE: This study aimed to explore the effects of SY-009 on plasma metabolomics in patients with T2DM and the potential metabolic regulatory mechanism involved.STUDY DESIGN: In the phase Ib study, a total of 50 participants with T2DM were enrolled and randomly assigned to the 0.5 mg BID, 1 mg BID, 2 mg BID, 1 mg QD, and 2 mg QD dose groups, with a 4:1 random allocation within each group to receive either the SY-009 capsule or placebo. We conducted untargeted and targeted metabolomics analyses on plasma samples from the phase Ib clinical study.RESULTS: Untargeted metabolomics revealed that, after SY009 treatment, there were differences in metabolic pathways, including primary bile acid biosynthesis; biosynthesis of unsaturated fatty acid; steroid hormone biosynthesis; purine metabolism; phenylalanine, tyrosine and tryptophan biosynthesis. In particular, the increase in bile acid-related metabolites in the 2 mg BID group was significantly greater than that in the placebo group, and unsaturated fatty acid-related metabolites decreased in both the 2 mg BID group and the placebo group, but there was no significant difference between the two groups. After comprehensive consideration, bile acids were taken as our target for accurate quantification via targeted metabolomics. Compared with those in the placebo group, the levels of several bile acids were significantly greater in the SY-009-treated groups. Moreover, the proportion of free bile acids decreased significantly, the proportion of glycine-conjugated bile acids increased significantly, the proportion of taurine-conjugated bile acids tended to be stable, and PBA/SBA significantly increased after SY-009 administration.CONCLUSIONS: SY-009 caused a series of postprandial plasma metabolite changes in patients with T2DM, especially significant changes in the bile acid profile, which provides a new perspective on the mechanism by which SY-009 lowers blood glucose.CLINICAL TRIAL REGISTRATION: https://www.clinicaltrials.gov, identifier NCT04345107.PMID:39936104 | PMC:PMC11810745 | DOI:10.3389/fendo.2025.1487058