PubMed

J Proteome Res. 2025 Feb 21. doi: 10.1021/acs.jproteome.4c00729. Online ahead of print.ABSTRACTChronic liver diseases exhibit diverse backgrounds, and it is believed that numerous factors contribute to progression to cancer. To achieve effective prevention of nonviral hepatocellular carcinoma, it is imperative to identify fundamental molecular abnormalities at the patient level. Utilizing cancer-adjacent liver tissues obtained from hepatocellular carcinoma patients (chronic liver disease), we conducted RNA-Seq and metabolome analyses. In the chronic liver disease cohort, upregulation of inflammation-associated signals was observed, concomitant with accumulation of acylcarnitine and fatty acid and depletion of NADP+, gamma-tocopherol, and dehydroisoandrosterone-3-sulfate-1 (DHEAS). To minimize heterogeneity, we performed multiomics clustering, successfully categorizing the chronic liver disease cases into two distinct subtypes. Subtype 1 demonstrated elevated inflammatory levels, whereas Subtype 2 included a disproportionately high proportion of elderly cases. Furthermore, RNA-Seq analysis revealed upregulation of inflammatory signals in Subtype 1, while both subtypes exhibited downregulation of fatty acid metabolism. Metabolome analysis indicated a tendency of increased acylcarnitine levels in Subtype 1 and augmented fatty acid accumulation in Subtype 2. Validation of differentially expressed genes using the Gene Expression Omnibus (GEO) data set revealed the potential for amelioration through supplementation with antioxidants such as epigallocatechin gallate (EGCG).PMID:39982271 | DOI:10.1021/acs.jproteome.4c00729

Epidemiologia (Basel). 2025 Jan 25;6(1):4. doi: 10.3390/epidemiologia6010004.ABSTRACTSynthetic turf has become a popular alternative to natural grass due to low upkeep costs; however, its health impacts have not been clearly elucidated. This review examines and consolidates the existing literature on rubber crumb in infill in synthetic turf and its associated adverse health outcomes, along with recommendations for future research. A database search was conducted in PubMed, Web of Science, Scopus, Embase, and Google Scholar of studies on exposures to rubber crumb in infills in synthetic turf. The search focused on epidemiological and toxicological laboratory studies (including exposure simulation and animal studies), as well as government reports. Non-English studies and those addressing injuries (musculoskeletal and burn injuries) were not considered. Eighteen laboratory studies examined concentrations of PAHs found in synthetic turf rubber infill. The total level of PAHs detected in samples varied between 0.4 mg/kg and 3196 mg/kg. The PAH levels were influenced by the age of the synthetic turf, with the older synthetic surface fields containing lower concentrations (compared to newly laid turfs). Synthetic turfs composed of industrial rubber crumb infill also had a lower PAH composition relative to end-of-life tyre-derived infill. In the six studies that investigated the metal content and composition of rubber crumb infill, Aluminium (5382 mg/kg), Zinc (5165 mg/kg), and Iron (489.6 mg/kg) had the highest median concentrations. There were minor differences in heavy metal concentrations found in newly installed synthetic turf compared to older turfs and synthetic sporting fields exposed to direct sunlight (versus indoor fields). There were two epidemiological studies on synthetic turf rubber crumb infill (one ecological and one cross-sectional study), which found no significant associations between synthetic turf exposure and the incidence of leukemia, non-Hodgkin lymphoma, and Hodgkin lymphoma. Similarly, one metabolomic study of urine samples from athletes taken pre- and post-match on synthetic turf, and two studies simulating dermal, ingestion, and inhalation exposure concluded that there was no elevated health risk associated with playing on synthetic turf pitches. Currently, there is very limited evidence of an association between synthetic turf use and adverse health outcomes. Considering the ubiquitous use of synthetic grass globally and the scarcity of epidemiological studies, there is a vital need for further research based on longitudinal study designs and more robust exposure assessments, to help improve our understanding of any potential health risks associated with synthetic turf infill exposures.PMID:39982256 | DOI:10.3390/epidemiologia6010004

Food Funct. 2025 Feb 21. doi: 10.1039/d4fo02647k. Online ahead of print.ABSTRACTQuinoa bran is a by-product of quinoa processing and is rich in polyphenolic bioactives. Previous studies have shown that polyphenol compounds can help alleviate metabolic diseases, but studies on quinoa bran polyphenols intervening in non-alcoholic fatty liver disease (NAFLD) have not yet been reported. In this study, a C57BL/6J mouse NAFLD model was established using a high-fat diet (HFD) to explore the interventional effects of quinoa bran polyphenol extract (QBP) on NAFLD in mice. The results showed that QBP was effective in attenuating abnormal lipid metabolism and hepatic fat accumulation and reducing inflammation in NAFLD mice. 16S rRNA sequencing analysis showed that QBP regulated the composition of the gut microbiota by increasing the abundance of beneficial bacteria Clostridium_innocuum_group, Clostridium_sensu_stricto_13, Ruminococcus_gnavus_group, Coriobacteriaceae_UCG_002 and UBA1819. Untargeted metabolomics identified 51 differential metabolites due to QBP supplementation. Functional predictions indicated that starch and sucrose metabolism and pentose and gluconate interconversion are key metabolic pathways for QBP to attenuate NAFLD, which may be influenced by the gut microbiota. These results demonstrated the potential application of QBP interventions for NAFLD.PMID:39981953 | DOI:10.1039/d4fo02647k

CNS Neurosci Ther. 2025 Feb;31(2):e70290. doi: 10.1111/cns.70290.ABSTRACTOBJECTIVE: Xiao-Chai-Hu-Tang (XCHT) has been demonstrated to exert an antidepressant effect during long-term clinical practices. However, the potential mechanisms of XCHT remain unknown. This study aims to investigate the effect of XCHT on chronic unpredictable mild stress-induced mice with depressive-like behaviors and to explore the underlying mechanisms.METHODS: The active compositions and potential related targets of XCHT in the brain were obtained through UPLC-Q-TOF-MS, network pharmacology, and bioinformatics analyses, verified by experimental validation. Then, the protein-protein interaction (PPI), Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses, and molecular docking were used to predict the core targets and mechanisms of XCHT on depression. After being treated with XCHT standard decoction, based on enzyme-linked immunosorbent assay (ELISA), non-targeted metabolism, targeted LC-MS analyses, RNA-seq, quantitative RT-PCR, immunofluorescence, and western blotting were determined to clarify the mechanism of XCHT in the treatment of anxiety and depression disorder.RESULTS: In total, 166 active ingredients and 525 related targets of XCHT were detected and selected from the network databases. The inflammatory response and metabolism of neurotransmitters were the main related signaling pathways predicted by KEGG enrichment analyses. Behavioral testing shows that XCHT has antidepressant effects, and untargeted metabolomic studies showed it significantly reduced levels of the neurotoxic substance quinoline acid. Combining the results of molecular docking, RNA-seq, and western blot revealed that XCHT regulated nerve regeneration via BDNF/TrkB/CREB and PI3K/AKT signaling pathways. Immunofluorescence analysis revealed that XCHT downregulated the chronic stress-induced activation of microglia and astrocytes in the hippocampus.CONCLUSION: XCHT exerts antidepressant functions by modulating neuroinflammation and neuroregeneration.PMID:39981856 | DOI:10.1111/cns.70290

Heliyon. 2025 Feb 1;11(3):e42412. doi: 10.1016/j.heliyon.2025.e42412. eCollection 2025 Feb 15.ABSTRACTAlzheimer's disease (AD) is a progressive condition marked by multiple underlying mechanisms. Therefore, the investigation of natural products that can target multiple pathways presents a potential gate for the understanding and management of AD. This study aimed to assess the neuroprotective effects of the hydroalcoholic extract of Dracocephalum moldavica (DM) on cognitive impairment, biomarker changes, and putative metabolic pathways in a rat model of AD induced by intracerebroventricular streptozotocin (ICV-STZ). The DM extract was standardized and quantified based on examining total phenolic, total flavonoid, rosmarinic acid, and quercetin contents using colorimetry and high-performance liquid chromatography (HPLC) methods. The antioxidant potential of the extract was evaluated by 2,2-Diphenyl-1-picrylhydrazyl and nitric oxide radical scavenging assays. Male Wistar rats were injected with STZ (3 mg/kg, single dose, bilateral ICV) to induce a sporadic AD (sAD) model. Following model induction, rats were orally administered with DM extract (100, 200, and 400 mg/kg/day) or donepezil (5 mg/kg/day) for 21 days. Cognitive function was assessed using the radial arm water maze behavioral test. The histopathological evaluations were conducted in the cortex and hippocampus regions. Matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) was used to assess metabolite changes in various brain regions. DM extract significantly attenuated cognitive dysfunction induced by ICV-STZ according to behavioral and histopathological investigations. Thirty-two discriminating metabolites related to the amino acid metabolism; the glutamate/gamma-aminobutyric acid/glutamine cycle; nucleotide metabolism; lipid metabolism (glycerophospholipids, sphingomyelins, ceramides, phosphatidylserines, and prostaglandins), and glucose metabolic pathways were identified in the brains of rats with sAD simultaneously for the first time in this model. Polyphenols in DM extract may contribute to the regulation of these pathways. After treatment with DM extract, 10 metabolites from the 32 identified ones were altered in the brain tissue of a rat model of sAD, most commonly at doses of 200 and 400 mg/kg. In conclusion, this study demonstrates the neuroprotective potential of DM by upregulation/downregulation of various pathophysiological biomarkers such as adenine, glycerophosphoglycerol, inosine, prostaglandins, and sphingomyelin induced by ICV-STZ in sAD. These findings are consistent with cognitive behavioral results and histopathological outcomes.PMID:39981356 | PMC:PMC11840490 | DOI:10.1016/j.heliyon.2025.e42412

J Clin Med Res. 2025 Feb;17(2):89-96. doi: 10.14740/jocmr6145. Epub 2025 Feb 13.ABSTRACTBACKGROUND: Rheumatoid arthritis (RA) significantly increases the overall risk of cardiovascular disease (CVD). In addition to conventional risk factors, the inflammatory activity of the disease itself and medications that promote atherosclerosis contribute to an even greater risk. In this study, we performed metabolomic analysis in RA patients, both on and off disease-modifying anti-rheumatic drug (DMARD) therapy, with the aim of identifying new candidates for more sophisticated cardiovascular risk (CVR) assessment.METHODS: This is an observational, cross-sectional investigation that included patients with established RA. DMARD therapy, if prescribed, consisted of methotrexate (MTX) alone or in combination with other conventional disease-modifying anti-rheumatic drugs (cDMARDs) or biologic disease-modifying anti-rheumatic drugs (bDMARDs), or other cDMARDs or bDMARDs without MTX, respectively. Metabolomic profiling was conducted using a Bruker AVANCE NEO 600 MHz nuclear magnetic resonance (NMR) spectrometer. The spectra obtained were Fourier transformed using TopSpin software (version 4.0, Bruker Biospin, Germany). All spectra were automatically phased and subjected to baseline correction. Subsequently, the spectra were analyzed using the proprietary Profiler software (version 1.4_Blood, lifespin GmbH, Germany), and a quantitative metabolite list was generated.RESULTS: In total, 200 patients were included in the study, 54 subjects were not receiving any DMARDs (n = 47 untreated at the time of inclusion, n = 7 with established disease but not receiving DMARD therapy), and 146 were receiving DMARD treatment. No metabolic differences were found in relation to drug therapy or RA activity. The following CVR factors were associated with significant metabolic abnormalities: distress, arterial hypertension, diabetes mellitus and an average higher Framingham score. Distressed individuals showed abnormalities in histidine metabolism.CONCLUSIONS: Our findings have aided in the identification of potential surrogate markers for assessing the burden of CVD in individuals with RA. Histidine may be of particular diagnostic importance in CVR assessment in RA.PMID:39981338 | PMC:PMC11835553 | DOI:10.14740/jocmr6145

PeerJ. 2025 Feb 17;13:e18941. doi: 10.7717/peerj.18941. eCollection 2025.ABSTRACTBACKGROUND: Olive (Olea europaea L.) oil is well-known commercial product worldwide for its nutritional and therapeutic properties. The molecular mechanisms underlying lipid variations in different olive cultivars remain unclear.METHODS: To investigate the molecular mechanism involved in lipid synthesis and metabolism, untargeted metabolome and RNA-Seq analyses were performed based on two varieties of olive fruits, i.e., Kalinjot (JZ) with low oil content and Coratina (KLD) with high oil content.RESULTS: Totally, 38 lipid compounds of 375 differentially accumulated metabolites (DAMs) were identified in JZ and KLD fruits, with 24 metabolites showing higher contents in KLD than those in JZ. Integrated transcriptome and metabolome analyses identified 48 differentially expressed genes (DEGs) associated with six lipid DAMs from JZ and KLD fruits. The contents of decanoic acid, sphinganine, and leukotriene D4 in KLD fruits were 2.33, 1.91, and 1.53 times greater than that of JZ fruits, respectively. In particular, two BCCP, one ACC, seven KAR, one EAR, one FATA and one SPT genes were observed involving to the content and quality of lipids in olive fruits. These DEGs were associated with the pathways of fatty acid biosynthesis, arachidonic acid metabolism, and limonene degradation. This study provides a strong theoretical and experimental foundation for further revealing the molecular mechanisms regulating lipid synthesis and metabolism in different olive cultivars.PMID:39981043 | PMC:PMC11841613 | DOI:10.7717/peerj.18941

Kidney Med. 2024 Dec 26;7(3):100955. doi: 10.1016/j.xkme.2024.100955. eCollection 2025 Mar.ABSTRACTA comprehensive review of known uremic retention molecules goes back to more than 10 years ago and did not consider metabolomic analyses. The present analysis searches for as of yet unclassified solutes retained in chronic kidney disease (CKD) by analyzing metabolites associated with relevant outcomes of CKD. This untargeted metabolomics-based approach is compared with a conventional targeted literature search. For the selected molecules, the literature was screened for arguments regarding toxic (harmful), beneficial, or neutral effects in experimental or clinical studies. Findings were independently crosschecked. In total, 103 molecules were selected. No literature on any effect was found for 55 substances, 3 molecules had no significant effect, and 13 others showed beneficial effects. For the remaining 32 compounds, we found at least one report of a toxic effect. Whereas 62.5% of the compounds with at least one study on a toxic effect was retrieved via the bottom-up approach, 69.2% of the substances originating from metabolomics-based approaches showed a beneficial effect. Our results suggest that untargeted metabolomics offer a more balanced view of uremic retention than the targeted approaches, with higher chances of revealing the beneficial potential of some of the metabolites.PMID:39980938 | PMC:PMC11841090 | DOI:10.1016/j.xkme.2024.100955

Front Endocrinol (Lausanne). 2025 Feb 6;16:1561447. doi: 10.3389/fendo.2025.1561447. eCollection 2025.NO ABSTRACTPMID:39980851 | PMC:PMC11839433 | DOI:10.3389/fendo.2025.1561447

Front Microbiol. 2025 Feb 6;16:1557933. doi: 10.3389/fmicb.2025.1557933. eCollection 2025.ABSTRACT[This corrects the article DOI: 10.3389/fmicb.2023.1306039.].PMID:39980696 | PMC:PMC11841895 | DOI:10.3389/fmicb.2025.1557933

Front Nutr. 2025 Feb 5;12:1519905. doi: 10.3389/fnut.2025.1519905. eCollection 2025.ABSTRACTNutritional interventions facilitating the consumption of natural, affordable, and environment-compatible health-promoting functional foods are a promising strategy for controlling non-communicable diseases. Given that the complex of tomato micronutrients produces healthier outcomes than lycopene, its major antioxidant component, new strategies to improve the health-supporting properties of the berry are ongoing. In this context, a whole tomato food supplement (WTFS), enriched by 2% olive wastewater containing a complex of healthy nutrients with converging biologic activities, has recently been developed, which is superior to those present in tomato commodities or obtained with whole tomato conventional processing methods. WTFS equals the antioxidant activity of N-acetyl-cysteine and interferes with multiple inflammation and cellular transformation-sustaining metabolic pathways. In interventional studies, WTFS inhibits prostate experimental tumors and improves benign prostate hypertrophy-associated symptoms with no associated side-effects. Although WTFS may be susceptible to further improvements and clinical scrutiny, its composition embodies the features of advanced functional foods to ease adherence to dietary patterns, that is, the Mediterranean diet, aimed at contrasting and mitigating the low-grade inflammation, thus being interceptive or preventive of non-communicable diseases.PMID:39980679 | PMC:PMC11841393 | DOI:10.3389/fnut.2025.1519905

J Transl Med. 2025 Feb 20;23(1):206. doi: 10.1186/s12967-024-05996-w.ABSTRACTBACKGROUND: Cystinosis is a rare, incurable lysosomal storage disease caused by mutations in the CTNS gene encoding the cystine transporter cystinosin, which leads to lysosomal cystine accumulation in all cells of the body. Patients with cystinosis display signs of podocyte damage characterized by extensive loss of podocytes into the urine at early disease stages, glomerular proteinuria, and the development of focal segmental glomerulosclerosis (FSGS) lesions. Although standard treatment with cysteamine decreases cellular cystine levels, it neither reverses glomerular injury nor prevents the loss of podocytes. Thus, pathogenic mechanisms other than cystine accumulation are involved in podocyte dysfunction in cystinosis.METHODS: We used immortalized patient-derived cystinosis, healthy, and CTNS knockdown podocytes to investigate podocyte dysfunction in cystinosis. The results were validated in our newly in-house developed fluorescent ctns-/-[Tg(fabp10a:gc-EGFP)] zebrafish larvae model. To understand impaired podocyte functionality, static and dynamic permeability assays, tracer-metabolomic analysis, flow cytometry, western blot, and chemical and dynamic redox-sensing fluorescent probes were used.RESULTS: In the current study, we discovered that cystinosis podocytes demonstrate increased ferroptotic cell death caused by mitochondrial reactive oxygen species (ROS)-driven membrane lipid peroxidation. Moreover, cystinosis cells present a fragmented mitochondrial network with impaired tricarboxylic acid cycle (TCA) cycle and energy metabolism. Targeting mitochondrial ROS and lipid peroxidation improved podocyte function in vitro and rescued proteinuria in vivo in cystinosis zebrafish larvae.CONCLUSIONS: Mitochondrial ROS contribute to podocyte injury in cystinosis by driving lipid peroxidation and ferroptosis, which in turn lead to podocyte detachment. This finding adds cystinosis to the list of podocytopathies associated with mitochondrial dysfunction. The identified mechanisms reveal new therapeutic targets and highlight lipid peroxidation as an exploitable vulnerability of cystinosis podocytes.PMID:39980044 | DOI:10.1186/s12967-024-05996-w

J Transl Med. 2025 Feb 20;23(1):207. doi: 10.1186/s12967-024-06024-7.ABSTRACTBACKGROUND: Extracellular vesicles (EVs) represent a sophisticated mechanism of intercellular communication that is implicated in health and disease. Specifically, the role of EVs in metabolic regulation and their implications in metabolic pathologies, such as obesity and its comorbidities, remain unclear.METHODS: Extracellular vesicles (EVs) were isolated through serial ultracentrifugation from murine adipocytes treated with palmitate or oleic acid, whole visceral and subcutaneous adipose tissue (obesesomes) of bariatric surgery obese donors, and human hepatocytes under steatosis (steatosomes) for functional in vitro experiments. Functional effects on inflammation and glucose and lipid metabolism of target cells (human and murine macrophages and hepatocytes) were assessed using ELISA, RT-PCR, and immunodetection. Isolated EVs from human steatotic (steatosomes) and control hepatocytes (hepatosomes) were characterized for quantity, size, and tetraspanin profile by NTA and Single Particle Interferometric Reflectance Imaging Sensor (SP-IRIS), and their protein cargo analyzed by qualitative (DDA) and quantitative (DIA-SWATH) proteomics using LC-MS/MS. Proteins identified by proteomics were validated by capturing EVs on functionalized chips by SP-IRIS.RESULTS AND CONCLUSIONS: In this study, we investigated the role of EVs in the local communication between obese adipocytes and immune cells within adipose tissue, and the interaction of steatotic and healthy hepatocytes in the context of fatty liver disease progression. Furthermore, we analyzed obese adipose tissue-to-liver interactions through EV-obesesomes to elucidate their role in obesity-associated hepatic metabolic dysregulation. Our findings reveal that obesesomes promote inflammation and the secretion of pro-inflammatory cytokines upon interaction with macrophages, exerting a significant impact on reducing insulin resistance and altering lipid and glucose metabolism upon interaction with hepatocytes; in both cases, EVs from palmitate-loaded adipocytes and obesesomes from human visceral adipose depots demonstrated the most deleterious effect. Additionally, EVs secreted by steatotic hepatocytes (steatosomes) induced insulin resistance and altered lipid and glucose metabolism in healthy hepatocytes, suggesting their involvement in MASLD development. Proteomic analysis of steatosomes revealed that these vesicles contain liver disease-associated proteins, rendering them significant repositories of real-time biomarkers for the early stages and progression of MASLD.PMID:39979938 | DOI:10.1186/s12967-024-06024-7

J Transl Med. 2025 Feb 20;23(1):209. doi: 10.1186/s12967-025-06203-0.ABSTRACTBACKGROUND: In the last two decades, many studies based on omics technologies have contributed to defining the clinical, immunological, and histological fingerprints of chronic antibody-mediated rejection (CAMR), the leading cause of long-term kidney allograft failure. However, the full biological machinery underlying CAMR has only been partially defined, likely due to the fact thatsingle-omics technologies capture only specific aspects of the biological system and fail to provide a comprehensive understanding of this clinical complication.METHODS: This study integrated mass spectrometry-based proteomic profiling of serum samples from 19 patients with clinical and histological evidence of CAMR and 26 kidney transplant recipients with normal graft function and histology (CTR) with transcriptomic analysis of peripheral blood mononuclear cells (PBMCs) from an independent cohort of 10 CAMR and 8 CTR patients. Data analysis was conducted using unsupervised hierarchical clustering (multidimensional scaling with k-means) and Spearman's correlation test. Partial least squares discriminant analysis (PLS-DA) with the importance in projection (VIP) score identified key proteins differentiating CAMR from CTR. ELISA was used to validate the omics results.RESULTS: Proteomic analysis identified 18 proteins that significantly differentiated CAMR from CTR (p < 0.01): five were more abundant (CHI3L1, LYZ, PRSS2, CPQ, IGLV3-32), while 13 were less abundant (SERPINA5, SERPING1, KNG1, CAMP, VNN1, BTD, WDR1, PON3, AHNAK2, MELTF, CA1, CD44, CUL1). Transcriptomic profiling revealed 6 downregulated and 33 upregulated genes in CAMR versus CTR (p < 0.01). Notably, only 2 biological elements were significantly deregulated in both omics analyses: chitinase-3-like protein 1 (CHI3L1) and plasma protease inhibitor C1 (SERPING1). CHI3L1, previously associated with the severity of tissue damage in kidney diseases, was up-regulated in CAMR in both transcriptomics and proteomics, while SERPING1, a serine esterase inhibitor that blocks the classical and lectin pathway of complement, was up-regulated in CAMR in transcriptomics but down-regulated in proteomics. ELISA validated the omics results, and the ROC curve showed that CHI3L1 has good discrimination power between CAMR and CTR (AUC of ROC curve of 0.81).CONCLUSIONS: Our multi-omics data, although performed in a relatively small cohort of patients, revealed new systemic biological elements involved in the pathogenesis of CAMR and identified CHI3L1 as a new potential biomarker and/or therapeutic target for this important clinical complication. Future validation of these findings in larger patient cohorts should be conducted to better evaluate their clinical utility.PMID:39979925 | DOI:10.1186/s12967-025-06203-0

BMC Plant Biol. 2025 Feb 20;25(1):233. doi: 10.1186/s12870-025-06132-6.ABSTRACTCurcuma wenyujin, a perennial herb of the ginger family, is renowned for its significant medicinal properties. Phosphorus (P), a vital nutrient for plant growth and development, has seen its levels, particularly organic P, increase in the soils of agricultural regions in southern China, presenting new challenges for nutrient management. This study aimed to uncover the molecular responses of C. wenyujin seedlings to both normal and high phosphorus (HP) conditions, shedding light on their adaptation strategies to P stress. Through transcriptome and metabolome analyses of the seedlings under normal and HP conditions, we identified 1,793 metabolites, with 195 showing differential expression. Notably, KEGG enrichment analysis highlighted 35 significantly differential accumulation metabolites (DAMs). Comparing the control group (CK) and HP treated groups (T) revealed 840 differentially expressed genes (DEGs), pinpointing the molecular divergences in response to varying P levels. Importantly, we found a potential gene, purple acid phosphatase 17 (pap17) that may cofer HP stress conditions in C. wenyujin. That elucidated the response variations of C. wenyujin seedlings to diverse P concentrations. The research suggested that C. wenyujin may adjust to varying P levels by modulating metabolites and genes linked to amino acid and phenylpropane metabolism. It highlighted the sophisticated mechanisms plants utilize to manage P stress, offering insights into their survival tactics in settings where P availability changes.PMID:39979802 | DOI:10.1186/s12870-025-06132-6

Metabolomics. 2025 Feb 20;21(2):27. doi: 10.1007/s11306-025-02229-z.ABSTRACTINTRODUCTION: Nuclear Magnetic Resonance (NMR) spectroscopy has emerged as a transformative technology in agricultural research, offering powerful analytical capabilities for field crop improvement. With global challenges such as food security and climate change intensifying, there is an urgent need for innovative methodologies to enhance our understanding of plant health, metabolic pathways, and crop-environment interactions. NMR's ability to provide nondestructive, real-time analysis of plant metabolites and soil chemistry positions it as a critical tool for addressing these pressing concerns.OBJECTIVE: This review aims to elucidate the potential of NMR spectroscopy in advancing field crop improvement by highlighting its applications, challenges, and future perspectives in agricultural methodologies. The focus is on the evolution and application of NMR in agricultural research, particularly in metabolomics, phenotyping, and quality assessment.METHOD: A comprehensive literature review was conducted to analyze recent advancements in NMR applications in agriculture. Particular emphasis was given to high-resolution magic angle spinning (HR-MAS) and time-domain NMR techniques, which have been instrumental in elucidating plant metabolites and soil chemistry. Studies showcasing the integration of NMR with complementary technologies for enhanced metabolic profiling and genetic marker identification were reviewed.RESULTS: Findings indicate that NMR spectroscopy is an indispensable tool in agriculture due to its ability to identify biomarkers indicative of crop resilience, monitor soil composition, and contribute to food safety and quality assessments. The integration of NMR with other technologies has accelerated metabolic profiling, aiding in the breeding of high-yielding and stress-resistant crop varieties. However, challenges such as sensitivity limitations and the need for standardization remain.CONCLUSION: NMR spectroscopy holds immense potential for revolutionizing agricultural research and crop improvement. Overcoming existing challenges, such as sensitivity and standardization, is crucial for its broader application in practical agricultural settings. Collaborative efforts among researchers, agronomists, and policymakers will be essential for leveraging NMR technology to address global food security challenges and promote sustainable agricultural practices.PMID:39979661 | DOI:10.1007/s11306-025-02229-z

Metabolomics. 2025 Feb 20;21(2):29. doi: 10.1007/s11306-024-02216-w.ABSTRACTINTRODUCTION: The identification of lipids is a cornerstone of lipidomics, and due to the specific characteristics of lipids, it requires dedicated analysis workflows. Identifying novel lipids and lipid species for which no reference spectra are available is tedious and often involves a lot of manual work. Integrating high-resolution mass spectrometry with enhancements from chromatographic and ion mobility separation enables the in-depth investigation of intact lipids.OBJECTIVES: We investigated phosphorylated glycosphingolipids from the nematode Caenorhabditis elegans, a biomedical model organism, and aimed to identify different species from this class of lipids, which have been described in one particular publication only. We checked if these lipids can be detected in lipid extracts of C. elegans.METHODS: We used UHPLC-UHR-TOF-MS and UHPLC-TIMS-TOF-MS in combination with dedicated data analysis to check for the presence of phosphorylated glycosphingolipids. Specifically, candidate features were identified in two datasets using Mass Spec Query Language (MassQL) to search fragmentation data. The additional use of retention time (RT) and collisional cross section (CCS) information allowed to filter false positive annotations.RESULTS: As a result, we detected all previously described phosphorylated glycosphingolipids and novel species as well as their biosynthetic precursors in two different lipidomics datasets. MassQL significantly speeds up the process by saving time that would otherwise be spent on manual data investigations. In total over 20 sphingolipids could be described.CONCLUSION: MassQL allowed us to search for phosphorylated glycosphingolipids and their potential biosynthetic precursors systematically. Using orthogonal information such as RT and CCS helped filter false positive results. With the detection in two different datasets, we demonstrate that these sphingolipids are a general part of the C. elegans lipidome.PMID:39979652 | DOI:10.1007/s11306-024-02216-w

Metabolomics. 2025 Feb 20;21(2):30. doi: 10.1007/s11306-025-02225-3.ABSTRACTINTRODUCTION: Maternal tobacco smoking in the perinatal period increases the risk for adverse outcomes in offspring.OBJECTIVE: To better understand the biological pathways through which maternal tobacco use may have long-term impacts on child metabolism, we performed a high-resolution metabolomics (HRM) analysis in newborns, following an untargeted metabolome-wide association study workflow.METHODS: The study population included 899 children without cancer diagnosis before age 6 and born between 1983 and 2011 in California. Newborn dried blood spots were collected by the California Genetic Disease Screening Program between 12 and 48 h after birth and stored for later research use. Based on HRM, we considered mothers to be active smokers if they were self- or provider-reported smokers on birth certificates or if we detected any cotinine or high hydroxycotinine intensities in newborn blood. We used partial least squares discriminant analysis and Mummichog pathway analysis to identify metabolites and metabolic pathways associated with maternal tobacco smoking.RESULTS: A total of 26,183 features were detected with HRM, including 1003 that were found to be associated with maternal smoking late in pregnancy and early postpartum (Variable Importance in Projection (VIP) scores > = 2). Smoking affected metabolites and metabolic pathways in neonatal blood including vitamin A (retinol) metabolism, the kynurenine pathway, and tryptophan and arachidonic acid metabolism.CONCLUSION: The smoking-associated metabolites and pathway perturbations that we identified suggested inflammatory responses and have also been implicated in chronic diseases of the central nervous system and the lung. Our results suggest that infant metabolism in the early postnatal period reflects smoking specific physiologic responses to maternal smoking with strong biologic plausibility.PMID:39979646 | DOI:10.1007/s11306-025-02225-3

Acta Pharmacol Sin. 2025 Feb 20. doi: 10.1038/s41401-025-01495-w. Online ahead of print.ABSTRACTNon-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. NAFLD encompasses a spectrum of liver damage starting with liver steatosis and lipid disorders presented as the hallmark. Cannabinoid-2 receptor (CB2R) is the receptor of endocannabinoids mainly expressed in immune cells. Our preliminary study revealed the preventative role of CB2R in liver injury related to lipid metabolism. In this study, we aimed to explore the role of CB2R in NAFLD and the underlying mechanism related to microbial community. High-fat diet-induced NAFLD model was established in mice. We found that hepatic CB2R expression was significantly reduced in NAFLD mice and CB2R-/- mice fed with normal chow. Interestingly, cohousing with or transplanted with microbiota from WT mice, or treatment with an antibiotic cocktail ameliorated the NAFLD phenotype of CB2R-/- mice. The gut dysbiosis in CB2R-/- mice including increased Actinobacteriota and decreased Bacteroidota was similar to that of NAFLD patients and NAFLD mice. Microbial functional analysis and metabolomics profiling revealed obviously disturbed tryptophan metabolism in NAFLD patients and NAFLD mice, which were also seen in CB2R-/- mice. Correlation network showed that the disordered tryptophan metabolites such as indolelactic acid (ILA) and xanthurenic acid in CB2R-/- mice were mediated by gut dysbiosis and related to NAFLD severity indicators. In vitro and in vivo validation experiments showed that the enriched tryptophan metabolites ILA aggravated NAFLD phenotypes. These results demonstrate the involvement of CB2R in NAFLD, which is related to gut microbiota-mediated tryptophan metabolites. Our findings highlight CB2R and the associated microbes and tryptophan metabolites as promising targets for the treatment of NAFLD.PMID:39979552 | DOI:10.1038/s41401-025-01495-w

Metabolomics. 2025 Feb 20;21(2):28. doi: 10.1007/s11306-025-02230-6.ABSTRACTNeoadjuvant therapy is a standard treatment for breast cancer, but its effectiveness varies among patients. This highlights the importance of developing accurate predictive models. Our study uses metabolomics and machine learning to predict the response to neoadjuvant therapy in breast cancer patients.OBJECTIVE: To develop and validate predictive models using machine learning and circulating metabolites for forecasting responses to neoadjuvant therapy among breast cancer patients, enhancing personalized treatment strategies.METHODS: Based on pathological analysis after neoadjuvant chemotherapy and surgery, this retrospective study analyzed 30 young women breast cancer patients from a single institution, categorized as responders or non-responders. Utilizing liquid chromatography-tandem mass spectrometry, we investigated the plasma metabolome, explicitly targeting 40 metabolites, to identify relevant biomarkers linked to therapy response, using machine learning to generate a predictive model and validate the results.RESULTS: Eighteen significant biomarkers were identified, including specific acylcarnitines and amino acids. The most effective predictive model demonstrated a remarkable accuracy of 90.7% and an Area Under the Curve (AUC) of 0.999 at 95% confidence, illustrating its potential utility as a web-based application for future patient management. This model's reliability underscores the significant role of circulating metabolites in predicting therapy outcomes.CONCLUSION: Our study's findings highlight the crucial role of metabolomics in advancing personalized medicine for breast cancer treatment by effectively identifying metabolite biomarkers correlated with neoadjuvant therapy response. This approach signifies a critical step towards tailoring treatment plans based on individual metabolic profiles, ultimately improving patient outcomes in breast cancer care.PMID:39979511 | DOI:10.1007/s11306-025-02230-6