PubMed

Food Chem X. 2025 Feb 24;26:102318. doi: 10.1016/j.fochx.2025.102318. eCollection 2025 Feb.ABSTRACTLacticaseibacillus casei Zhang (L. casei Zhang) was used as an auxiliary starter culture to explore its application in camel milk fermentation. This study evaluated the effects of L. casei Zhang supplementation on viable cell count, acidity, texture, insulin-like growth factor 1 (IGF-1) retention, and metabolite profiles over a 21-day storage period. L. casei Zhang enhanced the retention rate of active IGF-1 from 52.95% to 59.13% and mitigated the progression of acidity (from 125 °T to 97.5 °T) compared with the control group. Additionally, L. casei Zhang significantly improved viscosity and promoted the formation of gel structures. Furthermore, its addition significantly influenced the production of key metabolites, including adenosine diphosphate, oleuropein, and threonine-tryptophan (P < 0.05). These findings highlight the potential of L. casei Zhang as an effective auxiliary starter culture for camel milk fermentation, enhancing its physicochemical properties and modulating its metabolomic profile.PMID:40092409 | PMC:PMC11910121 | DOI:10.1016/j.fochx.2025.102318

Open Vet J. 2025 Jan;15(1):162-170. doi: 10.5455/OVJ.2024.v15.i1.15. Epub 2025 Jan 31.ABSTRACTBACKGROUND: Pelvic organ prolapse increases in prevalence and incidence in older women and hypoestrogenic conditions. Treatment with native tissue surgery has a fairly high recurrence rate. Mesh-augmented surgery is one of the most promising treatments for pelvic organ prolapse, with high effectiveness and low recurrence. Mesh-augmented surgery has a side effect of tissue erosion. The addition of secretome is expected to improve tissue integrity and reduce tissue erosion.AIM: This study aimed to investigate the effect of adding the umbilical cord mesenchymal stem cell (UC-MSC) secretome on preventing tissue inflammatory responses, improving tissue integrity, and accelerating wound healing.METHODS: A total of 32 female New Zealand white rabbit hypoestrogenic models were divided into two groups: the control group with normal mesh and the secretome group with artificial mesh. Hypoestrogenic models were created using the bilateral ovariectomy method. Mesh implantation was performed using a surgical method on hypoestrogenic rabbits. The animals were euthanized on days 7, 14, 28, and 90 after mesh implantation. Histopathology parameters included angiogenesis formation, fibroblast number, and collagen deposition area.RESULT: The results of this study showed that the number of angiogenesis, fibroblast, and collagen deposition data in the secretome group showed higher significantly (p < 0.05) than those in the control group on days 7, 14, 28, and 90 post mesh implantation. The formation of new blood vessels (angiogenesis) in the secretome group demonstrated a mean value of 9.81 ± 2.2 compared to 0.37 ± 0.03 in the control. The number of fibroblasts in the secretome group averaged 151.00 ± 8.14, in contrast to 34.00 ± 13.37 in the control group. Collagen formation in the secretome group was also higher, with a mean value of 80.02 ± 6.71 compared to 59.49 ± 4.61 in the control group over 90 days of observation.CONCLUSION: The administration of secretomes from UC-MSC improved tissue integrity and accelerated wound healing.PMID:40092191 | PMC:PMC11910305 | DOI:10.5455/OVJ.2024.v15.i1.15

Front Neurosci. 2025 Feb 28;19:1478304. doi: 10.3389/fnins.2025.1478304. eCollection 2025.ABSTRACTThe gut and brain interact through various metabolic and signaling pathways, each of which influences mental health. Gut dysbiosis caused by antibiotics is a well-known phenomenon that has serious implications for gut microbiota-brain interactions. Although antibiotics disrupt the gut microbiota's fundamental structure, the mechanisms that modulate the response and their impact on brain function are still unclear. It is imperative to comprehend and investigate crucial regulators and factors that play important roles. We aimed to study the effect of long-term antibiotic-induced disruption of gut microbiota, host metabolomes, and brain function and, particularly, to determine the basic interactions between them by treating the C57BL/6 mice with two different, most commonly used antibiotics, ciprofloxacin and amoxicillin. Anxiety-like behavior was confirmed by the elevated plus-maze test and open field test. Gut microbes and their metabolite profiles in fecal, serum, and brain samples were determined by 16S rRNA sequencing and untargeted metabolomics. In our study, long-term antibiotic treatment exerted anxiety-like effects. The fecal microbiota and metabolite status revealed that the top five genera found were Lactobacillus, Bacteroides, Akkermansia, Ruminococcus_gnavus_group, and unclassified norank_f_Muribaculaceae. The concentration of serotonin, L-Tyrosine, 5-Hydroxy-L-tryptophan, L-Glutamic acid, L-Glutamate, 5-Hydroxyindole acetic acid, and dopaminergic synapsis was comparatively low, while adenosine was high in antibiotic-treated mice. The KEGG enrichment analysis of serum and brain samples showed that amino acid metabolism pathways, such as tryptophan metabolism, threonine metabolism, serotonergic synapsis, methionine metabolism, and neuroactive ligand-receptor interaction, were significantly decreased in antibiotic-treated mice. Our study demonstrates that long-term antibiotic use induces gut dysbiosis and alters metabolic responses, leading to the dysregulation of brain signaling molecules and anxiety-like behavior. These findings highlight the complex interactions between gut microbiota and metabolic functions, providing new insights into the influence of microbial communities on gut-brain communication.PMID:40092066 | PMC:PMC11906700 | DOI:10.3389/fnins.2025.1478304

Front Microbiol. 2025 Feb 28;16:1550337. doi: 10.3389/fmicb.2025.1550337. eCollection 2025.ABSTRACTINTRODUCTION: "Sweating," a key step in the processing and production of Eucommiae Cortex (EC), which plays a vital role in the formation of the medicinal quality of EC. However, the mechanism of the effect of this traditional treatment of herbs on the quality of herbs is still unclear.METHODS: In this study, high performance liquid chromatography (HPLC), UPLC/MS-based untargeted metabolomics and high-throughput sequencing were applied to investigate the dynamic changes of the main active ingredients, differential metabolites and bacterial communities in the process of "sweating" in EC. The samples were prepared by the traditional stacking "sweating" method, and the samples were collected once a day for five consecutive days.RESULTS: The results showed that the contents of the main active constituents, geniposidic acid (GPA), chlorogenic acid (CA), rutin (AU), pinoresinol diglucoside (PD) and total flavonoids (TFS), increased significantly after steaming, followed by a slight decrease. Furthermore, 807 metabolites were identified as crucial factors contributing to the metabolic alterations induced by the "sweating" process. Microbial diversity analysis showed considerable changes in microbiota characteristics, and the main functional microorganisms before and after "sweating" of EC were Gluconobacter, unclassified_c_Gammaproteobacteria, Pseudomonas, Pantoea, Pedobacter, and Parecoccus, which were involved in the five metabolic pathways of other secondary metabolites leading to significant changes in alkaloids, amino acid related compounds, flavonoids, phenylpropanoids and terpenoids.DISCUSSION: The correlation network established between core bacterial communities, active ingredients, and metabolic pathways elucidates the microbial regulation of EC quality during sweating. These findings provide a scientific foundation for optimizing processing duration and advancing quality control strategies through targeted microbial community management.PMID:40092042 | PMC:PMC11906693 | DOI:10.3389/fmicb.2025.1550337

Front Microbiol. 2025 Feb 28;16:1544641. doi: 10.3389/fmicb.2025.1544641. eCollection 2025.ABSTRACTReforestation plays a vital role in restoring the soil degradation areas. However, the mechanisms by which different restoration approaches affect the soil properties and microbial communities remain unclear. Aiming to understand the interactions between plant species, soil properties, and microbial communities in different restoration approaches, we investigated the soil microbial community using nontargeted metabolomics to explore how the reforestation approach affects soil physicochemical properties, soil metabolites, and soil microbial communities. The results showed that the reforestation approach, soil layer, and their interactive effects significantly affected soil organic carbon, total nitrogen, dissolved organic carbon, available phosphorus concentrations, and root traits. The diversity and composition of bacterial and fungal communities in natural reforestation (NR) were different from those in artificial mono-plantations, and their network interactions were more significant in NR than in artificial plantations. A clear separation of metabolites between the artificial plantations and NR was observed in the soil metabolite analysis. Two pathways, linoleic acid metabolism, and valine, leucine, and isoleucine biosynthesis, were significantly regulated between the artificial mono-plantations and NR. Different soil traits were significantly correlated with dominant microbial taxa in the four reforestation approaches. 13-L-hydroperoxylinoleic acid, 13-S-hydroxyoctadecadienoic acid, homovanillin, and 9,10-epoxyoctadecenoic acid showed the highest correlation with the microbial taxa in the network. Partial least squares path modeling (PLS-PM) shows that root-mediated soil physicochemical properties were the primary factors affecting the bacterial community among the reforestation approaches. The soil fungal community is directly regulated by plant roots in the subsoil and indirectly regulated by the root-mediated physicochemical properties in the topsoil. We conclude that different reforestation approaches affect the soil microbial community through root and soil physicochemical properties rather than soil metabolites.PMID:40092039 | PMC:PMC11906678 | DOI:10.3389/fmicb.2025.1544641

Cureus. 2025 Feb 12;17(2):e78918. doi: 10.7759/cureus.78918. eCollection 2025 Feb.ABSTRACTThe oral microbiome, consisting of a mixture of bacteria, fungi, and viruses, is an important contributor to oral and systemic health. Microbial balance disruptions are associated with oral pathologies like dental caries and periodontitis as well as systemic diseases such as cardiovascular diseases, adverse pregnancy outcomes, and respiratory diseases. This review explores the mechanistic pathways linking oral dysbiosis to systemic inflammation, endothelial dysfunction, and immune modulation. The roles of key microbial species in health and disease are analyzed, with an emphasis on how hematogenous dissemination leads to systemic pathologies through inflammatory signaling. Also, advances in high throughput sequencing are discussed, as well as microbial diversity and its implications for diagnostics and therapeutics. The review highlights the potential of oral microbiota-targeted interventions to mitigate systemic diseases through dentistry and medicine integration, by throwing light on interdisciplinary strategies. Future work should focus on the evaluation of the mechanisms by which the oral microbiome plays a role in systemic diseases through the integration of multi-omics approaches such as metagenomics, transcriptomics, and metabolomics. Furthermore, clinical trials need to be designed in a way to evaluate the efficacy of microbiome-targeted therapies in the prevention of cardiovascular diseases, adverse pregnancy outcomes, and autoimmune disorders.PMID:40091996 | PMC:PMC11909285 | DOI:10.7759/cureus.78918

Mol Ecol. 2025 Mar 17:e17722. doi: 10.1111/mec.17722. Online ahead of print.ABSTRACTCoral reefs and their photosynthetic algae form one of the most ecologically and economically impactful symbioses in the animal kingdom. The stability of this nutritional mutualism and this ecosystem is, however, at risk due to increasing sea surface temperatures that cause corals to expel their symbionts. Symbioses with these microeukaryotes have independently evolved multiple times, and non-coral cnidarians (e.g., sea anemones) serve as a valuable and insightful comparative system due to their ease of husbandry in the laboratory and their ability to shuffle different strains of their photosymbionts to acclimate to thermal conditions. This breadth of symbiont shuffling is exemplified by the sea anemone Anthopleura elegantissima, which naturally occurs in symbiosis with the dinoflagellate Breviolum muscatinei (formerly Symbiodinium) or the chlorophyte Elliptochloris marina as well as being aposymbiotic. Here, we assembled a draft genome and used multi-omics to characterise multiple physiological levels of each phenotype. We find that A. elegantissima has symbiont-specific transcriptional and metabolomic signatures, but a similar bacterial community dominated by a single Sphingomonas species that is commonly found in the cnidarian microbiome. Symbiosis with either eukaryotic symbiont resulted in differential gene expression and metabolic abundance for diverse processes spanning metabolism and immunity to reproduction and development, with some of these processes being unique to either symbiont. The ability to culture A. elegantissima with its phylogenetically divergent photosymbionts and perform experimental manipulations makes A. elegantissima another tractable sea anemone system to decode the symbiotic conversations of coral reef ecosystems and aid in wider conservation efforts.PMID:40091861 | DOI:10.1111/mec.17722

Phytochem Anal. 2025 Mar 17. doi: 10.1002/pca.3530. Online ahead of print.ABSTRACTINTRODUCTION: In metalliferous ecosystems, bacteria could develop membrane efflux pumps to extrude heavy metals. Native plants, frequently exposed to such bacteria, may serve as rich chemical reservoirs for discovering potential antibacterial and/or resistance-modifying agents.OBJECTIVES: This study aims to investigate the antibacterial properties of Pteris vittata L., a metal hyperaccumulator abundant in metal-rich environments, against Stenotrophomonas maltophilia K279a, an opportunistic nosocomial pathogen linked to severe respiratory tract infections.MATERIAL AND METHODS: A novel approach was used, employing the metabolome of P. vittata in a partial least squares regression model to predict the correlation between the whole chemical profile and activity. Marked compounds were then subjected to in vitro test for bactericidal and synergistic properties using broth dilution and time-kill assays.RESULTS: The multivariate analysis demonstrated a strong synergistic effect among a range of flavonoids compared to the individual responses. Notably, nine flavonoids were confirmed to reduce the minimum inhibitory concentration and minimal bactericidal concentration values of active compounds, cyanidin-3,5-O-diglucoside and perlagonin, from 64.0 and 108 μg/mL to 0.25 and 3.38 μg/mL, respectively.CONCLUSION: These results provide insights into the possibility of combating clinical infections caused by S. maltophilia and highlight the potential of exploring new synergetic interactions among natural products as an alternative to the conventional bio-guided isolation strategy.PMID:40091649 | DOI:10.1002/pca.3530

Ann Lab Med. 2025 Mar 17. doi: 10.3343/alm.2024.0482. Online ahead of print.ABSTRACTBreast cancer is the most common cancer and the second leading cause of cancer death in women worldwide. Novel biomarkers for early diagnosis, treatment, and prognosis in breast cancer are needed and extensively studied. Metabolites, which are small molecules produced during metabolic processes, provide links between genetics, environment, and phenotype, making them useful biomarkers for diagnosis, prognosis, and disease classification. With recent advancements in metabolomics techniques, metabolomics research has expanded, which has led to significant progress in biomarker research. In breast cancer, alterations in metabolic pathways result in distinct metabolomic profiles that can be harnessed for biomarker discovery. Studies using mass spectrometry and nuclear magnetic resonance spectroscopy have helped identify significant changes in metabolites, such as amino acids, lipids, and organic acids, in the tissues, blood, and urine of patients with breast cancer, highlighting their potential as biomarkers. Integrative analysis of these metabolite biomarkers with existing clinical parameters is expected to improve the accuracy of breast cancer diagnosis and to be helpful in predicting prognosis and treatment responses. However, to apply these findings in clinical practice, larger cohorts for validation and standardized analytical methods for QC are necessary. In this review, we provide information on the current state of metabolite biomarker research in breast cancer, highlighting key findings and their clinical implications.PMID:40091629 | DOI:10.3343/alm.2024.0482

Plant Cell Environ. 2025 Mar 17. doi: 10.1111/pce.15473. Online ahead of print.ABSTRACTThe metabolome, encompassing small molecules within organisms, provides critical insights into physiology, environmental influences, and stress responses. Metabolomics enables comprehensive analysis of plant metabolites, uncovering biomarkers and mechanisms underlying stress adaptation. Regulatory genes such as MYB and WRKY are central to secondary metabolite synthesis and environmental resilience. By integrating metabolomics with genomics, researchers can explore stress-related pathways and advance crop improvement efforts. This review examines metabolomic profiling under stress conditions, emphasizing drought tolerance mechanisms mediated by amino acids and organic acids. Additionally, it highlights the shikimate pathway's pivotal role in synthesizing amino acids and secondary metabolites essential for plant defense. These insights contribute to understanding metabolic networks that drive plant resilience, informing strategies for agricultural sustainability.PMID:40091600 | DOI:10.1111/pce.15473

J Extracell Vesicles. 2025 Mar;14(3):e70048. doi: 10.1002/jev2.70048.ABSTRACTEndometriosis, a chronic debilitating disease affects 1 in 7-10 girls and women, who have symptoms of severe chronic pain and subfertility and significantly impacts the overall quality of life. Currently, no effective early diagnostic methods are available for early stages of endometriosis. We used menstrual fluid-derived small extracellular vesicles (MF-sEVs) from women with self-reported endometriosis (laparoscopically diagnosed, n = 8) and self-reported without endometriosis and no painful periods (n = 9). MF-sEVs were separated using differential ultracentrifugation and characterised using nanoparticle tracking analysis (NTA), transmission electron microscopy (TEM), Western Blot, flow cytometry, mass-proteomics analysis and functional assays. Spherical-shaped sEVs were identified with a median diameter of ∼120 nm, expressing sEV marker proteins. The MF-sEV proteins were classified as endometrial origin. Over 5000 proteins were identified, ∼77% of which were decreased whilst only 22 proteins (largely comprising immunoglobulins) were increased in endometriosis/MF-sEVs compared to control/MF-sEVs. Decreased proteins were involved in nitrogen compound metabolism, immune response, intracellular signal transduction, regulation of programmed cell death, maintenance of cell polarity and actin cytoskeleton organisation. Flow cytometry demonstrated a significant increase in CD86 expression (immune activation marker) in endometriosis/MF-sEVs. Mesothelial cells showed a significant decrease in cellular resistance and junctional protein expression. MF-sEVs are possible contributors to the pathogenesis of endometriosis and may have the potential for early detection of the disease.PMID:40091455 | DOI:10.1002/jev2.70048

J Extracell Vesicles. 2025 Mar;14(3):e70049. doi: 10.1002/jev2.70049.ABSTRACTQuantitative lipidomic analysis performed by mass spectrometry is required for determination of the lipid content of extracellular vesicles (EVs). Such methods can provide information about the total amount of lipids, the lipid species composition, the purity of EV samples as well as the cellular origin of the EVs. There are, however, many pitfalls when performing lipid analyses. Thus, any non-specialist should collaborate with experts in lipidomics. In addition to many good review articles giving advice about lipid analyses, we recommend the information and guidelines published by the Lipidomic Standard Initiative, an interest group affiliated with the International Lipidomics Society.PMID:40091364 | DOI:10.1002/jev2.70049

J Med Primatol. 2025 Apr;54(2):e70013. doi: 10.1111/jmp.70013.ABSTRACTBalantidium coli (B. coli) is a prevalent intestinal parasite in monkeys, significantly impacting their health. Previous studies have demonstrated that B. coli infection in pigs leads to severe dysregulation of the gut microbiota. However, there has been no report on the alterations in fecal microbiota and metabolites in rhesus monkeys infected with B. coli. In order to investigate the differences in gut microbiota and metabolites between healthy rhesus monkeys and those infected with B. coli, we conducted gene sequencing and gas chromatography-mass spectrometry (GC-MS) analysis of fecal samples from 6 healthy rhesus monkeys and 5 rhesus monkeys infected with B. coli. The results revealed significant differences in the composition of gut microbiota between rhesus monkeys infected with B. coli and healthy ones (p < 0.01). The abundance of Campylobacterota was significantly increased (p < 0.01), while the abundance of Bacteroidota was significantly decreased (p < 0.05). Prevotella 9 was the dominant genus in both groups, showing a significant increase in the infected group (p < 0.05). At the species level, Brachyspira hampsonii was significantly increased in the infected group (p < 0.01), whereas Prevotella copri, which was the dominant species in both groups, showed a significant decrease in the infected group (p < 0.05). Metabolomics studies indicated a significant decrease in levels of metabolites such as dihydrolipoamide, 9(Z),11(E)-Conjugated Linoleic Acid, and 8,9-DiHETrE within fecal samples from rhesus monkeys infected with B. coli (p < 0.05). Correlation analysis of the microbiome and metabolome suggested a close relationship between differential microbiota and metabolites. In conclusion, this study suggests that the colonization of B. coli is associated with dysbiosis of the monkey gut microbiota. This study provides a new insight that using intestinal microbes instead of antibiotics to treat balantidiosis can also serve as a reference for further research on the relationship between gut microbiota and metabolomics in host infections by other protozoa.PMID:40091309 | DOI:10.1111/jmp.70013

J Nat Prod. 2025 Mar 16. doi: 10.1021/acs.jnatprod.4c01446. Online ahead of print.ABSTRACTAn investigation of living phosphatic stromatolites from Schoenmakerskop barrage pool near Gqeberha (Port Elizabeth), South Africa, yielded new cyclic octadepsipeptides, amatyemides A (1) and B (2), named using the Xhosa word 'amatye' for 'rock'. The amatyemides were isolated from methanol extracts of a targeted stromatolite sample collection, following an initial metabolomic survey of the Schoenmakerskop pool. Planar structure elucidation of 1 and 2 relied on NMR and LCMS2 data, which delineated the same six amino acids and one 2-hydroxy-3-methylpentanoic acid (Hmpa) residues in each compound. The two octadepsipeptides differed only in the presence of a 2-hydroxydodecanoic acid (Hdda) residue in 1 and a 2-hydroxydecanoic acid (Hda) residue in 2. The absolute configurations of most amino acid residues in 1 were determined using an enhanced Marfey's reagent. The configurations of the 2-hydroxy acids and O-methylthreonine were assigned, and the absolute structures of amatyemides A (1) and B (2) were confirmed, by total solid-phase peptide synthesis of two possible diastereomers for each natural product. Biological testing of natural and synthetic amatyemides against human U87-MG glioblastoma, HCT116 colon, and SH-SY5Y neuroblastoma cells revealed weak, cell-type specific, cytotoxic potential where 2 > 1, and this was attributed to induction of oxidative stress by 2.PMID:40091268 | DOI:10.1021/acs.jnatprod.4c01446

BMC Vet Res. 2025 Mar 17;21(1):174. doi: 10.1186/s12917-025-04642-x.ABSTRACTBACKGROUND: Cystic echinococcosis (CE) is a chronic zoonotic parasitic disease caused by the parasite Echinococcus granulosus (E. granulosus). Currently, pharmacologic treatments are limited to albendazole and mebendazole; however, these treatments are associated with significant side effects and limited therapeutic efficacy, highlighting the urgent need for the development of new drugs. Harmine (HM) has been reported to exhibit potent antiparasitic effects, although it is also accompanied by notable neurotoxicity. H-2-104, a derivative of HM obtained through structural modification of its parent nucleus, represents a promising candidate for further investigation. This study aims to assess the in vivo and in vitro efficacy of H-2-104 against E. granulosus and to elucidate the mechanism of action of H-2-104 against CE from a metabolomics perspective.METHODS: In vitro pharmacodynamics experiments were conducted to assess the inhibitory activity of H-2-104 against E. granulosus protoscoleces (PSCs). Following this, a mouse model of E. granulosus infection was established to explore the inhibitory effects against E. granulosus of H-2-104 at low, medium, and high concentrations. Additionally, non-targeted metabolomic approaches were utilized to analyze the serum and liver samples from mice in the control group, model group, and H-2-104 treatment group with the aim of identifying relevant biomarkers and crucial metabolic pathways involved in the response to H-2-104 treatment.RESULTS: The in vitro results demonstrated that H-2-104 exhibited significantly superior inhibitory activity against PSCs compared to harmine and albendazole. Morphological observations revealed marked alterations in the ultrastructural characteristics of PSCs treated with H-2-104. In vivo pharmacodynamic studies showed that H-2-104 at a dosage of 100 mg/kg exhibited the highest cyst inhibition rate, which was (73.60 ± 4.71)%. Metabolomics analysis revealed that 64 serum metabolites were significantly altered, primarily involving metabolic pathways such as necroptosis, linoleic acid metabolism, and phenylalanine metabolism. Additionally, 81 liver metabolites were identified with significant differences, mainly involving metabolic pathways like fructose and mannose metabolism, and glycerophospholipid metabolism.CONCLUSIONS: H-2-104 exhibits significant activity both in vitro and in vivo, suggesting its potential as a promising new drug for the treatment of CE. The anti-CE effects of H-2-104 may be attributed to its regulation of multiple biological pathways, including cell apoptosis, amino acid metabolism, and glucose metabolism.PMID:40091052 | DOI:10.1186/s12917-025-04642-x

BMC Pediatr. 2025 Mar 17;25(1):204. doi: 10.1186/s12887-025-05561-4.ABSTRACTOBJECTIVE: This study aims to explore the characteristics and functional changes of intestinal metabolites in children with obstructive sleep apnea hypopnea syndrome (OSAHS) aged 4-6 years old through metabolomic approaches, screen potential biomarkers and analyze their correlation with clinical indicators and preliminary discuss the roles of intestinal metabolites in the occurrence and development of OSAHS.METHODS: We collected fecal samples from 40 OSAHS children and 40 healthy controls aged 4-6 years and recorded some OSAHS-related clinical indicators. Fecal specimens were used to detect all metabolites through untargeted metabolomics.RESULTS: This study identified a total of 1164 intestinal metabolites and screened out 254 differential metabolites. In the OSAHS group, the relative content of 96 metabolites were higher than the control group, while the relative content of 158 metabolites were lower. The receiver operating characteristic curve analysis results showed that the area under the curve of 14 differential metabolites was greater than 0.8. The area under the curve of Formononetin is the highest, at 0.9100, with sensitivity and specificity of 82.5% and 90.0%, respectively, and is positively correlated with OAHI. The differential metabolite functions mainly include the metabolism of fatty acids and other lipid substances, cellular signaling, protein and amino acid related metabolism, disease-related functions, glucose metabolism, and vitamin metabolism.CONCLUSION: The intestinal metabolites and metabolic function of 4-to-6-year-old children with OSAHS altered. There was a correlation between differential metabolites and clinical indicators such as uric acid, hemoglobin, and blood sugar, which has potential diagnostic value for OSAHS screening.PMID:40091027 | DOI:10.1186/s12887-025-05561-4

BMJ Open Ophthalmol. 2025 Mar 15;10(1):e002149. doi: 10.1136/bmjophth-2025-002149.ABSTRACTBACKGROUND/AIMS: To investigate the association between plasma metabolomic profiles and treatment response after intravitreal anti-vascular endothelial growth factor (VEGF) injections in treatment-naïve neovascular age-related macular degeneration (nAMD).METHODS: This is part of a prospective longitudinal study that included patients with treatment-naïve nAMD who have undergone three loading intravitreal anti-VEGF injections. All patients underwent ophthalmological examinations including spectral domain optical coherence tomography (SD OCT). Fasting blood samples were collected at the time of study enrolment (not to first anti-VEGF injection) and metabolomic profiling was conducted using ultra-performance liquid chromatography-mass spectrometry. Treatment response was defined as no evidence of any subretinal and intraretinal fluid on SD OCT 4-6 weeks after the third injection. Multilevel mixed-effects linear modelling was used to assess associations between plasma metabolites and treatment response. Multiple comparisons were accounted for using the effective number of tests to explain 80% of the variance (ENT80), with a p value threshold of 0.0017.RESULTS: We included 131 eyes of 101 patients, and 69 patients (68.3%) were female. 51 eyes (38.9%) were treatment responders. Taurodeoxycholate (TDCA) was the only plasma metabolite significantly associated with treatment response (β=1.6, ENT80=0.001).CONCLUSION: In our study, TDCA was the most significant plasma metabolite associated with treatment response after three-loading dose of anti-VEGF therapy in patients with nAMD. Bile acids may have a beneficial impact on treatment response in nAMD through their neuroprotective property. Plasma metabolites may be used as biomarkers to predict responses to initial anti-VEGF therapy in patients with nAMD, providing a more individualised treatment plan.PMID:40090700 | DOI:10.1136/bmjophth-2025-002149

Toxicol Appl Pharmacol. 2025 Mar 14:117295. doi: 10.1016/j.taap.2025.117295. Online ahead of print.ABSTRACTTetrabromobisphenol A (TBBPA), a commonly utilized flame retardant, presents potential risks to both environmental and human health, with particular concern regarding its impact on embryonic development.This study employed zebrafish embryos as a model organism to investigate the comprehensive toxicological effects of TBBPA exposure, integrating metabolomics analysis with molecular and biochemical approaches. Embryos exposed to TBBPA concentrations ranging from 0.5 to 1.5 mg/L exhibited significant dose-dependent developmental abnormalities, including pericardial edema, yolk sac enlargement, and body axis curvature. At 96 h, we observed 50 % mortality at 1 mg/L. At 144 h of exposure to 0.1 mg/L TBBPA, automated behavioral analysis revealed significant changes in larval swimming patterns, characterized by reduced total distance moved, shortened active swimming time, impaired acceleration parameters, and abnormal spatial distribution. UHPLC-Q-TOF-MS-based metabolomics analysis revealed substantial perturbations in multiple biochemical pathways, particularly affecting neurotransmitter metabolism, energy homeostasis, and oxidative stress responses. TBBPA exposure significantly disrupted dopamine and serotonin metabolism, evidenced by altered enzyme expression and metabolite levels. Notable changes in oxidative stress markers, including GSH, MDA, and SOD, indicated significant cellular damage, while inflammatory responses showed dysregulation of both pro- and anti-inflammatory cytokines. Energy metabolism was comprehensively affected, with disruptions in glycolysis, TCA cycle, and amino acid metabolism pathways. The study identified key metabolic signatures of TBBPA toxicity and elucidated the interconnected mechanisms underlying its developmental impacts, providing valuable insights for environmental risk assessment and regulatory considerations. These findings emphasize the complex nature of TBBPA toxicity and highlight the need for careful evaluation of its environmental impact, particularly concerning early developmental exposure.PMID:40090624 | DOI:10.1016/j.taap.2025.117295

J Biol Chem. 2025 Mar 14:108409. doi: 10.1016/j.jbc.2025.108409. Online ahead of print.ABSTRACTPancreatic ductal adenocarcinoma (PDAC) is a highly aggressive form of pancreatic cancer with the worst prognosis. Treating PDAC poses significant challenges, as tumor cells adapt metabolic alterations to thrive in the hypoxic environment created by desmoplasia surrounding the tumor cells. p21-activated kinase (Pak1), a serine-threonine kinase is found to be upregulated in many solid tumors and promotes tumor progression via diverse signalling pathways. In this study, we focussed on exploring the role of Pak1 in mediating tumor cell metabolism. Deletion of the Pak1 gene reduced the tumorigenic potential of PDAC cells. Also, Pak1 regulated both glycolysis and mitochondrial respiration in PDAC cells, contributing to the Warburg phenomenon. Untargeted metabolomic analysis revealed that Pak1 was strongly associated with Pyruvate metabolism. Interestingly, we found that Pak1 interacted and phosphorylated Pyruvate dehydrogenase E1α (PDHA1) at Serine 152. This phosphorylation negatively regulates PDHA1 activity, implying the direct regulatory role of Pak1 in Pyruvate metabolism. Moreover, deleting the Pak1 gene altered the expression and activity of PDHA1 and LDHA, as both are involved in regulating the direction of pyruvate flux inside the cells. Our study demonstrated that Pak1 plays a significant role in PDAC metabolism and Warburg effect, partly by phosphorylating PDHA1.PMID:40090587 | DOI:10.1016/j.jbc.2025.108409

Cancer Lett. 2025 Mar 14:217633. doi: 10.1016/j.canlet.2025.217633. Online ahead of print.ABSTRACTThe Hedgehog Signaling Pathway plays an important role in cancer development and chemotherapy resistance. However, whether the pathway functions depend on the metabolic reprogramming of cancer cells has not been well studied. In this study, we found that the expression level of Gli1, a key transcription factor downstream of the Hedgehog Signaling Pathway, is significantly increased in patients with pancreatic cancer resistant to gemcitabine neoadjuvant chemotherapy. Through metabolomics analysis, we confirmed that Gli1 can promote the transformation of cancer cells from a glycolytic-dominated metabolic pattern to a unique metabolic pattern called "Pentose Phosphate Recycling". Transcriptome sequencing and in vitro experiments suggest that Gli1 promotes pentose phosphate recycling through transcriptional activation of key enzymes Phosphogluconate dehydrogenase (PGD) and Transketolase (TKT). The identified metabolic rerouting in oxidative and non-oxidative pentose phosphate pathway has important physiological roles in maximizing NADPH reduction and nucleotide synthesis. Therefore, the pentose phosphate cycle driven by Gli1 can resist gemcitabine-induced DNA damage by promoting pyrimidine synthesis and resist gemcitabine-induced ferroptosis by scavenging lipid Reactive Oxygen Species (Lipid ROS). Combining the Gli1 inhibitor GANT21 with gemcitabine exerts a maximal tumour suppressor effect by simultaneously promoting DNA damage and ferroptosis. Collectively, these results reveal that Gli1 drives chemotherapy resistance in cancer cells by inducing metabolic reprogramming, providing a novel target and therapeutic strategy for reversing chemotherapy resistance.PMID:40090571 | DOI:10.1016/j.canlet.2025.217633