PubMed

Gut Microbes. 2025 Dec;17(1):2505269. doi: 10.1080/19490976.2025.2505269. Epub 2025 May 14.ABSTRACTClostridioides difficile infection (CDI) has been recognized as a leading cause of healthcare-associated infections and a considerable threat to public health globally. Increasing evidence suggests that the gut microbiota plays a key role in the pathogenesis of CDI. The taxonomic composition and functional capacity of the gut microbiota associated with CDI have not been studied systematically. Here, we performed a comprehensive shotgun metagenomic sequencing in a well-characterized human cohort to reveal distinct patterns of gut microbiota and potential functional features associated with CDI. Fecal samples were collected from 104 inpatients, including : (1) patients with clinically significant diarrhea and positive nucleic acid amplification testing (NAAT) and received CDI treatment (CDI, n = 47); (2) patients with positive stool NAAT but without diarrhea (Carrier, n = 17); (3) patients with negative stool NAAT but with diarrhea (Diarrhea, n = 14); and (4) patients with negative stool NAAT and without diarrhea (Control, n = 26). Downstream statistical analyses (including alpha and beta diversity analysis, differential abundance analysis, correlation network analysis, and potential functional analysis) were then performed. The gut microbiota in the Control group showed higher Chao1 index (p < 0.05), while Shannon index at KEGG module level was higher in CDI than in Carrier and Control (p < 0.05). Beta diversity for species composition differed significantly between CDI vs Carrier/Control cohorts (p < 0.05). Microbial Linear discriminant analysis Effect Size and ANCOM analysis both identified 8 species (unclassified_f_Enterobacteriaceae, Veillonella_parvula, unclassified_g_Klebsiella and etc.) were enriched in CDI, Enterobacter_aerogenes was enriched in Diarrhea, Collinsella_aerofaciens, Collinsella_sp_4_8_47FAA, Collinsella_tanakaei and Collinsella_sp_CAG_166 were enriched in Control (LDA >3.0, adjusted p < 0.05). Correlation network complexity was higher in CDI with more negative correlations than in other three cohorts. Modules involved in iron complex transport system (M00240) was enriched in CDI, ABC-2 type transport system (M00254), aminoacyl-tRNA biosynthesis (M00359), histidine biosynthesis (M00026) and inosine monophosphate biosynthesis (M00048) were enriched in Carrier, ribosome (M00178 and M00179) was enriched in Diarrhea, fluoroquinolone resistance (M00729) and aminoacyl-tRNA biosynthesis (M00360) were enriched in Control (LDA > 2.5, adjusted p < 0.05). Resistance functions of acriflavine and glycylcycline were enriched in CDI, while resistance function of bacitracin was enriched in Carrier (LDA > 3.0, adjusted p < 0.05), and the contributions of phylum and species to resistance functions differed among the four groups. Our results reveal alterations of gut microbiota composition and potential functions among four groups of differential colonization/infection status of Clostridioides difficile. These findings support the potential roles of gut microbiota and their potential functions in the pathogenesis of CDI.PMID:40366862 | DOI:10.1080/19490976.2025.2505269

Methods Mol Biol. 2025;2916:17-24. doi: 10.1007/978-1-0716-4470-6_2.ABSTRACTAuxin plays a critical role in the inhibition of organ abscission. The changing of auxin gradient across the abscission zone (AZ) is the primary determinant of the abscission initiation and activation. To better understand the role of auxin, the distribution and content of auxin at different developmental stages of AZ need to be determined. This protocol provides a convenient and efficient procedure for precise localization of auxin in the petal AZ of rose (Rosa hybrida). It can be combined with plant hormone metabolomics to more accurately reflect changes in auxin during the abscission process. This method serves as a powerful tool for auxin detection and can be applied to broader plant hormone research.PMID:40366582 | DOI:10.1007/978-1-0716-4470-6_2

Mol Neurobiol. 2025 May 14. doi: 10.1007/s12035-025-05035-9. Online ahead of print.ABSTRACTThis study aims to identify the underlying mechanism by which melatonin protects neurons. Firstly, the inhibitory effect of melatonin on ferroptosis was verified by treating HT22 cells with melatonin, Erastin, and Ferrostatin-1. Secondly, transcriptomic and metabolomic analyses were performed. Melatonin-related hub genes were identified by differential gene expression analysis, and lipid metabolism-related critical signaling pathways and biological processes (BPs) were determined by gene set enrichment analysis (GSEA). Finally, the expression of hub genes was verified by quantitative real-time PCR (qRT-PCR) or Western Blot (WB), and the involvement of Tribble 3 (Trib3) in the regulation of lipid metabolism and ferroptosis by melatonin was confirmed by Cell Counting Kit 8 (CCK-8) assay, ROS analysis, and WB. Assay results showed that melatonin significantly increased Gpx4 activity, decreased ROS generation, and inhibited ferroptosis in HT22 cells. The hub gene Trib3 was obtained by transcriptomic analysis, and its expression was upregulated with Erastin treatment. Lipid metabolomic analysis suggested that the regulation of lipid metabolism by melatonin was associated with glycerophospholipids. In vitro experiments showed that Trib3 was regulated by the upstream factor Atf4, and the protein levels of Trib3 and Atf4 were significantly increased after Erastin treatment. However, melatonin can reduce the protein levels of Trib3 and Atf4, increase the survival rate of HT-22 cells and the activity of GPX4, and reduce the ROS content. Melatonin inhibits neuronal ferroptosis by affecting the Atf4/Trib3 axis via the modulation of lipid metabolism.PMID:40366559 | DOI:10.1007/s12035-025-05035-9

Stem Cell Rev Rep. 2025 May 14. doi: 10.1007/s12015-025-10889-6. Online ahead of print.ABSTRACTA primary therapeutic characteristic of mesenchymal stem/stromal cells (MSCs) is their immunomodulatory activity. Adipose-derived stem/stromal cells (ASCs) are an abundant and easily isolated source of MSCs shown to have high immunosuppressive activity, making them attractive for therapy. Understanding the heterogeneous immunomodulatory potential of ASCs within the stromal vascular fraction (SVF) of adipose tissue could better inform treatment strategies. In this study, we integrate single-cell RNA sequencing (scRNA seq) with bulk proteomics to characterize subpopulations of SVF-derived ASCs that are phenotypically similar to cytokine-licensed, cultured ASCs. To better define the licensing process, we present scRNA seq and bulk proteomics data of cultured (P2) ASCs exposed to inflammatory cytokines, showing enrichment of pathways related to inflammation and apoptosis that positively correlate to the cytokine-mediated, trajectory-derived pseudotime. Using the Scissor algorithm, we integrate the proteomics data with uncultured (P0) SVF scRNA seq data, identifying an ASC subpopulation that is phenotypically like the cytokine-stimulated ASCs (Scissor-positive). Interactome analysis identifies Scissor-positive ASCs as stress adaptive immune regulators that function through IL6 and broad SEMA4 interactions and higher Visfatin signaling, while Scissor-negative ASCs show strong signatures of ECM remodeling through FN1 and immunosuppression through THY1 and MIF signaling. Our multimodal, integrative approach enabled identification of previously unidentified, distinct ASC subpopulations with differing immunomodulatory phenotypes that are present in, and can potentially be selected from, P0 SVF ASCs.PMID:40366552 | DOI:10.1007/s12015-025-10889-6

Fish Physiol Biochem. 2025 May 14;51(3):96. doi: 10.1007/s10695-025-01507-w.ABSTRACTArtificial breeding and releasing can effectively restore fishery resources. However, it is important to note that released juvenile fish were highly susceptible to starvation during their adaptation to the natural environment. This study investigated the metabolomic changes in the liver of Onychostoma sima after 14 days using ultra-high pressure liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) analysis under starvation exposure. The experiment was divided into a control group (C Group) and a starvation group (S Group), with six biological replicates in each group and one fish per replicate. The results indicated significant changes in the starvation group compared to the control group, as demonstrated by the principal component analysis (PCA) score plots and orthogonal partial least squares discriminant analysis (OPLS-DA). The 297 differential metabolites screened were mainly involved in the metabolism of organic acids and derivatives, and lipids and lipid-like molecules. Furthermore, KEGG results revealed that differential metabolites were primarily enriched in 33 metabolic pathways. The majority of the amino acid metabolic pathways in the liver were significantly affected by starvation stress. Moreover, biosynthesis of amino acids, protein digestion and absorption, and mineral absorption were upregulated, while glycerophospholipid metabolism and the hedgehog signaling pathway were downregulated in response to energy demands during starvation. In conclusion, these findings provide physiological insights into the metabolism of juvenile O. sima under starvation stress, offering new perspectives for the optimization of fish proliferation and release technology.PMID:40366427 | DOI:10.1007/s10695-025-01507-w

Cancer Med. 2025 May;14(10):e70948. doi: 10.1002/cam4.70948.ABSTRACTBACKGROUND: Gastric cancer is one of the most prevalent malignancies of the digestive system and is associated with a poor prognosis, particularly in advanced metastatic stages, where the 5-year survival rate is significantly low.METHODS: Recent research has demonstrated that metabolic reprogramming-including alterations in glucose, lipid, and amino-acid metabolism-plays a critical role in both the development and progression of this disease. To gain deeper insights into these metabolic shifts, scientists have increasingly employed metabolomics, a non-invasive technique that detects and quantifies small molecules within cancerous tissues, thereby enhancing prognostic assessments.AIM: Analyzing the metabolic profiles of gastric-cancer tissues can reveal significant changes in key metabolic pathways, which may open new avenues for targeted therapies and ultimately improve patient outcomes.CONCLUSION: This article reviews recent advancements in the study of metabolic reprogramming in gastric cancer, aiming to identify potential therapeutic targets and offer new hope to patients.PMID:40365984 | DOI:10.1002/cam4.70948

Int J Mol Sci. 2025 May 6;26(9):4405. doi: 10.3390/ijms26094405.ABSTRACTThe global demand for animal protein presents significant challenges in the production of nutritionally rich foods, such as milk and meat. Traditionally, the quality of these products is assessed using physicochemical, microbiological, and sensory methods. Although effective, these techniques are constrained by time limiting their widespread application. Furthermore, growing concerns regarding sustainability, animal welfare, and transparency have driven the development of technologies to enhance the rapid and precise assessment of food quality. In this context, omics technologies have transformed the characterization of animal-origin food by providing in-depth molecular understanding of their composition and quality. These tools enable the identification of biomarkers, adulteration detection, optimization of nutritional profiles, and enhancement of authentication and traceability, facilitating the development of functional foods. Despite their potential, several barriers persist, including high implementation cost, the need for specialized infrastructure, and the complexity of integrating multi-omics data. The main aim of this review was to provide information on advances in the application of omics technologies in dairy and meat production systems and studies that use them in food quality, authentication, and sustainability. It also outlines opportunities in areas such as fraud prevention and functional product development to support the transition to safer, healthier, and more transparent food systems.PMID:40362642 | DOI:10.3390/ijms26094405

CNS Neurosci Ther. 2025 May;31(5):e70433. doi: 10.1111/cns.70433.ABSTRACTBACKGROUND: Stress is closely related to life, and it can also cause many mental disorders. However, there are significant sex differences in neuropsychiatric disorders associated with stress, particularly in depression, where the lifetime risk of depression in women is approximately twice that of men. However, the specific mechanism of this process has not been explained in detail.METHODS: Chronic restraint stress (CRS) + chronic and unpredictable mild stress (CUMS) was used to simulate social stress, and behavioral experiments, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, and metabolomics analysis of hippocampal and intestinal contents were performed.RESULTS: The results showed that stress induced anxiety-like behavior in female mice and depression-like behavior in male mice. Sex differences in behavior may be related to monoamine neurotransmitters, hyperactivity of HPA axis, inflammatory factors, gut microbiota, and brain-gut metabolism. It is worth noting that stress caused opposite trends in DA (dopamine) levels, abundance of f-lactobaciliaceae, and levels of metabolites (1, 2-distearoyl-SN-glycero-3-phosphocholine) and PC(20:5(5Z,8Z,11Z,14Z,17Z)/20:1(11Z)) in male and female mice.CONCLUSION: The difference in neurotransmitter levels, the disorder of gut microbiota, and the abnormal brain and gut metabolism may lead to the gender difference in stress behavior.PMID:40365748 | DOI:10.1111/cns.70433

New Phytol. 2025 May 14. doi: 10.1111/nph.70217. Online ahead of print.ABSTRACT'Pollination syndromes', where convergent floral signals reflect selection from a functional pollinator group, are often characterized by physical features, yet floral rewards such as nectar may also reflect selection from pollinators. We asked whether nectar chemistry shows evidence of convergence across functional pollinator groups, i.e. a 'chemical pollination syndrome'. We used untargeted metabolomics to compare nectar and leaf chemical profiles across 19 bee- and bird-syndrome species, focusing on Salvia spp. (Lamiaceae), selected to maximize switching events between pollination syndromes. We found that independently derived bird-syndrome nectar showed convergence on nectar traits distinct from bee-syndrome nectar, primarily driven by the composition and concentration of alkaloid profiles. We did not find evidence for 'passive leaking' of nectar compounds from leaves since metabolite abundances were uncorrelated across tissues and many nectar metabolites were not present in leaves. Nectar and leaf metabolomes were strongly decoupled from phylogenetic relationships within Salvia. These results suggest that functional pollinator groups may drive the evolution of floral reward chemistry, consistent with our 'chemical pollination syndrome' hypothesis and indicative of selection by pollinators, but we also consider alternative explanations. In addition, our results support the notion that nectar chemistry can be decoupled from that of other tissues.PMID:40365744 | DOI:10.1111/nph.70217

CNS Neurosci Ther. 2025 May;31(5):e70442. doi: 10.1111/cns.70442.ABSTRACTOBJECTIVES: 7,8-Dihydroxyflavone (7,8-DHF) activates the TrkB receptor, offering neuroprotection, yet its pharmacological limitations restrict its safe and effective delivery to the eye and brain, impeding clinical translation. This study explores the protective effects of oral 7,8-DHF on retinal ganglion cells (RGCs) by inhibiting ferroptosis and investigates the involvement of the gut-retina axis, particularly the Indoleacrylic acid (IDA)-AhR-ALDH1A3-FSP1 pathway, with potential clinical implications.METHODS: To evaluate the neuroprotective effects of oral 7,8-DHF, retinal 3D cultures were used for axon regeneration and GCL cell apoptosis, and ONC models for RGC survival and electrophysiology. Mechanisms were investigated by assessing ferroptosis-related proteins via Western blotting, screening differential metabolites in PC12 cells, analyzing mitochondrial changes with TEM, evaluating gut microbiota shifts, and examining metabolite changes in retina and feces.RESULTS: Oral 7,8-DHF enhanced RGC survival and retinal function in the ONC model by inhibiting ferroptosis, independent of TrkB activation. This effect was blocked by antibiotics and AHR, ALDH1A3, and FSP1 inhibitors. Metabolomics showed increased IDA in retina and feces, with IDA inhibiting ferroptosis in PC12 cells and promoting axonal regeneration in retinal explants. Western blot revealed upregulation of nAhR and ALDH1A3, while non-FSP1 ferroptosis proteins were unaffected. 7,8-DHF also altered gut microbiota, increasing Parasutterella, which correlated with higher IDA levels.CONCLUSIONS: 7,8-DHF regulates the gut microbiota to increase IDA levels in the intestine, which subsequently leads to the accumulation of IDA in the retina. This activates the AhR-ALDH1A3-FSP1 axis in the retina, thereby inhibiting retinal ferroptosis and exerting neuroprotective effects.PMID:40365730 | DOI:10.1111/cns.70442

Front Plant Sci. 2025 Apr 29;16:1557190. doi: 10.3389/fpls.2025.1557190. eCollection 2025.ABSTRACTThis study aimed to investigate the differences in volatile compound composition and metabolites in cigar tobacco leaves from different regions of Yunnan. Cigar tobacco leaves from various regions and varieties in Yunnan were analysed using gas chromatography-ion mobility spectrometry and non-targeted metabolomics techniques. Results showed that 109 volatile compounds, including 26 esters, 17 aldehydes, 14 alcohols, 14 ketones, 9 olefins, 5 pyrazines, 4 ethers, 4 acids and 16 others, were identified in cigar tobacco leaves. Through GC-IMS analysis of volatile compounds in cigar tobacco from 10 regions, 1-methylethyl acetate, diethyl acetal, butanal, 1-hexanol, pyridine, and toluene were identified as common compounds with consistently high content across all regions. For regional characteristics, BS-Y1-1 is featured by high levels of 2,3-diethyl-6-methylpyrazine and phenylacetaldehyde; PE-Y2 shows the highest content of 3-methyl-1-pentanol; and WS-Y38 is characterised by significantly high levels of butan-2-one. These differences reflect the uniqueness of volatile components in cigar tobacco from different producing areas. The volatile compounds in Yunnan cigar tobacco leaves were greatly influenced by the origin and species, with cigar tobacco leaves from the Baoshan region differing from those in other regions. According to the Kyoto Encyclopedia of Genes and Genomes enrichment analysis, amino acid metabolism, nucleotide metabolism and glyoxylate and dicarboxylate metabolism were the main metabolic pathways, and their metabolites contributed to the formation of flavour in Yunnan cigar tobacco leaves.PMID:40365566 | PMC:PMC12069380 | DOI:10.3389/fpls.2025.1557190

Front Cell Infect Microbiol. 2025 Apr 29;15:1597214. doi: 10.3389/fcimb.2025.1597214. eCollection 2025.NO ABSTRACTPMID:40365537 | PMC:PMC12069356 | DOI:10.3389/fcimb.2025.1597214

Front Transplant. 2025 Apr 29;4:1572852. doi: 10.3389/frtra.2025.1572852. eCollection 2025.ABSTRACTBACKGROUND: Renal dysfunction is a common and serious complication in patients with end-stage liver diseases. While some patients recover renal function after liver transplantation (LT), others do not. Additionally, patients with normal kidney function (Normal-KF) before LT may develop post-transplant renal dysfunction. Early identification of patients at risk for impaired kidney function (Impaired-KF) post-LT is critical to improving outcomes. This study integrated metabolomic and proteomic analyses to investigate molecular profiles distinguishing Normal-KF from Impaired-KF post-LT.METHODS: Nine LT recipients were classified into Normal-KF (n = 5) and Impaired-KF (n = 4) groups. One additional recipient with pre-transplant renal function impairment who recovered renal function after LT, was analyzed separately. Serum samples were collected at 2- and 5-weeks post-LT. The metabolomic and proteomic profiles were assessed by untargeted liquid chromatography-tandem mass spectrometry.RESULTS: Metabolomic analysis identified 29 significantly altered metabolites between Normal-KF and Impaired-KF (fold change > 2, p < 0.05). Proteomic analysis revealed 45 differentially expressed proteins (fold change > 1.25, p < 0.05). For the recovered patient, the metabolomic profile closely resembled Normal-KF, whereas the proteomic profile remained aligned with Impaired-KF at both 14- and 35-days post-LT. From week 2 to week 5, both the metabolomic and proteomic profiles of the recovered patient showed trends toward the Normal-KF.CONCLUSION: This study revealed distinct metabolomic and proteomic signatures associated with renal dysfunction post-LT. Proteomic profiles indicated a delayed recovery compared to metabolomic profiles, suggesting a dynamic and muti-layered renal recovery process. Further research is warranted to elucidate the functional implications of the differential proteins and metabolites for improved monitoring and therapeutic strategies.PMID:40365354 | PMC:PMC12069452 | DOI:10.3389/frtra.2025.1572852

Theranostics. 2025 Apr 28;15(12):5910-5930. doi: 10.7150/thno.110207. eCollection 2025.ABSTRACTRationale: Adipose tissue buffers dietary lipids to maintain postprandial lipid homeostasis. Adipose tissue macrophages (ATMs) mediate the phagocytosis of postprandial lipids from the exogenous diet, generating high-density lipoprotein (HDL) particles that facilitate lipid circulation and excretion. However, the underlying mechanisms remain poorly understood. This study investigates the effects of esculetin, a coumarin compound, on postprandial cholesterol circulation and excretion following a high-fat meal. Methods: Mice were fed a lipid-rich meal for three days to assess the effects of esculetin on postprandial lipid circulation, using serum lipid profiling and metabolomics analysis. Epididymal white adipose tissue (eWAT) removal and flow cytometry were performed to analyze ATMs and confirm their role in mediating esculetin's effects on postprandial lipemia. Epigenetic profiling, transcriptome analysis, chromatin immunoprecipitation, and Terahertz chemical microscopy were employed to elucidate the molecular targets and mechanisms of esculetin. Results: Esculetin significantly elevates postprandial HDL cholesterol levels to values comparable to pitavastatin and modifies serum metabolites involved in bile-mediated cholesterol excretion, leading to increased bile acid concentrations in the bile. This effect is mediated by an increased ratio and phagocytic activity of a subset of ATMs expressing the scavenger receptor CD36, as eWAT removal and CD36 blockade inhibit this response. Furthermore, esculetin enhances the uptake of oxidized LDL via CD36, as demonstrated in cultured macrophages, and induces epigenetic changes controlled by the key transcription factor C/EBPβ, accompanied by increased C/EBPβ binding to the Cd36 promoter. A direct interaction between esculetin and C/EBPβ was observed using Terahertz chemical microscopy. Additionally, the activation of C/EBPβ by esculetin in ATMs was confirmed in vivo. Conclusion: Esculetin accelerates postprandial lipid circulation by binding to C/EBPβ and enhancing CD36-dependent phagocytosis in ATMs.PMID:40365299 | PMC:PMC12068311 | DOI:10.7150/thno.110207

Theranostics. 2025 Apr 22;15(12):5826-5845. doi: 10.7150/thno.108817. eCollection 2025.ABSTRACTBackground: Glutathione peroxidase 4 (GPX4), an important factor regulating redox homeostasis, plays an important role in tumor microenvironment and progression. However, the role of GPX4 in gastric cancer (GC) is unclear. Methods: Spectral flow cytometry and multiplex immunohistochemistry were employed to assess the correlation between GPX4 expression and immune cell infiltration. Metabolomics analysis of conditioned media from GPX4 knockdown NUGC3 cells identified metabolic alterations. Additionally, both in vitro and in vivo functional studies were conducted to elucidate the mechanistic role of GPX4 in regulating the tumor microenvironment and progression. Results: Knockdown of GPX4 in GC cells inhibited tumor growth, enhanced CD8+ T cell infiltration, and suppressed the polarization of tumor-associated macrophages (TAMs) toward the pro-tumor M2 phenotype. Multiplex immunohistochemistry revealed a positive correlation between GPX4 expression and M2 macrophage infiltration in clinical samples from patients with GC. Metabolomics revealed that GPX4 knockdown regulate kynurenine metabolism pathway. Furthermore, mechanistic studies reveal that GPX4 silencing elevates lipid peroxidation, triggering the conversion of KYNU ubiquitin chain modifications from K48 to K63. Such ubiquitination remodeling stabilizes KYNU expression (a key kynurenine-metabolizing enzyme), reduces kynurenine accumulation, and ultimately reprograms TAM polarization to enhance antitumor immunity. We also identified that the K96 and K163 sites are important for KYNU's modification by K48 and K63 ubiquitin chains. Conclusion: Our study not only affirm the role of GPx4 in GC progression but also highlight it as a promising target for reshaping the immune microenvironment.PMID:40365295 | PMC:PMC12068284 | DOI:10.7150/thno.108817

Front Physiol. 2025 Apr 29;16:1524939. doi: 10.3389/fphys.2025.1524939. eCollection 2025.ABSTRACTINTRODUCTION: Amino acids are fundamental in several metabolic processes, and their levels can reflect metabolism impairments that contribute to obesity and related diseases. Our objective was to identify a urinary amino acid fingerprint in obese and overweight children in prepuberty and to correlate this profile with cardiometabolic alterations.METHODS: The study included 110 children, boys and girls aged 9-10 years, they were classified according to their BMI-for-age (Body Mass Index for age) into three groups: normal weight (NW) (n = 45), overweight (OW) (n = 21), and obese (OB) (n = 44). The 12-h urine samples were analyzed by LC-MS/MS to quantify 47 amino acids using the Amino Acids Analysis Kit (Zivak®, Turkey), values were corrected by creatinine concentration. Anthropometric measurements, cardiovascular parameters, and biochemical profiles were assessed following standard protocols.RESULTS: When compared to NW, anthropometric measures, systolic and diastolic blood pressure, and serum uric acid levels were progressively elevated in the OW and OB groups. The OB group was characterized by elevated alpha-aminoadipic acid, asparagine, cystathionine, 1-methyl-histidine, serine, tryptophan, phenylalanine, and tyrosine. In contrast, the OW group presented the most expressive levels of glutamine, alpha-diaminopimelic, and sarcosine.DISCUSSION: Our findings indicate that obese and overweight children exhibit a particular urinary amino acid fingerprint which is similar to that reported in studies with plasma. The altered amino acids, particularly tyrosine, are frequently associated with impairments in glucose homeostasis, insulin resistance, and diabetes mellitus type 2. Potential mechanisms for increasing the levels of these amino acids in excess of weight may include enhanced protein degradation and impaired oxidative metabolism.PMID:40365082 | PMC:PMC12069889 | DOI:10.3389/fphys.2025.1524939

Therap Adv Gastroenterol. 2025 May 12;18:17562848251338647. doi: 10.1177/17562848251338647. eCollection 2025.ABSTRACTBACKGROUND: The period prior to the diagnosis of inflammatory bowel disease (IBD), defined as the preclinical phase, has emerged as a potential target for disease modification strategies. Despite the relevance of an early diagnosis to the prognosis of the disease, only a limited number of patients are diagnosed during this window of opportunity.OBJECTIVES: To determine the risk of developing symptoms after an incidental diagnosis of IBD and to describe the clinical, genetic, and immunological characteristics of IBD during its preclinical phase.DESIGN: This study protocol describes a prospective, multicenter cohort study in which incidental (i.e., asymptomatic) IBD within the colorectal cancer screening program will be characterized from a clinical and multi-omic perspective and compared with symptomatic patients and healthy non-IBD controls.METHODS: Samples from blood, urine, stool, and intestinal endoscopic biopsies will be obtained at baseline. A second sample set will be obtained after 52 weeks from those who remain asymptomatic; samples will also be obtained in those with new-onset symptoms. Medical treatment will be prescribed in all patients following current guidelines. Follow-up visits will be performed every 6 months for 10 years, and all new-onset symptoms, changes in disease behavior, extraintestinal manifestations, IBD-related medical therapies, or surgeries will be recorded. Two control cohorts will be included: one including recently diagnosed symptomatic IBD patients (<3 months), and another with healthy non-IBD controls after a normal ileocolonoscopy, in whom samples will be obtained at baseline. Samples from patients and controls will undergo genetic, proteomic, transcriptomic, single-cell RNA sequencing, metabolomic, and microbiome analyses, and integration of data between the different omic perspectives will also be performed. The study has been approved by the Basque Country Ethics Committee (PI2021116).CONCLUSION: EARLY will generate a unique dataset addressing a previously unexplored area of IBD, with the final aim of describing the prognosis of patients from its earlier phases on the disease and integrating clinical and omic data into useful tools for the long-term prediction of disease outcomes.TRIAL REGISTRATION: NCT05698745.PMID:40365077 | PMC:PMC12069952 | DOI:10.1177/17562848251338647

Angew Chem Int Ed Engl. 2025 May 14:e202425303. doi: 10.1002/anie.202425303. Online ahead of print.ABSTRACTAndrographolide is a prominent labdane diterpenoid extracted from Andrographis paniculata, celebrated for its exceptional anti-inflammatory properties. Commercial production of andrographolide relies exclusively on extraction from plant resources. Although the scaffold of andrographolide referring to ent-copalol has previously been biosynthesized, further oxidative modifications remain elusive. In this study, by taking an integrated analysis of transcriptomes and metabolomes approach, we were able to identify four cytochrome P450 enzymes constituting the minimal set of andrographolide biosynthetic genes. Specifically, ApCYP71D587 catalyzes the conversion of ent-copalol to 19-hydroxy-ent-copalol. Subsequently, ApCYP71BE50 mediates the formation of the lactone ring, ultimately yielding andrograpanin. Then ApCYP706U5 accomplishes the third step by mediating the C-3 hydroxylation reaction, thereby allowing the formation of 14-deoxyandrographolide. Ultimately, ApCYP72F1 completes the biosynthetic generation of andrographolide with C-14 hydroxylation of the lactone and rearrangement of the olefin bond. In addition, co-expression of the minimal gene set in N. benthamiana engineered to produce ent-copalol feasibly produces andrographolide, thus establishing an innovative metabolic engineering strategy to produce this medicine of historical importance, circumventing the need for plant extraction.PMID:40364767 | DOI:10.1002/anie.202425303

J Agric Food Chem. 2025 May 14. doi: 10.1021/acs.jafc.4c10847. Online ahead of print.ABSTRACTMaternal obesity significantly increases the risk of adverse outcomes for the mother and fetus. Fermented wheat germ (FWG) has demonstrated the potential to improve metabolic disorders, yet its effects have not been explored in maternal obesity models. This study investigated the ameliorating impact of FWG in rats with maternal obesity, focusing on its mechanisms through biochemical, gut microbiome, and serum metabolomics analysis. The results demonstrated that FWG was more effective than wheat germ in reducing body weight gain and fat accumulation, improving glycolipid metabolism disorders, and alleviating inflammation. Specifically, FWG modulated the composition of gut microbiota by fostering the growth of beneficial bacteria (e.g., Corynebacterium) while suppressing genera associated with maternal obesity (e.g., Blautia, Akkermansia, Dorea_A, and Faecousia). Furthermore, FWG modified high-fat diet-induced metabolites, primarily affecting pyrimidine metabolism and amino acid metabolism. These findings suggest that FWG may serve as a promising dietary intervention for mitigating maternal obesity and improving pregnancy outcomes.PMID:40364743 | DOI:10.1021/acs.jafc.4c10847

Clin Respir J. 2025 May;19(5):e70083. doi: 10.1111/crj.70083.ABSTRACTINTRODUCTION: Previous observational studies have suggested a potential association between smoking exposure and influenza infection risk. However, the impact of different smoke exposure statuses on susceptibility to influenza infection remains insufficiently explored. This study employs Mendelian randomization analysis to investigate the causal relationship between smoking exposure statuses, including current tobacco use, household smoking exposure, past smoking history, and the risk of influenza infection.METHODS: The summary-level data for this study were obtained from the FinnGen Consortium R11 and Neale Lab, both outcomes and exposures. To ensure robust results, we employed multiplicative random-effects inverse variance weighting, MR-Egger, and weighted median (WM) methods to analyze single-nucleotide polymorphisms (SNPs). We also conducted Cochran's Q test, MR-PRESSO, and the MR-Egger intercept test to assess heterogeneity and horizontal pleiotropy, ensuring accurate and reliable findings.RESULTS: Our analysis demonstrated that elevated exposure to current tobacco smoking causally increased the risk of influenza infection, with (OR = 2.032, 95% CI 1.672-2.538, p < 0.001) or without pneumonia (OR = 2.081, 95% CI 1.824-2.338, p = 0.015). No reverse causal relationship was found, and no bidirectional effects were observed for past smoking (OR = 1.108, 95% CI 0.543-2.258, p = 0.779) or household exposure (OR = 1.127, 95% CI -0.209-2.462, p = 0.939).CONCLUSION: This analysis identified a significant causal association between current tobacco smoking and increased risk of influenza infection. However, no significant association was observed for other smoking exposures (e.g., former or household smoking). These findings emphasized the importance of considering different types of smoking exposure in clinical influenza prevention and treatment strategies.PMID:40364530 | DOI:10.1111/crj.70083