Integrative Molecular Phenotyping
INTEGRATIVE MOLECULAR
PHENOTYPING
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY
DEPARTMENT OF MEDICAL
BIOCHEMISTRY AND BIOPHYSICS
WHEELOCK LABORATORY

PubMed

Butyrate improves testicular spermatogenic dysfunction induced by a high-fat diet

Mon, 14/04/2025 - 12:00
Transl Androl Urol. 2025 Mar 30;14(3):627-636. doi: 10.21037/tau-2024-660. Epub 2025 Mar 26.ABSTRACTBACKGROUND: Obesity is closely associated with low male fertility and decreased sperm quality. Obesity is accompanied by an ecological imbalance in the gut microbiota, so it is of great significance to intervene in male infertility caused by obesity from the perspective of gut microbiota metabolites. This study aimed to evaluate the efficacy of butyrate in ameliorating obesity-induced spermatogenic dysfunction and to explore the potential molecular mechanisms.METHODS: This study explored the role of butyrate in recovering the dysfunctions of spermatogenesis caused by obesity by inducing an obese model of male mice with a high-fat diet (HFD). The effects of HFD and butyrate on testicular function were explored based on metabolomics.RESULTS: The results of the study showed that HFD caused a decrease in sperm count, a decrease in sperm motility, and an increase in sperm malformation rate in mice. After adding butyrate to the HFD, the various sperm indicators of mice were significantly improved. Through the analysis of metabolomics data from mouse testes, this study found that an HFD significantly altered the metabolic status of mice testes, involving multiple metabolic pathways. However, after adding butyrate, some metabolic characteristics tended to be similar to those of normal diet mice, and the steroid biosynthesis and primary bile acid biosynthesis pathways were significantly improved.CONCLUSIONS: This study clarified the effect of butyrate on improving sperm quality, providing experimental evidence for the treatment of obesity-induced abnormal spermatogenesis with butyrate.PMID:40226081 | PMC:PMC11986523 | DOI:10.21037/tau-2024-660

Discovery of biological markers for schizophrenia based on metabolomics: a systematic review

Mon, 14/04/2025 - 12:00
Front Psychiatry. 2025 Mar 28;16:1540260. doi: 10.3389/fpsyt.2025.1540260. eCollection 2025.ABSTRACTINTRODUCTION AND METHODS: To discover biomarkers for schizophrenia (SCZ) at the metabolomics level, we registered this systematic review (CRD42024572133 (https://www.crd.york.ac.uk/PROSPERO/home)) including 56 qualified articles, and we identified the characteristics of metabolites, metabolite combinations, and metabolic pathways associated with SCZ.RESULTS: Our findings showed that decreased arachidonic acid, arginine, and aspartate levels, and the increased levels of glucose 6-phosphate and glycylglycine were associated with the onset of SCZ. Metabolites such as carnitine and methionine sulfoxide not only helped to identify SCZ in Miao patients, but also were different between Miao patients and Han patients. The decrease in benzoic acid and betaine and the increase in creatine were the notable metabolic characteristics of first-episode schizophrenia (FESCZ). The metabolite combination formed by metabolites such as methylamine, dimethylamine and other metabolites had the best diagnostic effect. Arginine and proline metabolism and arginine biosynthesis had a clear advantage in identifying SCZ and acute SCZ. Butanoate metabolism played an important role in identifying SCZ, toxoplasma infection and SCZ comorbidity. Biosynthesis of unsaturated fatty acids was also significantly enriched in the diagnosis and treatment of SCZ.DISCUSSION: This study summarizes the current progress in clinical metabolomic research related to SCZ, deepens understanding of the pathogenesis of SCZ, and lays a foundation for subsequent research on SCZ-related metabolites.SYSTEMATIC REVIEW REGISTRATION: https://www.crd.york.ac.uk/PROSPERO/home, identifier CRD42024572133.PMID:40225847 | PMC:PMC11985778 | DOI:10.3389/fpsyt.2025.1540260

Periodic dietary restriction of animal products induces metabolic reprogramming in humans with effects on cardiometabolic health

Mon, 14/04/2025 - 12:00
NPJ Metab Health Dis. 2025;3(1):14. doi: 10.1038/s44324-025-00057-2. Epub 2025 Apr 9.ABSTRACTDietary interventions constitute powerful approaches for disease prevention and treatment. However, the molecular mechanisms through which diet affects health remain underexplored in humans. Here, we compare plasma metabolomic and proteomic profiles between dietary states for a unique group of individuals who alternate between omnivory and restriction of animal products for religious reasons. We find that short-term restriction drives reductions in levels of lipid classes and of branched-chain amino acids, not detected in a control group of individuals, and results in metabolic profiles associated with decreased risk for all-cause mortality. We show that 23% of proteins whose levels are affected by dietary restriction are druggable targets and reveal that pro-longevity hormone FGF21 and seven additional proteins (FOLR2, SUMF2, HAVCR1, PLA2G1B, OXT, SPP1, HPGDS) display the greatest magnitude of change. Through Mendelian randomization we demonstrate potentially causal effects of FGF21 and HAVCR1 on risk for type 2 diabetes, of HPGDS on BMI, and of OXT on risk for lacunar stroke. Collectively, we find that restriction-associated reprogramming improves metabolic health and emphasise high-value targets for pharmacological intervention.PMID:40225784 | PMC:PMC11981922 | DOI:10.1038/s44324-025-00057-2

Effects of Chenpi Jiaosu on serum metabolites and intestinal microflora in a dyslipidemia population: a randomized controlled pilot trial

Mon, 14/04/2025 - 12:00
Front Endocrinol (Lausanne). 2025 Mar 28;16:1552117. doi: 10.3389/fendo.2025.1552117. eCollection 2025.ABSTRACTINTRODUCTION: Dyslipidemia is a critical risk factor for atherosclerosis and cardiovascular/cerebrovascular events, necessitating effective long-term management. However, conventional lipid-lowering drugs such as statins and fibrates are limited by adverse effects, including hepatotoxicity and myopathy, which restrict their prolonged use. Traditional Chinese medicine (TCM) and natural health products offer potential alternatives with multi-target mechanisms and improved safety profiles. Tangerine Peel Enzyme Drink (CPJS), a fermented health product derived from tangerine peel, has demonstrated lipid-modulating properties. This study aimed to evaluate the efficacy and safety of CPJS in improving dyslipidemia and explore its underlying metabolic and microbiological mechanisms.METHODS: A randomized, double-blind, parallel-controlled clinical trial was conducted with 72 participants (55 completers). Participants were divided into CPJS and control groups, receiving an 8-week intervention. Primary outcomes included changes in body weight and serum triglycerides (TG), while safety was assessed via liver/kidney function, creatine kinase, blood, and urine tests. Serum metabolomics (93 differential metabolites identified) and intestinal microbiota analysis were performed to elucidate metabolic pathways and microbial shifts. KEGG enrichment analysis mapped metabolites to biological pathways, such as lipid and amino acid metabolism.RESULTS: The CPJS group exhibited significant reductions in body weight and TG levels post-intervention (p < 0.05), with no adverse effects observed in safety biomarkers. Metabolomic profiling revealed alterations in fatty acyl, glycerophospholipid, and organic acid metabolites, indicating CPJS modulates lipid metabolism and energy homeostasis. KEGG analysis linked these changes to pathways including triglyceride degradation and amino acid metabolism. Additionally, CPJS increased specific gut microbial taxa associated with lipid regulation, suggesting a microbiome-mediated mechanism.DISCUSSION: CPJS demonstrates efficacy in improving dyslipidemia through dual mechanisms: direct modulation of triglyceride metabolism and indirect regulation via gut microbiota. Its safety profile aligns with findings from natural products like Cyclocarya paliurus and tempeh, which mitigate lipid abnormalities without hepatotoxicity. The multi-target action of CPJS mirrors TCM principles, where compounds like quercetin and flavonoids in CPJS may synergistically inhibit cholesterol synthesis and enhance lipid clearance. However, further research is needed to isolate active components and validate microbial contributions. Compared to synthetic drugs, CPJS offers a safer adjunct therapy, addressing limitations of current pharmacotherapies. Future studies should explore dose-response relationships and long-term outcomes in diverse populations.PMID:40225325 | PMC:PMC11985429 | DOI:10.3389/fendo.2025.1552117

Linalool exhibit antimicrobial ability against <em>Elizabethkingia miricola</em> by disrupting cellular and metabolic functions

Mon, 14/04/2025 - 12:00
Curr Res Microb Sci. 2025 Mar 23;8:100380. doi: 10.1016/j.crmicr.2025.100380. eCollection 2025.ABSTRACTElizabethkingia miricola is a gram-negative bacillus, a life-threatening pathogen in humans and animals. Linalool, a naturally occurring monoterpene alcohol found in plant volatile oils, exhibits highly effective antibacterial properties. This study investigated the antibacterial activity and mechanism of linalool against E. miricola. Initially, linalool showed potent antibacterial activity against E. miricola, with inhibition zone (ZOI), MIC, and MBC values of 36.41 ± 1.23 mm, 0.125 % (v/v, 1.0775 mg/mL), and 0.125 % (v/v, 1.0775 mg/mL), respectively. Secondly, it was observed by electron microscopy that linalool caused crumpling, depression, and size reduction of the cells. Linalool affected cell membrane integrity, causing membrane damage and rupture. Thirdly, transcriptome analysis suggested that linalool affected C5-branched-chain dicarboxylic acid metabolism and the biosynthesis of valine, leucine, and isoleucine, result in increased energy production to linalool stress. Linalool disrupted cell division and RNA function in E. miricola, and the cells responded to linalool-induced oxidative damage by up-regulating the expression of msrB and katG genes. Fourthly, metabolome analysis revealed an increase in metabolites related to the glycerophospholipid metabolic pathway and NADP content in E. miricola, which may be a metabolic response to linalool stress. Taken together, these findings provide a theoretical basis for the antibacterial mechanism of linalool and suggest potential applications for preventing E. miricola infections.PMID:40225044 | PMC:PMC11986607 | DOI:10.1016/j.crmicr.2025.100380

Wheat seeds exposed to heat during formation can germinate at high temperatures

Mon, 14/04/2025 - 12:00
Front Plant Sci. 2025 Mar 28;16:1539926. doi: 10.3389/fpls.2025.1539926. eCollection 2025.ABSTRACTA capacity for reliable germination under elevated temperatures is a crucial factor in maintaining the stability of bread wheat (Triticum aestivum) yields in the context of climate change. Although the environment of the parent plant during growth is a known factor affecting seed germinability, the effect of this environment on the heat tolerance of wheat seeds has not been investigated in detail. To investigate the effect of exposure to high temperatures during growth, plants were exposed to 38°C at various growth stages. In germination test, seeds exposed to heat during their development had better heat germinability than the control. On the other hand, high temperatures before the seed development stage resulted in a lower temperature germinability compared to the control. To identify critical factors that altered heat germinability, we analyzed heat shock protein expression, fatty acid composition, and metabolite profiles. High-temperature treatment during seed formation increased the expression of heat shock proteins and reduced the degree of unsaturation of fatty acids in the seeds, which may enhance the ability of seeds to survive and germinate at high temperatures. There was a significant treatment effect on the overall metabolite content of the seeds. PLS regression analysis using the germination test results revealed that taurine, thymidine, beta-alanine, sinapic acid, and deoxyguanosine contributed significantly to germination rate. These findings suggest that the combined influence of these metabolites may play a role in acquiring seed germinability under high-temperature conditions during the growth period of the parent plants. These findings suggest potential components of a molecular mechanism in bread wheat that is triggered by high temperature during seed development and results in the acquisition of heat germinability.PMID:40225031 | PMC:PMC11985767 | DOI:10.3389/fpls.2025.1539926

Multidimensional evaluation of quality differences for Dendrobium officinale stems grown under different cultivation environments based on widely targeted metabolomics, network pharmacology, molecular docking, and cell experiments

Mon, 14/04/2025 - 12:00
Front Plant Sci. 2025 Mar 28;16:1501545. doi: 10.3389/fpls.2025.1501545. eCollection 2025.ABSTRACTINTRODUCTION: Dendrobium officinale is an endangered perennial epiphytic herbaceous plant. In the Chinese Pharmacopoeia, the dried stems of D. officinale are used medicinally and are commonly utilized as a medicinal and food homologous product. Notable variations in the quality of D. officinale stems are observed across different cultivation environments; however, the underlying mechanisms remain unclear.METHODS: Metabolites in D. officinale stems grown in stone epiphytic, tree epiphytic, and greenhouse environments were identified using UPLC-MS/MS-based widely targeted metabolomics. Differential metabolites from stems grown in different cultivation environments were selected for studies on quality differences. Network pharmacology was employed to investigate the core targets of these differential metabolites, and molecular docking validation was conducted with these metabolites to identify quality markers. Finally, a combination of network pharmacology and in vitro experimental results was used to explore the reasons behind the differences in therapeutic effects of D. officinale stems grown in various cultivation environments.RESULTS: A total of 1929 primary and secondary metabolites were identified. Compared to the tree epiphytic and greenhouse environments, 58 primary and secondary metabolites were up-regulated in the stone epiphytic environment. Among these, 7 amino acids and their derivatives were exclusively found as up-regulated primary metabolites, while 18 flavonoids constituted the main up-regulated secondary metabolites. The binding affinities of the 18 flavonoids to the core targets (MAOA and TNF) were superior to those of other up-regulated metabolites, and they can be utilized in quality difference studies, particularly nicotiflorin and isoquercitrin. Stems grown in the stone epiphytic environment showed a superior protective effect on chronic atrophic gastritis cells compared to the other two environments. This was associated with increased binding of differential metabolites to targets such as MAOA and TNF and decreased binding to targets such as SRC and PTGS2.DISCUSSION: The composition and content of metabolites in D. officinale stems are influenced by the cultivation environment, which in turn affects the therapeutic effects of the stems. The change of the target preference could be the reason for the difference in drug efficacy. This study introduces a novel approach for distinguishing the quality of D. officinale stems grown under different cultivation environments and exploring the variations in their therapeutic effects.PMID:40225029 | PMC:PMC11985527 | DOI:10.3389/fpls.2025.1501545

Effects of <em>feruloyl-CoA 6'-hydroxylase 1</em> overexpression on lignin and cell wall characteristics in transgenic hybrid aspen

Mon, 14/04/2025 - 12:00
Front Plant Sci. 2025 Mar 28;16:1543168. doi: 10.3389/fpls.2025.1543168. eCollection 2025.ABSTRACTIn plant cell walls, lignin, cellulose, and the hemicelluloses form intricate three-dimensional structures. Owing to its complexity, lignin often acts as a bottleneck for the efficient utilization of polysaccharide components as biochemicals and functional materials. A promising approach to mitigate and/or overcome lignin recalcitrance is the qualitative and quantitative modification of lignin by genetic engineering. Feruloyl-CoA 6'-hydroxylase (F6'H1) is a 2-oxoglutarate-dependent dioxygenase that catalyzes the conversion of feruloyl-CoA, one of the intermediates of the lignin biosynthetic pathway, into 6'-hydroxyferuloyl-CoA, the precursor of scopoletin (7-hydroxy-6-methoxycoumarin). In a previous study with Arabidopsis thaliana, we demonstrated that overexpression of F6'H1 under a xylem-preferential promoter led to scopoletin incorporation into the cell wall. This altered the chemical structure of lignin without affecting lignin content or saccharification efficiency. In the present study, the same F6'H1 construct was introduced into hybrid aspen (Populus tremula × tremuloides T89), a model woody plant, and its effects on plant morphology, lignin chemical structure, global gene expression, and phenolic metabolism were examined. The transgenic plants successfully overproduced scopoletin while exhibiting severe growth retardation, a phenotype not previously observed in Arabidopsis. Scopoletin accumulation was most pronounced in the secondary walls of tracheary elements and the compound middle lamella, with low levels in the fiber cell walls. Overexpression of F6'H1 also affected the metabolism of aromatics, including lignin precursors. Heteronuclear single-quantum coherence (HSQC) NMR spectroscopy revealed that scopoletin in cell walls was bound to lignin, leading to a reduction in lignin content and changes in its monomeric composition and molar mass distribution. Furthermore, the enzymatic saccharification efficiency of the transgenic cell walls was more than three times higher than that of the wild-type plants, even without pretreatment. Although addressing growth inhibition remains a priority, incorporating scopoletin into lignin demonstrates significant potential for improving woody biomass utilization.PMID:40225026 | PMC:PMC11985793 | DOI:10.3389/fpls.2025.1543168

Analysis of Modified Plant Metabolites Using Widely Targeted Metabolite Modificomics

Mon, 14/04/2025 - 12:00
Bio Protoc. 2025 Apr 5;15(7):e5259. doi: 10.21769/BioProtoc.5259. eCollection 2025 Apr 5.ABSTRACTMetabolite modifications play a critical role in enhancing plants' adaptability to environmental changes and serve as a major source of functional diversity in metabolites. However, current metabolomics approaches are limited to targeted analyses of a small number of known modified metabolites and lack comprehensive, large-scale studies of plant metabolite modifications. Here, we describe a widely targeted metabolite modificomics (WTMM) strategy, developed using ultra-high-performance liquid chromatography-quadrupole linear ion trap (UHPLC-Q-Trap) and ultra-high-performance liquid chromatography-Q-Exactive Orbitrap (UHPLC-QE-Orbitrap) technologies. This strategy enables high-throughput identification and sensitive quantification of modified metabolites. Using tomato as a model, we conducted a metabolite modificomics study and constructed a WTMM database, identifying 165 novel modified metabolites. The WTMM strategy is broadly applicable and can be extended to the study of other plant species. Key features • WTMM enables large-scale detection and quantitative analysis of plant-modified metabolites. • Integration of UHPLC-Q-Trap and UHPLC-QE-Orbitrap technologies. • The WTMM database is extensible and applicable to other plant species.PMID:40224656 | PMC:PMC11986708 | DOI:10.21769/BioProtoc.5259

Ultrasound irradiation activates purine metabolism and mitochondrial respiration via the MAPK signaling pathway in myotubes

Mon, 14/04/2025 - 12:00
Biochem Biophys Rep. 2025 Mar 26;42:101984. doi: 10.1016/j.bbrep.2025.101984. eCollection 2025 Jun.ABSTRACTBACKGROUND: Pulsed ultrasound (US) is widely used both as a diagnostic imaging tool and a therapeutic approach. However, many of the mechanisms underlying the therapeutic effects of non-thermal US remain unclear, especially in skeletal muscles, which play a crucial role in the body's metabolism. The aim of this study was to investigate the effects of US on myotubes.METHODS: In this study, C2C12 myoblasts were utilized. After differentiating into myotubes, the cells were exposed to US irradiation at an intensity of 3.0 W/cm2, with a 20 % duty cycle, an acoustic frequency of 1 MHz, and a pulse repetition frequency of 100 Hz for 5 min. The cells were then collected and analyzed for genomic and metabolomic alterations, as well as mitochondrial function.RESULTS: Cell viability remained unaffected after US irradiation. The mitogen-activated protein kinase (MAPK) signaling pathway was the most activated, while the expression of various RNAs was significantly altered. Purine metabolism was highly activated, with an increase in the abundance of metabolites associated with this pathway. Furthermore, mitochondrial respiration in the myotubes increased following US irradiation.CONCLUSION: This study investigated the impact of US irradiation on myotubes using genomic analysis, metabolomic analysis, and mitochondrial function. US irradiation activated the MAPK signaling pathway, which in turn enhanced purine metabolism and improved mitochondrial respiration.PMID:40224539 | PMC:PMC11986604 | DOI:10.1016/j.bbrep.2025.101984

Investigating the role of <em>Lactococcus lactis</em> D1813, salinity, and dissolved oxygen on the nutritional, chromatic, and textural profile of <em>Litopenaeus vannamei</em>

Mon, 14/04/2025 - 12:00
Food Chem X. 2025 Mar 19;27:102404. doi: 10.1016/j.fochx.2025.102404. eCollection 2025 Apr.ABSTRACTThe present study investigated the effect of L. lactis D1813, salinity (8 and 25 ppt), dissolved oxygen (8.5 and 3.5 mg/L), and freshwater shrimp reared in natural freshwater conditions (0 ppt salinity, ∼7.5 mg/L DO) without probiotic addition on its nutritional, chromatic and textural profile. Among the nutritional composition results, the highest protein, ash, and fiber contents were observed in the Huang group meat, i.e., 15.25, 4.50, and 3.99 g/100 g, respectively. Likewise, the results for the analysis of the mineral anticipated that the highest levels of K, Cu, Se, Fe, and Zn were found in Huang head group, i.e., 536, 6.3, 603, 9.2 and 4.6 mg/kg, respectively with high levels of astaxanthin, i.e., 270 μg/g. The Huang meat group also observed maximum chewiness and cohesiveness, i.e., 79.5 and 0.4, respectively. Furthermore, the results for amino acids elucidated the presence of the highest concentrations in the Huang meat group, such as isoleucine, valine, threonine, methionine, and arginine, i.e., 1.85, 1.33, 1.17, 1.44, and 1.33 g/100 g, respectively when compared with control. The highest levels of polyunsaturated fatty acids, such as eicosapentaenoic acid and docosahexaenoic acid, were observed in the Huang head group, i.e., 11.29 and 5.57 g/100 g. Our findings suggest that using L. lactis D1813 as probiotics along with the salinity and dissolved oxygen of 8 ppt and 7.5 mg/L significantly improves the nutritional profile of L. vannamei with better nutrient efficiencies. Furthermore, the study suggests probing the different probiotics in shrimp physiology, such as immune response and disease resistance.PMID:40224345 | PMC:PMC11987004 | DOI:10.1016/j.fochx.2025.102404

Telomere-to-telomere gap-free genome assembly provides genetic insight into the triterpenoid saponins biosynthesis in <em>Platycodon grandiflorus</em>

Mon, 14/04/2025 - 12:00
Hortic Res. 2025 Feb 1;12(5):uhaf030. doi: 10.1093/hr/uhaf030. eCollection 2025 May.ABSTRACTPlatycodon grandiflorus has been widely used in Asia as a medicinal herb and food because of its anti-inflammatory and hepatoprotective properties. P. grandiflorus has important clinical value because of the active triterpenoid saponins in its roots. However, the biosynthetic pathway of triterpenoid saponins in P. grandiflorus remains unclear, and the related genes remain unknown. Therefore, in this study, we assembled a high-quality and integrated telomere-to-telomere P. grandiflorus reference genome and combined time-specific transcriptome and metabolome profiling to identify the cytochrome P450s (CYPs) responsible for the hydroxylation processes involved in triterpenoid saponin biosynthesis. Nine chromosomes were assembled without gaps or mismatches, and nine centromeres and 18 telomere regions were identified. This genome eliminated redundant sequences from previous genome versions and incorporated structural variation information. Comparative analysis of the P. grandiflorus genome revealed that P. grandiflorus underwent a core eudicot γ-WGT event. We screened 211 CYPs and found that tandem and proximal duplications may be crucial for the expansion of CYP families. We outlined the proposed hydroxylation steps, likely catalyzed by the CYP716A/72A/749A families, in platycodin biosynthesis and identified three PgCYP716A, seven PgCYP72A, and seven PgCYP749A genes that showed a positive correlation with platycodin biosynthesis. By establishing a T2T assembly genome, transcriptome, and metabolome resource for P. grandiflorus, we provide a foundation for the complete elucidation of the platycodins biosynthetic pathway, which consequently leads to heterologous bioproduction, and serves as a fundamental genetic resource for molecular-assisted breeding and genetic improvement of P. grandiflorus.PMID:40224331 | PMC:PMC11992332 | DOI:10.1093/hr/uhaf030

Fermented chrysanthemum stem as a source of natural phenolic compounds to alleviate tomato bacterial wilt disease

Mon, 14/04/2025 - 12:00
Hortic Res. 2025 Jan 27;12(5):uhaf027. doi: 10.1093/hr/uhaf027. eCollection 2025 May.ABSTRACTNatural antimicrobial compounds (NACs) in the plant stem are crucial for replacing conventional synthetic pesticides in the control of soil-borne diseases, and microbial fermentation can enhance their concentration and bioactivity. In this study, the stems of 10 plant species were collected for fermentation by probiotic bacteria Bacillus amyloliquefaciens T-5 to identify the most effective plant resource for controlling tomato bacterial wilt disease and discover key NACs. Chrysanthemum stem was identified as an optimal fermentation substrate, as its water-soluble extracts (WSEs) significantly inhibited the growth of pathogenic Ralstonia solanacearum and effectively alleviated tomato wilt under greenhouse conditions. Key metabolites, primarily phenolic acids including 2-hydroxy-3-phenylpropanoic acid (PLA), 3-(4-hydroxyphenyl)-propionic acid (HPPA), and mandelic acid (MA), were determined by metabolomics, all of which significantly inhibited the growth of R. solanacearum at a concentration of 0.2 mM, with only HPPA effectively controlling tomato wilt. Thus, fermented chrysanthemum stem contains NACs that are effective against bacterial wilt, providing a green option for controlling soil-borne diseases.PMID:40224330 | PMC:PMC11986583 | DOI:10.1093/hr/uhaf027

Editorial: Metabolomics in human and animal ophthalmic research

Mon, 14/04/2025 - 12:00
Front Mol Biosci. 2025 Mar 28;12:1594647. doi: 10.3389/fmolb.2025.1594647. eCollection 2025.NO ABSTRACTPMID:40224209 | PMC:PMC11985458 | DOI:10.3389/fmolb.2025.1594647

Unraveling Leishmania major Metacyclogenesis: A Comprehensive Analysis of Transcriptomic and Metabolomic Profiles

Mon, 14/04/2025 - 12:00
Iran Biomed J. 2025 Jan 1;29(1 & 2):68-81.ABSTRACTBACKGROUND: Metacyclogenesis is a critical developmental process in the life cycle of Leishmania parasites, particularly in their transition from non-infective procyclic to infective metacyclic promastigotes. This transformation is closely linked to the metabolic adaptation of the parasite, optimizing its survival and infectivity under varying environmental conditions. In this study, we integrated metabolomics and transcriptomics data to gain deeper insights into the underlying molecular mechanisms of L. major metacyclogenesis.METHODS: The metabolic profiles of procyclic and metacyclic promastigotes were first identified using ¹H-NMR spectroscopy. Multivariate statistical analysis revealed 44 significantly different metabolites between the two forms. Metabolic pathway analysis for differentially expressed metabolites identified 10 significantly different pathways (p < 0.05 and impact > 0.05). Finally, the differential gene expression analysis was conducted on transcriptomic data retrieved from public repositories.RESULT: Results indicated the upregulation of 238 genes and the downregulation of 49 genes during metacyclogenesis. These genes underwent GO and KEGG pathway analyses, revealing upregulated GO categories in the metacyclic phase, including protein phosphorylation, ion transport, signal transduction, and phosphorylation reactions, as well as several downregulated GO categories. Integrating metabolomic and transcriptomic data demonstrated seven significantly different KEGG pathways between procyclic and metacyclic forms, including fructose and mannose, galactose, ascorbate and aldarate, arginine and proline, histidine, inositol phosphate, and pyruvate metabolism.CONCLUSION: Our findings suggest distinct metabolic profiles and changes in gene expression associated with the transition from procyclic to metacyclic promastigotes. By integrating diverse omics data, we could identify more reliable altered pathways and biomarkers.PMID:40223480

Thermal Desorption and Extraction Coupled With Gas Chromatography and Mass Spectrometry for the Quantification of Polystyrene Nanoplastic in Pak Choi

Mon, 14/04/2025 - 12:00
Rapid Commun Mass Spectrom. 2025 Jul 30;39(14):e10046. doi: 10.1002/rcm.10046.ABSTRACTRATIONALE: It has been demonstrated that microplastics and nanoplastics (MNPs) can be found in soil and that MNPs can be taken up by plants. In order to conduct a risk assessment for human consumption, it is necessary to have an estimate of the mass concentration of plastics in crops. A new thermal extraction and desorption coupled with gas chromatography and mass spectrometry (TED-GC/MS) method has been developed for the analysis of polystyrene (PS) in pak choi.METHODS: In this study, a thermogravimetric analyser (TGA) equipped with a thermal absorption unit (TAU), was coupled with a GC system equipped with a thermal desorption unit (TDU2), a (5%-phenyl)-methylpolysiloxane GC column and a GC/MSD single quadrupole mass spectrometer. The systems were connected via an MultiPurposeSampler (MPS). Samples were pyrolyzed in the TGA; the pyrolysis products were trapped on a PDMS polymer bar, desorbed in the TDU, separated and analysed on the GC/MS system.RESULTS: The purpose of this study was to investigate the qualitative and quantitative detection of PS MNPs in pak choi. The determined limit of detection (LOD) was 0.09 μg, and the limit of quantification (LOQ) was 0.28 μg PS absolute. Plants treated with 100 nm of particles 19.0 ± 6.7 μg/g DM PS and in the plants treated with 500 nm of particles 64.1 ± 8.6 μg/g DM PS have been found.CONCLUSIONS: This study was the first to use a TED-GC/MS method for the detection of PS nanoplastics of different sizes in pak choi and thus provides an important basis for the determination and risk assessment of PS in vegetables.PMID:40223436 | DOI:10.1002/rcm.10046

Alterations in the Plasma Metabolome Associated With Maternal Smoking During the First Trimester and Foetal Growth

Mon, 14/04/2025 - 12:00
Basic Clin Pharmacol Toxicol. 2025 May;136(5):e70037. doi: 10.1111/bcpt.70037.ABSTRACTTobacco smoking during pregnancy has been associated with an increased risk of adverse outcomes like low birth weight. This study determined changes in the circulating metabolome linked to maternal smoking in the first trimester and correlated these changes to the growth of the foetus. The circulating metabolome was examined from first trimester plasma samples by non-targeted (global) liquid chromatography mass spectrometry-based metabolite profiling of 227 pregnant women (99 smokers and 117 non-smokers) from the Kuopio Birth Cohort Study. Tobacco smoking was self-reported through a questionnaire and verified with cotinine measurements from plasma samples. In summary, 64 significant differences were observed between the groups after correction for multiple testing e.g. in metabolites indicating endocrine disruption (e.g. dehydroepiandrosterone sulphate [DHEA-S], VIP = 2.70, d = 0.68, p < 0.0001), metabolites associated with oxidative stress (e.g. bilirubin, VIP = 2.00, d = 0.50, p < 0.0001) and lipid metabolism (e.g. LysoPC 16:1, VIP = 2.07, d = 0.51, p < 0.0001). Some of these metabolites, e.g. DHEA-S and bilirubin, correlated with low birth weight, and some, e.g. LysoPC 16:1, correlated with small head circumference at birth. In conclusion, maternal smoking during the first trimester of pregnancy was associated with an altered metabolite profile linked to endocrine disruption and increased oxidative stress.PMID:40223348 | DOI:10.1111/bcpt.70037

Advancing Gut Microbiome Research: The Shift from Metagenomics to Multi-Omics and Future Perspectives

Mon, 14/04/2025 - 12:00
J Microbiol Biotechnol. 2025 Mar 26;35:e2412001. doi: 10.4014/jmb.2412.12001.ABSTRACTThe gut microbiome, a dynamic and integral component of human health, has co-evolved with its host, playing essential roles in metabolism, immunity, and disease prevention. Traditional microbiome studies, primarily focused on microbial composition, have provided limited insights into the functional and mechanistic interactions between microbiota and their host. The advent of multi-omics technologies has transformed microbiome research by integrating genomics, transcriptomics, proteomics, and metabolomics, offering a comprehensive, systems-level understanding of microbial ecology and host-microbiome interactions. These advances have propelled innovations in personalized medicine, enabling more precise diagnostics and targeted therapeutic strategies. This review highlights recent breakthroughs in microbiome research, demonstrating how these approaches have elucidated microbial functions and their implications for health and disease. Additionally, it underscores the necessity of standardizing multi-omics methodologies, conducting large-scale cohort studies, and developing novel platforms for mechanistic studies, which are critical steps toward translating microbiome research into clinical applications and advancing precision medicine.PMID:40223273 | DOI:10.4014/jmb.2412.12001

Impact of Probiotic Formula (Lacto-5X) on Constipation: Improvements in Gastrointestinal Symptoms, Gut Microbiome, and Metabolites

Mon, 14/04/2025 - 12:00
J Microbiol Biotechnol. 2025 Apr 9;35:e2412056. doi: 10.4014/jmb.2412.12056.ABSTRACTConstipation is characterized by low frequent stools and difficult stool passage. Approximately 16% of the global population experiences these symptoms. Probiotics have shown promise in improving constipation symptoms by modulating the gut microbiome. This study aims to evaluate the effects of a probiotic formula (Lacto-5X) on bowel habits, gastrointestinal symptoms, gut microbiome, and metabolites in adults with mild constipation using a randomized, double-blind, placebo-controlled clinical trial design. At the 4-week endpoint, the Probiotic group had significant improvements in stool consistency, stool frequency, abdominal pain, and straining compared to the Placebo group. Satisfaction with bowel habits and improvement in overall intestinal health were significantly higher in the Probiotic group. Microbiome analysis revealed a significant increase in the abundance of Lactobacillus and L. plantarum in the Probiotic group at the 4-week endpoint. Metabolome analysis showed that L-proline level in the Probiotic group decreased, while threonic acid level increased at the 4-week endpoint compared to the Placebo group. However, these improvements were not sustained at the 8-week follow-up point. Lacto-5X changes the gut microbiome, leading to changes in metabolites, and it induced improved constipation symptoms. Continuous intake may be necessary to maintain these effects. Further studies are needed to explore the long-term efficacy of Lacto-5X.PMID:40223270 | DOI:10.4014/jmb.2412.12056

Comprehensive analysis of faecal metagenomic and serum metabolism revealed the role of gut microbes and related metabolites in detecting colorectal lateral spreading tumours

Mon, 14/04/2025 - 12:00
Virulence. 2025 Dec;16(1):2489154. doi: 10.1080/21505594.2025.2489154. Epub 2025 Apr 13.ABSTRACTColorectal lateral spreading tumours (LST), early-stage lesions of colorectal cancer (CRC), are associated with gut microbiota dysbiosis. However, the functional alterations in gut microbiota and their metabolic pathways remain inadequately understood. This study employed propensity score matching to compare 35 LST patients with 35 healthy controls. Metagenomic and metabolomic analyses revealed notable differences in gut microbiota composition and metabolic pathways. LST patients exhibited a marked reduction in short-chain fatty acid (SCFA)-producing probiotics, such as Roseburia, Clostridium, and Butyricicoccus sp-OF13-6, alongside anti-inflammatory metabolites. In contrast, potential intestinal pathogens linked to inflammatory bowel disease (IBD), including Escherichia and Citrobacter amalonaticus, were significantly enriched. Orthogonal partial least squares discriminant analysis (OPLS-DA) highlighted significant metabolic disparities between the groups, with enrichment in pathways associated with cholesterol metabolism, choline metabolism in cancer, and amino acid metabolism - all relevant to cancer progression. Key biomarkers identified for LST included fumarate, succinate, glutamic acid, glycine, and L-aspartic acid, which were closely linked to these pathways. Functional studies demonstrated that these metabolites promoted the proliferation and invasion of HCT-116 and SW480 human colorectal cancer cells in vitro. Metagenomic and metabolomic analysis revealed a strong positive correlation between Escherichia and Ruminococcus sp-AM41-2AC abundance and the enriched pathways, whereas reductions in Roseburia species, including Roseburia-OF03-24 and Roseburia intestinalis_CAG13-exhibited negative correlations. These results suggest that gut microbiota and metabolite alterations in LST contribute to intestinal inflammation and CRC development, underscoring their potential as biomarkers for early detection and therapeutic targets.PMID:40223231 | DOI:10.1080/21505594.2025.2489154

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