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

Root-knot nematode infection enhances the performance of a specialist root herbivore via plant-mediated interactions

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Plant Physiol. 2025 Mar 20:kiaf109. doi: 10.1093/plphys/kiaf109. Online ahead of print.ABSTRACTHerbivores sharing host plants are often temporally and spatially separated, limiting direct interactions between them. Nevertheless, as observed in numerous aboveground study systems, they can reciprocally influence each other via systemically induced plant responses. In contrast, examples of such plant-mediated interactions between belowground herbivores are scarce; however, we postulated that they similarly occur, given the large diversity of root-interacting soil organisms. To test this hypothesis, we analyzed the performance of cabbage root fly (Delia radicum) larvae feeding on the main roots of field mustard (Brassica rapa) plants whose fine roots were infected by the root-knot nematode (Meloidogyne incognita). Simultaneously, we studied the effects of M. incognita on D. radicum-induced defense responses and the accumulation of primary metabolites in the main root. We observed that almost 1.5 times as many D. radicum adults emerged from nematode-infected plants, indicating a facilitation effect of M. incognita infection. Although we observed increases in the accumulation of proteins and two essential amino acids, the strongest effect of nematode infection was visible in the defense response to D. radicum. We observed a 1.5 times higher accumulation of the defense-related phytohormone JA-Ile in response to D. radicum on nematode-infected plants, coinciding with a 75% increase in indole glucosinolate concentrations. Contrastingly, concentrations of aliphatic glucosinolates, secondary metabolites negatively affecting D. radicum, were 10-25% lower in nematode-infected plants. We hypothesize that the attenuated aliphatic glucosinolate concentrations result from antagonistic interactions between biosynthetic pathways of both glucosinolate classes, which was reflected in the expression of key biosynthesis genes. Our results provide explicit evidence of plant-mediated interactions between belowground organisms, likely via systemically induced responses in roots.PMID:40112263 | DOI:10.1093/plphys/kiaf109

Correction to Supporting Information for Wang et al., Metabolomic insights into pathogenesis and therapeutic potential in adult acute lymphoblastic leukemia

Thu, 20/03/2025 - 11:00
Proc Natl Acad Sci U S A. 2025 Apr;122(13):e2504173122. doi: 10.1073/pnas.2504173122. Epub 2025 Mar 20.NO ABSTRACTPMID:40112102 | DOI:10.1073/pnas.2504173122

Rubber biosynthesis drives the biogenesis and development of rubber particles, the rubber-producing organelles

Thu, 20/03/2025 - 11:00
Plant Biotechnol J. 2025 Mar 20. doi: 10.1111/pbi.70052. Online ahead of print.ABSTRACTRubber particles (RPs) are specialized organelles for the biosynthesis and storage of natural rubber in rubber-producing plants. However, the mechanisms underlying the biogenesis and development of RPs remain unclear. In this study, two latex-specific cis-prenyltransferases (CPTs), TkCPT1 and TkCPT2, were identified in Taraxacum kok-saghyz, with almost identical orthologues retained across other Taraxacum species. For the first time, Tkcpt1 single and Tkcpt1/2 double mutants were successfully generated using the CRISPR/Cas9 system. Rubber biosynthesis was significantly depressed in Tkcpt1 mutants and completely blocked in Tkcpt1/2 mutants. The absence of RPs in the Tkcpt1/2 was confirmed using oil red O and Nile red staining, high-speed centrifugal stratification, cryo-SEM and TEM on fresh latex or laticifer cells. Transcriptomic and proteomic analyses revealed that, in the latex of Tkcpt1/2, rubber biosynthesis was blocked at the protein level, while metabolomic profiling indicated an enrichment of lipids and terpenoids. Furthermore, knockout of TkCPTL1, a latex-specific CPT-like gene that encodes a rubber transferase activator, resulted in outright disruption of rubber biosynthesis and RP ontogeny, a phenotype similar to that of Tkcpt1/2 mutants. These findings indicate that rubber biosynthesis is a driving force for the biogenesis and development of RPs, providing new insights into rubber production mechanisms.PMID:40112038 | DOI:10.1111/pbi.70052

A new isolation of vincamajine from <em>Vinca difformis</em> subsp. <em>sardoa</em> Stearn

Thu, 20/03/2025 - 11:00
Nat Prod Res. 2025 Mar 20:1-5. doi: 10.1080/14786419.2025.2477219. Online ahead of print.ABSTRACTThe continuation of the phytochemical analysis to determine the alkaloid content of Vinca difformis subsp. sardoa Stearn, led to the isolation of the further compound vincamajine (1) which was reported from the species for the first time during this study. Its structure was established by means of extensive NMR, IR and MS analyses which are completely reported in this paper for the first time. In addition, the first chemophenetic evaluation about this compound was also carried out evidencing some important results which were fully described and discussed in this paper.PMID:40112011 | DOI:10.1080/14786419.2025.2477219

The murine lung microbiome is disbalanced by the human-pathogenic fungus Aspergillus fumigatus resulting in enrichment of anaerobic bacteria

Thu, 20/03/2025 - 11:00
Cell Rep. 2025 Mar 19;44(3):115442. doi: 10.1016/j.celrep.2025.115442. Online ahead of print.ABSTRACTHere, we report significant changes in the composition of the lung microbiome and metabolome of mice under immune suppression, infection of immunosuppressed mice with virulent and avirulent strains of the clinically important human-pathogenic fungus Aspergillus fumigatus, and treatment with the clinically used antifungal drug voriconazole. Our data also indicate the important role of the gut microbiome for lung homeostasis mediated by the plasma metabolome. In the lung microbiome, DNA sequencing indicates that infection by A. fumigatus leads to a significant increase of anaerobic bacteria, most prominently of Ligilactobacillus murinus; the latter has been confirmed by qPCR analyses. We also isolated live bacteria, including L. murinus, from the murine lower respiratory tract. Co-cultivation of L. murinus and A. fumigatus leads to a reduction in oxygen concentration accompanied by an increase of L. murinus cells, suggesting that A. fumigatus establishes a microaerophilic niche, thereby promoting growth of anaerobic bacteria.PMID:40111997 | DOI:10.1016/j.celrep.2025.115442

Metabolomics Analysis of Functional Activity Changes in Residual Tumour Cells After IOCS Treatment

Thu, 20/03/2025 - 11:00
J Cell Mol Med. 2025 Mar;29(6):e70452. doi: 10.1111/jcmm.70452.ABSTRACTHepatocellular carcinoma (HCC) is a serious and often lethal cancer, particularly in patients with chronic liver disease. Currently, no specific treatment has been utilised to prevent HCC. The detailed mechanism of HCC is still elusive, and this study aims to identify and characterise the functional activity changes in residual tumour cells following intraoperative cell salvage (IOCS) treatment during HCC surgery. This research is a retrospective case-control study, involving the selection of 60 patients with HCC who underwent radical surgery; then blood and tumour tissue were collected for further testing. GC-MS assay, immunofluorescence, Western blot and qRT-PCR techniques were employed. Our study found comparable demographic and baseline clinical characteristics between the experimental group (n = 30), which received IOCS treatment during surgery, and the control group (n = 30), which did not receive IOCS treatment, validating subsequent analyses. Metabolomic analysis revealed six key metabolites differing between groups, indicating improvement in liver tumours in the experimental group. TP53 expression was significantly upregulated, potentially mediating therapeutic effects. The intervention reduced HCC cell migration and apoptosis, decreased E2F1 and MDM2 protein and mRNA levels, and increased TP53 and CTNNB1 levels. These findings support the potential clinical application of the intervention in improving treatment outcomes for HCC patients, warranting further investigation to elucidate the underlying mechanisms and optimise therapeutic strategies.PMID:40111872 | DOI:10.1111/jcmm.70452

Multi-omics analysis reveals tissue-specific biosynthesis and accumulation of diterpene alkaloids in Aconitum japonicum

Thu, 20/03/2025 - 11:00
J Nat Med. 2025 Mar 20. doi: 10.1007/s11418-025-01881-y. Online ahead of print.ABSTRACTAconitum japonicum, native to the mountainous regions of Japan, is a toxic perennial plant widely recognized for its therapeutic potential. Despite its pharmacological importance, the complete biosynthetic pathway of diterpene alkaloids, bioactive compounds with significant pharmaceutical implications and derived from Aconitum species, remains elusive. In this study, leveraging high-throughput metabolome and transcriptome analyses, we conducted a comprehensive investigation using four tissues of A. japonicum, including leaf, mother root, daughter root, and rootlet. By integrating these multi-omics datasets, we achieved a holistic insight into the gene expression patterns and metabolite profiles intricately linked with diterpene alkaloid biosynthesis. Our findings unveil potential regulatory networks and pinpoint key candidate genes pivotal in diterpene alkaloid synthesis. Through comparative analyses across tissues, we delineate tissue-specific variations in gene expression and metabolite accumulation, shedding light on the spatial regulation of these biosynthetic pathways within the plant. Furthermore, this study contributes to a deeper understanding of the molecular mechanisms dictating the production of diterpene alkaloids in A. japonicum. Besides advancing our knowledge of plant secondary metabolism in A. japonicum, this study also provides a high-quality multi-omics resource for future studies aimed at functionally characterizing the target genes involved in different metabolic processes.PMID:40111723 | DOI:10.1007/s11418-025-01881-y

Symbiosis Between the Oral Microbiome and the Human Host: Microbial Homeostasis and Stability of the Host

Thu, 20/03/2025 - 11:00
Adv Exp Med Biol. 2025;1472:31-51. doi: 10.1007/978-3-031-79146-8_3.ABSTRACTThe oral cavity presents a highly diverse microbial composition. All the three domains of life, Bacteria, Eukarya, and Archaea, as well as viruses constitute the oral microbiome. Bacteria are among the most abundant microorganisms in the oral cavity, followed by viruses, fungi, and Archaea. These microorganisms tend to live in harmony with each other and with the host by preventing the colonization of oral sites by exogenous microorganisms. Interactions between the host and its microbiota are crucial for keeping ecological stability in the oral cavity and a condition compatible with oral health. This chapter focuses on describing the oral microbiota in healthy individuals based on both targeted and nontargeted genome sequencing methods and the functional activity played by those microorganisms based on metagenomic, metatranscriptomic, metaproteomic, and metabolomic analyses. Additionally, this chapter explores mutualistic and antagonistic microbe-microbe relationships. These interactions are mediated by complex mechanisms like cross-feeding networks, production of bacteriocins and secondary metabolites, synthesis of pH-buffering compounds, and the use of universal signaling molecules. At last, the role played by host-microbe interactions on colonization resistance and immune tolerance will help provide a better understanding about the harmonious and peaceful coexistence among host and microbial cells under oral health-related conditions.PMID:40111684 | DOI:10.1007/978-3-031-79146-8_3

Isorhamnetin ameliorates hyperuricemia by regulating uric acid metabolism and alleviates renal inflammation through the PI3K/AKT/NF-κB signaling pathway

Thu, 20/03/2025 - 11:00
Food Funct. 2025 Mar 20. doi: 10.1039/d4fo04867a. Online ahead of print.ABSTRACTHyperuricemia is a chronic metabolic disease with high incidence, and it has become a severe health risk in modern times. Isorhamnetin is a natural flavonoid found in a variety of plants, especially fruits such as buckthorn. The in vivo hyperuricemia ameliorating effect of isorhamnetin and the specific molecular mechanism were profoundly investigated using a hyperuricemia mouse model in this study. Results indicated that isorhamnetin showed a significant uric acid-lowering effect in mice. Isorhamnetin was able to reduce uric acid production by inhibiting XOD activity. Furthermore, it reduced the expression of GLUT9 to inhibit uric acid reabsorption and enhanced the expression of ABCG2, OAT1, and OAT3 to promote uric acid excretion. Metabolomics analysis revealed that gavage administration of isorhamnetin restored purine metabolism and riboflavin metabolism disorders and thus significantly alleviated hyperuricemia in mice. Furthermore, the alleviating effect of isorhamnetin on hyperuricemia-induced renal inflammation and its specific mechanism were explored through network pharmacology and molecular validation experiments. Network pharmacology predicted that seven targets were enriched in the PI3K/AKT pathway (CDK6, SYK, KDR, RELA, PIK3CG, IGF1R, and MCL1) and four targets were enriched in the NF-κB pathway (SYK, PARP1, PTGS2, and RELA). Western blot analysis validated that isorhamnetin inhibited the phosphorylation of PI3K and AKT and down-regulated the expression of NF-κB p65. It indicated that isorhamnetin could inhibit the PI3K/AKT/NF-κB signaling pathway to reduce the levels of renal inflammatory factors (TNF-α, IL-β and IL-6) and ultimately ameliorate hyperuricemia-induced renal inflammation in mice. This study provides a comprehensive and strong theoretical basis for the application of isorhamnetin in the field of functional foods or dietary supplements to improve hyperuricemia.PMID:40111208 | DOI:10.1039/d4fo04867a

Cultivation technology optimization and identification of secondary metabolites from elm oyster mushroom Hypsizygus ulmarius (Bull.) Redhead (Agaricomycetes) through GC-MS metabolomic profiling from India

Thu, 20/03/2025 - 11:00
Mycologia. 2025 Mar 20:1-27. doi: 10.1080/00275514.2025.2452307. Online ahead of print.ABSTRACTHypsizygus ulmarius, a novel oyster mushroom species, offers potential scope due to its low-cost production, high biological efficiency, and notable nutritional, medicinal, and therapeutic properties. The present study standardized commercial cultivation technology for H. ulmarius in the Trans-Gangetic Plains of India. The mycelium grew well on potato dextrose agar and carrot extract broth at pH 8.0 and temperature 25 C. Wheat straw supplemented with the cotton seed hull at the rate of 10.0% dose, spawned with pearl millet grain spawn at the rate of 5.0% spawn dose, gave the highest mushroom yield (953.66 g/0.4 kg dry substrate) with biological efficiency (238.41%). The first flush sporocarps were freeze-dried for physicochemical characterization, revealing 16 strong peaks and 8 functional groups via Fourier transform infrared (FTIR) analysis. Particle size averaged 45.97 µm of mushroom powder, and scanning electron microscopy (SEM) analysis showed diverse surface textures. Gas chromatography-mass spectrometry metabolic profiling identified 20 key secondary metabolites each from hexane and methanolic extracts, with therapeutic uses that are valuable for pharmaceutical, nutraceutical, and food industry applications.PMID:40111001 | DOI:10.1080/00275514.2025.2452307

Proton-Nuclear Magnetic Resonance Metabolomics of Gingival Crevicular Fluid During Orthodontic Tooth Movement With Aligners

Thu, 20/03/2025 - 11:00
Orthod Craniofac Res. 2025 Mar 20. doi: 10.1111/ocr.12916. Online ahead of print.ABSTRACTOBJECTIVES: To determine the correlation between orthodontic tooth movement and a pre-defined set of gingival crevicular fluid (GCF) metabolites through proton nuclear magnetic resonance (1H-NMR) spectroscopy.MATERIALS AND METHODS: A clinical randomised prospective split-mouth study comparing the GCF metabolites around stationary and moving second maxillary molars. Twenty-four healthy subjects diagnosed with dental class II malocclusion undergoing orthodontic clear aligner treatment (CAT) were enrolled. GCF samples from the mesial and distal sulcus of second molars under stationary conditions or under 1 N of distalising force were harvested at baseline, 1 h, 7 days and 21 days after the application of CAT. 1H-NMR was utilised for GCF sample analysis. The 2-dimensional total correlation spectroscopy spectral signature of 35 known GCF metabolites was compared in moving and stationary teeth. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), variable importance in projection (VIP) score and area under the curve (AUC) were computed utilising MetaboAnalyst 5.0 software.RESULTS: VIP-score values showed statistically significant differences between the metabolites involved in moving and stationary molars (p < 0.05). PCA and PLS-DA results showed potential differences between the metabolite clusters. The variation of the 1H-NMR signals of Glutamine, Uracil, N-Acetylneuraminate and alpha-ketoglutarate contributes primarily to the variance across metabolites in moving versus stationary teeth at 1 h, 7 days and 21 days.CONCLUSION: High values of Glutamine and low values of Uracil, N-Acetylneurinamate and alpha-ketoglutarate could be utilised to predict the progress of orthodontic tooth movement over time. Knowledge of metabolites predictive of tooth movement could contribute to the design of tailored orthodontic treatment planning, reducing time, costs and side-effects.PMID:40110902 | DOI:10.1111/ocr.12916

Targeted Nutritional Metabolomic Analysis of Marine Species (Tursiops truncatus, Phoca vitulina, Otaria flavescens and Pygoscelis papua)

Thu, 20/03/2025 - 11:00
Vet Med Sci. 2025 Mar;11(2):e70302. doi: 10.1002/vms3.70302.ABSTRACTEcological nutrition aims to unravel the extensive web of nutritional links that drive animals in their interactions with their habitat. Metabolomic profiling of species could increase the knowledge of their ecology, as well as allowing us to better understand the interactions of environment, including distribution, availability of food and fitness of the species, among others. Metabolomic profile is affected by several causes such as nutrition, physiological status, metabolism and species. Thus, the main aim of this work will be to provide, for the first time, values of the nutritional metabolome profile in marine species, as well as to study the differences in the metabolomic profile due to the classification group. To achieve this, blood samples from marine animals (n = 55) were used in this experiment, including Gentoo penguin (Pygoscelis papua), Patagonian sea lion (Otaria flavescens), Harbour seal (Phoca vitulina) and Bottlenose dolphin (Tursiops truncatus). Blood samples were analysed to determine the nutritional metabolites, specifically non-esterified fatty acid (NEFA), glucose, triglyceride, uric acid, cholesterol, albumin, total protein and inorganic phosphorous (iP). Pygoscelis papua exhibited the most statistically significant differences compared to the other groups, showing higher levels of plasma glucose, triglycerides, uric acid, and cholesterol, and lower levels of albumin, total protein, urea, and iP relative to the average values (simple means) observed in the other species. Also, it can be concluded that nutritional metabolome of Tursiops truncatus is different from that of Otaria flavescens, due to the differences in urea and albumin. These results show the potential of metabolomics to elucidate the relationship between metabolism and external factors in species. However, more molecular ecology studies are necessary to deepen the study of the interrelationships between the environment and metabolism, with the aim of including this tool in specific programmes for conservation and biological study.PMID:40110733 | DOI:10.1002/vms3.70302

Exploratory analysis of the proteomic profile in plasma in adults with Down syndrome in the context of Alzheimer's disease

Thu, 20/03/2025 - 11:00
Alzheimers Dement. 2025 Mar;21(3):e70040. doi: 10.1002/alz.70040.ABSTRACTINTRODUCTION: Adults with Down syndrome (DS) show increased risk for Alzheimer's disease (AD) due to the triplication of chromosome 21 encoding the amyloid precursor protein gene. Further, this triplication possibly contributes to dysregulation of the immune system, furthering AD pathophysiology.METHODS: Using Olink Explore 3072, we measured ∼3000 proteins in plasma from 73 adults with DS and 15 euploid, healthy controls (HC). Analyses for differentially expressed proteins (DEP) were carried out, and pathway and protein network enrichment using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes (KEGG), and STRING database was investigated. Within DS, the LASSO (least absolute shrinkage and selection operator) feature selection was applied.RESULTS: We identified 253 DEP between DS and HC and 142 DEP between symptomatic and asymptomatic DS. Several pathways regarding inflammatory and neurodevelopmental processes were dysregulated in both analyses. LASSO feature selection within DS returned 15 proteins as potential blood markers.DISCUSSION: This exploratory proteomic analysis found potential new blood biomarkers for diagnosing DS-AD in need of further investigation.HIGHLIGHTS: Inflammatory pathways are dysregulated in symptomatic versus asymptomatic DS. NFL and GFAP are confirmed as powerful biomarkers in DS with clinical and/or cognitive decline. Further circulating proteins were identified as potential blood biomarkers for symptomatic DS.PMID:40110647 | DOI:10.1002/alz.70040

Myocardial Lipidomics Revealed Glycerophospholipid and Sphingolipid Metabolism as Therapeutic Targets of Qifu Decoction Against Heart Failure

Thu, 20/03/2025 - 11:00
Biomed Chromatogr. 2025 May;39(5):e70063. doi: 10.1002/bmc.70063.ABSTRACTQifu decoction (QFD) has shown potential benefits in treating heart failure. However, the potential mechanism of QFD remains unclear. In this study, myocardial lipidomics, based on ultra-high-performance liquid chromatography coupled with an electrospray ionization hybrid quadrupole Orbitrap mass spectrometry (UPLC-ESI-Q-Exactive/MS), was employed to identify potential therapeutic targets of QFD for treating heart failure in a mice model induced by ligating the left anterior descending coronary artery. It was found that 47 lipid metabolites were associated with heart failure, of which 35 showed a significant reversal during QFD treatment. The QFD-reversed lipid metabolites were mainly located on phosphatidylcholine, lysophosphatidylcholine, sphingomyelin, and ceramide, which were involved in glycerophospholipid and sphingolipid metabolism. The results of Western blotting analysis revealed that QFD could effectively alleviate heart failure through increasing the levels of lysophosphatidylcholine acyltransferase 1 (LPCAT1) and sphingomyelin synthase 1 (SMS1) and reducing the levels of acid sphingomyelinase (aSMase) and phospholipase A2 (PLA2) to regulate the metabolic disorders of glycerophospholipid and sphingolipid metabolism. All these results could be concluded that glycerophospholipid and sphingolipid metabolism were the two crucial target pathways for QFD against heart failure, which laid the theoretical groundwork for its clinical application.PMID:40110617 | DOI:10.1002/bmc.70063

Novel gastrointestinal tools (GI Tools) for evaluating gut functional capacity in adults with environmental enteropathy in Zambia and Zimbabwe: A cross-sectional study protocol

Thu, 20/03/2025 - 11:00
F1000Res. 2025 Mar 4;13:956. doi: 10.12688/f1000research.154471.2. eCollection 2024.ABSTRACTBACKGROUND: Environmental enteropathy (EE) is a highly prevalent subclinical inflammatory intestinal disorder associated with growth failure, impaired neurocognitive development, poor response to oral vaccines, and micronutrient deficiencies. However, EE research and clinical trials are hampered by the lack of non-invasive tools for measuring intestinal function in detail. This study aims to develop new tools for the measurement of multiple domains of gut functional capacity.METHODS: The GI TOOLS project is a cross-sectional study that will recruit adults aged 18-65 years with EE in Lusaka, Zambia. Each participant will undergo assessment of gut functional capacity using novel near-point-of-care tools and provide multiple samples for detailed laboratory analyses. Participants will also undergo endoscopy for collection of duodenal biopsies. Novel techniques include stable isotopes approaches to measuring digestion, absorption, and bidirectional transmucosal amino acid flux, a non-invasive fluorescence tool for real-time evaluation of gut permeability, and assessment of reverse permeation of intravenous antibiotics to be carried out separately in Zimbabwe. Stool and duodenal microbiome sequencing using MinION sequencing, metabolome analysis applied to plasma and intestinal fluids, blood immune cell phenotyping, in vitro epithelial barrier models, and duodenal immunohistochemistry will also be used to explore EE in depth. These will all be integrated with gold standard histology and mucosal morphometry, alongside lactulose permeation data, and stool and plasma biomarker analysis. The protocol has been approved by ethics committees and regulators in Zambia, Zimbabwe, and the UK. Participants will give informed consent before they can participate.ANTICIPATED OUTCOMES: Based on this extensive phenotyping, tests will be developed which can be simplified and refined for use in adults and children with EE, and for clinical trials. Findings from this project will be disseminated through in-person meetings with caregivers and regulatory bodies, presentations at conferences and in peer-reviewed journals.PMID:40110548 | PMC:PMC11920692 | DOI:10.12688/f1000research.154471.2

A novel, high throughput, and low-cost method for the detection of 40 amines relevant to inborn errors of metabolism, in under 60 min, using reverse phase high performance liquid chromatography

Thu, 20/03/2025 - 11:00
Mol Genet Metab Rep. 2025 Feb 28;43:101202. doi: 10.1016/j.ymgmr.2025.101202. eCollection 2025 Jun.ABSTRACTOBJECTIVES: An assessment of amino acid and amine concentrations is important for the diagnosis and management of inherited metabolic disorders (IMDs). Methods exist that measure these biologically important metabolites but are cost-prohibitive and/or time consuming. We therefore sought to develop a novel methodology, applicable to IMDs, that is both high-throughput and low cost.METHODS: Previously, we developed a methodology for rapid, repeatable, and cost-efficient separation of approximately 20 amines as a proof of concept and now expand it to amines relevant to IMDs. We describe our separation methodology using reverse phase high performance liquid chromatography with ultraviolet-visible spectrum absorbance paired with pre-column derivatization with o-pthalaldehyde.RESULTS: We show reproducibility via concentration assessments, in triplicate, for each amine. We assess amines in prepared standard solutions and in biologic samples from patients with IMDs. We also detected and assessed the amino group containing compounds glutathione (oxidized and reduced forms) and ammonia. Validation was established using absolute area under the curve (AUC) and via comparison using a single internal standard.CONCLUSIONS: We report good separation of 40 primary amino group containing metabolites, in a single, 53 min run. This rapid, low cost, and accurate methodology only requires a small volume of sample and can greatly increase availability and access. Finally, the numerous amines and unique compounds detected in our single run has large utility and can potentially increase clinical efficiency and broaden access to research, both important as the need for analysis of amines grows globally.PMID:40110492 | PMC:PMC11919291 | DOI:10.1016/j.ymgmr.2025.101202

Metabolomics analysis of acute lung injury induced by aortic dissection in mice

Thu, 20/03/2025 - 11:00
Ann Med Surg (Lond). 2025 Jan 31;87(2):497-505. doi: 10.1097/MS9.0000000000002885. eCollection 2025 Feb.ABSTRACTThoracic aortic aneurysm/dissection (TAA/D) is a complicated vascular disorder with galloping development and high mortality. Phenotype switching plays an important role in the pathological process of TAA/D. Previous studies indicated the potential correlation between the expression level of lncRNA RP11-465L10.10 and MMP9 involved in the development of TAA/D. Here, our results showed that RP11-465L10.10 and MMP9 were highly increased in TAD patient tissues, which was consistent in Ang II-induced vascular smooth muscle cell (VSMC) phenotype switching. However, the effects and underlying mechanism of RP11-465L10.10 on VSMC phenotypic switching remain uncertain. Therefore, the expression of SM22α, cell proliferation, and migration were investigated when ectopically expressed RP11-465L10.10 in VSMCs. The results showed that RP11-465L10.10 overexpression decreased SM22α expression and facilitated VSMC proliferation, migration, and MMP9 expression. Furthermore, the NF-κB signaling pathway was enriched in transcriptome data analysis, indicating that NF-κB signaling may be involved in RP11-465L10.10-induced VSMC phenotype switching and MMP9 expression. In conclusion, this study demonstrated that RP11-465L10.10 induces VSMC phenotype switching and MMP9 expression via the NF-κB signaling pathway, suggesting that RP11-465L10.10 might be a potential therapeutic target for TAA/D treatment.PMID:40110328 | PMC:PMC11918661 | DOI:10.1097/MS9.0000000000002885

Serum metabolic profiling analysis of chronic gastritis and gastric cancer by untargeted metabolomics

Thu, 20/03/2025 - 11:00
Ann Med Surg (Lond). 2024 Dec 19;87(2):583-597. doi: 10.1097/MS9.0000000000002977. eCollection 2025 Feb.ABSTRACTChronic gastritis (CG), particularly when associated with Helicobacter pylori (H. pylori) infection, is a significant precursor to gastric cancer (GC), a leading cause of cancer-related deaths worldwide. The persistent inflammation in CG, driven by factors such as H. pylori, induces oxidative stress and DNA damage in gastric epithelial cells, which can lead to malignant transformation. Atrophic gastritis, a form of CG, can be categorized into autoimmune and H. pylori-associated types, both of which increase the risk of GC development, particularly when compounded by external factors like smoking and dietary habits. This manuscript explores the pathophysiological mechanisms underlying CG and its progression to GC, highlighting the critical role of metabolomics in advancing our understanding of these processes. Metabolomics, the comprehensive study of metabolites, offers a novel approach to identifying biomarkers that could facilitate early detection and improve the accuracy of GC diagnosis and prognosis. The analysis of metabolic alterations, particularly in glucose, lipid, and amino acid metabolism, reveals distinct biochemical pathways associated with the progression from benign gastritis to malignancy. Integrating metabolomic profiling with traditional diagnostic methods can revolutionize GC management, enabling more personalized treatment strategies and improving clinical outcomes. However, significant challenges remain, including the need to validate biomarkers across diverse populations and standardize metabolomic techniques. Future research should address these challenges to fully realize the potential of metabolomics in early GC detection and treatment, ultimately aiming to reduce the global burden of this deadly disease.PMID:40110261 | PMC:PMC11918594 | DOI:10.1097/MS9.0000000000002977

Sex differences in asthma: omics evidence and future directions

Thu, 20/03/2025 - 11:00
Front Genet. 2025 Mar 5;16:1560276. doi: 10.3389/fgene.2025.1560276. eCollection 2025.ABSTRACTAsthma is a common and complex heterogeneous disease, with prevalence and severity varying across different age groups and sexes. Over the past few decades, with the development of high-throughput technologies, various "omics" analyses have emerged and been applied to asthma research, providing us with significant opportunities to study the genetic mechanisms underlying asthma. However, despite these advancements, the differences and specificities in the genetic mechanisms of asthma between sexes remain to be fully explored. Moreover, clinical guidelines have yet to incorporate or recommend sex-specific asthma management based on high-quality omics evidence. In this article, we review recent omics-level findings on sex differ-ences in asthma and discuss how to better integrate these multidimensional findings to generate further insights and advance the precision and effectiveness of asthma treatment.PMID:40110046 | PMC:PMC11920188 | DOI:10.3389/fgene.2025.1560276

Multi-omics analysis reveals Jianpi formula-derived bioactive peptide-YG-22 potentially inhibited colorectal cancer via regulating epigenetic reprogram and signal pathway regulation

Thu, 20/03/2025 - 11:00
Front Genet. 2025 Mar 5;16:1560172. doi: 10.3389/fgene.2025.1560172. eCollection 2025.ABSTRACTINTRODUCTION: Colorectal cancer (CRC) is a prevalent malignancy worldwide, often treated with chemotherapy despite its limitations, including adverse effects and resistance. The traditional Chinese medicine (TCM) Jianpi formula has been demonstrated to improve efficacy of chemotherapy, however the underlying mechanisms still need to be explored. In this study, we aim to screen bioactive peptides derived from the blood of CRC patients through peptidomics and explore the molecular mechanisms of the candidate peptides in the inhibition of CRC using multi-omics analysis.METHODS: In this study, we recruited 10 patients with CRC who had received either adjuvant chemotherapy or adjuvant chemotherapy combined with the traditional Chinese medicine Jianpi formula after surgery. We collected plasma samples at 2 cycles of adjuvant therapy and performed peptidomic analysis on these samples. The differentially bioactive peptides were screened using a model of HCT116 cells in vitro. To investigate the molecular mechanism underlying YG-22's inhibition of the colorectal cancer cell line HCT116, we performed a multi-omics analysis, including transcriptome, metabolome, chromatin accessibility, H3K4Me3 histone methylation, and NF-κB binding site analyses.RESULTS: Differential peptides were identified in plasma samples from patients treated with adjuvant chemotherapy combined with the Jianpi formula. Among these peptides, YG-22 exhibited the strongest cytotoxic effect on HCT116 cells, reducing cell viability in a dose- and time-dependent manner. Transcriptome analysis highlighted that YG-22 treatment in CRC modulates key pathways associated with lysosome-mediated degradation and apoptosis. Metabolomic profiling further indicated disruptions in tumor-supportive metabolic pathways. Chromatin accessibility and histone modification analyses suggested that YG-22 induces epigenetic reprogramming. Additionally, treatment with YG-22 resulted in significant changes in NF-κB binding and pathway activation.CONCLUSIONS: This study demonstrates that combining chemotherapy with TCM Jianpi formula enriches the molecular landscape and generates bioactive peptides with strong antitumor activity. Furthermore, this study also lays the foundation for further development of peptide-based therapies and highlights the value of combining traditional and modern therapeutic strategies for CRC management.PMID:40110036 | PMC:PMC11919836 | DOI:10.3389/fgene.2025.1560172

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