PubMed

Nat Commun. 2024 Aug 20;15(1):7136. doi: 10.1038/s41467-024-51433-3.ABSTRACTUntargeted metabolomic analysis using mass spectrometry provides comprehensive metabolic profiling, but its medical application faces challenges of complex data processing, high inter-batch variability, and unidentified metabolites. Here, we present DeepMSProfiler, an explainable deep-learning-based method, enabling end-to-end analysis on raw metabolic signals with output of high accuracy and reliability. Using cross-hospital 859 human serum samples from lung adenocarcinoma, benign lung nodules, and healthy individuals, DeepMSProfiler successfully differentiates the metabolomic profiles of different groups (AUC 0.99) and detects early-stage lung adenocarcinoma (accuracy 0.961). Model flow and ablation experiments demonstrate that DeepMSProfiler overcomes inter-hospital variability and effects of unknown metabolites signals. Our ensemble strategy removes background-category phenomena in multi-classification deep-learning models, and the novel interpretability enables direct access to disease-related metabolite-protein networks. Further applying to lipid metabolomic data unveils correlations of important metabolites and proteins. Overall, DeepMSProfiler offers a straightforward and reliable method for disease diagnosis and mechanism discovery, enhancing its broad applicability.PMID:39164279 | DOI:10.1038/s41467-024-51433-3

Nat Commun. 2024 Aug 20;15(1):6408. doi: 10.1038/s41467-024-50470-2.ABSTRACTVenomous animals have evolved diverse molecular mechanisms to incapacitate prey and defend against predators. Most venom components disrupt nervous, locomotor, and cardiovascular systems or cause tissue damage. The discovery that certain fish-hunting cone snails use weaponized insulins to induce hypoglycemic shock in prey highlights a unique example of toxins targeting glucose homeostasis. Here, we show that, in addition to insulins, the deadly fish hunter, Conus geographus, uses a selective somatostatin receptor 2 (SSTR2) agonist that blocks the release of the insulin-counteracting hormone glucagon, thereby exacerbating insulin-induced hypoglycemia in prey. The native toxin, Consomatin nG1, exists in several proteoforms with a minimized vertebrate somatostatin-like core motif connected to a heavily glycosylated N-terminal region. We demonstrate that the toxin's N-terminal tail closely mimics a glycosylated somatostatin from fish pancreas and is crucial for activating the fish SSTR2. Collectively, these findings provide a stunning example of chemical mimicry, highlight the combinatorial nature of venom components, and establish glucose homeostasis as an effective target for prey capture.PMID:39164229 | DOI:10.1038/s41467-024-50470-2

Adv Biol (Weinh). 2024 Aug 20:e2400128. doi: 10.1002/adbi.202400128. Online ahead of print.ABSTRACTEarly allograft dysfunction (EAD) is a frequent phenomenon, leading to increased graft loss and higher mortality after liver transplantation (LT). Despite significant efforts for early diagnosis of EAD, there is no existing approach that can predict EAD on the first post-operative day. The aim is to define a metabolite-based biomarker on the first day after LT complicated with EAD. Ten patients diagnosed with EAD and 26 non-EAD are recruited for the study. A HPLC-MS/MS is used to determine 14 amino acids and 15 bile acids serum concentration. Comparative analyses are conducted between EAD and non-EAD groups. Arginine is identified as the most significant metabolite distinguishing the EAD and non-EAD groups, and therefore, is identified as a potential biomarker of EAD. The optimal cut-off value for arginine is 52.09 µmol L-1, with an AUROC of 0.804 (95% confidence interval: 0.638-0.917, p < 0.001), yielding a sensitivity of 100%, specificity of 53.8%, and Youden index of 0.54, NPVof 100%, and PPV of 45.45%. In summary, the study indicated that targeted metabolomics analysis would be a promising strategy for discovering novel biomarkers to predict EAD. The identified arginine may be helpful in developing an objective diagnostic method for EAD.PMID:39164220 | DOI:10.1002/adbi.202400128

J Appl Toxicol. 2024 Aug 20. doi: 10.1002/jat.4692. Online ahead of print.ABSTRACTThe coking industry in China is the largest coke supplier in the world. Contaminated soil in industrial areas poses a serious threat to human and ecosystems. Most of the studies investigated the toxicity of soil from coking plant on soil microorganisms, while the toxic effects of soil leaching liquor on aquatics are limited. In this study, the composition of soil leaching liquor from a coking plant in Taiyuan (TY) was analyzed, and the developmental toxicity on zebrafish was evaluated. The results showed that a total of 91 polycyclic aromatic hydrocarbons were detected in the leaching liquor, followed by phenols and benzene series. The leaching liquor induced developmental impairment in zebrafish larvae, including delayed incubation, deficits in locomotor behavior, vascular and cardiac dysplasia, and impaired neurodevelopment. The results of metabolomics analysis showed that TY soil leaching liquor induced significant metabolic profile disturbances in zebrafish embryos/larvae. The developmental toxicity of the leaching liquor metabolic disorders may be associated with the leaching liquor-induced abnormalities in zebrafish embryonic development. Metabolic pathways were identified by arginine and proline metabolism, phosphotransferase system, starch and sucrose metabolism, steroid biosynthesis, beta-alanine metabolism, and nucleotide metabolism pathways.PMID:39164216 | DOI:10.1002/jat.4692

Am J Chin Med. 2024 Aug 21:1-28. doi: 10.1142/S0192415X24500605. Online ahead of print.ABSTRACTAstragaloside IV (AS-IV), a natural triterpenoid isolated from Astragalus membranaceus, has been used traditionally in Chinese medicine. Previous studies have highlighted its benefits against carcinoma, but its interaction with the gut microbiota and effects on adenomatous polyps are not well understood. This present study investigates the effects of AS-IV on colonic adenomatous polyp (CAP) development in high-fat-diet (HFD) fed [Formula: see text] mice. [Formula: see text] mice were fed an HFD with or without AS-IV or Naringin for 8 weeks. The study assessed CAP proliferation and employed 16S DNA-sequencing and untargeted metabolomics to explore correlations between microbiome and metabolome in CAP development. AS-IV was more effective than Naringin in reducing CAP development, inhibiting colonic proinflammatory cytokines (IL-1[Formula: see text], IL-6, and TNF-[Formula: see text]), tumor associated biomarkers (c-Myc, Cyclin D1), and Wnt/[Formula: see text]-catenin pathway proteins (Wnt3a, [Formula: see text]-catenin). AS-IV also inhibited the proliferative capabilities of human colon cancer cells (HT29, HCT116, and SW620). Multiomics analysis revealed AS-IV increased the abundance of beneficial genera such as Bifidobacterium pseudolongum and significantly modulated serum levels of certain metabolites including linoleate and 2-trans,6-trans-farnesal, which were significantly correlated with the number of CAP. Finally, the anti-adenoma efficacy of AS-IV alone was significantly suppressed post pseudoaseptic intervention in HFD-fed [Formula: see text] mice but could be reinstated following a combined with Bifidobacterium pseudolongum transplant. AS-IV attenuates CAP development in HFD-fed [Formula: see text] mice by regulating gut microbiota and metabolomics, impacting the Wnt3a/[Formula: see text]-catenin signaling pathway. This suggests a potential new strategy for the prevention of colorectal cancer, emphasizing the role of gut microbiota in AS-IV's antitumor effects.PMID:39164214 | DOI:10.1142/S0192415X24500605

Dig Liver Dis. 2024 Aug 19:S1590-8658(24)00886-7. doi: 10.1016/j.dld.2024.07.022. Online ahead of print.ABSTRACTBACKGROUND AND AIMS: Bevacizumab-based chemotherapy is a recommended first-line treatment for metastatic colorectal cancer (mCRC). Robust biomarkers with clinical practice applicability have not been identified for patients with this treatment. We aimed to evaluate the prognostic yield of serum mid-infrared spectroscopy (MIRS) on patients receiving first-line bevacizumab-based chemotherapy for mCRC.METHODS: We conducted an ancillary analysis from a multicentre prospective study (NCT00489697). All baseline serums were screened by attenuated total reflection method. Principal component analysis and unsupervised k-mean partitioning methods were performed blinded to all patients' data. Endpoints were progression-free survival (PFS) and overall survival (OS).RESULTS: From the 108 included patients, MIRS discriminated two prognostic groups. First group patients had significantly lower body mass index (p = 0.026) and albumin levels (p < 0.001), and higher levels of angiogenic markers, lactate dehydrogenase and carcinoembryonic antigen (p < 0.001). In univariate analysis, their OS and PFS were shorter with respective medians: 17.6 vs 27.9 months (p = 0.02) and 8.7 vs 11.3 months (p = 0.03). In multivariate analysis, PFS was significantly shorter (HR = 1.74, p = 0.025) with a similar trend for OS (HR = 1.69, p = 0.061).CONCLUSION: By metabolomic fingerprinting, MIRS proves to be a promising prognostic tool for patients receiving first-line bevacizumab-based chemotherapy for mCRC.PMID:39164167 | DOI:10.1016/j.dld.2024.07.022

Gut Microbes. 2024 Jan-Dec;16(1):2388295. doi: 10.1080/19490976.2024.2388295. Epub 2024 Aug 20.ABSTRACTFecal Microbiota Transplantation (FMT) has emerged as a potential modality for mitigating microbiome-associated diseases. Despite this potential, the precise causal pathways by which specific gut microbiota strains induce remission remain inadequately elucidated. In this study, we aimed to discern the impact of engraftment of donor-infused strains on alterations in plasma metabolites, subsequently contributing to the amelioration of clinical parameters involved in subjects with metabolic syndrome (MetSyn) receiving an FMT. We observed that a higher fraction of donor strains engrafted in the recipient is correlated to a reduction in diastolic blood pressure and found specific strain associations through canonical correlation analysis. Integrating the metabolomics profile shows that engraftment of Collinsella aerofaciens and Fusocatenibacter saccharovorans was related to a reduction in 2-oxoarginine in plasma, which was subsequently correlated to a reduction in diastolic blood pressure. In conclusion, we applied a novel framework to elucidate on the complex and heterogenous FMT intervention, establishing a connection between engrafted microbiota and clinical outcome parameters. Our findings underscore the potential therapeutic efficacy of FMT in ameliorating MetSyn, demonstrating a potential contribution of microbial strain engraftment to the improvement of MetSyn via modulation of circulating metabolites.PMID:39163526 | DOI:10.1080/19490976.2024.2388295

Metab Syndr Relat Disord. 2024 Aug 20. doi: 10.1089/met.2024.0106. Online ahead of print.ABSTRACTBackground: Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, MBS effects on glucocorticoid metabolites are unknown. Objective: To evaluate (i) changes in the cortisol/cortisone ratio in youth with obesity 12 months after sleeve gastrectomy (SG) compared with nonsurgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. Methods: A total of 38 participants 13-25 years old with obesity (29 female) were followed for 12 months. Half underwent SG, and the other half were followed with routine care (nonsurgical, NS). Fasting blood was assessed for cortisol and cortisone using liquid chromatography-mass spectroscopy as part of metabolomic analysis, and the cortisol/cortisone ratio was calculated. A single-slice MRI of the abdomen was performed to assess subcutaneous and visceral adipose tissue (SAT, VAT). Hepatic steatosis was assessed by computed tomography (CT). Results: SG did not differ from NS for baseline clinical characteristics, other than the mean age (SG 18.0 ± 0.46 vs. NS 16.6 ± 0.50 years, P = 0.041), BMI (BMI, 47.23 ± 1.5 vs. 41.32 ± 1.1 kg/m2, P = 0.003) weight and VAT, which were higher in SG. Significant reductions were noted over 12 months in BMI, BMI z-score, VAT, and SAT within the SG versus NS groups (P ≤ 0.001). Over 12 months, groups did not differ for changes in cortisol/cortisone ratio after controlling for age at baseline (P = 0.293). The ratio trended to decrease within the SG group [-1.40 (-5.08, 0.06), P = 0.080], particularly among those that had completed puberty (P = 0.048). No associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Conclusions: The cortisol/cortisone ratio trended to decrease 12 months following SG. However, no associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Studies with larger numbers of participants are necessary to confirm these findings.PMID:39163292 | DOI:10.1089/met.2024.0106

Planta. 2024 Aug 20;260(4):76. doi: 10.1007/s00425-024-04505-z.ABSTRACTAfter the most comprehensive analysis of the phenolic composition in Cannabis reported to date, a total of 211 compounds were identified, phenolic profiles were able to discriminate cannabis varieties and a complex regulatory network for phenolics accumulation in Cannabis chemovars was highlighted. Female inflorescences of Cannabis sativa L. are plenty of secondary metabolites, of which flavonoids and phenolic acids have been investigated by far less than phytocannabinoids and terpenoids. Understanding the biochemical composition in phenylpropanoids of Cannabis inflorescences, the molecular basis of flavonoid synthesis and how their content can be modulated by specific transcription factors will shed light on the variability of this trait in the germplasm, allowing the identification of biologically active metabolites that can be of interest to diverse industries. In this work, an untargeted metabolomic approach via UHPLC-HRMS was adopted to investigate the composition and variability of phenylpropanoids in thirteen Cannabis genotypes differentiated for their profile in phytocannabinoids, highlighting that phenolic profiles can discriminate varieties, with characteristic, unique genotype-related patterns. Moreover, the transcription profile of candidate phenolics regulatory MYB and bHLH transcription factors, analyzed by RT-qPCR, appeared strongly genotype-related, and specific patterns were found to be correlated between biochemical and transcriptional levels. Results highlight a complex regulatory network for phenolic accumulation in Cannabis chemovars that will need further insights from the functional side.PMID:39162869 | DOI:10.1007/s00425-024-04505-z

J Proteome Res. 2024 Aug 20. doi: 10.1021/acs.jproteome.3c00924. Online ahead of print.ABSTRACTA comprehensive understanding of the exact influence of type 2 diabetes mellitus (T2DM) on the metabolic status of non-small cell lung cancer (NSCLC) is still lacking. This study explores metabolic alterations in tumor tissues among patients with coexisting NSCLC and T2DM in comparison with NSCLC patients. A combined approach of clinical analysis and metabolomics was employed, including 20 NSCLC patients and 20 NSCLC+T2DM patients. Targeted metabolomics analysis was performed on tumor tissues using the liquid chromatography-mass spectrometry (LC-MS) approach. A clear segregation was observed between NSCLC+T2DM and matched NSCLC tissue samples in Orthogonal Partial Least Squares Discrimination Analysis (OPLS-DA). Furthermore, the levels of 7 metabolites are found to be significantly different between diabetes/nondiabetes tumor tissue samples. The related pathways included arginine biosynthesis, glutathione metabolism, arginine and proline metabolism, purine metabolism, biotin metabolism, and histidine metabolism. 3-Phenyllactic acid, carnitine-C5, carnitine-C12, and serotonin showed a positive linear correlation with fasting blood glucose levels in NSCLC patients. Uridine, pipecolic acid, cytosine, and fasting blood glucose levels were found to have a negative correlation. Our results suggest that NSCLC patients with concurrent T2DM exhibit distinct metabolic shifts in tumor tissues compared to those of solely NSCLC patients.PMID:39162688 | DOI:10.1021/acs.jproteome.3c00924

Microbiol Spectr. 2024 Aug 20:e0029124. doi: 10.1128/spectrum.00291-24. Online ahead of print.ABSTRACTTryptophan (TRP) metabolites have been identified as potent biomarkers for complications of type 2 diabetes mellitus (T2DM). However, it remains unclear whether the therapeutic effect of metformin in T2DM is related to the modulation of TRP metabolic pathway. This study aims to investigate whether metformin affects TRP metabolism in T2DM mice through the gut microbiota. A liquid chromatography-tandem mass spectrometry method was established to determine 16 TRP metabolites in the serum, colon content, urine, and feces of T2DM mice, and the correlations between metabolites and the T2DM mice gut microbiota were performed. The method demonstrated acceptable linearity (R2 > 0.996), with the limit of quantification ranging from 0.29 to 69.444 nmol/L for 16 analytes, and the limit of detection ranging from 0.087 to 20.833 nmol/L. In T2DM mice, metformin treatment effectively restored levels of indole-3-lactic acid (ILA), indole-3-propionic acid (IPA), and the ILA/IPA ratio, along with several aryl hydrocarbon receptor ligands in the serum, with a notable impact in the colon but not in the urine. This restoration was accompanied by a shift in the relative abundance of Dubosiella, Turicibacter, RF39, Clostridia_UCG-014, and Alistipes. Spearman's correlation analysis revealed positive correlations between Turicibacter and Alistipes with IPA and indole-3-acetic acid. Conversely, these genera displayed negative correlations with ILA and kynurenine. In addition, our study revealed the presence of endogenous indole pathway in germ-free mice, and the impact of metformin on endogenous TRP metabolism in T2DM mice cannot be disregarded. Further research is needed to investigate the regulation of TRP metabolism by metformin.IMPORTANCE: This study provides valuable insights into the interrelationship between metformin administration, changes in the tryptophan (TRP) metabolome, and gut microbiota in type 2 diabetes mellitus (T2DM) mice. Indole-3-lactic acid (ILA)/indole-3-propionic acid (IPA) emerges as a potential biomarker for the development of T2DM and prediction of therapeutic response. While the indole metabolic pathway has long been associated exclusively with the gut microbiome, recent research has demonstrated the ability of host interleukin-4-induced-1 to metabolize TRP. The detection of indole derivatives in the serum of germ-free mice suggests the existence of inherent endogenous indole metabolic pathways. These findings deepen our understanding of metformin's efficacy in correcting TRP metabolic disorders and provide valuable directions for further investigation. Moreover, this knowledge may pave the way for the development of targeted treatment strategies for T2DM, focusing on the gut microbiome and restoration of associated TRP metabolism.PMID:39162538 | DOI:10.1128/spectrum.00291-24

Microbiol Spectr. 2024 Aug 20:e0094424. doi: 10.1128/spectrum.00944-24. Online ahead of print.ABSTRACTThis study explores the dynamics of immune gene expression, ruminal metabolome, and gut microbiota in cows due to the duration of high-grain feeding, shedding light on host response and microbial dynamics in parallel. Cows consumed forage for a week, then gradually transitioned to a high-grain diet, which they consumed for 4 weeks. Immune response was evaluated in ruminal papillae by expression of genes related to the nuclear factor-kappaB (NFkB) pathway and correlated with the microbiota. Rumen metabolome was evaluated with high-performance liquid chromatography coupled with mass spectrometry and anion-exchange chromatography. Rumen and fecal microbiota were evaluated with 16S rRNA gene amplicon sequencing. In the rumen, expression of inflammation-associated genes increased with the duration on high grain, indicating activation of pro-inflammatory cascades; microbial diversity decreased with a high-grain diet but stabilized after week 3 on high grain. Changes in microbial relative abundance and metabolite enrichment were observed throughout the 4 weeks on high grain, with increments in propionogenic taxa (i.e., Succinivibrionaceae). Metabolite enrichment analysis showed that at the start of high-grain feeding, simple carbohydrates were enriched; then, these were substituted by their fermentation products. There were correlations between certain ruminal bacterial taxa (i.e., Ruminococcaceae UCG-005) and expression of genes of the NFkB pathway, suggesting the influence of these taxa on host immune response. In feces, microbial diversity and several Ruminococcaceae members initially declined but recovered by weeks 3 and 4. Overall, despite the stabilization of microbial diversity, changes in microbial relative abundance and proinflammatory genes were observed throughout high-grain feeding, suggesting that cows need more than 4 weeks to fully adjust once consuming a high-grain diet.IMPORTANCEDespite the stepwise diet transition typically assumed to serve for animal adaptation, expression of signaling receptors, mediators, and downstream targets of nuclear factor-kappaB pathway were found throughout the 4 weeks on high grain, which correlated with changes in the rumen microbial profile. In addition, although microbial diversity recovered in the feces and stabilized in the rumen in week 3 on high grain, we observed changes in microbial relative abundance throughout the 4 weeks on high grain, suggesting that cows need more than 4 weeks to adjust once consuming this diet. Findings are particularly important to consider when planning experiments involving dietary changes.PMID:39162517 | DOI:10.1128/spectrum.00944-24

Adv Cancer Res Clin Imaging. 2024;4(3):587. doi: 10.33552/acrci.2024.04.000587. Epub 2024 Jul 5.ABSTRACTInhibitors of kinases involved in signaling and other intracellular pathways, have revolutionized cancer treatment by providing highly targeted and effective therapies. However, timely monitoring treatment response remains a considerable challenge since conventional methods such as assessing changes in tumor volume do not adequately capture early responses or resistance development, due to the predominantly cytostatic rather than cytotoxic effect of kinase inhibitors. Magnetic resonance spectroscopy (MRS) is a non-invasive imaging technique that can provide insights into cellular metabolism by detecting changes in metabolite concentrations. By measuring metabolite levels, MRS offers a means to assess treatment response in real-time, providing earlier indications of efficacy or resistance compared to conventional imaging modalities. Bruton's Tyrosine Kinase (BTK) is a critical enzyme involved in B-cell receptor signaling. BTK inhibitors have been approved for the treatment of Mantle Cell Lymphoma (MCL) and other B-cell malignancies. Recent studies involving genome-scale gene expression, metabolomic, and fluxomic analyses have demonstrated that ibrutinib, an index BTK inhibitor, profoundly affects the key metabolic pathways in MCL cells., including glycolysis, glutaminolysis, pentose shunt, TCA cycle and phospholipid metabolism. Importantly, the effects of ibrutinib on MCL cells directly and proportionately correlates with their sensitivity to the drug. Consequently, changes in specific metabolite concentrations detectable non-invasively by MRS such as lactate and alanine reflecting mostly the status of cellular glycolysis and glutaminolysis, respectively, have emerged as potential biomarkers for predicting response and resistance of MCL cells to BTK inhibition, both in vitro and in vivo. Preparations to validate the utility of these biomarkers in clinical setting are under way. These studies may pave the way to monitor therapeutic response to kinase inhibitors also in other types of cancer.PMID:39161974 | PMC:PMC11332593 | DOI:10.33552/acrci.2024.04.000587

Front Pharmacol. 2024 Aug 5;15:1404021. doi: 10.3389/fphar.2024.1404021. eCollection 2024.ABSTRACTBACKGROUND: Influenza virus is one of the most common pathogens that cause viral pneumonia. During pneumonia, host immune inflammation regulation involves microbiota in the intestine and glycolysis in the lung tissues. In the clinical guidelines for pneumonia treatment in China, Ma Xing Shi Gan Decoction (MXSG) is a commonly prescribed traditional Chinese medicine formulation with significant efficacy, however, it remains unclear whether its specific mechanism of action is related to the regulation of intestinal microbiota structure and lung tissue glycolysis.OBJECTIVE: This study aimed to investigate the mechanism of action of MXSG in an animal model of influenza virus-induced pneumonia. Specifically, we aimed to elucidate how MXSG modulates intestinal microbiota structure and lung tissue glycolysis to exert its therapeutic effects on pneumonia.METHODS: We established a mouse model of influenza virus-induced pneumoni, and treated with MXSG. We observed changes in inflammatory cytokine levels and conducted 16S rRNA gene sequencing to assess the intestinal microbiota structure and function. Additionally, targeted metabolomics was performed to analyze lung tissue glycolytic metabolites, and Western blot and enzyme-linked immunosorbent assays were performed to assess glycolysis-related enzymes, lipopolysaccharides (LPSs), HIF-1a, and macrophage surface markers. Correlation analysis was conducted between the LPS and omics results to elucidate the relationship between intestinal microbiota and lung tissue glycolysis in pneumonia animals under the intervention of Ma Xing Shi Gan Decoction.RESULTS: MXSG reduced the abundance of Gram-negative bacteria in the intestines, such as Proteobacteria and Helicobacter, leading to reduced LPS content in the serum and lungs. This intervention also suppressed HIF-1a activity and lung tissue glycolysis metabolism, decreased the number of M1-type macrophages, and increased the number of M2-type macrophages, effectively alleviating lung damage caused by influenza virus-induced pneumonia.CONCLUSION: MXSG can alleviate glycolysis in lung tissue, suppress M1-type macrophage activation, promote M2-type macrophage activation, and mitigate inflammation in lung tissue. This therapeutic effect appears to be mediated by modulating gut microbiota and reducing endogenous LPS production in the intestines. This study demonstrates the therapeutic effects of MXSG on pneumonia and explores its potential mechanism, thus providing data support for the use of traditional Chinese medicine in the treatment of respiratory infectious diseases.PMID:39161892 | PMC:PMC11331264 | DOI:10.3389/fphar.2024.1404021

Front Neurol. 2024 Aug 5;15:1403312. doi: 10.3389/fneur.2024.1403312. eCollection 2024.ABSTRACTThere is compelling evidence that a dysregulated immune inflammatory response in neuroinfectious diseases results in modifications in metabolic processes and altered metabolites, directly or indirectly influencing lipid metabolism within the central nervous system (CNS). The challenges in differential diagnosis and the provision of effective treatment in many neuroinfectious diseases are, in part, due to limited understanding of the pathophysiology underlying the disease. Although there are numerous metabolomics studies, there remains a deficit in neurolipidomics research to provide a comprehensive understanding of the connection between altered metabolites and changes in lipid metabolism. The brain is an inherently high-lipid organ; hence, understanding neurolipidomics is the key to future breakthroughs. This review aims to provide an integrative summary of altered cerebrospinal fluid (CSF) metabolites associated with neurolipid metabolism in bacterial and viral CNS infections, with a particular focus on studies that used liquid chromatography-mass spectrometry (LC-MS). Lipid components (phospholipids) and metabolites (carnitine and tryptophan) appear to be the most significant indicators in both bacterial and viral infections. On the basis of our analysis of the literature, we recommend employing neurolipidomics in conjunction with existing neurometabolomics data as a prospective method to enhance our understanding of the cross link between dysregulated metabolites and lipid metabolism in neuroinfectious diseases.PMID:39161867 | PMC:PMC11330781 | DOI:10.3389/fneur.2024.1403312

Front Oncol. 2024 Aug 5;14:1413264. doi: 10.3389/fonc.2024.1413264. eCollection 2024.ABSTRACTBACKGROUND AND AIMS: Aberrations in the immunoglobulin heavy chain (IgH) locus are associated with poor prognosis in pediatric precursor B-cell acute lymphoblastic leukemia (BCP-ALL) patients. The primary objective of this pilot study is to enhance our understanding of the IgH phenotype by exploring the intracellular chiral metabolome.MATERIALS AND METHODS: Leukemia cells were isolated from the bone marrow of BCP-ALL pediatric patients at diagnosis. The samples' metabolome and transcriptome were characterized using untargeted chiral metabolomic and next-generation sequencing transcriptomic analyses.RESULTS: For the first time D- amino acids were identified in the leukemic cells' intracellular metabolome from the bone marrow niche. Chiral metabolic signatures at diagnosis was indicative of a resistant phenotype. Through integrated network analysis and Pearson correlation, confirmation was obtained regarding the association of the IgH phenotype with several genes linked to poor prognosis.CONCLUSION: The findings of this study have contributed to the understanding that the chiral metabolome plays a role in the poor prognosis observed in an exceptionally rare patient cohort. The findings include elevated D-amino acid incorporation in the IgH group, the emergence of several unknown, potentially enantiomeric, metabolites, and insights into metabolic pathways that all warrant further exploration.PMID:39161381 | PMC:PMC11332069 | DOI:10.3389/fonc.2024.1413264

CNS Neurosci Ther. 2024 Aug;30(8):e70003. doi: 10.1111/cns.70003.ABSTRACTAIMS: We evaluated the potential of Parkinson's disease (PD) fecal microbiota transplantation to initiate or exacerbate PD pathologies and investigated the underlying mechanisms.METHODS: We transplanted the fecal microbiota from PD patients into mice by oral gavage and assessed the motor and intestinal functions, as well as the inflammatory and pathological changes in the colon and brain. Furthermore, 16S rRNA gene sequencing combined with metabolomics analysis was conducted to assess the impacts of fecal delivery on the fecal microbiota and metabolism in recipient mice.RESULTS: The fecal microbiota from PD patients increased intestinal inflammation, deteriorated intestinal barrier function, intensified microglia and astrocyte activation, abnormal deposition of α-Synuclein, and dopaminergic neuronal loss in the brains of A53T mice. A mechanistic study revealed that the fecal microbiota of PD patients stimulated the TLR4/NF-κB/NLRP3 pathway in both the brain and colon. Additionally, multiomics analysis found that transplantation of fecal microbiota from PD patients not only altered the composition of the gut microbiota but also influenced the fecal metabolic profile of the recipient mice.CONCLUSION: The fecal microbiota from PD patients intensifies inflammation and neurodegeneration in A53T mice. Our findings demonstrate that imbalance and dysfunction in the gut microbiome play significant roles in the development and advancement of PD.PMID:39161161 | DOI:10.1111/cns.70003

Physiol Rep. 2024 Aug;12(16):e70005. doi: 10.14814/phy2.70005.ABSTRACTMaintenance hemodialysis (MHD) patients exhibit compromised immune responses, leading to lower immunogenicity to the COVID-19 vaccine than the general population. The metabolomic factors influencing COVID-19 vaccine response in MHD patients remain elusive. A cross-sectional study was conducted with 30 MHD patients, divided into three vaccine regimen groups (N= 10 per group): homologous CoronaVac® (SV-SV), homologous ChAdOx1 nCoV-19 (AZ-AZ), and heterologous prime-boost (SV-AZ). Plasma samples were collected at baseline and at 28 days after the final dose to analyze 92 metabolomic levels using targeted metabolomics. The study included 30 MHD patients (mean age 56.67 ± 10.79 years) with similar neutralizing antibody (nAb) levels across vaccine regimens. The most significant differences in metabolomics were found between AZ-AZ and SV-SV, followed by SV-AZ versus SV-SV, and AZ-AZ versus SV-AZ. Overall, the metabolomic changes involved amino acids like glutamate and phenylalanine, and phospholipids. Prevaccination metabolomic profiles, including PG (38:1), lysoPE (20:2), lysoPC (18:2), lysoPI (18:1), and PC (34:2), exhibited negative correlations with postvaccination nAb levels. Different COVID-19 vaccine regimens had unique interactions with the immune response in MHD patients. Amino acid and phospholipid metabolisms play crucial roles in nAb formation, with the phospholipid metabolism being a potentially predictive marker of vaccine immunogenicity among MHD patients.PMID:39161065 | DOI:10.14814/phy2.70005

Food Res Int. 2024 Oct;193:114858. doi: 10.1016/j.foodres.2024.114858. Epub 2024 Aug 2.ABSTRACTNoni fruit is renowned for its abundance of bioactive compounds. Drying is an important method for processing functional products derived from noni. However, limited information exists on how drying methods affect the active metabolite profiles of noni fruit. This study investigated the impact of four common drying methods, including hot-air drying (HAD), vacuum freeze drying (VFD), microwave drying (MWD), and far infrared drying (FID), on the physicochemical indexes, bioactive components, and functional properties of dried noni fruit slices using targeted and untargeted metabonomics analysis. The results showed significant variations in appearance, water migration, and microstructure of dried noni fruit slices subjected to the four drying methods. VFD treatment yielded better dried noni fruit products when compared to other drying methods. The superiority of VFD treatment was due to its uniform stratification, reduced collapse, better retention of bioactive components and antioxidants, and higher enzyme inhibitory rates. These findings suggest that VFD method is ideal for obtaining premium bioactive profiles and maintaining the biological activity of noni fruit.PMID:39160054 | DOI:10.1016/j.foodres.2024.114858

Food Res Int. 2024 Oct;193:114867. doi: 10.1016/j.foodres.2024.114867. Epub 2024 Aug 4.ABSTRACTThe flavor stability of tea beverages during storage has long been a concern. The study aimed to explore the flavor stability of Longjing green tea beverage using accelerated heat treatment trials, addressing the shortage of lengthy storage trials. Sensory evaluations revealed changes in bitterness, umami, overall harmonization, astringency, and ripeness as treatment duration increased. Accompanied by a decrease in L-values, ΔE and an increase in a and b-values. Seventeen non-volatile metabolites and three volatile metabolites were identified differential among samples by metabolomics, with subsequent correlation analysis indicating associations between sensory attributes and specific metabolites. Umami was linked to epigallocatechin 3,5-digallate and alpha-D-glucopyranose, astringency was correlated with ellagic acid and 1-ethyl-1H-pyrrole. Ripeness showed associations with ellagic acid, 6,7-dihydroxycoumarin, heptanal, and benzaldehyde, and overall harmonization was linked to 6,7-dihydroxycoumarin, β-myrcene, α-terpineol, and heptanal. A series of verification tests confirmed the feasibility of accelerated heat treatment trials to replace traditional storage trials. These results offer valuable insights into unraveling the complex relationship between sensory and chemical profiles of green tea beverages.PMID:39160050 | DOI:10.1016/j.foodres.2024.114867