PubMed

Toxicology. 2023 Apr 28:153530. doi: 10.1016/j.tox.2023.153530. Online ahead of print.ABSTRACTEndemic fluorosis is a global public health problem. Cardiovascular diseases caused by fluoride are closely related to endothelial cell injury. Metabolism disorder of endothelial cells (ECs) are recognized as the key factor of endothelial dysfunction which has been a hot topic in recent years. However, the toxic effect of fluoride on vascular endothelium has not been elucidated. The aim of this study was to explore the alteration of endothelial cell metabolites in Human Umbilical Vein Endothelial Cells (HUVECs) exposed to NaF using LC-MS/MS technique. The screening conditions were Variable Importance for the Projection (VIP) > 1 and P < 0.05. It was found that the expression of the metabolites Lumichrome and S-Methyl-5'-thioadenosine was upregulated and of the other metabolites, such as Creatine, L-Glutamate, Stearic acid was downregulated. Differential metabolites were found to be primarily related to FoxO、PI3K/Akt and apoptosis signaling pathways by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. From the perspective of metabolism, this study explored the possible mechanism of fluoride induced endothelial cell injury which providing theories and clues for subsequent studies.PMID:37121536 | DOI:10.1016/j.tox.2023.153530

J Ethnopharmacol. 2023 Apr 28:116546. doi: 10.1016/j.jep.2023.116546. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: P. lobata and P. thomsonii are medicinal plants with similar pharmacological functions but different therapeutic effects. A novel method is presented herein to investigate metabolites in terms of their distribution and qualification, quantification is necessary to elucidate the different therapeutic effects of the two Puerariae species.AIM OF THE STUDY: The aim of the present study was to perform spatially resolved metabolomics combined with bioactivity analyses to systematically compare the metabolite differences in P. lobata and P. thomsonii by distribution, qualification, quantification, and biological activity to evaluate their pharmacological properties.MATERIALS AND METHODS: Air flow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI) was performed to characterize the differences in the metabolite distributions of P. lobata and P. thomsonii. Further qualitative and quantitative analyses of the differential metabolites were performed using liquid chromatography-mass spectrometry (LC-MS). Biological activities correlated with the differences in the metabolites were validated by MTT assays.RESULTS: Some metabolites showed complementary distributions of the phloem and xylem in the two species, saccharide, vitamin, and inosine levels were higher in the phloem of P. thomsonii but higher in the xylem of P. lobata. The 3'-hydroxyl puerarin level was higher in the xylem of P. thomsonii but higher in the phloem of P. lobata. Qualitative and quantitative analyses of the metabolites revealed a total of 52 key differential metabolites. MTT assays showed that daidzein, daidzin, puerarin, ononin, genistin, formononetin, 3'-hydroxy puerarin, 3'-methoxy puerarin, mirificin, and 3'-methoxy daidzin exerted protective effects on H9c2 cells against hypoxia/reoxygenation injury. P. lobata extracts exhibited a significantly better protective efficacy than P. thomsonii extracts.CONCLUSIONS: In this study, AFADESI-MSI combined with LC-MS and biological activities comprehensively elucidated metabolite differences in the distribution, qualification, quantification, and pharmacological properties of P. lobata and P. thomsonii. The results of this study could provide a novel strategy for species identification and quality assessment of similar Chinese herbal medicines.PMID:37121451 | DOI:10.1016/j.jep.2023.116546

Anal Chem. 2023 Apr 25. doi: 10.1021/acs.analchem.3c00369. Online ahead of print.ABSTRACTUrine is a preferred object for noninvasive diagnostic strategies. Urinary metabolic analysis is speculatively regarded as an ideal tool for screening diseases closely related to the genitourinary system in view of the intimate relationship between metabolomics and phenotype. Herein, we propose a urinary metabolic fingerprint-based noninvasive diagnostic strategy by designing hollow core-shell metal oxide heterojunctions (denoted as MOHs). With outstanding light absorption and electron-hole separation ability, MOHs aid in the extraction of high-performance urine metabolic fingerprints. Coupled with optimized machine learning algorithms, we establish a metabolic marker panel for accurate diagnosis of prostate cancer (PCa), which is the most common malignant tumor of the male genitourinary system, achieving accuracies of 84.72 and 83.33% in the discovery and validation sets, respectively. Furthermore, metabolite variations and related pathway analyses confirm the credibility and change correlation of key metabolic features in PCa. This work tends to advance the noninvasive diagnostic strategy toward clinical realities.PMID:37121232 | DOI:10.1021/acs.analchem.3c00369

J Hazard Mater. 2023 Apr 28;454:131532. doi: 10.1016/j.jhazmat.2023.131532. Online ahead of print.ABSTRACTTriclosan (TCS) is an antiseptic incorporated in consumer goods and personal care products that can be absorbed via the skin, raising public health concerns for its continuous detection in human biofluids and tissues. Epidemiology has associated TCS exposure with thyroid function disturbances and decreasing serum thyroid hormone (TH) levels, but the underlying mechanism remains unclear. In this study, we revealed hypothyroidism and histological alternation in the thyroid of mice with chronic percutaneous exposure to TCS, indicating a TCS-caused thyroid impairment. Subsequently, multi-omics approaches were performed to investigate the molecular mechanism of the thyroid in response to long-term dermal TCS exposure. We discovered that TCS interfered with the TH synthesis as indicated by the changes in the levels of the synthetic materials for TH (iodide, Tg, and H2O2) and affected TH release by the downregulation of lysosomal enzymes. The upregulation of glycolysis, tricarboxylic acid cycle, fatty acid, amino acid metabolism, and adenine salvage in the thyroid was also observed after TCS exposure. All these changes led to the elevation of ATP, serving as a rescue for the decreasing thyroid functions. Together, our study demonstrated TCS-induced thyroid damage and identified the interrupted pathways, providing meaningful insight into the molecular mechanisms underpinning the potential health influence of TCS in humans.PMID:37121033 | DOI:10.1016/j.jhazmat.2023.131532

Aquat Toxicol. 2023 Apr 26;259:106547. doi: 10.1016/j.aquatox.2023.106547. Online ahead of print.ABSTRACTSince glass eels are continuously exposed to contamination throughout their migratory journey in estuaries, to a certain extent the fall in the population of this endangered species might be attributed to this exposure, which is especially acute in estuaries under high urban pressure. In this work, metabolomics was used to address the main objective of this study, to evaluate the effects of two pharmaceuticals previously identified as potential concerning chemicals for fish (diazepam and irbesartan) on glass eels. An exposure experiment to diazepam, irbesartan and their mixture was carried out over 7 days followed by 7 days of depuration phase. After exposure, glass eels were individually sacrificed using a lethal bath of anesthesia, and then an unbiased sample extraction method was used to extract separately the polar metabolome and the lipidome. The polar metabolome was submitted to targeted and non-targeted analysis, whereas for the lipidome only the non-targeted analysis was carried out. A combined strategy using partial least squares discriminant analysis and univariate and multivariate statistical analysis (ANOVA, ASCA, t-test, and fold-change analysis) was used to identify the metabolites altered in the exposed groups with respect to the control group. The results of the polar metabolome analysis revealed that glass eels exposed to the diazepam-irbesartan mixture were the most impacted ones, with altered levels for 11 metabolites, some of them belonging to the energetic metabolism, which was confirmed to be sensitive to these contaminants. Additionally, the dysregulation of the levels of twelve lipids, most of them with energetic and structural functions, was also found after exposure to the mixture, which might be related to oxidative stress, inflammation, or alteration of the energetic metabolism.PMID:37120958 | DOI:10.1016/j.aquatox.2023.106547

J Anim Sci Biotechnol. 2023 May 1;14(1):68. doi: 10.1186/s40104-023-00865-w.ABSTRACTBACKGROUND: The mechanism by which Meishan (MS) sows are superior to white crossbred sows in ovarian follicle development remains unclear. Given gut microbiota could regulate female ovarian function and reproductive capacity, this study aimed to determine the role of gut microbiota-ovary axis on follicular development in sows.METHODS: We compared the ovarian follicular development, gut microbiota, plasma metabolome, and follicular fluid metabolome between MS and Landrace × Yorkshire (L × Y) sows. A H2O2-induced cell apoptosis model was used to evaluate the effects of multi-omics identified metabolites on the apoptosis of porcine ovarian granulosa cells in vitro.RESULTS: Compared with L × Y sows, MS sows have greater ovary weight and improved follicular development, including the greater counts of large follicles of diameter ≥ 5 mm, secondary follicles, and antral follicles, but lesser atretic follicles. The ovarian granulosa cells in MS sows had alleviated apoptosis, which was indicated by the increased BCL-2, decreased caspases-3, and decreased cleaved caspases-3 than in L × Y sows. The ovarian follicular fluid of MS sows had higher concentrations of estradiol, progesterone, follicle-stimulating hormone, luteinizing hormone, and insulin like growth factor 1 than L × Y sows. Gut microbiota of MS sows formed a distinct cluster and had improved alpha diversity, including increased Shannon and decreased Simpson than those of L × Y sows. Corresponding to the enhanced function of carbohydrate metabolism and elevated short-chain fatty acids (SCFAs) in feces, the differential metabolites in plasma between MS and L × Y sows are also mainly enriched in pathways of fatty acid metabolism. There were significant correlations among SCFAs with follicular development, ovarian granulosa cells apoptosis, and follicular fluid hormones, respectively. Noteworthily, compared with L × Y sows, MS sows had higher follicular fluid SCFAs concentrations which could ameliorate H2O2-induced porcine granulosa cells apoptosis in vitro.CONCLUSION: MS sows have more secondary and antral follicles, but fewer atretic follicles and apoptotic ovarian granulosa cells, as well as harbored a distinctive gut microbiota than L × Y sows. Gut microbiota may participate in regulating ovarian follicular development via SCFAs affecting granulosa cells apoptosis in sows.PMID:37122038 | DOI:10.1186/s40104-023-00865-w

Exp Mol Med. 2023 May 1. doi: 10.1038/s12276-023-00996-0. Online ahead of print.ABSTRACTDysregulation of cellular metabolism is a hallmark of breast cancer progression and is associated with metastasis and therapeutic resistance. Here, we show that the breast tumor suppressor gene SIM2 promotes mitochondrial oxidative phosphorylation (OXPHOS) using breast cancer cell line models. Mechanistically, we found that SIM2s functions not as a transcription factor but localizes to mitochondria and directly interacts with the mitochondrial respiratory chain (MRC) to facilitate functional supercomplex (SC) formation. Loss of SIM2s expression disrupts SC formation through destabilization of MRC Complex III, leading to inhibition of electron transport, although Complex I (CI) activity is retained. A metabolomic analysis showed that knockout of SIM2s leads to a compensatory increase in ATP production through glycolysis and accelerated glutamine-driven TCA cycle production of NADH, creating a favorable environment for high cell proliferation. Our findings indicate that SIM2s is a novel stabilizing factor required for SC assembly, providing insight into the impact of the MRC on metabolic adaptation and breast cancer progression.PMID:37121978 | DOI:10.1038/s12276-023-00996-0

Acta Neurol Belg. 2023 Apr 30. doi: 10.1007/s13760-023-02266-2. Online ahead of print.ABSTRACTPURPOSE: The purpose of this mini review is to describe metabolomics in cerebrospinal fluid (CSF) and its potential in aneurysmal subarachnoid hemorrhage (aSAH). In brain injury, patients' micro dialysis enables detecting biochemical change in brain tissue. Indicators for ischemia were detected such as lactate, pyruvate, glucose, and glutamate. In aSAH patients, the pathophysiology and the factor for poor outcome are not completely understood yet. Routine use of biomarkers in CSF, particularly in aSAH patients, is still lacking.METHODS: This mini review was performed on the role of metabolomics alterations after aneurysmal subarachnoid hemorrhage.RESULTS: We identified five clinical studies that addressed metabolomics in patients with aneurysmal subarachnoid hemorrhage.CONCLUSION: There is increasing evidence suggesting that biomarkers can give insight in the pathogenesis and can serve as an outcome predictor. In this mini review, we present a brief overview of metabolomics profiling in neuroscience and wish to discuss the predictive and therapeutic value in aSAH patients.PMID:37121932 | DOI:10.1007/s13760-023-02266-2

Nat Commun. 2023 Apr 29;14(1):2485. doi: 10.1038/s41467-023-38009-3.ABSTRACTCirculating tumor cells (CTCs) are recognized as direct seeds of metastasis. However, CTC count may not be the "best" indicator of metastatic risk because their heterogeneity is generally neglected. In this study, we develop a molecular typing system to predict colorectal cancer metastasis potential based on the metabolic fingerprints of single CTCs. After identification of the metabolites potentially related to metastasis using mass spectrometry-based untargeted metabolomics, setup of a home-built single-cell quantitative mass spectrometric platform for target metabolite analysis in individual CTCs and use of a machine learning method composed of non-negative matrix factorization and logistic regression, CTCs are divided into two subgroups, C1 and C2, based on a 4-metabolite fingerprint. Both in vitro and in vivo experiments demonstrate that CTC count in C2 subgroup is closely associated with metastasis incidence. This is an interesting report on the presence of a specific population of CTCs with distinct metastatic potential at the single-cell metabolite level.PMID:37120634 | DOI:10.1038/s41467-023-38009-3

Transl Psychiatry. 2023 Apr 29;13(1):140. doi: 10.1038/s41398-023-02437-y.ABSTRACTWe studied the genetic associations of a previously developed Metabolomic Risk Score (MRS) for Mild Cognitive Impairment (MCI) and beta-aminoisobutyric acid metabolite (BAIBA)-the metabolite highlighted by results from a genome-wide association study (GWAS) of the MCI-MRS, and assessed their association with MCI in datasets of diverse race/ethnicities. We first performed a GWAS for the MCI-MRS and BAIBA, in Hispanic/Latino adults (n = 3890) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). We identified ten independent genome-wide significant (p value <5 × 10-8) variants associated with MCI-MRS or BAIBA. Variants associated with the MCI-MRS are located in the Alanine-Glyoxylate Aminotransferase 2 (AGXT2 gene), which is known to be associated with BAIBA metabolism. Variants associated with BAIBA are located in the AGXT2 gene and in the SLC6A13 gene. Next, we tested the variants' association with MCI in independent datasets of n = 3178 HCHS/SOL older individuals, n = 3775 European Americans, and n = 1032 African Americans from the Atherosclerosis Risk In Communities (ARIC) study. Variants were considered associated with MCI if their p value <0.05 in the meta-analysis of the three datasets and their direction of association was consistent with expectation. Rs16899972 and rs37369 from the AGXT2 region were associated with MCI. Mediation analysis supported the mediation effect of BAIBA between the two genetic variants and MCI (p value = 0.004 for causal mediated effect). In summary, genetic variants in the AGXT2 region are associated with MCI in Hispanic/Latino, African, and European American populations in the USA, and their effect is likely mediated by changes in BAIBA levels.PMID:37120436 | DOI:10.1038/s41398-023-02437-y

Trends Microbiol. 2023 Apr 27:S0966-842X(23)00113-0. doi: 10.1016/j.tim.2023.04.001. Online ahead of print.ABSTRACTChronic infection with Helicobacter pylori is the primary risk factor for the development of gastric cancer. Hindering our ability to comprehend the precise role of autophagy during H. pylori infection is the complexity of context-dependent autophagy signaling pathways. Recent and ongoing progress in understanding H. pylori virulence allows new frontiers of research for the crosstalk between autophagy and H. pylori. Novel approaches toward discovering autophagy signaling networks have further revealed their critical influence on the structure of gut microbiota and the metabolome. Here we intend to present a holistic view of the perplexing role of autophagy in H. pylori pathogenesis and carcinogenesis. We also discuss the intermediate role of autophagy in H. pylori-mediated modification of gut inflammatory responses and microbiota structure.PMID:37120362 | DOI:10.1016/j.tim.2023.04.001

Chin J Nat Med. 2023 Apr;21(4):308-320. doi: 10.1016/S1875-5364(23)60439-X.ABSTRACTViscum coloratum (Kom.) Nakai is a well-known medicinal plant. However, the optimal harvest time for V. coloratum is unknown. Few studies were performed to analyze compound variation during storage and to improve post-harvest quality control. Our study aimed to comprehensively evaluate the quality of V. coloratum in different growth stages, and determine the dynamic variation of metabolites. Ultra-performance liquid chromatography tandem mass spectrometry was used to quantify 29 compounds in V. coloratum harvested in six growth periods, and the associated biosynthetic pathways were explored. The accumulation of different types of compounds were analyzed based on their synthesis pathways. Grey relational analysis was used to evaluate the quality of V. coloratum across different months. The compound variation during storage was analyzed by a high-temperature high-humidity accelerated test. The results showed that the quality of V. coloratum was the hightest in March, followed by November, and became the lowest in July. During storage, compounds in downstream steps of the biosynthesis pathway were first degraded to produce the upstream compounds and some low-molecular-weight organic acids, leading to an increase followed by a decrease in the content of some compounds, and resulted in a large gap during the degradation time course among different compounds. Due to the rapid rate and large degree of degradation, five compounds were tentatively designated as "early warning components" for quality control. This report provides reference for better understanding the biosynthesis and degradation of metabolites in V. coloratum and lays a theoretical foundation for rational application of V. coloratum and better quality control of V. coloratum during storage.PMID:37120249 | DOI:10.1016/S1875-5364(23)60439-X

Food Res Int. 2023 Jun;168:112739. doi: 10.1016/j.foodres.2023.112739. Epub 2023 Mar 21.ABSTRACTVanilla is a globally treasured commodity, and the consequences of its unstable value affect social, environmental, economic, and academic ambits. The extensive range of aroma molecules found in cured vanilla beans is crucial to the complexity of this natural condiment and knowledge about their recovery is of the essence. Many strategies aim on reproducing the chemical intricacies of vanilla flavor, such as biotransformation and de novo biosynthesis. Few studies, however, aim at the exhaustion of the cured pods, of which the bagasse, after the traditional ethanolic extraction, might still bear a highly valued flavor composition. An untargeted liquid chromatography coupled with mass spectrometry (LC-MSE) approach was applied to elucidate if sequential alkaline-acidic hydrolysis was effective in extracting flavor related molecules and chemical classes from the hydro-ethanolic fraction. Important vanilla flavor related compounds present in the hydro-ethanolic fraction were further extracted from the residue through alkaline hydrolysis, such as vanillin, vanillic acid, 3-methoxybenzaldehyde, 4-vinylphenol, heptanoic acid, and protocatechuic acid. Acid hydrolysis was effective on further extracting features from classes such as phenols, prenol lipids, and organooxygen compounds, though representative molecules remain unknown. Finally, sequential alkaline-acidic hydrolysis rendered natural vanilla's ethanolic extraction residues as an interesting supplier of its own products, which could be used as a food additive, and many other applications.PMID:37120198 | DOI:10.1016/j.foodres.2023.112739

Food Res Int. 2023 Jun;168:112742. doi: 10.1016/j.foodres.2023.112742. Epub 2023 Mar 21.ABSTRACTPlant extracts have recently received increased attention as alternative sources of antimicrobial agents in the fight against multidrug-resistant bacteria. Non-targeted metabolomics liquid chromatography-quadrupole time-of-flight tandem mass spectrometry, molecular networking, and chemometrics were used to evaluate the metabolic profiles of red and green leaves of two Brassica juncea (L.) varieties, var. integrifolia (IR and IG) and var. rugosa (RR and RG), as well as to establish a relationship between the elucidated chemical profiles and antivirulence activity. In total, 171 metabolites from different classes were annotated and principal component analysis revealed higher levels of phenolics and glucosinolates in var. integrifolia leaves and color discrimination, whereas fatty acids were enriched in var. rugosa, particularly trihydroxy octadecadienoic acid. All extracts demonstrated significant antibacterial activity against Staphylococcus aureus and Enterococcus faecalis, presenting the IR leaves the highest antihemolytic activity against S. aureus (99 % inhibition), followed by RR (84 %), IG (82 %), and RG (37 %) leaves. Antivirulence of IR leaves was further validated by reduction in alpha-hemolysin gene transcription (∼4-fold). Using various multivariate data analyses, compounds positively correlated to bioactivity, primarily phenolic compounds, glucosinolates, and isothiocyanates, were also identified.PMID:37120197 | DOI:10.1016/j.foodres.2023.112742

Fish Shellfish Immunol. 2023 Apr 27:108779. doi: 10.1016/j.fsi.2023.108779. Online ahead of print.ABSTRACTDepuration is a vital stage to ensure the safety of oyster consumption, and salinity had a great impact on the environmental adaptability of oysters, but the underlying molecular mechanism was poorly understood during depuration stage. Here, Crassostrea gigas was depurated for 72 h at different salinity (26, 29, 32, 35, 38 g/L, corresponding to ±20%, ±10% salinity fluctuation away from oyster's production area) and then analyzed by using transcriptome, proteome, and metabolome combined with bioinformatics techniques. The transcriptome showed that the salinity stress led to 3185 differentially expressed genes and mainly enriched in amino acid metabolism, carbohydrate metabolism, lipid metabolism, etc. A total of 464 differentially expressed proteins were screened by the proteome, and the number of up-regulated expression proteins was less than the down-regulated, indicating that the salinity stress would inhibit the regulation of metabolism and immunity in oysters. 248 metabolites significantly changed in response to depuration salinity stress in oysters, including phosphate organic acids and their derivatives, lipids, etc. The results of integrated omics analysis indicated that the depuration salinity stress induced abnormal metabolism of the citrate cycle (TCA cycle), lipid metabolism, glycolysis, nucleotide metabolism, ribosome, ATP-binding cassette (ABC) transport pathway, etc. By contrast with Pro-depuration, more radical responses were observed in the S38 group. Based on the results, we suggest that the 10% salinity fluctuation was suitable for oyster depuration and the combination of multi-omics analysis could provide a new perspective for the analysis of the mechanism changes.PMID:37120087 | DOI:10.1016/j.fsi.2023.108779

Mol Cell Proteomics. 2023 Apr 27:100561. doi: 10.1016/j.mcpro.2023.100561. Online ahead of print.ABSTRACTThe world has witnessed a steady rise in both non-infectious and infectious chronic diseases, prompting a cross-disciplinary approach to understand and treat disease. Current medical care focuses on treating people after they become patients rather than to preventing illness, leading to high costs in treating chronic and late-stage diseases. Additionally, a 'one-size-fits all' approach to healthcare does not take into account individual differences in genetics, environment, or lifestyle factors, decreasing the number of people benefiting from interventions. Rapid advances in omics technologies and progress in computational capabilities have led to the development of multi-omics deep phenotyping, which profiles the interaction of multiple levels of biology over time and empowers precision health approaches. This review highlights current and emerging multi-omics modalities for precision health and discusses applications in the following areas: genetic variation, cardio-metabolic diseases, cancer, infectious diseases, organ transplantation, pregnancy, and longevity/aging. We will briefly discuss the potential of multi-omics approaches in disentangling host-microbe and host-environmental interactions. We will touch on emerging areas of electronic health record and clinical imaging integration with muti-omics for precision health. Finally, we will briefly discuss the challenges in clinical implementation of multi-omics and their future prospects.PMID:37119971 | DOI:10.1016/j.mcpro.2023.100561

Talanta. 2023 Apr 22;260:124578. doi: 10.1016/j.talanta.2023.124578. Online ahead of print.ABSTRACTClinical metabolomics studies often have to cope with limited sample amounts, thus miniaturized liquid chromatography (LC) systems are a promising alternative. Their applicability has already been demonstrated in various fields, including a few metabolomics studies that mainly used reversed-phase chromatography. However, hydrophilic interaction chromatography (HILIC), which is widely used in metabolomics due to its particular suitability for the analysis of polar molecules, has rarely been tested for miniaturized LC-MS analysis of small molecules. In the present work, the suitability of a capillary HILIC (CapHILIC)-QTOF-MS system for non-targeted metabolomics was evaluated based on extracts of porcine formalin-fixed, paraffin-embedded (FFPE) tissue samples. The performance was assessed with respect to the number and retention time span of metabolic features as well as the analytical repeatability, the signal-to-noise ratio and the signal intensity of 16 annotated metabolites from different compound classes. The results were compared with a well established narrow-bore HILIC-QTOF-MS system. Both platforms have detected a similar number of features and performed excellent with respect to retention time stability (median RT span <0.05 min) and analytical repeatability (>75% of features with CV < 20%). The signal areas of all metabolites assessed were increased up to 18-fold by the use of CapHILIC, although the signal-to-noise ratio was only improved for 50% of the metabolites. An even better reproducibility (median CV = 5.2%) and up to 80-fold increase in signal intensity were observed after optimization of CapHILIC conditions for analysis of bile acid standard solutions. Even though the observed improvement for specific bile acids (e.g. taurocholic acid) in biological matrix needs to be evaluated, the platform comparison indicates, that the tested CapHILIC system is particularly suitable for analyses of a less broad metabolite spectrum, and specifically optimized chromatography.PMID:37119797 | DOI:10.1016/j.talanta.2023.124578

EBioMedicine. 2023 Apr 27;91:104589. doi: 10.1016/j.ebiom.2023.104589. Online ahead of print.ABSTRACTBACKGROUND: Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy.METHODS: Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1-17.1) were examined. The patients were separated into a primary inflammatory disorder group (n = 90) and epilepsy group (n = 80), who were compared with three control groups including neurogenetic and structural (n = 76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n = 63), and headache (n = 32).FINDINGS: There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p < 0.0003). As biomarkers, at thresholds with 95% specificity, CSF neopterin had the best sensitivity for defining neuroinflammation (82%, CI 73-89), then quinolinic acid (57%, CI 47-67), KYN/TRP ratio (47%, CI 36-56) and kynurenine (37%, CI 28-48). CSF pleocytosis had sensitivity of 53%, CI 42-64). The area under the receiver operating characteristic curve (ROC AUC) of CSF neopterin (94.4% CI 91.0-97.7%) was superior to that of CSF pleocytosis (84.9% CI 79.5-90.4%) (p = 0.005). CSF kynurenic acid/kynurenine ratio (KYNA/KYN) was statistically decreased in the epilepsy group compared to all control groups (all p ≤ 0.0003), which was evident in most epilepsy subgroups.INTERPRETATION: Here we show that CSF neopterin, kynurenine, quinolinic acid and KYN/TRP are useful diagnostic and monitoring biomarkers of neuroinflammation. These findings provide biological insights into the role of inflammatory metabolism in neurological disorders and provide diagnostic and therapeutic opportunities for improved management of neurological diseases.FUNDING: Financial support for the study was granted by Dale NHMRC Investigator grant APP1193648, University of Sydney, Petre Foundation, Cerebral Palsy Alliance and Department of Biochemistry at the Children's Hospital at Westmead. Prof Guillemin is funded by NHMRC Investigator grant APP 1176660 and Macquarie University.PMID:37119734 | DOI:10.1016/j.ebiom.2023.104589

Schizophr Bull. 2023 Apr 29:sbad026. doi: 10.1093/schbul/sbad026. Online ahead of print.ABSTRACTBACKGROUND AND HYPOTHESIS: Schizophrenia (SCZ) is associated with complex crosstalk between the gut microbiota and host metabolism, but the underlying mechanism remains elusive. Investigating the aberrant neurotransmitter processes reflected by alterations identified using multiomics analysis is valuable to fully explain the pathogenesis of SCZ.STUDY DESIGN: We conducted an integrative analysis of multiomics data, including the serum metabolome, fecal metagenome, single nucleotide polymorphism data, and neuroimaging data obtained from a cohort of 127 drug-naïve, first-episode SCZ patients and 92 healthy controls to characterize the microbiome-gut-brain axis in SCZ patients. We used pathway-based polygenic risk score (PRS) analyses to determine the biological pathways contributing to genetic risk and mediation effect analyses to determine the important neuroimaging features. Additionally, a random forest model was generated for effective SCZ diagnosis.STUDY RESULTS: We found that the altered metabolome and dysregulated microbiome were associated with neuroactive metabolites, including gamma-aminobutyric acid (GABA), tryptophan, and short-chain fatty acids. Further structural and functional magnetic resonance imaging analyses highlighted that gray matter volume and functional connectivity disturbances mediate the relationships between Ruminococcus_torgues and Collinsella_aerofaciens and symptom severity and the relationships between species Lactobacillus_ruminis and differential metabolites l-2,4-diaminobutyric acid and N-acetylserotonin and cognitive function. Moreover, analyses of the Polygenic Risk Score (PRS) support that alterations in GABA and tryptophan neurotransmitter pathways are associated with SCZ risk, and GABA might be a more dominant contributor.CONCLUSIONS: This study provides new insights into systematic relationships among genes, metabolism, and the gut microbiota that affect brain functional connectivity, thereby affecting SCZ pathogenesis.PMID:37119525 | DOI:10.1093/schbul/sbad026

Plant J. 2023 May;114(3):461-462. doi: 10.1111/tpj.16243.NO ABSTRACTPMID:37119519 | DOI:10.1111/tpj.16243