PubMed

Hepatol Commun. 2023 Jan 18;7(2):e0014. doi: 10.1097/HC9.0000000000000014. eCollection 2023 Feb 1.ABSTRACTPediatric NAFLD has distinct and variable pathology, yet causation remains unclear. We have shown that maternal Western-style diet (mWSD) compared with maternal chow diet (CD) consumption in nonhuman primates produces hepatic injury and steatosis in fetal offspring. Here, we define the role of mWSD and postweaning Western-style diet (pwWSD) exposures on molecular mechanisms linked to NAFLD development in a cohort of 3-year-old juvenile nonhuman primates offspring exposed to maternal CD or mWSD followed by CD or Western-style diet after weaning. We used histologic, transcriptomic, and metabolomic analyses to identify hepatic pathways regulating NAFLD. Offspring exposed to mWSD showed increased hepatic periportal collagen deposition but unchanged hepatic triglyceride levels and body weight. mWSD was associated with a downregulation of gene expression pathways underlying HNF4α activity and protein, and downregulation of antioxidant signaling, mitochondrial biogenesis, and PPAR signaling pathways. In offspring exposed to both mWSD and pwWSD, liver RNA profiles showed upregulation of pathways promoting fibrosis and endoplasmic reticulum stress and increased BiP protein expression with pwWSD. pwWSD increased acylcarnitines and decreased anti-inflammatory fatty acids, which was more pronounced when coupled with mWSD exposure. Further, mWSD shifted liver metabolites towards decreased purine catabolism in favor of synthesis, suggesting a mitochondrial DNA repair response. Our findings demonstrate that 3-year-old offspring exposed to mWSD but weaned to a CD have periportal collagen deposition, with transcriptional and metabolic pathways underlying hepatic oxidative stress, compromised mitochondrial lipid sensing, and decreased antioxidant response. Exposure to pwWSD worsens these phenotypes, triggers endoplasmic reticulum stress, and increases fibrosis. Overall, mWSD exposure is associated with altered expression of candidate genes and metabolites related to NAFLD that persist in juvenile offspring preceding clinical presentation of NAFLD.PMID:36691970 | DOI:10.1097/HC9.0000000000000014

Exp Physiol. 2023 Jan 24. doi: 10.1113/EP090911. Online ahead of print.ABSTRACTNEW FINDINGS: What is the central question of this study? Whole-body substrate utilisation is altered during exercise in hot environments, characterised by increased glycolytic metabolism: does heat stress alter the serum metabolome in response to high intensity exercise? What are the main finding and its importance? Alongside increases in glycolytic metabolite abundance, circulating amino acid concentrations are reduced following exercise under heat stress. Prior research has overlooked the impact of heat stress on protein metabolism during exercise, raising important practical implications for protein intake recommendations in the heat.ABSTRACT: Using untargeted metabolomics, we aimed to characterise the systemic impact of environmental heat stress during exercise. Twenty-three trained male triathletes ( V ̇ O 2 peak ${\dot V_{{{\rm{O}}_2}{\rm{peak}}}}$ = 64.8 ± 9.2 ml kg min-1 ) completed a 30-min exercise test in hot (35°C) and temperate (21°C) conditions. Venous blood samples were collected immediately pre- and post-exercise, and the serum fraction was assessed via untargeted 1 H-NMR metabolomics. Data were analysed via uni- and multivariate analyses to identify differences between conditions. Mean power output was higher in temperate (231 ± 36 W) versus hot (223 ± 31 W) conditions (P < 0.001). Mean heart rate (temperate, 162 ± 10 beats min-1 , hot, 167 ± 9 beats min-1 , P < 0.001), peak core temperature (Trec ), core temperature change (ΔTrec ) (P < 0.001) and peak rating of perceived exertion (P = 0.005) were higher in hot versus temperate conditions. Change in metabolite abundance following exercise revealed distinct clustering following multivariate analysis. Six metabolites increased (2-hydroxyvaleric acid, acetate, alanine, glucarate, glucose, lactate) in hot relative to temperate (P < 0.05) conditions. Leucine and lysine decreased in both conditions but to a greater extent in temperate conditions (P < 0.05). Citrate (P = 0.04) was greater in temperate conditions whilst creatinine decreased in hot conditions only (P > 0.05). Environmental heat stress increased glycolytic metabolite abundance and led to distinct alterations in the circulating amino acid availability, including increased alanine, glutamine, leucine and isoleucine. The data highlight the need for additional exercise nutrition and metabolism research, specifically focusing on protein requirements for exercise under heat stress.PMID:36691850 | DOI:10.1113/EP090911

Curr Res Food Sci. 2023 Jan 6;6:100435. doi: 10.1016/j.crfs.2023.100435. eCollection 2023.ABSTRACTThe consumption of a healthy diet is critical for maintaining and promoting human health. In the context of the rapid transformation from a high-fat diet (HFD) to a Mediterranean diet (MD) leading to major systemic changes, we explored the necessity of a transitional standard diet (TSD) between these two varied diets and the adjuvant effect of probiotics. HFD-fed mice were used for studying the changes and benefits of a dietary intervention and probiotic treatment. By measuring multiple systemic alterations such as weight (group B vs. group E, P < 0.05), liver function (AST, group C vs. group E, P < 0.001), and histopathology, we found that an MD, TSD and Bifidobacterium longum all contribute to alleviating lipid deposition and liver injury. The downregulation of IL-17 (group B vs. group E, P < 0.01) and MIP-1α (group B vs. group E, P < 0.001) also demonstrated the anti-inflammatory effects of the TSD. Moreover, we performed multi-omics analysis combined with the 16S sequencing, transcriptome and metabolome results and found that the TSD increased the abundance of the Lactobacillus genus (group C vs. group E, P < 0.01) and effectively lowered lipid accumulation and systemic inflammation. Furthermore, B. longum played an important role in the synergistic effect. The results showed that a TSD might be useful for HFD-induced obesity before drastic dietary changes, and probiotics were also beneficial.PMID:36691590 | PMC:PMC9860293 | DOI:10.1016/j.crfs.2023.100435

Heliyon. 2022 Dec 21;9(1):e12515. doi: 10.1016/j.heliyon.2022.e12515. eCollection 2023 Jan.ABSTRACTMetabolic reprogramming is one of the essential features of tumor that may dramatically contribute to metastasis and collapse. The metabolic profiling is investigated on the patient derived tissue and cancer cell line derived mouse metastasis xenograft. As well-recognized "seeds" for remote metastasis of tumor, role of circulating tumor cells (CTCs) in the study of metabolic reprogramming feature of tumor is yet to be elucidated. More specifically, whether there is difference of metabolic features of liver metastasis in colorectal cancer (CRC) derived from either CTCs or cancer cell line is still unknown. In this study, comprehensive untargeted metabolomics was performed using high performance liquid chromatography-mass spectrometry (HPLC-MS) in liver metastasis tissues from CT26 cells and CTCs derived mouse models. We identified 288 differential metabolites associated with the pathways such as one carbon pool by folate, folate biosynthesis and histidine metabolism through bioinformation analysis. Multiple gene expression was upregulated in the CTCs derived liver metastasis, specifically some specific enzymes. These results indicated that the metabolite phenotype and corresponding gene expression in the CTCs derived liver metastasis tissues was different from the parental CT26 cells, displaying a specific up-regulation of mRNAs involved in the above metabolism-related pathways. The metabolic profile of CTCs was characterized on the liver metastatic process in colorectal cancer. The invasion ability and chemo drug tolerance of the CTCs derived tumor and metastasis was found to be overwhelming higher than cell line derived counterpart. Identification of the differential metabolites will lead to a better understanding of the hallmarks of the cancer progression and metastasis, which may suggest potential attractive target for treating metastatic CRC.PMID:36691542 | PMC:PMC9860459 | DOI:10.1016/j.heliyon.2022.e12515

Phytochem Anal. 2023 Jan 23. doi: 10.1002/pca.3210. Online ahead of print.ABSTRACTINTRODUCTION: Atractylodes chinensis is a Chinese herb that is used in traditional medicine; it contains volatile components that have enormous potential for pharmaceutical, food, and cosmetic applications. The destruction of wild resources demands significant improvement in the quality of artificial cultivation of Atractylodes chinensis. However, little is known about the compositional differences in the volatile substances derived from the wild and cultivated varieties of Atractylodes chinensis.OBJECTIVES: We aimed to evaluate the specific components of Atractylodes chinensis and analyse the similarities and differences between the volatile components and metabolic pathways in the wild and cultivated varieties.MATERIAL AND METHODS: Metabolomic analysis using gas chromatography-mass spectrometry (GC-MS) was employed following the extraction of volatile components from Atractylodes chinensis using headspace solid-phase microextraction (HS-SPME).RESULTS: A total of 167 volatile metabolites were extracted, and 137 substances were matched with NIST and Wiley databases. Among them, 76 compounds exhibited significant differences between the two sources; these mainly included terpenes, aromatics, and esters. KEGG enrichment analysis indicated that the differential metabolites were primarily involved in the biosynthesis of secondary metabolites, terpene biosynthesis, and limonene and pinene degradation; all these pathways have geranyl diphosphate (GDP) as the common link.CONCLUSION: The total content of volatile substances extracted from wild Atractylodes chinensis was 2.5 times higher than that from the cultured variety; however, each source had different dominant metabolites. This study underscores the necessity for protecting wild Atractylodes chinensis resources, while enhancing the quality of cultivated Atractylodes chinensis.PMID:36691258 | DOI:10.1002/pca.3210

Lett Appl Microbiol. 2023 Jan 23;76(1):ovac036. doi: 10.1093/lambio/ovac036.ABSTRACTThe present study aimed to evaluate the effects of delayed harvest and storage length on fermentation products, bacterial community, and metabolic shifts of elephant grass silage. The late-harvested elephant grass (LG) was naturally fermented (NLG) for 1, 3, 7, 15, 30, and 60 days, respectively. After 60-day ensiling, NLG displayed homolactic fermentation with low pH value, butyric acid, and ammonia nitrogen concentrations, and high lactic acid concentration, and ratio of lactic acid to acetic acid. Pseudomonas, Sphingomonas, and Pantoea dominated the bacterial community in LG, but Lactobacillus, Lactococcus, and Pediococcus were the advantageous genera in a 3-day and 60-day NLG. The correlation heatmap revealed that Acetobacter was positively related to acetic acid, ethanol, ammonia nitrogen, and butyric acid concentrations. There were distinct differences in the KEGG (Kyoto Encyclopedia of Genes and Genomes) metabolic profiles of fresh and ensiled LG. Ensiling suppressed the metabolism of amino acid, vitamins, and energy, while promoted the metabolism of carbohydrate. The LG can be well-fermented without additives, but its low crude protein content should not be ignored when applied in agricultural practice. The ensiling process remarkably affected the fermentation quality, bacterial community, and metabolic profiles of NLG.PMID:36688771 | DOI:10.1093/lambio/ovac036

Plant Physiol. 2023 Jan 24:kiad035. doi: 10.1093/plphys/kiad035. Online ahead of print.ABSTRACTMitochondria are often considered the power stations of the cell, playing critical roles in various biological processes such as cellular respiration, photosynthesis, stress responses and programmed cell death. To maintain the structural and functional integrities of mitochondria, it is crucial to achieve a defined membrane lipid composition between different lipid classes wherein specific proportions of individual lipid species are present. Although mitochondria are capable of self-synthesizing a few lipid classes, many phospholipids are synthesized in the endoplasmic reticulum and transferred to mitochondria via membrane contact sites, as mitochondria are excluded from the vesicular transportation pathway. However, knowledge on the capability of lipid biosynthesis in mitochondria and the precise mechanism of maintaining the homeostasis of mitochondrial lipids is still scarce. Here we describe the lipidome of mitochondria isolated from Arabidopsis (Arabidopsis thaliana) leaves, including the molecular species of glycerolipids, sphingolipids and sterols, to depict the lipid landscape of mitochondrial membranes. In addition, we define proteins involved in lipid metabolism by proteomic analysis and compare our data with mitochondria from cell cultures since they still serve as model systems. Proteins putatively localized to the membrane contact sites are proposed based on the proteomic results and online databases. Collectively, our results suggest that leaf mitochondria are capable - with the assistance of membrane contact site-localized proteins - of generating several lipid classes including phosphatidylethanolamines, cardiolipins, diacylgalactosylglycerols and free sterols. We anticipate our work to be a foundation to further investigate the functional roles of lipids and their involvement in biochemical reactions in plant mitochondria.PMID:36691154 | DOI:10.1093/plphys/kiad035

Cancer Metab. 2023 Jan 23;11(1):2. doi: 10.1186/s40170-023-00302-6.ABSTRACTAcute lymphoblastic leukemia (ALL) and its treatment continue to pose substantial risks. To understand ALL more deeply, the metabolome in fasting plasma of 27 ALL patients before and after high-dose methotrexate therapies (consolidation therapy) including methotrexate and 6-mercaptopurine (6-MP) was investigated. Plasma metabolites were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS). Orthogonal projections to latent structures discriminant analysis and significance analysis of microarrays were used to evaluate the metabolic changes. Pathway enrichment and co-expression network analyses were performed to identify clusters of molecules, and 2826 metabolites were identified. Among them, 38 metabolites were identified by univariate analysis, and 7 metabolites that were altered by conditioning therapy were identified by multivariate analysis. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database was used for pathway enrichment analysis. Among the enriched KEGG pathways, the 3 significantly altered metabolic pathways were pyrimidine metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis; and phenylalanine metabolism. In addition, L-phenylalanine was significantly correlated with blood urea nitrogen (BUN), and palmitoylcarnitine was correlated with aspartate aminotransferase (AST). In summary, consolidation therapy significantly affected pyrimidine- and phenylalanine-associated metabolic pathways in pediatric ALL patients. These findings may provide an insight into the role of metabolic profiling in consolidation treatment and as a potential for pediatric ALL patients.PMID:36691092 | DOI:10.1186/s40170-023-00302-6

Microbiome. 2023 Jan 23;11(1):13. doi: 10.1186/s40168-022-01444-3.ABSTRACTBACKGROUND: It is well-known that the microbiome produces a myriad of specialised metabolites with diverse functions. To better characterise their structures and identify their producers in complex samples, integrative genome and metabolome mining is becoming increasingly popular. Metabologenomic co-occurrence-based correlation scoring methods facilitate the linking of metabolite mass fragmentation spectra (MS/MS) to their cognate biosynthetic gene clusters (BGCs) based on shared absence/presence patterns of metabolites and BGCs in paired omics datasets of multiple strains. Recently, these methods have been made more readily accessible through the NPLinker platform. However, co-occurrence-based approaches usually result in too many candidate links to manually validate. To address this issue, we introduce a generic feature-based correlation method that matches chemical compound classes between BGCs and MS/MS spectra.RESULTS: To automatically reduce the long lists of potential BGC-MS/MS spectrum links, we match natural product (NP) ontologies previously independently developed for genomics and metabolomics and developed NPClassScore: an empirical class matching score that we also implemented in the NPLinker platform. By applying NPClassScore on three paired omics datasets totalling 189 bacterial strains, we show that the number of links is reduced by on average 63% as compared to using a co-occurrence-based strategy alone. We further demonstrate that 96% of experimentally validated links in these datasets are retained and prioritised when using NPClassScore.CONCLUSION: The matching genome-metabolome class ontologies provide a starting point for selecting plausible candidates for BGCs and MS/MS spectra based on matching chemical compound class ontologies. NPClassScore expedites genome/metabolome data integration, as relevant BGC-metabolite links are prioritised, and researchers are faced with substantially fewer proposed BGC-MS/MS links to manually inspect. We anticipate that our addition to the NPLinker platform will aid integrative omics mining workflows in discovering novel NPs and understanding complex metabolic interactions in the microbiome. Video Abstract.PMID:36691088 | DOI:10.1186/s40168-022-01444-3

BMC Infect Dis. 2023 Jan 23;23(1):42. doi: 10.1186/s12879-022-07979-y.ABSTRACTBACKGROUND: Coronavirus disease 2019 is a type of acute infectious pneumonia and frequently confused with influenza since the initial symptoms. When the virus colonized the patient's mouth, it will cause changes of the oral microenvironment. However, few studies on the alterations of metabolism of the oral microenvironment affected by SARS-CoV-2 infection have been reported. In this study, we explored metabolic alterations of oral microenvironment after SARS-CoV-2 infection.METHODS: Untargeted metabolomics (UPLC-MS) was used to investigate the metabolic changes between oral secretion samples of 25 COVID-19 and 30 control participants. To obtain the specific metabolic changes of COVID-19, we selected 25 influenza patients to exclude the metabolic changes caused by the stress response of the immune system to the virus. Multivariate analysis (PCA and PLS-DA plots) and univariate analysis (students' t-test) were used to compare the differences between COVID-19 patients and the controls. Online hiplot tool was used to perform heatmap analysis. Metabolic pathway analysis was conducted by using the MetaboAnalyst 5.0 web application.RESULTS: PLS-DA plots showed significant separation of COVID-19 patients and the controls. A total of 45 differential metabolites between COVID-19 and control group were identified. Among them, 35 metabolites were defined as SARS-CoV-2 specific differential metabolites. Especially, the levels of cis-5,8,11,14,17-eicosapentaenoic acid and hexanoic acid changed dramatically based on the FC values. Pathway enrichment found the most significant pathways were tyrosine-related metabolism. Further, we found 10 differential metabolites caused by the virus indicating the body's metabolism changes after viral stimulation. Moreover, adenine and adenosine were defined as influenza virus-specific differential metabolites.CONCLUSIONS: This study revealed that 35 metabolites and tyrosine-related metabolism pathways were significantly changed after SARS-CoV-2 infection. The metabolic alterations of oral microenvironment in COVID-19 provided new insights into its molecular mechanisms for research and prognostic treatment.PMID:36690957 | DOI:10.1186/s12879-022-07979-y

BMC Infect Dis. 2023 Jan 23;23(1):46. doi: 10.1186/s12879-023-07983-w.ABSTRACTSepsis is one of the most important problems to be addressed in pediatrics, characterized by insidious onset, rapid progression, and high rates of severe infection and even mortality. Biomarkers with high sensitivity and robustness are urgently required for the early diagnosis of infant sepsis. Serum metabolomic approaches based on liquid chromatography-mass spectrometry were used to analyze the samples from 30 infants with sepsis at an early stage and 30 infants with noninfectious diseases. Multivariate statistical analysis was used to screen for differential metabolites and ROC curves were generated to find potential biomarkers. Six metabolites, including phosphatidic acid (PA (8:0/14:0)), phosphatidyl ethanolamine (PE (16:0/18:2(9Z,12Z))), cytidine 5'-diphosphocholine (CDP-CHO), sphingomyelin (SM (d18:0/16:1(9Z))), prolylhydroxyproline and phosphorylcholine (P-CHO), were identified between the two groups. ROC curve analysis showed that prolylhydroxyproline (AUC = 0.832) had potential diagnostic values for infant sepsis. The AUC value was 0.859 (CI: 0.764, 0.954) in the combined model. Prolylhydroxyproline were found to be correlated with CRP and PCT levels, while PE and CDP-CHO associated with PCT levels. Pathway analysis indicated that glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis and necroptosis pathways played important roles in infant sepsis. Network analysis showed that the differential metabolites were linked to ERK/ MAPK, NF-κB, AMPK, mTOR, and other classical inflammatory and metabolic signaling pathways. This study identified serum metabolite profiles and three metabolites as potential biomarkers in infants with sepsis. The findings will help improve the early diagnosis of sepsis in infants.PMID:36690951 | DOI:10.1186/s12879-023-07983-w

Mol Neurobiol. 2023 Jan 24. doi: 10.1007/s12035-022-03157-y. Online ahead of print.ABSTRACTParkinson's disease (PD) is a progressive neurodegenerative disorder, characterized by high morbidity, high disability rate, and slow course of disease. The clinical diagnostic method of PD is complex and time-consuming, and there is no clear biomarker for clinical use. We aimed to investigate the plasma metabolites in PD and find out potential biomarkers with diagnostic ability. In the analysis of more than 40 metabolites including short-chain fatty acids, long-chain fatty acids, amino acids, and carbohydrates, the difference of short-chain fatty acids was observed. Acetic acid concentration was higher in PD than in healthy controls, and propanoic acid and 2,3,4-trihydroxybutyric acid were lower in PD. Compared with the early stage of PD, acetic acid increased significantly in the advanced stage of PD. Propanoic acid increased significantly in medicated PD compared with drug naïve PD. ROC analysis revealed acetic acid discriminated PD from healthy controls with 100% sensitivity, 88.9% specificity, and an area under the curve (AUC) of 0.981, and propanoic acid discriminated PD from healthy controls with an AUC of 0.981, 100% sensitivity, and 94.4% specificity. Acetic acid and propanoic acid may be a potential biomarker for differentiating PD from health, and the propanoic acid was evaluated as the most potential diagnostic marker because of its extremely high sensitivity and specificity.PMID:36690885 | DOI:10.1007/s12035-022-03157-y

Nat Cancer. 2023 Jan 23. doi: 10.1038/s43018-022-00506-7. Online ahead of print.ABSTRACTImmunotherapy efficacy is limited in melanoma, and combinations of immunotherapies with other modalities have yielded limited improvements but also adverse events requiring cessation of treatment. In addition to ineffective patient stratification, efficacy is impaired by paucity of intratumoral immune cells (itICs); thus, effective strategies to safely increase itICs are needed. We report that dietary administration of L-fucose induces fucosylation and cell surface enrichment of the major histocompatibility complex (MHC)-II protein HLA-DRB1 in melanoma cells, triggering CD4+ T cell-mediated increases in itICs and anti-tumor immunity, enhancing immune checkpoint blockade responses. Melanoma fucosylation and fucosylated HLA-DRB1 associate with intratumoral T cell abundance and anti-programmed cell death protein 1 (PD1) responder status in patient melanoma specimens, suggesting the potential use of melanoma fucosylation as a strategy for stratifying patients for immunotherapies. Our findings demonstrate that fucosylation is a key mediator of anti-tumor immunity and, importantly, suggest that L-fucose is a powerful agent for safely increasing itICs and immunotherapy efficacy in melanoma.PMID:36690875 | DOI:10.1038/s43018-022-00506-7

Insights Imaging. 2023 Jan 24;14(1):14. doi: 10.1186/s13244-022-01356-8.ABSTRACTPURPOSE: To investigate the generalizability of transfer learning (TL) of automated tumor segmentation from cervical cancers toward a universal model for cervical and uterine malignancies in diffusion-weighted magnetic resonance imaging (DWI).METHODS: In this retrospective multicenter study, we analyzed pelvic DWI data from 169 and 320 patients with cervical and uterine malignancies and divided them into the training (144 and 256) and testing (25 and 64) datasets, respectively. A pretrained model was established using DeepLab V3 + from the cervical cancer dataset, followed by TL experiments adjusting the training data sizes and fine-tuning layers. The model performance was evaluated using the dice similarity coefficient (DSC).RESULTS: In predicting tumor segmentation for all cervical and uterine malignancies, TL models improved the DSCs from the pretrained cervical model (DSC 0.43) when adding 5, 13, 26, and 51 uterine cases for training (DSC improved from 0.57, 0.62, 0.68, 0.70, p < 0.001). Following the crossover at adding 128 cases (DSC 0.71), the model trained by combining data from adding all the 256 patients exhibited the highest DSCs for the combined cervical and uterine datasets (DSC 0.81) and cervical only dataset (DSC 0.91).CONCLUSIONS: TL may improve the generalizability of automated tumor segmentation of DWI from a specific cancer type toward multiple types of uterine malignancies especially in limited case numbers.PMID:36690870 | DOI:10.1186/s13244-022-01356-8

ISME Commun. 2023 Jan 23;3(1):4. doi: 10.1038/s43705-023-00217-9.ABSTRACTThe environmental impacts of genetically modified (GM) plants remain a controversial global issue. To address these issues, comprehensive environmental risk assessments of GM plants is critical for the sustainable development and application of transgenic technology. In this paper, significant differences were not observed between microbial metagenomic and metabolomic profiles in surface waters of the Bt rice (T1C-1, the transgenic line) and non-Bt cultivars (Minghui 63 (the isogenic line) and Zhonghua 11 (the conventional japonica cultivar)). In contrast, differences in these profiles were apparent in the rhizospheres. T1C-1 planting increased soil microbiome diversity and network stability, but did not significantly alter the abundances of potential probiotic or phytopathogenic microorganisms compared with Minghui 63 and Zhonghua 11, which revealed no adverse effects of T1C-1 on soil microbial communities. T1C-1 planting could significantly alter soil C and N, probably via the regulation of the abundances of enzymes related to soil C and N cycling. In addition, integrated multi-omic analysis of root exudate metabolomes and soil microbiomes showed that the abundances of various metabolites released as root exudates were significantly correlated with subsets of microbial populations including the Acidobacteria, Actinobacteria, Chloroflexi, and Gemmatimonadetes that were differentially abundant in T1C-1 and Mnghui 63 soils. Finally, the potential for T1C-1-associated root metabolites to exert growth effects on T1C-1-associated species was experimentally validated by analysis of bacterial cultures, revealing that Bt rice planting could selectively modulate specific root microbiota. Overall, this study indicate that Bt rice can directly modulate rhizosphere microbiome assemblages by altering the metabolic compositions of root exudates that then alters soil metabolite profiles and physiochemical properties. This study unveils the mechanistic associations of Bt plant-microorganism-environment, which provides comprehensive insights into the potential ecological impacts of GM plants.PMID:36690796 | DOI:10.1038/s43705-023-00217-9

Sci Rep. 2023 Jan 23;13(1):1273. doi: 10.1038/s41598-023-27375-z.ABSTRACTMedulloblastoma (MB) is the most common malignant brain tumour in children. High-risk MB patients harbouring MYC amplification or overexpression exhibit a very poor prognosis. Aberrant activation of MYC markedly reprograms cell metabolism to sustain tumorigenesis, yet how metabolism is dysregulated in MYC-driven MB is not well understood. Growing evidence unveiled the potential of BET-bromodomain inhibitors (BETis) as next generation agents for treating MYC-driven MB, but whether and how BETis may affect tumour cell metabolism to exert their anticancer activities remains unknown. In this study, we explore the metabolic features characterising MYC-driven MB and examine how these are altered by BET-bromodomain inhibition. To this end, we employed an NMR-based metabolomics approach applied to the MYC-driven MB D283 and D458 cell lines before and after the treatment with the BETi OTX-015. We found that OTX-015 triggers a metabolic shift in both cell lines resulting in increased levels of myo-inositol, glycerophosphocholine, UDP-N-acetylglucosamine, glycine, serine, pantothenate and phosphocholine. Moreover, we show that OTX-015 alters ascorbate and aldarate metabolism, inositol phosphate metabolism, phosphatidylinositol signalling system, glycerophospholipid metabolism, ether lipid metabolism, aminoacyl-tRNA biosynthesis, and glycine, serine and threonine metabolism pathways in both cell lines. These insights provide a metabolic characterisation of MYC-driven childhood MB cell lines, which could pave the way for the discovery of novel druggable pathways. Importantly, these findings will also contribute to understand the downstream effects of BETis on MYC-driven MB, potentially aiding the development of new therapeutic strategies to combat medulloblastoma.PMID:36690651 | DOI:10.1038/s41598-023-27375-z

Biochim Biophys Acta Mol Cell Biol Lipids. 2023 Jan 20:159285. doi: 10.1016/j.bbalip.2023.159285. Online ahead of print.ABSTRACTAlkylglycerol monooxygenase (AGMO) and plasmanylethanolamine desaturase (PEDS1) are enzymes involved in ether lipid metabolism. While AGMO degrades plasmanyl lipids by oxidative cleavage of the ether bond, PEDS1 exclusively synthesizes a specific subclass of ether lipids, the plasmalogens, by introducing a vinyl ether double bond into plasmanylethanolamine phospholipids. Ether lipids are characterized by an ether linkage at the sn-1 position of the glycerol backbone and they are found in membranes of different cell types. Decreased plasmalogen levels have been associated with neurological diseases like Alzheimer's disease. Agmo-deficient mice do not present an obvious phenotype under unchallenged conditions. In contrast, Peds1 knockout mice display a growth phenotype. To investigate the molecular consequences of Agmo and Peds1 deficiency on the mouse lipidome, five tissues from each mouse model were isolated and subjected to high resolution mass spectrometry allowing the characterization of up to 2013 lipid species from 42 lipid subclasses. Agmo knockout mice moderately accumulated plasmanyl and plasmenyl lipid species. Peds1-deficient mice manifested striking changes characterized by a strong reduction of plasmenyl lipids and a concomitant massive accumulation of plasmanyl lipids resulting in increased total ether lipid levels in the analyzed tissues except for the class of phosphatidylethanolamines where total levels remained remarkably constant also in Peds1 knockout mice. The rate-limiting enzyme in ether lipid metabolism, FAR1, was not upregulated in Peds1-deficient mice, indicating that the selective loss of plasmalogens is not sufficient to activate the feedback mechanism observed in total ether lipid deficiency.PMID:36690320 | DOI:10.1016/j.bbalip.2023.159285

Neurobiol Dis. 2023 Jan 20:106008. doi: 10.1016/j.nbd.2023.106008. Online ahead of print.ABSTRACTWe explore how functional genomics approaches that integrate datasets from human and non-human model systems can improve our understanding of the effect of gene-environment interplay on the risk for mental disorders.We start by briefly defining the G-E paradigm and its challenges and then discuss the different levels of regulation of gene expression and the corresponding data existing in humans (genome wide genotyping, transcriptomics, DNA methylation, chromatin modifications, chromosome conformational changes, non-coding RNAs, proteomics and metabolomics), discussing novel approaches to the application of these data in the study of the origins of mental health. Finally, we discuss the multilevel integration of diverse types of data. Advance in the use of functional genomics in the context of a G-E perspective improves the detection of vulnerabilities, informing the development of preventive and therapeutic interventions.PMID:36690304 | DOI:10.1016/j.nbd.2023.106008

Am J Obstet Gynecol MFM. 2023 Jan 20:100865. doi: 10.1016/j.ajogmf.2023.100865. Online ahead of print.NO ABSTRACTPMID:36690183 | DOI:10.1016/j.ajogmf.2023.100865

Curr Opin Plant Biol. 2023 Jan 21;73:102335. doi: 10.1016/j.pbi.2022.102335. Online ahead of print.ABSTRACTWhilst the study of metabolites can arguably be traced back several hundred years it began in earnest in the 20th century with studies based on single metabolites or simple metabolic pathways. The advent of metabolomics and in particular the adoption of high-resolution mass spectrometry now means we can faithfully annotate and quantify in excess of 1000 plant metabolites. Whilst this is an impressive leap it falls well short of the estimated number of metabolites in the plant kingdom. This, whilst considerable and important insights have been achieved using commonly utilized approaches, there is a need to improve the coverage of the metabolome. Here, we review three largely complementary strategies (i) methods based on using chemical libraries (ii) methods based on molecular networking and (iii) approaches that link metabolomics and genetic variance. It is our contention that using all three approaches in tandem represents the best approach to tackle this challenge.PMID:36689903 | DOI:10.1016/j.pbi.2022.102335