PubMed

BMC Plant Biol. 2023 Jun 21;23(1):328. doi: 10.1186/s12870-023-04326-4.ABSTRACTBACKGROUND: New vegetable production systems, such as vertical farming, but also well-established in-door production methods led to the implementation of light emitting diodes (LEDs). LEDs are the most important light sources in modern indoor-production systems and offer the possibility for enhancing growth and specific metabolites in planta. Even though the number of studies investigating the effects of LED lighting on vegetable quality has increased, the knowledge about genus variability is limited. In the present study, the effect of different LED spectra on the metabolic and transcriptional level of the carotenoid metabolism in five different Brassica sprouts was investigated. Cruciferous vegetables are one of the main food crops worldwide. Pak choi (Brassica rapa ssp. chinensis), cauliflower (Brassica oleracea var. botrytis), Chinese cabbage (Brassica rapa ssp. pekinensis), green kale (Brassica oleracea ssp. sabellica) and turnip cabbage (Brassica oleracea spp. gongylodes) sprouts were grown under a combination of blue & white LEDs, red & white LEDs or only white LEDs to elucidate the genus-specific carotenoid metabolism.RESULTS: Genus-specific changes in plant weight and on the photosynthetic pigment levels as well as transcript levels have been detected. Interestingly, the transcript levels of the three investigated carotenoid biosynthesis genes phytoene synthase (PSY), β-cyclase (βLCY) and β-carotene hydroxylase (βOHASE1) were increased under the combination of blue & white LEDs in the majority of the Brassica sprouts. However, only in pak choi, the combination of blue & white LEDs enhanced the carotenoid levels by 14% in comparison to only white LEDs and by ~ 19% in comparison to red & white LEDs.CONCLUSIONS: The effects of light quality differ within a genus which leads to the conclusion that production strategies have to be developed for individual species and cultivars to fully benefit from LED technology.PMID:37340342 | DOI:10.1186/s12870-023-04326-4

Commun Biol. 2023 Jun 20;6(1):653. doi: 10.1038/s42003-023-05035-2.ABSTRACTThe extracellular microenvironment modulates glioma behaviour. It remains unknown if blood-brain barrier disruption merely reflects or functionally supports glioma aggressiveness. We utilised intra-operative microdialysis to sample the extracellular metabolome of radiographically diverse regions of gliomas and evaluated the global extracellular metabolome via ultra-performance liquid chromatography tandem mass spectrometry. Among 162 named metabolites, guanidinoacetate (GAA) was 126.32x higher in enhancing tumour than in adjacent brain. 48 additional metabolites were 2.05-10.18x more abundant in enhancing tumour than brain. With exception of GAA, and 2-hydroxyglutarate in IDH-mutant gliomas, differences between non-enhancing tumour and brain microdialysate were modest and less consistent. The enhancing, but not the non-enhancing glioma metabolome, was significantly enriched for plasma-associated metabolites largely comprising amino acids and carnitines. Our findings suggest that metabolite diffusion through a disrupted blood-brain barrier may largely define the enhancing extracellular glioma metabolome. Future studies will determine how the altered extracellular metabolome impacts glioma behaviour.PMID:37340056 | DOI:10.1038/s42003-023-05035-2

Am J Physiol Gastrointest Liver Physiol. 2023 Jun 20. doi: 10.1152/ajpgi.00242.2022. Online ahead of print.ABSTRACTAlcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for three hours of fasting followed by three hours of intravenous PN (SmofKabiven 1206 mL: Amino acid 38 g, carbohydrates 85 g, fat 34 g) 4 ml/kg/hour. We measured leg blood flow, sampled paired femoral arterio-venous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-2D5]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, p<0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, p<0.05), and CT-verified leg muscle loss (ALC: 5922 ± 246 vs. controls: 8110 ± 345 mm2, p<0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle*min-1; p <0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle*min-1; p <0.001), but with higher net muscle phenylalanine uptake in ALC than controls (p <0.001). Insulin concentrations were substantially higher in ALC patients during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable ALC patients with sarcopenia compared with healthy controls.PMID:37339940 | DOI:10.1152/ajpgi.00242.2022

Spine J. 2023 Jun 18:S1529-9430(23)00233-4. doi: 10.1016/j.spinee.2023.06.005. Online ahead of print.ABSTRACTBACKGROUND CONTEXT: Intervertebral disc degeneration (IVDD) is an incurable, specific treatment-orphan disease with an increasing burden worldwide. Although great efforts have been made to develop new regenerative therapies, their clinical success is limited.PURPOSE: Characterize the metabolomic and gene expression changes underpinning human disc degeneration. This study also aimed to disclose new molecular targets for developing and optimizing novel biological approaches for IVDD.STUDY DESIGN: Intervertebral disc cells were obtained from IVDD patients undergoing circumferential arthrodesis surgery or from healthy subjects. Mimicking the harmful microenvironment of degenerated discs, cells isolated from the nucleus pulposus (NP) and annulus fibrosus (AF) were exposed to the pro-inflammatory cytokine IL-1β and the adipokine leptin. The metabolomic signature and molecular profile of human disc cells were unraveled for the first time.METHODS: The metabolomic and lipidomic profiles of IVDD and healthy disc cells were analyzed by high-performance liquid chromatography-mass spectrometry (UHPLC-MS). Gene expression was investigated by SYBR green-based quantitative real-time RT-PCR. Altered metabolites and gene expression were documented.RESULTS: Lipidomic analysis revealed decreased levels of triacylglycerols (TG), diacylglycerol (DG), fatty acids (FA), phosphatidylcholine (PC), lysophosphatidylinositols (LPI) and sphingomyelin (SM), and increased levels of bile acids (BA) and ceramides, likely promoting disc cell metabolism changing from glycolysis to fatty acid oxidation and following cell death. The gene expression profile of disc cells suggests LCN2 and LEAP2/GHRL as promising molecular therapeutic targets for disc degeneration and demonstrates the expression of genes related to inflammation (NOS2, COX2, IL-6, IL-8, IL-1β, and TNF-α) or encoding adipokines (PGRN, NAMPT, NUCB2, SERPINE2, and RARRES2), matrix metalloproteinases (MMP9 and MMP13), and vascular adhesion molecules (VCAM1).CONCLUSIONS: Altogether, the presented results disclose the NP and AF cell biology changes from healthy to degenerated discs, allowing the identification of promising molecular therapeutic targets for intervertebral disc degeneration.CLINICAL SIGNIFICANCE: Our results are relevant to improving current biological-based strategies aiming to repair IVD by restoring cellular lipid metabolites as well as adipokines homeostasis. Ultimately, our results will be valuable for successful, long-lasting relief of painful IVDD.PMID:37339697 | DOI:10.1016/j.spinee.2023.06.005

J Clin Endocrinol Metab. 2023 Jun 20:dgad370. doi: 10.1210/clinem/dgad370. Online ahead of print.ABSTRACTBACKGROUND: Patients with adrenal insufficiency (AI) require life-long glucocorticoid (GC) replacement therapy. Within tissues, cortisol (F) availability is under the control of the isozymes of 11β-hydroxysteroid dehydrogenase (11β-HSD). We hypothesize that corticosteroid metabolism is altered in patients with AI due to the non-physiological pattern of current immediate release hydrocortisone (IR-HC) replacement therapy. The use of once-daily dual-release hydrocortisone (DR-HC) preparation, (Plenadren®), offers a more physiological cortisol profile and may alter corticosteroid metabolism in vivo.STUDY DESIGN AND METHODS: Prospective cross-over study assessing the impact of 12 weeks of DR-HC on systemic GC metabolism (urinary steroid metabolome profiling) and cortisol activation in the liver (cortisone acetate challenge test) and subcutaneous adipose tissue (microdialysis, biopsy for gene expression analysis) in 51 patients with AI (primary and secondary) in comparison to IR-HC treatment and age-and BMI-matched controls.RESULTS: Patients with AI receiving IR-HC had a higher median 24-hour urinary excretion of cortisol compared to healthy controls [72.1 µg/24 hrs (IQR 43.6-124.2) vs 51.9 µg/24 hrs (35.5-72.3), p = 0.02], with lower global activity of 11β-HSD2 and higher 5-alpha reductase activity. Following the switch from IR-HC to DR-HC therapy, there was a significant reduction in urinary cortisol and total GC metabolite excretion, which was most significant in the evening. There was an increase in 11β-HSD2 activity. Hepatic 11β-HSD1 activity was not significantly altered after switching to DR-HC, but there was a significant reduction in the expression and activity of 11β-HSD1 in subcutaneous adipose tissue.CONCLUSION: Using comprehensive in-vivo techniques, we have demonstrated abnormalities in corticosteroid metabolism in patients with primary and secondary AI receiving IR-HC. This dysregulation of pre-receptor glucocorticoid metabolism results in enhanced glucocorticoid activation in adipose tissue, which was ameliorated by treatment with DR-HC.PMID:37339332 | DOI:10.1210/clinem/dgad370

J Proteome Res. 2023 Jun 20. doi: 10.1021/acs.jproteome.2c00845. Online ahead of print.ABSTRACTLeishmania donovani infection of macrophages drives profound changes in the metabolism of both the host macrophage and the parasite, which undergoes different phases of development culminating in replication and propagation. However, the dynamics of this parasite-macrophage cometabolome are poorly understood. In this study, a multiplatform metabolomics pipeline combining untargeted, high-resolution CE-TOF/MS and LC-QTOF/MS with targeted LC-QqQ/MS was followed to characterize the metabolome alterations induced in L. donovani-infected human monocyte-derived macrophages from different donors at 12, 36, and 72 h post-infection. The set of alterations known to occur during Leishmania infection of macrophages, substantially expanded in this investigation, characterized the dynamics of the glycerophospholipid, sphingolipid, purine, pentose phosphate, glycolytic, TCA, and amino acid metabolism. Our results showed that only citrulline, arginine, and glutamine exhibited constant trends across all studied infection time points, while most metabolite alterations underwent a partial recovery during amastigote maturation. We determined a major metabolite response pointing to an early induction of sphingomyelinase and phospholipase activities and correlated with amino acid depletion. These data represent a comprehensive overview of the metabolome alterations occurring during promastigote-to-amastigote differentiation and maturation of L. donovani inside macrophages that contributes to our understanding of the relationship between L. donovani pathogenesis and metabolic dysregulation.PMID:37339249 | DOI:10.1021/acs.jproteome.2c00845

Sci Signal. 2023 Jun 20;16(790):eadf1947. doi: 10.1126/scisignal.adf1947. Epub 2023 Jun 20.ABSTRACTTransforming growth factor-β (TGF-β) signaling is a critical driver of epithelial-to-mesenchymal transition (EMT) and cancer progression. In SMAD-dependent TGF-β signaling, activation of the TGF-β receptor complex stimulates the phosphorylation of the intracellular receptor-associated SMADs (SMAD2 and SMAD3), which translocate to the nucleus to promote target gene expression. SMAD7 inhibits signaling through the pathway by promoting the polyubiquitination of the TGF-β type I receptor (TβRI). We identified an unannotated nuclear long noncoding RNA (lncRNA) that we designated LETS1 (lncRNA enforcing TGF-β signaling 1) that was not only increased but also perpetuated by TGF-β signaling. Loss of LETS1 attenuated TGF-β-induced EMT and migration in breast and lung cancer cells in vitro and extravasation of the cells in a zebrafish xenograft model. LETS1 potentiated TGF-β-SMAD signaling by stabilizing cell surface TβRI, thereby forming a positive feedback loop. Specifically, LETS1 inhibited TβRI polyubiquitination by binding to nuclear factor of activated T cells (NFAT5) and inducing the expression of the gene encoding the orphan nuclear receptor 4A1 (NR4A1), a component of a destruction complex for SMAD7. Overall, our findings characterize LETS1 as an EMT-promoting lncRNA that potentiates signaling through TGF-β receptor complexes.PMID:37339182 | DOI:10.1126/scisignal.adf1947

Curr Opin Neurol. 2023 Jun 20. doi: 10.1097/WCO.0000000000001164. Online ahead of print.ABSTRACTPURPOSE OF THE REVIEW: Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disease of the motor system due to the selective and progressive degeneration of both upper and lower motor neurons. Disturbances in energy homeostasis were repeatedly associated with the ALS pathogenesis and appear early during the disease process. In this review, we highlight recent work demonstrating the crucial role of energy metabolism in ALS and discuss its potential clinical relevance.RECENT FINDINGS: The alteration of various metabolic pathways contributes to the heterogeneity of the clinical phenotype of ALS. Recent work showed that different ALS mutations selectively impact these pathways and translate to the disease phenotypes in patients and disease models. Strikingly, a growing number of studies point towards an early, even presymptomatic, contribution of abnormal energy homeostasis to the ALS pathogenesis. Advances in metabolomics generated valuable tools to study altered metabolic pathways, to test their therapeutic potential, and to develop personalized medicine. Importantly, recent preclinical studies and clinical trials demonstrated that targeting energy metabolism is a promising therapeutic approach.SUMMARY: Abnormal energy metabolism is a key player in ALS pathogenesis, emerging as a source of potential disease biomarkers and therapeutic targets.PMID:37338894 | DOI:10.1097/WCO.0000000000001164

Metabolomics. 2023 Jun 20;19(7):59. doi: 10.1007/s11306-023-02021-x.ABSTRACTINTRODUCTION: Cervical artificial insemination (AI) with frozen-thawed semen in sheep has yielded unacceptably low pregnancy rates. The exception is in Norway where vaginal AI yields non-return rates in excess of 60%, which has been attributed to the ewe breed used.OBJECTIVES AND METHODS: This study aimed to characterise, for the first time, the ovine follicular phase cervical mucus metabolome, with a focus on the amino acid profile. Cervical mucus was collected from four European ewe breeds with known differences in pregnancy rates following cervical AI with frozen-thawed semen. These were Suffolk (low fertility), Belclare (medium fertility), Norwegian White Sheep (NWS) and Fur (both high fertility).RESULTS: A total of 689 metabolites were identified in the cervical mucus of all the four ewe breeds. Of these, 458 metabolites were altered by ewe breed, which had the greatest effect in the dataset (P < 0.05). We detected 194 metabolites involved in the amino acid pathway, of which 133, 56 and 63 were affected by ewe breed, type of cycle and their interaction, respectively (P < 0.05). N-methylhydantoin and N-carbamoylsarcosine (degradation products of creatinine pathway) exhibited the greatest fold change decrease in the Suffolk breed compared to Fur and NWS (P < 0.001). Oxidized metabolites were also decreased in Suffolk compared to high fertility breeds (P < 0.05). In contrast, other metabolites such as 3-indoxyl-sulfate, putrescine, cadaverine were significantly increased in Suffolk at the synchronised cycle.CONCLUSION: The suboptimal amino acid profile in the cervical mucus of the low fertility Suffolk breed may have negative consequences for sperm transport.PMID:37338596 | DOI:10.1007/s11306-023-02021-x

Eur Radiol. 2023 Jun 20. doi: 10.1007/s00330-023-09827-2. Online ahead of print.ABSTRACTOBJECTIVES: To use convolutional neural network for fully automated segmentation and radiomics features extraction of hypopharyngeal cancer (HPC) tumor in MRI.METHODS: MR images were collected from 222 HPC patients, among them 178 patients were used for training, and another 44 patients were recruited for testing. U-Net and DeepLab V3 + architectures were used for training the models. The model performance was evaluated using the dice similarity coefficient (DSC), Jaccard index, and average surface distance. The reliability of radiomics parameters of the tumor extracted by the models was assessed using intraclass correlation coefficient (ICC).RESULTS: The predicted tumor volumes by DeepLab V3 + model and U-Net model were highly correlated with those delineated manually (p < 0.001). The DSC of DeepLab V3 + model was significantly higher than that of U-Net model (0.77 vs 0.75, p < 0.05), particularly in those small tumor volumes of < 10 cm3 (0.74 vs 0.70, p < 0.001). For radiomics extraction of the first-order features, both models exhibited high agreement (ICC: 0.71-0.91) with manual delineation. The radiomics extracted by DeepLab V3 + model had significantly higher ICCs than those extracted by U-Net model for 7 of 19 first-order features and for 8 of 17 shape-based features (p < 0.05).CONCLUSION: Both DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images, whereas DeepLab V3 + had a better performance than U-Net.CLINICAL RELEVANCE STATEMENT: The deep learning model, DeepLab V3 + , exhibited promising performance in automated tumor segmentation and radiomics extraction for hypopharyngeal cancer on MRI. This approach holds great potential for enhancing the radiotherapy workflow and facilitating prediction of treatment outcomes.KEY POINTS: • DeepLab V3 + and U-Net models produced reasonable results in automated segmentation and radiomic features extraction of HPC on MR images. • DeepLab V3 + model was more accurate than U-Net in automated segmentation, especially on small tumors. • DeepLab V3 + exhibited higher agreement for about half of the first-order and shape-based radiomics features than U-Net.PMID:37338554 | DOI:10.1007/s00330-023-09827-2

Plant Physiol. 2023 Jun 20:kiad357. doi: 10.1093/plphys/kiad357. Online ahead of print.ABSTRACTSingle-cell metabolomics is a powerful tool that can reveal cellular heterogeneity and can elucidate the mechanisms of biological phenomena in detail. It is a promising approach in studying plants, especially when cellular heterogeneity has an impact on different biological processes. In addition, metabolomics, which can be regarded as a detailed phenotypic analysis, is expected to answer previously unanswered questions which will lead to expansion of crop production, increased understanding of resistance to diseases, and in other applications as well. In this review, we will introduce the flow of sample acquisition, and single-cell metabolomics techniques to facilitate the adoption of single-cell metabolomics. Furthermore, the applications of single cell metabolomics will be summarized and reviewed.PMID:37338502 | DOI:10.1093/plphys/kiad357

Eur J Mass Spectrom (Chichester). 2023 Jun 20:14690667231179565. doi: 10.1177/14690667231179565. Online ahead of print.ABSTRACTThe objective of this study is to gain insights into the underlying metabolic transformations that occurred during the whole progression of cecal ligation and puncture (CLP)-induced sepsis, thus providing new targets for its treatment. High-performance liquid chromatography of quadrupole time of flight mass spectrometry (HPLC-Q-TOF-MS/MS) combined with multivariate statistical techniques was used to detect the s in serum from septic mice. Fifty male mice were divided into two groups, including the sham group (n = 7) and the CLP-induced sepsis group (n = 43). Animals were sacrificed at 1, 3, 5, and 7 days post-CLP and then serum were collected for metabolomic analysis. Multivariate regression analysis was carried out through MetaboAnalyst 5.0, including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA), to identify the s and screen out the related differential metabolites. Besides, the KEGG pathway analysis was used to analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change (FC > 2.0 or <0.5), variable important in projection (VIP > 1.2), and P value (P < 0.05), we found 26, 17, 21, and 17 metabolites in septic mice at 1, 3, 5, and 7 days post-CLP, respectively, compared with that of the sham group. The PCA and PLS-DA pattern recognition showed a cluster-type distribution between the sham group and the CLP group. Dysregulated amino acid metabolism, as well as disturbed nucleotide metabolism, is observed. Several important metabolic pathways were identified between the sham group and the CLP group. Among them, phenylalanine metabolism, phenylalanine, tyrosine, and tryptophan biosynthesis showed striking at day 1 post-CLP. At day 3, phenylalanine, tyrosine, and tryptophan biosynthesis changed significantly. However, as the disease process, only pyrimidine metabolism showed the most significant alternation, compared to the sham group. Several differential metabolites were identified in the CLP group compared with that of the sham group and they were presented with dynamic alternation at different time points post-CLP, indicating metabolic disturbance occurred throughout the whole sepsis progression.PMID:37338428 | DOI:10.1177/14690667231179565

Mol Omics. 2023 Jun 20. doi: 10.1039/d3mo00051f. Online ahead of print.ABSTRACTDrought alone causes more annual loss in crop yield than the sum of all other environmental stresses. There is growing interest in harnessing the potential of stress-resilient PGPR in conferring plant resistance and enhancing crop productivity in drought-affected agroecosystems. A detailed understanding of the complex physiological and biochemical responses will open up the avenues to stress adaptation mechanisms of PGPR communities under drought. It will pave the way for rhizosphere engineering through metabolically engineered PGPR. Therefore, to reveal the physiological and metabolic networks in response to drought-mediated osmotic stress, we performed biochemical analyses and applied untargeted metabolomics to investigate the stress adaptation mechanisms of a PGPR Enterobacter bugendensis WRS7 (Eb WRS7). Drought caused oxidative stress and resulted in slower growth rates in Eb WRS7. However, Eb WRS7 could tolerate drought stress and did not show changes in cell morphology under stress conditions. Overproduction of ROS caused lipid peroxidation (increment in MDA) and eventually activated antioxidant systems and cell signalling cascades, which led to the accumulation of ions (Na+, K+, and Ca2+), osmolytes (proline, exopolysaccharides, betaine, and trehalose), and modulated lipid dynamics of the plasma membranes for osmosensing and osmoregulation, suggesting an osmotic stress adaption mechanism in PGPR Eb WRS7. Finally, GC-MS-based metabolite profiling and deregulated metabolic responses highlighted the role of osmolytes, ions, and intracellular metabolites in regulating Eb WRS7 metabolism. Our results suggest that understanding the role of metabolites and metabolic pathways can be exploited for future metabolic engineering of PGPR and developing bio inoculants for plant growth promotion under drought-affected agroecosystems.PMID:37338418 | DOI:10.1039/d3mo00051f

Anal Methods. 2023 Jun 20. doi: 10.1039/d3ay00560g. Online ahead of print.ABSTRACTWith the increasing prevalence of diabetes mellitus (DM) and diabetic nephropathy (DN), effective treatment is particularly important for the recovery of patients. However, the currently approved drugs are usually tailored to clinical symptoms and no mechanism-targeted drugs are available. In this study, the combination of metabolomics and network pharmacology was applied to provide reasonable medication combination regimens to meet the different clinical needs for the targeted treatment of DM and DN. An NMR-based metabolomic strategy was applied to identify the potential urinary biomarkers of DM or/and DN, while network pharmacology was used to identify the therapy targets of DM and DN by intersecting the targets of diseases and currently approved drugs. According to the enriched signaling pathways using the potential biomarkers and the therapy targets, the specific medication combinations were recommended for the specific clinical demands in terms of hypoglycemic, hypertensive, and/or lipid-lowering. For DM, 17 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 34 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension, and hypoglycemia, hypertension, and lipid-lowering were administered. For DN, 22 potential urinary biomarkers and 12 disease-related signaling pathways were identified, and 21 combined medication regimens related to hypoglycemia, hypoglycemia, and hypertension were proposed. Molecular docking was used to verify the binding ability, docking sites, and structure of the drug molecules to target proteins. Moreover, an integrated biological information network of the drug-target-metabolite-signaling pathways was constructed to provide insights into the underlined mechanism of DM and DN as well as clinical combination therapy.PMID:37338009 | DOI:10.1039/d3ay00560g

Scand J Gastroenterol. 2023 Jun 20:1-7. doi: 10.1080/00365521.2023.2225667. Online ahead of print.ABSTRACTOBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by the accumulation of excessive fat in the liver, which can lead to fibrosis and has an increasing prevalence. NAFLD requires non-invasive diagnostic biomarkers. While typically observed in overweight individuals, it can also occur in non-obese/non-overweight individuals. Comparative studies on non-obese NAFLD patients are scarce. This study aimed to conduct a using liquid chromatography-high resolution mass spectrometry (LC-MS/MS)-based metabolic profiling of non-obese NAFLD patients and healthy controls.MATERIALS AND METHODS: The patient group consisted of 27 individuals with NAFLD, while the healthy control group included 39 individuals. Both groups were between 18 and 40 years old, had a BMI of less than 25 and had alcohol consumption less than 20 g/week for men and 10 g/week for women. Serum samples were collected and analyzed using LC-MS/MS. The data were analyzed using the TidyMass and MetaboAnalyst.RESULTS: The LC-MS/MS analyses detected significant changes in D-amino acid metabolism, vitamin B6 metabolism, apoptosis, mTOR signaling pathway, lysine degradation, and phenylalanine metabolism pathways in non-obese NAFLD patients. Significant changes were also observed in the metabolites D-pantothenic acid, hypoxanthine, citric acid, citramalic acid, L-phenylalanine, glutamine, and histamine-trifluoromethyl-toluidide, β-hydroxymyristic acid, DL-Lactic acid, and 3-methyl-2-oxopentanoic. Overall, the study provides valuable insights into the metabolic changes associated with non-obese NAFLD patients and can contribute to the development of non-invasive diagnostic biomarkers for NAFLD.CONCLUSIONS: This study sheds light on the metabolic changes in non-obese NAFLD patients. Further research is needed to better understand the metabolic changes associated with NAFLD and to develop effective treatment options.PMID:37337892 | DOI:10.1080/00365521.2023.2225667

J Agric Food Chem. 2023 Jun 19. doi: 10.1021/acs.jafc.3c01531. Online ahead of print.ABSTRACTPlants growing in open environments are frequently coinfected by multiple strains of the same pathogen. However, few investigations have been carried out to reveal the outcomes and underlying mechanisms of such infections. This study aimed to observe the behaviors of two different strains under coinfection and cocultivation. We constructed an experimental system to study such interactions directly by labeling Magnaporthe oryzae strains with the green fluorescent proteins and mushroom cherry fluorescent protein to observe mixed strain behavior in vivo and in vitro. Moreover, multiomics analyses were conducted to explore the underlying mechanisms at the genomic, transcriptomic, and metabolomic levels. Our results revealed that coinfection with two strains can affect disease severity and that the more weakly virulent strain benefits from the coinfection system. We also found that amino acid variation might negatively influence such interactions at transcriptomic and metabolomic levels. In addition, we showed that the overexpression of a glutamine-related gene improved strain competitiveness during mixture cultivation. Collectively, our results provided experimental methods to analyze the interaction between two strains of M. oryzae and preliminarily explored the interacted mechanism of two strains under cocultivation through multiomics analyses.PMID:37337365 | DOI:10.1021/acs.jafc.3c01531

Trials. 2023 Jun 19;24(1):417. doi: 10.1186/s13063-023-07432-8.ABSTRACTBACKGROUND: Aneurysmal subarachnoid hemorrhage (aSAH) is a neurological emergency, affecting a younger population than individuals experiencing an ischemic stroke; aSAH is associated with a high risk of mortality and permanent disability. The noble gas xenon has been shown to possess neuroprotective properties as demonstrated in numerous preclinical animal studies. In addition, a recent study demonstrated that xenon could attenuate a white matter injury after out-of-hospital cardiac arrest.METHODS: The study is a prospective, multicenter phase II clinical drug trial. The study design is a single-blind, prospective superiority randomized two-armed parallel follow-up study. The primary objective of the study is to explore the potential neuroprotective effects of inhaled xenon, when administered within 6 h after the onset of symptoms of aSAH. The primary endpoint is the extent of the global white matter injury assessed with magnetic resonance diffusion tensor imaging of the brain.DISCUSSION: Despite improvements in medical technology and advancements in medical science, aSAH mortality and disability rates have remained nearly unchanged for the past 10 years. Therefore, new neuroprotective strategies to attenuate the early and delayed brain injuries after aSAH are needed to reduce morbidity and mortality.TRIAL REGISTRATION: ClinicalTrials.gov NCT04696523. Registered on 6 January 2021. EudraCT, EudraCT Number: 2019-001542-17. Registered on 8 July 2020.PMID:37337295 | DOI:10.1186/s13063-023-07432-8

Genome Biol. 2023 Jun 19;24(1):141. doi: 10.1186/s13059-023-02984-z.ABSTRACTBACKGROUND: Seed oil content is an important agronomic trait of Brassica napus (B. napus), and metabolites are considered as the bridge between genotype and phenotype for physical traits.RESULTS: Using a widely targeted metabolomics analysis in a natural population of 388 B. napus inbred lines, we quantify 2172 metabolites in mature seeds by liquid chromatography mass spectrometry, in which 131 marker metabolites are identified to be correlated with seed oil content. These metabolites are then selected for further metabolite genome-wide association study and metabolite transcriptome-wide association study. Combined with weighted correlation network analysis, we construct a triple relationship network, which includes 21,000 edges and 4384 nodes among metabolites, metabolite quantitative trait loci, genes, and co-expression modules. We validate the function of BnaA03.TT4, BnaC02.TT4, and BnaC05.UK, three candidate genes predicted by multi-omics analysis, which show significant impacts on seed oil content through regulating flavonoid metabolism in B. napus.CONCLUSIONS: This study demonstrates the advantage of utilizing marker metabolites integrated with multi-omics analysis to dissect the genetic basis of agronomic traits in crops.PMID:37337206 | DOI:10.1186/s13059-023-02984-z

Nat Metab. 2023 Jun 19. doi: 10.1038/s42255-023-00825-8. Online ahead of print.ABSTRACTAdaptive thermogenesis by brown adipose tissue (BAT) dissipates calories as heat, making it an attractive anti-obesity target. Yet how BAT contributes to circulating metabolite exchange remains unclear. Here, we quantified metabolite exchange in BAT and skeletal muscle by arteriovenous metabolomics during cold exposure in fed male mice. This identified unexpected metabolites consumed, released and shared between organs. Quantitative analysis of tissue fluxes showed that glucose and lactate provide ~85% of carbon for adaptive thermogenesis and that cold and CL316,243 trigger markedly divergent fuel utilization profiles. In cold adaptation, BAT also dramatically increases nitrogen uptake by net consuming amino acids, except glutamine. Isotope tracing and functional studies suggest glutamine catabolism concurrent with synthesis via glutamine synthetase, which avoids ammonia buildup and boosts fuel oxidation. These data underscore the ability of BAT to function as a glucose and amino acid sink and provide a quantitative and comprehensive landscape of BAT fuel utilization to guide translational studies.PMID:37337122 | DOI:10.1038/s42255-023-00825-8

Nat Metab. 2023 Jun 19. doi: 10.1038/s42255-023-00817-8. Online ahead of print.ABSTRACTTumour metabolism is controlled by coordinated changes in metabolite abundance and gene expression, but simultaneous quantification of metabolites and transcripts in primary tissue is rare. To overcome this limitation and to study gene-metabolite covariation in cancer, we assemble the Cancer Atlas of Metabolic Profiles of metabolomic and transcriptomic data from 988 tumour and control specimens spanning 11 cancer types in published and newly generated datasets. Meta-analysis of the Cancer Atlas of Metabolic Profiles reveals two classes of gene-metabolite covariation that transcend cancer types. The first corresponds to gene-metabolite pairs engaged in direct enzyme-substrate interactions, identifying putative genes controlling metabolite pool sizes. A second class of gene-metabolite covariation represents a small number of hub metabolites, including quinolinate and nicotinamide adenine dinucleotide, which correlate to many genes specifically expressed in immune cell populations. These results provide evidence that gene-metabolite covariation in cellularly heterogeneous tissue arises, in part, from both mechanistic interactions between genes and metabolites, and from remodelling of the bulk metabolome in specific immune microenvironments.PMID:37337120 | DOI:10.1038/s42255-023-00817-8