PubMed

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

Trends Plant Sci. 2023 Jun 17:S1360-1385(23)00170-X. doi: 10.1016/j.tplants.2023.05.013. Online ahead of print.NO ABSTRACTPMID:37336692 | DOI:10.1016/j.tplants.2023.05.013

Fitoterapia. 2023 Jun 17:105583. doi: 10.1016/j.fitote.2023.105583. Online ahead of print.ABSTRACTPhytochemical investigation of the volatile oil of Yueju (YJVO) and its constituent herbs induced the detection of 52 compounds in YJVO, mainly monoterpenes and sesquiterpenes as well as a small amount of aromatic and aliphatic compounds. 5 of these compounds were found only in the YJVO instead of the volatile oil of its constituent herbs. The anti-depressant effect of YJVO was proved by behavioral tests in chronic unpredictable mild stress (CUMS) mice. An acute oral toxicity evaluation determined the LD50 of YJVO was 5.780 mL/kg. Doppler ultrasound and laser speckle imaging have detected that the YJVO could improve depression-related cerebral blood flow. In addition, related neurotransmitters and proteins were analyzed through targeted metabolomics and immunofluorescence. The potential antidepressant mechanisms of YJVO related to significantly decreasing Glu in CUMS mice by up-regulating the ERK/AKT-mediated expression of GLT-1.PMID:37336418 | DOI:10.1016/j.fitote.2023.105583

Environ Pollut. 2023 Jun 17:122030. doi: 10.1016/j.envpol.2023.122030. Online ahead of print.ABSTRACTHumans are constantly exposed to complicated chemical mixtures from the environment and food rather than being exposed to a single pollutant. The underlying mechanisms of the complicated combined toxicity of endocrine disrupting chemicals (EDCs) are still mainly unexplored. In this study, two representative EDCs, 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153) and atrazine (ATZ), were selected to explore their combined effects on MCF-7 cell proliferation at environmental exposure concentrations by an integrated analysis of metabolomics and transcriptomics. The results showed that 1 μM ATZ and PCB153 combined exposure significantly accelerated MCF-7 cell growth by 18.2%. More than 400 metabolites detected by UHPLC-QTOF/MS were used to observe metabolism differences induced by binary mixtures. Metabolomics analysis verified that ATZ and PCB153 exposure alone or in combination could have an additive effect on metabolism and induce significant disruption to glycolysis, purine metabolism and the TCA cycle, which provide energy demand and biosynthetic substrates for cell proliferation. Compared to PCB153 and ATZ exposure alone, a combined effect was observed in purine and pyrimidine metabolic pathways. Hexokinase 3 (HK3) and cytochrome P450 19 subfamily A1 (CYP19A1) were identified as differentially expressed genes based on transcriptomic analysis. By integrating metabolome and transcriptome analysis, the proliferation effects of ATZ and PCB153 were induced at low doses in MCF-7 cells through potential interference with the downstream transcription signaling of CYP19A1. Furthermore, molecular docking indicated that PCB153 and ATZ directly affected CYP19A1. Altogether, the regulation of pivotal metabolites and differentially expressed genes could provide helpful information to reveal the mechanism by which PCB153 and ATZ affect MCF-7 cell proliferation.PMID:37336346 | DOI:10.1016/j.envpol.2023.122030

Neurobiol Aging. 2023 May 26;129:178-184. doi: 10.1016/j.neurobiolaging.2023.05.013. Online ahead of print.ABSTRACTLipids are essential components of brain structure and shown to affect brain function. Previous studies have shown that aging men undergo greater brain atrophy than women, but whether the associations between lipids and brain atrophy differ by sex is unclear. We examined sex differences in the associations between circulating lipids by liquid chromatography-tandem mass spectrometry and the progression of MRI-derived brain atrophy index Spatial Patterns of Atrophy for Recognition of Brain Aging (SPARE-BA) over an average of 4.7 (SD = 2.3) years in 214 men and 261 women aged 60 or older who were initially cognitively normal using multivariable linear regression, adjusted for age, race, education, and baseline SPARE-BA. We found significant sex interactions for beta-oxidation rate, short-chain acylcarnitines, long-chain ceramides, and very long-chain triglycerides. Lower beta-oxidation rate and short-chain acylcarnitines in women and higher long-chain ceramides and very long-chain triglycerides in men were associated with faster increases in SPARE-BA (accelerated brain aging). Circulating lipid profiles of accelerated brain aging are sex-specific and vary by lipid classes and structure. Mechanisms underlying these sex-specific lipid profiles of brain aging warrant further investigation.PMID:37336172 | DOI:10.1016/j.neurobiolaging.2023.05.013

Environ Int. 2023 Jun 15;178:108039. doi: 10.1016/j.envint.2023.108039. Online ahead of print.ABSTRACTResorcinol-bis(diphenyl)-phosphate (RDP), an emerging organophosphate flame retardant, is increasingly used as a primary alternative for decabromodiphenyl ether and is frequently detected in global environmental matrices. However, the long-term effects of its exposure to humans remain largely unknown. To investigate its intergenerational transfer capacity and health risks, female Sprague Dawley rats were orally exposed to RDP from the beginning of pregnancy to the end of the lactation period. The RDP content, gut microbiota homeostasis, and metabolic levels were determined. RDP accumulation occurred in the livers of maternal rats and offspring and increased with exposure time. 16S rRNA gene sequencing showed that exposure to RDP during pregnancy and/or lactation significantly disrupted gut microbiota homeostasis, as evidenced by decreased abundance and diversity. In particular, the abundance of Turicibacter, Adlercreutzia, and YRC22 decreased, correlating significantly with glycollipic metabolism. This finding was consistent with the reduced levels of short-chain fatty acids, the crucial gut microbial metabolites. Meanwhile, RDP exposure resulted in changes in gut microbiome-related metabolism. Nine critical overlapping KEGG metabolic pathways were identified, and the levels of related differential metabolites decreased. Our results suggest that the significant adverse impacts of RDP on gut microbiota homeostasis and metabolic function may increase the long-term risks related to inflammation, obesity, and metabolic diseases.PMID:37336026 | DOI:10.1016/j.envint.2023.108039

Plant Physiol. 2023 Jun 19:kiad340. doi: 10.1093/plphys/kiad340. Online ahead of print.ABSTRACTThe selective turnover of macromolecules by autophagy provides a critical homeostatic mechanism for recycling cellular constituents and for removing superfluous and damaged organelles, membranes, and proteins. To better understand how autophagy impacts seed maturation and nutrient storage, we studied maize (Zea mays) endosperm in its early and middle developmental stages via an integrated multi-omics approach using mutants impacting the core macroautophagy factor AUTOPHAGY (ATG)-12 required for autophagosome assembly. Surprisingly, the mutant endosperm in these developmental windows accumulated normal amounts of starch and Zein storage proteins. However, the tissue acquired a substantially altered metabolome, especially for compounds related to oxidative stress and sulfur metabolism, including increases in cystine, dehydroascorbate, cys-glutathione disulfide, glucarate and galactarate, and decreases in peroxide and the anti-oxidant glutathione. While changes in the associated transcriptome were mild, the proteome was strongly altered in the atg12 endosperm, especially for increased levels of mitochondrial proteins without a concomitant increase in mRNA abundances. Although fewer mitochondria were seen cytologically, a heightened number appeared dysfunctional based on the accumulation of dilated cristae, consistent with attenuated mitophagy. Collectively, our results confirm that macroautophagy plays a minor role in the accumulation of starch and storage proteins during maize endosperm development, but likely helps protect against oxidative stress and clears unneeded/dysfunctional mitochondria during tissue maturation.PMID:37335933 | DOI:10.1093/plphys/kiad340

Arthritis Rheumatol. 2023 Jun 19. doi: 10.1002/art.42632. Online ahead of print.ABSTRACTOBJECTIVE: Patients with connective tissue disease-associated pulmonary arterial hypertension (CTD-PAH) experience worse survival and derive less benefit from pulmonary vasodilator therapies than patients with idiopathic PAH (IPAH). We sought to identify differential metabolism in CTD-PAH versus IPAH patients that might underlie these observed clinical differences.METHODS: Adult subjects with CTD-PAH (n=141) and IPAH (n=165) from the PVDOMICS (Pulmonary Vascular Disease Phenomics) Study were included. Detailed clinical phenotyping was performed at cohort enrollment, including broad-based global metabolomic profiling of plasma samples. Subjects were followed prospectively for ascertainment of outcomes. Supervised and unsupervised machine learning algorithms and regression models were used to compare CTD-PAH versus IPAH metabolomic profiles and to measure metabolite-phenotype associations and interactions. Gradients across the pulmonary circulation were assessed using paired mixed venous and wedged samples in a subset of 115 subjects.RESULTS: Metabolomic profiles distinguished CTD-PAH from IPAH, with CTD-PAH patients demonstrating aberrant lipid metabolism, with lower circulating levels of sex steroid hormones and higher free fatty acids (FA) and FA intermediates in CTD-PAH. Acylcholines were taken up by the right ventricular-pulmonary vascular circulation, particularly in CTD-PAH, while free FAs and acylcarnitines were released. In both PAH subtypes, dysregulated lipid metabolites, among others, were associated with hemodynamic and right ventricular measurements and with transplant-free survival.CONCLUSIONS: CTD-PAH is characterized by aberrant lipid metabolism that may signal shifted metabolic substrate utilization. Abnormalities in RV-pulmonary vascular FA metabolism may imply reduced capacity for mitochondrial beta oxidation within the diseased pulmonary circulation.PMID:37335853 | DOI:10.1002/art.42632

Medicine (Baltimore). 2023 May 19;102(20):e33730. doi: 10.1097/MD.0000000000033730.ABSTRACTFebrile seizure (FS) is a highly recurrent neuro-system disorder in children that affects their nervous system development and quality of life. However, the pathogenesis of febrile seizures remains unclear. Our study aims to investigate the potential differences in the intestinal flora and metabolomics between healthy children and those with FS. By examining the relationship between specific flora and different metabolites, we hope to shed light on the pathogenesis of FS. Fecal specimens were collected from healthy children (n = 15) and children with febrile seizures (n = 15), and 16S rDNA sequencing was conducted to characterize intestinal flora. Subsequently, fecal samples from healthy (n = 6) and febrile seizure children (n = 6) were used to characterize metabolomics using linear discriminant analysis of effect size, orthogonal partial least squares discriminant analysis, Kyoto Encyclopedia of Genes and Genomes (pathway enrichment analysis), and Kyoto encyclopedia of genes and genomes topology analysis. Liquid chromatography-mass spectrometry was used to identify metabolites in the fecal samples. The intestinal microbiome in the febrile seizure children significantly differed from that in the healthy children at the phylum level. Ten differentially accumulated metabolites (xanthosine, (S)-abscisic acid, N-palmitoylglycine, (+/-)-2-(5-methyl-5-vinyl-tetrahydrofuran-2-yl) propionaldehyde, (R)-3-hydroxybutyrylcarnitine, lauroylcarnitine, oleoylethanolamide, tetradecyl carnitine, taurine, and lysoPC [18:1 (9z)/0:0] were considered the potential febrile seizure markers. Three metabolic pathways (taurine metabolism; glycine, serine, and threonine metabolism; and arginine biosynthesis) were found essential in febrile seizure. Bacteroides were significantly correlated with the 4 differential metabolites. Adjusting the balance of intestinal flora may be an effective method for preventing and treating febrile seizures.PMID:37335742 | DOI:10.1097/MD.0000000000033730

Medicine (Baltimore). 2023 Jun 9;102(23):e33715. doi: 10.1097/MD.0000000000033715.ABSTRACTBACKGROUND: Parkinson's disease (PD) is by now the second of the most prevalent neurodegenerative diseases in the world, and its incidence is increasing rapidly as the global population ages, with 14.2 million PD patients expected worldwide by 2040.METHODS: We gathered a completion of 45 serum samples, including 15 of healthy controls and 30 from the PD group. We used non-targeted metabolomics analysis based on liquid chromatography-mass spectrometry to identify the molecular changes in PD patients, and conducted bioinformatics analysis on this basis to explore the possible pathogenesis of PD.RESULTS: We found significant metabolomics changes in the levels of 30 metabolites in PD patients compared with healthy controls.CONCLUSION: Lipids and lipid-like molecules accounted for the majority of the 30 differentially expressed metabolites. Also, pathway enrichment analysis showed significant enrichment in sphingolipid metabolic pathway. These assessments can improve our perception on the underlying mechanism of PD as well as facilitate a better targeting on therapeutic interventions.PMID:37335671 | DOI:10.1097/MD.0000000000033715