Plasma Metabolic Profiling of Pediatric Sepsis in a Chinese Cohort

Sepsis represents one of the most pressing problems in pediatrics, characterized by pathogenic bacteria invading the blood, growing and multiplying in the blood circulation, and ultimately causing severe infections. Most children with sepsis have a rapid disease onset and frequently exhibit sudden high fever or first chills. Here we performed comprehensive metabolomic profiling of plasma samples collected from pediatric sepsis patients to identify specific metabolic alterations associated with these patients (n = 84, designated as case subjects) as compared to healthy cohorts (n = 59, designated as control subjects). Diagnostic models were constructed using MetaboAnalyst, R packages, and multiple statistical methods, such as orthogonal partial least squares-discriminant analysis, principal component analysis, volcano plotting, and one-way ANOVA. Our study revealed a panel of metabolites responsible for the discrimination between case and control subjects with a high predictive value of prognosis. Moreover, significantly altered metabolites in sepsis survivors versus deceased patients (non-survivors) were identified as those involved in amino acids, fatty acids, and carbohydrates metabolism. Nine metabolites including organic acids and fatty acids were also identified with significantly higher abundance in sepsis patients with related microbes, implicating greater potentials to distinguish bacterial species using metabolomic analysis than blood culture. Pathway enrichment analysis further revealed that fatty acid metabolism might play an important role in the pathogenesis of sepsis.

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1H NMR-Based Analysis of Serum Metabolites in Monocrotaline-Induced Pulmonary Arterial Hypertensive Rats

Disease Markers ◽

10.1155/2016/5803031 ◽

2016 ◽

Vol 2016 ◽

pp. 1-11 ◽

Cited By ~ 5

Author(s):

Taijie Lin ◽

Jinping Gu ◽

Caihua Huang ◽

Suli Zheng ◽

Xu Lin ◽

...

Keyword(s):

Intraperitoneal Injection ◽

Ventricular Hypertrophy ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Metabolic Profiles ◽

Metabolic Dysfunction ◽

Sprague Dawley ◽

Mean Pulmonary Arterial Pressure ◽

Pulmonary Arterial

Aims. To study the changes of the metabolic profile during the pathogenesis in monocrotaline (MCT) induced pulmonary arterial hypertension (PAH).Methods. Forty male Sprague-Dawley (SD) rats were randomly divided into 5 groups (n=8, each). PAH rats were induced by a single dose intraperitoneal injection of 60 mg/kg MCT, while 8 rats given intraperitoneal injection of 1 ml normal saline and scarified in the same day (W0) served as control. Mean pulmonary arterial pressure (mPAP) was measured through catherization. The degree of right ventricular hypertrophy and pulmonary hyperplasia were determined at the end of first to fourth weeks; nuclear magnetic resonance (NMR) spectra of sera were then acquired for the analysis of metabolites. Principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used to discriminate different metabolic profiles.Results. The prominent changes of metabolic profiles were seen during these four weeks. Twenty specific metabolites were identified, which were mainly involved in lipid metabolism, glycolysis, energy metabolism, ketogenesis, and methionine metabolism. Profiles of correlation between these metabolites in each stage changed markedly, especially in the fourth week. Highly activated methionine and betaine metabolism pathways were selected by the pathway enrichment analysis.Conclusions. Metabolic dysfunction is involved in the development and progression of PAH.

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Metabonomic-Transcriptome Integration Analysis on Osteoarthritis and Rheumatoid Arthritis

International Journal of Genomics ◽

10.1155/2020/5925126 ◽

2020 ◽

Vol 2020 ◽

pp. 1-9 ◽

Cited By ~ 1

Author(s):

Ningyang Gao ◽

Li Ding ◽

Jian Pang ◽

Yuxin Zheng ◽

Yuelong Cao ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gap Junction ◽

Molecular Mechanisms ◽

Linear Models ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Nf Kappa B ◽

Linear Module ◽

Hedgehog Acyltransferase

Purpose. This study is aimed at exploring the potential metabolite/gene biomarkers, as well as the differences between the molecular mechanisms, of osteoarthritis (OA) and rheumatoid arthritis (RA). Methods. Transcriptome dataset GSE100786 was downloaded to explore the differentially expressed genes (DEGs) between OA samples and RA samples. Meanwhile, metabolomic dataset MTBLS564 was downloaded and preprocessed to obtain metabolites. Then, the principal component analysis (PCA) and linear models were used to reveal DEG-metabolite relations. Finally, metabolic pathway enrichment analysis was performed to investigate the differences between the molecular mechanisms of OA and RA. Results. A total of 976 DEGs and 171 metabolites were explored between OA samples and RA samples. The PCA and linear module analysis investigated 186 DEG-metabolite interactions including Glycogenin 1- (GYG1-) asparagine_54, hedgehog acyltransferase- (HHAT-) glucose_70, and TNF receptor-associated factor 3- (TRAF3-) acetoacetate_35. Finally, the KEGG pathway analysis showed that these metabolites were mainly enriched in pathways like gap junction, phagosome, NF-kappa B, and IL-17 pathway. Conclusions. Genes such as HHAT, GYG1, and TRAF3, as well as metabolites including glucose, asparagine, and acetoacetate, might be implicated in the pathogenesis of OA and RA. Metabolites like ethanol and tyrosine might participate differentially in OA and RA progression via the gap junction pathway and phagosome pathway, respectively. TRAF3-acetoacetate interaction may be involved in regulating inflammation in OA and RA by the NF-kappa B and IL-17 pathway.

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Tissue-based metabolomics profiling reveals metabolic signatures and major metabolic pathways of gastric cancer

10.21203/rs.3.rs-326163/v1 ◽

2021 ◽

Author(s):

Yaqin Wang ◽

Wenchao Chen ◽

Kun Li ◽

Gang Wu ◽

Wei Zhang ◽

...

Keyword(s):

Gastric Cancer ◽

Predictive Ability ◽

Principal Component ◽

Enrichment Analysis ◽

Pentose Phosphate ◽

P Value ◽

Pathway Enrichment Analysis ◽

Dodecanoic Acid ◽

Orthogonal Projections ◽

Latent Structures

Abstract Purpose This study was aimed to screen differential metabolites between gastric cancer (GC) and paracancerous (PC) tissues and find new biomarkers of GC. Methods GC (n = 28) and matched PC (n = 28) tissues were collected and LC-MS/MS analyses were performed to detect metabolites of GC and PC tissues in positive and negative models. Principal component analysis (PCA) and orthogonal projections to latent structures-discriminate analysis (OPLS-DA) were conducted to describe distribution of origin data and general separation and estimate the robustness and the predictive ability of our mode. Differential metabolites were screened based on criterion of variables with p value < 0.05 and VIP (variable importance in the projection) > 1.0. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic power of differential metabolites. Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed to search for metabolite pathways and MetaboAnalyst was used for pathway enrichment analysis. Results Several metabolites were significantly changed in GC group compared with PC group. Thirteen metabolites with high VIP were chose and among which 1-methylnicotinamide, dodecanoic acid and sphinganine possessed high AUC values (AUC > 0.8) indicating an excellent discriminatory ability on GC. Pathways such as pentose phosphate pathway and histidine metabolism were focused based on differential metabolites demonstrating their effects on progress of GC. Conclusions In conclusion, we investigated the tissue-based metabolomics profile of GC and several differential metabolites and signaling pathways were focused. Further study is needed to verify those results.

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Nanopore Sequencing Reveals Global Transcriptome Signatures of Mitochondrial and Ribosomal Gene Expressions in Various Human Cancer Stem-like Cell Populations

Cancers ◽

10.3390/cancers13051136 ◽

2021 ◽

Vol 13 (5) ◽

pp. 1136

Author(s):

Kaya E. Witte ◽

Oliver Hertel ◽

Beatrice A. Windmöller ◽

Laureen P. Helweg ◽

Anna L. Höving ◽

...

Keyword(s):

Human Cancer ◽

Principal Component ◽

Enrichment Analysis ◽

Therapy Resistance ◽

Ribosomal Gene ◽

Pathway Enrichment Analysis ◽

Nanopore Sequencing ◽

Gene Expressions ◽

Metastasis Therapy ◽

Novel Therapeutic Strategies

Cancer stem cells (CSCs) are crucial mediators of tumor growth, metastasis, therapy resistance, and recurrence in a broad variety of human cancers. Although their biology is increasingly investigated within the distinct types of cancer, direct comparisons of CSCs from different tumor types allowing comprehensive mechanistic insights are rarely assessed. In the present study, we isolated CSCs from endometrioid carcinomas, glioblastoma multiforme as well as adenocarcinomas of lung and prostate and assessed their global transcriptomes using full-length cDNA nanopore sequencing. Despite the expression of common CSC markers, principal component analysis showed a distinct separation of the CSC populations into three clusters independent of the specific type of tumor. However, GO-term and KEGG pathway enrichment analysis revealed upregulated genes related to ribosomal biosynthesis, the mitochondrion, oxidative phosphorylation, and glycolytic pathways, as well as the proteasome, suggesting a great extent of metabolic flexibility in CSCs. Interestingly, the GO term “NF-kB binding” was likewise found to be elevated in all investigated CSC populations. In summary, we here provide evidence for high global transcriptional similarities between CSCs from various tumors, which particularly share upregulated gene expression associated with mitochondrial and ribosomal activity. Our findings may build the basis for identifying novel therapeutic strategies targeting CSCs.

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DNA Methylation and Asthma Acquisition During and Post-Adolescence, an Epigenome-Wide Longitudinal Study.

10.21203/rs.3.rs-757593/v1 ◽

2021 ◽

Author(s):

Aniruddha Rathod ◽

Hongmei Zhang ◽

Hasan Arshad ◽

Susan Ewart ◽

Caroline Relton ◽

...

Keyword(s):

Birth Cohort ◽

Repeated Measures ◽

Statistical Power ◽

Transition Period ◽

Disease Onset ◽

Enrichment Analysis ◽

Interaction Effects ◽

Biological Assessment ◽

Pathway Enrichment Analysis ◽

Interaction Terms

Abstract Background- While the majority of asthma starts in early childhood, asthma onset in some individuals occurs during adolescence or in adulthood. However, the pathogenesis of later onset asthma as well as the observed sex specificity are not well understood. Objective- We hypothesized that DNAm at specific CpG sites measured before disease onset, either in pre- or post-adolescence would be associated with asthma acquisition both during adolescence and in later adulthood. Methods- Subjects from the Isle of Wight Birth Cohort (IOWBC) were included. DNAm in blood at ages 10 (pre-adolescence) and 18 (post-adolescence), and asthma acquisition from age 10-18, and 18-26 years was studied. To improve statistical power, we first screened epigenome-wide CpGs based on the association of DNAm at 10 years with asthma acquisition from 10-18 years. Logistic regression with repeated measures were then applied to the CpGs that survived screening to examine the associations of pre-adolescence DNAm with asthma acquisition from pre-to post-adolescence, and post-adolescence DNAm with asthma acquisition from post-adolescence to adulthood. The effect of DNAm on asthma acquisition at different transition period was evaluated using interaction terms. The ALSPAC birth cohort was used for independent replication. For biological assessment of identified CpGs, pathway enrichment analysis and Differentially Methylated Regions were assessed. Results- Significant interaction effects of DNAm and transition period (10-18 or 18-26 years) on asthma acquisition were found for 17 CpGs in males and 98 CpGs in females (FDR=0.05) in IOWBC. Consistent interaction effects were observed for 9 CpGs in males and 53 CpGs in females in ALSPAC. For CpGs not showing interaction effects (i.e., effect of DNAm is stable over time), association with asthma acquisition was found for 38 CpGs in males and 52 CpGs in females in IOWBC. Of these 90 CpGs, at 13 CpG in males and 37 CpG in females, consistent direction of associations was observed in ALSPAC. Genes that the identified CpGs were mapped to, e.g., AKAP1 and ENO1, have shown to be associated with asthma. Conclusion- DNAm at specific CpGs is associated with asthma acquisition and such association is likely to be sex and transition period specific.

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Multi-omics analysis of m6A modification-related patterns based on m6A regulators and tumor microenvironment infiltration in lung adenocarcinoma

Scientific Reports ◽

10.1038/s41598-021-00272-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Xincheng Wu ◽

Zhengping Bai

Keyword(s):

Tumor Microenvironment ◽

Lung Adenocarcinoma ◽

Cytotoxic T Lymphocyte ◽

Principal Component ◽

Enrichment Analysis ◽

Comprehensive Analysis ◽

Survival Advantage ◽

Pathway Enrichment Analysis ◽

Mutation Burden

AbstractEpigenetic modifications, especially N6-methyladenosine (m6A) modification, play a key role in tumor microenvironment (TME) infiltration. However, the regulatory role of m6A modification in the TME of lung adenocarcinoma (LUAD) remains unclear. A total of 2506 patients with LUAD were included in the analysis and divided into different groups according to distinct m6A modification-related patterns based on 23 m6A regulators. A comprehensive analysis was performed to explore TME infiltration in different m6A modification-related patterns. Principal component analysis was performed to obtain the m6Ascore and to quantify m6A modification-related patterns in different individuals. Three distinct m6A modification-related patterns were identified by 23 m6A regulators. The pathway enrichment analysis showed that m6Acluster-A was associated with immune activation; m6Acluster-B was associated with carcinogenic activation; m6Acluster-C was prominently related to substance metabolism. M6Acluster-A was remarkably rich in TME-infiltrating immune cells and patients with this pattern showed a survival advantage. The m6Ascore could predict TME infiltration, tumor mutation burden (TMB), the effect of tumor immunotherapy, and the prognosis of patients in LUAD. High m6Ascore was characterized by increased TME infiltration, reduced TMB, and survival advantage. Patients with a high m6Ascore exhibited significantly improved clinical response to anti-cytotoxic T lymphocyte antigen-4 (anti-CTLA4) immunotherapy. This study explored the regulatory mechanisms of TME infiltration in LUAD. The comprehensive analysis of m6A modification-related patterns may contribute to the development of individualized immunotherapy and the improvement of the overall effectiveness of immunotherapy for LUAD patients.

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Antimicrobial Activity of EPA and DHA against Oral Pathogenic Bacteria Using an In Vitro Multi-Species Subgingival Biofilm Model

Nutrients ◽

10.3390/nu12092812 ◽

2020 ◽

Vol 12 (9) ◽

pp. 2812

Author(s):

Honorato Ribeiro-Vidal ◽

María Carmen Sánchez ◽

Andrea Alonso-Español ◽

Elena Figuero ◽

Maria José Ciudad ◽

...

Keyword(s):

Fatty Acids ◽

Antimicrobial Activity ◽

Structural Damage ◽

Pathogenic Bacteria ◽

Quantitative Polymerase Chain Reaction ◽

Bacterial Species ◽

Laser Scanning Microscopy ◽

Biofilm Model ◽

Epa And Dha

In search for natural products with antimicrobial properties for use in the prevention and treatment of periodontitis, the purpose of this investigation was to evaluate the antimicrobial activity of two omega-3 fatty acids, docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), using an in vitro multi-species subgingival biofilm model including Streptococcus oralis, Actinomyces naeslundii, Veillonella parvula, Fusobacterium nucleatum, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The antimicrobial activities of EPA and DHA extracts (100 µM) and the respective controls were assessed on 72 h biofilms by their submersion onto discs for 60 s. Antimicrobial activity was evaluated by quantitative polymerase chain reaction (qPCR), confocal laser scanning microscopy (CLSM) and scanning electron microscopy (SEM). ANOVA with Bonferroni correction was used to evaluate the antimicrobial activity of each of the fatty acids. Both DHA and EPA significantly reduced (p < 0.001 in all cases) the bacterial strains used in this biofilm model. The results with CLSM were consistent with those reported with qPCR. Structural damage was evidenced by SEM in some of the observed bacteria. It was concluded that both DHA and EPA have significant antimicrobial activity against the six bacterial species included in this biofilm model.

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Metabolomic Analysis of Aqueous Humor Identifies Aberrant Amino Acid and Fatty Acid Metabolism in Vogt-Koyanagi-Harada and Behcet’s Disease

Frontiers in Immunology ◽

10.3389/fimmu.2021.587393 ◽

2021 ◽

Vol 12 ◽

Author(s):

Jing Xu ◽

Guannan Su ◽

Xinyue Huang ◽

Rui Chang ◽

Zhijun Chen ◽

...

Keyword(s):

Amino Acids ◽

Fatty Acids ◽

Behçet’S Disease ◽

Aqueous Humor ◽

Behcet’S Disease ◽

Behçet's Disease ◽

Enrichment Analysis ◽

Control Group ◽

Pathway Enrichment Analysis ◽

Behcet's Disease

To investigate aqueous metabolic profiles in Vogt-Koyanagi-Harada (VKH) and Behcet’s disease (BD), we applied ultra-high-performance liquid chromatography equipped with quadrupole time-of flight mass spectrometry in aqueous humor samples collected from these patients and controls. Metabolite levels in these three groups were analyzed by univariate logistic regression. The differential metabolites were subjected to subsequent pathway analysis by MetaboAnalyst. The results showed that both partial-least squares discrimination analysis and hierarchical clustering analysis showed specific aqueous metabolite profiles when comparing VKH, BD, and controls. There were 28 differential metabolites in VKH compared to controls and 29 differential metabolites in BD compared to controls. Amino acids and fatty acids were the two most abundant categories of differential metabolites. Furthermore, pathway enrichment analysis identified several perturbed pathways, including pantothenate and CoA biosynthesis when comparing VKH with the control group, and D-arginine and D-ornithine metabolism and phenylalanine metabolism when comparing BD with the control group. Aminoacyl-tRNA biosynthesis was altered in both VKH and BD when compared to controls. Our findings suggest that amino acids metabolism as well as two fatty acids, palmitic acid and oleic acid, may be involved in the pathogenesis of BD and VKH.

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CSF microRNAs discriminate MS activity and share similarity to other neuroinflammatory disorders

Neurology Neuroimmunology & Neuroinflammation ◽

10.1212/nxi.0000000000000673 ◽

2020 ◽

Vol 7 (2) ◽

pp. e673

Author(s):

Océane Perdaens ◽

Hong Anh Dang ◽

Ludovic D'Auria ◽

Vincent van Pesch

Keyword(s):

Disease Activity ◽

Mirna Expression ◽

Inflammatory Diseases ◽

Principal Component ◽

In Silico Analysis ◽

Enrichment Analysis ◽

Mirna Expression Profile ◽

Pathway Enrichment Analysis ◽

Peripheral Blood Mononuclear ◽

Cross Sectional

ObjectiveTo perform a comprehensive multicompartment analysis of microRNA (miRNA) expression in multiple sclerosis (MS) linked to disease activity and compared with other neuroinflammatory diseases through a retrospective cross-sectional study.MethodsOne hundred twenty-seven miRNAs were measured by PCR arrays on pooled CSF, serum, and peripheral blood mononuclear cell (PBMC) samples of 10 patients with relapsing MS and 10 controls. Sixty-four miRNAs were then measured by quantitative PCR on individual CSF samples of patients with relapsing or remitting MS and controls (n = 68). Fifty-seven miRNAs were analyzed in the CSF from a second cohort (n = 75), including patients with MS, neuroinfectious, or neuroinflammatory diseases and controls. MiRNAs significantly dysregulated in the CSF were analyzed on individual serum/PBMC samples (n = 59/48) of patients with relapsing or remitting MS and controls. Post hoc analysis consisted of principal component analysis (PCA), gene set, and pathway enrichment analysis.ResultsTwenty-one miRNAs were differentially expressed, mainly upregulated in the CSF during MS relapses. Relapsing MS and neuroinfectious/inflammatory diseases exhibited a partially overlapping CSF miRNA expression profile. Besides confirming the association of miR-146a-5p/150-5p/155-5p with MS, 7 miRNAs uncharacterized for MS emerged (miR-15a-3p/124-5p/149-3p/29c-3p/33a-3p/34c-5p/297). PCA showed that distinct miRNA sets segregated MS from controls and relapse from remission. In silico analysis predicted the involvement of these miRNAs in cell cycle, immunoregulation, and neurogenesis, but also revealed that the signaling pathway pattern of remitting MS is more akin to controls rather than patients with relapsing MS.ConclusionsThis study highlights the CSF-predominant dysregulation of miRNAs in MS by identifying a signature of disease activity and intrathecal inflammation among neuroinflammatory disorders.

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Bioinformatic and Metabolomic Analysis Reveal Intervention Effects of Chicory in a Quail Model of Hyperuricemia

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2018/5730385 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Meng Bian ◽

Zhijian Lin ◽

Yu Wang ◽

Bing Zhang ◽

Gaoxi Li ◽

...

Keyword(s):

Uric Acid ◽

Inositol Phosphate ◽

Principal Component ◽

Enrichment Analysis ◽

Pathway Enrichment Analysis ◽

Metabolomic Analysis ◽

Obvious Effect ◽

Inositol Phosphate Metabolism ◽

Target Network ◽

Hormone Biosynthesis

Background. Hyperuricemia (HUA) is a kind of a metabolic disease that seriously threatens human health worldwide. Chicory, a natural herbal medicine, has an obvious effect of reducing uric acid. The aim of this study is to explore the potential components and pharmacological pathways that may play a role in hypouricemia activity of chicory. Bioinformatics and metabonomics were applied to this research. Firstly, component-target network was used to identify possible components related to the pharmacological properties and their corresponding mechanisms pathway of chicory. Afterwards, animal pharmacodynamic experiments were performed. Blood and stool samples were collected for untargeted metabolomic analysis by dint of UHPLC-Q-TOF/MS methods, and principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA) were performed for the pattern recognition and characteristic metabolites identification. Significant enriched function pathways were used in bioinformatics suggesting that chicory might have the effect of regulation of lipolysis in adipocytes. PLS-DA analysis was applied to discover differentiating metabolites, and pathway enrichment analysis indicated that chicory had powerful effects of glycosylphosphatidylinositol- (GPI-) anchor biosynthesis, inositol phosphate metabolism, glycerophospholipid metabolism, and steroid hormone biosynthesis. Combining bioinformatics and metabolomics results, we consider that chicory may develop on lowering uric acid by adjusting lipid metabolism. In addition, we chose quail as animal model innovatively and discussed the treatment of hyperuricemia with chicory in multiple methods, which may render reference for the research of HUA.

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