scholarly journals An Evidence-Based Review of Related Metabolites and Metabolic Network Research on Cerebral Ischemia

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Mengting Liu ◽  
Liying Tang ◽  
Xin Liu ◽  
Jing Fang ◽  
Hao Zhan ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Metabolic Network ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Evidence Based ◽  
Kegg Database ◽  
Pathway Enrichment ◽  
Network Research

In recent years, metabolomics analyses have been widely applied to cerebral ischemia research. This paper introduces the latest proceedings of metabolomics research on cerebral ischemia. The main techniques, models, animals, and biomarkers of cerebral ischemia will be discussed. With analysis help from the MBRole website and the KEGG database, the altered metabolites in rat cerebral ischemia were used for metabolic pathway enrichment analyses. Our results identify the main metabolic pathways that are related to cerebral ischemia and further construct a metabolic network. These results will provide useful information for elucidating the pathogenesis of cerebral ischemia, as well as the discovery of cerebral ischemia biomarkers.

scholarly journals MetNet: A two-level approach to reconstructing and comparing metabolic networks

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246962
Author(s):  
Nicoletta Cocco ◽  
Mercè Llabrés ◽  
Mariana Reyes-Prieto ◽  
Marta Simeoni
Keyword(s):  
Metabolic Network ◽  
Metabolic Pathway ◽  
Metabolic Networks ◽  
Medical Science ◽  
Similarity Measures ◽  
Human Intervention ◽  
Kegg Database ◽  
Global Comparison ◽  
Local Comparison ◽  
Different Sources

Metabolic pathway comparison and interaction between different species can detect important information for drug engineering and medical science. In the literature, proposals for reconstructing and comparing metabolic networks present two main problems: network reconstruction requires usually human intervention to integrate information from different sources and, in metabolic comparison, the size of the networks leads to a challenging computational problem. We propose to automatically reconstruct a metabolic network on the basis of KEGG database information. Our proposal relies on a two-level representation of the huge metabolic network: the first level is graph-based and depicts pathways as nodes and relations between pathways as edges; the second level represents each metabolic pathway in terms of its reactions content. The two-level representation complies with the KEGG database, which decomposes the metabolism of all the different organisms into “reference” pathways in a standardised way. On the basis of this two-level representation, we introduce some similarity measures for both levels. They allow for both a local comparison, pathway by pathway, and a global comparison of the entire metabolism. We developed a tool, MetNet, that implements the proposed methodology. MetNet makes it possible to automatically reconstruct the metabolic network of two organisms selected in KEGG and to compare their two networks both quantitatively and visually. We validate our methodology by presenting some experiments performed with MetNet.

Identification of novel cardiovascular disease associated metabolites using untargeted metabolomics

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shams Tabrez ◽  
Mohammed Razeeth Shait Mohammed ◽  
Nasimudeen R. Jabir ◽  
Mohammad Imran Khan
Keyword(s):  
Cardiovascular Disease ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Healthy Individuals ◽  
Great Opportunity ◽  
Pathway Enrichment ◽  
Pathophysiological Role ◽  
The World ◽  
Metabolomic Approach

Abstract Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality around the world. Early diagnosis of CVD could provide the opportunity for sensible management and better clinical outcome along with the prevention of further progression of the disease. In the current study, we used an untargeted metabolomic approach to identify possible metabolite(s) that associate well with the CVD and could serve either as therapeutic target or disease-associated metabolite. We identified 26 rationally adjusted unique metabolites that were differentially present in the serum of CVD patients compared with healthy individuals, among them 15 were found to be statistically significant. Out of these metabolites, we identified some novel metabolites like UDP-l-rhamnose and N1-acetylspermidine that have not been reported to be linked with CVD directly. Further, we also found that some metabolites like ethanolamide, solanidine, dimethylarginine, N-acetyl-l-tyrosine, can act as a discriminator of CVD. Metabolites integrating pathway enrichment analysis showed enrichment of various important metabolic pathways like histidine metabolism, methyl histidine metabolism, carnitine synthesis, along with arginine and proline metabolism in CVD patients. Our study provides a great opportunity to understand the pathophysiological role and impact of the identified unique metabolites and can be extrapolated as specific CVD specific metabolites.

scholarly journals Novel Drivers of Virulence in Clostridioides difficile Identified via Context-Specific Metabolic Network Analysis

mSystems ◽  
2021 ◽  
Author(s):  
Matthew L. Jenior ◽  
Jhansi L. Leslie ◽  
Deborah A. Powers ◽  
Elizabeth M. Garrett ◽  
Kimberly A. Walker ◽  
...  
Keyword(s):  
Network Analysis ◽  
Metabolic Network ◽  
Virulence Factors ◽  
Metabolic Pathways ◽  
Content Type ◽  
Hospital Acquired Infections ◽  
Metabolic Network Analysis ◽  
Clostridioides Difficile ◽  
Context Specific ◽  
Hospital Acquired

Clostridioides difficile has become the leading single cause of hospital-acquired infections. Numerous studies have demonstrated the importance of specific metabolic pathways in aspects of C. difficile pathophysiology, from initial colonization to regulation of virulence factors.

scholarly journals Farmakokinetika dan Bioavailability Senyawa Golongan Santon Revew Komprehensif

2019 ◽  
Vol 8 (2) ◽  
pp. 46-51
Author(s):  
Meri Susanti
Keyword(s):  
Active Compound ◽  
Metabolic Pathways ◽  
Herbal Medicines ◽  
Bioactive Compound ◽  
Pharmacokinetic Profile ◽  
Evidence Based ◽  
Clinical Effects ◽  
Dosage Regimens ◽  
Link Data ◽  
Detailed Picture

The use of herbs for treating various ailment dates back several centuries. Evidence-based verification of the efficacy of Herbal medicines is still frequently lacking. Of particular interest is the question of bioavailability to assess to what degree and how fast compounds are absorbed after administration of herbal. Of further interest is the elucidation of metabolic pathways, and the assessment of elimination routes and their kinetics. These data become an important issue to link data from pharmacological assays and clinical effects. A better understanding of the pharmacokinetics and bioavailability of phytopharmaceuticals can also help in designing rational dosage regimens. To provide provide a detailed picture on ADME parameters (absorption, distribution, metabolism, and excretion) of some xanthone active compound, this article reviews the pharmacokinetic profile of 7 xanthones bioactive compound from the year 2009 onward.  

IDENTIFYING RELEVANT PATHWAYS AND BIOMARKERS IN CROHN’S DISEASE USING CONTEXTUALIZED METABOLIC NETWORK MODEL

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S9-S10
Author(s):  
Brooklyn McGrew ◽  
Aman Shrivastava ◽  
Philip Fernandes ◽  
Lubaina Ehsan ◽  
Yash Sharma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Crohn’S Disease ◽  
Fatty Acid ◽  
Crohn's Disease ◽  
Fatty Acid Synthesis ◽  
Metabolic Pathway ◽  
Metabolic Pathways ◽  
Acid Synthesis ◽  
Transcriptomic Data ◽  
Context Specific

Abstract Background Candidate markers for Crohn’s Disease (CD) may be identified via gene expression-based construction of metabolic networks (MN). These can computationally describe gene-protein-reaction associations for entire tissues and also predict the flux of reactions (rate of turnover of specific molecules via a metabolic pathway). Recon3D is the most comprehensive human MN to date. We used publicly available CD transcriptomic data along with Recon3D to identify metabolites as potential diagnostic and prognostic biomarkers. Methods Terminal ileal gene expression profiles (36,372 genes; 218 CD. 42 controls) from the RISK cohort (Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease) and their transcriptomic abundances were used. Recon3D was pruned to only include RISK dataset transcripts which determined metabolic reaction linkage with transcriptionally active genes. Flux balance analysis (FBA) was then run using RiPTiDe with context specific transcriptomic data to further constrain genes (Figure 1). RiPTiDe was independently run on transcriptomic data from both CD and controls. From the pruned and constricted MN obtained, reactions were extracted for further analysis. Results After applying the necessary constraints to modify Recon3D, 527 CD and 537 control reactions were obtained. Reaction comparison with a publicly available list of healthy small intestinal epithelial reactions (n=1282) showed an overlap of 80 CD and 84 control reactions. These were then further grouped based on their metabolic pathways. RiPTiDe identified context specific metabolic pathway activity without supervision and the percentage of forward, backward, and balanced reactions for each metabolic pathway (Figure 2). The metabolite concentrations in the small intestine was altered among CD patients. Notably, the citric acid cycle and malate-aspartate shuttle were affected, highlighting changes in mitochondrial metabolic pathways. This is illustrated by changes in the number of reactions at equilibrium between CD and control. Conclusions The results are relevant as cytosolic acetyl-CoA is needed for fatty acid synthesis and is obtained by removing citrate from the citric acid cycle. An intermediate removal from the cycle has significant cataplerotic effects. The malate-aspartate shuttle also allows electrons to move across the impermeable membrane in the mitochondria (fatty acid synthesis location). These findings are reported by previously published studies where gene expression for fatty acid synthesis is altered in CD patients along with mitochondrial metabolic pathway changes, resulting in altered cell homeostasis. In-depth analysis is currently underway with our work supporting the utility of potential metabolic biomarkers for CD diagnosis, management and improved care.

scholarly journals Metabolic Constants and Plasticity of Cancer Cells in a Limiting Glucose and Glutamine Microenvironment—A Pyruvate Perspective

2020 ◽  
Vol 10 ◽  
Author(s):  
Angela M. Otto
Keyword(s):  
Cancer Cells ◽  
Metabolic Network ◽  
Metabolic Pathways ◽  
Cancer Cell Line ◽  
Tca Cycle ◽  
Reaction Rates ◽  
Diagnostic Methods ◽  
Metabolic Reprogramming ◽  
Amino Acid Synthesis ◽  
The Tca Cycle

The metabolism of cancer cells is an issue of dealing with fluctuating and limiting levels of nutrients in a precarious microenvironment to ensure their vitality and propagation. Glucose and glutamine are central metabolites for catabolic and anabolic metabolism, which is in the limelight of numerous diagnostic methods and therapeutic targeting. Understanding tumor metabolism in conditions of nutrient depletion is important for such applications and for interpreting the readouts. To exemplify the metabolic network of tumor cells in a model system, the fate 13C6-glucose was tracked in a breast cancer cell line growing in variable low glucose/low glutamine conditions. 13C-glucose-derived metabolites allowed to deduce the engagement of metabolic pathways, namely glycolysis, the TCA-cycle including glutamine and pyruvate anaplerosis, amino acid synthesis (serine, glycine, aspartate, glutamate), gluconeogenesis, and pyruvate replenishment. While the metabolic program did not change, limiting glucose and glutamine supply reduced cellular metabolite levels and enhanced pyruvate recycling as well as pyruvate carboxylation for entry into the TCA-cycle. Otherwise, the same metabolic pathways, including gluconeogenesis, were similarly engaged with physiologically saturating as with limiting glucose and glutamine. Therefore, the metabolic plasticity in precarious nutritional microenvironment does not require metabolic reprogramming, but is based on dynamic changes in metabolite quantity, reaction rates, and directions of the existing metabolic network.

scholarly journals Metabolomic Links Between Sweetened Beverage Intake and Obesity (OR31-05-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Chao-Qiang Lai ◽  
Reiko Ichikawa ◽  
Bingjie Zhou ◽  
Laurence Parnell ◽  
Sabrina Noel ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Metabolic Pathways ◽  
Enrichment Analysis ◽  
Health Study ◽  
Pathway Enrichment Analysis ◽  
Linear Regression Models ◽  
Obesity Risk ◽  
Pathway Enrichment ◽  
Sweetened Beverage ◽  
Increased Risk

Abstract Objectives Sweetened beverage (SB) consumption is highly associated with obesity, but the mechanism underlying this correlation is not understood. Our objective was to examine metabolomic links between SB intake and obesity to understand metabolic mechanisms. Methods We examined the association of plasma metabolomic profiles with SB intake and obesity risk in 782 participants, aged 45–75y, in the Boston Puerto Rican Health Study (BPRHS) using linear regression models, controlling for potential confounding factors. Based on identified metabolites, we conducted pathway enrichment analysis to identify potential metabolic pathways that link SB intake and obesity risk. Genetic variants in identified metabolic pathways were examined for their interaction with SB intake on metabolites of interest and obesity. Interactions between SB and genotypes on obesity were evaluated for replication in the Framingham Heart Study (FHS). Results In BPRHS, SB intake was highly correlated with BMI (β = 0.455, P < 0.05). Among 526 measurable metabolites, 109 metabolites showed significant correlation with SB intake and 170 metabolites with BMI (P < 0.05); and 43 were correlated with both SB intake and BMI. Pathway enrichment analysis identified two metabolic pathways: phosphatidylethanolamine (PE) and lysophospholipid pathways linking SB intake and obesity, after correction for multiple testing. Focusing on the PE pathway, we identified 12 SNPs in nine genes that were significantly associated with BMI. At least four genetic variants showed suggestive interaction with SB intake on obesity risk and obesity-associated metabolites. In particular, CC carriers of rs4646360 in the PEMT (Phosphatidylethanolamine N-Methyltransferase) gene had increased risk of obesity when consuming SB. We replicated this finding in the FHS study. Conclusions We identified two key metabolic pathways linking SB intake to obesity, revealing potential mechanisms by which SB intake increases the risk of obesity. The interaction between genetic variants in the identified pathway and SB intake on obesity and obesity-associated metabolites further supports the mechanism. Funding Sources This work was funded by the US Department of Agriculture, under agreement no. 8050-51,000-098-00D, and NIH grants P01 AG023394, P50 HL105185, and R01 AG027087.

scholarly journals Transcriptomic Identification of Floral Transition and Development-Associated Genes in Styrax japonicus

Forests ◽  
2019 ◽  
Vol 11 (1) ◽  
pp. 10
Author(s):  
Wei Li ◽  
Zhengzhao Xu ◽  
Cuiping Zhang ◽  
Xinqiang Jiang ◽  
Kuiling Wang
Keyword(s):  
Gene Expression ◽  
Protein Kinase ◽  
Flower Development ◽  
Floral Development ◽  
Differentially Expressed ◽  
Cdna Libraries ◽  
Expression Data ◽  
Kegg Database ◽  
Pathway Enrichment ◽  
Gene Expression Dynamics

Styrax japonicus (S. japonicus) is an important flowering tree species in temperate regions, and it is regarded as a nectariferous plant. However, there have been few studies to date analyzing floral development in this species. In order to understand gene expression dynamics during S. japonicus flower development, we; therefore, prepared cDNA libraries from three distinct stages of S. japonicus. Illumina sequencing generated 31,471 differentially expressed unigenes during flower development. We additionally conducted pathway enrichment analyses using the GO and KEGG database in order to assess the functions of genes differentially expressed during different stages of the floral development process, revealing these genes to be associated with pathways including phytohormone signaling, Transcription factor, protein kinase, and circadian rhythms. In total, 4828 TF genes, 8402 protein kinase genes, and 78 DEGs related to hormone pathways were identified in flower development stages. Six genes were selected for confirmation of expression levels using quantitative real-time PCR. The gene expression data presented herein represent the most comprehensive dataset available regarding the flowering of S. japonicus, thus offering a reference for future studies of the flowering of this and other Styracaceae species.

scholarly journals Abnormal arachidonic acid metabolic network may reduce sperm motility via P38 MAPK

Open Biology ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 180091 ◽  
Author(s):  
Lisha Yu ◽  
Xiaojing Yang ◽  
Bo Ma ◽  
Hanjie Ying ◽  
Xuejun Shang ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Cytochrome P450 ◽  
Metabolic Network ◽  
P38 Mapk ◽  
Sperm Motility ◽  
Seminal Plasma ◽  
Metabolic Pathways ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Activation

Asthenozoospermia is a common cause of male infertility, the aetiology of which remains unclear in 50–60% of cases. The current study aimed to characterize metabolic alterations in asthenozoospermic seminal plasma and to explore the signalling pathways involved in sperm motility regulation. At first, high-performance liquid chromatography–electrospray ionization–tandem mass spectrometry was used to detect the targeted metabolic network of arachidonic acid (AA). Metabolomic multivariate data analysis showed significant distinction of AA metabolites between asthenozoospermic and healthy seminal plasma. AA as well as its lipoxygenase (LOX) and cytochrome P450 metabolites were found to be abnormally increased, while cyclooxygenase (COX) metabolites were complicatedly disturbed in asthenozoospermic volunteers compared with those in healthy ones. In vitro experiments and western blot analysis of sperm cells revealed a decrease in sperm motility and upregulation of sperm phosphor-P38 induced by AA. P38 inhibitor could increase AA-reduced sperm motility. Also, all the inhibitors of the three metabolic pathways of AA could block AA-induced P38 mitogen-activated protein kinase (MAPK) activation and further improve sperm motility. We report here for the first time that an abnormal AA metabolic network could reduce sperm motility via P38 MAPK activation through the LOX, cytochrome P450 and COX metabolic pathways, which might be an underlying pathomechanism of asthenozoospermia.

Sign in / Sign up

Export Citation Format

Share Document