scholarly journals Untargeted metabolomic analysis and pathway discovery in perinatal asphyxia and hypoxic-ischaemic encephalopathy

2017 ◽  
Vol 39 (1) ◽  
pp. 147-162 ◽  
Author(s):  
Niamh M Denihan ◽  
Jennifer A Kirwan ◽  
Brian H Walsh ◽  
Warwick B Dunn ◽  
David I Broadhurst ◽  
...  
Keyword(s):  
Pathway Analysis ◽  
Metabolic Pathways ◽  
Perinatal Asphyxia ◽  
Metabolic Effects ◽  
Metabolomic Analysis ◽  
False Discovery ◽  
Metabolic Feature ◽  
Pathway Discovery ◽  
New Treatment ◽  
Neonatal Population

Elucidating metabolic effects of hypoxic-ischaemic encephalopathy (HIE) may reveal early biomarkers of injury and new treatment targets. This study uses untargeted metabolomics to examine early metabolic alterations in a carefully defined neonatal population. Infants with perinatal asphyxia who were resuscitated at birth and recovered (PA group), those who developed HIE (HIE group) and healthy controls were all recruited at birth. Metabolomic analysis of cord blood was performed using direct infusion FT-ICR mass spectrometry. For each reproducibly detected metabolic feature, mean fold differences were calculated HIE vs. controls (ΔHIE) and PA vs. controls (ΔPA). Putative metabolite annotations were assigned and pathway analysis was performed. Twenty-nine putatively annotated metabolic features were significantly different in ΔPA after false discovery correction ( q < 0.05), with eight of these also significantly altered in ΔHIE. Altered putative metabolites included; melatonin, leucine, kynurenine and 3-hydroxydodecanoic acid which differentiated between infant groups (ΔPA and ΔHIE); and D-erythrose-phosphate, acetone, 3-oxotetradecanoic acid and methylglutarylcarnitine which differentiated across severity grades of HIE. Pathway analysis revealed ΔHIE was associated with a 50% and 75% perturbation of tryptophan and pyrimidine metabolism, respectively. We have identified perturbed metabolic pathways and potential biomarkers specific to PA and HIE, which measured at birth, may help direct treatment.

scholarly journals Brain gene expression in a novel mouse model of postpartum mood disorder

2019 ◽  
Vol 10 (1) ◽  
pp. 168-174
Author(s):  
Trevor Humby ◽  
William Davies
Keyword(s):  
Gene Expression ◽  
Pathway Analysis ◽  
Quantitative Polymerase Chain Reaction ◽  
Late Pregnancy ◽  
Maternal Behaviour ◽  
Aberrant Expression ◽  
Brain Gene Expression ◽  
False Discovery ◽  
Expression Activity ◽  
Polymerase Chain

Abstract Background Steroid sulfatase (STS) cleaves sulfate groups from steroid hormones; its expression/activity increases in late pregnancy and into the postpartum period. STS-deficient human and mouse mothers display elevated psychopathology and abnormal behaviour respectively; in mice, these effects can be partially normalised by antipsychotic (ziprasidone) administration. Methodology We compared brain gene expression in new mouse mothers administered the STS inhibitor 667-Coumate, or vehicle; significant changes were followed-up with pathway analysis and quantitative polymerase chain reaction (qPCR). Finally, the effects of combined 667-Coumate and ziprasidone administration on expression of the most robustly differentially-expressed genes were examined. Results Surprisingly, no between-group gene expression changes were detected at a False Discovery Rate (FDR)-corrected p<0.1. 1,081 unique expression changes were detected at p<0.05, two top hits were verified by qPCR, and pathway analysis indicated enrichment of genes involved in olfactory transduction. The expression of Stoml3 and Cyp2g1 was unaffected by ziprasidone administration. Conclusions Postpartum behavioural abnormalities in STS-deficient mothers are likely to be the culmination of many small gene expression changes. Our data are consistent with the idea that olfactory function is key to maternal behaviour in mice, and suggest that aberrant expression of olfactory system genes may underlie abnormal maternal behaviour in STS-deficient women.

Metabolic Organization of a Primitive Fish, the Bowfin (Amia calva)

1991 ◽  
Vol 48 (4) ◽  
pp. 611-618 ◽  
Author(s):  
Thomas D. Singer ◽  
James S. Ballantyne
Keyword(s):  
Metabolic Pathways ◽  
Evolutionary History ◽  
Nonesterified Fatty Acid ◽  
Metabolic Feature ◽  
Red Muscle ◽  
History Of ◽  
Extrahepatic Tissues ◽  
Hydroxyacyl Coa Dehydrogenase ◽  
Metabolic Organization ◽  
Amia Calva

Key enzymes in several metabolic pathways in five tissues were measured in primitive osteichthyan, the bowfin (Amia calva), the only living representative of the group of extant fishes most closely allied to the teleosts. Aspects of the metabolism of Amia differ from those of most teleosts studied. These differences include detectable levels of β-hydroxybutyrate dehydrogenase in all tissues, possibly a primitive metabolic feature of vertebrates, subsequently lost in most more advanced teleosts. Based on 3-hydroxyacyl CoA dehydrogenase and carnitine palmitoyltransferase activities, lipid metabolism in extrahepatic tissues of bowfin more closely resembles that of an elasmobranch rather than that of a teleost. The overall level of metabolism is lower than most teleosts as indicated by enzyme activities in red muscle and heart. Bowfin plasma nonesterified fatty acid concentrations are lower than most teleosts, but higher than those detected in any elasmobranch. These data suggest that the metabolic organization, especially lipid and ketone body metabolism, at least in part, reflects the evolutionary history of this group.

scholarly journals Comparative metabolomic analysis reveals the variations in taxoids and flavonoids among three Taxus species

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Ting Zhou ◽  
Xiujun Luo ◽  
Chengchao Zhang ◽  
Xinyun Xu ◽  
Chunna Yu ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Side Chain ◽  
Biosynthesis Pathway ◽  
Metabolomic Analysis ◽  
Active Ingredients ◽  
Cancer Treatments ◽  
Taxol Biosynthesis ◽  
Metabolite Pool ◽  
Derivatives Of ◽  
Targeted Approach

Abstract Background Trees of the genus Taxus are highly valuable medicinal plants with multiple pharmacological effects on various cancer treatments. Paclitaxel from Taxus trees is an efficient and widely used anticancer drug, however, the accumulation of taxoids and other active ingredients can vary greatly among Taxus species. In our study, the metabolomes of three Taxus species have been investigated. Results A total of 2246 metabolites assigned to various primary and secondary metabolic pathways were identified using an untargeted approach. Analysis of differentially accumulated metabolites identified 358 T. media-, 220 T. cuspidata-, and 169 T. mairei-specific accumulated metabolites, respectively. By searching the metabolite pool, 7 MEP pathway precursors, 11 intermediates, side chain products and derivatives of paclitaxel, and paclitaxel itself were detected. Most precursors, initiated intermediates were highly accumulated in T. mairei, and most intermediate products approaching the end point of taxol biosynthesis pathway were primarily accumulated in T. cuspidata and T. media. Our data suggested that there were higher-efficiency pathways to paclitaxel in T. cuspidata and T. media compared with in T. mairei. As an important class of active ingredients in Taxus trees, a majority of flavonoids were predominantly accumulated in T. mairei rather than T. media and T. cuspidata. The variations in several selected taxoids and flavonoids were confirmed using a targeted approach. Conclusions Systematic correlativity analysis identifies a number of metabolites associated with paclitaxel biosynthesis, suggesting a potential negative correlation between flavonoid metabolism and taxoid accumulation. Investigation of the variations in taxoids and other active ingredients will provide us with a deeper understanding of the interspecific differential accumulation of taxoids and an opportunity to accelerate the highest-yielding species breeding and resource utilization.

scholarly journals Gut Microbiota and Metabolic Specificity in Ulcerative Colitis and Crohn's Disease

2020 ◽  
Vol 7 ◽  
Author(s):  
Jagadesan Sankarasubramanian ◽  
Rizwan Ahmad ◽  
Nagavardhini Avuthu ◽  
Amar B. Singh ◽  
Chittibabu Guda
Keyword(s):  
Ulcerative Colitis ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Gut Microbiota ◽  
Gut Microbiome ◽  
Metabolic Pathways ◽  
Meta Analysis ◽  
Metabolic Effects ◽  
Taxonomic Rank ◽  
Disease Specific

Background: Inflammatory bowel disease (IBD) represents multifactorial chronic inflammatory conditions in the gastrointestinal tract and includes Crohn's disease (CD) and ulcerative colitis (UC). Despite similarities in pathobiology and disease symptoms, UC and CD represent distinct diseases and exhibit diverse therapeutic responses. While studies have now confirmed that IBD is associated with dramatic changes in the gut microbiota, specific changes in the gut microbiome and associated metabolic effects on the host due to CD and UC are less well-understood.Methods: To address this knowledge gap, we performed an extensive unbiased meta-analysis of the gut microbiome data from five different IBD patient cohorts from five different countries using QIIME2, DIAMOND, and STAMP bioinformatics platforms. In-silico profiling of the metabolic pathways and community metabolic modeling were carried out to identify disease-specific association of the metabolic fluxes and signaling pathways.Results: Our results demonstrated a highly conserved gut microbiota community between healthy individuals and IBD patients at higher phylogenetic levels. However, at or below the order level in the taxonomic rank, we found significant disease-specific alterations. Similarly, we identified differential enrichment of the metabolic pathways in CD and UC, which included enriched pathways related to amino acid and glycan biosynthesis and metabolism, in addition to other metabolic pathways.Conclusions: In conclusion, this study highlights the prospects of harnessing the gut microbiota to improve understanding of the etiology of CD and UC and to develop novel prognostic, and therapeutic approaches.

Characteristics of Acute Kidney Injury in Neonatal Age At - Intensive Care Unit

2015 ◽  
Vol 69 (1) ◽  
pp. 20-25
Author(s):  
Silvana Naunova-Timovska
Keyword(s):  
Intensive Care Unit ◽  
Acute Kidney Injury ◽  
Intensive Care ◽  
Neonatal Intensive Care Unit ◽  
Neonatal Intensive Care ◽  
Perinatal Asphyxia ◽  
Kidney Injury ◽  
Predisposing Factor ◽  
Neonatal Kidney ◽  
Neonatal Population

Abstract Introduction. Acute kidney injury is a serious condition which damages the kidney as a central mediator of the homeostasis of bodily fluids and electrolytes. It is not a rare problem in the intensive care units, particularly in the neonatal population. Perinatal asphyxia is a common predisposing factor associated with neonatal kidney injury. The aim of this study was to determine the characteristics of acute kidney injury in newborns from neonatal intensive care unit and to explore the association with perinatal asphyxia. Methods. The study was conducted at the Children’s University Hospital in Skopje, R. Macedonia. It was a clinical, prospective study. In the period of two years (January 2013 to December 2014) 29 patients hospitalized at the Neonatal Intensive Care Unit (NICU) with documented neonatal kidney injury were analyzed. Medical data records of admitted neonates with kidney injury were analyzed. The material was statistically analyzed using methods of descriptive statistics. Results. We evaluated 29 neonates with documented acute kidney injury who at the period of 2 years were treated in NICU. The prevalence of kidney injury was 6.4%. Most of involved neonates were born at term (66%). Prerenal injury was evaluated in 80% of cases. Perinatal asphyxia was the most common predisposing factors for kidney injury in our study, revealed in 56% of cases with predominance of term-infants and male gender. Sepsis was present in 44% of cases, prematurity in 34%, and congenital malformation in 27% of cases. Mortality rate was 27.5% and it was higher in patients with assisted ventilation and sepsis. Conclusion. Perinatal asphyxia is a dominant predisposing factor associated with neonatal kidney injury. Often, the occurrence of kidney damage in the neonatal population is multifactorial (more than 40%) and caused by several associated comorbidities

Metabolomic analysis identifies altered metabolic pathways in Multiple Sclerosis

2017 ◽  
Vol 93 ◽  
pp. 148-155 ◽  
Author(s):  
Simone Poddighe ◽  
Federica Murgia ◽  
Lorena Lorefice ◽  
Sonia Liggi ◽  
Eleonora Cocco ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Metabolic Pathways ◽  
Metabolomic Analysis

scholarly journals Overview of Metabolomic Analysis and the Integration with Multi-Omics for Economic Traits in Cattle

Metabolites ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 753
Author(s):  
Dan Hao ◽  
Jiangsong Bai ◽  
Jianyong Du ◽  
Xiaoping Wu ◽  
Bo Thomsen ◽  
...  
Keyword(s):  
Biological Networks ◽  
Metabolic Pathways ◽  
Genetic Architecture ◽  
Metabolic Responses ◽  
Metabolomic Analysis ◽  
Metabolomic Profile ◽  
Economic Traits ◽  
Breeding Programs ◽  
Integrated Omics

Metabolomics has been applied to measure the dynamic metabolic responses, to understand the systematic biological networks, to reveal the potential genetic architecture, etc., for human diseases and livestock traits. For example, the current published results include the detected relevant candidate metabolites, identified metabolic pathways, potential systematic networks, etc., for different cattle traits that can be applied for further metabolomic and integrated omics studies. Therefore, summarizing the applications of metabolomics for economic traits is required in cattle. We here provide a comprehensive review about metabolomic analysis and its integration with other omics in five aspects: (1) characterization of the metabolomic profile of cattle; (2) metabolomic applications in cattle; (3) integrated metabolomic analysis with other omics; (4) methods and tools in metabolomic analysis; and (5) further potentialities. The review aims to investigate the existing metabolomic studies by highlighting the results in cattle, integrated with other omics studies, to understand the metabolic mechanisms underlying the economic traits and to provide useful information for further research and practical breeding programs in cattle.

scholarly journals Evaluating Causal Relationship Between Metabolites and Six Cardiovascular Diseases Based on GWAS Summary Statistics

2021 ◽  
Vol 12 ◽  
Author(s):  
Jiahao Qiao ◽  
Meng Zhang ◽  
Ting Wang ◽  
Shuiping Huang ◽  
Ping Zeng
Keyword(s):  
Cardiovascular Diseases ◽  
Causal Relationship ◽  
Metabolic Pathways ◽  
Causal Effect ◽  
Treatment Strategies ◽  
Sensitivity Analyses ◽  
Biological Processes ◽  
Summary Statistics ◽  
False Discovery ◽  
Pathological Mechanism

Cardiovascular diseases (CVDs) remain the main cause of morbidity and mortality worldwide. The pathological mechanism and underlying biological processes of these diseases with metabolites remain unclear. In this study, we conducted a two-sample Mendelian randomization (MR) analysis to evaluate the causal effect of metabolites on these diseases by making full use of the latest GWAS summary statistics for 486 metabolites and six major CVDs. Extensive sensitivity analyses were implemented to validate our MR results. We also conducted linkage disequilibrium score regression (LDSC) and colocalization analysis to investigate whether MR findings were driven by genetic similarity or hybridization between LD and disease-associated gene loci. We identified a total of 310 suggestive associations across all metabolites and CVDs, and finally obtained four significant associations, including bradykinin, des-arg(9) (odds ratio [OR] = 1.160, 95% confidence intervals [CIs]: 1.080–1.246, false discovery rate [FDR] = 0.022) on ischemic stroke, N-acetylglycine (OR = 0.946, 95%CIs: 0.920–0.973, FDR = 0.023), X-09026 (OR = 0.845, 95%CIs: 0.779–0.916, FDR = 0.021) and X-14473 (OR = 0.938, 95%CIs = 0.907–0.971, FDR = 0.040) on hypertension. Sensitivity analyses showed that these causal associations were robust, the LDSC and colocalization analyses demonstrated that the identified associations were unlikely confused by LD. Moreover, we identified 15 important metabolic pathways might be involved in the pathogenesis of CVDs. Overall, our work identifies several metabolites that have a causal relationship with CVDs, and improves our understanding of the pathogenesis and treatment strategies for these diseases.

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