scholarly journals EXPRESS: Metabolic Endophenotype Associated with Right Ventricular Glucose Uptake in Pulmonary Hypertension

2021 ◽  
pp. 204589402110543
Author(s):  
Samar Farha ◽  
Suzy Comhair ◽  
Yuan Hou ◽  
Margaret Park ◽  
Jacqueline Sharp ◽  
...  
Keyword(s):  
Pulmonary Hypertension ◽  
Glucose Uptake ◽  
Global Longitudinal Strain ◽  
Hypoxia Inducible Factor ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Pathway Enrichment Analysis ◽  
Nitric Oxide Metabolism ◽  
Positron Emission ◽  
Interactome Network

Alterations in metabolism and bioenergetics are hypothesized in the mechanisms leading to pulmonary vascular remodeling and heart failure in pulmonary hypertension (PH). To test this, we performed metabolomic analyses on 30 PH individuals and 12 controls. Furthermore, using 2-[18F]fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET), we dichotomized PH patients into metabolic phenotypes of high and low right ventricle (RV) glucose uptake and followed them longitudinally. In support of metabolic alterations in PH and its progression, the high RV glucose group had higher RVSP (p < 0.001), worse RV function as measured by RV fractional area change and peak global longitudinal strain (both p < 0.05) and may be associated with poorer outcomes (33% death or transplantation in the high glucose RV uptake group compared to 7% in the low RV glucose uptake group at 5 years follow up, log-ranked p = 0.07). Pathway enrichment analysis identified key metabolic pathways including fructose catabolism, arginine-nitric oxide metabolism, tricarboxylic acid (TCA) cycle, and ketones metabolism. Integrative human protein-protein interactome network analysis of metabolomic and transcriptomic data identified key pathobiological pathways: arginine biosynthesis, TCA cycle, purine metabolism, hypoxia-inducible factor 1 and apelin signaling. These findings identify a PH metabolomic endophenotype, and for the first time link this to disease severity and outcomes.

Metabolic responses of shrimp Palaemonetes sinensis to isopod Tachaea chinensis parasitization

2020 ◽  
Vol 138 ◽  
pp. 227-235 ◽  
Author(s):  
Y Li ◽  
W Xu ◽  
X Li ◽  
Z Han ◽  
R Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Inflammatory Responses ◽  
Grass Shrimp ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Metabolic Responses ◽  
Pathway Enrichment Analysis ◽  
Primary Metabolite ◽  
Mineral Absorption ◽  
Host Interaction

Tachaea chinensis, a parasitic isopod, negatively affects the production of several commercially important shrimp species in China. The mechanism of parasite-host interaction cannot be accurately described by transcriptomic and proteomic approaches individually. Here, comparative metabolite profiling was used to achieve a broad coverage of primary metabolite changes in Chinese grass shrimp Palaemonetes sinensis following T. chinensis parasitization. In total, 66 metabolites were significantly differentially accumulated between the control and infected groups; of these, 19 were upregulated and 47 were downregulated after T. chinensis infection. Moreover, the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis revealed that 10 pathways were significantly enriched. The protein digestion and absorption pathways were highly enriched, followed by the mineral absorption, aminoacyl-tRNA biosynthesis, biosynthesis of amino acids, and metabolic metabolism pathways. Parasitization by T. chinensis enhanced the glycolytic pathway and tricarboxylic acid (TCA) cycle in P. sinensis, thereby releasing more energy for swimming, foraging, and evading predation. Glucogenic amino acids such as alanine, histidine, glutamine, and proline were consumed to generate glutamate and enhance the TCA cycle. Nucleotide-related metabolic pathways were downregulated, possibly because T. chinensis can secrete molecules to degrade nucleotides and inhibit hemostasis and inflammatory responses. These results suggest that the isopod parasite can increase the host’s metabolic burden by enhancing the host’s TCA cycle and secreting molecules to degrade host proteins, thereby enabling the parasite to feed on the host and inhibit an inflammatory response. The results will be a valuable contribution to understanding the metabolic responses of crustaceans to isopod parasitism.

Pulmonary glucose uptake measured by positron emission tomography in pulmonary hypertension

2015 ◽  
Author(s):  
Armin Frille ◽  
Karen Geva Steinhoff ◽  
Swen Hesse ◽  
Hubert Wirtz ◽  
Osama Sabri ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Pulmonary Hypertension ◽  
Glucose Uptake ◽  
Emission Tomography ◽  
Positron Emission

scholarly journals Dysregulated paired related homeobox 1 impacts on hepatocellular carcinoma phenotypes

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Weronika Piorońska ◽  
Zeribe Chike Nwosu ◽  
Mei Han ◽  
Michael Büttner ◽  
Matthias Philip Ebert ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Overall Survival ◽  
Cell Lines ◽  
Transcriptional Control ◽  
Epithelial Mesenchymal Transition ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Pathway Enrichment Analysis ◽  
Mesenchymal Transition ◽  
Cancer Hallmarks

Abstract Background Hepatocellular carcinoma (HCC) is a major cause of cancer-related death. Paired related homeobox 1 (PRRX1) is a transcription factor that regulates cell growth and differentiation, but its importance in HCC is unclear. Methods We examined the expression pattern of PRRX1 in nine microarray datasets of human HCC tumour samples (n > 1100) and analyzed its function in HCC cell lines. In addition, we performed gene set enrichment, Kaplan-Meier overall survival analysis, metabolomics and functional assays. Results PRRX1 is frequently upregulated in human HCC. Pathway enrichment analysis predicted a direct correlation between PRRX1 and focal adhesion and epithelial-mesenchymal transition. High expression of PRRX1 and low ZEB1 or high ZEB2 significantly predicted better overall survival in HCC patients. In contrast, metabolic processes correlated inversely and transcriptional analyses revealed that glycolysis, TCA cycle and amino acid metabolism were affected. These findings were confirmed by metabolomics analysis. At the phenotypic level, PRRX1 knockdown accelerated proliferation and clonogenicity in HCC cell lines. Conclusions Our results suggest that PRRX1 controls metabolism, has a tumour suppressive role, and may function in cooperation with ZEB1/2. These findings have functional relevance in HCC, including in understanding transcriptional control of distinct cancer hallmarks.

scholarly journals Metabolomic and Proteomic Analyses of Persistent Valvular Atrial Fibrillation and Non-Valvular Atrial Fibrillation

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo Hu ◽  
Wen Ge ◽  
Yuliang Wang ◽  
Xiaobin Zhang ◽  
Tao Li ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Enrichment Analysis ◽  
Heart Rhythm ◽  
Tca Cycle ◽  
Inorganic Pyrophosphatase ◽  
Pathway Enrichment Analysis ◽  
Increased Risk ◽  
Novel Biomarkers ◽  
Glycerol 3 Phosphate Dehydrogenase ◽  
Altered Proteins

Atrial fibrillation (AF) is an abnormal heart rhythm related to an increased risk of heart failure, dementia, and stroke. The distinction between valvular and non-valvular AF remains a debate. In this study, proteomics and metabolomics were integrated to describe the dysregulated metabolites and proteins of AF patients relative to sinus rhythm (SR) patients. Totally 47 up-regulated and 41 down-regulated proteins in valvular AF, and 59 up-regulated and 149 down-regulated proteins in non-valvular AF were recognized in comparison to SR patients. Moreover, 58 up-regulated and 49 significantly down-regulated metabolites in valvular AF, and 47 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF patients were identified in comparison to SR patients. Based on analysis of differential levels of metabolites and proteins, 15 up-regulated and 22 down-regulated proteins, and 13 up-regulated and 122 down-regulated metabolites in persistent non-valvular AF were identified relative to valvular AF. KEGG pathway enrichment analysis showed the altered proteins and metabolites were significantly related to multiple metabolic pathways, such as Glycolysis/Gluconeogenesis. Interestingly, the enrichment pathways related to non-valvular AF were obviously different from those in valvular AF. For example, valvular AF was significantly related to Glycolysis/Gluconeogenesis, but non-valvular AF was more related to Citrate cycle (TCA cycle). Correlation analysis between the differentially expressed proteins and metabolites was also performed. Several hub proteins with metabolites were identified in valvular AF and non-valvular AF. For example, Taurine, D-Threitol, L-Rhamnose, and DL-lactate played crucial roles in valvular AF, while Glycerol-3-phosphate dehydrogenase, Inorganic pyrophosphatase 2, Hydroxymethylglutaryl-CoAlyase, and Deoxyuridine 5-triphosphate nucleotidohydrolase were crucial in non-valvular AF. Then two hub networks were recognized as potential biomarkers, which can effectively distinguish valvular AF and non-valvular persistent AF from SR samples, with areas under curve of 0.75 and 0.707, respectively. Hence, these metabolites and proteins can be used as potential clinical molecular markers to discriminate two types of AF from SR samples. In summary, this study provides novel insights to understanding the mechanisms of AF progression and identifying novel biomarkers for prognosis of non-valvular AF and valvular AF by using metabolomics and proteomics analyses.

scholarly journals Metabolic responses to elevated pCO2 in the gills of the Pacific Oyster (Magallana gigas) using a GC-TOF-MS-based metabolomics approach

2018 ◽  
Author(s):  
Zengjie Jiang ◽  
Xiaoqin Wang ◽  
Samuel P.S. Rastrick ◽  
Jinghui Fang ◽  
Meirong Du ◽  
...  
Keyword(s):  
Atmospheric Carbon Dioxide ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Potential Effect ◽  
Metabolic Responses ◽  
Pathway Enrichment Analysis ◽  
Human Fossil ◽  
Flight Mass Spectrometry ◽  
Tof Ms

Rising atmospheric carbon dioxide (CO2), primarily from human fossil fuel combustion and cement production, are resulting in increasing absorption of CO2 by the oceans, which has led to a decline in ocean pH in a process known as ocean acidification (OA). There is a growing body of evidence demonstrating the potential effect of OA on life-history traits of marine organisms. Consequently, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) based metabolic profiling approach was applied to examine the metabolic responses of Magallana gigas to elevated pCO2 levels, under otherwise natural field conditions. CO2. Oysters were exposed natural environmental pCO2 (~625.40 μatm) and elevated pCO2 (~1432.94 μatm) levels for 30 days. Results indicated that 36 differential metabolites with variable importance in the projection (VIP) value greater than 1 and Student's t-test lower than 0.05 were identified. Differential metabolites were mapped in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to search for the related metabolic pathways. Pathway enrichment analysis indicates that alanine, aspartate and glutamate metabolism and glycine, serine and threonine metabolism were the most statistically enriched pathways. Further analysis suggested that elevated pCO2 disturb the TCA cycle via succinate accumulation and Magallana gigas most likely adjust their energy metabolic via alanine and GABA accumulation accordingly to cope with elevated pCO2. These findings provide an understanding of the molecular mechanisms involved in modulating metabolism under elevated pCO2 levels associated with predicted OA.

scholarly journals Fucoidan–Fucoxanthin Ameliorated Cardiac Function via IRS1/GRB2/ SOS1, GSK3β/CREB Pathways and Metabolic Pathways in Senescent Mice

Marine Drugs ◽  
2019 ◽  
Vol 17 (1) ◽  
pp. 69 ◽  
Author(s):  
Po-Ming Chang ◽  
Kuan-Lun Li ◽  
Yen-Chang Lin
Keyword(s):  
Cardiac Function ◽  
Metabolic Pathways ◽  
High Performance ◽  
Cardiac Tissue ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Pathway Enrichment Analysis ◽  
Whole Cell Patch Clamp ◽  
The Tca Cycle ◽  
Hormone Biosynthesis

The effects of low molecular weight fucoidan (LMWF) in combination with high-stability fucoxanthin (HSFUCO) on cardiac function and the metabolic pathways of aging mice (Mus musculus) were investigated. We demonstrated that LMWF and HSFUCO could improve cardiac function in aging mice. Aging mice were treated with LMWF and HSFUCO, either on their own or in combination, on 28 consecutive days. Electrocardiography and whole-cell patch-clamp were used to measure QT interval and action potential duration (APD) of the subjects. Cardiac tissue morphology, reactive oxygen species, and Western blot were also applied. Ultra-high-performance liquid chromatography–quadrupole time-of-flight (UPLC-QTOF) mass spectrometry was used for investigating metabolic alterations. The use of LMWF and HSFUCO resulted in improvements in both ventricular rhythms (QT and APD). Treatment with fucoidan and fucoxanthin reduced the expression levels of SOS1 and GRB2 while increasing GSK3β, CREB and IRS1 proteins expression in the aging process. Three main metabolic pathways, namely the TCA cycle, glycolysis, and steroid hormone biosynthesis, were highly enriched in the pathway enrichment analysis. When taken together, the LMWF and HSFUCO treatment improved both the ventricular rhythm and the muscular function of aging subjects by interfering with the metabolism and gene function.

scholarly journals Metabolic responses to elevated pCO2 in the gills of the Pacific Oyster (Magallana gigas) using a GC-TOF-MS-based metabolomics approach

2018 ◽  
Author(s):  
Zengjie Jiang ◽  
Xiaoqin Wang ◽  
Samuel P.S. Rastrick ◽  
Jinghui Fang ◽  
Meirong Du ◽  
...  
Keyword(s):  
Atmospheric Carbon Dioxide ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Tca Cycle ◽  
Potential Effect ◽  
Metabolic Responses ◽  
Pathway Enrichment Analysis ◽  
Human Fossil ◽  
Flight Mass Spectrometry ◽  
Tof Ms

Rising atmospheric carbon dioxide (CO2), primarily from human fossil fuel combustion and cement production, are resulting in increasing absorption of CO2 by the oceans, which has led to a decline in ocean pH in a process known as ocean acidification (OA). There is a growing body of evidence demonstrating the potential effect of OA on life-history traits of marine organisms. Consequently, gas chromatography time-of-flight mass spectrometry (GC-TOF-MS) based metabolic profiling approach was applied to examine the metabolic responses of Magallana gigas to elevated pCO2 levels, under otherwise natural field conditions. CO2. Oysters were exposed natural environmental pCO2 (~625.40 μatm) and elevated pCO2 (~1432.94 μatm) levels for 30 days. Results indicated that 36 differential metabolites with variable importance in the projection (VIP) value greater than 1 and Student's t-test lower than 0.05 were identified. Differential metabolites were mapped in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to search for the related metabolic pathways. Pathway enrichment analysis indicates that alanine, aspartate and glutamate metabolism and glycine, serine and threonine metabolism were the most statistically enriched pathways. Further analysis suggested that elevated pCO2 disturb the TCA cycle via succinate accumulation and Magallana gigas most likely adjust their energy metabolic via alanine and GABA accumulation accordingly to cope with elevated pCO2. These findings provide an understanding of the molecular mechanisms involved in modulating metabolism under elevated pCO2 levels associated with predicted OA.

A Method of Pathway Enrichment Analysis Based Gene Expression Variability

2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Expression Variability ◽  
Pathway Enrichment
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