Metabolomic alterations associated with copper stress in Cryptococcus neoformans

2021 ◽  
Author(s):  
Tianshu Sun ◽  
Xiaogang Li ◽  
Wei Song ◽  
Shuying Yu ◽  
Linqi Wang ◽  
...  
Keyword(s):  
Cryptococcus Neoformans ◽  
Metabolic Profile ◽  
Pathogenic Fungus ◽  
Copper Toxicity ◽  
Enrichment Analysis ◽  
Copper Stress ◽  
Pathway Enrichment Analysis ◽  
Flight Mass Spectrometry ◽  
Opportunistic Pathogenic ◽  
Better Than

Background: Copper stress is an effective host strategy in resisting the opportunistic pathogenic fungus Cryptococcus neoformans. We studied metabolic changes in C. neoformans under copper stress. Materials & methods: Wild-type and metallothionein-null C. neoformans were treated with copper on agar containing glucose, glycerol or ethanol as the carbon source and their metabolites were analyzed by untarget metabolomics strategy using gas chromatography coupled with time of flight mass spectrometry. Results: The metabolic profile of C. neoformans varied in the presence and absence of copper. Pathway enrichment analysis showed that the differentially abundant metabolites were related to amino acid and carbohydrate metabolism. C. neoformans grown on glycerol or ethanol resisted copper toxicity better than C. neoformans grown on glucose. Conclusion: Copper stress alters the metabolic profile of C. neoformans.

scholarly journals Identification of Urine Metabolic Biomarkers for Vogt-Koyanagi-Harada Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Rui Chang ◽  
Ying Zhu ◽  
Jing Xu ◽  
Lin Chen ◽  
Guannan Su ◽  
...  
Keyword(s):  
High Performance ◽  
Area Under The Curve ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Multivariate Statistical ◽  
Flight Mass Spectrometry ◽  
Laboratory Biomarkers ◽  
Vkh Disease

The diagnosis of Vogt-Koyanagi-Harada (VKH) disease is mainly based on a complex clinical manifestation while it lacks objective laboratory biomarkers. To explore the potential molecular biomarkers for diagnosis and disease activity in VKH, we performed an untargeted urine metabolomics analysis by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS). Through univariate and multivariate statistical analysis, we found 9 differential metabolites when comparing VKH patients with healthy controls, and 26 differential metabolites were identified when comparing active VKH patients with inactive VKH patients. Pathway enrichment analysis showed that glycine, serine and threonine metabolism, and arginine and proline metabolism were significantly altered in VKH versus healthy controls. Lysine degradation and biotin metabolism pathways were significantly altered in active VKH versus inactive VKH. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that the combination of acetylglycine and gamma-glutamylalanine could differentiate VKH from healthy controls with an area under the curve (AUC) of 0.808. A combination of ureidopropionic acid and 5′-phosphoribosyl-5-amino-4-imidazolecarboxamide (AICAR) had an excellent AUC of 0.958 for distinguishing active VKH from inactive VKH. In summary, this study identified abnormal metabolites in urine of patients with VKH disease. Further studies are needed to confirm whether these metabolites are specific for this disease.

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 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 Proteomic Analysis of Copper Toxicity in Human Fungal Pathogen Cryptococcus neoformans

2021 ◽  
Vol 11 ◽  
Author(s):  
Tianshu Sun ◽  
Yanjian Li ◽  
Yingxing Li ◽  
Hailong Li ◽  
Yiyi Gong ◽  
...  
Keyword(s):  
Protein Degradation ◽  
Cryptococcus Neoformans ◽  
Proteomic Analysis ◽  
Fungal Pathogen ◽  
Copper Ions ◽  
Reactive Oxygen Species Generation ◽  
Copper Toxicity ◽  
Protein Translation ◽  
Copper Stress ◽  
Human Fungal Pathogen

Cryptococcus neoformans is an invasive human fungal pathogen that causes more than 181,000 deaths each year. Studies have demonstrated that pulmonary C. neoformans infection induces innate immune responses involving copper, and copper detoxification in C. neoformans improves its fitness and pathogenicity during pulmonary C. neoformans infection. However, the molecular mechanism by which copper inhibits C. neoformans proliferation is unclear. We used a metallothionein double-knockout C. neoformans mutant that was highly sensitive to copper to demonstrate that exogenous copper ions inhibit fungal cell growth by inducing reactive oxygen species generation. Using liquid chromatography-tandem mass spectrometry, we found that copper down-regulated factors involved in protein translation, but up-regulated proteins involved in ubiquitin-mediated protein degradation. We propose that the down-regulation of protein synthesis and the up-regulation of protein degradation are the main effects of copper toxicity. The ubiquitin modification of total protein and proteasome activity were promoted under copper stress, and inhibition of the proteasome pathway alleviated copper toxicity. Our proteomic analysis sheds new light on the antifungal mechanisms of copper.

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

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

Determination of Usnic Acid Responsive miRNAs in Breast Cancer Cell Lines

2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman
Keyword(s):  
Breast Cancer ◽  
Hedgehog Signaling ◽  
Treatment Options ◽  
Usnic Acid ◽  
Enrichment Analysis ◽  
Breast Cancer Cell Lines ◽  
Pathway Enrichment Analysis ◽  
Molecular Heterogeneity ◽  
Proliferative Effect ◽  
Mcf 7

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.

scholarly journals Signature RNAS and related regulatory roles in type 1 diabetes mellitus based on competing endogenous RNA regulatory network analysis

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinghong Shi ◽  
Hanxin Yao
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Network Analysis ◽  
Type 1 Diabetes Mellitus ◽  
Regulatory Network ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Competing Endogenous Rna ◽  
Pathway Enrichment

Abstract Background Our study aimed to investigate signature RNAs and their potential roles in type 1 diabetes mellitus (T1DM) using a competing endogenous RNA regulatory network analysis. Methods Expression profiles of GSE55100, deposited from peripheral blood mononuclear cells of 12 T1DM patients and 10 normal controls, were downloaded from the Gene Expression Omnibus to uncover differentially expressed long non-coding RNAs (lncRNAs), mRNAs, and microRNAs (miRNAs). The ceRNA regulatory network was constructed, then functional and pathway enrichment analysis was conducted. AT1DM-related ceRNA regulatory network was established based on the Human microRNA Disease Database to carry out pathway enrichment analysis. Meanwhile, the T1DM-related pathways were retrieved from the Comparative Toxicogenomics Database (CTD). Results In total, 847 mRNAs, 41 lncRNAs, and 38 miRNAs were significantly differentially expressed. The ceRNA regulatory network consisted of 12 lncRNAs, 10 miRNAs, and 24 mRNAs. Two miRNAs (hsa-miR-181a and hsa-miR-1275) were screened as T1DM-related miRNAs to build the T1DM-related ceRNA regulatory network, in which genes were considerably enriched in seven pathways. Moreover, three overlapping pathways, including the phosphatidylinositol signaling system (involving PIP4K2A, INPP4A, PIP4K2C, and CALM1); dopaminergic synapse (involving CALM1 and PPP2R5C); and the insulin signaling pathway (involving CBLB and CALM1) were revealed by comparing with T1DM-related pathways in the CTD, which involved four lncRNAs (LINC01278, TRG-AS1, MIAT, and GAS5-AS1). Conclusion The identified signature RNAs may serve as important regulators in the pathogenesis of T1DM.

scholarly journals Plasma Metabolome Profiling Identifies Metabolic Subtypes of Pancreatic Ductal Adenocarcinoma

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1821
Author(s):  
Ujjwal Mukund Mahajan ◽  
Ahmed Alnatsha ◽  
Qi Li ◽  
Bettina Oehrle ◽  
Frank-Ulrich Weiss ◽  
...  
Keyword(s):  
Pancreatic Ductal Adenocarcinoma ◽  
Enrichment Analysis ◽  
Response Prediction ◽  
Ductal Adenocarcinoma ◽  
Pathway Enrichment Analysis ◽  
Metabolome Analysis ◽  
Dismal Prognosis ◽  
Chemotherapeutic Response ◽  
Plasma Metabolome ◽  
Metabolome Profiling

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers. Developing biomarkers for early detection and chemotherapeutic response prediction is crucial to improve the dismal prognosis of PDAC patients. However, molecular cancer signatures based on transcriptome analysis do not reflect intratumoral heterogeneity. To explore a more accurate stratification of PDAC phenotypes in an easily accessible matrix, plasma metabolome analysis using MxP® Global Profiling and MxP® Lipidomics was performed in 361 PDAC patients. We identified three metabolic PDAC subtypes associated with distinct complex lipid patterns. Subtype 1 was associated with reduced ceramide levels and a strong enrichment of triacylglycerols. Subtype 2 demonstrated increased abundance of ceramides, sphingomyelin and other complex sphingolipids, whereas subtype 3 showed decreased levels of sphingolipid metabolites in plasma. Pathway enrichment analysis revealed that sphingolipid-related pathways differ most among subtypes. Weighted correlation network analysis (WGCNA) implied PDAC subtypes differed in their metabolic programs. Interestingly, a reduced expression among related pathway genes in tumor tissue was associated with the lowest survival rate. However, our metabolic PDAC subtypes did not show any correlation to the described molecular PDAC subtypes. Our findings pave the way for further studies investigating sphingolipids metabolisms in PDAC.

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