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 Metabolite Changes in the Aqueous Humor of Patients With Retinal Vein Occlusion Macular Edema: A Metabolomics Analysis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaojing Xiong ◽  
Xu Chen ◽  
Huafeng Ma ◽  
Zheng Zheng ◽  
Yazhu Yang ◽  
...  
Keyword(s):  
Macular Edema ◽  
Retinal Vein Occlusion ◽  
Aqueous Humor ◽  
High Performance ◽  
Coenzyme A ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Roc Curve Analysis ◽  
Vein Occlusion ◽  
Coenzyme A Biosynthesis

Macular edema (ME) is the main cause of visual impairment in patients with retinal vein occlusion (RVO). The degree of ME affects the prognosis of RVO patients, while it lacks objective laboratory biomarkers. We aimed to compare aqueous humor samples from 28 patients with retinal vein occlusion macular edema (RVO-ME) to 27 age- and sex-matched controls by ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry, so as to identify the key biomarkers and to increase the understanding of the mechanism of RVO-ME at the molecular level. Through univariate and multivariate statistical analyses, we identified 60 metabolites between RVO-ME patients and controls and 40 differential metabolites in mild RVO-ME [300 μm ≤ central retinal thickness (CRT) < 400 μm] patients compared with severe RVO-ME (CRT ≥ 400 μm). Pathway enrichment analysis showed that valine, leucine, and isoleucine biosynthesis; ascorbate and aldarate metabolism; and pantothenate and coenzyme A biosynthesis were significantly altered in RVO-ME in comparison with controls. Compared with mild RVO-ME, degradation and biosynthesis of valine, leucine, and isoleucine; histidine metabolism; beta-alanine metabolism; and pantothenate and coenzyme A biosynthesis were significantly changed in severe RVO-ME. Furthermore, the receiver operating characteristic (ROC) curve analysis revealed that adenosine, threonic acid, pyruvic acid, and pyro-L-glutaminyl-l-glutamine could differentiate RVO-ME from controls with an area under the curve (AUC) of >0.813. Urocanic acid, diethanolamine, 8-butanoylneosolaniol, niacinamide, paraldehyde, phytosphingosine, 4-aminobutyraldehyde, dihydrolipoate, and 1-(beta-D-ribofuranosyl)-1,4-dihydronicotinamide had an AUC of >0.848 for distinguishing mild RVO-ME from severe RVO-ME. Our study expanded the understanding of metabolomic changes in RVO-ME, which could help us to have a good understanding of the pathogenesis of RVO-ME.

Identification of Potential Tumor-educated Platelets RNA Biomarkers for Pan Cancer Detection and Staging

2020 ◽  
Author(s):  
Xinxin Ge ◽  
Liuxia Yuan ◽  
Ying Hu ◽  
Bin Cheng ◽  
Khan Muhammad Shoaib ◽  
...  
Keyword(s):  
Correlation Analysis ◽  
Enrichment Analysis ◽  
Diagnostic Value ◽  
Metabolic Process ◽  
Pathway Enrichment Analysis ◽  
High Morbidity ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Pathway Enrichment ◽  
Pan Cancer

Abstract Cancer is a disturbing disease with high morbidity and mortality. Although medical technology has been developed rapidly, diagnosis of cancer is still complicated, difficult, as well as expensive. Furthermore, cancers are mostly diagnosed at an advanced stage. Platelets mRNA profiles are altered after educated by tumors. Thereby, tumor-educated platelets (TEPs) mRNA profiles have the potentially diagnostic value for cancers currently. We downloaded and analyzed the next-generation sequencing datasets, GSE68086 and GSE89843, by integrated bioinformatics. A total of 43 biomarker genes were selected for further pathway enrichment analysis and correlation analysis, as well as diagnostic analysis. Gene ontology (GO) analysis showed these 43 TEPs mRNAs were mostly involved in protein binding, extracellular matrix and cellular protein metabolic process. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis revealed that genes were mainly enriched in metabolic process. Eventually, after taking these 43 genes into spearman correlation analysis and receiving operating characteristic (ROC) curve analysis, we identified: 1) TEPs RSL24D1 mRNA was negatively related to early pan cancer as compared to healthy controls, and potential for early pan cancer diagnosis with a sensitivity of 71.8%, and a specificity of 64.3%; 2) HPSE, IFI27, LGALS3BP, CRYM, HBD, COL6A3, LAMB2, and IFITM3 showed an upward trend in the expression from early to more advanced pan cancer stages. The sensitivity of the diagnostic value for pan cancer of these genes was 60.9%, 59.1%, 56.5%, 57.8%, 54.3%, 55.2%, 55.2%, 60.9%, and a specificity of 94.5%, 90.9%, 87.3%, 89.1%, 72.7%, 85.5%, 89.1%, 94.5% respectively; 3) ARL2, FCGR2A, and KLHDC8B were positively associated with advanced, metastatic pan cancer as compared to healthy controls and could be diagnostic indicators for advanced pan cancer with a sensitivity of 59.2%, 61.8%, 59.7%, and a specificity of 80%, 89.1%, 83.6%, respectively. In summary, our findings identified that the 12-gene TEP liquid-biopsy biomarkers will not only facilitate early diagnosis of pan cancer, but also be beneficial to pan cancer staging.

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 Metabolomics profiling of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata extracts using UPLC-Q/TOF-MS

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Zhaoyan Zhang ◽  
Liang Yang ◽  
Xiaoyan Huang ◽  
Yue Gao
Keyword(s):  
High Performance ◽  
Principal Component ◽  
Partial Least Square ◽  
Least Square ◽  
Alpha Linolenic Acid ◽  
Multivariate Statistical ◽  
Biochemical Indicators ◽  
Flight Mass Spectrometry ◽  
Underlying Mechanisms ◽  
Tof Ms

Abstract Background The side effects caused by Polygoni Multiflori Radix (PMR) and Polygoni Multiflori Radix Praeparata (PMRP) have often appeared globally. There is no research on the changes of endogenous metabolites among PMR- and PMRP-treated rats. The aim of this study was to evaluate the varying metabolomic effects between PMR- and PMRP-treated rats. We tried to discover relevant differences in biomarkers and endogenous metabolic pathways. Methods Hematoxylin and eosin staining and immunohistochemistry staining were performed to find pathological changes. Biochemical indicators were also measured, one-way analysis of variance with Dunnett’s multiple comparison test was used for biochemical indicators comparison among various groups. Metabolomics analysis based on ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UPLC-Q/TOF-MS) was performed to find the changes in metabolic biomarkers. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal partial least square-discriminant analysis (OPLS-DA) were applied to reveal group clustering trend, evaluate and maximize the discrimination between the two groups. MetaboAnalyst 4.0 was performed to find and confirm the pathways. Results PMR extracts exhibited slight hepatotoxic effects on the liver by increasing aspartate and alanine aminotransferase levels. Twenty-nine metabolites were identified as biomarkers, belonging to five pathways, including alpha-linolenic acid metabolism, taurine and hypotaurine metabolism, glycerophospholipid metabolism, arginine and proline metabolism, and primary bile acid biosynthesis. Conclusion This study provided a comprehensive description of metabolomic changes between PMR- and PMRP-treated rats. The underlying mechanisms require further research.

scholarly journals Mass spectrometry-based metabolomics for irritable bowel syndrome biomarkers

2019 ◽  
Vol 12 ◽  
pp. 175628481988642 ◽  
Author(s):  
Qihong Yu ◽  
Xinru Liu ◽  
Haojie Huang ◽  
Xingfeng Zheng ◽  
Xue Pan ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Irritable Bowel Syndrome ◽  
Gastrointestinal Disorder ◽  
Ultra Performance Liquid Chromatography ◽  
Healthy Controls ◽  
Multivariate Statistical ◽  
Clinical Trial Registration ◽  
Flight Mass Spectrometry ◽  
Hormone Biosynthesis ◽  
Irritable Bowel

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder without obvious structural abnormalities or consistent associated biomarkers, making its diagnosis difficult. In the present study, we used a urine-based metabolomics approach to identify IBS biomarkers. Methods: We used an ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS) on urine samples from patients suffering from IBS and healthy controls. Data were coupled for multivariate statistical analysis methods. Results: We selected 30 differential metabolites associated with IBS and found steroid hormone biosynthesis and histidine metabolism alterations in patients with IBS that may be involved in the pathogenesis of the disease. In addition, we identified a panel of five metabolite markers composed of cortisone, citric acid, tiglylcarnitine, N6,-N6,-N6-trimethyl-L-lysine and L-histidine that could be used to discriminate between patients and healthy controls and may be appropriate as IBS diagnosis biomarkers. Conclusion: Our findings indicate that metabolomics combined with pattern recognition can be useful to identify disease diagnostic IBS markers. Clinical trial registration: ChiCTR1800020072

scholarly journals Transcriptome Sequencing Identifies PLAUR as an Important Player in Patients With Dermatomyositis-Associated Interstitial Lung Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan Chen ◽  
Ruixian Zhang ◽  
Min Xie ◽  
Chunyan Luan ◽  
Xiaolan Li
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Healthy Controls ◽  
Biological Processes ◽  
Blood Samples ◽  
Important Player ◽  
Key Genes

Dermatomyositis (DM), an inflammatory disorder, is often associated with interstitial lung disease (ILD). However, the underlying mechanism remains unclear. Our study performed RNA sequencing (RNA-seq) and integrative bioinformatics analysis of differentially expressed genes (DEGs) in patients with dermatomyositis-associated interstitial lung disease (DM-ILD) and healthy controls. A total of 2,018 DEGs were identified between DM-ILD and healthy blood samples. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis showed that DEGs were mainly involved in immune- and inflammatory-related biological processes and pathways. Disease ontology (DO) enrichment analysis identified 35 candidate key genes involved in both skin and lung diseases. Meanwhile, a total of 886 differentially expressed alternative splicing (AS) events were found between DM-ILD and healthy blood samples. After overlapping DEGs with differential AS genes, the plasminogen activator and urokinase receptor (PLAUR) involved in immune-related biological processes and complement and coagulation cascades was screened and identified as the most important gene associated with DM-ILD. The protein–protein interaction (PPI) network revealed that PLAUR had interactions with multiple candidate key genes. Moreover, we observed that there were significantly more neutrophils and less naive B cells in DM-ILD samples than in healthy samples. And the expression of PLAUR was significantly positively correlated with the abundance of neutrophils. Significant higher abundance of PLAUR in DM-ILD patients than healthy controls was validated by RT-qPCR. In conclusion, we identified PLAUR as an important player in regulating DM-ILD by neutrophil-associated immune response. These findings enrich our understanding, which may benefit DM-ILD patients.

scholarly journals Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Seyedeh Zahra Hosseini Imani ◽  
Zohreh Hojati ◽  
Sheyda Khalilian ◽  
Fariba Dehghanian ◽  
Majid Kheirollahi ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Family History ◽  
Area Under The Curve ◽  
Group Versus ◽  
Expression Level ◽  
Inflammatory Factors ◽  
Control Group ◽  
Healthy Controls ◽  
Roc Curve Analysis ◽  
Axonal Dysfunction

AbstractMultiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Our results showed that the expression level of IL7R was decreased in the sporadic patients in comparison with other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls, and familial group versus FDR was also seen. Our results also represented an increased expression level of RNF213 in familial patients as compared to the control group. The similar RNF213 expression between sporadic and control group, as well as FDR and familial group was also seen. Diagnostic evaluation was performed by receiver operating characteristic (ROC) curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and Expanded Disability Status Scale (EDSS) with our gene expression levels were also assessed. Overall, decreased expression level of IL7R in the sporadic cases and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. Confirmation of the effects of differential expression of RNF213 gene requires further studies in the wider statistical populations.

scholarly journals L-Carnitine and Acetyl-L-Carnitine: Potential Novel Biomarkers for Major Depressive Disorder

2021 ◽  
Vol 12 ◽  
Author(s):  
Li-Juan Nie ◽  
Jun Liang ◽  
Feng Shan ◽  
Bao-Shi Wang ◽  
Yuan-Yuan Mu ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Treatment Group ◽  
Depressive Disorder ◽  
Neural Plasticity ◽  
High Performance ◽  
Pearson Correlation ◽  
Area Under The Curve ◽  
Healthy Controls ◽  
Major Depressive ◽  
Novel Biomarkers

The lack of biomarkers greatly limits the diagnosis and treatment of major depressive disorder (MDD). Endogenous L-carnitine (LC) and its derivative acetyl-L-carnitine (ALC) play antidepressant roles by improving brain energy metabolism, regulating neurotransmitters and neural plasticity. The levels of ALC in people and rodents with depression are significantly reduced. It is necessary to determine whether serum LC and ALC might be used as novel biomarkers for the diagnosis of MDD. Here, ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to determine the concentration of LC and ALC in the serum of healthy controls and patients with MDD; among the latter, in patients who were responsive (effective group) and non-responsive (ineffective group) after 2 weeks of treatment. The diagnostic value of serum LC and ALC for MDD was assessed. Compared with healthy controls, the serum LC and ALC concentrations in patients with MDD were significantly decreased (P < 0.001). Pearson correlation analysis shows that the HDRS-24 score was negatively associated with serum ALC (r = −0.325, P = 0.007). Receiver operating characteristic (ROC) analysis revealed an area under the curve (AUC) of 0.801 with 83.1% sensitivity and 66.3% specificity for LC, and an AUC of 0.898 with 88.8% sensitivity and 76.4% specificity for ALC, differentiating patients with MDD from healthy controls. Furthermore, the concentration of LC and ALC in patients with depression was significantly increased in the effective treatment group, and no significant change was observed in the ineffective treatment group. These results suggest that serum LC and ALC may be novel biomarkers for the diagnosis of MDD.

scholarly journals Seminal plasma AnnexinA2 protein is a relevant biomarker for stallions which require removal of seminal plasma for sperm survival upon refrigeration†

2020 ◽  
Vol 103 (6) ◽  
pp. 1275-1288
Author(s):  
Gemma Gaitskell-Phillips ◽  
Francisco E Martín-Cano ◽  
José M Ortiz-Rodríguez ◽  
Antonio Silva-Rodríguez ◽  
Heriberto Rodríguez-Martínez ◽  
...  
Keyword(s):  
Seminal Plasma ◽  
High Performance ◽  
Semen Quality ◽  
Enrichment Analysis ◽  
Bioinformatic Analysis ◽  
Protein Glycosylation ◽  
Pathway Enrichment Analysis ◽  
Post Translational Modification ◽  
Specific Proteins ◽  
Discriminant Variable

Abstract Some stallions yield ejaculates that do not tolerate conservation by refrigeration prior to artificial insemination (AI), showing improvement after removal of most of the seminal plasma (SP) by centrifugation. In this study, the SP-proteome of 10 different stallions was defined through high-performance liquid chromatography with tandem mass spectrometry and bioinformatic analysis in relation to the ability of the ejaculates to maintain semen quality when cooled and stored at 5°C. Stallions were classified into three groups, depending on this ability: those maintaining good quality after direct extension in a commercial extender (good), stallions requiring removal of seminal plasma (RSP) to maintain seminal quality (good-RSP), and stallions, unable to maintain good semen quality even after RSP (poor). Pathway enrichment analysis of the proteins identified in whole equine SP using human orthologs was performed using g: profiler showing enriched Reactome and the Kyoto Encyclopedia of Genes and Genomes pathways related to hexose metabolism, vesicle mediated transport, post translational modification of proteins and immune response. Specific proteins overrepresented in stallions tolerating conservation by refrigeration included a peroxiredoxin-6 like protein, and transcobalamin-2, a primary vitamin B12-binding, and transport protein. Also, the protein involved in protein glycosylation, ST3 beta-galactoside alpha-2,3-sialyltransferase 1 was present in good stallions. These proteins were nearly absent in poor stallions. Particularly, annexinA2 appeared as to be the most powerful discriminant variable for identification of stallions needing RSP prior to refrigeration, with a P = 0.002 and a q value = 0.005. Overall this is the first detailed study of the equine SP-proteome, showing the potential value of specific proteins as discriminant bio-markers for clinical classification of stallions for AI.

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