scholarly journals Metabolomic Urine Profile: Searching for New Biomarkers of SDHx-Associated Pheochromocytomas and Paragangliomas

2019 ◽  
Vol 104 (11) ◽  
pp. 5467-5477
Author(s):  
Raquel G Martins ◽  
Luís G Gonçalves ◽  
Nuno Cunha ◽  
Maria João Bugalho
Keyword(s):  
Enrichment Analysis ◽  
Urine Samples ◽  
Proton Nuclear Magnetic Resonance ◽  
Metabolomic Profile ◽  
Pronounced Increase ◽  
Mutation Carriers ◽  
Urinary Levels ◽  
Metabolite Set Enrichment Analysis ◽  
New Biomarkers

Abstract Context Metabolomic studies of pheochromocytoma and paraganglioma tissue showed a correlation between metabolomic profile and presence of SDHx mutations, especially a pronounced increase of succinate. Objective To compare the metabolomic profile of 24-hour urine samples of SDHx mutation carriers with tumors (affected mutation carriers), without tumors (asymptomatic mutation carriers), and patients with sporadic pheochromocytomas and paragangliomas. Methods Proton nuclear magnetic resonance spectroscopic profiling of urine samples and metabolomic analysis using pairwise comparisons were complemented by metabolite set enrichment analysis to identify meaningful patterns. Results The urine of the affected SDHx carriers showed substantially lower levels of seven metabolites than the urine of asymptomatic mutation carriers (including, succinate and N-acetylaspartate). The urine of patients with SDHx-associated tumors presented substantially higher levels of three metabolites compared with the urine of patients without mutation; the metabolite set enrichment analysis identified gluconeogenesis, pyruvate, and aspartate metabolism as the pathways that most probably explained the differences found. N-acetylaspartate was the only metabolite the urinary levels of which were significantly different between the three groups. Conclusions The metabolomic urine profile of the SDHx mutation carriers with tumors is different from that of asymptomatic carriers and from that of patients with sporadic neoplasms. Differences are likely to reflect the altered mitochondria energy production and pseudohypoxia signature of these tumors. The urinary levels of N-acetylaspartate and succinate contrast with those reported in tumor tissue, suggesting a defective washout process of oncometabolites in association with tumorigenesis. The role of N-acetylaspartate as a tumor marker for these tumors merits further investigation.

Construction of a Competitive Endogenous RNA Network Associated with Angiogenesis in Ischemic Stroke Using a Bioinformatics Approach

2021 ◽  
Author(s):  
Jia Wang ◽  
Xuxiang Zhang ◽  
Yibo Xie ◽  
Jiachen Li ◽  
Xiaokun Wang ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Enrichment Analysis ◽  
Gene Expression Omnibus ◽  
Gene Set Enrichment Analysis ◽  
Differentially Expressed ◽  
Gene Set Enrichment ◽  
Differentially Expressed Mirnas ◽  
New Biomarkers ◽  
Competitive Endogenous Rna

Abstract Ischemic stroke (IS) is one of the leading causes of death and disability worldwide, and angiogenesis is an important target for its treatment. However, the mechanism of angiogenesis of endogenous RNA (ceRNA) in IS remains poorly understood. This study aims to explore the role of ceRNA in the angiogenesis of IS, to provide a possible target for the treatment of IS. First, GSE22255 (mRNA), GSE55937 (miRNA) and GSE102541 (lncRNA) were downloaded from the Gene Expression Omnibus (GEO) database. Then, a total of 21 mRNA modules were identified by WGCNA analysis, among which NR4A1, PTGS2, ERG3, and VEGFA in cyan module were identified as key genes for angiogenesis. Subsequently, 1454 differentially expressed lncRNAs (DELs) were screened and a lncRNA-mRNA co-expression network consisting of 40 lncRNAs and 4 mRNAs was constructed by correlation analysis. Then, 16 differentially expressed miRNAs (DEMs) were screened and the online database was used to predict the interaction information between miRNAs, lncRNAs and mRNAs. The angiogenesis-related ceRNA network was finally constructed based on ceRNA theory, in which 1 DEL was predicted as a ceRNA for 2 DEMs to regulate 4 hub genes, specifically, HCG18-has-let-7i-5p-NR4A1/PTGS2/ERG3, HCG18-miR-148a-3p-PTGS2/ERG3/VEGFA interaction axis. The results of gene set enrichment analysis (GSEA) suggest that HCG18 may regulate angiogenesis through NF-kB-TNFA signaling pathway, hypoxia and other pathways. In conclusion, the above genes may be new biomarkers and potential targets for the treatment of IS.

scholarly journals Transglutaminases and Obesity in Humans: Association of F13A1 to Adipocyte Hypertrophy and Adipose Tissue Immune Response

2020 ◽  
Vol 21 (21) ◽  
pp. 8289
Author(s):  
Mari T. Kaartinen ◽  
Mansi Arora ◽  
Sini Heinonen ◽  
Aila Rissanen ◽  
Jaakko Kaprio ◽  
...  
Keyword(s):  
Immune Response ◽  
Adipose Tissue ◽  
Family Members ◽  
Enrichment Analysis ◽  
Human Adipose Tissue ◽  
Adipocyte Size ◽  
Gene Enrichment ◽  
Adipocyte Hypertrophy ◽  
Mz Twins

Transglutaminases TG2 and FXIII-A have recently been linked to adipose tissue biology and obesity, however, human studies for TG family members in adipocytes have not been conducted. In this study, we investigated the association of TGM family members to acquired weight gain in a rare set of monozygotic (MZ) twins discordant for body weight, i.e., heavy–lean twin pairs. We report that F13A1 is the only TGM family member showing significantly altered, higher expression in adipose tissue of the heavier twin. Our previous work linked adipocyte F13A1 to increased weight, body fat mass, adipocyte size, and pro-inflammatory pathways. Here, we explored further the link of F13A1 to adipocyte size in the MZ twins via a previously conducted TWA study that was further mined for genes that specifically associate to hypertrophic adipocytes. We report that differential expression of F13A1 (ΔHeavy–Lean) associated with 47 genes which were linked via gene enrichment analysis to immune response, leucocyte and neutrophil activation, as well as cytokine response and signaling. Our work brings further support to the role of F13A1 in the human adipose tissue pathology, suggesting a role in the cascade that links hypertrophic adipocytes with inflammation.

scholarly journals Sub-Inhibitory Concentrations of Ciprofloxacin Alone and Combinations with Plant-Derived Compounds against P. aeruginosa Biofilms and Their Effects on the Metabolomic Profile of P. aeruginosa Biofilms

Antibiotics ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 414
Author(s):  
Didem Kart ◽  
Tuba Reçber ◽  
Emirhan Nemutlu ◽  
Meral Sagiroglu
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Quorum Sensing ◽  
Inhibitory Concentration ◽  
Molecular Level ◽  
Metabolomic Profile ◽  
Gene Expressions ◽  
New Agents ◽  
Qrt Pcr ◽  
Metabolomic Approach

Introduction: Alternative anti-biofilm agents are needed to combat Pseudomonas aeruginosa infections. The mechanisms behind these new agents also need to be revealed at a molecular level. Materials and methods: The anti-biofilm effects of 10 plant-derived compounds on P. aeruginosa biofilms were investigated using minimum biofilm eradication concentration (MBEC) and virulence assays. The effects of ciprofloxacin and compound combinations on P. aeruginosa in mono and triple biofilms were compared. A metabolomic approach and qRT-PCR were applied to the biofilms treated with ciprofloxacin in combination with baicalein, esculin hydrate, curcumin, and cinnamaldehyde at sub-minimal biofilm inhibitory concentration (MBIC) concentrations to highlight the specific metabolic shifts between the biofilms and to determine the quorum sensing gene expressions, respectively. Results: The combinations of ciprofloxacin with curcumin, baicalein, esculetin, and cinnamaldehyde showed more reduced MBICs than ciprofloxacin alone. The quorum sensing genes were downregulated in the presence of curcumin and cinnamaldehyde, while upregulated in the presence of baicalein and esculin hydrate rather than for ciprofloxacin alone. The combinations exhibited different killing effects on P. aeruginosa in mono and triple biofilms without affecting its virulence. The findings of the decreased metabolite levels related to pyrimidine and lipopolysaccharide synthesis and to down-regulated alginate and lasI expressions strongly indicate the role of multifactorial mechanisms for curcumin-mediated P. aeruginosa growth inhibition. Conclusions: The use of curcumin, baicalein, esculetin, and cinnamaldehyde with ciprofloxacin will help fight against P. aeruginosa biofilms. To the best of our knowledge, this is the first study of its kind to define the effect of plant-based compounds as possible anti-biofilm agents with low MBICs for the treatment of P. aeruginosa biofilms through metabolomic pathways.

scholarly journals VEGF as a potential molecular target in periodontitis: a meta-analysis and microarray data validation

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Bo Ren ◽  
Que Feng ◽  
Shan He ◽  
Yanfeng Li ◽  
Jiadong Fan ◽  
...  
Keyword(s):  
Growth Factor ◽  
Clinical Sample ◽  
Meta Analysis ◽  
Enrichment Analysis ◽  
Therapeutic Drug ◽  
Data Validation ◽  
Control Groups ◽  
Vegf Expression ◽  
Healthy Control

Abstract Background Anti-vascular endothelial growth factor (VEGF) has been used as a therapeutic drug for the treatment of some human diseases. However, no systematic evidence is performed for assessing the role of VEGF in periodontitis. We carried out a comprehensive analysis to explore the role of VEGF in patients with periodontitis. Methods Multiple databases were searched for eligible studies. The pooled standardized mean difference (SMD) and odds ratio (OR) with the corresponding 95% confidence interval (CI) were applied to evaluate the effect sizes. Clinical data validation from microarray analysis was used. Pathway and process enrichment analysis were also investigated. Results Finally, 16 studies were included in this analysis. Overall, there was a significantly higher level of VEGF expression in periodontitis than in healthy control groups (OR = 16.64, 95% CI = 6.01–46.06, P < 0.001; SMD = 2.25, 95% CI = 1.25–3.24, P < 0.001). Subgroup analysis of ethnicity showed that VEGF expression was still correlated with periodontitis in the Asian and European populations. No correlation was observed between VEGF expression and age, gender, and pathological type. A large clinical sample data (427 periodontitis patients and 136 healthy controls) further validated that VEGF expression was higher in periodontitis than in healthy control groups (P = 0.023). VEGF was involved in many functions such as blood vessel development, response to growth factor, cell proliferation, and cell adhesion. Conclusions High levels of VEGF were credible implications for the development of periodontitis. Anti-VEGF therapy may be valuable for the treatment of periodontitis in clinical management.

scholarly journals The role of epigenetic modifications for the pathogenesis of Crohn's disease

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
M. Hornschuh ◽  
E. Wirthgen ◽  
M. Wolfien ◽  
K. P. Singh ◽  
O. Wolkenhauer ◽  
...  
Keyword(s):  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Bowel Diseases ◽  
Inflammatory Bowel ◽  
New Biomarkers ◽  
Insight Into ◽  
Specific Evaluation

AbstractEpigenetics has become a promising field for finding new biomarkers and improving diagnosis, prognosis, and drug response in inflammatory bowel disease. The number of people suffering from inflammatory bowel diseases, especially Crohn's disease, has increased remarkably. Crohn's disease is assumed to be the result of a complex interplay between genetic susceptibility, environmental factors, and altered intestinal microbiota, leading to dysregulation of the innate and adaptive immune response. While many genetic variants have been identified to be associated with Crohn's disease, less is known about the influence of epigenetics in the pathogenesis of this disease. In this review, we provide an overview of current epigenetic studies in Crohn's disease. In particular, we enable a deeper insight into applied bioanalytical and computational tools, as well as a comprehensive update toward the cell-specific evaluation of DNA methylation and histone modifications.

scholarly journals Integrative and Comprehensive Pancancer Analysis of Regulator of Chromatin Condensation 1 (RCC1)

2021 ◽  
Vol 22 (14) ◽  
pp. 7374
Author(s):  
Changwu Wu ◽  
Yingjuan Duan ◽  
Siming Gong ◽  
Sonja Kallendrusch ◽  
Nikolas Schopow ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Chromatin Condensation ◽  
Treatment Strategies ◽  
Enrichment Analysis ◽  
Tissue Expression ◽  
The Cancer Genome Atlas ◽  
Malignant Neoplasms ◽  
Nucleotide Exchange ◽  
Genome Database

Regulator of Chromatin Condensation 1 (RCC1) is the only known guanine nucleotide exchange factor that acts on the Ras-like G protein Ran and plays a key role in cell cycle regulation. Although there is growing evidence to support the relationship between RCC1 and cancer, detailed pancancer analyses have not yet been performed. In this genome database study, based on The Cancer Genome Atlas, Genotype-Tissue Expression and Gene Expression Omnibus databases, the potential role of RCC1 in 33 tumors’ entities was explored. The results show that RCC1 is highly expressed in most human malignant neoplasms in contrast to healthy tissues. RCC1 expression is closely related to the prognosis of a broad variety of tumor patients. Enrichment analysis showed that some tumor-related pathways such as “cell cycle” and “RNA transport” were involved in the functional mechanism of RCC1. In particular, the conducted analysis reveals the relation of RCC1 to multiple immune checkpoint genes and suggests that the regulation of RCC1 is closely related to tumor infiltration of cancer-associated fibroblasts and CD8+ T cells. Coherent data demonstrate the association of RCC1 with the tumor mutation burden and microsatellite instability in various tumors. These findings provide new insights into the role of RCC1 in oncogenesis and tumor immunology in various tumors and indicate its potential as marker for therapy prognosis and targeted treatment strategies.

scholarly journals Lack of HPV in pterygium with no evidence of autoinoculation and the role of cytokines in pterygium with dry eye

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Lita Uthaithammarat ◽  
Ngamjit Kasetsuwan ◽  
Yuda Chongpison ◽  
Pimpetch Kasetsuwan ◽  
Usanee Reinprayoon ◽  
...  
Keyword(s):  
Dry Eye ◽  
Hpv Infection ◽  
Cross Sectional Study ◽  
Urine Samples ◽  
Vascular Endothelial ◽  
Cross Sectional ◽  
Hpv Dna ◽  
Polymerase Chain ◽  
Endothelial Growth Factor

AbstractThis study evaluated human papillomavirus’s (HPV) role in pterygium pathogenesis, its autoinoculation from genitalia to ocular surface, potential cytokines involved, and crosstalk cytokines between pterygium and dry eye (DE). This cross-sectional study enrolled 25 healthy controls (HCs) and 116 pterygium patients. Four subgroups of pterygium and DE were used in cytokine evaluations. Conjunctival and pterygium swabs and first-void urine samples (i.e., genitalia samples) were collected for HPV DNA detection using real-time polymerase chain reaction. Tear cytokines interleukin (IL)-6, IL-18, and vascular endothelial growth factor (VEGF) in tears were evaluated. No HPV DNA was detected in conjunctival or pterygium swabs. No association was found between HPV DNA in urine samples and that from conjunctival or pterygium swabs. Tear VEGF levels were significantly higher in pterygium patients than in HCs, with no markedly different levels between primary and recurrent pterygia. Tear IL-6, IL-18, and tear VEGF were significantly higher in participants with DE, regardless of pterygium status. In conclusion, HPV infection was not a pathogenic factor of pterygia. The hypothesis of HPV transmitting from the genitals to ocular surfaces was nullified. Tear VEGF was involved in both pterygia and DE, whereas tear IL-6 and IL-18 played roles only in DE.

Knockdown of PGM1 Synergistically Enhances Anticancer Effects of Orlistat in Gastric Cancer Under Glucose Deprivation

2021 ◽  
Author(s):  
Bo Cao ◽  
Huan Deng ◽  
Hao Cui ◽  
Ruiyang Zhao ◽  
Hanghang Li ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Lipid Metabolism ◽  
Fatty Acid Synthase ◽  
Enrichment Analysis ◽  
Glucose Deprivation ◽  
Metabolic Reprogramming ◽  
The Cancer Genome Atlas

Abstract Background Phosphoglucomutase 1 (PGM1) acts as an important regulator in glucose metabolism. However, the role of PGM1 in gastric cancer (GC) remains unclear. This study aims to investigate the role of PGM1 and develop novel regimens based on metabolic reprogramming in GC. MethodsCorrelation and enrichment analysis of PGM1 was conducted based on The Cancer Genome Atlas database. Data derived from the Kaplan-Meier Plotter database were analyzed for correlations between PGM1 expression and survival time of GC patients. CCK-8, EdU, flow cytometry assays, generation of subcutaneous tumor and lung metastasis mouse models were used to determine growth and metastasis in vitro and in vivo. Cell glycolysis was detected by a battery of glycolytic indicators, including lactate, pyruvic acid, ATP production and glucose uptake. Fatty Acid Synthase (FASN) activity and detection of lipid regulators levels by western blot were used to reflect on the cell lipid metabolism. ResultsCorrelation and enrichment analysis suggested that PGM1 was closely associated with cell proliferation and metabolism. PGM1 was overexpressed in GC tissues and cell lines. High PGM1 expression served as an indicator of shorter survival for specific subpopulation of GC patients, which was also correlated with some clinicopathological features, including T stage and TNM stage. Under low glucose conditions, knockdown of PGM1 significantly suppressed cell proliferation and glycolysis levels, whereas lipid metabolism was enhanced. Orlistat, as a drug that was designed to inhibit FASN activity for obesity treatment, effectively induced apoptosis, suppressed FASN activity. However, orlistat conversely increased glycolytic levels in GC cells. Orlistat exhibited more significant inhibitive effects on GC progression after knockdown of PGM1 under glucose deprivation due to combination of glycolysis and lipid metabolism. ConclusionsDownregulation of PGM1 expression under glucose deprivation synergistically enhanced anti-cancer effects of orlistat. This combination application may serve as a novel strategy for GC treatment.

scholarly journals miRNA-mRNA integrative analysis in primary myelofibrosis CD34+ cells: role of miR-155/JARID2 axis in abnormal megakaryopoiesis

Blood ◽  
2014 ◽  
Vol 124 (13) ◽  
pp. e21-e32 ◽  
Author(s):  
Ruggiero Norfo ◽  
Roberta Zini ◽  
Valentina Pennucci ◽  
Elisa Bianchi ◽  
Simona Salati ◽  
...  
Keyword(s):  
Expression Analysis ◽  
Mirna Expression ◽  
Therapeutic Targets ◽  
Primary Myelofibrosis ◽  
Integrative Analysis ◽  
Cd34 Cells ◽  
Key Points ◽  
Differential Gene ◽  
New Biomarkers

Key Points Differential gene and miRNA expression analysis in PMF granulocytes identifies new biomarkers and putative therapeutic targets. Activation of the miR-155/JARID2 axis in PMF CD34+ cells results in overproduction of MK precursors.

scholarly journals High Expression of PRMT6 Associated With Prognosis and Immune Infiltration in Glioma

2020 ◽  
Author(s):  
Yi Yang ◽  
Zhenshuang Wang ◽  
Shengrong Long ◽  
Jinhai Huang ◽  
Chengran Xu ◽  
...  
Keyword(s):  
Enrichment Analysis ◽  
Clinical Work ◽  
High Expression ◽  
Clinical Indicators ◽  
Immune Infiltration ◽  
Tumor Tissues ◽  
Potential Biomarker ◽  
Patient Prognosis ◽  
The Relationship

Abstract Background: Gliomas are characterised by easy invasion of surrounding tissues, high mortality and poor prognosis. Moreover, with the increase of grade, the prognosis of glioma is increasingly poor and not optimistic. Therefore, biological markers for glioma are needed in clinical work, which can be utilized to detect and evaluate the situation and prognosis of glioma patients. Many studies have found that the protein arginine methyltransferase 6 (PRMT6) expression is elevated in various tumors and is associated with patient prognosis. However, the role of PRMT6 in glioma has not been reported or analyzed. Methods: In this study, we used a variety of tumor related databases to analyze the mechanism of PRMT6 in tumors, especially gliomas, from the perspective of bioinformatics, and carried out relevant experimental verification with tumor tissues extracted from patients during surgery. In addition, we analyzed the relationship between PRMT6 expression and immune infiltration and immune-related cells, and discussed the possible mechanisms. We also discussed the role of PRMT6 expression in glioma from the perspectives of mutation, clinical indicators, enrichment analysis, and immunohistochemical results. Results: PRMT6 is significantly differentially expressed in a variety of tumors and is associated with survival and prognosis. Especially in gliomas, the expression of PRMT6 gradually increased with the increase of grade. In addition, PRMT6 can be used as an independent prognostic risk factor in the nomogram and has been verified in a variety of databases. Conclusions: Our results indicate that high expression of PRMT6 is a potential biomarker for predicting glioma prognosis and progression.

Sign in / Sign up

Export Citation Format

Share Document