scholarly journals LncRNAs Landscape in the patients of primary gout by microarray analysis

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0232918
Author(s):  
Yu-Feng Qing ◽  
Jian-Xiong Zheng ◽  
Yi-Ping Tang ◽  
Fei Dai ◽  
Zeng-Rong Dong ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Roc Curve ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Acute Gout ◽  
Expression Levels ◽  
Control Subjects ◽  
Primary Gout ◽  
Healthy Control ◽  
Gout Flare

To determine the expression profile and clinical significance of long non-coding RNAs (lncRNAs) in peripheral blood mononuclear cells (PBMCs) of patients with primary gout and healthy control subjects. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary gout patients (n = 6) and healthy control subjects (n = 6). Bioinformatics analyses were performed to predict the roles of differently expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression levels of 8 lnRNAs in 64 primary gout patients and 32 healthy control subjects. Spearman’s correlation was used to analyze the correlation between these eight lncRNAs and the laboratory values of gout patients. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 1479 differentially expressed lncRNAs (879 more highly expressed and 600 more lowly expressed), 862 differentially expressed mRNAs (390 more highly expressed and 472 more lowly expressed) in primary gout (fold change > 2, P < 0.05), respectively. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the acute gout flare group than those in the intercritical gout group or healthy subjects (P<0.01). Moreover, inflammation indicators were positive correlated with TCONS_00004393 and ENST00000566457 expression levels. The areas under the ROC curve of ENST00000566457 and NR-026756 were 0.868 and 0.948, respectively. Our results provide novel insight into the mechanisms of primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate targets for the treatment of gout flare; ENST00000566457 and NR-026756 could effectively discriminate between the gout and the healthy control groups.

scholarly journals LncRNAs Landscape in the patients of primary gout by Microarray Analysis

2020 ◽  
Author(s):  
Yu-Feng Qing ◽  
Jian-Xiong Zheng ◽  
Yi-Ping Tang ◽  
Fei Dai ◽  
Zeng-Rong Dong ◽  
...  
Keyword(s):  
Microarray Analysis ◽  
Roc Curve ◽  
Healthy Subjects ◽  
Mononuclear Cells ◽  
Differentially Expressed ◽  
Acute Gout ◽  
Qrt Pcr ◽  
Control Subjects ◽  
Primary Gout ◽  
Healthy Control

AbstractTo determine the differential profiles of long non-coding RNAs (lncRNAs) in Peripheral blood mononuclear cells (PBMCs) among acute gout (AG) patients, intercritical gout (IG) patients and healthy control subjects, and to explore the specific biomarkers for acute gout diagnosis and treatment in future. Human lncRNA microarrays were used to identify the differentially expressed lncRNAs and mRNAs in primary AG (n=3), IG (n=3) and healthy subjects (n=3). For comparison Bioinformatics analyses were performed to predict the roles of abberrantly expressed lncRNAs and mRNAs. Quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the results in 32 AG, 32 IG patients and 32 healthy control subjects. A receiver operating characteristic (ROC) curve was constructed to evaluate the diagnostic value of the lncRNAs identified in gout. The microarray analysis identified 3421 and 1739 differentially expressed lncRNAs, 2240 and 1027 differentially expressed mRNAs in AG and IG (fold change>1.5, P<0.05; respectively), respectively. qRT-PCR results of 9 dysregulated genes were consistent with the microarray data. The bioinformatic analysis indicated that the differentially expressed lncRNAs regulated the abnormally expressed mRNAs, which were involved in the pathogenesis of gout through several different pathways. The expression levels of TCONS_00004393 and ENST00000566457 were significantly increased in the AG group than those in the IG group or healthy subjects (P<0.01, respectively). Moreover, the areas under the ROC curve were 0.955 and 0.961 for TCONS_00004393 and ENST00000566457,respectively. Our results provide novel insight into the mechanisms of the primary gout, and reveal that TCONS_00004393 and ENST00000566457 might be as candidate diagnostic biomarkers and targets for the treatment of acute gout.

scholarly journals Expression Profile and Potential Function of Circular RNAs in Peripheral Blood Mononuclear Cells in Male Patients With Primary Gout

2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Dai ◽  
Quan-Bo Zhang ◽  
Yi-Ping Tang ◽  
Yi-Xi He ◽  
Ting Yi ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Fold Change ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Primary Gout ◽  
Blood Mononuclear Cells

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change &gt;1.5, p &lt; 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change &gt;1.5, p &lt; 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730–0.871; p &lt; 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.

scholarly journals POS1142 INTERLEUKIN-37: ASSOCIATIONS OF PLASMA LEVELS AND GENETIC VARIANTS IN GOUT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 850.2-851
Author(s):  
A. Navrátilová ◽  
V. Voclonová ◽  
H. Hulejova ◽  
L. Andres Cerezo ◽  
J. Zavada ◽  
...  
Keyword(s):  
Genetic Variants ◽  
Plasma Levels ◽  
European Population ◽  
Enzyme Linked Immunosorbent Assay ◽  
Acute Gout ◽  
Tophaceous Gout ◽  
Control Subjects ◽  
Primary Gout ◽  
Anti Inflammatory ◽  
Gout Flare

Background:IL-37, recently characterized IL-1 family member, has anti-inflammatory effects by suppression of IL-1ß and other proinflammatory cytokines. In this study we investigated the effects of genetics variants in IL-37 link with IL-37 plasma levels in a cohorts of patients with hyperuricemia/gout.Objectives:The aim of this study was to determine the association of IL-37 gene polymorphism and plasma IL-37 levels in patients with hyperuricemia and gout.Methods:The cohorts consisted of 50 control subjects, 50 subjects of primary hyperuricemia, 50 subjects of primary gout, 28 subjects of tophaceous gout and 19 subjects of acute gout flare. The analyzed cohorts were selected from a previously reported set of 250 hyperuricemia/gout patients and 132 normouricemic subjects (1) according to the descending level of serum urate. All coding regions and intron-exon boundaries of IL-37, exon 1-5, were amplified and sequenced directly. Comparisons of presence/absence of identified variants was performed using P-values binomial test. Levels of plasma IL-37 were measured using Enzyme-Linked ImmunoSorbent Assay. All tests were performed in accordance with standards set by the institutional ethics committees, which approved the project in Prague (no.6181/2015).Results:We identified 12 IL-37 genetic variants: five intron (rs28947188, rs2466448, rs3811045, rs3811048, rs2708944), and seven non-synonymous allelic variants (rs3811046, rs3811047, rs2708943, rs2723183, rs2723187, rs2708947, rs27231927). Minor allele frequency (MAF) of those variants in European population from ExAC databases were used for comparison. Our data showed that the rs28947188, rs3811045, rs3811046, rs3811047, rs2723187, rs2708947, and rs27231927 variants were under-represented in the Czech hyperuricemia, gout, and tophaceous gout cohort compared with the control cohort and general European population (P = 0.0082 – 0.0395).The levels of plasma IL-37 were significantly higher in patients with tophaceous gout compared to control subjects (P 0.0329) whereas no changes were observed in subjects with primary hyperuricemia, primary gout or acute gout flare compared to control subjects. However, IL-37 was elevated in cohorts of patients with gout, tophaceous gout and acute gout flare compared to primary hyperuricemia subjects (P 0.0198, 0.0005, 0.0099; respectively).Conclusion:Although further analyzes are needed to elucidate the role of IL-37 in the gout, our results show that genetic variants in anti-inflammatory cytokine IL-37 are probably implicated in the pathogenesis of gout.References:[1]Toyoda Y, et al. Functional characterization of clinically-relevant rare variants in ABCG2 identified in a gout and hyperuricemia cohort. Cells. 2019 Apr 18;8(4).Acknowledgements:This study was supported by the grant from the Czech Republic Ministry of Health RVO 00023728.Disclosure of Interests:None declared.

Novel severe traumatic brain injury blood outcome biomarkers identified with proximity extension assay

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Douglas D. Fraser ◽  
Michelle Chen ◽  
Annie Ren ◽  
Michael R. Miller ◽  
Claudio Martin ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Severe Traumatic Brain Injury ◽  
Roc Curve ◽  
Vascular Pathology ◽  
Targeted Proteomics ◽  
Control Subjects ◽  
Matched Healthy Control ◽  
Healthy Control ◽  
Age And Sex

Abstract Objectives Severe traumatic brain injury (sTBI) patients suffer high mortality. Accurate prognostic biomarkers have not been identified. In this exploratory study, we performed targeted proteomics on plasma obtained from sTBI patients to identify potential outcome biomarkers. Methods Blood sample was collected from patients admitted to the ICU suffering a sTBI, using standardized clinical and computerized tomography (CT) imaging criteria. Age- and sex-matched healthy control subjects and sTBI patients were enrolled. Targeted proteomics was performed on plasma with proximity extension assays (1,161 proteins). Results Cohorts were well-balanced for age and sex. The majority of sTBI patients were injured in motor vehicle collisions and the most frequent head CT finding was subarachnoid hemorrhage. Mortality rate for sTBI patients was 40%. Feature selection identified the top performing 15 proteins for identifying sTBI patients from healthy control subjects with a classification accuracy of 100%. The sTBI proteome was dominated by markers of vascular pathology, immunity/inflammation, cell survival and macrophage/microglia activation. Receiver operating characteristic (ROC) curve analyses demonstrated areas-under-the-curves (AUC) for identifying sTBI that ranged from 0.870-1.000 (p≤0.005). When mortality was used as outcome, ROC curve analyses identified the top 3 proteins as vWF, WIF-1, and CSF-1. Combining vWF with either WIF-1 or CSF-1 resulted in excellent mortality prediction with AUC of 1.000 for both combinations (p=0.011). Conclusions Targeted proteomics with feature classification and selection distinguished sTBI patients from matched healthy control subjects. Two protein combinations were identified that accurately predicted sTBI patient mortality. Our exploratory findings require confirmation in larger sTBI patient populations.

Increased Expression of TLR2 and TLR4 in Mononuclear Cells in Patient with Immune Thrombocytopenic Purpura.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3847-3847 ◽  
Author(s):  
Yunfeng Cheng ◽  
Shanhua Zou ◽  
Feng Li
Keyword(s):  
Plasma Concentration ◽  
Mrna Expression ◽  
Mononuclear Cells ◽  
Control Group ◽  
Gene Expressions ◽  
Expression Levels ◽  
Tnf Α ◽  
Healthy Control ◽  
Ifn Γ ◽  
Mrna Expression Levels

Abstract Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by platelet destruction resulting from autoantibodies against self-antigens and T-cell mediated cytotoxicity. Toll-like receptors (TLRs) are pattern recognition receptors important in mediating the immune response and their activation can lead to production of cytokines. Recent data suggest that TLR2 and TLR4 are crucial for the production of inflammatory cytokines and play central role in autoimmune diseases, yet little is known about their roles in ITP. Here we examined the gene expressions of TLR2 and TLR4 in ITP patients. We hypothesize that significant differences will exist between pre-treatment and post-treatment in ITP patients with similar changes reflected in the plasma concentration of cytokines. Total RNA was extracted from mononuclear cells obtained from 12 ITP patients and 15 healthy subjects. TLR2 and TLR4 mRNA expression levels were analyzed using a quantitative real-time PCR method and their protein expressions were validated by western blot. Plasma concentrations of cytokines IL-2, IFN-γ and TNF-α were measured by ELISA. Correlation analyses were carried out between the mRNA expression levels of TLR2 or TLR4 and the plasma levels of IL-2, IFN-γ and TNF-α. The gene expression of TLR2 and TLR4 were significantly increased in ITP patients comparing to healthy control group (p < 0.05 and p < 0.01, respectively). In addition their mRNA expression levels were decreased back into normal range after remission in 8 patients (p > 0.05, compared to healthy control group). Significantly positive correlations were found between the TLR2 mRNA expression level and the plasma concentration of IFN-γ or TNF-α (R = 0.75, p < 0.05; R = 0.83, p < 0.05, respectively). Changes in the gene expression of TLR4 and in the plasma concentration of IFN-γ or TNF-α were also significantly correlated (R = 0.82, p < 0.05; R = 0.88, p < 0.05, respectively). Directional changes in TLR2 / TLR4 and IFN-γ /TNF-α expression were concordant. However, there was no correlation found between TLR2 / TLR4 and IL-2. Differences in TLR2 and TLR4 expression strongly correlated with changes in IFN-γ and TNF-α suggest that the increased gene expressions of TLR2 and TLR4 in ITP patients may contribute to the pathophysiological progression of this disease by increasing the secretion of IFN-γ and TNF-α. Additional studies need to be performed to further clarify the role of TLRs -cytokines pathway in ITP.

No evidence of acute Chlamydia pneumoniae infection in patients with Bell's palsy

2002 ◽  
Vol 126 (4) ◽  
pp. 415-416 ◽  
Author(s):  
Anne Pitkäranta ◽  
Antti Vaheri ◽  
Tuula Penttilä ◽  
Mirja Puolakkainen
Keyword(s):  
Chlamydia Pneumoniae ◽  
Mononuclear Cells ◽  
Bell’S Palsy ◽  
Tear Fluid ◽  
Bell's Palsy ◽  
Peripheral Blood Mononuclear ◽  
Neurologic Diseases ◽  
Control Subjects ◽  
Healthy Control ◽  
Polymerase Chain

The cause of Bell's palsy remains unknown even though available evidence suggests that infection could be a factor. In recent studies, Chlamydia pneumoniae has been associated with neurologic diseases such as multiple sclerosis. In the present study, the association of C pneumoniae with Bell's palsy was studied with the use of serology and polymerase chain reaction to test tear fluid and peripheral blood mononuclear cells from 21 patients with Bell's palsy and 21 control subjects. C pneumoniae DNA was detected from tear fluid samples in 1 patient with Bell's palsy and in 2 healthy control subjects. Whether this indicates earlier disease or subclinical infection remains to be studied. However, an association between Bell's palsy and acute C pneumoniae infection could not be shown.

Serum Mir-4254, Mir-19a and Mir-33b Are Potential Markers For Diagnosis and Prognostic Evaluation In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3222-3222 ◽  
Author(s):  
Mu Hao ◽  
Meirong Zang ◽  
Qin Yu ◽  
Li Fei ◽  
Wenjuan Yang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Roc Curve ◽  
Diagnostic Tool ◽  
Healthy Subjects ◽  
Healthy Controls ◽  
Newly Diagnosed ◽  
Prognostic Evaluation ◽  
Control Subjects ◽  
Healthy Control ◽  
Powerful Diagnostic Tool

Abstract Introduction A sensitive, noninvasive diagnosis and better disease classification would be very useful for improve the outcome of multiple myeloma. In this study, we proposed a microarray based biology approach to identify miRNAs as new biomarkers for the diagnosis and prognostic evaluation of multiple myeloma. Methods and Results Microarray-based miRNAs expression profiling data indicated that 95 mature miRNAs were differentially expressed between myeloma patients (n=7) and healthy subjects (n=5, fold change>3.0 with P<0.01). The decrease of miR-19a/miR-92a (P<0.0001) and the increase of miR-214, 135b, 4254, 3658 and 33b (P<0.05) in myeloma patients were further validation confirmed by Q-PCR. The expression pattern of these miRNAs (miR-19a, miR-92a, miR-214, miR-135b, miR-3658, miR-4254 and miR-33b) were further detected by Taqman probes Q-PCR in 84 newly diagnosed patients, 34 cases in remission, 40 relapsed patients and 34 healthy controls. The data showed the expression of miR-19a (1.39±0.33 vs 2.56±0.18) and miR-92a (0.35±0.20 vs 1.73±0.13) were significantly lower in newly diagnosed patients compared with healthy control subjects (all P<0.05).Whereas, miR-214 (1.68±0.12 vs 1.08±0.10), miR-135b (2.25±0.28 vs 0.01±0.05), miR-4254 (1.11±0.09 vs -0.21±0.16), miR-3658 (2.26±0.29 vs 0.47±0.09) and miR-33b (2.71±0.24 vs 2.03±0.39) were significantly higher in patients than the healthy subjects (all P<0.001). Among these miRNAs, the expression of miR-19a, miR-4254 and miR-33b were closely associated with disease progressions. The expression of miR-19a in healthy control subjects and patients in remission were significantly higher than that in newly diagnosed and relapsed patients. While miR-4254 and miR-33b were significantly lower in healthy subjects and CR patients compared to newly diagnosed and relapsed patients. ROC (receiver operating characteristic) analysis was conducted in this study and the results showed that serum miR-4254 yielded an AUC (area under the ROC curve) of 0.9261 (P<0.001) with 79.3% sensitivity and 98.5% specificity for discriminating myeloma patients from healthy controls at a cut-off value of 0.66 (RQ value). Therefore, use of miR-4254 alone provides an excellent discrimination between healthy subjects and myeloma patients. Similarly, serum miR-19a is also a potential marker with an AUC of 0.722 ( P<0.001). At a cut-off value of 2.08 (RQ value), the sensitivity for miR-19a was 77.30% and the specificity was 70.00%. However, the AUC of miR-33b was 0.63 (P<0.05). At a cutoff value of 1.015 (RQ value), the sensitivity for miR-33b was 84.10% and the specificity was 61.0%. miR-33b is not a reliable independent marker to discriminate myeloma patients from healthy controls. Then we preformed PLS-DA in various miRNA biomarkers and found that the combination of miR-4254 and miR-19a together was an even more powerful diagnostic tool for myeloma distinguishing. The ROC curve of the classifier had an AUC of 0.950 (P<0.05). miR-4254 combined with miR-33b provided the same powerful diagnostic tool for myeloma. Moreover, Kaplan-Meier survival analysis showed that patients with higher expression of miR-19a or miR-33b had significantly favorite PFS and OS than those with low expression. However, our data did not show the expression of miR-4254 correlated with favorite survival in myeloma patient. Conclusion Serum miR-4254, miR-19a and miR-33b are novel, non-invasive, sensitive and reliable biomarkers for multiple myeloma diagnosis and prognosis evaluation. Footnotes * Asterisk with author names denotes non-ASH members. Disclosures: No relevant conflicts of interest to declare.

Dead or alive: gene expression profiles of advanced atherosclerotic plaques from autopsy and surgery

2007 ◽  
Vol 30 (3) ◽  
pp. 335-341 ◽  
Author(s):  
Judith C. Sluimer ◽  
Natasja Kisters ◽  
Kitty B. Cleutjens ◽  
Oscar L. Volger ◽  
Anton J. Horrevoets ◽  
...  
Keyword(s):  
Gene Expression ◽  
Microarray Analysis ◽  
Basal Cell ◽  
Protein Level ◽  
Expression Profiles ◽  
Cell Metabolism ◽  
Gene Expression Profiles ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Atherosclerotic Lesions

Since inclusion of atherosclerotic tissues from different sources is often indispensable to study the full atherogenic spectrum, we investigated to what extent the expression profiles of advanced, stable atherosclerotic lesions obtained during autopsy and surgery are comparable. The gene expression profiles of human carotids with advanced atherosclerosis obtained at autopsy and at vascular surgery were studied by microarray analysis. Expression analysis was performed both at the single gene (Rosetta, Gene Ontology) and at the pathway level using Ingenuity and Gene Set Enrichment Analysis. In addition, mRNA and protein expression levels were validated using quantitative (q) RT-PCR and immunohistochemistry on unrelated advanced carotid lesions from autopsy and surgery. Microarray analysis indicated that the 97.2% of genes showed similar expression levels in advanced atherosclerotic lesions from autopsy and surgery. While the expression data revealed no differences in common atherosclerotic related pathways such as lipid metabolism and inflammation, the differentially expressed genes were mainly involved in basal cell metabolism and hypoxia driven pathways. qRT-PCR confirmed the differential expression of hypoxia-driven genes VEGF-A (2.3-fold ↑), glucose transporter (GLUT)-1 (2.5-fold ↑), GLUT3 (8.3-fold ↑), and hexokinase 1 (2.4-fold ↑) in autopsy vs. surgical specimens. Immunohistochemistry revealed that the transcriptional differences in these hypoxia-related genes were not reflected at the protein level. The gene expression profiles of advanced atherosclerotic lesions from autopsy and surgery are largely similar. However, >500 genes, mostly involved in basal cell metabolism and hypoxia were differentially expressed at mRNA, but not at the protein level.

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