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 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.

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.

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.

scholarly journals The Differentially Expressed Circular RNAs in the Substantia Nigra and Corpus Striatum of Nrf2-Knockout Mice

2018 ◽  
Vol 50 (3) ◽  
pp. 936-951 ◽  
Author(s):  
Jun-Hui Yang ◽  
Run-Jiao Zhang ◽  
Jia-Jie Lin ◽  
Ming-Chao Cao ◽  
Qie Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Substantia Nigra ◽  
Microarray Analysis ◽  
Corpus Striatum ◽  
Neuronal Damage ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Related Factor ◽  
Qrt Pcr

Background/Aims: The nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway plays a protective role in both acute neuronal damage and chronic neurodegeneration-related oxidative stress. Circular RNAs (circRNAs) are involved with various diseases in the central nervous system (CNS). This study aimed to identify the key circRNAs involved in Nrf2-neuroprotection against oxidative stress. Methods: The differentially expressed circRNAs (DEcircRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice were identified by microarray analysis. Quantitative real-time polymerase chain reaction (qRT-PCR) was then used to validate the expression of selected DEcircRNAs in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice. Based on our previous microarray analysis of the differentially expressed mRNAs (DEmRNAs) in the substantia nigra and corpus striatum between Nrf2 (-/-) and Nrf2 (+/+) mice, the DEcircRNA-miRNA-DEmRNA interaction network was constructed. Functional annotation of DEmRNAs that shared the same binding miRNAs with DEcircRNAs was performed using gene ontology (GO) and pathway analyses. Results: A total of 65 and 150 significant DEcircRNAs were obtained in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, respectively, and seventeen shared DEcircRNAs were found in both these two tissues. The qRT-PCR results were generally consistent with the microarray results. The DEcircRNA-miRNA-DEmRNA interaction network and pathway analysis indicated that mmu_circRNA_34132, mmu_circRNA_017077 and mmu-circRNA-015216 might be involved with Nrf2-mediated neuroprotection against oxidative stress. Mmu_circRNA_015216 and mmu_circRNA_017077 might play roles in the Nrf2-related transcriptional misregulation and Nrf2-mediated processes of rheumatoid arthritis, respectively. In addition to these two processes, mmu_circRNA_34132 may be a potential regulator of Nrf2-mediated protection for diabetes mellitus and Nrf2-mediated defence against ROS in hearts. Conclusion: In conclusion, our study identified the key DEcircRNAs in the substantia nigra and corpus striatum of Nrf2 (-/-) mice, which might provide new clues for further exploring the mechanism of Nrf2-mediated neuroprotection against oxidative stress and other Nrf2-mediated processes.

Integrative Analysis of Long Noncoding RNAs in Patients with Graft-versus-Host Disease

2020 ◽  
Vol 143 (6) ◽  
pp. 533-551 ◽  
Author(s):  
Feiyan Wang ◽  
Lan Luo ◽  
Zhenyang Gu ◽  
Nan Yang ◽  
Li Wang ◽  
...  
Keyword(s):  
B Cells ◽  
Signaling Pathway ◽  
Microarray Analysis ◽  
Graft Versus Host Disease ◽  
Differentially Expressed ◽  
Hematopoietic Stem ◽  
Host Disease ◽  
Graft Versus Host ◽  
Qrt Pcr ◽  
Bcr Signaling

<b><i>Background:</i></b> Chronic graft-versus-host disease (cGVHD) remains a major cause of late non-recurrence mortality despite remarkable improvements in the field of allogeneic hematopoietic stem cell transplantation. Although recent studies have found that B-cell receptor (BCR)-activated B cells contribute to pathogenesis in cGVHD, the specific molecular mechanisms of B cells in this process remain unclear. <b><i>Methods:</i></b> In our study, human long noncoding RNA (lncRNA) microarrays and bioinformatic analysis were performed to identify different expressions of lncRNAs in peripheral blood B cells from cGVHD patients compared with healthy ones. The differential expression of lncRNA was confirmed in additional samples by quantitative real-time polymerase chain reaction (qRT-PCR). <b><i>Results:</i></b> The microarray analysis revealed that 106 of 198 differentially expressed lncRNAs were upregulated and 92 were downregulated in cGVHD patients compared with healthy controls. Intergenic lncRNAs accounted for the majority of differentially expressed lncRNAs. A KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis showed that the differentially expressed mRNAs, which were coexpressed with lncRNA, between the cGVHD group and the healthy group were significantly enriched in the BCR signaling pathway. Further analysis of the BCR signaling pathway and its coexpression network identified three lncRNAs with the strongest correlation with BCR signaling and cGVHD, as well as a series of protein-coding genes and transcription factors associated with them. The three candidate lncRNAs were further validated in another group of cGVHD patients by qRT-PCR. <b><i>Conclusions:</i></b> This is the first study on the correlation between lncRNA and cGVHD using lncRNA microarray analysis. Our study provides novel enlightenment in exploring the molecular pathogenesis of cGVHD.

Platelet Microrna-mRNA Co-Expression Profiles Correlate with Platelet Reactivity

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2016-2016
Author(s):  
Srikanth Nagalla ◽  
Chad Shaw ◽  
Xianguo Kong ◽  
Lin Ma ◽  
Altaf A. Kondkar ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Protein Expression ◽  
Reporter Gene ◽  
Microarray Analysis ◽  
Individual Variation ◽  
Healthy Subjects ◽  
Platelet Reactivity ◽  
Human Platelets ◽  
Differentially Expressed ◽  
Cell Physiology

Abstract Abstract 2016 Background: There is extreme inter-individual variation in platelet reactivity, which likely impacts the variation in both risk and clinical outcome of ischemic vascular disease since platelet hyperreactivity has prospectively been shown to be a risk for recurrent coronary syndromes. Although heritability strongly influences the inter-individual variation in platelet reactivity, there is a lack of understanding of the molecular and genetic mechanisms responsible for this variability. To understand some of these mechanisms, we have previously performed mRNA microarray analysis on platelets of subjects with differing levels of platelet reactivity. We showed a differentially expressed (DE) transcript (VAMP8) was associated with platelet reactivity. Intriguingly, we identified a possible role for microRNA (miRNA)-96 in the regulation of VAMP8 mRNA and protein expression. MiRNAs regulate numerous aspects of normal cell physiology and cause disease by altering protein expression, and recent data demonstrate a role for miRNAs in both normal and diseased human megakaryocytopoiesis. Although others and we have observed miRNAs in platelets, their biology is largely unexplored. Aims: To test whether platelet miRNA levels were associated with platelet reactivity in 19 healthy subjects. Because we had previously obtained platelet mRNA profile data on these 19 subjects, we also had a unique opportunity to test for relationships between differentially expressed miRNAs and target DE mRNAs. Methods: MiRNA microarray analysis was performed on leukocyte depleted platelets from 19 healthy subjects with marked variability in platelet responsiveness. Bioinformatics approaches were used analyze the miRNA data in platelets. Subsequently transfection experiments in cell lines to assess miRNA knockdown of target gene products and reporter gene assays were used for functional assessment of miRNA binding to 3’UTRs of the target genes. Results: We found that human platelets express 284 miRNAs, some at very high levels. Unsupervised hierarchical clustering of miRNA profiles resulted in two groups of subjects that appeared to cluster by platelet aggregation phenotypes. Seventy-four miRNAs were differentially expressed between subjects grouped according to platelet aggregation to epinephrine, a subset of which predicted the platelet reactivity response. We profiled miRNAs from HEL and Meg-01 cells and found a strong correlation between normal human platelets and both HEL cells and Meg-01 cells. Using whole-genome mRNA expression data on these same 19 subjects, we computationally generated a high-priority list of miRNA-mRNA pairs where the differentially expressed platelet miRNAs had binding sites in 3’UTRs of differentially expressed mRNAs, and the levels were negatively correlated. From this list, three miRNA-mRNA pairs (miR-200b:PRKAR2B, miR-495:KLHL5 and miR-107:CLOCK) were selected, and all three miRNAs knocked down the protein expression of the target mRNA. Co-transfection experiments using reporter gene constructs engineered to contain the candidate mRNA 3’UTR and corresponding miRNA demonstrated that the miRNA of interest directly targeted the 3’UTR of the candidate mRNA. Conclusions: Results from this study demonstrated (1) platelet miRNAs are able to repress expression of platelet proteins; (2) platelet miRNA profiles are associated with and may predict platelet reactivity and (3) bioinformatic approaches can successfully identify functional miRNAs in platelets. Our findings suggest that selected platelet miRNAs may have potential as biomarkers for vascular thrombosis. It will be important to consider the repertoire and levels of miRNAs when attempting to elucidate the molecular mechanisms responsible for inter-individual variation in platelet reactivity. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Analysis of Eyelid Blink Characteristics in Patients with Ptosis Using a Smartphone Camera

2021 ◽  
Vol 62 (7) ◽  
pp. 873-880
Author(s):  
Taesung Joo ◽  
Jin-Ho Joo ◽  
In-Ki Park ◽  
Jae-Ho Shin
Keyword(s):  
Receiver Operating Characteristic ◽  
Roc Curve ◽  
Healthy Subjects ◽  
Operating Characteristic ◽  
Control Group ◽  
Palpebral Fissure ◽  
Blink Rate ◽  
Healthy Controls ◽  
Healthy Control ◽  
Receiver Operating

Purpose: To compare eyelid blink characteristics between patients with ptosis and healthy controls using a smartphone camera. Methods: The ptosis group consisted of 20 senile aponeurotic ptosis patients with margin reflex distance1 ≤2.5 mm and the control group consisted of 10 healthy subjects without ptosis. The ptosis group was further divided into two groups based on an age cutoff of 70 years. Palpebral fissure height, levator function, margin reflex distance1, inter-blink interval, blink duration, blink rate, and blink velocity were measured and compared between the three groups based on photographs of the eyelids and videos of blinking taken with a smartphone camera. Results: The palpebral fissure height, levator function, margin reflex distance1, and blink velocity were lower in the ptosis groups than in the control group but these values did not differ between the two ptosis groups. The palpebral fissure height, levator function, and margin reflex distance1 were correlated with blink velocity. In the receiver operating characteristic (ROC) curve of blink velocity, the area under the receiver operating characteristic (AUROC) curve value was as high as 0.969 and the cut-off value was 32.36 mm/s. Conclusions: It is possible to analyze eyelid blink characteristics using a smartphone camera and the results confirmed that palpebral fissure height, levator function, margin reflex distance1, and blink velocity were lower in the senile aponeurotic ptosis group than in the healthy control group and were unaffected by age. Additionally, blink velocity is valuable for diagnosis of ptosis due to the correlation between the degree of ptosis, blink velocity, and the ROC curve of blink velocity.

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.

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