Differential long noncoding RNA expressions in peripheral blood mononuclear cells for detection of acute ischemic stroke

Long noncoding RNAs (lncRNAs) have been highlighted to be involved in the pathological process of ischemic stroke (IS). The purpose of the present study was to investigate the expression profile of lncRNAs in peripheral blood mononuclear cells (PBMCs) of acute IS patients and to explore their utility as biomarkers of IS. Distinctive expression patterns of PBMC lncRNAs were identified by an lncRNA microarray and individual quantitative real-time PCR (qRT-PCR) in four independent sets for 206 IS, 179 healthy controls (HCs), and 55 patients with transient ischemic attack (TIA). A biomarker panel (lncRNA-based combination index) was established using logistic regression. LncRNA microarray analysis showed 70 up-regulated and 128 down-regulated lncRNAs in IS patients. Individual qRT-PCR validation demonstrated that three lncRNAs (linc-DHFRL1-4, SNHG15, and linc-FAM98A-3) were significantly up-regulated in IS patients compared with HCs and TIA patients. Longitudinal analysis of lncRNA expression up to 90 days after IS showed that linc-FAM98A-3 normalized to control levels by day 7, while SNHG15 remained increased, indicating the ability of lncRNAs to monitor IS dynamics. Receiver-operating characteristic (ROC) curve analysis showed that the lncRNA-based combination index outperformed serum brain-derived neurotrophic factor (BDNF) and neurone-specific enolase (NSE) in distinguishing IS patients from TIA patients and HCs with areas under ROC curve of more than 0.84. Furthermore, the combination index increased significantly after treatment and was correlated with neurological deficit severity of IS. The panel of these altered lncRNAs was associated with acute IS and could serve as a novel diagnostic method.

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Brain-derived neurotrophic factor in peripheral blood mononuclear cells and stroke outcome

Experimental Biology and Medicine ◽

10.1177/1535370218815612 ◽

2018 ◽

Vol 243 (15-16) ◽

pp. 1207-1211 ◽

Cited By ~ 1

Author(s):

Martin Pedard ◽

Céline Brenière ◽

Nicolas Pernet ◽

Catherine Vergely ◽

Yannick Béjot ◽

...

Keyword(s):

Ischemic Stroke ◽

Functional Outcome ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Stroke Outcome ◽

Stroke Patients ◽

Peripheral Blood Mononuclear ◽

Ischemic Brain ◽

Blood Mononuclear Cells

Stroke outcome is dependent on brain-derived neurotrophic factor (BDNF)-dependent neuroplasticity. As peripheral blood mononuclear cells (PBMC) contain BDNF, diapedesis of these cells might be followed by BDNF delivery to the ischemic brain. To test this hypothesis, we investigated the association between BDNF levels in PBMC and functional outcome in patients with ischemic stroke. BDNF was measured in PBMC that were isolated from ischemic stroke patients ( n = 40) just before (day 0) and after (days 1 and 3) fibrinolysis. Three months after stroke, patients were stratified using the modified Rankin Scale (mRS) according to the unfavorable (mRS scores 3–6) and favorable (mRS scores 0–2) functional outcome. We used univariate and multivariate logistic regressions to assess the relationship between BDNF levels in PBMC and functional outcome. BDNF levels in PBMC decreased from day 0 to day 3 in patients with unfavorable outcome, while they remained stable in patients with favorable outcome. Patients with favorable outcome exhibited at day 3 higher PBMC-BDNF levels than patients with unfavorable outcome and the levels were associated with good outcome (odd ratio: 12.0; 95% confidence interval, 1.4–106.2, P = 0.023). PBMC-BDNF levels remained a predictor of stroke outcome after adjusting from cardiovascular risk, interval between admission and fibrinolysis, stroke severity from hospital admission to discharge, lymphocytes count, neutrophils/lymphocytes ratio at admission. Favorable functional outcome in ischemic stroke patients that benefited from fibrinolysis was predicted by a high BDNF level in PBMC, suggesting that PBMC might serve as a cellular vector to deliver BDNF to the ischemic brain. Impact statement There are a great number of arguments suggesting that BDNF could be involved in stroke recovery dependent of neuroplasticity. Methods that can enhance BDNF levels in the ischemic brain could therefore have great clinical value. Peripheral blood mononuclear cells (PBMC) that contain BDNF and infiltrate early and sustainably the ischemic brain might be used as a cellular vector to deliver BDNF to the ischemic brain and consequently promote recovery. This work is important in this field to show if this BDNF derived from BDNF could exert a positive action on stroke recovery. Our main results showed that a high BDNF level at day 3 after hospital admission was associated with a 12.4 fold increase in favorable outcome after adjusting for still recognized prognostic markers. The new information in this field is this finding identifies PBMC as an attractive cellular vector to deliver BDNF to the ischemic brain.

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Gene expression in human peripheral blood mononuclear cells upon acute ischemic stroke

Journal of Neurology ◽

10.1007/s00415-008-0784-z ◽

2008 ◽

Vol 255 (5) ◽

pp. 723-731 ◽

Cited By ~ 38

Author(s):

C. Grond-Ginsbach ◽

M. Hummel ◽

T. Wiest ◽

S. Horstmann ◽

K. Pfleger ◽

...

Keyword(s):

Gene Expression ◽

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Human Peripheral Blood ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

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Circular RNA expression profiles and bioinformatic analysis in coronary heart disease

Epigenomics ◽

10.2217/epi-2019-0369 ◽

2020 ◽

Vol 12 (5) ◽

pp. 439-454 ◽

Cited By ~ 2

Author(s):

Fangpu Yu ◽

Yuanyuan Tie ◽

Ya Zhang ◽

Zunzhe Wang ◽

Liwen Yu ◽

...

Keyword(s):

Coronary Heart Disease ◽

Heart Disease ◽

Coronary Arteries ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Expression Profiles ◽

Peripheral Blood Mononuclear ◽

Qrt Pcr ◽

Blood Mononuclear Cells

Aim: We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary heart disease (CHD). Materials & methods: We performed sequence analysis of circRNAs in peripheral blood mononuclear cells of 70 CHD patients and 30 controls. Eight selected circRNAs were validated using quantitative real-time polymerase chain reaction (qRT-PCR) in human atherosclerotic coronary arteries. Results: In total, 2283 downregulated and 85 upregulated circRNAs were identified in CHD. Parental genes of top 100 dysregulated-circRNAs are related to metabolism and protein modification, and 12 circRNAs might upregulate their CHD-related parental genes through miRNA sponges. Of the eight circRNAs validated in atherosclerotic coronary arteries by qRT-PCR, six were consistent with sequencing results of peripheral blood mononuclear cells. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in CHD pathophysiology.

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Oropouche Virus Infects, Persists and Induces IFN Response in Human Peripheral Blood Mononuclear Cells as Identified by RNA PrimeFlow™ and qRT-PCR Assays

Viruses ◽

10.3390/v12070785 ◽

2020 ◽

Vol 12 (7) ◽

pp. 785

Author(s):

Mariene Ribeiro Amorim ◽

Marjorie Cornejo Pontelli ◽

Gabriela Fabiano de Souza ◽

Stéfanie Primon Muraro ◽

Daniel A. Toledo-Teixeira ◽

...

Keyword(s):

T Cells ◽

B Cells ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Peripheral Blood Mononuclear ◽

Human Leukocytes ◽

Qrt Pcr ◽

Viral Antigens ◽

Blood Mononuclear Cells

Oropouche orthobunyavirus (OROV) is an emerging arbovirus with a high potential of dissemination in America. Little is known about the role of peripheral blood mononuclear cells (PBMC) response during OROV infection in humans. Thus, to evaluate human leukocytes susceptibility, permissiveness and immune response during OROV infection, we applied RNA hybridization, qRT-PCR and cell-based assays to quantify viral antigens, genome, antigenome and gene expression in different cells. First, we observed OROV replication in human leukocytes lineages as THP-1 monocytes, Jeko-1 B cells and Jurkat T cells. Interestingly, cell viability and viral particle detection are maintained in these cells, even after successive passages. PBMCs from healthy donors were susceptible but the infection was not productive, since neither antigenome nor infectious particle was found in the supernatant of infected PBMCs. In fact, only viral antigens and small quantities of OROV genome were detected at 24 hpi in lymphocytes, monocytes and CD11c+ cells. Finally, activation of the Interferon (IFN) response was essential to restrict OROV replication in human PBMCs. Increased expression of type I/III IFNs, ISGs and inflammatory cytokines was detected in the first 24 hpi and viral replication was re-established after blocking IFNAR or treating cells with glucocorticoid. Thus, in short, our results show OROV is able to infect and remain in low titers in human T cells, monocytes, DCs and B cells as a consequence of an effective IFN response after infection, indicating the possibility of leukocytes serving as a trojan horse in specific microenvironments during immunosuppression.

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miR-106a Is Downregulated in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B and Associated with Enhanced Levels of Interleukin-8

Mediators of Inflammation ◽

10.1155/2015/629862 ◽

2015 ◽

Vol 2015 ◽

pp. 1-9 ◽

Cited By ~ 6

Author(s):

Zhongsi Hong ◽

Haiyu Hong ◽

Jian Liu ◽

Xiaobin Zheng ◽

Mingxing Huang ◽

...

Keyword(s):

Chronic Hepatitis ◽

Hepatitis B ◽

Peripheral Blood Mononuclear Cells ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Luciferase Activity ◽

Peripheral Blood Mononuclear ◽

Protein Levels ◽

Qrt Pcr ◽

Blood Mononuclear Cells

Aims. This study aimed to investigate miR-106a expression in peripheral blood mononuclear cells (PBMCs) of chronic hepatitis B (CHB) patients and to analyze the function of miR-106a.Materials and Methods. miR-106a expression levels in PBMCs from 40 healthy controls and 56 CHB patients were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). The luciferase activity assays were used to determine whether miR-106a binds to 3′UTR of IL-8. miR-106a mimics and inhibitors were transfected into healthy PBMCs. IL-8 mRNA and protein levels were detected and determined by qRT-PCR and ELISA, respectively.Results. The qRT-PCR results suggested that the PBMC miR-106a levels were decreased in CHB patients. IL-8 was augmented in CHB patients and was inversely correlated with miR-106a levels. The luciferase activity assays indicated that IL-8 is a target of miR-106a. Exogenous expression of miR-106a could significantly repress IL-8 expression at both mRNA and protein levels in PBMCs, whereas miR-106a inhibitor had the opposite effects.Conclusions. This study suggested that miR-106a is downregulated in PBMCs of CHB patients and that miR-106a may play an important role in CHB by targeting IL-8.

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Microarray Expression Profile of Circular RNAs in Peripheral Blood Mononuclear Cells from Rheumatoid Arthritis Patients

Cellular Physiology and Biochemistry ◽

10.1159/000477883 ◽

2017 ◽

Vol 42 (2) ◽

pp. 651-659 ◽

Cited By ~ 59

Author(s):

Qingqing Ouyang ◽

Jing Wu ◽

Zhenlan Jiang ◽

Jinjun Zhao ◽

Ran Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Peripheral Blood Mononuclear Cells ◽

Roc Curve ◽

Peripheral Blood ◽

Mononuclear Cells ◽

Circular Rnas ◽

Screening Methods ◽

Roc Curve Analysis ◽

Peripheral Blood Mononuclear ◽

Blood Mononuclear Cells

Background/Aims: Circular RNAs (circRNAs) compose a large class of RNAs that can be used as biomarkers in clinical blood samples. This study aimed to determine the expression of circRNAs in peripheral blood mononuclear cells (PBMCs) from rheumatoid arthritis (RA) patients to identify novel biomarkers for RA screening. Methods: We started with a microarray screening of circRNA changes in PBMCs from 5 RA patients and 5 healthy controls. We then confirmed the selected circRNA changes in PBMCs from 30 RA patients and 25 age- and sex-matched controls using the real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman correlation test was performed to assess the correlation of circRNAs and clinical variables. Receiver operating characteristic (ROC) curve was calculated to evaluate the diagnostic value. Results: We identified and verified five circRNAs (092516, 003524, 103047, 104871, 101873) that were significantly elevated in PBMCs from RA patients. Among these RA patients, we detected no significant correlation between the five circRNAs and the disease severity, including disease activity score (DAS28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and health assessment questionnaire (HAQ). Yet, ROC curve analysis suggested that circRNA_104871 has significant value of RA diagnosis (AUC=0.833, P<0.001), followed by circRNA_003524 (AUC = 0.683, P = 0.020), circRNA_101873 (AUC = 0.676, P = 0.026), and circRNA_103047 (AUC = 0.671, P = 0.030). Conclusions: This study suggests that increased expression of circRNAs circRNA_104871, circRNA_003524, circRNA_101873 and circRNA_103047 in PBMC from RA patients may serve as potential biomarkers for RA patient diagnosis.

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