scholarly journals miR-224-5p and miR-545-5p Levels Relate to Exacerbations and Lung Function in a Pilot Study of X-Linked MicroRNA Expression in Cystic Fibrosis Monocytes

2021 ◽  
Vol 12 ◽  
Author(s):  
Paul J. McKiernan ◽  
Kevin P. Molloy ◽  
Arlene M. A. Glasgow ◽  
Noel G. McElvaney ◽  
Catherine M. Greene
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Microrna Expression ◽  
Mrna Levels ◽  
Microrna Target ◽  
Exacerbation Rate ◽  
Functional Changes ◽  
Qrt Pcr

Altered microRNA expression patterns in bronchial brushings from people with versus without cystic fibrosis (CF) relate to functional changes and disease pathophysiology. The expression of microRNAs encoded on the X chromosome is also altered in peripheral blood monocytes of p. Phe508del homozygous versus non-CF individuals. Here we investigate whether levels of the top seven X-linked microRNAs (miR-224-5p, miR-452-5p, miR-450b-5p, miR-542-3p, miR-450a-5p, miR-424-5p, and miR-545-5p) that are significantly increased over 1.5 fold in CF versus non-CF monocytes correlate with lung function. CD14+ monocytes were isolated from males and females with (n = 12) and without cystic fibrosis (n = 12) and examined for the expression of X-linked microRNAs by qRT-PCR array. MicroRNA target mRNA levels were quantified using qRT-PCR. Clinical correlations with lung function data were analysed in the CF cohort. Increasing levels of miR-545-5p correlated moderately with FEV1% predicted (r = -0.4553, p > 0.05) and strongly with exacerbation rate (r = 0.5858, p = 0.0483). miR-224-5p levels were significantly higher in the severe (FEV1 <40%) versus mild (FEV1 ≥80%, p = 0.0377) or moderate (FEV1 40–79%, p = 0.0350) groups. MiR-224-5p expression inversely correlated with lung function (FEV1%: r = -0.5944, p = 0.0457) and positively correlated with exacerbation rates (r = 0.6139, p = 0.0370). These data show that peripheral blood monocyte miR-545-5p and miR-224-5p levels correlate with exacerbation rate, whilst miR-224-5p levels also correlate with lung function in cystic fibrosis.

scholarly journals High Peripheral Blood Th17 Percent Associated with Poor Lung Function in Cystic Fibrosis

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120912 ◽  
Author(s):  
Emily M. Mulcahy ◽  
Jo B. Hudson ◽  
Sean A. Beggs ◽  
David W. Reid ◽  
Louise F. Roddam ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Function ◽  
Peripheral Blood

scholarly journals Peripheral blood myeloid-derived suppressor cells reflect disease status in idiopathic pulmonary fibrosis

2016 ◽  
Vol 48 (4) ◽  
pp. 1171-1183 ◽  
Author(s):  
Isis E. Fernandez ◽  
Flavia R. Greiffo ◽  
Marion Frankenberger ◽  
Julia Bandres ◽  
Katharina Heinzelmann ◽  
...  
Keyword(s):  
T Cell ◽  
Lung Function ◽  
Idiopathic Pulmonary Fibrosis ◽  
Pulmonary Fibrosis ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Myeloid Derived Suppressor Cells ◽  
Peripheral Blood Mononuclear

Idiopathic pulmonary fibrosis (IPF) is a fibroproliferative disease with irreversible lung function loss and poor survival. Myeloid-derived suppressor cells (MDSC) are associated with poor prognosis in cancer, facilitating immune evasion. The abundance and function of MDSC in IPF is currently unknown.Fluorescence-activated cell sorting was performed in 170 patients (IPF: n=69; non-IPF interstitial lung disease (ILD): n=56; chronic obstructive pulmonary disease (COPD): n=23; healthy controls: n=22) to quantify blood MDSC and lymphocyte subtypes. MDSC abundance was correlated with lung function, MDSC localisation was performed by immunofluorescence. Peripheral blood mononuclear cell (PBMC) mRNA levels were analysed by qRT-PCR.We detected increased MDSC in IPF and non-IPF ILD compared with controls (30.99±15.61% versus 18.96±8.17%, p≤0.01). Circulating MDSC inversely correlated with maximum vital capacity (r= −0.48, p≤0.0001) in IPF, but not in COPD or non-IPF ILD. MDSC suppressed autologous T-cells. The mRNA levels of co-stimulatory T-cell signals were significantly downregulated in IPF PBMC. Importantly, CD33+CD11b+ cells, suggestive of MDSC, were detected in fibrotic niches of IPF lungs.We identified increased MDSC in IPF and non-IPF ILD, suggesting that elevated MDSC may cause a blunted immune response. MDSC inversely correlate with lung function only in IPF, identifying them as potent biomarkers for disease progression. Controlling expansion and accumulation of MDSC, or blocking their T-cell suppression, represents a promising therapy in IPF.

scholarly journals Microarray based circRNA expression profiles in uremic plasma and PBMCs due to chronic glomerulonephritis

2017 ◽  
Vol 69 (3) ◽  
pp. 523-534 ◽  
Author(s):  
Xi Wang ◽  
Yong Dai ◽  
Wanfan Zhang ◽  
S SunDonglin ◽  
Xinzhou Zhang
Keyword(s):  
Expression Profile ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Differentially Expressed ◽  
Circular Rnas ◽  
Chronic Glomerulonephritis ◽  
Qrt Pcr ◽  
Uremic Patients

Circular RNAs (circRNAs) have been identified in many diseases and shown to play important roles in pathological processes. The expression patterns of circRNA in uremia remains unknown. The aim of this study was to screen circRNA in plasma and peripheral blood mononuclear cells (PBMCs)in healthy controls and patients with uremia due to chronic glomerulonephritis, and to provide evidence for further exploration of the pathogenesis, diagnosis and treatment of uremic patients. Twenty individuals were included in this study, of which 10 were healthy and 10 were patients with uremia caused by chronic glomerulonephritis without systemic lupus erythematosus(SLE). Peripheral blood was collected from each individual in the two groups and the PBMCs were separated. The circRNAs expression profile was examined using a human circRNA microarray. The expression of differently expressed circRNAs was further validated by qRT-PCR. Seven hundred ten circRNAs were differentially expressed in the plasma in the two groups, accounting for 27.58% of the total circRNA(710/2578). Three hundred eighty-five up regulated circRNAs accounted for 14.93% and 325 down regulated circRNAs accounted for 12.60% of the total circRNAs. Additionally, 968 circRNAs were differentially expressed in PBMCs in the two groups, accounting for 29.24% of all circRNAs (968/3310).Six hundred seventy upregulated circRNAs accounted for 20.24% and 298 down regulated circRNAs accounted for 9.00% of the total circRNAs. The results of qRT-PCR validation were consistent with the microarray gene expression results. The expression profile of circRNAs was altered in the plasma and PBMCs of patients with uremia, which suggests that the changed circRNAs may be potential diagnostic biomarkers that play an important role in the pathogenesis of uremic patients. We speculate that hsa_circ_0053958, hsa_circ_0103281 may be associated with the pathogenesis of uremia and may be potential biological molecular markers for the diagnosis and prognosis of uremia.

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

2018 ◽  
Vol 132 (14) ◽  
pp. 1597-1614 ◽  
Author(s):  
Qi-Wen Deng ◽  
Shuo Li ◽  
Huan Wang ◽  
Hui-Ling Sun ◽  
Lei Zuo ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Peripheral Blood Mononuclear Cells ◽  
Roc Curve ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Combination Index ◽  
Expression Patterns ◽  
Peripheral Blood Mononuclear ◽  
Qrt Pcr ◽  
Blood Mononuclear Cells

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.

scholarly journals Expression of Adiponectin Receptors on Peripheral Blood Leukocytes of Hypertensive Children Is Associated with the Severity of Hypertension

2015 ◽  
Vol 2015 ◽  
pp. 1-11 ◽  
Author(s):  
Lidia Gackowska ◽  
Mieczyslaw Litwin ◽  
Joanna Trojanek ◽  
Andrzej Eljaszewicz ◽  
Izabela Kubiszewska ◽  
...  
Keyword(s):  
Protein Expression ◽  
Peripheral Blood ◽  
Expression Patterns ◽  
Intima Media Thickness ◽  
Peripheral Blood Leukocyte ◽  
Carotid Intima Media Thickness ◽  
Serum Adiponectin ◽  
Mrna Levels ◽  
Adiponectin Receptors ◽  
Blood Leukocytes

The aim of the study was to find out whether peripheral blood leukocyte adiponectin receptors 1 and 2 (AdipoR1, AdipoR2) protein expression patterns (flow cytometry) differ between the primary hypertension children (n=57) and healthy controls (n=19) and if their expression levels are related to selected clinical parameters. The group of 26 patients [AdipoR(−)] showed lower and the group of 31 patients [AdipoR(+)] showed higher AdipoRs protein expression than the control and each other (P<0.01for neutrophils,P<0.05for monocytes). The AdipoR(+) leukocytes expressed higher AdipoR1 mRNA levels (RT-PCR) than AdipoR(−) ones and controls (P=0.022andP=0.007, resp.). Despite greater BMI, the AdipoR(−) patients had unchanged serum adiponectin levels. In contrast, AdipoR(+) patients had lower serum adiponectin concentrations than the AdipoR(−) ones and controls (P<0.001). The AdipoR(+) patients had higher blood pressure (P=0.042) and greater carotid intima-media thickness (P=0.017) than the AdipoR(−) ones. The stage of hypertension was associated with increased neutrophil but not monocyte AdipoR1 density (AdipoR1 MFI) (P<0.05). Severe ambulatory hypertension was presented more often in AdipoR(+) patients than in AdipoR(−) ones (51.6% versus 26.9%, resp.;P<0.01). In conclusion, neutrophil AdipoRs upregulation was associated with early stages of vascular injury, hypertension severity, and low serum levels of adiponectin.

scholarly journals The Role of Ferroptosis in Bronchoalveolar Epithelial Cell Injury Induced by Cigarette Smoke Extract

2021 ◽  
Vol 12 ◽  
Author(s):  
Ningfang Lian ◽  
Qiaoxian Zhang ◽  
Jia Chen ◽  
Mengxue Chen ◽  
Jiefeng Huang ◽  
...  
Keyword(s):  
Epithelial Cell ◽  
Cigarette Smoke ◽  
Molecular Mechanisms ◽  
Expression Patterns ◽  
Cigarette Smoke Extract ◽  
Control Group ◽  
Chronic Obstructive ◽  
Mrna Levels ◽  
Qrt Pcr

Background: Cigarette smoking is a major risk factor for bronchoalveolar epithelial cell (BAEC) injury. Understanding the relevant pathogenesis is important for the treatment of cigarette smoke–related chronic airway diseases such as chronic obstructive pulmonary disease.Methods: In this study, BAECs were cultured in 5% cigarette smoke extract (CSE) or regular culture medium for 24 h. Differentially expressed genes (DEGs) were detected by next-generation RNA sequencing (RNA-seq) and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Bioinformatic analysis was performed on DEGs. Co-treated BAECs with 5% CSE and the ferroptosis inhibitor, ferrostatin-1 was applied to observe the role of ferroptosis.Results: In the CSE group, 210 upregulated genes and 159 downregulated genes were identified compared with the control group. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses showed that the DEGs were related to oxidative stress and ferroptosis. Ferroptosis-related genes were further verified by qRT-PCR. The mRNA level of GPX4 decreased; the mRNA levels of ACSL4, FTH1 and SLC7A11 increased (p &lt; 0.05). Pretreatment with the ferroptosis inhibitor ferrostatin-1 mitigated CSE-induced ROS accumulation and inflammatory mediator expression in BAECs (p &lt; 0.05).Conclusion: CSE treatment altered ferroptosis-related gene expression patterns in cultured BAECs. Inhibition of ferroptosis reduced the inflammatory response of CSE-treated BAECs. These data provide a better understanding of the underlying molecular mechanisms of CSE-related lung injury.

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