scholarly journals Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease

Antioxidants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 28
Author(s):  
Lee E. Neilson ◽  
Joseph F. Quinn ◽  
Nora E. Gray
Keyword(s):  
Clinical Trials ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Related Factor ◽  
Peripheral Blood Mononuclear ◽  
Duration Of Action ◽  
Nrf2 Activation ◽  
Health And Disease

Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.

Circulating soluble RAGE and cell surface RAGE on peripheral blood mononuclear cells in healthy children

2018 ◽  
Vol 31 (6) ◽  
pp. 649-654 ◽  
Author(s):  
Alberto García-Salido ◽  
Gustavo Melen ◽  
Vanesa Gómez-Piña ◽  
Gonzalo Oñoro-Otero ◽  
Ana Serrano-González ◽  
...  
Keyword(s):  
Negative Correlation ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Adult Population ◽  
Critical Role ◽  
Enzyme Linked Immunosorbent Assay ◽  
Healthy Children ◽  
Peripheral Blood Mononuclear ◽  
Srage Level ◽  
Soluble Rage

Abstract Background: The receptor for advanced glycation end products (RAGE) has a critical role in the pathogenesis of inflammation. In healthy children, its basal expression on the peripheral blood mononuclear cell (PBMC) and the basal circulating soluble RAGE (sRAGE) levels are unknown. The aim of this study was to describe both. Methods: This is a monocentric, observational and descriptive study of samples obtained from healthy children. The RAGE expression on PBMC was analyzed using flow cytometry. The sRAGE values were determined with a specific sandwich enzyme-linked immunosorbent assay (ELISA) kit, later the relation between cellular RAGE and sRAGE was described. Results: Forty-three children were included. The median sRAGE level was 849.0±579.0 pg/mL. The RAGE mean fluorescence intensity (MFI) was 1382±506 in monocytes and 792±506 in lymphocytes. There were no differences between genders. A negative correlation was found between sRAGE and RAGE MFI in lymphocytes (r=−0.3; p=0.04). Conclusions: We describe for the first time the RAGE surface levels on PBMC in children. It showed a negative correlation with sRAGE. The sRAGE circulating level is lower than the sRAGE level described in adult population or non-healthy children. Our findings should be confirmed in order to apply them as reference values for future investigations.

The Expression of miRNA-146a in Peripheral Blood Mononuclear Cells of Patients with Myasthenia Gravis and Its Bioinformatics Analysis

2019 ◽  
Vol 9 (12) ◽  
pp. 1670-1675
Author(s):  
Pan Huang ◽  
Xiao-Ying He ◽  
Min Xu
Keyword(s):  
Myasthenia Gravis ◽  
Signaling Pathways ◽  
Peripheral Blood ◽  
Target Gene ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Kegg Pathway ◽  
Control Group ◽  
Pathway Enrichment Analysis ◽  
Peripheral Blood Mononuclear

The study is to investigate the expression of miRNA-146a in PBMC of myasthenia Gravis (MG), and to explore the molecular regulatory network of miRNA-146a in the pathogenesis of MG by bioinformatics. 108 patients with MG were selected as the experimental group (MG group), and 50 healthy subjects were selected as the control group. The relative expression of miRNA-146a in PBMC was detected by RT-PCR. The cross-target gene of miRNA-146a was predicted by TargetScan and CoMeTa database. miRNA-146a target gene GO enrichment and KEGG Pathway enrichment analysis was performed using the DAVID database. Our results shows that the expression level of miRNA-146a in peripheral blood of MG patients was significantly higher than that of the control group, the difference was statistically significant (P < 0 05), and the nucleotide sequence was highly conserved. The potential target genes of miRNA-146a include 88 kinds; GO analysis showed that miRNA-146a target gene function is mainly enriched in cell proliferation regulation, neuronal differentiation, etc. KEGG Pathway analysis shows that miRNA-146a is mainly enriched in Toll-like receptor signaling pathway, neurotransmitter regulatory signaling pathways, EB signaling pathways and other signaling pathways. In conclusion, the expression of miRNA-146a in PBMC of MG patients is up-regulated and participates in the pathogenesis of MG by acting on multiple signaling pathways.

Immune dysregulation in peripheral blood mononuclear cells from patients with liver cancer.

2018 ◽  
Vol 36 (5_suppl) ◽  
pp. 55-55
Author(s):  
Juhua Zhou
Keyword(s):  
Liver Cancer ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Immune Cell ◽  
Critical Role ◽  
Immune Dysregulation ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Underlying Mechanisms

55 Background: Immune regulation may play an important role in cancer development. The immune dysregulation and underlying mechanisms in patients with liver cancer have not fully understood. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from patients with liver cancer. Deep-sequencing, FACS analysis, ELISA and real-time PCR were used to analyze the immune dysregulation and underlying mechanisms in patients with liver cancer. Results: Our analysis discovered that the percentages of immune cell populations in PBMC from patients with liver cancer were significantly different from those in normal controls. Specifically, the percents of B cells and regulatory T cells were high in PBMC from patients with liver cancer. Expression of 161 genes such as EGF, IRF3, CD177, MAP2K2 and MMP9 was found to be significantly inhibited, but 66 genes including CD19, CD70, FOXP1 and IL-32 were significantly up-regulated in PBMC from patients with liver cancer. Further analysis showed that 190 long non-coding RNAs (lncRNAs) were significantly down-regulated; whereas150 lncRNAs were significantly up-regulated in PBMC from patients with liver cancer. Dysregulated lncRNAs were involved in the control of immune cell signaling, cell division and differentiation. Conclusions: The results suggest that the immune dysregulation may play a critical role in the pathogenesis of liver cancer. It also has a great implication in the development of immune therapeutic methods for patients with liver cancer.

scholarly journals Substantial Improvements in Performance Indicators Achieved in a Peripheral Blood Mononuclear Cell Cryopreservation Quality Assurance Program Using Single Donor Samples

2006 ◽  
Vol 14 (1) ◽  
pp. 52-59 ◽  
Author(s):  
Wayne B. Dyer ◽  
Sarah L. Pett ◽  
John S. Sullivan ◽  
Sean Emery ◽  
David A. Cooper ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Quality Assurance ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
High Standard ◽  
Direct Access ◽  
Quality Assurance Program ◽  
Improve Performance ◽  
High Quality ◽  
Peripheral Blood Mononuclear

ABSTRACT Storage of high-quality cryopreserved peripheral blood mononuclear cells (PBMC) is often a requirement for multicenter clinical trials and requires a reproducibly high standard of practice. A quality assurance program (QAP) was established to assess an Australia-wide network of laboratories in the provision of high-quality PBMC (determined by yield, viability, and function), using blood taken from single donors (human immunodeficiency virus [HIV] positive and HIV negative) and shipped to each site for preparation and cryopreservation of PBMC. The aim of the QAP was to provide laboratory accreditation for participation in clinical trials and cohort studies which require preparation and cryopreservation of PBMC and to assist all laboratories to prepare PBMC with a viability of >80% and yield of >50% following thawing. Many laboratories failed to reach this standard on the initial QAP round. Interventions to improve performance included telephone interviews with the staff at each laboratory, two annual wet workshops, and direct access to a senior scientist to discuss performance following each QAP round. Performance improved substantially in the majority of sites that initially failed the QAP (P = 0.002 and P = 0.001 for viability and yield, respectively). In a minority of laboratories, there was no improvement (n = 2), while a high standard was retained at the laboratories that commenced with adequate performance (n = 3). These findings demonstrate that simple interventions and monitoring of PBMC preparation and cryopreservation from multiple laboratories can significantly improve performance and contribute to maintenance of a network of laboratories accredited for quality PBMC fractionation and cryopreservation.

scholarly journals Coding and non-coding RNA interactions reveal immune-related pathways in peripheral blood mononuclear cells derived from patients with proliferative vitreoretinopathy

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Yao Ni ◽  
Fangyuan Liu ◽  
Xiao Hu ◽  
Yingyan Qin ◽  
Zhaotian Zhang
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Proliferative Vitreoretinopathy ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Differentially Expressed ◽  
Prognostic Indicators ◽  
Related Factors ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Abstract Background Peripheral immune response has been revealed to play a critical role in proliferative vitreoretinopathy (PVR). However, the reliable immune-related factors that are acting as prognostic indicators or therapeutic targets for PVR remain to explore further. Methods In the current study, we applied whole-transcriptome sequencing to profile peripheral blood mononuclear cells from PVR patients and also analyzed lncRNA-mRNA interactions in peripheral immune cells to explore the pathways that might mediate immunopathology and resultant retinal damage in PVR. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and Ingenuity Pathway Analysis (IPA) were employed to classify the function of these differentially expressed genes. Results Compared to the controls, there were 319 genes upregulated, and 191 genes downregulated in PVR patients. GO, and KEGG enrichment analyses as well as IPA showed that these upregulated genes were significantly enriched in immune-related and infection-relate terms. Immune-related gene NFKBIA, CXCL2, and CXCL8 were detected as hub-genes in the co-expression network, while lncRNAs such as AC007032.1, AC037198.2, AL929472.2, and SLED1 were highly co-expressed with them. lncRNA-mRNA interactions analysis also showed that putative targeted genes of these differentially expressed lncRNAs were also significantly enriched in immune-related or infection-relate pathways. Conclusion Our study highlights the transformation of immune-related genes/pathways in PVR by comparing controls, and validates several critical genes and lncRNAs, which are serving as potential diagnostic markers for PVR patients.

scholarly journals Dysregulation of circRNA Expression in the Peripheral Blood of Individuals With Schizophrenia and Bipolar Disorder

2021 ◽  
Author(s):  
Ebrahim Mahmoudi ◽  
Melissa J. Green ◽  
Murray Cairns
Keyword(s):  
Bipolar Disorder ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Circular Rna ◽  
Control Group ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Rna Transcripts ◽  
Behavioural Syndromes

Abstract Circular RNA (circRNA) are head-to-tail back-spliced RNA transcripts that have been linked to several biological processes and their perturbation is evident in human diseases, including neurological disorders. There is also emerging research suggesting circRNA expression may also be altered in psychiatric and behavioural syndromes. Here, we provide a comprehensive analysis of circRNA expression in peripheral blood mononuclear cells (PBMCs) from 39 patients with schizophrenia and bipolar disorder as well as 20 healthy individuals using deep RNA-seq. We observed systematic alternative splicing leading to a complex and diverse profile of RNA transcripts including 8,762 high confidence circRNAs. More specific scrutiny of the circular transcriptome in schizophrenia and bipolar disorder, compared to a non-psychiatric control group, revealed significant dysregulation of 55 circRNAs with a bias towards downregulation. These molecules were predicted to interact with a large number of miRNAs that target genes enriched in psychiatric disorders. Further replication and cross validation to determine the specificity of these circRNAs across broader diagnostic groups and subgroups in psychiatry will enable their potential utility as biomarkers to be established.

scholarly journals Regulatory T Cells and Their Prognostic Relevance in Hematologic Malignancies

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Giovanni D’Arena ◽  
Candida Vitale ◽  
Marta Coscia ◽  
Agostino Festa ◽  
Nicola Matteo Dario Di Minno ◽  
...  
Keyword(s):  
T Cells ◽  
Regulatory T Cells ◽  
Peripheral Blood ◽  
Hematological Malignancies ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Prognostic Significance ◽  
Hematologic Malignancies ◽  
Published Data ◽  
Peripheral Blood Mononuclear

Regulatory T cells (Tregs) have a fundamental function in monitoring the immune homeostasis in healthy individuals. In cancer and, in particular, in hematological malignancies, Tregs exert a major immunosuppressive activity, thus playing a critical role in tumor cell growth, proliferation, and survival. Here, we summarize published data on the prognostic significance of Tregs in hematological malignancies and show that they are highly conflicting. The heterogeneity of the experimental approaches that were used explains—at least in part—the discordant results reported by different groups that have investigated the role of Tregs in cancer. In fact, different tissues have been studied (i.e., peripheral blood, bone marrow, and lymph node), applying different methods (i.e., flow cytometry versus immunohistochemistry, whole blood versus isolated peripheral blood mononuclear cells versus depletion of CD25+ cells, various panels of monoclonal antibodies, techniques of fixation and permeabilization, and gating strategies). This is of relevance in order to stress the need to apply standardized approaches in the study of Tregs in hematological malignancies and in cancer in general.

MicroRNA profiling of human myeloid angiogenic cells derived from peripheral blood mononuclear cells

2020 ◽  
Vol 98 (2) ◽  
pp. 203-207
Author(s):  
Qiuwang Zhang ◽  
Anthony Cannavicci ◽  
Si-Cheng Dai ◽  
Chenxi Wang ◽  
Michael J.B. Kutryk
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Mirna Signature ◽  
Array Analysis ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Qpcr Array

Human myeloid angiogenic cells (MACs), also termed early endothelial progenitor cells, play an important role in neovascularization and vascular repair. MicroRNAs (miRNAs) are a class of naturally occurring, noncoding, short (∼22 nucleotides), single-stranded RNAs that regulate gene expression post-transcriptionally. MiRNAs have been shown to regulate MAC function. A miRNA signature of MACs was described approximately a decade ago, and many new miRNAs have been discovered in recent years. In this study, we aimed to provide an up-to-date miRNA signature for human MACs. MACs were obtained by culture of human peripheral blood mononuclear cells in endothelial medium for 7 days. Using qPCR array analysis we identified 72 highly expressed miRNAs (CT value < 30) in human MACs. RT–qPCR quantification of select miRNAs revealed a strong correlation between the CT values detected by the array analysis and RT–qPCR, suggesting the miRNA signature generated by the qPCR array assay is accurate and reliable. Experimentally validated target genes of the 10 most highly expressed miRNAs were retrieved. Only a few of the targets and their respective miRNAs have been studied for their role in MAC biology. Our study therefore provides a valuable repository of miRNAs for future exploration of miRNA function in MACs.

scholarly journals Current Landscape of NRF2 Biomarkers in Clinical Trials

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 716 ◽  
Author(s):  
Yoko Yagishita ◽  
Tonibelle N. Gatbonton-Schwager ◽  
Melissa L. McCallum ◽  
Thomas W. Kensler
Keyword(s):  
Clinical Trials ◽  
Target Genes ◽  
Critical Role ◽  
Dimethyl Fumarate ◽  
Related Factor ◽  
Oxidative Stress Biomarkers ◽  
Cellular Redox ◽  
Nrf2 Pathway ◽  
Drug Candidates ◽  
Carcinogen Metabolism

The transcription factor NF-E2 p45-related factor 2 (NRF2; encoded by NFE2L2) plays a critical role in the maintenance of cellular redox and metabolic homeostasis, as well as the regulation of inflammation and cellular detoxication pathways. The contribution of the NRF2 pathway to organismal homeostasis is seen in many studies using cell lines and animal models, raising intense attention towards targeting its clinical promise. Over the last three decades, an expanding number of clinical studies have examined NRF2 inducers targeting an ever-widening range of diseases. Full understanding of the pharmacokinetic and pharmacodynamic properties of drug candidates rely partly on the identification, validation, and use of biomarkers to optimize clinical applications. This review focuses on results from clinical trials with four agents known to target NRF2 signaling in preclinical studies (dimethyl fumarate, bardoxolone methyl, oltipraz, and sulforaphane), and evaluates the successes and limitations of biomarkers focused on expression of NRF2 target genes and others, inflammation and oxidative stress biomarkers, carcinogen metabolism and adduct biomarkers in unavoidably exposed populations, and targeted and untargeted metabolomics. While no biomarkers excel at defining pharmacodynamic actions in this setting, it is clear that these four lead clinical compounds do touch the NRF2 pathway in humans.

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