scholarly journals Inflexibility of the plasma miRNA response following a high-carbohydrate meal in overweight insulin-resistant women

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
F. Ramzan ◽  
R. F. D’Souza ◽  
B. R. Durainayagam ◽  
A. M. Milan ◽  
N. C. Roy ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Trial Registration ◽  
Healthy Weight ◽  
Peripheral Blood Mononuclear ◽  
Insulin Resistant ◽  
High Carbohydrate ◽  
Metabolic Inflexibility ◽  
Carbohydrate Meal

Abstract Context Metabolic inflexibility is a characteristic of insulin resistance, limiting the ability to transiently regulate oxidative metabolism and gene expression in response to nutrient availability. Little is known of the flexibility of post-transcriptional regulation, including circulatory miRNAs (c-miRNAs). Design The abundances of targeted c-miRNAs, with reported functions in metabolic regulation, were analysed in response to a high-carbohydrate meal in healthy weight insulin-sensitive (IS) and overweight insulin-resistant (IR) women. Participants Age-matched healthy weight IS (n = 20, BMI = 24.3 ± 0.70) and overweight IR (n = 20, BMI = 28.6 ± 0.67) women. Methods An abundance of c-miRNAs was quantified prior to and following a high-carbohydrate breakfast meal (2500 kJ; 50% carbohydrate, 20% fat and 27% protein). Target genes of the differentially regulated c-miRNA were measured in RNA extracted from circulatory peripheral blood mononuclear cells (PBMCs). Results In healthy weight IS women, both miR-15a-5p (p = 0.03) and miR-17-5p (p < 0.01) levels were halved at 4 h post-meal. These miRNA remained unaltered following the same meal in the overweight IR women. Furthermore, amongst genes targeted by these miRNA, CPT1A (p = 0.01) and IL8 (p = 0.03) had also reduced expression 4 h post-meal only in the healthy weight IS women. Conclusions The study findings provide preliminary evidence for a possible extension of metabolic inflexibility to include c-miRNAs. Trial registration The clinical trial is registered with Australian New Zealand Clinical Trials Registry under Trial registration: ANZCTR: ACTRN12615001108505. Registered on 21 October 2015.

Proteomic Analysis of Peripheral Blood Mononuclear Cells after a High-Fat, High-Carbohydrate Meal with Orange Juice

2017 ◽  
Vol 16 (11) ◽  
pp. 4086-4092 ◽  
Author(s):  
Daniela F. S. Chaves ◽  
Paulo C. Carvalho ◽  
Elisa Brasili ◽  
Marcelo M. Rogero ◽  
Neuza A. Hassimotto ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Orange Juice ◽  
Proteomic Analysis ◽  
Mononuclear Cells ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
High Carbohydrate ◽  
Blood Mononuclear Cells ◽  
Carbohydrate Meal

scholarly journals DBC1, p300, HDAC3, and Siah1 coordinately regulate ELL stability and function for expression of its target genes

2020 ◽  
Vol 117 (12) ◽  
pp. 6509-6520 ◽  
Author(s):  
Subham Basu ◽  
Mahesh Barad ◽  
Dipika Yadav ◽  
Arijit Nandy ◽  
Bidisha Mukherjee ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Rna Polymerase Ii ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Elongation Factor ◽  
Diabetes Patient ◽  
Elongation Complex ◽  
Peripheral Blood Mononuclear ◽  
And Function

Among all of the Super Elongation Complex (SEC) components, ELL1 (also known as ELL) is the only bona fide elongation factor that directly stimulates transcription elongation by RNA polymerase II. However, the mechanism(s) of functional regulation of ELL1 (referred to as ELL hereafter), through its stabilization, is completely unknown. Here, we report a function of human DBC1 in regulating ELL stability involving HDAC3, p300, and Siah1. Mechanistically, we show that p300-mediated site-specific acetylation increases, whereas HDAC3-mediated deacetylation decreases, ELL stability through polyubiquitylation by the E3 ubiquitin ligase Siah1. DBC1 competes with HDAC3 for the same binding sites on ELL and thus increases its acetylation and stability. Knockdown of DBC1 reduces ELL levels and expression of a significant number of genes, including those involved in glucose metabolism. Consistently, Type 2 diabetes patient-derived peripheral blood mononuclear cells show reduced expression of DBC1 and ELL and associated key target genes required for glucose homeostasis. Thus, we describe a pathway of regulating stability and functions of key elongation factor ELL for expression of diverse sets of genes, including ones that are linked to Type 2 diabetes pathogenesis.

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.

Changes in Gene Expression in PBMCs Profiles of PPARα Target Genes in Obese and Non-Obese Individuals During Fasting

2014 ◽  
Vol 66 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Ingrid Felicidade ◽  
Juliana Cristina Marcarini ◽  
Clísia Mara Carreira ◽  
Marla Karine Amarante ◽  
Lydia A. Afman ◽  
...  
Keyword(s):  
Gene Expression ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Obese Group ◽  
World Health ◽  
Peripheral Blood Mononuclear ◽  
Expression Levels ◽  
Patients With Diabetes ◽  
Health Organization

Background: The prevalence of obesity has risen dramatically and the World Health Organization estimates that 700 million people will be obese worldwide by 2015. Approximately, 50% of the Brazilian population above 20 years of age is overweight, and 16% is obese. Aim: This study aimed to evaluate the differences in the expression of PPARα target genes in human peripheral blood mononuclear cells (PBMCs) and free fatty acids (FFA) in obese and non-obese individuals after 24 h of fasting. We first presented evidence that Brazilian people exhibit expression changes in PPARα target genes in PBMCs under fasting conditions. Methods: Q-PCR was utilized to assess the mRNA expression levels of target genes. Results: In both groups, the FFA concentrations increased significantly after 24 h of fasting. The basal FFA mean concentration was two-fold higher in the obese group compared with the non-obese group. After fasting, all genes evaluated in this study showed increased expression levels compared with basal expression in both groups. Conclusion: However, our results reveal no differences in gene expression between the obese and non-obese, more studies are necessary to precisely delineate the associated mechanisms, particularly those that include groups with different degrees of obesity and patients with diabetes mellitus type 2 because the expression of the main genes that are involved in β-oxidation and glucose level maintenance are affected by these factors. © 2014 S. Karger AG, Basel

scholarly journals Decreased miR-4512 Levels in Monocytes and Macrophages of Individuals With Systemic Lupus Erythematosus Contribute to Innate Immune Activation and Neutrsophil NETosis by Targeting TLR4 and CXCL2

2021 ◽  
Vol 12 ◽  
Author(s):  
Binbin Yang ◽  
Xinwei Huang ◽  
Shuangyan Xu ◽  
Li Li ◽  
Wei Wu ◽  
...  
Keyword(s):  
Systemic Lupus Erythematosus ◽  
Lupus Erythematosus ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Therapeutic Potential ◽  
Luciferase Reporter ◽  
Systemic Lupus ◽  
Peripheral Blood Mononuclear ◽  
Monocytes And Macrophages

ObjectiveSystemic lupus erythematosus (SLE) is an autoimmune disease with complex etiology that is not yet entirely understood. We aimed to elucidate the mechanisms and therapeutic potential of microRNAs (miRNAs) in SLE in a Tibetan population.MethodsPeripheral blood mononuclear cells from SLE patients (n = 5) and healthy controls (n = 5) were used for miRNA–mRNA co-sequencing to detect miRNAs related to immune abnormalities associated with SLE. Luciferase reporter assay was used to identify potential targets of candidate miRNA. The target genes were verified in miRNA-agomir/antagomir transfection assays with multiple cells lines and by expression analysis. The effects of candidate miRNA on monocyte and macrophage activation were evaluated by multiple cytokine profiling. Neutrophil extracellular traps (NETs) formation was analyzed in vitro by cell stimulation with supernatants of monocytes and macrophages transfected with candidate miRNA. The rodent MRL/lpr lupus model was used to evaluate the therapeutic effect of CXCL2Ab on SLE and the regulation effect of immune disorders.ResultsIntegrated miRNA and mRNA expression profiling identified miRNA-4512 as a candidate miRNA involved in the regulation of neutrophil activation and chemokine-related pathways. MiR-4512 expression was significantly reduced in monocytes and macrophages from SLE patients. MiR-4512 suppressed the TLR4 pathway by targeting TLR4 and CXCL2. Decreased monocyte and macrophage miR-4512 levels led to the expression of multiple proinflammatory cytokines in vitro. Supernatants of miR-4512 antagomir-transfected monocytes and macrophages significantly promoted NETs formation (P &lt; 0.05). Blocking of CXCL2 alleviated various pathogenic manifestations in MRL/lpr mice, including kidney damage and expression of immunological markers of SLE.ConclusionsWe here demonstrated the role of miR-4512 in innate immunity regulation in SLE. The effect of miR-4512 involves the regulation of monocytes, macrophages, and NETs formation by direct targeting of TLR4 and CXCL2, indicating the miR-4512-TLR4-CXCL2 axis as a potential novel therapeutic target in SLE.

scholarly journals Restored lncRNAs After ART Therapy Have Potential Key Roles in the Recovery From AIDS

2021 ◽  
Author(s):  
Yingying Zhou ◽  
Yuqing Huang ◽  
Tielong Chen ◽  
Wenjia Hu ◽  
Xiaoping Chen ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Differential Expression ◽  
Art Therapy ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Expression Profiles ◽  
Effective Control ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Hiv Pathogenesis

Abstract Background: Many studies have shown that long noncoding RNAs (lncRNAs) derived from the host and human immunodeficiency virus (HIV) itself play important roles in virus-host interactions and viral pathogenesis. To identify potential key lncRNAs in the regulation of HIV pathogenesis, transcriptome analysis of peripheral blood mononuclear cells (PBMCs), which were derived from 6 HIV/acquired immunodeficiency syndrome (AIDS) subjects pre-HAART and post-HAART with effective control of plasma viremia (<20 HIV RNA copies/ml) and 6 healthy subjects, was performed by RNA sequencing (RNA-seq).Results: We identified a total of 974 lncRNAs whose expression levels were restored to normal after ART therapy. The results of the cis-acting analysis showed that only six lncRNAs have cis-regulated target genes, among which the target gene RP11-290F5.1, interferon regulatory factors 2 (IRF2), could promote HIV replication. We also identified lncRNA CTB-119C2.1, which regulates most mRNAs with differential expression between pre- and post-HAART, and the differences were significant. We selected lncRNA CTB-119C2.1 for qRT–PCR verification, and the results were consistent with those of RNA-seq. RAB3A and GADD45A, two of the lncRNA CTB-119C2.1-associated genes, have been shown to be associated with HIV infection. KEGG analysis of lncRNA CTB-119C2.1-associated genes revealed that most of the genes are involved in the p53 signaling pathway or pathways related to cell circulation and DNA replicationConclusion: In this study, we used RNA-seq to systematically compare the expression profiles of lncRNAs in HIV subjects between untreated and treated time points. We successfully identified some lncRNAs with differential expression during certain periods (no HIV infection, HIV infection before treatment, and after treatment). Their expression is associated with viral loads, and some of their regulating genes were found to be involved in HIV pathogenesis through bioinformatic analysis. These findings could help to reveal the underlying molecular mechanism of the progression of AIDS.

PhosSNPs-Regulated Gene Network and Pathway Significant for Rheumatoid Arthritis

2021 ◽  
pp. 1-11
Author(s):  
Pei He ◽  
Fei Jiang ◽  
Wei Guo ◽  
Yu-Fan Guo ◽  
Shu-Feng Lei ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Oxidative Phosphorylation ◽  
Protein Phosphorylation ◽  
Gene Network ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Peripheral Blood Mononuclear ◽  
Chinese Sample ◽  
Oxidative Phosphorylation Pathway ◽  
Public Datasets

<b><i>Objectives:</i></b> Peripheral blood mononuclear cells (PBMCs) are critical for immunity and participate in multiple human diseases, including rheumatoid arthritis (RA). PhosSNPs are nonsynonymous SNPs influencing protein phosphorylation, thus probably modulate cell signaling and gene expression. We aimed to identify phosSNPs-regulated gene network/pathway potentially significant for RA. <b><i>Methods:</i></b> We collected genome-wide phosSNP genotyping data and transcriptome-wide mRNA expression data from PBMCs of a Chinese sample. We discovered and verified with public datasets differentially expressed genes (DEGs) associated with RA, and replicated RA-associated SNPs in our study sample. We performed a targeted expression quantitative trait locus (eQTL) study on significant phosSNPs and DEGs. <b><i>Results:</i></b> We identified 29 nominally significant eQTL phosSNPs and 83 target genes, and constructed comprehensive regulatory/interaction networks, highlighting the vital effects of two eQTL phosSNPs (rs371513 and rs4824675, FDR &#x3c;0.05) and four critical node genes (HSPA4, NDUFA2, MRPL15, and ATP5O). Besides, two node/key genes NDUFA2 and ATP5O, regulated by rs371513, were significantly enriched in mitochondrial oxidative phosphorylation pathway. Besides, four pairs of eQTL effects were replicated independently in whole blood and/or transformed fibroblasts. <b><i>Conclusions:</i></b> The findings delineated a potential role of protein phosphorylation and genetic variations in RA and warranted the significant roles of phosSNPs in regulating RA-associated genes expression in PBMCs. The results pointed out the relevance and significance of oxidative phosphorylation pathway to RA.

scholarly journals Molecular characterization of atherosclerosis in HIV positive persons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Adam Cornwell ◽  
Rohith Palli ◽  
Meera V. Singh ◽  
Lauren Benoodt ◽  
Alicia Tyrell ◽  
...  
Keyword(s):  
Mirna Expression ◽  
Regulatory Networks ◽  
Target Genes ◽  
Mononuclear Cells ◽  
People Living With Hiv ◽  
Data Types ◽  
Peripheral Blood Mononuclear ◽  
Bicarbonate Transporter ◽  
Persons Living With Hiv ◽  
Living With Hiv

AbstractPeople living with HIV are at higher risk of atherosclerosis (AS). The pathogenesis of this risk is not fully understood. To assess the regulatory networks involved in AS we sequenced mRNA of the peripheral blood mononuclear cells (PBMCs) and measured cytokine and chemokine levels in the plasma of 13 persons living with HIV and 12 matched HIV-negative persons with and without AS. microRNAs (miRNAs) are known to play a role in HIV infection and may modulate gene regulation to drive AS. Hence, we further assessed miRNA expression in PBMCs of a subset of 12 HIV+ people with and without atherosclerosis. We identified 12 miRNAs differentially expressed between HIV+ AS+ and HIV+ , and validated 5 of those by RT-qPCR. While a few of these miRNAs have been implicated in HIV and atherosclerosis, others are novel. Integrating miRNA measurements with mRNA, we identified 27 target genes including SLC4A7, a critical sodium and bicarbonate transporter, that are potentially dysregulated during atherosclerosis. Additionally, we uncovered that levels of plasma cytokines were associated with transcription factor activity and miRNA expression in PBMCs. For example, BACH2 activity was associated with IL-1β, IL-15, and MIP-1α. IP10 and TNFα levels were associated with miR-124-3p. Finally, integration of all data types into a single network revealed increased importance of miRNAs in network regulation of the HIV+ group in contrast with increased importance of cytokines in the HIV+ AS+ group.

scholarly journals Altered Expressions of miR-1238-3p, miR-494, miR-6069, and miR-139-3p in the Formation of Chronic Brucellosis

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Ferah Budak ◽  
Salih Haldun Bal ◽  
Gulcin Tezcan ◽  
Halis Akalın ◽  
Guher Goral ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Target Genes ◽  
Mononuclear Cells ◽  
Acute Infection ◽  
Mapk Signaling ◽  
Receptor Interaction ◽  
Chronic Infections ◽  
Peripheral Blood Mononuclear ◽  
Mirna Array ◽  
Chemokine Signaling

Brucellosis is a zoonotic disease that is still endemic in developing countries. Despite early diagnosis and treatment of patients, chronic infections are seen in 10–30% of patients. In this study, we aimed to investigate the immunological factors that play roles in the transition of brucellosis from acute infection into chronic infection. Here, more than 2000 miRNAs were screened in peripheral blood mononuclear cells (PBMCs) of patients with acute or chronic brucellosis and healthy controls by using miRNA array, and the results of the miRNA array were validated through qRT-PCR. Findings were evaluated using GeneSpring GX (Agilent) 13.0 software and KEGG pathway analysis. Four miRNAs were expressed in the chronic group but were not expressed in acute and control groups. Among these miRNAs, the expression level of miR-1238-3p was increased while miR-494, miR-6069, and miR-139-3p were decreased (p<0.05, fold change > 2). These miRNAs have the potential to be markers for chronic cases. The differentially expressed miRNAs and their predicted target genes involved in endocytosis, regulation of actin cytoskeleton, MAPK signaling pathway, and cytokine-cytokine receptor interaction and its chemokine signaling pathway indicate their potential roles in chronic brucellosis and its progression. It is the first study of miRNA expression analysis of human PBMC to clarify the mechanism of inveteracy in brucellosis.

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