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.

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.

scholarly journals Autologous Peripheral Blood Mononuclear Cells for Limb Salvage in Diabetic Foot Patients with No-Option Critical Limb Ischemia

2021 ◽  
Vol 10 (10) ◽  
pp. 2213
Author(s):  
Alessia Scatena ◽  
Pasquale Petruzzi ◽  
Filippo Maioli ◽  
Francesca Lucaroni ◽  
Cristina Ambrosone ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Critical Limb Ischemia ◽  
Diabetic Foot ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Limb Ischemia ◽  
Control Group ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Peripheral blood mononuclear cells (PBMNCs) are reported to prevent major amputation and healing in no-option critical limb ischemia (NO-CLI). The aim of this study is to evaluate PBMNC treatment in comparison to standard treatment in NO-CLI patients with diabetic foot ulcers (DFUs). The study included 76 NO-CLI patients admitted to our centers because of CLI with DFUs. All patients were treated with the same standard care (control group), but 38 patients were also treated with autologous PBMNC implants. Major amputations, overall mortality, and number of healed patients were evaluated as the primary endpoint. Only 4 out 38 amputations (10.5%) were observed in the PBMNC group, while 15 out of 38 amputations (39.5%) were recorded in the control group (p = 0.0037). The Kaplan–Meier curves and the log-rank test results showed a significantly lower amputation rate in the PBMNCs group vs. the control group (p = 0.000). At two years follow-up, nearly 80% of the PBMNCs group was still alive vs. only 20% of the control group (p = 0.000). In the PBMNC group, 33 patients healed (86.6%) while only one patient healed in the control group (p = 0.000). PBMNCs showed a positive clinical outcome at two years follow-up in patients with DFUs and NO-CLI, significantly reducing the amputation rate and improving survival and wound healing. According to our study results, intramuscular and peri-lesional injection of autologous PBMNCs could prevent amputations in NO-CLI diabetic patients.

scholarly journals RNA-Seq Transcriptome Analysis Reveals Long Terminal Repeat Retrotransposon Modulation in Human Peripheral Blood Mononuclear Cells after In Vivo Lipopolysaccharide Injection

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Maria Paola Pisano ◽  
Olivier Tabone ◽  
Maxime Bodinier ◽  
Nicole Grandi ◽  
Julien Textoris ◽  
...  
Keyword(s):  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Ltr Retrotransposon ◽  
Ltr Retrotransposons ◽  
Rna Seq ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

ABSTRACT Human endogenous retroviruses (HERVs) and mammalian apparent long terminal repeat (LTR) retrotransposons (MaLRs) are retroviral sequences that integrated into germ line cells millions of years ago. Transcripts of these LTR retrotransposons are present in several tissues, and their expression is modulated in pathological conditions, although their function remains often far from being understood. Here, we focused on the HERV/MaLR expression and modulation in a scenario of immune system activation. We used a public data set of human peripheral blood mononuclear cells (PBMCs) RNA-Seq from 15 healthy participants to a clinical trial before and after exposure to lipopolysaccharide (LPS), for which we established an RNA-Seq workflow for the identification of expressed and modulated cellular genes and LTR retrotransposon elements. IMPORTANCE We described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4% of the LTR retrotransposon loci were expressed and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERV and MaLR loci that were modulated as a result of in vivo stimulation with LPS. The HERV-H group showed the highest number of differentially expressed most intact proviruses. We characterized the HERV and MaLR loci as differentially expressed, checking their genomic context of insertion and observing a general colocalization with genes that are involved and modulated in the immune response, as a consequence of LPS stimulation. The analyses of HERV and MaLR expression and modulation show that these LTR retrotransposons are expressed in PBMCs and regulated in inflammatory settings. The similar regulation of HERVs/MaLRs and genes after LPS stimulation suggests possible interactions of LTR retrotransposons and the immune host response.

scholarly journals The circular RNA landscape in specific peripheral blood mononuclear cells of critically ill patients with sepsis

Critical Care ◽  
2020 ◽  
Vol 24 (1) ◽  
Author(s):  
Hina N. Khan ◽  
Xanthe Brands ◽  
Simona Aufiero ◽  
Arie J. Hoogendijk ◽  
Augustijn M. Klarenbeek ◽  
...  
Keyword(s):  
Critically Ill ◽  
Peripheral Blood Mononuclear Cells ◽  
Critically Ill Patients ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Circular Rna ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

scholarly journals Defective HIV-1 proviruses produce viral proteins

2020 ◽  
Vol 117 (7) ◽  
pp. 3704-3710 ◽  
Author(s):  
Hiromi Imamichi ◽  
Mindy Smith ◽  
Joseph W. Adelsberger ◽  
Taisuke Izumi ◽  
Francesca Scrimieri ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Viral Proteins ◽  
Open Reading Frames ◽  
Peripheral Blood Mononuclear ◽  
Hiv Rna ◽  
Rna Transcripts ◽  
Extracellular Virus ◽  
Hiv 1

HIV-1 proviruses persist in the CD4+ T cells of HIV-infected individuals despite years of combination antiretroviral therapy (cART) with suppression of HIV-1 RNA levels <40 copies/mL. Greater than 95% of these proviruses detected in circulating peripheral blood mononuclear cells (PBMCs) are referred to as “defective” by virtue of having large internal deletions and lethal genetic mutations. As these defective proviruses are unable to encode intact and replication-competent viruses, they have long been thought of as biologically irrelevant “graveyard” of viruses with little significance to HIV-1 pathogenesis. Contrary to this notion, we have recently demonstrated that these defective proviruses are not silent, are capable of transcribing novel unspliced forms of HIV-RNA transcripts with competent open reading frames (ORFs), and can be found in the peripheral blood CD4+ T cells of patients at all stages of HIV-1 infection. In the present study, by an approach of combining serial dilutions of CD4+ T cells and T cell–cloning technologies, we are able to demonstrate that defective proviruses that persist in HIV-infected individuals during suppressive cART are translationally competent and produce the HIV-1 Gag and Nef proteins. The HIV-RNA transcripts expressed from these defective proviruses may trigger an element of innate immunity. Likewise, the viral proteins coded in the defective proviruses may form extracellular virus-like particles and may trigger immune responses. The persistent production of HIV-1 proteins in the absence of viral replication helps explain persistent immune activation despite HIV-1 levels below detection, and also presents new challenges to HIV-1 eradication.

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