scholarly journals Diurnal differences in the transcriptome of peripheral blood mononuclear cells in response to a meal

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Rochelle Davis ◽  
Chiara Murgia ◽  
Aimee Dordevic ◽  
Maxine Bonham ◽  
Catherine Huggins

AbstractEating at night has been linked to impaired glucose metabolism and dyslipidaemia that is likely a consequence of an underlying disrupted circadian rhythm in metabolic processes. An understanding of the mechanisms causing metabolic disruption after eating at night is important for prevention and management of disease risk factors. The aim of this study was to explore the transcriptomic differences in nutrient metabolism after eating a meal at night compared with the same meal in the morning. In a cross over design, 10 healthy adults fasted for > 10 hours and then completed two acute meal challenges at 8am and 8pm on non-consecutive days separated by a wash out. Fasting and postprandial blood samples were collected to assess glucose and insulin responses. For a subset of five participants RNA sequencing was completed on the Illumina NextSeq500. Total RNA was extracted from peripheral blood mononuclear cells at fasting (baseline) and 2 h after the test meal, the quality of all samples was above RIN 8 (AATI Fragment Analyzer). Differential expression analysis was completed using the DESeq2 package. False discovery rate correction was applied at the pathway analysis level, conducted in PathVisio. Postprandial blood glucose was significantly higher at 8pm vs. 8am (208.8(154.1)mmol/L.3hr vs 36.4(99.6)mmol/L.3hr, p = 0.005) no concurrent changes in insulin responses were observed (p = 0.100). Under fasting conditions, 704 genes were differentially expressed between morning and night, with 60% of these genes being down regulated at night. The meal challenges were associated with changes in gene expression compared with fasting in the morning 552 genes were differentially expressed and 532 genes were differentially expressed in the evening, however only 7% were commonly differentially regulated at both times of day. Pathway analysis of the differentially expressed genes identified that more immune system and signal transduction pathways were enriched after eating at night compared with morning, where as a greater number of pathways involved in lipid metabolism were enriched in the morning. The time of day a meal is consumed has an effect on which genes are differentially regulated in the acute postprandial period, and the biological pathways they are involved in. Investigating the differences in the transcriptomic response to food at night provides a greater understanding of the mechanisms underlying the phenotypic dissimilarities observed in circulating metabolic biomarkers according to the time of day.

Pathogens ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 43
Author(s):  
Lila M. Zarski ◽  
Patty Sue D. Weber ◽  
Yao Lee ◽  
Gisela Soboll Hussey

Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory disease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell-associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathology results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA sequencing. When comparing transcriptomes of PBMCs during peak viremia to those prior to EHV-1 infection, we found 51 differentially expressed equine genes (48 upregulated and 3 downregulated). After gene ontology analysis, processes such as the interferon defense response, response to chemokines, the complement protein activation cascade, cell adhesion, and coagulation were overrepresented during viremia. Additionally, transcripts for EHV-1, EHV-2, and EHV-5 were identified in pre- and post-EHV-1-infection samples. Looking at micro RNAs (miRNAs), 278 known equine miRNAs and 855 potentially novel equine miRNAs were identified in addition to 57 and 41 potentially novel miRNAs that mapped to the EHV-2 and EHV-5 genomes, respectively. Of those, 1 EHV-5 and 4 equine miRNAs were differentially expressed in PBMCs during viremia. In conclusion, this work expands our current knowledge about the role of PBMCs during EHV-1 viremia and will inform the focus on future experiments to identify host and viral factors that contribute to clinical EHM.


2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Yu Peng ◽  
Xuan Luo ◽  
Yingying Chen ◽  
Linyi Peng ◽  
Chuiwen Deng ◽  
...  

AbstractThe aim of this study was to elucidate the expression profile and the potential role of long non-coding RNA (LncRNA) in the peripheral blood mononuclear cells of primary Sjögren’s syndrome (pSS) patients. RNA-seq technology was used to detect the differentially expressed LncRNAs and mRNAs between five age-and sex-matched paired pSS patients and healthy control PBMCs. The selected LncRNAs were detected in the validation study by RT-qPCR in 16 paired pSS patients and healthy controls. The GO, KEGG, co-localization, and co-expression analysis were performed to enrich the potential gene functions and pathways. In this study, 44 out of 1772 LncRNAs and 1034 out of 15,424 mRNAs were expressed differentially in the PBMCs of pSS patients. LINC00426, TPTEP1-202, CYTOR, NRIR, and BISPR were validated as aberrantly expressed, and these LncRNAs strongly correlated with disease activity of pSS. GO and KEGG pathway analysis revealed the significant enrichment of biological processes, cellular components, and molecular function of the up and down-regulated mRNAs, which were mainly concentrated in the immune response and immune system processes. Co-localization and co-expression analysis also revealed that differentially expressed LncRNAs in the PBMCs of pSS were strongly correlated to the mRNA functioning associated with immune response and cell metastasis. Numerous LncRNAs and mRNAs were found differentially expressed in the PBMCs of pSS patients, especially NRIR and BISPR; they interacted with the co-localized and co-expressed mRNAs, which might participate in the pathogenesis of pSS through the NF-κB, JAK-STAT, and other signaling pathways that regulate cell metastasis.


2019 ◽  
Author(s):  
Maria Paola Pisano ◽  
Olivier Tabone ◽  
Maxime Bodinier ◽  
Nicole Grandi ◽  
Julien Textoris ◽  
...  

AbstractHuman Endogenous Retroviruses (HERVs) and Mammalian apparent LTR-retrotransposons (MaLRs) are retroviral sequences that integrated into the germline cells millions year 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. In this work, we focused on the HERVs/MaLRs expression and modulation in a scenario of immune system activation. We used a public dataset of Human Peripheral Blood Mononuclear Cells (PBMCs) RNA-seq from 15 healthy participants to a clinical trial before and after the 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.ImportanceWe described the HERV and MaLR transcriptome in PBMCs, finding that about 8.4 % of the LTR-retrotransposons loci were expressed, and identifying the betaretrovirus-like HERVs as those with the highest percentage of expressed loci. We found 4,607 HERVs and MaLRs 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 differentially expressed checking their genomic context of insertion and, interestingly, we found a general co-localization with genes that are involved and modulated in the immune response, as consequence of LPS stimulation. The analyses of HERVs and MaLRs expression and modulation show that this 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.


Author(s):  
Wen-Feng Ji ◽  
Jia-Xin Chen ◽  
Shu He ◽  
Ya-Qing Zhou ◽  
Lei Hua ◽  
...  

Objective: Circular RNAs (circRNAs) function as promising biomarkers and therapeutic targets for coronary artery disease due to their high stability, covalently closed structure and potential gene regulation. We aimed to identify the expression profile and role of circular RNAs (circRNAs) in coronary artery disease (CAD). Methods: We performed RNA sequence analysis of circRNAs in peripheral blood mononuclear cells of 5 CAD patients and 5 controls. Bioinformatics analyses was adopted to explore biological functions of differentially expressed circRNAs. The miRanda and TargetScan tools were used to predict the miRNA targeting interactions and to construct a triple network of differentially expressed gene-circRNA-miRNA-mRNA. Results: In total, 13160 downregulated and 12905 upregulated circRNAs were identified in CAD. A gene ontology annotation analysis showed that genes in the network were involved in organelle organization, cell cycle, mitotic cycle and cellular metabolic process. Parental genes of the 10 dysregulated-circRNAs were involved in metabolism and protein modification, and these circRNAs might regulate gene expression associated with CAD via miRNA sponges. Conclusion: As potential ceRNAs, dysregulated circRNAs may be involved in the pathogenesis of CAD, which provides new insights into diagnosis and prognosis of coronary artery disease.


2021 ◽  
Vol 8 ◽  
Author(s):  
Sajad Ahmad Wani ◽  
Amit Ranjan Sahu ◽  
Raja Ishaq Nabi Khan ◽  
Manas Ranjan Praharaj ◽  
Shikha Saxena ◽  
...  

In the present study, healthy goats and sheep (n = 5) that were confirmed negative for peste des petits ruminants virus (PPRV) antibodies by monoclonal antibody-based competitive ELISA and by serum neutralization test and for PPRV antigen by s-ELISA were vaccinated with Sungri/96. A quantitative study was carried out to compare the proteome of peripheral blood mononuclear cells (PBMCs) of vaccinated goat and sheep [5 days post-vaccination (dpv) and 14 dpv] vs. unvaccinated (0 day) to divulge the alteration in protein expression following vaccination. A total of 232 and 915 proteins were differentially expressed at 5 and 14 dpv, respectively, in goats. Similarly, 167 and 207 proteins were differentially expressed at 5 and 14 dpv, respectively, in sheep. Network generated by Ingenuity Pathway Analysis was “infectious diseases, antimicrobial response, and inflammatory response,” which includes the highest number of focus molecules. The bio functions, cell-mediated immune response, and humoral immune response were highly enriched in goats at 5 dpv and at 14 dpv. At the molecular level, the immune response produced by the PPRV vaccine virus in goats is effectively coordinated and stronger than that in sheep, though the vaccine provides protection from virulent virus challenge in both. The altered expression of certain PBMC proteins especially ISG15 and IRF7 induces marked changes in cellular signaling pathways to coordinate host immune responses.


2021 ◽  
Vol 12 ◽  
Author(s):  
Fei Dai ◽  
Quan-Bo Zhang ◽  
Yi-Ping Tang ◽  
Yi-Xi He ◽  
Ting Yi ◽  
...  

Circular RNAs (circRNAs) are non-coding RNAs (ncRNAs) with a single-stranded covalently closed-loop structure, and their abnormal expression may participate in the pathogenesis of various human diseases. Currently, knowledge of circRNAs in gout is limited. In this case-control study, human circRNA microarrays were used to identify differentially expressed circRNAs in peripheral blood mononuclear cells (PBMCs) from patients with primary gout (n = 5) and healthy controls (HC; n = 3). Bioinformatics methods were used to analyze significantly different circRNAs (fold change >1.5, p < 0.05). In addition, four significantly differentially expressed circRNAs were selected for quantitative real-time polymerase chain reaction to detect expression levels in 90 gout patients and 60 HC. Subsequently, circRNA-miRNA-mRNA network was established to predict the function of circRNAs of interest. Microarray analysis indicated that 238 circRNAs were upregulated and 41 circRNAs were down-regulated in the gout group (fold change >1.5, p < 0.05). Bioinformatics analysis showed that differentially expressed circRNAs were involved in the pathogenesis of gout via various pathways. Moreover, the expression levels of hsa_circRNA_103657 and hsa_circRNA_000241 were significantly higher in the gout group than those in the HC group, and both correlated significantly with lipid metabolism parameters. Furthermore, the area under the curve of hsa_circRNA_103657 was 0.801 (95% confidence interval (CI): 0.730–0.871; p < 0.001). Our results provide novel insights into the pathogenesis of primary gout. Differentially expressed circRNAs were identified in the PBMCs of gout patients, and these differential circRNAs may play important roles in the development and progression of gout.


Sign in / Sign up

Export Citation Format

Share Document