scholarly journals Signature transcriptome analysis of stage specific atherosclerotic plaques of patients

2021 ◽  
Author(s):  
SONIA VERMA ◽  
Abhay Kumar ◽  
Rajiv Narang ◽  
Akshay K Bisoi ◽  
Dipendra Mitra
Keyword(s):  
Mirna Expression ◽  
Peripheral Blood ◽  
Early Stage ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Atherosclerotic Plaques ◽  
Altered Expression ◽  
Cabg Surgery ◽  
Mammary Arteries ◽  
Inflammatory Processes

Background: Inflammation plays an important role in all the stages of atherosclerotic plaque development. The current study aimed at assessing the altered expression of genes functioning in inflammation within the early stage (ES) and advanced stage (AS) atherosclerotic plaques obtained from patients undergoing coronary artery bypass grafting (CABG) surgery and identifying biomarker panel/s that may detect the status of plaque stages using peripheral blood samples. Methods: A section of ES and AS plaques and normal left internal mammary arteries (LIMA) were obtained from 8 patients undergoing the CABG surgery. Total RNA isolated was analysed for mRNA and miRNA expression profile by Affymetrix arrays. Significant number of mRNAs was found to be differentially expressed in ES and AS plaque tissues relative to LIMA. The pathway analysis of differentially expressed mRNAs in the two plaque stages was also performed using DAVID Bioinformatics Database. Results: The mRNAs were found to be involved in critical inflammatory processes such as Toll-like receptor signalling pathway and cytokine-cytokine receptor interaction. Few miRNAs targeting these mRNAs were also altered in the two plaque conditions. QRT-PCR results showed similar expression pattern of few of the mRNAs and miRNAs in peripheral blood of same patients relative to healthy controls. Conclusion: Changes in mRNA and miRNA expression associated with various inflammatory processes occur in different atherosclerotic stage plaques as well as peripheral blood. Detection of such variations in patients blood can be used as a possible prognostic tool to detect and/or predict the risk and stage of atherosclerosis.

scholarly journals Comparative transcriptomic analysis of porcine peripheral blood reveals differentially expressed genes from the cytokine–cytokine receptor interaction pathway related to health status

Genome ◽  
2017 ◽  
Vol 60 (12) ◽  
pp. 1021-1028 ◽  
Author(s):  
M.H. Ye ◽  
H. Bao ◽  
Y. Meng ◽  
L.L. Guan ◽  
P. Stothard ◽  
...  
Keyword(s):  
Health Status ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Cytokine Receptor ◽  
Functional Enrichment ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Marker Genes

While some research has looked into the host genetic response in pigs challenged with specific viruses or bacteria, few studies have explored the expression changes of transcripts in the peripheral blood of sick pigs that may be infected with multiple pathogens on farms. In this study, the architecture of the peripheral blood transcriptome of 64 Duroc sired commercial pigs, including 18 healthy animals at entry to a growing facility (set as a control) and 23 pairs of samples from healthy and sick pen mates, was generated using RNA-Seq technology. In total, 246 differentially expressed genes were identified to be specific to the sick animals. Functional enrichment analysis for those genes revealed that the over-represented gene ontology terms for the biological processes category were exclusively immune activity related. The cytokine–cytokine receptor interaction pathway was significantly enriched. Nine functional genes from this pathway encoding members (as well as their receptors) of the interleukins, chemokines, tumor necrosis factors, colony stimulating factors, activins, and interferons exhibited significant transcriptional alteration in sick animals. Our results suggest a subset of novel marker genes that may be useful candidate genes in the evaluation and prediction of health status in pigs under commercial production conditions.

scholarly journals mRNA transcriptome analysis of bone in a mouse model of implant-associated Staphylococcus aureus osteomyelitis

2021 ◽  
Author(s):  
Yihuang Lin ◽  
Jianwen Su ◽  
Yutian Wang ◽  
Daorong Xu ◽  
Xianrong Zhang ◽  
...  
Keyword(s):  
Mouse Model ◽  
Differentially Expressed Genes ◽  
Post Infection ◽  
Early Stage ◽  
Molecular Pathogenesis ◽  
Differentially Expressed ◽  
Transcriptional Analysis ◽  
Receptor Interaction ◽  
Pathological Changes ◽  
Ifn Γ

To investigate the molecular pathogenesis of bone with osteomyelitis, we developed implant-associated osteomyelitis (IAOM) models in mice. An orthopedic stainless pin was surgically placed in the right femoral mid-shaft of mice followed by an inoculation of S. aureus into the medullary cavity. Typical characteristics of IAOM, like periosteal reaction and intra-osseous abscess, occurred by day 14 post-infection. By day 28 post-infection, necrotic abscess, sequestrum formation and deformity of the whole femur were observed. Transcriptional analysis identified 101 and 1,702 differentially expressed genes (DEGs) between groups by days 3 and 14 post-infection, respectively. Analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes revealed the enrichment of pathways in response to bacterium, receptor-ligand activity and chemokine signaling by day 3 post-infection. However, by day 14 post-infection, the enrichment switched to angiogenesis, positive regulation of cell motility and migration, skeletal system development and cytokine-cytokine receptor interaction. Furthermore, protein-protein interaction network analysis identified 4 cytokines (Il6, Cxcl10, IFN-γ and Cxcl9) associated with IAOM at an early stage of infection. Overall, as the pathological changes in this mouse model were consistent with those in human IAOM, our model may be used to investigate the mechanism and treatment of IAOM. Furthermore, the data of transcriptome sequencing and bioinformatic analysis will be an important resource for dissecting the molecular pathogenesis of bone with IAOM. Highlights 1. An implant-associated osteomyelitis (IAOM) mice model was developed. 2. The pathological changes in this mouse model were consistent with those in human IAOM. 3. 101 and 1,702 differentially expressed genes (DEGs) were identified between groups by days 3 and 14 post-infection, respectively. 4. Il6, Cxcl10, IFN-γ and Cxcl9 were screened out as the most important genes associated with early stage IAOM

scholarly journals miRNA Expression Profiles in Luminal A Breast Cancer—Implications in Biology, Prognosis, and Prediction of Response to Hormonal Treatment

2020 ◽  
Vol 21 (20) ◽  
pp. 7691
Author(s):  
Erik Kudela ◽  
Marek Samec ◽  
Lenka Koklesova ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mirna Expression ◽  
Early Stage ◽  
Expression Profiles ◽  
Classification Systems ◽  
Molecular Characteristics ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Altered Expression ◽  
Cancer Subtypes

Breast cancer, which is the most common malignancy in women, does not form a uniform nosological unit but represents a group of malignant diseases with specific clinical, histopathological, and molecular characteristics. The increasing knowledge of the complex pathophysiological web of processes connected with breast cancercarcinogenesis allows the development of predictive and prognostic gene expressionand molecular classification systems with improved risk assessment, which could be used for individualized treatment. In our review article, we present the up-to-date knowledge about the role of miRNAs and their prognostic and predictive value in luminal A breast cancer. Indeed, an altered expression profile of miRNAs can distinguish not only between cancer and healthy samples, but they can classify specific molecular subtypes of breast cancer including HER2, Luminal A, Luminal B, and TNBC. Early identification and classification of breast cancer subtypes using miRNA expression profilescharacterize a promising approach in the field of personalized medicine. A detection of sensitive and specific biomarkers to distinguish between healthy and early breast cancer patients can be achieved by an evaluation of the different expression of several miRNAs. Consequently, miRNAs represent a potential as good diagnostic, prognostic, predictive, and therapeutic biomarkers for patients with luminal A in the early stage of BC.

scholarly journals Proteome Modulation in Peripheral Blood Mononuclear Cells of Peste des Petits Ruminants Vaccinated Goats and Sheep

2021 ◽  
Vol 8 ◽  
Author(s):  
Sajad Ahmad Wani ◽  
Amit Ranjan Sahu ◽  
Raja Ishaq Nabi Khan ◽  
Manas Ranjan Praharaj ◽  
Shikha Saxena ◽  
...  
Keyword(s):  
Immune Response ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Vaccine Virus ◽  
Differentially Expressed ◽  
Peripheral Blood Mononuclear ◽  
Altered Expression ◽  
Virus Challenge ◽  
Blood Mononuclear Cells

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.

Regulation of microRNAs in coronary atherosclerotic plaque

Epigenomics ◽  
2019 ◽  
Vol 11 (12) ◽  
pp. 1387-1397
Author(s):  
Öcal Berkan ◽  
Serdal Arslan ◽  
Torkia Lalem ◽  
Lu Zhang ◽  
Nil Özbilum Şahin ◽  
...  
Keyword(s):  
Atherosclerotic Plaque ◽  
Differentially Expressed ◽  
Arterial Stenosis ◽  
Atherosclerotic Plaques ◽  
Mammary Arteries ◽  
Coronary Atherosclerotic Plaque ◽  
Internal Mammary ◽  
Artery Disease ◽  
High Level ◽  
Novel Therapeutic

Aim: Identification of microRNAs (miRNAs) associated with atherosclerosis may unravel novel therapeutic targets and biomarkers. We studied miRNAs differentially expressed between coronary atherosclerotic plaques (CAP) and healthy arteries. Materials & methods: Paired CAP and internal mammary arteries (IMA) were collected from 14 coronary artery disease patients. The miRNA profiles between diseased (CAP) and healthy (IMA) tissues were compared using microarrays and quantitative PCR. Results: Thirty-one miRNAs were differentially expressed between CAP and IMA. Among these, miR-486-5p showed a high level of regulation (12-fold), had predicted interactions with atherosclerosis-associated genes and correlated with triglyceride levels and arterial stenosis. Regulation of miR-486-5p was validated by PCR (p = 0.004). Conclusion: The miRNAs are regulated in the atherosclerotic plaque. We highlight miR-486-5p whose role in atherosclerosis requires further investigation.

scholarly journals MicroRNA Expression Profile in Peripheral Blood Lymphocytes of Sheep Vaccinated with Nigeria 75/1 Peste Des Petits Ruminants Virus

Viruses ◽  
2019 ◽  
Vol 11 (11) ◽  
pp. 1025
Author(s):  
Yang Yang ◽  
Xiaodong Qin ◽  
Xuelian Meng ◽  
Xueliang Zhu ◽  
Xiangle Zhang ◽  
...  
Keyword(s):  
Expression Profile ◽  
Mirna Expression ◽  
Peripheral Blood ◽  
Antigen Processing ◽  
Time Course ◽  
Expression Patterns ◽  
Small Ruminants ◽  
Vaccine Virus ◽  
Differentially Expressed ◽  
Peste Des Petits Ruminants

Peste des petits ruminants (PPR) is one of the highly contagious transboundary viral diseases of small ruminants. Host microRNA (miRNA) expression patterns may change in response to virus infection, and it mainly works as a post-transcriptional moderator in gene expression and affects viral pathogenesis and replication. In this study, the change of miRNA expression profile in peripheral blood lymphocyte (PBMC) from sheep inoculated with PPR vaccine virus in vivo as well as primary sheep testicular (ST) cells inoculated with PPR vaccine virus in vitro were determined via deep sequencing technology. In PBMC cells, 373 and 115 differentially expressed miRNAs (DEmiRNAs) were identified 3 days and 5 days post inoculated (dpi), respectively. While, 575 DEmiRNAs were identified when comparing miRNA profiles on 5 dpi with 3 dpi. Some of the DEmiRNAs were found to change significantly via time-course during PPR vaccine virus inoculated. Similarly, in ST cells, 136 DEmiRNAs were identified at 3 dpi in comparison with mock-inoculation. A total of 12 DEmiRNAs were validated by real-time quantitative PCR (RT-qPCR). The oar-miR-150, oar-miR-370-3p and oar-miR-411b-3p were found common differentially expressed in both PPR vaccine virus-inoculated PBMC cells and ST cells. Targets prediction and functional analysis of the DEmiRNAs uncovered mainly gathering in antigen processing and presentation pathways, protein processing in endoplasmic reticulum pathways and cell adhesion molecules pathways. Our study supplies information about the DEmiRNAs in PPR vaccine virus-inoculated PBMC cells and ST cells, and provides clues for further understanding the function of miRNAs in PPR vaccine virus replication.

Comparative analysis of gene expression in vascular cells of patients with advanced atherosclerosis

2018 ◽  
Vol 64 (5) ◽  
pp. 416-422
Author(s):  
M.S. Nazarenko ◽  
A.V. Markov ◽  
A.A. Sleptsov ◽  
I.A. Koroleva ◽  
D.V. Sharysh ◽  
...  
Keyword(s):  
Gene Expression ◽  
Signaling Pathway ◽  
Metal Ion ◽  
Cellular Response ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Receptor Interaction ◽  
Atherosclerotic Plaques ◽  
Mammary Arteries ◽  
Significant Gene

In this study we performed a comparative gene expression analysis of carotid arteries in the area of atherosclerotic plaques and healthy internal mammary arteries of patients with advanced atherosclerosis by using microarray HumanHT-12 BeadChip (“Illumina”). The most down-regulated genes were APOD, FABP4, CIDEC and FOSB, and up-regulated gene was SPP1 (|FC|>64; pFDR<0.05). The majority of differentially expressed genes were down-regulated in advanced atherosclerotic plaques. Unexpectedly, genes involved in immune and inflammatory responses were down-regulated in advanced atherosclerotic plaques to compare with the healthy arteries (arachidonic acid metabolism, cytokine-cytokine receptor interaction, NOD-like receptor signaling pathway, Jak-STAT signaling pathway, TNF signaling pathway). “Cellular response to metal ion” (metallothioneins) and “Extracellular matrix organization” were the most significant Gene ontology terms among the down- and up-regulated genes, respectively.

Expression profile of circulating lncRNAs in patients with atrial fibrillation

2019 ◽  
Author(s):  
Zhong-bao Ruan ◽  
Bing-di Gongben ◽  
Ge-cai Chen ◽  
Li Zhu
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Rna Binding ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Molecular Function ◽  
Rt Pcr ◽  
Chip Technology

Abstract Background: Atrial fibrillation (AF) is one of the most common cardiac arrhythmias. However, the exact pathophysiology and mechanisms about AF remains unclear. Accumulating studies have demonstrated that long non-coding RNAs (lncRNAs) play a vital role in the regulation of almost all biological processes. However, relationships between AF and lncRNAs are still unknown. Methods: The peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways. Results: There were 19 lncRNAs differentially expressed (FC ≥ 2, p <0.05), of which 6 were up-regulated and 13 were down-regulated. Two of three upregulated lncRNAs (P=0.014 and 0.006 for HNRNPU-AS1and LINC00861, respectively) and two of three downregulated lncRNAs (P=0.028 and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT‐PCR. And showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen and cytoplasm et al. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding and molecular function et al. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include Calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction and Toll-like receptor signaling pathway, etc. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks. Conclusions: The expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play a important role in the pathophysiology and mechanisms of AF.

scholarly journals Identification of Circulating lncRNA Expression Profiles in Patients with Atrial Fibrillation

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Zhong-bao Ruan ◽  
Fei Wang ◽  
Bing-di Gongben ◽  
Ge-cai Chen ◽  
Li Zhu
Keyword(s):  
Atrial Fibrillation ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Peripheral Blood ◽  
Rna Binding ◽  
Expression Profiles ◽  
Differentially Expressed ◽  
Receptor Interaction ◽  
Molecular Function ◽  
Rt Pcr

Purpose. To investigate the expression profiles of long noncoding RNAs (lncRNAs) in patients with atrial fibrillation (AF). Methods. The peripheral blood monocytes of a total of 20 patients with AF and 20 healthy subjects were collected for gene chip technology to detect differentially expressed lncRNAs from 2017.01 to 2017.08. Reverse transcription polymerase chain reaction (RT-PCR) was applied for further verification. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to identify the functions of differentially expressed genes and related pathways. Results. There were 19 lncRNAs differentially expressed ( FC ≥ 2 , P < 0.05 ), of which 6 were upregulated and 13 were downregulated. Two of three upregulated lncRNAs ( P = 0.014 and 0.006 for HNRNPU-AS1 and LINC00861, respectively) and two of three downregulated lncRNAs ( P = 0.028 and 0.032 for RP11-443B7.3 and CTD-2616J11.14, respectively) were randomly confirmed by RT-PCR and showed a significantly different expression with the RNA-seq results. GO analysis showed that differentially expressed genes enriched in differentially expressed transcripts in biological process were mainly involved in metabolic process, catabolic process, and biosynthetic process. Differentially expressed transcripts in cellular component were mainly involved in nuclear lumen, organelle lumen, and cytoplasm. Differentially expressed transcripts in molecular function were mainly involved in protein binding, RNA binding, and molecular function. KEGG enrichment pathway analysis showed that some of the enrichment pathways associated with differentially expressed lncRNAs include calcium signaling pathway, NF-kappa B signaling pathway, cytokine-cytokine receptor interaction, and Toll-like receptor signaling pathway. HNRNPU-AS1 was the highest positive correlated lncRNA in the networks. Conclusions. The expression of lncRNA in peripheral blood of AF patients is different from that of normal people. The physiological functions of these differentially expressed lncRNAs may be related to the pathogenesis of AF, which provide experimental basis and new therapeutic target for prognosis and treatment of patients with AF. HNRNPU-AS1 may play an important role in the pathophysiology and mechanisms of AF.

scholarly journals 3D Cell Culture-Based Global miRNA Expression Analysis Reveals miR-142-5p as a Theranostic Biomarker of Rectal Cancer Following Neoadjuvant Long-Course Treatment

Biomolecules ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 613 ◽  
Author(s):  
Linas Kunigenas ◽  
Vaidotas Stankevicius ◽  
Audrius Dulskas ◽  
Elzbieta Budginaite ◽  
Gediminas Alzbutas ◽  
...  
Keyword(s):  
Cell Adhesion ◽  
Cell Lines ◽  
Mirna Expression ◽  
Molecular Mechanisms ◽  
Tumor Tissue ◽  
Differentially Expressed ◽  
Altered Expression ◽  
Expression Levels ◽  
3D Microenvironment ◽  
Long Course

Altered expression of miRNAs in tumor tissue encourages the translation of this specific molecular pattern into clinical practice. However, the establishment of a selective biomarker signature for many tumor types remains an inextricable challenge. For this purpose, a preclinical experimental design, which could maintain a fast and sensitive discovery of potential biomarkers, is in demand. The present study suggests that the approach of 3D cell cultures as a preclinical cancer model that is characterized to mimic a natural tumor environment maintained in solid tumors could successfully be employed for the biomarker discovery and validation. Subsequently, in this study, we investigated an environment-dependent miRNA expression changes in colorectal adenocarcinoma DLD1 and HT29 cell lines using next-generation sequencing (NGS) technology. We detected a subset of 16 miRNAs differentially expressed in both cell lines cultivated in multicellular spheroids compared to expression levels in cells grown in 2D. Furthermore, results of in silico miRNA target analysis showed that miRNAs, which were differentially expressed in both cell lines grown in MCS, are involved in the regulation of molecular mechanisms implicated in cell adhesion, cell-ECM interaction, and gap junction pathways. In addition, integrins and platelet-derived growth factor receptors were determined to be the most significant target genes of deregulated miRNAs, which was concordant with the environment-dependent gene expression changes validated by RT-qPCR. Our results revealed that 3D microenvironment-dependent deregulation of miRNA expression in CRC cells potentially triggers essential molecular mechanisms predominantly including the regulation of cell adhesion, cell–cell, and cell–ECM interactions important in CRC initiation and development. Finally, we demonstrated increased levels of selected miR-142-5p in rectum tumor tissue samples after neoadjuvant long course treatment compared to miR-142-5p expression levels in tumor biopsy samples collected before the therapy. Remarkably, the elevation of miR-142-5p expression remained in tumor samples compared to adjacent normal rectum tissue as well. Therefore, the current study provides valuable insights into the molecular miRNA machinery of CRC and proposes a potential miRNA signature for the assessment of CRC in further clinical research.

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