scholarly journals Identification of upregulated NF-κB inhibitor alpha and IRAK3 targeting lncRNA following intracranial aneurysm rupture-induced subarachnoid hemorrhage

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Wei Leng ◽  
Dan Fan ◽  
Zhong Ren ◽  
Qiaoying Li
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Intracranial Aneurysm ◽  
Signaling Pathway ◽  
Aneurysm Rupture ◽  
Cytokine Receptor ◽  
Gene Set Enrichment Analysis ◽  
Receptor Interaction ◽  
Regulatory Pathways ◽  
Ruptured Intracranial Aneurysm ◽  
Neurotrophin Signaling

Abstract Background This study was performed to identify genes and lncRNAs involved in the pathogenesis of subarachnoid hemorrhage (SAH) from ruptured intracranial aneurysm (RIA). Methods Microarray GSE36791 was downloaded from Gene Expression Omnibus (GEO) database followed by the identification of significantly different expressed RNAs (DERs, including lncRNA and mRNA) between patients with SAH and healthy individuals. Then, the functional analyses of DEmRNAs were conducted and weighted gene co-expression network analysis (WGCNA) was also performed to extract the modules associated with SAH. Following, the lncRNA-mRNA co-expression network was constructed and the gene set enrichment analysis (GSEA) was performed to screen key RNA biomarkers involved in the pathogenesis of SAH from RIA. We also verified the results in a bigger dataset GSE7337. Results Totally, 561 DERs, including 25 DElncRNAs and 536 DEmRNAs, were identified. Functional analysis revealed that the DEmRNAs were mainly associated with immune response-associated GO-BP terms and KEGG pathways. Moreover, there were 6 modules significantly positive-correlated with SAH. The lncRNA-mRNA co-expression network contained 2 lncRNAs (LINC00265 and LINC00937) and 169 mRNAs. The GSEA analysis showed that these two lncRNAs were associated with three pathways (cytokine-cytokine receptor interaction, neurotrophin signaling pathway, and apoptosis). Additionally, IRAK3 and NFKBIA involved in the neurotrophin signaling pathway and apoptosis while IL1R2, IL18RAP and IL18R1 was associated with cytokine-cytokine receptor interaction pathway. The expression levels of these genes have the same trend in GSE36791 and GSE7337. Conclusion LINC00265 and LINC00937 may be implicated with the pathogenesis of SAH from RIA. They were involved in three important regulatory pathways. 5 mRNAs played important roles in the three pathways.

Abstract WMP30: Circulating MicroRNAs as Potential Novel Diagnostic Biomarkers for Ruptured Intracranial Aneurysm

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Zhang Xin ◽  
Liu L Ping
Keyword(s):  
Intracranial Aneurysm ◽  
Target Genes ◽  
Bioinformatic Analysis ◽  
Aneurysm Rupture ◽  
Pathological Process ◽  
Differentially Expressed ◽  
Diagnostic Biomarkers ◽  
Ruptured Intracranial Aneurysm ◽  
Novel Biomarkers ◽  
Aneurysm Development

Background and Objective: MicroRNAs have been shown to regulate in several pathological process of intracranial aneurysms. The study aimed to estimate whether miRNAs have the potential to become novel biomarkers for intracranial aneurysm rupture. Materials and methods Forty-five ruptured intracranial aneurysm patients were enrolled according to the inclusion criteria, meanwhile thirty-five healthy individuals were recruited in this study. Differentially expressed plasma miRNA profiles were screened in five pairs of patients and controls in microarray study. Then validation was performed in the rest of the objects using quantitative real-time PCR assays. Results: Fourteen significantly changed miRNAs were screened out from patients with aneurysms compared with healthy controls. More than three thousand target genes related to these disregulated miRNAs were found and bioinformatic analysis revealed that these miRNA were involved in intracranial aneurysm development and rupture. Ultimately four miRNAs from screening profile and one supplementary miRNA were demonstrated to be significantly altered. Conclusion: We demonstrated that several miRNAs were differentially expressed among ruptured aneurysm patients and healthy participants, and plasma miRNAs may be novel diagnostic biomarkers in intracranial aneurysm rupture.

scholarly journals The Role of Circular RNA CDR1as/ciRS-7 in Regulating Tumor Microenvironment: A Pan-Cancer Analysis

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 429 ◽  
Author(s):  
Zou ◽  
Zheng ◽  
Deng ◽  
Yang ◽  
Xie ◽  
...  
Keyword(s):  
Tumor Microenvironment ◽  
Signaling Pathway ◽  
Malignant Tumors ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Circular Rna ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Receptor Interaction

Circular RNA CDR1as/ciRS-7 functions as an oncogenic regulator in various cancers. However, there has been a lack of systematic and comprehensive analysis to further elucidate its underlying role in cancer. In the current study, we firstly performed a bioinformatics analysis of CDR1as among 868 cancer samples by using RNA-seq datasets of the MiOncoCirc database. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), CIBERSORT, Estimating the Proportion of Immune and Cancer cells (EPIC), and the MAlignant Tumors using Expression data (ESTIMATE) algorithm were applied to investigate the underlying functions and pathways. Functional enrichment analysis suggested that CDR1as has roles associated with angiogenesis, extracellular matrix (ECM) organization, integrin binding, and collagen binding. Moreover, pathway analysis indicated that it may regulate the TGF-β signaling pathway and ECM-receptor interaction. Therefore, we used CIBERSORT, EPIC, and the ESTIMATE algorithm to investigate the association between CDR1as expression and the tumor microenvironment. Our data strongly suggest that CDR1as may play a specific role in immune and stromal cell infiltration in tumor tissue, especially those of CD8+ T cells, activated NK cells, M2 macrophages, cancer-associated fibroblasts (CAFs) and endothelial cells. Generally, systematic and comprehensive analyses of CDR1as were conducted to shed light on its underlying pro-cancerous mechanism. CDR1as regulates the TGF-β signaling pathway and ECM-receptor interaction to serve as a mediator in alteration of the tumor microenvironment.

scholarly journals The role of andrographolide and its derivative in COVID-19 associated proteins and immune system

2020 ◽  
Author(s):  
Yadu Nandan Dey ◽  
Pukar Khanal ◽  
B. M. Patil ◽  
Manish M. Wanjari ◽  
Bhavana Srivast ◽  
...  
Keyword(s):  
Immune System ◽  
Signaling Pathway ◽  
Immune Modulation ◽  
Killer Cell ◽  
Mapk Signaling ◽  
Binding Energies ◽  
Gene Set Enrichment Analysis ◽  
Spike Protein ◽  
Network Pharmacology ◽  
Receptor Interaction

Abstract Aim: In view of the strong immunomodulatory and antiviral activity of andrographolide and its derivative, the present study aimed to investigate the binding affinities of andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide with 3 major targets of COVID-19 i.e. 3CLpro, PLpro and spike protein followed by their gene-set enrichment analysis with special reference to immune modulation.Materials and methods: SMILES of the compounds were retrieved from DigepPred database and the proteins identified were queried in STRING to evaluate the protein-protein interaction and modulated pathways were identified concerning the KEGG database. Drug-likeness and ADMET profiles were evaluated using MolSoft and admet SAR 2.0, respectively. Molecular docking was carried using autodock 4.0.Results: Andrographolide and 14-Deoxy-11,12-didehydroandrographolide were predicted to have a high binding affinity with papain-like protease i.e. -6.7 kcal/mol and -6.5 kcal/mol, respectively while they interact with equal binding energies with 3clpro (-6.8 kcal/mol) and spike protein (-6.9 kcal/mol). Network pharmacology analysis revealed that both compounds modulated the immune system through the regulation of chemokine signaling pathway, Rap1 signaling pathway, Cytokine-cytokine receptor interaction, MAPK signaling pathway, NF-kappa B signaling pathway, Rassignaling pathway, p53 signaling pathway, HIF-1 signaling pathway, and Natural killer cell-mediated cytotoxicity. Although the 14-deoxy-11,12-didehydroandrographolide scored higher drug-likeness character, it showed less potency to interaction with targeted proteins of COVID-19.Conclusion: The study suggests the strong interaction of the andrographolide and its derivative 14-deoxy-11,12-didehydroandrographolide against target proteins associated with COVID-19. Further, network pharmacology analysis elucidated the different pathways of immunomodulation. However, clinical research should be conducted to confirm the current findings.

scholarly journals INHBB Is a Novel Prognostic Biomarker Associated with Cancer-Promoting Pathways in Colorectal Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Jinpeng Yuan ◽  
Aosi Xie ◽  
Qiangjian Cao ◽  
Xinxin Li ◽  
Juntian Chen
Keyword(s):  
Colorectal Cancer ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Transforming Growth Factor ◽  
Cox Regression ◽  
Prognostic Biomarker ◽  
Disease Free Survival ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Receptor Interaction

Background. Inhibin subunit beta B (INHBB) is a protein-coding gene that participated in the synthesis of the transforming growth factor-β (TGF-β) family members. The study is aimed at exploring the clinical significance of INHBB in patients with colorectal cancer (CRC) by bioinformatics analysis. Methods. Real-time PCR and analyses of Oncomine, Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases were utilized to evaluate the INHBB gene transcription level of colorectal cancer (CRC) tissue. We evaluated the INHBB methylation level and the relationship between expression and methylation levels of CpG islands in CRC tissue. The corresponding clinical data were obtained to further explore the association of INHBB with clinical and survival features. In addition, Gene Set Enrichment Analysis (GSEA) was performed to explore the gene ontology and signaling pathways of INHBB involved. Results. INHBB expression was elevated in CRC tissue. Although the promoter of INHBB was hypermethylated in CRC, methylation did not ultimately correlate with the expression of INHBB. Overexpression of INHBB was significantly and positively associated with invasion depth, distant metastasis, and TNM stage. Cox regression analyses and Kaplan-Meier survival analysis indicated that high expression of INHBB was correlated with worse overall survival (OS) and disease-free survival (DFS). GSEA showed that INHBB was closely correlated with 5 cancer-promoting signaling pathways including the Hedgehog signaling pathway, ECM receptor interaction, TGF-β signaling pathway, focal adhesion, and pathway in cancer. INHBB expression significantly promoted macrophage infiltration and inhibited memory T cell, mast cell, and dendritic cell infiltration. INHBB expression was positively correlated with stromal and immune scores of CRC samples. Conclusion. INHBB might be a potential prognostic biomarker and a novel therapeutic target for CRC.

Abstract WP353: Assessing the Accuracy of ICD-10 Codes for Ruptured Intracranial Aneurysm Location

Stroke ◽  
2020 ◽  
Vol 51 (Suppl_1) ◽  
Author(s):  
Christopher Roark ◽  
Sheila Kubes ◽  
David Mayer ◽  
Laura K Wiley
Keyword(s):  
Subarachnoid Hemorrhage ◽  
Aneurysmal Subarachnoid Hemorrhage ◽  
Significant Risk ◽  
Significant Risk Factor ◽  
Aneurysm Rupture ◽  
Administrative Database ◽  
Risk Modeling ◽  
Billing Data ◽  
Ruptured Intracranial Aneurysm ◽  
Advanced Analysis

The adoption of ICD10 in October 2015 offers important opportunities for administrative database and EHR-based aneurysm research as it includes more than twenty distinct codes for subarachnoid hemorrhage (SAH), for the first time labeling the specific location for common sites of aneurysm rupture. Aneurysm location is a significant risk factor for rupture, but was not specified in any previous ICD classification. This has limited the value of “big-data” research for aneurysm risk modeling. Currently, it is not clear how frequently - or accurately - the codes are being used in practice. This study reviewed three years of records (10/2015-9/2018) from the UCHealth system in Colorado to assess the accuracy and utility of these codes for stroke research. Over this time, ICD10 codes for SAH (I60.x) were used a total of 5,090 times in 1,842 patients. After removing non-aneurysmal SAH (I60.8), the majority (92.7%) of the codes had no location specified (I60.7, I60.9). Of the codes with a location (I60.00-I60.6), upon review of the clinical record 9 (2.5%) did not have any evidence of subarachnoid hemorrhage, 3 (0.8%) did not have an aneurysm, and 5 (1.4%) had a pseudoaneurysm. Of the 338 verified instances of aneurysmal subarachnoid hemorrhage, 82 (24%) had multiple aneurysms and were excluded from further analysis. Within those records that had only a single aneurysm 197/256 (77%) had the location coded correctly. Of the 23% that were incorrectly coded, 1 was coded as the correct artery on the wrong side, all remaining (n=58) were the wrong artery. Although ICD10 codes offers the possibility of more advanced analysis due to the inclusion of aneurysm location, based on these data, we found that codes specifying location are frequently incorrect. Future studies are needed to validate these findings in other settings. However, researchers should be cautious about their ability to detect aneurysm location from administrative billing data using ICD10 location mapping.

Differential Gene Signature and Signaling Pathways in Childhood Burkitt (BL) vs Diffuse Large B-Cell Lymphoma (DLBCL).

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4142-4142
Author(s):  
Nancy S. Day ◽  
Janet Ayello ◽  
Ian Waxman ◽  
Evan Shereck ◽  
Catherine McGuinn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cell Lines ◽  
Expression Profiles ◽  
B Cell Lymphoma ◽  
Cytokine Receptor ◽  
Receptor Interaction ◽  
Signal Pathways ◽  
Type I

Abstract The prognosis and treatment of both major forms of advanced childhood B-NHL (BL and DLBCL) is similar with short and intensive multi-agent chemotherapy (Cairo/Patte et al., Blood, 2007 and Patte/Cairo et al., Blood, 2007). Despite both BL and DLBCL being germinal center derived, our recent cytogenetic results of BL vs DLBCL in the FAB LMB 96 study have demonstrated significant differences in secondary chromosomal aberrations in BL vs DLBCL and a differential prognosis based on secondary cytogenetic findings (Poirel/Cairo/Patte, Blood, 2003a). Thus, we sought to identify genes that could uniquely differentiate childhood BL vs DLBCL and discover potential genetic mechanisms of differential molecular pathogenesis and to determine the signal pathways that contribute to the genetic disparity between these two histological types of childhood B-NHL. Nine BL (7 patient samples and 2 cell lines, Raji and Ramos) and 3 DLBCL (1 patient sample and 2 cell lines, Pfeiffer and DB) were compared. Total RNA was isolated, reverse transcribed to cDNA biotinylated cRNA and hybridized to Affymetrix U133A_2 as we have previously described (Jiang/Cairo et al., Journal of Immunology, 2004). Data were analyzed using Agilent GeneSpring 7.3. Signal intensities were compared using one way ANOVA and Welch Test for statistical analysis. Two-fold changes between BL and DLBCL were considered as significant (p<0.05). KEGG Pathways were evaluated for the genes identified. There were 120 genes over-expressed and 217 genes under-expressed in BL vs DLBCL. BL expressed significantly higher level of Ki-67 (a measure of lymphoma-cell proliferation) than DLBCL (2.68F). BL also expressed higher level of the pro-apoptotic gene, p53 compared to DLBCL (1.46F). Over-expressed genes in BL vs DLBCL included TNFSF10 (11.87F), RHOQ (3.16F), PIP5K1B (5.22F) among many others. The genes significantly under-expressed in BL vs DLBCL included PIGL (0.45F), Inositol (myo)-1 (or 4)-monophosphatase 1 (IMPA1; 0.28F), cAMP-dependent regulatory type I, alpha protein kinase (PRKAR1A; 0.37F) among many others. TNFSF10 induces apoptosis in transformed and tumor cells and is known to participate in pathways including cytokine-cytokine receptor interaction and induction of apoptosis through DR3 and DR4/5 death receptors. PIP5K1B is involved in the Rho signaling pathway and PIGL catalyzes the second step of glycosylphosphatidylinositol (GPI) biosynthesis. Since activation of IL3R-mediated cAMP-dependent protein kinase leads to increased cell survival, we searched gene expression profiles in BL vs DLBCL that were involved in IL signaling pathways. The genes that were identified to be over-expressed in BL vs DLBCL included IL2RG (2.24F), IL8RB, IL18 receptor accessory protein (IL18RAP), IL18, IL18R1, and IL1R2 (natural log values of 11.11, 22.95, 2.16, 1.73 and 11.84, respectively in BL vs non-detectable values in DLBCL). Taken together, since IL1, IL2, IL8, and IL18 all belong to IL1 super family, these results suggest significant involvement of TNF (TRAIL) and IL1 super family via cytokine-cytokine receptor interaction and activation of the Rho signaling pathway in Burkitt vs DLBCL lymphomagenesis.

scholarly journals Expression profiles of long noncoding RNAs and messenger RNAs in the border zone of myocardial infarction in rats

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Qingkun Meng ◽  
Zhijun Sun ◽  
Hui Gu ◽  
Jiaying Luo ◽  
Jingjing Wang ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Signaling Pathway ◽  
Expression Profiles ◽  
Noncoding Rnas ◽  
Long Noncoding Rnas ◽  
Cytokine Receptor ◽  
Border Zone ◽  
Receptor Interaction ◽  
Messenger Rnas ◽  
Chromosomal Distribution

Abstract Background The participation of long noncoding RNAs (lncRNAs) in myocardial infarction has recently been noted. However, their underlying roles in the border zone of myocardial infarction remain unclear. This study uses microarrays to determine the profiles of lncRNAs and mRNAs in the border zone. Methods Bioinformatics methods were employed to uncover their underlying roles. Highly dysregulated lncRNAs was further validated via PCR. Results Four hundred seven lncRNAs and 752 mRNAs were upregulated, while 132 lncRNAs and 547 mRNAs were downregulated in the border zone of myocardial infarction. A circos graph was constructed to visualize the chromosomal distribution and classification of the dysregulated lncRNAs and mRNAs. The upregulated mRNAs in the border zone were most highly enriched in cytokine activity, binding, cytokine receptor binding and related processes, as ascertained through Go analysis. Pathway analysis of the upregulated mRNAs showed the most significant changes were in the TNF signaling pathway, cytokine–cytokine receptor interaction and chemokine signaling pathway and similar pathways and interactions. An lncRNA–mRNA co-expression network was established to probe into the underlying functions of the 10 most highly dysregulated lncRNAs based on their co-expressed mRNAs. In the co-expression network, we found 16 genes directly involved in myocardial infarction, including Alox5ap, Itgb2 and B4galt1. The lncRNAs AY212271, EF424788 and MRAK088538, among others, might be associated with myocardial infarction. BC166504 is probably a key lncRNA in the border zone of myocardial infarction. Conclusions The results may have revealed some aberrantly expressed lncRNAs and mRNAs that contribute to the underlying pathophysiological mechanisms of myocardial infarction.

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