scholarly journals SAT0008 INDIVIDUAL FUNCTIONS OF THE HISTONE-ACETYLTRANSFERASES CBP AND P300 IN REGULATING THE INFLAMMATORY RESPONSE BY AFFECTING HISTONE ACETYLATION AND MRNA STABILITY

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 934.1-934
Author(s):  
M. Krosel ◽  
M. Gabathuler ◽  
K. Walker ◽  
M. Tomsic ◽  
O. Distler ◽  
...  
Keyword(s):  
Inflammatory Response ◽  
Signaling Pathway ◽  
Mrna Stability ◽  
Biological Process ◽  
Enrichment Analysis ◽  
Histone Acetyltransferases ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Research Support ◽  
Pathway Enrichment

Background:Prolonged TNF-induced H3K27 acetylation (H3K27ac) and increased mRNA stability in rheumatoid arthritis (RA) synovial fibroblasts (SF) are leading to a sustained inflammatory response. Underlying enzymes coordinately regulating these pathways have not been identified so far. The histone acetyltransferases cAMP-response element binding protein binding protein (CBP) and p300 are writers of activating H3K27ac marks and close homologues with widely accepted redundant functions.Objectives:To analyze individual functions of CBP and p300 in regulating the inflammatory response of RA SF.Methods:SF were isolated from patients with RA undergoing joint replacement surgery. The expression of CBP and p300 was silenced by transfection of antisense LNA gapmeRs (12.5 nM). SF were stimulated with TNF (10 ng/ml) for 24h. Actinomycin D (10 µg/ml) was added 4h after TNF-treatment for 2h and 4h (n=3) to test mRNA stability. Transcriptomes were determined by RNA-seq (Illumina NovaSeq 6000, n=6). We mapped raw reads from RNA-seq reference genome using STAR. Counts for genes were obtained using Feature counts. We searched for differential expression genes (DEG) across experimental conditions using general linear models (glm) implemented in ‘edgeR’ package of R. Significantly affected genes (± fold change > 1.5, FDR < 0.05, top 3000 genes included) entered pathway enrichment analysis for Gene Ontology (GO) biological process, and KEGG pathways in DAVID. Changes in the mRNA (n=12-14) and protein expression (n=6-12) were confirmed by quantitative Real-time PCR and ELISA. The levels of activating histone marks H3K27ac and nuclear localization of p50 and p65 were analyzed by Western blotting.Results:DEG revealed that silencing of p300 affected the expression of 6026 and 5138 genes in unstimulated and stimulated SF, respectively. In contrast, only 285 and 1911 genes were affected by CBP silencing in unstimulated and stimulated SF, respectively. In TNF-stimulated SF, pathway enrichment analysis of DEG revealed a key role of CBP in regulating the “type I interferon signaling pathway” (p=2.12x10-6). Both, silencing of CBP and p300 regulated genes enriched in the “TNF signaling pathway” (CBP: p=0.005; p300: p=0.031). In contrast to CBP silencing that had anti-inflammatory effects, silencing of p300 had pro-and anti-inflammatory effects. ELISA experiments suggested that silencing of CBP reduced the secretion of IL6 (p<0.01), CCL2, CXC3L1 (p<0.05), and CXCL12 (p<0.001). Silencing of p300 reduced the secretion of CCL2 (p<0.001) and CXC3L1 (p<0.05) but increased the expression of IL8 (p<0.001) and CXCL2 (p<0.05). Western blotting revealed that neither CBP, nor p300 silencing affected the nuclear expression of the NF-ĸB subunits p65 and p50. Silencing of p300 reduced the levels of H3K27ac by 30% in unstimulated SF, and by 61.4% (p<0.05) in presence of TNF. In addition to regulating H3K27ac, silencing of p300 regulated the expression of TNF-induced cytokines by increasing the mRNA stability of IL8, IL6 and CCL2 mRNA but not of CXCL2. Silencing of CBP reduced H3K27ac by 43.5% only in presence of TNF and did not affect TNF-induced mRNA stability of cytokines. This is in line with the enrichment of the GO biological process “regulation of mRNA stability” (p=2.61x10-8) being enriched only after silencing of p300.Conclusion:Our results suggested that p300 is the major writer for H3K27ac marks in SF. Additionally, p300 regulated cytokine expression by affecting mRNA stability in a target-specific manner. We identified overlapping and distinct functions for CBP and p300 in regulating the inflammatory response of SF.Disclosure of Interests:Monika Krosel: None declared, Marcel Gabathuler: None declared, Kellie Walker: None declared, Matija Tomsic: None declared, Oliver Distler Grant/research support from: Grants/Research support from Actelion, Bayer, Boehringer Ingelheim, Competitive Drug Development International Ltd. and Mitsubishi Tanabe; he also holds the issued Patent on mir-29 for the treatment of systemic sclerosis (US8247389, EP2331143)., Consultant of: Consultancy fees from Actelion, Acceleron Pharma, AnaMar, Bayer, Baecon Discovery, Blade Therapeutics, Boehringer, CSL Behring, Catenion, ChemomAb, Curzion Pharmaceuticals, Ergonex, Galapagos NV, GSK, Glenmark Pharmaceuticals, Inventiva, Italfarmaco, iQvia, medac, Medscape, Mitsubishi Tanabe Pharma, MSD, Roche, Sanofi and UCB, Speakers bureau: Speaker fees from Actelion, Bayer, Boehringer Ingelheim, Medscape, Pfizer and Roche, Caroline Ospelt Consultant of: Consultancy fees from Gilead Sciences., Kerstin Klein: None declared

Systematic Investigation of Quercetin for Treating Cardiovascular Disease Based on Network Pharmacology

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao
Keyword(s):  
Cardiovascular Disease ◽  
Cardiovascular Diseases ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Therapeutic Effects ◽  
Pathway Enrichment ◽  
Compound Target

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.

scholarly journals ­Transcriptome profiling of non-climacteric ‘Yellow’ melon during ripening: insights on sugar metabolism

2020 ◽  
Author(s):  
Michelle Orane Schemberger ◽  
Marília Aparecida Stroka ◽  
Letícia Reis ◽  
Kamila Karoline de Souza Los ◽  
Gillize Aparecida Telles de Araujo ◽  
...  
Keyword(s):  
Cucumis Melo ◽  
Sugar Content ◽  
Sugar Metabolism ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Sucrose Metabolism ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Pathway Enrichment ◽  
Maturation Stages

Abstract Background: The non-climacteric ‘Yellow’ melon ( Cucumis melo , inodorus group) is an economically important crop and its quality is mainly determined by the sugar content. Thus, knowledge of sugar metabolism and its related pathways can contribute to the development of new field management and post-harvest practices, making it possible to deliver better quality fruits to consumers. Results: The RNA-seq associated with RT-qPCR analyses of four maturation stages were performed to identify important enzymes and pathways that are involved in the ripening profile of non-climacteric ‘Yellow’ melon fruit focusing on sugar metabolism. We identified 895 genes 10 days after pollination (DAP)-biased and 909 genes 40 DAP-biased. The KEGG pathway enrichment analysis of these differentially expressed (DE) genes revealed that ‘hormone signal transduction’, ‘carbon metabolism’, ‘sucrose metabolism’, ‘protein processing in endoplasmic reticulum’ and ‘spliceosome’ were the most differentially regulated processes occurring during melon development. In the sucrose metabolism, five DE genes are up-regulated and twelve are down-regulated during fruit ripening. Conclusions: The results demonstrated important enzymes in the sugar pathway that are responsible for the sucrose content and maturation profile in non-climacteric ‘Yellow’ melon. New DE genes were first detected for melon in this study such as invertase inhibitor LIKE 3 ( CmINH3 ), trehalose phosphate phosphatase ( CmTPP1 ) and trehalose phosphate synthases ( CmTPS5 , CmTPS7 , CmTPS9 ). Furthermore, the results of the protein-protein network interaction demonstrated general characteristics of the transcriptome of young and full-ripe melon and provide new perspectives for the understanding of ripening.

scholarly journals ­Transcriptome profiling of non-climacteric ‘Yellow’ melon during ripening: insights on sugar metabolism

2020 ◽  
Author(s):  
Michelle Orane Schemberger ◽  
Marília Aparecida Stroka ◽  
Letícia Reis ◽  
Kamila Karoline de Souza Los ◽  
Gillize Aparecida Telles de Araujo ◽  
...  
Keyword(s):  
Cucumis Melo ◽  
Sugar Content ◽  
Sugar Metabolism ◽  
Enrichment Analysis ◽  
Transcriptome Profiling ◽  
Sucrose Metabolism ◽  
Pathway Enrichment Analysis ◽  
Rna Seq ◽  
Pathway Enrichment ◽  
Maturation Stages

Abstract Background: The non-climacteric ‘Yellow’ melon ( Cucumis melo , inodorus group) is an economically important crop and its quality is mainly determined by the sugar content. Thus, knowledge of sugar metabolism and its related pathways can contribute to the development of new field management and post-harvest practices, making it possible to deliver better quality fruits to consumers. Results: The RNA-seq associated with RT-qPCR analyses of four maturation stages were performed to identify important enzymes and pathways that are involved in the ripening profile of non-climacteric ‘Yellow’ melon fruit focusing on sugar metabolism. We identified 895 genes 10 days after pollination (DAP)-biased and 909 genes 40 DAP-biased. The KEGG pathway enrichment analysis of these differentially expressed (DE) genes revealed that ‘hormone signal transduction’, ‘carbon metabolism’, ‘sucrose metabolism’, ‘protein processing in endoplasmic reticulum’ and ‘spliceosome’ were the most differentially regulated processes occurring during melon development. In the sucrose metabolism, five DE genes are up-regulated and twelve are down-regulated during fruit ripening. Conclusions: The results demonstrated important enzymes in the sugar pathway that are responsible for the sucrose content and maturation profile in non-climacteric ‘Yellow’ melon. New DE genes were first detected for melon in this study such as invertase inhibitor LIKE 3 ( CmINH3 ), trehalose phosphate phosphatase ( CmTPP1 ) and trehalose phosphate synthases ( CmTPS5 , CmTPS7 , CmTPS9 ). Furthermore, the results of the protein-protein network interaction demonstrated general characteristics of the transcriptome of young and full-ripe melon and provide new perspectives for the understanding of ripening.

scholarly journals Integrating Network Pharmacology and Experimental Validation Deciphers the Mechanism of Guizhi Fuling Wan against Adenomyosis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Haoxian Wang ◽  
Jihong Zhang ◽  
Qinqin Zhu ◽  
Xianyun Fu ◽  
Chenjie Li
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Kegg Pathway ◽  
Animal Experiments ◽  
Enrichment Analysis ◽  
Estrogen Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Verification Methods

Aim. This study aimed to predict the key targets and endocrine mechanisms of Guizhi Fuling Wan (GZFLW) in treating adenomyosis (AM) through network pharmacology, molecular docking, and animal experiment verification. Methods. The related ingredients and targets of GZFLW in treating AM were screened out using TCMSP, BATMAN-TCM, SwissTargetPrediction, and PubChem Database. Then, the protein-protein interaction (PPI) analysis and the network of compound-hub targets were constructed. At the same time, the key targets were uploaded to the Metascape Database for KEGG pathway enrichment analysis. After that, the molecular docking technology of the main active components and hub targets was performed. Furthermore, animal experiments were used to verify the results of network pharmacology analysis. Results. A total of 55 active ingredients of GZFLW and 44 overlapping targets of GZFLW in treating AM were obtained. After screening, 25 hub targets were collected, including ESR1, EGF, and EGFR. Then, the KEGG pathway enrichment analysis results indicated that the endocrine therapeutic mechanism of GZFLW against AM is mainly associated with the estrogen signaling pathway, endocrine resistance, and an EGFR tyrosine kinase signaling pathway. Then, molecular docking showed that the significant compounds of GZFLW had a strong binding ability with ERα and EGFR. More importantly, the animal experiments confirmed that the GZFLW could downregulate the abnormal infiltration of the endometrial epithelium into the myometrium and had no interference with the normal sexual cycle. This effect may be directly related to intervening the local estrogen signaling pathway of the endometrial myometrial interface (EMI). It may also be associated with the myometrium cells’ estrogen resistance via GPER/EGFR signaling pathway. Conclusion. The endocrine mechanism of GZFLW in treating AM was explored based on network pharmacology, molecular docking, and animal experiments, which provided a theoretical basis for the clinical application of GZFLW.

scholarly journals LncRNA HOTAIR promotes proliferation and inhibits apoptosis by sponging miR-214-3p in HPV16 positive cervical cancer cells

2021 ◽  
Author(s):  
Yu Zhou ◽  
Yuqing Wang ◽  
Mingying Lin ◽  
Daiqian Wu ◽  
Min Zhao
Keyword(s):  
Cervical Cancer ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Binding Sites ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Pathway Enrichment ◽  
Cervical Cancer Cells ◽  
Lncrna Hotair

Abstract Background Cervical cancer (CC) is one of the most common gynecological malignancies all around the world. The mechanisms of cervical carcinoma formation remain under close scrutiny. The long non-coding RNAs (lncRNA) and microRNAs (miRNAs) play important roles in controlling gene expression and promoting the development and progression of cervical cancer by acting as competitive endogenous RNA (ceRNA). However, the roles of lncRNA associated with ceRNAs in cervical carcinogenesis remains unknown. In this study, the expression of LncRNA HOTAIR was investigated in HPV16 positive cervical cancer cells, the candidate miRNAs and target genes were identified to clarify putative ceRNAs of HOTAIR/miRNA in cervical cancer cells. Methods The proliferate ability of cells was measured by CCK8 and EdU incorporation assays and cell apoptosis was analyzed by flow cytometry. The expression of HOTAIR, miR-214-3p, HPV16 E7 mRNA were detected by qRT-PCR. As for searching for the interaction between miR-214-3p and HOTAIR, the binding sites for miR-214-3p on HOTAIR was predicted by starbase v2.0 database, then dual-luciferase assay was used to verify the binding sites. In addition, Gene Ontology (GO) and protein-protein interaction (PPI) network analysis of target genes of miR-214-3p were performed with bioinformatics analysis. For potential signaling pathway regulated by miR-214-3p, we conducted pathway enrichment analysis by KEGG analysis and obtained key pathways in cervical cancer cells. Results Our results showed that the expression of HOTAIR was up-regulated, while that of miR-214-3p was down-regulated in HPV16-positive cervical cancer cells. The expression status of HPV16 E7 played an important role in regulating the expression of HOTAIR or miR-214-3p in cervical cancer cells. LncRNA HOTAIR knockdown could significantly inhibited cell proliferate ability and promote cellular apoptosis, whereas the inhibition of miR-214-3p expression partially reversed such results. Bioinformatics analysis identified 1451 genes as target genes of miR-214-3p. The Gene ontology (GO) and KEGG Pathway enrichment analysis showed that these target genes were mainly related to regulation of cell communication, protein binding, enzyme binding and transferase activity, and Wnt ligand biogenesis. Pathway enrichment analysis results showed that the predicted target genes were significantly enriched in Wnt/β-catenin signaling pathway. Finally, our results confirmed that miR-214-3p could significantly inhibit β-catenin expression in HPV16 positive cancer cells by qPCR and WB analysis. Conclusion HOTAIR could act as a ceRNA through binding to miR-214-3p, promote cell proliferation and inhibit the apoptosis of HPV16 positive cervical cancer. HOTAIR/miR-214-3p/Wnt/β-catenin signaling pathway might play important roles related with HPV16 positive cervical cancer. Our results provided a new perspective for identifying novel biomarkers for cervical cancer.

Identification of Differentially Expressed Genes and Signaling Pathways Related to Ovarian Endometriosis by Integrated Bioinformatics Analysis

2020 ◽  
Author(s):  
Kainan Lin ◽  
Zhenyan Pan ◽  
Renke He ◽  
Hanchu Wang ◽  
Kai Zhou ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Signaling Pathway ◽  
Differentially Expressed Genes ◽  
Kegg Pathway ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Go Analysis ◽  
Pathway Enrichment

Abstract Purpose: Endometriosis was a common gynecological disease, however, the specific mechanism and the key molecules of endometriosis remained uncertain. This study aimed to single out key genes associated with poor prognosis, and further uncover underlying mechanisms.Methods: Data regarding mRNA expression profiles used in this study were retrieved from the Gene Expression Omnibus (GEO) database, a total of three mRNA expression profiles were included for subsequent analysis (GSE31515, GSE58178 and GSE120103). Then, we conducted Gene Ontology analysis (GO analysis), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and protein-protein interaction (PPI) analysis by the software R.Results: A total of 304 differentially expressed genes (DEGs) between endometriosis tissues and normal endometrium tissues were identified in integrated analysis, including 185 up-regulated genes and 119 down-regulated genes. GO analysis reveals that the DEGs of endometriosis were closely associated with molecular origin of bacteria. KEGG pathway enrichment analysis indicates that the DEGs were mainly involved in AGE-RAGE signaling pathway in diabetic complications. In addition, PPI of these DEGs was visualized by Cytoscape platform with utilization of Search Tool for the Retrieval of Interacting Genes (STRING). PPI analysis identifies 10 potential DEGs-related protein targets, including CCND1, IL6, CCL2, COL1A2, PTGS2, VCAM1, COL3A1, ELN, SERPINE1, HSP90B1. Conclusion: In conclusion, the present study reveals that bacterial contamination, defect of female reproductive system development, retrograde menstruation and the AGE-RAGE signaling pathway may be involved in the development of endometriosis In addition, these identified DEGs may be of clinical significance for the diagnosis and treatment of the endometriosis.

Systematic evaluation of the mechanisms of Mulberry leaf (Morus alba Linne) acting on diabetes based on network pharmacology and molecular docking

2020 ◽  
Vol 23 ◽  
Author(s):  
Qiguo Wu ◽  
Yeqing Hu
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Compounds ◽  
Pathway Network ◽  
Pathway Enrichment ◽  
Mulberry Leaves ◽  
Mulberry Leaf

Background: Diabetes mellitus is one of the most common endocrine metabolic disorder diseases. The application of herbal medicine to control glucose levels and improve insulin action might be a useful approach in the treatment of diabetes. Mulberry leaves (ML) has been reported to exert important activities of anti-diabetic. Objective: In this work, we aimed to explore the multi-targets and multi-pathways regulatory molecular mechanism of Mulberry leaves (ML, Morus alba Linne) acting on diabetes. Methods: Identification of active compounds of Mulberry leaves using Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Bioactive components were screened by FAF-Drugs4 website (Free ADME-Tox Filtering Tool). The targets of bioactive components were predicted from SwissTargetPrediction website, and the diabetes related targets were screened from GeneCards database. The common targets of ML and diabetes are used for Gene Ontology (GO) and pathway enrichment analysis. The visualization networks were constructed by Cytoscape 3.7.1 software. The construction of biological networks were performed to analyze the mechanisms as follows: (1) Compound-Target network; (2) Common target-Compound network; (3) Common targets protein interaction network; (4) Compound-Diabetes protein-protein interactions (PPI) network; (5) Target-Pathway network; (6) Compound-Target-Pathway network. At last, the prediction results of network pharmacology were verified by molecular docking method. Results: 17 active components were obtained by TCMSP database and FAF-Drugs4 website. 51 potential targets (11 common targets and 40 associated indirect targets) were obtained and used to build the PPI network by String database. Furthermore, the potential targets were used to GO and pathway enrichment analysis. 8 key active compounds (quercetin, Iristectorigenin A, 4-Prenylresveratrol, Moracin H, Moracin C, Isoramanone, Moracin E and Moracin D) and 8 key targets (AKT1, IGF1R, EIF2AK3, PPARG, AGTR1, PPARA, PTPN1 and PIK3R1) were obtained to play major roles in Mulberry leaf acting on diabetes. And the signal pathways involved in the mechanisms mainly include AMPK signaling pathway, PI3K-Akt signaling pathway, mTOR signaling pathway, insulin signaling pathway and insulin resistance. The molecular docking results show that the 8 key active compounds have good affinity with the key target of AKT1, and the 5 key targets (IGF1R, EIF2AK3, PPARG, PPARA and PTPN1) have better affinity than AKT1 with the key compound of quercetin. Conclusion: Based on network pharmacology and molecular docking of this work provided an important systematic and visualized basis for further understanding the synergy mechanism of ML acting on diabetes.

scholarly journals Diagnosis of thyroid neoplasm using support vector machine algorithms based on platelet RNA-seq

Endocrine ◽  
2020 ◽  
Author(s):  
Yuling Shen ◽  
Yi Lai ◽  
Dong Xu ◽  
Le Xu ◽  
Lin Song ◽  
...  
Keyword(s):  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Thyroid Neoplasm ◽  
Support Vector ◽  
Pathway Enrichment Analysis ◽  
Papillary Thyroid ◽  
Rna Seq ◽  
Training Set ◽  
Pathway Enrichment ◽  
Validation Set

Abstract Objective To assess the capacity of support vector machine (SVM) algorithms that are developed based on platelet RNA-seq data in identifying thyroid neoplasm patients and differentiating patients with thyroid adenomas, papillary thyroid cancer and metastasized papillary thyroid cancer. Methods Platelets were collected and isolated from 109 patients and 63 healthy controls. RNA-seq was performed to find transcripts with differential levels. Genes corresponding to these altered transcripts were identified using R packages. All samples were subsampled into a training set and a validation set. Two SVM algorithms were developed and trained with the training set, using the genes with differential transcript levels (GDTLs) as classifiers, and validated with the validation set. GO and KEGG pathway enrichment analysis were performed using the R package clusterProfiler. Results We detected 765 GDTLs (442 up-regulated and 323 down-regulated) in platelets of patients and healthy controls. The algorithm identifying thyroid neoplasm patients achieved an accuracy of 97%, with an AUC (area under curve) of 0.998. The other algorithm differentiating patients with multiclass thyroid neoplasms had an average accuracy of 80.5%. GO analysis showed that GDTLs were strongly involved in biological processes such as neutrophil degranulation, neutrophil activation, autophagy and regulation of multi-organism process. KEGG pathway enrichment analysis revealed that GDTLs were mainly enriched in NOD-like receptor signaling pathway and pathways in endocytosis, osteoclast differentiation, human cytomegalovirus infection and tuberculosis. Conclusion Our results indicated that the combination of SVM algorithms and platelet RNA-seq data allowed for thyroid neoplasm diagnostics and multiclass thyroid neoplasm classification.

scholarly journals BioinformaticsAnalysis of the Muscle-invasive Bladder Cancer Subtypes

1970 ◽  
Vol 2 (2) ◽  
Author(s):  
Wenbin Xu ◽  
Weiying Zheng ◽  
Hong Xia ◽  
Lin Hua
Keyword(s):  
Extracellular Matrix ◽  
Bladder Cancer ◽  
Inflammatory Response ◽  
Differentially Expressed Genes ◽  
Kegg Pathway ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Pathway Enrichment Analysis ◽  
Cancer Subtypes ◽  
Pathway Enrichment

Objective In order to improve the accuracy in distinguishing subtypes of bladder cancer and to explore its potential therapeutic targets, we identify differences between two kinds of bladder cancer subtypes (basal-like and luminal) in molecular mechanism and molecular characteristics based on the bioinformatics analysis. Methods In this study, the RMA (robust multichip averaging) was applied to normalize the mRNA profile which included 22 samples from basal-like subtype and 132 from luminal subtype, and the differential expression analysis of genes with top 1000 highest standard deviation was performed. Then, the Gene Ontology and KEGG pathway enrichment analysis of differentially expressed genes was performed. In addition, the protein-protein interactions networks analysis for the top 100 most significant differentially expressed genes was performed. Results A total of 742 differentially expressed genes distinguishing basal-like and luminal subtypes were found, of which 405 were up-regulated and 337 genes were down-regulated in basal-like subtype. GO enrichment analysis showed that differentially expressed genes were significantly enriched in the extracellular matrix, chemotaxis and inflammatory response. KEGG pathway enrichment analysis showed that the differentially expressed genes were significantly enriched in the pathway of extracellular matrix receptor interaction. The hub proteins we founded in protein-protein interaction networks were LNX1, MSN and PPARG. Conclusion In this study, the mainly difference of molecular mechanism between basal-like and luminal subtypes are alteration in extracellular matrix region, cell chemotaxis and inflammatory response. Genes such as LNX1, MSN and PPARG were forecast to play important roles in the classification of bladder carcinoma subtypes.

scholarly journals A Study on the Mechanism of Milkvetch Root in the treatment of Diabetic Nephropathy based on Network Pharmacology

2020 ◽  
Author(s):  
Chunli Piao ◽  
Qi Zhang ◽  
De Jin ◽  
Li Wang ◽  
Cheng Tang ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Signaling Pathway ◽  
Diabetic Complications ◽  
Drug Targets ◽  
Topological Analysis ◽  
Enrichment Analysis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Systems Pharmacology ◽  
Pathway Enrichment

Abstract Background: Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. Milkvetch Root has been extensively used to treat DN in clinical practice in China for many years, but the active ingredients, drug targets, and its exact molecular mechanism are not known. The aim of this study was to decrypt the underlying mechanisms of Milkvetch Root in the treatment of DN by using a systems pharmacology approach. Methods: The components and targets of Milkvetch Root were analyzed using the Traditional Chinese Medicine Systems Pharmacology database. Then we found the common target of Milkvetch Root and disease, constructed a protein-protein interaction (PPI) network using String, and screened the key targets from these common targets through topological analysis. Analyses of enrichment of Gene Ontology (GO) pathways and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Subsequently, the major hubs were imported to the Database for Annotation, Visualization and Integrated Discovery to perform a pathway enrichment analysis. Results: There were 20 active compounds of Milkvetch Root and 10 diabetic nephropathy -associated targets (AKT1, VEGFA, IL6, PPARG, CCL2, NOS3, SERPINE1, CRP, ICAM1, SLC2A4) that were obtained. Then, the results of GO and KEGG pathway enrichment analyses suggested that the AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, PI3K-Akt signaling pathway and TNF signaling pathway in diabetic complications might serve as the key points and principal pathways for DN treatment. Conclusions: In brief, Milkvetch Root has multiple components, multiple targets and multiple pharmacological effects in the treatment of DN, which provides clues for further research on DN.

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