scholarly journals Identification of the Crucial Gene in Overflow Arteriovenous Fistula by Bioinformatics Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Zhengde Zhao ◽  
Qining Fu ◽  
Liangzhu Hu ◽  
Yangdong Liu
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Intimal Hyperplasia ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Biological Processes ◽  
Hub Genes ◽  
Av Fistula ◽  
Core Genes

Objective: The aim was to study the preliminary screening of the crucial genes in intimal hyperplasia in the venous segment of arteriovenous (AV) fistula and the underlying potential molecular mechanisms of intimal hyperplasia with bioinformatics analysis.Methods: The gene expression profile data (GSE39488) was analyzed to identify differentially expressed genes (DEGs). We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis of DEGs. Gene set enrichment analysis (GSEA) was used to understand the potential activated signaling pathway. The protein–protein interaction (PPI) network was constructed with the STRING database and Cytoscape software. The Venn diagram between 10 hub genes and gene sets of 4 crucial signaling pathways was used to obtain core genes and relevant potential pathways. Furthermore, GSEAs were performed to understand their biological functions.Results: A total of 185 DEGs were screened in this study. The main biological function of the 111 upregulated genes in AV fistula primarily concentrated on cell proliferation and vascular remodeling, and the 74 downregulated genes in AV fistula were enriched in the biological function mainly relevant to inflammation. GSEA found four signaling pathways crucial for intimal hyperplasia, namely, MAPK, NOD-like, Cell Cycle, and TGF-beta signaling pathway. A total of 10 hub genes were identified, namely, EGR1, EGR2, EGR3, NR4A1, NR4A2, DUSP1, CXCR4, ATF3, CCL4, and CYR61. Particularly, DUSP1 and NR4A1 were identified as core genes that potentially participate in the MAPK signaling pathway. In AV fistula, the biological processes and pathways were primarily involved with MAPK signaling pathway and MAPK-mediated pathway with the high expression of DUSP1 and were highly relevant to cell proliferation and inflammation with the low expression of DUSP1. Besides, the biological processes and pathways in AV fistula with the high expression of NR4A1 similarly included the MAPK signaling pathway and the pathway mediated by MAPK signaling, and it was mainly involved with inflammation in AV fistula with the low expression of NR4A1.Conclusion: We screened four potential signaling pathways relevant to intimal hyperplasia and identified 10 hub genes, including two core genes (i.e., DUSP1 and NR4A1). Two core genes potentially participate in the MAPK signaling pathway and might serve as the therapeutic targets of intimal hyperplasia to prevent stenosis after AV fistula creation.

scholarly journals Integrated lncRNA and mRNA Transcriptome Analyses in the Ovary of Cynoglossus semilaevis Reveal Genes and Pathways Potentially Involved in Reproduction

2021 ◽  
Vol 12 ◽  
Author(s):  
Yani Dong ◽  
Likang Lyu ◽  
Daiqiang Zhang ◽  
Jing Li ◽  
Haishen Wen ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Target Genes ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Cynoglossus Semilaevis ◽  
Gene Set Enrichment Analysis ◽  
Functional Enrichment ◽  
Biological Processes ◽  
Tongue Sole ◽  
Oocyte Meiosis

Long non-coding RNAs (lncRNAs) have been reported to be involved in multiple biological processes. However, the roles of lncRNAs in the reproduction of half-smooth tongue sole (Cynoglossus semilaevis) are unclear, especially in the molecular regulatory mechanism driving ovarian development and ovulation. Thus, to explore the mRNA and lncRNA mechanisms regulating reproduction, we collected tongue sole ovaries in three stages for RNA sequencing. In stage IV vs. V, we identified 312 differentially expressed (DE) mRNAs and 58 DE lncRNAs. In stage V vs. VI, we identified 1,059 DE mRNAs and 187 DE lncRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses showed that DE mRNAs were enriched in ECM-receptor interaction, oocyte meiosis and steroid hormone biosynthesis pathways. Furthermore, we carried out gene set enrichment analysis (GSEA) to identify potential reproduction related-pathways additionally, such as fatty metabolism and retinol metabolism. Based on enrichment analysis, DE mRNAs with a potential role in reproduction were selected and classified into six categories, including signal transduction, cell growth and death, immune response, metabolism, transport and catabolism, and cell junction. The interactions of DE lncRNAs and mRNAs were predicted according to antisense, cis-, and trans-regulatory mechanisms. We constructed a competing endogenous RNA (ceRNA) network. Several lncRNAs were predicted to regulate genes related to reproduction including cyp17a1, cyp19a1, mmp14, pgr, and hsd17b1. The functional enrichment analysis of these target genes of lncRNAs revealed that they were involved in several signaling pathways, such as the TGF-beta, Wnt signaling, and MAPK signaling pathways and reproduction related-pathways such as the progesterone-mediated oocyte maturation, oocyte meiosis, and GnRH signaling pathway. RT-qPCR analysis showed that two lncRNAs (XR_522278.2 and XR_522171.2) were mainly expressed in the ovary. Dual-fluorescence in situ hybridization experiments showed that both XR_522278.2 and XR_522171.2 colocalized with their target genes cyp17a1 and cyp19a1, respectively, in the follicular cell layer. The results further demonstrated that lncRNAs might be involved in the biological processes by modulating gene expression. Taken together, this study provides lncRNA profiles in the ovary of tongue sole and further insight into the role of lncRNA involvement in regulating reproduction in tongue sole.

scholarly journals Targeting ERK-Hippo Interplay in Cancer Therapy

2020 ◽  
Vol 21 (9) ◽  
pp. 3236 ◽  
Author(s):  
Karel Vališ ◽  
Petr Novák
Keyword(s):  
Cancer Therapy ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cross Talk ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Cancer Therapies ◽  
Anti Cancer ◽  
Targeted Inhibition

Extracellular signal-regulated kinase (ERK) is a part of the mitogen-activated protein kinase (MAPK) signaling pathway which allows the transduction of various cellular signals to final effectors and regulation of elementary cellular processes. Deregulation of the MAPK signaling occurs under many pathological conditions including neurodegenerative disorders, metabolic syndromes and cancers. Targeted inhibition of individual kinases of the MAPK signaling pathway using synthetic compounds represents a promising way to effective anti-cancer therapy. Cross-talk of the MAPK signaling pathway with other proteins and signaling pathways have a crucial impact on clinical outcomes of targeted therapies and plays important role during development of drug resistance in cancers. We discuss cross-talk of the MAPK/ERK signaling pathway with other signaling pathways, in particular interplay with the Hippo/MST pathway. We demonstrate the mechanism of cell death induction shared between MAPK/ERK and Hippo/MST signaling pathways and discuss the potential of combination targeting of these pathways in the development of more effective anti-cancer therapies.

scholarly journals Exploring the Pharmacological Mechanism of Duhuo Jisheng Decoction in Treating Osteoporosis Based on Network Pharmacology

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Zhencheng Xiong ◽  
Can Zheng ◽  
Yanan Chang ◽  
Kuankuan Liu ◽  
Li Shu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Hub Genes ◽  
Active Compounds ◽  
Treatment Of Osteoporosis ◽  
Target Proteins

Objective. The purpose of this work is to study the mechanism of action of Duhuo Jisheng Decoction (DHJSD) in the treatment of osteoporosis based on the methods of bioinformatics and network pharmacology. Methods. In this study, the active compounds of each medicinal ingredient of DHJSD and their corresponding targets were obtained from TCMSP database. Osteoporosis was treated as search query in GeneCards, MalaCards, DisGeNET, Therapeutic Target Database (TTD), Comparative Toxicogenomics Database (CTD), and OMIM databases to obtain disease-related genes. The overlapping targets of DHJSD and osteoporosis were identified, and then GO and KEGG enrichment analysis were performed. Cytoscape was employed to construct DHJSD-compounds-target genes-osteoporosis network and protein-protein interaction (PPI) network. CytoHubba was utilized to select the hub genes. The activities of binding of hub genes and key components were confirmed by molecular docking. Results. 174 active compounds and their 205 related potential targets were identified in DHJSD for the treatment of osteoporosis, including 10 hub genes (AKT1, ALB, IL6, MAPK3, VEGFA, JUN, CASP3, EGFR, MYC, and EGF). Pathway enrichment analysis of target proteins indicated that osteoclast differentiation, AGE-RAGE signaling pathway in diabetic complications, Wnt signaling pathway, MAPK signaling pathway, PI3K-Akt signaling pathway, JAK-STAT signaling pathway, calcium signaling pathway, and TNF signaling pathway were the specifically major pathways regulated by DHJSD against osteoporosis. Further verification based on molecular docking results showed that the small molecule compounds (Quercetin, Kaempferol, Beta-sitosterol, Beta-carotene, and Formononetin) contained in DHJSD generally have excellent binding affinity to the macromolecular target proteins encoded by the top 10 genes. Conclusion. This study reveals the characteristics of multi-component, multi-target, and multi-pathway of DHJSD against osteoporosis and provides novel insights for verifying the mechanism of DHJSD in the treatment of osteoporosis.

scholarly journals A network pharmacology analysis on drug-like compounds from Ganoderma lucidum for alleviation of Atherosclerosis

2021 ◽  
Author(s):  
Ki Kwang Oh ◽  
Md. Adnan ◽  
Dong Ha Cho
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Ganoderma Lucidum ◽  
Mapk Signaling ◽  
Mendelian Inheritance ◽  
Chronic Inflammatory Disease ◽  
Mapk Signaling Pathway ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Overlapping Genes

Abstract Background: Ganoderma lucidum (GL) is known as a potent alleviator against chronic inflammatory disease like atherosclerosis (AS), but its critical bioactive compounds and their mechanisms against AS have not been unveiled. This research aimed to identify the key compounds(s) and mechanism(s) of GL against AS through network pharmacology.Methods: The compounds from GL were identified by gas chromatography-mass spectrum (GC-MS), and SwissADME screened their physicochemical properties. Then, the gene(s) associated with the screened compound(s) or AS related genes were identified by public databases, and we selected the overlapping genes using a Venn diagram. The networks between overlapping genes and compounds were visualized, constructed, and analyzed by RStudio. Finally, we performed molecular docking test (MDT) to identify key gene(s), compound(s) on AutoDockVina.Results: A total of 35 compounds in GL was detected via GC-MS, and 34 compounds (accepted by the Lipinski's rule) were selected as drug-like compounds (DLCs). A total of 34 compounds were connected to the number of 785 genes and 2,606 AS-related genes were identified by DisGeNET and Online Mendelian Inheritance in Man (OMIM). The final 98 overlapping genes were extracted between the compounds-genes network and AS-related genes. On Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, the number of 27 signaling pathways were sorted out, and a hub signaling pathway (MAPK signaling pathway), a core gene (PRKCA), and a key compound (Benzamide, 4-acetyl-N-(2,6-dimethylphenyl)) were selected among the 27 signaling pathways via MDT. Conclusion: Overall, we found that the identified 3 DLCs from GL have potent anti-inflammatory efficacy, improving AS by inactivating the MAPK signaling pathway.

scholarly journals Identification of Neuropeptides as Potential Crosstalks Linking Down Syndrome and Periodontitis Revealed by Transcriptomic Analyses

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Yue Chen ◽  
Xiaofei Yu ◽  
Jia Kong
Keyword(s):  
Down Syndrome ◽  
Signaling Pathway ◽  
Differential Expression Analysis ◽  
Enrichment Analysis ◽  
Functional Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Expression Omnibus ◽  
Functional Enrichment ◽  
Future Research ◽  
Biological Processes

Background. This bioinformatics study was aimed to investigate the relationship between periodontitis (PD) and Down Syndrome (DS) regarding potential crosstalk genes, related neuropeptides, and biological processes. Methods. Data for PD (GSE23586, GSE10334 and GSE16134) and DS (GSE35665) were downloaded from NCBI Gene Expression Omnibus (GEO). Following normalization and merging of PD data, differential expression analysis was performed ( p value < 0.05 and ∣ log   FC ∣ ≥ 0.5 ). The common deregulated genes between PD and DS were considered as crosstalk genes. The significantly differentially expressed genes were used to construct the coexpression network and to further identify coexpression gene modules. To acquire the significant modules, the significant expression level of genes in the module was used to analyze the enrichment of genes in each module. Neuropeptides were assessed from NeuroPedia database. Neuropeptide genes and crosstalk genes were merged and mapped into PPI network, and the correlation coefficient (Spearman) was determined for the crosstalk genes. Results. 138 crosstalk genes were predicted. According to the functional enrichment analysis, these genes significantly regulated different biological processes and pathways. In enrichment analysis, the significant module of DS was pink module, and turquoise module was significant in PD. Four common crosstalk genes were acquired, i.e., CD19, FCRL5, FCRLA, and HLA-DOB. In the complex network, INS and IGF2 interacted with CASP3 and TP53, which commonly regulated the MAPK signaling pathway. Moreover, the results showed that TP53 interacted with IGF2 and INS inducing the dysregulation of PI3K-Akt signaling pathway. UBL was positively correlated with crosstalk genes in both diseases. LEP was revealed to be both a neuropeptide and crosstalk gene and was positively correlated with other crosstalk genes. Conclusion. Different crosstalk genes, related neuropeptides, and biological pathways and processes were revealed between PD and DS, which can serve as a theoretical basis for future research.

scholarly journals To explore the material basis and mechanism of Lianhua Qingwen Prescription against COVID-19 based on network pharmacology

2020 ◽  
Vol 1 ◽  
pp. 3
Author(s):  
Wenpan Peng ◽  
Di Han ◽  
Yong Xu ◽  
Fanchao Feng ◽  
Zhichao Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
T Cell Activation ◽  
Mechanism Of Action ◽  
Cell Activation ◽  
Chemical Constituents ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Material Basis

Objective: In the treatment of COVID-19, the application of Lianhua Qingwen Prescription has become growingly widespread, however, the mechanism of action is still unclear. To explore the material basis and mechanism of Lianhua Qingwen Prescription against SARS-CoV-2, to provide a reference for the treatment of COVID-19. Methods: Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), SwissTargetPrediction, and Similarity Ensemble Approach (SEA) database were used to search the chemical constituents and targets of Lianhua Qingwen Prescription. The targets of COVID-19 were screened by GeneCards, Therapeutic Target Database (TTD), and Comparative Toxicogenomics Database (CTD). Cytoscape software was used to construct a “drug-component-target” network diagram and the mechanism of action was predicted by enrichment analysis. Results: Two hundred and twenty four active components, 246 drug therapeutic targets, and 16,611 potential targets of Lianhua Qingwen Prescription were mined out. Moreover, 163 common targets were obtained, including PTGS2, IL6, CASP3, mapk1, EGFR, ACE2, etc. Thirty seven items were obtained by Gene Ontology (GO) enrichment analysis, mainly involving T-cell activation, virus receptor, and inflammatory reaction, etc. One hundred and forty items were obtained by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enriched analysis, including TNF signaling pathway, MAPK signaling pathway, and IL-17 signaling pathway. Conclusion: Compounds such as quercetin and kaempferol play an important role in anti-COVID-19 through the TNF signaling pathway and MAPK signaling pathway.

scholarly journals TRF-Val-CAC-016 Modulates the Transduction of CACNA1d-Mediated MAPK Signaling Pathways to Suppress the Proliferation of Gastric Carcinoma

2022 ◽  
Author(s):  
Weiguo Xu ◽  
Junyu Zheng ◽  
Xiao Wang ◽  
Bin Zhou ◽  
Huanqiu Chen ◽  
...  
Keyword(s):  
Gastric Carcinoma ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Luciferase Reporter ◽  
Trna Derivatives ◽  
Mapk Signaling Pathways

Abstract Background: As a new kind of non-coding RNAs (ncRNAs), tRNA derivatives play an important role in gastric carcinoma (GC). Nevertheless, the underlying mechanism tRNA derivatives were involved in was rarely illustrated. Methods: We screened out the tRNA derivative, tRF-Val-CAC-016, based on the tsRNA sequencing and demonstrated the effect tRF-Val-CAC-016 exerted on GC proliferation in vitro and in vivo. We applied Dual-luciferase reporter assay, RIP assay, and bioinformatic analysis to discover the downstream target of tRF-Val-CAC-016. Then CACNA1d was selected, and the oncogenic characteristics were verified. Subsequently, we detected the possible regulation of the canonical MAPK signaling pathway to further explore the downstream mechanism of tRF-Val-CAC-016. Results: As a result, we found that tRF-Val-CAC-016 was low-expressed in GC, and upregulation of tRF-Val-CAC-016 could significantly suppress the proliferation of GC cell lines. Meanwhile, tRF-Val-CAC-016 regulated the canonical MAPK signaling pathway by targeting CACNA1d. Conclusions: tRF-Val-CAC-016 modulates the transduction of CACNA1d-mediated MAPK signaling pathways to suppress the proliferation of gastric carcinoma. This study discussed the function and mechanism of tRF-Val-CAC-016 in GC for the first time. The pioneering work has contributed to our present understanding of tRNA derivative, which might provide an alternative mean for the targeted therapy of GC.

scholarly journals Krill Oil Alleviated Methamphetamine-Induced Memory Impairment via the MAPK Signaling Pathway and Dopaminergic Synapse Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Qin Ru ◽  
Xiang Tian ◽  
Qi Xiong ◽  
Congyue Xu ◽  
Lin Chen ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Memory Impairment ◽  
Caspase 3 ◽  
Memory Deficits ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Krill Oil ◽  
Hub Genes ◽  
Target Network

Methamphetamine (METH) abuse exerts severe harmful effects in multiple organs, especially the brain, and can induce cognitive dysfunction and memory deficits in humans. Krill oil is rich in polyunsaturated fatty acids, while its effect on METH-induced cognitive impairment and mental disorders, and the underlying mechanism remain unknown. The aim of the present study was to investigate the protective effect of krill oil on METH-induced memory deficits and to explore the molecular mechanisms by using an integrated strategy of bioinformatics analysis and experimental verification. METH-exposed mice were treated with or without krill oil. Learning and memory functions were evaluated by the Morris water maze. The drug–component–target network was constructed in combination with network pharmacology. The predicted hub genes and pathways were validated by the Western blot technique. With krill oil treatment, memory impairment induced by METH was significantly improved. 210 predicted targets constituted the drug–compound–target network by network pharmacology analysis. 20 hub genes such as DRD2, MAPK3, CREB, BDNF, and caspase-3 were filtered out as the underlying mechanisms of krill oil on improving memory deficits induced by METH. The KEGG pathway and GO enrichment analyses showed that the MAPK signaling pathway, cAMP signaling pathway, and dopaminergic synapse pathway were involved in the neuroprotective effects of krill oil. In the hippocampus, DRD2, cleaved caspase-3, and γ-H2AX expression levels were significantly increased in the METH group but decreased in the krill oil–treated group. Meanwhile, krill oil enhanced the expressions of p-PKA, p-ERK1/2, and p-CREB. Our findings suggested that krill oil improved METH-induced memory deficits, and this effect may occur via the MAPK signaling pathway and dopaminergic synapse pathways. The combination of network pharmacology approaches with experimental validation may offer a useful tool to characterize the molecular mechanism of multicomponent complexes.

scholarly journals Based on Network Pharmacology to Explore the Potential Bioactive Compounds and Mechanisms of Zuojin Pill for the Treatment of Ulcerative Colitis

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Ying Wei ◽  
Sichen Ren ◽  
Ruilin Wang ◽  
Manyi Jing ◽  
Honghong Liu ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Signaling Pathway ◽  
Bioactive Compounds ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Network Pharmacology ◽  
Akt Signaling Pathway ◽  
Active Components

Background. Zuojin Pill (ZJP), a classic prescription, has the potential to prevent ulcerative colitis (UC). However, the active components and mechanisms of ZJP are still arcane. This study aimed to use a network pharmacology approach to find the bioactive compounds and potential action mechanisms of ZJP in the treatment of UC. Methods. Firstly, the components and putative targets of ZJP were collected based on herbal medicine target databases, and a network containing the interaction between the targets of ZJP and the potential therapeutic targets of UC was established. Then, topological parameters were calculated to identify the key targets in the network and, in turn, to import them into the David database to perform path enrichment analysis. Results. 14 potential therapeutic components of ZJP and 26 key targets were obtained. These targets were related to signal transduction, MAPK cascade, inflammatory response, immune response, and the apoptotic process of UC. Moreover, the PI3K-Akt signaling pathway, MAPK signaling pathway, toll-like receptor signaling pathway, and Prolactin signaling pathway were predicted to participate in ZJP treating UC. Among them, 14 active components of ZJP directly regulate these pathways. Conclusion. ZJP could alleviate UC through the predicted components and mechanisms. The 14 predicted active components of ZJP may mainly play a therapeutic role for UC through synergistic regulation of the PI3K-Akt signaling pathway and MAPK signaling pathway.

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