Cross-talk of Signaling Pathways in the Pathogenesis of Allergic Asthma and Cataract

2020 ◽  
Vol 27 (9) ◽  
pp. 810-822
Author(s):  
Yang Zhao ◽  
Sumei Liu ◽  
Xiangsheng Li ◽  
Zhenzhen Xu ◽  
Lifang Hao ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Allergic Asthma ◽  
Signaling Pathway ◽  
Academic Research ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Chronic Inflammatory Disease ◽  
Smad Signaling Pathway ◽  
Immune Imbalance ◽  
Cellular Components

: Allergic asthma is a chronic inflammatory disease, which involves many cellular and cellular components. Cataract is a condition that affects the transparency of the lens, which the opacity of the lens caused by any innate or acquired factor degrades its transparency or changes in color. Both of them belong to diseases induced by immune disorders or inflammation. We want to confirm the signaling pathways involved in the regulation of asthma and cataract simultaneously, and provide reference for the later related experiments. So we conducted a scoping review of many databases and searched for studies (Academic research published in Wiley, Springer and Bentham from 2000 to 2019) about the possible relationship between asthma and cataract. It was found that during the onset of asthma and cataract, Rho/Rock signaling pathway, Notch signaling pathway, Wnt/β-catenin signaling pathway, PI3K/AKT signaling pathway, JAK/STAT signaling pathway, MAPK signaling pathway, TGF-β1/Smad signaling pathway and NF-κB signaling pathway are all active, so they may have a certain correlation in pathogenesis. Asthma may be associated with cataract through the eight signaling pathways, causing inflammation or immune imbalance based on allergy that can lead to cataract. According to these studies, we speculated that the three most likely signaling pathways are PI3K/AKT, MAPK and NF-κB signaling pathway.

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 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 Interaction Between HIF-1α and Notch Signaling Pathways in Nucleus Pulposus Cells of Patients with Modic Changes

2020 ◽  
Author(s):  
Zekang Xiong ◽  
Xiaodong Guo ◽  
Jin Zheng ◽  
Jun Ding ◽  
Jinge Zhou ◽  
...  
Keyword(s):  
Notch Signaling ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Nucleus Pulposus ◽  
Notch Pathway ◽  
Notch Signaling Pathway ◽  
Modic Changes ◽  
Nucleus Pulposus Cells ◽  
Tissue Samples ◽  
Promising Target

Abstract Background The HIF-1α/Notch signaling pathway has been shown to regulate proliferation, apoptosis, and metabolism in the intervertebral disc (IVD). The NP is an important structure adjacent to the disc. However, the roles of HIF1α and Notch signaling pathways in NP cells of patients with different Modic changes (MCs) are unclear. The purpose of this research was to assess the expression and association of HIF-1α and components of the Notch pathway in nucleus pulposus (NP) tissue of patients with various MCs. Methods Eighty-five surgical NP tissue samples were obtained from patients undergoing microdiscectomy procedures for the treatment of low back and root pain caused by prolapse of the IVD. The NP tissues were divided into four groups based on the adjacent endplate degeneration: MC I, II, III, and negative MC groups. The expression of HIF-1α and Notch-related components were measured and compared. Results The expression of HIF-1α, Notch1, and Notch2 were gradually increased in the MC I and MC II groups compared with that of the negative MC group. Meanwhile, HIF-1α and Notch-related components were rarely detected in MC III group. Conclusions The expression of HIF-1α/Notch is increased in the NP cells of patients with MC I and MC II. Application of the association between HIF-1α/Notch signaling pathway could be promising target for clinical diagnosis and treatment of disc degeneration in MC patients.

scholarly journals Comprehensive circRNA Expression Profile and Construction of circRNAs-Related ceRNA Network in a Mouse Model of Autism

2021 ◽  
Vol 11 ◽  
Author(s):  
Ji Wang ◽  
Zhongxiu Yang ◽  
Canming Chen ◽  
Yang Xu ◽  
Hongguang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profile ◽  
Enrichment Analysis ◽  
Notch Signaling Pathway ◽  
Mapk Signaling ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Common Disease ◽  
Cerna Network

Autism is a common disease that seriously affects the quality of life. The role of circular RNAs (circRNAs) in autism remains largely unexplored. We aimed to detect the circRNA expression profile and construct a circRNA-based competing endogenous RNA (ceRNA) network in autism. Valproate acid was used to establish an in vivo model of autism in mice. A total of 1,059 differentially expressed circRNAs (477 upregulated and 582 downregulated) in autism group was identified by RNA sequencing. The expression of novel_circ_015779 and novel_circ_035247 were detected by real-time PCR. A ceRNA network based on altered circRNAs was established, with 9,715 nodes and 150,408 edges. Module analysis was conducted followed by GO and KEGG pathway enrichment analysis. The top three modules were all correlated with autism-related pathways involving “TGF-beta signaling pathway,” “Notch signaling pathway,” “MAPK signaling pathway,” “long term depression,” “thyroid hormone signaling pathway,” etc. The present study reveals a novel circRNA involved mechanisms in the pathogenesis of autism.

scholarly journals Proteins in cord blood as a new target for prevention and treatment of bronchopulmonary dysplasia: a proteomic analysis

2021 ◽  
Author(s):  
Juan Wang ◽  
Jianping Mao ◽  
Gang Chen ◽  
Yuanmei Huang ◽  
Jinjin Zhou ◽  
...  
Keyword(s):  
Cord Blood ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Bronchopulmonary Dysplasia ◽  
Proteomic Analysis ◽  
Mapk Signaling ◽  
Term Infants ◽  
Reproductive Process ◽  
Prevention And Treatment ◽  
Differential Proteins

Abstract This study aimed to explore the proteins in cord blood that could regulate the development of neonatal bronchi and lungs, and to find a new target for the prevention and treatment of bronchopulmonary dysplasia (BPD). In this study, proteomic analysis was used to analyze the proteins in cord blood of preterm and term infants. A total of 100 differentially expressed (57 up-regulated and 43 down-regulated) proteins were identified from preterm with BPD and term infants cord blood (fold change ≥ 1.5, P value < 0.05). GO analysis revealed that the major enrichment functions of these differential proteins were multi-organism process, stimulus, immune system process growth, reproductive process, development process and antioxidant activity. The signaling pathways involved included insulin resistance, insulin signaling pathway, IL−17 signaling pathway, PI3K−Akt signaling pathway, NF−kappa B signaling pathway, glucagon signaling pathway, apoptosis, MAPK signaling pathway, as well as glycolysis/gluconeogenesis. Further protein and protein interact (PPI) analysis revealed that the interacting proteins involved were PGAM1, CNN2, HSP90AA and DAG1, which were all crucial in the development of BPD. We found that these differential proteins in cord blood might regulate bronchopulmonary development through the abovementioned signaling pathways or their interaction proteins, which may provide a new research direction for the intervention of BPD.

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 Selenoproteins and their emerging roles in signaling pathways

2020 ◽  
Vol 11 (2) ◽  
pp. 186-199
Author(s):  
N. V. Stanishevska
Keyword(s):  
Endoplasmic Reticulum ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Thioredoxin Reductase ◽  
Methionine Sulfoxide ◽  
Mapk Signaling ◽  
Methionine Sulfoxide Reductase ◽  
Selenoprotein S ◽  
Selenoprotein K ◽  
Er Membrane

The functional activity of selenoproteins has a wide range of effects on complex pathogenetic processes, including teratogenesis, immuno-inflammatory, neurodegenerative. Being active participants and promoters of many signaling pathways, selenoproteins support the lively interest of a wide scientific community. This review is devoted to the analysis of recent data describing the participation of selenoproteins in various molecular interactions mediating important signaling pathways. Data processing was carried out by the method of complex analysis. For convenience, all selenoproteins were divided into groups depending on their location and function. Among the group of selenoproteins of the ER membrane, selenoprotein N affects the absorption of Ca2+ by the endoplasmic reticulum mediated by oxidoreductin (ERO1), a key player in the CHOP/ERO1 branch, a pathogenic mechanism that causes myopathy. Another selenoprotein of the ER membrane selenoprotein K binding to the DHHC6 protein affects the IP3R receptor that regulates Ca2+ flux. Selenoprotein K is able to affect another protein of the endoplasmic reticulum CHERP, also appearing in Ca2+ transport. Selenoprotein S, associated with the lumen of ER, is able to influence the VCP protein, which ensures the incorporation of selenoprotein K into the ER membrane. Selenoprotein M, as an ER lumen protein, affects the phosphorylation of STAT3 by leptin, which confirms that Sel M is a positive regulator of leptin signaling. Selenoprotein S also related to luminal selenoproteins ER is a modulator of the IRE1α-sXBP1 signaling pathway. Nuclear selenoprotein H will directly affect the suppressor of malignant tumours, p53 protein, the activation of which increases with Sel H deficiency. The same selenoprotein is involved in redox regulation. Among the cytoplasmic selenoproteins, abundant investigations are devoted to SelP, which affects the PI3K/Akt/Erk signaling pathway during ischemia/reperfusion, is transported into the myoblasts through the plasmalemma after binding to the apoER2 receptor, and into the neurons to the megaline receptor and in general, selenoprotein P plays the role of a pool that stores the necessary trace element and releases it, if necessary, for vital selenoproteins. The thioredoxin reductase family plays a key role in the invasion and metastasis of salivary adenoid cystic carcinoma through the influence on the TGF-β-Akt/GSK-3β pathway during epithelial-mesenchymal transition. The deletion of thioredoxin reductase 1 affects the levels of messengers of the Wnt/β-catenin signaling pathway. No less studied is the glutathione peroxidase group, of which GPX3 is able to inhibit signaling in the Wnt/β-catenin pathway and thereby inhibit thyroid metastasis, as well as suppress protein levels in the PI3K/Akt/c-fos pathway. A key observation is that in cases of carcinogenesis, a decrease in GPX3 and its hypermethylation are almost always found. Among deiodinases, deiodinase 3 acts as a promoter of the oncogenes BRAF, MEK or p38, while stimulating a decrease in the expression of cyclin D1. The dependence of the level of deiodinase 3 on the Hedgehog (SHH) signaling pathway is also noted. Methionine sulfoxide reductase A can compete for the uptake of ubiquitin, reduce p38, JNK and ERK promoters of the MAPK signaling pathway; methionine sulfoxide reductase B1 suppresses MAPK signaling messengers, and also increases PARP and caspase 3.

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