scholarly journals System Pharmacology-Based Strategy to Decode the Synergistic Mechanism of GanDouLing for Wilson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Juan Zhang ◽  
Hong Chen ◽  
Yuancheng Bao ◽  
Daojun Xie ◽  
Wenming Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Wilson’S Disease ◽  
Combined Therapy ◽  
Wilson's Disease ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Receptor Signaling ◽  
Chinese Medicinal Herb ◽  
Receptor Signaling Pathway

Ethnopharmacological Relevance. GanDouLing (GDL) is a Chinese medicinal herb produced by the preparation center of Anhui Hospital of TCM for preventing and treating Wilson’s disease (WD), an ATP7B mutation-inherited disease that affects copper transport and is characterized by liver and nervous system manifestations with variable and often unpredictable manifestations. However, the “multicomponent” and “multitarget” characteristics of TCM make it challenging to clarify the potential therapeutic mechanisms of GDL for WD. Aim of the Study. This study aimed at the systematic encoding of WD potential target for GDL and experimental verification for the relevant core targets, providing a deeper insight into the understanding of the mechanisms of GDL protection underlying WD with liver injury. Material and Methods. Following the strategy of the network pharmacology, we, firstly, predicted the active components of GDL and putative targets for WD. By employing clusterProfiler, the enrichment of functional and pathway terms was analyzed. Further, the protein-protein-interaction network was analyzed by STRING. Lastly, after establishing the toxic-milk mouse (TX) model with GDL treating, Hematoxylin and Eosin stain (HE) and western blotting (WB) for apoptosis biomarker were experimented. Results. Firstly, 324 active compounds have been identified in the GDL formula. Meanwhile, we identified 1496 human genes which are related to WD or liver cirrhosis. Functional and pathway enrichment analysis indicated that NOD-like receptor signaling pathway, bile secretion, calcium signaling pathway, steroid hormone biosynthesis, T cell receptor signaling pathway, apoptosis, MAPK signaling pathway, and so forth can be obviously regulated by GDL. Further, in a mouse model of WD, in vivo experiments showed that GDL treatment can not only reduce the pathological symptoms of the liver but also reduce the apoptosis of hepatocytes. Conclusions. In this study, systemic pharmacological methods were proposed and the mechanism of GDL combined therapy for WD was explored. This method can be used as a reference for the study of other mechanisms of traditional Chinese medicine.

scholarly journals Study on the Multitarget Mechanism of Sanmiao Pill on Gouty Arthritis Based on Network Pharmacology

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Huiqin Qian ◽  
Qianqian Jin ◽  
Yichen Liu ◽  
Ning Wang ◽  
Yuru Chu ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Signaling Pathway ◽  
Gouty Arthritis ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Regulation Of Transcription ◽  
Receptor Signaling ◽  
Active Compounds ◽  
Receptor Signaling Pathway ◽  
Compound Target

Sanmiao pill (SMP), a Chinese traditional formula, had been used to treat gouty arthritis (GA). However, the active compounds and underlying mechanism remained unclear. Hence, network pharmacology and molecular docking were utilized to explore bioactive compounds and potential mechanism of action of SMP in treating GA. In the study, the compounds of SMP, corresponding targets, and GA-related targets were mined from various pharmacological databases. Then, herb-compound-target, compound-target, PPI, and target-pathway networks were constructed. Ultimately, molecular docking was carried out to verify the predicted results. The results indicated that 47 active compounds, 338 targets, and 144 disease targets were collected. Network analysis implied that Phellodendron chinense Schneid. played a vital role in the whole formula. Moreover, 7 compounds (quercetin, kaempferol, wogonin, rutaecarpine, baicalein, beta-sitosterol, and stigmasterol) and 4 targets (NFKB1, RELA, MAPK1, and TNF) might be the kernel compounds and targets of SMP against GA. According to GOBP and KEGG pathway enrichment analysis and target-pathway network, SMP might exert a therapeutic role in GA by regulating numerous biological processes and pathways, including lipopolysaccharide-mediated signaling pathway, positive regulation of transcription, Toll-like receptor signaling pathway, JAK-STAT signaling pathway, NOD-like receptor signaling pathway, and MAPK signaling pathway. The results of molecular docking showcased that 11 pairs of compound with targets had tight binding strength. Thereinto, 4 compounds of MAPK1 and 5 compounds of NFKB1 possessed a better combination, suggesting that MAPK1 and NFKB1 might be considered as therapeutic targets in treatment of GA. This study verified that SMP had synergistic effect on GA by multicomponents, multitargets, and multipathways.

scholarly journals Comprehensive Analysis of the Immune and Prognostic Implication of MMP14 in Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-21
Author(s):  
Chun-long Zheng ◽  
Qiang Lu ◽  
Nian Zhang ◽  
Peng-yu Jing ◽  
Ji-peng Zhang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Signaling Pathway ◽  
Lung Squamous Cell Carcinoma ◽  
Enrichment Analysis ◽  
Cell Receptor ◽  
Risk Scores ◽  
Pathway Enrichment Analysis ◽  
Receptor Signaling ◽  
Immune Infiltration ◽  
Receptor Signaling Pathway

More and more studies have indicated an association between immune infiltration in lung cancer and clinical outcomes. Matrix metalloproteinase 14 (MMP14) has been reported to be dysregulated in many types of tumors and involved in the development and progression of tumors. However, its contribution to cancer immunity was rarely reported. In the study, we found that MMP14 expression was distinctly upregulated in lung cancer specimens compared with nontumor lung specimens. High MMP14 expression predicted a poor prognosis of lung squamous cell carcinoma (LUSC) patients. Increased MMP14 expressions were observed to be positively related to high immune infiltration levels in most of the immune cells. A pathway enrichment analysis of 32 MMP14-associated immunomodulators indicated the involvement of T cell receptor signaling pathway and Toll-like receptor signaling pathway. Based on MMP14-associated immunomodulators, we applied multivariate assays to construct multiple-gene risk prediction signatures. We observed that risk scores were independently associated with overall survival. These data highlighted that MMP14 was involved in tumor immunity, indicating that MMP14 could serve as a novel prognostic biomarker and therapeutic target for lung cancer. Our data suggest that the four genes identified in this study may serve as valuable biomarkers of lung cancer patient outcomes.

scholarly journals Uncovering the Mechanisms and Molecular Targets of Weibing Formula 1 against Gastritis: Coupling Network Pharmacology with GEO Database

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Ke Chen ◽  
Luojian Zhang ◽  
Zhen Qu ◽  
Feng Wan ◽  
Jia Li ◽  
...  
Keyword(s):  
Real Time ◽  
Signaling Pathway ◽  
Quantitative Pcr ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Gene Expression Omnibus ◽  
Network Pharmacology ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Real Time Quantitative Pcr

Weibing Formula 1, a classic traditional formula, has been widely used clinically to treat gastritis in recent years. However, the potential pharmacological mechanism of Weibing Formula 1 is still unclear to date. A network pharmacology-based strategy was performed to uncover the underlying mechanisms of Weibing Formula 1 against gastritis. Furthermore, we structured the drug-active ingredients-genes–disease network and PPI network of shared targets, and function enrichment analysis of these targets was carried out. Ultimately, Gene Expression Omnibus (GEO) datasets and real-time quantitative PCR were used to verify the related genes. We found 251 potential targets corresponding to 135 bioactive components of Weibing Formula 1. Then, 327 gastritis-related targets were known gastritis-related targets. Among which, 60 common targets were shared between potential targets of Weibing Formula 1 and known gastritis-related targets. The results of pathway enrichment analysis displayed that 60 common targets mostly participated in various pathways related to Toll-like receptor signaling pathway, MAPK signaling pathway, cytokine-cytokine receptor interaction pathway, chemokine signaling pathway, and apoptosis. Based on the GSE60427 dataset, 15 common genes were shared between differentially expressed genes and 60 candidate targets. The verification results of the GSE5081 dataset showed that except for DUOX2 and VCAM1, the other 13 genes were significantly upregulated in gastritis, which was consistent with the results in the GSE60427 dataset. More importantly, real-time quantitative PCR results showed that the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly upregulated and NOS2, EGFR, and IL-10 were downregulated in gastritis patients, while the expressions of PTGS2, MMP9, CXCL2, and CXCL8 were significantly downregulated and NOS2, EGFR, and IL-10 were upregulated after the treatment of Weibing Formula 1. PTGS2, NOS2, EGFR, MMP9, CXCL2, CXCL8, and IL-10 may be the important direct targets of Weibing Formula 1 in gastritis treatment. Our study revealed the mechanism of Weibing Formula 1 in gastritis from an overall and systematic perspective, providing a theoretical basis for further knowing and application of this formula in the future.

scholarly journals Network Pharmacology Identifies the Mechanisms of Sang-Xing-Zhi-Ke-Fang against Pharyngitis

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Yinhe Deng ◽  
Quanjiang Li ◽  
Menglin Li ◽  
Tiantian Han ◽  
Guixian Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Venn Diagram ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Ras Signaling ◽  
Clinical Effects ◽  
Overlapping Genes

Background. Sang-Xing-Zhi-Ke-Fang (SXZKF) demonstrates good therapeutic effect against pharyngitis. Nevertheless, the pharmacological mechanism underlying its effectiveness is still unclear. Objective. To investigate the underlying mechanisms of SXZKF against pharyngitis using network pharmacology method. Methods. Bioactive ingredients of SXZKF were collected and screened using published literature and two public databases. Using four public databases, the overlapping genes between these bioactive compound-related and pharyngitis-related genes were identified by Venn diagram. Protein-protein interaction (PPI) was obtained using “Search Tool for the Retrieval of Interacting Genes (STRING)” database. “Database for Annotation, Visualization, and Integrated Discovery ver. 6.8 (DAVID 6.8)” was used to perform Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the molecular mechanisms of SXZKF against pharyngitis. Finally, Cytoscape 3.7.2 software was used to construct and visualize the networks. Result. A total of 102 bioactive compounds were identified. Among them, 886 compounds-related and 6258 pharyngitis-related genes were identified, including 387 overlapping genes. Sixty-three core targets were obtained, including ALB, PPARγ, MAPK3, EGF, and PTGS2. Signaling pathways closely related to mechanisms of SXZKF for pharyngitis were identified, including serotonergic synapse, VEGF signaling pathway, Fc epsilon RI signaling pathway, Ras signaling pathway, MAPK signaling pathway, and influenza A. Conclusion. This is the first identification of in-depth study of SXZKF against pharyngitis using network pharmacology. This new evidence could be informative in providing new support on the clinical effects of SXZKF on pharyngitis and for the development of personalized medicine for pharyngitis.

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 Chemical Characteristics of Platycodon grandiflorum and its Mechanism in Lung Cancer Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Yaling Deng ◽  
Xianwen Ye ◽  
Yufan Chen ◽  
Hongmin Ren ◽  
Lanting Xia ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Molecular Docking ◽  
Signaling Pathway ◽  
Topological Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Triterpenoid Saponins ◽  
Platycodon Grandiflorum ◽  
Tof Ms

Objective: The technology, network pharmacology and molecular docking technology of the ultra performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) were used to explore the potential molecular mechanism of Platycodon grandiflorum (PG) in the treatment of lung cancer (LC).Methods: UPLC-Q-TOF-MS/MS technology was used to analyze the ingredients of PG and the potential LC targets were obtained from the Traditional Chinese Medicine Systems Pharmacology database, and the Analysis Platform (TCMSP), GeneCards and other databases. The interaction network of the drug-disease targets was constructed with the additional use of STRING 11.0. The pathway enrichment analysis was carried out using Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) in Metascape, and then the “Drug-Ingredients-Targets-Pathways-Disease” (D-I-T-P-D) network was constructed using Cytoscape v3.7.1. Finally, the Discovery Studio 2016 (DS) software was used to evaluate the molecular docking.Results: Forty-seven compounds in PG, including triterpenoid saponins, steroidal saponins and flavonoids, were identified and nine main bioactive components including platycodin D were screened. According to the method of data mining, 545 potential drug targets and 2,664 disease-related targets were collected. The results of topological analysis revealed 20 core targets including caspase 3 (CASP3) and prostaglandin-endoperoxide synthase 2 (PTGS2) suggesting that the potential signaling pathway potentially involved in the treatment of LC included MAPK signaling pathway and P13K-AKT signaling pathway. The results of molecular docking proved that the bound of the ingredients with potential key targets was excellent.Conclusion: The results in this study provided a novel insight in the exploration of the mechanism of action of PG against LC.

scholarly journals Systematic elucidation of the molecular mechanism of scutellarin against osteoarthritis based on network pharmacology

2020 ◽  
Author(s):  
Shijia Guo ◽  
Xinan Zhang ◽  
mingli Sun
Keyword(s):  
Molecular Docking ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Network Pharmacology ◽  
Signaling Proteins ◽  
Receptor Signaling ◽  
In Vivo Experiments ◽  
Receptor Signaling Pathway

Abstract Background Scutellarin was reported to exerted inhibitive effects on osteoarthritis, However, the detailed mechanisms remain unclear. In this study, we investigated underlying multi-target mechanisms of scutellarin against osteoarthritis by using network pharmacology analysis and molecular docking. Results Scutellarin exerted inhibitive effects on osteoarthritis by regulating the function of several new signaling pathways, such as TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway. Molecular docking analysis showed there was better interaction between scutellarin and several NF-kB signaling proteins, including NFKBIA, RELA and NFKB1. In addition, the results showed Pi-cation, Pi-donor-hydrogen and Pi-alkyl were the main forms of interaction between scutellarin and NFKB1 and NFKBIA, Pi-Pi T-shaped, Pi-alkyl and hydrogen bonding were the main forms of interaction between scutellarin and RELA. Conclusion Taken together, TNF signaling pathway, NOD-like receptor signaling pathway and HIF-1 signaling pathway were possible signaling pathways, NFKBIA, RELA and NFKB1were possible targets associated with the activities of scutellarin against osteoarthritis. However, it is imperative that these targets should be thoroughly verified by in vitro and in vivo experiments.

scholarly journals Exploring the mechanism of (-)-Epicatechin on premature ovarian insufficiency based on network pharmacology and experimental evaluation

2021 ◽  
Vol 41 (2) ◽  
Author(s):  
Fei Yan ◽  
Qi Zhao ◽  
Huanpeng Gao ◽  
Xiaomei Wang ◽  
Ke Xu ◽  
...  
Keyword(s):  
Gene Ontology ◽  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Related Factor ◽  
Nrf2 Signaling Pathway

Abstract Methods: Relevant potential targets for EC were obtained based on Traditional Chinese Medicine System Pharmacology Database (TCMSP), a bioinformatics analysis tool for molecular mechanism of Traditional Chinese Medicine (BATMAN-TCM) and STITCH databases. The Online Mendelian Inheritance in Man (OMIM) and GeneCards databases were utilized to screen the known POI-related targets, while Cytoscape software was used for network construction and visualization. Then, the Gene Ontology (GO) and pathway enrichment analysis were carried out by the Database for Annotation, Visualization and Integrated Discovery (DAVID) database. Furthermore, KGN cells were performed to validate the predicted results in oxidative stress (OS) model, and antioxidant effect was examined. Results: A total of 70 potential common targets for EC in the treatment of POI were obtained through network pharmacology. Metabolic process, response to stimulus and antioxidant activity occupied a leading position of Gene Ontology (GO) enrichment. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that PI3K/protein kinase B (AKT), TNF, estrogen, VEGF and MAPK signaling pathways were significantly enriched. In addition, cell experiments showed that EC exhibited antioxidant effects in an H2O2-mediated OS model in ovarian granulosa cells by regulating the expression of PI3K/AKT/nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and multiple downstream antioxidant enzymes. Conclusion: EC could regulate multiple signaling pathways and several biological processes (BPs). EC had the ability to down-regulate elevated OS level through the PI3K/AKT/Nrf2 signaling pathway and represented a potential novel treatment for POI.

scholarly journals Mapping the Multi-Organ miRNA-mRNA Regulatory Network in LPS-Mediated Endotoxemic Mice: Exploring the Shared Underlying Key Genes and Mechanisms

2020 ◽  
Vol 7 ◽  
Author(s):  
Cong Zhang ◽  
Ying Liao ◽  
Zhihao Liu ◽  
Lijin Zeng ◽  
Zhihua Peng ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Enrichment Analysis ◽  
Organ Damage ◽  
Pathway Enrichment Analysis ◽  
Receptor Signaling ◽  
Toll Like Receptor ◽  
Hub Genes ◽  
Liver And Kidney ◽  
Receptor Signaling Pathway ◽  
Key Genes

BackgroundTo this day, the molecular mechanism of endotoxin-induced multi-organ failure has not been completely clarified. This study aimed to construct an miRNA-mRNA regulatory network and identify main pathways and key genes in multi-organ of LPS-mediated endotoxemic mice.MethodsPublic datasets from six mRNA and three miRNA microarray datasets were downloaded from the GEO website to screen final differentially expressed genes (FDEGs) and hub genes in the heart, lung, liver, and kidney of LPS-mediated endotoxemic mice. Functional and pathway enrichment analysis of FDEGs was used to identify the main pathways in multi-organ damage of LPS-treated mice. Finally, hub genes of each organ were intersected to obtain the key genes of multi-organ.ResultsFirstly, 158, 358, 299, and 91 FDEGs were identified in the heart, lung, liver, and kidney, respectively. The pathway enrichment analysis of the FDEGs then showed that the TNF signaling pathway, Toll-like receptor signaling pathway, and some viral-infection-related pathways (influenza A, measles, and herpes simplex) were the main pathways in multi-organ damage of LPS-mediated endotoxemic mice. Moreover, miRNA-mRNA or PPI regulatory networks were constructed based on FDEGs. According to these networks, 31, 34, 34, and 31 hub genes were identified in the heart, lung, liver, and kidney, respectively. Among them, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) were enriched in Toll-like receptor signaling pathway and chemokine signaling pathway. Finally, seven potential drugs were predicted based on these key genes.ConclusionThe shared underlying molecular pathways in endotoxin-induced multi-organ damage that have been identified include Toll-like receptor signaling pathway and TNF signaling pathway. Besides, nine key genes (Cd274, Cxcl1, Cxcl9, Icam1, Ifit2, Isg15, Stat1, Tlr2, and Usp18) and seven potential drugs were identified. Our data provide a new sight and potential target for future therapy in endotoxemia-induced multi-organ failure.

scholarly journals Gene Expression Profiling Identifies Downregulation of the Neurotrophin-MAPK Signaling Pathway in Female Diabetic Peripheral Neuropathy Patients

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Lin Luo ◽  
Wen-Hua Zhou ◽  
Jiang-Jia Cai ◽  
Mei Feng ◽  
Mi Zhou ◽  
...  
Keyword(s):  
Peripheral Neuropathy ◽  
Signaling Pathway ◽  
Diabetic Peripheral Neuropathy ◽  
Cell Receptor ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Receptor Signaling ◽  
Major Mechanism ◽  
Receptor Signaling Pathway ◽  
Neurotrophin Signaling

Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients because its pathogenesis remains controversial. In this study, human whole genome microarrays identified 2898 and 4493 differentially expressed genes (DEGs) in DM and DPN patients, respectively. A further KEGG pathway analysis indicated that DPN and DM share four pathways, including apoptosis, B cell receptor signaling pathway, endocytosis, and Toll-like receptor signaling pathway. The DEGs identified through comparison of DPN and DM were significantly enriched in MAPK signaling pathway, NOD-like receptor signaling pathway, and neurotrophin signaling pathway, while the “neurotrophin-MAPK signaling pathway” was notably downregulated. Seven DEGs from the neurotrophin-MAPK signaling pathway were validated in additional 78 samples, and the results confirmed the initial microarray findings. These findings demonstrated that downregulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.

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