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 Ganghuo Kanggan Decoction in Influenza: Integrating Network Pharmacology and In Vivo Pharmacological Evaluation

2020 ◽  
Vol 11 ◽  
Author(s):  
Yanni Lai ◽  
Qiong Zhang ◽  
Haishan Long ◽  
Tiantian Han ◽  
Geng Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Influenza A ◽  
Target Prediction ◽  
Enrichment Analysis ◽  
New Drugs ◽  
Network Pharmacology ◽  
Pathway Enrichment Analysis ◽  
Active Components ◽  
Compound Screening

Background: Ganghuo Kanggan decoction (GHKGD) is a clinical experience prescription used for the treatment of viral pneumonia in the Lingnan area of China, and its clinical effect is remarkable. However, the mechanism of GHKGD in influenza is still unclear.Objective: To predict the active components and signaling pathway of GHKGD and to explore its therapeutic mechanism in influenza and to verified it in vivo using network pharmacology.Methods: The potential active components and therapeutic targets of GHKGD in the treatment of influenza were hypothesized through a series of network pharmacological strategies, including compound screening, target prediction and pathway enrichment analysis. Based on the target network and enrichment results, a mouse model of influenza A virus (IAV) infection was established to evaluate the therapeutic effect of GHKGD on influenza and to verify the possible molecular mechanism predicted by network pharmacology.Results: A total of 116 candidate active compounds and 17 potential targets were identified. The results of the potential target enrichment analysis suggested GHKGD may involve the RLR signaling pathway to reduce inflammation in the lungs. In vivo experiments showed that GHKGD had a protective effect on pneumonia caused by IAV-infected mice. Compared with the untreated group, the weight loss in the GHKGD group in the BALB/c mice decreased, and the inflammatory pathological changes in lung tissue were reduced (p < 0.05). The expression of NP protein and the virus titers in lung were significantly decreased (p < 0.05). The protein expression of RIG-I, NF-kB, and STAT1 and the level of MAVS and IRF3/7 mRNA were remarkably inhibited in GHKGD group (p < 0.05). After the treatment with GHKGD, the level of Th1 cytokines (IFN-γ, TNF-α, IL-2) was increased, while the expression of Th2 (IL-5, IL4) cytokines was reduced (p < 0.05).Conclusion: Through a network pharmacology strategy and in vivo experiments, the multi-target and multi-component pharmacological characteristics of GHKGD in the treatment of influenza were revealed, and regulation of the RLR signaling pathway during the anti-influenza process was confirmed. This study provides a theoretical basis for the research and development of new drugs from GHKGD.

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 Global DNA methylation pattern involved in the modulation of differentiation potential of adipogenic and myogenic precursors in skeletal muscle of pigs

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xin Zhang ◽  
Wenjuan Sun ◽  
Linjuan He ◽  
Liqi Wang ◽  
Kai Qiu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Dna Methylation ◽  
Signaling Pathway ◽  
Myogenic Differentiation ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Methylation Pattern ◽  
Pathway Enrichment Analysis ◽  
Differentiation Potential ◽  
Muscle Homeostasis

Abstract Background Skeletal muscle is a complex and heterogeneous tissue accounting for approximately 40% of body weight. Excessive ectopic lipid accumulation in the muscle fascicle would undermine the integrity of skeletal muscle in humans but endow muscle with marbling-related characteristics in farm animals. Therefore, the balance of myogenesis and adipogenesis is of great significance for skeletal muscle homeostasis. Significant DNA methylation occurs during myogenesis and adipogenesis; however, DNA methylation pattern of myogenic and adipogenic precursors derived from skeletal muscle remains unknown yet. Methods In this study, reduced representation bisulfite sequencing was performed to analyze genome-wide DNA methylation of adipogenic and myogenic precursors derived from the skeletal muscle of neonatal pigs. Integrated analysis of DNA methylation and transcription profiles was further conducted. Based on the results of pathway enrichment analysis, myogenic precursors were transfected with CACNA2D2-overexpression plasmids to explore the function of CACNA2D2 in myogenic differentiation. Results As a result, 11,361 differentially methylated regions mainly located in intergenic region and introns were identified. Furthermore, 153 genes with different DNA methylation and gene expression level between adipogenic and myogenic precursors were characterized. Subsequently, pathway enrichment analysis revealed that DNA methylation programing was involved in the regulation of adipogenic and myogenic differentiation potential through mediating the crosstalk among pathways including focal adhesion, regulation of actin cytoskeleton, MAPK signaling pathway, and calcium signaling pathway. In particular, we characterized a new role of CACNA2D2 in inhibiting myogenic differentiation by suppressing JNK/MAPK signaling pathway. Conclusions This study depicted a comprehensive landmark of DNA methylome of skeletal muscle-derived myogenic and adipogenic precursors, highlighted the critical role of CACNA2D2 in regulating myogenic differentiation, and illustrated the possible regulatory ways of DNA methylation on cell fate commitment and skeletal muscle homeostasis.

scholarly journals Key circular RNAs identified in male osteoporosis patients by whole transcriptome sequencing

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11420
Author(s):  
Haijin Zhang ◽  
Xue Song ◽  
Zongyan Teng ◽  
Sujun Cheng ◽  
Weigang Yu ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Expression Profile ◽  
Systemic Disease ◽  
Enrichment Analysis ◽  
Differentially Expressed ◽  
Male Osteoporosis ◽  
Circular Rnas ◽  
Healthy Controls ◽  
Regulation Of Cell Cycle ◽  
Whole Transcriptome

Background Osteoporosis (OP) is a systemic disease with bone loss and microstructural deterioration. Numerous noncoding RNAs (ncRNAs) have been proved to participate in various diseases, especially circular RNAs (circRNAs). However, the expression profile and mechanisms underlying circRNAs in male osteoporosis have not yet been explored. Methods The whole transcriptome expression profile and differences in mRNAs, circRNAs, and microRNAs (miRNAs) were investigated in peripheral blood samples of patients with osteoporosis and healthy controls consisting of males ≥ 60-years-old. Results A total of 398 circRNAs, 51 miRNAs, and 642 mRNAs were significantly and differentially expressed in osteoporosis compared to healthy controls. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the host genes of significantly differentially expressed circRNAs were mainly enriched in the regulation of cell cycle process: biological process (BP), organelle part cellular components (CC), protein binding molecular function (MF), Toll-like receptor signaling pathway, tumor necrosis factor (TNF) signaling pathway, and thyroid hormone signaling pathway. circRNA-miRNA-mRNA regulatory network was constructed using the differentially expressed RNAs. Moreover, key circRNAs (hsa_circ_0042409) in osteoporosis were discovered and validated by qPCR. Conclusions The key cicrRNAs plays a major role in the pathogenesis of osteoporosis and could be used as potential biomarkers or targets in the diagnosis and treatment of osteoporosis.

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 Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for lung adenocarcinoma

2021 ◽  
Author(s):  
Lei Gao ◽  
Ling Zhang
Keyword(s):  
Lung Adenocarcinoma ◽  
Drug Targets ◽  
Enrichment Analysis ◽  
Circular Rnas ◽  
Pathway Enrichment Analysis ◽  
Functional Roles ◽  
Cerna Network ◽  
Kaplan Meier ◽  
Underlying Mechanisms ◽  
Patient Prognosis

Abstract Background More and more studies have proven that circular RNAs (circRNAs) play vital roles in cancer development via sponging miRNAs. However, the expression pattern of competing endogenous RNA (ceRNA) in lung adenocarcinoma (LUAD) remains largely unclear. The current study explored functional roles and the regulatory mechanisms of circRNA as ceRNAs in LUAD and their potential impact on LUAD patient prognosis. Methods In this study, we systematically screened differential expression circRNAs (DEcircRNAs), miRNAs (DEmiRNAs) and mRNAs (DEGs) associated with LUAD. Then, DEcircRNAs, DEmiRNAs and DEGs were selected to construct a circRNA–miRNA–mRNA prognosis-related regulatory network based on interaction information from the ENCORI database. Subsequently, the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the genes in the network to predict the potential underlying mechanisms and functions of circRNAs in LUAD. In addition, Kaplan–Meier survival analysis was performed to evaluate clinical outcomes of LUAD patients, and drug sensitivity analysis was used to screen potential biomarkers for drug treatment of patients with LUAD. Results As a result, ten circRNAs were aberrantly expressed in LUAD tissues. The ceRNA network was built, which included 3 DEcircRNAs, 6 DEmiRNAs and 157 DEGs. The DEGs in the ceRNA network of hsa_circ_0049271 enriched in biological processes of cell proliferation and the Jak-STAT signaling pathway. We also detected 7 mRNAs in the ceRNA network of hsa_circ_0049271 that were significantly associated with the overall survival of LUAD patients (P < 0.05). Importantly, four genes (PDGFB, CCND2, CTF1, IL7R) identified were strongly associated with STAT3 activation and drugs sensitivity in GDSC. Conclusions In summary, a ceRNA network was successfully constructed, which including one circRNA, two miRNAs, and seven mRNAs. Seven mRNAs (PDGFB, TNFRSF19, CCND2, CTF1, IL11RA, IL7R and MAOA) were remarkably associated with the prognosis of LUAD patients. Among seven mRNA species, four genes (PDGFB, CCND2, CTF1, and IL7R) could be considered as drug targets in LUAD. Our research will provide new insights into the prognosis-related ceRNA network in LUAD.

scholarly journals Mechanistic Insight Into the Regulation of Immune-Related Genes Expression in Autism Spectrum Disorder

2021 ◽  
Vol 8 ◽  
Author(s):  
Hani Sabaie ◽  
Hossein Dehghani ◽  
Shadi Shiva ◽  
Mohammad Reza Asadi ◽  
Omidvar Rezaei ◽  
...  
Keyword(s):  
Autism Spectrum Disorder ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Enrichment Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Pathway Enrichment Analysis ◽  
Cerna Network ◽  
Immune Related Genes ◽  
Rna Interaction

Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder featuring impairment in verbal and non-verbal interactions, defects in social interactions, stereotypic behaviors as well as restricted interests. In recent times, the incidence of ASD is growing at a rapid pace. In spite of great endeavors devoted to explaining ASD pathophysiology, its precise etiology remains unresolved. ASD pathogenesis is related to different phenomena associated with the immune system; however, the mechanisms behind these immune phenomena as well as the potential contributing genes remain unclear. In the current work, we used a bioinformatics approach to describe the role of long non-coding RNA (lncRNA)-associated competing endogenous RNAs (ceRNAs) in the peripheral blood (PB) samples to figure out the molecular regulatory procedures involved in ASD better. The Gene Expression Omnibus database was used to obtain the PB microarray dataset (GSE89594) from the subjects suffering from ASD and control subjects, containing the data related to both mRNAs and lncRNAs. The list of immune-related genes was obtained from the ImmPort database. In order to determine the immune-related differentially expressed mRNAs (DEmRNAs) and lncRNAs (DElncRNAs), the limma package of R software was used. A protein-protein interaction network was developed for the immune-related DEmRNAs. By employing the Human MicroRNA Disease Database, DIANA-LncBase, and DIANA-TarBase databases, the RNA interaction pairs were determined. We used the Pearson correlation coefficient to discover the positive correlations between DElncRNAs and DEmRNAs within the ceRNA network. Finally, the lncRNA-associated ceRNA network was created based on DElncRNA-miRNA-DEmRNA interactions and co-expression interactions. In addition, the KEGG enrichment analysis was conducted for immune-related DEmRNAs found within the constructed network. This work found four potential DElncRNA-miRNA-DEmRNA axes in ASD pathogenesis, including, LINC00472/hsa-miR-221-3p/PTPN11, ANP32A-IT1/hsa-miR-182-5p/S100A2, LINC00472/hsa-miR-132-3p/S100A2, and RBM26-AS1/hsa-miR-182-5p/S100A2. According to pathway enrichment analysis, the immune-related DEmRNAs were enriched in the “JAK-STAT signaling pathway” and “Adipocytokine signaling pathway.” An understanding of regulatory mechanisms of ASD-related immune genes would provide novel insights into the molecular mechanisms behind ASD pathogenesis.

scholarly journals Bioinformatics Analysis of the Regulatory lncRNA-miRNA-mRNA Network in Patients with Neuropathic Pain

2020 ◽  
Author(s):  
Huai-Gen Zhang ◽  
Li Liu ◽  
Zhi-Ping Song ◽  
Da-Ying Zhang
Keyword(s):  
Neuropathic Pain ◽  
Signaling Pathway ◽  
Interaction Analysis ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Biological Information ◽  
Receptor Interaction ◽  
Pathway Enrichment Analysis ◽  
Protein Protein Interaction ◽  
Potential Therapeutic Application

Abstract Background: Neuropathic pain (NP) is the main form of chronic pain, caused by damage to the nervous system and dysfunction. Methods: Here, we explore the key molecules involved in the development of NP condition via identification of lncRNA-miRNA-mRNA expression pattern of patients with NP. We identified differentially expressed miRNAs, lncRNA and mRNA through a comprehensive analysis strategy. Subsequently, we used bioinformatics approach to perform pathway enrichment analysis on DEGs and protein-protein interaction analysis. Combined with the three datasets, the lncRNA-miRNA-mRNA network was constructed. It will then be used as targets for drug prediction. Results: The results showed that a total of 8,251 DEGs (4,193 upregulated and 4,058 downregulated) were identified from the three microarray datasets, 959 DEmiRs (455 upregulated and 504 downregulated), 2,848 DElncs (1,324 upregulated and 1,524 downregulated). GO analysis showed that DEGs are mainly enriched in blood circulation, regulation of membrane potential and regulation of ion transmembrane transport. KEGG results showed that DEGs are enriched in neuroactive ligand-receptor interaction, PI3K-Akt signaling pathway and MAPK signaling pathway. When the correlation is set to above 0.8, a total of 31 lncRNAs, 36 miRNAs and 24 mRNAs were screened in the lncRNA-miRNA-mRNAs network. The results of drug prediction indicated the targeted drugs mainly include INDOMETHACIN, GLUTAMIC ACID and PIRACETAM. Conclusion: The lncRNA-miRNA-mRNA network has been carried out a comprehensive biological information analysis and predicted the potential therapeutic application of drugs in patients with NP. The corresponding data has a certain reference for studying the pathological mechanism of NP.

Characterization of Methylation Patterns in Diffuse Large B Cell Lymphoma By Genome-Wide Methylation Analysis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1243-1243
Author(s):  
Fengyi Zhao ◽  
Lei Zhang ◽  
Yan Qin ◽  
Ming-Zhe Han ◽  
Xiaohong Han ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Signaling Pathway ◽  
Methylation Level ◽  
Enrichment Analysis ◽  
B Cell Lymphoma ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Pathway Enrichment Analysis ◽  
Ffpe Tissues ◽  
Methylation Patterns

Background: Diffuse large B cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma worldwide. Although the reference standard for identifying of the cell types is considered of gene expression profiling (GEP). But immunohistochemistry (IHC) is the most common method commercially available. The purpose of this study was to characterize the circulating cell-free DNA (cfDNA) methylation profile in DLBCL and to compare this profile with methylation observed in formalin fixed paraffin-embedded (FFPE) tissues. Additional efforts were made to correlate the observed methylation patterns with prognostic analysis and selected clinical features. Methods: The cfDNA and DNA of FFPE were extracted from 72 patients and 39 patients respectively. We assessed DNA methylation from plasma samples obtained from 29 individuals with GCB DLBCL at the time before treatment along with 43 samples of non-GCB DLBCL as controls. DNA from FFPE tissues were extracted from 11 individuals of GCB DLBCL and 28 individuals with non-GCB DLBCL. DNA methylation was analyzed with the Infinium MethylationEPIC BeadChip that quantitatively measures the methylation levels of more than 850,000 CpG sites across the genome. M values were used for visualization and intuitive interpretation of the results. Moreover, pathway enrichment analysis was performed with the Kyoto Encyclopedia of Genes and Genomes (KEGG) Pathway Database. Results: We found a total of 207 significant differentional differentially methylated positions (DMPs) of cfDNA between the GCB and non-GCB groups, identified with a p value of 0.001 (Fig. 1A). Of these, 65 presented at least 10% (|Δbeta| > 0.1) difference in the methylation level between GCB and non-GCB. 29 (44.6%) were found hypermethylated in GCB DLBCL, while 36 (55.4%) appeared hypomethylated (Fig. 1B). The distribution of the DMPs identified according to their location relative to CpG islands (CGI) were represented in Fig. 1C. Unsupervised clustering performed on DNA methylation values for the 207 DMPs identified is presented in Fig. 1D. These results highlight the differences between GCB and non-GCB samples. There are 1549 significant DMPs of DNA from FFPE between the GCB and non-GCB groups, identified with a p value of 0.001 (Fig. 1E). Of these, 1512 presented at least 10% (|Δbeta| > 0.1) difference in the methylation level between GCB and non-GCB . 1370 (90.6%) were found hypermethylated in GCB DLBCL, while 142 (9.4%) appeared hypomethylated (Fig. 1F). The distribution of the DMPs identified according to their location relative to CpG islands (CGI) were represented in Fig. 1G. Unsupervised clustering performed on DNA methylation values for the 1549 DMPs identified is presented in Fig. 1H. These results highlight the differences between GCB and non-GCB in FFPE samples which according with that in serum. The KEGG pathway enrichment analysis of DNA from FFPE tissue methylation revealed that the process "PI3K/Akt, Ras, MAPK signaling pathway" and "Human papillomavirus infection" are likely major contributors to Hans pathological type. In addition, the enrichment analysis of cfDNA methylation revealed that the process "MAPK signaling pathway" is likely the most important factor. Furthermore, we also have analyzed the methylation level between refractory or relapsed (R/R) DLBCL patients and individuals with a good prognosis. The differential methylation patterns were also found both in serums and FFPE tissues. Conclusions: The DNA methylation differs in GCB and non-GCB DLBCL patients. MAPK signaling pathway plays an important role in it. The mechanism needs to be further explored. Figure 1 Disclosures No relevant conflicts of interest to declare.

scholarly journals Network Pharmacology Approach and Experimental Verification of Huashi Dingtong Decoction Against Knee Osteoarthritis

2020 ◽  
Author(s):  
Ge Hai-Ya ◽  
Yan Lai-Jun ◽  
Zhang Yan ◽  
Zhang Ying-Sheng ◽  
Lai Yu-Yang ◽  
...  
Keyword(s):  
Synovial Fluid ◽  
Knee Osteoarthritis ◽  
Signaling Pathway ◽  
Interaction Network ◽  
Enrichment Analysis ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Model Group ◽  
Target Network

Abstract Background: The aim of this study is to clarify the ingredients and targets of HSDTT against KOA by network pharmacology,and to verify the mechanism of HSDTT in treatment of KOA in vivo.Methods: Ingredient-target network for HSDTT and KOA was created to identify the potential targets, protein-protein interaction network was used to find the key targets of HSDTT in treatment for KOA, GO enrichment and KEGG pathway was conducted to illuminate the pathway related to KOA treat by HSDTT. Rat model of KOA was established by joint injection in papain.The morphology of cartilage were assessed by H&E. ELISA was used to detect the contents of inflammation cytokines in synovial fluid and synovium. The expression of the pathway protein were assessed by PCR.Results: The results of network pharmacology demonstrate that there are 440 ingredients of HSDTT against knee osteoarthritis by 478 targets.The KEGG enrichment analysis showed that PI3K-Akt signaling pathway, MAPK signaling pathway were the key pathways for HSDTT to treat KOA. Morphology of cartilage was improved in the HSDTT group when compared with the model group. Our experiment show that HSDTT can reduced the expressions of p38 and p53 in cartilage, increased the expression of collagenⅡ. The contents of IL-1β and TNF-α in the synovium and COX-2 and PGE-2 in synovial fluid were decreased significantly in the HSDTT group when compared with the model group.Conclusions: Our study indicadites that HSDTT is capable to alleviate inflammation and delay the progression of KOA by p38MAPK signaling pathway.

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