Kyoto Encyclopedia Of Genes And Genomes Pathway Analysis Research Articles

Network Pharmacology Analysis, Molecular Docking, and In Vitro Verification Reveal the Action Mechanism of Prunella vulgaris L. in Treating Breast Cancer.

Background Prunella vulgaris L. is effective in the treatment of breast cancer (BRCA); however, the underlying mechanism is still unclear. The aim of this study was to elucidate the mechanism of treatment of BRCA by P. vulgaris using network pharmacology and molecular docking technology, and to verify the experimental results using human BRCA MDA-MB-231 cells. Methods Active components and action targets of P. vulgaris were determined using the TCMSP™, SwissTarget Prediction™, and TargetNet™ databases. GeneCards™ and OMIM™ provided BRCA targets. After obtaining common targets, a protein-protein interaction (PPI) network was constructed using the STRING™ database, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted using the Xiantao™ academic database. Cytoscape™ was used to construct “single drug-disease-component-target” and “single drug-disease-component-target-pathway” networks. The Human Protein Atlas™ was used to determine protein expression levels in BRCA cell lines. AutoDock tools™ were used to carry out molecular docking for the first 10 targets of quercetin and the PPI network. Finally, the abovementioned results were verified using cell experiments. Results We obtained 11 active components, 198 targets, and 179 common targets, including DUOX2, MET, TOP2A, and ERBB3. The results of KEGG pathway analysis screened 188 related signaling pathways and indicated the potential key role of PI3K-Akt and MAPK signaling pathways in the antibreast cancer process of P. vulgaris. The results of molecular docking showed that the first 10 targets of quercetin interacted well with the protein network. Cell experiments showed that quercetin effectively inhibited the proliferation of MDA-MB-231 cells by regulating apoptosis and cell cycle, which may be partly related to the MAPK signaling pathway. Conclusion Synergistic effects of multiple components, targets, and pathways on the anti-BRCA activity of P. vulgaris could provide a theoretical basis for further study on its complex anti-BRCA mechanism.

Histology study and transcriptome analysis of the testis of Loach(Misgurnus anguillicaudatus) in response to phenanthrene exposure

Phenanthrene (PHE) is one of the most abundant polycyclic aromatic hydrocarbon compounds (PAHs) in the aquatic environment. The loaches were exposed at concentrations of 0.30、1.00、3.00 mg L−1 for 60 days. The effects of PHE on the testis development were evaluated by calculating the survival rate, observing the structure of testis and analyzing transcriptome. Firstly, PHE markedly decreased the survival rate in a dose-dependent manner. Then, the number and density of spermatogonia, primary spermatocytes, secondary spermatocytes and spermatids were substantially reduced under PHE exposure. The space in the seminiferous tubule obviously increased in the high PHE concentration group. Meanwhile, transcriptome comparative analysis identified 5329 differentially expressed genes (DEGs) including 2928 up-regulated and 2401 down-regulated in the testis of loach exposed PHE for 60 days. Meiotic cell cycle, arganelle fission, ATPase activity and adenylate nucleotide binding were significantly differences by GO (Gene Ontology) enrichment. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that TNF (Tumor Necrosis Factor) signaling pathway, CAMs (Cell Adhesion Molecules), cytochrome P450 and lipid metabolism were markedly regulated. In addition, eight DEGs were randomly selected from the testis transcriptomics results for qPCR verification, the results were consistent with RNA-Seq. Finally, related genes (piwil2, dmc1, vasa, ubr2, dnd, rnf17, plcb2, c-fos, gpx4) of testis development were further confirmed and they were differentially regulated after PHE exposure. In summary, a survey of the mechanism of loach testis response to PHE was performed, and a large number of gene expression levels regarding metabolism, spermatogenesis and immunity genes were acquired from RNA-seq. This study provide informations for elucidating the molecular mechanism of PHE affected the testis development of loach.

Network Pharmacology and Molecular Docking Analysis on the Pharmacological Mechanisms of Modified Sanmiaosan in Treating Ulcerative Colitis.

Background Modified Sanmiaosan is an effective cure in the treatment of ulcerative colitis, but its mechanisms of action remain unclear. This study revealed the pharmacological mechanisms of Modified Sanmiaosan acting on ulcerative colitis through a pharmacology approach. Materials and Methods The active compounds and the targets of Modified Sanmiaosan were selected from the Traditional Chinese Medicine Systems Pharmacology database according to the absorption and metabolism. The UC-related therapeutic targets were collected from the PharmGKB database, the GeneCards database, the GADA database, and the OMIM database. The networks of “drug-component-target-disease” and “herbal-component-target” were constructed by the Cytoscape software. Protein–protein interaction network was generated by the STRING database. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed by the R software. Molecular docking technology was used to identify the affinity and activity between active compounds and targets. Results The 80 effective ingredients of MSM were collected. A total of 5180 UC-related genes and the 153 key targets of MSM and UC-related were obtained. JUN, Akt1, and MAPK1 were identified as the “hub targets” involved in the effects of Modified Sanmiaosan on ulcerative colitis. Hub targets were mainly involved in inflammatory response and oxidative stress. As the results of GO analysis, biological processes such as DNA-binding transcription and RNA polymerization may participate in the treatment process; KEGG pathway analysis showed that hub targets were mainly involved in IL-17 signal pathway and TNF signal pathway of ulcerative colitis. The high affinity and activity of the active compounds and targets were verified through molecular docking. Conclusion These findings demonstrate the active ingredients in Modified Sanmiaosan reduce inflammatory response by TNF and IL-17 signaling pathways to treat ulcerative colitis. Anti-inflammation and immune regulation may be the main mechanism of Modified Sanmiaosan in the treatment of ulcerative colitis. This study not only provide new insights into the development of a natural therapy for the prevention and treatment of ulcerative colitis but also proves a feasible method for discovering potential activated compounds from Chinese herbs.

The fecal microbiota of gravidas with fetal growth restriction newborns characterized by metagenomic sequencing

BackgroundFetal growth restriction (FGR) is a complex obstetric complication with various causes and of great harm. However, the specific pathogenesis of FGR is unclear, which limits its effective treatment. Gut microbiota dysbiosis was found to be important in pathogenesis of various diseases. However, its role in FGR development remains unclear and needs to be clarified. MethodsIn our case-control study, we recruited eight FGR and eight control female participants and collected their fecal samples in third trimester before delivery. We performed metagenomic sequencing and bioinformatic analysis to compare the gut microbiota composition and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways between the two groups. ResultsOur results showed that totally 20 gut microbes were significantly different between two groups (p<0•05), and the correlation analysis found that g__Roseomonas and g__unclassified_f__Propionibacteriaceae were significantly positive correlated with both maternal body mass index (BMI) before delivery, placental weight, and neonatal birth weight (BW) percentile (all p<0•05), while g__Marinisporobacter and g__Sphingomonas were significantly negative correlated with both neonatal BMI and neonatal BW percentile (all p<0•05). Through KEGG pathway analysis, we found that the abundance of the Nitrogen metabolism pathway decreased significantly (p<0•05) whereas the abundance of the Amoebiasis pathway increased significantly in the FGR group (p<0•05). ConclusionIn this study, we demonstrated that the occurrence of FGR is associated with the change of gut microbiota of pregnant women.

Screening of Candidate Pathogenic Genes for Spontaneous Abortion Using Whole Exome Sequencing

Spontaneous abortion is a common disease in obstetrics and reproduction. This study aimed to screen candidate pathogenic genes for spontaneous abortion using whole-exome sequencing. Genomic DNA was extracted from abortion tissues of spontaneous abortion patients and sequenced using the Illumina HiSeq2500 high-throughput sequencing platform. Whole exome sequencing was performed to select harmful mutations, including SNP and insertion and deletion sites, associated with spontaneous abortion. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses and gene fusion analyses were performed. MUC3A and PDE4DIP were two novel mutation genes that were screened and verified by PCR in abortion tissues of patients. A total of 83,633 SNPs and 13,635 Indel mutations were detected, of which 29172 SNPs and 3093 Indels were screened as harmful mutations. The 7 GO-BP, 4 GO-CC, 9 GO-MF progress, and 3 KEGG pathways were enriched in GO and KEGG pathway analyses. A total of 746 gene fusion mutations were obtained, involving 492 genes. MUC3A and PDE4DIP were used for PCR verification because of their high number of mutation sites in all samples. There are extensive SNPs and Indel mutations in the genome of spontaneous abortion tissues, and the effect of these gene mutations on spontaneous abortion needs further experimental verification.

Integrated analysis of mRNA-single nucleotide polymorphism-microRNA interaction network to identify biomarkers associated with prostate cancer.

Background: Prostate cancer is one of the most common malignancies among men worldwide currently. However, specific mechanisms of prostate cancer were still not fully understood due to lack of integrated molecular analyses. We performed this study to establish an mRNA-single nucleotide polymorphism (SNP)-microRNA (miRNA) interaction network by comprehensive bioinformatics analysis, and search for novel biomarkers for prostate cancer. Materials and methods: mRNA, miRNA, and SNP data were acquired from Gene Expression Omnibus (GEO) database. Differential expression analysis was performed to identify differentially expressed genes (DEGs) and miRNAs (DEMs). Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, protein-protein interaction (PPI) analysis and expression quantitative trait loci (eQTL) analysis of DEGs were conducted. SNPs related to DEMs (miRSNPs) were downloaded from the open-source website MirSNP and PolymiRTS 3.0. TargetScan and miRDB databases were used for the target mRNA prediction of miRNA. The mRNA-SNP-miRNA interaction network was then constructed and visualized by Cytoscape 3.9.0. Selected key biomarkers were further validated using the Cancer Genome Atlas (TCGA) database. A nomogram model was constructed to predict the risk of prostate cancer. Results: In our study, 266 DEGs and 11 DEMs were identified. KEGG pathway analysis showed that DEGs were strikingly enriched in focal adhesion and PI3K-Akt signaling pathway. A total of 60 mRNA-SNP-miRNAs trios were identified to establish the mRNA-SNP-miRNA interaction network. Seven mRNAs in mRNA-SNP-miRNA network were consistent with the predicted target mRNAs of miRNA. These results were largely validated by the TCGA database analysis. A nomogram was constructed that contained four variables (ITGB8, hsa-miR-21, hsa-miR-30b and prostate-specific antigen (PSA) value) for predicting the risk of prostate cancer. Conclusion: Our study established the mRNA-SNP-miRNA interaction network in prostate cancer. The interaction network showed that hsa-miR-21, hsa-miR-30b, and ITGB8 may be utilized as new biomarkers for prostate cancer.

Exploring the Mechanism of Curcumin on Retinoblastoma Based on Network Pharmacology and Molecular Docking.

Background Curcumin shows great effects of inhibiting tumor cell proliferation, inducing apoptosis, inhibiting tumor metastasis, and inhibiting angiogenesis on a variety of tumors. However, the biological activity and possible mechanisms of curcumin in the treatment of retinoblastoma have not been fully elucidated. This study explored the potential therapeutic targets and pharmacological mechanisms of curcumin against retinoblastoma based on network pharmacology and molecular docking. Methods The genes corresponding to curcumin targets were screened from the HERB, PharmMapper, and SwissTargetPrediction databases. Protein-protein interaction (PPI) networks were constructed for the intersecting targets in the STRING database. Cytoscape 3.7.0 was used for network topology analysis and screening of important targets. R 4.1.0 software was used for Gene Ontology (GO) function enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of intersection targets. The molecular structures of curcumin and core target proteins were obtained from PubChem and PDB databases, and the two were preprocessed and molecularly docked using AutoDockTools and PyMOL software. Results Through network data mining, we obtained 504 curcumin targets and 966 retinoblastoma disease targets, and 44 potential targets for curcumin treatment of retinoblastoma were obtained by mapping. Three core targets were obtained from network topology analysis. 462 biological processes, 21 cellular compositions, and 34 molecular functions were obtained by GO enrichment analysis. KEGG pathway analysis revealed 94 signaling pathways, mainly involving chemical carcinogenesis-receptor activation, chemical carcinogenesis-reactive oxygen species, viral carcinogenesis, Th17 cell differentiation, etc. The molecular docking results indicated that the binding energy of curcumin to the core targets was less than 0 kJ mol−1, among which the binding energy of RB1 and CDKN2A to curcumin was less than −5 kJ mol−1 with significant binding activity. Conclusion Based on molecular docking technology and network pharmacology, we initially revealed that curcumin exerts its therapeutic effects on retinoblastoma with multitarget, multipathway, and multibiological functions, providing a theoretical basis for subsequent studies.

Screening of four key genes in esophageal carcinoma based on TCGA and GEO data and verification of anti-proliferative effect of LAPTM4B knockdown in esophageal carcinoma cells invitro

Esophageal carcinoma (ESCA) is one of the most prevalent and aggressive malignancies of the gastrointestinal tract and constitutes sixth primary cause of cancer-related death worldwide. It is urgently needed to identify effective therapeutic targets. Differentially expressed genes (DEGs) involved in ESCA were identified via bioinformatics analysis. Four DEGs were selected for further analysis using Gene Expression Profiling Interactive Analysis, Human Protein Atlas, UALCAN web portal, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. 5-ethynyl-2′-deoxyuridine incorporation and cell counting kit-8 assays were used to evaluate cell proliferation. Western blot analysis was used to detect the protein levels of lysosomal-associated transmembrane protein 4B (LAPTM4B), Notch1, hairy and enhancer of split 1 (Hes1), and hairy and enhancer of split-related with YRPW motif 1 (Hey1). Results showed that LAPTM4B, Bcl-2 homology domain 3 (BH3)-interacting domain death agonist (BID), epithelial cell transforming sequence 2 (ECT2), and aurora kinase A (AURKA) were upregulated in several types of tumors including ESCA and correlated with tumor stage and tumor histology based on bioinformatics analysis. KEGG pathway analysis suggested that LAPTM4B-associated genes were significantly enriched in Notch pathway. Meanwhile, BID-, ECT2-, and AURKA-correlated genes were particularly enriched in p53 signaling pathway. Additionally, we found that LAPTM4B silencing inhibited cell proliferation and Notch pathway in ESCA cells. Notch1 overexpression abrogated LAPTM4B knockdown-induced proliferation reduction in ESCA cells. In conclusion, LAPTM4B silencing inhibited proliferation in ESCA cells by inactivating the Notch pathway.

Novel LncRNA ZFHX4-AS1 as a Potential Prognostic Biomarker That Affects the Immune Microenvironment in Ovarian Cancer.

BackgroundOvarian cancer (OvCa) is a malignant disease of the female reproductive system with a high mortality rate. LncRNA has been confirmed to play a crucial role in the development and progression of various cancer types. Novel lncRNA ZFHX4-AS1 has been reported in several cancers, albeit its functional mechanisms in OvCa remain unclear.MethodsWith reference to the public databases and based on integrating bioinformatics analyses, we explored the expression of ZFHX4-AS1 and its roles in the prognosis of OvCa. We employed the Kaplan-Meier curves to investigate the outcome of patients with different ZFHX4-AS1 expressions. Furthermore, its biological function and the related hallmark pathways were assessed through Gene Ontology (GO) annotation, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, and Gene-set enrichment analysis (GSEA). We explored the correlation between lncRNA ZFHX4-AS1 and tumor-infiltrating immune cells through CIBERSORT. The immune checkpoints associated with lncRNA ZFHX4-AS1 and its related genes were investigated. The effect of lncRNA ZFHX4-AS1 on proliferation, invasion and migration of OvCa cells was verified through Cell Counting Kit (CCK)-8, colony formation, wound healing and transwell assays.ResultsThe expression of lncRNA ZFHX4-AS1 was upregulated in OvCa relative to that in normal tissues. Increased lncRNA ZFHX4-AS1 expression was associated with poor overall survival and progression-free survival in OvCa. The GO and KEGG pathway analyses revealed the role of lncRNA ZFHX4-AS1 in cell metabolism, protein synthesis, cell proliferation, and cell cycle. GSEA indicated the hallmark gene sets that were significantly enriched in the high and low expression groups. The CIBERSORT database revealed M2 macrophages, memory B-cells, naïve B cells, and activated NK cells were affected by lncRNA ZFHX4-AS1 expression (all P < 0.05). The expression of lncRNA ZFHX4-AS1 and its related differential genes MRPS11, NSA2, and MRPL13 were significantly correlated with the immune checkpoints. Knockdown of lncRNA ZFHX4-AS1 could inhibit the proliferation, invasion and migration of OvCa cells.ConclusionsThe results suggested that lncRNA ZFHX4-AS1 is a novel prognostic biomarker associated with cell proliferation, metabolism, infiltration, and distribution of tumor-infiltrating immune cells in OvCa, indicating that lncRNA ZFHX4-AS1 can be used as a potential therapeutic target for OvCa in the future.

Identification of molecular mechanisms underlying the therapeutic effects of Xintong granule in coronary artery disease by a network pharmacology and molecular docking approach.

Coronary artery disease (CAD) is a cardiovascular disease characterized by atherosclerosis, angiogenesis, thrombogenesis, inflammation, etc. Xintong granule (XTG) is considered a practical therapeutic strategy in China for CAD. Although its therapeutic role in CAD has been reported, the molecular mechanisms of XTG in CAD have not yet been explored.A network pharmacology approach including drug-likeness (DL) evaluation, oral bioavailability (OB) prediction, protein-protein interaction (PPI) network construction and analysis, and Gene Ontology term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses was used to predict the active ingredients, potential targets, and molecular mechanisms of XTG associated with the treatment of CAD. Molecular docking analysis was performed to investigate the interactions between the active compounds and the underlying targets.Fifty-one active ingredients of XTG and 294 CAD-related targets were screened for analysis. Gene Ontology enrichment analysis showed that the therapeutic targets of XTG in CAD are mainly involved in blood circulation and vascular regulation. KEGG pathway analysis indicated that XTG intervenes in CAD mainly through the regulation of fluid shear stress and atherosclerosis, the AGE-RAGE signaling pathway in diabetic complications, and the relaxin signaling pathway. Molecular docking analysis showed that each key active ingredient (quercetin, luteolin, kaempferol, stigmasterol, resveratrol, fisetin, gamma-sitosterol, and beta-sitosterol) of XTG can bind to the core targets of CAD (AKT1, JUN, RELA, MAPK8, NFKB1, EDN1, and NOS3).The present study revealed the CAD treatment-related active ingredients, underlying targets, and potential molecular mechanisms of XTG acting by regulating fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, and relaxin signaling pathway.

Integrating network pharmacology and experimental models to investigate the efficacy of QYHJ on pancreatic cancer

Ethnopharmacological relevanceThe Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear. Aim of the studyThis study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro. Materials and methodsThe bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting. ResultsA total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment. ConclusionsQYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

Genome-Wide Analysis of microRNAs Identifies the Lipid Metabolism Pathway to Be a Defining Factor in Adipose Tissue From Different Sheep.

microRNAs are a class of important non-coding RNAs, which can participate in the regulation of biological processes. In recent years, miRNA has been widely studied not only in humans and mice, but also in animal husbandry. However, compared with other livestock and poultry breeds, the study of miRNA in subcutaneous adipose tissue of sheep is not comprehensive. Transcriptome analysis of miRNAs in subcutaneous adipose tissue of Duolang sheep, and Small Tail Han sheep was performed using RNA-Seq technology. Differentially expressed miRNAs were screened between different breeds. Target genes were predicted, and then the joint analysis of candidate genes were conducted based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Finally, the RNA-Seq data were verified by real-time quantitative polymerase chain reaction (qRT-PCR). Herein, we identified 38 differentially expressed miRNAs (9 novel miRNAs and 29 known miRNAs). In addition, a total of 854 target genes were predicted by miRanda software. GO and KEGG pathway analysis demonstrated that regulation of lipolysis in adipocytes plays a key role in the deposition of subcutaneous adipose tissue in Duolang sheep and Small Tail Han sheep. The miRNAs might regulate fat deposits by regulating genes involved in regulation of lipolysis in adipocytes. Specifically, NC_ 040278.1_ 37602, oar-mir-493-3p, NC_ 040278.1_ 37521 and NC_ 040255.1_ 11627 might target PTGS2, AKT2, AKT3, and PIK3CA, respectively, and then play critical regulatory role. In conclusion, all the results provide a good idea for further revealing the mechanism of subcutaneous adipose tissue deposition and improving the meat production performance of sheep, and lay a foundation for promoting the development of animal husbandry.

MRNA, lncRNA and Circular RNA Expression Profiles in Granulosa Cells of Infertile Women with Ovarian Endometriosis.

To explore the expression profiles of mRNAs, long-noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and construct the competitive endogenous RNA networks in granulosa cells (GCs) of infertile women with ovarian endometriosis. RNA sequencing was conducted for RNA expression profiling from GCs of five women with ovarian endometriosis and five with tubal factor infertility. The differential expression of mRNAs, lncRNAs and circRNAs was compared. Then, the lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA networks were constructed. Finally, the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were performed to determine the role of the differential expression of mRNA. A total of 12,498 mRNAs, 724 lncRNAs and 2269 circRNAs were identified in ovarian endometriosis and controls. 37 mRNAs, 51 lncRNAs and 101 circRNAs were detected to be differentially expressed in women with ovarian endometriosis. Ten lncRNAs and 22 differentially expressed mRNAs were selected to build the lncRNA-miRNA-mRNA network, while 12 circRNAs and four differentially expressed mRNAs were selected to build the circRNA-miRNA-mRNA network. GO analysis suggested that the differentially expressed mRNAs were mainly involved in regulation of cell differentiation, cell cycle while KEGG pathway analysis showed that pathways involved in the MAPK signaling pathway and FoxO signaling pathway were enriched with differentially upregulated mRNAs. We generated mRNAs, lncRNAs and circRNAs expression profiles and identified differentially expressed RNAs of GCs in infertile women with ovarian endometriosis. These findings provide a basis for further understanding of the underlying etiology of endometriosis-related infertility.

Identification of genes and key pathways underlying the pathophysiological association between nonalcoholic fatty liver disease and atrial fibrillation

BackgroundAtrial fibrillation (AF) is one of the most prevalent sustained cardiac arrhythmias. The latest studies have revealed a tight correlation between nonalcoholic fatty liver disease (NAFLD) and AF. However, the exact molecular mechanisms underlying the association between NAFLD and AF remain unclear. The current research aimed to expound the genes and signaling pathways that are related to the mechanisms underlying the association between these two diseases.Materials and methodsNAFLD- and AF- related differentially expressed genes (DEGs) were identified via bioinformatic analysis of the Gene Expression Omnibus (GEO) datasets GSE63067 and GSE79768, respectively. Further enrichment analysis of Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), the construction of a protein–protein interaction (PPI) network, the identification of significant hub genes, and receiver operator characteristic curve analysis were conducted. The gene-disease interactions were analyzed using the Comparative Toxicogenomics Database. In addition, the hub genes were validated by quantitative Real-Time PCR (qRT-PCR) in NAFLD cell model.ResultsA total of 45 co-expressed differentially expressed genes (co-DEGs) were identified between the NAFLD/AF and healthy control individuals. GO and KEGG pathway analyses revealed that the co-DEGs were mostly enriched in neutrophil activation involved in the immune response and cytokine-cytokine receptor interactions. Moreover, eight hub genes were selected owing to their high degree of connectivity and upregulation in both the NAFLD and AF datasets. These genes included CCR2, PTPRC, CXCR2, MNDA, S100A9, NCF2, S100A12, and S100A8.ConclusionsIn summary, we conducted the gene differential expression analysis, functional enrichment analysis, and PPI analysis of DEGs in AF and NAFLD, which provides novel insights into the identification of potential biomarkers and valuable therapeutic leads for AF and NAFLD.

Matrix metalloproteinase 14 and plasma kallikrein 1 may be potential biomarkers in the diagnosis and treatment of sepsis: a proteomics and bioinformatics analysis

To analyze protein profiles in septic patients, and to find potential new targets for the diagnosis and treatment of sepsis. A cross sectional observational study was conducted. From January to December 2019, 12 septic patients and 9 healthy volunteers were recruited in the emergency intensive care unit (EICU) of the emergency department of the Affiliated Hospital of Southwest Medical University. The peripheral blood of the two groups was collected for protein mass spectrometry analysis, and the data-independent acquisition technology was used to obtain the expression data of each protein. The obtained data was imported into the online network tool Integrated Differential Expression and Pathway analysis (IDEP2), the data underwent ID converted and were homogenized to verify their comparability, and then principal component analysis was used to eliminate outlier data. Then data with P < 0.05, log2fold change (FC) > 1 or log2FC < -1 were considered to have a statistically significant difference, and the differential proteins were screened out. On the DAVID website, the screened differential proteins would be analyzed by gene ontology (GO), and the biological process, cellular components, and molecular function of the proteins would be analyzed. Protein enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed. Protein-protein interaction (PPI) analysis was performed through the Search Tool for the Retrieval of Interacting Genes Database (STRING) website to find closely related proteins. The data in this study were shown to be comparable after normalization. A total of 125 differential proteins were screened, of which 99 were up-regulated and 26 were down-regulated. GO enrichment analysis discovered that these proteins were mainly extracellular, with cellular regulatory functions and catalytic functions involved in biological regulation, metabolic process and immune process. KEGG pathway analysis suggested that these proteins were involved in amino acid, carbohydrate metabolism and immune-related pathways. PPI analysis showed that key proteins included matrix metalloproteinase 14 (MMP14), fibulin 1 (FBLN1), plasma kallikrein 1 (KLKB1), etc., and finally screened out MMP14 and KLKB1, which were closely related to inflammation and immunity. Both might be potential new targets for early diagnosis and treatment of sepsis. MMP14 and KLKB1 may be potential biomarkers for the diagnosis, treatment and prognosis of sepsis.

To study the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer based on network pharmacology.

The aim of the study wasto explore the target and potential mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer infection by network pharmacology.The target information of baicalein and flavonin was mined from CTD database and Swiss database. Genecards database, DRUGBANK database, and OMIM database were used to search for lung cancer related genes. The target protein network map (PPI) was drawn by using the STRING database analysis and Cytoscape3.7.1 software. With the help of Perl language, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis and gene function analysis (GO) enrichment analysis were carried out by using the biological program package of R language.In total, 347 biological targets of Astragaloside and Scutellariae Radix were identified through the collection and analysis of multiple databases. In total, 1526 lung cancer targets were obtained from a multi-disease database. The “component-target” network of Astragaloside and Scutellariae Radix was constructed, and the protein interaction network (PPI) of the overlapping targets was analyzed to identify the key targets of drug-influenced diseases. In addition, KEGG pathway analysis and GO enrichment analysis were performed on the overlapping targets to explore the mechanism of Scutellariae Radix and Astragaloside in the treatment of lung cancer.Scutellariae Radix and Astragaloside have the characteristics of multi-component, multi-target and multi-pathway in the treatment of lung cancer, which provides a new idea and scientific basis for further research on the molecular mechanism of the antilung cancer effect of Scutellariae Radix and Astragaloside.

Identification of key apoptosis-related genes and immune infiltration in the pathogenesis of psoriasis

BackgroundPsoriasis is a condition in which skin cells build up and form itchy scales and dry patches. It is also considered a common lifelong disease with an unclear pathogenesis. Furthermore, an effective cure for psoriasis is still unavailable. Reductive apoptosis of keratinocytes and immune infiltration are common in psoriasis. This study aimed to explore underlying functions of key apoptosis-related genes and the characteristics of immune infiltration in psoriasis. We used GSE13355 and GSE30999 to screen differentially expressed apoptosis related genes (DEARGs) in our study. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway, and gene set enrichment analysis (GSEA) were performed using clusterProfiler package. Protein–protein interaction (PPI) network was constructed to acquire key DEARGs. Transcription factor (TF)–target and miRNA–mRNA network analyses, drug sensitivity prediction, and immune infiltration were applied. Key DEARGs were validated using real-time quantitative PCR (RT-qPCR).ResultsWe identified 482 and 32 DEARGs from GSE13355 and GSE30999, respectively. GO analysis showed that DEARGs were commonly enriched in cell chemotaxis, receptor ligand activity, and signaling receptor activator activity. KEGG pathway analysis indicated that viral protein interaction with cytokine and cytokine receptor was maximally enriched pathway. The GSEA analysis of GSE13355 and GSE30999 demonstrated a high consistency degree of enriched pathways. Thirteen key DEARGs with upregulation were obtained in the PPI network. Eleven key DEARGs were confirmed using RT-qPCR. Additionally, 5 TFs and 553 miRNAs were acquired, and three novel drugs were predicted. Moreover, Dendritic.cells.activated exhibited high levels of immune infiltration while Mast.cells.resting showed low levels of immune infiltration in psoriasis groups.ConclusionResults of this study may reveal some insights into the underlying molecular mechanism of psoriasis and provide novel targeted drugs.

Genome-Wide Identification of Binding Sites for SmTCP7a Transcription Factors of Eggplant during Bacterial Wilt Resistance by ChIP-Seq.

Teosinte branched 1/cycloidea/proliferating cell factor (TCP) transcription factors play a key role in the regulation of plant biotic and abiotic stresses. In this study, our results show that SmTCP7a positively regulated bacterial wilt that was caused by Ralstonia solanacearum. ChIP-seq was conducted to analyze the transcriptional regulation mechanism of SmTCP7a before (R0 h) and 48 h after infection (R48 h). SmTCP7a regulated a total of 92 and 91 peak-associated genes in R0 h and R48 h, respectively. A KEGG (Kyoto encyclopedia of genes and genomes) pathway analysis showed that phenylpropanoid biosynthesis, MAPK (mitogen-activated protein kinas) signaling pathway, plant hormone signal transduction and plant-pathogen interactions were involved. The difference in peaks between R0 h and R48 h showed that there were three peak-associated genes that were modulated by infection. A better understanding of the potential target genes of SmTCP7a in response to R. solanacearum will provide a comprehensive understanding of the SmTCP7a regulatory mechanism during the eggplant defense response to bacterial wilt.

Abstract 2727: Overexpression of protocadherin related 15 (PCDH15) gene predicts better prognosis in low-grade glioma patients

Abstract Background: Gliomas are the most common tumors arising from the brain. According to the WHO classification, gliomas are divided into low- and high-grade gliomas based on their aggressiveness and degrees of differentiation. Protocadherin Related 15 (PCDH15) gene is a member of the cadherin superfamily that encode membrane proteins involved in cell-cell adhesion. In this study, we aimed to investigate the prognostic value of PCDH15 expression in Low-Grade Gliomas (LGG) and Glioblastoma Multiforme (GBM). Methods: We conducted a bioinformatics analysis for PCDH15 in LGG and GBM patients’ data using their respective datasets from the Cancer Genomic Atlas (TCGA). GEPIA and GENT2 web-based tools were used to confirm the differential expression of PCDH15 in LGG and GBM patients in comparison with normal brain tissue. We used the cBioPortal database to compare PCDH15 expression across molecular and histological glioma subtypes. Also, the SurvExpress tool was used to assess the prognostic value of PCDH15 on overall survival (OS). To further understand the underlying molecular biology of PCDH15’s function, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for significantly co-expressed genes (|spearman correlation coefficient|≥ 0.5) with PCDH15 using the DAVID 6.8 bioinformatics tool. Results: LGG and GBM both had statistically significant differences in PCDH15 expression compared with normal brain tissue. PCDH15 expression was significantly higher in LGG patients compared with GBM patients (mean log2 (TPM + 1): 9.5 vs 5.6, P &amp;lt; 0.0001), with the highest expression in patients with mutated IDH genes. In the LGG cohort, higher PCDH15 expression was associated with longer OS (hazard ratio: 2.44, 95% confidence interval: 1.69 - 3.53, P = 1.949E-6) while no significant difference was found in the GBM cohort (hazard ratio: 1.07, 95% confidence interval: 0.74 - 1.53, P = 0.7304). GO analyses for co-expressed genes in LGG indicated a role in the biological process (BP) DNA-templated regulation of transcription with a cellular component (CC) in the nucleus and the molecular functions (MF) “histone demethylase activity”, “hydrolase activity, acting on acid anhydrides” and “zinc ion binding”. While in GBM, GO analysis showed enrichment in the BP terms, “neuron cell-cell adhesion”, “positive regulation of synapse assembly”, and the CC terms, “cell junction”, “axon”, “plasma membrane”. KEGG pathway analysis did not retrieve any significantly enriched pathways in both diseases. Conclusion: Our findings demonstrate a unique pattern of PCDH15 overexpression in low-grade gliomas which was translated into a substantial impact on patients’ survival. Functional enrichment analysis indicated transcription regulation as a potential mechanism for PCDH15 in LGG, further supporting PCDH15's potential as a therapeutic target. Citation Format: Hassan Mohammed Abushukair, Bayan Osama Abu Alragheb. Overexpression of protocadherin related 15 (PCDH15) gene predicts better prognosis in low-grade glioma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2727.

Abstract 5957: Molecular characteristics of gut microbiota in patients with gastric cancer: The DELIVER trial (JACCRO GC-08)

Abstract Microbiome analysis has attracted attention in recent years as a tool to monitor individual health status. In particular, gut microbiota is closely related to autoimmunity, and detailed study of gut microbiota may enable prediction of the health status of individuals.Here, we aimed to conduct a detailed study to identify gastric cancer-specific gut microbiota and compare the data between patients with gastric cancer and healthy individuals. Toward this, we extracted DNA from feces of patients with advanced gastric cancer enrolled in the observational/translational study, the DELIVER trial (JACCRO GC-08: UMIN000030850) which evaluated clinical outcomes of nivolumab and developed host-related biomarkers for nivolumab in 500 patients with advanced gastric cancer, and obtained their sequence data at an average of 5 Gbps using whole-genome shotgun sequencing. We then performed genus classification and functional pathway analysis using Kyoto Encyclopedia of Genes and Genomes (KEGG).We analyzed differences in bacterial composition using the data of 476 Japanese patients with advanced gastric cancer (median age 70y, median BMI 20.0, 71% male, 37.0% of patients with relapse, 55.5% with previous gastrectomy) and public database of 106 healthy cases. Bifidobacterium, Anaerostipes, and Parabacteroides were predominant in the healthy individuals, whereas Streptococcus, Lactobacillus, and Odoribacter were predominant in patients with advanced gastric cancer. Furthermore, the KEGG pathway analysis showed that butanoate and pyruvate metabolism were enriched in the healthy individuals, whereas factors such as ABC transporters and ribosomes were enriched in the patients with advanced gastric cancer. Clustering analysis broadly classified the patients with advanced gastric cancer and healthy individuals into two clusters, and the clustering using pathway data enabled clearer classification of the patients with advanced gastric cancer and healthy individuals than the clustering using flora analysis. Additionally, the healthy individuals had higher bacterial flora diversity compared to the patients with advanced gastric cancer.We thus successfully identified the molecular characteristic of microbial genera and functional pathways in the gut in patients with advanced gastric cancer. We conclude that fecal metagenomic shotgun sequencing analysis might be used to detect gastric cancer. Citation Format: Ryo Matoba, Hiroshi Iijima, Yasuhiro Sakamoto, Ryohei Kawabata, Atsushi Ishiguro, Yusuke Akamaru, Yosuke Kito, Hiroshi Yabusaki, Jin Matsuyama, Masazumi Takahashi, Akitaka Makiyama, Takahisa Suzuki, Masahiro Tsuda, Hisateru Yasui, Jun Hihara, Toru Masuzawa, Hiroyuki Okuda, Junji Kawada, Shuhei Suzuki, Hisato Kawakami, Takako Eguchi Nakajima, Kei Muro, Wataru Ichikawa, Masashi Fujii, Yu Sunakawa. Molecular characteristics of gut microbiota in patients with gastric cancer: The DELIVER trial (JACCRO GC-08) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5957.