Mechanism of Camellia nitidissima Chi in Treating Premature Ovarian Failure Based on Network Pharmacology and Molecular Docking

[Objectives]This study was conducted to explore active components and molecular biological mechanisms of Camellia nitidissima Chi in the treatment of premature ovarian failure(POF).[Methods]The active components and corresponding targets of C.nitidissima Chi were retrieved through literature and the TCMSP database.POF-related disease targets were identified using the OMIM and Genecards databases.A PPI network was constructed using the STRING database and Cytoscape 3.10.2.A herb-active component-target-pathway network diagram was also constructed with Cytoscape 3.10.2.The CytoNCA plugin was used to screen out the top five core targets and core active components.GO and KEGG enrichment analyses of the intersecting targets were performed using DAVID.Finally,molecular docking was conducted using Auto Dock to verify the interaction between core targets and active components,and visualization was done using PyMol.[Results]A total of 26 active components and 461 targets of C.nitidissima Chi were identified,with 154 intersecting targets related to POF.The core components of the herb included 1,1'-bi-2-naphthol,3',4-O-dimethylcedrusin,eriodictyol,quercetin,and vanillin.The PPI network revealed that the main targets were epidermal growth factor receptor(EGFR),protein kinase B1(AKT1),proto-oncogene Src(SRC),hypoxia-inducible factor 1α(HIF1A),and estrogen receptor 1(ESR1).KEGG enrichment analysis revealed 10 pathways closely related to POF,mainly involving the PI3K-Akt signaling pathway,chemical carcinogenesis-reactive oxygen species,endocrine resistance,and the HIF-1 signaling pathway.Molecular docking results showed that the core active components had strong binding activity with the targets.[Conclusions]C.nitidissima Chi has multi-component,multi-target,and multi-pathway characteristics in the comprehensive treatment of POF,providing informational support for its clinical application.

Identification and characteristic analysis of enhancers across 13 major cancer types

Enhancers are often mutated and dysregulated in various diseases such as cancer.By integrating the function annotation of the mammalian genome(FANTOM)enhancers expression profiles and RNA-seq data from The Cancer Genome Atlas(TCGA)of 13 cancers and their corresponding para-cancerous tissues,we systematically identified a total of 4702 significantly differentially expressed(DE)enhancers.Furthermore,a total of 1036 DE genes regulated by DE enhancerswere identified.Itwas found that in these 13 cancers,most(61.13%)enhancers were ubiquitously expressed,whereas DE enhancers were more likely to be tissue-specific expressed,and the DE genes regulated by DE enhancers were significantly enriched in cancer-related pathways.Finally,it was manifested that 74 single nucleotide polymorphisms(SNPs)were located in 37 DE enhancers,and these SNPs affected the gain and loss of functional transcription factor binding sites of 758 transcription factors,which were shown to be highly correlated with tumorigenesis and development.