Genetic mutations and abnormal gene regulation are key mechanisms underlying tumorigenesis. Nucleosomes, which consist of DNA wrapped around histone cores, represent the basic units of chromatin. The fifth amino group (N ε) of histone lysine residues is a common site for post-translational modifications (PTMs), and of these, acetylation is the second most common. Histone acetylation is modulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), and is involved in the regulation of gene expression. Over the past two decades, numerous studies characterizing HDACs and HDAC inhibitors (HDACi) have provided novel and exciting insights concerning their underlying biological mechanisms and potential anti-cancer treatments. In this review, we detail the diverse structures of HDACs and their underlying biological functions, including transcriptional regulation, metabolism, angiogenesis, DNA damage response, cell cycle, apoptosis, protein degradation, immunity and other several physiological processes. We also highlight potential avenues to use HDACi as novel, precision cancer treatments.
Context. Kuntai capsule (KTC), a proprietary Chinese medicine, have been used for the treatment of polycystic ovary syndrome (PCOS). Objective. This study elucidates the potential therapeutic targets and molecular mechanisms of KTC in the treatment of PCOS. Materials and Methods. Using the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP), the active ingredients and potential targets of KTC were obtained. The Gene Expression Omnibus (GEO) database was used to find differentially expressed genes (DEGs) related to PCOS. Search the CTD, DisGeNet, genecards, NCBI, OMIM, and PharmGKB databases for therapeutic targets related to PCOS. The intersection of potential targets, DEGs, and therapeutic targets was submitted to perform bioinformatics analysis by R language. Finally, the analyses’ core targets and their corresponding active ingredients were molecularly docked. Results. 88 potential therapeutic targets of KTC for PCOS were discovered by intersecting the potential targets, DEGs, and therapeutic targets. According to bioinformatics analysis, the mechanisms of KTC treatment for PCOS could be linked to IL-17 signaling route, p53 signaling pathway, HIF-1 signaling pathway, etc. The minimal binding energies of the 5 core targets and their corresponding ingredients were all less than -6.5. Further research found that quercetin may replace KTC in the treatment of PCOS. Discussion and Conclusions. We explored the active ingredients and molecular mechanisms of KTC in the treatment of PCOS and found that quercetin may be the core ingredient of KTC in the treatment of PCOS.
ObjectivesIn this research, we aim to explore the bioinformatic mechanism of infertile endometriosis in order to identify new treatment targets and molecular mechanism.MethodsThe Gene Expression Omnibus (GEO) database was used to download MRNA sequencing data from infertile endometriosis patients. The “limma” package in R software was used to find differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) was used to classify genes into modules, further obtained the correlation coefficient between the modules and infertility endometriosis. The intersection genes of the most disease-related modular genes and DEGs are called gene set 1. To clarify the molecular mechanisms and potential therapeutic targets for infertile endometriosis, we used Gene Ontology (GO), Kyoto Gene and Genome Encyclopedia (KEGG) enrichment, Protein-Protein Interaction (PPI) networks, and Gene Set Enrichment Analysis (GSEA) on these intersecting genes. We identified lncRNAs and miRNAs linked with infertility and created competing endogenous RNAs (ceRNA) regulation networks using the Human MicroRNA Disease Database (HMDD), mirTarBase database, and LncRNA Disease database.ResultsFirstly, WGCNA enrichment analysis was used to examine the infertile endometriosis dataset GSE120103, and we discovered that the Meorangered1 module was the most significantly related with infertile endometriosis. The intersection genes were mostly enriched in the metabolism of different amino acids, the cGMP-PKG signaling pathway, and the cAMP signaling pathway according to KEGG enrichment analysis. The Meorangered1 module genes and DEGs were then subjected to bioinformatic analysis. The hub genes in the PPI network were performed KEGG enrichment analysis, and the results were consistent with the intersection gene analysis. Finally, we used the database to identify 13 miRNAs and two lncRNAs linked to infertility in order to create the ceRNA regulatory network linked to infertile endometriosis.ConclusionIn this study, we used a bioinformatics approach for the first time to identify amino acid metabolism as a possible major cause of infertility in patients with endometriosis and to provide potential targets for the diagnosis and treatment of these patients.
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