Background. Compound fuling granule (CFG) is a traditional Chinese medicine formula that is used for more than twenty years to treat ovarian cancer (OC) in China. However, the underlying processes have yet to be completely understood. This research is aimed at uncovering its molecular mechanism and identifying possible therapeutic targets. Methods. Significant genes were collected from Therapeutic Target Database and Database of Gene‐Disease Associations. The components of CFG were analyzed by LC‐MS/MS, and the active components of CFG were screened according to their oral bioavailability and drug‐likeness index. The validated targets were extracted from PharmMapper and PubChem databases. Venn diagram and STRING website diagrams were used to identify intersection targets, and a protein–protein interaction network was prepared using STRING. The ingredient‐target network was established using Cytoscape. Molecular docking was performed to visualize the molecule–protein interactions using PyMOL 2.3. Enrichment and pathway analyses were performed using FunRich software and Reactome pathway, respectively. Experimental validations, including CCK‐8 assay, wound‐scratch assay, flow cytometry, western blot assay, histopathological examination, and immunohistochemistry, were conducted to verify the effects of CFG on OC cells. Results. A total of 56 bioactive ingredients of CFG and 185 CFG‐OC‐related targets were screened by network pharmacology analysis. The potential therapeutic targets included moesin, glutathione S‐transferase kappa 1, ribonuclease III (DICER1), mucin1 (MUC1), cyclin‐dependent kinase 2 (CDK2), E1A binding protein p300, and transcription activator BRG1. Reactome analysis showed 51 signaling pathways (P < 0.05), and FunRich revealed 44 signaling pathways that might play an important role in CFG against OC. Molecular docking of CDK2 and five active compounds (baicalin, ignavine, lactiflorin, neokadsuranic acid B, and deoxyaconitine) showed that baicalin had the highest affinity to CDK2. Experimental approaches confirmed that CFG could apparently inhibit OC cell proliferation and migration in vitro; increase apoptosis; decrease the protein expression of MUC1, DICER1, and CDK2; and suppress the progression and distant metastasis of OC in vivo. DICER1, a tumor suppressor, is essential for microRNA synthesis. Our findings suggest that CFG may impair the production of miRNAs in OC cells. Conclusion. Based on network pharmacology, molecular docking, and experimental validation, the potential mechanism underlying the function of CFG in OC was explored, which supplies the theoretical groundwork for additional pharmacological investigation.

Purpose: To explore the mechanism of Huashi Jiedu Decoction (HJD) synergizing with 5-fluorouracil (5-Fu) in gastric cancer (GC) therapy. Methods: MicroRNAs (miRNAs) and genes involved in HJD-mediated GC treatment were identified using ultra-high-performance liquid chromatography coupled with quadrupole-Orbitrap mass spectrometry, network pharmacology, Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, and molecular docking. The effects of HJD on 5-Fu sensitivity in BGC-823 cells were evaluated with 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays, reverse transcription quantitative polymerase chain reaction (RT-qPCR), and Western blotting. Synergistic effects in vector-transfected and miRNA-21-3p knockdown cells were assessed by colony formation, wound healing, transwell assays, and flow cytometry (FCM). An in vivo study evaluated the impact of HJD on 5-Fu sensitivity, measuring miRNA-21-3p, tumor protein p53 (p53), N-cadherin, vimentin, and E-cadherin in tumors, along with tumor volume and weight. Results: miRNA-21-3p and p53 were key targets in HJD’s therapeutic effect on GC. RT-qPCR showed that HJD combined with 5-Fu reduced miRNA-21-3p and upregulated p53 in vector cells and increased p53 mRNA (p < 0.01) and protein (p < 0.05) compared to 5-Fu alone. These effects were abolished in miRNA-21-3p knockdown cells. The combination reduced colony formation by 48.92% (p < 0.01), suppressed transwell migration by 28.5% (p < 0.01), and inhibited wound healing by 81.9% compared to 5-Fu monotherapy (p < 0.001), with no effects in knockdown cells. FCM showed a 15.1% increase in G₀/G₁ phase arrest (p < 0.05). In vivo, the combination significantly reduced tumor volume (p < 0.05) and weight by 18.7%, with concomitant miRNA-21-3p downregulation (p < 0.0001), EMT marker suppression (N-cadherin, vimentin), and tumor suppressor activation (p53, E-cadherin) versus 5-Fu alone. Conclusion: HJD enhances 5-Fu’s effects on GC by regulating the miRNA-21-3p/p53 pathway and modulating cadherin expression, supporting its potential as an adjunctive treatment in GC.

Background: Advanced stomach adenocarcinoma (ASTAD) is a highly malignant and prognostically poor stage of gastric cancer. Recently, long noncoding RNA (lncRNA) was found to play a crucial role, including as competing endogenous RNA (ceRNA) in cancer. However, studies on large-scale sample in ASTAD are still lacking, thus we constructed the ceRNA network of ASTAD to explore its molecular mechanism.

Article: Effects of bladder perfusion of pentosan polysulfate sodium and hyaluronic acid on mucosal mast cells of rats with interstitial cystitis - Minerva Surgery 2022 Jun 16 - Minerva Medica - Journals