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.

This study utilized a comprehensive approach by integrating multi-omics data to systematically assess lactate modification levels across diverse cell types employing AUCell, JASMINE, and singscore algorithms. An epithelial subpopulation exhibiting the highest lactylation score was successfully pinpointed, and differentially expressed genes linked to lactylation were identified. Through machine learning techniques, a prognostic model was developed based on three genes (TMEM126B, PYGL, and NDUFS6). This model displayed significant associations with immune tumor microenvironment characteristics, microsatellite instability, immune checkpoint expression, and tumor mutation burden. Elevated lactylation risk was linked to the activation of cell cycle and oncogenic pathways, dampened anti-tumor immune responses, and increased expression of immune checkpoints, indicating potential limitations in immunotherapy efficacy. Noteworthy, NDUFS6 exhibited significant upregulation in ovarian cancer (OC) tissues and correlated with an unfavorable prognosis. Functional investigations demonstrated that NDUFS6 knockdown suppressed OC cell proliferation and induced cell cycle arrest. Remarkably, D-lactose emerged as a promising therapeutic agent targeting NDUFS6, underscoring its potential for precise OC treatment.

Objectives: Ovarian granulosa cell tumors (GCTs) are rare ovarian malignancies with limited therapeutic options, particularly in advanced stages. SIRT3, an NAD + -dependent deacetylase, is upregulated in GCTs and implicated in tumorigenesis, yet its functional role and underlying mechanisms remain poorly understood. This study aims to investigate the therapeutic efficacy of a novel SIRT3-specific inhibitor, 77-39, in GCTs by targeting SIRT3 and to elucidate the molecular mechanisms underlying its effects.Methods: This study investigated the effects of a SIRT3-specific inhibitor, 77-39, on GCT cell growth and explored its underlying mechanisms. Using human GCT cell lines KGN and COV434, we assessed the impact of 77–39 on cell viability and proliferation. RNA sequencing and gene set enrichment analyses were performed to elucidate the pathways affected by 77–39. Western blot assays were used to confirm the activation of specific signaling pathways. Additionally, SIRT3 was silenced or overexpressed to observe the corresponding effects on GCT cells. In vivo studies were conducted using xenograft tumor models to evaluate the efficacy and toxicity of 77–39 compared to cisplatin.Results: We demonstrated that 77–39 significantly suppressed cell viability and proliferation while inducing cellular senescence in human GCT cell lines KGN and COV434. RNA sequencing and gene set enrichment analyses revealed that 77–39 led to the activation of the p53 and NF-κB signaling pathways, which were confirmed by Western blot assay. Silencing SIRT3 recapitulated the effects of 77–39, while SIRT3 overexpression reversed these effects. Inhibition of p53 or NF-κB rescued GCT cells from 77-39-induced growth arrest and senescence. In vivo studies using xenograft tumor models showed that 77-39 effectively inhibited tumor growth without significant toxicity, contrasting with the higher toxicity of cisplatin.Conclusion: These findings suggest that 77–39 may serve as a novel therapeutic agent for GCTs by targeting SIRT3 and modulating the p53 and NF-κB pathways.