BACKGROUND: Since the molecular mechanisms of cervical cancer (CC) have not been completely discovered, it is of great significance to identify the hub genes and pathways of this disease to reveal the molecular mechanisms of cervical cancer. OBJECTIVE: The study aimed to identify the biological functions and prognostic value of hub genes in cervical cancer. METHODS: The gene expression data of CC patients were downloaded from the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. The core genes were screened out by differential gene expression analysis and weighted gene co-expression network analysis (WGCNA). R software, the STRING online tool and Cytoscape software were used to screen out the hub genes. The GEPIA public database was used to further verify the expression levels of the hub genes in normal tissues and tumour tissues and determine the disease-free survival (DFS) rates of the hub genes. The protein expression of the survival-related hub genes was identified with the Human Protein Atlas (HPA) database. RESULTS: A total of 64 core genes were screened, and 10 genes, including RFC5, POLE3, RAD51, RMI1, PALB2, HDAC1, MCM4, ESR1, FOS and E2F1, were identified as hub genes. Compared with that in normal tissues, RFC5, POLE3, RAD51,RMI1, PALB2, MCM4 and E2F1 were all significantly upregulated in cervical cancer, ESR1 was significantly downregulated in cervical cancer, and RFC5 expression in CC patients was significantly related to OS. In the DFS analysis, no significant difference was observed in the expression level of RFC5 in cervical cancer patients. Finally, RFC5 protein levels verified by the HPA database were consistently upregulated with mRNA levels in CC samples. CONCLUSIONS: RFC5 may play important roles in the occurrence and prognosis of CC. It could be further explored and validated as a potential predictor and therapeutic target for CC.

BACKGROUND: With the rapid development of genomics and molecular biology, not only have biochemical indicators been used as tumour markers, but many new molecular markers have emerged. Epigenetic abnormalities are a new type of molecular marker, and DNA methylation is an important part of epigenetics. OBJECTIVE: This study used weighted gene coexpression network analysis (WGCNA) to analyse key methylation-driven genes in breast cancer. METHODS: The RNA-seq transcriptome data, DNA methylation data, and clinical information data of breast cancer patients were downloaded from The Cancer Genome Atlas (TCGA) database, and the MethylMix R package was used to screen methylation-driven genes in breast cancer. The ClusterProfiler package and enrichplot package in R software were used to further analyse the function and signalling pathway of methylation-driven genes. Through univariate and multivariate Cox regression analyses, methylation-driver genes related to prognostic were obtained, a prognostic model was constructed and prognostic characteristics were analysed. RESULTS: The 17 methylation-driven genes related to prognosis were obtained by the WGCNA method in breast cancer, and the prognostic significance of these methylation-driven genes was determined by transcriptome and methylation combined survival analysis. Analysis of functions and signalling pathways showed that these genes were mainly enriched in biological processes and signalling pathway. Through univariate and multivariate Cox regression analyses, a prognostic model of 5 methylation-driven genes was constructed. CONCLUSIONS: The AUC of the receiver operating characteristic (ROC) curve of this model was 0.784, showing that the model had a good prediction effect. Based on WGCNA screening, it was found that only CDO1 was the key methylation-driven gene for prognosis in breast cancer, indicating that CDO1 may be an important indicator of the prognosis of breast cancer patients.

Tachypleus tridentatus (T. tridentatus) is a marine animal and traditional Chinese medicine. T. tridentatus plasma is a valuable resource for important medical and health-based functions. In this experiment, in order to evaluate the effect and mechanism of T. tridentatus plasma with respect to the promotion of bone tissue growth in rats, the processes of ultrafiltration and mass spectrometry were first used to separate and identify the components of T. tridentatus plasma. Then, a comparison of the effects of the T. tridentatus plasma samples, which each possessed different molecular weights, regarding the growth of the long bones of rats was conducted. Finally, transcriptomics, proteomics, and bioinformatics were all used to analyze the biological functions and related signaling pathways of the T. tridentatus plasma in order to promote rat bone growth. The results showed that the contents of amino acid residues in peptides are related to the growth promotion that was contained in the 10–30 kDa plasma group. Moreover, the T. tridentatus plasma samples were found to be higher in this respect than those in the whole plasma group. In addition, the 10–30 kDa plasma group could significantly promote bone growth activity in rats. The proteomic analysis showed that the proteins that were differentially expressed in the 10–30 kDa plasma group were mainly enriched in the PI3K-AKT signal pathway. Our study suggested that the T. tridentatus plasma possesses promising potential for the purposes of clinical use, whereby it can serve the role of a growth-promoting agent.

Cyclic pentapeptide compounds have garnered much attention as a drug discovery resource. This study focused on the characterization and anti-benign prostatic hyperplasia (BPH) properties of avellanin A from Aspergillus fumigatus fungus in marine sediment samples collected in the Beibu Gulf of Guangxi Province in China. The antiproliferative effect and molecular mechanism of avellanin A were explored in testosterone propionate (TP)-induced RWPE-1 cells. The transcriptome results showed that avellanin A significantly blocked the ECM–receptor interaction and suppressed the downstream PI3K-Akt signalling pathway. Molecular docking revealed that avellanin A has a good affinity for the cathepsin L protein, which is involved in the terminal degradation of extracellular matrix components. Subsequently, qRT-PCR analysis revealed that the expression of the genes COL1A1, COL1A2, COL5A2, COL6A3, MMP2, MMP9, ITGA2, and ITGB3 was significantly downregulated after avellanin A intervention. The Western blot results also confirmed that it not only reduced ITGB3 and FAK/p-FAK protein expression but also inhibited PI3K/p-PI3K and Akt/p-Akt protein expression in the PI3K-Akt signalling pathway. Furthermore, avellanin A downregulated Cyclin D1 protein expression and upregulated Bax, p21^WAF1/Cip1, and p53 proapoptotic protein expression in TP-induced RWPE-1 cells, leading to cell cycle arrest and inhibition of cell proliferation. The results of this study support the use of avellanin A as a potential new drug for the treatment of BPH.

Talaromyces marneffei (TM) is an opportunistic pathogenic fungus that mainly infects immunocompromised patients. Currently, the global prevalence of talaromycosis caused by TM is increasing, leading to an increased demand for anti-TM drugs. In our previous study, a novel 28-membered macrolide compound, antifungalmycin B (ANB), was isolated from Streptomyces hiroshimensis GXIMD 06359, exhibiting significant antifungal properties. However, its in vivo mechanisms and direct antifungal effects warrant further investigation. In this study, we employed a mouse model in conjunction with transcriptomic and proteomic approaches to explore the antifungal activity of ANB against T. marneffei. In an in vivo mouse model infected with T. marneffei infection, ANB significantly reduced fungal burdens in the liver, spleen, lungs, and kidneys. Additionally, it markedly decreased the levels of reactive oxygen species (ROS) and cytokines, including interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α. Proteomic and transcriptomic studies, complemented by parallel reaction monitoring (PRM) analysis, revealed that ANB effectively disrupted acid biosynthesis and cellular energy metabolism, thereby impairing mitochondrial functions in T. marneffei. These effects were exerted through multiple pathways. These findings highlight the potential of ANB as a versatile inhibitor of polyene macrolide-resistant fungi, offering a promising therapeutic avenue for the treatment of talaromycosis.