Kunming Medical University

Prostate cancer (PCa) presents a significant risk to the health of men, and its metastatic spread greatly affects patient survival rates and quality of life. This research investigated the role of DNA methyltransferase 1 (DNMT1) in the progression of PCa.

By performing bioinformatics analysis and in vivo and in vitro experiments, we investigated the expression levels of DNMT1 and LAMA2 in PCa. Additionally, we evaluated how they influence the proliferation and tumor microenvironment (TME) of PCa cells.

DNMT1 was upregulated in PCa, whereas LAMA2 was downregulated. DNMT1 inhibited the expression of LAMA2 by promoting methylation of the LAMA2 promoter, thereby activating the PI3K/AKT signaling pathway, promoting the proliferation of PCa cells, and inducing M2 polarization of macrophages in the TME. Furthermore, DNMT1 promoted the release of the cytokines CCL5, VEGF, MMP9, and PTX3 by PC-3 cells and affected the TME.

This research highlights the crucial function of DNMT1 in the progression of PCa, providing new strategies for the treatment of PCa, particularly therapeutic strategies that focus on DNA methylation and tumor-associated macrophages.

Bacterial biofilm-associated infections, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA), present a major challenge in clinical wound management due to their intrinsic resistance to conventional antibiotics and their capacity to severely impair tissue repair and wound healing. To address the limitations of current therapeutic approaches in combating biofilm-associated infections, we developed a multifunctional bimetal-doped nanozyme system, Cu,Fe,S,N-GQDs@Ru-NO, which synergistically integrates chemodynamic therapy (CDT), photothermal therapy (PTT), photodynamic therapy (PDT), and nitric oxide (NO) gas therapy to achieve enhanced antibiofilm efficacy through multiple complementary mechanisms. The nanozyme was synthesized via a hydrothermal method, during which Cu and Fe co-doped graphene quantum dots (Cu,Fe,S,N-GQDs) were covalently conjugated to an NO-releasing prodrug (Ru-NO) through amide bond formation, enabling precise functionalization. This nanozyme architecture confers multiple catalytic and therapeutic functionalities: the bimetallic doping significantly enhances the catalytic generation of reactive oxygen species (ROS), including hydroxyl radicals (•OH) and singlet oxygen (¹O₂); concurrently, the nanozyme demonstrates efficient photothermal conversion under 808 nm near-infrared (NIR) irradiation and facilitates controlled release of NO. These multimodal actions act synergistically to disrupt bacterial membranes, oxidize NADH (Nicotinamide adenine dinucleotide), and deplete ATP, leading to effective biofilm disintegration and achieving over 99 % bacterial eradication along with complete biofilm clearance in vitro. In a murine model of MRSA-infected wounds, treatment with the nanozyme markedly accelerated wound closure, characterized by attenuated inflammatory responses (reduced IL-6 levels) and enhanced angiogenesis (upregulated VEGF and α-SMA expression), with no detectable cytotoxicity or systemic adverse effects. This study presents a multimodal nanozyme platform that not only achieves potent eradication of multidrug-resistant biofilms but also actively promotes tissue regeneration, offering a promising paradigm for the development of next-generation antimicrobial therapeutics.

The tumor vaccine is regarded as a promising immunotherapeutic approach for the treatment of malignant tumors by activating dendritic cell (DC) and eliciting T-cell responses. Toll-like receptor (TLR) ligands are recognized as effective stimulators of DC maturation. Another critical factor in DC maturation is interferon-γ (IFN-γ), which amplifies the TLR signaling pathway and elevates the expression of inflammatory cytokines in DCs. Furthermore, IFN-γ can markedly enhance the synthesis of interleukin-12 (IL-12) and facilitates T cells in recognizing tumor cells. Consequently, IFN-γ and TLR ligands is utilized to generate mature DCs (mDCs) for the development of clinical tumor vaccines aimed at treating solid tumors. However, the technology facilitating the co-delivery of IFN-γ and TLR ligands to DCs is currently limited. Here, we engineered a strategy utilizing modified bacterial biomimetic vesicles (BBVs) as a delivery system, which effectively stimulated the maturation and migration of DCs, facilitating the differentiation of CD4⁺ Th1 cells and CD8⁺ CTLs, thereby surface displaying IFN-γ and TLR ligands on the BBVs. The engineered BBV/IFN-γ which carry human papillomavirus type 16 (HPV 16) E7 protein and a fusion peptide of three 4T1 neoantigens, respectively triggered Th1/CTLs-polarized T cell responses, promoted tumoral effector T cells infiltration and reshaped the tumor microenvironment, and significantly inhibited tumor growth and metastasis in the TC-1 tumor and orthotopic immune cold 4T1 breast tumor model. Furthermore, the tumor vaccine exhibited synergistic effects with anti- PD-L1 monoclonal antibodies in 4T1 tumor-bearing mice. In conclusion, the functionally modified BBVs demonstrate significant potential to overcome immunosuppression and elicit effective anti-tumor immunity.