Copper is an important trace element for maintaining key biological functions such as cellular respiration, nerve conduction, and antioxidant defense. Maintaining copper homeostasis is critical for human health, and its imbalance has been linked to various diseases, especially cancer. Cuproptosis, a novel mechanism of copper-induced cell death, provides new therapeutic opportunities for metal ion regulation to interact with cell fate. This review provides insights into the complex mechanisms of copper metabolism, the molecular basis of cuproptosis, and its association with cancer development. We assess the role of cuproptosis-related genes (CRGs) associated with tumorigenesis, their importance as prognostic indicators and therapeutic targets, and the impact of copper homeostasis on the tumor microenvironment (TME) and immune response. Ultimately, this review highlights the complex interplay between copper, cuproptosis, and cancer immunotherapy.

Periodontitis is a bacteria-induced inflammatory disease characterized by the progressive destruction of periodontal supporting tissues. Periodontal ligament stem cells (PDLSCs) are capable of differentiating into osteoblasts, which is an important stem cell source for endogenous periodontal tissue regeneration. Lysine lactylation (Kla) is a novel post-translational modification of proteins that is recently thought to be associated with osteogenic differentiation. Here, we found that lactylation levels are reduced both in the periodontal tissue of rats with periodontitis and lipopolysaccharide (LPS)-stimulated human PDLSCs. Proanthocyanidins were able to promote the osteogenesis of inflamed PDLSCs by restoring lactylation levels. Mechanistically, proanthocyanidins increased lactate production and restored the lactylation levels of PDLSCs, which recovered osteogenesis of inflamed PDLSCs via the Wnt/β-catenin pathway. These results provide evidence on how epigenetic regulation by pharmacological agents influence the osteogenic phenotype of stem cells and the process of periodontal tissue repair. Our current study highlights the valuable potential of natural product proanthocyanidins in the regenerative engineering of periodontal tissues.

Investigating cancer metabolism is of paramount importance for understanding tumor biology and developing novel therapeutic strategies. Lactylation, a posttranslational modification facilitated by the glycolytic product lactate, plays a crucial role in regulating oncogenic signalling pathways. This review provides a comprehensive analysis of lactate metabolism, including its biosynthesis, compartmentalized transport, enzymatic network and structural features of lactate dehydrogenases, transporters, lactyltransferases and deacetylases. These enzymes contribute to malignant tumor progression through metabolic reprogramming and modulation of the immune microenvironment. Importantly, we emphasize that integrating cancer subtype-specific lactylation profiles with core signatures reveals promising therapeutic opportunities for targeting lactate shuttles, histone, and nonhistone lactylation mechanisms, and transcriptional networks regulated by lactylation. In the present review, we highlight the significant potential of targeting glycolysis and lactylation modifications in tumors to improve the efficacy of cancer treatments.

Oral squamous cell carcinoma (OSCC) is a prevalent form of malignant tumor, characterized by a persistently high incidence and mortality rate. The extracellular matrix (ECM) plays a crucial role in the initiation, progression, and diverse biological behaviors of OSCC, facilitated by mechanisms such as providing structural support, promoting cell migration and invasion, regulating cell morphology, and modulating signal transduction. This study investigated the involvement of ECM-related genes, particularly THBS1, in the prognosis and cellular behavior of OSCC. The analysis of ECM-related gene data from OSCC samples identified 165 differentially expressed genes forming two clusters with distinct prognostic outcomes. Seventeen ECM-related genes showed a significant correlation with survival. Experimental methods were employed to demonstrate the impact of THBS1 on proliferation, migration, invasion, and ECM degradation in OSCC cells. A risk-prediction model utilizing four differentially prognostic genes demonstrated significant predictive value in overall survival. THBS1 exhibited enrichment of the PI3K/AKT pathway, indicating its potential role in modulating OSCC. In conclusion, this study observed and verified that ECM-related genes, particularly THBS1, have the potential to influence the prognosis, biological behavior, and immunotherapy of OSCC. These findings hold significant implications for enhancing survival outcomes and providing guidance for precise treatment of OSCC.

In clinical practice and research, bone defects due to tumor growth, trauma, and different pathological conditions are significant challenges. Although bone possesses an intrinsic capacity for regeneration, extensive bone abnormalities necessitate applying advanced methods for regenerating bone. Bone organoids have made methodological breakthroughs in this field, and the use of bone organoids to repair bone defects has gained wide acceptance in the scientific community, supported by a large body of experimental evidence. This review synthesizes existing literature and ground-breaking studies to provide an in-depth examination of the bone organoid model, exploring the fundamental architecture and development of bone and emphasizing recent advancements in bone organoid fabrication, such as the application of 3D bioprinting technology in bone organoid fabrication. Furthermore, the study suggests potential directions for future research, highlighting the critical role of interdisciplinary collaboration in fully harnessing the potential of this rapidly evolving field. Key scientific concepts of review Bone organoids involve the 3D self-organization of in vitro-cultured bone-associated stem cells, optionally including extracellular matrix components. This process generates tissue closely resembling the original bone tissue's functional, genetic, and structural features. Bone organoids are more promising than traditional methods of bone defect repair. In addition, tissue engineering technologies such as 3D bioprinting have opened up new opportunities for constructing bone organoids. Future research should prioritize the development of composite bone organoids, enhancement of bone organoid stiffness, and improvement of bioactive materials, as well as the exploration and development of novel bioinks to facilitate the application of bone organoids in bone repair and regeneration.