ROS, RNS, and carcinogenic metabolites generate excessive oxidative stress, which changes the basal cellular status and leads to epigenetic modification, genomic instability, and initiation of cancer. Epigenetic modification may inhibit tumor-suppressor genes and activate oncogenes, enabling cells to have cancer promoting properties. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that in humans is encoded by the NFE2L2 gene, and is activated in response to cellular stress. It can regulate redox homoeostasis by expressing several cytoprotective enzymes, including NADPH quinine oxidoreductase, heme oxygenase-1, UDP-glucuronosyltransferase, glutathione peroxidase, glutathione-S-transferase, etc. There is accumulating evidence supporting the idea that dietary nutraceuticals derived from commonly used fruits, vegetables, and spices have the ability to produce cancer chemopreventive activity by inducing Nrf2-mediated detoxifying enzymes. In this review, we discuss the importance of these nutraceuticals in cancer chemoprevention and summarize the role of dietary terpenoids in this respect. This approach was taken to accumulate the mechanistic function of these terpenoids to develop a comprehensive understanding of their direct and indirect roles in modulating the Keap1-Nrf2-ARE signaling system.

Articular cartilage has a limited self-healing capacity, leading to joint degeneration and osteoarthritis over time. Therefore, bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering. In this study, we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM, tempo-oxidized cellulose nanofiber (TOCN), and alginate carriers for TGF-β1, FGF-18, and ADSCs to repair cartilage defects. The characterization results demonstrate that the 3D scaffolds are physically stable and facilitate a controlled dual release of TGF-β1 and FGF-18. Moreover, the key biological proteins within the bioactive scaffold actively interact with the biological systems to create a favorable microenvironment for cartilage regeneration. Importantly, the in vitro, in vivo, and in silico simulation showed that the scaffolds promote stem cell recruitment, migration, proliferation, and ECM deposition, and synergistic effects of TGF-β1/FGF-18 with the bioactive scaffolds significantly regulate stem cell chondrogenesis by activating the PI3K/AKT and TGFβ1/Smad4 signaling pathways. After implantation, the proteinaceous bioactive scaffold led to the regeneration of mechanically robust, full-thickness cartilage tissue that closely resembles native cartilage. Thus, these findings may provide a promising approach for regulating stem cell chondrogenesis and treating in situ cartilage regeneration.