Vitamin E Inhibits Osteoclastogenesis in Protecting Osteoporosis

The most common orthopedic condition affecting senior adults is osteoporosis, which is defined by a decrease in bone mass and strength as well as microstructural degradation that leads to fragility fractures. Bone remodeling is a well-planned, ongoing process that replaces deteriorated, old bone with new, healthy bone. Bone resorption and bone creation work together during the cycle of bone remodeling to preserve the bone’s volume and microarchitecture. The only bone-resorbing cells in the human body, mononuclear preosteoclasts fuse to form osteoclasts, are multinucleated cells. In numerous animal models or epidemiological studies, vitamin E’s anti-osteoporotic characteristics have been extensively described. This review aims to summarize recent developments in vitamin E’s molecular features as a bone-protective agent. In RANKL/RANK/OPG signaling pathway, vitamin E inhibits synthesis of RANKL, stimulation of c-Fos, and increase level of OPG. Vitamin E also inhibits inflammatory cytokines, such as TNF-α, IL-1, IL-6, IL-27, and MCP-1, negative regulating the JAK–STAT, NF-κB, MAPK signaling pathways. Additionally, vitamin E decreases malondialdehyde and increases superoxide dismutase, GPx and heme oxygenase-1, in suppressing osteoclasts. In this article, we aim to give readers the most recent information on the molecular pathways that vitamin E uses to enhance bone health

circGprc5a Promoted Bladder Oncogenesis and Metastasis through Gprc5a-Targeting Peptide

Bladder cancer is a serious cancer in the world, especially in advanced countries. Bladder cancer stem cells (CSCs) drive bladder tumorigenesis and metastasis. Circular RNAs (circRNAs) are involved in many biological processes, but their roles in bladder oncogenesis and bladder CSCs are unclear. Here, we identified that circGprc5a is upregulated in bladder tumors and CSCs. circGpr5a knockdown impairs the self-renewal and metastasis of bladder CSCs, and its overexpression exerts an opposite role. circGpr5a has peptide-coding potential and functions through a peptide-dependent manner. circGprc5a-peptide binds to Gprc5a, a surface protein highly expressed in bladder CSCs. Gprc5a knockout inhibits the bladder CSC self-renewal and metastasis. circGprc5a-peptide-Gprc5a can be utilized to target bladder cancer and bladder CSCs. Keywords: bladder cancer, cancer stem cells, Gprc5a, peptid

Bone-targeting exosome nanoparticles activate Keap1 / Nrf2 / GPX4 signaling pathway to induce ferroptosis in osteosarcoma cells

Abstract Background In recent years, the development of BMSCs-derived exosomes (EXO) for the treatment of osteosarcoma (OS) is a safe and promising modality for OS treatment, which can effectively deliver drugs to tumor cells in vivo. However, the differences in the drugs carried, and the binding of EXOs to other organs limit their therapeutic efficacy. Therefore, improving the OS-targeting ability of BMSCs EXOs and developing new drugs is crucial for the clinical application of targeted therapy for OS. Results In this study, we constructed a potential therapeutic nano platform by modifying BMSCs EXOs using the bone-targeting peptide SDSSD and encapsulated capreomycin (CAP) within a shell. These constructed nanoparticles (NPs) showed the ability of homologous targeting and bone-targeting exosomes (BT-EXO) significantly promotes cellular endocytosis in vitro and tumor accumulation in vivo. Furthermore, our results revealed that the constructed NPs induced ferroptosis in OS cells by prompting excessive accumulation of reactive oxygen species (ROS), Fe2+ aggregation, and lipid peroxidation and further identified the potential anticancer molecular mechanism of ferroptosis as transduced by the Keap1/Nrf2/GPX4 signaling pathway. Also, these constructed NP-directed ferroptosis showed significant inhibition of tumor growth in vivo with no significant side effects. Conclusion These results suggest that these constructed NPs have superior anticancer activity in mouse models of OS in vitro and in vivo, providing a new and promising strategy for combining ferroptosis-based chemotherapy with targeted therapy for OS