3 research outputs found

    Iron Metabolism Regulates p53 Signaling through Direct Heme-p53 Interaction and Modulation of p53 Localization, Stability, and Function

    Get PDF
    Iron excess is closely associated with tumorigenesis in multiple types of human cancers, with underlying mechanisms yet unclear. Recently, iron deprivation has emerged as a major strategy for chemotherapy, but it exerts tumor suppression only on select human malignancies. Here, we report that the tumor suppressor protein p53 is downregulated during iron excess. Strikingly, the iron polyporphyrin heme binds to p53 protein, interferes with p53-DNA interactions, and triggers both nuclear export and cytosolic degradation of p53. Moreover, in a tumorigenicity assay, iron deprivation suppressed wild-type p53-dependent tumor growth, suggesting that upregulation of wild-type p53 signaling underlies the selective efficacy of iron deprivation. Our findings thus identify a direct link between iron/heme homeostasis and the regulation of p53 signaling, which not only provides mechanistic insights into iron-excess-associated tumorigenesis but may also help predict and improve outcomes in iron-deprivation-based chemotherapy

    The ā€œPure Marriageā€ between 3D Printing and Well-Ordered Nanoarrays by Using PEALD Assisted Hydrothermal Surface Engineering

    No full text
    For the first time, homogeneous and well-ordered functional nanoarrays were grown densely on the complex structured three-dimensional (3D) printing frameworks through a general plasma enhanced atomic layer deposition (PEALD) assisted hydrothermal surface engineering process. The entire process was free from toxic additives or harmful residues and, therefore, can meet the critical requirements of high-purity products. As a practical example, 3D customized earplugs were precisely manufactured according to the model of ear canals at the 0.1 mm level. Meanwhile, well-ordered ZnO nanoarrays, formed on the surfaces of these 3D printed earplugs, could effectively prevent the growth of five main pathogens derived from the patients with otitis media and exhibited excellent wear resistance as well. On the basis of both animal experiments and volunteersā€™ investigations, the 3D customized earplugs showed sound insulation capabilities superior to those of traditional earplugs. Further animal experiments demonstrated the potential of as-modified implant scaffolds in practical clinical applications. This work, exemplified with earplugs and implant scaffolds, oriented the development direction of 3D printing in biomedical devices, which precisely integrated customized architecture and tailored surface performance

    The ā€œPure Marriageā€ between 3D Printing and Well-Ordered Nanoarrays by Using PEALD Assisted Hydrothermal Surface Engineering

    No full text
    For the first time, homogeneous and well-ordered functional nanoarrays were grown densely on the complex structured three-dimensional (3D) printing frameworks through a general plasma enhanced atomic layer deposition (PEALD) assisted hydrothermal surface engineering process. The entire process was free from toxic additives or harmful residues and, therefore, can meet the critical requirements of high-purity products. As a practical example, 3D customized earplugs were precisely manufactured according to the model of ear canals at the 0.1 mm level. Meanwhile, well-ordered ZnO nanoarrays, formed on the surfaces of these 3D printed earplugs, could effectively prevent the growth of five main pathogens derived from the patients with otitis media and exhibited excellent wear resistance as well. On the basis of both animal experiments and volunteersā€™ investigations, the 3D customized earplugs showed sound insulation capabilities superior to those of traditional earplugs. Further animal experiments demonstrated the potential of as-modified implant scaffolds in practical clinical applications. This work, exemplified with earplugs and implant scaffolds, oriented the development direction of 3D printing in biomedical devices, which precisely integrated customized architecture and tailored surface performance
    corecore