Role of c-Fos in DNA damage repair.

c-Fos, a member of the immediate early gene, serves as a widely used marker of neuronal activation induced by various types of brain damage. In addition, c-Fos is believed to play a regulatory role in DNA damage repair. This paper reviews the literature on c-Fos' involvement in the regulation of DNA damage repair and indicates that genes of the Fos family can be induced by various forms of DNA damage. In addition, cells lacking c-Fos have difficulties in DNA repair. c-Fos is involved in tumorigenesis and progression as a proto-oncogene that maintains cancer cell survival, which may also be related to DNA repair. c-Fos may impact the repair of DNA damage by regulating the expression of downstream proteins, including ATR, ERCC1, XPF, and others. Nonetheless, the underlying mechanisms necessitate further exploration.

Synthesis of Renal-Clearable Multicolor Fluorescent Silicon Nanodots for Tumor Imaging and In Vivo H2O2 Profiling.

Fluorescent silicon nanodots have shown great prospects for bioimaging and biosensing applications. Although various fluorescent silicon-containing nanodots (SiNDs) have been developed, there are few reports about renal-clearable multicolor SiNDs. Herein, renal-clearable multicolor fluorescent SiNDs are synthesized by using silane molecules and organic dyes through a facile one-step hydrothermal method. The fluorescence of the resulting SiNDs can be tuned to blue (bSiNDs), green (gSiNDs), and red (rSiNDs) by simply changing the categories of silane reagents or dye molecules. The as-prepared SiNDs exhibit strong fluorescence with a quantum yield up to 72%, excellent photostability, and good biocompatibility with 12 h renal clearance rate as high as 86% ID. These properties enabled the SiNDs for tumor fluorescence imaging and H2O2 imaging in living cells and tissue through in situ reduction reaction-lighted fluorescence of the nanoprobe. Our results provide an invaluable methodology for the synthesis of renal-clearable multicolor SiNDs and their potential applications for fluorescence imaging and biomarker sensing. These SiNDs are also promising for various biological and biomedical applications.

Near infrared imaging of intracellular GSH by AuNCs@MnO2 core-shell nanoparticles based on the absorption competition mechanism.

Dynamically monitoring intracellular glutathione (GSH), a crucial biomarker of oxidative stress, is of significance for the diagnosis and treatment of certain diseases. Although manganese dioxide (MnO2) based GSH fluorescent sensors have exhibited high sensitivity and good selectivity owing to the specific reactivity between GSH and MnO2, near-infrared (NIR) MnO2 based nanoprobes for GSH detection are scarce. Herein, we have developed a NIR activatable fluorescence nanoprobe for the imaging and determination of intracellular GSH based on a core-shell nanoparticle, consisting of NIR emitted gold nanocluster doped silica as the fluorescent core and manganese dioxide as the GSH-responsive shell (named AuNCs@MnO2). Due to the absorption competition mechanism, the outer MnO2 shell rather than the inner AuNCs core preferentially absorbed the excitation light, thus leading to fluorescence quenching of the inner AuNCs core. Upon addition of GSH, the fluorescence of the nanoprobe restored along with the reduction of MnO2 to Mn2+ because of the absorption competition disappearance-induced emission. The activatable fluorescence linearly increased upon changing the GSH concentration in the range of 2 to 5000 µM with a detection limit of 0.67 µM. The cytotoxicity test shows that the AuNCs@MnO2 nanoprobes have a good biocompatibility. After entering the cancer cells, the intracellular GSH degraded the outermost MnO2 shell and initiated the NIR fluorescence restoration of AuNCs, which can be used to monitor the dynamic change of intracellular GSH. This strategy provides an NIR-activatable way to detect GSH levels in living cells and offers a promising platform for the diagnosis and treatment of GSH-related diseases.

Nanomediator-Effector Cascade Systems for Amplified Protein Kinase Activity Imaging and Phosphorylation-Induced Drug Release In Vivo.

Protein kinases constitute a rich pool of biomarkers and therapeutic targets of tremendous diseases including cancer. However, sensing kinase activity in vivo while implementing treatments according to kinase hyperactivation remains challenging. Herein, we present a nanomediator-effector cascade system that can in situ magnify the subtle events of kinase-catalyzed phosphorylation via DNA amplification machinery to achieve kinase activity imaging and kinase-responsive drug release in vivo. In this cascade, the phosphorylation-mediated disassembly of DNA/peptide complex on the nanomediators initiated the detachment of fluorescent hairpin DNAs from the nanoeffectors via hybridization chain reaction (HCR), leading to fluorescence recovery and therapeutic cargo release. We demonstrated that this nanosystem simultaneously enabled trace protein kinase A (PKA) activity imaging and on-demand drug delivery for inhibition of tumor cell growth both in vitro and in vivo, affording a kinase-specific sense-and-treat paradigm for cancer theranostics.