Background: Macrophages robustly secrete MMP-9 upon activation, and mechanisms for active delivery of MMP-9 vesicles to the cell surface have not been described. Results: MMP-9 is packaged into unique ER protein-containing vesicles that associate with microtubule motors in activated macrophages. Conclusion: Macrophage activation requires enhanced microtubule stabilization for rapid secretion of up-regulated MMP-9. Significance: Understanding the nature and mechanisms of intracellular trafficking of MMP-9 is relevant to both immunology and cancer biology fields.

Cervical cancer is a major disease with high mortality. All cervical cancers are caused by infection with human papillomaviruses (HPV). Although preventive vaccines for cervical cancer are successful, treatment of cervical cancer is far less satisfactory because of multidrug resistance and side effects. In this review, we summarize the recent application of nanotechnology to the diagnosis and treatment of cervical cancer as well as the development of HPV vaccines. Early detection of cervical cancer enables tumours to be efficiently removed by surgical procedures, leading to increased survival rate. The current method of detecting cervical cancer by Pap smear can only achieve 50% sensitivity, whereas nanotechnology has been used to detect HPVs with greatly improved sensitivity. In cervical cancer treatment, nanotechnology has been used for the delivery of anticancer drugs to increase treatment efficacy and decrease side effects. Nanodelivery of HPV preventive and therapeutic vaccines has also been investigated to increase vaccine efficacy. Overall, these developments suggest that nanoparticle-based vaccine may become the most effective way to prevent and treat cervical cancer, assisted or combined with some other nanotechnology-based therapy.

Multifunctional nanoparticles for cancer theranosis have been widely explored for effective cancer detection and therapy. In this work, dually functionalised manganese-based layered double hydroxide nanoparticles (Mn-LDH) were examined as an effective anticancer drug/gene delivery system and for T -weighted magnetic resonance imaging (MRI) in brain cancer theranostics. Such Mn-LDH have been shown to accommodate dsDNA/siRNAs and efficiently deliver them to Neuro-2a cells (N2a). Mn-LDH have also shown high biocompatibility with low cytotoxicity. Importantly, the cell-death siRNA (CD-siRNA) delivered with Mn-LDH more efficiently kills brain cancer cells than the free CD-siRNA. Moreover, Mn-LDH can act as excellent contrast agents for MRI, with an r value of 4.47 mm s , which is even higher than that of commercial contrast agents based on Gd complexes (r =3.4 mm s ). Altogether, the high delivery efficacy and MRI contrast capability make dual-functional Mn-LDH potential bimodal agents for simultaneous cancer diagnosis and therapy.

Abstract. The purpose of the present study was to evaluate the effects of uric acid in promoting tubular cell apoptosis and verify the role of nicotinamide adenine dinucleotide phosphate oxidase 4 (Nox4)-induced oxidative stress in this process. HK-2 cells were used as a human proximal tubular cell model and co-cultured with various concentrations of uric acid with or without pre-treatment with the Nox4 inhibitor diphenylene iodonium (DPI). The apoptotic rate and the amount of reactive oxygen species (ROS) were examined by flow cytometry. Furthermore, levels of Nox4, phosphorylated (p)-P38, p-extracellular signal-regulated kinase (ERK), B-cell lymphoma 2 (Bcl-2) and Bcl-2-extra large (Bax) were detected by western blot analysis. The results showed that treatment with uric acid decreased HK-2 cell viability and promoted apoptosis in a dose-dependent manner. This was paralleled with an upregulation of Nox4 as well as ROS overproduction, which activated the phosphorylation of P38/ERK and caused an imbalance of Bax/Bcl-2 in HK-2 cells. Of note, inhibition of Nox4 with DPI prevented uric acid-induced cell injury by suppressing ROS generation and P38/ERK activation. In conclusion, it was demonstrated that elevated uric acid promoted ROS-induced tubular cell apoptosis by upregulating Nox4 expression. The present study therefore provided possible mechanisms and a potential therapeutic target of uric acid-induced chronic kidney disease.