IntroductionAdministration of bone marrow mesenchymal stem cells (MSCs) or secreted microvesicles improves recovery from acute kidney injury (AKI). However, the potential roles and mechanisms are not well understood. In the current study, we focused on the protective effect of exosomes derived from human umbilical cord mesenchymal stem cells (hucMSC-ex) on cisplatin-induced nephrotoxicity in vivo and in vitro.MethodsWe constructed cisplatin-induced AKI rat models. At 24 h after treatment with cisplatin, hucMSC-ex were injected into the kidneys via the renal capsule; human lung fibroblast (HFL-1)-secreted exosomes (HFL-1-ex) were used as controls. All animals were killed at day 5 after administration of cisplatin. Renal function, histological changes, tubular apoptosis and proliferation, and degree of oxidative stress were evaluated. In vitro, rat renal tubular epithelial (NRK-52E) cells were treated with or without cisplatin and after 6 h treated with or without exosomes. Cells continued to be cultured for 24 h, and were then harvested for western blotting, apoptosis and detection of degree of oxidative stress.ResultsAfter administration of cisplatin, there was an increase in blood urea nitrogen (BUN) and creatinine (Cr) levels, apoptosis, necrosis of proximal kidney tubules and formation of abundant tubular protein casts and oxidative stress in rats. Cisplatin-induced AKI rats treated with hucMSC-ex, however, showed a significant reduction in all the above indexes. In vitro, treatment with cisplatin alone in NRK-52E cells resulted in an increase in the number of apoptotic cells, oxidative stress and activation of the p38 mitogen-activated protein kinase (p38MAPK) pathway followed by a rise in the expression of caspase 3, and a decrease in cell multiplication, while those results were reversed in the hucMSCs-ex-treated group. Furthermore, it was observed that hucMSC-ex promoted cell proliferation by activation of the extracellular-signal-regulated kinase (ERK)1/2 pathway.ConclusionsThe results in the present study indicate that hucMSC-ex can repair cisplatin-induced AKI in rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis, promoting cell proliferation in vivo and in vitro. This suggests that hucMSC-ex could be exploited as a potential therapeutic tool in cisplatin-induced nephrotoxicity.
Monodispersed, hydrophilic, superparamagnetic magnetic nanospheres with a high fraction of magnetite were synthesized by combining modified miniemulsion/emulsion polymerization and sol-gel technique for the first time. The surface of the nanospheres was coated by a silica layer with controlled thickness. Transmission electron microscopy experimental results showed well-proportioned, equal-sized, magnetite/polystyrene (Fe3O4/PS) nanospheres with a thin silica shell. Based on the TGA data, the fraction of magnetite in the Fe3O4/PS nanospheres core was estimated to be 80 wt %. Magnetization measurements indicated that the superparamagnetic nature of the nanospheres had high saturation magnetization of 40 emu/g at 300 K. The procedures of the novel synthesis are described in detail. Also discussed are the mechanisms of the novel combined miniemulsion/emulsion polymerization processes.
Quantum effects in plasmonic systems play an important role in defining the optical response of structures with subnanometer gaps. Electron tunneling across the gaps can occur, altering both the far-field optical response and the near-field confinement and enhancement. In this study, we experimentally and theoretically investigate plasmon coupling in gold "nanomatryoshka" (NM) nanoparticles with different core−shell separations. Plasmon coupling effects between the core and the shell become significant when their separation decreases to 15 nm. When their separation decreases to below 1 nm, the near-and far-field properties can no longer be described by classical approaches but require the inclusion of quantum mechanical effects such as electron transport through the self-assembled monolayer of molecular junction. In addition, surface-enhanced Raman scattering measurements indicate strong electron-transport induced charge transfer across the molecular junction. Our quantum modeling provides an estimate for the AC conductances of molecules in the junction. The insights acquired from this work pave the way for the development of novel quantum plasmonic devices and substrates for surface-enhanced Raman scattering.
For early cancer diagnosis and treatment, a nanocarrier system is designed and developed with key components uniquely structured at nanoscale according to medical requirements. For imaging, quantum dots with emissions in the near-infrared range (∼800 nm) are conjugated onto the surface of a nanocomposite consisting of a spherical polystyrene matrix (∼150 nm) and the internally embedded, high fraction of superparamagnetic Fe(3)O(4) nanoparticles (∼10 nm). For drug storage, the chemotherapeutic agent paclitaxel (PTX) is loaded onto the surfaces of these composite multifunctional nanocarriers by using a layer of biodegradable poly(lactic-co-glycolic acid) (PLGA). A cell-based cytotoxicity assay is employed to verify successful loading of pharmacologically active drug. Cell viability of human, metastatic PC3mm2 prostate cancer cells is assessed in the presence and absence of various multifunctional nanocarrier populations using the MTT assay. PTX-loaded composite nanocarriers are synthesized by conjugating anti-prostate specific membrane antigen (anti-PSMA) for targeting. Specific detection studies of anti-PSMA-conjugated nanocarrier binding activity in LNCaP prostate cancer cells are carried out. LNCaP cells are targeted successfully in vitro by the conjugation of anti-PSMA on the nanocarrier surfaces. To further explore targeting, the nanocarriers conjugated with anti-PSMA are intravenously injected into tumor-bearing nude mice. Substantial differences in fluorescent signals are observed ex vivo between tumor regions treated with the targeted nanocarrier system and the nontargeted nanocarrier system, indicating considerable targeting effects due to anti-PSMA functionalization of the nanocarriers.
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