Bone marrow mesenchymal stem cell-derived extracellular vesicles containing miR-181d protect rats against renal fibrosis by inhibiting KLF6 and the NF-κB signaling pathway.

Recent studies have investigated the ability of extracellular vesicles (EVs) in regulating neighboring cells by transferring signaling molecules, such as microRNAs (miRs) in renal fibrosis. EVs released by bone marrow mesenchymal stem cells (BMSCs) contain miR-181d, which may represent a potential therapy for renal fibrosis. miR-181d has been speculated to regulate Krüppel-like factor 6 (KLF6), which activates the nuclear factor-kappa B (NF-κB) signaling pathway. Luciferase assays were performed to confirm the relationship between miR-181d and KLF6. Gain- and loss-of-function studies in vivo and in vitro were performed to assess the effect of BMSC-derived EVs (BMSC-EVs), which contained miR-181d, on KLF6, NF-κB, and renal fibrosis. Transforming growth factor-ß (TGF-ß)-induced renal tubular epithelial HK-2 cells were treated with EVs derived from BMSCs followed by evaluation of collagen type IV α1 (Col4α1), Collagen I and α-smooth muscle actin (α-SMA) as indicators of the extent of renal fibrosis. Renal fibrosis was induced in rats by unilateral ureteral obstruction (UUO) followed by the subsequent analysis of fibrotic markers. BMSC-EVs had higher miR-181d expression. Overexpression of miR-181d correlated with a decrease in KLF6 expression as well as the levels of IκBα phosphorylation, α-SMA, Col4α1, TGF-ßR1 and collagen I in HK-2 cells. In vivo, treatment with miR-181d-containing BMSC-derived EVs was able to restrict the progression of fibrosis in UUO-induced rats. Together, BMSC-EVs suppress fibrosis in vitro and in vivo by delivering miR-181d to neighboring cells, where it targets KLF6 and inhibits the NF-κB signaling pathway.

L-Histidine-DNA interaction: a strategy for the improvement of the fluorescence signal of poly(adenine) DNA-templated gold nanoclusters.

An interesting phenomenon is described that the fluorescence signal of poly(adenine) (A) DNA-templated gold nanoclusters (AuNCs) is greatly improved in the presence of L-histidine by means of L-histidine-DNA interaction. The modified nanoclusters display strong fluorescence emission with excitation/emission maxima at 290/475 nm. The fluorescence quantum yield (QY) is improved from 1.9 to 6.5%. Fluorescence enhancement is mainly ascribed to the L-histidine-DNA interaction leading to conformational changes of the poly(A) DNA template, which offer a better microenvironment to protect AuNCs. The assay enables L-histidine to be determined with good sensitivity and a linear response that covers the 1 to 50 nM L-histidine concentration range with a 0.3 nM limit of detection. The proposed method has been applied to the determination of imidazole-containing drugs in pharmaceutical samples. A turn-on fluorescent method has been designed for the sensitive detection of L-histidine as well as imidazole-containing drugs on the basis of the L-histidine-DNA interaction.

A turn-on fluorescence strategy for cellular glutathione determination based on the aggregation-induced emission enhancement of self-assembled copper nanoclusters.

As a class of ideal fluorescent nanomaterials, self-assembled copper nanoclusters (CuNCs) have attracted increasing interest. Unfortunately, most of these CuNCs only possessed bright luminescence in acidic solution, which limited their practical applications in a physiological environment. Retaining the strong fluorescence of these CuNCs in neutral or alkaline solution is still a challenging task. In this strategy, self-assembled CuNCs were prepared by using 4-methylthiophenol as the protecting ligand. The self-assembled CuNCs display stable and bright luminescence with excitation/emission maxima at 330/605 nm even in neutral and alkaline environments. Interestingly, with the addition of glutathione (GSH), the fluorescence intensity of CuNCs is enhanced strongly through the GSH-controlled aggregation-induced emission enhancement of self-assembled CuNCs. The turn-on fluorescence strategy can determine the GSH concentration in the range from 1 to 100 µM with a limit of detection of 300 nM. In addition, the method is employed for the determination of GSH levels in cells. Therefore, the turn-on fluorescence strategy is reliable, sensitive and suitable for the determination of cellular GSH levels.

A turn-on fluorescence strategy for biothiols determination by blocking Hg(II)-mediated fluorescence quenching of adenine-rich DNA-templated gold nanoclusters.

Fluorescent adenine (A)-rich DNA-templated gold nanoclusters were demonstrated to be a novel probe for determination of biothiols (including cysteine, glutathione, and homocysteine). Fluorescence intensity of adenine-rich DNA-templated gold nanoclusters could be greatly quenched by Hg(II) ions through the formation of a gold nanoclusters-Hg(II) system. When biothiols (cysteine as the model) were introduced into the system, the fluorescence intensity recovered due to the formation of a more stable Hg(II)-thiol coordination complex using Hg-S metal-ligand bonds, which inhibited the Hg(II)-mediated fluorescence quenching of adenine-rich DNA-templated gold nanoclusters. Based on this fluorescence phenomenon, an on-off-on fluorescence strategy was designed for the sensitive determination of biothiols. The method allowed sensitive detection of cysteine with a linear detection range from 100 nM to 5 µM and a limit of detection of 30 nM. Additionally, the assay can be applied for detection of biothiol levels in human plasma samples. Therefore, it can provide a simple and rapid fluorescent platform for biothiol detection.

Poly(adenine)-templated fluorescent Au nanoclusters for the rapid and sensitive detection of melamine.

A rapid and label-free fluorescence sensing strategy has been established for the sensitive determination of melamine (MA) on the basis of poly(adenine) (poly (A))-templated Au nanoclusters (AuNCs). The poly(A)-templated AuNCs possessed excellent luminescence and photo-stability. In the presence of Hg2+, the luminescence of AuNCs was quenched by Hg2+ through the metallophilic interactions between Au+ and Hg2+. When melamine was introduced, the fluorescence intensity of sensing system could be recovered. There was a greater coordination interaction between Hg2+ and melamine, which blocked the Hg2+-mediated fluorescence quenching of AuNCs. The assay allowed sensitive determination of melamine with a linear detection range from 50 nM to 100 µM. The limit of detection was as low as 16.6 nM. Furthermore, the label-free strategy was successfully employed for the detection of melamine concentration in real samples.