Astragalus Polysaccharide Regulates miR-182/Bcl-2 Axis to Relieve Metabolic Memory through Suppressing Mitochondrial Damage-Mediated Apoptosis in Retinal Pigment Epithelial Cells.

INTRODUCTION: Metabolic memory is one of the causes of diabetic retinopathy, and astragalus polysaccharide (APS) has great advantages in the treatment of diabetes. However, the effect of APS on metabolic memory remains to be investigated. METHODS: Retinal pigment epithelial cell line ARPE-19 and primary retinal pigment epithelial cells were used to verify the effect of APS on mitochondria damage and apoptosis induced by high glucose-induced metabolic memory. The relationship between miR-182 and Bcl-2 was confirmed by a luciferase activity assay. Western blotting and quantitative reverse-transcriptase polymerase chain reaction were conducted to investigate the changes in mitochondrial damage- and apoptosis-associated markers. The cell mitochondrial membrane potential was assessed by JC-1 fluorescence. Terminal deoxynucleotidyl transferase dUTP nick end labelling staining and flow cytometry assays were performed to determine the occurrence of apoptosis. RESULTS: Treatment with high glucose followed by normal glucose significantly upregulated the expression of miR-182 and downregulated the expression of its target Bcl-2, and APS treatment reversed the above effects. Additionally, APS treatment restored mitochondrial function and inhibited apoptosis in cells in a state of metabolic memory. The effects of APS against mitochondrial damage and apoptosis were partially inhibited after miR-182 overexpression. CONCLUSION: APS alleviated mitochondrial damage and apoptosis induced by metabolic memory by regulating the miR-182/Bcl-2 axis, which might serve as a new strategy for the treatment of diabetic retinopathy.

CircAPLP2 regulates the proliferation and metastasis of colorectal cancer by targeting miR-101-3p to activate the Notch signalling pathway.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers, and it has a poor prognosis. Emerging evidence shows that circular RNAs (circRNAs) may act as good therapeutic targets for cancers due to their abundance and stability. However, their regulatory role in CRC needs further investigation. This study revealed that circAPLP2 was upregulated and miR-101-3p was downregulated in CRC tissues and cells compared to normal controls. Knockdown of circAPLP2 and overexpression of miR-101-3p inhibited the cell proliferation, migration and invasion and induced the apoptosis of CRC cells. circAPLP2 acted as a miR-101-3p sponge to upregulate its target gene Notch1, which activated cascades of proliferation- and metastasis-related proteins (c-Myc, cyclin D1, MMP-2 and MMP-9). Additionally, knockdown of circAPLP2 suppressed tumour growth and liver metastases of CRC in nude mice. Taken together, these results indicate that circAPLP2 promotes proliferation and metastasis by targeting miR-101-3p to activate the Notch signalling pathway in CRC, which provides new insights into the mechanisms underlying CRC malignancy and suggests a new therapeutic target.

Electrospun polyvinyl alcohol/carbon dioxide modified polyethyleneimine composite nanofiber scaffolds.

A novel biocompatible polyvinyl alcohol/carbon dioxide modified polyethyleneimine (PVA/PEI-CO2) composite nanofiber was fabricated by a green and facile protocol, which reduces the cytotoxicity of PEI through the surface modification of the PEI with CO2. The (13)C NMR spectrum, elemental analysis, and TGA show that CO2 has been incorporated in the PEI surface resulting in a relatively stable structure. The resulting PVA/PEI-CO2 composite nanofibers have been characterized by attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), contact angle, and scanning electron microscopy (SEM). The results show that the average diameters of the nanofibers range from 265 ± 53 nm to 423 ± 80 nm. The cytotoxicity of PVA/PEI-CO2 composite nanofibers was assessed by cytotoxicity evaluation using the growth and cell proliferation of normal mice Schwann cells. SEM and the MTT assay demonstrated the promotion of cell growth and proliferation on the PVA/PEI-CO2 composite scaffold. It suggests that PEI-CO2 can have tremendous potential applications in biological material research.