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Introduction Diabetic patients are often accompanied by complications of diabetic vascular disease, which could lead to heart failure or stroke. In this work, we explored the role of miR-503/Apelin-12 in diabetic angiopathy (DA) in vitro. Methods ELISA and qPCR were applied to assess the expression of miR-503 and Apelin-12 in high glucose (HG)-treated microvascular endothelial cells (HMEC-1). The effects of miR-503 on apoptosis, inflammation and oxidative stress were assessed by flow cytometry, western blotting, qPCR, and ELISA. The interaction between miR-503 and Apelin-12 was evaluated by dual-luciferase reporter assay, qPCR and ELISA, respectively. Western blotting was performed to examine the function of miR-503/Apelin-12 on JNK and p38MAPK activation. Results MiR-503 was markedly increased and Apelin-12 was decreased in HG-treated HMEC-1 cells. MiR-503 inhibitor significantly assuaged apoptosis, inflammation and oxidative stress in HMEC-1 cells. MiR-503 could specifically bind to the 3′UTR of Apelin and inversely downregulate Apelin-12 expression. Furthermore, Apelin-12 suppressed apoptosis, inflammation and oxidative stress. Inhibition of Apelin-12 could partially reverse the decrease of p-JNK and p-p38 expression levels induced by miR-503 suppression. Conclusion In HG-induced microvascular cells injury, miR-503/Apelin-12 enhances inflammation and oxidative stress by regulating JNK and p38MAPK pathway, suggesting a potential therapeutic target for DA.

Background The current COVID-19 pandemic is caused by SARS-CoV-2 which belongs to coronaviridae family. Despite the global prevalence, there are currently no vaccines or drugs. Dietary plant derived exosome-like vesicles are known as edible nanoparticles (ENPs). ENPs are filled with microRNAs (miRNAs), in bioavailable form. Recently, cross-kingdom regulation of human transcripts by plant miRNAs have been demonstrated. However, ENP derived miRNAs targeting SARS-CoV-2 has not been described. Study design Mature ENP-derived miRNA sequences were retrieved from small RNA sequencing datasets available in the literature. In silico target prediction was performed to identify miRNAs that could target SARS-CoV-2. ENPs were isolated from ginger and grapefruit plants and the expression of SARS-CoV-2 targeting miRNAs were confirmed by qRT-PCR. Results From a total of 260 ENP-derived miRNAs, we identified 22 miRNAs that could potentially target SARS-CoV-2 genome. 11 miRNAs showed absolute target specificity towards SARS-CoV-2 but not SARS-CoV. ENPs from soybean, ginger, hamimelon, grapefruit, tomato and pear possess multiple miRNAs targeting different regions within SARS-CoV-2. Interestingly, osa/cme miR-530b-5p specifically targeted the ribosomal slippage site between ORF1a and ORF1b. We validated the relative expression of six miRNAs (miR-5077, miR-6300, miR-156a, miR-169, miR-5059 and miR-166 m) in ginger and grapefruit ENPs by RT-PCR which showed differential enrichment of specific miRNAs in ginger and grapefruit ENPs. Conclusion Since administration of ENPs leads to their accumulation into lung tissues in vivo, ENP derived miRNAs targeting SARS-CoV-2 genome has the potential to be developed as an alternative therapy., Graphical abstract Unlabelled Image, Highlights • Edible plant derived nanoparticles (ENPs) are non-toxic, exosome-like vesicles from plants. • We identified 22 ENP miRNAs targeting both structural and non-structural SARS-CoV-2 genes. • Each edible plant ENPs contains ~3–7 miRNAs targeting SARS-CoV-2. • Expression of SARS-CoV-2 targeting miRNAs in ginger and grapefruit ENPs confirmed by qRT-PCR.