Biscarbamate cross-linked polyethylenimine derivative (PEI-Et) has been reported as a novel nonviral vector for efficient and safe gene transfer in our previous work. However, it had no cell-specificity. To achieve specific delivery of genes to hepatocytes, galactosylated poly(ethylene glycol)-graft-polyethylenimine derivative (GPE) was prepared through modification of PEI-Et with poly(ethylene glycol) and lactobionic acid, bearing a galactose group as a hepatocyte-targeting moiety. The composition of GPE was characterized by proton nuclear magnetic resonance. The weight-average molecular weight of GPE measured with a gel permeation chromatography instrument was 9489 Da, with a polydispersity of 1.44. GPE could effectively condense plasmid DNA (pDNA) into nanoparticles. Gel retardation assay showed that GPE/pDNA complexes were completely formed at weigh ratios (w/w) over 3. The particle size of GPE/pDNA complexes was 79–100 nm and zeta potential was 6–15 mV, values which were appropriate for cellular uptake. The morphology of GPE/pDNA complexes under atomic force microscopy appeared spherical and uniform in size, with diameters of 53–65 nm. GPE displayed much higher transfection efficiency than commercially available PEI 25 kDa in BRL-3A cell lines. Importantly, GPE showed good hepatocyte specificity. Also, the polymer exhibited significantly lower cytotoxicity compared to PEI 25 kDa at the same concentration or weight ratio in BRL-3A cell lines. To sum up, our results indicated that GPE might carry great potential in safe and efficient hepatocyte-targeting gene delivery.

Angiotensinogen (AGT) has been shown to have a role in cardiac hypertrophy, while depletion of the AGT gene in spontaneously hypertensive rats (SHR) has not been investigated. The present study investigated the effect of AGT knockdown on cardiac hypertrophy in SHR. For this, small hairpin (sh)RNAs were intravenously injected into SHRs, using a nanoparticle‑mediated transfection system. The experimental rats were divided into the following groups: a) Blank control with water treatment only, b) negative control with biscarbamate‑crosslinked Gal‑polyethylene glycol polyethylenimine nanoparticles (GPE)/negative shRNA, c) AGT‑RNA interference (RNAi) group with GPE/AGT‑shRNA, and 4) normotensive control using Wistar‑Kyoto rats (WKY) with water treatment. Three and five days following the first injection, the levels of hepatic AGT mRNA and AGT protein as well as plasma levels of AGT were markedly decreased in the AGT‑RNAi group (P<0.05). Furthermore, a significant decrease in systolic blood pressure (SBP), left ventricular weight to body weight ratio and heart weight to body weight ratio were observed in the AGT‑RNAi group compared with those in the control groups. The depletion of AGT in SHR led to a reduction in SBP by 30±4 mmHg, which was retained for >10 days. Cardiac hypertrophy was also significantly improved in AGT‑knockdown rats. In conclusion, the present study showed that AGT‑silencing had a significant inhibitory effect on hypertension and hypertensive‑induced cardiac hypertrophy in SHRs.

Background: In this study, we investigated the relationship between long-chain non-coding RNAs (lncRNAs) and respiratory syncytial virus (RSV)- exacerbated asthma. Methods: Transcriptome microarray was used to detect differentially expressed lncRNAs in dendritic cells (DCs) co-cultured with RSV-infected human airway epithelial cells and DCs infected with RSV. The identified downregulation of lncRNA n337374 was validated using fluorescence RT-qPCR. LncRNA n337374-overexpressing DCs and RSV-exacerbated asthmatic mouse models were established. Airway hyperreactivity and bronchoalveolar lavage fluid (BALF) were examined, and pathological changes in lung tissues were observed in mice. Surface molecules in DCs were detected by flow cytometry and RT-qPCR and the expression of CD86 and mitogen-activated protein kinases was determined by western blot. Results: In an RSV-exacerbated asthmatic mouse model, the airway wall was thickened, luminal stenosis was observed, a large number of inflammatory cells were infiltrated in the lung tissue, lung function was impaired, and counts of inflammatory cells in the BALF were increased. The overexpression of lncRNA n337374 ameliorated these pathological changes and improved impaired lung function and inflammation in an asthmatic mouse model. In DCs co-cultured with RSV-infected human airway epithelial cells, CD86 expression was promoted and ERK was markedly phosphorylated. When lncRNA n337374-overexpressing DCs were used in the co-cultures, the expression of CD86 and phosphorylated ERK was decreased. Conclusion: The results suggest that lncRNA n337374 overexpression may suppress DC maturation by downregulating the CD86 and ERK pathway, subsequently relieving the symptoms of RSV-induced asthma. LncRNA n337374 may be a promising target in the treatment of RSV infection-induced asthma.