LncRNA H19 Inhibits Proliferation and Migration of Airway Smooth Muscle Cells Induced by PDGF-BB Through miR-21/PTEN/Akt Axis.

BACKGROUND: LncRNA H19 expression is down-regulated in patients with asthma. The hyperplasia of airway smooth muscle cells (ASMCs) promotes the development of airway remodeling in asthma. Therefore, we attempted to evaluate the regulatory function of H19 in the proliferation and migration of ASMCs. METHODS: The expressions of H19 and miR-21 were detected using qRT-PCR. PDGF-BB-induced abnormal proliferation and migration of ASMCs was used as the airway remodeling model in vitro. The expressions of H19 and miR-21 were modified by transfection with pcDNA3.1-H19 and miR-21 mimic, respectively. CCK-8 assay, flow cytometry-based cell cycle analysis was conducted to examine the proliferation ability of ASMCs. The migration ability was measured by transwell assay. Dual-luciferase reporter system was carried out to find the potential relationship between miR-21 and H19 or PTEN. Western blot was conducted to detect the expressions of PCNA, MMP-9, α-SMA, PTEN, and the phosphorylation level of Akt. RESULTS: LncRNA-H19 expression was decreased and microRNA-21 expression was increased in serum samples of children with asthma and PDGF-BB-stimulated ASMCs. Overexpression of H19 reduced the proliferation and migration ability of ASMCs with PDGF-BB treatment and these changes were reversed by miR-21 mimic. H19 promoted the protein level of PTEN via sponging miR-21. Overexpression of H19 suppressed miR-21-induced phosphorylation of Akt, and the suppression effect of H19 on phosphorylation of Akt was significantly reduced after transfecting shPTEN in ASMCs. CONCLUSION: In this study, overexpression of H19 suppressed the proliferation and migration of ASMCs induced by PDGF-BB via miR-21/PTEN/Akt axis, which could be a potential biomarker and target for treating hyperplasia of airway smooth muscle cells.

Rescue of four pediatric patients with severe influenza A (H3N2) in Weifang, China.

In this report, we summarize our experience of rescuing four children with severe type A H3N2 influenza from January to February 2017 in Weifang People's Hospital, Shandong Province, China for reference in clinical treatment. Two boys and two girls, ranging in age from 3 months to 6 years, with fever, cough, and asthma, were admitted to the pediatric intensive care unit. All children had severe pulmonary infection with respiratory distress. Three children had myocardial damage, two had liver damage, and one had encephalitis. One child had a history of bronchial asthma and one had severe spinal muscular atrophy. After all four children were admitted to the pediatric intensive care unit, they were provided active and effective organ function support and ventilator-assisted respiration. They were treated with gamma globulin, methylprednisolone, and antibiotics. Three children were treated with anti-influenza drugs and recovered from influenza; one child died even before antiviral treatment intervention on the first day. Definite diagnosis of the cases was through clinical manifestations, supplemented by laboratory tests, such as influenza virus H3N2 rapid antigen detection and nucleic acid detection. Early antiviral therapy, high-dose glucocorticoids and immunoglobulins, and systemic comprehensive rescue might be important for rescuing children with severe influenza A (H3N2).

Self-assembled drug delivery systems. Part 5: self-assemblies of a bolaamphiphilic prodrug containing dual zidovudine.

A bolaamphiphilic prodrug containing dual zidovudine, pentadecanedioyl dizidovudine (PDDZ), was prepared. The vesicular self-assemblies were formed in aqueous media through injecting the methanol solution of PDDZ into water. Hydrophobic interaction between lipid chains should drive molecular self-assembly. The nonionic surfactant, Tween 20, was used to increase the physical stability of self-assemblies because the surfactant micelles could prevent the assemblies from aggregating. The doping hydroxylpropylmethylcellulose (HPMC) slowed down the degradation of prodrugs due to adsorption. The self-assemblies were nanoscale with the mean particle size of 156 nm. Degradation of PDDZ was very slow in buffered solutions, but very rapid in enzyme and plasma, and the parent drug zidovudine (AZT) was the unique product. PDDZ self-assemblies showed strong anti-HIV activity on MT4 cell model. The 50% effective concentration (EC(50)) of PDDZ was 5 nM, equal to that of AZT. PDDZ was rapidly eliminated from circulation and mainly distributed into liver, spleen and testis followed by the rapid production of AZT after intravenous administration of the self-assemblies to rabbits. Macrophages in liver, spleen and testis are the reservoir of HIV so that the macrophage targeting effect of PDDZ self-assemblies would benefit to anti-HIV therapy. The self-assemblies composed of bolaamphiphilic PDDZ are a promising self-assembled drug delivery system (SADDS).