LncRNA H19 functions as an Aquaporin 1 competitive endogenous RNA to regulate microRNA-874 expression in LPS sepsis.

OBJECTIVE: Sepsis is a whole-body inflammation disease after severe trauma, burn injury, infection and major surgeries, accompanied by multiple organs failure. We sought to investigate the potential mechanism of Aquaporin 1 (AQP1), miRNA-874, and lncRNA H19 in lipopolysaccharide (LPS) sepsis and the anti-inflammatory responses related to sepsis myocardial dysfunction. MATERIAL AND METHODS: Serum from peripheral blood samples of sepsis patients and in vivo mice model were collected for AQP1, H19, and miR-874 expression. In vitro model in cardiomyocytes was established using LPS. H19 and miR-874 expressions were interfered in LPS induced mice and cardiomyocytes to explore the association between them and its effect on anti-inflammatory responses. RESULTS: H19 and AQP1 decreased and accompanied with elevated miR-874 expression in sepsis samples, in vivo mice model and in vitro cells. There was negative relationship between expression of H19 and miR-874, and a positive correlation between H19 and AQP1 expression. However, H19 overexpression transfection significantly reversed LPS induced dysregulation in expression of miR-874 and AQP1, secretion of anti-inflammatory cytokines, and myocardial dysfunction in vivo and in vitro. CONCLUSION: We determined that H19 acted as AQP1 ceRNA in regulating miR-874. H19 acted as AQP1 ceRNA in regulating miR-874 and restoring LPS dysregulated inflammatory responses and myocardial dysfunction. H19 expression might be used as a potential therapeutic target for LPS induced sepsis and myocardial dysfunction.

Brain-derived neurotrophic factor ameliorates learning deficits in a rat model of Alzheimer's disease induced by aß1-42.

An emerging body of data suggests that the early onset of Alzheimer's disease (AD) is associated with decreased brain-derived neurotrophic factor (BDNF). Because BDNF plays a critical role in the regulation of high-frequency synaptic transmission and long-term potentiation in the hippocampus, the up-regulation of BDNF may rescue cognitive impairments and learning deficits in AD. In the present study, we investigated the effects of hippocampal BDNF in a rat model of AD produced by a ventricle injection of amyloid-ß1-42 (Aß1-42). We found that a ventricle injection of Aß1-42 caused learning deficits in rats subjected to the Morris water maze and decreased BDNF expression in the hippocampus. Chronic intra-hippocampal BDNF administration rescued learning deficits in the water maze, whereas infusions of NGF and NT-3 did not influence the behavioral performance of rats injected with Aß1-42. Furthermore, the BDNF-related improvement in learning was ERK-dependent because the inhibition of ERK, but not JNK or p38, blocked the effects of BDNF on cognitive improvement in rats injected with Aß1-42. Together, our data suggest that the up-regulation of BDNF in the hippocampus via activation of the ERK signaling pathway can ameliorate Aß1-42-induced learning deficits, thus identifying a novel pathway through which BDNF protects against AD-related cognitive impairments. The results of this research may shed light on a feasible therapeutic approach to control the progression of AD.