RNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system Show more
RNA interference (RNAi) harbors significant potential for treating neurological disorders; nevertheless, limited efficacy has been discerned. The presence of barriers within the central nervous system, coupled with the inherent instability of nucleic acids within biological conditions, poses formidable challenges in advancing effective gene delivery strategies. In this study, we designed and prepared a virus-mimic non-viral gene vector, rabies virus glycoprotein (RVG29)-decorated liposome (f(Lipo)-RVG29), to deliver small interfering RNAs to the brain. Alzheimer's disease (AD) was chosen as a model of neurodegenerative disease in this context, and b-site APP cleaving enzyme silencing siRNA (siBACE1) was used. The developed liposomal delivery system has a particle size of under 80 nm with a spherical shape, positive zeta potential, and the ability to protect siRNA against nucleases. In vitro studies demonstrate that functionalizing the cationic liposome by the RVG29 targeting ligand significantly enhances the effectiveness of gene delivery and silencing. Examination through ex vivo imaging illustrates an increased deposition of fluorescent-labeled f(Lipo)-RVG29 within brain tissue after 12 h post application. Additionally, the in vivo delivery of f(Lipo)-RVG29 carrying siRNA has substantially suppressed BACE1 expression at both mRNA and protein levels within the brain tissue. Our results suggest that the developed non-viral vector could be a promising gene carrier system combining the synergistic effect of virus-mimic RVG29 ligand with bioinspired liposome that imitates the natural lipid bilayers of cell membranes for brain-targeted RNAi therapeutics. Show less
Gestational diabetes mellitus (GDM) is defined as glucose intolerance during pregnancy. We aimed to investigate the potential effects of betatrophin and ApoC2 in GDM, focusing on their roles in LPL (l Show more
Gestational diabetes mellitus (GDM) is defined as glucose intolerance during pregnancy. We aimed to investigate the potential effects of betatrophin and ApoC2 in GDM, focusing on their roles in LPL (lipoprotein lipase) regulation and their relationship with hPL to elucidate the possible impact of hPL on lipid metabolism and its potential contribution to the development of GDM. Thirty pregnant women with normal glucose tolerance and 29 with gestational diabetes mellitus (diagnosed by 75g OGTT between 24 and 28 weeks) were included in the study. Serum betatrophin, hPL, and ApoC2 were measured by Elisa and HOMA-IR was calculated. In the GDM group, hPL levels correlated with betatrophin and ApoC2 (r = 0.552, p < 0.05; r = 0.588, p < 0.05 respectively) while betatrophin correlated with the ApoC2 (r = 0.584, p < 0.05). A linear relationship between hPL and betatropin and also between hPL and ApoC2 values in the control group (r = 0.454, p < 0.05; r = 0.779, p < 0.01 respectively) were observed. ApoC2 levels in the GDM group (n = 20) with HOMA-IR cut-off >2.5 were significantly higher than the control group (n = 10) (p < 0.05). There was also a positive relationship between betatrophin and ApoC2 (r = 0.591) (p < 0.05). GDM patients may have impaired LPL enzyme regulation in addition to insulin resistance, with hPL potentially contributing to this disruption. Impaired lipoprotein lipase activity and its dysregulation secondary to genetic disorders may play a role in the etiopathogenesis of GDM. Further investigation into the correlation between betatrophin, ApoC2, and other LPL modulators in patients with various forms of diabetes could be beneficial for understanding this interaction more comprehensively. Show less