Abstract. The aim was to develop a liposomal oxymatrine conjugating D-alpha tocopheryl polyethylene glycol 1000 succinate (OMT-LIP) for enhanced therapeutics of hepatic fibrosis. OMT-LIP was prepared using the remote loading method. The influences of formulation compositions on the encapsulation efficiency of OMT-LIP were investigated. Mean particle size, zeta potential, morphology, in vitro release, fibrotic liver targeting, and therapeutics of OMT-LIP were thoroughly assessed. The intraliposomal buffer composition and concentration, extraliposomal phase composition and pH, types of phospholipid, lipid molar ratio composition, and theoretical drug loading are crucial factors to entrap OMT into liposomes. The optimum OMT-LIP presented spherically unilamellar microstructures with entrapment efficiency of 79.7±3.9%, mean particle size of 121.6±52.9 nm, and zeta potential of −5.87 mV. OMT-LIP significantly increased the accumulation of OMT in the fibrotic liver with an 11.5-fold greater AUC than OMT solution in the dimethylnitrosamine (DMN)-induced hepatic fibrosis animals. OMT-LIP could be a potential strategy to improve treatment outcomes for hepatic fibrosis, showing the protective effects to mice given CCl 4 and the enhanced therapeutics to mice with either DMN or CCl 4 -induced hepatic fibrosis.
MN1 C‐terminal truncation (MCTT) syndrome is a newly recognized neurodevelopmental disorder due to heterozygous gain‐of‐function C‐terminal truncating mutations clustering in the last or penultimate exon of MN1 gene (MIM: 156100). Up to date, only 25 affected patients have been reported. Here, we report a 2‐year‐old Chinese girl with MCTT syndrome. The girl presented with the characteristic features of the syndrome, including global developmental delay (GDD), facial dysmorphism and hearing impairment. Notably, the patient did not have other frequently observed symptoms such as hypotonia, cranial or brain abnormalities, indicating variability of the phenotype of patients with MN1 C‐terminal truncating mutations. Trio whole‐exome sequencing revealed a novel de novo heterozygous nonsense variant in the extreme 3′ region of penultimate exon of MN1 (NM_002430.3: c.3743G > A, p.Trp1248*). This rare truncating variant was classified as pathogenic due to its predicted gain‐of‐function effect, given that the gain‐of‐function MN1 truncating variants producing C‐terminally truncated proteins have been confirmed to cause the recognizable syndrome. Additionally, a systematic review of previously reported MN1 variants including C‐terminal truncating variants and N‐terminal truncating variants shows that different location of MN1 truncating variants causes two distinct clinical subtypes. To our knowledge, this is the first reported case of MCTT syndrome caused by a novel MN1 C‐terminal truncating variant in a Chinese population, which enriched the mutation spectrum of MN1 gene and further supporting the association of the novel MCTT syndrome with MN1 C‐terminal truncating variants.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.