No abstract

Purpose We designed a novel isoliquiritigenin (ISL) loaded micelle prepared with DSPE-PEG 2000 as the drug carrier modified with the brain-targeting polypeptide angiopep-2 to improve the poor water solubility and low bioavailability of ISL for the treatment of acute ischemic stroke. Methods Thin film evaporation was used to synthesize the ISL micelles (ISL-M) modified with angiopep-2 as the brain targeted ligands. The morphology of the micelles was observed by the TEM. The particle size and zeta potential were measured via the nanometer particle size analyzer. The drug loading, encapsulation and in vitro release rates of micelles were detected by the HPLC. The UPLC-ESI-MS/MS methods were used to measure the ISL concentrations of ISL in plasma and main tissues after intravenous administration, and compared the pharmacokinetics and tissue distributions between ISL and ISL-M. In the MCAO mice model, the protective effects of ISL and ISL-M were confirmed via the behavioral and molecular biology experiments. Results The results showed that the drug loading of ISL-M was 7.63 ± 2.62%, the encapsulation efficiency was 68.17 ± 6.23%, the particle size was 40.87 ± 4.82 nm, and the zeta potential was −34.23 ± 3.35 mV. The in vitro release experiments showed that ISL-M had good sustained-release effect and pH sensitivity. Compared with ISL monomers, the ISL-M could significantly prolong the in vivo circulation time of ISL and enhance the accumulation in the brain tissues. The ISL-M could ameliorate the brain injury induced by the MCAO mice via inhibition of cellular autophagy and neuronal apoptosis. There were no the cellular structural damages and other adverse effects for ISL-M on the main tissues and organs. Conclusion The ISL-M could serve as a promising and ideal drug candidate for the clinical application of ISL in the treatment of acute ischemic stroke.

Background: Bronchial asthma often causes cognitive impairment, especially attentional de cit, which has a serious impact on children's learning, but the lack of functional imaging evidence has affected targeted intervention for children.Methods: Thirty-one asthmatic and typically developing children (TDC) were studied by functional magnetic resonance imaging (fMRI). Brain network-based degree centricity and voxel-mirrored homotopic connectivity (VMHC) methods were used.Results: Compared with the TDC group, asthmatic children had lower DC values in the right superior frontal gyrus (after FDR correction, P<0.05). Meanwhile, VMHC values of bilateral superior frontal gyrus and bilateral superior parietal lobule in asthmatic children were lower than those in TDC children (after FDR correction, P<0.05).Conclusions: In this study, impaired superior frontal gyrus and parietal lobe function are associated with attentional de cit in asthmatic children, and these brain regions are key brain regions in attention-related networks.

Metformin, an antidiabetic drug, has been reported to be involved in atherosclerosis (AS).