No abstract

Fe0.74Sn5 nanospheres are synthesized from a mixture of Sn nanospheres (obtained by reduction of SnCl2 with NaBH4 in tetraethylene glycol at 170 °C) and FeCl3 in tetraethylene glycol (205 °C, 2 h).

New aconitine‐type C19‐diterpenoid alkaloids, N‐deethylaconine (I) and beiwutinine (II), are isolated together with hypaconine, mesaconine and 14α‐hydroxyneoline.

Aims Pathogenesis of diabetic encephalopathy (DE) is not completely understood until now. The purposes of this study were to illustrate the changes in morphology, function, and important transporters in neurons and glia during DE, as well as to reveal the potential therapeutic effects of medicines and the diet control on DE. Methods Spontaneous obese KK‐Ay mice were used to investigate diabetes‐induced cognitive disorder, the morphology, function, and protein expression changes in impact animal and the cell level studies. The new drug candidate PHPB, donepezil, and low‐fat food were used to observe the therapeutic effects. Results KK‐Ay mice at 5 months of age showed typical characteristics of type 2 diabetes mellitus (T2DM） and appeared significant cognitive deficits. Morphological study showed microtubule‐associated protein 2 (MAP2) expression was increased in hippocampal neurons and glial fibrillary acidic protein (GFAP) expression decreased in astrocytes. Meanwhile, the vesicular glutamate transporter 1 (vGLUT1) expression was increased and glucose transporter 1 (GLUT1) decreased, and the expression of brain‐derived neurotrophic factor (BDNF) and glial cell‐derived neurotrophic factor (GDNF) was also reduced in KK‐Ay mice. Microglia were activated, and IL‐1β and TNF‐α were increased obviously in the brains of the KK‐Ay mice. Most of the above changes in the KK‐Ay mice at 5 months of age could be relieved by diet intervention (DR) or by treatment of donepezil or new drug candidate PHPB. Conclusion KK‐Ay mouse is a useful animal model for studying DE. The alterations of morphology, structure, and function of astrocyte and microglia in KK‐Ay mice might be rescued by DR and by treatment of medicine. The proteins we reported in this study could be used as biomarkers and the potential drug targets for DE study and treatment.

Aims dl‐PHPB (potassium 2‐(1‐hydroxypentyl)‐benzoate) has been shown to have neuroprotective effects against acute cerebral ischemia, vascular dementia, and Alzheimer's disease. The aim of this study was to investigate the effects of dl‐PHPB on memory deficits and preliminarily explore the underlying molecular mechanism. Methods Blood glucose and behavioral performance were evaluated in the KK‐Ay diabetic mouse model before and after dl‐PHPB administration. Two‐dimensional difference gel electrophoresis (2D‐DIGE)‐based proteomics was used to identify differentially expressed proteins in brain tissue. Western blotting was used to study the molecular mechanism of the related signaling pathways. Results Three‐month‐old KK‐Ay mice were given 150 mg/kg dl‐PHPB by oral gavage for 2 months, which produced no effect on the level of serum glucose. In the Morris water maze test, KK‐Ay mice treated with dl‐PHPB showed significant improvements in spatial learning and memory deficits compared with vehicle‐treated KK‐Ay mice. Additionally, we performed 2D‐DIGE to compare brain proteomes of 5‐month KK‐Ay mice treated with and without dl‐PHPB. We found 14 altered proteins in the cortex and 11 in the hippocampus; two of the 25 altered proteins and another four proteins that were identified in a previous study on KK‐Ay mice were then validated by western blot to further confirm whether dl‐PHPB can reverse the expression levels of these proteins. The phosphoinositide 3‐kinase/protein kinase B/glycogen synthase kinase‐3β (PI3K/Akt/GSK‐3β) signaling pathway was also changed in KK‐Ay mice and dl‐PHPB treatment could reverse it. Conclusions These results indicate that dl‐PHPB may play a potential role in diabetes‐associated cognitive impairment through PI3K/Akt/GSK‐3β signaling pathway and the differentially expressed proteins may become putative therapeutic targets.