Screening a specific Zn(ii)-binding peptide for improving the cognitive decline of Alzheimer's disease in APP/PS1 transgenic mice by inhibiting Zn2+-mediated amyloid protein aggregation and neurotoxicity.

Zn2+ has been implicated in the progression of Alzheimer's disease (AD), as amyloid-ß protein (Aß) aggregation and neurotoxicity are mediated by zinc ions. Therefore, development of metal chelators for inhibiting and regulating metal-triggered Aß aggregation has received attention as a strategy for treating AD. Here, we used an approach based on phage display to screen for a Zn(ii)-binding peptide that specifically blocks Zn-triggered Aß aggregation. A fixed Zn(ii) resin was prepared using Ni-IDA affinity resin, and the target Zn(ii) was screened by interaction with a heptapeptide phage library. After negative biopanning against IDA and four rounds of positive biopanning against Zn(ii), high specificity Zn(ii)-binding phages were obtained. Through DNA sequencing and ELISA, 15 sets of Zn(ii)-binding peptides with high histidine contents were identified. We chose a highly specific peptide against Zn(ii) with the sequence of H-M-Q-T-N-H-H, and its abilities to chelate Zn2+ and inhibit Zn2+-mediated Aß aggregation were assessed in vitro. We loaded the Zn(ii)-binding peptide onto PEG-modified chitosan nanoparticles (NPs) to improve the stability and the bioavailability of the Zn(ii) binding peptide. PEG-modified chitosan NPs loaded with Zn(ii)-binding peptide (PEG/PZn-CS NPs) reduced Zn2+ concentrations and Aß secretion in mouse neuroblastoma (N)2a cells stably over-expressing the APP Swedish mutation (N2aswe). Zn2+-Induced neurotoxicity, oxidative stress, and apoptosis were attenuated by PEG/PZn-CS NPs. Intranasal administration of PEG/PZn-CS NPs improved the cognitive ability of APPswe/PS1d9 (APP/PS1) double-transgenic mice and reduced Aß plaques in the mouse brain. This study indicated that a Zn(ii)-binding peptide and its NPs have promise as a potential anti-AD agent.

[Investigation on Qidong in Qidongzeyou in Book of Pulse (Maishu), the bamboo slips of Han Dynasty in Zhangjiashan].

Qidong ( qi change) in Qidongzeyou (（）, pulse change indicates the abnormal changes inside body) in the Book of Pulse (Maishu), the Bamboo Slips of Han Dynasty in Zhangjiashan is related to the classical thought on qi and the theory on meridians at early era. The connotation of qidong was explored in views of interdisciplinary perspectives, such as Chinese medicine, philology and qi philosophy in the ancient time. It refers to the pulse changes as mentioned in ancient medical books, indicating the abnormal changes in the body. Before the ancient medical canonization marked as sphygmology, the ancient medical scholar focused on qi monism. Based on the thinking mode as analogy and detecting the root from the phenomenon, it is believed that qidong refers to the imbalance of qi activity inside the body, manifested with the abnormal pulse change at relevant pulse region on the body surface. Accordingly, the disorders inside the body are detected by palpation.