作者: Cao, Jinxu ; Li, Yixian ; Cheng, Yunlong ; Wei, Yan ; Yang, Peng ; Qian, Kang ; Luo, Haichang ; Zhang, Qizhi ; Guo, Qian ; Wang, Pengzhen ; Sheng, Dongyu ; Meng, Ran ; Wang, Liuchang ; Xu, Shuting

Since the complex interactions of multiple mechanisms involved in Alzheimer's disease (AD) preclude the monotherapeutic approaches from clinical application, combination therapy has become an attractive strategy for AD treatment. However, to be emphasized, the realization of the edges of combination therapy greatly depends on the reasonable choice of targets and the rational design of combination scheme. Acknowledgedly, amyloid plaques and hyperphosphorylated tau (p-tau) are two main hallmarks in AD with close pathological correlations, implying the hopeful prospect of combined intervention in them for AD treatment. Herein, we developed the nano-combination system, neuron-targeting PEG-PLA nanoparticles (CT-NP) loading two peptide drugs H102, a β-sheet breaker acting on Aβ, and NAP, a microtubule stabilizer acting on p-tau. Compared with free peptide combination, nano-combination system partly aligned the in vivo behaviors of combined peptides and enhanced peptide accumulation in lesion neurons by the guidance of targeting peptide CGN and Tet1, facilitating the therapeutic performance of peptide combination. Further, to maximize the therapeutic potential of nano-combination system, the combination ratio and mode were screened by the quantitative evaluation with combination index and U test, respectively, in vitro and in vivo. The results showed that the separated-loading CT-NP at the combination molar ratio of 2:1 (H102:NAP), CT-NP/H102 + CT-NP/NAP(2:1), generated the strongest synergistic therapeutic effects on Aβ, p-tau and their linkage, and effectually prevented neuroinflammation, reversed the neuronal damage and restored cognitive performance in 3 × Tg-AD transgenic mice. Our studies provide critical data on the effectiveness of nano-combination therapy simultaneously intervening in Aβ and p-tau, confirming the promising application of nano-combination strategy in AD treatment.

2020-02-01·Carbohydrate polymers1区 · 化学

A separable paper adhesive based on the starch―lignin composite

1区 · 化学

Article

作者: Wu, Qin ; Kong, Fangong ; Xia, Nannan ; Wang, Ping ; Shao, Weilong

One major defect in paper adhesives is that it is difficult to remove the adhesive in waste paper. These adhesives can easily adhere to paper-making equipment, which hampers recycling. Herein, the hyperbranched polyester H₁₀₂ is used to act as dispersant, and grafting copolymerization of lignin onto the starch backbone was carried out by initiation of free radicals to prepare a bio-based paper adhesive in water. The results show that the adhesive can achieve the best adhesion properties under m(H₂O)/m(St) = 15:1, m(SLS)/m(St) = 0.15:1, m(APS)/m(St) = 0.02:1, and pH = 4 at 80 °C for 6 h. The addition of H₁₀₂ stabilizes the performance of the adhesive and extends the shelf life. The feasibility was verified by Fourier transform infrared spectroscopy (FT-IR), Ultraviolet-visible Spectrophotometry (UV-vis), Thermogravimetric analysis (TG), X-ray diffraction (XRD) and rheological property analysis. Moreover, the as-prepared adhesive can be dissolved in H₂O by heating, which is beneficial to improve the recovery and recycling of waste paper compared with the traditional adhesives.

2019-01-01·Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology

[Effects of H102 on the memory recognition ability and AMPK-mTOR autophagy-related pathway in AD mice].

Article

作者: Xu, Shu Mei ; Jiang, Fang ; Shan, Shang Ran

OBJECTIVE:

To study the effect of β-sheet blocking peptide H102 on the expression of AMPK-mTOR autophagy pathway-related protein in APP/PS1 double transgenic AD mice.

METHODS:

Thirty male APP/PS1 transgenic male AD mice of 6 months old were randomly divided into AD group and H102 intervention group, and C57BL/6J male mice of the same age were used as control group (n=15). The mice in the HF group were administered with 5 μl (5.8 mg/kg) of H102 polypeptide solution through the nasal cavity at the same time period, and the mice in the control group and the AD group were given the same amount of blank adjuvant solution daily. The memory recognition ability was tested by a new object recognition experiment 30 days after continuous administration. Immunohistochemistry and Western blot were used to detect the expressions of phosphorylated AMP-activated protein kinase(P-AMPK),phosphorylated mammalian target of rapamycin (P-mTOR) and ratio of LC32to LC31(LC3II/I )in brain tissue.

RESULTS:

Compared with the control group, the new object recognition index (RI) of the AD group was significantly lower (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain of the mice were significantly lower (P＜0.05). The expression of P-mTOR protein was increased significantly (P＜0.05). Compared with the AD group, the RI of the H102 intervention group was increased significantly (P＜0.05), and the P-AMPK and LC3II/I ratios in the brain tissue of the mice were increased significantly (P＜0.05). The expression of P-mTOR protein was decreased significantly (P＜0.05).

CONCLUSION:

H102 can improve the recognition and memory ability of AD mice by activating the AMPK-mTOR autophagy-related pathway.

100 项与 H102 相关的药物交易

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