Publications by authors named "Xiao Long Shi"

5 Publications

  • Page 1 of 1

A Unique GSK-3β inhibitor B10 Has a Direct Effect on Aβ, Targets Tau and Metal Dyshomeostasis, and Promotes Neuronal Neurite Outgrowth.

Cells 2020 03 7;9(3). Epub 2020 Mar 7.

Key Laboratory of Chemical Biology (Ministry of Education), Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China.

Due to the complicated pathogenesis of Alzheimer's disease (AD), the development of multitargeted agents to simultaneously interfere with multiple pathological processes of AD is a potential choice. Glycogen synthase kinase-3β (GSK-3β) plays a vital role in the AD pathological process. In this study, we discovered a novel 1-pyrrolo[2,3-b]pyridine derivative B10 as a GSK-3β inhibitor that features with a quinolin-8-ol moiety to target the metal dyshomeostasis of AD. B10 potently inhibited GSK-3β with an IC of 66 ± 2.5 nM. At the concentration of 20 μM, B10 increased β-catenin abundance (β-catenin/GAPDH: 0.83 ± 0.086 vs. 0.30 ± 0.016), phosphorylated GSK-3β at Ser9 (p-GSK-3β/GAPDH: 0.53 ± 0.045 vs. 0.35 ± 0.012), and decreased the phosphorylated tau level (p-tau/GAPDH: 0.33 ± 0.065 vs. 0.83 ± 0.061) in SH-SY5Y cells. Unlike other GSK-3β inhibitors, B10 had a direct effect on Aβ by inhibiting Aβ aggregation and promoting the Aβ aggregate disassociation. It selectively chelated with Cu, Zn, Fe and Al, and targeted AD metal dyshomeostasis. Moreover, B10 effectively increased the mRNA expression of the recognized neurogenesis markers, GAP43, N-myc, and MAP-2, and promoted the differentiated neuronal neurite outgrowth, possibly through the GSK-3β and β-catenin signal pathways. Therefore, B10 is a potent and unique GSK-3β inhibitor that has a direct on Aβ and serves as a multifunctional anti-AD agent for further investigations.
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http://dx.doi.org/10.3390/cells9030649DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7140427PMC
March 2020

Synthesis and evaluation of novel GSK-3β inhibitors as multifunctional agents against Alzheimer's disease.

Eur J Med Chem 2019 Apr 8;167:211-225. Epub 2019 Feb 8.

Institute of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, Jinan, 250012, PR China. Electronic address:

To target the multi-facets of Alzheimer's disease (AD), a series of novel GSK-3β inhibitors containing the 2,3-diaminopyridine moiety were designed and synthesized. The amide derivatives 5a-f showed moderate potency against GSK-3β with weak Cu, Zn and Al chelating ability. The imine derivatives 9a, 9b and 9e were potent GSK-3β inhibitors and selective Cuand Al chelators. The 1,2-diamine derivatives 10a-e were strong metal-chelators, but decreased or lost their GSK-3β inhibitory potency. In vitro, compounds 9a, 9b and 9e, especially 9b, exhibited good Cu-induced Aβ aggregation inhibition, Cu-Aβ complex disaggregation, ROS formation inhibition, and antioxidant activities. In cells, compounds 9a, 9b and 9e can inhibit tau protein phosphorylation and protect neuro cells against Cu-Aβ and HO-induced cell damage. Furthermore, compound 9b was predicted to have the ability to pass the BBB with drug likeness properties. Therefore, compound 9b might be a good lead for the development of novel GSK-3β inhibitors targeting multi-facets of AD.
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http://dx.doi.org/10.1016/j.ejmech.2019.02.001DOI Listing
April 2019

Effects of calcium fertilizer application on absorption and distribution of nutrients in peanut under salt stress.

Ying Yong Sheng Tai Xue Bao 2018 Oct;29(10):3302-3310

Shandong Peanut Research Institute, Qingdao 266100, Shandong, China.

In order to solve the problems of nutrient absorption and accumulation and provide theoretical basis for rational amount of calcium fertilization of peanut in saline land, the effects of calcium fertilizer application on absorption and accumulation of nutrients including nitrogen, phosphorus, potassium, calcium and magnesium in peanut under salt stress were examined. Using 'Huayu 25' as experimental material, four Ca levels [T (0), T (75), T (150) and T (225) kg·hm CaO] were set under 0.3% salt stress in a pot experiment. The results showed that nutrient contents in peanut followed the order of nitrogen > potassium > calcium > phosphorus > magnesium. At the seedling stage, leaves were the absorption center of nitrogen and calcium, while stems were the center of phosphorus, potassium and magnesium, with nearly half of nutrient accumulation being distributed in the corresponding growth center. At mature stage, the absorption centers of nitrogen, phosphorus and potassium were transferred to pod. The accumulation of nitrogen and phosphorus in seed kernel reached to 72.3%-78.9%. The absorption centers of calcium and magnesium was still in the leaves and stems, with a distribution ratio of 49.8% and 32.6%, respectively. Salt stress significantly inhibited nutrient absorption and distribution in peanut, especially decreased the nitrogen accumulation in leaves and seed kernels. However, salt stress increased the magnesium accumulation in pod. Exogenous calcium application had significant positive effect on absorption and accumulation of nitrogen, phosphorus, calcium and magnesium in different organs of peanut under salt stress. It had significant adjustment on phosphorus accumulation in seed kernel, which was increased by more than 50%. Appropriate calcium content could significantly promote the peanut nutrient absorption and accumulation under salt stress and improve the distribution ratio of nitrogen, phosphorus, potassium in mature pods of peanut. According to the responses of nutrient absorption and distribution, the optimized application amount for calcium fertilizer under 0.3% salt stress was 150 kg·hm CaO.
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http://dx.doi.org/10.13287/j.1001-9332.201810.026DOI Listing
October 2018

[Features of contrast-enhanced ultrasound imaging in malignant lymphoma after treatment with integrated Chinese and Western medicine].

Zhongguo Zhong Xi Yi Jie He Za Zhi 2009 May;29(5):410-3

Department of Ultrasound, Zhoushan Hospital, Zhejiang.

Objective: To investigate the typical features of contrast-enhanced ultrasound imaging in malignant lymphoma after treatment with integrated Chinese and Western medicine.

Methods: Ten patients with malignant lymphoma after different treatment cycles were examined with contrast-enhanced sonography, including 21 lymphnodes (in the neck, space of iliac blood vessels, retroperitoneum) and 7 spleen infiltrations.

Results: The blood flow pattern distribution in lymph node before freatment was significantly different from that after trentment showed either by color Doppler flow imaging (CDFI) or by contrast-enhanced ultrasound (CEUS, P < 0.05), and the difference in splenic lesion was shown by CEUS (P < 0.05).

Conclusion: Contrast-enhanced ultrasound imaging is a valuable tool for the follow-ups of malignant lymphoma after chemotherapy and guiding subsequent treatment.
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May 2009

[Diagnosis of thyroid space-occupying lesions using real-time contrast-enhanced ultrasonography with sulphur hexafluoride microbubbles].

Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2009 Apr;44(4):277-81

Ultrasound Department, Zhoushan People's Hospital, Zhoushan, Zhejiang 316000, China.

Objective: To explore the value of contrast-enhanced ultrasound (CEUS) in the diagnosis of thyroid occupied lesions with injection of sulphur hexafluoride microbubbles.

Methods: Fifty nine cases of conventional ultrasonic diagnosis of thyroid lesions in patients with 73 lesions re-sulfur hexafluoride microbubble ultrasound contrast real-time inspection, the use of CEUS and contrast pulse sequencing (CPS).

Results: Seventy-three lesions were satisfied with the dynamic contrast perfusion imaging. Ultrasound contrast prompted the 15 lesions (13 cases) of malignant lesions by postoperative pathology confirmed papillary thyroid carcinoma, ultrasound images showed a low or mixed echo, boundary ambiguity, accompanied by Microcalcification foci, blood flow distribution I rank or grade III. Ultrasound prompted 58 lesions (46 cases) of benign lesions, blood flow distribution of grade II or III, the performance of a variety of two-dimensional ultrasound image, showing cystic, solid or liquid-solid mass, border clearance. Contrast with the surrounding thyroid tissue, lesionsor=20 mm papillary thyroid carcinoma, manifested prior to the beginning of the adjacent thyroid substance to enhance and dissection, showing the form of high-enhanced perfusion; thyroid follicular adenoma as early as the beginning of the adjacent thyroid substance to enhance and dissection, mass retained within the contrast agent longer time, showing the form of high-enhanced perfusion; nodular goiter enhanced for thyroid nodules and adjacent synchronization started to pick up in real terms, after the 6 lesions showed nodular contrast slightly earlier than the adjacent thyroid substance started to pick up, 28 lesions with synchronous real beginning of the adjacent thyroid dissection, 11 lesions of nodular dissipated early on (started receding time < or = 25 s) adjacent to thyroid substance.

Conclusion: The real-time CEUS with injecting sulphur hexafluoride microbubbles is valuable in the diagnosis and differential diagnosis of the thyroid occupied lesions.
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April 2009
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