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neurobiology of Supporting Syntactic Chains of Self-Grooming in Rodents and Its Biochecmical Characteristics

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Journal of Biosciences and Medicines 2024年第4期12卷 330-352页

作者： Giorgi Andronikashvili Tea Gurashvili Khatuna Dondoladze Marina Nikolaishvili Malkhaz Makashvili Beritashvili Center for Experimental Biomedicine Laboratory of Neurology Tbilisi Georgia Department of neuro Physiology Grigor Robakidze University Tbilisi Georgia Department of Physiology Ilia State University Tbilisi Georgia

Grooming is an innate behavior that serves multiple purposes and has a dual nature, reflecting both comfort and stress. Auto-grooming, in particular, is highly sensitive to stressors and can be influenced by natural and synthetic anxiolytics. Researchers believe that rodent grooming can be a valuable tool in translational neurobiological studies, specifically focusing on aberrant grooming, such as the syntactic chain of grooming, which can serve as an experimental model for certain human psycho-nervous disorders.

关键词： Grooming Microstructure Translational Medicine Clinical Medicine Stress

Regulation of autophagic flux by CHIP

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neuroscience Bulletin 2015年第4期31卷 469-479页

作者： Dongkai Guo Zheng Ying Hongfeng Wang Dong Chen Feng Gao Haigang Ren Guanghui Wang Laboratory of Molecular neuropathology Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-Diseases and College of Pharmaceutical SciencesSoochow University

Autophagy is a major degradation system which processes substrates through the steps of auto- phagosome formation, autophagosome-lysosome fusion, and substrate degradation. Aberrant autophagic flux is present in many pathological conditions including neurodegeneration and tumors. CHIP/STUB1, an E3 ligase, plays an important role in neurodegeneration. In this study, we identified the regulation of autophagic flux by CHIP （carboxy-terminus of HscT0-interacting protein）. Knockdown of CHIP induced autophagosome formation through increasing the PTEN protein level and decreasing the AKT/mTOR activity as well as decreasing phosphorylation of ULK1 on Ser757. However, degradation of the autophagic substrate p62 was disturbed by knockdown of CHIP, suggesting an abnormality of autophagic flux. Furthermore, knockdown of CHIP increased the susceptibility of cells to autophagic cell death induced by bafilomycin AI. Thus, our data suggest that CHIP plays roles in the regulation of autophagic flux.

关键词： CHIP/STUB1 autophagic flux neuro-degeneration mTOR AKT

Pharmacokinetics,distribution,and excretion of sodium oligomannate,a recently approved anti-Alzheimer's disease drug in China

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Journal of Pharmaceutical Analysis 2022年第1期12卷 145-155页

作者： Jiaojiao Lu Qiongqun Pan Jieqiang Zhou Yan Weng Kaili Chen Lv Shi Guanxiu Zhu Chunlin Chen Liang Li Meiyu Geng Zhenqing Zhang Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases College of Pharmaceutical SciencesSoochow UniversitySuzhouJiangsu215021China Shanghai Green Valley Pharma.Corp. Shanghai201203China Medicilon Preclinical Research(Shanghai)LLC Shanghai201299China State Key Laboratory of Drug Research Shanghai Institute of Materia MedicaChinese Academy of SciencesShanghai201203China

The National Medical Products Administration has authorized sodium oligomannate for treating mild-to-moderate Alzheimer’s *** this study,an LC-MS/MS method was developed and validated to quantitate sodium oligomannate in different *** plasma pharmacokinetics,tissue distribution,and excretion of sodium oligomannate in Sprague-Dawley rats and beagle dogs were systematically *** its complicated structural composition,the absorption,distribution,metabolism,and excretion profiles of the oligosaccharides in sodium oligomannate of different sizes and terminal derivatives were *** oligomannate mainly crossed the gastrointestinal epithelium through paracellular transport following oral administration,with very low oral bioavailability in rats(0.6%-1.6%)and dogs(4.5%-9.3%).Absorbed sodium oligomannate mainly resided in circulating body fluids in free form with minimal distribution into erythrocytes and major *** oligomannate could penetrate the blood-cerebrospinal fluid(CSF)barrier of rats,showing a constant area under the concentration-time curve ratio(CSF/plasma)of approximately 5%.The cumulative urinary excretion of sodium oligomannate was commensurate with its oral bioavailability,supporting that excretion was predominantly renal,whereas no obvious biliary secretion was observed following a single oral dose to bile duct-cannulated ***,only 33.7%(male)and 26.3%(female)of the oral dose were recovered in the rat excreta within 96 h following a single oral administration,suggesting that the intestinal flora may have ingested a portion of unabsorbed sodium oligomannate as a nutrient.

关键词： Sodium oligomannate Alzheimer’s disease Pharmacokinetics LC-MS/MS Oligosaccharide

N-glycans released from glycoproteins using a commercial kit and comprehensively analyzed with a hypothetical database

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Journal of Pharmaceutical Analysis 2017年第2期7卷 87-94页

作者： Xue Sun Lei Tao Lin Yi Yilan Ouyang Naiyu Xu Duxin Li Robert J.Linhardt Zhenqing Zhang Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases and College of Pharmaceutical Sciences Soochow University Center for Biotechnology and Interdisciplinary Studies Rensselaer Polytechnic Institute

The glycosylation of proteins is responsible for their structural and functional roles in many cellular *** work describes a strategy that combines an efficient release, labeling and liquid chromatography–mass spectral analysis with the use of a comprehensive database to analyze N-glycans. The analytical method described relies on a recently commercialized kit in which quick deglycosylation is followed by rapid labeling and cleanup of labeled glycans. This greatly improves the separation, mass spectrometry（MS） analysis and fluorescence detection of N-glycans. A hypothetical database, constructed using Glyc Resoft, provides all compositional possibilities of N-glycans based on the common sugar residues found in N-glycans. In the initial version this database contains ＆gt; 8,700 N-glycans, and is compatible with MS instrument software and expandable. N-glycans from four different well-studied glycoproteins were analyzed by this strategy. The results provided much more accurate and comprehensive data than that had been previously reported. This strategy was then used to analyze the N-glycans present on the membrane glycoproteins of gastric carcinoma cells with different degrees of differentiation. Accurate and comprehensive N-glycan data from those cells was obtained efficiently and their differences were compared corresponding to their differentiation states. Thus, the novel strategy developed greatly improves accuracy, efficiency and comprehensiveness of N-glycan analysis.

关键词： N-glycan Hypothetical database Glycoproteins Gastric carcinoma cells Glycomics

Purification, structure characterization and antioxidant activity of polysaccharides from Saposhnikovia divaricata

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Chinese Journal of Natural Medicines 2019年第10期17卷 792-800页

作者： MENG Yao YI Lin CHEN Lei HAO Jie LI Du-Xin XUE Jie XU Nai-Yu ZHANG Zhen-Qing College of Pharmaceutical Sciences Soochow UniversitySuzhou 215123China Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases Soochow UniversitySuzhou 215021China

Polysaccharide from traditional Chinese herb, Saposhnikovia divaricata(Turcz.) Schischk.(SD) was extracted, fractionated and characterized in this work. Four fractions were prepared. Their molecular weight, monosaccharide compositions, linkage modes and structural properties were characterized with SEC-MALS-RI, HPAEC-PAD, GC-MS and NMR. SDP1 was assigned as a 1, 4-α-glucan with small amount of O-6 linked branches. SDP2 contained a big amount of the 1, 4-α-glucan and a small amount of arabinogalactan, while SDP3 possessed relatively lower amount of the 1, 4-α-glucan and a big amount of the arabinogalactan. SDP4 was defined as a pectic arabinogalactan. Four fractions showed antioxidant activities in both molecular and cellular levels and their activity was ranked as SDP4 ≈ SDP3>SDP2>SDP1. The 1, 4-α-glucan in SDP1 had the weakest, while SDP3 and SDP4 showed similar and the highest antioxidant activity. The arabinogalactan was the major component of both SDP3 and SDP4, which significantly contributed to the antioxidant activity of SDP.

关键词： Saposhnikovia divaricata Polysaccharides Arabinogalactan Antioxidant activity

Structural optimization and biological evaluation of 1,5-disubstituted pyrazole-3-carboxamines as potent inhibitors of human 5-lipoxygenase

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Acta Pharmaceutica Sinica B 2016年第1期6卷 32-45页

作者： Yu Zhou Jun Liu Mingyue Zheng Shuli Zheng Chunyi Jiang Xiaomei Zhou Dong Zhang Jihui Zhao Deju Ye Mingfang Zheng Hualiang Jiang Dongxiang Liu Jian Cheng Hong Liu CAS Key Laboratory of Receptor Research Shanghai Institute of Materia MedicaChinese Academy of Sciences China Pharmaceutical University Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases and Institute of neuroscience Soochow University

Human 5-lipoxygenase(5-LOX)is a well-validated drug target and its inhibitors are potential drugs for treating leukotriene-related *** previous work on structural optimization of the hit compound 2 from our in-house collection identified two lead compounds,3a and 3b,exhibiting a potent inhibitory profile against 5-LOX with IC_(50) values less than 1 mmol/L in cell-based ***,we further optimized these compounds to prepare a class of novel pyrazole derivatives by opening the fusedring *** new compounds exhibited more potent inhibitory activity than the lead compounds against *** particular,compound 4e not only suppressed lipopolysaccharide-induced inflammation in brain inflammatory cells and protected neurons from oxidative toxicity,but also significantly decreased infarct damage in a mouse model of cerebral *** docking analysis further confirmed the consistency of our theoretical results and experimental *** conclusion,the excellent in vitro andin vivo inhibitory activities of these compounds against 5-LOX suggested that these novel chemical structures have a promising therapeutic potential to treat leukotriene-related disorders.

关键词： 5-Lipoxygenase 5-LOX inhibitors Pyrazole derivatives Leukotrienes-related diseases In vivo Benzo-fused heterocycle Ischemic incults Brain inflammation

Trehalose ameliorates autophagy dysregulation in aged cortex and acts as an exercise mimetic to delay brain aging in elderly mice

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Food Science and Human Wellness 2022年第4期11卷 1036-1044页

作者： Shanyao Pan Shanshan Guo Jiaru Dai Yanrong Gu Guoxiang Wang Yulong Wang Zhenghong Qin Li Luo School of Physical Education and Sports Science Soochow UniversitySuzhou 215021China School of Life Sciences Fudan UniversityShanghai 200032China Department of Rehabilitation Shenzhen Second People's HospitalThe First Affi liated HospitalShenzhen University School of MedicineShenzhen 518035China Department of Pharmacology and Laboratory of Aging and Nervous Diseases Jiangsu Key Laboratory of Translational Research and Therapy for Neuro-Psycho-DiseasesCollege of Pharmaceutical SciencesSoochow UniversitySuzhou 215123China

Exercise is recognized as an effective strategy to delay brain aging, which is related to the activation of autophagy. Trehalose is a natural compound that can activate autophagy and exert beneficial effects in delaying brain aging. In this study, we investigated whether trehalose may exert neuroprotection similar to those of exercise in delaying age-related cognitive decline. Fifteen-month-old male C57BL/6 mice underwent swim exercise and/or were treated with 2% trehalose for 12 weeks. Trehalose, exercise and the combination of exercise and trehalose intervention improved the learning and memory of aged mice. They also improved the ratio of LC3-II/LC3-I, the protein level of LC3-II, Bnip3L, and Parkin respectively. Additionally, both exercise and trehalose increased the phosphorylation of AMPK. Exercise decreased cortical phosphorylation of m TOR and S6k, whereas trehalose did not change these cortical levels. These data indicated that exercise and trehalose might modulate autophagy through m TOR-dependent or m TOR-independent pathways, respectively. However, a combination of exercise and trehalose did not play a synergistic role in improving cognitive function and modulation of autophagy. Taken together, our findings suggest that trehalose exerts similar effects to those of exercise in delaying age-related cognitive decline and that it may thus represent an exercise mimetic to delay brain aging.

关键词： Exercise Trehalose Cognitive function Autophagy

Scorpion toxin BmKI directly activates Nav1.8 in primary sensory neurons to induce neuronal hyperexcitability in rats

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Protein & Cell 2015年第6期6卷 443-452页

作者： Pin Ye Yunlu Jiao Zhenwei Li Liming Hua Jin Fu Feng Jiang Tong Liu Yonghua Ji Laboratory of neuropharmacology and neurotoxicology Shanghai University Shanghai 200436 China Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases and the Second Affiliated Hospital of Soochow University Institute of Neuroscience Soochow University Suzhou 215021 China

Voltage-gated sodium channels （VGSCs） in primary sensory neurons play a key role in transmitting pain signals to the central nervous system. BmK I, a site-3 sodium channel-specific toxin from scorpion Buthus martensi Karsch, induces pain behaviors in rats. How- ever, the subtypes of VGSCs targeted by BmK I were not entirely clear. We therefore investigated the effects of BmK I on the current amplitude, gating and kinetic properties of Nav1.8, which is associated with neuronal hyperexcitability in DRG neurons. It was found that BmK I dose-dependently increased Nav1.8 current in small- sized （〈25 μm） acutely dissociated DRG neurons, which correlated with its inhibition on both fast and slow in- activation. Moreover, voltage-dependent activation and steady-state inactivation curves of Nay1.8 were shifted in a hyperpolarized direction. Thus, BmK I reduced the threshold of neuronal excitability and increased action potential firing in DRG neurons. In conclusion, our data clearly demonstrated that BmK I modulated Nav1.8 re- markably, suggesting BmK I as a valuable probe for studying Nay1.8. And Navl.8 is an important target re- lated to BmK I-evoked pain.

关键词： voltage-gated sodium channel Nay1.8,primary sensory neurons BmK I

Endovascular Treatment of a Distal C1 Dissecting Aneurysm in a Patient with Double Aortic Arch

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Chinese Medical Journal 2016年第1期129卷 112-113页

作者： Jia-Ping Xu Ji-Jun Shi Guo-Dong Xiao Guang-Xin Duan Chun-YuanZhang Yong-Jun Cao Department of neurology The Second Affiliated Hospital of Soochow University Suzhou Jiangsu 215004 China Jiangsu Key Laboratory of Translational Research and Therapy for neuro-psycho-Diseases and Institute of neuroscience Soochow University Suzhou Jiangsu 215123 China

To the Editor： Double aortic arch （DAA）, a rare congenital cardiovascular disorder, is usually diagnosed and surgically corrected at an early age due to dyspnea or dysphagia caused by an obstruction of trachea or esophagus. Here, we report a case with DAA and a dissecting aneurysm, which was successfully performed by stent-assisted coiling.

关键词： INTRACRANIAL ANEURYSMS