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Green tea polyphenol ameliorates spatial learning and memory impairment and tau protein hyperphosphorylation of hippocampal neurons induced by okadaic acid in rats

Green tea polyphenol ameliorates spatial learning and memory...

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中国生理学会第23届全国会员代表大会暨生理学学术大会

作者： Hong-Yu LI~1,Xiu-Kui WU~1,Mei-Jun SHI~1,Jun ZHANG~1,Liu JING~1,De-Zheng GONG~1,Liang ZHU~1,Li-Li GUAN~1,Qiong WU~1,Bo YUAN~1,Guo-Zhu HAN~2,Yuan ZOU~(1,*) 1 Department of Physiology 2 faculty of pharmacology,dalian medical university,dalian 116044,china

＜正＞Objective:Green tea polyphenols（GTPs） are now being considered as possible protective agents in neurodegenerative diseases such as Alzheimer’s disease（AD）.Previous studies suggested that GTPs could inhibit amyloid fibril formation and protect neurons from toxicity induced byβ-amyloid in ***,it is still unclear that whether GTPs decrease hyperphosphorylation of tau protein and ameliorate learning and memory impairments induced by okadaic acid（OA） in *** aim of this study is to explore the effects of GTPs on the hyperphosphorylation of tau protein and the learning and memory impairments in ***:SD rats were pretreated with GTPs by intragastric administration,and microinjected with OA into the right dorsal *** ethological test was examined,and hyperphosphorylation of tau protein was examined both in vivo and in ***: With the increase of training,the escape latency of each group shortened gradually,and that of rats with GTPs shortened more obviously than control *** staying time in the target quadrant was significantly decreased after OA microinjection,whereas rats pretreated with GTPs stayed for longer time,and had a longer swimming distance in target quadrant compared with control group ***,GTPs could greatly attenuate the loss of primary hippocampal neurons and inhibit neurite degeneration induced by OA-induced toxicity,and also reduce the accumulation of PHF-13-positve ***:These results suggested that GTPs could ameliorate OA-induced spatial memory impairment and diminish tau *** had protective effects against OA-induced *** data indicated that green tea may be beneficial for preventing AD.

关键词： green tea polyphenols tau protein okadaic acid Alzheimer’s disease

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Mitophagy and cGAS-STING crosstalk in neuroinflammation

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Acta Pharmaceutica Sinica B 2024年第8期14卷 3327-3361页

作者： Xiaogang Zhou Jing Wang Lu Yu Gan Qiao dalian Qin Betty Yuen-Kwan Law Fang Ren Jianming Wu Anguo Wu Sichuan Key medical Laboratory of New Drug Discovery and Drugability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia MedicaKey Laboratory of Medical Electrophysiology of Ministry of EducationSchool of PharmacySouthwest Medical UniversityLuzhou 646000China State Key Laboratory of Quality Research in Chinese Medicine Macao University of Science and TechnologyMacao SAR 999078China Chongqing Key Laboratory of Sichuan-Chongqing Co-construction for Diagnosis and Treatment of Infectious Diseases Integrated Traditional Chinese and Western Medicine Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Mitophagy,essential for mitochondrial health,selectively degrades damaged *** is intricately linked to the cGAS-STING pathway,which is crucial for innate *** pathway responds to mitochondrial DNA and is associated with cellular stress *** review explores the molecular details and regulatory mechanisms of mitophagy and the cGAS-STING *** critically evaluate the literature demonstrating how dysfunctional mitophagy leads to neuroinflammatory conditions,primarily through the accumulation of damaged mitochondria,which activates the cGAS-STING *** activation prompts the production of pro-inflammatory cytokines,exacerbating *** review emphasizes the interaction between mitophagy and the cGAS-STING *** mitophagy may suppress the cGAS-STING pathway,offering protection against ***,impaired mitophagy may activate the cGAS-STING pathway,leading to chronic ***,we explored how this interaction influences neurodegenerative disorders,suggesting a common mechanism underlying these *** conclusion,there is a need for additional targeted research to unravel the complexities of mitophagy-cGAS-STING interactions and their role in *** review highlights potential therapies targeting these pathways,potentially leading to new treatments for neuroinflammatory and neurodegenerative *** synthesis enhances our understanding of the cellular and molecular foundations of neuroinflammation and opens new therapeutic avenues for neurodegenerative disease research.

关键词： Neuroinflammation Mitophagy cGAS-STING Innate immunity Mitochondrial DNA Crosstalk Therapeutic avenues Neurodegenerative diseases

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Influence of Trace Amount of Calponin on Smooth Muscle Myosin in Different States

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Acta Biochimica et Biophysica Sinica 2004年第8期36卷 529-536页

作者： Jing-Xian YANG, Xiao-Hua FENG, Ying ZHANG, and Yuan LIN Department of pharmacology, dalian medical university, dalian 116027, china Department of pharmacology Dalian Medical UniversityDalian 116027China

Calponin (CaP), a thin filament-associated protein, is thought to be involved in modulating smooth muscle contractile activity, but the role and mechanism keep unknown. In this study, trace amount of calponin (TAC) was found to obviously influence myosin in different states in Ca2+-independent manner, suggesting a high efficient interaction between TAC and myosin. In this assay, the lowest ratio of CaP vs. myosin was 1:10,000, with the concentration of CaP 10,000-fold lower than that used previously. Myosin phosphorylation, myosin Mg2+-ATPase activity and protein binding activity were detected to determine the effects of TAC on the myosin in different states. The amount of precipitated myosin that bound to TAC was used as the index to determine the interaction between myosin and TAC in binding assay. Our data showed that in the absence of actin, TAC significantly increased the precipitation of unphosphorylated myosin, Ca2+- dependently or independently phosphorylated myosin by MLCK, and stimulated the Mg2+-ATPase activities of these myosins slightly but significantly. However, no obvious change of precipitation of myosin phospho- rylated by PKA was observed, indicating the relatively selective effect of TAC. In the presence of actin, the increase of myosin precipitations was abolished, and no obvious change of actin precipitations and actin- activated myosin Mg2+-ATPase activities were observed implicating the high efficiency of TAC on myosin being present in the absence of actin. Although we can not give conclusive comments to our results, we propose that the high efficiency of TAC-myosin interaction is present when actin is dissociated from myosin, even if CaP/myosin ratio is very low; this high efficient interaction can be abolished by actin. However, why and how TAC can possess such a high efficiency to influence myosin and how the physiological significance of the high efficiency of TAC is in regulating the interaction between myosin and actin remain to be inve

关键词： trace amount of calponin protein binding phosphorylation myosin Mg2+-ATPase

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Distribution and excretion of N-Ile1 Thr2-63-desulfatohirudin in rats

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沈阳药科大学学报 2008年第S1期25卷 118-119页

作者： SU Yun-jiang1,GUO Zhu-han2(1.dalian Institute for Drug Control,dalian 116021,china 2.Department of pharmacology,dalian medical university,dalian 116044,china)

Objective To investigate distribution and excretion of N-Ile1Thr2-63-desulfatohirudin(rH)a recombinant hirudin newly developed in china,in rats for its development as a novel anticoagulant *** ELISA was used to determine the rH concentration in related tissues and body *** were collected at 15,60 and 180min respectively,after iv administration of rH 1.0 mg·kg-1 to 3 groups of 5 rats,and ***,bile and feces were collected at pre-selected intervals of time after iv dosing 1.0 mg·kg-1 to 3 groups of 5 rats and *** rH following iv dosing was distributed rapidly,the rH levels in all tissues being found to be the highest at 15 min post-injection,afterwards gradually *** highest concentration of rH was found in blood,the next in lung and heart,the lowest in *** 15 min post dose as an example,the rH contents in tissues were ranked in order of plasma>lung>heart >adipose>skeletal muscles>kidney>liver>spleen>*** 12 h-cumulative excretion amount of rH in urine and feces accounted for 0.03%and 0.001% of administered dose,respectively;the 6 h-cumulative excretion amount in bile was 0.02%of the *** The rH is distributed mainly in blood circulation system with very low content in other *** drug is excreted from urine,feces and bile of rats in extremely minute amount(only 0.051% dose),suggesting that rH undergoes extensive metabolic elimination in rat body.

关键词： r-hirudin distribution excretion rat

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Activation of autophagy by Citri Reticulatae Semen extract ameliorates amyloid-beta-induced cell death and cognition deficits in Alzheimer’s disease

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Neural Regeneration Research 2024年第11期19卷 2467-2479页

作者： Yong Tang Jing Wei Xiao-Fang Wang Tao Long Xiaohong Xiang Liqun Qu Xingxia Wang Chonglin Yu Xingli Xiao Xueyuan Hu Jing Zeng Qin Xu Anguo Wu Jianming Wu dalian Qin Xiaogang Zhou Betty Yuen-Kwan Law Dr.Neher’s Biophysics Laboratory for Innovative Drug Discovery State Key Laboratory of Quality Research in Chinese MedicineMacao University of Science and TechnologyMacao Special Administrative RegionChina Sichuan Key medical Laboratory of New Drug Discovery and Druggability Evaluation Luzhou Key Laboratory of Activity Screening and Druggability Evaluation for Chinese Materia Medica Southwest Medical UniversityLuzhouSichuan ProvinceChina Eye School and Key Laboratory of Sichuan Province Ophthalmopathy Prevention&Cure and Visual Function Protection of Chengdu university of TCM ChengduSichuan ProvinceChina School of Basic medical Sciences Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Ophthalmology The Affiliated Hospital of Southwest Medical UniversityLuzhouSichuan ProvinceChina Department of Neurology The First People’s Hospital of NeijiangNeijiangSichuan ProvinceChina

Amyloid-beta-induced neuronal cell death contributes to cognitive decline in Alzheimer’s *** Reticulatae Semen has diverse beneficial effects on neurodegenerative diseases,including Parkinson’s and Huntington’s diseases,however,the effect of Citri Reticulatae Semen on Alzheimer’s disease remains *** the current study,the anti-apoptotic and autophagic roles of Citri Reticulatae Semen extract on amyloid-beta-induced apoptosis in PC12 cells were first *** Reticulatae Semen extract protected PC12 cells from amyloid-beta-induced apoptosis by attenuating the Bax/Bcl-2 ratio via activation of *** addition,Citri Reticulatae Semen extract was confirmed to bind amyloid-beta as revealed by biolayer interferometry in vitro,and suppress amyloid-beta-induced pathology such as paralysis,in a transgenic Caenorhabditis elegans in vivo ***,genetically defective Caenorhabditis elegans further confirmed that the neuroprotective effect of Citri Reticulatae Semen extract was *** importantly,Citri Reticulatae Semen extract was confirmed to improve cognitive impairment,neuronal injury and amyloid-beta burden in 3×Tg Alzheimer’s disease *** revealed by both in vitro and in vivo models,these results suggest that Citri Reticulatae Semen extract is a potential natural therapeutic agent for Alzheimer’s disease via its neuroprotective autophagic effects.

关键词： Alzheimer’s disease amyloid-beta apoptosis autophagy Caenorhabditis elegans Citri Reticulatae Semen

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Risk analysis of flood control operation mode with forecast information based on a combination of risk sources

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Science china(Technological Sciences) 2010年第7期53卷 1949-1956页

作者： DIAO YanFang & WANG BenDe School of faculty of Infrastructure Engineering, dalian university of Technology, dalian 116024, china 1. School of faculty of Infrastructure Engineering Dalian University of Technology Dalian 116024 China

Risk analysis of reservoir flood control operation mode with forecast information (FCOMFI) is an important basis for the design and implementation of FCOMFI. Most of current researches on this issue are incomplete as they only consider flood forecast errors, but not many other uncertainties in reservoir routing. In order to obtain an integrated risk rate of FCOMFI, this paper analyzes four uncertainties, i.e. hydrological, hydraulic, stage-storage uncertainty and time-delay uncertainty, as well as their probability distributions. On the basis of this analysis, an integrated risk analysis model of FCOMFI for reservoirs and its lower reach is established involving the above-mentioned four uncertainties, and this model is solved by Monte Carlo simulation based on Latin hypercube sampling. The simulation results, with Baiguishan reservoir as the example, show that the integrated risk rates of FCOMFI are less than those of the flood control operation mode without forecast information. This article presents the highest limited water level that satisfies flood control safety requirements of the lower reach.

关键词： flood control operation mode with forecast information risk analysis Monte Carlo simulation

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Salvianic acid A inhibits induction of inflammatory mediators by blocking Nuclear Factor-κB activation in macrophages

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沈阳药科大学学报 2008年第S1期25卷 104-105页

作者： YUAN Jun,YAO Ji-hong,ZHOU Qin(dalian medical university,dalian 116044,china)

Objective To investigate the anti-inflammation effect and possible mechanism of Salvianic acid A(SAA)in mouse peritoneal *** Peritoneal macrophages were obtained from BALB/c *** induced nitric oxide(NO),tumor necrosis factor-alpha(TNF-α)and interleukin-6(IL-6)in supernatant,protein expression of inducible nitric oxide synthase(iNOS),matrix metalloproteinase-9(MMP-9)and activation of nuclear factor-kappa B(NF-κB)in the extract were *** SAA strongly inhibited the excessive production of NO,TNF-α and IL-6 in LPS-induced peritoneal macrophages in a concentration-dependent manner and blocked the expression of iNOS and *** with LPS alone increased the translocation of NF-κB(p65)from cytosol to the nucleus,but the SAA inhibited the translocation of NF-κB(p65).Conclusions The results showed that SAA had strong anti-inflammatory effects in LPS-stimulated peritoneal *** important mechanism is due to its inhibition of NF-κB activation.

关键词： salvianic acid a tumor necrosis factor-α nterleukin-6 inducible nitric oxide synthase matrix metalloproteinase-9 nuclear factor-kappa B

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Numerical simulation of soft palate movement and airflow in human upper airway by fluid-structure interaction method

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Acta Mechanica Sinica 2007年第4期23卷 359-367页

作者： Xiuzhen Sun Chi Yu Yuefang Wang Yingxi Liu State Key Lab.of Struct.Anal.for Ind.Equip.,dalian university of Technology,dalian 116024,china The Second Affiliated Hospital,dalian medical university,dalian 116027,china State Key Lab. of Struct. Anal. for Ind. Equip. Dalian University of Technology Dalian 116024 China The Second Affiliated Hospital Dalian Medical University Dalian 116027 China

In this paper, the authors present airflow field characteristics of human upper airway and soft palate movement attitude during breathing. On the basis of the data taken from the spiral computerized tomography images of a healthy person and a patient with Obstructive Sleep Apnea-Hypopnea Syndrome （OSAHS）, three-dimensional models of upper airway cavity and soft palate are reconstructed by the method of surface rendering. Numerical simulation is performed for airflow in the upper airway and displacement of soft palate by fluid-structure interaction analysis. The reconstructed threedimensional models precisely preserve the original configuration of upper airways and soft palate. The results of the pressure and velocity distributions in the airflow field are quantitatively determined, and the displacement of soft palate is presented. Pressure gradients of airway are lower for the healthy person and the airflow distribution is quite uniform in the case of free breathing. However, the OSAHS patient remarkably escalates both the pressure and velocity in the upper airway, and causes higher displacement of the soft palate. The present study is useful in revealing pathogenesis and quantitative mutual relationship between configuration and function of the upper airway as well as in diagnosingdiseases related to anatomical structure and function of the upper airway.

关键词： Obstructive sleep apnea-hypopnea syndrome Upper airway Soft palate Three-dimensional finiteelement reconstruction Fluid-structure interaction Numerical simulation

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Comparative study on pharmacokinetics of Cephradine in diabetic and normal rats

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沈阳药科大学学报 2008年第S1期25卷 114-115页

作者： LIANG Jun,FU Ting,HAN Guo-zhu,LU Li(Department of Clinical pharmacology,College of Pharmacy,dalian medical university,dalian 116044 china)

Objective To study effects of diabetes mellitus(DM)on pharmacokinetics of cephradine(CED)by comparing the difference in pharmacokinetic behaviours of CED between diabetic and normal *** DM was induced in male rats by a single iv injection of alloxan 60 mg·kg-1;rats whose blood glucose was over 16 mmol·L-1 were taken as DM *** rats were divided into DM group and normal control(CTL)group,which were subdivided into low dose(90 mg·kg-1)and high dose(180 mg·kg-1)*** was administered by iv or po *** samples collected at different time post dosing were analyzed by RP-HPLC to yield CED plasma concentration time *** separation was achieved on a Kromasil C18 column(250×4.6 mm ID,5 μm);mobile phase,consisting of 0.025 mol·L-1 KH2PO4-MeOH-CH3CN(87;6∶7 v/v),was delivered at 1.0 mL·min-1;UV detector was set at 261 *** peak area ratio of CED to cephalexin(CEX)as internal standard vs concentraion of CED was used to construct calibration curve.50 μL aliquots of TCA-deproteined plasma samples were injected into *** The methodology validation including specificity,precision,accuracy,recovery,limit of quantitation,linearity,stability,etc.,showed that the HPLC assay developed by us completely met requirements of pharmacokinetic study Both DM and CTL groups showed the two-compartment model for iv dosing and extravascular one-compartment model for po dosing as well as first-order ***,in iv experiment,DM group,when compared with CTL group,presented a significantly shortened t1/2β and MRT as well as increased CL,reflected by t1/2 β 84-91 vs 116-120 min,MRT 61-70 vs 103-119 min;CL 23-25 vs 18-19 mL·min-1·kg-1(P2 K and tmax as well as greater CL and Cmax in DM group than in CTL group were found;meanwhile,DM rats suffered from remarkably increased kidney weight(KW)and KW/BW ratio relative to CTL *** DM pathological status can speed up elimination of

关键词： cephradine diabetes mellitus pharmacokinetics HPLC rats

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NUMERICAL PREDICTION OF FATIGUE DAMAGE IN STEEL CATENARY RISER DUE TO VORTEX-INDUCED VIBRATION

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Journal of Hydrodynamics 2011年第2期23卷 154-163页

作者： GAO Yun ZONG Zhi SUN Lei State Key Laboratory of Structural Analysis for Industrial Equipment and Department of Naval Architecture and faculty of Vehicle Engineering and Mechanics Dalian University of Technology Dalian 116024 China State Key Laboratory of Structural Analysis for Industrial Equipment Dalian University of Technology Dalian116024 China faculty of Vehicle Engineering and Mechanics Dalian University of Technology Dalian 116024 China

For studying the characteristics of Steel Catenary Riser （SCR）, a simplified pinned-pinned cable model of vibration is established. The natural frequencies, the normalized mode shapes and mode curvatures of the SCR are calculated. The fatigue damage of the SCR can be obtained by applying the modal superposition method combined with the parameters of S -N curve. For analyzing the relation between the current velocity and the SCR＇s fatigue damage induced by the vortex-induced vibration, ten different current states are evaluated. Then, some useful conclusions are drawn, especially an important phenomenon is revealed that the maximum fatigue damage in the riser usually occurs near the area of the boundary ends.

关键词： vortex-induced vibration Steel Catenary Riser (SCR) fatigue damage modal superposition method

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