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AD-16 Protects Against Hypoxic-Ischemic Brain Injury by Inhibiting Neuroinflammation

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Neuroscience Bulletin 2022年第8期38卷 857-870页

作者： Zhihua Huang Zhengwei Luo Andrea Ovcjak Jiangfan Wan nai-hong chen Wenhui Hu hong-Shuo Sun Zhong-Ping Feng Department of Physiology Temerty Faculty of MedicineUniversity of TorontoTorontoONM5S 1A8Canada Department of Surgery Temerty Faculty of MedicineUniversity of TorontoTorontoONM5S 1A8Canada State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia MedicaNeuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing100050China Key Laboratory of Molecular Target and Clinical Pharmacology State Key Laboratory of Respiratory DiseaseSchool of Pharmaceutical Sciences and the Fifth Affiliated HospitalGuangzhou Medical UniversityGuangzhou511436GuangdongChina Leslie Dan Faculty of Pharmacy University of TorontoTorontoONM5S 3M2Canada

Neuroinflammation is a key contributor to the pathogenic cascades induced by hypoxic-ischemic(HI)insult in the neonatal ***-16 is a novel anti-inflammatory compound,recently found to exert potent inhibition of the lipopolysaccharide-induced production of pro-inflammatory and neurotoxic *** this study,we evaluated the effect of AD-16 on primary astrocytes and neurons under oxygen-glucose deprivation(OGD)in vitro and in mice with neonatal HI brain injury in *** demonstrated that AD-16 protected against OGD-induced astrocytic and neuronal cell *** dose post-treatment with AD-16(1 mg/kg)improved the neurobehavioral outcome and reduced the infarct volume with a therapeutic window of up to 6 *** administration reduced the mortality rate and preserved whole-brain morphology following neonatal *** in vitro and in vivo effects suggest that AD-16 offers promising therapeutic efficacy in attenuating the progression of HI brain injury and protecting against the associated mortality and morbidity.

关键词： Neuroinflammation Neonatal hypoxic-ischemic brain injury Neuroprotection AD-16

20C,a new bibenzyl compound,plays a significant role in rotenone-induced oxidative insult

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中国药理学与毒理学杂志 2017年第10期31卷 1008-1009页

作者： Xiao-ling ZHANG Yu-he YUAN nai-hong chen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College College of Pharmacy Hunan University of Chinese Medicine

20C,a bibenzyl compound isolated from Gastrodia elata,possesses antioxidative properties in PC12 cells,but its in-depth molecular mechanisms against rotenone-induced neurotoxicity remains *** studies indicate that without intact DJ-1,nuclear factor erythroid 2-related factor(Nrf2)protein becomes unstable,and the activity of Nrf2-mediated downstream antioxidant enzymes are thereby ***,increasing the nuclear translocation of Nrf2 by DJ-1 may present a helpful means for the prevention and treatment of chronic diseases related to oxidative *** results showed that 20C clearly protected PC12 and SH-SY5Y cells against rotenone-induced oxidative injury in a concentration-dependent ***,20C markedly up-regulated the levels of DJ-1,which in turn activated phosphoinositide-3-kinase(PI3K)/Akt signaling and inhibited glycogen synthase kinase 3β(GSK3β)activation,eventually promoting Nrf2 nuclear translocation and inducing the expression of Nrf2-mediated downstream antioxidative enzymes such as *** antioxidative effects of 20C could be partially blocked by ShR NA-mediated knockdown of DJ-1 and inhibition of the PI3K/Akt pathways with Akt1/2 kinase inhibitor in PC12 and SH-SY5Y cells,***,our findings confirm that DJ-1 is necessary for 20C-mediated protection against rotenone-induced oxidative damage,at least in part,by activating PI3K/Akt signaling,and subsequently enhancing the nuclear accumulation of *** findings from our investigation suggest that 20C should be developed as a novel candidate for preventing or alleviating the consequences of PD in the future.

关键词： 20C Parkinson disease DJ-1 Akt oxidative stress nuclear factor erythroid 2-related factor(Nrf2)

Ginsenoside Rg1 attenuates motor impairment and neuroinflammation in the MPTP-probenecid-induced parkinsonism mouse model

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中国药理学与毒理学杂志 2017年第10期31卷 999-1000页

作者： Qian-hang SHAO Yu-he YUAN nai-hong chen State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College College of Pharmacy Hunan University of Chinese Medicine

OBJECTIVE To evaluate these activities of Rg1 in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/probenecid(MPTP/p)-induced PD mouse model for the first time and to elucidate the underlying *** Male C57BL/6 mice were randomly assigned to six *** hour prior to MPTP/p injection,GroupⅢ-Ⅵmice received 10 mg·kg^(-1),20 mg·kg^(-1),or 40 mg·kg^(-1) Rg1 or 3 mg·kg^(-1) selegiline,respectively,orally from D(-3) to ***Ⅰ-Ⅱmice received solvent ***,GroupⅡ-Ⅵmice received by injection MPTP-HCl(25 mg·kg^(-1) bw dissolved in0.9%saline,sc)on a 40-d schedule at intervals of 4 d between consecutive doses in combination with an adjuvant drug,probenecid(250 mg·kg^(-1) bw in 0.03 mL of DMSO,ip);GroupⅠmice were injected with saline and *** performance was assessed in the open field test,pole test and rotarod *** in the striatum were detected using *** levels were measured by Western *** characteristics were examined by *** changes were observed by electron *** Oral treatment with Rg1 significantly attenuated the high MPTP-induced mortality,behavior defects,loss of dopamine neurons and abnormal ultrastructure changes in the *** assays indicated that the protective effect of Rg1 may be mediated by its anti-neuroinflammatory ***1 regulated MPTP-induced reactive astrocytes and microglia and decreased the release of cytokines such as tumor necrosis factor-α(TNF-α)and interleukin-1b(IL^(-1)b)in the ***1 also al eviated the unusual MPTP induced increase in oligomeric,phosphorylated and disease-related a-synuclein in the *** Rg1 protects dopaminergic neurons,most likely by reducing aberrant a-synuclein-mediated neuroinflammation,and holds promise for Parkinson disease therapeutics.

关键词： Parkinson disease neuroinflammation a-synuclein ginsenoside Rg1 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Evaluation of frictional pressure drop correlations for air-water and air-oil two-phase flow in pipeline-riser system

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Petroleum Science 2024年第2期21卷 1305-1319页

作者： nai-Liang Li Bin chen School of Low-carbon Energy and Power Engineering China University of Mining and TechnologyXuzhou221116JiangsuChina State Key Laboratory of Multiphase Flow in Power Engineering Xi’an Jiaotong UniversityXi’an710049ShaanxiChina

Accurate prediction of the frictional pressure drop is important for the design and operation of subsea oil and gas transporting system considering the length of the pipeline. The applicability of the correlations to pipeline-riser flow needs evaluation since the flow condition in pipeline-riser is quite different from the original data where they were derived from. In the present study, a comprehensive evaluation of 24prevailing correlation in predicting frictional pressure drop is carried out based on experimentally measured data of air-water and air-oil two-phase flows in pipeline-riser. Experiments are performed in a system having different configuration of pipeline-riser with the inclination of the downcomer varied from-2°to-5°to investigated the effect of the elbow on the frictional pressure drop in the riser. The inlet gas velocity ranges from 0.03 to 6.2 m/s, and liquid velocity varies from 0.02 to 1.3 m/s. A total of885 experimental data points including 782 on air-water flows and 103 on air-oil flows are obtained and used to access the prediction ability of the correlations. Comparison of the predicted results with the measured data indicate that a majority of the investigated correlations under-predict the pressure drop on severe slugging. The result of this study highlights the requirement of new method considering the effect of pipe layout on the frictional pressure drop.

关键词： Frictional pressure drop Pipeline-riser Gas-liquid two-phase flow Severe slugging Correlation

NLRP3 inflammasome pathway is involved in olfactory bulb pathological alteration induced by MPTP

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Acta Pharmacologica Sinica 2019年第8期40卷 991-998页

作者： Ying chen Qiu-shuang Zhang Qian-hang Shao Shuo Wang Yu-he Yuan nai-hong chen hong-bo Wang State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University) Ministry of EducationYantai University

Olfactory bulb,as one of sensory organs opening to the outside,is susceptible to toxic environment and easy to *** studies in Parkinson’s disease(PD)patients and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-treated monkeys have shown that abnormal a-synuclein is accumulated in the olfactory glomeruli,suggesting that the lesions of PD are not only confined to the substantia nigra(SN)but also located in the olfactory ***,olfactory bulb might be the region of onset in PD pathogenesis and a targeted region for diagnosis and treatment of ***,the relationship between olfactory bulb and pathogenesis of PD remains *** the present study,we investigated the inflammatory pathological alterations in olfactory bulb and the underlying mechanisms in chronic MPTP *** were treated with MPTP/P, i.e.,MPTP(25 mg/kg,s.c.)plus probenecid(250 mg/kg,i.p.)every 4 days,for ten *** mice displayed typical parkinsonian *** we examined their olfactory function and the pathologic changes in olfactory *** mice showed obvious olfactory dysfunction in a buried pellet *** studies revealed that tyrosine hydroxylase(TH)protein levels were significantly decreased,whereas abnormal a-synuclein was significantly increased in the olfactory ***,the olfactory bulbs in MPTP/P-treated mice showed significantly increased levels of interleukin-1β(IL-1β),caspase-1,glial fibrillary acidic protein(GFAP),Toll receptor 4(TLR4),phosphorylation of p65,as well as activated molecules of NOD-like receptor protein 3(NLRP3)that were associated with *** results demonstrate that MPTP/P-caused olfactory bulb damage might be related to NLRP3-mediated inflammation.

关键词： Parkinson’s disease olfactory bulb α-synuclein TLR4 NF-κB NLRP3 neuroinflammation MPTP probenecid

Comparison of antioxidant activities between salvianolic acid B and Ginkgo biloba extract(EGb 761)

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Acta Pharmacologica Sinica 2006年第9期27卷 1137-1145页

作者： Chang-suo LIU Yong chenG Jin-feng HU Wei ZHANG nai-hong chen Jun-tian ZHANG~2 Department of Neuropharmacology,Institute of Materia Medica,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100050.China Department of Neuropharmacology Institute of Materia Medica Chinese Academy of Medical Sciences and Peking Union Medical College Beijing China

Aim:To investigate and compare the antioxidant activities of salvianolic acid B(SalB)and Ginkgo biloba extract(EGb 761)in aqueous solution,rat microsomesand the cellular ***:Superoxide anion(O2~-)was generated usingxanthine/xanthine oxidase system and phenazine methosulate/NADH system,andthe effects of SalB and EGb 761 on the generation of O2~- were achieved by spectro-photometric measurement of the product formed on reduction of nitro *** different methods were used to assess the scavenging effects ofthe extracts on hydroxyl radical(.OH):HPLC method was used for quantitation *** by oxy-radical trapping of 5,5-dimethyl- 1-pyrroline-N-oxide(DMPO)to formDMPO-OH adducts in Fe2+-*** confirm the HPLC data,.OHwas also measured by spectrophotometry using a commercial detection ***-lipid peroxidation effects of the extracts in microsomes of rat brain,liver andkidney induced by ascorbate-NADPH were determined by thiobarbituric acid(TBA)*** protective effects of the extracts on peroxide hydrogen(H2O2)-induced oxidative damage in SH-SY5Y cells were investigated by assessing cellviability assay,the level of lipid peroxidation,and the lactate dehydrogenase(LDH)***:Both SalB and EGb 761 were able to scavenge O2~- ***,inhibit lipid peroxidation of microsomes,and protect SH-SY5Y ceils againstH2O2-induced oxidative ***,the concentration of SalB was far lowerthan that of EGb 761 when a similar effect was ***:The antioxi-dant efficiency of SalB was greater than that of EGb *** results suggestthat SalB,like EGb 761,has promising potential in treating oxidative damage-derived neurodegenerative disorders.

关键词： antioxidant Ginkgo biloba extract 761 free radical salvianolic acid B SH-SY5Y cells

The mTORC1 signaling network underlying the pathogenesis and treatment of depression: new insights into rapid-acting antidepressant therapies

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中国药理学与毒理学杂志 2018年第4期32卷 331-331页

作者： Ting ZENG Zhen-zhen WANG nai-hong chen College of Pharmacy Hunan University of Chinese Medicine State Key Laboratory of Bioactive Substances and Functions of Natural Medicines Institute of Materia Medica & Neuroscience CenterChinese Academy of Medical Sciences and Peking Union Medical College

Depression is a devastating mental disorder and major depressive disorder(MDD) that afflicts 16% of the global population at some point in their *** available classical ***(SSRIs,SNRIs,TCAs and MOIs),require a minimum of 2–4 weeks of continuous *** to elicit therapeutic relief in depressed patients and are associated with high rates of ***,and limited duration of ***,faster-acting antidepressant therapies are ***,particularly for patients at risk for suicide for current therapies for *** the *** mechanisms underlying the pathogenesis of depression are still largely unclear,previous studies have suggested that modulators of mammalian target of rapamycin complex 1(mTORC1) signaling may have beneficial neuroprotective and antidepressant ***,we review recent advances in understanding mTORC1 signaling in depression and potential therapeutic strategies resulting from modulation of the mTORC1 signaling *** also highlight recent studies considered to support mTORC1 signaling modulation as a rapid-acting antidepressant therapy(***,scopolamine,GLYX-13,(2R,6 R)-HNK,Ro-256891 etc.) and discuss future research *** on *** next-generation rapid-acting antidepressant therapies should focus on developing more selective glutamate receptors(e.g.α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors(AMPARs)agonists or activators) that activate the mTORC1 signaling pathway free of ketamine's adverse effects.

关键词：抑郁症治疗方法心理健康临床分析

Mixed H_(∞)/Passive Exponential Synchronization for Delayed Memristive Neural Networks with Switching Event-Triggered Control

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Journal of Systems Science & Complexity 2024年第1期37卷 294-317页

作者： WU Wenhuang GUO Lulu chen hong Shanghai Research Institute for Intelligent Autonomous Systems Tongji UniversityShanghai 200092China Department of Control Science and Engineering Tongji UniversityShanghai 201804China

This paper is devoted to event-triggered synchronization of delayed memristive neural networks with H∞and passivity *** aim is to guarantee the exponential synchronization and mixed H∞and passivity control for memristive neural networks by using event-triggered ***,a switching system is constructed under the event-triggered control ***,by adopting a piece-wise Lyapunov functional,a sufficient condition is established for the exponential synchronization and mixed H_(∞)and passivity ***,an event-triggered controller design scheme is proposed using matrix decoupling ***,the effectiveness of the designed controller is exemplified by a numerical example.

关键词： Event-triggered control exponential synchronization memristive neural networks time delays.

Equalizer Zero-Determinant Strategy in Discounted Repeated Stackelberg Asymmetric Game

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Journal of Systems Science & Complexity 2024年第1期37卷 184-203页

作者： chenG Zhaoyang chen Guanpu hong Yiguang Key Laboratory of Systems and Control Academy of Mathematics and Systems ScienceChinese Academy of SciencesBeijing 100190China School of Mathematical Sciences University of Chinese Academy of SciencesBeijing 100049China School of Electrical Engineering and Computer Science KTH Royal Institute of Technology10044 StockholmSweden. Department of Control Science and Engineering Tongji UniversityShanghai 201804China Shanghai Research Institute for Intelligent Autonomous Systems Tongji UniversityShanghai 210201China

This paper focuses on the performance of equalizer zero-determinant(ZD)strategies in discounted repeated Stackelberg asymmetric *** the leader-follower adversarial scenario,the strong Stackelberg equilibrium(SSE)deriving from the opponents’best response(BR),is technically the optimal strategy for the ***,computing an SSE strategy may be difficult since it needs to solve a mixed-integer program and has exponential complexity in the number of *** this end,the authors propose an equalizer ZD strategy,which can unilaterally restrict the opponent’s expected *** authors first study the existence of an equalizer ZD strategy with one-to-one situations,and analyze an upper bound of its performance with the baseline SSE *** the authors turn to multi-player models,where there exists one player adopting an equalizer ZD *** authors give bounds of the weighted sum of opponents’s utilities,and compare it with the SSE ***,the authors give simulations on unmanned aerial vehicles(UAVs)and the moving target defense(MTD)to verify the effectiveness of the proposed approach.

关键词： Discounted repeated Stackelberg asymmetric game equalizer zero-determinant strategy strong Stackelberg equilibrium strategy