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Advantages of Rho-associated kinases and their inhibitor fasudil for the treatment of neurodegenerative diseases

Neural Regeneration Research 2022年第12期17卷 2623-2631页

作者： qing Wang li-Juan Song Zhi-Bin Ding Zhi Chai Jie-Zhong Yu Bao-Guo Xiao Cun-gen Ma Research Center of Neurobiology The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese MedicineShanxi University of Chinese MedicineJinzhongShanxi ProvinceChina Department of Physiology Shanxi Medical UniversityTaiyuanShanxi ProvinceChina Institute of Brain Science Shanxi Key Laboratory of Inflammatory Neurodegenerative DiseasesShanxi Datong UniversityDatongShanxi ProvinceChina Department of Neurology Datong Fifth People’s HospitalDatongShanxi ProvinceChina Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Ras homolog(Rho)-associated kinases(ROCKs)belong to the serine-threonine kinase family,which plays a pivotal role in regulating the damage,survival,axon guidance,and regeneration of *** are also involved in the biological effects of immune cells and glial cells,as well as the development of neurodegenerative disorders such as Alzheimer’s disease,Parkinson’s disease,and multiple *** studies by us and others confirmed that ROCKs inhibitors attenuated the symptoms and progression of experimental models of the abovementioned neurodegenerative diseases by inhibiting neuroinflammation,regulating immune imbalance,repairing the blood-brain barrier,and promoting nerve repair and myelin ***,the first ROCKs inhibitor to be used clinically,has a good therapeutic effect on neurodegenerative *** increases the activity of neural stem cells and mesenchymal stem cells,thus optimizing cell *** review will systematically describe,for the first time,the effects of abnormal activation of ROCKs on T cells,B cells,microglia,astrocytes,oligodendrocytes,and pericytes in neurodegenerative diseases of the central nervous system,summarize the therapeutic potential of fasudil in several experimental models of neurodegenerative diseases,and clarify the possible cellular and molecular mechanisms of ROCKs *** review also proposes that fasudil is a novel potential treatment,especially in combination with cell-based *** from this review add support for further investigation of ROCKs and its inhibitor fasudil for the treatment of neurodegenerative diseases.

关键词： Alzheimer’s disease cell-based therapy central nervous system cells fasudil immunocytes multiple sclerosis Parkinson’s disease pericytes Rho kinase inhibitor Rho-associated kinases

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Gastrolatathioneine,an unusual ergothioneine derivative from an aqueous extract of "tian ma":A natural product co-produced by plant and symbiotic fungus

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Chinese Chemical letters 2016年第10期27卷 1577-1581页

作者： qing-lan Guo Sheng lin Ya-Nan Wang Cheng-gen Zhu Cheng-Bo Xu Jian-Gong Shi State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

Gastrolatathioneine （1）, an unusual natural product derived from ergothioneine, a fungal amino acid containing an imidazole-2-thione moiety, was isolated from an aqueous extract of ＂tian ma＂（the Gastrodia elata rhizomes）. The structure of 1 including the absolute configuration was determined by extensive spectroscopic data analysis, combined with comparison of an experimental circular dichroism spectrum and calculated electronic circular dichroism spectra of stereoisomers, and confirmed by X-ray crystallography. The natural origin of 1 was proved by HPlC-ESIMS analysis of the crude extract. A biogenetic pathway of I is proposed on the basis of metabolic post-modification of ergothioneine that is biosynthesized by a symbiotic fungus. The plant and symbiotic fungus are co-uroducers of 1.

关键词： Gastrodia elataorchidaceaeErgothioneine(+)-l-N N-bis(4-hydroxybenzyl)ergothioneineGastrolatathioneine

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Cucurbit[8]uril-mediated phosphorescent supramolecular foldamer for antibiotics sensing in water and cells

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Chinese Chemical letters 2022年第2期33卷 851-854页

作者： De-ao Xu qing-Yang Zhou Xianyin Dai Xin-Kun Ma Ying-Ming Zhang Xiufang Xu Yu liu College of Chemistry State Key Laboratory of Elemento-Organic ChemistryNankai UniversityTianjin 300071China

A phosphorescent supramolecular foldamer is conveniently constructed by the 1:1 host-guest complexation with cucurbit[8]uril and 1,2-diaminocyclohexane-bridged 4-(4-bromophenyl)-pyridinium salt. The tightly compact host-guest complexation in molecular foldamer can greatly suppress the fluorescence emissive channel and promote the intersystem crossing from singlet to triplet states, thus leading to the green phosphorescence at ambient temperature in aqueous solution. More intriguingly, the phosphorescence emission shows very rapid and sensitive responsiveness to different antibiotics in both inanimate milieu and living cells. Remarkably, the limit of detection of such binary inclusion complex toward sulfamethazine can reach as low as 1.86 × 10^(-7) mol/l. Thus, it is envisaged that this supramolecular nanoplatform featuring unique complexation-enhanced phosphorescence emission may hold great promise in sensing and detecting many other biological targets under physiological environment.

关键词： Supramolecular assembly Cucurbiturils Supramolecular foldamer Phosphorescence sensing Antibiotics detection

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Gastradefurphenol,a minor 9,9＇-neolignan with a new carbon skeleton substituted by two p-hydroxybenzyls from an aqueous extract of “tian ma”

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Chinese Chemical letters 2017年第6期28卷 1185-1189页

作者： Xue Zhou qing-lan Guo Cheng-gen Zhu Cheng-Bo Xu Ya-Nan Wang Jian-Gong Shi State Key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical College

Gastradefurphenol（1）,a minor 9.9＇-neolignan with a novel carbon skeleton substituted by two phydroxybenzyls was isolated from an aqueous extract of the Gastrodia elata rhizomes（tian ma）.Its structure was determined by extensive spectroscopic data ***-dependent free rotational restriction of bonds and equilibrium of two molecular states are discussed by comparison of the NMR spectroscopic data of 1 in acetone-d6 with those in CD3OD.A biogenetic pathway of 1 is postulated to be associated with metabolic processes of l-tyrosine.

关键词： Gastrodia elata Orchidaceae 9 9'-Neolignan Gastradefurphenol Minor constituent

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Neural stem cell transplantation alleviates functional cognitive deficits in a mouse model of tauopathy

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Neural Regeneration Research 2022年第1期17卷 152-162页

作者： He-ao Zhang Chun-Xu Yuan Ke-Fu liu Qi-Fan Yang Juan Zhao Hui li qing-Hu Yang Da Song Zhen-Zhen Quan Hong qing Key laboratory of Molecular Medicine and Biotherapy School of Life ScienceBeijing Institute of TechnologyBeijingChina

The mechanisms of the transplantation of neural stem cells(NSCs)in the treatment of Alzheimer’s disease remain poorly *** this study,NSCs were transplanted into the hippocampal CA1 region of the rTg(tau P301l)4510 mouse model,a tauopathy model that is thought to reflect the tau pathology associated with Alzheimer’s *** results revealed that NSC transplantation reduced the abnormal aggregation of tau,resulting in significant improvements in the short-term memory of the tauopathy model *** with wild-type and phosphate-buffered saline(PBS)-treated mice,mice that received NSC transplantations were characterized by changes in the expression of multiple proteins in brain tissue,particularly those related to the regulation of tau aggregation or *** Encyclopedia of genes and genomes(KEGG)pathway analysis and gene Ontology(GO)function analysis revealed that these proteins were primarily enriched in pathways associated with long-term potentiation,neurogenesis,and other neurobiological *** in the expression levels of key proteins were verified by western blot *** data provided clues to improve the understanding of the functional capacity associated with NSC transplantation in Alzheimer’s disease *** study was approved by the Beijing Animal Ethics Association and Ethics Committee of Beijing Institute of Technology(approval ***-BIT-school of life science-2017-M03)in 2017.

关键词： Alzheimer’s disease cell transplantation neural differentiation neural stem cells proteomic analysis short-term memory tauopathy

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Synthesis and bioactivity of novel 3-(1-hydroxyethylidene)-5-substituted-pyrrolidine-2,4-dione derivatives

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Chinese Chemical letters 2012年第9期23卷 1023-1026页

作者： B ao Feng Han qing Ming Shi Xian Feng Wang Jian Bo liu Sheng Qiang Chun long Yang Key laboratory of Monitoring and Management of Crop Diseases and Pest Insects Ministry of AgricultureNanjing Agricultural UniversityChina Nanjing 210095 Jiangsu Key laboratory of Pesticide Science Nanjing Agricultural UniversityChina Nanfing 210095 College of life Science Nanjing Agricultural UniversityChina Nanjing 210095

Ten novel 5-substituted derivatives of 3-（1-hydroxyethylidene）pyrrolidine-2,4-dione were synthesized. The compounds were confirmed by IR, 1H NMR, MS and elemental analysis. The bioassay indicated that these compounds showed noticeable herbicidal activities, and compounds 6f and 6j exhibited excellent inhibitory activities against the stalk of Echinochloa crusgalli, with ECso values of 94.4 and 72.7 rag/l, respectively.

关键词： Tenuazonic acid Pyrrolidine-2,4-dione Synthesis Herbicidal activity

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Grape Seed Extract Attenuates Demyelination in Experimental Autoimmune Encephalomyelitis Mice by Inhibiting Inflammatory Response of Immune Cells

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Chinese Journal of Integrative Medicine 2023年第5期29卷 394-404页

作者： WANG qing CHEN Yang-yang YANG Zhi-chao YUAN Hai-jun DONG Yi-wei MIao Qiang lI Yan-qing WANG Jing YU Jie-zhong XIao Bao-guo MA Cun-gen Research Center of Neurobiology the Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese MedicineShanxi University of Chinese MedicineJinzhongShanxi Province(030619)China Department of Neurology the First Affiliated HospitalShanxi Medical UniversityTaiyuan(030001)China Institute of Brain Science Shanxi Key Laboratory of Inflammatory Neurodegenerative DiseasesShanxi Datong UniversityDatongShanxi Province(037009)China Department of Neurology Datong Fifth People's HospitalDatongShanxi Province(037009)China Institute of Neurology Huashan HospitalInstitutes of Brain Science and State Key Laboratory of Medical NeurobiologyFudan UniversityShanghai(200000)China

Objective: To examine the anti-inflammatory effect of grape seed extract(GSE) in animal and cellular models and explore its mechanism of action. Methods: This study determined the inhibitory effect of GSE on macrophage inflammation and Th1 and Th17 polarization in vitro. Based on the in vitro results, the effects and mechanisms of GSE on multiple sclerosis(MS)-experimental autoimmune encephalomyelitis(EAE) mice model were further explored. The C57Bl/6 mice were intragastrically administered with 50 mg/kg of GSE once a day from the 3rd day to the 27th day after immunization. The activation of microglia, the polarization of Th1 and Th17and the inflammatory factors such as tumor necrosis factor-α(TNF-α), interleukin-1β(Il-1β), Il-6, Il-12, Il-17and interferon-γ(IFN-γ) secreted by them were detected in vitro and in vivo by flow cytometry, enzyme linked immunosorbent assay(ElISA), immunofluorescence staining and Western blot, respectively. Results: GSE reduced the secretion of TNF-α, Il-1β and Il-6 in bone marrow-derived macrophages stimulated by lipopolysaccharide(Pl-1β, Il-6, Il-12, Il-17 and IFN-γ in spleen cells of EAE mice immunized for 9 days(Ply improved the clinical symptoms of EAE mice, and inhibited spinal cord demyelination and inflammatory cell infiltration. Peripherally, GSE downregulated the expression of toll-like-receptor 4(TlR4) and Rho-associated kinase(ROCKⅡ, Plammatory factors(Pl nervous system, GSE inhibited the infiltration of CD45+CD11b+and CD45+CD4+cells, and weakened the differentiation of Th1 and Th17(Plammatory factors(Plia(Plusion: GSE had a beneficial effect on the pathogenesis and progression

关键词： grape seed extract experimental autoimmune encephalomyelitis demyelination inﬂammatory cell inﬂammatory factor

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Synthesis and biological evaluation of 12-benzyl matrinic amide derivatives as a novel family of anti-HCV agents

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Chinese Chemical letters 2016年第7期27卷 1052-1057页

作者： Sheng Tang Zong-gen Peng Xin Zhang Xin-Yue Cheng Wen-Jing li Jian-Dong Jiang Ying-Hong li Dan-qing Song Beijing Key laboratory of Anti-infective Agents Institute of Medicinal Biotechnology Chinese Academy of Medical Science & Peking Union Medical College

A new series of 12-benzyl matrinic amide/ethanamide derivatives were synthesized from matrinine（1）and evaluated for their anti-HCV activity,taking compound 2 as the *** revealed that the introduction of a suitable substituent at the N’-end of matrinic amide might greatly enhance the *** them,matrinic acid 17 and N’-substituted matrinic amides 18a-d exhibited promising potency with low micromolar EC50 values ranging from 1.03μmol/l to 7.54 μmol/l,and better therapeutic window with SI from 66 to ***,compound 17 displayed an excellent PK and safety profile in vivo,demonstrating good drug-like ***,it has been selected for further investigation,with an advantage of decreased chances of inducing drug-resistance mutations.

关键词： Matrinic acid Matrinic amide Hepatitis C virus Structure–activity relationship

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The structural rule of Mo-Fe-S cluster compounds

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Chinese Journal of Chemistry 1987年第1期5卷 48-55页

作者： TANG ao-qing lI Qian-Shu SUN Jia-Zhong Institute of Theoretical Chemistry, Jilin University, Changchun Institute of Theoretical Chemistry Jilin University Changchun

By means of the structural rule, 9N-l, of transition metal cluster compournds, a relationshipbetween the spin property and the structure of Mo--Fe--S clusters is proposed. The relationship canbe further revealed by performing EHMO quantum chemical calculations. Also the theoretical max-imum values of spin are in accordance with experimental results.

关键词： Fe Mo

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Electrodeposition of Copper by IMPC Method

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Journal of Central South University 2000年第4期12卷 186-190页

作者： ZHOU Kang gen,lI qing gang,ZHANG Qi xiu (Metallurgical Separation Science and Engineering lab., Central South University, Changsha 410083, China) Metallurgical Separation Science and Engineering lab. Central South University Changsha China

In order to develop an energy saving electrodeposition process of copper, the electrodeposition of copper in copper sulfate solution by the ion exchange membrane primary cell (IMPC) method has been studied. The experiments were carried out in an ion exchange membrane primary cell with dimensions of 200 mm in length, 52 mm in width and 90 mm in height. The influences of temperature(294 323 K), interval between the anode and cathode (1.5 3.5 cm), mass concentrations of Cu 2+ (6 40 g/l), H 2SO 4(0 120 g/l) and Fe 3+ (3 9 g/l) in catholyte and solution flow rate (0 8 cm/s) on current density and current efficiency were investigated experimentally. The current density increases with the increase of temperature and concentrations of Cu 2+ and H 2SO 4 in catholyte. Cathode current efficiency decreases with the increase of concentration of Fe 3+ in catholyte and anode current efficiency decreases with the increase of temperature. The high quality cathodic copper can be obtained and the current density of membrane can be higher than 150 A/m 2 and the current density of cathode can be higher than 300 A/m 2. The experiment results show that IMPC method is effective for electrodeposition of copper.

关键词： ion exchange membrane primary cell copper electrodeposition

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