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Neural stem cells derived from sporadic Alzheimer disease iPSCs exhibit excessive cell apoptosis and premature neuronal differentiation

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中国药理学与毒理学杂志 2018年第4期32卷 335-336页

作者： Lin zhang Ning JIANG Wen-xia ZHOU yong-xiang zhang Institute of Pharmacology and Toxicology Beijing 100850 China State Key Laboratory ofToxicology and Medical Countermeasures Beijing 100850 China School of Life Science and Biopharmaceutical Sciences Shenyang Pharmaceutical University Shenya

OBJECTIVE To establish an in vitro cell model based on patient-specific human neural stem cells to study the pathomechanism of sporadic AD as well as screen candidate *** The peripheral blood cells from sporadic AD patients and cognitive normal controls were *** into inducedpluripotent stem cells(iPSCs),which were further induced into neural stem cells and *** cell growth curve during the differentiation process was recorded by the IncuCyte ZOOM,and neural stem cells and neurons were identified by *** apoptosis of neural stem cells and neurons was detected by Click-iT~Plus TUNEL *** Neural stem cells derived from AD patients and cognitive normal controls can express neural stem cell markers ***,Sox1,Sox2 and *** assay results showed that the number of TUNEL-positive cells in *** stem cells derived from AD patients was significantly higher than that of cognitive normal controls(P<0.01).When neural stem cells were differentiated into neurons,the percentage of MAP2 positive cells in the neural stem cell-derived culture dish of AD patients was significantly higher than the *** normal controls at day 16 of neuronal differentiation(P<0.01);the TUNEL assay showed that the number of TUNEL-positive cells in AD-derived neurons was significantly greater than that in cognitive normal controls(P<0.01) at day 16 of neuronal *** Our study revealed that AD-iPSC-derived neural stem cells exhibit premature neuronal differentiation and increased neural apoptosis,which might be relevant to the neuronal loss of AD,thus may provide valuable new tools to screen candidate drugs for the disease and to discover the mechanisms underlying AD pathogenesis.

关键词：神经干细胞神经元临床分析治疗方法

Therapeutic efficacy and safety of various botulinum toxin A doses and concentrations in spastic foot after stroke: a randomized controlled trial

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Neural Regeneration Research 2017年第9期12卷 1451-1457页

作者： Jiang Li Ru zhang Bo-li Cui yong-xiang zhang Guang-tao Bai Si-shan Gao Wen-jian Li Affiliated Hospital of Qingdao University Department of Neurology Traditional Medicine Hospital of Huangdao District

No recommended guidelines currently exist for the therapeutic concentration or dose of botulinum toxin type A （BTXA） injected into the muscle to treat limb spasticity. Therefore, in this randomized controlled trial, we explored the safety and efficacy of two concentrations and two doses of BTXA in the treatment of spastic toot after stroke to optimize this treatment in these patients. Eligible patients （n = 104） were randomized into four groups. The triceps surae and tibialis posterior on the affected side were injected with BTXA at one of two doses （200 U or 400 U） and two concentrations （50 U/mL or 100 U/mL）. 2he following assessments were conducted before as well as 4 days and 1, 2, 4, and 12 weeks after treatment： spasticity, assessed using the modified Ashworth scale; basic functional mobility, assessed using a timed up and go test; pace, assessed using a 10-meter timed walking test; and the ability to walk, assessed using Holden＇s graded scale and a visual analog scale. The reported results are based on the 89 patients that completed the study. We found significant differences for the two doses and concentrations of BTXA to improve the ability of patients to walk independently, with the high-dose/low-concentration combination providing the best effect. Onset and duration of the ameliorating effects of BTXA were 4-7 days and 12 weeks, respectively. Thus, BTXA effectively treated foot spasms after stroke at an optimal dose of 400 U and concentration of 50 U/mL.

关键词： nerve regeneration stroke Jbot spasms botulinum toxin type A foot varus foot drop walking function neural regeneration

LW-AFC and its active components ameliorate corticosterone-induced long-term potentiation impairment in mice

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中国药理学与毒理学杂志 2017年第10期31卷 989-990页

作者： Yan HUANG Dong LI Wen-xia ZHOU yong-xiang zhang State Key Laboratory of Toxicology and Medical Countermeasures Beijing 100850 China Department of TCM and Neuroimmunopharmacology Beijing Institute of Pharmacology and Toxicology Beijing 100850 China

OBJECTIVE LW-AFC is extracted from the classical traditional Chinese medicinal prescription-Liuwei Dihuang *** studies have showed that LW-AFC could improve learning&memory ability in amny animal *** this study,we focused on evaluating the effect of several main active components fromLW-AFC(B-B;loganin,LOG;morroniside,MOR;paeoniflorin,PF and stachyose,STA)on *** In vivo recording of LTP was used in this study to evaluate the effects of LW-AFC and it′s active components on coticorsterone(Cort)induced LTP *** The results showed that LW-AFC could ameliorate Cort-induced LTP *** effect of LW-AFC was abolished when the immune function was *** administration(ig,ip,icv)of any of the components had no effect on Cort-induced LTP *** intragastric administration or intraperitoneal injections(chronic administration)of B-B,LOG,MOR or PF for 7 d showed protective effect on Cort-induced LTP *** administration of STA for 7 d protected LTP from impairment induced by Cort,while there was little improving effect when STA was administrated via intraperitoneal *** addition,when the intestinal microbiota was disrupted by applying the antibiotic cocktail,STA showed little protective effect against *** In conclusion,LW-AFC and it′s components showed positive effects against cort induced LTP impairment,it seems that all displayed protective effects via indirectly,immune modulation might be the common pathway for all components;the exact pathways are different in each component,B-B,LOG,MOR and PF could be absorbed into the bloods tream and then modulate the peripheral immune function,while STA could not be absorbed and modulates the immune function via modulating intestinal *** studies are needed to invesgate the underlying mechanisms and the synergetic effects of all components.

关键词： LW-AFC active components synaptic plasticity long-term potentiation intestinal microbiota

Effects of Liuwei Dihuang decoction and its compatible prescriptions on the function of hypothalamus-pituitary-adrenal axis in senescence-accelerated mouse

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中国药理学与毒理学杂志 2015年第S1期29卷 74-75页

作者： Ning JIANG Si-di LI Wen-xia ZHOU yong-xiang zhang Beijing Institute of Pharmacology and Toxicology China Beijing 100850

OBJECTIVE To investigate age-related functional change of hypothalamus-pituitary-adrenal(HPA)axis in senescence accelerated mouse(SAM)and the effects of Liuwei Dihuang decoction(LW)and its San-bu(three tonics)and San-xie(three eliminators)components on the function of HPA *** Male SAM-resistance/1(SAMR1)and SAM-prone/8(SAMP8)at the ages of 6and 12 months old were ***8 were orally administered with LW,three tonics and three eliminators at the doses of 10,6.4and 3.6g·kg-1·d-1,respectively,for consecutive 60 *** level of CORT was assayed with ELISA *** levels of hypothalamic CRH and pituitary ACTH was determined with *** The levels of hypothalamic CRH,pituitary ACTH and serous CORT were much higher in 6 and 12 months old SAMP8 than those in age-matched SAMR1,which suggested the abnormal function of HPA axis in *** administration of LW and three tonics significantly decreased the level of hypothalamic CRH of 6 and 12 months old SAMP8,and reduced the levels of pituitary ACTH and serous CORT of 6 month old *** eliminators significantly decreased the level of hypothalamic CRH of 6 months old *** results indicated that oral administration of LW,three tonics and three eliminators improved the function of HPA axis of *** The results showed the hyperactivity of HPA axis of SAMP8,and LW improved the hyperactivity of 6 month old *** tonics and three eliminators had similar effects as LW,which had better effect after compatibility.

关键词： Liuwei Dihuang decoction senescence accelerated mo

Immunopotentiating activities and TLR4/MAPK related molecular mechanisms research of Lycium barbarum polysaccharide

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中国药理学与毒理学杂志 2018年第4期32卷 263-264页

作者： Xiao-rui zhang Ying-jie LI Chun-hui QI Wen-xia ZHOU yong-xiang zhang State Key Laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and Toxicology Beijing China

OBJECTIVE To observe the effect and molecular mechanisms of Lycium barbarum polysaccharide(LBP) and glycopeptides on T,B lymphocytes and *** ~3H-TdR incorporation method was used to compare the effects of LBP and glycopeptides on the proliferation *** macrophages induced by sodium thioglycolate were used to compare the effects of LBP and glycopeptides.T and B lymphocytes were purified by immunomagnetic beads *** antibody blocking methods screening polysaccharide activity related receptors.C3H/HeJ mice were further used to observe the activity of *** interference method was used to observe the binding kinetics of LBP with TLR4 in ***4 level was tested by flow *** blotting was used to observe the phosphorylation of p-38,SAPK/JNK and *** The monosaccharide *** of LBP is rhamnose,arabinose and galactose,and does not contain amino *** mixed lymphocyte proliferation experiment showed that LBP had more obvious effect on the proliferation of B cells,and glycosides induced T cells proliferation was more *** the purify lymphocytes,it was found that LBP-induced B cells proliferation requires the involvement of *** research found that anti-TLR4 antibody had significant inhibitory effect on LBP-induced macrophage release of TNF-α and IL-1β but not the anti-CR3 treatment.C3 H/HeJ mice related results further demonstrated that TLR4 is necessary for LBP *** biolayer interference showed no obvious binding of TLR4/MD2 with LBP,flow cytometry confirmed that LBP could increase TLR4 *** Blot experiments showed that the effect of LBP on macrophage was related to its activation of p-38/MAPK pathway and inhibition of ERK/MAPK and JNK/MAPK *** TLR4 is the activity related receptors of *** cannot directly bind to TLR4/MD2 complex in vitro,but can increase TLR4 expression and activate macrophage p-38/MAPK signaling pathway,inhi

关键词：枸杞多糖糖肽淋巴细胞治疗方法

ZHOU　Jin-Huang　──Outstanding　Pharmacologist

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Chinese Journal of Integrative Medicine 1997年第2期3卷 138-139页

作者： yong-xiang zhang

ＺＨＯＵ　Ｊｉｎ－Ｈｕａｎｇ　──Ｏｕｔｓｔａｎｄｉｎｇ　ＰｈａｒｍａｃｏｌｏｇｉｓｔＺｈｏｕＪｉｎｈｕａｎｇ，ｔｈｅｓｏｎｏｆａｃｏｕｎｔｒｙｄｏｃｔｏｒ，ｗａｓｂｏｒｎｉｎＪｌｌｈｅ，１９０９ｉｎｔｈｅＸｉｎｚｈ...

ＺＨＯＵ　Ｊｉｎ－Ｈｕａｎｇ　──Ｏｕｔｓｔａｎｄｉｎｇ　ＰｈａｒｍａｃｏｌｏｇｉｓｔＺｈｏｕＪｉｎｈｕａｎｇ，ｔｈｅｓｏｎｏｆａｃｏｕｎｔｒｙｄｏｃｔｏｒ，ｗａｓｂｏｒｎｉｎＪｌｌｈｅ，１９０９ｉｎｔｈｅＸｉｎｚｈｏｕｃｏｕｎｔｙｏｆＨｕｂｅｉｐｒ...

关键词：

Construction of NIM sub-network regulated by Liuwei Dihuang decoction and its characteristics

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中国药理学与毒理学杂志 2018年第4期32卷 306-307页

作者： Tong-xing WANG Lu HAN Xiao-rui CHENG Wen-xia ZHOU yong-xiang zhang Beijing Institute of Pharmacology and Toxicology Beijing 100850 China The State Key Laboratory of Toxicology and Medical Countermeasures Beijing 100850 China

OBJECTIVE To construct the neuroendocrine immunomodulation(NIM) sub-network regulated by Liuwei Dihuang decoction(LW) and analyze its *** We took the GSE57273 in GEO database and screened the differentially expressed genes(DEGs)(P10).Among them,there were 19 NIM signaling molecules in which only ESR1 changed significantly and 3 non-DEGs(NFATC2,RARA,TP53).However,the *** of the hub nodes were significantly *** The results suggested that LW might mainly regulate the non-hub nodes to recovery of the network imbalance of the body in the state of disease.

关键词：六味地黄汤神经内分泌治疗方法临床分析

Cancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cellsCancerous multi-drug resistance is reduced by Leptomycin B treatment in CCRF-CEM/Taxol cells

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Health 2012年第10期4卷 845-855页

作者： Jin-Wu Zhu yong-xiang zhang yong-Biao Guan Beijing Institute of Pharmacology and Toxicology Beijing China Institute of Aviation Medicine Beijing China

Objectives: Multi-drug resistance (MDR) to chemotherapy remains a major obstacle to overcome in the successful treatment of patients with cancers. It was recently discovered that Leptomycin B (LMB) reduces the paclitaxel-induced MDR in CCRF-CEM/Taxol cells. However, the mechanism remains unclear. Here we sought to explore the mechanism of LMB to reduce the MDR induced by paclitaxel. Results: LMB has remarkable cytotoxic effects in both sensitive CCRF-CEM and resistant CCRF-CEM/Taxol cell lines. The paclitaxel-induced MDR was reduced by 0.013 μm of LMB. Lower concentration of LMB regulated cell cycle progress, in situ expressions of P-gp, MRP1, and LRP, expression of CRM1, and localization of P-gp and CRM1 in CCRF-CEM/taxol cells. Study Design: Cytotoxicity of LMB on cancerous cell lines was determined by MTT assay. Cell cycle progress and in situ expressions of P-gp, MRP1, and LRP were analyzed by flow cytometry. Expression of CRM1 in the cells was examined by Western blot. And co-localization between P-gp and CRM1 was determined by laser confocal microscopy. Conclusion: The paclitaxel-induced MDR of CCRFCEM/Taxol cells was reduced by lower concentration of LMB. The mechanisms might be related to decreasing in situ expression of drug transporter proteins, promoting cell cycle progress, and altering co-localization between P-gp and CRM1 in the resistant cells.

关键词： Leptomycin B CCRF-CEM Multi-Drug Resistance CRM1 Paclitaxel

Calculations for the Pre-Calibration of LAMOST Active Optics

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Chinese Journal of Astronomy and Astrophysics 2005年第3期5卷 302-314页

作者： yong zhang and xiang-Qun Cui National Astronomical Observatories / Nanjing Institute of Astronomical Optics & Technology, Chinese Academy of Sciences, Nanjing 210042 Graduate School of the Chinese Academy of Sciences, Beijing 100039 National Astronomical Observatories / Nanjing Institute of Astronomical Optics & Technology Chinese Academy of Sciences Nanjing 210042 Graduate School of the Chinese Academy of Sciences Beijing 100039

Large Sky Area Multi-Object Fibre Spectroscopic Telescope (LAMOST) is one of the major on-going national large scientific projects in China. Active optics is a key technology for the LAMOST with which the thin-mirror active optics and segmented-mirror active optics are tied in. A pre-calibration method considering all active forces and displacements specially for LAMOST has been developed in early 2004. We give a detailed mathematical derivation and calculation including numerical simulation and computer program realization of the pre-calibration method of LAMOST open-loop control for the third-order aspherical aberration. We have also carried out calculations on the application of the pre-calibration method and the parameters of actuator design in LAMOST active optics in observation mode, including estimations of the actuator ranges, the interval of active optics correction and the ranges and trends of load changes on all the actuators during LAMOST tracking a given star.

关键词： active optics telescopes instrumentation