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Action of trichostatin A on Alzheimer’s disease-like pathological changes in SH-SY5Y neuroblastoma cells 预览
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作者 Li-Hua Li Wen-Na Peng +2 位作者 Yu Deng1 Jing-Jing Li Xiang-Rong Tian 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第2期293-301,共9页
The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effe... The histone deacetylase inhibitor, trichostatin A, is used to treat Alzheimer’s disease and can improve learning and memory but its underlying mechanism of action is unknown. To determine whether the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the nuclear factor erythroid 2-related factor 2(Nrf2) and Kelch-like epichlorohydrin-related protein-1(Keap1) signaling pathway, amyloid β-peptide 25–35(Aβ25–35) was used to induce Alzheimer’s disease-like pathological changes in SH-SY5 Y neuroblastoma cells. Cells were then treated with trichostatin A. The effects of trichostatin A on the expression of Keap1 and Nrf2 were detected by real-time quantitative polymerase chain reaction, western blot assays and immunofluorescence. Total antioxidant capacity and autophagy activity were evaluated by total antioxidant capacity assay kit and light chain 3-I/II levels, respectively. We found that trichostatin A increased cell viability and Nrf2 expression, and decreased Keap1 expression in SH-SY5 Y cells. Furthermore, trichostatin A increased the expression of Nrf2-related target genes, such as superoxide dismutase, NAD(P)H quinone dehydrogenase 1 and glutathione S-transferase, thereby increasing the total antioxidant capacity of SH-SY5 Y cells and inhibiting amyloid β-peptide-induced autophagy. Knockdown of Keap1 in SH-SY5 Y cells further increased trichostatin A-induced Nrf2 expression. These results indicate that the therapeutic effect of trichostatin A on Alzheimer’s disease is associated with the Keap1-Nrf2 pathway. The mechanism for this action may be that trichostatin A increases cell viability and the antioxidant capacity of SH-SY5 Y cells by alleviating Keap1-mediated inhibition Nrf2 signaling, thereby alleviating amyloid β-peptide-induced cell damage. 展开更多
关键词 Alzheimer's disease amyloid-β peptide autophagy KEAP1 signal neurocytotoxicity oxidative stress damage SH-SY5Y cells total antioxidant capacity transcription factor Nrf2 TSA
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A mimetic peptide ofα2,6-sialyllactose promotes neuritogenesis 预览
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作者 Shuang-Xi Chen Jia-Hui He +3 位作者 Yong-Jian Mi Hui-Fan Shen Melitta Schachner Wei-Jiang Zhao 《中国神经再生研究:英文版》 SCIE CAS CSCD 2020年第6期1058-1065,共8页
Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(... Oxidative stress contributes to the pathogenesis of neurodegenerative diseases.With the aim to find reagents that reduce oxidative stress,a phage display library was screened for peptides mimicking a2,6-sialyllactose(6'-SL),which is known to beneficially influence neural functions.Using Sambucus nigra lectin,which specifically binds to 6'-SL,we screened a phage display library and found a peptide comprising identical sequences of 12 amino acids.Mimetic peptide,reverse peptide and scrambled peptide were tested for inhibition of 6'-SL binding to the lectin.Indeed,lectin binding to 6'-SL was inhibited by the most frequently identified mimetic peptide,but not by the reverse or scrambled peptides,showing that this peptide mimics 6'-SL.Functionally,mimetic peptide,but not the reverse or scrambled peptides,increased viability and expression of neural cell adhesion molecule L1 in SK-N-SH human neuroblastoma cells,and promoted survival and neurite outgrowth of cultured mouse cerebellar granule neurons challenged by H_20_2-induced oxidative stress.The combined results indicate that the 6'-SL mimetic peptide promotes neuronal survival and neuritogenesis,thus raising hopes for the treatment of neurodegenerative diseases.This study was approved by the Medical Ethics Committee of Shantou University Medical College,China(approval No.SUMC 2014-004)on February 20,2014. 展开更多
关键词 central nervous system cerebellar granule neurons mimetic peptide neural cell adhesion molecule L1 NEURITOGENESIS neurodegenerative disease neuronal survival oxidative stress phage display Sambucus nigra lectin α2 6-sialyllactose
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Differential effects of atrial and brain natriuretic peptides on human pulmonary artery: An in vitro study 预览
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作者 Azar Hussain Robert T Bennett +5 位作者 Zaheer Tahir Emmanuel Isaac Mubarak A Chaudhry Syed S Qadri Mahmoud Loubani Alyn H Morice 《世界心脏病学杂志:英文版(电子版)》 2019年第10期236-243,共8页
BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(... BACKGROUND The prevalence of cardiovascular diseases,especially heart failure,continues to rise worldwide.In heart failure,increasing levels of circulating atrial natriuretic peptide(ANP)and brain natriuretic peptide(BNP)are associated with a worsening of heart failure and a poor prognosis.AIM To test whether a high concentration of BNP would inhibit relaxation to ANP.METHODS Pulmonary arteries were dissected from disease-free areas of lung resection,as well as pulmonary artery rings of internal diameter 2.5–3.5 mm and 2 mm long,were prepared.Pulmonary artery rings were mounted in a multiwire myograph,and a basal tension of 1.61gf was applied.After equilibration for 60 min,rings were pre-constricted with 11.21μmol/L PGF2α(EC80),and concentration response curves were constructed to vasodilators by cumulative addition to the myograph chambers.RESULTS Although both ANP and BNP were found to vasodilate the pulmonary vessels,ANP is more potent than BNP.pEC50 of ANP and BNP were 8.96±0.21 and 7.54±0.18,respectively,and the maximum efficacy(Emax)for ANP and BNP was-2.03 gf and-0.24 gf,respectively.After addition of BNP,the Emax of ANP reduced from-0.96gf to-0.675gf(P=0.28).CONCLUSION BNP could be acting as a partial agonist in small human pulmonary arteries,and inhibits relaxation to ANP.Elevated levels of circulating BNP could be responsible for the worsening of decompensated heart failure.This finding could also explain the disappointing results seen in clinical trials of ANP and BNP analogues for the treatment of heart failure. 展开更多
关键词 Heart failure Atrial natriuretic peptide Brain natriuretic peptide In-vitro Humans
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生物肽不同结构肽链对生物修饰金属材料疏水性能的影响 预览
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作者 麻春英 袁成清 肖劲飞 《表面技术》 EI CAS CSCD 北大核心 2019年第1期141-146,共6页
目的通过调整与金属反应的肽的肽链结构,提高反应后金属表面的疏水性。方法取同种肽两种不同结构(L-型和D-型反序结构)分别与金属不锈钢作用,通过CA测定材料疏水性的变化,采用FTIR显示有机肽在材料表面的附着情况。分别在L-型和D-型肽... 目的通过调整与金属反应的肽的肽链结构,提高反应后金属表面的疏水性。方法取同种肽两种不同结构(L-型和D-型反序结构)分别与金属不锈钢作用,通过CA测定材料疏水性的变化,采用FTIR显示有机肽在材料表面的附着情况。分别在L-型和D-型肽上接入疏水基团十二烷酸,获得两种新的不同结构的肽:L.-型肽和D.-型肽。两种肽分别与金属不锈钢作用,利用FTIR和CA研究疏水基团的接入及其对材料疏水性的影响情况。结果与金属不锈钢作用之后,D型肽反序结构修饰的不锈钢表面接触角比L型肽修饰有所提高,由原来的39.7.变成80.1.。接入疏水基团后的肽在PBS中的溶解度减小,用有机溶剂初溶之后再溶入PBS中,生物肽全部溶解。该肽溶液与金属材料作用之后,D.型肽比L.型肽作用的表面接触角更高,分别为89.4.和87.4.,前者作用效果更好。结论通过调整生物肽肽链的结构,可以改变改性金属材料表面的疏水特性,为进一步通过调整金属反应肽的肽链结构和疏水基团的种类得到具有良好疏水性能的金属材料提供了有力的数据支撑。 展开更多
关键词 生物肽 肽链结构 手性异构 表面改性 疏水性 接触角
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蛋白质组学在人乳蛋白质研究中的应用 预览
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作者 于文皓 祁艳霞 靳艳 《色谱》 CAS CSCD 北大核心 2019年第5期471-476,共6页
人乳是新生儿最理想的天然食物,蛋白质是人乳中最主要的营养成分之一。随着蛋白质组学技术的发展,利用蛋白质组学的方法研究人乳蛋白质也取得了一些研究成果。本文综述了近年来蛋白质组学技术在人乳蛋白质研究中的应用,分别从人乳蛋白... 人乳是新生儿最理想的天然食物,蛋白质是人乳中最主要的营养成分之一。随着蛋白质组学技术的发展,利用蛋白质组学的方法研究人乳蛋白质也取得了一些研究成果。本文综述了近年来蛋白质组学技术在人乳蛋白质研究中的应用,分别从人乳蛋白质的组成研究、动态变化、人乳与其他来源乳汁的蛋白质差异比较、人乳磷酸化蛋白和糖基化蛋白研究、人乳内源肽的研究及人乳蛋白与疾病等几个方面进行了阐述。蛋白质组学技术使人乳蛋白质的研究进入了微量营养研究的时代,人乳蛋白质组学的研究成果将为母婴健康提供更好的保障。 展开更多
关键词 人乳 蛋白质组学 蛋白质 综述
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预消化的肠内营养对ICU危重症患者的营养状况及肠内营养耐受性的影响
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作者 孙丽娟 薛森海 +3 位作者 闫凤 代玉洁 徐赤红 赵长海 《现代生物医学进展》 CAS 2019年第10期1883-1888,共6页
目的:研究预消化的肠内营养制剂对ICU危重症患者营养状况及肠内营养耐受性的影响。方法:本试验为前瞻、随机、对照、单盲研究,将符合入组条件的ICU患者随机分为试验组和对照组。试验组给予预消化型肠内营养制剂,而对照组给予整蛋白型肠... 目的:研究预消化的肠内营养制剂对ICU危重症患者营养状况及肠内营养耐受性的影响。方法:本试验为前瞻、随机、对照、单盲研究,将符合入组条件的ICU患者随机分为试验组和对照组。试验组给予预消化型肠内营养制剂,而对照组给予整蛋白型肠内营养制剂进行营养支持。比较两组患者入组及营养支持2周后的营养指标、肠内营养耐受性及ICU住院天数等。结果:治疗2周后,试验组前白蛋白、转铁蛋白较对照组明显升高(P<0.05),肠内营养不耐受、腹内压升高、腹泻、肠鸣音减弱及胃肠道出血发生率较对照组明显降低(P<0.05),ICU住院时间也较对照组明显缩短(P<0.05)。结论:预消化的肠内营养制剂对ICU患者有良好的治疗效果,可降低胃肠道不良反应发生率,提高耐受性,明显改善患者营养状况。 展开更多
关键词 肠内营养 短肽 危重症患者
Relationship between different healing degree and C peptide in elderly patients with diabetic foot ulcers
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作者 Lin Qu Ya-Li Zhou +1 位作者 Teng Zhou Yan-Hu Dong 《海南医科大学学报(英文版)》 2019年第4期50-55,共6页
Objective:To explore the relationship between different healing degree and C peptide in elderly patients with diabetic foot ulcers.Methods:Totally, two hundred and forty-one DFU patients were selected into our researc... Objective:To explore the relationship between different healing degree and C peptide in elderly patients with diabetic foot ulcers.Methods:Totally, two hundred and forty-one DFU patients were selected into our research from September 2nd, 2011 to September 2nd, 2012. After admission, the patients' sex, age, the course of diabetes, the days of hospitalization, and BMI were recorded. After examination, blood routine and blood biochemistry, urine routine, hepatorenal work were recorded. Follow up 5 years, patients with unhealed ulcers were selected into bad prognosis group during follow-up, and patients with ulcerative healing into good prognosis group. Single factor analysis showed factors affecting the healing of DFU patients;Cox proportional risk model was further evaluated the effect of all factors with statistical significance on the healing of DFU patients. Using the ROC curve to analyze the statistically significant factors and to calculate the area under the curve to evaluate the predictive ability of the healing of the patients with DFU.Results: At the end of the follow-up, 6 patients were lost, 177 had the end point, and the healing rate was 73.44%. Single factor and multifactor analysis showed that the course of diabetes and HbA1C were independent risk factors affecting the prognosis. FCP was an independent protective factor affecting the prognosis. In ROC, the AUC of diabetes course was 0.754 under the ROC curve. The AUC of HbA1C under the line is 0.791, while the AUC of FCP level is 0.581 under the ROC curve.Conclusion: Low FCP is an independent risk factor for DFU healing, but FCP has little predictive effect on patient healing. 展开更多
关键词 DIABETIC FOOT C PEPTIDE OLD age HEALING
Effect of Jiawei Shenfu decoction on tumor necrosis factor-alpha and nuclear factor-kappa B in patients who have chronic heart failure with syndromes of deficiency of heart Yang
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作者 Yu Mei Guo Hangyuan +3 位作者 Ye Lingling Bian Jiaping Ma Lijuan Zheng Chunli 《中医杂志:英文版》 SCIE CAS CSCD 2019年第3期418-424,共7页
OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of def... OBJECTIVE:To examine the clinical efficacy of Jiawei Shenfu decoction on tumor necrosis factor-alpha (TNF-cα) and nuclear factor-kappa B (NF-KB) levels in patients who have chronic heart failure with syndromes of deficiency of heart Yang.METHODS:A total of 63 patients with syndromes of deficiency of heart Yang (chronic heart failure)were enrolled.Patients were randomly divided into the control group and Jiawei Shenfu group.All patients received standard medications for treatment of chronic heart failure.Patients in the Jiawei Shenfu group were additionally provided Jiawei Shenfu decoction one dose daily.Treatments continued for 4 consecutive weeks.The primary endpoint was the change in plasma B-type natriuretic peptide (BNP),NF-KB,and TNF-cα levels during 4 weeks of treatment.RESULTS:At the 4-week follow-up,a significant reduction in BNP levels compared with baseline was observed in both groups,but the Jiawei Shenfu decoction group showed a significantly greater reduction than did the control group.The Jiawei Shenfu group also showed superior performance regarding the Minnesota Living with Heart Failure Questionnaire score,the Chinese medicine syndrome score,heart rate,left ventricular ejection fraction,and 6-min walking distance compared with the control group.The degree of changes in NF-KB and TNF-α levels in the Jiawei Shenfu group was more significant than that in the control group.CONCLUSION:Routine medicine combined with Jiawei Shenfu decoction for patients with heart Yang deficiency syndrome in chronic heart failure can improve the left ventricular ejection fraction and cardiac function,and reduce BNP levels.The mechanism may be related to inhibition of pro-inflammatory cytokines and the NF-KB-induced kinase pathway,leading to amelioration of the inflammatory response. 展开更多
关键词 HEART failure NATRIURETIC peptide brain Tumor necrosis FACTOR-ALPHA NF-KAPPA B Heart-Yang DEFICIENCY Jiawei SHENFU decoction
Tauroursodeoxycholic acid(TUDCA) inhibits influenza A viral infection by disrupting viral proton channel M2
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作者 Ning Li Yanxu Zhang +9 位作者 Shuangxiu Wu Ruodan Xu Zhiqing Li Jindong Zhu Hongliang Wang Xiao Li Mingyao Tian Huijun Lu Ningyi Jin Chengyu Jiang 《科学通报:英文版》 SCIE EI CSCD 2019年第3期180-188,共9页
Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seaso... Influenza is a persistent threat to human health and there is a continuing requirement for updating antiinfluenza strategies. Initiated by observations of different endoplasmic reticulum(ER) responses of host to seasonal H1N1 and highly pathogenic avian influenza(HPAI) A H5N1 infections, we identified an alternative antiviral role of tauroursodeoxycholic acid(TUDCA), a clinically available ER stress inhibitor, both in vitro and in vivo. Rather than modulating ER stress in host cells, TUDCA abolished the proton conductivity of viral M2 by disrupting its oligomeric states, which induces inefficient viral infection. We also showed that M2 penetrated cells, whose intracellular uptake depended on its proton channel activity,an effect observed in both TUDCA and M2 inhibitor amantadine. The identification and application of TUDCA as an inhibitor of M2 proton channel will expand our understanding of IAV biology and complement current anti-IAV arsenals. 展开更多
关键词 INFLUENZA TUDCA M2 proton channel Virus ENTRY Cell-penetrating peptide OLIGOMERIZATION inhibitor
Biofilm Disruption Utilizing α/β Chimeric Polypeptide Molecular Brushes
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作者 Si Zhang Xi-Mian Xiao +5 位作者 Fan Qi Peng-Cheng Ma Wei-Wei Zhang Cheng-Zhi Dai Dan-Feng Zhang Run-Hui Liu 《高分子科学:英文版》 CSCD 2019年第11期1105-1112,共8页
Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gramnegative bacteria are notorious for their frequently encountered resistance toward antibiotics. ... Gram-negative bacteria can cause serious infections and are well known problems in biomedical practices. Biofilms of gramnegative bacteria are notorious for their frequently encountered resistance toward antibiotics. We demonstrate that α/β chimeric polypeptide molecular brush (α/β CPMB) exerts potent activities against antibiotic-resistant gram-negative bacteria. MTT viability assay, bacterial colony counting, and live/dead staining all indicate that α/β CPMB not only inhibits biofilm formation of gram-negative Pseudomonas aeruginosa and Acinetobacter baumannii, but also effectively disrupts mature biofllms that are highly resistant to one of the most active antibiotics-colistin. The superior antibacterial performance of the α/β CPMB implies its potential topical applications in treating biofilms. 展开更多
关键词 Molecular BRUSH CHIMERIC POLYPEPTIDE BIOFILM ANTIMICROBIAL resistance Host defense peptide
NGR与iso DGR对抗菌肽在CD13^-/αvβ3^+乳腺癌中抗瘤活性影响 预览
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作者 侯磊 赵永丽 +2 位作者 安改丽 何莉 陈鑫 《山西医科大学学报》 CAS 2019年第6期767-772,共6页
目的比较携带NGR结构抗菌肽(CNAK)与携带isoDGR结构抗菌肽(CDAK)在CD13^-/αvβ3^+乳腺癌细胞(MDA-MB-231)中靶向识别与和诱导凋亡能力。方法MTT法计算不同浓度CDAK与CNAK作用MDA-MB-231细胞24h的细胞存活率与半抑制浓度(IC50)。CRLK(... 目的比较携带NGR结构抗菌肽(CNAK)与携带isoDGR结构抗菌肽(CDAK)在CD13^-/αvβ3^+乳腺癌细胞(MDA-MB-231)中靶向识别与和诱导凋亡能力。方法MTT法计算不同浓度CDAK与CNAK作用MDA-MB-231细胞24h的细胞存活率与半抑制浓度(IC50)。CRLK(随机肽)、CDAK与CNAK作用MDA-MB-231和HFF细胞12h,荧光显微镜观察识别能力,流式细胞仪分析结合能力。CRLK、CDAK与CNAK作用MDA-MB-231细胞24h,流式细胞仪与Western-blot分析凋亡与Caspase-3蛋白表达。结果CDAK与CNAK对MDA-MB-231细胞生长抑制呈剂量依赖性,IC50分别为227μg/ml与210μg/ml。CDAK与CNAK仅进入MDA-MB-231细胞,CRLK未进入细胞内。CDAK与CNAK细胞结合能力分别为22±2.16与28±2.98(P<0.05)。CDAK组与CNAK组细胞凋亡率分别为23.56%±2.16%与25.33%±2.77%,Caspase-3相对蛋白表达量分别为1.6±0.14与1.87±0.21,差异均无统计学意义(P>0.05)。各指标中,CRLK与CDAK和CNAK之间差异均有统计学意义(P<0.05)。结论NGR较isoDGR能够促进更多抗菌肽与CD13^-/αvβ3^+乳腺癌细胞结合,但抑制细胞生长与诱导凋亡能力无明显差异。 展开更多
关键词 乳腺癌 多肽 整合素 细胞凋亡
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μ-TRTX-Ca1a: a novel neurotoxin from Cyriopagopus albostriatus with analgesic effects
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作者 Yun-xiao Zhang De-zheng Peng +6 位作者 Qing-feng Zhang Biao Huang Qiu-chu Yang Dong-fang Tang Min-zhi Chen Ming-qiang Rong Zhong-hua Liu 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第7期859-866,共8页
Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the a... Human genetic and pharmacological studies have demonstrated that voltage-gated sodium channels (VGSCs) are promising therapeutic targets for the treatment of pain. Spider venom contains many toxins that modulate the activity of VGSCs. To date, only 0.01% of such spider toxins has been explored, and thus there is a great potential for discovery of novel VGSC modulators as useful pharmacological tools or potential therapeutics. In the current study, we identi?ed a novel peptide,μ-TRTX-Ca1a (Ca1a), in the venom of the tarantula Cyriopagopus albostriatus. This peptide consisted of 38 residues, including 6 cysteines, i.e. IFECSISCEIEKEGNGKKCKPKKCKGGWKCKFNICVKV. In HEK293T or ND7/23 cells expressing mammalian VGSCs, this peptide exhibited the strongest inhibitory activity on Nav1.7 (IC50 378 nM), followed by Nav1.6 (IC50 547 nM), Nav1.2 (IC50 728 nM), Nav1.3 (IC50 2.2 μM) and Nav1.4 (IC50 3.2 μM), and produced negligible inhibitory effect on Nav1.5, Nav1.8, and Nav1.9, even at high concentrations of up to 10 μM. Furthermore, this peptide did not signi?cantly affect the activation and inactivation of Nav1.7. Using site-directed mutagenesis of Nav1.7 and Nav1.4, we revealed that its binding site was localized to the DIIS3-S4 linker region involving the D816 and E818 residues. In three different mouse models of pain, pretreatment with Cala (100, 200, 500 μg/kg) dose-dependently suppressed the nociceptive responses induced by formalin, acetic acid or heat. These results suggest that Ca1a is a novel neurotoxin against VGSCs and has a potential to be developed as a novel analgesic. 展开更多
关键词 μ-TRTX-Ca1a TARANTULA SPIDER PEPTIDE hNav1.7 ELECTROPHYSIOLOGY ANALGESIC activity
Activation of α7 nAChR by PNU improves synaptic and cognitive function through restoring the expression of synaptic-associated proteins 预览
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作者 WANG Xiao-lin DENG Yu-xin +5 位作者 GAO Yu-mei DONG Yang-ting WANG Fan GUAN Zhi-zhong HONG Wei QI Xiao-lan 《中国药理学与毒理学杂志》 CAS 北大核心 2019年第6期474-475,共2页
OBJECTIVE Alzheimer disease(AD) is the most common type of dementia and is featured by the accumulation of β-amyloid peptide(Aβ) in the brain. The Alpha 7 nicotinic acetylcholine receptor family(α7 nAChR) was widel... OBJECTIVE Alzheimer disease(AD) is the most common type of dementia and is featured by the accumulation of β-amyloid peptide(Aβ) in the brain. The Alpha 7 nicotinic acetylcholine receptor family(α7 nAChR) was widely considered to interact with that Aβ, mediate neuroprotection and improve cognitive performance. However, the mechanisms underlying these interactions remain elusive. The present study aimed to determine how this interaction contribute to AD pathology. METHODS In vitro model of AD(primary culture of mice hippocampus treated with Aβ) and in vivo, a mouse model of AD(APPswe/PSEN1 d E9 double transgenic mice, APP/PS1_DT mice) were used to study to the possible inter-action of α7 nAChR and Aβ in the pathogenesis of AD. In vitro experiments, the primary hippocampal neurons cell was exposed to Aβ1-42 peptides in combination with PNU. In vivo experiments, different drugs/operations was applied to APP/PS1_DT mice for setting up of the following groups: WP group, wild-type C57 mice treated with PNU(α7 nAChR specific agonist);AP group, APP/PS1_DT mice treated with PNU;APP/PS1 group, the APP/PS1_DT mice injected intraperitoneally with the same amount of normal saline for 5 d;Control group, wild-type C57 mice injected intraperitoneally with the same amount of normal saline for 5 d. A transmission electron microscope was used to observed the synaptic morphological changes of hippocampal neurons. Reverse transcription quantitative PCR(RT-q PCR) and Western blot analysis were used to detect the expression levels of synaptic-associated proteins(SYN, SNAP25 etc). The learning and memory abilities of mice were detected by Morris water maze. RESULTS In vitro, it was found that α7 nAChR acts as an anti-Aβ-induced synaptic injury to nerve cell by increased the expression of synaptic-associated proteins and attenuated apoptosis induced by Aβ oligomers. In vivo, α7 nAChR attenuated synaptic loss induced by Aβ1-42, reduced the deposition of Aβ1-42 in the hippocampus and maintained the integrity of synaptic stru 展开更多
关键词 α7 NACHR Β-AMYLOID peptide SYNAPTIC CaM-CaMKⅡ-CREB signalling pathway ALZHEIMER disease
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以二肽为连接臂的新型聚乙二醇修饰阿霉素的合成 预览
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作者 宁喜波 周昊 +1 位作者 丁振伟 沈鸿雁 《合成化学》 CAS 北大核心 2019年第6期480-484,共5页
采用Fmoc固相合成策略,以Wang树脂为载体,Fmoc保护的L-氨基酸为原料,EDC/HOBt为缩合剂,合成了8种聚乙二醇修饰的二肽。以HATU/DIPEA为缩合剂,通过酰化反应将修饰后的多肽连接到阿霉素上,合成了一系列新型阿霉素前药,纯度高于90%,收率高... 采用Fmoc固相合成策略,以Wang树脂为载体,Fmoc保护的L-氨基酸为原料,EDC/HOBt为缩合剂,合成了8种聚乙二醇修饰的二肽。以HATU/DIPEA为缩合剂,通过酰化反应将修饰后的多肽连接到阿霉素上,合成了一系列新型阿霉素前药,纯度高于90%,收率高于52%,其结构经^1H NMR和MS(ESI)表征。 展开更多
关键词 聚乙二醇 多肽 合成 阿霉素 修饰 前药
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Notoginseng Saponin Rg1 Prevents Cognitive Impairment through Modulating APP Processing in Aβ1-42-injected Rats 预览
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作者 Shang-zhi LIU Wei CHENG +6 位作者 Jia-wei SHAO Yun-fan GU Yi-yi ZHU Qi-jing DONG Si-yu BAI Ping WANG Li LIN 《当代医学科学(英文)》 SCIE CAS 2019年第2期196-203,共8页
With the intensification of the aging process of the world,Alzheimer's disease(AD),which is the main type of senile dementia,has become a primary problem in the present society.Lots of strategies have been used to... With the intensification of the aging process of the world,Alzheimer's disease(AD),which is the main type of senile dementia,has become a primary problem in the present society.Lots of strategies have been used to prevent and treat AD in animal nlodels and clinical trials,but most of them ended in failure.Panax notoginseng saponins(PNS)contain a variety of monomer compositions which have been separated and identified.Among of the monomer compositions,notoginseng saponin Rg1(Rg1)accounts for 20%of the cultivation of panax notoginseng roots.And now PNS have been reported to be widely used to treat cardicerebrovascular diseases and have neuroprotective effects to restrain theβ-amyloid peptide(Aβ)25-35-niediated apoptosis.Moreover,it is reported that PNS could accelerate the growth of nerve cells,increase the length of axons and promote synaptic plasticity.Whether Rg1 can ameliorate the cognitive impairment and the underlying mechanism has not been elucidated.To study the preventive effect of Rg1 on cognitive impairment and the possible mechanism,we established the cognitive impairment model in rats through Aβ1-42(2.6μg/μL,5μL)injection and then treated the rats with Rg1(25,50 and 100 mg/kg)administered intragastrically for 4 weeks.We observed that Aβ1-42 could induce spatial learning and memory deficits in rats.Simultaneously,Aβ1-42 injection also resulted in the reduced neuron number in comuammonis 1(CA1)and dentate gyrus(DG)of hippocampus,as well as the increased level of hyperphosphorylatedβ-amyloid precursor protein(APP)at Thr668 site with up-regulation ofβ-APP cleaving enzyme 1(BACE1)and presenilin 1(PS1)and down-regulation of a disintegrin and metalloprotease domain-containing protein 10(ADAM 10)and insulindegrading enzyme(IDE).Administration of Rg1 effectively rescued the cognitive impairment and neuronal loss,and inhibited theβ-secretase processing of APP through reducing APP-Thr668 phosphorylation and BACE1/PS1 expression,and increasing the expression of ADAM 10 and IDE.We concluded that Rg1 migh 展开更多
关键词 notoginseng SAPONIN RG1 Alzheimer's disease spatial learning and memory deficits Β-AMYLOID peptide SECRETASE degrading cnzyme
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多肽药物关键水解酶体外高通量分析方法的建立 预览
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作者 张凡 田浤 姚文兵 《中国药科大学学报》 CAS CSCD 北大核心 2019年第3期352-356,共5页
为了建立测定多肽药物体内代谢关键水解酶的高通量分析方法,本研究基于高效液相色谱技术,确定通用的体外酶解反应条件为:pH7.8或9.0,缓冲体系为0.01mol/LPBS或50mmol/L Tris缓冲液,实现对多肽药物关键水解酶的统一高通量体外检测。利用... 为了建立测定多肽药物体内代谢关键水解酶的高通量分析方法,本研究基于高效液相色谱技术,确定通用的体外酶解反应条件为:pH7.8或9.0,缓冲体系为0.01mol/LPBS或50mmol/L Tris缓冲液,实现对多肽药物关键水解酶的统一高通量体外检测。利用该方法对多肽药物普兰林肽的关键水解酶进行分析,研究结果显示,基肽释放相关酶5和二肽基肽酶4对普兰林肽的水解作用最强,与微量热泳动分析结果一致。因此,本研究所建立的方法可用于分析多肽药物的关键水解酶,为优化多肽药物的酶稳定性提供方法参考与指导。 展开更多
关键词 多肽 酶解代谢 高效液相色谱 蛋白水解酶 高通量分析 普兰林肽
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Cleavage of the Babuvirus Movement Protein B4 into Functional Peptides Capable of Host Factor Conjugation is Required for Virulence
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作者 Jun Zhuang Wenwu Lin +4 位作者 Christopher J.Coates Pengxiang Shang Taiyun Wei Zujian Wu Lianhui Xie 《中国病毒学:英文版》 CAS CSCD 2019年第3期295-305,共11页
Banana bunchy top virus(BBTV)poses a serious danger to banana crops worldwide.BBTV-encoded protein B4 is a determinant of pathogenicity.However,the relevant molecular mechanisms underlying its effects remain unknown.I... Banana bunchy top virus(BBTV)poses a serious danger to banana crops worldwide.BBTV-encoded protein B4 is a determinant of pathogenicity.However,the relevant molecular mechanisms underlying its effects remain unknown.In this study,we found that a functional peptide could be liberated from protein B4,likely via proteolytic processing.Site-directed mutagenesis indicated that the functional processing of protein B4 is required for its pathogenic effects,including dwarfism and sterility,in plants.The released protein fragment targets host proteins,such as the large subunit of RuBisCO(RbcL)and elongation factor 2(EF2),involved in protein synthesis.Therefore,the peptide released from B4(also a precursor)may act as a non-canonical modifier to influence host-pathogen interactions involving BBTV and plants. 展开更多
关键词 BANANA bunchy top virus(BBTV) MOVEMENT protein B4 Functional peptide PATHOGENICITY
基于纳升电喷雾离子化质谱技术(nano ESI-MS)建立登革病毒检测方法
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作者 王玉娜 刘丽娟 +2 位作者 李丽丽 张丽萍 赵景波 《中国国境卫生检疫杂志》 CAS 2019年第1期5-8,共4页
目的建立基于纳升电喷雾离子化质谱技术(nano ESI-MS)检测登革病毒的方法。方法采用生物工程技术,合成Ⅱ型登革病毒(DENV-Ⅱ)NS1蛋白特异性肽段作为识别标志,通过优化实验条件,建立基于nano ESI-MS技术的DENV-ⅡNS1蛋白特异性肽段的检... 目的建立基于纳升电喷雾离子化质谱技术(nano ESI-MS)检测登革病毒的方法。方法采用生物工程技术,合成Ⅱ型登革病毒(DENV-Ⅱ)NS1蛋白特异性肽段作为识别标志,通过优化实验条件,建立基于nano ESI-MS技术的DENV-ⅡNS1蛋白特异性肽段的检测方法;借助特异性胰蛋白酶酶解技术,实现对DENV-ⅡNS1蛋白的检测验证。结果在2.5 kV电压、以甲醇、水按体积比6∶4比例并加入0.1%甲酸作为蛋白稀释液条件下,应用nano ESI-MS技术可成功检测出DENV-ⅡNS1蛋白特异性标志性肽段,灵敏度达10 ng/ml。结论 nano ESI-MS技术灵敏度高,操作简单,可在敞开式大气压环境下实现检测。该方法的建立为扩展nano ESI-MS技术应用范围提供了新思路。 展开更多
关键词 纳升电喷雾离子化质谱 登革病毒 非结构蛋白 肽段
Cytoprotective Mechanism of the Novel Gastric Peptide BPC157 in Gastrointestinal Tract and Cultured Enteric Neurons and Glial Cells
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作者 Xi-Yu Wang Meihua Qu +6 位作者 Rui Duan Dengping Shi Ling Jin Jinping Gao Jackie D.Wood Junhua Li Guo-Du Wang 《神经科学通报:英文版》 SCIE CAS CSCD 2019年第1期167-170,共4页
Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Thei... Dear Editor,Body protection compound (BPC) 157 is a stable gastric pentadecapeptide. Predrag Sikiric’s team has carried out many investigations of its cytoprotective effects in different organs and tissues (1, 2)Their evidence indicates that BPC157 has potent cytoprotection in neural injury and gastrointestinal (GI) ulcers. Nevertheless. 展开更多
关键词 BPC HT GI CYTOPROTECTIVE Mechanism of the NOVEL GASTRIC PEPTIDE BPC157 in Gastrointestinal Tract and CULTURED ENTERIC Neurons and Glial Cells
A Polysaccharide-based Hydrogel and PLGA Microspheres for Sustained P24 Peptide Delivery: An In vitro and In vivo Study Based on Osteogenic Capability
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作者 CAI Qing QIAO Chunyan +3 位作者 NING Jun DING Xinxin WANG Haoyang ZHOU Yanmin 《高等学校化学研究:英文版》 SCIE CAS CSCD 2019年第5期908-915,共8页
A bone morphogenetic protein-2(BMP-2) derived synthetic oligopeptide, S [PO4]KIPKASSVPTELSAISTLYLDDD(P24), has shown great potential for facilitating bone regeneration. However, P24 cannot be directly used onto bone d... A bone morphogenetic protein-2(BMP-2) derived synthetic oligopeptide, S [PO4]KIPKASSVPTELSAISTLYLDDD(P24), has shown great potential for facilitating bone regeneration. However, P24 cannot be directly used onto bone defects, while a continuous sustained delivery of P24 may lead to a better formation of bone tissue. Based on this issue, we have developed a sustained delivery system incorporating P24-loaded poly(lactide-co-glycolide)(PLGA) microspheres and nano-hydroxyapatite(n-HA) into the composite hydrogel. The P24-contained compound material was characterized with NMR, FTIR and SEM to demonstrate the fomiation of compound structure containing P24, PLGA and n-HA. A continuous drug release of P24 was observed for over 60 d that evidently enhanced the efficiency in promoting the proliferation of MC3T3-E1 cells and the secrete of alkaline phosphatase(ALP) in vitro. Moreover, the osteoinduction eflect of the hydrogel system with P24 peptide niicrospheres was demonstrated in vivo and manifested by the result of immunohistochemistry. This novel injectable composite hydrogel is expected to be applied to improving the bone defect treatment in bone tissue engineering. 展开更多
关键词 BMP-2 derived peptide HYDROGEL PLGA MICROSPHERE OSTEOGENESIS Tissue engineering
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