期刊文献+
共找到24篇文章
< 1 2 >
每页显示 20 50 100
联合吸入糖皮质激素和长效β_2激动剂治疗COPD疗效观察
1
作者 支学军 《河北北方学院学报(医学版)》 2006年第5期34-35,共2页
目的:探讨联合吸入糖皮质激素与长效β2激动剂对慢性阻塞性肺疾病(COPD)的治疗作用。方法:急性加重期COPD病人60例,给予吸入布地奈德干粉400μg,2次/d,同时吸入福莫特罗干粉9μg,2次/d。观察1月、3月、6月,并测定痰液中炎性介质白细胞介... 目的:探讨联合吸入糖皮质激素与长效β2激动剂对慢性阻塞性肺疾病(COPD)的治疗作用。方法:急性加重期COPD病人60例,给予吸入布地奈德干粉400μg,2次/d,同时吸入福莫特罗干粉9μg,2次/d。观察1月、3月、6月,并测定痰液中炎性介质白细胞介素(IL-8)的量。结果:肺功能治疗前后有明显提高(P<0·05)。呼吸症状均有所改善,尤其是喘息症状改善明显;痰中IL-8治疗后明显下降(P<0·05)。结论:联合吸入糖皮质激素与长效β2激动剂对COPD患者的肺功能、自觉症状均有改善,痰中IL-8水平降低,可能与糖皮质激素加强了对气道炎症的作用有关。 展开更多
关键词 慢性阻塞性肺疾病 糖皮质激素 &激动剂 疗效 联合用药 白介素8(IL-8)
下载PDF
Construction and Evaluation of Merged Pharmacophore Based on Peroxisome Proliferator Receptor-Alpha Agonists 被引量:3
2
作者 乔连生 贺昱甦 +5 位作者 霍晓乾 蒋芦荻 陈艳昆 陈茜 张燕玲 李贡宇 《Chinese Journal of Chemical Physics》 SCIE CAS CSCD 2016年第4期508-516,I0002,共10页
Pharmacophore is a commonly used method for molecular simulation, including ligand-based pharmacophore (LBP) and structure-based pharmacophore (SBP). LBP can be utilized to identify active compounds usual with low... Pharmacophore is a commonly used method for molecular simulation, including ligand-based pharmacophore (LBP) and structure-based pharmacophore (SBP). LBP can be utilized to identify active compounds usual with lower accuracy, and SBP is able to use for distin- guishing active compounds from inactive compounds with frequently higher missing rates. Merged pharmacophore (MP) is presented to integrate advantages and avoid shortcomings of LBP and SBP. In this work, LBP and SBP models were constructed for the study of per- oxisome proliferator receptor-alpha (PPARα) agonists. According to the comparison of the two types of pharmacophore models, mainly and secondarily pharmacological features were identified. The weight and tolerance values of these pharmacological features were adjusted to construct MP models by single-factor explorations and orthogonal experimental design based on SBP model. Then, the reliability and screening efficiency of the best MP model were validated by three databases. The best MP model was utilized to compute PPARα activity of compounds from traditional Chinese medicine. The screening efficiency of MP model outperformed individual LBP or SBP model for PPARα agonists, and was similar to combinatorial screening of LBP and SBP. However, MP model might have an advantage over the combination of LBP and SBP in evaluating the activity of compounds and avoiding the inconsistent prediction of LBP and SBP, which would be beneficial to guide drug design and optimization. 展开更多
关键词 Merged pharmacophore Ligand-based pharmacophore Structure-based pharmaeophore Peroxisome proliferator receptor-alpha DOCKING Combinatorial screening
下载PDF
Expression of PPAR-γ in Lung Cancer and the Role of PPAR-γ in Apoptosis of Lung Cancer 被引量:2
3
作者 张敏 游泳 +4 位作者 邹萍 刘芳 白明 陶晓南 何伟 《The Chinese-German Journal of Clinical Oncology》 CAS 2005年第1期36-39,67,共5页
Objective: To investigate the relationship between peroxisomeproliferators-activated receptor-gamma (PPAR-γ) and clinical pathology of lung cancer, and to studythe inhibitory effect of PPAR-γ activators on lung canc... Objective: To investigate the relationship between peroxisomeproliferators-activated receptor-gamma (PPAR-γ) and clinical pathology of lung cancer, and to studythe inhibitory effect of PPAR-γ activators on lung cancer growth and the mechanism of inducingapoptosis of lung cancer. Methods: Expression of PPAR-γ in 15 cases of non-cancerous lung tissuesand 64 cases of lung cancer tissues was detected by using immunohistochemistry. The average A valueswere measured by using image analysis. The expression of PPAR-γ in lung cancer cells was detectedby using RT-PCR. After being treated with PPAR-γ activators, apoptosis was detected by using flowcytometry, and meanwhile, the change in caspase-3 activity was detected by caspase-3 kits. Results:Expression levels of PPAR-γ in cancerous tissues were higher than those in non-cancerous lungtissues. In four types of lung cancer, the sequence of PPAR-γ expression from high to low levelswas small-cell lung cancer, squamous carcinom, large-cell lung cancer, adenocarcinoma in turns. Theexpression of PPAR-γ was correlated with differentiation and postoperative TNM staging of lungcancer tissues, but not with lymph node metastasis. PPAR-γ expressed in two lung cancer cell lines,which could induce apoptosis of lung cancer cells after being treated with PPAR-γ activators, andcaspase-3 activity in cells treated with PPAR-γ activators was significantly increased. Conclusion:PPAR-γ is correlated with clinical pathology and apoptosis of lung cancer closely, and activatedPPAR-γ can increase caspase-3 activity to induce cells apoptosis. PPAR-γ will be able to become anew target for therapy of lung cancer in the future. 展开更多
关键词 PPAR-Γ ACTIVATORS lung cancer clinical pathology APOPTOSIS
下载PDF
New lead discovery for novel M_1 agonists:pharmacophore model based on DISCO computation and virtual screening
4
作者 高广涛 牛彦 +2 位作者 王栋 雷小平 胡应和 《Journal of Chinese Pharmaceutical Sciences》 CAS 2008年第1期75-78,共4页
To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons (DISCO) method without the previous knowledge of the... To discover new lead compounds for M1 agonists. Ten typical M1 agonists were superimposed to build a M1 agonists 3D-pharmacophore model using distance-comparisons (DISCO) method without the previous knowledge of the three-dimensional structure of M1 receptor. Virtual screening strategy was used to analyze the Available Chemicals Directory-Screening Compounds (ACD-SC) to identify possible new hits. Twenty-two compounds which fit the pharmacophore model well and are not similar with known M1 agonists were purchased in order to evaluate their M1 receptor agonist activity. One of them shows M1 receptor agonist activity with EC50 of 4.90 μmol/L and maximum response. Multiple of 10.0 which shows it worthy of further study as a new lead compound for M1 agonists. 展开更多
关键词 DISCO M1 agonists Pharmacophore model Virtual screening Alzheimer's disease
下载PDF
Mangiferin,a natural xanthone,accelerates gastrointestinal transit in mice involving cholinergic mechanism 被引量:3
5
作者 Talita Cavalcante Morais Synara Cavalcante Lopes +5 位作者 Karine Maria Martins Bezerra Carvalho Bruno Rodrigues Arruda Francisco Thiago Correia de Souza Maria Teresa Salles Trevisan Vietla Satyanarayana Rao Flávia Almeida Santos 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第25期3207-3214,共8页
AIM: To investigate the effects of mangiferin on gas- trointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism.METHODS: Intragastrically-administered charcoal mealwas used t... AIM: To investigate the effects of mangiferin on gas- trointestinal transit (GIT) in normal and constipated mice, together with the possible mechanism.METHODS: Intragastrically-administered charcoal mealwas used to measure GIT in overnight starved Swiss mice. In the first experiments, mangiferin (3 mg/kg, 10 mg/kg, 30 mg/kg, and 100 mg/kg, po) or tegaserod (1 mg/kg, ip) were administered 30 min before the char- coal meal to study their effects on normal transit. In the second series, mangiferin (30 mg/kg) was tested on delayed GIT induced by several different pharma- cological agonists (morphine, clonidine, capsaicin) or antagonists (ondansetron, verapamil, and atropine) whereas in the third series, mangiferin (30 mg/kg, 100 mg/kg and 300 mg/kg) or tegaserod (1 mg/kg) were tested on 6 h fecal pellets outputted by freely fed mice. The ratio of wet to dry weight was calculated and used as a marker of fecal water content. RESULTS: Mangiferin administered orally significantly (P 〈 0.05) accelerated GIT at 30 mg/kg and 100 mg/kg (89% and 93%, respectively), similarly to 5-hydroxytrypta- mine4 (5-H%) agonist tegaserod (81%) when compared to vehicle-treated control (63%). Co-administered man- giferin (30 mg/kg) totally reversed the inhibitory effect of opioid agonist morphine, 5-HT3-receptor antagonist ondansetron and transient receptor potential vanilloid-1 receptor agonist capsaicin on GIT, but only to a partial extent with the GIT-delay induced by ~2-adrenoceptor agonist clonidine, and calcium antagonist verapamil. However, co-administered atropine completely blocked the stimulant effect of mangiferin on GIT, suggesting the involvement of muscarinic acetylcholine receptor activation. Although mangiferin significantly enhanced the 6 h fecal output at higher doses (245.5±10.43 mg vs 161.9±10.82 mg and 227.1±20.11 mg vs 161.9±10.82 mg of vehicle-treated control, at 30 and 100 mg/ kg, P 〈 0.05, respectively), the effect of tegaserod was more potent (297.4±7.42 mg vs 161.9±10.82 mg of vehicle-treated control, P 〈 0.05). Unlike tegaserod, which showed an enhanced water content in fecal pel- lets (59.20%±1.09% vs 51.44%±1.19% of control, P 〈 0.05), mangiferin evidenced no such effect, indi-cating that it has only a motor and not a secretomotor effect. CONCLUSION: Our data indicate the prokinetic action of mangiferin. It can stimulate the normal GIT and also overcome the drug-induced transit delay, via a choliner- gic physiological mechanism. 展开更多
关键词 MANGIFERIN Glucosylxanthone Gastrointes-tinal transit Prokinetic action Cholinergic mechanism
下载PDF
EP4 agonist alleviates indomethacin-induced gastric lesions and promotes chronic gastric ulcer healing 被引量:1
6
作者 Wha Bin Im Yariv Donde Larry A Wheeler 《World Journal of Gastroenterology》 SCIE CAS CSCD 2009年第41期5149-5156,共8页
AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indo... AIM: To investigate EP4-selective agonist effect on indomethacin-induced gastric lesions and on the spontaneous healing of chronic gastric ulcers. METHODS: In a mouse model of gastric bleeding with high dose of indomethacin (20 mg/kg), an EP4-selective agonist was administered orally. Stomach lesions and gastric mucous regeneration were monitored. In a mouse model of chronic gastric ulcer induced by acetic acid, EP4 agonist effect on the healing of chronic gastric ulcer was evaluated in the presence or absence of low dose indomethadn (3 mg/kg). In cultured human gastric mucous cells, EP4 agonist effect on indomethacin- induced apoptosis was assessed by flow cytometry. RESULTS: The EP4-selective agonist reduced high dose indomethacin-induced acute hemorrhagic damage and promoted mucous epithelial regeneration. Low-dose indomethacin aggravated ulcer bleeding and inflammation, and delayed the healing of the established chronic gastric ulcer. The EP4 agonist, when applied locally, not only offset indomethacin-induced gastric bleeding and inflammation, but also accelerated ulcer healing. In the absence of indomethacin, the EP4 agonist even accelerated chronic gastric ulcer healing and suppressed inflammatory cell infiltration in the granulation tissue. In vitro, the EP4 agonist protected human gastric mucous cells from indomethacin-induced apoptosis.CONCLUSION: EP4-selective agonist may prevent indomethacin-induced gastric lesions and promote healing of existing and i ulcers, via promoting mucous epithelial cells. proliferation and survival of mucous epithelial cells. 展开更多
关键词 Prostaglandin E2 Non-steroidal anti-inflam- matory drugs Gastric bleeding Gastric ulcer EP4- subtype receptor
下载PDF
Ciliotherapy: a novel intervention in polycystic kidney disease 被引量:1
7
作者 Sarmed H. Kathem Ashraf M. Mohieldin +8 位作者 Shakila Abdul-Majeed Sajida H. Ismail Qaiss H. Altaei Ibrahim K. Alshimmari Mohanned M. Alsaidi Hussein Khammas Andromeda M. Nauli Bina Joe Surya M. Nauli 《Journal of Geriatric Cardiology》 SCIE CAS CSCD 2014年第1期63-73,共11页
Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertensio... Background Ciliopathies are a group of diseases associated with abnormal structure or function of primary cilia. Ciliopathies include polycystic kidney disease (PKD), a pathology associated with vascular hypertension. We previously showed that cilia length regulates cilia function, and cilia function is required for nitric oxide (NO) biosynthesis in endothelial cells. Because patients with PKD show abnormal sensory cilia function, the aim of our current study was to search for a targeted therapy focused on primary cilia, which we refer to as 'cilio- therapy'. Methods and Results In the present studies, our in vitro analyses refined fenoldopam as an equipotent and more specific dopa- minergic agonist to regulate cilia length and function. Our in vivo studies indicated that fenoldopam increased cilia length and serum NO thereby reducing blood pressure in a PKD mouse model. Our crossover, multicenter, double-blind and placebo-controlled clinical study further indicated that cilia-targeting therapy showed an overall reduction in mean arterial pressure in PKD patients. Conclusions Overall, our studies provide the first evidence of ciliotherapy as an innovative intervention in patients with abnormal primary cilia. 展开更多
关键词 Primary cilium Blood pressure MECHANOSENSOR MECHANOTRANSDUCTION Chemosensor Fluid-shear stress
下载PDF
Effect of Synthetic Leucopyrokinin Analog [D-AlaS]-[2-8]-Leucopyrokinin ([D-AlaS]-[2-8]-LPK) on Opioid-lnduced Analgesia in Rats
8
作者 Andrzej Plech Monika Rykaczewska-Czerwifiska +1 位作者 Adam Sipifiski Danuta Konopifiska 《Journal of Agricultural Science and Technology(A)》 2012年第5期682-689,共8页
The study was undertaken in order to evaluate effect of synthetic insect neuropeptide leucopyrokinin analog, [D-Ala5]-[2-8]-LPK, on analgesia induced by selective agonists of/a-, 6- and l〈-opioid receptors. The study... The study was undertaken in order to evaluate effect of synthetic insect neuropeptide leucopyrokinin analog, [D-Ala5]-[2-8]-LPK, on analgesia induced by selective agonists of/a-, 6- and l〈-opioid receptors. The study was performed on male Wistar rats, which a week before the experiments were implanted with polyethylene cannulas into the lateral brain ventricle (icv). Effect of prior administration of [D-Ala5]-[2-8]-LPK on analgesia induced in rats by next icv administration of equimolar dose of μ-, δ- and -opioid agonists: DAMGO, DPDPE and GR fumarate respectively, was evaluated. Antinociceptive effect was determined in rats by the test of the tail immersion. It was found that two doses of 5 and 10 nmols icv of [D-AlaS]-[2-8]-LPK inhibited analgesia in rats by equimolar doses of DAMGO. This analog also transiently (only in two time intervals) and in one dose of 10 nmols inhibited analgesia induced in rats by icv administration of equimolar DPDPE dose of 10 nmols icv. Obtained results indicate that [D-AlaS]-[2-8]-LPK inhibits antinociceptive effect of DAMGO and in part of DPDPE, i.e. mainly antagonized ~t-opioid receptors. These results correspond with results of our previous study that selective antagonists of μ- and δ-opioid receptors blocked antinociceptive effect of synthetic insect neuropeptide leucopyrokinin and of it active analog [2-8]-leucopyrokinin. We regard that [D-AIaS]-[2-8]-LPK, the first discovered antagonist of leucopyrokinin may be a useful as a probable tool substance in the study of biological effects of insect-derived peptides either in invertebrates or in mammals. 展开更多
关键词 [D-Ala5]-[2-8]-leucopyrokinin opioid receptors agonists antinociceptive effect rats.
下载PDF
Thymoquinone and Poloxin are slow-irreversible inhibitors to human Polo-like kinase 1 Polo-box domain 被引量:3
9
作者 Yin Zhou Chen Jianhua Peter H. Rehse 《Journal of Medical Colleges of PLA(China)》 CAS 2010年第3期136-142,共7页
Objective: To provide a kinetic model(s) and reveal the mechanism of thymoquinone and Poloxin blocking an emerging anti-cancer target, human Polo-like kinase 1 (hPlkl) Polo-box domain (PBD). Methods: The bindi... Objective: To provide a kinetic model(s) and reveal the mechanism of thymoquinone and Poloxin blocking an emerging anti-cancer target, human Polo-like kinase 1 (hPlkl) Polo-box domain (PBD). Methods: The binding kinetics was determined by using a fluorescence polarization based assay. The putative mechanism was examined with a competition test. Results: Thymoquinone follows a one-step binding with an association rate constant (k1) of 6.635× 10^3 L.mol^-1 min^-1.Poloxin fit a two-step binding with a dissociation constant (Ki) of 118 μmol/L for the intermediate complex and its isomerization rate (k4) of 0.131 5 minJ to form an irreversible adduct. No significant dissociation was observed for either ligand up to 13 h. The inhibitors responded insignificantly to the presence of Michael donors as hPIkl-PBD competitors. Conclusion: Thymoquinone and Poloxin are slow-tight ligands to the hPlkl-PBD with kinetic models distinct from each other. Michael addition as the mechanism is excluded. 展开更多
关键词 Polo-like kinase Irreversible inhibitor KINETICS Fluorescence polarization
下载PDF
Angle Control of a Pneumatically Driven Musculoskeletal Model Based on Coordination of Agonist-Antagonist Muscle
10
作者 Yuki Honda Fumio Miyazaki Atsushi Nishikawa 《Journal of Mechanics Engineering and Automation》 2012年第12期709-719,共11页
In recent years, researchers have been actively pursuing research into developing robots that can be useful in many fields of industry (e.g., service, medical, and aging care). Such robots must be safe and flexible ... In recent years, researchers have been actively pursuing research into developing robots that can be useful in many fields of industry (e.g., service, medical, and aging care). Such robots must be safe and flexible so that they can coexist with people. Pneumatic actuators are useful for achieving this goal because they are lightweight units with natural compliance. Our research focuses on joint angle control for a pneumatically driven musculoskeletal model. In such a model, we use a one-degree-of-freedom joint model and a five-fingered robot hand as test beds. These models are driven by low pressure-driven pneumatic actuators, and mimic the mechanism of the human hand and musculoskeletal structure, which has an antagonistic muscle pair for each joint. We demonstrated a biologically inspired control method using the parameters antagonistic muscle ratio and antagonistic muscle activity. The concept of the method is based on coordination of an antagonistic muscle pair using these parameters. We have investigated the validity of the proposed method both theoretically and experimentally, developed a feedback control system, and conducted joint angle control by implementing the test beds. 展开更多
关键词 Musculoskeletal model pneumatic actuator position control muscle coordination agonist-antagonist muscle.
下载PDF
Computational Analysis for Residue-Specific CDK2-Inhibitor Bindings
11
作者 Yun-peng Yang Li-ping He +2 位作者 Jing-xiao Bao Yi-fei Qi John Z. H. Zhang 《Chinese Journal of Chemical Physics》 SCIE CAS CSCD 2019年第1期134-142,I0003,共10页
Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, le... Cyclin-dependent kinase 2 (CDK2) is a key macromolecule in cell cycle regulation. In cancer cells, CDK2 is often overexpressed and its inhibition is an effective therapy of many cancers including breast carcinomas, leukemia, and lymphomas. Quantitative characterization of the interactions between CDK2 and its inhibitors at atomic level may provide a deep understanding of protein-inhibitor interactions and clues for more effective drug discovery. In this study, we have used the computational alanine scanning approach in combination with an efficient interaction entropy method to study the microscopic mechanism of binding between CDK2 and its 13 inhibitors. The total binding free energy from the method shows a correlation of 0.76?0.83 with the experimental values. The free energy component reveals two binding mode in the 13 complexes, namely van der Waals dominant, and electrostatic dominant. Decomposition of the total energy to per-residue contribution allows us to identify five hydrophobic residues as hot spots during the binding. Residues that are responsible for determining the strength of the binding were also analyzed. 展开更多
关键词 CDK2 MD simulation INHIBITOR Hot-spot residue Binding free energy
下载PDF
Redox physiology in animal function:The struggle of living in an oxidant environment
12
作者 David COSTANTINI 《Current Zoology》 SCIE CAS CSCD 北大核心 2010年第6期687-702,共16页
A strong focus of ecological research for several decades has been to understand the factors underlying the variation in animal life-histories. In recent times, ecological studies have begun to show that oxidative str... A strong focus of ecological research for several decades has been to understand the factors underlying the variation in animal life-histories. In recent times, ecological studies have begun to show that oxidative stress may represent another important modulator of competitive trade-offs among fitness traits or of positively integrated patterns of traits. Therefore, incorporating mechanisms underlying oxidative physiology into evolutionary ecology has the potential to help understand variation in life-history strategies. In this review, I provide a general overview of oxidative stress physiology, and subsequently focus on topics that have been neglected in previous ecological reviews on oxidative stress. Specifically, I introduce and discuss the adaptations that animals have evolved to cope with oxidative stress; the environmental stressors that can generate changes in oxidative balance; the role of reactive species in transduction of environmental stimuli and cell signaling; and the range of hormetic responses to oxidative stress [Current Zoology 56 (6): 687-702, 2010]. 展开更多
关键词 ANTIOXIDANTS Free radicals LIFE-HISTORY Oxidative stress Stress response Vertebrates
下载PDF
Advancements in glucagon-like peptide-1 receptor agonist therapy for type 2 diabetes
13
作者 Yaping Peng Ying Fu 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2024年第8期667-685,共19页
Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglyce... Glucagon-like peptide-1 receptor agonists(GLP-1RAs)are novel hypoglycemic agents that have garnered widespread acceptance in the treatment of type 2 diabetes,largely attributed to their safety profile,potent hypoglycemic effects,and metabolic advantages.Their primary mechanisms of action encompass promoting insulin release,inhibiting glucagon secretion,bolstering pancreatic islet cell function,curbing appetite,and slowing gastric emptying.This article delves into the clinical evidence underscoring the efficacy of various GLP-1RAs.Notably,these agents have demonstrated marked improvements in glycemic control,significant weight reduction,and substantial cardiovascular and renal protection.Nonetheless,certain adverse effects of GLP-1RAs,such as pancreatitis and intestinal obstruction,have been reported,warranting vigilant monitoring by healthcare professionals.In sum,GLP-1RAs hold significant promise in the management of type 2 diabetes,offering notable cardiovascular and renal advantages. 展开更多
关键词 Glucagon-like peptide-1 receptor agonist Type 2 diabetes Metabolic diseases
原文传递
Three-dimensional common-feature hypotheses for Toll-like receptor 7 agonists
14
作者 齐世光 于慧 +1 位作者 金宏威 王占黎 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2013年第2期148-153,共6页
Toll-like receptor 7 (TLR7), the best known TLRs, has been demonstrated to be useful in fighting against infectious disease. In our study, three-dimensional (3D) pharmacophore models were constructed from a set of... Toll-like receptor 7 (TLR7), the best known TLRs, has been demonstrated to be useful in fighting against infectious disease. In our study, three-dimensional (3D) pharmacophore models were constructed from a set of 5 TLR7 agonists. Among the 10 common-featured models generated by program Discovery Studio/HipHop, a hypothesis (Hypo2) including one hydrogen-bond donor (D), one hydrogen-bond acceptor (A), and two hydrophobic (H) features was considered to be important in evaluating the ligands with TLR7 agonistic activity. The obtained pharmacophore model was further validated using a set of test molecules and the Catalyst TLR7-agonist-subset database. Hypo2 has been shown to identify a range of highly potent TLR7 agonists. Finally, the obtained pharmacophore was further validated using docking studies. Taken together, this model can be utilized as a guide for future studies to design the structurally novel TLR7 agonists. 展开更多
关键词 Toll-like receptor 7 Agonist Common-feature hypothesis Molecular docking
原文传递
Pharmacophore identification and validation for human nAChR α7 agonists 被引量:1
15
作者 于博 金宏威 +1 位作者 张亮仁 王超 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2013年第5期393-402,共10页
Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure... Human nAChR u7 is the potential target for schizophrenia cognitive disorders, and it is meaningful to develop selective human nAChR α7 agonists for the clinical treatment of the disease. Because the crystal structure ofα7 receptor has not been resolved, ligand-based drug design strategy was took in this work. A 3D QSAR pharmacophore model was built by HypoGen method, and its quality was evaluated by cost function. Furthermore, the pharmacophore model was validated with activity prediction of test set and was cross-validated based on Fisher's Randomization Method. By Enrichment Factor and AU-ROC analysis, the final pharmacophore, which is consisted of one HBA, two Hydrophobic and one PosIonizable, was selected and it fitted well with the docking result of α7 homology model and the ligand. The pharmacophore is expected for the following virtual screening and lead optimization of human nAChR α7 agonists, which is important for the development and discovery of novel antipsychotics. 展开更多
关键词 SCHIZOPHRENIA Human nAChR α7 AGONISTS Pharmacophore modeling Molecular docking
原文传递
Distinct actions of intermittent and sustained β-adrenoceptor stimulation on cardiac remodeling 被引量:15
16
作者 MA XiaoWei1,3,SONG Yao1,3,CHEN Chao1,3,FU YongNan1,3,SHEN Qiang2,3,LI ZiJian1,3 & ZHANG YouYi1,3 1Institute of Vascular Medicine,Peking University Third Hospital,Beijing 100191,China 2Institute of Cardiovascular Science,Peking University,Beijing 100191,China 3Key Laboratory of Molecular Cardiovascular Sciences,Ministry of Education,Beijing 100191,China 《Science China(Life Sciences)》 SCIE CAS 2011年第6期493-501,共9页
Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathologic... Heart disease is associated with increased sympathetic nerve activity and elevated levels of circulating catecholamines,resulting in chronic stimulation of the β-adrenergic receptors (β-AR) and consequent pathological cardiac remodeling.Experimentally,chronic administration of the β-AR agonist isoproterenol (ISO) has been most commonly used to model β-AR-induced cardiac remodeling.However,it remains unclear whether β-AR-mediated cardiac remodeling and dysfunction differs between sustained versus pulsatile (intermittent) exposure to a β-agonist.Here,we compare the effects of intermittent versus sustained administration of ISO on cardiac remodeling and function in mice.Animals were administered 5 mg (kg d)-1 ISO for 2 weeks either by daily subcutaneous injection,or continuous infusion via an implanted osmotic minipump.Cardiac function and remodeling were determined by echocardiography,micromanometry and histology.Moreover,Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were utilized to define the proteins and genes involved.Both sustained and intermittent administration of ISO resulted in a similar degree of cardiac hypertrophy (16% and 19%,respectively).However,mice receiving ISO by daily injection developed more severe ventricular systolic and diastolic dysfunction and myocardial fibrosis compared with mice receiving ISO via the osmotic minipump.The disparity in results between the delivery methods is suggested to be due,at least in part,to increased expression of fibrogenic factors,including connective tissue growth factor (CTGF) and NADPH oxidase (NOX4),in mice receiving intermittent application of ISO.In summary,compared with sustained exposure to a β-AR agonist,intermittent β-AR stimulation leads to more severe cardiac dysfunction and fibrosis.These findings not only further our understanding of β-AR function in the setting of cardiac pathophysiology,but also highlight that significant differences can result dependent upon the mode of experimental β-AR stimulation in inducing cardiomyopathy. 展开更多
关键词 Β-ADRENOCEPTOR reactive oxygen species NADPH oxidase cardiac hypertrophy cardiac fibrosis
原文传递
Temperature-dependent THz vibrational spectra of clenbuterol hydrochloride 被引量:9
17
作者 YANG YuPing LEI XiangYun +1 位作者 YUE Ai ZHANG ZhenWei 《Science China(Physics,Mechanics & Astronomy)》 SCIE EI CAS 2013年第4期713-717,共5页
Using the high-resolution Terahertz Time-domain spectroscopy (THz-TDS) and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride (CH), a 2 -adrenergic agonist for decr... Using the high-resolution Terahertz Time-domain spectroscopy (THz-TDS) and the standard sample pellet technique, the far-infrared vibrational spectra of clenbuterol hydrochloride (CH), a 2 -adrenergic agonist for decreasing fat deposition and enhancing protein accretion, were measured in temperature range of 77-295 K. Between 0.2 and 3.6 THz (6.6-120.0 cm-1 ), seven highly resolved spectral features, strong line-narrowing and a frequency blue-shift were observed with cooling. However, ractopamine hydrochloride, with some structural and pharmacological similarities to clenbuterol hydrochloride, showed no spectral features, indicating high sensitivity and strong specificity of THz-TDS. These results could be used for the rapid and nondestructive CH residual detection in food safety control. 展开更多
关键词 Terahertz Time-domain spectroscopy clenbuterol hydrochloride ractopamine hydrochloride
原文传递
Pharmacodynamic model of dopamine D1 receptor agonists in the treatment of breast cancer lung metastasis 被引量:2
18
作者 Liang Yang Ye Yao +2 位作者 Yaoyao Feng Wei Lu Tianyan Zhou 《Journal of Chinese Pharmaceutical Sciences》 CAS CSCD 2020年第1期45-54,共10页
Previous study has shown that dopamine D1 receptor(D1DR)agonists,fenoldopam(FEN)and l-stepholidine(l-SPD),have inhibitory effects on breast cancer lung metastasis.To quantitatively describe and predict the pharmacodyn... Previous study has shown that dopamine D1 receptor(D1DR)agonists,fenoldopam(FEN)and l-stepholidine(l-SPD),have inhibitory effects on breast cancer lung metastasis.To quantitatively describe and predict the pharmacodynamic(PD)properties of FEN and l-SPD and to explore the PD model structure of cancer metastasis treating drugs,we used the data of lung metastasis in 4T1 breast cancer mice under the treatment of either FEN or l-SPD,and established a PD model.The PD model assumed an exponential growth for both primary tumor and metastasis.The primary tumor emitted cells to form metastases,and the cell emitting rate was proportional to power form of the primary tumor weight.The total number of lung metastasis was set as the target value.D1DR agonists inhibited metastasis by inhibiting cell emitting rate instead of the growth rate of primary tumor or metastasis.The model results showed that the decrease in the number of lung metastases was roughly proportional to the square of the drug dose.The values of PD coefficient reflected the inhibitory ability of the drugs,and that of l-SPD(0.274 kg/mg)was greater than that of FEN(0.0393 kg/mg).This PD model can quantitatively describe the effects of FEN and l-SPD on the progression of lung metastasis in 4T1 primary breast cancer mice and can predict the time course of drug efficacy at multiple doses,providing a reference for PD model structure of other drugs for cancer metastasis indication. 展开更多
关键词 Pharmacodynamic model Dopamine D1 receptor agonist Cancer metastasis Breast cancer
原文传递
A system for screening agonists targeting β_2-adrenoceptor from Chinese medicinal herbs 被引量:3
19
作者 Hui WANG Shi-you LI +1 位作者 Chuan-ke ZHAO Xin ZENG 《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》 SCIE CAS CSCD 2009年第4期243-250,共8页
In order to develop a model for screening the agonists of human β2-adrenoceptor from Chinese medicinal herbs extracts, we used a cell-based functional assay based on a common G protein-coupled receptor (GPCR) regul... In order to develop a model for screening the agonists of human β2-adrenoceptor from Chinese medicinal herbs extracts, we used a cell-based functional assay based on a common G protein-coupled receptor (GPCR) regulation mechanism and destabilized enhanced green fluorescent protein (d2EGFP) reporter gene technique. The positive cell clone was confirmed by real-time polymerase chain reaction (PCR) and imaging analysis. To assess the value of this model, we screened over 2000 high performance liquid chromatography (HPLC)-fractionated samples from the ethanol extracts of Chinese medicinal herbs. Six fractions (isolated from Panax japonicus, Veratrum nigrum, Phellodendron amurense, Fructus Aurantii lmmaturus, Chaenomeles speciosa, and Dictamnus dasycarpus) showed significant effects on active reporter gene expression, three of which (isolated from Phellodendron amurense, Fructus Aurantii lmmaturus, and Chaenomeles speciosa) were selected for further concentration response analysis and the half maximal effective concentration (EC1/2 max) values were 4.2, 2.7, and 4.8 μg/ml, respectively. Therefore, this reporter gene assay was suitable for screening β2-adrenoceptor agonists. The results suggest that the six herbal extracts are the possible agonists of β2-adrenoceptor. 展开更多
关键词 β2-adrenoceptor Enhanced green fluorescent protein (EGFP) Chinese medicinal herbs SCREENING
原文传递
Targeting sphingosine-1-phosphate signaling for cancer therapy 被引量:7
20
作者 Zuoquan Xie Hong Liu Meiyu Geng 《Science China(Life Sciences)》 SCIE CAS CSCD 2017年第6期585-600,共16页
Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P ... Sphingosine-1-phosphate(S1P) is a potent pleotropic bioactive lipid mediator involved in immune cell trafficking, cell survival,cell proliferation, cell migration, angiogenesis and many other cellular processes. S1 P either activates S1 P receptors(S1PR1-5) through "inside-out signaling" or acts directly on intracellular targets to regulate various cellular processes. In the past two decades, much progress has been made in exploring S1 P signaling and its pathogenic roles in diseases as well as in developing modulators of S1 P signaling, including S1 P agonists, S1 P antagonists and sphingosine kinase(SphK) inhibitors.Ceramide and S1 P have been defined as reciprocal regulators of cell fate, and S1 P signaling has been shown to be crucial for the pathogenesis of various diseases, including autoimmune diseases, inflammation and cancer; therefore, targeting S1 P signaling may curtail the process of pathogenesis and serve as a potential therapeutic target for the treatment of these diseases. In this review, we describe recent advances in our understanding of S1 P signaling in cancer development(particularly in inflammationassociated cancer) as well as in innate and adaptive immunity, and we also discuss modulators of S1 P signaling in cancer treatment. 展开更多
关键词 sphingosine-1-phosphate sphingosine ceramide cancer inflammation immunity
原文传递
上一页 1 2 下一页 到第
使用帮助 返回顶部