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Crosstalk between gut microbiota and antidiabetic drug action 预览
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作者 Yevheniia Kyriachenko Tetyana Falalyeyeva +2 位作者 Oleksandr Korotkyi Nataliia Molochek Nazarii Kobyliak 《世界糖尿病杂志:英文版(电子版)》 2019年第3期154-168,共15页
Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreadi... Type 2 diabetes (T2D) is a disorder characterized by chronic inflated blood glucose levels (hyperglycemia), at first due to insulin resistance and unregulated insulin secretion but with tendency towards global spreading. The gut microbiota is recognized to have an influence on T2D, although surveys have not formed a clear overview to date. Because of the interactions between gut microbiota and host homeostasis, intestinal bacteria are believed to play a large role in various diseases, including metabolic syndrome, obesity and associated disease. In this review, we highlight the animal and human studies which have elucidated the roles of metformin,α-glucosidase inhibitors, glucagon-like peptide-1 agonists, peroxisome proliferator-activated receptors γ agonists, inhibitors of dipeptidyl peptidase-4, sodium/glucose cotransporter inhibitors, and other less studied medications on gut microbiota. This review is dedicated to one of the most widespread diseases, T2D, and the currently used antidiabetic drugs and most promising new findings. In general, the gut microbiota has been shown to have an influence on host metabolism, food consumption, satiety, glucose homoeostasis, and weight gain. Altered intestinal microbiota composition has been noticed in cardiovascular diseases, colon cancer, rheumatoid arthritis, T2D, and obesity. Therefore, the main effect of antidiabetic drugs is on the microbiome composition, basically increasing the short-chain fatty acids-producing bacteria, responsible for losing weight and suppressing inflammation. 展开更多
关键词 Type 2 diabetes Gut microbiota Metformin Α-GLUCOSIDASE INHIBITORS Glucagon-like peptide-1 AGONISTS PEROXISOME proliferator-activated receptors γ AGONISTS Dipeptidyl peptidase-4 INHIBITORS Sodium/glucose COTRANSPORTER INHIBITORS
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3D-QSAR and Docking Studies of 1,3,4-Thiazolidinone Derivatives Using R-Group Search and Surflex-dock 预览
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作者 仝建波 王洋 +1 位作者 雷珊 秦尚尚 《结构化学》 SCIE CAS CSCD 2019年第3期464-475,共12页
In this paper, a three-dimensional quantitative structure-activity relationships(3 D-QSAR) study for 20 HIV-1 reverse transcriptase(RT) inhibitors was established using Topomer Co MFA. The models were built based on d... In this paper, a three-dimensional quantitative structure-activity relationships(3 D-QSAR) study for 20 HIV-1 reverse transcriptase(RT) inhibitors was established using Topomer Co MFA. The models were built based on different fragment cutting models, with the most effective model of the multiple correlation coefficients of fitting(r2) to be 0.920, cross-validation(q2) of 0.575, and external validation(Qext2) being 0.701. The results indicated that the model obtained has both favorable estimation stability and good prediction capability. Topomer Search was used to search R-group from ZINC database. As a result, a series of R-groups with relatively high activity contribution was obtained. By No. 6 molecule filtering, 3 R1 and 15 R2 groups were selected, and employed to alternately substitute for the R1 and R2 of sample 6. Finally, 45 new compounds were designed, and the Topomer CoMFA model was used to predicate the biological activity, so the Topomer Search is effective in screening and can guide the design of new HIV/AIDS drugs. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HIV-1 RT active site, which revealed the likely bioactive conformations. This study showed that there are extensive interactions between the 1,3,4-thiazolidinone revertase inhibitors and His84, Asp145, Lys33 and Leu83 residues in the active site of HIV-1 RT. These results provide useful insights for the design of potent new inhibitors of RT. 展开更多
关键词 QSAR RT INHIBITORS Topomer COMFA Topomer SEARCH design of new INHIBITORS molecular DOCKING
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Wnt signaling pathways in myocardial infarction and the therapeutic effects of Wnt pathway inhibitors
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作者 Wen-bin Fu Wei Eric Wang Chun-yu Zeng 《中国药理学报:英文版》 SCIE CAS CSCD 2019年第1期9-12,共4页
Myocardial infarction (MI)is one of the most serious health threats,resulting in huge physical and economic burdens worldwide. Wnt signaling pathways play an important role in developmental processes such as tissue pa... Myocardial infarction (MI)is one of the most serious health threats,resulting in huge physical and economic burdens worldwide. Wnt signaling pathways play an important role in developmental processes such as tissue patterning,cell differentiation and cell division.Appropriate regulation of the activities of Wnt signaling pathways is also important for heart development and healing in post-MI heart.Moreover,Wnt pathway inhibitors have been identified as novel antitumor drugs and applied in ongoing clinical trials.This research progress has generated increasing interests for investigating the effects of Wnt pathway inhibitors on MI healing.In this short review,we summarize the roles of Wnt signaling pathways in post-MI heart and the therapeutic effects of Wnt pathway inhibitors on MI,and discuss the underlying mechanisms of Wnt pathway inhibitors in cardiac repairing. 展开更多
关键词 Wnt pathway INHIBITORS MYOCARDIAL INFARCTION CARDIAC repairing THERAPEUTIC effect
胱硫醚β合酶新型抑制剂的发现和机制研究
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作者 刘帆 周越洋 +1 位作者 吴方 于晶 《生物技术》 CAS 2019年第3期231-239,共9页
[目的]旨在发现胱硫醚β合酶(Cystathionineβ-synthase,CBS)的新型抑制剂并研究其作用机制。[方法]通过构建血红素结合位点缺失或氧化还原位点突变的CBS突变体(CBS70-413和CBS C272A/C275A),基于该酶的测活方法和PLP荧光光谱分析,研究3... [目的]旨在发现胱硫醚β合酶(Cystathionineβ-synthase,CBS)的新型抑制剂并研究其作用机制。[方法]通过构建血红素结合位点缺失或氧化还原位点突变的CBS突变体(CBS70-413和CBS C272A/C275A),基于该酶的测活方法和PLP荧光光谱分析,研究3个CBS新型抑制剂的抑制有效性及其分子作用机制。[结果]亲和纯化得到了有活性的CBS70-413和CBS C272A/C275A突变蛋白以用于抑制剂的机制研究。研究发现,CBS70-413突变体可高效拮抗这些抑制剂的抑制效果,而C272A/C275A突变则不行,提示这些抑制剂可与该酶的血红素结合位点结合而抑制该酶活力。进一步研究结果表明,它们可别构调控该酶辅基PLP的含量。[结论]3个抑制剂的分子作用机制为,通过与该酶的Heme位点结合,并通过该位点去别构调控PLP辅基与活力位点的结合,从而抑制该酶的活力。 展开更多
关键词 胱硫醚Β合酶 抑制剂 血红素 机制
圆二色谱法分析金属离子对鲍鱼脯氨酰内肽酶的作用 预览
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作者 李越 颜龙杰 +2 位作者 翁凌 章骞 曹敏杰 《集美大学学报:自然科学版》 CAS 2019年第3期167-173,共7页
使用原核表达系统表达了皱纹盘鲍( Haliotis discus hannai )脯氨酰内肽酶(prolyl endopeptidase,PEP),并对其进行高度纯化。SDS-PAGE结果表明,该酶的相对分子质量约为85 ku,其二级结构主要由α-螺旋(28.3%)、反向平行结构(17.4%)、平... 使用原核表达系统表达了皱纹盘鲍( Haliotis discus hannai )脯氨酰内肽酶(prolyl endopeptidase,PEP),并对其进行高度纯化。SDS-PAGE结果表明,该酶的相对分子质量约为85 ku,其二级结构主要由α-螺旋(28.3%)、反向平行结构(17.4%)、平行结构(8.70%)、β转角(19.0%)、无规卷曲(28.5%)组成。选取PEP特异性荧光底物Suc-Gly-Pro-MCA测定其活性,并选取了多种常见金属盐溶液对其进行抑制作用分析。结果发现,Al^3+、Cu^2+、 Zn^2+、Ag^+和 Pb^2+能够抑制PEP的活性。利用圆二色谱法,对金属离子作用下PEP的二级结构变化进行分析和计算。分析结果表明,不同金属离子对PEP的作用效果不同:Al^3+、Cu^2+和Zn^2+在影响PEP结构时也影响其活性;Ca^2+、Mg^2+对PEP的结构和活性均不产生明显影响,而Ag^+和 Pb^2+可在不影响PEP二级结构的前提下抑制其活性。 展开更多
关键词 脯氨酰内肽酶 皱纹盘鲍 金属离子 圆二色谱 抑制剂
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Pharmacogenetics of the systemic treatment in advanced hepatocellular carcinoma 预览
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作者 Elena De Mattia Erika Cecchin +5 位作者 Michela Guardascione Luisa Foltran Tania Di Raimo Francesco Angelini Mario D’Andrea Giuseppe Toffoli 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第29期3870-3896,共27页
Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., re... Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. To date, most patients with HCC are diagnosed at an advanced tumor stage, excluding them from potentially curative therapies (i.e., resection, liver transplantation, percutaneous ablation). Treatments with palliative intent include chemoembolization and systemic therapy. Among systemic treatments, the small-molecule multikinase inhibitor sorafenib has been the only systemic treatment available for advanced HCC over 10 years. More recently, other smallmolecule multikinase inhibitors (e.g., regorafenib, lenvatinib, cabozantinib) have been approved for HCC treatment. The promising immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab) are still under investigation in Europe while in the US nivolumab has already been approved by FDA in sorafenib refractory or resistant patients. Other molecules, such as the selective CDK4/6inhibitors (e.g., palbociclib, ribociclib), are in earlier stages of clinical development, and the c- MET inhibitor tivantinib did not show positive results in a phase III study. However, even if the introduction of targeted agents has led to great advances in patient response and survival with an acceptable toxicity profile, a remarkable inter-individual heterogeneity in therapy outcome persists and constitutes a significant problem in disease management. Thus, the identification of biomarkers that predict which patients will benefit from a specific intervention could significantly affect decision-making and therapy planning. Germ-line variants have been suggested to play an important role in determining outcomes of HCC systemic therapy in terms of both toxicity and treatment efficacy. Particularly, a number of studies have focused on the role of genetic polymorphisms impacting the drug metabolic pathway and membrane translocation as well as the drug mechanism of action as predictive/prognostic markers of HCC treatment. The aim of this review is to summarize and critically discuss the pharmacogenetic literatu 展开更多
关键词 Hepatocellular carcinoma PHARMACOGENETICS Genetic MARKERS SORAFENIB REGORAFENIB Immune CHECKPOINT inhibitors Cytochromes UDP GLUCURONOSYLTRANSFERASE 1A
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湛江市建筑行业BIM技术应用现状及阻碍研究 预览
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作者 万玲 黄建功 《建筑经济》 北大核心 2019年第8期116-120,共5页
以广东省湛江市为例,基于调研数据,分析湛江市建筑行业BIM技术应用现状及影响BIM技术应用推广的阻碍因素。在此基础上,采用DEMXTEL法分析各阻碍因素的影响程度,并找出各阻碍因素间的因果关系,进而提出促进湛江市建筑行业BIM技术发展的... 以广东省湛江市为例,基于调研数据,分析湛江市建筑行业BIM技术应用现状及影响BIM技术应用推广的阻碍因素。在此基础上,采用DEMXTEL法分析各阻碍因素的影响程度,并找出各阻碍因素间的因果关系,进而提出促进湛江市建筑行业BIM技术发展的建议。 展开更多
关键词 BIM 建筑业 标准 阻碍因素
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2种钼簇化合物对酪氨酸酶的抑制作用及对凡纳滨对虾的保鲜效果研究 预览
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作者 户晶晶 陈丙年 +1 位作者 王力 邓阳阳 《现代食品科技》 EI CAS 北大核心 2019年第1期44-50,197共8页
通过合成2种高核钼簇(NH4)12[Mo36O108(NO)4(H2O)16].33H2O(Mo36)和[Mo36O112(OH2)16(H2bipy)4].28H2O(Mo36-bipy),其对酪氨酸二酚酶活性的抑制作用机理以及对凡纳滨对虾的防黑变保鲜效果进行研究。结果表明Mo36和Mo36-bipy对酪氨酸二酚... 通过合成2种高核钼簇(NH4)12[Mo36O108(NO)4(H2O)16].33H2O(Mo36)和[Mo36O112(OH2)16(H2bipy)4].28H2O(Mo36-bipy),其对酪氨酸二酚酶活性的抑制作用机理以及对凡纳滨对虾的防黑变保鲜效果进行研究。结果表明Mo36和Mo36-bipy对酪氨酸二酚酶IC50值分别为0.0358 mmol/L和0.0601 mmol/L,Mo36对酪氨酸酶的抑制作用为可逆竞争性抑制,Mo36-bipy对酪氨酸酶的抑制作用为可逆混合性抑制,且Mo36对酪氨酸酶活性的抑制作用效果优于Mo36-bipy。将凡纳滨对虾在4℃环境下贮藏10 d,通过对感官评分、颜色、pH值、TVB-N和菌落总数等指标检测,发现高核钼簇对样品具有一定保鲜效果。其均能适当提升感官分值、L^*值,降低pH值与菌落总数。本研究结果为开发一种新型的抗虾体黑变的保鲜剂提供实验基础,并对多金属氧酸盐的应用研究拓展新的研究领域。 展开更多
关键词 酪氨酸酶 钼簇 抑制剂 虾保鲜
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Effects of three MAPK inhibitors on the expressions of TGF-β1 and α-SMA mRNA and protein in LX-2 cells induced by sodium arsenite
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作者 谢万生 《中国医学文摘:内科学分册(英文版)》 2019年第2期76-77,共2页
Objective To investigate the effects of three mitogen-activated protein kinase (MAPK) inhibitors on the expressions of transforming growth factor-β1 (TGF-β1),α-smooth actin (α-SMA) mRNA and protein in human liver ... Objective To investigate the effects of three mitogen-activated protein kinase (MAPK) inhibitors on the expressions of transforming growth factor-β1 (TGF-β1),α-smooth actin (α-SMA) mRNA and protein in human liver stellate cells (LX-2 cells) activated by sodium arsenite. 展开更多
关键词 Effects THREE MAPK INHIBITORS SMA MRNA LX-2 CELLS
Sensing carboxylesterase 1 in living systems by a practical and isoformspecific fluorescent probe
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作者 Lele Ding Zhenhao Tian +8 位作者 Jie Hou Tongyi Dou Qiang Jin Dandan Wang Liwei Zou Yadi Zhu Yunqing Song Jingnan Cui Guangbo Ge 《中国化学快报:英文版》 SCIE CAS CSCD 2019年第3期558-562,共5页
Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogeno... Carboxylesterase 1(CES1), one of the most abundant serine hydrolases in mammals, has drawn much attentions in recent years, owing to this enzyme involves in many physiological processes via hydrolysis of both endogenous esters and xenobiotic esters.Herein, to real-time monitor the activities of CES1 in various biological systems, a practical and iso form-specific fluorescent probe was developed on the basis of the substrate preference of CES1, as well as the structural and optical properties of BODIPY dyes.After screening of a panel of BODIPY ester derivatives, probe 1 displayed the best combination of specificity,sensitivity, enzymatic kinetics and applicability for monitoring CES1 activities in real samples.This probe was successfully used to detect CESl activities in several biological systems including tissue preparations,living cells, tissue slices and zebrafish.Furthermore, the biomedical applications of probe 1 for screening of CES1 inhibitors were also demonstrated using tissue preparations or living cells as enzyme sources.In summary, a practical and broadly applicable tool for real-time monitoring CES1 in biological systems was developed and well-characterized, which held great promise for further investigations on CES1-associated drug discovery, clinical practice and fundamental research. 展开更多
关键词 CARBOXYLESTERASE 1 FLUORESCENT probe Biological imaging LIVING cells based INHIBITORS screening BODIPY DYES
Optimizing radiotherapy with immune checkpoint blockade in hepatocellular carcinoma 预览
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作者 Changhoon Choi Gyu Sang Yoo +1 位作者 Won Kyung Cho Hee Chul Park 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第20期2416-2429,共14页
Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor o... Hepatocellular carcinoma (HCC) is the fifth most common cancer, and its incidence is rapidly increasing in North America and Western Europe as well as South-East Asia. Patients with advanced stage HCC have very poor outcomes;therefore, the discovery of new innovative approaches is urgently needed. Cancer immunotherapy has become a game-changer and revolutionized cancer treatment. A comprehensive understanding of tumor-immune interactions led to the development of immune checkpoint inhibitors (ICIs) as new therapeutic tools, which have been used with great success. Targeting immune checkpoint molecules such as programmed cell death-1 (PD-1) and cytotoxic T lymphocyteassociated protein-4 (CTLA-4) reinvigorates anti-tumor immunity by restoring exhausted T cells. Despite their effectiveness in several types of cancer, of the many immune suppressive mechanisms limit the efficacy of ICI monotherapy. Radiation therapy (RT) is an essential local treatment modality for a broad range of malignancies, and it is currently gaining extensive attention as a promising combination partner with ICIs because of its ability to trigger immunogenic cell death. The efficacy of combination approaches using RT and ICIs has been well documented in numerous preclinical and clinical studies on various types of cancers but not HCC. The application of ICIs has now expanded to HCC, and RT is recognized as a promising modality in HCC. This review will highlight the current roles of PD-1 and CTLA-4 therapies and their combination with RT in the treatment of cancers, including HCC. In addition, this review will discuss the future perspectives of the combination of ICIs and RT in HCC treatment. 展开更多
关键词 HEPATOCELLULAR carcinoma Radiation therapy IMMUNE CHECKPOINT INHIBITORS Abscopal effect
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Plasma relative abundance of epidermal growth factor receptor mutations predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors in patients with advanced lung adenocarcinoma
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作者 徐含烟 《中国医学文摘:内科学分册(英文版)》 2019年第2期103-104,共2页
Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in... Objective To determine whether relative abundance of epidermal growth factor receptor (EGFR) mutations in plasma predicts clinical response to epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced lung adenocarcinoma. Methods In this prospective study,adult patients with advanced lung adenocarcinoma were enrolled in our hospital from 1 April 2016 to 1 January 2017. EGFR mutations in tumortissues were detected by ADx-amplification refractory mutationsystem (ADx-ARMS). EGFR mutations of plasmafree tumor DNA were detected by ADx-ARMS and ADxsuperamplification refractory mutation system (ADx-SuperARMS)at the same time. Patients with EGFR-mutantin tumor tissues and receiving EGFR-TKIs were finallyenrolled. Plasma mutation-positive patients with bothmethods were high abundance group. Patients with positivemutations by ADx-SuperARMS but negative of ADx-ARMS were medium abundance group. 展开更多
关键词 PFS PLASMA relative abundance of EPIDERMAL GROWTH FACTOR RECEPTOR mutations predicts clinical response to EPIDERMAL GROWTH FACTOR receptor-tyrosine kinase inhibitors in PATIENTS with advanced lung adenocarcinoma
Hepatocellular carcinoma:Therapeutic advances in signaling,epigenetic and immune targets 预览
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作者 Daniel Neureiter Sebastian Stintzing +1 位作者 Tobias Kiesslich Matthias Ocker 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第25期3136-3150,共15页
Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besid... Hepatocellular carcinoma(HCC)remains a global medical burden with rising incidence due to chronic viral hepatitis and non-alcoholic fatty liver diseases.Treatment of advanced disease stages is still unsatisfying.Besides first and second generation tyrosine kinase inhibitors,immune checkpoint inhibitors have become central for the treatment of HCC.New modalities like epigenetic therapy using histone deacetylase inhibitors(HDACi)and cell therapy approaches with chimeric antigen receptor T cells(CAR-T cells)are currently under investigation in clinical trials.Development of such novel drugs is closely linked to the availability and improvement of novel preclinical and animal models and the identification of predictive biomarkers.The current status of treatment options for advanced HCC,emerging novel therapeutic approaches and different preclinical models for HCC drug discovery and development are reviewed here. 展开更多
关键词 Liver cancer IMMUNOTHERAPY CHECKPOINT inhibitors Targeted therapy Mouse model Biomarker Next-generation sequencing Non-alcoholic STEATOHEPATITIS Fibrosis Clinical trial
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In vitro antilithidtic activity of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on calcium oxalate crystallization
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作者 Sana Zaki Nasreen Jahan +1 位作者 Mohd Kalim Ghausia Islam 《结合医学学报:英文版》 CAS CSCD 2019年第4期273-281,共9页
Objective: The study examines the effect of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on crystallization of calcium oxalate. Methods: The antilithiatic effect of various concentrations of the hyd... Objective: The study examines the effect of the hydro-alcoholic extract of Cinnamomum zeylanicum Blume bark on crystallization of calcium oxalate. Methods: The antilithiatic effect of various concentrations of the hydro-alcoholic extract of C. zeylanicum was investigated at various stages of stone formation, using Cystone as a stan da rd refere nee drug. The effect on calcium oxalate crystallization was evaluated by measuring the change in turbidity over time, during crystal nucleation, growth and aggregation, in the metastable solution of calcium chloride and sodium oxalate. The slope from the change in turbidity over time was measured using a spectrophotometer at 620 and 214 nm in respective tests. The inhibition rate was estimated by comparing turbidity in the presence and absence of extract. Crystals formed under experimental conditions were observed under a light microscope, and number and shape of the crystals were assessed in a randomly selected field. Phytochemical analysis and high-performance thin-layer chromatography of the extract was also carried out. Results: C. zeylanicum significantly reduced crystal nucleation at concentrations of 4, 8 and 10 mg/mL (P< 0.001). The inhibition percentage of crystal growth was between 28.30% and 92.46% in the presence of C. zeylanicum extract and from 20.76% to 64.15% with various concentrations of Cystone. The maximum inhibition of crystal growth was obtained from C. zeylanicum at 2 mg/mL (92.46%). Microscopic examination revealed a reduction in the number and size of crystals. In the aggregation assay, the inhibition percentage of C. zeylanicum was between 16.27% and 100%, while Cystone was from -214.68% to 100% at different concentrations. The highest (100%) inhibition of aggregation was found at 4 mg/mL of both the test and standard drugs. Conclusion: We found that C. zeylanicum hydro-alcoholic extract has notable inhibitory effects on various stages of crystallization, in terms of turbidity of solution, as well as the crystal size, number and morphology. 展开更多
关键词 Antilithiatic ACTIVITY Calcium OXALATE Inorganic inhibitors In VITRO UNANI medicine
Calcium channel blocker monotherapy versus combination with reninangiotensin system inhibitors on the development of new-onset diabetes mellitus in hypertensive Korean patients 预览
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作者 Yong Hoon Kim Ae-Young Her +16 位作者 Seung-Woon Rha Byoung Geol Choi Se Yeon Choi Jae Kyeong Byun Yoonjee Park Dong Oh Kang Won Young Jang Woohyeun Kim Woong Gil Choi Tae Soo Kang Jihun Ahn Sang-Ho Park Ji Young Park Min-Ho Lee Cheol Ung Choi Chang Gyu Park Hong Seog Seo 《老年心脏病学杂志:英文版》 SCIE CAS CSCD 2019年第6期439-447,共9页
Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibi... Background In real practice, two or more antihypertensive drugs are needed to achieve target blood pressure. We investigated the comparative beneficial actions of combination therapy of renin-angiotensin system inhibitors (RASI), with calcium channel blockers (CCB) over CCB monotherapy on the development of new-onset diabetes mellitus (NODM) in Korean patients during four-year follow-up periods. Methods A total of 3208 consecutive hypertensive patients without a history of diabetes mellitus who had been prescribed CCB were retrospectively enrolled from January 2004 to December 2012. These patients were divided into the two groups according to the additional use of RASI (the RASI group, n = 1221 and the no RASI group, n = 1987). Primary endpoint was NODM, defined as a fasting blood glucose ≥ 126 mg/dL or hemoglobin A1c ≥ 6.5%. Secondary endpoint was major adverse cardiac events (MACE) defined as total death, myocardial infarction (MI) and percutaneous coronary intervention (PCI). Results After propensity score-matched (PSM) analysis, two propensity- matched groups (939 pairs, n = 1878, C-statistic = 0.743) were generated. The incidences of NODM (HR = 1.009, 95% CI: 0.700–1.452, P = 0.962), MACE (HR = 0.877, 95% CI: 0.544–1.413, P = 0.589), total death, MI, PCI were similar between the two groups after PSM during four years. Conclusions The use of RASI in addition to CCB showed comparable incidences of NODM and MACE compared to CCB monotherapy in non-diabetic hypertensive Korean patients during four-year follow-up period. However, large-scaled randomized controlled clinical trials will be required for a more definitive conclusion. 展开更多
关键词 Calcium channel BLOCKER Diabetes mellitus RENIN-ANGIOTENSIN system INHIBITORS
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适用于页岩气井的水基钻井液技术研究 预览
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作者 郭胜芳 《石化技术》 CAS 2019年第7期132-133,共2页
通过分析页岩水基钻井液存在的施工难点问题,开展了页岩气水基钻井液体系研究,优选了抑制剂、润滑剂以及降滤失剂,得到了适用于页岩气井的水基钻井液体系配方。
关键词 页岩气 水基钻井液 环保 抑制剂
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3D-QSAR and Surflex Docking Studies of a Series of Alkaline Phosphatase Inhibitors 预览
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作者 舒茂 武涛 +3 位作者 王必武 李静 徐春媚 林治华 《结构化学》 SCIE CAS CSCD 2019年第1期7-16,1共11页
Alkaline phosphatases(APs) include the placental AP(PLAP), germ cell AP(GCAP), intestinal AP(IAP) and tissue nonspecific AP(TNAP). Over expression of TNAP in smooth muscle cells of kidney and vessels provokes the prog... Alkaline phosphatases(APs) include the placental AP(PLAP), germ cell AP(GCAP), intestinal AP(IAP) and tissue nonspecific AP(TNAP). Over expression of TNAP in smooth muscle cells of kidney and vessels provokes the progress of such serious diseases as end-stage renal disease, idiopathic infantile arterial calcification, ankylosis, osteoarthritis and diabetes. In order to design and optimize the potent TNAP inhibitors, comparative molecular field analysis(CoMFA) and comparative molecular similarity indices analysis(CoMSIA) were used to analyze 3D structure-activity relationships(3D-QSAR) of TNAP inhibitors. The 3D-QSAR model(CoMFA with q^2 = 0.521, r^2 = 0.930;CoMSIA with q^2 = 0.529, r^2 = 0.933) had a good predictability. Surflex-dock was used to reveal the binding mode between the inhibitors and TNAP protein. CoMFA, CoMSIA and docking results provide guidance for the discovery of TNAP inhibitors. Finally, eight new compounds as potential TNAP inhibitors were designed. 展开更多
关键词 3D-QSAR surflex-dock ALKALINE PHOSPHATASE INHIBITORS
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Purification and characterization of a novel anti-coagulant from the leech Hirudinaria manillensis
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作者 Ruo-Mei Cheng Xiao-Peng Tang +5 位作者 Ai-Lin Long James Mwangi Ren Lai Rui-Pu Sun Cheng-Bo Long Zhen-Qing Zhang 《动物学研究》 CAS CSCD 2019年第3期205-210,共6页
Protease inhibitors have been reported rarely from the leech Hirudinaria manillensis.In this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from H.manillensis.With a molecular ... Protease inhibitors have been reported rarely from the leech Hirudinaria manillensis.In this study,we purified a novel protease inhibitor(bdellin-HM-2)with anticoagulant properties from H.manillensis.With a molecular weight of 1.4x104,bdellin-HM-2 was also characterized with three intra?molecular disulfide bridges at the N-terminus and multiple HHXDD and HXDD motifs at theC-terminus.cDNAcloning revealed that the putative nucleotide-encoding protein of bdellin-HM-2 contained 132 ami no acids and was encoded by a 399 bp open reading frame(ORF).Sequence alignment showed that bdellin-HM-2 shared similarity with the“non-classical"Kazal-type serine protease inhibitors,but had no inhibitory effect on trypsin,elastase,chymotrypsin,kallikrein,factor Xlla(FXIIa),factor Xia(FXIa),factor Xa(FXa),thrombin,or plasmin.Bdellin-HM-2 showed anticoagulant effects by proIonging the activated partial thromboplastin time(aPTT),indicating a role in enabling H.manillensis to obtain a blood meal from its host.Our results suggest that bdellin-HM丒2 may play a crucial role in blood-sucking in this leech species and may be a pote ntial can didate for the development of clinical anti-thrombotic drugs. 展开更多
关键词 Hirudinaria manillensis Bdellin-HM-2 "Non-classical"Kazal INHIBITORS Blood SUCKING ANTICOAGULANT Anti-thrombotic drugs
Comprehensive 3D-QSAR and Binding Mode of DAPY Inhibitors Using R-group Search and Molecular Docking 预览
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作者 仝建波 王洋 +1 位作者 雷珊 秦尚尚 《结构化学》 SCIE CAS CSCD 2019年第1期25-36,1共13页
The diarylpyrimidine(DAPY) compounds are important in the nonnucleoside reverse enzyme inhibitors. The present study is aimed at studying the three-dimensional quantitative structure-activity relationship(3D-QSAR) of ... The diarylpyrimidine(DAPY) compounds are important in the nonnucleoside reverse enzyme inhibitors. The present study is aimed at studying the three-dimensional quantitative structure-activity relationship(3D-QSAR) of DAPY inhibitors and their binding mode. We build a 3D-QSAR model involving 24 training DAPY inhibitors based on Topomer CoMFA, and 8 molecules are employed to validate the external predictive power of the model obtained. The multiple correlation coefficients of fitting, cross-validation and external validation were 0.979, 0.597 and 0.756, respectively. Topomer Search was employed as a tool for virtual screening in drug-like compounds of ZINC database(2012). Finally, we successfully design 30 new molecules with higher activity than that of all training and test inhibitors. The results indicated that Topomer CoMFA model had both favorable estimation stability and good predictive capability. Topomer Search technology could be effectively used to screen and design new compound, and had good predictive capability to guide the design of new Anti-HIV drugs. The molecular docking method was also used to study the interactions of these drugs by docking the ligands into HIV-1 reverse transcriptase active site, which revealed the likely bioactive conformations. This study showed extensive interactions between the DAPY derivatives and MET230, TRP229, PHE227, TYR318, TYR183, PRO95, GLY99, ILE100,TYR188, VAL106, TYR181, GLY190, GLU138, VAL179, THR139, ASN103 and LYS101 residues in the active site of HIV-1 reverse transcriptase. These results provide useful insights for the design of potent new inhibitors of HIV-1 reverse transcriptase. 展开更多
关键词 3D-QSAR DAPY INHIBITORS Topomer COMFA Topomer SEARCH molecular DOCKING
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Prevention of macrovascular complications in patients with type 2 diabetes mellitus: Review of cardiovascular safety and efficacy of newer diabetes medications 预览
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作者 Ravi Kant Kashif M Munir +1 位作者 Arshpreet Kaur Vipin Verma 《世界糖尿病杂志:英文版(电子版)》 2019年第6期324-332,共9页
Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized cont... Lack of conclusive beneficial effects of strict glycemic control on macrovascular complications has been very frustrating for clinicians involved in care of patients with diabetes mellitus (DM). Highly publicized controversy surrounding cardiovascular (CV) safety of rosiglitazone resulted in major changes in United States Food and Drug Administration policy in 2008 regarding approval process of new antidiabetic medications, which has resulted in revolutionary data from several large CV outcome trials over the last few years. All drugs in glucagon-like peptide-1 receptor agonist (GLP-1 RA) and sodium-glucose cotransporter-2 (SGLT-2) inhibitor classes have shown to be CV safe with heterogeneous results on CV efficacy. Given twofold higher CV disease mortality in patients with DM than without DM, GLP-1 RAs and SGLT-2-inhibitors are important additions to clinician’s armamentarium and should be second line-therapy particularly in patients with T2DM and established atherosclerotic CV disease or high risks for CV disease. Abundance of data and heterogeneity in CV outcome trials results can make it difficult for clinicians, particularly primary care physicians, to stay updated with all the recent evidence. The scope of this comprehensive review will focus on all major CV outcome studies evaluating CV safety and efficacy of GLP-1 RAs and SGLT-2 inhibitors. 展开更多
关键词 Newer antidiabetic MEDICATIONS Glucagon-like peptide-1 receptor agonist Sodium-glucose cotransporter-2 inhibitors Type 2 DIABETES MELLITUS Macrovascular complications CARDIOVASCULAR outcome trials Major CARDIOVASCULAR events HEART failure PREVENTION of HEART disease
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