Pharmacophore-based drug design for potential AChE inhibitors from Traditional Chinese Medicine Database

Alzheimer's disease (AD) is a neurodegenerative disorder. Substrate-specific Acetylcholinesterase (AChE) plays a vital role in the AD treatment. Flavonoids with AChE inhibitory activities and low toxicity are used to developing new anti-AD agents. In this study, the best 3D QSAR pharmacophore model Hypo1 was generated by HypoGen program in Discovery Studio2016 based on the training set of flavonoids. We performed a virtual screening from Traditional Chinese Medicine (TCM), Druglike and MiniMaybridge databases using Hypo1. From docking analyses, we got the top 10 AChE inhibitors which were further evaluated by 8 different scoring functions. De Novo Evolution designed the top 10 derivatives, and three potential AChE inhibitor candidates were obtained eventually.     

Virtual Screening and Drug Design for PDE-5 Receptor from Traditional Chinese Medicine Database

Abstract

Erectile dysfunction (ED) is a sexual disorder mainly caused by decrease in cellular concentration of cyclic guanosine monophosphate (cGMP), which is degraded by phosphodiesterase type-5 (PDE-5). As a potent therapeutic target, inhibitors such as Viagra®, Cialis®, and Levitra® have already been developed to target PDE-5 for treating ED; traditional Chinese medicine, Epimedium sagittatum, also has shown prominent results as well. To developed new PDE-5 inhibitors, we performed a virtual screening of traditional Chinese medicine (TCM) database and docking analyses to identify candidates. Known PDE-5 inhibitors were used to construct a three dimensional quantitative structure-activity relationship (3D QSAR) model by HypoGen program. From docking analyses, isochlorogenic acid b was identified as the most potential inhibitory compound. De novo evolution designed 47 derivatives. Of the 47 derivatives, seven were able to map into the pharmacophore model, and these seven compounds were suggested to be the most promising leads for inhibiting PDE-5. An analysis of the hydrogen bond interactions formed between the docked ligands and PDE-5 identified ASN662, SER663 and GLN817 as the most frequently interacting residues. A total of eight novel leading compounds were identified to have favorable interaction with PDE-5. These compounds all had hydrogen bond interactions with three key residues that could be further investigated for understanding of PDE-5 and ligands interaction.     

DIACAN: Integrated Database for Antidiabetic and Anticancer Medicinal Plants

Medicinal plants and plant derived molecules are widely used in traditional cultures all over the world and they are becoming large popular among biomedical researchers and pharmaceutical companies as a natural alternative to synthetic medicine. Information related to medicinal plants and herbal drugs accumulated over the ages are scattered and unstructured which make it prudent to develop a curated database for medicinal plants. The Antidiabetic and Anticancer Medicinal Plants Database (DIACAN) aims to collect and provide an integrated platform for plants and phytochemiclas having antidiabetic or anticancer activity.

Availability

http://www.kaubic.in/diacan     

pDAWG: An Integrated Database for Plant Cell Wall Genes

We have recently developed a database, pDAWG, focused on information related to plant cell walls. Currently, pDAWG contains seven complete plant genomes, 12 complete algal genomes, along with computed information for individual proteins encoded in these genomes of the following types: (a) carbohydrate active enzyme (CAZy) family information when applicable; (b) phylogenetic trees of cell wall-related CAZy family proteins; (c) protein structure models if available; (d) physical and predicted interactions among proteins; (e) subcellular localization; (f) Pfam domain information; and (g) homology-based functional prediction. A querying system with a graphical interface allows a user to quickly compose information of different sorts about individual genes/proteins and to display the composite information in an intuitive manner, facilitating comparative analyses and knowledge discovery about cell wall genes. pDAWG can be accessed at http://csbl1.bmb.uga.edu/pDAWG/.     

DAVID: Database for Annotation,Visualization, and Integrated Discovery

The distributed nature of biological knowledge poses a major challenge to the interpretation of genome-scale datasets, including those derived from microarray and proteomic studies. This report describes DAVID, a web-accessible program that integrates functional genomic annotations with intuitive graphical summaries. Lists of gene or protein identifiers are rapidly annotated and summarized according to shared categorical data for Gene Ontology, protein domain, and biochemical pathway membership. DAVID assists in the interpretation of genome-scale datasets by facilitating the transition from data collection to biological meaning.     

中药网络药理学研究中的生物信息学方法

为了更有效地治疗癌症、心血管疾病、免疫系统疾病等复杂疾病,基于分子网络的多靶点药物发现理念逐渐成为一种新的趋势,而中药整体、辨证、协同的用药观再一次引起了药物发现领域的极大兴趣。中药在治疗复杂慢性疾病方面有确切的疗效和较小的毒副作用。中药网络药理学从分子网络调控的水平上阐明中药的作用机制,为多靶点药物发现提供有益的启示和借鉴,并有可能从临床有效的中药反向开发现代多组分、多靶点新药。针对基于生物分子网络的中药药理学研究路线中的4 个步骤,介绍近年来中药网络药理学研究中相关的生物信息学方法。     

中西医结合治疗慢性盆腔炎102 例临床观察

目的：观察中西医结合治疗慢性盆腔炎的临床疗效．方法：将102例患者随机分为2组,治疗组52例,中药＋抗生素治疗;对照组50例;用抗生素治疗。两组均治疗10天为1个疗程。结果：治疗组总有效率86．54％;对照组总有效率50．00％（两组总有效率比较,差异有显著性意义（P〈0．05）。结论：中西医结合治疗慢性盆腔炎疗效显著。     

BGVD:An Integrated Database for Bovine Sequencing Variations and Selective Signatures

Next-generation sequencing has yielded a vast amount of cattle genomic data for global characterization of population genetic diversity and identification of genomic regions under natural and artificial selection. However, efficient storage, querying, and visualization of such large datasets remain challenging. Here, we developed a comprehensive database, the Bovine Genome Variation Database (BGVD). It provides six main functionalities: gene search, variation search, genomic signature search, Genome Browser, alignment search tools, and the genome coordinate conversion tool. BGVD contains information on genomic variations comprising ~60.44 M SNPs, ~6.86 M indels, 76,634 CNV regions, and signatures of selective sweeps in 432 samples from modern cattle worldwide. Users can quickly retrieve distribution patterns of these variations for 54 cattle breeds through an interactive source of breed origin map, using a given gene symbol or genomic region for any of the three versions of the bovine reference genomes (ARS-UCD1.2, UMD3.1.1, and Btau 5.0.1). Signals of selection sweep are displayed as Manhattan plots and Genome Browser tracks. To further investigate and visualize the relationships between variants and signatures of selection, the Genome Browser integrates all variations, selection data, and resources, from NCBI, the UCSC Genome Browser, and Animal QTLdb. Collectively, all these features make the BGVD a useful archive for in-depth data mining and analyses of cattle biology and cattle breeding on a global scale. BGVD is publicly available at http://animal.nwsuaf.edu.cn/BosVar.     

BIND: the Biomolecular Interaction Network Database

The Biomolecular Interaction Network Database (BIND: http://bind.ca) archives biomolecular interaction, complex and pathway information. A web-based system is available to query, view and submit records. BIND continues to grow with the addition of individual submissions as well as interaction data from the PDB and a number of large-scale interaction and complex mapping experiments using yeast two hybrid, mass spectrometry, genetic interactions and phage display. We have developed a new graphical analysis tool that provides users with a view of the domain composition of proteins in interaction and complex records to help relate functional domains to protein interactions. An interaction network clustering tool has also been developed to help focus on regions of interest. Continued input from users has helped further mature the BIND data specification, which now includes the ability to store detailed information about genetic interactions. The BIND data specification is available as ASN.1 and XML DTD.     

YPED:An Integrated Bioinformatics Suite and Database for Mass Spectrometry-based Proteomics Research

We report a significantly-enhanced bioinformatics suite and database for proteomics research called Yale Protein Expression Database(YPED) that is used by investigators at more than 300 institutions worldwide. YPED meets the data management, archival, and analysis needs of a high-throughput mass spectrometry-based proteomics research ranging from a singlelaboratory, group of laboratories within and beyond an institution, to the entire proteomics community. The current version is a significant improvement over the first version in that it contains new modules for liquid chromatography–tandem mass spectrometry(LC–MS/MS) database search results, label and label-free quantitative proteomic analysis, and several scoring outputs for phosphopeptide site localization. In addition, we have added both peptide and protein comparative analysis tools to enable pairwise analysis of distinct peptides/proteins in each sample and of overlapping peptides/proteins between all samples in multiple datasets. We have also implemented a targeted proteomics module for automated multiple reaction monitoring(MRM)/selective reaction monitoring(SRM) assay development. We have linked YPED's database search results and both label-based and label-free fold-change analysis to the Skyline Panorama repository for online spectra visualization. In addition, we have built enhanced functionality to curate peptide identifications into an MS/MS peptide spectral library for all of our protein database search identification results.     

中西医结合治疗功能性消化不良的临床分析

目的:探讨中西医结合治疗功能性消化不良的临床疗效。方法:对228例的功能性消化不良患者给予中西医结合治疗,并与120例西医治疗的患者进行疗效对照。结果:中西医结合组与对照组显效率和总有效率分别为1.3%和22.5%、97.8%和71.7%,均有显著性差异(P<0.05)两组患者都没有发生严重的不良反应。结论:中西医结合辨证治疗疗效显著,值得临床推广。     

中西医结合治疗功能性消化不良的临床分析

目的：探讨中西医结合治疗功能性消化不良的临床疗效。方法：对228例的功能性消化不良患者给予中西医结合治疗,并与120例西医治疗的患者进行疗效对照。结果：中西医结合组与对照组显效率和总有效率分别为1.3％和22．5％、97．8％和71．7％,均有显著性差异（P〈0．05）两组患者都没有发生严重的不良反应。结论：中西医结合辨证治疗疗效显著,值得临床推广。     

中西医结合治疗胆汁返流性胃炎的观察

目的：探讨中西医结合在胆汁反流性胃炎治疗中的应用及疗效。方法：将64例胆汁反流性胃炎患者随机平均分为对照组和观察组,对照组采用多潘立酮和铝碳酸镁进行治疗,观察组在对照组的基础上加用中药大柴胡汤,疗程为6周。观察治疗后患者主要症状改善情况和胃镜下表现情况,并行疗效比较。结果：观察组患者上腹痛、恶心、胃内胆汁、胃黏膜充血、胃黏膜糜烂等症状的改善率高于对照组（P〈0．05）;观察组治愈14例、显效9例、有效6例、无效3例,疗效优于对照组,差异有显著性（Z=2．864,P〈0．01）。结论：中西医结合是治疗胆汁反流性胃炎的有效治疗方案,建议临床推广应用。     

中西医结合治疗膜性肾病的疗效及机制研究

摘要 目的：探究中西医结合对膜性肾病的治疗效果,并就其机制进行研究。方法：选择2015年12月至2019年12月于我院接受治疗的98例肾病综合征患者,按照随机数字表法将其均分为研究组与对照组（每组各49例）,对照组接受常规西医治疗,研究组在对照组基础上加用中医疗法,对比两组治疗有效率,分别检测并对比治疗前后两组免疫球蛋白A（immunoglobulin A,IgA）、免疫球蛋白G（immunoglobulin G,IgG）、免疫球蛋白M（immunoglobulin M,IgM）、蛋白排泄率（urinary albumin excretion rates,UAER）、血浆白蛋白（albumin,Alb）、尿素氮（blood urea nitrogen,BUN）、血肌酐（serum creatinine,Scr）等指标,并就治疗安全性进行对比。结果：（1）研究组治疗有效率显著高于对照组（95.92 % vs. 81.63 %,P<0.05）;（2）治疗前两组IgA、IgG、IgM水平对比无统计学意义（P>0.05）,干预后研究组上述指标均优于对照组（P<0.05）;（3）治疗前两组UAER、Alb、BUN及Scr水平对比无统计学意义（P>0.05）,治疗后研究组上述指标均优于对照组（P<0.05）;（4）研究组治疗中不良反应发生率低于对照组（P<0.05）。结论：中西医结合疗法对膜性肾病具有较好的治疗效果,能够显著改善患者免疫功能及肝肾功能,同时还能够降低治疗中不良反应发生率。     

中西医结合治疗消化性溃疡并H.yilori感染的效果分析

目的：研究消化性溃疡并幽门螺杆菌(H3pylori )感染初治失败患者血浆网膜素-1 (Omentin-1)水平的变化及中西医结合干预 治疗的效果。方法：选择2011 年9 月～2015 年9 月在我院进行诊治的消化性溃疡患者82 例观察组,采用阿莫西林,奥美拉唑、拉 霉素和清幽口服液等中西医结合治疗,并选择20 例健康体检者为对照组。采用ELISA 法检测血浆Omentin-1 水平,分析血浆 Omentin-1 水平与一氧化氮（NO）、白细胞介素-2（IL-2）、内皮素-1(ET-1)、肿瘤坏死因子alpha（TNF-alpha）的关系。观察中西医结合治疗 前后病例组血浆Omentin-1 水平的变化并评价根除的疗效及安全性。结果：进行中西医结合治疗后, H.pylori根除率达 88.6%;有34 例溃疡痊愈,22 例显效,33 例有效,3 例无效,愈合率为68.29% (56 /82),有效率为96.34% (79/82);观察组血浆 Omentin-1 水平为(18.15 ± 3.96) ng/mL,明显低于对照组的(23.12 ± 6.03) ng /mL(P<0.05);与对照组相比,观察组的NO、IL-2 水 平明显降低(P<0.05),ET-1,TNF-alpha和IL-6 水平明显升高(P<0.05);与治疗前相比,经中西医结合治疗后NO、IL-2 水平明显降低 (P<0.05),ET-1,TNF-琢和IL-6 水平明显升高(P<0.05);观察组血浆Omentin-1 与IL-2、NO 呈明显正相关( r = 0.412,P<0.05 和r = 0.382,P<0.05),与IL-6 和TNF-琢呈明显负相关( r =-0.246,P<0.05 和r = -0.258,P<0.05)。结论：中西医结合治疗能升高血浆 Omentin-1 水平,有效提高溃疡愈合率及H.pylori根除率,抑制炎性因子的分泌,增强内源性NO保护作用和机体免疫功能。