Arbuscular mycorrhizal symbiosis and active ingredients of medicinal plants: current research status and prospectives

Medicinal plants have been used world-wide for thousands of years and are widely recognized as having high healing but minor toxic side effects. The scarcity and increasing demand for medicinal plants and their products have promoted the development of artificial cultivation of medicinal plants. Currently, one of the prominent issues in medicinal cultivation systems is the unstable quality of the products. Arbuscular mycorrhiza (AM) affects secondary metabolism and the production of active ingredients of medicinal plants and thus influence the quality of herbal medicines. In this review, we have assembled, analyzed, and summarized the effects of AM symbioses on secondary metabolites of medicinal plants. We conclude that symbiosis of AM is conducive to favorable characteristics of medicinal plants, by improving the production and accumulation of important active ingredients of medicinal plants such as terpenes, phenols, and alkaloids, optimizing the composition of different active ingredients in medicinal plants and ultimately improving the quality of herbal materials. We are convinced that the AM symbiosis will benefit the cultivation of medicinal plants and improve the total yield and quality of herbal materials. Through this review, we hope to draw attention to the status and prospects of, and arouse more interest in, the research field of medicinal plants and mycorrhiza.     

Phenotypic Heterogeneity Generated by Histidine Kinase-Based Signaling Networks

A complex relationship exists between environmental factors, signaling networks and phenotypic individuality in bacteria. In this review, we will focus on the organization, function and control points of multiple-input histidine kinase-based signaling cascades as a source of phenotypic heterogeneity. In particular, we will examine the quorum sensing cascade in Vibrio harveyi and the pyruvate sensor network in Escherichia coli. We will describe and compare these histidine kinase-based signaling networks in terms of robustness, the molecular mechanisms of signal transduction and the role of RNA switches. Finally, we will discuss the biological significance of phenotypic heterogeneity for the respective bacteria in relation to environmental factors.     

药用植物资源在水产动物疾病控制中的研究进展*

随着生活水平的不断提高,人们对水产品的需求量日益增加,水产养殖业得到飞速发展。然而,各种寄生虫、细菌和病毒诱发的疾病给水产养殖业造成了巨大的经济损失,严重制约了水产养殖业的快速稳定发展。作为传统的防治手段,抗生素等化学合成药物常用于水产养殖过程。大量化学合成药物的滥用诱发了药物残留、耐药菌等环境污染问题,危害人类健康。因此,具有多种有效活性成分的中草药因其天然、安全、副作用小等原因,成为探索新型防控水产病害暴发手段的研究对象。当前,中草药常被用于调节水产动物的免疫力、生长速度和预防疾病暴发等。同时,中草药还可用于改善养殖环境,降低环境因子对水产动物的胁迫。然而,目前的研究主要集中在从中草药中获取防控疾病暴发的复合有效成分,存在药效不稳定、活性成分不明确等问题,无法满足生产高效、廉价、稳定防治剂的需求。论述了当前中草药在防控水产动物疾病暴发中的应用及其作用机制,揭示了对中草药活性分子作用机制研究的不足,强调了中草药作为一种更环保、更有效的水产养殖疾病防控手段进行应用的潜力,对其抗病机制的深入研究尤为重要。     

Management of cytoskeleton architecture by molecular chaperones and immunophilins

Cytoskeletal structure is continually remodeled to accommodate normal cell growth and to respond to pathophysiological cues. As a consequence, several cytoskeleton-interacting proteins become involved in a variety of cellular processes such as cell growth and division, cell movement, vesicle transportation, cellular organelle location and function, localization and distribution of membrane receptors, and cell-cell communication. Molecular chaperones and immunophilins are counted among the most important proteins that interact closely with the cytoskeleton network, in particular with microtubules and microtubule-associated factors. In several situations, heat-shock proteins and immunophilins work together as a functionally active heterocomplex, although both types of proteins also show independent actions. In circumstances where homeostasis is affected by environmental stresses or due to genetic alterations, chaperone proteins help to stabilize the system. Molecular chaperones facilitate the assembly, disassembly and/or folding/refolding of cytoskeletal proteins, so they prevent aberrant protein aggregation. Nonetheless, the roles of heat-shock proteins and immunophilins are not only limited to solve abnormal situations, but they also have an active participation during the normal differentiation process of the cell and are key factors for many structural and functional rearrangements during this course of action. Cytoskeleton modifications leading to altered localization of nuclear factors may result in loss- or gain-of-function of such factors, which affects the cell cycle and cell development. Therefore, cytoskeletal components are attractive therapeutic targets, particularly microtubules, to prevent pathological situations such as rapidly dividing tumor cells or to favor the process of cell differentiation in other cases. In this review we will address some classical and novel aspects of key regulatory functions of heat-shock proteins and immunophilins as housekeeping factors of the cytoskeletal network.     

脂肪组织中的miRNAs研究进展

miRNA是近年来发现的一类长约22 nt的内源性非编码RNA,在动物中主要通过抑制靶mRNA翻译,在转录后水平调控基因表达。大量研究表明脂肪组织中的miRNAs参与了脂肪细胞分化、脂代谢等多种生物过程调控,其自身也受到转录因子、脂肪细胞因子和环境因子等调控,这些复杂的相互作用关系构成了脂肪组织中miRNA的调控网络,循环miRNA的发现为这个网络加入了新元素。对肥胖等代谢疾病的研究,应该从这个复杂的动态网络中寻找答案。文中综述了脂肪组织中miRNA的最新研究进展,以期为利用miRNA进行肥胖等相关代谢失调疾病的治疗提供新思路。     

A review on potentiality of medicinal plants as the source of new contraceptive principles.

Recently, a review has already been made on the synthetic contraceptive agents whereas this review embraces the natural contraceptives upto year 2001 with 355 references. It also includes the isolation of their active principles, methods of analysis of active ingredients through TLC, HPLC, their side effects and pharmacological action.     

Drivers shaping the diversity and biogeography of total and active bacterial communities in the South China Sea

To test the hypothesis that different drivers shape the diversity and biogeography of the total and active bacterial community, we examined the bacterial community composition along two transects, one from the inner Pearl River estuary to the open waters of the South China Sea (SCS) and the other from the Luzon Strait to the SCS basin, using 454 pyrosequencing of the 16S rRNA and 16S rRNA gene (V1‐3 regions) and thereby characterizing the active and total bacterial community, respectively. The diversity and biogeographic patterns differed substantially between the active and total bacterial communities. Although the composition of both the total and active bacterial community was strongly correlated with environmental factors and weakly correlated with geographic distance, the active bacterial community displayed higher environmental sensitivity than the total community and particularly a greater distance effect largely caused by the active assemblage from deep waters. The 16S rRNA vs. rDNA relationships indicated that the active bacteria were low in relative abundance in the SCS. This might be due to a high competition between active bacterial taxa as indicated by our community network models. Based on these analyses, we speculate that high competition could cause some dispersal limitation of the active bacterial community resulting in a distinct distance‐decay relationship. Altogether, our results indicated that the biogeographic distribution of bacteria in the SCS is the result of both environmental control and distance decay.     

基于HPLC-Q-TOF-MS/MS技术的蒲公英化学成分分析及其抗癌机制的网络药理学研究

为了探究蒲公英主要成分,分析其抗癌的可能机制及作用靶点,借助HPLC-Q-TOF-MS/MS技术对蒲公英提取物进行分析,利用SwissADME、Swiss Target Prediction和GeneCards数据库获取蒲公英主要活性成分和抗癌的作用靶点,通过String在线数据库构建靶蛋白相互作用网络,并利用DVIAD在线数据库对关键靶点进行GO和KEGG富集分析。最终从蒲公英提取物中共鉴定出29个化合物,主要包括有机酸类、黄酮类等化学成分,筛选到10个活性成分,成分-疾病的共同靶点84个。网络分析显示,主要活性成分为槲皮素、木犀草素、芹菜素等,关键靶点为AKT1、EGFR、SRC、ESR1、PTGS2、MMP9、KDR、MMP2、PIK3R1,并且涉及氧化-还原、负调控凋亡、蛋白质自磷酸化、ATP结合、蛋白激酶活性、蛋白丝氨酸/苏氨酸激酶活性、酶结合等过程,和癌症通路、癌症蛋白聚糖、PI3K-Akt信号通路等通路。综上,蒲公英是通过多成分、多靶点、多途径来发挥抗癌作用的。     

植物提取物及其活性成分抑制细菌生物被膜的研究进展北大核心CSCD

大量研究报道生物被膜细菌对抗生素的耐药性是浮游菌的10–1 000倍,据报道细菌生物被膜是80%以上细菌感染的罪魁祸首,对医疗保健领域构成了严峻的挑战。植物提取物及其活性成分对细菌生物被膜有明显的抑制作用,包括减少生物被膜量、生物被膜活菌数以及清除已经成熟的生物被膜等。该文对这些有效的植物提取物及其活性成分进行了总结,并分析了其抗细菌生物被膜的作用机制。旨在为防治细菌生物被膜感染的植物类药物的开发提供参考。     

Wild aromatic plants bioactivity: a function of their (poly)phenol seasonality? A case study from Mediterranean area

Wild medicinal and aromatic plants are in the market as herbal raw or processed and packaged materials, playing, even today, a strategic role in the production of plant-based products. Indeed, their content in active ingredients, mainly specialized secondary metabolites, is not constant; it undergoes significant seasonal variations, as abiotic stress heavily affects secondary metabolism network. The present review deals with the seasonality influence on the polyphenolic composition on antioxidant and anti-inflammatory properties of medicinal and aromatic plants. To this aim, firstly the factors influencing the content of active ingredients in a plant drug will be discussed, and, in particular, the increased occurrence of phenols as a response to abiotic stress. In the last part of the review a brief reference will be made to four meaningful case studies, which involve wild medicinal aromatic herbs, native to the Mediterranean area: Calamintha nepeta L. Savi, Foeniculum vulgare Mill., Ruta graveolens L. and Thymus longicaulis C. Presl. These species, grown in the same geographical area and collected at the same harvesting time, showed a great variability in phenol constituents throughout the year. The comparison among data acquired clearly evidences that the seasonal variation in polyphenols’ occurrence and amount leads to a more/less pronounced antioxidant and anti-inflammatory activity of the hydroalcoholic extract therefrom. It is worth of note that the presence of the same metabolite, but in different phytochemical complexes, could result in different biological activities.     

Environmental impact of adjuvants in crop protection

The overall performance of chemical and biological plant protection products is enhanced by the use of adjuvants in the formulation (formulation adjuvants) or in the spray tank (spray adjuvants). Both types of adjuvants aim to stabilize the formulation, to improve the efficiency of the active ingredients and to reduce application and environmental risks. As an important part of the formulation, both quantitatively and qualitatively, the environmental impact and toxicology of adjuvants can not always be considered as inert. However, little is known of their impact as part of plant protection products compared with the active substances. Therefore an experimental framework is needed as a tool for a consistent environmental legislation.     

Active Ingredients and Anti‐Arthritic Mechanisms of Ba‐Wei‐Long‐Zuan Granule Revealed by 1H‐NMR‐Based Metabolomics Combined with Network Pharmacology Analysis

Ba‐Wei‐Long‐Zuan granule (BWLZ) is a traditional herbal preparation. It has been widely used for the treatment of rheumatoid arthritis (RA). However, its active ingredients and mechanisms of action are still unclear. The present study aims to reveal the active compounds and anti‐arthritic mechanisms of BWLZ against collagen‐induced arthritis (CIA) by using ¹H‐NMR‐based metabolomics, molecular docking and network pharmacology methods. After 30 days of administration, BWLZ could effectively improve the metabolic disorders in CIA rats. The anti‐arthritic effect of BWLZ was related to its restoration of 16 disturbed serum metabolites. Molecular docking and network analysis showed that 20 compounds present in BWLZ could act on multiple targets. Among them, coclaurine and hesperidin showed the highest hit rates for target proteins related to both metabolic regulation and RA, indicating that these two compounds might be potential active ingredients of BWLZ. Moreover, pathway enrichment analysis suggested that the anti‐arthritic mechanisms of BWLZ might be attributed to its network regulation of several biological processes, such as steroid hormone biosynthesis, mTOR signaling pathway, alanine, aspartate and glutamate metabolism, and synthesis and degradation of ketone bodies. These results provide further evidence for the anti‐arthritic properties of BWLZ and are beneficial for its quality control and clinical application. The potential targets and biological processes found in this study may provide valuable information for further studying the molecular mechanisms of BWLZ against RA. In addition, our work provides new insights for revealing the active ingredients and regulatory mechanisms of complex herbal preparations.     

Regulatory demands for biocides today and in the 1990s

This paper will review the regulatory requirements for the introduction of new substances in Europe and illustrate where differences exist in USA and Japan.Registration requirements, which exist in every member state of the EEC for each type of application for new formulations using existing or new biocide active ingredients, will be described with examples. Proposed EEC directives which affect the use of biocide active ingredients will also be described.The impact of the Preparations Directive for formulations containing biocides will be discussed.     

Scientific basis for uncertainty factors used to establish occupational exposure limits for pharmaceutical active ingredients

The traditional “safety factor”; method has been used for years to establish occupational exposure limits (OELs) for active ingredients used in drugs. In the past, a single safety factor was used to address all sources of uncertainty in the limit setting process. The traditional 100‐fold safety factor commonly used to derive an acceptable daily intake value incorporates a default factor of 10 each to account for interindividual variability and interspecies extrapolation. Use of these defaults can lead to overly conservative health‐based limits, especially when they are combined with other (up to 10‐fold) factors to adjust for inadequacies in the available database. In recent years, attempts have been made to quantitate individual sources of uncertainty and variability to improve the scientific basis for OELs. In this paper we discuss the science supporting reductions in the traditional default uncertainty factors. A number of workplace‐specific factors also support reductions in these factors. Recently proposed alternative methodologies provide a framework to make maximum use of preclinical and clinical information, e.g., toxicokinetic and toxicodynamic data, to reduce uncertainties when establishing OELs for pharmaceutical active ingredients.     

On your mark, get set: brainstem circuitry underlying saccadic initiation

Saccades are rapid eye movements that are used to move the visual axis toward targets of interest in the visual field. The time to initiate a saccade is dependent upon many factors. Here we review some of the recent advances in our understanding of the these processes in primates. Neurons in the superior colliculus and brainstem reticular formation are organised into a network to control saccades. Some neurons are active during visual fixation, while others are active during the preparation and execution of saccades. Several factors can influence the excitability levels of these neurons prior to the appearance of a new saccadic target. These pre-target changes in excitability are correlated to subsequent changes in behavioural performance. Our results show how neuronal signals in the superior colliculus and brainstem reticular formation can be shaped by contextual factors and demonstrate how situational experience can expedite motor behaviour via the advanced preparation of motor programs.     

基于网络药理学和分子对接技术探究清震汤治疗偏头痛的作用机制

基于网络药理学及分子对接技术探究清震汤治疗偏头痛的作用机制。利用中药系统药理学平台,结合文献报道,获取清震汤中3味中药的活性成分和作用靶点,借助UniProt数据库对靶点蛋白名称进行规范。通过DrugBank、GeneCards等数据库获取偏头痛相关靶点。运用在线Venny作图平台,得到清震汤治疗偏头痛的潜在作用靶点。通过STRING平台构建潜在靶点PPI网络,将所得蛋白互作信息导入Cytoscape 3.7.1进行图像优化及提取核心基因,运用DAVID数据库对潜在作用靶点进行富集分析,采用Cytoscape 3.7.1构建“中药-化合物-靶点-通路”调控网络并进行拓扑分析,使用Autodock软件进行分子对接验证。网络药理学分析结果显示,清震汤中治疗偏头痛可能与槲皮素、山奈酚、豆甾醇等40个化学成分有关,IL6、CXCL8、TNF、PTGS2等为关键靶点。富集分析得到GO条目436条,KEGG通路92条,主要涉及TNF信号通路,神经信号传递通路等。分子对接结果显示,上述活性成分与相关靶点具有较好的结合活性。该研究初步表明,清震汤中多种活性成分通过作用于IL6、CXCL8、TNF、PT...     

组蛋白泛素化修饰及其在DNA损伤应答中的作用

泛素化修饰是真核生物细胞内重要的翻译后修饰类型,通过调节蛋白质活性、稳定性和亚细胞定位广泛参与细胞内各项信号传导与代谢过程,对维持正常生命活动具有重要意义。组蛋白作为染色质中主要的蛋白成分,与DNA复制转录、修复等行为密切相关,是研究翻译后修饰的热点。DNA损伤后,组蛋白泛素化修饰通过调节核小体结构、激活细胞周期检查点、影响修复因子的招募与装配等诸多途径参与损伤应答。同时,组蛋白泛素化修饰还能调节其他位点翻译后修饰,并通过这种串扰(crosstalk)作用调节DNA损伤应答。本文介绍了组蛋白泛素化修饰的主要位点和相关组分(包括E3连接酶、去泛素化酶与效应分子),以及这些修饰作用共同编译形成的信号网络在DNA损伤应答中的作用,最后总结了目前该领域研究所面临的一些问题,以期为科研人员进一步探索组蛋白密码在DNA损伤应答中的作用提供参考。