中国药用当归属植物研究进展及质量标志物的预测分析*

中国药用当归属植物资源丰富,包括当归、白芷、独活等34种药材,临床使用广且药用价值极高,富含香豆素类、多糖类、有机酸类、苯酚类、挥发油类等成分,除补血活血、调经止痛、润肠通便的传统功效,还具有抗氧化、抗衰老、保护神经元、抗肿瘤等药理作用,应用前景广阔。综述了中国药用当归属植物的分布及其药用功效、化学成分和药理作用的研究进展,为当归属植物的开发利用提供参考。并且根据质量标志物(Q-marker)概念,把影响中国药用当归属植物质量的因素概括为当归属药用植物品种、植物产区、化学成分、炮制方法,以及传统功效和网络药理学的预测分析等。从不同方面对中国药用当归属植物进行分析和论述,为建立和完善中国药用当归属植物的质量控制及评价方法提供参考。     

Effects of Barbiturates on Facilitative Glucose Transporters are Pharmacologically Specific and Isoform Selective

Barbiturates inhibit GLUT-1-mediated glucose transport across the blood-brain barrier, in cultured mammalian cells, and in human erythrocytes. Barbiturates also interact directly with GLUT-1. The hypotheses that this inhibition of glucose transport is (i) selective, preferring barbiturates over halogenated hydrocarbon inhalation anesthetics, and (ii) specific, favoring some GLUT-# isoforms over others were tested. Several oxy- and thio-barbiturates inhibited [³H]-2-deoxyglucose uptake by GLUT-1 expressing murine fibroblasts with IC₅₀s of 0.2–2.9 mm. Inhibition of GLUT-1 by barbiturates correlates with their overall lipid solubility and pharmacology, and requires hydrophobic side chains on the core barbiturate structure. In contrast, several halogenated hydrocarbons and ethanol (all ≤10 mm) do not significantly inhibit glucose transport. The interaction of these three classes of anesthetics with purified GLUT-1 was evaluated by quenching of intrinsic protein fluorescence and displayed similar specificities and characteristics. The ability of barbiturates to inhibit other facilitative glucose transporters was determined in cell types expressing predominantly one isoform. Pentobarbital inhibits [³H]-2-deoxyglucose and [¹⁴C]-3-O-methyl-glucose uptake in cells expressing GLUT-1, GLUT-2, and GLUT-3 with IC₅₀s of ∼1 mm. In contrast, GLUT-4 expressed in insulin-stimulated rat adipocytes was much less sensitive than the other isoforms to inhibition by pentobarbital (IC₅₀ of >10 mm). Thus, barbiturates selectively inhibit glucose transport by some, but not all, facilitative glucose transporter isoforms. Received: 10 November 1998/Revised: 3 February 1999     

奥得福尔制剂的药效学研究与临床

对奥得福尔制剂的药效学定量杀菌试验、抗病毒试验及临床应用的结果表明： 得福尔制剂原液,１：１稀释液及１：５稀释液对大肠杆菌、金黄色葡萄球菌和白色念珠菌作用１０ｍｉｎ,杀灭率均可达９９．９％以上;消毒液放置室温下稳定,有机物的存在对杀灭作用有轻度影响,但杀灭率仍可达９９．９％以上;体外抗病毒试验结果表明,该制剂的主要抗病毒功效成分－黄精多糖,对单纯疱疹病毒的空斑抑制率达到１００％;稳定性试验表明,该     

Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection

The cantilever sensor, which acts as a transducer of reactions between model bacterial cell wall matrix immobilized on its surface and antibiotic drugs in solution, has shown considerable potential in biochemical sensing applications with unprecedented sensitivity and specificity^1-5. The drug-target interactions generate surface stress, causing the cantilever to bend, and the signal can be analyzed optically when it is illuminated by a laser. The change in surface stress measured with nano-scale precision allows disruptions of the biomechanics of model bacterial cell wall targets to be tracked in real time. Despite offering considerable advantages, multiple cantilever sensor arrays have never been applied in quantifying drug-target binding interactions.Here, we report on the use of silicon multiple cantilever arrays coated with alkanethiol self-assembled monolayers mimicking bacterial cell wall matrix to quantitatively study antibiotic binding interactions. To understand the impact of vancomycin on the mechanics of bacterial cell wall structures^1,6,7. We developed a new model¹ which proposes that cantilever bending can be described by two independent factors; i) namely a chemical factor, which is given by a classical Langmuir adsorption isotherm, from which we calculate the thermodynamic equilibrium dissociation constant (K_d) and ii) a geometrical factor, essentially a measure of how bacterial peptide receptors are distributed on the cantilever surface. The surface distribution of peptide receptors (p) is used to investigate the dependence of geometry and ligand loading. It is shown that a threshold value of p ~10% is critical to sensing applications. Below which there is no detectable bending signal while above this value, the bending signal increases almost linearly, revealing that stress is a product of a local chemical binding factor and a geometrical factor combined by the mechanical connectivity of reacted regions and provides a new paradigm for design of powerful agents to combat superbug infections.     

后疫情时代全球可持续发展目标加速行动的推动

“SDGs加速行动”是国际组织、政府部门、私营机构和其他利益攸关方为加快落实2030年可持续发展议程采取的全球行动。2019年联合国可持续发展目标峰会后,政府、国际组织、私营部门等提出了214项SDGs加速行动。2019年爆发的新型冠状病毒肺炎（Corona Virus Disease 2019,COVID-19）对实现可持续发展目标带来了系列影响,后疫情时代如何推动全球SDGs加速行动的实施成为重要的问题。对可持续发展评估报告（2019）和可持续发展目标加速行动等政策文件进行信息提取,建立加速行动匹配性指数模型和各国应对新冠疫情的恢复力指数模型,根据匹配性-恢复力分类体系将各国按照17项可持续发展目标分为9类,为推动后疫情时代全球可持续发展目标加速行动提供支撑。研究发现：（1）现有可持续发展目标加速行动的实施与区域需求不匹配,且这种不匹配的情况在COVID-19爆发前已经出现;（2）加速行动的实施受限于现有可持续发展水平和国家经济基础,区域关注的可持续发展目标与其自然地理位置和社会发展水平有着密切的关系,多边组织机构和其他利益攸关方需要在发展中国家大力推动可持续发展加速行动;（3）下一步实施加速行动需要加强国际间的合作,根据分类框架和可持续发展目标的关联关系,分重点推进加速行动的实施,完善可持续发展指标监测体系,分类设立后疫情时代不同时期的阶段目标,分阶段循序渐进,定期反馈追踪,以在2030年促进17项可持续目标的实现。     

Progesterone receptors in the human uterus and their possible role in parturition

An overview is given on the role of progesterone in parturition in the human. Progesterone withdrawal is considered to be a major event for the beginning of parturition. However, in the human, no evidence exists in favour of a decline in placental progesterone production prior to labour. Progesterone actions are mediated by two functionally different but structurally highly related intranuclear proteins, progesterone receptor (PR) A and PRB. In the human, functional progesterone withdrawal is thought to play a role. This may be mediated by a change in the expression of the two isoforms of the PR, with an increase in the PRA:PRB ratio, and this is accompanied by an increase in the expression of the estrogen receptor. These mechanisms are considered to be critical for the endocrine control of parturition.     

Cell Death Associated with Abnormal Mitosis Observed by Confocal Imaging in Live Cancer Cells

Phenanthrene derivatives acting as potent PARP1 inhibitors prevented the bi-focal clustering of supernumerary centrosomes in multi-centrosomal human cancer cells in mitosis. The phenanthridine PJ-34 was the most potent molecule. Declustering of extra-centrosomes causes mitotic failure and cell death in multi-centrosomal cells. Most solid human cancers have high occurrence of extra-centrosomes. The activity of PJ-34 was documented in real-time by confocal imaging of live human breast cancer MDA-MB-231 cells transfected with vectors encoding for fluorescent γ-tubulin, which is highly abundant in the centrosomes and for fluorescent histone H2b present in the chromosomes. Aberrant chromosomes arrangements and de-clustered γ-tubulin foci representing declustered centrosomes were detected in the transfected MDA-MB-231 cells after treatment with PJ-34. Un-clustered extra-centrosomes in the two spindle poles preceded their cell death. These results linked for the first time the recently detected exclusive cytotoxic activity of PJ-34 in human cancer cells with extra-centrosomes de-clustering in mitosis, and mitotic failure leading to cell death. According to previous findings observed by confocal imaging of fixed cells, PJ-34 exclusively eradicated cancer cells with multi-centrosomes without impairing normal cells undergoing mitosis with two centrosomes and bi-focal spindles. This cytotoxic activity of PJ-34 was not shared by other potent PARP1 inhibitors, and was observed in PARP1 deficient MEF harboring extracentrosomes, suggesting its independency of PARP1 inhibition. Live confocal imaging offered a useful tool for identifying new molecules eradicating cells during mitosis.     

Prevention of damage in acute spinal cord injury by peptides and pharmacologic agents

Cats were used as models of traumatic spinal cord injury. Each experimental animal received a 500 g-cm force to the exposed dura at the level of thoracic fourth vertebra. Somatosensory evoked potentials (SEPs), carotid arterial blood pressure (BP), and abdominal aorta blood flow in the treated groups were compared with those of the control group. The three treated groups received naloxone (5 mg/kg), TRH (5 mg/kg), and a combination of methyl-prednisolone sodium succinate (MP, 35 mg/kg) and epsilon-aminocaproic acid (EACA, 350 mg/kg). The SEPs which were done only in the naloxone treated group approached "normalcy" 24-26 hours after trauma as compared with the absence of SEPs in traumatized untreated group. In all three groups, the treatment increased the blood flow in abdominal aorta significantly. Morphine sulfate increased substance P (SP) immunoreactivity in the dorsal and ventral gray matter. Naloxone not only reversed this effect, it depleted SP below the saline control level. In order to establish that lipid free radicals are responsible for damage to biological membranes, their effects were also investigated in vitro: 14C-GABA uptake by mouse cortical slices which had decreased by 33% in the presence of superoxide (. O-2) generating system, horseradish peroxidase (HRP), was reduced only by 9% when superoxide dismutase was added to the medium. The latter also protected the nerve endings from damage by (. O-2) as examined by electron microscopy. It is concluded that the agents used in this study produce their ameliorating effects by virtue of their anti-inflammatory, anti-oxidant, and membrane stabilizing properties in addition to their effect on enhancing the regional microcirculation. The release of SP by naloxone may be responsible for the increase in blood flow. The consequences of traumatic injury as depicted in Fig. 1 are discussed at length.     

党参属药用植物研究状况

本文介绍了近年来党参属药用植物化学成分的研究状况及党参的药理作用,对党参的开发利用提出了建议。     

进口血竭与国内血竭的研究对比

血竭是我国传统名贵中药,在世界各地广泛使用。本文对进口血竭与国产血竭在植物基源及生物学特征进行了比较,我们又把国内血竭称为"龙血竭",并对血竭真伪的鉴别提供了几种简单的方法。进口与国产的血竭虽然在化学成分上有很大不同,但是药理作用很相似,所以我国的龙血竭完全可以替代进口血竭在临床上使用,市场上出现了很多不同的血竭剂型。针对现在国内外血竭资源的处于濒危的状况,我们需要增强血竭资源保护意识,使血竭资源能可持续利用。