2种新型ω-芋螺毒素的合成及作用靶点鉴定

目的:合成2个来自泡芋螺的新型ω-芋螺毒素Bu1、Bu13,测定其作用靶标,为研制新型镇痛药提供先导化合物。方法:固相合成线性肽,然后在折叠液(0.5 mol/L乙酸铵、1 mmol/L谷胱甘肽、0.1 mmol/L氧化谷胱甘肽)中于4℃折叠24～48 h,富集纯化得目标肽;利用膜片钳技术,测定其对N、P/Q及L型钙离子通道的抑制活性。结果:Bu1、Bu13对N型钙离子通道的半抑制浓度(IC50)分别为0.86、1.02μmol/L,抑制作用低于MⅦA(IC50=0.21μmol/L);10μmol/L Bu1、Bu13对P/Q型钙离子通道的抑制率分别为17.05%±1.34%、13.1%±2.69%,稍高于MⅦA(8.92%±2.12%);10μmol/L Bu1、Bu13对L型钙离子通道的抑制率分别为19.31%±6.22%、4.78%±0.77%,高于MⅦA(<5%)。结论:Bu1、Bu13选择性作用于N型钙离子通道,对P/Q、L型钙离子通道的抑制作用较低。     

肠道菌群调控慢性疼痛机制的研究进展

近年来,肠道菌群与肠-脑轴的相互作用逐渐被认识,肠道菌群参与调控神经系统相关疾病的机制也日益被关注,其中肠道菌群可参与调控多种慢性疼痛,包括内脏痛、炎性痛、神经病理性疼痛和头痛等。肠道菌群本身的成分以及其代谢产物和副产物会通过调控多种细胞信号通路及神经递质干预慢性疼痛的发生和发展。本文对已发表的肠道菌群调控慢性疼痛的相关研究进行了广泛检索及总结,并在此基础上综述肠道菌群参与慢性疼痛的机制,以期为研发通过调控肠道菌群而发挥镇痛作用的靶点药物提供理论基础。     

非药物疗法在慢性疼痛干预中的应用和治疗机制

疼痛是一种由身体组织的真实或潜在损伤引起的不舒服感觉，慢性疼痛为持续时间超过3个月以上的疼痛。慢性疼痛可以由多种疾病引起，发病率高。然而应用药物治疗慢性疼痛存在一定的局限性。非阿片类药物对部分类型的慢性痛，如神经病理性疼痛，疗效不佳。而阿片类镇痛药物则因成瘾和易诱发胃肠道副作用而受限，因此非药物干预治疗逐渐受到关注。目前临床上对于治疗慢性疼痛常用的非药物疗法包括脉冲射频（pulsed radiofrequency,PRF）、脊髓电刺激（spinal cordstimulation, SCS）、光生物调节（photobiomodulation, PBM）和重复经颅磁刺激（repetitive transcranial magnetic stimulation,rTMS）。最新研究揭示了光照和声音的中枢镇痛机制，提示光疗和声疗在临床转化上的潜力。鉴于光照和声音都属于非侵入性治疗，因此这两者在临床应用上具有广阔的前景。本文通过梳理以上非药物镇痛手段的干预方法、优缺点以及镇痛机制，希望为深入理解慢性痛的发病机制提供依据，为优化疼痛的非药物干预手段提供新的思路。     

多巴胺对鲫鱼视网膜H1型水平细胞上电压门控钙离子通道的调控特性

利用细胞内的钙离子成像技术,研究了多巴胺对鲫鱼视网膜H1型水平细胞上L型电压门控钙离子通道的调控特性。研究发现,在不同胞外pH(6.8、7.4、8.0)条件下,不同浓度多巴胺(50和500μmol/L、1 mmol/L)对L型电压门控钙离子通道均具有上调作用。50μmol/L多巴胺在不同pH下的上调程度没有显著性差异;高浓度多巴胺(500μmol/L和1 mmol/L)在pH8.0条件下比pH6.8和7.4条件下具有更显著的上调作用。这些结果表明,在鲫鱼视网膜H1型水平细胞上,多巴胺对电压门控钙离子通道的调控与胞外pH环境密切相关。在光照情况下,L型电压门控钙离子通道活性被相对高浓度多巴胺上调,并被胞外碱性环境协同增强。这种协同增强效应有助于阐明视网膜对光反应的信息传递机制。     

放射损伤、烧伤与放烧复合伤血清成份对心肌细胞钙离子通道活动的影响

本实验研究了放射损伤、烧伤与放烧复合伤后血清成份对培养心肌细胞Ｌ－型钙离子通道活动的影响,结果表明：伤后血清对上述通道均有激活作用,从而改变细胞内钙离子水平,此可能为伤后心脏功能抑制的一个重要机理。在作用强度上,复合伤血清重于单一伤、烧伤重于放射损伤,这是导致不同伤后血清对心功能抑制程度不一的重要因素。对伤后血清成分作用的进一步研究表明：伤后血清大分子的作用不明显,主要是血清低分子与血清脂质起作用。其中,放烧复合伤血清低分子不仅使通道开放增加,还使膜片噪声增加,提示其作用包括改变其Ｌ－型钙离子通道活动与改变膜的物理特性二个方面,它们共同导致细胞的功能变化;血清脂质对钙通道的作用可被ＳＯＤ所抑制,表明其作用与氧自由基反应有关。至于伤后血清低分子与血清脂质中的具体毒性成分以及它们对Ｌ－型钙离子通道影响的调控机制,有待于进一步研究     

酪丝亮肽对人肝癌BEL-7402细胞钙稳态影响的实验研究

目前寻找有效的药物仍是治疗肿瘤的关键环节之一. 酪丝亮肽为中国新近研发并具有自主知识产权的三肽化合物. 观察了酪丝亮肽的抗肝癌作用, 并研究了其对肿瘤细胞钙稳态的影响, 以初步探讨它的抗肿瘤作用机制. 结果发现, 酪丝亮肽能显著抑制人肝癌BEL-7402裸鼠移植瘤的生长, 160 mg/(kg·d)治疗组肿瘤生长抑制率可达41.34%, 电子显微镜观察发现酪丝亮肽可引起移植瘤细胞的坏死和凋亡, 细胞器线粒体和内质网损伤, 并出现钙沉积. 应用激光扫描共聚焦显微镜及流式细胞仪观察发现, 10 mg/mL酪丝亮肽在400 s内可引起体外培养BEL-7402细胞胞浆钙离子浓度迅速升高, 最高幅度可达239.13%; 持续作用1 h后BEL-7402胞浆钙离子维持在高水平, 作用2 h后胞浆钙离子浓度开始下降, 4和24 h时的胞浆钙离子水平均低于对照, 相同剂量的药物对人正常肝细胞株Chang氏肝无明显影响; 酪丝亮肽还可使体外培养的BEL-7402细胞线粒体跨膜电位明显下降, 提示其抗肝癌机制可能是通过影响肿瘤细胞的钙稳态, 诱导其发生坏死或凋亡.     

盐酸曲马多血药浓度测定方法概况

盐酸曲马多（tramadol hydrachloride,TMD）是中枢类镇痛药,镇痛效果好,临床上广泛地应用于中、重度急、慢性疼痛的治疗。本文就近年来有关其血药浓度的测定方法作一综述。     

低氧预适应下BDNF/TrkB和cAMP/PKA信号通路调控电压依赖性钙离子通道的研究进展

本文探析了低氧预适应对神经系统的保护作用尤其是改善学习记忆能力的相关机制,回顾了电压依赖性钙离子通道在神经系统中的作用以及与学习记忆之间的关系。重点总结了低氧预适应诱导下电压依赖性钙离子通道特性的变化情况,并深入归纳了BDNF/TrkB和cAMP/PKA信号通路对电压依赖性钙离子通道的调节机制以及低氧预适应与这些信号通路之间的关系。通过总结低氧预适应调控BDNF/TrkB和cAMP/PKA信号通路影响电压依赖性钙离子通道相关的最新研究进展,为将来阐明低氧预适应提升认知能力的可能机制奠定理论基础。     

猫外膝体中继细胞低阈值钙通道的动力学特性

在猫外膝体脑片上用单电极电压钳位的方法研究了低阈值T-型钙离子通道的动力学特性.采用阻断各种钾和钠离子通道、减小钙离子电流和选择适当的维持电位等方法,改善了脑片实验的空间钳位.所得结果与大鼠外膝体急性分离神经元的结果一致.说明猫外膝体神经元T-型钙离子通道的动力学特性与大鼠的相同.     

Ca2+在水杨酸诱发的丹参培养细胞培养基碱化过程中的作用

利用质膜钙离子通道抑制剂LaCl3、异搏定(Verapamil,VP),钙离子载体A23187,内膜系统钙离子通道抑制剂2-APB和LiCl处理,研究水杨酸(SA)诱发的丹参培养细胞内Ca2+迸发在培养基碱化过程中的作用。结果显示:SA处理诱发丹参培养细胞培养基碱化,质膜钙离子通道抑制剂LaCl3和VP、内膜系统钙离子通道抑制剂2-APB和LiCl单独处理均可显著抑制SA处理诱发的培养基碱化过程,但质膜钙离子通道抑制剂对SA处理诱发的培养基碱化的抑制作用要显著强于内膜系统钙离子通道抑制剂;当两类钙离子通道抑制剂同时使用,培养基碱化过程被完全抑制,甚至培养基出现酸化趋势;钙离子载体A23187可以显著促进培养基碱化过程。以上结果说明,由水杨酸诱发的胞外Ca2+内流与胞内钙库Ca2+释放均参与了丹参培养基碱化的诱导过程,但胞外Ca2+内流的作用更重要。本研究揭示了SA诱发的Ca2+与丹参细胞培养基碱化之间的关系,为更深层次地阐明植物次生代谢调控机制提供理论基础。     

My Child Redeems My Broken Dreams: On Parents Transferring Their Unfulfilled Ambitions onto Their Child

From the early days of psychology, theorists have observed that parents sometimes transfer their own unfulfilled ambitions onto their child. We propose that parents are especially inclined to do so when they see their child as part of themselves, more so than as a separate individual. When parents see their child as part of themselves, their child’s achievements may easily come to function as a surrogate for parents’ own unfulfilled ambitions. In the present experiment, 73 parents (89% women, M _age = 43 years) were randomly assigned to reflect on either their own or others’ unfulfilled ambitions. Results showed that, when faced with their own unfulfilled ambitions, parents who see their child as part of themselves want their child to fulfill their unfulfilled ambitions. This study provides the first experimental evidence to suggest that parents may desire their child to redeem their broken dreams.     

Enterococci from foods

Enterococci have recently emerged as nosocomial pathogens. Their ubiquitous nature determines their frequent finding in foods as contaminants. In addition, the notable resistance of enterococci to adverse environmental conditions explains their ability to colonise different ecological niches and their spreading within the food chain through contaminated animals and foods. Enterococci can also contaminate finished products, such as fermented foods and, for this reason, their presence in many foods (such as cheeses and fermented sausages) can only be limited but not completely eliminated using traditional processing technologies. Enterococci are low grade pathogens but their intrinsic resistance to many antibiotics and their acquisition of resistance to the few antibiotics available for treatment in clinical therapy, such as the glycopeptides, have led to difficulties and a search for new drugs and therapeutic options. Enterococci can cause food intoxication through production of biogenic amines and can be a reservoir for worrisome opportunistic infections and for virulence traits. Clearly, there is no consensus on the acceptance of their presence in foodstuffs and their role as primary pathogens is still a question mark. In this review, the following topics will be covered: (i) emergence of the enterococci as human pathogens due to the presence of virulence factors such as the production of adhesins and aggregation substances, or the production of biogenic amines in fermented foods; (ii) their presence in foods; (iii) their involvement in food-borne illnesses; (iv) the presence, selection and spreading of antibiotic-resistant enterococci as opportunistic pathogens in foods, with particular emphasis on vancomycin-resistant enterococci.     

Oligothiophene molecular beacons

Oligomers of thiophene are widely studied compounds for their electronic and optoelectronic properties. Despite their strong fluorescence, their use as markers for biomolecules, especially for oligonucleotides (ONs), is still largely unexplored. Here, we describe the synthesis of a series of ON molecular beacons employing different oligothiophenes as fluorescent probes and discuss their fluorescence emissions in comparative experiments with and without dabcyl as a quencher, in their hairpin and linear conformations, and as duplexes after hybridization with a complementary target.     

Macrophages in the embryo and beyond: much more than just giant phagocytes

Originally recognized as an essential part of the innate and acquired immune systems, macrophages emerged as omnipresent and influential regulators of embryo- and organo-genesis, as well as of tissue and tumor growth. Macrophages are present essentially in all tissues, beginning with embryonic development and, in addition to their role in host defense and in the clearance of apoptotic cells, are being increasingly recognized for their trophic function and role in regeneration. Some tissue macrophages are also found to possess a substantial potential for autonomous self-renewal. Macrophages are associated with a significant proportion of malignant tumors and are widely recognized for their angiogenesis-promoting and trophic roles, making them one of the new promising targets for cancer therapies. Recent expression profiling of embryonic macrophages from different tissues revealed remarkable consistency of their gene expression profiles, independent of their tissue of origin, as well as their similarities with tumor-associated macrophages. Macrophages are also capable of fusion with other cells in tissue repair and metastasizing tumors, as well as with each other in the immune response and osteoclastogenesis.     

Focus: Addiction: Video Game Use in the Treatment of Amblyopia: Weighing the Risks of Addiction

Video games have surged in popularity due to their entertainment factor and, with recent innovation, their use in health care. This review explores the dual facets of video games in treating vision impairment in amblyopia as well as their potential for overuse and addiction. Specifically, this review examines video game addiction from a biopsychosocial perspective and relates the addictive qualities of video games with their use as a therapeutic treatment for amblyopia. Current literature supports both the identification of video game addiction as a disease, as well as the therapeutic potential of video games in clinical trials. We show the need for clinicians to be aware of the dangers associated with video game overuse and the need for future studies to examine the risks associated with their health care benefits.     

Predators are less likely to misclassify masquerading prey when their models are present

Masquerading animals have evolved striking visual resemblances to inanimate objects. These animals gain protection from their predators not simply by avoiding detection, but by causing their predators to misclassify them as the ‘models’ that they appear to resemble. Using domestic chicks as predators and twig-mimicking caterpillars as prey, we demonstrated that masquerading prey were more likely to be misclassified as their models when viewed in isolation from their models than when viewed alongside examples of their model, although they benefitted from masquerade to some extent in both conditions. From this, we predict a selection pressure on masqueraders to use microhabitats that reduce the risk of them being viewed simultaneously with examples of their model, and/or to more closely resemble their model in situations where simultaneous viewing is commonplace.     

Diel vertical migration arising in a habitat selection game

Predator and prey react to each other, adjusting their behavior to maximize their fitness and optimizing their food intake while keeping their predation risk as low as possible. In a pelagic environment, prey reduce their predation mortality by adopting a diel vertical migration (DVM) strategy, avoiding their predator during their peak performance by finding refuge in deep layers during daylight hours and feeding at the surface during the night. Due to the duality of the interaction between prey and predator, we used a game theory approach to investigate whether DVM can be a suitable strategy for the predator as well as the prey. We formulated three scenarios in plankton ecology in order to address this question. A novel finding is that mixed strategies emerge as optimal over a range of the parameter space, where part of the predator or prey population adopts a DVM while the rest adopt one or other “sit and wait” strategies.     

Campylobacter bacteriophages and bacteriophage therapy

Members of the genus Campylobacter are frequently responsible for human enteric disease with occasionally very serious outcomes. Much of this disease burden is thought to arise from consumption of contaminated poultry products. More than 80% of poultry in the UK harbour Campylobacter as a part of their intestinal flora. To address this unacceptably high prevalence, various interventions have been suggested and evaluated. Among these is the novel approach of using Campylobacter-specific bacteriophages, which are natural predators of the pathogen. To optimize their use as therapeutic agents, it is important to have a comprehensive understanding of the bacteriophages that infect Campylobacter, and how they can affect their host bacteria. This review will focus on many aspects of Campylobacter-specific bacteriophages including: their first isolation in the 1960s, their use in bacteriophage typing schemes, their isolation from the different biological sources and genomic characterization. As well as their use as therapeutic agents to reduce Campylobacter in poultry their future potential, including their use in bio-sanitization of food, will be explored. The evolutionary consequences of naturally occurring bacteriophage infection that have come to light through investigations of bacteriophages in the poultry ecosystem will also be discussed.     

Biofeedback use of common objects

Many common devices can be used as biofeedback devices. The feedback use of the bathroom scale in rehabilitation medicine(physical therapy) has been explored with stroke patients. These patients used two scales, one under each foot, to relearn their sense of weight distribution. In addition, the scale was used to teach patients to shift their weight distribution from their knees to their hands as they learned to crawl, and from their feet to their buttocks and the chair as they learned to sit down.