Toxicity of Naphthalene on Caenorhabditis elegans

Naphthalene is a common environmental contaminant substance. The toxic effects of naphthalene on Caenorhabditis elegans were investigated at the molecular, biochemical and physiological levels. To assess the molecular-level effect, stress-related gene expression was investigated such as those of hsp-16.1, sod-3, ctl-2, cep-1, cyp35a2, ugt-44, gst-1 and dhs-28. Cell apoptosis was assessed at the biochemical level. Life span, locomotion behaviors and brood size were investigated at the physiological level. Th...     

基于微流控芯片技术的秀丽隐杆线虫研究进展

秀丽隐杆线虫具有体积小、生命周期短、结构简单和高基因保守性等特点,是生命科学研究领域中的一种重要模式生物。微流控芯片的通道尺寸与线虫大小相匹配,并可实现灵活集成的线虫操控,为线虫研究提供了一种全新的平台。在微流控平台上,线虫长期培养、固定、分选、精确刺激传递和单线虫包裹等单元操作已经实现,并被应用于线虫神经生物学、行为学、衰老及发育、药物筛选等研究中。该文着重介绍近几年基于微流控芯片技术的线虫研究最新进展,并对其应用前景予以展望。     

Triazine Dendrimers for Drug Delivery: Evaluation of Solubilization Properties,Activity in Cell Culture,and In Vivo Toxicity of a Candidate Vehicle

Three criteria are evaluated to assess the potential of a dendrimer based on triazines, 1, for use as a vehicle for drug delivery. These criteria are: (1) its ability to solubilize small hydrophobic guests as measured spectrophotometrically; (2) its ability to deliver a drug in vitro as evaluated using a gene reporter assay; and (3) its in vivo toxicity in mice as determined by autopsy and screens of liver and kidney function. Vehicle 1 solubilizes pyrene to a similar extent to dendrimers based on poly(arylether)s, 4, encapsulating approximately 0.2 molecules of pyrene per dendrimer. This activity is approximately 10-fold greater than that of the more polar poly(propyleneimine) and poly(amidoamine) dendrimers, 2 and 3. Gas-phase computational models reveal that both 1 and 4 have cores that are accessible to solvent, suggesting that these dendrimers can occupy much greater volumes than 2 and 3 whose cores are confined toward the interior of the structure. Electrostatic potential maps can be used to rationalize differences in solubilization between 1 and 4. Precipitation results from mixing cationic 1 with the anionic indomethacin, but not with methotrexate, suggesting that the composition of the drug may dictate the scope of delivery applications. Dendrimer 1 solubilizes 10-hydroxycamptothecin and a novel bisindolemethane; approximately four and five molecules of drug per dendrimer are solubilized, respectively. In cell-culture experiments using a luciferase reporter gene assay, the dendrimer:bisindolemethane conjugate shows comparable activity to the bisindolemethane delivered in aqueous DMSO, suggesting that the dendrimer does not preclude delivery of the molecule to an intracellular target. Preliminary toxicology studies of 1 in mice show that this molecule has no adverse toxicity to the kidneys or the liver in single doses delivered intraperitoneally up to 10?mg/kg.     

抗肿瘤药物输送系统

大多数小分子抗肿瘤药物均存在水溶性差、给药量大、体内半衰期短等问题,它们经口服或静脉注射给药后,只能通过自由扩散方式进入细胞,往往缺乏选择性,同时,对肿瘤细胞和正常细胞产生细胞毒性,具有较强的毒副作用,甚至对患者造成二次伤害。因此,它们在临床应用上受到很大限制。通过选择适宜的载体材料构筑抗肿瘤药物输送系统（如胶束、凝胶、纳米粒子等）,不仅可以延长小分子抗肿瘤药物的半衰期、降低其毒副作用,而且还可提高其溶解性和生物利用度,因而受到广大科研人员及制药企业的广泛重视。到目前为止,抗肿瘤药物输送系统的发展历史已有60多年,大致可分为传统型、智能型和靶向型三个不同的发展阶段。本文将从这三个不同发展阶段来综述抗肿瘤药物输送系统及其最新的研究进展,并对其未来的发展进行展望。     

智能水凝胶双抗癌药物控释体系

近年来,基于联合用药策略的双药物控释体系的研究为降低抗癌药物毒性和提高疗效提供了有效途径。水凝胶作为一类高临床应用价值的药物载体,在药物控释方面具有广泛的应用前景。癌症是危害人类健康和生命的疾病之一,当人体内正常细胞发生癌变后,癌变细胞周围会发生一些显著的变化。因此,根据肿瘤细胞与正常细胞在体内环境及体外环境的差异,发展了多种智能型水凝胶双抗癌药物控释载体。它能够在感知外界因素的刺激下发生内部结构的变化,从而实现对药物的可控释放。与此同时,随着新的治疗手段的兴起和更多抗癌作用靶点的发现,水凝胶载体也成功实现了化学药物和生物治疗因子的同时负载和可控释放。本文将从不同智能型水凝胶载体如何负载、控释双抗癌药物及水凝胶药物载体中药物的组合方式两方面综述智能型水凝胶双抗癌药物控释体系最新研究进展,并展望其发展前景。     

Effectively controlled microfluidic trap for spatiotemporal analysis of the electrotaxis of Caenorhabditis elegans

C. elegans is a popular model organism with a well‐developed neural network. Approximately 60% of the genes in C. elegans have genomic counterparts in humans, including those involved in building neural circuits. Therefore, we can extend the study of human neural network mechanisms to C. elegans which is easy to genetically manipulate. C. elegans shows behavioural responses to various external physical and chemical stimuli. Electrotaxis is one of its distinct behavioural responses, which is defined as movement towards the cathode in an electric field. In this study, we developed an effective microfluidic trap system for analysing electrotaxis in C. elegans. In addition, two mutant strains (unc‐54(s74) and unc‐6(e78)) from wild‐type (N2) worms were screened using the system. Wild‐type (N2) worms and the two mutant strains clearly showed different behavioural responses to the applied electric field, thus enabling the effective screening of the mutant worms from the wild type (N2). This microfluidic system can be utilized as a platform for the study of behavioural responses, and for the sorting and mutant screening of C. elegans.     

两亲性柱[5]芳烃超分子纳米载药体系的构筑及其抗肿瘤活性研究

合成了一种新型的丙氨酸取代水溶性柱[5]芳烃DAP5,以此作为构建单元可与十二烷基苯磺酸钠(SDBS)通过主客体作用构筑出可高效包载抗癌药物阿霉素(DOX)的超分子纳米载体SDBS(∪)DAP5,包封率为62.6％.该纳米载药体系不仅具有较好的pH响应性能并在模拟肿瘤弱酸性微环境中可持续释放药物,而且对正常肝细胞(LO...     

Analysis of Caenorhabditis elegans in microfluidic devices

Caenorhabditis elegans (C. elegans) is widely adopted as a model organism for a variety of biological studies including development, genetics and neurobiology. Micro-scale microfluidic technology is capable of handling single or populations of C. elegans in high throughput format and allows for the precise spatial and temporal control of their environment, which is well suited for the study of worms in different aspects. In this review, we highlight the recent advances in microfluidic technology for the analysis of worms ranging from behavioral studies to neurobiology. We believe that microfluidic device can further be applied to study the different aspects of worms, extending from fundamental investigation of behavioral dynamics to more complicated biological processes including neurochemistry and learning behaviors.     

Cinnamomum cassia and Syzygium aromaticum Essential Oils Reduce the Colonization of Salmonella Typhimurium in an In Vivo Infection Model Using Caenorhabditis elegans

The regulation of intestinal colonization in livestock by means of non-bactericidal additives is an important management lever for zoonotic bacteria such as Salmonella spp. Caenorhabditis elegans is proposed here as a model for the evaluation of five essential oils (EOs) as anti-colonization products against Salmonella Typhimurium. An evaluation of the toxicity of EOs for C. elegans showed LD₅₀ values ranging from 74.5 ± 9.6 µg/mL for Cinnamomum cassia (CEO) to 271.6 ± 14.9 µg/mL for Syzygium aromaticum (SyEO). Both EOs significantly inhibited bacterial colonization in the digestive tract of C. elegans with reductions of 0.88 and 0.70 log CFU/nematode at nontoxic concentrations of 50 µg/mL and 150 µg/mL, respectively. With the minimal bactericidal concentrations of CEO and SyEO against S. Typhimurium being 312.5 µg/mL and 625 µg/mL, respectively, an antibacterial effect can be excluded to explain the inhibition of the bacterial load. The anti-colonizing activity of these two EOs could, however, be related to an inhibition of the swimming motility, which was significantly reduced by 23.47% for CEO at 50 µg/mL and 19.56% for SyEO at 150 µg/mL. This study shows the potential of C. elegans as a predictive in vivo model of anti-colonizing activities that is suitable for the evaluation of essential oils.     

基于类芬顿反应的Mn3O4/DOX@Lip纳米递药体系的构建及应用

利用肿瘤微环境与普通组织的差异,我们设计了一种基于类芬顿反应(Fenton-like reaction)的微环境响应的纳米递药体系(Mn3O4/DOX@Lip).首先利用热分解法制备得到锰的氧化物(Mn3O4)纳米粒子,基于化疗药物阿霉素(DOX)与Mn原子的配位作用,该纳米粒子可以负载并递送DOX,其最外层包裹的酸敏...     

Cellular Evaluation of Synthesized Insulin/Transferrin Bioconjugates for Oral Insulin Delivery Using Intelligent Complexation Hydrogels

Insulin transport across the epithelial cell layer in the small intestine was studied using insulin/transferrin conjugates with and without the presence of P(MAA‐g‐EG) microparticles in contact with a co‐culture of Caco‐2/HT29‐MTX cells. The insulin/transferrin conjugate was shown to increase transport relative to pure insulin by a factor of 7, achieving an apparent permeability of 37 × 10⁹ cm · s^?1. The presence of P(MAA‐g‐EG) microparticles increased conjugate transport by a factor of 14 times relative to insulin, achieving an apparent permeability of 72.8 × 10⁹ cm · s^?1. The presence of the microparticles in solution was found to improve conjugate transport by nearly 100% with little to no change in cell monolayer integrity.

     

萘普生在新型缓释系统中的释药

亲水凝胶;萘普生;二醋酸纤维素;致孔剂;新型药物缓释系统     

聚氨酯生物吸收材料及其作为缓释药物载体的研究

合成了一系列新的紫外光固化生物吸收性聚氨酯水凝胶网络，测定了材料的含水率及水解性能，并以之为载体，研究了对异烟肼的药物缓释性能。结果表明，该水凝胶的含水率及降解速率与其结构有关，该水凝胶对异烟肼具有缓释作用，释放行为受扩散控制并符合Ｈｉｇｕｃｈｉ方程，表观扩散系数与水凝胶的含水率有关。     

Green Algae as a Drug Delivery System for the Controlled Release of Antibiotics

New strategies to efficiently treat bacterial infections are crucial to circumvent the increase of resistant strains and to mitigate side effects during treatment. Skin and soft tissue infections represent one of the areas suffering the most from these resistant strains. We developed a new drug delivery system composed of the green algae, Chlamydomonas reinhardtii, which is generally recognized as safe, to target specifically skin diseases. A two-step functionalization strategy was used to chemically modify the algae with the antibiotic vancomycin. Chlamydomonas reinhardtii was found to mask vancomycin and the insertion of a photocleavable linker was used for the release of the antibiotic. This living drug carrier was evaluated in presence of Bacillus subtilis and, only upon UVA1-mediated release, growth inhibition of bacteria was observed. These results represent one of the first examples of a living organism used as a drug delivery system for the release of an antibiotic by UVA1-irradiation.     

量子点给药载体研究进展

量子点因其优良的发光性质,易于修饰的表面结构,在化学、医学和材料等研究领域显示了极其广阔的应用前景,受到科研工作者越来越多的关注。本文介绍了量子点的独特光学性质、制备方法、水溶性修饰和量子点与生物分子的偶联,重点讨论了量子点作为给药载体和给药载体标记物,以及以量子点为平台建立的多功能纳米给药体系的近年研究进展,阐述了当前研究中的主要发展方向和仍需解决的问题。     

栓塞型新型微包纳药物控释载体的制备及性能

为了抑制药物的突释效应, 减缓药物的释放速率, 实现不同药物的空间分配及顺序释放, 采用乳化法结合高压静电液滴法, 制备了内部包埋有几丁聚糖/海藻酸钙纳米囊的聚精氨酸/几丁聚糖/海藻酸盐微包纳体系(Nano-in-micro drug delivery system, NiM). 通过荧光标记的方法证实了“微包纳”结构并考察了NiM的理化性能. 以牛血清白蛋白及氟尿嘧啶作为药物模型, 考察了聚精氨酸/几丁聚糖/海藻酸盐微包纳体系对单一蛋白类药物和负载两种药物的缓释性能并进行了动力学模型拟合. 结果表明, Ritger-Peppas模型能够较好地模拟该溶胀控释系统的药物释放过程, 与实验结果比较吻合. 同时也证明了该新型载体体系具有无突释、释放速率减缓及顺序释放的功能, 为新型药物载体体系的研究提供了新的思路.     

Preparation of Dendrobium officinale Flower Anthocyanin and Extended Lifespan in Caenorhabditis elegans

The Dendrobium officinale flower is a non-medicinal part of the plant, rich in a variety of nutrients and bioactive ingredients. The purpose of this article was to explore the preparation conditions of anthocyanins (ACNs) from the D. officinale flower. Subsequently, its anti-aging effects were evaluated with Caenorhabditis elegans. Results showed that the ACNs had antioxidant activities on scavenging free radicals (DPPH· and ABTS⁺·), and the clearance rate was positively correlated with the dose. Additionally, ACNs significantly increased the activity of superoxide dismutase (SOD) in C. elegans, which was 2.068-fold higher than that of the control. Treatment with ACNs at 150 μL extended the lifespan of C. elegans by 56.25%, and treatment with ACNs at 50 μL promoted fecundity in C. elegans. Finally, the protective effect of ACNs enhanced stress resistance, thereby increasing the survival numbers of C. elegans, which provided insights for the development and practical application of functional products.     

Chemistry and the worm: Caenorhabditis elegans as a platform for integrating chemical and biological research

This Review discusses the potential usefulness of the worm Caenorhabditis elegans as a model organism for chemists interested in studying living systems. C. elegans, a 1 mm long roundworm, is a popular model organism in almost all areas of modern biology. The worm has several features that make it attractive for biology: it is small (<1000 cells), transparent, and genetically tractable. Despite its simplicity, the worm exhibits complex phenotypes associated with multicellularity: the worm has differentiated cells and organs, it ages and has a well-defined lifespan, and it is capable of learning and remembering. This Review argues that the balance between simplicity and complexity in the worm will make it a useful tool in determining the relationship between molecular-scale phenomena and organism-level phenomena, such as aging, behavior, cognition, and disease. Following an introduction to worm biology, the Review provides examples of current research with C. elegans that is chemically relevant. It also describes tools-biological, chemical, and physical-that are available to researchers studying the worm.