Ricin

蓖麻毒素
  • 文章类型: Journal Article
    大鱼科,也被称为Spurge家族,是一大群开花植物。尽管是热带本地人,它们现在很普遍。由于其医药和商业重要性,这个植物家族在科学界引起了很多关注。这个家庭的独特特征是生产乳白色乳胶,这是几种凝集素的丰富来源,结合碳水化合物的蛋白质。虽然功能不明确,它们被认为可以保护植物免受有害的植物病原微生物的侵害,昆虫,和掠食性动物。此外,它们在各种压力下充当关键的代谢调节剂。检测,分离,净化,40多年前开始对来自大的话科的凝集素进行表征-主要来自植物的乳胶。这项工作产生了超过35篇发表的原始研究论文。然而,尚未提供对这些已发布数据进行系统审查。这篇综述总结并描述了用于提取和纯化属于该家族的凝集素的几种程序和方案。凝集素的理化性质和生物活性,连同它们的药用和药理特性,也进行了分析。此外,使用蓖麻毒素和蓖麻毒素凝集素的例子,我们在结构上分析了属于该家族的被称为核糖体失活蛋白II型(RIP-II型)的凝集素的特征。我们预计这篇综述文章将提供有关这一重要凝集素家族的有用信息汇编,向参与凝集素研究的科学家展示我们知识的差距,并为未来的研究提供见解。
    Euphorbiaceae, also known as the spurge family, is a large group of flowering plants. Despite being tropical natives, they are now widespread. Due to its medicinal and commercial importance, this family of plants attracted a lot of attention in the scientific community. The distinctive characteristic of the family is production of milky latex, which is a rich source of several lectins, the proteins that bind carbohydrates. Although their function is unclear, they are believed to defend plants against damaging phytopathogenic microorganisms, insects, and predatory animals. Additionally, they serve as crucial metabolic regulators under a variety of stressors. Detection, separation, purification, and characterization of lectins from the Euphorbiaceae family - mostly from the latex of plants - began over 40 years ago. This effort produced over 35 original research papers that were published. However, no systematic review that compiles these published data has been presented yet. This review summarizes and describes several procedures and protocols employed for extraction and purification of lectins belonging to this family. Physicochemical properties and biological activities of the lectins, along with their medicinal and pharmacological properties, have also been analyzed. Additionally, using examples of ricin and ricin agglutinin, we have structurally analyzed characteristics of the lectin known as Ribosome Inactivating Protein Type II (RIP-Type II) that belongs to this family. We anticipate that this review article will offer a useful compendium of information on this important family of lectins, show the scientists involved in lectin research the gaps in our knowledge, and offer insights for future research.
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  • 文章类型: Journal Article
    蓖麻毒素(RT)属于毒素的核糖体失活蛋白(RIP)家族,被美国疾病控制与预防中心(CDC)认为是中度威胁。RT对公众构成了巨大的潜在威胁,但是到目前为止还缺乏有效的治疗方案。在过去的几十年里,已经对预防和治疗RT中毒的研究进行了调查,其中特异性靶向RT的中和抗体一直是研究热点。在这次审查中,我们总结了RT的作用机制,RT中和抗体的研究结果和设计策略,并讨论了RT中和抗体研究发展中的关键问题。
    Ricin toxin (RT) belongs to the ribosome-inactivating protein (RIP) family of toxins and is considered to be a moderate threat by the US Center of Disease Control and Prevention (CDC). RT poses a great potential threat to the public, but there has been a lack of effective treatment options so far. Over the past few decades, researches on the prevention and treatment of RT poisoning have been investigated, among which neutralizing antibodies targeting RT specifically have always been a research hotspot. In this review, we have summarized the mechanism of action of RT, the research results and the design strategies of RT neutralizing antibodies, and discussed the key issues in the development of RT neutralizing antibody researches.
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  • 文章类型: Journal Article
    Ⅱ型核糖体失活蛋白(RIPs)是一类重要的蛋白毒素,由A链和B链通过链间二硫键连接而成。具有凝集素样活性的B链负责与真核细胞表面的含半乳糖受体结合,这对于通过内吞作用实现A链内化至关重要。A链具有N-糖苷酶活性,可从28S核糖体RNA(28SrRNA)中不可逆地纯化特定的腺嘌呤并终止蛋白质合成。A-B链的协同作用使核糖体失活,抑制蛋白质合成,并表现出高细胞毒性。蓖麻和Abrusprecatorius植物表达的蓖麻毒素和abrin,分别,是典型的Ⅱ型RIP。蓖麻毒素和abrin的毒性分别是385倍和2885倍,分别,更多的是神经毒剂VX。由于它们易于准备,广泛的可用性,以及作为生物恐怖主义代理人的潜在用途,Ⅱ型RIP近年来受到越来越多的关注。蓖麻毒素被列为《化学武器公约》(CWC)附表1A的违禁物质。近年来蓖麻毒素相关生物恐怖事件的发生,敏感,Ⅱ型RIPs的快速检测与识别技术。Ⅱ型RIPs的毒性机制和检测方法的研究取得了重大进展,主要涉及定性和定量分析方法,包括免疫测定,质谱分析方法,和基于脱嘌呤和细胞毒性的毒素活性检测方法。免疫测定通常涉及抗原和抗体的特异性识别,它基于称为适体的寡核苷酸分子识别元件。这些方法快速且高度灵敏,但是对于复杂样本中高度同源的蛋白质,他们提供假阳性结果。随着生物质谱检测技术的快速发展,电喷雾电离(ESI)和基质辅助激光解吸电离(MALDI)等技术被广泛用于蛋白质的鉴定。这些方法不仅提供了有关蛋白质分子量和结构的准确信息,但也证明了准确的量化。酶消化结合质谱是主要使用的检测方法。通过酶消化的肽的指纹分析可以实现蛋白质毒素的准确鉴定。为了分析复杂样品中的蛋白质毒素,使用多酶消化策略获得丰富的肽标记。肽标记的靶向质谱分析用于获得准确的定性和定量信息,有效地提高了Ⅱ型RIP毒素鉴定的准确性和灵敏度。虽然免疫分析和质谱检测方法可以准确鉴定Ⅱ型RIPs,他们无法确定毒素是否会保持效力。Ⅱ型RIPs活性分析中广泛使用的检测方法包括基于N-糖苷酶活性的脱嘌呤试验和细胞毒性试验。这两种方法都提供了简单的,快速,Ⅱ型RIP毒性的敏感性分析,并补充其他检测方法。由于Ⅱ型RIP毒素的重要性,禁止化学武器组织(OPCW)提出了明确的技术要求,以识别和分析相关样品。我们在这里回顾了结构特征,作用机制,以及Ⅱ型RIP检测方法的发展和应用;引用了近70项Ⅱ型RIP毒素及其检测方法的研究。除了禁化武组织明确鉴定生物毒素的技术要求外,探讨了Ⅱ型RIP检测技术的未来发展趋势。
    Type Ⅱ ribosome-inactivating proteins (RIPs) are an important class of protein toxins that consist of A and B chains linked by an interchain disulfide bond. The B-chain with lectin-like activity is responsible for binding to the galactose-containing receptors on eukaryotic cell surfaces, which is essential for A-chain internalization by endocytosis. The A-chain has N-glycosidase activity that irreversibly depurinates a specific adenine from 28S ribosomal RNA (28S rRNA) and terminates protein synthesis. The synergistic effect of the A-B chain inactivates the ribosome, inhibits protein synthesis, and exhibits high cytotoxicity. Ricin and abrin that are expressed by the plants Ricinus communis and Abrus precatorius, respectively, are typical type Ⅱ RIPs. The toxicity of ricin and abrin are 385 times and 2885 times, respectively, more that of the nerve agent VX. Owing to their ease of preparation, wide availability, and potential use as a bioterrorism agent, type Ⅱ RIPs have garnered increasing attention in recent years. Ricin is listed as a prohibited substance under schedule 1A of the Chemical Weapons Convention (CWC). The occurrence of ricin-related bioterrorism incidents in recent years has promoted the development of accurate, sensitive, and rapid detection and identification technology for type Ⅱ RIPs. Significant progress has been made in the study of toxicity mechanisms and detection methods of type Ⅱ RIPs, which primarily involve qualitative and quantitative analysis methods including immunological assays, mass spectrometry analysis methods, and toxin activity detection methods based on depurination and cytotoxicity. Immunoassays generally involve the specific recognition of antigens and antibodies, which is based on oligonucleotide molecular recognition elements called aptamers. These methods are fast and highly sensitive, but for highly homologous proteins in complex samples, they provide false positive results. With the rapid development of biological mass spectrometry detection technology, techniques such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) are widely used in the identification of proteins. These methods not only provide accurate information on molecular weight and structure of proteins, but also demonstrate accurate quantification. Enzyme digestion combined with mass spectrometry is the predominantly used detection method. Accurate identification of protein toxins can be achieved by fingerprint analysis of enzymatically digested peptides. For analysis of protein toxins in complex samples, abundant peptide markers are obtained using a multi-enzyme digestion strategy. Targeted mass spectrometry analysis of peptide markers is used to obtain accurate qualitative and quantitative information, which effectively improves the accuracy and sensitivity of the identification of type Ⅱ RIP toxins. Although immunoassay and mass spectrometry detection methods can provide accurate identification of type Ⅱ RIPs, they cannot determine whether the toxins will retain potency. The widely used detection methods for activity analysis of type Ⅱ RIPs include depurination assay based on N-glycosidase activity and cytotoxicity assay. Both the methods provide simple, rapid, and sensitive analysis of type Ⅱ RIP toxicity, and complement other detection methods. Owing to the importance of type Ⅱ RIP toxins, the Organization for the Prohibition of Chemical Weapons (OPCW) has proposed clear technical requirements for the identification and analysis of relevant samples. We herein reviewed the structural characteristics, mechanism of action, and the development and application of type Ⅱ RIP detection methods; nearly 70 studies on type Ⅱ RIP toxins and their detection methods have been cited. In addition to the technical requirements of OPCW for the unambiguous identification of biotoxins, the trend of future development of type Ⅱ RIP-based detection technology has been explored.
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  • 文章类型: Journal Article
    背景:蓖麻毒素,一种来源于蓖麻植物的有毒糖蛋白,是世界上已知的最有效的毒药之一。蓖麻毒素中毒是一种致命且不常见的医学状况,最近也有报道将其用作潜在的生物恐怖主义剂。这项研究旨在确定全球诊断为蓖麻毒素中毒病例的主要特征,以提高人群和临床医生对这种毒素的认识。
    方法:收集了世界上蓖麻毒素中毒的人类案例研究。数据库Pubmed,Sciencedirect和GoogleScholar用于提取1980年1月至2020年6月的文章。
    结果:已经确定了文献中描述的全球50名蓖麻毒素中毒患者。大多数病例在亚洲发现(19例),欧洲(12例)和美国(15例)。中毒主要是偶然的(37例)。蓖麻中毒的特征是急性胃肠炎样疾病作为主要表现,导致严重的液体和电解质失衡。死亡的机制是中毒后10h-72h发生的外周血管塌陷和进展性多器官功能衰竭。患者和家人的询问使得有可能检索蓖麻籽或蓖麻油摄入史患者接受对症治疗,主要包括静脉输液补液和在摄入后一天内使用活性炭和/或洗胃进行消化净化,减少胃肠道对蓖麻毒素的吸收。早期施用的这种去污处理非常有效。仅观察到6人死亡。
    结论:目前,没有解药,疫苗,或其他特定的有效治疗方法可用于蓖麻毒素中毒或预防。及时给予支持性治疗对于限制发病率和死亡率是必要的。迄今为止,病人的教育对于防止这种意外中毒至关重要。
    结论:临床医生和卫生保健专业人员在面对严重的呼吸道或胃肠道疾病爆发时,应高度怀疑。
    BACKGROUND: Ricin, a toxic glycoprotein derived from the castor bean plant, is one of the most potent poisons known in the world. Ricin intoxication is a fatal and uncommon medical condition and recently its use as a potential bioterrorism agent has also been reported. This study aims to identify the main characteristics of diagnosed ricin poisoning cases worldwide in order to raise awareness of this toxin among the population and clinicians.
    METHODS: A collection of human case studies of ricin intoxication in the world was produced. The databases Pubmed, Sciencedirect and Google Scholar were used to extract articles from January 1980 to June 2020.
    RESULTS: Fifty ricin-intoxicated patients worldwide described in the literature have been identified. Most cases were found in Asia (19 cases), Europe (12 cases) and America (15 cases). Intoxication was mostly accidental (37 cases). Intoxication by castor bean is characterized by acute gastroenteritis-like disease as primary manifestations leading to severe fluid and electrolyte imbalance. The mechanism of death was peripheral vascular collapse and progressing multiple organ failure occurring 10h-72h after intoxication. The questioning of patients and family made it possible to retrieve an history of castor seeds or castor oil ingestion Patients received symptomatic treatment consisting mostly to rehydration with intravenous fluids and digestive decontamination performed with activated charcoal and/or gastric lavage within one day after the ingestion, to reduce gastrointestinal absorption of ricin. This decontamination treatment administered early has been very effective. Only six deaths were observed.
    CONCLUSIONS: Currently, no antidote, vaccine, or other specific effective treatment is available for ricin poisoning or prevention. Prompt treatment with supportive care was necessary to limit morbidity and mortality. To date, patient education is essential to prevent this accidental poisoning.
    CONCLUSIONS: Clinicians and health care professionals should have a high level of suspicion when faced with an outbreak of serious respiratory or gastrointestinal illness.
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  • 文章类型: Case Reports
    UNASSIGNED: >1000 ricin poisoning cases secondary to intentional castor bean consumption have been reported in the literature since the late 1800s. The lethality of ricin poisoning after oral ingestion is determined by a few factors.
    UNASSIGNED: We present a case that highlights the erratic absorption of ricin after accidental oral ingestion. On admission, the physical examination found a somnolent patient, with miosis, and a generalized abdominal tenderness. Her blood tests showed metabolic acidosis. Thanks to her early management, the discharge was possible three days later.
    UNASSIGNED: The toxicity of ricin is dependent on the dose delivered and the route of the exposure. Supportive care is the mainstay of treatment. As shown in our case, early management is crucial for a good outcome.
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    文章类型: Journal Article
    Ricinus cmmunis L. (Castor oil plant) is an important medicinal plant belonging to family Euphorbiaceae. Its phytochemistry, biological and pharmacological activities, and ethnomedicinal uses have been reviewed in the present study. The reported chemical constituents showed the presence of flavonoids, phenolic compounds, fatty acids, amino acids, terpenoids, phytosterol etc. The compounds have been reported to exhibit anticonceptive, antidiabetic, antifertility, anti-inflammatory, antimicrobial, antioxidant, hepatoprotective, insecticidal and wound-healing activities. They also showed free radical scavenging and Hg scavenging activities, and repellent properties. Various parts of R. communis have been widely used in traditional medicine such as abdominal disorders, arthritis, backache, muscle aches, bilharziasis, chronic backache and sciatica, chronic headache, constipation, expulsion of placenta, gallbladder pain, period pain, menstrual cramps, rheumatism, sleeplessness, and insomnia. Castor oil plant has also revealed toxic effects due to the presence of ricin (protein) and ricinine (alkaloid). Comparatively, ricin is more toxic. But still there is need of more research to be conducted with reference to its medicinal importance (particularly exploring of medicinal recipes) and active compounds responsible for various activities.
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  • 文章类型: Case Reports
    背景:蓖麻毒素是一种源自蓖麻植物蓖麻的蛋白质毒素。已经发表了一些继发于其消费的案例,最近,它作为一种潜在的生物恐怖主义剂也有报道。蓖麻毒素的口服吸收非常不稳定,导致广泛的症状。此外,常规尿液药物筛选测试将无法检测到这种化合物,构成诊断挑战。
    方法:一名男性青少年打算在与果汁混合后摄入200粒蓖麻豆而死亡。八个小时后,他表现出软弱,头脑清醒,恶心,呕吐和求医。患者入院并保守治疗。基于免疫的标准尿毒理学药物筛选小组报告为阴性。一项全面的非目标尿液药物筛查测试显示存在蓖麻碱,蓖麻毒素中毒的替代标记。入院后3天,他被转移到精神病院。为什么一个紧急医生应该意识到这一点?:这个案例强调了了解蓖麻毒素在口服摄入蓖麻毒素和通过咀嚼释放毒素后独特的药代动力学特性的重要性。急诊医生应该意识到蓖麻毒素的口服吸收取决于几个因素,这种类型和大小的种子和地理收获区域,这使得仅根据摄入的豆类数量来估计其杀伤力极其困难。最后,在这种情况下,全面的非目标尿液药物筛查测试作为诊断工具非常有价值。
    BACKGROUND: Ricin is a protein toxin derived from the castor bean plant Ricinus communis. Several cases secondary to its consumption have been published and, more recently, its use as a potential bioterrorism agent has also been reported. Oral absorption of ricin is highly erratic, leading to a wide spectrum of symptoms. In addition, conventional urine drug screening tests will not be able to detect this compound, posing a diagnostic challenge.
    METHODS: A male teenager intended to die by ingesting 200 castor beans after mixing and blending them with juice. Eight hours later, he presented with weakness, light-headedness, nausea, and vomiting and sought medical treatment. The patient was admitted and treated conservatively. An immune-based standard urine toxicology drug screen panel was reported as negative. A comprehensive untargeted urine drug screen test showed the presence of ricinine, a surrogate marker of ricin intoxication. He was transferred to the psychiatric service 3 days after admission. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: This case highlights the importance of knowing the peculiar pharmacokinetic properties of ricin after oral ingestion of castor beans and toxin release through mastication. Emergency physicians should be aware that oral absorption of ricin is dependent on several factors, such type and size of seeds and the geographic harvesting region, making it extremely difficult to estimate its lethality based solely on the number of ingested beans. Finally, comprehensive untargeted urine drug screening testing is highly valuable as a diagnostic tool in this context.
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  • 文章类型: Journal Article
    Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes. This article will also review different generations of immunotoxins with special focus on immunotoxins which are under clinical trials or approved for clinical use. Finally, current deimmunization strategies for development of new less-immunogenic recombinant immunotoxins will be discussed.
    mAbs: Monoclonal antibodies; EF2: elongation factor 2; ITs: Immunotoxins; DT: Diphtheria toxin; PE: Pseudomonas exotoxin; dgA: de-glycosylated A-chain of ricin; rGel: recombinant de-glycosylated form of gelonin; NKC: natural killer cells; HTR: human transferrin receptor; EGF: epidermal growth factor; GM-CSF: granulocyte-macrophage colony-stimulating factor; DAB389: truncated Diphtheria toxin; B-CCL: B-cell chronic lymphocytic leukemia; RCC: renal cell carcinoma; GVHD: Graft-versus-host disease; EGFR: epidermal growth factor receptor; AML: acute myeloid leukemia; Fab: fragment antigen-binding; dsFv: disulfide-stabilized fragment variable; scFv: single-chain fragment variable; B-ALL: B-lineage Acute Lymphoblastic Leukemia; Fv: fragment variable; HCL: hairy cell leukemia; IL-2R: Interleukin-2 receptor; CR: complete response; CLL: chronic lymphocytic leukemia; ATL: adult T-cell leukemia; DARPins: designed Ankyrin repeat proteins; pmol: picomolar; HAMA: human-anti mouse antibody.
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  • 文章类型: Journal Article
    Toxins are hazardous biochemical compounds derived from bacteria, fungi, or plants. Some have mechanisms of action and physical properties that make them amenable for use as potential warfare agents. Currently, some toxins are classified as potential biological weapons, although they have several differences from classic living bio-terror pathogens and some similarities to manmade chemical warfare agents. This review focuses on category A and B bio-terror toxins recognized by the Centers for Disease Control and Prevention: Botulinum neurotoxin, staphylococcal enterotoxin B, Clostridium perfringens epsilon toxin, and ricin. Their derivation, pathogenesis, mechanism of action, associated clinical signs and symptoms, diagnosis, and treatment are discussed in detail. Given their expected covert use, the primary diagnostic challenge in toxin exposure is the early detection of morbidity clusters, apart from background morbidity, after a relatively short incubation period. For this reason, it is important that clinicians be familiar with the clinical manifestations of toxins and the appropriate methods of management and countermeasures.
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  • 文章类型: Journal Article
    Exposure of the lungs to airborne toxicants from different sources in the environment may lead to acute and chronic pulmonary or even systemic inflammation. Cigarette smoke is the leading cause of chronic obstructive pulmonary disease, although wood smoke in urban areas of underdeveloped countries is now recognized as a leading cause of respiratory disease. Mycotoxins from fungal spores pose an occupational risk for respiratory illness and also present a health hazard to those living in damp buildings. Microscopic airborne particulates of asbestos and silica (from building materials) and those of heavy metals (from paint) are additional sources of indoor air pollution that contributes to respiratory illness and is known to cause respiratory illness in experimental animals. Ricin in aerosolized form is a potential bioweapon that is extremely toxic yet relatively easy to produce. Although the aforementioned agents belong to different classes of toxic chemicals, their pathogenicity is similar. They induce the recruitment and activation of macrophages, activation of mitogen-activated protein kinases, inhibition of protein synthesis, and production of interleukin-1 beta. Targeting either macrophages (using nanoparticles) or the production of interleukin-1 beta (using inhibitors against protein kinases, NOD-like receptor protein-3, or P2X7) may potentially be employed to treat these types of lung inflammation without affecting the natural immune response to bacterial infections.
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