Search Results (199)

Plant-derived toxins such as ricin and abrin represent some of the most potent biological agents known, posing significant threats to public health and security due to their high toxicity, relative ease of extraction, and widespread availability. These ribosome-inactivating proteins (RIPs) have been implicated in politically and criminally motivated events, underscoring their critical importance in the context of biodefense. Public safety agencies, including law enforcement, customs, and emergency response units, require rapid, sensitive, and portable detection methods to effectively counteract these threats. However, many existing screening technologies lack the capability to detect biotoxins unless specifically designed for this purpose, revealing a critical gap in current biodefense preparedness. Consequently, there is an urgent need for robust, field-deployable detection platforms that operate reliably under real-world conditions. End-users in the security and public health sectors demand analytical tools that combine high specificity and sensitivity with operational ease and adaptability. This review provides a comprehensive overview of the biochemical characteristics of ricin and abrin, their documented misuse, and the challenges associated with their detection. Furthermore, it critically assesses key detection platforms—including immunoassays, mass spectrometry, biosensors, and lateral flow assays—focusing on their applicability in operational environments. Advancing detection capabilities within frontline services is imperative for effective prevention, timely intervention, and the strengthening of biosecurity measures. Full article

Ricin, a type 2 ribosome-inactivating protein, is a lethal toxin found in castor bean seeds. Although the systemic toxicity of ricin has been extensively studied, its localized effect on the gastrointestinal tract remains a critical concern, particularly in the case of oral ingestion. This study investigates the cytotoxic effects of ricin on human intestinal epithelial cell lines and its impact on epithelial barrier integrity. Ricin cytotoxicity was assessed on the intestinal-derived HT29 and Caco-2 cell lines using dose– and time–response assays, while the epithelial integrity was evaluated via Trans-Epithelial Electrical Resistance (TEER) measurements in Caco-2 monolayers. Cell death was determined through flow cytometry analysis, and the protective effects of cell death inhibitors and antioxidant scavengers were investigated on ricin-intoxicated cells. Ricin showed high cytotoxicity on HT29 and Caco-2 cells, with EC₅₀ values in the nM range after 24–72 h of intoxication. Moreover, ricin strongly reduced TEER values in Caco-2 cells at 0.1–1 nM after 24 h of treatment. At a 1 nM concentration, ricin cytotoxicity can be significantly prevented by pre-incubating cells with the cell death inhibitors Z-VAD or necrostatin-1 and the antioxidant scavenger catalase, butylated hydroxyanisole or sodium pyruvate, demonstrating the involvement of apoptosis/necroptosis and oxidative stress in ricin cell death pathways and mechanisms. Full article

Ricinus communis (Euphorbiaceae), commonly known as the castor oil plant, is prized for its versatile applications in medicine, industry, and agriculture. It features large, deeply lobed leaves with vibrant colours, robust stems with anthocyanin pigments, and extensive root systems for nutrient absorption. Its terminal panicle-like inflorescences bear monoecious flowers, and its seeds are enclosed in prickly capsules. Throughout its various parts, R. communis harbours a diverse array of bioactive compounds. Leaves contain tannins, which exhibit astringent and antimicrobial properties, and alkaloids like ricinine, known for anti-inflammatory properties, as well as flavonoids like rutin, offering antioxidant and antibacterial properties. Roots contain ellagitannins, lupeol, and indole-3-acetic acid, known for anti-inflammatory and liver-protective effects. Seeds are renowned for ricin, ricinine, and phenolic compounds crucial for industrial applications such as biodegradable polymers. Pharmacologically, it demonstrates antioxidant effects from flavonoids and tannins, confirmed through minimum inhibitory concentration (MIC) assays for antibacterial activity. It shows potential in managing diabetes via insulin signalling pathways and exhibits anti-inflammatory properties by activating nuclear factor erythroid 2-related factor 2 (Nrf2). Additionally, it has anti-fertility effects and potential anticancer activity against cancer stem cells. This review aims to summarize Ricinus communis’s botanical properties, therapeutic uses, chemical composition, pharmacological effects, and industrial applications. Integrating the current knowledge offers insights into future research directions, emphasizing the plant’s diverse roles in agriculture, medicine, and industry. Full article

As a type II ribosome-inactivating protein (RIP-II) toxin, Ricin has garnered widespread recognition due to its inherent qualities as an easily prepared and highly stable substance, posing serious implications as a potential chemical and biological terrorist threat. For the detection of ricin, traditional immunoassay technologies, including methods like peptide cleavage combined with liquid chromatography mass spectrometry (LC-MS) or the more commonly used enzyme-linked immunosorbent assay (ELISA), have offered reliable results. However, these techniques are unfortunately limited by the requirement of a complex sample pretreatment process, which can be time-consuming and labor-intensive. In an effort to overcome these limitations, a highly sensitive and selective method was introduced via metal element labeling combined with inductively coupled plasma mass spectrometry (ICP-MS) in this research. The method centered on designing and synthesizing a europium-labeled compound (DOTA-NHS-Eu) that specifically targets the amino groups (-NH₂) on ricin. The compound, coupled with the application of specific magnetic beads, achieved the specific enrichment and subsequent quantitative detection of ricin by ICP-MS, which is based on the amount of europium element present. The established method demonstrated high specificity for ricin recognition, with a signal response to bovine serum protein that was found to be less than 10% of that for ricin. Furthermore, the calibration curve created for the method (y = 81.543x + 674.02 (R² > 0.99)) for quantifying ricin in a concentration range of 1.0–100 μg/mL demonstrated good linearity. The method was further evidenced by the limit of detection and quantitation results of 0.1 and 1.89 μg/mL, respectively. Collectively, these findings suggested that the research has offered a highly sensitive and selective method for ricin detection, which was not only easy to operate but also provided efficient results. The scheme showed great potential for the verification of chemical weapons and the destruction of toxic chemicals, therefore representing a significant advancement in the field of biomolecular detection and analysis. Full article

Ricin is a highly potent toxin that causes severe lung injury upon inhalation by initiating a complex cascade of cellular responses that ultimately leads to cell death. The low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in various physiological processes, including ricin-mediated toxicity. This study explores the role of LRP1 shedding in the development of ricin-induced lung injury. Analysis of bronchoalveolar lavage fluid (BALF) from ricin-intoxicated mice and swine showed a significant increase in soluble LRP1 (sLRP1) levels, whereas serum LRP1 levels remained largely unchanged, suggesting the lungs are the primary source of sLRP1 release. In vitro assays demonstrated the formation of ricin-sLRP1 complexes, indicating that sLRP1 in BALF retained ricin-binding capability. Flow cytometric analysis of lung cells revealed a reduction in both the percentage and total number of LRP1-expressing cells following ricin exposure. Further investigation of specific lung cell populations showed that alveolar epithelial type II (AT-II) cells, despite experiencing significant injury, exhibited minimal LRP1 shedding. No shedding of LRP1 occurred in neutrophils. In contrast, fibroblasts, which were resistant to ricin-induced cell death, exhibited increased shedding of LRP1 and a corresponding decrease in membrane-bound LRP1 expression. This shedding of the LRP1 ectodomain was mediated by metalloproteinases. Immunohistochemical staining further confirmed decreased LRP1 expression in fibroblasts from ricin-exposed mice. Macrophages also showed substantial LRP1 shedding, despite undergoing significant depletion. These findings highlight the complex cell-specific nature of LRP1 shedding in response to ricin intoxication and suggests the potential role of LRP1 in modulation of cellular susceptibility and resistance to ricin-induced lung injury. Full article

Ricin, a highly toxic glycoprotein derived from the seeds of Ricinus communis, poses significant risks in bioterrorism and toxicology due to its rapid absorption and ease of dissemination. Rapid, ultra-sensitive detection is crucial for timely medical intervention and implementing security measures. However, existing methods often lack sufficient sensitivity or require lengthy processing, limiting their utility for trigger-to-treat scenarios. Here, we present an optical modulation biosensing (OMB)-based ricin assay capable of detecting low concentrations of ricin in buffer, plasma, and biological samples. The assay combines magnetic-bead-based target capture with fluorescent signal enhancement, achieving a limit of detection (LoD) of 15 pg/mL in buffer and 62 pg/mL in plasma, with a 4-log dynamic range. Optimized protocols reduced the assay time to 60 min, maintaining an LoD of 114 pg/mL in plasma while preserving accuracy and reproducibility. The assay successfully detected ricin in bronchoalveolar lavage fluid and serum from mice that were intranasally exposed to ricin, with signals persisting up to 48 h post exposure. Its rapid, high-throughput capabilities and simplified workflow make the OMB-based assay a powerful tool for toxicology, forensic analysis, and counter-bioterrorism. This study highlights the OMB platform’s potential as a sensitive and robust diagnostic tool for detecting hazardous biological agents. Full article

TM9SF2 belongs to a family of highly conserved nonaspanin proteins, and has been frequently identified as one of the important host factors for a plethora of lethal pathogens and toxins in previous genome-wide screening studies. We reported herein a novel molecular mechanism of TM9SF2 in mediating the cytotoxicity of ricin, a type II ribosome-inactivating protein. We first showed that TM9SF2 displays a non-redundant requirement for ricin-induced cytotoxicity within the nonaspanin family. Then we found that genetic interference of TM9SF2 substantially affects/remodels intracellular cholesterol trafficking, which results in abnormal cholesterol accumulation in Golgi compartments and causes severe Golgi fragmentation. The disruption of Golgi integrity and network impedes the retrograde transport of ricin and thus attenuates ricin-induced cytotoxicity. We further verified this mechanism by pharmacological manipulation of cholesterol metabolism (e.g., by using A939572 and avasimibe, etc.), which well restores the integrity of the Golgi apparatus and reverses the ricin-resistant phenotype induced by TM9SF2 knockdown. Our finding provides new mechanistic insights into the pathology and toxicology of ricin and could potentially be applied to other ribosome-inactivating toxins. Full article

The nature and epidemiology of plant intoxications are still not well understood, with recent data being limited. The present study aims to report cases of plant poisoning in the clinical practice of the Clinical Toxicology Department at the Naval Hospital—Varna, Bulgaria, over a 20-year period (2003–2023). A documentary retrospective analysis of the hospitalized cases of poisoning with poisonous plants and their grouping into toxidromes was performed. During the study period, patients with plant poisoning admitted to our hospital unit accounted for 0.35% of a total of 12,857 hospitalized individuals. The distribution across the toxidromes based on clinical presentation revealed the highest frequency of anticholinergic, cyanogen, and ricin toxidromes. The majority of the intoxications resulted from unintentional exposure to plant toxins in adult individuals. Most cases followed a mild to severe clinical course, with patient discharge occurring between 2 and 5 days. No fatalities were recorded, thanks to the reported treatment methods. A relatively low incidence of plant-related poisonings was observed, with their predominant manifestations affecting the gastrointestinal, nervous, and cardiovascular systems. Increased reporting of epidemiological data and clinical experiences in the management of plant intoxications would substantially enhance researchers’ understanding of them and facilitate the development of a standardized treatment protocol. Full article

Ricin (RT) and abrin (AT) are plant toxins extracted from Ricinus communis and Abrus precatorius, respectively, and both have N-glycosidase activity. The detection of these toxins is vital because of their accessibility and bioterrorism potential. While ricin can be effectively detected based on its depurination activity, only a few tests are available for detecting the depurination activity of abrin. Therefore, it is unclear whether they share the same optimal reaction substrate and conditions. Here, we established optimum depurination conditions for ricin and abrin, facilitating the in vitro detection of their depurination activity using high-performance liquid chromatography–tandem mass spectrometry. The parameters optimized were the reaction substrate, bovine serum albumin (BSA), buffer, pH, temperature, time, antibodies, and magnetic beads. Both toxins showed better depurination with single-stranded DNA. However, substrate length, adenine content, BSA concentration, buffer concentration, reaction temperature, and reaction time differed between the two toxins. The optimal conditions for ricin depurination involved a reaction in 1 mM ammonium acetate solution (0.5 μM DNA15A, 20 μg/mL BSA, and 1 mM Zn²⁺, with pH 4.0) at 55 °C for 1 h. The optimal conditions for abrin depurination involved a reaction in 1 mM ammonium citrate solution (0.2 μM DNA20A, 10 μg/mL BSA, 1 mM Mg²⁺, and 0.5 mM EDTA, with pH 4.0) at 45 °C for 2 h. After optimization, the limits of detection (LOD) for ricin and abrin were 0.506 ng/mL and 0.168 ng/mL, respectively. The detection time was also significantly reduced. Full article

Abrin is a highly toxic plant protein encompassing four isoforms, abrin-a, -b, -c and -d. An abrin reference material was isolated from Abrus precatorius and certified (EURM-113) by the EuroBioTox consortium. Here, we present a detailed characterisation of the N-glycosylation profile of EURM-113. The monosaccharide composition of the N-glycans was determined and quantified. Release of the N-glycans yielded 13 different partially xylosylated, oligomannosidic and paucimannosidic glycan structures. Two N-glycans were found at N82 and N110 of the abrin-b A-chain and another two at N100 and N140 of the B-chains. The N-glycosylation sites N200 in the A-chain and N141 in the B-chain were non-glycosylated. Whereas N82 and N110 of abrin-b comprised paucimannosidic glycans, N100 and N140 of the B-chains revealed oligomannosidic N-glycans. Xylose was absent in the glycans at N100 but was present in about half of the glycans at N140. Hence, this study revealed substantially different types of glycan structures within the B-chains compared to the abrin-b A-chain. Furthermore, the most C-terminal N-glycosylation site in the A-chain was found to be non-glycosylated in all abrin isoforms detected. Additionally, the establishment of the N-glycosylation profile of the abrin reference material led to the identification of the abrin isoforms -a, -b and -c. In conclusion, the abrin N-glycosylation profile is highly similar to the one of ricin and yields high analytical value to be further exploited as a fingerprint in forensic investigations to uncover toxin production or toxin provenance. Full article

Soil salinization poses a serious threat to global food security, as high Na⁺ contents in soils hinder nitrogen use efficiency (NUE), affecting the growth and yield of crop plants. The present study aims to explore the effects of different nitrogen fertilizer types viz., NO₃⁻ (N1) and NH₄⁺ (N2) and planting densities, viz., D1: 30 × 10 cm, D2: 20 × 20 cm, and D3: 30 × 20 cm, on growth and development, nitrogen absorption and utilization, and yield formation. The salt-tolerant rice variety ‘Jingliangyou 3261’ was exposed to 0.3% salt irrigation water. Results revealed that N2 substantially improved the rice yield by increasing the number of effective panicles and the rate of grain-setting compared to N1. In addition, the N2 also increased leaf chlorophyll content, dry matter accumulation, antioxidant enzyme activity such as superoxide dismutase, peroxidase, and catalase activity and reduced the content of malondialdehyde. In comparison with N1, the N2 treatment resulted in an increase of 12.21%, 31.89%, and 37.53% in total nitrogen accumulation, nitrogen recovery efficiency (NRE), and nitrogen agronomic efficiency (NAE), respectively. This increase can be attributed to enhanced leaf nitrogen metabolic enzyme activity, including nitrate reductase and glutamine synthetase, and a more robust root system. Under N1 and N2 conditions, compared to D3, D1 resulted in an increase in the number of tillers but decreased the percentage of productive tillers, the grains per panicle, the grain-filling rate, and the thousand-grain weight, thereby reducing yield. Additionally, the D3 treatment also significantly improved NRE and NAE compared to the D1 treatment. Therefore, the rational selection of nitrogen fertilizer type (N2) and planting density (D3) is crucial for improving the yield and nitrogen use efficiency of salt-tolerant rice. This would broaden the scope of agricultural solutions for saline soils, potentially improving food security in regions where soil salinization is a widespread issue. Full article

The COVID-19 and mpox crisis has reminded the world of the potentially catastrophic consequences of biological agents. Aside from the natural risk, biological agents can also be weaponized or used for bioterrorism. Dissemination in a population or among livestock could be used to destabilize a nation by creating a climate of terror, by negatively impacting the economy and undermining institutions. The Centers for Disease Control and Prevention (CDC) classify biological agents into three categories (A or Tier 1, B and C) according to the risk they pose to the public and national security. Category A or Tier 1 consists of the six pathogens with the highest risk to the population (Bacillus anthracis, Yersinia pestis, Francisella tularensis, botulinum neurotoxins, smallpox and viral hemorrhagic fevers). Several medical countermeasures, such as vaccines, antibodies and chemical drugs, have been developed to prevent or cure the diseases induced by these pathogens. This review presents an overview of the primary medical countermeasures, and in particular, of the antibodies available against the six pathogens on the CDC’s Tier 1 agents list, as well as against ricin. Full article

Botulinum neurotoxins (BoNTs), ricin, and many other biological toxins are called AB toxins possessing heterogeneous A and B subunits. We propose herein a quick and safe sensing approach to AB toxins based on their unique quaternary structures. The proposed approach utilizes IgG antibodies against their A-subunits in combination with those human cell-membrane glycolipids that act as the natural ligands of B-subunits. In practice, an IgG antibody against the A-subunit of a target toxin is selected from commercially available sources and immobilized on the surface of Au nanoparticles to constitute a multivalent IgG/Au nanoconjugate. The derived IgG/Au conjugate is used in the pretreatment process of test samples for deactivating biological toxins in the form of a ternary toxin/antibody/Au complex. This process is implemented in advance to reduce the risk of handling biological toxins in laboratory work. On the other hand, the human glycolipid is immobilized on a tiny glass plate and used as a biosensor chip. The biosensor chip is set in the chamber of a flow sensing system using localized surface plasmon resonance (LSPR) spectrometry available in portable size at relatively low cost. In principle, the LSPR sensing system enables us to perform a rapid and selective detection for different kinds of biological toxins if the human glycolipid is correctly selected and installed in the sensing system. In the present LSPR sensing approach, a target AB toxin may have been deactivated during the pretreatment process. The test sample containing the deactivated AB toxin becomes a real target to be analyzed by the sensing system. In the present, we describe the concept of employing the commercially available IgG antibody in the pretreatment process followed by a typical procedure for converting it into the multivalent antibody/Au nanoconjugate and its preliminary applications in the LSPR detection of a ricin homologue (RCA₁₂₀) and BoNTs in different serotypes. The tested LSPR sensing approach has worked very well for the ricin homologue and certain serotypes of botulinum neurotoxins like BoNT/A, indicating that the prior deactivation process at their A-domains causes no significant damage to the function of their B-domains with respect to determining the host cell-membrane glycolipid. The experimental results also indicated that LSPR responses from these pretreated AB toxins are significantly amplified. That is obviously thanks to the presence of Au nanoparticles in the multivalent IgG/Au nanoconjugate. We suggest in conclusion that the proposed LSPR sensing approach will provide us with a safe and useful tool for the study of biological AB toxins based on their unique quaternary protein structures. Full article

Background/Objectives: Ricin’s high toxicity and potential as a bioweapon underscore the need for effective antidotes. Monoclonal antibodies, though effective, are limited by complex production. This study aimed to develop a graphene oxide-based aptamer nanoarray (ARMAN) for improved neutralization and protection against ricin. Methods: High-affinity aptamers targeting ricin’s RTA and RTB subunits were selected using SELEX technology and conjugated to graphene oxide (GO) via click chemistry. ARMAN’s characteristics, including morphology, stability, and biosecurity, were assessed. Its performance was evaluated in terms of affinity for ricin, neutralization capacity, and therapeutic effects in cellular assays and a mouse model of ricin poisoning. Results: ARMAN exhibited a uniform morphology with an average particle size of 217 nm and demonstrated significantly enhanced affinity for ricin compared to free aptamers. ARMAN showed rapid and effective neutralization ability, significantly increasing cell viability in BEAS-2B, GES-1, and HL7702 cell lines exposed to ricin. In vivo, ARMAN treatment led to a notable prolongation of survival in ricin-poisoned mice, highlighting its potential for both pre- and post-exposure treatment. These findings indicate that ARMAN not only neutralizes ricin effectively but also provides a therapeutic window for treatment. Conclusions: ARMAN’s superior binding affinity, serum stability, biocompatibility, and broad therapeutic efficacy make it a promising new antidote against ricin poisoning. This study’s findings represent significant progress in the development of rapid-response antidotes, with ARMAN offering a potential solution for both military and civilian emergency response scenarios. Full article

Malanin is a new type II ribosome-inactivating protein (RIP) purified from Malania oleifera, a rare, endangered tree is only found in the southwest of Guangxi Province and the southeast of Yunnan Province, China. The gene coding sequence of malanin was found from the cDNA library of M. oleifera seeds by employing the ten N-terminal amino acid sequences of malanin, DYPKLTFTTS for chain-A and DETXTDEEFN (X was commonly C) for chain-B. The results showed a 65% amino acid sequence homology between malanin and ricin by DNAMAN 9.0 software, the active sites of the two proteins were consistent, and the four disulfide bonds were in the same positions. The primary sequence and three-dimensional structures of malanin and ricin are likely to be very similar. Our studies suggest that the mechanism of action of malanin is expected to be analogous to ricin, indicating that it is a member of the type II ribosome-inactivating proteins. This result lays the foundation for further study of the anti-tumor activities of malanin, and for the application of malanin as a therapeutic agent against cancers. Full article