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Occurrence of Staphylococcus aureus TSST-1 in Foods: A Review. 金黄色葡萄球菌TSST-1在食品中的发生:综述。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-18 DOI: 10.3390/toxins17120606
Maria Govari, Andreana Pexara

Toxic Shock Syndrome Toxin-1 (TSST-1) is produced by Staphylococcus aureus strains encoded by the tst gene. Toxic shock syndrome (TSS) is a severe disease caused by TSST-1 toxin and associated with staphylococcal food poisoning (SFP). The aim of the present review was to present data on the occurrence of S. aureus TSST-1 in foods published in various countries. PCR-based assays are most frequently used for the detection of S. aureus TSST-1 in foods. S. aureus TSST-1 is predominantly detected in foods of animal origin. The highest occurrence has been observed in mastitic ruminants' milk, indicating that mastitis is a risk of milk contamination with the pathogen. High occurrence rates of S. aureus TSST-1 have also been identified in raw milk and artisanal cheeses. Various occurrence levels have also been reported in beef, pork, lamb, and chicken meat. Low occurrence levels have also been reported for fish or other seafood products. The tst gene was also found in combination with other toxigenic genes in S. aureus TSST-1 isolates (e.g., MRSA or Panton-Valentine Leukocidin, PVL). Monitoring S. aureus TSST-1 in food is important for public health because food can be a vehicle for transmitting the antibiotic-resistant pathogen to humans.

中毒性休克综合征毒素-1 (TSST-1)是由金黄色葡萄球菌菌株由tst基因编码产生的。中毒性休克综合征(TSS)是一种由TSST-1毒素引起的严重疾病,与葡萄球菌性食物中毒(SFP)有关。本综述的目的是介绍在不同国家发表的食品中金黄色葡萄球菌tst -1的发生数据。基于pcr的检测方法最常用于食品中金黄色葡萄球菌tst -1的检测。金黄色葡萄球菌tst -1主要在动物源性食品中检测到。在乳糜反刍动物的乳汁中观察到的发病率最高,表明乳腺炎是乳汁被病原体污染的风险。金黄色葡萄球菌TSST-1在原料牛奶和手工奶酪中也有很高的发生率。在牛肉、猪肉、羊肉和鸡肉中也有不同程度的报告。据报道,鱼类或其他海产品的发病率也很低。在金黄色葡萄球菌tst -1分离株(如MRSA或pton - valentine Leukocidin, PVL)中也发现了tst基因与其他产毒基因的结合。监测食品中的金黄色葡萄球菌tst -1对公共卫生很重要,因为食品可能是将耐抗生素病原体传播给人类的媒介。
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引用次数: 0
Venom-Induced Recurrent Thrombocytopenia: A Model of Intervention-Driven Platelet Modulation. 毒液诱导的复发性血小板减少症:干预驱动的血小板调节模型。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-17 DOI: 10.3390/toxins17120605
Mojca Dobaja Borak, Katarina Reberšek, Tihana Kurtović, Adrijana Leonardi, Igor Križaj, Miran Brvar

We present the case of a Vipera ammodytes ammodytes (Vaa, nose-horned viper)-bitten patient with recurrent thrombocytopenia. A 53-year-old patient envenomated by Vaa experienced three episodes of venom-dependent thrombocytopenia (4, 57 and 11 × 109/L), all of which we managed with antivenom Fab fragments. Despite these three severe episodes of thrombocytopenia within 24 h, platelet function remained intact, as demonstrated by normal thromboelastometry and aggregometry (96, 126, and 150 U) results after antivenom was administered and the platelet count normalized. Furthermore, flow cytometry showed only 0.3-1.7% expression of P-selectin on platelets, indicating that platelets did not activate but remained functional during and after thrombocytopenia. We assessed platelet function using rotational thromboelastometry, which evaluates the overall kinetics of hemostasis, including clot formation and stability. We performed aggregometry, which also reflects platelet function, only when the platelet count was within the normal range. Flow cytometry quantified P-selectin expression as a key marker of platelet activation. This case demonstrates that a component of Vaa venom can repeatedly induce venom-dependent thrombocytopenia, which is reversible by intervention, while platelet function remains intact.

我们提出的情况下,毒蛇ammodytes ammodytes (Vaa,鼻角毒蛇)咬伤患者复发性血小板减少症。一名53岁的Vaa中毒患者经历了三次毒液依赖性血小板减少(4,57和11 × 109/L),我们均使用抗蛇毒血清Fab片段进行治疗。尽管在24小时内发生了三次严重的血小板减少,血小板功能仍保持完整,抗蛇毒血清治疗后血小板计数恢复正常,血小板弹性测量和聚集测量(96、126和150 U)结果显示血小板功能正常。此外,流式细胞术显示p -选择素在血小板上的表达仅为0.3-1.7%,表明血小板在血小板减少期间和之后没有激活,但仍保持功能。我们使用旋转血栓弹性测量法评估血小板功能,该方法评估了整体止血动力学,包括凝块形成和稳定性。只有当血小板计数在正常范围内时,我们才进行聚集测定,这也反映了血小板功能。流式细胞术定量p -选择素的表达作为血小板活化的关键标志物。该病例表明,Vaa毒液的一种成分可以反复诱导毒液依赖性血小板减少症,这是通过干预可逆的,而血小板功能保持完整。
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引用次数: 0
Microorganism-Based Strategies for the Control of Cyanobacterial Blooms: A Review of Recent Progress. 基于微生物的蓝藻华控制策略:最新进展综述
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-17 DOI: 10.3390/toxins17120604
Wangle Zhang, Shiyuan Meng, Xiaoxu Wu, Hong Shen, Dongqin Wang, Tong Qiu, Weijie Li, Jiping Chen, Ling Li, Bingbing Liang, Mengdi Zhao, Xuwei Deng, Chi Zhou

Cyanobacterial blooms, which are increasingly exacerbated by eutrophication and climate change, pose threats to ecosystems and public health. This paper systematically reviews recent advances in microbial intervention strategies for controlling cyanobacterial blooms. Current approaches primarily comprise direct lysis methods, indirect suppression methods, and integrated strategies. Direct algicide methods rapidly lyse cyanobacterial cells and degrade toxins, although their application is constrained by environmental sensitivity and host specificity. Indirect approaches offer sustainable preventive strategies by inhibiting cyanobacterial growth, yet require careful environmental management. Integrated methods combine microbial strategies with other technologies, enhancing both the efficiency and ecological safety of managing cyanobacterial blooms. While microbial strategies demonstrate significant potential, practical implementation faces challenges, including environmental adaptability, ecological safety, and regulatory frameworks. Future research should focus on integrating synthetic biology, intelligent delivery systems, and multi-omics technologies to achieve more effective and environmentally friendly management of cyanobacterial blooms.

由于富营养化和气候变化,藻华日益加剧,对生态系统和公众健康构成威胁。本文系统地回顾了控制蓝藻华的微生物干预策略的最新进展。目前的方法主要包括直接裂解法、间接抑制法和综合策略。直接杀藻方法快速分解蓝藻细胞和降解毒素,尽管它们的应用受到环境敏感性和宿主特异性的限制。间接的方法提供可持续的预防策略,抑制蓝藻生长,但需要仔细的环境管理。综合方法将微生物策略与其他技术相结合,提高了管理蓝藻华的效率和生态安全性。虽然微生物策略显示出巨大的潜力,但实际实施面临挑战,包括环境适应性、生态安全性和监管框架。未来的研究应集中在合成生物学、智能输送系统和多组学技术的整合上,以实现更有效和更环保的蓝藻华管理。
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引用次数: 0
Why, When, and How to Treat Dynamic Forehead Lines with Botulinum Toxin Type A. 为什么,何时,以及如何用A型肉毒杆菌毒素治疗动态额头纹。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-17 DOI: 10.3390/toxins17120603
Carla de Sanctis Pecora, Martina Kerscher, Mariana Muniz, Ada Trindade de Almeida

Recent advances in the understanding of facial anatomy have contributed significantly to the refinement of injection techniques for the treatment of dynamic forehead lines. A comprehensive assessment of eyebrow shape, position, and the aging process is essential, as the latter are closely linked to the functional balance between the frontalis muscle and the upper facial depressors. Optimal outcomes also depend on the accurate determination of dosage per injection point, injection depth, and strategic distribution of injection sites within the frontalis, which should be carefully considered and tailored to the individual's anatomical characteristics and therapeutic goals-whether the aim is neuromodulation for muscle activity reduction or intradermal application for skin quality enhancement. A round table discussion session among three experienced international dermatology experts in aesthetic botulinum toxin type A was performed during a MERZ LATAM-sponsored medical education session. Recent insights in facial anatomy, including the precise location and distribution of motor endplates, as well as the direction of muscular force vectors during contraction; aging processes; and interindividual variability in facial musculature and mimicry patterns are discussed, and the results are described herein. These factors play a critical role in customizing personalized injection strategies and improving aesthetic outcomes in the treatment of forehead lines.

在面部解剖的理解的最新进展,显著地促进了注射技术的改进,以治疗动态额纹。全面评估眉毛的形状、位置和衰老过程是必不可少的,因为后者与额肌和上面部降肌之间的功能平衡密切相关。最佳结果还取决于准确确定每个注射点的剂量、注射深度和额肌内注射部位的策略分布,这应该仔细考虑并根据个人的解剖特征和治疗目标进行调整——无论目的是神经调节以减少肌肉活动还是皮内应用以提高皮肤质量。在MERZ latam赞助的医学教育会议期间,三位经验丰富的国际皮肤病学专家对A型美容肉毒杆菌毒素进行了圆桌讨论。面部解剖学的最新见解,包括运动终板的精确位置和分布,以及收缩过程中肌肉力矢量的方向;老化的过程;并讨论了面部肌肉组织和模仿模式的个体间差异,并在此描述了结果。这些因素在定制个性化注射策略和改善前额皱纹治疗的美学结果中起着关键作用。
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引用次数: 0
Ai-Assisted Discovery of a Direct Physical Interaction Between a Venom Serpin from the Parasitoid Wasp Liragathis javana and a Host Serine Carboxypeptidase. 人工智能辅助发现拟寄生蜂(Liragathis javana)毒液丝氨酸与宿主丝氨酸羧肽酶之间的直接物理相互作用。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-16 DOI: 10.3390/toxins17120600
Jiale Wang, Xunyuan Jiang, Zemiao Xiao, Xuemei Tang, Kai Wan

Parasitoid wasp venoms represent highly specialized biochemical arsenals that evolved to manipulate host physiology and ensure successful development of the parasitoid offspring. However, the molecular targets and mechanisms underlying this complex host modulation remain poorly understood. To address this, we employed an AI-driven discovery pipeline, integrating the sequence-based predictor D-SCRIPT with the structural modeler AlphaFold3, to characterize LjSPI-1, a venom serpin from Liragathis javana. This computational workflow highlighted a previously unreported candidate partner-a host serine carboxypeptidase (Chr09G02510). Crucially, we detected a direct physical interaction between these two proteins through both in vitro pull-down and in vivo yeast two-hybrid assays, supporting this AI-prioritized interaction under experimental conditions. Our study identifies a high-priority molecular pairing and demonstrates the utility of an AI-guided strategy for uncovering candidate targets of venom proteins. In addition, guided by the predicted biochemical role of Chr09G02510, we propose several plausible physiological hypotheses linking this interaction to host peptide metabolism and immune modulation. These hypotheses serve as a conceptual basis for future mechanistic and toxicological investigations.

寄生蜂的毒液是寄生蜂高度特化的生化武器,它通过进化来操纵宿主的生理机能,确保寄生蜂后代的成功发育。然而,这种复杂宿主调节的分子靶点和机制仍然知之甚少。为了解决这个问题,我们采用了人工智能驱动的发现管道,将基于序列的预测器D-SCRIPT与结构建模器AlphaFold3集成在一起,来表征LjSPI-1,这是一种来自爪牙Liragathis javana的蛇毒。该计算工作流程突出了以前未报道的候选伙伴-宿主丝氨酸羧肽酶(Chr09G02510)。至关重要的是,我们通过体外拉下和体内酵母双杂交试验检测到这两种蛋白质之间的直接物理相互作用,在实验条件下支持这种人工智能优先的相互作用。我们的研究确定了一个高优先级的分子配对,并证明了人工智能指导策略在发现毒液蛋白候选靶点方面的实用性。此外,根据预测的Chr09G02510的生化作用,我们提出了几个似是而非的生理假设,将这种相互作用与宿主肽代谢和免疫调节联系起来。这些假设为未来的机制和毒理学研究提供了概念基础。
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引用次数: 0
Characterization of Alpha-Bungarotoxin Antibodies Prepared by Different Strategies. 不同制备方法制备α -虫毒抗体的研究。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-16 DOI: 10.3390/toxins17120601
Huijuan Lu, Guowen Zhang, Lin Zhao, Ying Yuan, Bing Gong, Bin Han, Wen-Hui Lee

The preparation of an antibody to treat snake envenomation requires a large amount of snake venom. In China, only four types of anti-snake venom sera are clinically available, and the production and immunization strategies for clinically approved anti-snake venom sera still mainly rely on detoxified antigens, which is a mature technical route commonly adopted by domestic pharmaceutical enterprises. At present, researchers immunize animals with low doses of certain snake venom toxic components or prokaryotically expressed toxic components to reduce the amount of venom needed, and use prepared antisera for their specific investigation purposes. However, it is unclear if low-dose immunized antibody titers and toxin-neutralizing activities are consistent with those of high-dose detoxified crude venom immunized antibodies. In this study, we developed a method for the preparation of highly effective rabbit polyclonal antisera while saving a large amount of toxin. Rabbit polyclonal antisera prepared by low-dose natural α-bungarotoxin (α-BGT) had strong neutralizing effects on the toxin itself and achieved the same antibody titers as antisera prepared with high doses of detoxified α-BGT. Antigen of A maltose binding protein (MBP) fused with α-BGT (MBP-α-BGT) expressed in prokaryotes had low antibody titer and low neutralizing activity. This study provides an effective dosage selection guide and methods for the preparation of polyclonal antibodies and antiserum for investigation purposes.

制备治疗蛇毒的抗体需要大量的蛇毒。在中国,临床可用的抗蛇毒血清只有4种,临床批准的抗蛇毒血清的生产和免疫策略仍主要依靠解毒抗原,这是国内制药企业普遍采用的成熟技术路线。目前,研究人员用低剂量的蛇毒毒性成分或原核表达的毒性成分对动物进行免疫,以减少所需的毒液量,并使用制备的抗血清来进行特定的研究。然而,目前尚不清楚低剂量免疫抗体滴度和毒素中和活性是否与高剂量解毒的粗毒免疫抗体一致。在本研究中,我们开发了一种制备高效且节省大量毒素的兔多克隆抗血清的方法。低剂量天然α-兔毒(α-BGT)制备的兔多克隆抗血清对毒素本身具有较强的中和作用,抗体效价与高剂量解毒α-BGT制备的抗血清相同。在原核生物中表达的麦芽糖结合蛋白(MBP)与α-BGT融合抗原(MBP-α-BGT)抗体效价低,中和活性低。本研究为研究用多克隆抗体和抗血清的制备提供了有效的剂量选择指导和方法。
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引用次数: 0
Functional Coupling and Evolutionary Relationships Between Toxin-Antitoxin Systems and CRISPR-Cas Systems. 毒素-抗毒素系统与CRISPR-Cas系统的功能耦合和进化关系
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-16 DOI: 10.3390/toxins17120602
Yibo Meng, Jiyun Chen, Liang Liu

Bacteria encode a broad range of survival and defence systems, including CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas systems, restriction-modification systems, and toxin-antitoxin (TA) systems, which are involved in bacterial regulation and immunity. The traditional view holds that CRISPR-Cas systems and TA systems are two independent defense lines in prokaryotes. However, groundbreaking studies in recent years have revealed multi-level functional coupling between them. This review systematically elaborates on this mechanism, focusing on three types of TA systems that mediate the core correlation of CRISPR-Cas systems: CreTA maintains the evolutionary stability of CRISPR-Cas systems through an addiction mechanism; CreR enables self-regulation of CRISPR-Cas expression; and CrePA provides herd immunity by triggering abortive infection after the CRISPR-Cas system has been destroyed by Anti-CRISPRS protein. Additionally, we discuss the evolutionary homology between the type III toxin AbiF and the type VI CRISPR effector Cas13, offering a new perspective for understanding the origin of CRISPR-Cas systems. These findings not only reveal the functional coupling of prokaryotic defense systems but also provide a powerful theoretical framework and practical solutions for addressing stability challenges in CRISPR technology applications.

细菌编码了广泛的生存和防御系统,包括参与细菌调节和免疫的CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas系统、限制性修饰系统和毒素-抗毒素(TA)系统。传统观点认为,CRISPR-Cas系统和TA系统是原核生物中两条独立的防线。然而,近年来突破性的研究揭示了它们之间多层次的功能耦合。本文系统阐述了这一机制,重点介绍了介导CRISPR-Cas系统核心相关性的三种TA系统:CreTA通过成瘾机制维持CRISPR-Cas系统的进化稳定性;CreR能够自我调节CRISPR-Cas的表达;在CRISPR-Cas系统被Anti-CRISPRS蛋白破坏后,CrePA通过触发流产感染提供群体免疫。此外,我们讨论了III型毒素AbiF与VI型CRISPR效应物Cas13之间的进化同源性,为理解CRISPR- cas系统的起源提供了新的视角。这些发现不仅揭示了原核防御系统的功能耦合,而且为解决CRISPR技术应用中的稳定性挑战提供了强大的理论框架和实践解决方案。
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引用次数: 0
Targeting the Gut-Kidney Axis: Modulation of Gut Microbiota by Traditional Chinese Medicine for Chronic Kidney Disease Management. 以肠肾轴为靶点:中药调节肠道微生物群治疗慢性肾脏疾病。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-15 DOI: 10.3390/toxins17120599
Yijing Xin, Libin Pan

The interaction between gut microbiota dysbiosis and CKD progression via the "gut-kidney axis" is increasingly recognized. Gut-derived uremic toxins (e.g., indoxyl sulfate and p-cresyl sulfate) accumulate systemically, while beneficial metabolites like short-chain fatty acids (SCFAs) decrease, contributing to inflammation, oxidative stress, and kidney fibrosis. Traditional Chinese Medicine (TCM), including complex formulae, single herbs, and active ingredients, has long been used to manage CKD. Emerging evidence-primarily from animal studies-highlights its potential to alleviate the disease by modulating the gut microbiota. This review summarizes how TCM interventions re-establish gut microbial symbiosis by regulating microbial composition, reducing toxin load, and reinforcing intestinal barrier integrity, thereby ameliorating systemic inflammation and protecting kidney function. Targeting the gut microbiota represents a promising therapeutic frontier for CKD, and TCM offers a rich resource for developing novel microbiota-modulating strategies. However, future research must focus on validating molecular mechanisms, standardizing TCM preparations, and conducting rigorous clinical trials to facilitate clinical translation.

通过“肠肾轴”,肠道菌群失调与CKD进展之间的相互作用越来越被认识到。肠道源性尿毒症毒素(如硫酸吲哚酚和对甲酚硫酸盐)在全身积累,而有益的代谢物如短链脂肪酸(SCFAs)减少,导致炎症、氧化应激和肾纤维化。中药(Traditional Chinese Medicine, TCM),包括复方、单药和有效成分,长期以来被用于治疗慢性肾病。新出现的证据——主要来自动物研究——强调了它通过调节肠道微生物群来减轻疾病的潜力。本文综述了中医药干预如何通过调节微生物组成、减少毒素负荷、增强肠道屏障完整性,从而改善全身炎症和保护肾功能,重建肠道微生物共生关系。针对肠道菌群是CKD治疗的一个有前景的前沿,中医药为开发新的微生物群调节策略提供了丰富的资源。然而,未来的研究必须集中在验证分子机制,规范中药制剂,并进行严格的临床试验,以促进临床翻译。
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引用次数: 0
Fifty Years and Counting: Searching for the "Silver Bullet" or the "Silver Shotgun" to Mitigate Preharvest Aflatoxin Contamination. 50年和计数:寻找减轻收获前黄曲霉毒素污染的“银弹”或“银猎枪”。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-15 DOI: 10.3390/toxins17120596
Baozhu Guo, Idrice Carther Kue Foka, Dongliang Wu, Josh P Clevenger, Rong Di, Jake C Fountain

The year 2025 marks two significant milestones for aflatoxin research: 65 years since aflatoxin was first identified in 1960, and 50 years of focused research on preharvest aflatoxin contamination since it was first recognized in 1975. Studies in the 1970s revealed that A. flavus could infect crops like maize and produce aflatoxin in the field before harvest and made it possible to investigate the potential genetic resistance in crops to mitigate the issues. Tremendous efforts have been made to learn about the process and regulation of aflatoxin production along with interactions between A. flavus and host plants as influenced by environmental factors. This has allowed for the breeding of more resistant crops and investigations into the underlying genetic and genomic components of resistance mechanisms in crops like maize and peanut. However, despite decades of studies, many questions remain. One established "dogma" is that drought stress, especially when combined with high temperatures, is the single greatest contributing factor to preharvest aflatoxin contamination and is a perennial risk faced throughout the major agricultural production regions of the world. Although there are many reviews summarizing the decades' long wealth of information about A. flavus, aflatoxin biosynthesis, management and host plant resistance, there are few reports that put the spotlight on why aflatoxin contamination is exacerbated by drought stress, which places plants under severe physiological stress and weakens immune systems. Therefore, here we will focus on three major areas of research in maize: the "living embryo" theory and host resistance mechanisms, the "Key Largo hypothesis" and the causes of drought-exacerbated aflatoxin contamination, and recent advancements in CRISPR-based genome editing for enhancing drought tolerance and increasing plant immune responses. This will highlight key breakthroughs and future prospects for the continuing development of superior crop germplasm and cultivars and for mitigating aflatoxin contamination in food and feed supply chains.

2025年标志着黄曲霉毒素研究的两个重要里程碑:自1960年首次发现黄曲霉毒素以来已有65年,以及自1975年首次确认黄曲霉毒素污染以来对收获前黄曲霉毒素污染的重点研究已有50年。20世纪70年代的研究表明,黄曲霉可以感染玉米等作物,并在收获前在田间产生黄曲霉毒素,这使得研究作物潜在的遗传抗性成为可能,以减轻这一问题。人们对黄曲霉毒素产生的过程和调控以及黄曲霉与寄主植物之间受环境因素影响的相互作用进行了大量的研究。这使得培育更具抗性的作物成为可能,并对玉米和花生等作物抗性机制的潜在遗传和基因组成分进行了调查。然而,尽管经过了几十年的研究,仍然存在许多问题。一个既定的“教条”是,干旱压力,特别是当与高温结合时,是收获前黄曲霉毒素污染的最大单一因素,是世界主要农业生产区面临的长期风险。尽管有许多综述总结了几十年来关于黄曲霉、黄曲霉毒素的生物合成、管理和寄主植物抗性的丰富信息,但很少有报道关注为什么黄曲霉毒素污染会因干旱胁迫而加剧,干旱胁迫使植物处于严重的生理压力下,并削弱免疫系统。因此,本文将重点介绍玉米的三个主要研究领域:“活胚”理论和寄主抗性机制,“Key Largo假说”和干旱加剧黄曲霉毒素污染的原因,以及基于crispr的基因组编辑技术在增强耐旱性和增强植物免疫应答方面的最新进展。这将突出突出持续开发优良作物种质和品种以及减轻食品和饲料供应链中的黄曲霉毒素污染的关键突破和未来前景。
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引用次数: 0
Immunological Considerations of Polysorbate as an Excipient in Botulinum Neurotoxin Type A Formulations: A Narrative Review. 聚山梨酸酯作为A型肉毒毒素制剂赋形剂的免疫学考虑:叙述性综述。
IF 4 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2025-12-15 DOI: 10.3390/toxins17120598
Michael Uwe Martin, Jürgen Frevert, Je-Young Park, Haiyan Cui, Andy Curry, Wei Qi Loh

Recent botulinum neurotoxin type A (BoNT/A) formulations have shifted towards the use of polysorbate 20 (PS20) and polysorbate 80 (PS80) as a non-human-derived excipient to enhance product stability. Polysorbates are a distinct class of synthetic non-ionic surfactants with high heterogeneity in chemical structure and properties. Accumulating mechanistic and clinical evidence suggests that they may trigger immunological reactions, including hypersensitivity and immunogenicity. Such risks are largely associated with their susceptibility to degradation via hydrolysis and oxidation, forming reactive byproducts that can interact with proteins and immune pathways. Despite these mechanistic insights, data on the association between polysorbate excipients and observed immune outcomes in practice is relatively sparse and excipient-related immunogenicity and hypersensitivity is often underrecognized in practice. This review provides a summary of polysorbate excipients in BoNT/A formulations, focusing on their chemical properties and degradation pathways, characterizing downstream immune effects and appraising available clinical data of polysorbate-containing BoNT/A formulations. Finally, we discuss potential risk mitigation strategies including process modifications that could prevent degradation, and consideration of alternative excipients, such as human serum albumin, that has been shown to be immunologically inert and has an established safety profile. By integrating chemical, mechanistic, and clinical perspectives, this review seeks to clarify the implications of polysorbate use in BoNT/A formulations and inform both clinical practice and future formulation strategies.

最近A型肉毒杆菌神经毒素(BoNT/A)配方已转向使用聚山梨酯20 (PS20)和聚山梨酯80 (PS80)作为非人类来源的赋形剂,以提高产品的稳定性。聚山梨酯是一类独特的合成非离子表面活性剂,在化学结构和性质上具有高度的非均质性。越来越多的机制和临床证据表明,它们可能引发免疫反应,包括过敏和免疫原性。这些风险很大程度上与它们通过水解和氧化降解的易感性有关,形成可与蛋白质和免疫途径相互作用的活性副产物。尽管有这些机制的见解,关于聚山梨酯赋形剂和实际观察到的免疫结果之间的关联的数据相对较少,而且赋形剂相关的免疫原性和超敏性在实践中经常被低估。本文综述了BoNT/ a制剂中的聚山梨酸酯赋形剂,重点介绍了它们的化学性质和降解途径,表征了下游免疫效应,并评价了含有聚山梨酸酯的BoNT/ a制剂的现有临床数据。最后,我们讨论了潜在的风险缓解策略,包括可以防止降解的工艺修改,以及考虑替代赋形剂,如人类血清白蛋白,已被证明具有免疫惰性并具有既定的安全性。通过整合化学、机理和临床观点,本综述旨在阐明聚山梨酯在BoNT/A制剂中的应用,并为临床实践和未来的制剂策略提供信息。
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引用次数: 0
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Toxins
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