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DNA Repair and Mutagenesis of ADP-Ribosylated DNA by Pierisin DNA 修复和 Pierisin 对 ADP-核糖基化 DNA 的诱变作用
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-26 DOI: 10.3390/toxins16080331
Masanobu Kawanishi, Takashi Yagi, Yukari Totsuka, Keiji Wakabayashi
Pierisin is a DNA-targeting ADP-ribosyltransferase found in cabbage white butterfly (Pieris rapae). Pierisin transfers an ADP-ribosyl moiety to the 2-amino group of the guanine residue in DNA, yielding N2-(ADP-ribos-1-yl)-2′-deoxyguanosine (N2-ADPR-dG). Generally, such chemically modified DNA is recognized as DNA damage and elicits cellular responses, including DNA repair pathways. In Escherichia coli and human cells, it has been experimentally demonstrated that N2-ADPR-dG is a substrate of the nucleotide excision repair system. Although DNA repair machineries can remove most lesions, some unrepaired damages frequently lead to mutagenesis through DNA replication. Replication past the damaged DNA template is called translesion DNA synthesis (TLS). In vitro primer extension experiments have shown that eukaryotic DNA polymerase κ is involved in TLS across N2-ADPR-dG. In many cases, TLS is error-prone and thus a mutagenic process. Indeed, the induction of G:C to T:A and G:C to C:G mutations by N2-ADPR-dG in the hypoxanthine phosphoribosyltransferase gene mutation assay with Chinese hamster cells and supF shuttle vector plasmids assay using human fibroblasts has been reported. This review provides a detailed overview of DNA repair, TLS and mutagenesis of N2-ADPR-dG induced by cabbage butterfly pierisin-1.
Pierisin 是一种 DNA 靶向 ADP 核糖基转移酶,存在于卷心菜白蝶(Pieris rapae)中。Pierisin 能将 ADP-核糖基分子转移到 DNA 中鸟嘌呤残基的 2-氨基上,生成 N2-(ADP-核糖-1-基)-2′-脱氧鸟苷(N2-ADPR-dG)。一般来说,这种经过化学修饰的 DNA 被认为是 DNA 损伤,会引起细胞反应,包括 DNA 修复途径。在大肠杆菌和人类细胞中,实验证明 N2-ADPR-dG 是核苷酸切除修复系统的底物。尽管 DNA 修复机制可以清除大多数病变,但一些未修复的损伤经常会通过 DNA 复制导致突变。通过受损 DNA 模板进行的复制称为转座子 DNA 合成(TLS)。体外引物延伸实验表明,真核生物 DNA 聚合酶 κ 参与了跨 N2-ADPR-dG 的 TLS。在许多情况下,TLS 容易出错,因此是一个诱变过程。事实上,在用中国仓鼠细胞进行的次黄嘌呤磷酸核糖转移酶基因突变试验和用人成纤维细胞进行的 supF 穿梭载体质粒试验中,N2-ADPR-dG 都诱导了 G:C 到 T:A 和 G:C 到 C:G 的突变。本综述详细概述了甘蓝蝴蝶穿刺素-1 诱导的 DNA 修复、TLS 和 N2-ADPR-dG 诱变。
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引用次数: 0
X-ray Irradiation Reduces Live Aspergillus flavus Viability but Not Aflatoxin B1 in Naturally Contaminated Maize X 射线辐照能降低天然污染玉米中黄曲霉菌的存活率,但不能降低黄曲霉毒素 B1 的含量
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-25 DOI: 10.3390/toxins16080329
Hannah Glesener, Darya Abdollahzadeh, Christopher Muse, Rosa Krajmalnik-Brown, Mark A. Weaver, Lee E. Voth-Gaeddert
Food crops around the world are commonly contaminated with Aspergillus flavus, which can produce the carcinogenic mycotoxin aflatoxin B1 (AFB1). The objective of this study is to test an X-ray irradiation sterilization method for studying AFB1 in contaminated maize samples in the laboratory. Maize that had been naturally contaminated with 300 ppb AFB1 by the growth of aflatoxigenic A. flavus was ground and then irradiated at 0.0, 1.0, 1.5, 2.0, 2.5, and 3.0 kGy. A. flavus was quantified by dilution plating on potato dextrose agar (PDA) and modified Rose Bengal media (MDRB) for viability and qPCR for gene presence. AFB1 was quantified by HPLC and ELISA. A. flavus viability, but not gene copies, significantly decreased with increasing doses of radiation (PDA: p < 0.001; MDRB: p < 0.001; qPCR: p = 0.026). AFB1 concentration did not significantly change with increasing doses of radiation (HPLC: p = 0.153; ELISA: p = 0.567). Our results imply that X-ray irradiation is an effective means of reducing viable A. flavus without affecting AFB1 concentrations. Reducing the hazard of fungal spores and halting AFB1 production at the targeted dose are important steps to safely and reproducibly move forward research on the global mycotoxin challenge.
世界各地的粮食作物普遍受到黄曲霉菌的污染,黄曲霉菌可产生致癌的霉菌毒素黄曲霉毒素 B1(AFB1)。本研究的目的是测试一种 X 射线辐照灭菌法,用于在实验室研究受污染玉米样本中的 AFB1。将因黄曲霉毒素黄曲霉菌的生长而自然污染了 300 ppb AFB1 的玉米磨碎,然后用 0.0、1.0、1.5、2.0、2.5 和 3.0 kGy 的射线进行辐照。在马铃薯葡萄糖琼脂(PDA)和改良玫瑰孟加拉培养基(MDRB)上稀释培养,检测黄曲霉的活力,并通过 qPCR 检测基因的存在。AFB1 通过 HPLC 和 ELISA 进行定量。随着辐射剂量的增加,黄曲霉的存活率(PDA:p < 0.001;MDRB:p < 0.001;qPCR:p = 0.026)显著下降,但基因拷贝数没有显著下降。随着辐射剂量的增加,AFB1 的浓度没有明显变化(HPLC:p = 0.153;ELISA:p = 0.567)。我们的研究结果表明,X 射线辐照是减少存活黄曲霉而不影响 AFB1 浓度的有效方法。在目标剂量下减少真菌孢子的危害并阻止 AFB1 的产生,是安全、可重复地推进全球霉菌毒素挑战研究的重要步骤。
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引用次数: 0
Structural and Functional Insights into the Delivery Systems of Bacillus and Clostridial Binary Toxins 芽孢杆菌和梭状芽孢杆菌二元毒素输送系统的结构和功能透视
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-25 DOI: 10.3390/toxins16080330
Spiridon E. Sevdalis, Kristen M. Varney, Mary E. Cook, Joseph J. Gillespie, Edwin Pozharski, David J. Weber
Pathogenic Bacillus and clostridial (i.e., Clostridium and Clostridioides) bacteria express a diverse repertoire of effector proteins to promote disease. This includes production of binary toxins, which enter host epithelial cells and seriously damage the intestinal tracts of insects, animals, and humans. In particular, binary toxins form an AB-type complex composed of a catalytic subunit that is toxic (A) and an oligomeric cell-binding and delivery subunit (B), where upon delivery of A into the cytoplasm of the host cell it catalytically ADP-ribosylates actin and rapidly induces host cell death. In this review, binary toxins expressed by Bacillus thuringiensis, Clostridioides difficile, and Clostridium perfringens will be discussed, with particular focus placed upon the structural elucidations of their respective B subunits and how these findings help to deconvolute how toxic enzyme delivery into target host cells is achieved by these deadly bacteria.
致病性芽孢杆菌和梭状芽孢杆菌(即梭状芽孢杆菌和梭状芽孢杆菌)表达多种效应蛋白,以促进疾病的发生。这包括产生二元毒素,进入宿主上皮细胞,严重损害昆虫、动物和人类的肠道。特别是,二元毒素会形成一个 AB 型复合物,由一个具有毒性的催化亚基(A)和一个低聚细胞结合和输送亚基(B)组成,当 A 被输送到宿主细胞的细胞质中时,它会催化 ADP-核糖基化肌动蛋白,并迅速诱导宿主细胞死亡。本综述将讨论苏云金芽孢杆菌、难辨梭状芽孢杆菌和产气荚膜梭状芽孢杆菌所表达的二元毒素,重点是它们各自的 B 亚基的结构阐释,以及这些发现如何帮助解密这些致命细菌如何将有毒酶输送到目标宿主细胞。
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引用次数: 0
Oxidation of Microcystis aeruginosa and Microcystins with Peracetic Acid 过乙酸对铜绿微囊藻和微囊藻毒素的氧化作用
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-23 DOI: 10.3390/toxins16080328
Mennatallah Alnahas, Husein Almuhtaram, Ron Hofmann
Peracetic acid (PAA) shows potential for use in drinking water treatment as an alternative to prechlorination, such as for mussel control and disinfection by-product precursor destruction, though its impact as a preoxidant during cyanobacterial blooms remains underexplored. Here, Microcystis aeruginosa inactivation and microcystin-LR and -RR release and degradation using PAA were explored. The toxin degradation rates were found to be higher in alkaline conditions than in neutral and acidic conditions. However, all rates were significantly smaller than comparable rates when using free chlorine. The inactivation of M. aeruginosa cells using PAA was faster at acidic pH, showing immediate cell damage and subsequent cell death after 15–60 min of exposure to 10 mg/L PAA. In neutral and alkaline conditions, cell death occurred after a longer lag phase (3–6 h). During cell inactivation, microcystin-LR was released slowly, with <35% of the initial intracellular toxins measured in solution after 12 h of exposure to 10 mg/L PAA. Overall, PAA appears impractically slow for M. aeruginosa cell inactivation or microcystin-LR and -RR destruction in drinking water treatment, but this slow reactivity may also allow it to continue to be applied as a preoxidant for other purposes during cyanobacterial blooms without the risk of toxin release.
过乙酸(PAA)在饮用水处理中具有替代预氯化的潜力,如用于控制贻贝和销毁消毒副产物前体,但其作为蓝藻藻华期间的预氧化剂所产生的影响仍未得到充分探索。在此,我们利用 PAA 对铜绿微囊藻的灭活以及微囊藻毒素-LR 和-RR 的释放和降解进行了研究。研究发现,碱性条件下的毒素降解率高于中性和酸性条件下的降解率。不过,所有降解率都明显低于使用游离氯时的降解率。在酸性 pH 条件下,使用 PAA 对铜绿微囊藻细胞进行灭活的速度更快,在暴露于 10 mg/L PAA 15-60 分钟后,细胞立即受到破坏,随后死亡。在中性和碱性条件下,细胞在较长的滞后期(3-6 小时)后死亡。在细胞失活过程中,微囊藻毒素-LR 释放缓慢,在暴露于 10 毫克/升 PAA 12 小时后,溶液中测得的初始细胞内毒素小于 35%。总的来说,在饮用水处理中,PAA 对于铜绿微囊藻细胞灭活或微囊藻毒素-LR 和-RR 破坏的作用似乎并不实际,但这种缓慢的反应性也可能使其在蓝藻藻华期间继续作为前氧化剂用于其他用途,而不会有毒素释放的风险。
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引用次数: 0
Venomics of Scorpion Ananteris platnicki (Lourenço, 1993), a New World Buthid That Inhabits Costa Rica and Panama 蝎子 Ananteris platnicki(Lourenço,1993 年)的毒液组学,这是一种栖息在哥斯达黎加和巴拿马的新世界屠夫
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-23 DOI: 10.3390/toxins16080327
Cecilia Díaz, Bruno Lomonte, Arturo Chang-Castillo, Fabián Bonilla, Adriana Alfaro-Chinchilla, Felipe Triana, Diego Angulo, Julián Fernández, Mahmood Sasa
Ananteris is a scorpion genus that inhabits dry and seasonal areas of South and Central America. It is located in a distinctive morpho-group of Buthids, the ‘Ananteris group’, which also includes species distributed in the Old World. Because of the lack of information on venom composition, the study of Ananteris species could have biological and medical relevance. We conducted a venomics analysis of Ananteris platnicki, a tiny scorpion that inhabits Panama and Costa Rica, which shows the presence of putative toxins targeting ion channels, as well as proteins with similarity to hyaluronidases, proteinases, phospholipases A2, members of the CAP-domain family, and hemocyanins, among others. Venom proteolytic and hyaluronidase activities were corroborated. The determination of the primary sequences carried out by mass spectrometry evidences that several peptides are similar to the toxins present in venoms from Old World scorpion genera such as Mesobuthus, Lychas, and Isometrus, but others present in Tityus and Centruroides toxins. Even when this venom displays the characteristic protein families found in all Buthids, with a predominance of putative Na+-channel toxins and proteinases, some identified partial sequences are not common in venoms of the New World species, suggesting its differentiation into a distinctive group separated from other Buthids.
Ananteris 是蝎属的一种,栖息于南美洲和中美洲的干燥和季节性地区。它属于丁钩蝎的一个独特形态群,即 "Ananteris 群",其中还包括分布在旧大陆的物种。由于缺乏有关毒液成分的信息,对 Ananteris 种类的研究可能具有生物学和医学意义。我们对一种栖息于巴拿马和哥斯达黎加的小蝎子 Ananteris platnicki 进行了毒液组学分析,结果表明该毒液中存在针对离子通道的假定毒素,以及与透明质酸酶、蛋白酶、磷脂酶 A2、CAP-domain 家族成员和血蓝蛋白等相似的蛋白质。毒液的蛋白水解活性和透明质酸酶活性得到了证实。通过质谱法确定的主序列证明,有几种肽与旧世界蝎属(如 Mesobuthus、Lychas 和 Isometrus)毒液中的毒素相似,但也有一些肽与 Tityus 和 Centruroides 毒液中的毒素相似。即使这种毒液显示了所有布氏蝎属中的特征蛋白家族,其中以假定的 Na+ 通道毒素和蛋白酶为主,但一些已确定的部分序列在新世界物种的毒液中并不常见,这表明该毒液与其他布氏蝎属区分开来,成为一个独特的组别。
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引用次数: 0
Rapid and Sensitive Detection of Shiga Toxin-Producing Escherichia coli (STEC) from Food Matrices Using the CANARY Biosensor Assay 利用 CANARY 生物传感器测定法快速灵敏地检测食品基质中产志贺毒素大肠杆菌 (STEC)
IF 4.2 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-22 DOI: 10.3390/toxins16070325
Christina C. Tam, Wen-Xian Du, Yangyang Wang, Andrew R. Flannery, Xiaohua He
Shiga toxin-producing Escherichia coli (STEC) causes a wide spectrum of diseases including hemorrhagic colitis and hemolytic uremic syndrome (HUS). Previously, we developed a rapid, sensitive, and potentially portable assay that identified STEC by detecting Shiga toxin (Stx) using a B-cell based biosensor platform. We applied this assay to detect Stx2 present in food samples that have been implicated in previous STEC foodborne outbreaks (milk, lettuce, and beef). The STEC enrichment medium, modified Tryptone Soy Broth (mTSB), inhibited the biosensor assay, but dilution with the assay buffer relieved this effect. Results with Stx2a toxoid-spiked food samples indicated an estimated limit of detection (LOD) of ≈4 ng/mL. When this assay was applied to food samples inoculated with STEC, it was able to detect 0.4 CFU/g or 0.4 CFU/mL of STEC at 16 h post incubation (hpi) in an enrichment medium containing mitomycin C. Importantly, this assay was even able to detect STEC strains that were high expressors of Stx2 at 8 hpi. These results indicate that the STEC CANARY biosensor assay is a rapid and sensitive assay applicable for detection of STEC contamination in food with minimal sample processing that can complement the current Food Safety Inspection Service (US) methodologies for STEC.
产志贺毒素大肠杆菌(STEC)可导致出血性结肠炎和溶血性尿毒症(HUS)等多种疾病。此前,我们开发了一种快速、灵敏、便携的检测方法,利用基于 B 细胞的生物传感器平台检测志贺毒素 (Stx),从而识别 STEC。我们将这种检测方法应用于检测以前发生过 STEC 食源性疫情的食品样本(牛奶、生菜和牛肉)中的 Stx2。STEC 富集培养基--改良胰蛋白胨大豆肉汤(mTSB)会抑制生物传感器检测,但用检测缓冲液稀释可减轻这种影响。对添加了 Stx2a 类毒素的食品样本进行检测的结果表明,估计检测限(LOD)为≈4 纳克/毫升。当这种检测方法用于接种了 STEC 的食品样品时,在含有丝裂霉素 C 的富集培养基中培养 16 小时后(hpi),它能够检测到 0.4 CFU/g 或 0.4 CFU/mL 的 STEC。这些结果表明,STEC CANARY 生物传感器检测法是一种快速、灵敏的检测方法,只需对样品进行最少的处理,就能检测出食品中的 STEC 污染,是美国食品安全检验局(US)目前检测 STEC 方法的补充。
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引用次数: 0
Urea Level and Depression in Patients with Chronic Kidney Disease. 慢性肾病患者的尿素水平与抑郁。
IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-22 DOI: 10.3390/toxins16070326
Hélène Levassort, Julie Boucquemont, Oriane Lambert, Sophie Liabeuf, Solene M Laville, Laurent Teillet, Abdel-Hay Tabcheh, Luc Frimat, Christian Combe, Denis Fouque, Maurice Laville, Christian Jacquelinet, Catherine Helmer, Natalia Alencar de Pinho, Marion Pépin, Ziad A Massy, On Behalf Of Ckd-Rein Study Collaborators

Depression is common in patients with chronic kidney disease (CKD). Experimental studies suggest the role of urea toxicity in depression. We assessed both the incidence of antidepressant prescriptions and depressive symptoms (measured by CESD (Center for Epidemiologic Depression) scale) in 2505 patients with CKD (Stage 3-4) followed up over 5 years in the Chronic Kidney Disease Renal Epidemiology and Information Network (CKD-REIN) cohort. We used a joint model to assess the association between the serum urea level and incident antidepressant prescriptions, and mixed models for the association between the baseline serum urea level and CESD score over the 5-year follow-up. Among the 2505 patients, 2331 were not taking antidepressants at baseline. Of the latter, 87 started taking one during a median follow-up of 4.6 years. After adjustment for confounding factors, the hazard ratio for incident antidepressant prescription associated with the serum urea level (1.28 [95%CI, 0.94,1.73] per 5 mmol/L increment) was not significant. After adjustment, the serum urea level was associated with the mean change in the CESD score (β = 0.26, [95%CI, 0.11,0.41] per 5 mmol/L increment). Depressive symptoms burden was associated with serum urea level unlike depression events. Further studies are needed to draw firm conclusions and better understand the mechanisms of depression in CKD.

抑郁症在慢性肾脏病(CKD)患者中很常见。实验研究表明,尿素毒性对抑郁症有一定的影响。我们对慢性肾脏病肾脏流行病学和信息网络(CKD-REIN)队列中随访5年的2505名慢性肾脏病(3-4期)患者的抗抑郁药处方和抑郁症状(通过CESD(流行病学抑郁中心)量表测量)的发生率进行了评估。我们使用联合模型评估了血清尿素水平与抗抑郁药物处方之间的关系,并使用混合模型评估了基线血清尿素水平与 5 年随访期间 CESD 评分之间的关系。在2505名患者中,有2331人在基线时未服用抗抑郁药。后者中有 87 人在中位随访 4.6 年期间开始服用抗抑郁药。在对混杂因素进行调整后,与血清尿素水平相关的抗抑郁药物处方事件危险比(每 5 mmol/L 递增 1.28 [95%CI, 0.94,1.73])并不显著。经调整后,血清尿素水平与 CESD 评分的平均变化相关(β = 0.26,[95%CI, 0.11,0.41],每 5 mmol/L 增量)。与抑郁事件不同,抑郁症状负担与血清尿素水平相关。要得出确切的结论并更好地了解 CKD 患者抑郁的机制,还需要进一步的研究。
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引用次数: 0
Effects of Different Shelling Methods on Data Variability during Field Screening for Reduced Aflatoxin Contamination in Maize. 不同剥壳方法对减少玉米黄曲霉毒素污染田间筛选过程中数据变异性的影响
IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-19 DOI: 10.3390/toxins16070324
Alison Adams, Daniel Jeffers, Shien Lu, Baozhu Guo, W Paul Williams, Jake C Fountain

Non-genetic variation limits the identification of novel maize germplasm with genetic markers for reduced Aspergillus flavus infection and aflatoxin contamination. Aflatoxin measurements can vary substantially within fields containing the same germplasm following inoculation with A. flavus. While some variation is expected due to microenvironmental differences, components of field screening methodologies may also contribute to variability in collected data. Therefore, the objective of this study is to test the effects of three different shelling methods (whole ear (WE), ear end removal (EER), and inoculation site-surrounding (ISS)) to obtain bulk samples from maize on aflatoxin measurements. Five ears per row of three inbred lines and two hybrids were inoculated with A. flavus, then shelled using the three different methods, and aflatoxin was quantified. Overall, EER and ISS resulted in reduced coefficients of variance (CVs) in comparison to WE for both inbred and hybrid maize lines, with two exceptions. Susceptible B73 showed increased CVs with both EER and ISS compared to WE, and resistant Mp719's EER CVs marginally increased compared to WE. While WE is the standard practice for most breeding programs due to its technical simplicity, EER and ISS may allow for finely phenotyping parental lines for further breeding applications.

非遗传变异限制了具有减少黄曲霉感染和黄曲霉毒素污染遗传标记的新型玉米种质的鉴定。黄曲霉菌接种后,在含有相同种质的田块中,黄曲霉毒素的测量结果会有很大差异。虽然微环境的差异会导致一些差异,但田间筛选方法的一些组成部分也可能导致所收集数据的差异。因此,本研究的目的是测试三种不同的脱壳方法(整穗法(WE)、去穗端法(EER)和接种点包围法(ISS))对玉米黄曲霉毒素测量结果的影响。用黄曲霉菌接种三个近交系和两个杂交种的玉米,每行五穗,然后用三种不同的方法脱壳,并对黄曲霉毒素进行定量。总体而言,EER 和 ISS 与 WE 相比,降低了玉米近交系和杂交种的方差系数(CV),但有两个例外。与 WE 相比,抗性 B73 的 EER 和 ISS 的方差系数都有所增加;与 WE 相比,抗性 Mp719 的 EER 方差系数略有增加。虽然 WE 因其技术简单而成为大多数育种项目的标准做法,但 EER 和 ISS 可对亲本品系进行精细表型,以便进一步育种应用。
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引用次数: 0
Gait Reconstruction Strategy Using Botulinum Toxin Therapy Combined with Rehabilitation. 肉毒杆菌毒素疗法结合康复治疗的步态重建策略
IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-19 DOI: 10.3390/toxins16070323
Takatoshi Hara, Toru Takekawa, Masahiro Abo

Numerous studies have established a robust body of evidence for botulinum toxin A (BoNT-A) therapy as a treatment for upper motor neuron syndrome. These studies demonstrated improvements in spasticity, range of joint motion, and pain reduction. However, there are few studies that have focused on improvement of paralysis or functional enhancement as the primary outcome. This paper discusses the multifaceted aspects of spasticity assessment, administration, and rehabilitation with the goal of optimising the effects of BoNT-A on lower-limb spasticity and achieving functional improvement and gait reconstruction. This paper extracts studies on BoNT-A and rehabilitation for the lower limbs and provides new knowledge obtained from them. From these discussion,, key points in a walking reconstruction strategy through the combined use of BoNT-A and rehabilitation include: (1) injection techniques based on the identification of appropriate muscles through proper evaluation; (2) combined with rehabilitation; (3) effective spasticity control; (4) improvement in ankle joint range of motion; (5) promotion of a forward gait pattern; (6) adjustment of orthotics; and (7) maintenance of the effects through frequent BoNT-A administration. Based on these key points, the degree of muscle fibrosis and preintervention walking speed may serve as indicators for treatment strategies. With the accumulation of recent studies, a study focusing on walking functions is needed. As a result, it is suggested that BoNT-A treatment for lower limb spasticity should be established not just as a treatment for spasticity but also as a therapeutic strategy in the field of neurorehabilitation aimed at improving walking function.

大量研究为 A 型肉毒毒素(BoNT-A)疗法治疗上运动神经元综合征提供了有力的证据。这些研究表明,肉毒杆菌毒素 A 疗法可改善痉挛、关节活动范围和减轻疼痛。然而,很少有研究将改善瘫痪或增强功能作为主要结果。本文讨论了痉挛评估、用药和康复的多个方面,目的是优化 BoNT-A 对下肢痉挛的影响,实现功能改善和步态重建。本文摘录了有关 BoNT-A 和下肢康复的研究,并提供了从中获得的新知识。通过这些讨论,BoNT-A 与康复相结合的步行重建策略的要点包括(1)通过正确评估确定合适肌肉的注射技术;(2)与康复训练相结合;(3)有效控制痉挛;(4)改善踝关节活动范围;(5)促进前倾步态;(6)调整矫形器;(7)通过频繁注射 BoNT-A 维持效果。根据这些要点,肌肉纤维化程度和干预前步行速度可作为治疗策略的指标。随着近期研究的不断积累,需要开展一项以步行功能为重点的研究。因此,有人建议,BoNT-A 治疗下肢痉挛不仅应作为痉挛的治疗方法,还应作为神经康复领域的一种治疗策略,旨在改善步行功能。
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引用次数: 0
Identification of a Chimera Mass Spectrum of Isomeric Lipid A Species Using Negative Ion Tandem Mass Spectrometry. 利用负离子串联质谱鉴定异构脂质 A 的嵌合质谱。
IF 3.9 3区 医学 Q2 FOOD SCIENCE & TECHNOLOGY Pub Date : 2024-07-18 DOI: 10.3390/toxins16070322
Ágnes Dörnyei, Anikó Kilár, Viktor Sándor

The toxic nature of bacterial endotoxins is affected by the structural details of lipid A, including the variety and position of acyl chains and phosphate group(s) on its diglucosamine backbone. Negative-ion mode tandem mass spectrometry is a primary method for the structure elucidation of lipid A, used independently or in combination with separation techniques. However, it is challenging to accurately characterize constitutional isomers of lipid A extracts by direct mass spectrometry, as the elemental composition and molecular mass of these molecules are identical. Thus, their simultaneous fragmentation leads to a composite, so-called chimera mass spectrum. The present study focuses on the phosphopositional isomers of the classical monophosphorylated, hexaacylated Escherichia coli-type lipid A. Collision-induced dissociation (CID) was performed in an HPLC-ESI-QTOF system. Energy-resolved mass spectrometry (ERMS) was applied to uncover the distinct fragmentation profiles of the phosphorylation isomers. A fragmentation strategy applying multi-levels of collision energy has been proposed and applied to reveal sample complexity, whether it contains only a 4'-phosphorylated species or a mixture of 1- and 4'-phosphorylated variants. This comparative fragmentation study of isomeric lipid A species demonstrates the high potential of ERMS-derived information for the successful discrimination of co-ionized phosphorylation isomers of hexaacylated lipid A.

细菌内毒素的毒性受脂质 A 结构细节的影响,包括其二糖胺骨架上酰基链和磷酸基的种类和位置。负离子模式串联质谱法是阐明脂质 A 结构的主要方法,可单独使用或与分离技术结合使用。然而,通过直接质谱法准确表征脂质 A 提取物的构型异构体具有挑战性,因为这些分子的元素组成和分子质量完全相同。因此,它们的同时破碎会产生复合质谱,即所谓的嵌合质谱。本研究的重点是经典的单磷酸化、六酰化大肠杆菌型脂质 A 的磷酸化异构体。能量分辨质谱法(ERMS)用于揭示磷酸化异构体的不同碎片特征。我们提出并应用了一种采用多级碰撞能量的碎裂策略,以揭示样品的复杂性,即样品中是否只含有 4'- 磷酸化物种或 1- 和 4'- 磷酸化变体的混合物。这项关于脂质 A 异构体的比较碎片研究表明,ERMS 衍生信息在成功鉴别六酰化脂质 A 的共电离磷酸化异构体方面具有很大的潜力。
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引用次数: 0
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Toxins
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