Toxicon最新文献

英文中文

Ursolic acid enhances radiosensitivity in esophageal squamous cell carcinoma by modulating p53/SLC7A11/GPX4 pathway-mediated ferroptosis 熊果酸通过调节p53/SLC7A11/GPX4通路介导的铁下垂增强食管鳞状细胞癌的放射敏感性。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108233

Nuran Bedolla, Linyu Liu, Xueting Liu, Qiuxian Xie, Yanli Ren

Background

Radiotherapy is essential for the management of esophageal squamous cell carcinoma (ESCC). However, ESCC cells are highly susceptible to developing resistance to radiotherapy, leading to poor prognosis. Ursolic acid (UA) is a herbal monomer, has multiple medicinal benefits like anti-tumor. The impact of UA on the sensitivity of ESCC cells to radiotherapy is currently unclear.

Methods

The impact of UA and ionizing radiation (IR) on the viability of TE-1 and KYSE30 cells was assessed by the MTT assay. EdU staining, flow cytometry, clone formation, Wound healing and Transwell assay detected the biological properties of ESCC cells. FerroOrange, DCFH-DA, and kits to detect the influences of UA and/or IR treatment on cellular ferroptosis. The levels of p53/solute carrier family 7a member 11 (SLC7A11)/glutathione peroxidase 4 (GPX4) pathway proteins were detected by Western blot. Additionally, a subcutaneous graft tumor model was constructed in nude mice.

Results

10 μM UA reduced the viability and induced death of ESCC cells. UA enhanced the impacts of IR by suppressing cell proliferation, migration and invasion, inducing cell death, and causing cell cycle arrest. Ferroptosis inhibitor impaired the inhibitory impacts of UA and IR on the biological properties of ESCC cells. The combination of UA and IR led to ferroptosis through the modulation of the p53/SLC7A11/GPX4 pathway, and UA enhanced the responsiveness of ESCC cells to IR both in vitro and in vivo.

Conclusion

UA inhibits the malignant biological behavior of ESCC by modulating ferroptosis through the p53/SLC7A11/GPX4 pathway, and enhances the sensitivity of ESCC cells to IR.

背景：放疗对于食管鳞状细胞癌（ESCC）的治疗至关重要。然而，ESCC细胞极易对放疗产生耐药性，导致预后不良。熊果酸（UA）是一种草药单体，具有抗肿瘤等多种药用价值。UA对ESCC细胞放疗敏感性的影响目前尚不清楚。方法：采用MTT法观察UA和IR对TE-1和KYSE30细胞活力的影响。EdU染色、流式细胞术、克隆形成、创面愈合和Transwell实验检测ESCC细胞的生物学特性。铁橙，DCFH-DA和试剂盒检测UA和/或IR处理对细胞铁下垂的影响。Western blot检测p53/溶质载体家族7a成员11 (SLC7A11)/谷胱甘肽过氧化物酶4 （GPX4）通路蛋白水平。建立裸鼠皮下移植瘤模型。结果：10 μM UA降低ESCC细胞活力，诱导细胞死亡。UA通过抑制细胞增殖、迁移和侵袭、诱导细胞死亡和引起细胞周期阻滞来增强IR的影响。铁下垂抑制剂削弱了UA和IR对ESCC细胞生物学特性的抑制作用。UA和IR联合作用通过调节p53/SLC7A11/GPX4通路导致铁凋亡，UA在体外和体内均增强了ESCC细胞对IR的反应性。结论：UA通过p53/SLC7A11/GPX4通路调控铁凋亡，抑制ESCC的恶性生物学行为，增强ESCC细胞对IR的敏感性。

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引用次数: 0

In silico antiviral effect assessment of some venom gland peptides from Odontobuthus doriae scorpion against SARS-CoV-2 多角蝎部分毒腺肽抗SARS-CoV-2的实验研究。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108229

Maryam Naderi Soorki

SARS-CoV-2 is from the enveloped virus family responsible for the COVID-19 pandemic. No efficient drugs are currently available to treat infection explicitly caused by this virus. Therefore, searching for effective treatments for severe illness caused by SARS-CoV-2 is crucial. Scorpion venoms are significant sources of peptides with pharmaceutical potential, including antivirals. Although some studies have determined the antiviral effects of some scorpion peptides on other members of the Coronaviridae family, a few anti-SARS-CoV-2 effects of these peptides have been reported until now. This study assessed the antiviral effects of five predicted antimicrobial peptides with potential for antiviral activities from the Iranian yellow scorpion “Odontobuthus doriae” by computational methods. These peptides were selected from the cDNA library that our research team constructed. A 3D model of peptides was designed with I-TASSER. The models were refined using a 200 ns Molecular Dynamics (MD) simulation using Gromacs 2021.2 software. Refined models were Docked with the RBD domain of SARS-CoV-2 spike protein using HADDOCK software. The docking of human ACE2 peptide with the RBD domain was also assessed. The docked complexes (RBD-peptide and RBD-ACE2) were refined again by a 100 ns MD simulation and then analyzed. The results from molecular docking after molecular dynamics simulation showed that ODAMP2 and ODAMP5 after stabilizing analysis and according to MMPBSA results (with −59.24 kcal/mol and −51.82 kcal/mol, respectively) have a strong binding affinity to the RBD domain of COVID-19 spike protein compared to human ACE2 and some other studied components. Therefore, this peptide can be an excellent candidate for use as an agent to inhibit the RBD domain of SARS-COV2 virus in clinical studies for medicinal purposes after in vitro and in vivo laboratory evaluations.

SARS-CoV-2来自导致COVID-19大流行的包膜病毒家族。目前还没有有效的药物来治疗这种病毒引起的感染。因此，寻找由SARS-CoV-2引起的严重疾病的有效治疗方法至关重要。蝎子毒液是具有药物潜力的肽的重要来源，包括抗病毒药物。虽然一些研究已经确定了一些蝎子肽对冠状病毒科其他成员的抗病毒作用，但到目前为止，这些肽的一些抗sars - cov -2作用已被报道。本研究通过计算方法评估了伊朗黄蝎“Odontobuthus doriae”中5种预测抗菌肽的抗病毒作用。这些肽是从我们研究小组构建的cDNA文库中选择的。利用I-TASSER软件设计了肽的三维模型。使用Gromacs 2021.2软件进行200 ns分子动力学（MD）模拟，对模型进行细化。利用HADDOCK软件将精细化模型与SARS-CoV-2刺突蛋白的RBD结构域对接。还评估了人ACE2肽与RBD结构域的对接。通过100 ns MD模拟，对对接物（RBD-peptide和RBD-ACE2）再次进行细化，然后进行分析。分子动力学模拟后的分子对接结果显示，经稳定分析和MMPBSA结果显示，ODAMP2和ODAMP5与人ACE2和其他研究成分相比，与新冠病毒刺突蛋白RBD结构域具有较强的结合亲和力（分别为-59.24 kcal/mol和-51.82 kcal/mol）。因此，经体外和体内实验室评价，该肽可作为抑制SARS-COV2病毒RBD结构域的药物在临床研究中具有良好的药用价值。

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引用次数: 0

Exploring high molecular weight components in Tityus serrulatus venom 探索蛇毒中的高分子量成分。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108240

Nicoly Malachize Alano-da-Silva, Isadora Sousa de Oliveira, Iara Aimê Cardoso, Karla de Castro Figueiredo Bordon, Eliane Candiani Arantes

Our study identified high-molecular-weight compounds from Tityus serrulatus venom (TsV), and most of them have not yet been well explored. TsV was fractionated using FPLC system with different columns, analyzed by SDS-PAGE, and characterized by MALDI-TOF/TOF. Our study showed that TsV contains several high-molecular-weight compounds, including CRISPs, metalloproteinase and hyaluronidase. We show how these molecules can be obtained from TsV, enabling future studies about their molecular structures and biological actions, expanding knowledge about this venom.

本研究鉴定出了一些高分子量化合物，其中大部分尚未被充分开发。采用不同色谱柱的FPLC分离TsV， SDS-PAGE分析，MALDI-TOF/TOF表征。我们的研究表明，TsV含有多种高分子量化合物，包括CRISPs、金属蛋白酶和透明质酸酶。我们展示了如何从TsV中获得这些分子，从而使未来对其分子结构和生物作用的研究成为可能，扩大了对这种毒液的认识。

引用次数: 0

Endemic scorpion species and subspecies in Morocco: A comprehensive overview

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108253

Meriem Es-Saadi , Salsabil Hamdi , Soukaina Khourcha , Khalid Sadki , Khaoula Errafii , Naoual Oukkache

Scorpion fauna is abundant in regions with arid and semi-arid climates, exposing these areas to a risk of envenomation, especially for children. Scorpion envenomations cause thousands of deaths each year, with notable incidences in the MENA region, South America, Latin and Central America, and India. Morocco is one of the countries most affected by this phenomenon; according to statistics from the Moroccan Poison Control and Pharmacovigilance Center (CAPM), approximately 8565 scorpion stings and envenomations were recorded annually between 2016 and 2022, mainly among children. A literature review was conducted to identify and catalog the endemic scorpion species in Morocco and explore the impact of climate change on their distribution. Sources included scientific journal articles, university theses, and field reports. The collected data were compiled and analyzed to create a distribution map of the endemic species. Our results identified fifty-five endemic species and subspecies in Morocco. The family Buthidae is the most widespread, with seventeen endemic species of the genus Buthus, nine of the genus Androctonus, five of the genus Butheoloides, four of the genus Buthacus, two each of the genera Orthochirus, Compsobuthus, and Hottentota, and one species each of the genera Microbuthus, Cicileiurus, and Saharobuthus. The family Scorpionidae includes nine endemic species, and two subspecies belonging to the genus Scorpio. A high level of endemism is observed in southern Morocco, highlighting a significant concentration of these species in this region. Ongoing climate change is likely to expand the population and distribution of scorpions, as well as the number of envenomations. The results underscore the importance of implementing control and prevention strategies to reduce the risks of envenomation, particularly in the context of climate change. Therefore, to develop management and prevention strategies is based on a thorough understanding of species distribution and their habitats to improve the safety of vulnerable populations.

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引用次数: 0

A novel bombesin-related peptide modulates glucose tolerance and insulin secretion in non-obese and hypothalamic-obese rats 一种新的炸弹素相关肽调节非肥胖和下丘脑肥胖大鼠的葡萄糖耐量和胰岛素分泌。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108230

Bruna Schumaker Siqueira , Marianela Andrea Díaz Urrutia , Vanessa Marieli Ceglarek , Daniel Carneiro Moreira , Felipe Torres Brasil Kuzniewski , José Roberto de Souza de Almeida Leite , Sabrina Grassiolli

This study investigated the effects of a novel bombesin-related peptide (BR-b), derived from the skin of the Chaco tree frog (Boana raniceps), on glucose homeostasis in non-obese and hypothalamic-obese male rats. Hypothalamic obesity was induced in neonatal rats through high-dose administration of monosodium glutamate (MSG; 4 g/kg), while control animals (CTL) received an equimolar saline solution. At 70 days of age, both MSG and CTL groups underwent an oral glucose tolerance test (OGTT; 2 g/kg) with or without prior intraperitoneal administration of BR-b at doses of 0.5 or 1.0 mg/kg, delivered 5 min before the glucose challenge. At 75 days of age, pancreatic islets were isolated and exposed to glucose in the presence or absence of BR-b (1.0 or 5.0 μM). MSG-treated rats developed obesity, hyperinsulinemia, and insulin resistance. BR-b administration exacerbated glucose intolerance during the OGTT, particularly at the 1.0 mg/kg dose, with more pronounced effects observed in the CTL group. Insulin secretion from pancreatic islets was influenced by both obesity status and glucose concentration. In islets from CTL rats, BR-b (5 μM) reduced insulin release under non-stimulatory glucose conditions but enhanced insulin secretion at stimulatory glucose levels. Conversely, in islets from MSG-obese rats, BR-b exhibited an inhibitory effect on insulin release at basal glucose concentrations, while the insulinotropic response to high glucose was abolished. In summary, BR-b administration shortly before the OGTT impaired glucose tolerance and modulated insulin secretion from pancreatic islets in a glucose-dependent manner in non-obese rats. These effects were attenuated or absent in MSG-obese rats, indicating that hypothalamic obesity alters the metabolic responses to bombesin-related peptides.

本研究研究了一种从查科树蛙（Boana raniceps）皮肤中提取的新型糖素相关肽（BR-b）对非肥胖和下丘脑肥胖雄性大鼠葡萄糖稳态的影响。大剂量谷氨酸钠(MSG；4 g/kg)，而对照动物（CTL）给予等摩尔盐溶液。70日龄时，味精组和CTL组均进行口服葡萄糖耐量试验(OGTT；2 g/kg)，同时或不事先腹腔注射BR-b，剂量为0.5或1.0 mg/kg，在葡萄糖激发前5分钟给药。在75日龄时，分离胰岛，在存在或不存在BR-b（1.0或5.0 μM）的情况下暴露于葡萄糖中。经味精治疗的大鼠出现肥胖、高胰岛素血症和胰岛素抵抗。BR-b在OGTT期间加重了葡萄糖耐受不良，特别是在1.0 mg/kg剂量时，在CTL组观察到更明显的效果。胰岛胰岛素分泌受肥胖状态和葡萄糖浓度的影响。在CTL大鼠胰岛中，BR-b （5 μM）在非刺激性葡萄糖条件下减少胰岛素释放，但在刺激性葡萄糖水平下增加胰岛素分泌。相反，在msg肥胖大鼠的胰岛中，BR-b在基础葡萄糖浓度下对胰岛素释放有抑制作用，而对高葡萄糖的促胰岛素反应被消除。总之，在OGTT前不久给药BR-b会损害非肥胖大鼠的葡萄糖耐量，并以葡萄糖依赖的方式调节胰岛的胰岛素分泌。这些影响在msg肥胖大鼠中减弱或不存在，表明下丘脑肥胖改变了对炸弹素相关肽的代谢反应。

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引用次数: 0

Novel tryptophyllin peptides from Physalaemus centralis inhibit oxidative stress-induced endothelial dysfunction in rat aorta preparation 新型中央泡浆菌色氨酸肽抑制氧化应激诱导的大鼠主动脉内皮功能障碍。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108234

Ariane Nogueira , José Brango-Vanegas , Andreanne G. Vasconcelos , Alex P. Coleone , Éder A. Barbosa , Daniel C. Moreira , Maria da Gloria da Silva , Wanessa F. Cabral , Jhones D. Nascimento , José Vinícius de Sousa França , Daniel Dias Rufino Arcanjo , Filipe Camargo D.A. Lima , Augusto Batagin-Neto , Selma A.S. Kückelhaus , Guilherme D. Brand , Alexandra Plácido , José Roberto S.A. Leite

Amphibian skin is a rich source of molecules with biotechnological potential, including the tryptophyllin family of peptides. Here, we report the identification and characterization of two tryptophyllin peptides, FPPEWISR and FPWLLS-NH₂, from the skin of the Central Dwarf Frog, Physalaemus centralis. These peptides were identified through cDNA cloning and sequence comparison. FPWLLS-NH₂ shares its primary structure with a previously identified peptide from the skin of Pelophylax perezi, named PpT-2. Another peptide, FPPEWISR, is novel and was named PcT-1. After solid-phase peptide synthesis, both peptides exhibited significant antioxidant activity, with PcT-1 and PpT-2 demonstrating ABTS radical scavenging capacities of 0.305 and 0.269 mg Trolox equivalents/mg peptide, respectively, and ORAC values of 0.319 and 0.248 mg Trolox equivalents/mg peptide. Additionally, PcT-1 and PpT-2 inhibited AAPH-induced hemolysis in human red blood cells, achieving a protection level comparable to Trolox at 0.2 mg/mL. In rat aorta preparations, both peptides partially restored acetylcholine-induced vasorelaxation following pyrogallol-induced oxidative stress, with a greater protective effect of PpT-2. Hemolytic activity assay indicated no cytotoxicity in human red blood cells, and tests on Galleria mellonella larvae confirmed their low toxicity in vivo. These findings highlight the biotechnological potential of PcT-1 and PpT-2 as antioxidant agents, paving the way for new therapeutic applications in combating oxidative stress-related diseases.

两栖动物的皮肤是具有生物技术潜力的分子的丰富来源，包括色氨酸肽家族。在这里，我们报道了从中央矮蛙（Physalaemus centralis）皮肤中鉴定和表征的两种色氨酸肽FPPEWISR和FPWLLS-NH2。通过cDNA克隆和序列比较鉴定了这些多肽。FPWLLS-NH2的初级结构与先前从佩罗彼亚皮中鉴定出的肽（称为pt -2）相同。另一种肽FPPEWISR是新的，被命名为PcT-1。固相肽合成后，两种肽均表现出显著的抗氧化活性，PcT-1和PpT-2的ABTS自由基清除能力分别为0.305和0.269 mg Trolox当量/mg肽，ORAC值分别为0.319和0.248 mg Trolox当量/mg肽。此外，PcT-1和PpT-2抑制aaph诱导的人红细胞溶血，达到与0.2 mg/mL的Trolox相当的保护水平。在大鼠主动脉制剂中，这两种多肽都能部分恢复乙酰胆碱诱导的血管松弛，其中PpT-2的保护作用更大。溶血活性测定表明对人红细胞无细胞毒性，对mellonella幼虫的体内试验证实其低毒性。这些发现突出了PcT-1和PpT-2作为抗氧化剂的生物技术潜力，为对抗氧化应激相关疾病的新治疗应用铺平了道路。

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引用次数: 0

Degradation of aﬂatoxin B1 in corn by water-assisted microwave irradiation and its kinetic 水助微波辐照降解玉米黄曲霉毒素B1及其动力学研究。

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108239

Yaolei Zhang , Lingling Zhang , Xiaoxia Zhang , Cheng Zhao , Mengmeng Li , Erqi Guan , Yangyong Lv , Ke Bian

Aflatoxin B₁ (AFB₁) is a highly toxic, carcinogenic, teratogenic, and mutagenic mycotoxin commonly found in corn. In this work, water-assisted microwave irradiation (WMI¹) was used to degrade AFB₁ in corn, during which the influencing factors and kinetics of AFB₁ degradation were also studied. The results showed that the degree of corn crushing, the heating rate of WMI, the temperature of WMI, the solid-liquid ratio, the initial content of AFB₁ and the microwave power were all important factors affecting the degradation of AFB₁. With the increase of WMI temperature, AFB₁ content in corn, microwave power and the decrease of solid-liquid ratio, the degradation rate of AFB₁ in corn by WMI rose continuously. Its maximum degradation rate was more than 90.6%. Meanwhile, the degradation kinetics of AFB₁ in corn revealed that the degradation process of WMI followed a pseudo-first-order kinetic equation. It was demonstrated that water molecules not only acted as solvents for AFB₁ but also actively participated in its degradation process within corn samples during WMI treatment. Consequently, the results indicated that WMI was an effective method for degrading AFB₁ in corn.

黄曲霉毒素B1 （AFB1）是一种高毒性、致癌性、致畸性和诱变性真菌毒素，常见于玉米中。本研究采用水辅助微波辐照（WMI1）降解玉米中AFB1，研究了AFB1降解的影响因素和动力学。结果表明，玉米破碎程度、WMI加热速率、WMI温度、料液比、AFB1初始含量和微波功率都是影响AFB1降解的重要因素。随着WMI温度的升高、玉米中AFB1含量的增加、微波功率的增大和料液比的降低，WMI对玉米中AFB1的降解率不断升高。其最大降解率大于90.6%。同时，玉米中AFB1的降解动力学表明，WMI的降解过程符合准一级动力学方程。结果表明，在WMI处理过程中，水分子不仅作为AFB1的溶剂，还积极参与了AFB1在玉米样品中的降解过程。综上所述，WMI是一种有效的玉米AFB1降解方法。

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引用次数: 0

Alternative biological models for evaluation of the toxic, genotoxic and mutagenic potential of Ectatomma brunneum Smith venom

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108256

Bruno do Amaral Crispim , Rafaella Caroline Bernardi , Sabrina Rodrigues da Luz , Hélina dos Santos Nascimento , Fabiana Gomes da Silva Dantas , Kelly Mari Pires de Oliveira , Marina Stefanes Schibichewski , Cláudia Andrea Lima Cardoso , Alexeia Barufatti

The venom of Ectatomma brunneum is considered promising for drugs development. Therefore, it is important to evaluate its toxic potential and genetic instability using biological assays. To this end, toxicity assays were performed with Artemia salina, cytotoxicity and genotoxicity with Allium cepa and mutagenicity with Ames. The results indicated toxicity to A. salina, and no cytotoxic, genotoxic or mutagenic potential at concentrations equal to or lower than 500 μg/mL for the other tests.

引用次数: 0

Botulinum toxin for essential tremor

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108273

Kartika Gulati, Sanjay Pandey

Essential tremor is one of the most common causes of action tremors, involving bilateral upper limbs, with or without tremor in other body regions such as the head, voice, or lower limbs. Pharmacotherapy is the first-line treatment for essential limb tremor; however, a significant number of patients fail to achieve adequate improvement with medical management. Therapeutic options, such as deep brain stimulation, lesioning surgeries, or magnetic resonance–guided focused ultrasound, are more invasive and carry inherent risks. Thus, botulinum toxin serves as an important alternative for managing medically resistant essential limb tremors and is considered clinically useful. Axial symptoms of essential tremor such as head or voice tremors rarely respond to medical management, making botulinum toxin a key therapeutic option in their management, despite safety concerns of weakness. This review aims to explore these considerations by examining existing literature on the application of botulinum toxin for essential limb, head, and voice tremors.

引用次数: 0

Deep, posterior muscles of the neck. A proposal for injection procedures

IF 2.6 4区医学 Q2 PHARMACOLOGY & PHARMACY

Toxicon

Pub Date : 2025-02-01 DOI: 10.1016/j.toxicon.2025.108271

Alexandre Kreisler , Matthias Herteleer

The emergence of the col-cap concept in the 2010s led to a focus on previously neglected muscles, hoping to improve the benefit of botulinum toxin injections in patients with movements disorders of the head and neck. The deep posterior cervical muscles are part of this. They include sub-occipital muscles, the semi-spinalis cervicis muscle and even deeper muscles such as the multifidus. Injecting them requires the use of ultrasound.

This article will take up the anatomical notions necessary to perform these injections in an accurate and safe manner. We will also describe how to find these muscles using ultrasound.

引用次数: 0

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