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Albuterol as an adjuvant in acute anticholinesterase pesticide poisoning: a randomized, placebo-controlled clinical trial. 阿布特罗作为急性抗胆碱酯酶农药中毒的辅助药物:随机安慰剂对照临床试验。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-03-28 eCollection Date: 2024-04-01 DOI: 10.1093/toxres/tfae048
Samar M M Zein-Elabdeen, Neven A Hassan, Ahmad A El-Ebiary, Amal S A F Hafez, Aliaa A Hodeib

Acute anticholinesterase pesticide poisoning is a serious clinical problem, particularly in developing countries. Atropine is the most acceptable treatment for acute anticholinesterase poisoning. However, it only stops fluid production. Albuterol is a beta-2 receptor agonist that can increase fluid removal and speed the return of effective oxygen exchange. This study aims to evaluate the safety and efficacy of nebulized albuterol as an adjuvant therapy in patients with acute anticholinesterase poisoning. This stratified block randomized, single-blinded, placebo-controlled, parallel-group clinical trial was conducted between November 2020 and October 2021. It enrolled 80 patients with acute anticholinesterase pesticide poisoning who were admitted to Tanta University Poison Control Center. Patients were allocated into two groups (40 patients each). The strata were based on the severity of poisoning (moderate and severe). Patients in group I received 10 mg of nebulized albuterol. Group II received an equivalent volume of nebulized normal saline. Additionally, standard treatment was provided to both groups. Outcomes included oxygenation, mortality, need for endotracheal intubation and mechanical ventilation, hospital stay duration, time to atropinization, and total doses of atropine and oxime. We found insignificant differences in sociodemographics, exposure characteristics, clinical manifestations, or routine laboratory tests between the studied groups. The median values of oxygen saturation by pulse oximetry were 99% in the albuterol moderate toxicity group and 98% in the control moderate toxicity group. Albuterol significantly improved oxygen saturation in moderate intoxicated patients (P = 0.039). Therefore, nebulized albuterol is a safe drug. Moreover, it may improve oxygenation in acute anticholinesterase pesticide poisoning.

急性抗胆碱酯酶农药中毒是一个严重的临床问题,尤其是在发展中国家。阿托品是治疗急性抗胆碱酯酶中毒最可接受的方法。然而,它只能阻止体液分泌。阿布特罗是一种 beta-2 受体激动剂,可增加液体排出量,加快有效氧交换的恢复。本研究旨在评估雾化阿布特罗作为急性抗胆碱酯酶中毒患者辅助治疗的安全性和有效性。这项分层阻断随机、单盲、安慰剂对照、平行组临床试验于 2020 年 11 月至 2021 年 10 月期间进行。坦塔大学中毒控制中心接收了 80 名急性抗胆碱酯酶农药中毒患者。患者被分为两组(每组 40 人)。根据中毒严重程度(中度和重度)进行分层。I 组患者接受 10 毫克的雾化阿布特罗。第二组接受等量的雾化生理盐水。此外,两组患者都接受了标准治疗。研究结果包括氧合作用、死亡率、气管插管和机械通气需求、住院时间、阿托品化时间以及阿托品和肟的总剂量。我们发现,研究组之间在社会人口统计学、接触特征、临床表现或常规实验室检查方面差异不大。阿布特罗中度中毒组和对照组的脉搏血氧饱和度中位值分别为 99%和 98%。阿布特罗能明显改善中度中毒患者的血氧饱和度(P = 0.039)。因此,雾化吸入阿布特罗是一种安全的药物。此外,它还可以改善急性抗胆碱酯酶农药中毒患者的氧饱和度。
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引用次数: 0
The Global Impact of COVID-19: A Comprehensive Analysis of Its Effects on Various Aspects of Life. COVID-19 的全球影响:全面分析其对生活各方面的影响。
IF 2.2 4区 医学 Q3 TOXICOLOGY Pub Date : 2024-03-25 eCollection Date: 2024-04-01 DOI: 10.1093/toxres/tfae045
Nabiha Naveed, Khalil Ahmad, Hammad Majeed, Khizar Qureshi, Irfan Ahmad, Mudassar Fareed Awan, Tehreema Iftikhar, Shakeel Ahmad, Fozia Noreen, Muhammad Awais Amin, Hifza Batool

In this study COVID-19 effects on different aspects of life that how this virus created a mess in every discipline of life starting from a small tuck shop of a street to a huge business with a chain between different countries; and some preventive measures are also suggested. Not only mental healthiness as well as physical health of people was also disturbed to a large extent. People being quarantined did not do any practice and had nothing to do, their boredom made them mentally and physically inactive. For minimization the effect of this pandemic on mental healthiness, interventions were practiced and psychological support systems were developed to help mentally effected people; on the other hand, to improve physical health the hospital workers worked day and night in return they got affected too either mentally or physically. Many of the youngsters started alcohol consumption during quarantine. Because of the closure of educational institutes, the students were sent back to their homes where there was no proper guidance for them and they lost their interests in studies; and in a sense educational impact of COVID-19 was also unbearable. Agricultural system was affected badly and the whole world passed through a huge economic loss. The flights and traffic were blocked throughout the world, and it is the only positive impact that COVID-19 led to the environment by improving water and air quality as there was a remarkable reduction in the emission of greenhouse gases.

在这项研究中,COVID-19 对生活的各个方面都产生了影响,从街头的小食店到跨国连锁的大型企业,这种病毒如何给生活的方方面面造成了混乱;同时还提出了一些预防措施。人们的精神健康和身体健康在很大程度上都受到了影响。被隔离的人们没有任何实践活动,无所事事,无聊的生活使他们的精神和身体都不活跃。另一方面,为了改善身体健康,医院工作人员夜以继日地工作,他们的身心也受到了影响。许多年轻人在隔离期间开始酗酒。由于教育机构的关闭,学生们被送回家中,没有人对他们进行适当的指导,他们失去了学习的兴趣;从某种意义上说,COVID-19 对教育的影响也是难以承受的。农业系统受到严重影响,整个世界蒙受了巨大的经济损失。COVID-19 对环境产生的唯一积极影响是改善了水和空气质量,显著减少了温室气体的排放。
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引用次数: 0
Moringa oleifera leaves ethanolic extract counteracts cortical neurodegeneration induced by aluminum chloride in rats. 油辣木叶乙醇提取物可对抗氯化铝诱导的大鼠大脑皮层神经变性。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-03-05 eCollection Date: 2024-04-01 DOI: 10.1093/toxres/tfae028
Rabab Fawzy Hindawy, Samia M Manawy, Ola Elsayed Nafea, Abeer A Abdelhameed, Fatma Fawzi Hendawi

Background: Aluminum, a well-recognized neurotoxin, is implicated in various neurodegenerative disorders. Moringa oleifera (M. oleifera), known as a miracle tree, is utilized as a functional food and nutritional supplement. This study investigates the potential preventive effects of M. oleifera extract on aluminum chloride (AlCl3)-induced cortical neurodegeneration in rats.

Materials and methods: Therefore, 24 adult male Wistar rats were randomly divided into four distinct groups: negative control, M. oleifera extract (MOE), AlCl3, and AlCl3 + MOE. Treatments were administered orally for 28 consecutive days. Cognitive performance, brain oxidative/nitrosative stress, neuroinflammation, apoptotic-cell death, and associated histopathological alterations were assessed.

Results: Our results showed that MOE improved spatial learning and memory, enhanced antioxidant superoxide dismutase enzyme activity, antagonized nitrosative stress, reduced inflammatory cytokines (tumor necrosis factor-alpha and interleukin-6), decreased caspase-3, increased Bcl-2, and facilitated repair of cortical and hippocampal structures.

Conclusions: We concluded that MOE exhibits protective effects against cortical neurodegeneration, making it a promising supplement to counteract aluminum-induced neurotoxic effects.

背景:铝是一种公认的神经毒素,与多种神经退行性疾病有关。油杉(Moringa oleifera,M. oleifera)被称为神奇之树,可作为功能性食品和营养补充剂。本研究探讨了油橄榄提取物对氯化铝(AlCl3)诱导的大鼠大脑皮层神经退行性病变的潜在预防作用:将 24 只成年雄性 Wistar 大鼠随机分为四组:阴性对照组、油橄榄提取物(MOE)组、AlCl3 组和 AlCl3 + MOE 组。连续 28 天口服治疗。对认知能力、脑氧化/亚硝基应激、神经炎症、细胞凋亡以及相关的组织病理学改变进行了评估:结果表明:MOE改善了空间学习和记忆,提高了抗氧化剂超氧化物歧化酶的活性,拮抗了亚硝基应激,减少了炎症细胞因子(肿瘤坏死因子-α和白细胞介素-6),降低了caspase-3,增加了Bcl-2,并促进了大脑皮层和海马结构的修复:我们得出结论:MOE 对大脑皮层神经退行性变具有保护作用,使其成为一种很有前景的补充剂,可对抗铝引起的神经毒性效应。
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引用次数: 0
Correction to: Metformin and Aspirin: Anticancer effects on A549 and PC3 cancer cells and the mechanisms of action. 更正:二甲双胍和阿司匹林:对 A549 和 PC3 癌细胞的抗癌作用及其作用机制。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-28 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae024

[This corrects the article DOI: 10.1093/toxres/tfad060.].

[此处更正了文章 DOI:10.1093/toxres/tfad060]。
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引用次数: 0
Effects of PM2.5 exposure on clock gene BMAL1 and cell cycle in human umbilical vein endothelial cells. PM2.5 暴露对人脐静脉内皮细胞时钟基因 BMAL1 和细胞周期的影响
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-26 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae022
Haochong Shen, Meidi Gong, Minghao Zhang, Shikun Sun, Rao Zheng, Qing Yan, Juan Hu, Xiaobin Xie, Yan Wu, Junjie Yang, Jing Wu, Jing Yang

Background: Fine particulate matter (PM2.5) exposure has been closely associated with cardiovascular diseases, which are relevant to cell cycle arrest. Brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) not only participates in regulating the circadian clock but also plays a role in modulating cell cycle. However, the precise contribution of the circadian clock gene BMAL1 to PM2.5-induced cell cycle change remains unclear. This study aims to explore the impact of PM2.5 exposure on BMAL1 expression and the cell cycle in human umbilical vein endothelial cells (HUVECs).

Methods: HUVECs was exposed to PM2.5 for 24 hours at different concentrations ((0, 12.5, 25, 75 and 100 μg.mL-1) to elucidate the potential toxic mechanism. Following exposure to PM2.5, cell viability, ROS, cell cycle, and the expression of key genes and proteins were detected.

Results: A remarkable decrease in cell viability is observed in the PM2.5-exposed HUVECs, as well as a significant increase in ROS production. In addition, PM2.5-exposed HUVECs have cycle arrest in G0/G1 phase, and the gene expression of p27 is also markedly increased. The protein expression of BMAL1 and the gene expression of BMAL1 are increased significantly. Moreover, the protein expressions of p-p38 MAPK and p-ERK1/2 exhibit a marked increase in the PM2.5-exposed HUVECs. Furthermore, following the transfection of HUVECs with siBMAL1 to suppress BMAL1 expression, we observed a reduction in both the protein and gene expression of the MAPK/ERK pathway in HUVECs exposed to PM2.5.

Conclusions: Overall, our results indicate that PM2.5 exposure significantly upregulates the circadian clock gene expression of BMAL1 and regulates G0/G1 cell cycle arrest in HUVECs through the MAPK/ERK pathway, which may provide new insights into the potential molecular mechanism regarding BMAL1 on PM2.5-induced cardiovascular diseases.

背景:细颗粒物(PM2.5)暴露与心血管疾病密切相关,而心血管疾病与细胞周期停滞有关。脑和肌肉芳香烃受体核转运体样蛋白1(BMAL1)不仅参与调节昼夜节律,还在调节细胞周期方面发挥作用。然而,昼夜节律钟基因 BMAL1 对 PM2.5 诱导的细胞周期变化的确切贡献仍不清楚。本研究旨在探讨 PM2.5 暴露对 BMAL1 表达和人脐静脉内皮细胞(HUVECs)细胞周期的影响。方法:将 HUVECs 暴露于不同浓度(0、12.5、25、75 和 100 μg.mL-1)的 PM2.5 24 小时,以阐明其潜在的毒性机制。暴露于 PM2.5 后,检测了细胞活力、ROS、细胞周期以及关键基因和蛋白质的表达:结果:在暴露于 PM2.5 的 HUVECs 中观察到细胞活力明显下降,ROS 生成显著增加。此外,PM2.5 暴露的 HUVEC 细胞周期停滞在 G0/G1 期,p27 的基因表达也明显增加。BMAL1 的蛋白表达和基因表达均显著增加。此外,PM2.5 暴露的 HUVEC 中 p-p38 MAPK 和 p-ERK1/2 的蛋白表达量也明显增加。此外,在用 siBMAL1 转染 HUVEC 以抑制 BMAL1 的表达后,我们观察到暴露于 PM2.5 的 HUVEC 中 MAPK/ERK 通路的蛋白和基因表达均有所减少:总之,我们的研究结果表明,PM2.5暴露会显著上调BMAL1的昼夜节律钟基因表达,并通过MAPK/ERK通路调控HUVECs的G0/G1细胞周期停滞,这可能会为BMAL1关于PM2.5诱发心血管疾病的潜在分子机制提供新的见解。
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引用次数: 0
In silico soil degradation and ecotoxicity analysis of veterinary pharmaceuticals on terrestrial species: first report. 兽药对陆生物种的土壤降解和生态毒性硅学分析:首次报告。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-26 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae020
Purusottam Banjare, Rekha Singh, Nilesh Kumar Pandey, Balaji Wamanrao Matore, Anjali Murmu, Jagadish Singh, Partha Pratim Roy

With the aim of persistence property analysis and ecotoxicological impact of veterinary pharmaceuticals on different terrestrial species, different classes of veterinary pharmaceuticals (n = 37) with soil degradation property (DT50) were gathered and subjected to QSAR and q-RASAR model development. The models were developed from 2D descriptors under organization for economic cooperation and development guidelines with the application of multiple linear regressions along with genetic algorithm. All developed QSAR and q-RASAR were statistically significant (Internal = R2adj: 0.721-0.861, Q2LOO: 0.609-0.757, and external = Q2Fn = 0.597-0.933, MAEext = 0.174-0.260). Further, the leverage approach of applicability domain assured the model's reliability. The veterinary pharmaceuticals with no experimental values were classified based on their persistence level. Further, the terrestrial toxicity analysis of persistent veterinary pharmaceuticals was done using toxicity prediction by computer assisted technology and in-house built quantitative structure toxicity relationship models to prioritize the toxic and persistent veterinary pharmaceuticals. This study will be helpful in estimation of persistence and toxicity of existing and upcoming veterinary pharmaceuticals.

为了分析兽药的持久性和对不同陆生物种的生态毒理影响,收集了具有土壤退化特性(DT50)的不同类别兽药(n = 37),并对其进行了 QSAR 和 q-RASAR 模型开发。这些模型是根据经济合作与发展组织的指导方针,应用多重线性回归和遗传算法,从二维描述符中建立的。所有开发的 QSAR 和 q-RASAR 都具有显著的统计学意义(内部 = R2adj:0.721-0.861,Q2LOO:0.609-0.757,外部 = Q2Fn = 0.597-0.933,MAEext = 0.174-0.260)。此外,适用性领域的杠杆方法确保了模型的可靠性。根据持久性水平对无实验值的兽药进行了分类。此外,通过计算机辅助毒性预测技术和内部建立的定量结构毒性关系模型,对持久性兽药进行了陆地毒性分析,以确定有毒持久性兽药的优先级。这项研究将有助于估算现有和未来兽药的持久性和毒性。
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引用次数: 0
In-vitro and preclinical testing of bacillus subtilis UBBS-14 probiotic in rats shows no toxicity. 在大鼠体内对枯草杆菌 UBBS-14 益生菌进行的体外和临床前测试表明,它没有毒性。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-22 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae021
Ankit Negi, Tulasi Pasam, Syed Muhammad Farqadain, Y Mahalaxmi, Manoj P Dandekar

Introduction: Probiotics made from Bacillus subtilis provide a wide spread of health benefits, particularly in the treatment of diarrhea and gastrointestinal problems. Herein, we employed in vitro and in vivo paradigms to assess the potential adverse effects and toxicity of B. subtilis UBBS-14.

Materials and methods: According to Organization for Economic Co-operation and Development (OECD) 423 and 407 requirements, a preclinical investigation was conducted in male and female Sprague-Dawley rats. Acute toxicity was examined following a single peroral (PO) administration of 5,000 mg/kg body weight (bw) i.e. equivalent to 500 billion colony-forming units (CFU) per kg bw. Single administration of B. subtilis UBBS-14 showed no mortality or adverse effects until the 14-day observation period, indicating LD50 is >5,000 mg/kg bw.

Results: Incubation of B. subtilis UBBS-14 with Caco2, HT29, and Raw 264.7 cell lines, showed no cytotoxic effects. This probiotic strain was also found responsive to the majority of antibiotics. For a 28-day repeated dose toxicity study, rats were administered 100, 500, and 1,000 mg/kg bw daily once (10, 50, and 100 billion CFU/kg bw/day, respectively) doses of B. subtilis UBBS-14. No notable changes were seen in the morphology, weight, and histopathology of the critical internal organs. The haematological, biochemical, electrolyte (sodium, potassium, chloride, and calcium), and urine analytical results were within the normal range and equivalent to the vehicle-treated group.

Conclusion: B. subtilis UBBS-14's no-observed-effect level (NOEL) was thus determined to be >1,000 mg/kg bw/day following a 28-day oral dosing.

导言:由枯草芽孢杆菌制成的益生菌具有广泛的健康益处,尤其是在治疗腹泻和胃肠道问题方面。在此,我们采用体外和体内范例来评估枯草芽孢杆菌 UBBS-14 的潜在不良影响和毒性:根据经济合作与发展组织(OECD)423 和 407 的要求,我们对雄性和雌性 Sprague-Dawley 大鼠进行了临床前调查。单次口服给药 5,000 毫克/千克体重(即相当于每千克体重 5,000 亿个菌落形成单位(CFU))后,对急性毒性进行了检测。单次服用枯草芽孢杆菌 UBBS-14 在 14 天的观察期内没有出现死亡或不良反应,表明半数致死剂量大于 5,000 毫克/千克体重:结果:将枯草杆菌 UBBS-14 与 Caco2、HT29 和 Raw 264.7 细胞系培养,未发现细胞毒性作用。这种益生菌株对大多数抗生素也有反应。在一项为期 28 天的重复剂量毒性研究中,大鼠每天一次分别服用 100、500 和 1,000 毫克/千克体重的枯草杆菌 UBBS-14(分别为 100、500 和 1,000 亿 CFU/千克体重/天)。重要内脏器官的形态、重量和组织病理学未见明显变化。血液学、生物化学、电解质(钠、钾、氯化物和钙)和尿液分析结果均在正常范围内,与车辆处理组相当:结论:因此,在口服 28 天后,枯草芽孢杆菌 UBBS-14 的无观测效应水平(NOEL)被确定为大于 1,000 毫克/千克体重/天。
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引用次数: 0
In vivo toxicological assessment of silver nanoparticle in edible fish, Oreochromis mossambicus. 银纳米粒子在食用鱼 Oreochromis mossambicus 中的体内毒理学评估。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-17 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae019
Gisha Sivan, Rajesh Pamanji, Srikanth Koigoora, Nimila Joseph, Joseph Selvin

Silver nanoparticles are the extensively utilized among all nanoparticles due to their antibacterial and wound healing properties making them highly suitable for medical and pharmaceutical applications. The field of nanoparticle toxicity is an emerging field and the present study aims to assess the biochemical, hematological and genotoxicity in Oreochromis mossambicus exposed to different concentrations of silver nanoparticles for 7 and 14 days. Silver nanoparticles were synthesized by reduction of silver nitrate using trisodium citrate and was characterized using X-ray diffraction, SEM, HRTEM and DLS. Hematological parameters like RBC, WBC, Hb, HCT and MCV and for biochemical analysis, antioxidant enzymes SOD, CAT and GPX and serum enzymes AST, ALT, ACP, ALP and LDH were analyzed. Genotoxicity was studied using comet assay. Results obtained showed decrease in erythrocytes, HCT, Hb and MCV while an increase was noted in WBC on day 7 and 14. The antioxidant enzymes SOD, CAT and GPx showed a decrease and the lipid peroxidation product MDA was elevated. The serum enzymes AST, ALT, ACP ALP and LDH showed an increased activity when compared to control. DNA damage was evident by an increase in % TDNA. The results indicate hematological, biochemical and genotoxicity of silver nanoparticles that might be mediated through ROS generation in O. mossambicus.

银纳米粒子具有抗菌和伤口愈合的特性,非常适合医疗和制药应用,因此在所有纳米粒子中被广泛使用。纳米颗粒的毒性是一个新兴领域,本研究旨在评估暴露于不同浓度的银纳米颗粒 7 天和 14 天的裸鲤的生化、血液学和遗传毒性。银纳米粒子是通过柠檬酸三钠还原硝酸银合成的,并使用 X 射线衍射、扫描电镜、HRTEM 和 DLS 进行表征。分析了 RBC、WBC、Hb、HCT 和 MCV 等血液学参数,以及 SOD、CAT 和 GPX 等抗氧化酶和 AST、ALT、ACP、ALP 和 LDH 等血清酶的生化分析。使用彗星试验研究了遗传毒性。结果表明,在第 7 天和第 14 天,红细胞、血细胞比容、血红蛋白和 MCV 都有所下降,而白细胞则有所增加。抗氧化酶 SOD、CAT 和 GPx 出现下降,脂质过氧化产物 MDA 升高。与对照组相比,血清酶 AST、ALT、ACP ALP 和 LDH 的活性都有所提高。DNA 损伤表现为 TDNA 百分比的增加。这些结果表明,银纳米颗粒可能通过产生 ROS 来介导莫桑比克鳗鱼的血液学、生物化学和遗传毒性。
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引用次数: 0
Hexaconazole exposure may lead to Parkinson via disrupting glucocerebrosidase and parkin: molecular interaction, dynamics, MMPBSA and DFT based in-silico predictive toxicology. 暴露于己康唑可能会通过干扰葡萄糖脑苷脂酶和帕金森而导致帕金森病:基于分子相互作用、动力学、MMPBSA 和 DFT 的室内预测毒理学。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-13 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae018
Faisal K Alkholifi, Sayed Aliul Hasan Abdi, Marwa Qadri, Shabihul Fatma Sayed, Amani Khardali, Sumathi Nagarajan, Alhamyani Abdulrahman, Nayef Aldabaan, Yahia Alghazwani

Hexaconazole is a known fungicide for agricultural purposes. It has bioaccumulation ability which makes it important for its toxicological characterization. There are various neurological impacts of pollutants on human health. Therefore, in this study, we have done predictive analyses of the interaction mechanism of hexaconazole by molecular interaction analysis, molecular dynamics simulation, and Poisson-Boltzmann surface area (MM-PBSA) to assess hexaconazole's potency to disrupt the homeostasis of glucocerebrosidase (-7.9 kcal/mol) and parkin (-5.67 kcal/mol) proteins which have significant roles in the manifestation of Parkinson disease. The findings reveal that hexaconazole has the potency to form stable interactions with glucocerebrosidase and parkin. This research provides a molecular and atomic-level understanding of how hexaconazole exposure may disrupt the homeostasis of glucocerebrosidase and parkin. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration, and hydrogen bonding exhibited the potent molecular interactions of hexaconazole, which may lead to neurological manifestations such as Parkinson disease.

己唑醇是一种已知的农用杀菌剂。它具有生物蓄积能力,因此对其进行毒理学特征描述非常重要。污染物对人体健康有各种神经影响。因此,在本研究中,我们通过分子相互作用分析、分子动力学模拟和泊松-波尔兹曼表面积(MM-PBSA)对己康唑的相互作用机制进行了预测分析,以评估己康唑破坏葡萄糖脑苷脂(-7.9 kcal/mol)和帕金森蛋白(-5.67 kcal/mol)平衡的效力,这两种蛋白在帕金森病的表现中具有重要作用。研究结果表明,己唑醇能与葡萄糖脑苷脂和帕金形成稳定的相互作用。这项研究从分子和原子水平上揭示了暴露于己康唑会如何破坏葡萄糖脑苷脂和帕金蛋白的平衡。均方根偏差(RMSD)、均方根波动(RMSF)、回转半径和氢键显示了己康唑的强大分子相互作用,这可能会导致帕金森病等神经系统表现。
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引用次数: 0
The detection of pomegranate (Punica granatum L.) peel apoptotic effects using AgNOR staining in MDA-MB-231. 利用 AgNOR 染色法检测石榴(Punica granatum L.)果皮在 MDA-MB-231 中的凋亡作用。
IF 2.1 4区 医学 Q2 Environmental Science Pub Date : 2024-02-13 eCollection Date: 2024-02-01 DOI: 10.1093/toxres/tfae015
Rabia Nur Ceyhan, Mustafa Nisari, Mehtap Nisari, Sümeyye Uçar, Fatih Mehmet Koca, Gülderen Kerek, Tuğçe Özcanlı, Neriman İnanç

In present study, it was purposed to determine the in vitro effect of the extract obtained from the pomegranate (Punica granatum L.) peel on the breast cancer cell line. MDA-MB-231 cells were exposed to pomegranate peel extract (PoPx) at 37 °C and 5% CO2 for varying durations (24 and 48 h) and doses (25 and 50 μg/mL). At the end of the incubation periods, argyrophilic nucleolus organizer regions (AgNOR) protein status, cell viability/apoptosis and cell cycle of MDA-MB-231 cells were examined in the Muse Cell Analyzer device. Cell viability was observed to be decreased when the groups treated with PoPx were compared with the control group. The group in which apoptosis was observed with the highest value was 50 μg/mL PoPx group (p < 0.05). In the cell cycle test, the number of cells in the G0/G1 stage was found to be significantly higher in the 25 μg/mL PoPx group compared to the control and 50 μg/mL PoPx groups at the end of the 24-h incubation period (p < 0.05) The results also supported cell cycle and apoptosis, and at the end of 24 h, Total AgNOR area(TAA)/Total nuclear area (NA) ratio and AgNOR numbered decreased on the 50 μg/mL PoPx group and were found to be statistically significant compared to the control group (p < 0.05). Consequently, it was determined that PoPx increased apoptosis on breast cancer cells by various mechanisms and inhibited cell viability/cell growth. This study showed that the widespread consumption of PoPx may be effective in preventing cancer formation and slowing its progression.

本研究旨在确定石榴(Punica granatum L.)果皮提取物对乳腺癌细胞系的体外效应。将 MDA-MB-231 细胞暴露于石榴皮提取物(PoPx)中,在 37 °C、5% CO2 下进行不同时间(24 和 48 小时)和剂量(25 和 50 μg/mL)的培养。培养期结束后,用 Muse 细胞分析仪检测 MDA-MB-231 细胞的嗜碱性核仁组织区(AgNOR)蛋白状态、细胞活力/凋亡和细胞周期。与对照组相比,用 PoPx 处理的组观察到细胞活力下降。在细胞周期测试中,与对照组和 50 μg/mL PoPx 组相比,在 24 小时培养期结束时,25 μg/mL PoPx 组处于 G0/G1 阶段的细胞数量显著增加(p)、在 24 小时结束时,50 μg/mL PoPx 组的总 AgNOR 面积(TAA)/总核面积(NA)比值和 AgNOR 数量减少,与对照组相比具有统计学意义(p)。因此,可以确定 PoPx 通过各种机制增加了乳腺癌细胞的凋亡,并抑制了细胞活力/细胞生长。这项研究表明,广泛食用 PoPx 可有效预防癌症的形成和减缓癌症的发展。
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Toxicology Research
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