Experimental parasitology最新文献_第2页

Effect of a low-protein diet on the spleen of Swiss Webster mice infected with Schistosoma mansoni 低蛋白饮食对感染曼氏血吸虫瑞士韦氏小鼠脾脏的影响。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-18 DOI: 10.1016/j.exppara.2025.109085

Joana Bernardo , Magda Sanches , Christiane Leal Corrêa , Luciana Brandão-Bezerra , José Roberto Machado-Silva , Renata Heisler Neves

Schistosomiasis is the second most prevalent parasitic disease globally. It is common in tropical and subtropical regions, with transmission dependent on human contact with contaminated water and the presence of an intermediate host. The disease is associated with poverty and coexists with inefficient nutrient consumption among populations lacking basic sanitation. In this study, we performed a histopathological analysis of the spleen in Schistosoma mansoni-infected mice fed a low-protein diet. Mice were divided into four groups (n = 5 animals per group): uninfected, standard diet (US); uninfected, low-protein diet (ULP); infected, standard diet (IS); and infected, low-protein diet (ILP). S. mansoni infection (BH strain, with approximately 100 cercariae via subcutaneous route) occurred at the 4th week of diet administration, and euthanasia was performed after 9 weeks of infection. After euthanasia, the spleen was excised, cleaved, fixed, and then underwent histological processing and staining for the relevant analyses. Splenic alterations were investigated through qualitative and quantitative histological analyses, utilizing white pulp and capsule morphometry, stereology (D36 method), and megakaryocyte quantification. Histopathological analyses of the ILP group revealed a notable increase in hemosiderin and bilirubin pigment deposits, a 100 % increase in the volume density of trabeculae and megakaryocytes (albeit with deficient synthesis), and intense organizational changes in the splenic parenchyma. Therefore, the presented data suggest that protein deficiency exacerbates splenic tissue disorganization, a common condition in schistosomiasis, significantly impacting disease pathogenesis and host response.

血吸虫病是全球第二大流行的寄生虫病。该病常见于热带和亚热带地区，传播依赖于人类接触受污染的水和中间宿主的存在。该病与贫困有关，并与缺乏基本卫生设施的人群中营养消耗效率低下并存。在这项研究中，我们对喂食低蛋白饮食的感染曼氏血吸虫的小鼠的脾脏进行了组织病理学分析。小鼠分为四组（每组n = 5只）：未感染，标准饮食（US）；未感染低蛋白饮食（ULP）；受感染，标准饮食（IS）；感染，低蛋白饮食（ILP）。进食第4周发生曼氏链球菌感染（BH株，皮下感染约100条尾蚴），感染9周后进行安乐死。安乐死后，切除脾脏，切开，固定，然后进行组织学处理和染色进行相关分析。通过定性和定量组织学分析，利用白髓和包膜形态测定、体视学（D36法）和巨核细胞定量来研究脾脏的改变。ILP组的组织病理学分析显示含铁血黄素和胆红素色素沉积明显增加，小梁和巨核细胞体积密度增加100%（尽管合成不足），脾实质组织改变强烈。因此，这些数据表明，蛋白质缺乏加剧了血吸虫病常见的脾组织紊乱，显著影响了疾病的发病机制和宿主的反应。

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引用次数: 0

Seaweed-derived nanoparticles for mosquito control: An eco-nanotechnology approach 用于蚊虫控制的海藻衍生纳米颗粒：生态纳米技术方法

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-17 DOI: 10.1016/j.exppara.2025.109084

Aravinth Annamalai

Mosquito-borne diseases such as malaria, dengue, and chikungunya remain major global health challenges, further exacerbated by escalating insecticide resistance and ecological risks linked to synthetic agents. This review highlights the potential of seaweed-derived nanoparticles (NPs) as sustainable biopesticides for vector control. While multiple types of seaweed-mediated NPs have been reported, particular emphasis is placed on silver nanoparticles (AgNPs), given their dominance in the literature, with additional coverage of TiO₂, ZnO, and AuNPs for broader context. Synthesized via green chemistry approaches using marine macroalgal metabolites such as polyphenols, flavonoids, and polysaccharides, these NPs exhibit potent larvicidal, adulticidal, and ovicidal effects against major mosquito vectors, including Aedes, Anopheles, and Culex species. Mechanistic studies reveal that seaweed-mediated NPs impair mosquito physiology through midgut epithelial disruption, oxidative stress induction, enzyme inhibition, reproductive interference, and apoptosis. Their nanoscale dimensions and multi-targeted actions reduce the likelihood of resistance development, while low toxicity toward non-target organisms and efficient biodegradability enhance ecological compatibility. Comparative evaluations suggest that seaweed-derived NPs often match or surpass conventional insecticides in efficacy under laboratory settings, with distinct advantages in environmental safety. Nonetheless, limitations persist, including the absence of standardized synthesis protocols, limited field trials, and insufficient data on long-term ecological impacts. Future research should focus on scalable synthesis, comprehensive toxicological evaluation, and integration into existing vector management frameworks. By uniting marine biotechnology with nanoscience, seaweed-derived NPs represent a promising, eco-safe alternative for mosquito control with implications for global health and environmental sustainability.

疟疾、登革热和基孔肯雅热等蚊媒疾病仍然是全球健康面临的主要挑战，杀虫剂耐药性不断升级以及与合成剂有关的生态风险进一步加剧了这种挑战。这篇综述强调了海藻衍生纳米颗粒（NPs）作为病媒控制的可持续生物农药的潜力。虽然已经报道了多种类型的海藻介导的纳米粒子，但鉴于其在文献中的主导地位，特别强调的是银纳米粒子（AgNPs），并在更广泛的背景下对TiO2， ZnO和AuNPs进行了额外的报道。这些NPs通过绿色化学方法合成，利用多酚、黄酮类化合物和多糖等海洋大藻代谢物，对伊蚊、按蚊和库蚊等主要蚊媒具有杀幼虫、杀成虫和杀卵作用。机制研究表明，海藻介导的NPs通过中肠上皮破坏、氧化应激诱导、酶抑制、生殖干扰和细胞凋亡等途径损害蚊子的生理机能。它们的纳米级尺寸和多靶点作用降低了耐药性发展的可能性，而对非靶标生物的低毒性和高效的生物降解性增强了生态相容性。对比评价表明，在实验室环境下，海藻衍生NPs的药效往往与传统杀虫剂相当或超过传统杀虫剂，在环境安全方面具有明显优势。尽管如此，限制仍然存在，包括缺乏标准化的合成方案，有限的实地试验，以及长期生态影响的数据不足。未来的研究应侧重于可扩展的合成、全面的毒理学评估以及与现有病媒管理框架的整合。通过将海洋生物技术与纳米科学结合起来，海藻衍生的NPs代表了一种有前途的、生态安全的蚊虫控制替代方案，对全球健康和环境可持续性具有影响。

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引用次数: 0

Histopathological changes, dynamics of macrophage polarization and deposition of type I and III collagen along the course of experimental hepatic toxocariasis 实验性肝弓形虫病过程中的组织病理学变化、巨噬细胞极化动态及I型和III型胶原沉积。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-16 DOI: 10.1016/j.exppara.2025.109082

Iman F. Abou-El-Naga , Eman Dorry Elkerdany , Rania G. Aly , Enas Mohammed Mostafa Zaytoun

Toxocariasis is a helminthic infection that predominantly affects the liver and induces significant pathological changes mediated by host immune response. Both M1 and M2 macrophage phenotypes exert opposing yet complementary functions during infection. This study aimed to characterize the sequential immunopathological and fibrogenic events in hepatic toxocariasis over 16 weeks post-infection (wpi) in a murine model. Liver samples were collected from infected mice at different time points, and immunohistochemical (IHC) examination revealed the presence of both macrophage phenotypes up to 8 wpi (group If), indicating mixed immune response. In early stages of infection, macrophage polarization was skewed toward M1 phenotype, with a statistically significant increase in functional M1/M2 macrophage ratio at 2 days post-infection (dpi), followed by a significant decrease in this ratio up to 4 wpi (group Ie) (p < 0.001 compared to 2 dpi ). Thereafter, polarization shifted toward M2 phenotype accompanied by a further significant reduction in M1/M2 ratio, whereas at 16 wpi (group Ig), no distinct polarization was observed, although M2 count remained significantly higher than that of the control group (p < 0.001). M1 predominance was associated with a higher grades and elevated liver enzyme levels, while M2 cells were associated with significantly lower inflammation grades but higher stages of fibrosis. Type III collagen fibers predominated in early stages of infection, while type I collagen fibers were dominant in the late stages (p < 0.001), suggesting a progression toward irreversible fibrotic lesions in chronic hepatic toxocariasis. These findings may support the development of stage-specific diagnostic markers and targeted therapeutic strategies throughout the course of hepatic toxocariasis.

弓形虫病是一种蠕虫感染，主要影响肝脏，引起宿主免疫反应介导的显著病理改变。在此过程中，M1和M2巨噬细胞发挥相反的功能。本研究旨在描述小鼠肝弓形虫病感染后16周（wpi）的顺序免疫病理和纤维化事件。在不同时间点从感染小鼠身上切除肝脏样本，检查显示两种巨噬细胞表型高达8 wpi （If组），表明混合类型的免疫反应。在感染早期，极化向M1表型倾斜，感染后2天（dpi） M1/M2巨噬细胞比例有统计学意义增加，随后表型和功能M1/M2巨噬细胞比例有统计学意义下降，高达4 wpi （Ie组），与2 dpi （Ib组）相比（p < 0.001）。到8 wpi时（If组），极化向M2转移，M1/M2巨噬细胞比例有统计学意义降低，而在16 wpi时（Ig组），虽然M2细胞仍显著高于对照组，但未观察到明显的极化（p < 0.001）。M1巨噬细胞与较高的炎症级别和肝酶升高有统计学相关性，而M2巨噬细胞与较低的炎症级别有统计学意义，但与较高的纤维化阶段有统计学意义。III型胶原蛋白在感染的早期阶段占主导地位，而I型胶原蛋白在晚期占主导地位（p < 0.001），这种胶原沉积模式可能是慢性肝弓形虫病中不可逆纤维化病变发展的基础。因此，这些数据可能支持在肝弓形虫病的整个过程中以阶段为导向的诊断标志物和靶向治疗策略的发展。

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引用次数: 0

Larvicidal and macrofilaricidal efficacy of closantel and morantel against mosquito larvae and Setaria digitata nematodes Closantel和Morantel对蚊虫幼虫和狗尾草线虫的杀幼虫和大丝虫效果。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-15 DOI: 10.1016/j.exppara.2025.109083

Megan Hall , Swetha Babu , Nallathambi Baranidharan , Priyabrata Bhattacharya , Manju Rahi , Appadurai Daniel Reegan

Vector-borne diseases are major public health problems in the growing world and insecticide resistance threatens the elimination programs. Repurposed drugs could be a solution to develop novel larvicides to combat growing insecticide resistance among mosquito vectors and novel macrofilaricides to eliminate lymphatic filariasis (LF). In the present study, two veterinary drugs, closantel, and morantel were assessed for larvicidal activity against three mosquito larvae and macrofilaricidal activity against Setaria digitata, a lymphatic filariasis model organism. The larvicidal activity was assessed with a bioassay against Aedes aegypti, Anopheles stephensi, and Culex quinquefasciatus larvae with concentrations between 0.1 ppm and 10 ppm. The macrofilaricidal activity was assessed using worm motility and MTT assays against Setaria digitata nematodes with concentrations between 0.05 mg/mL to 0.001 mg/mL. Among the two drugs tested, closantel was found to be effective against An. stephensi, Cx. quinquefasciatus and Ae. aegypti larvae with LC₅₀ values of 0.183, 0.658, 0.773 ppm, and LC₉₀ values of 1.577, 2.560, 2.108, respectively. Both closantel and morantel demonstrated macrofilaricidal activity. However, morantel showed strong macrofilaricidal activity with 87.29 % and 87.49 % inhibition at 492 and 510 nm, respectively, in the MTT assay at the lowest concentration of 0.01 mg/mL. But closantel showed 85.26 % and 86.28 % inhibition at 492 and 510 nm, respectively, in the MTT assay at 0.05 mg/mL. These findings suggest that closantel and morantel could be promising candidates as repurposed drugs for larvicides and macrofilaricides and may provide valuable insights into effective target mechanisms against vector-borne diseases.

媒介传播的疾病是日益增长的世界中主要的公共卫生问题，杀虫剂耐药性威胁着消除计划。重新利用的药物可能是开发新型杀幼虫剂的一种解决方案，以对抗蚊子媒介中日益增长的杀虫剂耐药性，以及开发大丝虫病剂来消除淋巴丝虫病（LF）。本文研究了closantel和morantel两种兽药对3种蚊子幼虫的杀虫活性和对淋巴丝虫病模式生物狗尾草（Setaria digitata）的杀虫活性。采用生物测定法对浓度为0.1 ppm ~ 10 ppm的埃及伊蚊、斯氏按蚊和致倦库蚊幼虫进行杀幼虫活性测定。对浓度为0.05mg/mL ~ 0.001mg/mL的数字狗尾草（Setaria digitata）线虫，采用虫动法和MTT法测定其大丝虫杀灭活性。在测试的两种药物中，发现closantel对An有效。stephensi,残雪。致倦库蚊和伊蚊。LC50分别为0.183、0.658、0.773 ppm， LC90分别为1.577、2.560、2.108。closantel和morantel均表现出杀灭大丝虫的活性。在MTT试验中，在最低浓度为0.01 mg/mL时，在492 nm和510 nm处，morantel的抑菌活性分别为87.29%和87.49%。在0.05 mg/mL的MTT条件下，closantel在492 nm和510 nm的抑制作用分别为85.26%和86.28%。这些发现表明，closantel和morantel可能是有希望作为杀幼虫剂和大丝虫剂的重新用途药物的候选药物，并可能为针对媒介传播疾病的有效靶标机制提供有价值的见解。

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引用次数: 0

Plasmodium vivax circumsporozoite protein and vaccine strategies in murine models: A scoping review 小鼠模型中间日疟原虫环孢子子蛋白和疫苗策略：范围综述

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-13 DOI: 10.1016/j.exppara.2025.109081

Marrara P. Sampaio , Marcelo Cerilo-Filho , Maria Naely G. Almeida , Maria Alice T. Matos , Amanda A. Silva , Dulce J.V. Fernando , Raisa P. Bras , Andréa R.S. Baptista , Tatiana X. de Castro , Ricardo L.D. Machado

引用次数: 0

IgG avidity and placenta real-time PCR in detection of active maternal toxoplasmosis: relation to pregnancy outcomes IgG亲和度及胎盘实时PCR检测活动性母体弓形虫病：与妊娠结局的关系。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109065

Amal Farahat Allam , Amel Youssef Shehab , Nashwa Abdelaleem Ahmed , Amel Gaber Elshereedy , Hoda Fahmy Farag , Sarah Mohamed Abdo , Heba Said Ibrahim

Toxoplasmosis diagnosis during pregnancy is important for the management of pregnant women suspected to have early T. gondii infection. This study aimed to detect T. gondii infection using ELISA and placenta real-time PCR among pregnant women. The study involved 149 women from El Shatby Hospital, Alexandria University; 50 experienced spontaneous abortion and 99 delivered normally, among whom four cases were spiramycin treated. Only 83 women agreed to submit blood samples that were ELISA tested for Toxoplasma IgG and IgM antibodies (ELISA Biokit, Barcelona, Spain). ELISA IgG positives were re-examined for IgG avidity. Placental samples were collected from all participants (about 20 g from each), and DNA was extracted using the Qiagen DNA kit, Hilden, Germany. The samples were examined by real-time PCR targeting the REP-529 gene. Out of the 83 women, 57 (68.7 %) were IgG positive and only one case was IgM positive. Fifty IgG cases had low IgG avidity and seven had high IgG avidity. Approximately one-third of the 149 placenta samples, 83 serologically examined cases, 57 IgG positives; 50 with low avidity, and 7 with high avidity, tested positive by real-time PCR, with detection rates of 29.5 %, 28.9 %, 31.5 %, 32 %, and 28.6 %, respectively. Moreover, it detected six positives among the IgG negatives, and two of the four spiramycin-treated cases tested positive. No significant difference between abortion and normal delivery rates was observed among T. gondii positive and negative women, either by ELISA IgG and/or real-time PCR. In conclusion, combining IgG avidity and placenta real-time PCR is promising for detecting T. gondii active infection and the probability of fetal infection.

妊娠期弓形虫病诊断对于怀疑早期弓形虫感染的孕妇的管理很重要。采用ELISA和胎盘实时荧光定量PCR检测孕妇弓形虫感染情况。这项研究涉及来自亚历山大大学El Shatby医院的149名妇女；自然流产50例，正常分娩99例，其中螺旋霉素治疗4例。只有83名妇女同意提交经ELISA检测弓形虫IgG和IgM抗体的血液样本（ELISA Biokit，巴塞罗那，西班牙）。再次检测ELISA IgG阳性。收集所有参与者的胎盘样本（每人约20 g），并使用Qiagen DNA试剂盒提取DNA， Hilden，德国。采用real-time PCR检测REP-529基因。83例女性中IgG阳性57例（68.7%），IgM阳性1例。IgG低贪婪50例，高贪婪7例。149份胎盘样本中约有三分之一，血清学检查病例83例，IgG阳性57例；实时荧光定量PCR检测阳性的低亲和度为50份，高亲和度为7份，检出率分别为29.5%、28.9%、31.5%、32%和28.6%。此外，它在IgG阴性中检测到6例阳性，并且在4例使用螺旋霉素治疗的病例中检测出2例阳性。弓形虫阳性和阴性妇女的流产率和正常分娩率在ELISA IgG和/或实时PCR检测中均无显著差异。综上所提，结合IgG亲和度和胎盘实时荧光定量PCR检测弓形虫活动性感染和胎儿感染的可能性是有希望的。

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引用次数: 0

Comparison of IgM and IgG ELISAs using recombinant thrombospondin-related adhesive protein (BgTRAP) for the differentiation of early and late Babesia gibsoni infections in canines 重组血小板反应相关黏附蛋白（BgTRAP） IgM和IgG elisa鉴别犬早期和晚期巴贝斯虫感染的比较

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109066

Nellikka Chalapron Sreenidhi , Chundayil Kalarickal Deepa , Anju Varghese , Karapparambu Gopalan Ajith Kumar , Aravindakshan Anaswara , Reghu Geethu , Ravindran Rajasekhar , Pulikottil Vinu David , Reghu Ravindran

Vector-borne illnesses pose a rising global threat to pet health, with Babesia gibsoni being the most common haemoprotozoan infection in canines of South India. Low parasitaemia either in early or late infection is a big hurdle in the diagnosis of canine babesiosis. The present study aimed to differentiate the early and late B. gibsoni infections in dogs using IgM/IgG ELISA based on recombinant thrombospondin-related adhesive protein (BgTRAP). The N-terminal BgTRAP gene was cloned into pET32a, expressed in BL21 Escherichia coli cells, and purified to get the recombinant protein. Using the recombinant antigen, IgM ELISA detected anti-B. gibsoni IgM antibodies in 73 out of 130 samples (56.15 per cent) while the IgG ELISA detected IgG antibodies in 77 out of 130 samples (59.23 per cent). Polymerase chain reaction of the 130 samples targeting the BgTRAP gene revealed 73.07 % positivity. When compared with the PCR, the sensitivity and a specificity of newly standardized indirect IgM ELISA were 36.54 % and 75.00 % while that of IgG ELISA were 42.31 % and 71.88 %. The accuracy, positive predictive value and negative predictive value of the IgM ELISA in comparison to PCR were 51.19 %, 70.4 %, 42.1 % while that of IgG ELISA were 53.57 %, 71.0 %, 43.4 % respectively. The area under the curve (AUC) and Youden Index in ROC curve for IgM and IgG ELISAs revealed a moderate diagnostic accuracy. The rBgTRAP antigen showed no cross-reactivity with common helminth parasites viz, Ancylostoma caninum, Dirofilaria immitis, D. repens, Spirometra spp., Toxocara canis and haemoparasites like Trypanosoma evansi, B. vogeli, Hepatozoon canis and Ehrlichia canis. The assay could clearly differentiate early (IgM) and late (IgG) infections, making it a valuable diagnostic tool for differentiating early and late infections with B. gibsoni.

媒介传播的疾病对宠物健康构成了日益严重的全球性威胁，而巴贝斯虫是南印度犬类中最常见的原虫感染。早期或晚期感染的低寄生血症是犬巴贝斯虫病诊断的一大障碍。本研究旨在利用基于重组血栓反应蛋白相关黏附蛋白（BgTRAP）的IgM/IgG酶联免疫吸附试验（ELISA）鉴别犬早期和晚期gibsoni感染。将n端BgTRAP基因克隆到pET32a中，在BL21大肠杆菌细胞中表达，纯化得到重组蛋白。采用重组抗原，IgM ELISA检测抗- b。130份样本中有73份（56.15%）检测到gibsoni IgM抗体，IgG ELISA检测到77份（59.23%）IgG抗体。130份BgTRAP基因的聚合酶链反应阳性率为73.07%。与PCR比较，新标准化IgM间接ELISA检测的灵敏度和特异性分别为36.54%和75.00%，IgG ELISA检测的灵敏度和特异性分别为42.31%和71.88%。IgM ELISA与PCR的准确率、阳性预测值、阴性预测值分别为51.19%、70.4%、42.1%，IgG ELISA的准确率分别为53.57%、71.0%、43.4%。IgM和IgG elisa的曲线下面积（AUC）和ROC曲线上的约登指数显示出中等的诊断准确性。rBgTRAP抗原与常见寄生虫如犬钩虫、免疫dirofilia、repens、螺虫、犬弓形虫和伊文氏锥虫、沃氏巴贝虫、犬肝虫、犬埃利希体等无交叉反应性。该方法可明确区分早期（IgM）和晚期（IgG）感染，是区分早期和晚期感染的有价值的诊断工具。

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引用次数: 0

Phytochemical-based discovery of a potent antimalarial candidate targeting PfPI4K: A hybrid structure-based and deep learning approach 基于植物化学的有效抗疟疾候选药物PfPI4K靶向的发现：基于结构和深度学习的混合方法。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109064

Sibasish Sarangi, Rajani Kanta Mahapatra

Malaria is a parasitic infection that poses a threat to life and continues to be a serious challenge to global health. The recent COVID-19 pandemic has further escalated the situation. The emergence of artemisinin partial resistance and insecticide resistance emphasizes the critical need for novel antimalarial drug targets and agents with alternative mechanisms of action. This study focuses on Plasmodium falciparum phosphatidylinositol 4-kinase (PfPI4K), a phosphoinositide lipid kinase essential for membrane trafficking and biogenesis across multiple stages of the Plasmodium life cycle. We investigated a dataset of 58 natural anthraquinones with reported antimalarial activity as potential PfPI4K inhibitors. Employing Modeller 10.5 for homology modeling, we constructed the PfPI4K structure, validated by quality testing parameters. Subsequent in silico screening identified potential drug candidates. The top-scoring inhibitors were investigated by ADMET analysis. The compound AD37 (6′-O-methyl-knipholone) was identified as a prominent candidate. It complied with Lipinski's rule of five, displayed favorable ADMET parameters, and reported the highest binding affinity of −5.983 kcal/mol to PfPI4K as determined by GLIDE analysis. The stability and molecular interactions of the PfPI4K-AD37 complex were further confirmed by a 100 ns molecular dynamics simulation employing GROMACS. This investigation identifies AD37 as a promising drug candidate for treating malaria and provides valuable information regarding the molecular interactions essential for the future design and development of antimalarial drugs.

疟疾是一种寄生虫感染，对生命构成威胁，并继续对全球健康构成严重挑战。最近的COVID-19大流行使局势进一步升级。青蒿素部分耐药和杀虫剂耐药的出现强调了迫切需要具有替代作用机制的新型抗疟药物靶点和制剂。本研究的重点是恶性疟原虫磷脂酰肌醇4-激酶（PfPI4K），这是一种磷脂酰肌醇脂激酶，对疟原虫生命周期多个阶段的膜运输和生物发生至关重要。我们调查了58种天然蒽醌类药物的数据集，这些药物被报道为潜在的PfPI4K抑制剂，具有抗疟疾活性。采用modelmodel10.5进行同源性建模，构建了PfPI4K结构，并通过质量测试参数进行了验证。随后的计算机筛选确定了潜在的候选药物。通过ADMET分析对得分最高的抑制剂进行了研究。化合物AD37（6′-O-methyl-knipholone）被认为是一个突出的候选化合物。它符合Lipinski的五法则，具有良好的ADMET参数，经GLIDE分析，对PfPI4K的结合亲和力最高，为-5.983 kcal/mol。采用GROMACS进行100 ns分子动力学模拟，进一步证实了PfPI4K-AD37复合物的稳定性和分子相互作用。这项研究确定了AD37作为治疗疟疾的有前途的候选药物，并为未来抗疟疾药物的设计和开发提供了重要的分子相互作用信息。

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引用次数: 0

Therapeutic potential of spiramycin-nanoparticles and Aluvia in experimental congenital toxoplasmosis 螺旋霉素纳米颗粒和Aluvia治疗实验性先天性弓形虫病的潜力。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109069

Yasmen Elsayed , Amal Farahat Allam , Amel Youssef Shehab , Naglaa Fathi Abd El-Latif , Shaimaa Makled , Nermine Mogahed Fawzy Hussein Mogahed

This study aimed to evaluate the efficacy of spiramycin, spiramycin-loaded chitosan nanoparticles (CSNPs) and Aluvia for the treatment of congenital toxoplasmosis in a murine model. The study was conducted on 60 pregnant Swiss albino mice, 30 controls and 30 experimental. After performing a pilot study, mice were injected subcutaneously with the virulent Toxoplasma gondii RH strain (30 tachyzoites/mouse) on day 15 of pregnancy (3rd gestation period). The drugs were evaluated based on pregnancy outcomes (number of mice with live birth, stillbirth and abortion), number of live offspring, live pups' weight and congenital anomalies. Histopathological changes in the offspring's brain were studied. Regarding pregnancy outcomes, all mice in the non-infected control group delivered live offspring. T. gondii infection significantly decreased the live birth rate, while treatment with spiramycin, spiramycin-loaded CSNPs, and Aluvia improved pregnancy outcomes without statistical significance compared to the non-infected control. The highest number of offspring was observed in the normal non-infected control subgroup (94 pups/10 mice). Among the treated groups, spiramycin-loaded CSNPs resulted in the highest offspring count (46 pups/10 mice) and ranked first in mean pups weight, followed by Aluvia. Congenital anomalies were observed among the offspring of both infected untreated and infected treated mothers. Offspring brain tissues revealed substantial histopathological improvement in the spiramycin-loaded CSNPs and Aluvia-treated groups. In conclusion, spiramycin-loaded CSNPs and Aluvia demonstrated low parasite burden and successfully restored normal brain architecture in the offspring. However, congenital anomalies persisted and remained a significant concern.

本研究旨在评价螺旋霉素、螺旋霉素负载壳聚糖纳米颗粒（csnp）和Aluvia治疗小鼠先天性弓形虫病的疗效。研究对象为60只怀孕的瑞士白化病小鼠、30只对照小鼠和30只实验小鼠。在进行初步研究后，小鼠在妊娠第15天（第三妊娠期）皮下注射毒性强的弓形虫RH株（30个速殖子/只）。根据妊娠结局（活产鼠数、死产鼠数、流产鼠数）、活仔鼠数、活仔鼠体重和先天性异常情况对药物进行评估。研究了后代大脑的组织病理学变化。关于妊娠结局，未感染对照组的所有小鼠都产下了活的后代。弓形虫感染显著降低了活产率，而螺旋霉素、螺旋霉素负载csnp和Aluvia治疗改善了妊娠结局，但与未感染的对照组相比，无统计学意义。正常未感染对照组的子代数量最多（94只/10只）。在处理组中，携带螺旋霉素的csnp导致最高的后代数量（46只/10只小鼠），平均幼崽体重排名第一，其次是Aluvia。在感染未治疗和感染治疗的母亲的后代中都观察到先天性异常。在螺旋霉素加载csnp和aluvia处理组中，后代脑组织显示出实质性的组织病理学改善。综上所述，携带螺旋霉素的csnp和Aluvia表现出较低的寄生虫负担，并成功地恢复了后代正常的大脑结构。然而，先天性异常持续存在，仍然值得关注。

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引用次数: 0

Axenic culture of Entamoeba histolytica alters its ability to interact with pathogenic bacteria and leads to loss of virulence and pathogenicity 溶组织内阿米巴的无菌培养改变了其与致病菌相互作用的能力，并导致毒性和致病性的丧失

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.exppara.2025.109072

Fabrício Marcus Silva Oliveira , Sávio Henrique de Cicco Sandes , Mario Abatemarco Junior , Elisabeth Neumann , Álvaro Cantini Nunes , Maria Aparecida Gomes , Marcelo Vidigal Caliari

Entamoeba histolytica is an anaerobic eukaryotic protozoan capable of infecting humans and causing amoebiasis, a disease responsible for approximately 50 million cases and an estimated 100,000 deaths annually worldwide. The virulence of Entamoeba histolytica trophozoites and their ability to cause amoebic colitis and hepatic abscesses in the host involve various molecules, such as a specific lectin that recognizes galactose and N-acetylgalactosamine residues, cysteine proteinases, and amoebapores. To determine whether axenization of the Entamoeba histolytica strain affects its ability to interact with and respond to the presence of other microorganisms, we cultured trophozoites of an Entamoeba histolytica EGG strain in both xenic and axenic media. We then associated them with Salmonella typhimurium and evaluated the expression of virulence factors by real-time PCR. Subsequently, we infected rats to assess whether the Enatmoeba histolytica EGG strain cultured under xenic and axenic conditions exhibited differences in pathogenicity. This study showed that the absence of bacterial microbiota in axenic culture led to a reduced capacity to produce virulence factors in vitro, even when stimulated with Salmonella typhimurium. Furthermore, in vivo analysis revealed that axenic culture altered the parasite's behavior by reducing its ability to produce intestinal lesions, even in a co-infection setting. We suggest that the expression profiles of virulence genes are influenced by continuous environmental stress and that the presence of microbiota in xenic cultures of Enatmoeba histolytica contributes to such stress and supports the maintenance of virulence gene expression.

溶组织内阿米巴原虫是一种厌氧真核原生动物，能够感染人类并引起阿米巴病，阿米巴病每年在全世界造成约5000万例病例和估计10万人死亡。溶组织内阿米巴滋养体的毒力及其在宿主中引起阿米巴结肠炎和肝脓肿的能力涉及各种分子，如识别半乳糖和n -乙酰半乳糖胺残基的特定凝集素、半胱氨酸蛋白酶和阿米巴孢子。为了确定溶组织内阿米巴菌株的无菌化是否会影响其与其他微生物相互作用和反应的能力，我们在xenic和xenic培养基中培养了溶组织内阿米巴卵细胞菌株的滋养体。然后，我们将它们与鼠伤寒沙门菌联系起来，并通过实时PCR评估毒力因子的表达。随后，我们感染了大鼠，以评估在无菌和无菌条件下培养的溶组织肠内巴卵细胞菌株是否具有不同的致病性。这项研究表明，无菌培养中细菌微生物群的缺乏导致体外产生毒力因子的能力降低，即使用鼠伤寒沙门菌刺激也是如此。此外，体内分析显示，即使在共同感染环境中，无菌培养也会通过降低其产生肠道病变的能力来改变寄生虫的行为。我们认为，毒力基因的表达谱受到持续环境胁迫的影响，而溶组织肠杆菌异种培养中微生物群的存在有助于这种胁迫，并支持毒力基因表达的维持。

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