Experimental parasitology最新文献_第3页

Cyanobacterial secondary metabolites as biocontrol agents: Targeting dengue vector larvae through histological and molecular pathways 蓝藻次级代谢物作为生物防治剂：通过组织学和分子途径靶向登革热媒介幼虫。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-11-05 DOI: 10.1016/j.exppara.2025.109051

Sanjana Vuppula , Dhanraj Ganapathy , Prabhalakshmi Balasubramaniyan , Anahas Perianaika Matharasi Antonyraj

The increasing resistance of Aedes aegypti to conventional insecticides necessitates the development of eco-friendly alternatives. This study investigates the larvicidal efficacy of Lyngbya sp. SMC 069 extracts, particularly focusing on fatty acid-rich chloroform fractions. Among the solvents tested, the chloroform extract showed the highest activity with 90.58 % mortality at 500 ppm against third-instar larvae. Column chromatography yielded a fast-eluting fraction (FR) with superior potency achieving 98.21 % mortality at 50 ppm and an LC₅₀ of 22.3 ppm. FT-IR analysis confirmed the presence of alkane, alkene, and ester functional groups, while GC-MS identified oleic acid derivatives as major constituents. Histopathological analysis revealed disruption of the larval midgut and cuticle. Molecular docking revealed that oleic acid binds strongly to larval targets, including fatty acid-binding protein (−6.6 kcal/mol) and acetylcholinesterase (−5.6 kcal/mol), suggesting dual mechanisms of metabolic disruption and neurotoxicity. These research findings demonstrate the potential of Lyngbya-derived fatty acids as sustainable larvicides. The bioactive fraction's efficacy at low concentrations supports its candidacy for inclusion in integrated mosquito management programs aimed at mitigating vector-borne diseases like dengue. This research advances SDG 3 (Good Health and Well-Being) by providing a sustainable biological alternative for reducing dengue transmission risk.

埃及伊蚊对常规杀虫剂的抗药性日益增强，因此有必要开发环保替代品。本研究考察了枸杞SMC 069提取物的杀幼虫效果，特别是对富含脂肪酸的氯仿部分进行了研究。其中，氯仿提取物在500 ppm浓度下对3龄幼虫的死亡率最高，达到90.58%。柱层析产生了高效的快速洗脱部分（FR），在50 ppm时达到98.21%的死亡率，LC50为22.3 ppm。FT-IR分析证实了烷烃、烯烃和酯官能团的存在，而GC-MS鉴定了油酸衍生物是主要成分。组织病理学分析显示幼虫中肠和角质层破裂。分子对接发现，油酸与幼虫靶蛋白（-6.6 kcal/mol）和乙酰胆碱酯酶（-5.6 kcal/mol）结合较强，提示油酸具有代谢紊乱和神经毒性的双重机制。这些研究结果证明了林子脂肪酸作为可持续杀幼虫剂的潜力。该生物活性组分在低浓度下的功效支持其被纳入旨在减轻登革热等媒介传播疾病的综合蚊子管理计划。

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引用次数: 0

Isolation of Bacillus altitudinis A7 from Eimeria-immunized chickens and its inhibitory effect on Eimeria tenella 艾美耳球虫免疫鸡中高原芽孢杆菌A7的分离及其对艾美耳球虫的抑制作用。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-11-12 DOI: 10.1016/j.exppara.2025.109048

Zhongchuang Wang , Peiyao Shang , Man Lei , Wenjie Zhang , Ruiting Zhang , Qiping Zhao , Shunhai Zhu , Hongyu Han , Hui Dong , Lili Hao , Xingju Song

Eimeria spp. are responsible for chicken coccidiosis, the most important enteric protozoan disease in poultry, resulting in significant economic losses for the poultry industry. With the prohibition of antibiotic use in animal husbandry, researchers must find alternative preventive agents. The objective of this study was to isolate Bacillus strains and evaluate the anti-Eimeria tenella effects of B. altitudinis A7. In total, four Bacillus strains (A1, A5, A6, and A7) were isolated from the fresh feces of E. tenella-immunized chickens, and three Bacillus species, B. pumilus T246 (A1), B. altitudinis 41KF2b (A5 and A7), and B. cereus NS26 (A6), were identified with morphological and molecular methods. The consumption of B. altitudinis A7 by chickens significantly reduced oocyst production and the cecal lesion score after infection with E. tenella and significantly increased the expression of tight-junction proteins, interleukin-8 (IL-8), interleukin-10 (IL-10), and superoxide dismutase 1 (SOD1) relative to those in the E. tenella-infected, non-B. altitudinis A7-fed group (CON). B. altitudinis A7 also significantly increased the relative abundances of Pediococcus, Fournierella, Clostridium sensu stricto 1, CAG:352, and Tuzzerella compared with those in both the CON group and the normal control (N) group. These findings indicate that B. altitudinis A7 isolated from the feces of E. tenella-immunized chickens promoted host resistance to E. tenella.

鸡球虫病是禽类中最重要的肠道原生动物疾病，艾美耳球虫引起鸡球虫病，给家禽业造成重大经济损失。由于禁止在畜牧业中使用抗生素，研究人员必须找到替代的预防剂。本研究的目的是分离芽孢杆菌菌株，并评价高原芽孢杆菌A7抗柔嫩艾美耳球虫的作用。从鸡鲜粪中分离到4株芽孢杆菌（A1、A5、A6、A7），并通过形态学和分子方法鉴定出细小芽孢杆菌T246 （A1）、高原芽孢杆菌41KF2b （A5、A7）和蜡样芽孢杆菌NS26 （A6）。食用高原白僵菌A7后，鸡的卵囊产量显著降低，盲肠病变评分显著降低，紧密连接蛋白、白细胞介素-8 （IL-8）、白细胞介素-10 （IL-10）和超氧化物歧化酶1 （SOD1）的表达显著高于未感染高原白僵菌的鸡。高原a7饲喂组（CON）。与CON组和正常对照(N)组相比，B. altitudinis A7也显著提高了Pediococcus、Fournierella、Clostridium sensu stricto 1、CAG:352和Tuzzerella的相对丰度。上述结果表明，从免疫的鸡粪便中分离出的高原芽胞杆菌A7可促进宿主对腱戎杆菌的抗性。

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引用次数: 0

Species diversity, benzimidazole resistance, and phytochemical synergy in gastrointestinal nematode nemabiomes from sheep farms in Portugal 葡萄牙绵羊农场胃肠道线虫的物种多样性、苯并咪唑抗性和植物化学协同作用。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-11-05 DOI: 10.1016/j.exppara.2025.109058

Natália Faria Campbell , Helga Waap , Helder Cortes

Anthelmintic resistance in gastrointestinal nematodes (GINs) threatens small ruminant production. This study assessed ovicidal activity of eight natural aromatic phytochemicals and interactions with synthetic benzimidazoles (BZs: albendazole [ABZ], thiabendazole [TBZ]) against nemabiome eggs of 14 BZ-resistant sheep farms across Trás-os-Montes, Beira Interior, Estremadura, and Alentejo regions of Portugal. Trans-cinnamaldehyde (TCL), octyl gallate (OGA), carvacrol (CRV), thymol (THY), and salicylaldehyde (SAL) achieved >90 % egg hatch inhibition (EHI) at 250 μg/mL in egg hatch tests (EHTs), unlike trans-cinnamic acid, gentisic acid, and curcumin (<90 % EHI). Effective concentrations (EC₁₀–EC₉₀) were determined for each compound against farm nemabiomes. TCL (EC₉₀ ≈ 27.0 μg/mL) and OGA (≈54.1 μg/mL) showed highest ovicidal efficacy, followed by CRV (≈120.3 μg/mL), THY (≈171.3 μg/mL), and SAL (≈155.2 μg/mL), requiring 25–220-fold higher concentrations than BZs. EC₁₀–EC₇₅ concentrations in checkerboard assays determined fractional inhibitory concentration indices (FICIs) to assess interactions. Compound interactions (FICI: 0.20–0.49; all ≤0.5) reduced ABZ mean EC₉₀ by 0.73 μg/mL (89.6 %) and TBZ by 0.72 μg/mL (94.7 %), with TCL and OGA showing strongest effects (FICI ≤0.25). ITS2 metabarcoding identified six GIN species, with Haemonchus contortus, Teladorsagia circumcincta, and Trichostrongylus colubriformis most prevalent. Nemabiome diversity (H': 0.09–1.17) and species prevalence showed no correlation with EHI EC₉₀ values (|r| < 0.418, p > 0.05), suggesting ovicidal efficacy or BZ-phytochemical interactions are not species-driven. Synergistic mechanisms involving aromatic phytochemical-induced eggshell damage, complementing BZ β-tubulin disruption, are discussed. BZ-phytochemical combinations offer a promising strategy for sustainable GIN control, warranting in vivo validation.

胃肠道线虫（GINs）的驱虫抗性威胁着小反刍动物的生产。本研究评估了8种天然芳香植物化学物质与合成苯并咪唑（BZs：阿苯达唑[ABZ]、噻苯达唑[TBZ]）对葡萄牙Trás-os-Montes、贝拉内河、埃斯特雷马杜拉和阿连特茹地区14个bz抗性绵羊养殖场的线虫卵的杀卵活性及其相互作用。反式肉桂醛（TCL）、没食子酸辛酯（OGA）、香芹酚（CRV）、百里香酚（THY）和水杨醛（SAL）在250 μg/mL的孵卵试验（EHTs）中，对农场nemabiomes的孵卵抑制率（EHI）达到90%，与反式肉桂酸、龙胆酸和姜黄素（10-EC90）不同。TCL （EC90≈27.0 μg/mL）和OGA（≈54.1 μg/mL）的杀卵效果最高，其次是CRV（≈120.3 μg/mL）、THY（≈171.3 μg/mL）和SAL(≈155.2 μg/mL)，所需浓度比bz高25-220倍。棋盘试验中EC10-EC75浓度测定分数抑制浓度指数（FICIs）以评估相互作用。复合相互作用（FICI: 0.20 ~ 0.49，均≤0.5）使ABZ平均EC90降低0.73 μg/mL (89.6%)， TBZ降低0.72 μg/mL(94.7%)，其中TCL和OGA作用最强（FICI≤0.25）。ITS2元条形码鉴定出6种GIN，其中以弯曲血蜱（Haemonchus contortus）、环皮绒球绦虫（Teladorsagia circulinta）和颜色毛线虫（Trichostrongylus colbriformis）最为常见。线虫组多样性（H′：0.09 ~ 1.17）和物种流行度与EHI EC90值无相关性（|r| < 0.418, p > 0.05），表明杀卵效果或bz -植物化学相互作用不是物种驱动的。讨论了芳香族植物化学诱导的蛋壳损伤的协同机制，以补充BZ β-微管蛋白的破坏。bz -植物化学组合为可持续的GIN控制提供了有前途的策略，需要在体内验证。

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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 Epub Date: 2025-11-17 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

Remodeling of liver tissue and the inflammatory profile in a dyslipidemic mice model infected with acute schistosomiasis 急性血吸虫病感染的血脂异常小鼠模型的肝组织重塑和炎症谱。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-10-31 DOI: 10.1016/j.exppara.2025.109043

Thainá de Melo , Isadora do Monte Silveira Bruno , Luciana Brandão-Bezerra , Christiane Leal Corrêa , Silvia Amaral G da Silva , Luciana Silva Rodrigues , Alba Cristina Miranda de Barros Alencar , José Roberto Machado-Silva , Renata Heisler Neves

Schistosomiasis is a neglected disease that affects millions of people in endemic areas and it is heavily influenced by changes in the host's metabolic profile. This study investigated liver tissue remodeling in acute experimental schistosomiasis and diet-induced dyslipidemia in female Swiss Webster mice. The mice were fed either a high-fat diet (HFD) or a standard diet (SD) for 29 weeks. At week 20, the animals were subcutaneously infected with 100 cercariae of Schistosoma mansoni (BH strain). After 9 weeks of infection, the mice were euthanized, and blood samples were collected for biochemical analysis. Additionally, peritoneal lavage was performed to evaluate cytokine profiles. Liver was collected, processed, and stained using Hematoxylin and Eosin, Gomori's Reticulin, and Picrosirius Red for histopathological, stereological, morphometric, and collagen granuloma analyses. Biochemical tests confirmed dyslipidemia in the HFD-fed mice. Peritoneal cells exhibited a proinflammatory immune response, and liver displayed a highly inflamed architectural morphology. Morphometric analysis of centrilobular and hepatic veins revealed that both HFD and schistosomiasis altered vessel morphology. The findings suggest that diet-induced dyslipidemia interferes with certain aspects of acute experimental schistosomiasis, contributing to immune cytokine profile remodeling by macrophages, liver disorganization, and modulation of the morphometric parameters of centrilobular and hepatic veins.

血吸虫病是一种被忽视的疾病，影响着流行地区的数百万人，它受到宿主代谢谱变化的严重影响。本研究探讨了急性实验性血吸虫病和饮食性血脂异常对雌性瑞士韦氏小鼠肝组织重塑的影响。小鼠被喂食高脂肪饮食（HFD）或标准饮食（SD） 29周。第20周皮下感染100条曼氏血吸虫尾蚴（BH株）。感染9周后，对小鼠实施安乐死，并采集血样进行生化分析。此外，进行腹膜灌洗以评估细胞因子谱。收集肝脏，用苏木精和伊红、Gomori’s Reticulin和Picrosirius Red染色，进行组织病理学、体视学、形态计量学和胶原肉芽肿分析。生物化学试验证实，饲喂hfd的小鼠存在血脂异常。腹膜细胞表现出促炎免疫反应，肝脏表现出高度炎症的建筑形态。小叶中心静脉和肝静脉的形态计量学分析显示，HFD和血吸虫病都改变了血管形态。研究结果表明，饮食诱导的血脂异常干扰了急性实验性血吸虫病的某些方面，促进了巨噬细胞的免疫细胞因子谱重塑，肝脏紊乱，以及小叶中心和肝静脉形态测量参数的调节。

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引用次数: 0

Parasitic competence of Telenomus remus: Response to age-structured and scale-protected eggs of Spodoptera frugiperda 长尾夜蛾的寄生能力：对年龄结构和有鳞片保护的夜蛾卵的反应

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.1016/j.exppara.2025.109050

Shushant Tuteja, P.S. Shera

Telenomus remus Nixon (Hymenoptera: Scelionidae) is an important egg parasitoid of Spodoptera frugiperda (J. E. Smith) (Lepidoptera: Noctuidae). Understanding the influence of host egg age and physical barriers on parasitism by T. remus is essential for optimizing its mass rearing and augmentative biological control program against this invasive pest. The aim of study was to know whether and to what extent age and presence of scales on host eggs influence the parasitism by T. remus. We investigated the parasitism potential of T. remus on 24- and 48-h-old eggs (with and without scales) of S. frugiperda. Significant differences were observed in daily and total parasitism when eggs of S. frugiperda with varying age were offered to parasitoid females. The parasitism was comparatively more on 24-h-old as compared to 48-h-old eggs. However, presence or absence of scales on the eggs had no significant impact on these parameters. There were no significant differences in adult emergence and proportion of the females in progeny (sex-ratio) from 24- and 48-h-old eggs offered to the parasitoid for parasitism. Further, the adult emergence was also not influenced by presence of scales on eggs. The present findings will help in mass rearing of this parasitoid and developing augmentative biological control programme under field conditions for this invasive pest.

膜翅目：夜蛾科)是一种重要的卵寄生蜂。了解寄主卵龄和物理屏障对夜蛾寄生的影响，对优化夜蛾的大规模饲养和加强对夜蛾的生物防治具有重要意义。本研究的目的是了解寄主卵的年龄和鳞片的存在是否以及在多大程度上影响黄颡鱼的寄生。研究了桔皮绦虫在24 h和48 h卵（带鳞和不带鳞）上的寄生潜力。不同龄期的卵对寄生雌虫的日寄生量和总寄生量有显著差异。卵龄24 h寄生率高于卵龄48 h。然而，卵上是否有鳞片对这些参数没有显著影响。24 h和48 h的卵供寄生蜂寄生，其成虫羽化率和雌虫占子代的比例（性别比）无显著差异。此外，成虫的羽化也不受卵上鳞片的影响。本研究结果将有助于该寄生蜂的大规模饲养，并在田间条件下对该入侵害虫制定增强型生物防治方案。

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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 Epub Date: 2025-11-19 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 Epub Date: 2025-11-19 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 Epub Date: 2025-11-19 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

Siglec homologs interact with membrane-bound Heat Shock Protein 70 (Hsp70) during early infection of the Schistosoma mansoni susceptible (BB02) Biomphalaria glabrata snail host Siglec同源物在曼氏血吸虫敏感型（BB02）光螺寄主早期感染过程中与膜结合热休克蛋白70 （Hsp70）相互作用。

IF 1.6 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-12-01 Epub Date: 2025-10-28 DOI: 10.1016/j.exppara.2025.109042

Eli Vanlal , Oumsalama Elhelu , Olayemi G. Fagunloye , Matty Knight

Sialic acid-binding immunoglobulin-like lectins (siglecs) are cell surface receptors involved in immune signaling. When Schistosoma mansoni infects its intermediate host, the Biomphalaria glabrata snail, early stress responses such as upregulation of heat shock protein 70 (Hsp70) are observed. We hypothesized that stress-induced Hsp70 translocates to the cell membrane and interacts with siglec homologs to modulate immune response in the snail. Utilizing in-silico approaches, we identified B. glabrata transcripts homologous to human and molluscan siglecs, followed by homology modeling and molecular docking, which predicted a salt bridge between glutamic acid 479 on Hsp70 and lysine 47 on a siglec homolog, (BgPrx), suggesting a plausible binding interface.

To validate this, we performed real-time qPCR from infected BB02 snails, revealing significant upregulation of siglec homolog transcripts shortly after infection. Additionally, protein fractionation and immunocytochemistry confirmed Hsp70 localization to the membrane post infection. These results support a model in which siglec–Hsp70 interactions dampen stress signaling and may suppress host immune defenses. Concurrently, S. mansoni employs glycan mimicry, presenting host-like sialylated structures that likely engage siglecs and further misdirect the immune response.

Together, our findings suggest that BgHsp70–siglec interactions, in combination with parasite glycan mimicry, constitute a potential immune evasion mechanism enabling schistosome establishment in susceptible B. glabrata snails.

唾液酸结合免疫球蛋白样凝集素（siglecs）是参与免疫信号传导的细胞表面受体。当曼氏血吸虫感染其中间宿主光螺时，观察到热休克蛋白70 （Hsp70）上调等早期应激反应。我们假设应激诱导的Hsp70易位到细胞膜上，并与siglec同源物相互作用以调节蜗牛的免疫反应。利用芯片技术，我们鉴定了与人类和软体动物siglecs同源的光斑拟合杆菌转录本，随后进行了同源建模和分子对接，预测了Hsp70上的谷氨酸479和siglecs同源物（BgPrx）上的赖氨酸47之间存在盐桥，表明可能存在结合界面。为了验证这一点，我们对受感染的BB02蜗牛进行了实时qPCR，发现在感染后不久siglec同源转录物显著上调。此外，蛋白分离和免疫细胞化学证实Hsp70在感染后定位于膜上。这些结果支持一个模型，其中siglec-Hsp70相互作用抑制应激信号，并可能抑制宿主免疫防御。同时，mansoni采用聚糖模仿，呈现宿主样唾液化结构，可能与siglecs结合并进一步误导免疫反应。总之，我们的研究结果表明，BgHsp70-siglec相互作用与寄生虫聚糖模仿相结合，构成了一种潜在的免疫逃避机制，使血吸虫能够在易感的光斑螺中建立。

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引用次数: 0