Molecular and biochemical parasitology最新文献

LinfCul1 interaction with LinfSkp1 affects different cellular processes in Leishmania infantum LinfCul1与LinfSkp1的相互作用影响幼年利什曼原虫的不同细胞过程。

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-12-08 DOI: 10.1016/j.molbiopara.2025.111712

Ellen Gomes , Camila Rolemberg Santana Travaglini Berti de Correia , Caroline Torres , Mariele Cristina de Carvalho , Taissa de Oliveira de Castro , Wesley Klaysson Pereira Regatieri , Nayore Tamie Takamiya , Luana Aparecida Rogerio , Adriano Cappellazzo Coelho , Juliana Ide Aoki , Sandra Regina Maruyama , Felipe Roberti Teixeira

LinfCul1 is a key component of the E3 ubiquitin ligase complex (LinfCRL1) in Leishmania infantum, which interacts with LinfSkp1 and LinfRbx1 at the N- and C-termini, respectively. To investigate the role of LinfCul1 in parasite proliferation, rosette formation, and macrophage infection, we generated a mutant LinfCul1 (mLinfCUL1) lacking the LinfSkp1 interaction region. Co-immunoprecipitation assays confirmed that mLinfCul1 exhibited reduced interaction with LinfSkp1, thereby disrupting LinfCRL1 function. Functional assays demonstrated that LinfCUL1 knockout (∆cul1) led to impaired proliferation and enhanced rosette formation, both of which were rescued by LinfCUL1 WT but not by mLinfCUL1 expression, confirming the requirement of the LinfCul1-LinfSkp1 interaction for these processes. Additionally, macrophage infection assays revealed that ∆cul1 parasites exhibited reduced infectivity and amastigote proliferation, which was restored upon LinfCUL1 WT expression in the parasites. Interestingly, mLinfCUL1 exhibited a lower infectivity index than ∆cul1, suggesting that LinfCul1 functions as a LinfCRL1 component that contributes to this process. These findings highlight the essential role of LinfCul1 in parasite proliferation and infectivity and reinforce its canonical function in ubiquitination-dependent parasite biology. Moreover, this study provides valuable insights into the molecular mechanisms governing parasite development and host interactions, thereby contributing to a better understanding of Leishmania infantum biology.

LinfCul1是婴儿利什曼原虫E3泛素连接酶复合物（LinfCRL1）的关键组分，它分别在N端和c端与LinfSkp1和LinfRbx1相互作用。为了研究LinfCul1在寄生虫增殖、莲座形成和巨噬细胞感染中的作用，我们产生了一个缺乏LinfSkp1相互作用区域的突变体LinfCul1 （mLinfCUL1）。共免疫沉淀实验证实，mLinfCul1与LinfSkp1的相互作用减少，从而破坏了LinfCRL1的功能。功能分析表明，敲除LinfCUL1（∆cul1）导致细胞增殖受损和花环形成增强，而这两种情况都是由LinfCUL1 WT而不是mLinfCUL1的表达所恢复的，这证实了LinfCUL1 - linfskp1相互作用对这些过程的要求。此外，巨噬细胞感染实验显示，∆cul1寄生虫的传染性和无马鞭毛体增殖能力降低，在疟原虫中表达LinfCUL1 WT后，无马鞭毛体增殖能力恢复。有趣的是，mLinfCUL1的感染指数低于∆cul1，这表明LinfCul1作为LinfCRL1的一个成分参与了这一过程。这些发现强调了LinfCul1在寄生虫增殖和感染中的重要作用，并加强了其在泛素化依赖性寄生虫生物学中的典型功能。此外，该研究为寄生虫发育和宿主相互作用的分子机制提供了有价值的见解，从而有助于更好地理解婴儿利什曼原虫生物学。

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引用次数: 0

The efficacy and accuracy of ribosomal RNA depletion methods in the parasitic nematode Strongyloides ratti 核糖体RNA耗散法在寄生线虫中的有效性和准确性

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-12-06 DOI: 10.1016/j.molbiopara.2025.111719

Mohammed Ahmed , Charmaine Bishop , Andrea Betancourt , Vicky Hunt , Mark Viney

The depletion of ribosomal RNA (rRNA) is a critical step in RNA-sequence analyses, used to enhance the detection of non-rRNA molecules, such as messenger RNAs and non-coding RNAs. However, the efficiency and potential biases introduced by different rRNA depletion methods remain poorly characterized. Here, we evaluated three commercially available rRNA depletion kits – QIAseq FastSelect, riboPOOL, Zymo-Seq RiboFree – for their performance with the parasitic nematode Strongyloides ratti. We assessed the kits’ efficiency in rRNA removal, the recovery of expressed genes and transposable elements, and the detection of spliced leader sequences and genes’ operonic organization. Zymo-Seq demonstrated the highest sensitivity and minimal bias in a measure of gene expression, while QIAseq showed the least rRNA depletion and significant differential expression biases. Our findings underscore the importance of empirical validation of rRNA depletion methods, particularly for parasites and non-model organisms, and we suggest that Zymo-Seq as the optimal choice for S. ratti and related nematodes.

核糖体RNA （rRNA）的损耗是RNA序列分析的关键步骤，用于增强对非rRNA分子的检测，如信使RNA和非编码RNA。然而，不同的rRNA消耗方法所带来的效率和潜在的偏差仍然没有得到很好的描述。在这里，我们评估了三种市售的rRNA消耗试剂盒- QIAseq FastSelect， riboPOOL， zymoseq RiboFree -它们对寄生线虫圆形线虫的性能。我们评估了该试剂盒在去除rRNA、恢复表达基因和转座元件、检测剪接的先导序列和基因的操纵子组织方面的效率。在基因表达的测量中，Zymo-Seq显示出最高的灵敏度和最小的偏差，而QIAseq显示出最小的rRNA缺失和显著的差异表达偏差。我们的研究结果强调了rRNA消耗方法的经验验证的重要性，特别是对于寄生虫和非模式生物，我们认为Zymo-Seq是S. ratti和相关线虫的最佳选择。

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引用次数: 0

Green-synthesised ZnO-Ag-CuO nanocomposites from Thymus vulgaris and their in vitro anticoccidial activity 绿色合成普通胸腺ZnO-Ag-CuO纳米复合材料及其体外抗球虫活性

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.molbiopara.2025.111711

Raghda R. Qadir , Hamin J. Mohammed , Samir M. Hamad , Yousef Mirzaei , Mukhtar H. Ahmed

Background

Coccidiosis is a significant parasitic disease affecting poultry, resulting in substantial economic losses due to its impact on growth, increased mortality, and compromised bird health.

Aim

This study aimed to evaluate the in vitro anticoccidial effects of a novel green-synthesised ZnO-Ag-CuO nanocomposite, using Thymus vulgaris extract.

Methods

The nanocomposite was synthesised through an eco-friendly method employing T. vulgaris as a stabilising and reducing agent. Characterisation was performed using UV-Vis spectroscopy, FTIR, XRD, SEM, and EDX, confirming its high crystallinity, nanoscale size, and the successful integration of ZnO, Ag, and CuO phases. Anticoccidial activity was assessed via a sporulation inhibition assay against Eimeria spp. Oocysts isolated from broiler chickens.

Results

The nanocomposite significantly reduced oocyst sporulation and increased the proportion of damaged and unpopulated oocysts in a dose-dependent manner ‎(0.1–1 mg/mL) (p < 0.0001). ZnO–Ag–CuO NCs showed a dose-dependent anticoccidial effect, reducing sporulated oocysts to 56.41 %, 33.63 % and 22.9 % at 0.1, 0.5 and 1.0 mg/mL (control 88.62 %; p < 0.0001). Unsporulated oocysts increased to 15.9–62.22 % (control 13.33 %), while damaged oocysts reached up to 14.82 % (control 0 %).

Conclusion

The green-synthesised ZnO-Ag-CuO nanocomposite demonstrated strong in vitro anticoccidial activity; however, further studies are needed to evaluate the nanocomposite’s potential toxicity, formulation, stability under biological conditions, safety before practical applications and potential environmental impact within a One Health framework.

Future plans

In vivo studies are recommended to validate the efficacy and safety of these approaches for large-scale applications.

球虫病是一种影响家禽的重要寄生虫病，由于其对生长、死亡率增加和鸟类健康的影响，造成了巨大的经济损失。目的研究绿色合成的以麝香提取物为原料的ZnO-Ag-CuO纳米复合材料的体外抗球虫作用。方法采用生态友好的方法，以黄芪为稳定还原剂合成纳米复合材料。利用紫外可见光谱、FTIR、XRD、SEM和EDX对其进行了表征，证实了其高结晶度、纳米级尺寸以及ZnO、Ag和CuO相的成功整合。通过对肉仔鸡艾美耳球虫卵囊的抑孢试验，评价其抗球虫活性。结果纳米复合材料显著降低卵囊产孢量，增加卵囊损伤和未卵囊比例，且呈剂量依赖性（0.1-1 mg/mL）（p <； 0.0001）。ZnO-Ag-CuO NCs表现出剂量依赖性的抗球虫作用，在0.1、0.5和1.0 mg/mL时，将孢子卵囊减少56.41 %，33.63 %和22.9 %（对照88.62 %;p <； 0.0001）。无孢子卵囊增加15.9 ~ 62.22 %（对照组13.33 %），损伤卵囊增加14.82 %（对照组0 %）。结论绿色合成的ZnO-Ag-CuO纳米复合材料具有较强的体外抗球虫活性；然而，需要进一步的研究来评估纳米复合材料的潜在毒性、配方、生物条件下的稳定性、实际应用前的安全性以及在“同一个健康”框架内的潜在环境影响。未来计划建议进行体内研究，以验证这些方法大规模应用的有效性和安全性。

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引用次数: 0

MBP - Journal scope update 日志范围更新。

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-12-01 DOI: 10.1016/j.molbiopara.2025.111701

Christian Doerig, Richard McCulloch, Patrick Skelly, Geoffrey Gobert

引用次数: 0

CRISPR-Cas systems: Pioneering next-generation diagnostic tools for parasitic diseases CRISPR-Cas系统：寄生虫病的新一代诊断工具

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-27 DOI: 10.1016/j.molbiopara.2025.111708

Rupesh Verma , Giridhari Das , Manjunathachar H.V. , Nirmala Muwel , Raunak Choudhary , Suman Kumar , Subhradal Nath , Anil Gattani , Vandana Gupta , Rajesh Kumar Sharma , Y. Ajith

Parasitic diseases pose significant threats to both human and veterinary health, causing morbidity, mortality, and economic losses. Effective diagnostics are critical, yet conventional methods such as microscopy, serology, and polymerase chain reaction (PCR) are limited by low sensitivity, cross-reactivity, or dependence on costly equipment and skilled personnel. Isothermal amplification techniques, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), have improved point-of-care (POC) applications but remain limited by nonspecific amplification and reduced sensitivity for low-copy targets. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems have emerged as transformative tools in molecular diagnostics, offering high sensitivity, specificity, rapidity, and cost-effectiveness. This review presents an overview of CRISPR-Cas systems, their historical development, classification (Class 1 and Class 2, Types I–VI), molecular mechanisms, and diagnostic potential in parasitic diseases, with illustrative examples from studies published between 2017 and May 2025. Despite significant progress, CRISPR-based diagnostics face challenges such as off-target activity, dependence on nucleic acid amplification, and complex sample preparation. Future directions focus on amplification-free detection, multiplexed assay development, and integration with nanotechnology, microfluidics, smartphone-based devices, and artificial intelligence. CRISPR-Cas technologies thus represent a promising frontier in next-generation diagnostics for parasitic disease surveillance, control, and personalized healthcare in both human and veterinary health.

寄生虫病对人类和兽医健康构成重大威胁，造成发病率、死亡率和经济损失。有效的诊断是至关重要的，然而传统的方法，如显微镜、血清学和聚合酶链反应（PCR）由于灵敏度低、交叉反应性或依赖昂贵的设备和熟练的人员而受到限制。等温扩增技术，如环介导的等温扩增（LAMP）和重组酶聚合酶扩增（RPA），已经改善了护理点（POC）的应用，但仍然受到非特异性扩增和低拷贝目标灵敏度降低的限制。聚集规律间隔短回文重复序列（CRISPR）相关（Cas）系统已成为分子诊断的变革性工具，具有高灵敏度、特异性、快速和成本效益。本文综述了CRISPR-Cas系统的历史发展、分类（1类和2类，I-VI型）、分子机制以及在寄生虫病中的诊断潜力，并举例说明了2017年至2025年5月发表的研究。尽管取得了重大进展，但基于crispr的诊断仍面临着脱靶活性、对核酸扩增的依赖以及复杂的样品制备等挑战。未来的方向将集中在无扩增检测、多路分析开发以及与纳米技术、微流体、基于智能手机的设备和人工智能的集成。因此，CRISPR-Cas技术代表了人类和兽医健康中用于寄生虫病监测、控制和个性化医疗保健的下一代诊断的一个有前途的前沿。

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引用次数: 0

Potential synergistic antifungal activity of microbially synthesized silver nanoparticles and vitamin D3 against Candida albicans: vitro and Galleria mellonella model studies 微生物合成银纳米颗粒和维生素D3对白色念珠菌的潜在协同抗真菌活性：体外和mellonella模型研究

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-26 DOI: 10.1016/j.molbiopara.2025.111710

Zainab Saberi Moqaddam , Pouria Khodavandi , Alireza Khodavandi , Fahimeh Alizadeh

Candida albicans poses a serious health threat, contributing to approximately 1.5 million deaths each year. Although azole drugs have been used to manage this pathogen, their effectiveness has been compromised by the emergence of drug-resistant strains. Therefore, silver nanoparticles (nano-Ag) and vitamin D_₃ are being explored as complementary rather than direct antifungal agents. The present study aims to investigate the effects of microbially synthesized nano-Ag alone and with vitamin D₃ against fluconazole-susceptible and fluconazole-resistant C. albicans. The broth microdilution method, checkerboard microdilution assay, hyphal formation inhibition, and gene expression analysis of key virulence genes were performed on C. albicans treated with microbially synthesized nano-Ag, either alone or combined with vitamin D₃. Furthermore, the survival rate, haemocyte density, and microbial load in haemolymph were assessed in C. albicans-infected Galleria mellonella larvae after treatment with microbially synthesized nano-Ag alone and with vitamin D₃. The results demonstrated that microbially synthesized nano-Ag exhibited synergistic and additive interactions with vitamin D₃ against C. albicans. This study also revealed that the combination of microbially synthesized nano-Ag and vitamin D₃ effectively inhibited hyphal formation and significantly downregulated the expression of SAP and HWP1 genes in C. albicans. In vivo experiments further demonstrated that this combined treatment enhanced larval survival, increased haemocyte density, and reduced microbial load in the haemolymph. Taken together, these findings underscore the potential of microbially synthesized nano-Ag with vitamin D₃ as a promising synergistic treatment for C. albicans infections, particularly those resistant to fluconazole.

白色念珠菌对健康构成严重威胁，每年造成约150万人死亡。虽然已经使用了唑类药物来控制这种病原体，但由于耐药菌株的出现，它们的有效性受到了损害。因此，人们正在研究将纳米银（纳米银）和维生素D₃作为互补剂，而不是直接的抗真菌剂。本研究旨在探讨微生物合成纳米银单独和与维生素D3对氟康唑敏感和耐氟康唑白色念珠菌的影响。采用微量肉汤稀释法、棋盘格微量稀释法、菌丝形成抑制和关键毒力基因表达分析，分别用微生物合成的纳米银单独或与维生素D3联合处理白色念珠菌。此外，在单独使用微生物合成的纳米银和维生素D3处理白色念珠菌感染的mellonella幼虫后，评估其存活率、血细胞密度和血淋巴微生物负荷。结果表明，微生物合成的纳米银与维生素D3对白色念珠菌具有协同作用和加性作用。本研究还发现，微生物合成的纳米ag与维生素D3结合可有效抑制白色念珠菌菌丝的形成，并显著下调SAP和HWP1基因的表达。体内实验进一步证明，这种联合处理提高了幼虫的存活率，增加了血细胞密度，减少了血淋巴中的微生物负荷。综上所述，这些发现强调了微生物合成纳米银与维生素D3作为一种有希望的协同治疗白色念珠菌感染的潜力，特别是那些对氟康唑耐药的念珠菌。

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引用次数: 0

Proteomic analysis reveals differential responses to praziquantel in two Schistosoma mansoni strains with distinct phenotypes 蛋白质组学分析揭示了两种具有不同表型的曼氏血吸虫菌株对吡喹酮的差异反应。

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-26 DOI: 10.1016/j.molbiopara.2025.111709

Marilia Bergamini Valentini, Tiago Manuel Fernandes Mendes, Fernanda Janku Cabral, Silmara Marques Allegretti

Different Schistosoma mansoni strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomic analysis to compare two strains of S. mansoni, Belo Horizonte (SmBH) and Sergipe (SmSE), which differ in phenotypic traits and susceptibility to praziquantel (PZQ). BALB/c mice were infected and treated with a sub-curative dose of PZQ (50 mg/kg) 45 days post-infection. Male and female worms were recovered 15 days after treatment, and pooled samples were processed for trypsin digestion and mass spectrometry. Over 1000 proteins were identified. No significant differences were observed in protein expression between untreated females of the two strains. In untreated males, 16 proteins showed differential expression: 11 upregulated in SmBH, mostly related to metabolic and energy production pathways, and 5 upregulated in SmSE. PZQ exposure did not significantly alter protein expression in SmBH worms. In contrast, SmSE males showed 74 differentially expressed proteins post-treatment, with 58 upregulated, including proteins with antioxidant and antiapoptotic functions commonly associated with drug resistance. SmSE females showed upregulation of three proteins after treatment, mostly related to cytoskeletal and muscular structure, suggesting less PZQ-induced damage. These results suggest that SmSE exhibits adaptive proteomic responses to PZQ-induced oxidative stress, which may contribute to its increased survival after treatment. Our findings provide molecular insight into strain-specific responses to PZQ and highlight potential mechanisms underlying reduced drug susceptibility in S. mansoni.

不同的曼氏血吸虫株可能表现出不同的表型，这可能影响寄生虫的分布、治疗结果和控制策略。本研究采用无标记定量蛋白质组学方法，比较了两株不同表型性状和对吡喹酮（PZQ）易感性的mansoni菌株Belo Horizonte （SmBH）和Sergipe （SmSE）。BALB/c小鼠感染后45天给予亚治愈剂量的PZQ （50mg/kg）治疗。治疗15天后，回收雄性和雌性蠕虫，并收集样本进行胰蛋白酶消化和质谱分析。超过1000种蛋白质被鉴定出来。未经处理的两株雌虫蛋白表达量无显著差异。在未处理的雄性中，16个蛋白出现差异表达：11个在SmBH中上调，主要与代谢和能量产生途径有关，5个在SmSE中上调。PZQ暴露没有显著改变SmBH虫的蛋白表达。相比之下，SmSE雄性小鼠在处理后出现74种差异表达蛋白，其中58种上调，包括抗氧化和抗凋亡功能的蛋白，这些蛋白通常与耐药性相关。治疗后，SmSE雌性小鼠出现三种蛋白上调，主要与细胞骨骼和肌肉结构有关，提示pzq诱导的损伤较小。这些结果表明，SmSE对pzq诱导的氧化应激表现出适应性蛋白质组反应，这可能有助于提高治疗后的存活率。我们的研究结果为菌株对PZQ的特异性反应提供了分子视角，并强调了曼氏梭菌药物敏感性降低的潜在机制。

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引用次数: 0

Recent advancements in the diagnosis of parasitic diseases 寄生虫病诊断的最新进展

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-24 DOI: 10.1016/j.molbiopara.2025.111706

Sundas Afresham , Muhammad Kasib Khan , Muhammad Adnan Sabir Mughal , Muhammad Shahid Mehmood , Sultan Ali , Maryam Bashir , Zaheer Abbas , Abdullah Azeem , Waqar Ahmed , Muhammad Imran , Rao Zahid Abbas , Zia-ud-Din Sindhu , Muhammad Sohail Sajid

Parasitic infections present a significant health risk to the public, affecting millions of people, particularly in underdeveloped and developing countries. In developing countries, these infections are also responsible for causing significant economic challenges due to elevated healthcare expenditure. Accurate diagnosis and effective treatment methods are essentially required to combat this global issue. For decades, traditional diagnostic methods such as microscopy, serological testing, histopathology, and culturing have been used for the diagnosis of these parasitic infections. While these methods can be effective and helpful in many ways, they often consume a lot of time, require an elevated level of expertise, and have limited applications particularly in endemic regions having issues like poor infrastructure and limited access to healthcare facilities. This review aims to highlight the urgent need for a revolution to replace these conventional techniques with more affordable, quick, and field-adjustable tools such as rapid diagnostic tests (RDTs) and molecular methods and provides a comprehensive picture of advanced diagnostic tools used in the identification of parasites. With the advancements in science and technology, molecular methods such as Polymerase chain reaction, Next generation sequencing, and isothermal loop-mediated amplification have remarkably enhanced the sensitivity and accuracy of parasite detection and identification. The range of these diagnostic methods has further extended by advanced serological methods, imaging techniques, and immunological methods. Moreover, the innovations in nanotechnology, CRISPR-Cas methods, and multi-omics techniques for identification of parasite DNA, antigens, metabolites, and host responses are invaluable for diagnostic accuracy, comprehensive understanding of parasite biology, and for the discovery of new therapeutic targets and diagnostic biomarkers. However, further research and developments are required for an effective and long-lasting impact of these advancements.

寄生虫感染对公众构成重大健康风险，影响到数百万人，特别是在不发达国家和发展中国家。在发展中国家，由于医疗保健支出的增加，这些感染也造成了重大的经济挑战。准确的诊断和有效的治疗方法是解决这一全球性问题的关键。几十年来，传统的诊断方法，如显微镜、血清学检测、组织病理学和培养已被用于诊断这些寄生虫感染。虽然这些方法在许多方面都是有效和有益的，但它们往往耗费大量时间，需要较高水平的专业知识，而且应用有限，特别是在存在基础设施差和获得医疗保健设施的机会有限等问题的流行地区。本综述旨在强调迫切需要进行一场革命，以更经济、快速和现场可调整的工具（如快速诊断测试和分子方法）取代这些传统技术，并提供用于鉴定寄生虫的先进诊断工具的全面情况。随着科学技术的进步，聚合酶链反应、下一代测序、等温环介导扩增等分子方法显著提高了寄生虫检测鉴定的灵敏度和准确性。这些诊断方法的范围通过先进的血清学方法、成像技术和免疫学方法进一步扩展。此外，用于鉴定寄生虫DNA、抗原、代谢物和宿主反应的纳米技术、CRISPR-Cas方法和多组学技术的创新对于诊断准确性、全面了解寄生虫生物学以及发现新的治疗靶点和诊断生物标志物具有不可估量的价值。然而，要使这些进步产生有效和持久的影响，还需要进一步的研究和发展。

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引用次数: 0

Can flukes cause cancer? Insight into molecular links between parasites and carcinogenesis 吸虫会致癌吗？深入了解寄生虫与致癌之间的分子联系。

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-24 DOI: 10.1016/j.molbiopara.2025.111707

Maria Paluch, Maja Cudzik, Aleksandra Kędra, Martyna Olszyna, Agata Dziura, Paulina Jaskulska, Grzegorz Król, Wioleta Kondziołka

Cancer deaths are increasing year by year worldwide. Many factors contribute to the development of cancer, including genetic and epigenetic factors, as well as environmental factors such as diet, physical activity, stimulants (tobacco, alcohol), exposure to excessive UV radiation, stress, and infections. In recent years, many studies have shown a strong correlation between parasitic infections and the oncogenic process leading to the development of human cancers. Studies indicate an association between progressive inflammation, risk of infection, or bacterial/viral co-infection during parasitosis and oncogenesis. This article discusses six species of flukes listed by the International Agency for Research on Cancer (Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Opisthorchis viverrini, Clonorchis sinensis, and Opisthorchis felineus) for their carcinogenic potential, biology, and epidemiology. Particular attention was paid to the molecular mechanisms that are altered during fluke invasion, which ultimately lead to the development of neoplastic lesions in humans and animals.

全世界癌症死亡人数逐年增加。许多因素导致癌症的发展，包括遗传和表观遗传因素，以及环境因素，如饮食、体育活动、兴奋剂（烟草、酒精）、过度暴露于紫外线辐射、压力和感染。近年来，许多研究表明，寄生虫感染与导致人类癌症发展的致癌过程之间存在很强的相关性。研究表明，在寄生虫病和肿瘤发生期间，进行性炎症、感染风险或细菌/病毒合并感染之间存在关联。本文讨论了国际癌症研究机构列出的六种吸虫（血血吸虫、日本血吸虫、曼氏血吸虫、猪腹吸虫、华支睾吸虫和猫腹吸虫）的致癌潜力、生物学和流行病学。特别关注的是在吸虫入侵过程中改变的分子机制，这最终导致人类和动物肿瘤病变的发展。

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引用次数: 0

Targeted inhibition of human Tankyrase-1 (TNKS1) by ZT-5483 exhibited anti-parasitic activity in Toxoplasma gondii: An in silico–based, high–throughput virtual screen and in vitro approach ZT-5483靶向抑制人tankyase -1 （TNKS1）对刚地弓形虫的抗寄生活性：基于硅的高通量虚拟筛选和体外方法

IF 1.5 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Molecular and biochemical parasitology

Pub Date : 2025-10-16 DOI: 10.1016/j.molbiopara.2025.111705

Yasser Alraey

Background and Aim

Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the Toxoplasma gondii parasite. Given the serious side effects and recurrence of resistance, there is an unmet need to develop effective novel drugs with low toxicity against T. gondii. This study aims to identify novel anti-parasitic compounds targeting human Tankyrase-1 involved in T. gondii infection using bioinformatics and in vitro approaches.

Methods

For lead identification, high-throughput virtual screening (HTVS) against the ChemBridge library was followed by Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques. Human TNKS1 (PARP5A) colorimetric assay was performed. The RH-2F strain of T. gondii tachyzoites that expressed beta-galactosidase was maintained in the human foreskin fibroblasts (HFFs) to determine the parasite growth-inhibitory efficacy of the lead candidate. MTT assay was used to detect the inhibition rate on host cell viability.

Results

HTVS identified ZT-5483 with favorable binding affinities of 8.8 kcal/mol towards TNKS1. Molecular dynamic simulations demonstrated stable binding interactions for ZT-5483 and TNKS1 with Root Mean Square Deviation values around 0.04 nm. The ΔG binding calculation was −43.09 kcal/mol, favoring sturdy binding. ADME analysis supported favorable small-molecule characteristics. ZT-5483 dose responsively inhibited TNKS1 activity with an IC₅₀ value of 140.8 nM. ZT-5483 suppressed the parasite growth with an IC₅₀ value of 297.8 nM. The compound's cytotoxicity to HFF host cells (TD₅₀ value) was determined to be 3354 nM. The in vitro toxicity index (TI) of ZT-5483 was 11.26 based on the IC₅₀ and TD₅₀ values.

Conclusion

Together, these ﬁndings suggest that ZT-5483 could be a potential novel candidate against T. gondii. However, further preclinical and pharmacological evaluations are warranted.

背景和目的：弓形虫病被认为是食源性疾病导致死亡的主要原因之一。这种疾病是由弓形虫寄生虫感染引起的。鉴于弓形虫的严重副作用和耐药复发，开发有效的低毒新型药物的需求尚未得到满足。本研究的目的是利用生物信息学和体外方法，鉴定新的抗寄生虫化合物，靶向与弓形虫感染有关的人tankyase -1。方法：针对ChemBridge文库进行高通量虚拟筛选（HTVS），然后使用蛋白质-配体相互作用谱仪（Protein-Ligand Interaction Profiler）、GROMACS和GMX_MMPBSA技术进行先导物鉴定。进行人TNKS1 （PARP5A）比色测定。在人包皮成纤维细胞（HFFs）中维持表达β -半乳糖苷酶的RH-2F株刚地弓形虫速殖子，以确定主要候选物的寄生虫生长抑制效果。采用MTT法检测对宿主细胞活力的抑制率。结果：HTVS鉴定出ZT-5483对TNKS1具有8.8kcal/mol的良好结合亲和力。分子动力学模拟表明，ZT-5483与TNKS1的结合相互作用稳定，均方根偏差约为0.04nm。ΔG结合计算值为-43.09kcal/mol，有利于牢固结合。ADME分析支持有利的小分子特性。ZT-5483剂量对TNKS1活性有应答性抑制作用，IC50值为140.8nM。ZT-5483抑制寄生虫生长，IC50值为297.8nM。测定化合物对HFF宿主细胞的细胞毒性（TD50值）为3354nM。根据IC50和TD50计算，ZT-5483的体外毒性指数（TI）为11.26。结论：这些发现提示ZT-5483可能是抗弓形虫的新候选基因。然而，进一步的临床前和药理学评估是必要的。

{"title":"Targeted inhibition of human Tankyrase-1 (TNKS1) by ZT-5483 exhibited anti-parasitic activity in Toxoplasma gondii: An in silico–based, high–throughput virtual screen and in vitro approach","authors":"Yasser Alraey","doi":"10.1016/j.molbiopara.2025.111705","DOIUrl":"10.1016/j.molbiopara.2025.111705","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the <em>Toxoplasma gondii</em> parasite. Given the serious side effects and recurrence of resistance, there is an unmet need to develop effective novel drugs with low toxicity against <em>T. gondii.</em> This study aims to identify novel anti-parasitic compounds targeting human Tankyrase-1 involved in <em>T. gondii</em> infection using bioinformatics and <em>in vitro</em> approaches.</div></div><div><h3>Methods</h3><div>For lead identification, high-throughput virtual screening (HTVS) against the ChemBridge library was followed by Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques. Human TNKS1 (PARP5A) colorimetric assay was performed. The RH-2F strain of <em>T. gondii</em> tachyzoites that expressed beta-galactosidase was maintained in the human foreskin fibroblasts (HFFs) to determine the parasite growth-inhibitory efficacy of the lead candidate. MTT assay was used to detect the inhibition rate on host cell viability.</div></div><div><h3>Results</h3><div>HTVS identified ZT-5483 with favorable binding affinities of 8.8 kcal/mol towards TNKS1. Molecular dynamic simulations demonstrated stable binding interactions for ZT-5483 and TNKS1 with Root Mean Square Deviation values around 0.04 nm. The ΔG binding calculation was −43.09 kcal/mol, favoring sturdy binding. ADME analysis supported favorable small-molecule characteristics. ZT-5483 dose responsively inhibited TNKS1 activity with an IC<sub>50</sub> value of 140.8 nM. ZT-5483 suppressed the parasite growth with an IC<sub>50</sub> value of 297.8 nM. The compound's cytotoxicity to HFF host cells (TD<sub>50</sub> value) was determined to be 3354 nM. The <em>in vitro</em> toxicity index (TI) of ZT-5483 was 11.26 based on the IC<sub>50</sub> and TD<sub>50</sub> values.</div></div><div><h3>Conclusion</h3><div>Together, these ﬁndings suggest that ZT-5483 could be a potential novel candidate against <em>T. gondii</em>. However, further preclinical and pharmacological evaluations are warranted.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111705"},"PeriodicalIF":1.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

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