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Neuroprotective effects of CysLT2R antagonist on Angiostrongylus cantonensis-induced edema and meningoencephalitis CysLT2R拮抗剂对绿脓杆菌引起的水肿和脑膜脑炎的神经保护作用
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-14 DOI: 10.1016/j.molbiopara.2024.111649
Ke-Min Chen , Kuang-Ping Lan , Shih-Chan Lai

Cysteinyl leukotrienes (CysLTs) can induce a disruption of the blood–brain barrier (BBB), and this reaction is mediated by cysteinyl-leukotriene receptors. In this study, we used A. cantonensis-induced eosinophilic meningoencephalitis as a model to investigate whether the CysLT2 receptor involved in the pathogenesis of angiostrongyliasis meningoencephalitis. The present study provides evidence that the CysLT2 receptor antagonist HAMI3379 reduced the number of infiltrated eosinophils and brain edema in eosinophilic meningoencephalitis. Additionally, we found that HAMI3379 significantly decreased the protein levels of M1 polarisation markers (CD80, iNOS, IL-5 and TNF-α), increased the expression of M2 polarisation markers (CD206, IL-10 and TGF-β) both in vivo and in vitro. Matrix metalloproteinase-9, S100B, GFAP, fibronectin, and claudin-5 were markedly lower after HAMI3379 treatment. Therefore, HAMI3379 reduced the BBB dysfunction in angiostrongyliasis meningoencephalitis. We have identified microRNA-155 as a BBB dysfunction marker in eosinophilic meningoencephalitis. The results showed that microRNA-155 was 15-fold upregulated in eosinophilic meningoencephalitis and 20-fold upregulated after HAMI3379 treatment. Our results suggest that CysLT2R may be involved in A. cantonensis-induced brain edema and eosinophilic meningoencephalitis and that down-regulation of CysLT2R could be a novel and potential therapeutic strategy for the treatment of angiostrongyliasis meningoencephalitis.

半胱氨酰白三烯(CysLTs)可诱导血脑屏障(BBB)的破坏,而这种反应是由半胱氨酰白三烯受体介导的。本研究以广州嗜酸性粒细胞诱发的脑膜脑炎为模型,探讨 CysLT2 受体是否参与了血管瘤脑膜脑炎的发病机制。本研究提供的证据表明,CysLT2 受体拮抗剂 HAMI3379 能减少嗜酸性粒细胞脑膜脑炎中浸润的嗜酸性粒细胞数量和脑水肿。此外,我们还发现 HAMI3379 能显著降低体内和体外 M1 极化标志物(CD80、iNOS、IL-5 和 TNF-α)的蛋白水平,增加 M2 极化标志物(CD206、IL-10 和 TGF-β)的表达。经 HAMI3379 处理后,基质金属蛋白酶-9、S100B、GFAP、纤连蛋白和 claudin-5 的表达明显降低。因此,HAMI3379 可减轻血管瘤脑膜脑炎患者的 BBB 功能障碍。我们发现 microRNA-155 是嗜酸性粒细胞脑膜脑炎的 BBB 功能障碍标志物。结果显示,microRNA-155 在嗜酸性粒细胞脑膜脑炎中上调 15 倍,在 HAMI3379 治疗后上调 20 倍。我们的研究结果表明,CysLT2R可能参与了A.cantonensis诱导的脑水肿和嗜酸性脑膜脑炎,而下调CysLT2R可能是治疗血管软骨病脑膜脑炎的一种新的、潜在的治疗策略。
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引用次数: 0
Avirulent UG10 Entamoeba histolytica mutant derived from HM-1:IMSS strain shows limited genome variability and aberrant 5-methyl cytosine genomic distribution 源自 HM-1:IMSS 菌株的无病毒 UG10 型组织溶解性恩塔米巴虫突变体显示出有限的基因组变异性和异常的 5-甲基胞嘧啶基因组分布。
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-07-11 DOI: 10.1016/j.molbiopara.2024.111647
Naurú Idalia Vargas-Maya , Alika K. Maunakea , Fátima Berenice Ramírez-Montiel , Razvan Sultana , Rafael Peres , Quetzalli Xiadany Macías-Cervantes , Ana Laura Medina-Nieto , Ángeles Rangel-Serrano , José A. Martínez-Álvarez , Itzel Páramo-Pérez , Fernando Anaya-Velázquez , Felipe Padilla-Vaca , Bernardo Franco

Entamoeba histolytica, an intestinal parasite of global significance, poses substantial health risks with its associated high morbidity and mortality rates. Despite the current repertoire of molecular tools for the study of gene function in, the regulatory mechanisms governing its pathogenicity remain largely unexplored. This knowledge gap underscores the need to elucidate key genetic determinants orchestrating cellular functions critical to its virulence. Previously, our group generated an avirulent strain, termed UG10, with the same genetic background as the HM1:IMSS strain. UG10 strain, despite showing normal expression levels of well-known virulence factors, was unable to perform in-vitro and in-vivo activities related to amoebic virulence. In this study, we aimed to uncover the genome-wide modifications that rendered the avirulent phenotype of the UG10 strain through whole-genome sequencing. As a complementary approach, we conducted Methylated DNA Immunoprecipitation coupled with sequencing (MeDIP-seq) analysis on both the highly virulent HM1:IMSS strain and the low-virulence UG10 strain to uncover the genome-wide methylation profile. These dual methodologies revealed two aspects of the UG10 avirulent strain. One is the random integration of fragments from the ribosomal gene cluster and tRNA genes, ranging from 120 to 400 bp; and secondly, a clear, enriched methylation profile in the coding and non-coding strand relative to the start codon sequence in genes encoding small GTPases, which is associated with the previously described avirulent phenotype. This study provides the foundation to explore other genetic and epigenetic regulatory circuitries in E. histolytica and novel targets to understand the pathogenic mechanism of this parasite.

组织溶解恩塔米巴虫是一种具有全球意义的肠道寄生虫,因其相关的高发病率和高死亡率而对健康构成严重威胁。尽管目前已有一系列分子工具用于研究其基因功能,但其致病性的调控机制在很大程度上仍未得到探索。这一知识空白凸显了阐明对其毒力至关重要的细胞功能的关键基因决定因素的必要性。此前,我们的研究小组在与 HM1:IMSS 菌株相同的遗传背景下产生了一种无毒菌株,称为 UG10。尽管 UG10 菌株显示出众所周知的毒力因子的正常表达水平,但它却无法进行与阿米巴毒力相关的体外和体内活动。在本研究中,我们旨在通过全基因组测序揭示导致 UG10 株无毒表型的全基因组修饰。作为补充方法,我们对高毒力的 HM1:IMSS 菌株和低毒力的 UG10 菌株进行了甲基化 DNA 免疫沉淀结合测序(MeDIP-seq)分析,以揭示全基因组的甲基化特征。这些双重方法揭示了 UG10 无毒菌株的两个方面。其一是核糖体基因簇和 tRNA 基因片段的随机整合,范围从 120bp 到 400bp 不等;其二是编码小 GTP 酶的基因的编码链和非编码链相对于起始密码子序列有明显的富集甲基化特征,这与之前描述的无毒表型有关。这项研究为探索组织溶血性大肠杆菌的其他遗传和表观遗传调控回路以及了解这种寄生虫的致病机制的新目标奠定了基础。
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引用次数: 0
Therapeutic potential of hydantoin and thiohydantoin compounds against Schistosoma mansoni: An integrated in vitro, DNA, ultrastructural, and ADMET in silico approach 海因和硫海因化合物对曼氏血吸虫的治疗潜力:综合体外、DNA、超微结构和 ADMET 的硅学方法。
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-29 DOI: 10.1016/j.molbiopara.2024.111646
Antônio Sérgio de Almeida Júnior , Mayse Manuele Freitas Viana Leal , Diego Santa Clara Marques , Anekécia Lauro da Silva , Rafael de Souza Bezerra , Yandra Flaviana Siqueira de Souza , Maria Eduardade Mendonça Silveira , Fábio AB Santos , Luiz Carlos Alves , André de Lima Aires , Iranildo José da Cruz Filho , Maria do Carmo Alves de Lima

The study aimed to conduct in vitro biological assessments of hydantoin and thiohydantoin compounds against mature Schistosoma mansoni worms, evaluate their cytotoxic effects and predict their pharmacokinetic parameters using computational methods. The compounds showed low in vitro cytotoxicity and were not considered hemolytic. Antiparasitic activity against adult S. mansoni worms was tested with all compounds at concentrations ranging from 200 to 6.25 μM. Compounds SC01, SC02, and SC03 exhibited low activity. Compounds SC04, SC05, SC06 and SC07 caused 100 % mortality within 24 h of incubation at a concentration of 100 and 200 μM. Thiohydantoin SC04 exhibited the highest activity, resulting in 100 % mortality after 24 h of incubation at a concentration of 50 μM and IC50 of 28 µM. In the ultrastructural analysis (SEM), the compound SC04 (200 µM) induced integumentary changes, formation of integumentary blisters, and destruction of tubercles and spicules. Therefore, the SC04 compound shows promise as an antiparasitic against S. mansoni.

该研究旨在针对成熟的曼氏血吸虫虫体对海因和硫代海因化合物进行体外生物学评估,评价其细胞毒性作用,并使用计算方法预测其药代动力学参数。这些化合物的体外细胞毒性较低,且不溶血。测试了所有化合物在 200 至 6.25μM 浓度范围内对曼氏成虫的抗寄生活性。化合物 SC01、SC02 和 SC03 的活性较低。浓度为 100 和 200μM 的化合物 SC04、SC05、SC06 和 SC07 在孵育 24 小时内造成 100%的死亡。硫代海因 SC04 的活性最高,当浓度为 50μM 和 IC50 为 28μM 时,培养 24 小时后死亡率为 100%。在超微结构分析(SEM)中,SC04 复合物(200µM)可诱导皮层变化,形成皮层水泡,破坏小瘤和棘突。因此,SC04 复合物有望成为曼氏沙门氏菌的抗寄生虫药。
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引用次数: 0
Strategies for diagnosing Nosema bombycis (Microsporidia: Nosematidae); the agent of pebrine disease 诊断小孢子虫(Nosema bombycis)(微孢子虫:Nosematidae)的策略;小孢子虫病的病原体。
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-20 DOI: 10.1016/j.molbiopara.2024.111645
Masoumeh Bagheri , Shirin Dehghan , Azadeh Zahmatkesh

Pebrine disease, caused by Nosema bombycis (N. bombycis), is the most important pathogen known to the silk industry. Historical evidence from several countries shows that the outbreaks of pebrine disease have largely caused the decline of the sericulture industry. Prevention is the first line to combat pebrine as a deadly disease in silkworm; however, no effective treatment has yet been presented to treat the disease. Many different methods have been used for detection of pebrine disease agent. This review focuses on the explanation and comparison of these methods, and describes their advantages and/or disadvantages. Also, it highlights the ongoing advances in diagnostic methods for N. bombycis that could enable efforts to halt this microsporidia infection. The detection methods are categorized as microscopic, immunological and nucleic acid-based approaches, each with priorities over the other methods; however, the suitability of each method depends on the available equipment in the laboratory, the mass of infection, and the speed and sensitivity of detection. The accessibility and economic efficiency are compared as well as the speed and the sensitivity for each method. Although, the light microscopy is the most common method for detection of N. bombycis, qPCR is the most preferred method for large data based on speed and sensitivity as well as early detection ability.

由诺瑟玛蝇(Nosema bombycis,N. bombycis)引起的布氏杆菌病是蚕丝业已知的最重要的病原体。一些国家的历史证据表明,蚕豆病的爆发在很大程度上导致了养蚕业的衰落。预防是防治家蚕致命病害 pebrine 的第一道防线;然而,目前还没有治疗该病的有效方法。人们使用了许多不同的方法来检测蚕病病原体。本综述重点解释和比较了这些方法,并介绍了它们的优点和/或缺点。此外,它还重点介绍了目前在诊断 N. bombycis 方法方面取得的进展,这些进展有助于阻止这种微孢子虫感染。检测方法分为显微镜检测法、免疫学检测法和核酸检测法,每种方法都有优于其他方法的优先权;但是,每种方法的适用性取决于实验室现有的设备、感染量以及检测速度和灵敏度。我们对每种方法的可及性、经济效益以及检测速度和灵敏度进行了比较。尽管光学显微镜是检测 N. bombycis 的最常用方法,但基于速度、灵敏度和早期检测能力,qPCR 是大量数据检测的首选方法。
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引用次数: 0
Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium 吡啶嘧啶酮作为隐孢子虫钙依赖蛋白激酶 1 (CDPK1) 抑制剂的新化学类型。
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-18 DOI: 10.1016/j.molbiopara.2024.111637
Elise Waldron-Young , Wissarut Wijitrmektong , Ryan Choi , Grant R. Whitman , Matthew A. Hulverson , Raheela Charania , Aidan Keelaghan , Li Li , Songpol Srinual , Sameer Nikhar , Case W. McNamara , Melissa S. Love , Lauren Huerta , Malina A. Bakowski , Ming Hu , Wesley C. Van Voorhis , Jan R. Mead , Gregory D. Cuny

The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of Cryptosporidium parvum (Cp) CDPK1 inhibitors. Structural comparison of CpCDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based CpCDPK1 inhibitor 7 (a.k.a. UH15–16, IC50 = 10 nM), which blocked the growth of three C. parvum strains (EC50 = 12–40 nM) as well as C. hominis (EC50 = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that 7 had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, 7 demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.

原生动物蛋白激酶钙依赖性蛋白激酶 1(CDPK1)已成为治疗隐孢子虫病的潜在治疗靶标。对已知激酶抑制剂的集中筛选发现,吡啶嘧啶酮是一种新的副隐孢子虫(Cp)CDPK1抑制剂化学类型。将 CpCDPK1 与两种具有代表性的人类激酶 RIPK2 和 Src 进行结构比较后发现,两者在 αC 螺旋的位置上存在差异。k.a. UH15-16,IC50 = 10nM),它能阻断三种副猪嗜血杆菌菌株(EC50 = 12-40nM)和人嗜血杆菌(EC50 = 85nM)在 HCT-8 宿主细胞中的生长。药代动力学和组织分布分析表明,口服 7 后的全身暴露量低,但胃肠道浓度高,Caco-2 细胞渗透性好。最后,7 在 IL-12 基因敲除的急性隐孢子虫病小鼠模型中显示出部分疗效。
{"title":"Pyridopyrimidinones as a new chemotype of calcium dependent protein kinase 1 (CDPK1) inhibitors for Cryptosporidium","authors":"Elise Waldron-Young ,&nbsp;Wissarut Wijitrmektong ,&nbsp;Ryan Choi ,&nbsp;Grant R. Whitman ,&nbsp;Matthew A. Hulverson ,&nbsp;Raheela Charania ,&nbsp;Aidan Keelaghan ,&nbsp;Li Li ,&nbsp;Songpol Srinual ,&nbsp;Sameer Nikhar ,&nbsp;Case W. McNamara ,&nbsp;Melissa S. Love ,&nbsp;Lauren Huerta ,&nbsp;Malina A. Bakowski ,&nbsp;Ming Hu ,&nbsp;Wesley C. Van Voorhis ,&nbsp;Jan R. Mead ,&nbsp;Gregory D. Cuny","doi":"10.1016/j.molbiopara.2024.111637","DOIUrl":"10.1016/j.molbiopara.2024.111637","url":null,"abstract":"<div><p>The protozoan protein kinase calcium-dependent protein kinase 1 (CDPK1) has emerged as a potential therapeutic target for the treatment of cryptosporidiosis. A focused screen of known kinase inhibitors identified a pyridopyrimidinone as a new chemotype of <em>Cryptosporidium parvum</em> (<em>Cp</em>) CDPK1 inhibitors. Structural comparison of <em>Cp</em>CDPK1 to two representative human kinases, RIPK2 and Src, revealed differences in the positioning of the αC-helix that was used in the design of a potent pyridopyrimidinone-based <em>Cp</em>CDPK1 inhibitor <strong>7</strong> (a.k.a. UH15–16, IC<sub>50</sub> = 10 nM), which blocked the growth of three <em>C. parvum</em> strains (EC<sub>50</sub> = 12–40 nM) as well as <em>C. hominis</em> (EC<sub>50</sub> = 85 nM) in HCT-8 host cells. Pharmacokinetic and tissue distribution analyses indicated that <strong>7</strong> had low systemic exposure after oral administration, but high gastrointestinal concentration, as well as good Caco-2 cell permeability. Finally, <strong>7</strong> demonstrated partial efficacy in an IL-12 knock-out mouse model of acute cryptosporidiosis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"260 ","pages":"Article 111637"},"PeriodicalIF":1.4,"publicationDate":"2024-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432317","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}
引用次数: 0
MicroRNAs in opisthorchiids and their definitive hosts: Current Status and Perspectives opisthorchiids 及其最终宿主体内的微RNA:现状与展望
IF 1.4 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-14 DOI: 10.1016/j.molbiopara.2024.111636
Xiang Li , Jian Ding , Xiaoli Zhang , Xueli Zhang , Xu Jiang , Rui Chen , Yang Cheng , Yifan Sun , Jie Wan , Yu Zhang , Jianping Cao , Su Han

Opisthorchis felineus, Opisthorchis viverrini, and Clonorchis sinensis (family Opisthorchiidae) are parasitic flatworms that pose serious threats to humans in certain countries and cause opisthorchiasis/clonorchiasis. Opisthorchiid flukes parasitize the biliary tract of the host, causing cholangitis, cholecystitis, cholelithiasis and cholangiocarcinoma. In this review, we primarily focus on recent microRNAs (miRNAs) studies of opisthorchiid flukes and their definitive hosts. Many miRNAs are conserved and expressed in a developmentally stage specific manner in the three opisthorchiid flukes, which play important roles in the growth and development of Opisthorchiidae spp., as well as host-pathogen interactions. Some miRNAs might be potential biomarkers related to carcinogenesis of cholangiocarcinoma. Therefore, this review provides the basis for further investigating the roles of miRNAs in opisthorchiid flukes and their definitive hosts, as well as promoting the development of novel approaches to prevent and treat opisthorchiasis/clonorchiasis.

Opisthorchis felineus、Opisthorchis viverrini 和 Clonorchis sinensis(Opisthorchiidae 科)是对某些国家的人类构成严重威胁的寄生扁形虫,可引起 opisthorchis/clonorchiasis。Opisthorchiid flukes 寄生于宿主的胆道,引起胆管炎、胆囊炎、胆石症和胆管癌。在这篇综述中,我们主要关注最近对口足吸虫及其最终宿主的微RNAs(miRNAs)研究。许多 miRNAs 在三种 opisthorchiid flukes 中是保守的,并以特定发育阶段的方式表达,它们在 Opisthorchiidae 的生长发育以及宿主与病原体的相互作用中发挥着重要作用。一些 miRNA 可能是与胆管癌发生有关的潜在生物标志物。因此,这篇综述为进一步研究 miRNAs 在 opisthorchiid flukes 及其最终宿主中的作用以及促进开发预防和治疗 opisthorchiasis/clonorchiasis 的新方法奠定了基础。
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引用次数: 0
Hematological changes due to malaria – An update 疟疾引起的血液学变化--最新进展。
IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-08 DOI: 10.1016/j.molbiopara.2024.111635
Rana Hussein Naser , Toktam Rajaii , Bibi Razieh Hosseini Farash , Seyyed javad Seyyedtabaei , Vahid Hajali , Fatemeh Sadabadi , Ehsan Saburi

Malaria, a parasitic infection caused by the genus Plasmodium, results to over 20 million reported cases annually worldwide. Most individuals exhibit various symptoms, and blood analysis plays a crucial role in determining the appropriate treatment approach. This study discusses various hematologic complications associated with different Plasmodium species. A review of scientific databases including PubMed, Science Direct, Web of Science, Scopus, EMBASE, Magiran, SID, IranMedex was conducted using standard keywords such as Plasmodium, malaria, anemia and blood disorders (hematologic disorder) between 2000 and 2024. The review focused on articles pertaining to clinical trials, prospective cohort, retrospective, cross-sectional and case-control studies. Articles evaluating the effects of malaria on blood cells and indices, with target groups including human and animals, were included. Articles not written in English or Farsi were excluded. Our review revealed that, apart from iron deficiency anemia and vascular dysfunction contributed in part by adhesion of infected RBC to endothelium, decreases in hematocrit and hemoglobin levels, as part of pancytopenia and thrombocytopenia, are characteristic of Plasmodium infection. Additionally, the occurrence of inflammation due to the release of inflammatory cytokines and complement activation can complicate the clinical features of malaria in individuals with hematologic conditions.

疟疾是一种由疟原虫引起的寄生虫感染,全世界每年报告的病例超过 2000 万。大多数人表现出各种症状,而血液分析在确定适当的治疗方法方面起着至关重要的作用。本研究讨论了与不同疟原虫种类相关的各种血液学并发症。本研究使用疟原虫、疟疾、贫血和血液疾病(血液病)等标准关键词对 2000-2024 年间的科学数据库(包括 PubMed、Science Direct、Web of Science、Scopus、EMBASE、Magiran、SID 和 IranMedex)进行了回顾。综述的重点是与临床试验、前瞻性队列研究、回顾性研究、横断面研究和病例对照研究有关的文章。其中包括评估疟疾对血细胞和指数影响的文章,研究对象包括人类和动物。非英语或波斯语的文章被排除在外。我们的综述显示,除了缺铁性贫血和血管功能障碍(部分原因是受感染的红细胞粘附在血管内皮上)外,血细胞比容和血红蛋白水平的下降以及全血细胞减少和血小板减少是疟原虫感染的特征。此外,炎症细胞因子的释放和补体激活导致的炎症也会使血液系统疾病患者的疟疾临床特征复杂化。
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引用次数: 0
Comparison of the effect of bacterial stimulation on the global epigenetic landscape and transcription of immune genes in primarily zoophilic members of the Anopheles gambiae complex (Diptera: Culicidae) 比较细菌刺激对冈比亚按蚊复合体(双翅目:恙虫科)中主要嗜动物成员的全球表观遗传景观和免疫基因转录的影响。
IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-04 DOI: 10.1016/j.molbiopara.2024.111631
Nashrin F. Patel , Blaženka D. Letinić , Leanne Lobb , Jacek Zawada , Dumsani M. Dlamini , Nondumiso Mabaso , Givemore Munhenga , Shüné V. Oliver

Members of the Anopheles gambiae complex vary in their vector competence, and this is often attributed to behavioural differences. Similarly, there are differences in transmission capabilities of the zoophilic members of this complex despite exhibiting similar behaviours. Therefore, behavioural differences alone cannot fully explain vector competence variation within members of the An. gambiae complex. The immune system of mosquitoes plays a key role in determining susceptibility to parasite infection and consequently transmission capacity. This study aimed to examine variations in the immune response of An. arabiensis, An. merus and An. quadriannulatus, a major, minor, and non-vector respectively. The global epigenetic landscape was characterised and the expression of Defensin-1 and Gambicin was assessed in response to Gram-positive (Streptococcus pyogenes) and Gram-negative (Escherichia coli) bacterial infections. The effect of insecticide resistance in An. arabiensis on these aspects was also assessed. The immune system was stimulated by a blood-borne bacterial supplementation. The 5mC, 5hmC, m6A methylation levels and Histone Acetyl Transferase activity were assessed with commercial ELISA kits. The transcript levels of Defensin-1 and Gambicin were assessed by quantitative Real-Time Polymerase Chain Reaction. Species-specific differences in 5mC and m6A methylation existed both constitutively as well as post immune stimulation. The epigenetic patterns observed in the laboratory strains were largely conserved in F1 offspring of wild-caught adults. The methylation patterns in the major vector typically differed from that of the minor/non-vectors. The differences between insecticide susceptible and resistant An. arabiensis were more reflected in the expression of Defensin-1 and Gambicin. The expression of these peptides differed in the strains only after bacterial stimulation. Anopheles merus and An. quadriannulatus expressed significantly higher levels of antimicrobial peptides, both constitutively and after immune stimulation. These findings suggest molecular variations in the immune response of members of the An. gambiae complex.

冈比亚按蚊复合体成员的病媒能力各不相同,这通常归因于行为差异。同样,尽管表现出相似的行为,但该种群中嗜动物成员的传播能力也存在差异。因此,仅凭行为差异并不能完全解释冈比亚疟蚊复合体成员之间的病媒能力差异。蚊子的免疫系统在决定对寄生虫感染的易感性以及传播能力方面起着关键作用。本研究旨在检测阿拉伯疟蚊(An. arabiensis)、小疟蚊(An. merus)和大疟蚊(An. quadriannulatus)的免疫反应变化。对全球表观遗传景观进行了描述,并评估了防御素-1和甘比星在革兰氏阳性(化脓性链球菌)和革兰氏阴性(大肠杆菌)细菌感染时的表达情况。还评估了阿拉伯蚂蚁对杀虫剂的抗药性对这些方面的影响。通过补充血液中的细菌来刺激免疫系统。使用商业 ELISA 试剂盒评估了 5mC、5hmC、m6A 甲基化水平和组蛋白乙酰转移酶活性。Defensin-1 和 Gambicin 的转录水平通过定量实时聚合酶链式反应进行评估。5mC和m6A甲基化在构成过程中和免疫刺激后都存在物种特异性差异。在实验室菌株中观察到的表观遗传模式在野生成虫的 F1 后代中基本保持不变。主要病媒的甲基化模式通常与次要/非病媒不同。对杀虫剂易感和抗性阿拉伯蚂蚁之间的差异更多地体现在防御素-1 和甘比星的表达上。只有在细菌刺激后,这些肽的表达才会出现差异。Anopheles merus和An. quadriannulatus表达的抗菌肽水平明显更高,无论是组成型还是免疫刺激后。这些发现表明冈比亚疟原虫复合体成员的免疫反应存在分子差异。
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引用次数: 0
Spirocerca lupi draft genome, vaccine and anthelmintic targets Spirocerca lupi 基因组草案、疫苗和驱虫药目标。
IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-06-02 DOI: 10.1016/j.molbiopara.2024.111632
Wiekolize Rothmann-Meyer , Kershney Naidoo , Pamela J. de Waal

Spirocerca lupi is a parasitic nematode affecting predominantly domestic dogs. It causes spirocercosis, a disease that is often fatal. The assembled draft genome of S. lupi consists of 13,627 predicted protein-coding genes and is approximately 150 Mb in length. Several known anthelmintic gene targets such as for β-Tubulin, glutamate, and GABA receptors as well as known vaccine gene targets such as cysteine protease inhibitor and cytokines were identified in S. lupi by comparing orthologs of C. elegans anthelmintic gene targets as well as orthologs to known vaccine candidates. New anthelmintic targets were predicted through an inclusion-exclusion strategy and new vaccine targets were predicted through an immunoinformatics approach. New anthelminthic targets include DNA-directed RNA polymerases, chitin synthase, polymerases, and other enzymes. New vaccine targets include cuticle collagens. These gene targets provide a starting platform for new drug identification and vaccine design.

Spirocerca lupi 是一种主要影响家犬的寄生线虫。它导致的螺旋体病通常是致命的。S. lupi 的基因组草案包括 13,627 个预测的蛋白编码基因,长度约为 150Mb。通过比较 C. elegans 抗蠕虫基因靶点的直向同源物以及已知候选疫苗的直向同源物,确定了 S. lupi 的几个已知抗蠕虫基因靶点,如 β-管蛋白、谷氨酸和 GABA 受体,以及已知疫苗基因靶点,如半胱氨酸蛋白酶抑制剂和细胞因子。通过包含-排除策略预测了新的驱虫药靶标,并通过免疫信息学方法预测了新的疫苗靶标。新的抗蠕虫药靶标包括DNA定向RNA聚合酶、几丁质合成酶、聚合酶和其他酶。新的疫苗靶点包括角质层胶原。这些基因靶点为新药鉴定和疫苗设计提供了一个起始平台。
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引用次数: 0
AlbuMAX supplemented media induces the formation of transmission-competent P. falciparum gametocytes AlbuMAX 补充培养基可诱导恶性疟原虫配子细胞的形成。
IF 1.5 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Pub Date : 2024-05-31 DOI: 10.1016/j.molbiopara.2024.111634
Wouter Graumans , Alex van der Starre , Rianne Stoter , Geert-Jan van Gemert , Chiara Andolina , Jordache Ramjith , Taco Kooij , Teun Bousema , Nicholas Proellochs

Asexual blood stage culture of Plasmodium falciparum is routinely performed but reproducibly inducing commitment to and maturation of viable gametocytes remains difficult. Culture media can be supplemented with human serum substitutes to induce commitment but these generally only allow for long-term culture of asexual parasites and not transmission-competent gametocytes due to their different lipid composition. Recent insights demonstrated the important roles lipids play in sexual commitment; elaborating on this we exposed ring stage parasites (20–24 hours hpi) for one day to AlbuMAX supplemented media to trigger induction to gametocytogenesis. We observed a significant increase in gametocytes after AlbuMAX induction compared to serum. We also tested the transmission potential of AlbuMAX inducted gametocytes and found a significant higher oocyst intensity compared to serum. We conclude that AlbuMAX supplemented media induces commitment, allows a more stable and predictable production of transmittable gametocytes than serum alone.

恶性疟原虫的无性血液阶段培养是常规操作,但要重复诱导有活力配子细胞的着床和成熟仍然很困难。可以在培养基中添加人血清替代物来诱导配子的形成,但由于人血清替代物的脂质成分不同,一般只能长期培养无性寄生虫,而不能培养具有传播能力的配子细胞。最近的研究表明,脂质在性承诺中发挥着重要作用;为了详细说明这一点,我们将环阶段寄生虫(20-24 小时 hpi)暴露在添加了 AlbuMAX 的培养基中一天,以诱导配子细胞的产生。与血清相比,我们观察到 AlbuMAX 诱导后配子细胞明显增加。我们还检测了AlbuMAX诱导配子细胞的传播潜力,发现与血清相比,卵囊强度明显更高。我们得出的结论是,与单纯的血清相比,添加了AlbuMAX的培养基能诱导出更稳定、更可预测的可传播配子细胞。
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Molecular and biochemical parasitology
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