Experimental parasitology最新文献_第2页

Imidazolium salt as potent Amoebicide for rapid inactivation of Acanthamoeba spp. trophozoites and cysts

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-03-01 DOI: 10.1016/j.exppara.2025.108921

Denise Leal dos Santos , Beni Jequicene Mussengue Chaúque , Francisco Kercher Berté , Larissa de Miranda Ribeiro , Fernanda Fraga Matiazo , Marilise Brittes Rott , Henri Stephan Schrekker , Leo Sekine

Acanthamoeba spp. are amphizoic protozoa capable of causing several severe diseases in humans and other animals, including granulomatous amoebic encephalitis and Acanthamoeba keratitis (AK). The high resistance of Acanthamoeba genus, especially in its cystic form, to most conventional disinfectants poses a challenge for its management through aseptic practices based on chemical disinfectants. The imidazolium salt (IS) (C₁₆MImCl) demonstrated significant acanthamoebicidal potency against both trophozoites and cysts. However, its biocidal efficacy over a short exposure time, which will shed light on its potential use as a disinfectant, still needs to be studied. Therefore, the acanthamoebicidal effect of IS against trophozoites and cysts of Acanthamoeba polyphaga and Acanthamoeba spp. exposed for 5 and 20 min to concentrations of 250, 125, 62.5, 31.25, 15.62, and 7.81 μg/mL was evaluated in the present study. Exposure of trophozoites of both strains to IS for 20 min significantly reduced trophozoite viability at concentrations ≥62.5 μg/mL. All trophozoites of both strains were inactived 20 min after cessation of IS exposure at concentrations of ≥125 μg/mL for 5 min or ≥15 μg/mL for 20 min. Cyst viability of all strains was significantly reduced after 20 min of exposure to IS at 62.5 and 125 μg/mL, based on the viability exclusion assay with trypan blue dye. However, all cysts exposed to IS at ≥ 125 μg/mL for 20 or 5 min were unable to excyst when incubated for 10 days on non-nutrient agar with Escherichia coli. The acanthamoebicidal efficacy of IS, upon short exposure to concentrations below the cytotoxic value for human keratinocyte cells (IC₅₀ = 171.50 μg/mL), combined with its previously reported bactericidal and fungicidal effects, suggests that IS has the potential to be used in the formulation of multipurpose disinfectants.

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引用次数: 0

Structural and functional implications of MIT2 and NT2 mutations in amodiaquine and piperaquine resistant Plasmodium berghei parasites

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-03-01 DOI: 10.1016/j.exppara.2025.108923

Brenda Muriithi , Jean Chepngetich , Beatrice Gachie , Kevin Thiong'o , Jeremiah Gathirwa , Francis Kimani , Peter Mwitari , Daniel Kiboi

Long-acting drugs, amodiaquine (AQ), lumefantrine (LM), and piperaquine (PQ), are vital components of artemisinin-based combination therapies (ACTs) for malaria treatment. However, the emergence of partial artemisinin-resistant parasites poses significant challenges, particularly in malaria-endemic regions. Despite extensive research, parasite's resistance mechanisms to these drugs still need complete elucidation. This study investigated the genetic basis of resistance to AQ, LM, and PQ using Plasmodium berghei, focusing on selected genes encoding transport proteins in Plasmodium species. In silico bioinformatics tools were used to map genes encoding transport proteins, their ligand-binding sites, and their conservation across different Plasmodium species. PCR amplification and sequence analysis were employed to examine single nucleotide polymorphisms (SNPs) in the genes encoding the selected transporters in AQ, LM, and PQ-resistant P. berghei. The structural impacts of the mutations were evaluated using AlphaFold, ITASSER, UCSF Chimera, and MOTIF Finder. Genes encoding CorA-like Mg2+ transporter protein (MIT2), nucleoside transporter 2 (NT2), ABC Transporter G family member 2 (ABCG2), and novel putative transporter 1 (NPT1) transport proteins with notable conserved motifs and ligand-binding motifs in Plasmodium species were selected and examined. In AQ-resistant (AQ^R) parasites, a non-synonymous mutation (I433∗) was found in MIT2. PQ-resistant (PQ^R) parasites possessed a non-synonymous mutation (D511H) in NT2 and a silent mutation in the NPT1 protein. No mutations were observed in the targeted regions of the transporters in LM-resistant (LM^R) parasites, nor in the ligand-binding motifs of ABCG2 across all resistant strains. These findings suggest that selection pressure from AQ and PQ leads to mutations in MIT2 and NT2. Further investigation is required to understand how these mutations affect drug susceptibility on a functional level.

{"title":"Structural and functional implications of MIT2 and NT2 mutations in amodiaquine and piperaquine resistant Plasmodium berghei parasites","authors":"Brenda Muriithi , Jean Chepngetich , Beatrice Gachie , Kevin Thiong'o , Jeremiah Gathirwa , Francis Kimani , Peter Mwitari , Daniel Kiboi","doi":"10.1016/j.exppara.2025.108923","DOIUrl":"10.1016/j.exppara.2025.108923","url":null,"abstract":"<div><div>Long-acting drugs, amodiaquine (AQ), lumefantrine (LM), and piperaquine (PQ), are vital components of artemisinin-based combination therapies (ACTs) for malaria treatment. However, the emergence of partial artemisinin-resistant parasites poses significant challenges, particularly in malaria-endemic regions. Despite extensive research, parasite's resistance mechanisms to these drugs still need complete elucidation. This study investigated the genetic basis of resistance to AQ, LM, and PQ using <em>Plasmodium berghei</em>, focusing on selected genes encoding transport proteins in Plasmodium species. In silico bioinformatics tools were used to map genes encoding transport proteins, their ligand-binding sites, and their conservation across different Plasmodium species. PCR amplification and sequence analysis were employed to examine single nucleotide polymorphisms (SNPs) in the genes encoding the selected transporters in AQ, LM, and PQ-resistant <em>P. berghei</em>. The structural impacts of the mutations were evaluated using AlphaFold, ITASSER, UCSF Chimera, and MOTIF Finder. Genes encoding CorA-like Mg2+ transporter protein (MIT2), nucleoside transporter 2 (NT2), ABC Transporter G family member 2 (ABCG2), and novel putative transporter 1 (NPT1) transport proteins with notable conserved motifs and ligand-binding motifs in Plasmodium species were selected and examined. In AQ-resistant (AQ<sup>R</sup>) parasites, a non-synonymous mutation (I433∗) was found in MIT2. PQ-resistant (PQ<sup>R</sup>) parasites possessed a non-synonymous mutation (D511H) in NT2 and a silent mutation in the NPT1 protein. No mutations were observed in the targeted regions of the transporters in LM-resistant (LM<sup>R</sup>) parasites, nor in the ligand-binding motifs of ABCG2 across all resistant strains. These findings suggest that selection pressure from AQ and PQ leads to mutations in MIT2 and NT2. Further investigation is required to understand how these mutations affect drug susceptibility on a functional level.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108923"},"PeriodicalIF":1.4,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540806","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

Synthetic peptides derived from hypothetical proteins as potential antigens for the diagnosis of canine visceral leishmaniasis and tegumentary leishmaniasis

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-06 DOI: 10.1016/j.exppara.2025.108914

Larissa Chaves Freire , Scarleth Silva Costa , Ana Luiza Filizzola Tedeschi , Lucas Magno Oliveira Santos , Naianda Rezende Ribeiro , Luiza dos Reis Cruz , Vivian Tamietti Martins , Nathalia Coral Galvani , Gabriel Paulino Luiz , Maria Eduarda de Oliveira , Ricardo Andrez Machado de Ávila , Ana Maria Ravena Severino Carvalho , Henrique Santos de Freitas André , Denise Utsh Gonçalves , Eduardo Antonio Ferraz Coelho , Bruno Mendes Roatt , Daniel Menezes-Souza , Mariana Costa Duarte

In the present study, we investigated the potential use of five linear peptides as a potential antigens for the immunodiagnosis of tegumentary leishmaniasis (TL) and canine visceral leishmaniasis (CVL). We used bioinformatics approaches to identify linear B-cell epitopes in five hypothetical proteins from a Leishmania (Leishmania) infantum proteome study. To obtain the peptide sequences of each hypothetical protein, we used the GenBank and SwissProt online databases. These peptides were synthesized and tested, alone or in a cocktail, in enzyme-linked immunosorbent assays (ELISAs) against serum samples from patients with TL and from dogs infected with CVL. Our data shows that for CVL diagnosis, the best results were found with peptides 1 and 5, which showed sensitivity values of 97.30% and 94.54%, and specificity values of 93.83% (pep 1) and 91.63% (pep 5), respectively. For TL, all peptides showed higher sensitivity and specificity when compared with SLALb, with the peptide cocktail obtaining a 99.10% accuracy. This study's outcome suggests that these peptides may constitute a potential tool for a more sensitive and specific serodiagnosis of TL and CVL.

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引用次数: 0

Comparative larvicidal, pupicidal, adulticidal activity of Artemisia nilagirica (C.B. Cl) pamp extract in controlling Culex quinquefasciatus, Anopheles stephensi, Aedes aegypti and Aedes albopictus

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-05 DOI: 10.1016/j.exppara.2025.108913

Sagorika Panda , Rajasri Sahoo , Santi Lata Sahoo , Ranjit Manoranjan , R.C Patra

Vector-borne diseases cause increase in burden, poverty, social liability and death all over the world. Mosquitoes serve as the vector for malaria, dengue, filariasis, yellow fever and also play a major role in transmission of chikungunya and Zika virus. The development of mosquitocidal resistance and associated health problems with the use of synthetic insecticides, have paved the way to control mosquito population by using plant-based botanicals. This study was carried out to evaluate the larvicidal, pupicidal and adulticidal properties of six solvent extracts of Artemisia nilagirica (C.B.Cl) against four infectious vector mosquitoes Anopheles stephensi, Aedes aegypti, Aedes albopictus and Culex quinquefasciatus, by assessing LC₅₀ and LC₉₀ mortality values. Among all six leaf solvent extracts, chloroform extract had higher toxicity (LC₅₀ = 127.27 ppm and LC₉₀ = 544.45 ppm) against fourth instar larva of C. quinquefasciatus and aqueous extract had lowest lethal effects (LC₅₀ = 583.33 ppm and LC₉₀ = 927.27 ppm) against fourth instar larva of A. aegypti. Moderate results were found in n-hexane, petroleum ether, methanol and ethanol plant extracts. Phytochemical analysis by GC-MS method confirms presence of significant 12 bioactive compounds like Bi-cyclo (3.1.1) heptanes-2, 4, 6 trimethyl, 3, 7, 11, 15- Tetramethyl-1.2 hexadecan-1-ol, Thiophene, Tetrahydro-2-methyl 1,3 propane diamine and camphor, which were responsible for insecticidal activity. Altogether, current study would serve as an initial step towards replacement of synthetic insecticides to plant-based bio-pesticide against dreadful vector mosquitoes in future.

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引用次数: 0

Ritonavir enhances the efficacy of amprenavir: A promising combination therapy by targeting Leishmania DNA topoisomerase I for treatment of visceral leishmaniasis 利托那韦通过靶向利什曼原虫DNA拓扑异构酶I治疗内脏利什曼病HIV-VL合并感染，增强了安普雷那韦的疗效。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2025.108898

Priyanka H. Mazire, Snehal Shingade, Amit Roy

Visceral leishmaniasis (VL) is an opportunistic infection in HIV patients with higher relapse and mortality rate. The number of HIV-VL patients is comparatively higher in areas where both infections are endemic. However, the conventional chemotherapeutic agents have limited success due to drug toxicity, efficacy variance and overall cost of treatment. Therefore, it is crucial to discover and develop newer potent antileishmanial agents for successful eradication of the disease. Our previous report, for the first time showed the leishminicidal effect of amprenavir (APV) mediated by inhibition of L.donovani Topoisomerase I (LdTopILS). So, we intended to demonstrate the effect of APV in combination with ritonavir (RTV). The present study revealed that the complete catalytic inhibition of LdTopILS by APV (10 μM) in combination with RTV (5 μM), compare to APV (20 μM) as previously reported (Roy et al., 2021). Moreover, APV (5 μM) in combination with RTV (4 μM) exhibited promastigote inhibition with IC₅₀ values of 2.4 ± 0.6 μM at 12 h and 1.6 ± 0.7 μM at 24 h, respectively. The study was extended in animal model where the in vivo antileishmanial efficacy of APV-RTV in BALB/c mice demonstrated that treatment of APV in combination with RTV led to significant splenic and hepatic protection as compared to single dose of APV. Moreover, the antileishmanial activity of APV in combination with RTV was exerted via inhibition of LdTopILS at much lower concentration of APV and this inhibition of the enzyme induced programmed cell death in Leishmania parasites by generating oxidative stress within the cells. From the in vitro, ex vivo and in vivo studies, it was indicated that lower dose of APV in combination with RTV elevated the effective killing of the parasites as compared to the single higher dose of APV. Thus, the current study highlights repurposing of available protease inhibitors in combination, which might be exploited further for the therapeutic development against VL as well as HIV-VL co-infection.

内脏利什曼病（VL）是HIV患者中一种复发率和死亡率较高的机会性感染。在两种感染都流行的地区，艾滋病毒- vl患者的人数相对较高。然而，由于药物毒性、疗效差异和总体治疗成本，传统化疗药物的成功有限。因此，发现和开发新的有效抗利什曼原虫药物对于成功根除该病至关重要。本研究首次报道了安普雷那韦（amprenavir， APV）通过抑制L.donovani拓扑异构酶I （LdTopILS）介导的杀利什微虫作用。因此，我们打算证明APV与利托那韦（RTV）联合使用的效果。本研究表明，与之前报道的APV （20 μM）相比，APV （10 μM）和RTV （5 μM）对LdTopILS具有完全的催化抑制作用（Roy等）。2021)。此外，APV （5μM）与RTV （4μM）联合使用对promastigote有抑制作用，12 h和24 h的IC50值分别为2.4±0.6 μM和1.6±0.7 μM。在动物模型中，APV-RTV在BALB/c小鼠体内抗利什曼原虫的功效表明，与单剂量APV相比，APV联合RTV治疗具有显著的脾和肝保护作用。此外，APV与RTV结合的抗利什曼原虫活性是通过在低浓度APV下抑制LdTopILS发挥的，这种抑制酶通过在细胞内产生氧化应激诱导利什曼原虫的程序性细胞死亡。体外、离体和体内研究表明，低剂量APV与RTV联合使用比单独使用高剂量APV更能提高对寄生虫的有效杀灭。因此，目前的研究重点是重新利用现有的蛋白酶抑制剂联合使用，这可能进一步用于VL以及HIV-VL合并感染的治疗开发。

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引用次数: 0

Galactokinase and galactose metabolism in Leishmania spp. 利什曼原虫半乳糖激酶和半乳糖代谢。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2024.108888

Ángel E. Lobo-Rojas , María A. Delgado-Chacón , Edward A. Valera-Vera , Marirene Chacón-Arnaude , Mary Carmen Pérez-Aguilar , Rocío Rondón-Mercado , Ender Quintero-Troconis , Wilfredo Quiñones , Juan L. Concepción , Ana J. Cáceres

In Leishmania, the nucleotide-sugar UDP-galactose can be synthesized by a salvage pathway, the Isselbacher route, involving phosphorylation of galactose and the action of UDP-sugar pyrophosphorylase. The first enzyme of the pathway, galactokinase, has yet to be studied in this parasite. Here, we report a molecular and biochemical characterization of this enzyme in Leishmania mexicana. We showed that recombinant galactokinase (LmxGALK) phosphorylates galactose in the presence of ATP with K_m values of 0.077 mM for galactose and 0.017 mM for ATP. We proved by immunodetection that GALK is expressed in promastigotes and amastigotes of L. mexicana, L. braziliensis and L. infantum. In agreement with the presence of a type 1 peroxisome-targeting signal sequence present at the C-terminus of LmxGALK, the protein is localized mostly within glycosomes as shown by selective membrane permeabilization with digitonin, differential centrifugation, and immunofluorescence. Indeed, LmxGALK enzymatic activity was measured in the fractions corresponding to the homogenate and glycosomes, proving that it is active in promastigotes. In addition, it was shown that galactose cannot serve as an important carbon source for sustaining parasite growth, as cultures of promastigotes from three Leishmania species in LIT medium containing either no sugar or supplemented with D-galactose (20 mM) grew to lower density compared to these cultured with D-glucose (20 mM). These results suggest that D-galactose is mainly used for UDP-galactose synthesis by the salvage route, functioning when glucose is depleted from the medium, similar to the conditions promastigotes experience in the gut of the insect vector during its life cycle.

在利什曼原虫中，核苷酸-糖udp -半乳糖可以通过Isselbacher途径合成，该途径涉及半乳糖磷酸化和udp -糖焦磷酸化酶的作用。该途径的第一种酶，半乳糖激酶，尚未在这种寄生虫中进行研究。在这里，我们报告了这种酶在墨西哥利什曼原虫的分子和生化特性。我们发现重组半乳糖激酶（LmxGALK）在ATP存在下磷酸化半乳糖，其Km值为半乳糖的0.077 mM和ATP的0.017 mM。我们通过免疫检测证实了GALK在L. mexicana， L. brasiliensis和L. infumtum的promastigotes和amastigotes中表达。与LmxGALK的c端存在1型过氧化物酶体靶向信号序列一致，通过洋地黄苷选择性膜渗透、差速离心和免疫荧光显示，该蛋白主要定位于糖体内。事实上，LmxGALK酶活性在匀浆和糖体对应的组分中被测量，证明它在promastigotes中是活跃的。此外，研究表明，半乳糖不能作为维持寄生虫生长的重要碳源，因为来自三种利什曼原虫的promastigotes在不含糖或添加d -半乳糖（20 mM）的LIT培养基中生长的密度低于添加d -葡萄糖（20 mM）的培养基。这些结果表明，d -半乳糖主要通过回收途径合成udp -半乳糖，当葡萄糖从培养基中耗尽时起作用，类似于原毛菌在昆虫媒介的肠道中经历的条件。

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引用次数: 0

Interaction of Meloidogyne incognita and Pseudomonas syringae pv. aptata in different types of soil on plant growth, photosynthetic pigments and proline contents of beetroot (Beta vulgaris L.) 不知名棉兰假单胞菌与丁香假单胞菌的相互作用。不同土壤类型对甜菜根生长、光合色素和脯氨酸含量的影响。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2024.108882

Aqib, Zaki Anwar Siddiqui

Effect of Meloidogyne incognita and Pseudomonas syringae pv. aptata (Psa) was observed singly, together and pre and post inoculations in 4 soil types on plant growth parameters, chlorophyll, carotenoid and proline contents of beetroot (Beta vulgaris L.). Plant growth, chlorophyll and carotenoid contents were greater in loam soil followed by 20% fly ash soil, 10% fly ash plus 10% sand amended soil and least in 20 % sand mix soil. However, proline contents were high in 20% sand mix soil and least in loam soil. Plant growth (root dry weight), chlorophyll and carotenoid contents were reduced in plants inoculated with any test pathogen while proline contents were increased in plants inoculated with pathogens under study. Inoculation of both pathogens together caused a greater reduction of plant growth, chlorophyll and carotenoid contents than their individual inoculation. Inoculation of M. incognita 20 days prior to Psa resulted in greatest reduction in plant growth, chlorophyll and carotenoid and maximum proline contents. Inoculation of Psa with M. incognita reduced galling and nematode multiplication while prior inoculation of Psa caused maximum reduction in galling and nematode multiplication. Galling and nematode multiplication was high in 20% sand mix soil followed by loam soil and least in 20% fly ash amended soil. Bacterial leaf spot indices by Psa was 3 when alone. Disease indices were 5 when Psa was inoculated with M. incognita. Prior inoculation of M. incognita predisposed beetroots to Psa and aggravates the disease. Influence of M. incognita, Psa and their interactions in different soil types on various studied parameters in diseased plants was demonstrated by Principal component analysis.

不明旋律性假单胞菌和丁香假单胞菌的作用。在4种土壤类型中，分别对甜菜根（Beta vulgaris L）的生长、参数、叶绿素、类胡萝卜素和脯氨酸含量进行了观察，其中壤土的植株生长、叶绿素和类胡萝卜素含量最高，其次是20%粉煤灰土、10%粉煤灰加10%沙土，20%沙土混合土的植株生长、叶绿素和类胡萝卜素含量最低。20%砂混合土脯氨酸含量较高，壤土脯氨酸含量最低。接种任一病原菌后，植株的生长（根干重）、叶绿素和类胡萝卜素含量均降低，而脯氨酸含量升高。两种病原菌一起接种比单独接种对植株生长、叶绿素和类胡萝卜素含量的影响更大。Psa前20天接种黑穗病菌对植株生长、叶绿素和类胡萝卜素的影响最大，脯氨酸含量最大。用隐殖芽孢杆菌接种Psa可减少虫瘿和线虫的繁殖，而事先接种Psa可最大程度地减少虫瘿和线虫的繁殖。其中，20%砂拌和土的线虫繁殖率最高，壤土次之，20%粉煤灰拌和土的线虫繁殖率最低。单独用Psa测定细菌性叶斑病指数为3。Psa接种后的疾病指数为5。事先接种M. incognita易使甜菜根Psa和加重疾病。通过主成分分析论证了不同土壤类型下黑穗病菌、Psa及其相互作用对病害植株各项研究参数的影响。

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引用次数: 0

Protection induced by recombinant vaccinia virus targeting the ROP4 of Toxoplasma gondii in mice 针对刚地弓形虫ROP4的重组痘苗病毒对小鼠的保护作用。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2025.108900

Keon-Woong Yoon , Gi-Deok Eom , Jie Mao , Min-Ju Kim , Su In Heo , Hae-Ji Kang , Ki Back Chu , Eun-Kyung Moon , Fu-Shi Quan

Toxoplasmosis is a parasitic disease affecting a significant portion of the global population, whose etiology can be attributed to the protozoan organism Toxoplasma gondii. Despite its public health importance, an efficacious vaccine to prevent human toxoplasmosis remains unavailable. To this end, we designed an experimental toxoplasmosis vaccine using recombinant vaccinia virus vectors (rVacv) expressing the T. gondii rhoptry protein 4 (ROP4) antigen and evaluated its efficacy in a murine model. Intranasal vaccination with ROP4-rVacvs induced parasite-specific serum antibody responses as early as 3 weeks post-immunization, with subsequent immunizations elevating antibody responses to a greater extent. When challenged with T. gondii ME49 strain, significantly enhanced levels of mucosal IgA antibodies were detected in the intestines of immunized mice. Additionally, ROP4-rVacv immunization ensured that T cells and germinal center B cell populations were retained at high levels. These immune responses mitigated the severity of neuroinflammation, reduced tissue cyst formation, and ensured the survival of immunized mice. Our findings indicate that ROP4-rVacv could be a promising toxoplasmosis vaccine candidate.

弓形虫病是一种影响全球很大一部分人口的寄生虫病，其病因可归因于原生动物有机体弓形虫。尽管具有重要的公共卫生意义，但预防人类弓形虫病的有效疫苗仍然缺乏。为此，我们利用表达弓形虫弓形体蛋白4 （ROP4）抗原的重组痘苗病毒载体（rVacv）设计了一种实验性弓形虫病疫苗，并在小鼠模型上评价了其有效性。早在免疫后3周，鼻内接种ROP4-rVacvs可诱导寄生虫特异性血清抗体反应，随后的免疫可在更大程度上提高抗体反应。弓形虫ME49菌株攻毒后，免疫小鼠肠道黏膜IgA抗体水平显著升高。此外，ROP4-rVacv免疫确保T细胞和生发中心B细胞群保持在高水平。这些免疫反应减轻了神经炎症的严重程度，减少了组织囊肿的形成，并确保了免疫小鼠的存活。我们的研究结果表明，ROP4-rVacv可能是一种有前途的弓形虫病候选疫苗。

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引用次数: 0

In vivo efficacy of uvangoletin from Piper aduncum (Piperaceae) against Schistosoma mansoni and in silico studies targeting SmNTPDases 胡椒科植物紫万素抗曼氏血吸虫体内药效及针对smntpases的硅片研究。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2025.108897

Everton Allan Ferreira , Igor Moreira Campos , Rayssa A. Cajas , Danilo de Souza Costa , Lara Soares Aleixo de Carvalho , Paula Fernandes da Costa Franklin , Nathália de Paula D. de Nigro , Priscila de Faria Pinto , PriscilaV.S.Z. Capriles , Josué de Moraes , Ademar A. da Silva Filho

Schistosomiasis stands as one of the most significant parasitic diseases on a global scale, with approximately 250 million infections worldwide. It is imperative to address this pressing issue by developing new antischistosomal drugs. Chalcones have emerged as a promising class of natural compounds, demonstrating noteworthy effects observed in vitro experiments with Schistosoma mansoni, and demonstrating the ability to inhibit SmNTPDases and apyrase from potatoes. In this study, we focused on uvangoletin, a naturally occurring dihydrochalcone from Piper aduncum. We isolated uvangoletin from P. aduncum fruits and conducted in vivo experiments to evaluate the efficacy of uvangoletin against adult Schistosoma parasites. Furthermore, we explored the inhibitory effects of uvangoletin on potato apyrase and employed molecular docking analyses to investigate its interactions with apyrase from potato and the two isoforms SmNTPDase 1 and 2 through in silico studies. Uvangoletin (400 mg/kg, p. o.), exhibited significant in vivo antiparasitic effects against adult S. mansoni, leading to a decrease of 53.7% in worm burden and 54.3% in egg production. The treatment also reduced hepatomegaly and splenomegaly. In silico investigations and ADMET studies indicated that uvangoletin possesses favorable drug-like properties and may interact with key residues involved in apyrase and SmNTPDases activities. Furthermore, uvangoletin demonstrated a substantial reduction in potato apyrase activity. These results suggest the potential for exploring other dihydrochalcones as promising candidates for antischistosomal agents.

血吸虫病是全球范围内最严重的寄生虫病之一，全世界约有2.5亿人感染。迫切需要开发新的抗血吸虫药物来解决这一紧迫问题。查尔酮已成为一类很有前途的天然化合物，在曼氏血吸虫的体外实验中显示出显著的效果，并显示出抑制马铃薯中smntpases和apyrase的能力。在这项研究中，我们重点研究了一种天然存在的二氢查尔酮。本研究从黄菖蒲果实中分离得到乌万素，并进行体内实验，评价乌万素对血吸虫成虫的抑制作用。此外，我们探索了uvangoletin对马铃薯apyrase的抑制作用，并通过分子对接分析研究了其与马铃薯apyrase以及smntpase 1和2两个异构体的相互作用。百万素（400mg /kg, p.o）对马氏夜蛾有显著的体内抗寄生作用，虫量减少53.7%，产蛋量减少54.3%。治疗还可减少肝和脾肿大。计算机研究和ADMET研究表明，uvangoltin具有良好的药物样性质，并可能与apyrase和smntpases活性的关键残基相互作用。此外，uvangoltin显示了马铃薯apyrase活性的显著降低。这些结果提示探索其他二氢查尔酮作为抗血吸虫药物的有希望的候选者的潜力。

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引用次数: 0

Bioactive-based spray and spot-on formulations: Development, characterization and in vitro efficacy against fleas and ticks 基于生物活性的喷雾和定点制剂：开发，表征和对跳蚤和蜱的体外功效。

IF 1.4 4区医学 Q3 PARASITOLOGY

Experimental parasitology

Pub Date : 2025-02-01 DOI: 10.1016/j.exppara.2024.108881

Ingrid Lins Raquel de Jesus , Fernando Rocha Miranda , Thais Paes Ferreira , Alice Ortega do Nascimento , Karen Kuhfuss da Silva de Lima , Bárbara Rauta de Avelar , Diefrey Ribeiro Campos , Yara Peluso Cid

The flea Ctenocephalides felis felis and the tick Rhipicephalus sanguineus are ectoparasites of great importance in veterinary medicine that can affect pets, also impacting the lives of owners due to the possible transmission of zoonoses. Due to the negative impact on animals, owners and the environment, synthetic chemicals are being replaced by natural alternatives. Eugenol and carvacrol stand out as bioactive substances with potential antiparasitic activity. The aim of the present study was to develop and characterize physicochemically spray and spot-on formulations containing bioactives alone and in combination and to evaluate their ectoparasiticidal activity through in vitro bioassays of the knockdown effect and residual efficacy against adult fleas and ticks. Regarding flea knockdown, spot-on formulations achieved maximum mortality in a shorter period than spray formulations, 2 h for carvacrol plus eugenol (SCE) and 4 h for carvacrol (SC) and eugenol (SE) alone, compared to 15, 30 and 45 min for the spot-on formulations of carvacrol (PC), both substances together (PCE) and eugenol alone (PE), respectively. For tick control, the formulations required longer exposure times than for fleas, so that 100% control took 6 h for PCE, followed by 12 h for SCE and PE, and 24 h for PC, SC and PE. Regarding residual efficacy against fleas, the spray and spot-on formulations remained active for approximately 90 and 45 days, respectively. In general, formulations containing associated bioactives had a faster knockdown effect than formulations with only one in their composition, indicating a synergistic effect of the two bioactive substances against fleas and ticks.

猫头蚤（Ctenocephalides felis felis）和血头蜱（Rhipicephalus sanguineus）是兽医学上非常重要的体外寄生虫，它们会影响宠物，也会因可能传播人畜共患病而影响主人的生活。由于对动物、主人和环境的负面影响，合成化学品正在被天然替代品所取代。丁香酚和香芹酚是具有潜在抗寄生虫活性的生物活性物质。本研究的目的是开发和表征含有单独和联合生物活性的物理化学喷雾和斑点制剂，并通过体外生物测定对成年跳蚤和蜱的击倒效果和残留功效来评估它们的体外杀虫活性。在灭蚤方面，与喷雾制剂相比，喷涂制剂在更短的时间内达到最大死亡率，香芹酚加丁香酚（SCE）为2小时，香芹酚（SC）和丁香酚（SE）单独为4小时，而香芹酚（PC）、两种物质一起（PCE）和单独丁香酚（PE）分别为15、30和45分钟。对于蜱虫的控制，制剂需要比跳蚤更长的暴露时间，因此PCE需要6小时才能达到100%的控制，其次是SCE和PE 12小时，PC、SC和PE 24小时。至于对跳蚤的残余功效，喷雾和定点制剂分别保持约90天和45天的有效。一般来说，含有相关生物活性物质的制剂比仅含有一种生物活性物质的制剂具有更快的抑制作用，这表明两种生物活性物质对跳蚤和蜱具有协同作用。

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