{"title":"Production and evaluation of a new set of recombinant antigens for the serological diagnosis of human cysticercosis","authors":"Jihen Melki , Thierry-Borel N'dri Kouadio , Mireille Nowakowski , Zara Razafiarimanga , Man-Koumba Soumahoro , Stephane Peltres , Ronan Jambou","doi":"10.1016/j.exppara.2024.108803","DOIUrl":"10.1016/j.exppara.2024.108803","url":null,"abstract":"<div><p>Human cysticercosis caused by <em>Taenia soliun</em> (<em>T</em>. <em>soliun</em>) is endemic in certain areas of Latin America, Asia and Sub-Saharan Africa. Neurocysticercosis (NCC) is mainly diagnosed by neuroimaging, which, in most cases, is unavailable in endemic areas. Due to their high sensitivity and specificity, serological tests such as enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) based on the <em>glycosylated</em> fraction of the cyst <em>CS50 are widely used for the detection of the anti-cysticercus IgG antibodies despite their significant cost and the need of cysticercus material.</em> Given their cost-effectivess and simplicity, immunoassays based on recombinant proteins could provide new alternatives for human cysticercosis diagnosis: such tests would be aimed at screening those people living in remote areas who need further examination. <em>To date, however, no test using recombinant antigens i</em>s commercially available.</p><p>Herein, five recombinant proteins (R14, R18, R93.1, R914.1, and R915.2) were produced, three of which (R93.1, R914.1, and R915.2) were newly identified from the cyst fluid. Evaluation of the diagnostic performance of these recombinant antigens by ELISA was done using sera from 200 epileptic and non-epileptic individuals in comparison with the WB-CS50 as the reference serological method.</p><p>Recombinant proteins-based ELISA showed a level of diagnostic performance that is inferior than the reference serological method, but similar to that of the native antigen ELISA for human cysticercosis (commonly used for screening). Further optimization of expression conditions is still needed in order to improve proteins solubility and enhance diagnostic performance for human cysticercosis detection. However, this preliminary evaluation of the recombinant antigens has shown their potential valuable use for screening cysticercosis in patients with epilepsy attending dispensaries in remote areas. Future studies should be conducted to evaluate our recombinant antigens in a large group of patients with different stages of NCC, and in correlation with imaging findings.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"263 ","pages":"Article 108803"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014489424001061/pdfft?md5=bc7bf98906b490f412a6443a421318ed&pid=1-s2.0-S0014489424001061-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141619734","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Doaa A. Hamdy , Enas Y. Abu-Sarea , Hala M. Elaskary , Eman Ahmed Abd Elmaogod , Gehad Abd-Elftah Abd-Allah , Heba Abdel-Tawab
{"title":"The potential prophylactic and therapeutic efficacy of progesterone and mifepristone on experimental trichinellosis with ultra-structural studies","authors":"Doaa A. Hamdy , Enas Y. Abu-Sarea , Hala M. Elaskary , Eman Ahmed Abd Elmaogod , Gehad Abd-Elftah Abd-Allah , Heba Abdel-Tawab","doi":"10.1016/j.exppara.2024.108805","DOIUrl":"10.1016/j.exppara.2024.108805","url":null,"abstract":"<div><p>Right up to now, there has not been an effective or safe therapy for trichinellosis. Thus, this study aimed to determine the efficacy of prophylactic and therapeutic regimens of progesterone and mifepristone on the intestinal and muscular phases of experimental <em>Trichinella spiralis</em> infection compared to albendazole. Seven distinct groups of mice were divided as follows: negative, positive, and drug control groups, as well as prophylactic and treatment groups using mifepristone and progesterone. Mice were sacrificed on the 7th and 37th days after infection. Treatment efficacy was evaluated using parasitological techniques, histopathological examination, immunohistochemical staining, and ultrastructural morphological analysis of adult worms by scanning electron microscopy. The mice groups received progesterone (300 ng/ml) and mifepristone (100 ng/ml). They demonstrated a significant improvement in intestinal and muscular inflammation and a statistically significant decline in the adult worm burden and encysted larvae (P < 0.001). Moreover, immunohistochemical staining of vascular endothelial growth factor and mucosal mast cell analyses were coincided with the obtained parasitological results. There was notable destruction and degeneration of the adult worm tegument by using both drugs. The current study pointed out that progesterone and mifepristone may provide new insights regarding the development of vaccines and drug protocols to treat trichinellosis through their combined action in reducing the inflammation, affecting the intestinal immune cell, and decreasing the adult worm burden, and larval capsule development.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"263 ","pages":"Article 108805"},"PeriodicalIF":1.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141733877","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}
Bárbara da Rocha Fonseca , Raquel Nascimento das Neves , Adriane Leites Strothmann , Ângela Sena-Lopes , Caroline Carapina da Silva , Paloma Taborda Birmann , Lucielli Savegnago , Claudio Martin Pereira de Pereira , Sibele Borsuk
{"title":"Antiparasitic activity of chalcones analogue against Trichomonas vaginalis: biochemical, molecular and in silico aspects","authors":"Bárbara da Rocha Fonseca , Raquel Nascimento das Neves , Adriane Leites Strothmann , Ângela Sena-Lopes , Caroline Carapina da Silva , Paloma Taborda Birmann , Lucielli Savegnago , Claudio Martin Pereira de Pereira , Sibele Borsuk","doi":"10.1016/j.exppara.2024.108809","DOIUrl":"10.1016/j.exppara.2024.108809","url":null,"abstract":"<div><p><em>Trichomonas vaginalis</em> is the etiologic agent of trichomoniasis, a worldwide distributed sexually transmitted infection (STI) that affects the genitourinary tract. Even though this disease already has a treatment in the prescription of drugs of the 5-nitroimidazole class, described low treatments adhesion, adverse side effects and cases of resistant isolates demonstrate the need for new formulations. With this in mind, chalcones emerge as a potential alternative to be tested, being compounds widely distributed in nature, easy to chemically synthesize and presenting several biological activities already reported. In this experiment, we evaluated the antiparasitic activity of 10 chalcone at a concentration of 100 μM against ATCC 30236 <em>T. vaginalis</em> isolates, considering negative (live trophozoites), positive (Metronidazole 100 μM) and vehicle (DMSO 0.6%) controls. Compounds 3a, 3c, 3 g and 3i showed promising results, with MICs set at 70 μM, 80 μM, 90 μM and 90 μM, respectively (p < 0,05). Cytotoxicity assays were performed on VERO and HMVII cell lines and revealed low inhibition rates at concentrations bellow 20 μM. To elucidate a possible mechanism of action for these molecules, the DPPH, ABTS and FRAP assays were performed, in which none of the four compounds presented antioxidant activity. Assays to verify ROS and lipid peroxidation in the parasite membrane were performed. None of the tested compounds identified ROS accumulation after incubation with trophozoites. 3 g molecule promoted an increase in MDA production after incubation. Results presented in this paper demonstrate the promising trichomonicidal profile, although further tests are still needed to optimize their performance and better elucidate the mechanisms of action involved.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"265 ","pages":"Article 108809"},"PeriodicalIF":1.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878589","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}
Quesia Nery dos Santos , Daiane Caroline S. Teles , Guilherme Rodolfo S. de Araujo , Odeanny Vitória A. Lima , Luiz André S. Silva , Rita de Cássia V. de Carvalho , Valéria Carlos de Sousa , Saulo S. Matos , Amanda Mendonça B. Costa , Valter V. Andrade-Neto , Eduardo Caio Torres-Santos , Adriano Antunes de S. Araújo , Victor Hugo V. Sarmento , Fernando Aécio de Amorim Carvalho , Rogéria de S. Nunes , Ana Amélia M. Lira
{"title":"Microemulsions strongly promoted the activity of α-bisabolol against different Leishmania species and its skin permeation","authors":"Quesia Nery dos Santos , Daiane Caroline S. Teles , Guilherme Rodolfo S. de Araujo , Odeanny Vitória A. Lima , Luiz André S. Silva , Rita de Cássia V. de Carvalho , Valéria Carlos de Sousa , Saulo S. Matos , Amanda Mendonça B. Costa , Valter V. Andrade-Neto , Eduardo Caio Torres-Santos , Adriano Antunes de S. Araújo , Victor Hugo V. Sarmento , Fernando Aécio de Amorim Carvalho , Rogéria de S. Nunes , Ana Amélia M. Lira","doi":"10.1016/j.exppara.2024.108808","DOIUrl":"10.1016/j.exppara.2024.108808","url":null,"abstract":"<div><p>This study aimed to develop microemulsions (MEs) containing α-bisabolol for the topical treatment of cutaneous leishmaniasis (CL). Initially, pseudoternary phase diagrams were developed using α-bisabolol as the oil phase, Eumulgin® CO 40 as the surfactant, Polymol® HE as the co-surfactant, and distilled water as the aqueous phase. Two transparent liquid systems (TLS) containing 5% of α-bisabolol were selected and characterized (F5E25 and F5EP25). Next, skin permeation and retention assays were performed using Franz cells. The interaction of the formulation with the stratum corneum (SC) was evaluated using the FTIR technique. The cytotoxicity was evaluated in murine peritoneal macrophages. Finally, the antileishmanial activity of microemulsions was determined in promastigotes and amastigotes of <em>L. amazonensis</em> (strain MHOM/BR/77/LTB 0016). As a result, the selected formulations showed isotropy, nanometric size (below 25 nm), Newtonian behavior and pH ranging from 6.5 to 6.9. The MEs achieved a 2.5-fold increase in the flux and skin-permeated amount of α-bisabolol. ATR-FTIR results showed that microemulsions promoted fluidization and extraction of lipids and proteins of the stratum corneum, increasing the diffusion coefficient and partition coefficient of the drug in the skin. Additionally, F5E25 and F5EP25 showed higher activity against promastigotes (IC<sub>50</sub> 13.27 and 18.29, respectively) compared to unencapsulated α-bisabolol (IC<sub>50</sub> 53.8). Furthermore, F5E25 and F5EP25 also showed antileishmanial activity against intracellular amastigotes of <em>L. amazonensis,</em> with IC<sub>50</sub> 50 times lower than free α-bisabolol and high selectivity index (up to 15). Therefore, the systems obtained are favorable to topical administration, with significant antileishmanial activity against <em>L. amazonensis</em> promastigotes and amastigotes, being a promising system for future <em>in vivo</em> trials.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"265 ","pages":"Article 108808"},"PeriodicalIF":1.4,"publicationDate":"2024-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141878590","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}
{"title":"Kato-Katz slide preservation technique: Extension of viability and the benefits for schistosomiasis control programs","authors":"Rodrigo Loyo , Elainne Christine Souza Gomes , Otavio Sarmento Pieri , Emília Carolle Azevedo de Oliveira , Wheverton Ricardo Correia Nascimento , Constança Simões Barbosa","doi":"10.1016/j.exppara.2024.108802","DOIUrl":"10.1016/j.exppara.2024.108802","url":null,"abstract":"<div><p>The World Health Organization recommends the use of the Kato-Katz method in the procedures of schistosomiasis control programs. Studies show the importance of a fast reading of the slides due to the decline of their viability, with the appearance of fungi or desiccation of the sample, which hinders diagnosis. It is necessary to establish a procedure to improve the long-term preservation of these Kato-Katz slides in order to accomplish the following: (1) preserve the slides for future quality control procedures and readings; (2) allow for the production of durable materials for training; and (3) train health professionals involved in diagnosing schistosomiasis. Therefore, this study aims to test a slide preservation methodology for these purposes. The results showed that the modifications made to the experimental slides demonstrated that egg loss was within the expected range and the limit accepted by quality control standards, as well as improved the diagnostic durability of the slides during the preservation times tested. We concluded that the application of the preservation technique to the slides promoted stabilization and permanence for long-term storage.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"265 ","pages":"Article 108802"},"PeriodicalIF":1.4,"publicationDate":"2024-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751468","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}
Ana Cláudia Calchi , Laíza de Queiroz Viana Braga , Ricardo Bassini-Silva , Ana Carolina Castro-Santiago , Heitor Miraglia Herrera , João Fábio Soares , Darci Moraes Barros-Battesti , Rosangela Zacarias Machado , Fabiana Lopes Rocha , Marcos Rogério André
{"title":"Phylogenetic inferences based on distinct molecular markers reveals a novel Babesia (Babesia pantanalensis nov. sp.) and a Hepatozoon americanum-related genotype in crab-eating foxes (Cerdocyon thous)","authors":"Ana Cláudia Calchi , Laíza de Queiroz Viana Braga , Ricardo Bassini-Silva , Ana Carolina Castro-Santiago , Heitor Miraglia Herrera , João Fábio Soares , Darci Moraes Barros-Battesti , Rosangela Zacarias Machado , Fabiana Lopes Rocha , Marcos Rogério André","doi":"10.1016/j.exppara.2024.108786","DOIUrl":"10.1016/j.exppara.2024.108786","url":null,"abstract":"<div><p>Piroplasmids and <em>Hepatozoon</em> spp. Are apicomplexan protozoa that may cause disease in several canid species. The present study aimed to expand the knowledge on the diversity of piroplasmids and <em>Hepatozoon</em> in crab-eating foxes (<em>Cerdocyon thous</em>; n = 12) sampled in the Pantanal of Mato Grosso do Sul State, central-western Brazil. PCR assays based on the 18S rRNA were used as screening. Three (25%) and 11 (91.7%) were positive for piroplasmids and <em>Hepatozoon</em> spp., respectively. Co-infection was found in three <em>C. thous</em>. Phylogenetic analyses based on the near-complete 18S rRNA, <em>cox-1</em> and <em>hsp70</em> genes evidenced the occurrence of a novel of <em>Babesia</em> spp. (namely <em>Babesia pantanalensis</em> nov. sp.) closely related to <em>Rangelia vitalii</em> and <em>Babesia</em> sp. ‘Coco’. This finding was supported by the genetic divergence analysis which showed (i) high divergence, ranging from 4.17 to 5.62% for 18 S rRNA, 6.16% for <em>hps70</em> and 4.91–9.25% for <em>cox-1</em> and (ii) the genotype network (which displayed sequences separated from the previously described Piroplasmida species by median vectors and several mutational events). Also, phylogenetic analysis based on the 18S rRNA gene of <em>Hepatozoon</em> spp. positioned the sequences obtained herein in a clade phylogenetically related to <em>Hepatozoon</em> sp. ‘Curupira 2’, <em>Hepatozoon</em> sp. detected in domestic and wild canids from Uruguay and <em>Hepatozoon americanum</em>. The present study described <em>Babesia pantanalensis</em> nov sp. and <em>Hepatozoon</em> closely related to <em>H. americanum</em> in crab-eating foxes from Brazil. Moreover, the coinfection by piroplasmids and <em>Hepatozoon</em> sp. for the first time in crab-eating foxes strongly suggesting that this wild canid species potentially acts as a bio-accumulate of hemoprotozoan in wild environment.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108786"},"PeriodicalIF":2.1,"publicationDate":"2024-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956802","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}
Blyssalyn V. Bieber , Sarah G. Lockett , Sonja K. Glasser , Faith A. St. Clair , Neida O. Portillo , Lynn S. Adler , Megan L. Povelones
{"title":"Genetic modification of the bee parasite Crithidia bombi for improved visualization and protein localization","authors":"Blyssalyn V. Bieber , Sarah G. Lockett , Sonja K. Glasser , Faith A. St. Clair , Neida O. Portillo , Lynn S. Adler , Megan L. Povelones","doi":"10.1016/j.exppara.2024.108789","DOIUrl":"10.1016/j.exppara.2024.108789","url":null,"abstract":"<div><p><em>Crithidia bombi</em> is a trypanosomatid parasite that infects several species of bumble bees (<em>Bombus</em> spp.), by adhering to their intestinal tract. <em>Crithidia bombi</em> infection impairs learning and reduces survival of workers and the fitness of overwintering queens. Although there is extensive research on the ecology of this host-pathogen system, we understand far less about the mechanisms that mediate internal infection dynamics. <em>Crithidia bombi</em> infects hosts by attaching to the hindgut via the flagellum, and one previous study found that a nectar secondary compound removed the flagellum, preventing attachment. However, approaches that allow more detailed observation of parasite attachment and growth would allow us to better understand factors mediating this host-pathogen relationship. We established techniques for genetic manipulation and visualization of cultured <em>C. bombi.</em> Using constructs established for <em>Crithidia fasciculata,</em> we successfully generated <em>C. bombi</em> cells expressing ectopic fluorescent transgenes using two different selectable markers. To our knowledge, this is the first genetic modification of this species. We also introduced constructs that label the mitochondrion and nucleus of the parasite, showing that subcellular targeting signals can function across parasite species to highlight specific organelles. Finally, we visualized fluorescently tagged parasites <em>in vitro</em> in both their swimming and attached forms, and <em>in vivo</em> in bumble bee (<em>Bombus impatiens</em>) hosts. Expanding our cell and molecular toolkit for <em>C. bombi</em> will help us better understand how factors such as host diet, immune system, and physiology mediate outcomes of infection by these common parasites.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108789"},"PeriodicalIF":2.1,"publicationDate":"2024-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956621","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}
Dongming Yang , Yingnan Liu , Yupeng Ren , Lili Hao , Xichen Zhang , Hongjun Chen , Jingyi Liu
{"title":"Giardia intestinalis extracellular vesicles induce changes in gene expression in human intestinal epithelial cells in vitro","authors":"Dongming Yang , Yingnan Liu , Yupeng Ren , Lili Hao , Xichen Zhang , Hongjun Chen , Jingyi Liu","doi":"10.1016/j.exppara.2024.108788","DOIUrl":"10.1016/j.exppara.2024.108788","url":null,"abstract":"<div><p>Giardiasis is a common waterborne zoonotic disease caused by <em>Giardia intestinalis</em>. Upon infection, <em>Giardia</em> releases excretory and secretory products (ESPs) including secreted proteins (SPs) and extracellular vesicles (EVs). Although the interplay between ESPs and intestinal epithelial cells (IECs) has been previously described, the functions of EVs in these interactions and their differences from those of SPs require further exploration. In the present study, EVs and EV-depleted SPs were isolated from <em>Giardia</em> ESPs. Proteomic analyses of isolated SPs and EVs showed 146 and 91 proteins, respectively. Certain unique and enriched proteins have been identified in SPs and EVs. Transcriptome analysis of Caco-2 cells exposed to EVs showed 96 differentially expressed genes (DEGs), with 56 upregulated and 40 downregulated genes. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA) indicated that Caco-2 genes related to metabolic processes, the HIF-1 signaling pathway, and the cAMP signaling pathway were affected. This study provides new insights into host-parasite interactions, highlighting the potential significance of EVs on IECs during infections.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108788"},"PeriodicalIF":2.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956797","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}
Denise da Gama Jaen Batista , Ludmila Ferreira de Almeida Fiuza , Frédérique Klupsch , Krislayne Nunes da Costa , Marcos Meuser Batista , Ketlym da Conceição , Hassiba Bouafia , Gérard Vergoten , Régis Millet , Xavier Thuru , Christian Bailly , Maria de Nazaré Correia Soeiro
{"title":"Activity of pyridyl-pyrazolone derivatives against Trypanosoma cruzi","authors":"Denise da Gama Jaen Batista , Ludmila Ferreira de Almeida Fiuza , Frédérique Klupsch , Krislayne Nunes da Costa , Marcos Meuser Batista , Ketlym da Conceição , Hassiba Bouafia , Gérard Vergoten , Régis Millet , Xavier Thuru , Christian Bailly , Maria de Nazaré Correia Soeiro","doi":"10.1016/j.exppara.2024.108787","DOIUrl":"10.1016/j.exppara.2024.108787","url":null,"abstract":"<div><p>New affordable drugs are needed for the treatment of infection with the protozoan parasite <em>Trypanosoma cruzi</em> responsible for the Chagas disease (CD). Only two old drugs are currently available, nifurtimox and benznidazole (Bz) but they exhibit unwanted side effects and display a weak activity in the late chronic phase of the disease. In this context, we evaluated the activity of a series of aryl-pyrazolone derivatives against <em>T cruzi</em>, using both bloodstream trypomastigote and intracellular amastigote forms of the parasite. The test compounds originate from a series of anticancer agents targeting the immune checkpoint ligand PD-L1 and bear an analogy with known anti-trypanosomal pyrazolones. A first group of 6 phenyl-pyrazolones was tested, revealing the activity of a single pyridyl-pyrazolone derivative. Then a second group of 8 compounds with a common pyridyl-pyrazolone core was evaluated. The <em>in vitro</em> testing process led to the identification of two non-cytotoxic and highly potent molecules against the intracellular form of <em>T. cruzi</em>, with an activity comparable to Bz. Moreover, one compound revealed an activity largely superior to that of Bz against bloodstream trypomastigotes, while being non-cytotoxic (selectivity index >1000). Unfortunately, the compound showed little activity <em>in vivo</em>, most likely due to its very limited plasma stability. However, the study opens novel perspectives for the design of new anti-trypanosomal products and the mechanism of action of the compounds is discussed.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108787"},"PeriodicalIF":2.1,"publicationDate":"2024-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0014489424000900/pdfft?md5=3cf146d6809f24859bf3cac37cc27e42&pid=1-s2.0-S0014489424000900-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140956678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Xiaoxu Wang , Bikash R. Giri , Zhoukai Cui , Tserendorj Munkhjargal , Chunren Wang , Ian Kendrich C. Fontanilla , Guofeng Cheng
{"title":"Development of a Gaussia luciferase immunoprecipitation assay for detecting Schistosoma japonicum infection","authors":"Xiaoxu Wang , Bikash R. Giri , Zhoukai Cui , Tserendorj Munkhjargal , Chunren Wang , Ian Kendrich C. Fontanilla , Guofeng Cheng","doi":"10.1016/j.exppara.2024.108776","DOIUrl":"10.1016/j.exppara.2024.108776","url":null,"abstract":"<div><p>Timely and accurate diagnosis of <em>Schistosoma</em> infection is important to adopt effective strategies for schistosomiasis control. Previously, we demonstrated that <em>Schistosoma japonicum</em> can secret extracellular vesicles and their cargos may serve as a novel type of biomarkers for diagnosing schistosomiasis. Here, we developed a <em>Gaussia</em> luciferase immunoprecipitation assay combined with <em>S. japonicum</em> extracellular vesicle (SjEV) protein to evaluate its potential for diagnosing schistosomiasis. A saposin-like protein (SjSLP) identified from SjEVs was fused to the <em>Gaussia</em> luciferase as the diagnostic antigen. The developed method showed good capability for detecting <em>S. japonicum</em> infection in mice and human patients. We also observed that the method could detect <em>S</em><em>chistosom</em><em>a</em> infection in mice as early as 7 days of post-infection, which showed better sensitivity than that of indirect ELISA method. Overall, the developed method showed a good potential for detecting <em>Schistosoma</em> infection particularly for early stage, which may provide an alternative strategy for identify <em>Schistosoma</em> infection for disease control.</p></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"262 ","pages":"Article 108776"},"PeriodicalIF":2.1,"publicationDate":"2024-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944439","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}