Pub Date : 2025-06-01Epub Date: 2025-04-25DOI: 10.1016/j.exppara.2025.108947
Sibasish Sarangi, Rajani Kanta Mahapatra
The Plasmodium falciparum Protein Kinase 6 (PfPK6) is a serine/threonine protein kinase categorized under the CMGC group, displaying both cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs) activity. Previous research has indicated that PfPK6 is expressed during the trophozoite and schizont stages of the Plasmodium falciparum asexual blood stage. Unlike typical cyclin-dependent kinases, PfPK6 demonstrates kinase activity independent of cyclin, making it a promising target for drug identification. In this study, we utilized a computational approach to identify a novel PfPK6 inhibitor through virtual screening of small inhibitor compounds from diverse datasets, employing a structure-based approach and a Deep Learning (DL) model. The most promising inhibitor molecule, TCMDC-132409 from the Tres Cantos Antimalarial Set, exhibited a binding affinity of −13.553 kcal/mol against PfPK6. Additionally, a 200ns molecular dynamics simulation study confirmed the stability of the binding mode, indicating the potential of TCMDC-132409 as an antiplasmodial inhibitor for further investigation.
恶性疟原虫蛋白激酶6 （PfPK6）是一种丝氨酸/苏氨酸蛋白激酶，属于CMGC组，具有细胞周期蛋白依赖性激酶（CDKs）和丝裂原活化蛋白激酶（MAPKs）活性。先前的研究表明，PfPK6在恶性疟原虫无性血期的滋养体和分裂体阶段表达。与典型的细胞周期蛋白依赖性激酶不同，PfPK6表现出独立于细胞周期蛋白的激酶活性，使其成为药物鉴定的一个有希望的靶点。在这项研究中，我们利用基于结构的方法和深度学习（DL）模型，通过对不同数据集中的小抑制剂化合物进行虚拟筛选，利用计算方法鉴定了一种新的PfPK6抑制剂。最有希望的抑制剂分子TCMDC-132409来自trescantos anti - malaria Set，对PfPK6的结合亲和力为−13.553 kcal/mol。此外，一项200ns分子动力学模拟研究证实了该结合模式的稳定性，表明TCMDC-132409作为抗疟原虫抑制剂的潜力有待进一步研究。
{"title":"Identification of therapeutics against PfPK6 protein of Plasmodium falciparum: Structure and Deep Learning approach","authors":"Sibasish Sarangi, Rajani Kanta Mahapatra","doi":"10.1016/j.exppara.2025.108947","DOIUrl":"10.1016/j.exppara.2025.108947","url":null,"abstract":"<div><div>The <em>Plasmodium falciparum</em> Protein Kinase 6 (PfPK6) is a serine/threonine protein kinase categorized under the CMGC group, displaying both cyclin-dependent kinases (CDKs) and mitogen-activated protein kinases (MAPKs) activity. Previous research has indicated that PfPK6 is expressed during the trophozoite and schizont stages of the <em>Plasmodium falciparum</em> asexual blood stage. Unlike typical cyclin-dependent kinases, PfPK6 demonstrates kinase activity independent of cyclin, making it a promising target for drug identification. In this study, we utilized a computational approach to identify a novel PfPK6 inhibitor through virtual screening of small inhibitor compounds from diverse datasets, employing a structure-based approach and a Deep Learning (DL) model. The most promising inhibitor molecule, TCMDC-132409 from the Tres Cantos Antimalarial Set, exhibited a binding affinity of −13.553 kcal/mol against PfPK6. Additionally, a 200ns molecular dynamics simulation study confirmed the stability of the binding mode, indicating the potential of TCMDC-132409 as an antiplasmodial inhibitor for further investigation.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"273 ","pages":"Article 108947"},"PeriodicalIF":1.4,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894559","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}
Pub Date : 2025-05-01Epub Date: 2025-03-13DOI: 10.1016/j.exppara.2025.108930
Mukhtar Gambo Lawal , Abdullahi Samaila , Rusliza Basir , Nur Aimi Liyana Abd Aziz , Abdusalam Abdullah Alarabei , Maizaton Atmadini Abdullah , Roslaini Abd Majid , Norshariza Nordin , Mohd Khairi Hussain , Elysha Nur Ismail
Malaria is a life-threatening disease, leading to significant morbidity and mortality. Malaria treatment remains a challenge due to its intricate pathophysiology and high levels of parasite resistance to many currently available antimalarial agents. Thus, there is an urgent need for more therapeutic strategies to combat the disease. OGG1 activity has been implicated in many inflammatory disease conditions, making suppressing OGG1 activity a potential target for therapeutic purposes. The current study aimed to determine the effect of suppressing OGG1 activity on the severity, survival, and histopathological features of P. berghei-infected mice. In this study, the effects of modulating OGG1 activity on parasitaemia development, disease progression, survival rate, and histopathological outcomes in major organs of Plasmodium berghei (P. berghei) infected mice were evaluated. A significant difference in the mean parasitaemia was observed between the Vehicle, TH5487-treated, and O8-treated mice (p < 0.001). Vehicle-treated mice exhibited markedly elevated mean percentage parasitaemia and succumbed to the infection earlier than TH5487 and O8-treated mice. The O8-treated mice showed the highest parasitaemia reduction of 39.60 ± 1.53 % compared to TH5487-treated mice. Histopathological examination revealed less severe pathological features associated with P. berghei infection in mice treated with OGG1 inhibitors than in vehicle-treated malaria mice. Significant differences were observed in the sequestration of PRBC, inflammation, hemozoin deposition, and architectural loss in mice treated with O8 and TH5487 compared to untreated malaria mice. The results of this study suggested that OGG1 suppression led to a decrease in parasitaemia and severity of the histopathological features in P. berghei-infected mice. The increased survival of treated malaria mice further supported this effect. These findings indicate that OGG1 suppression could be a potential therapeutic strategy during malaria.
{"title":"Suppression of 8-oxoguanine DNA glycosylase (OGG1) activity produced positive impacts on disease severity, survival, and histopathological features of mice infected with Plasmodium berghei","authors":"Mukhtar Gambo Lawal , Abdullahi Samaila , Rusliza Basir , Nur Aimi Liyana Abd Aziz , Abdusalam Abdullah Alarabei , Maizaton Atmadini Abdullah , Roslaini Abd Majid , Norshariza Nordin , Mohd Khairi Hussain , Elysha Nur Ismail","doi":"10.1016/j.exppara.2025.108930","DOIUrl":"10.1016/j.exppara.2025.108930","url":null,"abstract":"<div><div>Malaria is a life-threatening disease, leading to significant morbidity and mortality. Malaria treatment remains a challenge due to its intricate pathophysiology and high levels of parasite resistance to many currently available antimalarial agents. Thus, there is an urgent need for more therapeutic strategies to combat the disease. OGG1 activity has been implicated in many inflammatory disease conditions, making suppressing OGG1 activity a potential target for therapeutic purposes. The current study aimed to determine the effect of suppressing OGG1 activity on the severity, survival, and histopathological features of <em>P. berghei</em>-infected mice. In this study, the effects of modulating OGG1 activity on parasitaemia development, disease progression, survival rate, and histopathological outcomes in major organs of <em>Plasmodium berghei</em> (<em>P. berghei)</em> infected mice were evaluated. A significant difference in the mean parasitaemia was observed between the Vehicle, TH5487-treated, and O8-treated mice (p < 0.001). Vehicle-treated mice exhibited markedly elevated mean percentage parasitaemia and succumbed to the infection earlier than TH5487 and O8-treated mice. The O8-treated mice showed the highest parasitaemia reduction of 39.60 ± 1.53 % compared to TH5487-treated mice. Histopathological examination revealed less severe pathological features associated with <em>P. berghei</em> infection in mice treated with OGG1 inhibitors than in vehicle-treated malaria mice. Significant differences were observed in the sequestration of PRBC, inflammation, hemozoin deposition, and architectural loss in mice treated with O8 and TH5487 compared to untreated malaria mice. The results of this study suggested that OGG1 suppression led to a decrease in parasitaemia and severity of the histopathological features in <em>P. berghei</em>-infected mice. The increased survival of treated malaria mice further supported this effect. These findings indicate that OGG1 suppression could be a potential therapeutic strategy during malaria.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108930"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143633987","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}
Susceptibility or resistance to various diseases, especially parasitic infections, largely depends on immune system function and genetics. Single nucleotide polymorphisms on the TAP1-637 and TAP2-379 genes may play a role in hydatidosis by affecting the immune system.
This study was conducted as a case-control study. After confirmation by serological ELISA method, blood samples were collected from 76 people with hydatid cyst and also from 76 healthy people. DNA was extracted from the samples and the ARMS-PCR technique was used to identify mutations. To evaluate the accuracy and ensure the PCR results, some samples were also sequenced in two groups with different genotypes.
Compared to the control group, the case group (infected group) had a higher frequency of the heterozygous Asp/Gly codon 637 of the TAP1 gene. In addition, the frequency of the Gly phenotype and allele was higher in the infected group (P < 0.05). Furthermore, the infected group had a higher frequency of the heterozygous Val/Ile codon 379 of the TAP2 gene. The frequency of the Ile phenotype and allele was also higher in the infected group than in the control group (P < 0. 05).
The results of this study showed that the Gly allele and Asp/Gly genotype in codon 637 of the TAP1 gene, as well as the Ile allele and Val/Ile genotype in codon 379 of the TAP2 gene are considered genetic risk factors for cystic echinococcosis.
{"title":"Cystic echinococcosis susceptibility is increased by polymorphisms in the transporter associated with antigen processing 1 and 2 genes","authors":"Susan Jabbaripour , Siamak Sandoghchian Shotorbani , Adel Spotin , Ehsan Ahmadpour , Navid Shomali , Mahmoud Mahami-Oskouei","doi":"10.1016/j.exppara.2025.108943","DOIUrl":"10.1016/j.exppara.2025.108943","url":null,"abstract":"<div><div>Susceptibility or resistance to various diseases, especially parasitic infections, largely depends on immune system function and genetics. Single nucleotide polymorphisms on the TAP1-637 and TAP2-379 genes may play a role in hydatidosis by affecting the immune system.</div><div>This study was conducted as a case-control study. After confirmation by serological ELISA method, blood samples were collected from 76 people with hydatid cyst and also from 76 healthy people. DNA was extracted from the samples and the ARMS-PCR technique was used to identify mutations. To evaluate the accuracy and ensure the PCR results, some samples were also sequenced in two groups with different genotypes.</div><div>Compared to the control group, the case group (infected group) had a higher frequency of the heterozygous Asp/Gly codon 637 of the TAP1 gene. In addition, the frequency of the Gly phenotype and allele was higher in the infected group (<em>P</em> < 0.05). Furthermore, the infected group had a higher frequency of the heterozygous Val/Ile codon 379 of the TAP2 gene. The frequency of the Ile phenotype and allele was also higher in the infected group than in the control group (<em>P</em> < 0. 05).</div><div>The results of this study showed that the Gly allele and Asp/Gly genotype in codon 637 of the TAP1 gene, as well as the Ile allele and Val/Ile genotype in codon 379 of the TAP2 gene are considered genetic risk factors for cystic echinococcosis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108943"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917321","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}
Visceral leishmaniasis (VL) is mainly caused by Leishmania donovani (Ld) and Leishmania (L.) infantum, and it is prevalent in Brazil, India and East Africa. VL is a serious health issue, affecting millions of people worldwide and causing thousands of deaths annually. The current treatments for leishmaniasis are inadequate because of their low efficacy, toxicity and growing resistance, underscoring the pressing need to explore new drugs.
Among the various molecular targets explored, trypanothione reductase (TR) is of special relevance because of its crucial function in regulating the parasite's redox homeostasis. Inhibiting TR can disrupt the redox homeostasis of the parasites, offering a promising strategy for developing new drugs with improved efficacy and safety profiles. In this study, 3D structure model of TR was elucidated by homology modelling and potential novel inhibitors against Leishmania donovani TR (LdTR) were identified by performing high-throughput virtual screening of 1615 FDA-approved drugs from the ZINC database via molecular docking, selecting top ligands on the basis of their high binding score and number of hydrogen bonds. These best hits are further subjected to Molecular Dynamics (MD) simulation and Molecular Mechanics Poisson- Boltzmann Surface Area (MM-PBSA) analysis. The results indicated that the binding scores of Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin are −10.9 and −10.6, −10.1, −9.7 and −9.6 kcal/mol respectively. The lead compounds i.e. Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin complexes with our target TR were found to be stable during MD simulation studies. Furthermore, MM-PBSA analysis demonstrated that these compounds had a high negative binding free energy. Thus, in-silico results showed that Dasatinib, Regorafenib, Bicalutamide and Raloxifene and Silodosin seem to have efficacy against TR for the treatment of VL. With further in vitro and in vivo investigations Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin could be a good candidate of choice for combating leishmaniasis.
{"title":"In silico screening and molecular dynamic simulations of FDA-approved drugs as an inhibitor of trypanothione reductase of Leishmania donovani","authors":"Pooja Beniwal , Chandra Kanta Bhusal , Gajendra Choudhary , Rakesh Sehgal , Bikash Medhi , Ajay Prakash , Sukhbir Kaur","doi":"10.1016/j.exppara.2025.108942","DOIUrl":"10.1016/j.exppara.2025.108942","url":null,"abstract":"<div><div>Visceral leishmaniasis (VL) is mainly caused by <em>Leishmania donovani (Ld) and Leishmania (L.) infantum,</em> and it is prevalent in Brazil, India and East Africa. VL is a serious health issue, affecting millions of people worldwide and causing thousands of deaths annually. The current treatments for leishmaniasis are inadequate because of their low efficacy, toxicity and growing resistance, underscoring the pressing need to explore new drugs.</div><div>Among the various molecular targets explored, trypanothione reductase (TR) is of special relevance because of its crucial function in regulating the parasite's redox homeostasis. Inhibiting TR can disrupt the redox homeostasis of the parasites, offering a promising strategy for developing new drugs with improved efficacy and safety profiles. In this study, 3D structure model of TR was elucidated by homology modelling and potential novel inhibitors against <em>Leishmania donovani</em> TR (<em>Ld</em>TR) were identified by performing high-throughput virtual screening of 1615 FDA-approved drugs from the ZINC database <em>via</em> molecular docking, selecting top ligands on the basis of their high binding score and number of hydrogen bonds. These best hits are further subjected to Molecular Dynamics (MD) simulation and Molecular Mechanics Poisson- Boltzmann Surface Area (MM-PBSA) analysis. The results indicated that the binding scores of Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin are −10.9 and −10.6, −10.1, −9.7 and −9.6 kcal/mol respectively. The lead compounds i.e. Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin complexes with our target TR were found to be stable during MD simulation studies. Furthermore, MM-PBSA analysis demonstrated that these compounds had a high negative binding free energy. Thus, <em>in-silico</em> results showed that Dasatinib, Regorafenib, Bicalutamide and Raloxifene and Silodosin seem to have efficacy against TR for the treatment of VL. With further <em>in vitro</em> and <em>in vivo</em> investigations Dasatinib, Regorafenib, Bicalutamide, Raloxifene and Silodosin could be a good candidate of choice for combating leishmaniasis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108942"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742708","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}
The rise in popularity of raw or undercooked fish dishes like sushi, sashimi, and ceviche has led to an increase in human cases of anisakiasis. This study aimed to evaluate the resistance of Anisakis larvae to substances like bleach, salt, brine, and marinades. Batches of 10 larvae were exposed to various concentrations of commercial bleach (pure, 50 %, 25 %, 12.5 %, 6.25 %) and salt (dry, 360 g/L, 90 g/L, 45 g/L, 20 g/L). Larvae were also tested with two vinaigrettes (one with mustard and one without) and four marinades made with vinegar and salt. Sodium hypochlorite was highly effective, killing larvae within minutes, with pure bleach eliminating them in 40 s. Dry salt killed them in under 70 min, while different concentrations of brine inactivated them over a period ranging from 3 to 17 days. Dressings with mustard worked faster than those without, and vinegar with higher acetic acid content (8 %) killed larvae in 6 h, compared to 29 h for 6 % acetic acid. Salt and vinegar marinades were more effective together: a combination of 8 % acetic acid and 6 % salt killed larvae in 2.5 h. Overall, sodium hypochlorite proved to be the most effective, while the combination of salt and vinegar also significantly reduced larval survival. These findings highlight the importance of using bleach for disinfecting surfaces and utensils after handling fish to prevent cross-contamination and ensure food safety.
{"title":"Evaluation of the resistance of Anisakis spp. larvae to products regularly used in the industry and households","authors":"Abdelkader Biary , Salma Berrouch , Brahim Mimouni , Jamal Eddine Hafid","doi":"10.1016/j.exppara.2025.108932","DOIUrl":"10.1016/j.exppara.2025.108932","url":null,"abstract":"<div><div>The rise in popularity of raw or undercooked fish dishes like sushi, sashimi, and ceviche has led to an increase in human cases of anisakiasis. This study aimed to evaluate the resistance of Anisakis larvae to substances like bleach, salt, brine, and marinades. Batches of 10 larvae were exposed to various concentrations of commercial bleach (pure, 50 %, 25 %, 12.5 %, 6.25 %) and salt (dry, 360 g/L, 90 g/L, 45 g/L, 20 g/L). Larvae were also tested with two vinaigrettes (one with mustard and one without) and four marinades made with vinegar and salt. Sodium hypochlorite was highly effective, killing larvae within minutes, with pure bleach eliminating them in 40 s. Dry salt killed them in under 70 min, while different concentrations of brine inactivated them over a period ranging from 3 to 17 days. Dressings with mustard worked faster than those without, and vinegar with higher acetic acid content (8 %) killed larvae in 6 h, compared to 29 h for 6 % acetic acid. Salt and vinegar marinades were more effective together: a combination of 8 % acetic acid and 6 % salt killed larvae in 2.5 h. Overall, sodium hypochlorite proved to be the most effective, while the combination of salt and vinegar also significantly reduced larval survival. These findings highlight the importance of using bleach for disinfecting surfaces and utensils after handling fish to prevent cross-contamination and ensure food safety.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"272 ","pages":"Article 108932"},"PeriodicalIF":1.4,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669366","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}
Pub Date : 2025-04-01Epub Date: 2025-03-04DOI: 10.1016/j.exppara.2025.108925
Isabela Resende Ávila , Weder Gomes de Oliveira , Cíntia Aparecida de Jesus Pereira , Mônica Alves Neves Diniz Ferreira , Thales Augusto Barçante , Joziana Muniz de Paiva Barçante , Walter dos Santos Lima
Angiostrongylus vasorum parasitizes the pulmonary arteries and heart of dogs (definitive hosts - DHs). Various mollusk species act as intermediate hosts (IHs), becoming infected through ingestion and/or penetration of first-stage larvae (L1), which subsequently develop into second-stage larvae (L2) and then third-stage larvae (L3), the latter being infective to DHs. Additionally, paratenic hosts (PHs), such as frogs, chickens, and rats, can harbor L3. This study aimed to assess whether Biomphalaria glabrata could function as a PH for A. vasorum, identifying potential larval penetration routes, migratory routes, and histological alterations at different time points post-infection. L3 larvae were recovered from B. glabrata mollusks 30 days after exposure to 1000 L1 of A. vasorum, using the Baermann technique. The recovered L3 were used to infect B. glabrata, with the number of 100 L3+ (L3 obtained from mollusks previously infected with 100 L3). Viable and motile L3+ of A. vasorum were detected within mollusk tissues, demonstrating their permissiveness to L3+ infection. The other infected mollusks were fixed in 10% formalin for histological analysis, revealing the presence of larvae, with a tendency in the cephalopodal region. Regarding the viability of L3+, two mixed-breed dogs were fed canine pâté containing L3+, and L1 larvae were detected in their feces. This study demonstrates, for the first time, the potential of B. glabrata to function as a PH in the A. vasorum cycle.
{"title":"Biomphalaria glabrata (Say, 1818) as a paratenic host of Angiostrongylus vasorum (Baillet,1866) Kamensky, 1905","authors":"Isabela Resende Ávila , Weder Gomes de Oliveira , Cíntia Aparecida de Jesus Pereira , Mônica Alves Neves Diniz Ferreira , Thales Augusto Barçante , Joziana Muniz de Paiva Barçante , Walter dos Santos Lima","doi":"10.1016/j.exppara.2025.108925","DOIUrl":"10.1016/j.exppara.2025.108925","url":null,"abstract":"<div><div><em>Angiostrongylus vasorum</em> parasitizes the pulmonary arteries and heart of dogs (definitive hosts - DHs). Various mollusk species act as intermediate hosts (IHs), becoming infected through ingestion and/or penetration of first-stage larvae (L1), which subsequently develop into second-stage larvae (L2) and then third-stage larvae (L3), the latter being infective to DHs. Additionally, paratenic hosts (PHs), such as frogs, chickens, and rats, can harbor L3. This study aimed to assess whether <em>Biomphalaria glabrata</em> could function as a PH for <em>A. vasorum</em>, identifying potential larval penetration routes, migratory routes, and histological alterations at different time points post-infection. L3 larvae were recovered from <em>B. glabrata</em> mollusks 30 days after exposure to 1000 L1 of <em>A. vasorum</em>, using the Baermann technique. The recovered L3 were used to infect <em>B. glabrata</em>, with the number of 100 L3+ (L3 obtained from mollusks previously infected with 100 L3). Viable and motile L3+ of <em>A. vasorum</em> were detected within mollusk tissues, demonstrating their permissiveness to L3+ infection. The other infected mollusks were fixed in 10% formalin for histological analysis, revealing the presence of larvae, with a tendency in the cephalopodal region. Regarding the viability of L3+, two mixed-breed dogs were fed canine pâté containing L3+, and L1 larvae were detected in their feces. This study demonstrates, for the first time, the potential of <em>B. glabrata</em> to function as a PH in the <em>A. vasorum</em> cycle.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108925"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143562387","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}
Pub Date : 2025-04-01Epub Date: 2025-03-12DOI: 10.1016/j.exppara.2025.108931
Yue Gou, Laura Agudelo Vallejo, Ana Podadera, Kenneth Ng, Sirinart Ananvoranich
Natural antisense transcripts (NATs), as a major subset of long non-coding RNAs (lncRNAs), are derived from every chromosome of Toxoplasma gondii, with the highest occurrence from ChrIa (18.4 NATs per Mbp) and the lowest from ChrIX (3.9 NATs per Mbp). GO analysis indicates that genes, which mRNA-NAT pairs are derived, are important for house-keeping and essential activities of T. gondii. Approximately half of protein encoding genes, whose loci also generate NATs, are involved in biological processes of metabolic processes and protein biochemistry and have canonical catalytic or binding activities. Using NAT of ubiquitin-like protease 1 (TgUlp1-NAT) as our study model, we showed that TgUlp1-NAT expression is part of cellular stress responses. Using a nanoluc reporter system, we confirmed that electroporation or membrane destabilization significantly induced TgUlp1-NAT expression. When the extracellular parasites were exposed to media containing high potassium, high sodium or altered osmotic pressure, TgUlp1-NAT expression was significantly down-regulated. In addition, two TgUlp1-NAT variants were detected in stressed T. gondii. One is an intron-retained variant, and the other is a spliced variant, referred to as TgUlp1-NATa and TgUlp1-NATb, respectively. The intronic sequence is 368 nts long, where regulatory small ncRNAs were derived. Taken together, we have confirmed that NAT expressions and functions are involved in cellular adaptation that allows T. gondii recover from stresses.
{"title":"Involvement of Toxoplasma gondii natural antisense transcripts in cellular stress responses","authors":"Yue Gou, Laura Agudelo Vallejo, Ana Podadera, Kenneth Ng, Sirinart Ananvoranich","doi":"10.1016/j.exppara.2025.108931","DOIUrl":"10.1016/j.exppara.2025.108931","url":null,"abstract":"<div><div>Natural antisense transcripts (NATs), as a major subset of long non-coding RNAs (lncRNAs), are derived from every chromosome of <em>Toxoplasma gondii</em>, with the highest occurrence from ChrIa (18.4 NATs per Mbp) and the lowest from ChrIX (3.9 NATs per Mbp). GO analysis indicates that genes, which mRNA-NAT pairs are derived, are important for house-keeping and essential activities of <em>T. gondii</em>. Approximately half of protein encoding genes, whose loci also generate NATs, are involved in biological processes of metabolic processes and protein biochemistry and have canonical catalytic or binding activities. Using NAT of ubiquitin-like protease 1 (<em>TgUlp1</em>-NAT) as our study model, we showed that <em>TgUlp1</em>-NAT expression is part of cellular stress responses. Using a nanoluc reporter system, we confirmed that electroporation or membrane destabilization significantly induced <em>TgUlp1</em>-NAT expression. When the extracellular parasites were exposed to media containing high potassium, high sodium or altered osmotic pressure, <em>TgUlp1</em>-NAT expression was significantly down-regulated. In addition, two <em>TgUlp1</em>-NAT variants were detected in stressed <em>T. gondii</em>. One is an intron-retained variant, and the other is a spliced variant, referred to as <em>TgUlp1</em>-NATa and <em>TgUlp1</em>-NATb, respectively. The intronic sequence is 368 nts long, where regulatory small ncRNAs were derived. Taken together, we have confirmed that NAT expressions and functions are involved in cellular adaptation that allows <em>T. gondii</em> recover from stresses.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108931"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630281","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}
Pub Date : 2025-04-01Epub Date: 2025-03-04DOI: 10.1016/j.exppara.2025.108926
Muhammad Zahid Sarfaraz , Sidra Abbas , Muhammad Arfan Zaman , Asia Parveen , Safina Kousar , Muhammad Zulqarnain
More than 10 species of Eimeria is found in cattle but Eimeria zuernii is one of the most pathogenic protozoan parasites affecting the global livestock industry. At the herd level, E. zuernii can cause illness in 10–80% of animals and reduce gross margins by 8–9%, leading to estimated annual losses of $731 million. This review highlights the economic impact, prevalence, and current control methods for E. zuernii infections, as well as the challenges associated with treatment and the development of alternative control methods. In the past two decades, 22 studies have examined synthetic drugs for managing eimeriosis in cattle. Various anticoccidial drugs (AcDs; Amprolium, decoquinate, ionophores, monensin, lasalocid, toltrazuril etc) have been used, but the efficacy of these drugs is no more consistent. Because of this, E. zuernii develops resistance to some of these anticoccidials. This trend highlights the urgent need for alternative treatments. The medicinal plants being enriched with various phytochemicals like flavonoids, tannins, alkaloids, terpenes etc have been reported as potential anticoccidial, anthelmintic and antimicrobial efficacy against the different parasites including Eimeria species in chicken, pig and rabbits. However, this review suggests the research community to treat the E. zuernii with a plant based medication (oils and extracts). This review critically emphasizes the need to acknowledge the significant role of medicinal plants in controlling eimeriosis and also the large-scale trials or standardization of plant-based therapies is required. By incorporating plant-based remedies into integrated treatment strategies alongside synthetic drugs and improved sanitation practices, we can effectively minimize financial losses and safeguard livestock health.
{"title":"A step forward to revolutionize the eimeriosis controlling strategies in cattle by using traditional medication","authors":"Muhammad Zahid Sarfaraz , Sidra Abbas , Muhammad Arfan Zaman , Asia Parveen , Safina Kousar , Muhammad Zulqarnain","doi":"10.1016/j.exppara.2025.108926","DOIUrl":"10.1016/j.exppara.2025.108926","url":null,"abstract":"<div><div>More than 10 species of <em>Eimeria</em> is found in cattle but <em>Eimeria zuernii</em> is one of the most pathogenic protozoan parasites affecting the global livestock industry. At the herd level, <em>E. zuernii</em> can cause illness in 10–80% of animals and reduce gross margins by 8–9%, leading to estimated annual losses of $731 million. This review highlights the economic impact, prevalence, and current control methods for <em>E. zuernii</em> infections, as well as the challenges associated with treatment and the development of alternative control methods. In the past two decades, 22 studies have examined synthetic drugs for managing eimeriosis in cattle. Various anticoccidial drugs (AcDs; Amprolium, decoquinate, ionophores, monensin, lasalocid, toltrazuril etc) have been used, but the efficacy of these drugs is no more consistent. Because of this, <em>E. zuernii</em> develops resistance to some of these anticoccidials. This trend highlights the urgent need for alternative treatments. The medicinal plants being enriched with various phytochemicals like flavonoids, tannins, alkaloids, terpenes etc have been reported as potential anticoccidial, anthelmintic and antimicrobial efficacy against the different parasites including <em>Eimeria</em> species in chicken, pig and rabbits. However, this review suggests the research community to treat the <em>E. zuernii</em> with a plant based medication (oils and extracts). This review critically emphasizes the need to acknowledge the significant role of medicinal plants in controlling eimeriosis and also the large-scale trials or standardization of plant-based therapies is required. By incorporating plant-based remedies into integrated treatment strategies alongside synthetic drugs and improved sanitation practices, we can effectively minimize financial losses and safeguard livestock health.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108926"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143566384","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}
Rhipicephalus (Boophilus) microplus represents one of the greatest challenges for livestock production in tropical and subtropical regions. Its control has been based on the use of synthetic chemical acaricides, which has led to the development of resistance to active ingredients belonging to the pyrethroid and organophosphate groups. Therefore, the search for new compounds with acaricidal potential is a priority in the control of ticks in cattle. This study evaluated the effect of different concentrations of coumarin derivatives (CD) on the survival of R. (B.) microplus larvae by larval bundle testing. The data obtained were analyzed using the Cox proportional hazard model. A reduction in larval survival was observed with coumarins that had methyl substituents in the R4 or R7 positions, especially C12, while an opposite effect was detected with chloromethyl substituents in R4 or isobutyl in R3. These findings highlight the potential of coumarin derivatives in the development of new strategies for tick control and the management of resistance to conventional acaricides.
{"title":"Survival analysis of Rhipicephalus microplus larvae treated with coumarinic derivatives","authors":"Carlos Eduardo Rodríguez Molano , José Jobanni Martínez Zambrano , Nidya Alexandra Segura Guerrero , Sergio Ulloa Torres , Valentina Rodríguez Montaña , Melisa Daniela Munevar Romero , Néstor Julián Pulido Suarez","doi":"10.1016/j.exppara.2025.108927","DOIUrl":"10.1016/j.exppara.2025.108927","url":null,"abstract":"<div><div><em>Rhipicephalus (Boophilus) microplus</em> represents one of the greatest challenges for livestock production in tropical and subtropical regions. Its control has been based on the use of synthetic chemical acaricides, which has led to the development of resistance to active ingredients belonging to the pyrethroid and organophosphate groups. Therefore, the search for new compounds with acaricidal potential is a priority in the control of ticks in cattle. This study evaluated the effect of different concentrations of coumarin derivatives (CD) on the survival of <em>R. (B.) microplus</em> larvae by larval bundle testing. The data obtained were analyzed using the Cox proportional hazard model. A reduction in larval survival was observed with coumarins that had methyl substituents in the R4 or R7 positions, especially C12, while an opposite effect was detected with chloromethyl substituents in R4 or isobutyl in R3. These findings highlight the potential of coumarin derivatives in the development of new strategies for tick control and the management of resistance to conventional acaricides.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108927"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572328","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}
Pub Date : 2025-04-01Epub Date: 2025-03-01DOI: 10.1016/j.exppara.2025.108924
Brunna Vianna Braga , Ludmila Rocha Lima , Larissa Figueiredo Belem , Dayane Alvarinho de Oliveira , Kildare Rocha de Miranda , Eduardo José Lopes-Torres
Trichuriasis – a disease caused by Trichuris trichiura – affects underserved communities. Infection occurs by the ingestion of embryonated eggs, a resilient structure against environmental fluctuations – an essential feature for the survival and transmission of trichurids. This study aims to enhance our comprehension of the trichurid eggs by providing a characterization of the ultrastructure of eggshell and first-stage (L1) larvae of T. muris, a key experimental model for trichuriasis. We employed the following microscopy techniques: light, fluorescence, confocal, Cryo-SEM, and Transmission electron microscopy (TEM), analyzing unfixed, chemical and cryofixed samples. Light microscopy revealed the structure of the eggshell, consisting of three main layers: Pellicula ovi (PO), chitinous layer (CHI), and the electron-dense parietal coating (EdPC). Fluorescence microscopy showed the calcein's high affinity for the eggshell and polar plugs, while the DAPI distinctly stained the L1 larval cells. Using confocal microscopy and 3D modeling, we quantified an average of 151 larval cells. TEM of high-pressure frozen and freeze-substituted samples revealed that the PO and the EdPC layers lacked sublayers, while the CHI layer was composed of 12–14 sublayers. The CHI also contained continuous distinct organization structure forming the polar plugs. The combination of different sample fixation methods and advanced imaging techniques was crucial for revealing structural details of both the eggshell and L1 larva, including the arrangement of cells, cuticle, and an anterior pointed structure. These findings provide deeper insights into the structural biology of T. muris and offer valuable information for advancing parasite control strategies in both human and veterinary context.
{"title":"Structural insights into Trichuris muris eggs through 3D modeling, Cryo-SEM, and TEM of samples prepared with HPF-FS","authors":"Brunna Vianna Braga , Ludmila Rocha Lima , Larissa Figueiredo Belem , Dayane Alvarinho de Oliveira , Kildare Rocha de Miranda , Eduardo José Lopes-Torres","doi":"10.1016/j.exppara.2025.108924","DOIUrl":"10.1016/j.exppara.2025.108924","url":null,"abstract":"<div><div>Trichuriasis – a disease caused by <em>Trichuris trichiura</em> – affects underserved communities. Infection occurs by the ingestion of embryonated eggs, a resilient structure against environmental fluctuations – an essential feature for the survival and transmission of trichurids. This study aims to enhance our comprehension of the trichurid eggs by providing a characterization of the ultrastructure of eggshell and first-stage (L1) larvae of <em>T</em>. <em>muris</em>, a key experimental model for trichuriasis. We employed the following microscopy techniques: light, fluorescence, confocal, Cryo-SEM, and Transmission electron microscopy (TEM), analyzing unfixed, chemical and cryofixed samples. Light microscopy revealed the structure of the eggshell, consisting of three main layers: <em>Pellicula ovi</em> (PO), chitinous layer (CHI), and the electron-dense parietal coating (EdPC). Fluorescence microscopy showed the calcein's high affinity for the eggshell and polar plugs, while the DAPI distinctly stained the L1 larval cells. Using confocal microscopy and 3D modeling, we quantified an average of 151 larval cells. TEM of high-pressure frozen and freeze-substituted samples revealed that the PO and the EdPC layers lacked sublayers, while the CHI layer was composed of 12–14 sublayers. The CHI also contained continuous distinct organization structure forming the polar plugs. The combination of different sample fixation methods and advanced imaging techniques was crucial for revealing structural details of both the eggshell and L1 larva, including the arrangement of cells, cuticle, and an anterior pointed structure. These findings provide deeper insights into the structural biology of <em>T. muris</em> and offer valuable information for advancing parasite control strategies in both human and veterinary context.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"271 ","pages":"Article 108924"},"PeriodicalIF":1.4,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143540744","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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