Pub Date : 2025-02-01DOI: 10.1016/j.exppara.2024.108887
Gulnara N. Karimbayova , Eldar K. Gasimov , Farid R. Mahmudov , Fuad H. Rzayev , Rovshan Khalilov , Aziz Eftekhari , Ayşe Baran
A light and electron microscopic study of skin biopsies taken from 9 patients with ulcerative leishmaniasis of both sexes aged from 14 to 26 years in the territory of the Republic of Azerbaijan was carried out. Based on clinical, morphological and electron microscopic parameters, all patients were diagnosed with ulcerative cutaneous anthroponotic leishmaniasis (Leishmania (L.) tropica). Stained and unstained ultrathin (50–70 nm) sections were viewed and photographed using a JEM-1400 transmission electron microscope at an accelerating voltage of 80–120 kV. Analysis of data from light and electron microscopic studies at the ultrastructural level made it possible to describe the structure and identify the morphometric parameters of the amastigote form of the intracellular parasite. Besides, it was found that the distance between the plasmalemmas of the parasitophorous vacuoles and the parasite L. (L.) tropica is only 1 nm. This facilitates the passage of the necessary nutrients for the survival of this parasite. One of the important factors in the chronic course and relapse of leishmaniasis caused by L.(L.) tropica is the penetration of the amastigote stage into the cytoplasm along with macrophages, and also into fibroblasts with low phagocytic activity. Pathological changes (deformed nucleus, damage to plasmalemma, focal destruction of the cytoplasm structures, vacuolization, etc.) in the parasite L. (L.) tropica, localized in macrophages, were identified and described.
{"title":"Ultrastructural characteristics of leishmania (L.)tropica (Wright, 1903) and cell-parasite relationships in cutaneous leishmaniasis. Light and electron microscopic study","authors":"Gulnara N. Karimbayova , Eldar K. Gasimov , Farid R. Mahmudov , Fuad H. Rzayev , Rovshan Khalilov , Aziz Eftekhari , Ayşe Baran","doi":"10.1016/j.exppara.2024.108887","DOIUrl":"10.1016/j.exppara.2024.108887","url":null,"abstract":"<div><div>A light and electron microscopic study of skin biopsies taken from 9 patients with ulcerative leishmaniasis of both sexes aged from 14 to 26 years in the territory of the Republic of Azerbaijan was carried out. Based on clinical, morphological and electron microscopic parameters, all patients were diagnosed with ulcerative cutaneous anthroponotic leishmaniasis (<em>Leishmania</em> (<em>L.</em>) <em>tropica</em>). Stained and unstained ultrathin (50–70 nm) sections were viewed and photographed using a JEM-1400 transmission electron microscope at an accelerating voltage of 80–120 kV. Analysis of data from light and electron microscopic studies at the ultrastructural level made it possible to describe the structure and identify the morphometric parameters of the amastigote form of the intracellular parasite. Besides, it was found that the distance between the plasmalemmas of the parasitophorous vacuoles and the parasite <em>L. (L.) tropica</em> is only 1 nm. This facilitates the passage of the necessary nutrients for the survival of this parasite. One of the important factors in the chronic course and relapse of leishmaniasis caused by <em>L.(L.) tropica</em> is the penetration of the amastigote stage into the cytoplasm along with macrophages, and also into fibroblasts with low phagocytic activity. Pathological changes (deformed nucleus, damage to plasmalemma, focal destruction of the cytoplasm structures, vacuolization, etc.) in the parasite <em>L. (L.) tropica,</em> localized in macrophages, were identified and described.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108887"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913894","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108896
Marília A. Machado , Debora A. Borges , Diefrey R. Campos , Natália L. Lopes , Fabio B. Scott , Julio I. Fernandes
The aim of this study was to evaluate the efficacy of a single 20 mg/kg dose of lotilaner for treating rabbits with concomitant infection by P. ovis and L. gibbus. Fourteen rabbits with diagnoses of otitis and fur infection, caused respectively by P. ovis and L. gibbus, were included. Samples of otic crust were collected with tweezers, weighed and examined microscopically to identify ectoparasites, which were counted to determine the number of mites per gram of crust. Hair samples were collected from three areas of 1 cm2 in different regions of the body, for examination under a stereomicroscope to determine occurrences of the mite L. gibbus. The animals in the treated group received a single oral dose of 20 mg/kg of lotilaner and were evaluated on days 0, +3, +7, +14, +21, +28 and + 35. Parasitological efficacy of 100% for controlling P. ovis was observed after seven days. Total clinical remission was reached 14 days after treatment. For L. gibbus, parasitological cure was obtained seven days after treatment. We concluded that a single dose of lotilaner was effective for controlling P. ovis and L. gibbus, leading to parasitological control and clinical improvement of the animals.
{"title":"Efficacy of lotilaner for treating rabbits naturally infested by Psoroptes ovis and Leporacarus gibbus, in Rio de Janeiro, Brazil","authors":"Marília A. Machado , Debora A. Borges , Diefrey R. Campos , Natália L. Lopes , Fabio B. Scott , Julio I. Fernandes","doi":"10.1016/j.exppara.2025.108896","DOIUrl":"10.1016/j.exppara.2025.108896","url":null,"abstract":"<div><div>The aim of this study was to evaluate the efficacy of a single 20 mg/kg dose of lotilaner for treating rabbits with concomitant infection by <em>P. ovis</em> and <em>L. gibbus</em>. Fourteen rabbits with diagnoses of otitis and fur infection, caused respectively by <em>P. ovis</em> and <em>L. gibbus</em>, were included. Samples of otic crust were collected with tweezers, weighed and examined microscopically to identify ectoparasites, which were counted to determine the number of mites per gram of crust. Hair samples were collected from three areas of 1 cm<sup>2</sup> in different regions of the body, for examination under a stereomicroscope to determine occurrences of the mite <em>L. gibbus</em>. The animals in the treated group received a single oral dose of 20 mg/kg of lotilaner and were evaluated on days 0, +3, +7, +14, +21, +28 and + 35. Parasitological efficacy of 100% for controlling <em>P. ovis</em> was observed after seven days. Total clinical remission was reached 14 days after treatment. For L. <em>gibbus</em>, parasitological cure was obtained seven days after treatment. We concluded that a single dose of lotilaner was effective for controlling <em>P. ovis</em> and <em>L. gibbus,</em> leading to parasitological control and clinical improvement of the animals.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108896"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142947102","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 : 2025-02-01DOI: 10.1016/j.exppara.2025.108901
Anny Martínez-Mira , Carlos Castillo-Saldarriaga , Liz Uribe-Gutiérrez , Elizabeth Céspedes-Gutíerrez , Diego Cortés-Rojas , Martha Gómez-Álvarez , Mauricio Cruz-Barrera
Biological control, which utilizes nematophagous fungi to reduce gastrointestinal nematode populations, may effectively diminish the need for chemical anthelmintic treatments. However, the limited knowledge surrounding the mass production of chlamydospores hinders the widespread use of biological products as alternatives to traditional anthelmintics. This study aimed to evaluate the development of liquid culture media for the large-scale production of the nematophagous fungi Duddingtonia flagrans using a systematic procedure, progressing from microplates to bioreactor. The liquid culture media were successfully validated in a 13 L bioreactor, achieving a yield of 2.18x107 chlam/g per day, which is comparable to the standard process of solid-state fermentation (SSF). Moreover, the nematode predatory ability remained unaffected by the changes in scales and exhibited a superior efficacy of over 90%. Consequently, this study demonstrates that the submerged fermentation approach serves as a viable alternative for the mass production of nematophagous fungi like D. flagrans.
{"title":"Culture media design and scaling-up of submerged fermentation for the nematophagous fungus Duddingtonia flagrans","authors":"Anny Martínez-Mira , Carlos Castillo-Saldarriaga , Liz Uribe-Gutiérrez , Elizabeth Céspedes-Gutíerrez , Diego Cortés-Rojas , Martha Gómez-Álvarez , Mauricio Cruz-Barrera","doi":"10.1016/j.exppara.2025.108901","DOIUrl":"10.1016/j.exppara.2025.108901","url":null,"abstract":"<div><div>Biological control, which utilizes nematophagous fungi to reduce gastrointestinal nematode populations, may effectively diminish the need for chemical anthelmintic treatments. However, the limited knowledge surrounding the mass production of chlamydospores hinders the widespread use of biological products as alternatives to traditional anthelmintics. This study aimed to evaluate the development of liquid culture media for the large-scale production of the nematophagous fungi <em>Duddingtonia flagrans</em> using a systematic procedure, progressing from microplates to bioreactor. The liquid culture media were successfully validated in a 13 L bioreactor, achieving a yield of 2.18x10<sup>7</sup> chlam/g per day, which is comparable to the standard process of solid-state fermentation (SSF). Moreover, the nematode predatory ability remained unaffected by the changes in scales and exhibited a superior efficacy of over 90%. Consequently, this study demonstrates that the submerged fermentation approach serves as a viable alternative for the mass production of nematophagous fungi like <em>D. flagrans</em>.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108901"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142978097","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}
Pub Date : 2025-02-01DOI: 10.1016/j.exppara.2024.108886
Geovane Dias-Lopes , Maria Eduarda Pinto Gonçalves , Barara Cristina de Albuquerque-Melo , Juliana Figueiredo Peixoto , Luzia Monteiro de Castro Côrtes , Franklin Souza-Silva , Léa Cysne-Finkelstein , Bernardo Acácio Santini Pereira , Carlos Roberto Alves
Leishmania (Viannia) braziliensis is associated with distinct clinical manifestations such as cutaneous, mucocutaneous, and disseminated leishmaniasis. One factor related to this clinical spectrum is the structure of parasite populations. This study investigates in vivo binomial BALB/c-L. (V.) braziliensis exploring the phenotypic variability of subpopulations (Thor03, Thor10 and Thor22) of Thor strain, which have previously been described as causing distinct pattern infection in vitro. In the third week after infection, differences were observed in the development curves of the lesions, with larger lesions in the Thor03 and Thor10. At this point, lymph nodes of mice infected with the Thor03 and Thor10 exhibited lower IL-12 and TNF values compared to infection with the Thor strain and Thor22. The infection with the Thor10 showed highest values of the cytokine IL-10 compared to those infected with the Thor strain, Thor03 and Thor22. In addition, no statistical differences in parasite load wer observed in the footpad in seventh week post inoculation. In contrast, the higher parasite load values were observed in the lymph nodes for Thor03, Thor10 and Thor22 subpopulations. The data obtained here show these subpopulations cause transient and non-severe footpad lesions with parasite persistence in draining lymph nodes, although some mice developed non-healing lesions. Parasites isolated from the paws and lymph nodes of these animals were unable to establish persistent lesions in subsequent experimental infection assays. Collectively, these findings highlight consistent differences of infectionevolution and host immune response modulation, during infection among the Thor03, Thor10 and Thor22 subpopulations , all derived from a single strain.
{"title":"Exploring the binomial BALB/c-Leishmania (Viannia) braziliensis model to assess the in vivo performance of Thor strain subpopulations","authors":"Geovane Dias-Lopes , Maria Eduarda Pinto Gonçalves , Barara Cristina de Albuquerque-Melo , Juliana Figueiredo Peixoto , Luzia Monteiro de Castro Côrtes , Franklin Souza-Silva , Léa Cysne-Finkelstein , Bernardo Acácio Santini Pereira , Carlos Roberto Alves","doi":"10.1016/j.exppara.2024.108886","DOIUrl":"10.1016/j.exppara.2024.108886","url":null,"abstract":"<div><div><em>Leishmania (Viannia) braziliensis</em> is associated with distinct clinical manifestations such as cutaneous, mucocutaneous, and disseminated leishmaniasis. One factor related to this clinical spectrum is the structure of parasite populations. This study investigates <em>in vivo</em> binomial BALB/c-<em>L. (V.) braziliensis</em> exploring the phenotypic variability of subpopulations (Thor03, Thor10 and Thor22) of Thor strain, which have previously been described as causing distinct pattern infection <em>in vitro</em>. In the third week after infection, differences were observed in the development curves of the lesions, with larger lesions in the Thor03 and Thor10. At this point, lymph nodes of mice infected with the Thor03 and Thor10 exhibited lower IL-12 and TNF values compared to infection with the Thor strain and Thor22. The infection with the Thor10 showed highest values of the cytokine IL-10 compared to those infected with the Thor strain, Thor03 and Thor22. In addition, no statistical differences in parasite load wer observed in the footpad in seventh week post inoculation. In contrast, the higher parasite load values were observed in the lymph nodes for Thor03, Thor10 and Thor22 subpopulations. The data obtained here show these subpopulations cause transient and non-severe footpad lesions with parasite persistence in draining lymph nodes, although some mice developed non-healing lesions. Parasites isolated from the paws and lymph nodes of these animals were unable to establish persistent lesions in subsequent experimental infection assays. Collectively, these findings highlight consistent differences of infectionevolution and host immune response modulation, during infection among the Thor03, Thor10 and Thor22 subpopulations , all derived from a single strain.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"269 ","pages":"Article 108886"},"PeriodicalIF":1.4,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142913658","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 : 2025-01-28DOI: 10.1016/j.exppara.2025.108910
Cinthia Rodrigues Melo , Caliandra Maria Bezerra Luna Lima , Brenna Marceliane de Melo Marcelino , Claudio Gabriel Lima-Júnior , Abrahão Alves de Oliveira Filho , Igor Gabriel da Silva Ramalho , Kardilandia Mendes de Oliveira , Gabriela Tafaela Dias , Giciane Carvalho Vieira , Valter Ferreira de Andrade-Neto , Margareth de Fátima Formiga Melo Diniz
One of the main factors that have made it difficult to control malaria is the large number of parasites that are resistant to the usual antimalarial drugs. Therefore, the development of new drugs that are more effective and with low toxicity for humans is necessary. In this work, we evaluated the adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-yl)acrylonitrile, also called CH3ISACN, as a potential antimalarial through in vitro studies, and evaluated its effects in silico and in vivo toxicology. For this, the compound CH3ISACN was exposed to P. falciparum W2 strain in infected human erythrocytes. The results showed that the CH3ISACN adduct showed good antiplasmodial activity, moderate cytotoxicity, and good cell viability. In addition, it has been shown to have good theoretical oral bioavailability and did not pose a risk of toxicity in in-silico studies. Through the in vivo study, acute toxicity was evaluated, in which doses of 300 mg/kg and 2000 mg/kg of the test substance were administered to adult female Wistar rats. CH3ISACN did not cause death in any of the animals, thus presenting a high LD50 and therefore low toxicity. There was no behavioral change in the animals, as well as in the other parameters evaluated; the highest dose tested did not cause any significant change. Only a reduction in urea concentration, but that did not bring relevant clinical significance. Through the histological study, no changes were found that would indicate intoxication in the organs of the animals. Finally, the CH3ISACN adduct presents itself as a promising drug candidate for the treatment of malaria.
{"title":"Study of antiplasmodial activity, toxicity, pharmacokinetic profiles of n-methyl-isatin (CH3ISACN) derivative","authors":"Cinthia Rodrigues Melo , Caliandra Maria Bezerra Luna Lima , Brenna Marceliane de Melo Marcelino , Claudio Gabriel Lima-Júnior , Abrahão Alves de Oliveira Filho , Igor Gabriel da Silva Ramalho , Kardilandia Mendes de Oliveira , Gabriela Tafaela Dias , Giciane Carvalho Vieira , Valter Ferreira de Andrade-Neto , Margareth de Fátima Formiga Melo Diniz","doi":"10.1016/j.exppara.2025.108910","DOIUrl":"10.1016/j.exppara.2025.108910","url":null,"abstract":"<div><div>One of the main factors that have made it difficult to control malaria is the large number of parasites that are resistant to the usual antimalarial drugs. Therefore, the development of new drugs that are more effective and with low toxicity for humans is necessary. In this work, we evaluated the adduct 2-(3-hydroxy-1-methyl-2-oxoindolin-3-yl)acrylonitrile, also called CH<sub>3</sub>ISACN, as a potential antimalarial through <em>in vitro</em> studies, and evaluated its effects <em>in silico</em> and <em>in vivo</em> toxicology. For this, the compound CH<sub>3</sub>ISACN was exposed to <em>P. falciparum</em> W2 strain in infected human erythrocytes. The results showed that the CH<sub>3</sub>ISACN adduct showed good antiplasmodial activity, moderate cytotoxicity, and good cell viability. In addition, it has been shown to have good theoretical oral bioavailability and did not pose a risk of toxicity in <em>in-silico</em> studies. Through the <em>in vivo</em> study, acute toxicity was evaluated, in which doses of 300 mg/kg and 2000 mg/kg of the test substance were administered to adult female <em>Wistar</em> rats. CH<sub>3</sub>ISACN did not cause death in any of the animals, thus presenting a high LD<sub>50</sub> and therefore low toxicity. There was no behavioral change in the animals, as well as in the other parameters evaluated; the highest dose tested did not cause any significant change. Only a reduction in urea concentration, but that did not bring relevant clinical significance. Through the histological study, no changes were found that would indicate intoxication in the organs of the animals. Finally, the CH<sub>3</sub>ISACN adduct presents itself as a promising drug candidate for the treatment of malaria.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"270 ","pages":"Article 108910"},"PeriodicalIF":1.4,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064488","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 : 2025-01-23DOI: 10.1016/j.exppara.2025.108899
Edwin Correa , Sara M. Robledo , Fernando Echeverri , Wiston Quiñones , Natalia Arbeláez , Javier Murillo , Tatiana Pineda , Fernando Torres
Cutaneous Leishmaniasis and Chagas disease are neglected tropical diseases that affect millions worldwide. Despite the high morbidity associated with these infections, current treatments are often highly toxic and are showing diminishing efficacy. Thus, new therapeutic options are urgently needed. In this study, bio-guided assays were conducted on the sawdust of Tabebuia chrysantha ("guayacán") to identify promising bioactive compounds. The ethanolic crude extract, five chromatography fractions, pure isoflavans sativan and vestitol, and a mixture were evaluated in vitro against Leishmania braziliensis and Trypanosoma cruzi. High leishmanicidal and trypanocidal activities were observed in the crude extract, fraction F2 (rich in sativan and vestitol), and the two pure isoflavans. Given the abundance and ease of obtaining the isoflavan mixture, its therapeutic potential was further evaluated in vivo in hamsters infected with L. braziliensis and mice infected with T. cruzi. Remarkably, topical and intraperitoneal administration of the chromatography fraction achieved a 67% clinical cure in hamsters with L. braziliensis infection and a 75% reduction in parasitemia in T. cruzi-infected mice. While the antiparasitic effects of certain flavonoids have been documented, this study is the first to demonstrate the efficacy of isoflavans in animal models for both diseases. The potential efficacy observed against T. cruzi and L. braziliensis, two pathogens with limited treatment options and a significant drawback of the available treatments, highlights the therapeutic potential of this combination of sativan and vestitol, which can be derived from timber industry waste, presenting an abundant and accessible source for further development.
{"title":"In vitro and in vivo leishmanicidal and trypanocidal activities of isoflavans from Tabebuia chrysantha (Jacq.) G. Nicholson timber by-products","authors":"Edwin Correa , Sara M. Robledo , Fernando Echeverri , Wiston Quiñones , Natalia Arbeláez , Javier Murillo , Tatiana Pineda , Fernando Torres","doi":"10.1016/j.exppara.2025.108899","DOIUrl":"10.1016/j.exppara.2025.108899","url":null,"abstract":"<div><div>Cutaneous Leishmaniasis and Chagas disease are neglected tropical diseases that affect millions worldwide. Despite the high morbidity associated with these infections, current treatments are often highly toxic and are showing diminishing efficacy. Thus, new therapeutic options are urgently needed. In this study, bio-guided assays were conducted on the sawdust of <em>Tabebuia chrysantha</em> (\"guayacán\") to identify promising bioactive compounds. The ethanolic crude extract, five chromatography fractions, pure isoflavans sativan and vestitol, and a mixture were evaluated in vitro against <em>Leishmania braziliensis</em> and <em>Trypanosoma cruzi</em>. High leishmanicidal and trypanocidal activities were observed in the crude extract, fraction F2 (rich in sativan and vestitol), and the two pure isoflavans. Given the abundance and ease of obtaining the isoflavan mixture, its therapeutic potential was further evaluated <em>in vivo</em> in hamsters infected with <em>L. braziliensis</em> and mice infected with <em>T. cruzi</em>. Remarkably, topical and intraperitoneal administration of the chromatography fraction achieved a 67% clinical cure in hamsters with <em>L. braziliensis</em> infection and a 75% reduction in parasitemia in <em>T. cruzi</em>-infected mice. While the antiparasitic effects of certain flavonoids have been documented, this study is the first to demonstrate the efficacy of isoflavans in animal models for both diseases. The potential efficacy observed against <em>T. cruzi</em> and <em>L. braziliensis</em>, two pathogens with limited treatment options and a significant drawback of the available treatments, highlights the therapeutic potential of this combination of sativan and vestitol, which can be derived from timber industry waste, presenting an abundant and accessible source for further development.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"270 ","pages":"Article 108899"},"PeriodicalIF":1.4,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143036843","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}
Pub Date : 2025-01-19DOI: 10.1016/j.exppara.2025.108903
Saiaka Ingrid Parente Rocha , Victor Borges Fernandes , Wildson Max Barbosa da Silva , Lucas Soares Frota , Andreza Raposo Garcia , Flora Fernanda Schulze Spíndola , Caio Henrique Alexandre Roberto , Vanessa Maria Rodrigues de Souza , Klinger Antonio da Franca Rodrigues , Igor de Almeida Rodrigues , Emmanuel Silva Marinho , Márcia Machado Marinho , Nadja Soares Vila-Nova , Selene Maia de Morais
The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilisation of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against Leishmania donovani, the causative agent of visceral leishmaniasis, was reported for the first time. Hesperetin was obtained through the hydrolysis of hesperidin and subsequently subjected to chemical characterisation via Infrared and NMR spectroscopy. The antileishmanial activity and cytotoxicity against RAW 264.7 macrophages were evaluated using the MTT colorimetric assay. In order to investigate the potential mechanisms of action, in vitro acetylcholinesterase inhibition assays and molecular docking analyses were conducted. Hesperetin showed an antipromastigote effect (IC50: 62.89 μM) with no evidence of cytotoxicity (CC50: 612.8 μM), with a selectivity index (SI) of 9.74, being 5.4 times more effective than trivalent antimony. In comparison, antimony showed an IC50 of 80.16 μM, a CC50 of 145.04 μM and a SI of 1.8, indicating a limited safety margin. The compound was observed to inhibit acetylcholinesterase (IC50 of 18.44 μg/mL), present in mitochondrial and plasma membrane of the parasite. Molecular docking and dynamic simulations indicated that hesperetin inhibit sterol C-24 reductase, essential for ergosterol biosynthesis and membrane integrity of L. donovani and shows activity against N-myristoyl transferase, responsible for parasite proliferation cycle. These findings open promising avenues for the development of effective antileishmanial therapies.
{"title":"Antileishmanial activity of hesperetin on Leishmania donovani, in vitro and in silico inhibition of acetylcholinesterase and investigation of the targets sterol C-24 reductase and N-myristoyltransferase","authors":"Saiaka Ingrid Parente Rocha , Victor Borges Fernandes , Wildson Max Barbosa da Silva , Lucas Soares Frota , Andreza Raposo Garcia , Flora Fernanda Schulze Spíndola , Caio Henrique Alexandre Roberto , Vanessa Maria Rodrigues de Souza , Klinger Antonio da Franca Rodrigues , Igor de Almeida Rodrigues , Emmanuel Silva Marinho , Márcia Machado Marinho , Nadja Soares Vila-Nova , Selene Maia de Morais","doi":"10.1016/j.exppara.2025.108903","DOIUrl":"10.1016/j.exppara.2025.108903","url":null,"abstract":"<div><div>The current treatment of leishmaniasis is confronted with significant challenges, including limited efficacy, adverse effects, and parasite resistance to drugs. The search for alternative therapeutic options, including the utilisation of natural products, has demonstrated considerable promise. In this study, the antileishmanial activity of the flavonoid hesperetin against <em>Leishmania donovani</em>, the causative agent of visceral leishmaniasis, was reported for the first time. Hesperetin was obtained through the hydrolysis of hesperidin and subsequently subjected to chemical characterisation via Infrared and NMR spectroscopy. The antileishmanial activity and cytotoxicity against RAW 264.7 macrophages were evaluated using the MTT colorimetric assay. In order to investigate the potential mechanisms of action, <em>in vitro</em> acetylcholinesterase inhibition assays and molecular docking analyses were conducted. Hesperetin showed an antipromastigote effect (IC<sub>50</sub>: 62.89 μM) with no evidence of cytotoxicity (CC<sub>50</sub>: 612.8 μM), with a selectivity index (SI) of 9.74, being 5.4 times more effective than trivalent antimony. In comparison, antimony showed an IC<sub>50</sub> of 80.16 μM, a CC<sub>50</sub> of 145.04 μM and a SI of 1.8, indicating a limited safety margin. The compound was observed to inhibit acetylcholinesterase (IC<sub>50</sub> of 18.44 μg/mL), present in mitochondrial and plasma membrane of the parasite. Molecular docking and dynamic simulations indicated that hesperetin inhibit sterol C-24 reductase, essential for ergosterol biosynthesis and membrane integrity of <em>L. donovani</em> and shows activity against N-myristoyl transferase, responsible for parasite proliferation cycle. These findings open promising avenues for the development of effective antileishmanial therapies.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"270 ","pages":"Article 108903"},"PeriodicalIF":1.4,"publicationDate":"2025-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002784","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 : 2025-01-16DOI: 10.1016/j.exppara.2025.108902
Eman Attia Elmorsy
{"title":"Molecular host-parasite interaction at the site of vector bite","authors":"Eman Attia Elmorsy","doi":"10.1016/j.exppara.2025.108902","DOIUrl":"10.1016/j.exppara.2025.108902","url":null,"abstract":"","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"270 ","pages":"Article 108902"},"PeriodicalIF":1.4,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002785","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 : 2025-01-01DOI: 10.1016/j.exppara.2024.108867
Laura Isabel Vázquez-Carrillo , Jonathan Puente-Rivera , Julio Cesar Torres-Romero , Laura Itzel Quintas-Granados , María Elizbeth Alvarez-Sánchez
An active immunoproteome of Trichomonas vaginalis was obtained by 2D-Western blotting (2D-WB). Subsequent proteoform identification by mass spectrometry (MS) showed differential expression and specific immunoreactions of multiple proteins mediated by the presence of Zn2+. A total of 25 proteoforms were immunologically reactive, generally under Zn2+ conditions, and MS analysis revealed that the fimbrin (plastin) of T. vaginalis (TvFim1) was recognized by the sera of male patients with trichomoniasis but not by the sera of infected female patients. These findings suggest that the protein is immunogenic during active male trichomoniasis and that cytoskeletal proteins, including fimbrins, may also act as virulence factors in addition to their role in parasite morphogenesis.
{"title":"The Fimbrin TvFim1, an immunogenic protein involved in male trichomoniasis","authors":"Laura Isabel Vázquez-Carrillo , Jonathan Puente-Rivera , Julio Cesar Torres-Romero , Laura Itzel Quintas-Granados , María Elizbeth Alvarez-Sánchez","doi":"10.1016/j.exppara.2024.108867","DOIUrl":"10.1016/j.exppara.2024.108867","url":null,"abstract":"<div><div>An active immunoproteome of <em>Trichomonas vaginalis</em> was obtained by 2D-Western blotting (2D-WB). Subsequent proteoform identification by mass spectrometry (MS) showed differential expression and specific immunoreactions of multiple proteins mediated by the presence of Zn<sup>2+</sup>. A total of 25 proteoforms were immunologically reactive, generally under Zn<sup>2+</sup> conditions, and MS analysis revealed that the fimbrin (plastin) of <em>T. vaginalis</em> (TvFim1) was recognized by the sera of male patients with trichomoniasis but not by the sera of infected female patients. These findings suggest that the protein is immunogenic during active male trichomoniasis and that cytoskeletal proteins, including fimbrins, may also act as virulence factors in addition to their role in parasite morphogenesis.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"268 ","pages":"Article 108867"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142791459","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}
This study presents a comprehensive methodology for the synthesis, characterization, and evaluation of selenium nanoparticles (SeNPs) for their anthelmintic properties against Trichinella spiralis. SeNPs were synthesized via a chemical reduction method, with a color change from clear white to brownish-red indicating nanoparticle formation. X-ray diffraction (XRD) analysis revealed broad peaks at 2θ ranges of 20–33° and 48–58°, confirming the semi-crystalline nature of the nanoparticles. UV–Vis absorption spectroscopy identified a characteristic peak at around 295 nm. High-resolution transmission electron microscopy (HRTEM) showed spherical, monodispersed SeNPs with smooth surfaces, ranging from 30 to 106 nm in size, with an average diameter of 69 nm. Forty-two male rats were divided into six groups, including healthy controls and T. spiralis-infected rats treated with varying doses of SeNPs. Body and organ weight indexes were assessed at the start, during the intestinal and muscular phases. Significant body weight increases were observed during the intestinal phase, particularly in the positive control group. Organ weight analysis showed a significant decrease in liver weight in the high-dose SeNP group compared to controls. SeNP treatment significantly reduced the number of adult worms in the intestines and encysted larvae in muscles. The high-dose group reduced adult worms and encysted larvae more than the low-dose group. Scanning electron microscopy (SEM) revealed morphological alterations in adult T. spiralis worms, including wrinkled architecture, torn cuticles, and severe sloughing in high-dose treated worms. During the muscular phase, significant decreases in hemoglobin and red blood cell count were observed in the positive control group, while SeNP treatment restored these levels. Liver enzyme activities (AST, ALT, and ALP) were elevated in infected untreated groups but were enhanced with SeNP treatment. Antioxidant enzyme activities (CAT, and SOD) increased in SeNP-treated groups, with higher doses showing greater efficacy in reducing oxidative stress markers (MDA) and inflammatory markers (TNF-α, and IL-6). Histological analysis showed significant restoration of normal intestinal architecture in high-dose SeNP-treated infected rats, including the reduction of villus atrophy and leukocyte infiltration. In diaphragm muscles, high-dose SeNP treatment minimized encysted larval deposition and restored normal muscle architecture. We can conclude that the study demonstrates the potential of SeNPs as an effective anthelmintic agent against T. spiralis, highlighting their synthesis, characterization, and therapeutic efficacy.
{"title":"Antiparasitic and antioxidant effects of selenium nanoparticles on parasitic Trichinella spiralis","authors":"Yosra Adel Ebrahim Nagdy, Zohour Ebrahim Nabil, Nahla Soliman El-Shenawy, Elham Ali Elkhawass","doi":"10.1016/j.exppara.2024.108876","DOIUrl":"10.1016/j.exppara.2024.108876","url":null,"abstract":"<div><div>This study presents a comprehensive methodology for the synthesis, characterization, and evaluation of selenium nanoparticles (SeNPs) for their anthelmintic properties against <em>Trichinella spiralis</em>. SeNPs were synthesized via a chemical reduction method, with a color change from clear white to brownish-red indicating nanoparticle formation. X-ray diffraction (XRD) analysis revealed broad peaks at 2θ ranges of 20–33° and 48–58°, confirming the semi-crystalline nature of the nanoparticles. UV–Vis absorption spectroscopy identified a characteristic peak at around 295 nm. High-resolution transmission electron microscopy (HRTEM) showed spherical, monodispersed SeNPs with smooth surfaces, ranging from 30 to 106 nm in size, with an average diameter of 69 nm. Forty-two male rats were divided into six groups, including healthy controls and <em>T. spiralis</em>-infected rats treated with varying doses of SeNPs. Body and organ weight indexes were assessed at the start, during the intestinal and muscular phases. Significant body weight increases were observed during the intestinal phase, particularly in the positive control group. Organ weight analysis showed a significant decrease in liver weight in the high-dose SeNP group compared to controls. SeNP treatment significantly reduced the number of adult worms in the intestines and encysted larvae in muscles. The high-dose group reduced adult worms and encysted larvae more than the low-dose group. Scanning electron microscopy (SEM) revealed morphological alterations in adult <em>T. spiralis</em> worms, including wrinkled architecture, torn cuticles, and severe sloughing in high-dose treated worms. During the muscular phase, significant decreases in hemoglobin and red blood cell count were observed in the positive control group, while SeNP treatment restored these levels. Liver enzyme activities (AST, ALT, and ALP) were elevated in infected untreated groups but were enhanced with SeNP treatment. Antioxidant enzyme activities (CAT, and SOD) increased in SeNP-treated groups, with higher doses showing greater efficacy in reducing oxidative stress markers (MDA) and inflammatory markers (TNF-α, and IL-6). Histological analysis showed significant restoration of normal intestinal architecture in high-dose SeNP-treated infected rats, including the reduction of villus atrophy and leukocyte infiltration. In diaphragm muscles, high-dose SeNP treatment minimized encysted larval deposition and restored normal muscle architecture. We can conclude that the study demonstrates the potential of SeNPs as an effective anthelmintic agent against <em>T. spiralis</em>, highlighting their synthesis, characterization, and therapeutic efficacy.</div></div>","PeriodicalId":12117,"journal":{"name":"Experimental parasitology","volume":"268 ","pages":"Article 108876"},"PeriodicalIF":1.4,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142821950","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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