Pub Date : 2025-12-06DOI: 10.1016/j.molbiopara.2025.111719
Mohammed Ahmed , Charmaine Bishop , Andrea Betancourt , Vicky Hunt , Mark Viney
The depletion of ribosomal RNA (rRNA) is a critical step in RNA-sequence analyses, used to enhance the detection of non-rRNA molecules, such as messenger RNAs and non-coding RNAs. However, the efficiency and potential biases introduced by different rRNA depletion methods remain poorly characterized. Here, we evaluated three commercially available rRNA depletion kits – QIAseq FastSelect, riboPOOL, Zymo-Seq RiboFree – for their performance with the parasitic nematode Strongyloides ratti. We assessed the kits’ efficiency in rRNA removal, the recovery of expressed genes and transposable elements, and the detection of spliced leader sequences and genes’ operonic organization. Zymo-Seq demonstrated the highest sensitivity and minimal bias in a measure of gene expression, while QIAseq showed the least rRNA depletion and significant differential expression biases. Our findings underscore the importance of empirical validation of rRNA depletion methods, particularly for parasites and non-model organisms, and we suggest that Zymo-Seq as the optimal choice for S. ratti and related nematodes.
{"title":"The efficacy and accuracy of ribosomal RNA depletion methods in the parasitic nematode Strongyloides ratti","authors":"Mohammed Ahmed , Charmaine Bishop , Andrea Betancourt , Vicky Hunt , Mark Viney","doi":"10.1016/j.molbiopara.2025.111719","DOIUrl":"10.1016/j.molbiopara.2025.111719","url":null,"abstract":"<div><div>The depletion of ribosomal RNA (rRNA) is a critical step in RNA-sequence analyses, used to enhance the detection of non-rRNA molecules, such as messenger RNAs and non-coding RNAs. However, the efficiency and potential biases introduced by different rRNA depletion methods remain poorly characterized. Here, we evaluated three commercially available rRNA depletion kits – QIAseq FastSelect, riboPOOL, Zymo-Seq RiboFree – for their performance with the parasitic nematode <em>Strongyloides ratti</em>. We assessed the kits’ efficiency in rRNA removal, the recovery of expressed genes and transposable elements, and the detection of spliced leader sequences and genes’ operonic organization. Zymo-Seq demonstrated the highest sensitivity and minimal bias in a measure of gene expression, while QIAseq showed the least rRNA depletion and significant differential expression biases. Our findings underscore the importance of empirical validation of rRNA depletion methods, particularly for parasites and non-model organisms, and we suggest that Zymo-Seq as the optimal choice for <em>S. ratti</em> and related nematodes.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"265 ","pages":"Article 111719"},"PeriodicalIF":1.5,"publicationDate":"2025-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145705561","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 : 2025-12-01DOI: 10.1016/j.molbiopara.2025.111711
Raghda R. Qadir , Hamin J. Mohammed , Samir M. Hamad , Yousef Mirzaei , Mukhtar H. Ahmed
Background
Coccidiosis is a significant parasitic disease affecting poultry, resulting in substantial economic losses due to its impact on growth, increased mortality, and compromised bird health.
Aim
This study aimed to evaluate the in vitro anticoccidial effects of a novel green-synthesised ZnO-Ag-CuO nanocomposite, using Thymus vulgaris extract.
Methods
The nanocomposite was synthesised through an eco-friendly method employing T. vulgaris as a stabilising and reducing agent. Characterisation was performed using UV-Vis spectroscopy, FTIR, XRD, SEM, and EDX, confirming its high crystallinity, nanoscale size, and the successful integration of ZnO, Ag, and CuO phases. Anticoccidial activity was assessed via a sporulation inhibition assay against Eimeria spp. Oocysts isolated from broiler chickens.
Results
The nanocomposite significantly reduced oocyst sporulation and increased the proportion of damaged and unpopulated oocysts in a dose-dependent manner (0.1–1 mg/mL) (p < 0.0001). ZnO–Ag–CuO NCs showed a dose-dependent anticoccidial effect, reducing sporulated oocysts to 56.41 %, 33.63 % and 22.9 % at 0.1, 0.5 and 1.0 mg/mL (control 88.62 %; p < 0.0001). Unsporulated oocysts increased to 15.9–62.22 % (control 13.33 %), while damaged oocysts reached up to 14.82 % (control 0 %).
Conclusion
The green-synthesised ZnO-Ag-CuO nanocomposite demonstrated strong in vitro anticoccidial activity; however, further studies are needed to evaluate the nanocomposite’s potential toxicity, formulation, stability under biological conditions, safety before practical applications and potential environmental impact within a One Health framework.
Future plans
In vivo studies are recommended to validate the efficacy and safety of these approaches for large-scale applications.
{"title":"Green-synthesised ZnO-Ag-CuO nanocomposites from Thymus vulgaris and their in vitro anticoccidial activity","authors":"Raghda R. Qadir , Hamin J. Mohammed , Samir M. Hamad , Yousef Mirzaei , Mukhtar H. Ahmed","doi":"10.1016/j.molbiopara.2025.111711","DOIUrl":"10.1016/j.molbiopara.2025.111711","url":null,"abstract":"<div><h3>Background</h3><div>Coccidiosis is a significant parasitic disease affecting poultry, resulting in substantial economic losses due to its impact on growth, increased mortality, and compromised bird health.</div></div><div><h3>Aim</h3><div>This study aimed to evaluate the <em>in vitro</em> anticoccidial effects of a novel green-synthesised ZnO-Ag-CuO nanocomposite, using <em>Thymus vulgaris</em> extract.</div></div><div><h3>Methods</h3><div>The nanocomposite was synthesised through an eco-friendly method employing <em>T. vulgaris</em> as a stabilising and reducing agent. Characterisation was performed using UV-Vis spectroscopy, FTIR, XRD, SEM, and EDX, confirming its high crystallinity, nanoscale size, and the successful integration of ZnO, Ag, and CuO phases. Anticoccidial activity was assessed via a sporulation inhibition assay against <em>Eimeria</em> spp. Oocysts isolated from broiler chickens.</div></div><div><h3>Results</h3><div>The nanocomposite significantly reduced oocyst sporulation and increased the proportion of damaged and unpopulated oocysts in a dose-dependent manner (0.1–1 mg/mL) (p < 0.0001). ZnO–Ag–CuO NCs showed a dose-dependent anticoccidial effect, reducing sporulated oocysts to 56.41 %, 33.63 % and 22.9 % at 0.1, 0.5 and 1.0 mg/mL (control 88.62 %; p < 0.0001). Unsporulated oocysts increased to 15.9–62.22 % (control 13.33 %), while damaged oocysts reached up to 14.82 % (control 0 %).</div></div><div><h3>Conclusion</h3><div>The green-synthesised ZnO-Ag-CuO nanocomposite demonstrated strong <em>in vitro</em> anticoccidial activity; however, further studies are needed to evaluate the nanocomposite’s potential toxicity, formulation, stability under biological conditions, safety before practical applications and potential environmental impact within a One Health framework.</div></div><div><h3>Future plans</h3><div>In vivo studies are recommended to validate the efficacy and safety of these approaches for large-scale applications.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111711"},"PeriodicalIF":1.5,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620183","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}
Parasitic diseases pose significant threats to both human and veterinary health, causing morbidity, mortality, and economic losses. Effective diagnostics are critical, yet conventional methods such as microscopy, serology, and polymerase chain reaction (PCR) are limited by low sensitivity, cross-reactivity, or dependence on costly equipment and skilled personnel. Isothermal amplification techniques, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), have improved point-of-care (POC) applications but remain limited by nonspecific amplification and reduced sensitivity for low-copy targets. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems have emerged as transformative tools in molecular diagnostics, offering high sensitivity, specificity, rapidity, and cost-effectiveness. This review presents an overview of CRISPR-Cas systems, their historical development, classification (Class 1 and Class 2, Types I–VI), molecular mechanisms, and diagnostic potential in parasitic diseases, with illustrative examples from studies published between 2017 and May 2025. Despite significant progress, CRISPR-based diagnostics face challenges such as off-target activity, dependence on nucleic acid amplification, and complex sample preparation. Future directions focus on amplification-free detection, multiplexed assay development, and integration with nanotechnology, microfluidics, smartphone-based devices, and artificial intelligence. CRISPR-Cas technologies thus represent a promising frontier in next-generation diagnostics for parasitic disease surveillance, control, and personalized healthcare in both human and veterinary health.
{"title":"CRISPR-Cas systems: Pioneering next-generation diagnostic tools for parasitic diseases","authors":"Rupesh Verma , Giridhari Das , Manjunathachar H.V. , Nirmala Muwel , Raunak Choudhary , Suman Kumar , Subhradal Nath , Anil Gattani , Vandana Gupta , Rajesh Kumar Sharma , Y. Ajith","doi":"10.1016/j.molbiopara.2025.111708","DOIUrl":"10.1016/j.molbiopara.2025.111708","url":null,"abstract":"<div><div>Parasitic diseases pose significant threats to both human and veterinary health, causing morbidity, mortality, and economic losses. Effective diagnostics are critical, yet conventional methods such as microscopy, serology, and polymerase chain reaction (PCR) are limited by low sensitivity, cross-reactivity, or dependence on costly equipment and skilled personnel. Isothermal amplification techniques, such as loop-mediated isothermal amplification (LAMP) and recombinase polymerase amplification (RPA), have improved point-of-care (POC) applications but remain limited by nonspecific amplification and reduced sensitivity for low-copy targets. Clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) systems have emerged as transformative tools in molecular diagnostics, offering high sensitivity, specificity, rapidity, and cost-effectiveness. This review presents an overview of CRISPR-Cas systems, their historical development, classification (Class 1 and Class 2, Types I–VI), molecular mechanisms, and diagnostic potential in parasitic diseases, with illustrative examples from studies published between 2017 and May 2025. Despite significant progress, CRISPR-based diagnostics face challenges such as off-target activity, dependence on nucleic acid amplification, and complex sample preparation. Future directions focus on amplification-free detection, multiplexed assay development, and integration with nanotechnology, microfluidics, smartphone-based devices, and artificial intelligence. CRISPR-Cas technologies thus represent a promising frontier in next-generation diagnostics for parasitic disease surveillance, control, and personalized healthcare in both human and veterinary health.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111708"},"PeriodicalIF":1.5,"publicationDate":"2025-10-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145401241","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}
Candida albicans poses a serious health threat, contributing to approximately 1.5 million deaths each year. Although azole drugs have been used to manage this pathogen, their effectiveness has been compromised by the emergence of drug-resistant strains. Therefore, silver nanoparticles (nano-Ag) and vitamin D₃ are being explored as complementary rather than direct antifungal agents. The present study aims to investigate the effects of microbially synthesized nano-Ag alone and with vitamin D3 against fluconazole-susceptible and fluconazole-resistant C. albicans. The broth microdilution method, checkerboard microdilution assay, hyphal formation inhibition, and gene expression analysis of key virulence genes were performed on C. albicans treated with microbially synthesized nano-Ag, either alone or combined with vitamin D3. Furthermore, the survival rate, haemocyte density, and microbial load in haemolymph were assessed in C. albicans-infected Galleria mellonella larvae after treatment with microbially synthesized nano-Ag alone and with vitamin D3. The results demonstrated that microbially synthesized nano-Ag exhibited synergistic and additive interactions with vitamin D3 against C. albicans. This study also revealed that the combination of microbially synthesized nano-Ag and vitamin D3 effectively inhibited hyphal formation and significantly downregulated the expression of SAP and HWP1 genes in C. albicans. In vivo experiments further demonstrated that this combined treatment enhanced larval survival, increased haemocyte density, and reduced microbial load in the haemolymph. Taken together, these findings underscore the potential of microbially synthesized nano-Ag with vitamin D3 as a promising synergistic treatment for C. albicans infections, particularly those resistant to fluconazole.
{"title":"Potential synergistic antifungal activity of microbially synthesized silver nanoparticles and vitamin D3 against Candida albicans: vitro and Galleria mellonella model studies","authors":"Zainab Saberi Moqaddam , Pouria Khodavandi , Alireza Khodavandi , Fahimeh Alizadeh","doi":"10.1016/j.molbiopara.2025.111710","DOIUrl":"10.1016/j.molbiopara.2025.111710","url":null,"abstract":"<div><div><em>Candida albicans</em> poses a serious health threat, contributing to approximately 1.5 million deaths each year. Although azole drugs have been used to manage this pathogen, their effectiveness has been compromised by the emergence of drug-resistant strains. Therefore, silver nanoparticles (nano-Ag) and vitamin D<sub>₃</sub> are being explored as complementary rather than direct antifungal agents. The present study aims to investigate the effects of microbially synthesized nano-Ag alone and with vitamin D<sub>3</sub> against fluconazole-susceptible and fluconazole-resistant <em>C. albicans</em>. The broth microdilution method, checkerboard microdilution assay, hyphal formation inhibition, and gene expression analysis of key virulence genes were performed on <em>C. albicans</em> treated with microbially synthesized nano-Ag, either alone or combined with vitamin D<sub>3</sub>. Furthermore, the survival rate, haemocyte density, and microbial load in haemolymph were assessed in <em>C. albicans</em>-infected <em>Galleria mellonella</em> larvae after treatment with microbially synthesized nano-Ag alone and with vitamin D<sub>3</sub>. The results demonstrated that microbially synthesized nano-Ag exhibited synergistic and additive interactions with vitamin D<sub>3</sub> against <em>C. albicans</em>. This study also revealed that the combination of microbially synthesized nano-Ag and vitamin D<sub>3</sub> effectively inhibited hyphal formation and significantly downregulated the expression of <em>SAP</em> and <em>HWP1</em> genes in <em>C. albicans</em>. <em>In vivo</em> experiments further demonstrated that this combined treatment enhanced larval survival, increased haemocyte density, and reduced microbial load in the haemolymph. Taken together, these findings underscore the potential of microbially synthesized nano-Ag with vitamin D<sub>3</sub> as a promising synergistic treatment for <em>C. albicans</em> infections, particularly those resistant to fluconazole.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111710"},"PeriodicalIF":1.5,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145416513","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}
Different Schistosoma mansoni strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomic analysis to compare two strains of S. mansoni, Belo Horizonte (SmBH) and Sergipe (SmSE), which differ in phenotypic traits and susceptibility to praziquantel (PZQ). BALB/c mice were infected and treated with a sub-curative dose of PZQ (50 mg/kg) 45 days post-infection. Male and female worms were recovered 15 days after treatment, and pooled samples were processed for trypsin digestion and mass spectrometry. Over 1000 proteins were identified. No significant differences were observed in protein expression between untreated females of the two strains. In untreated males, 16 proteins showed differential expression: 11 upregulated in SmBH, mostly related to metabolic and energy production pathways, and 5 upregulated in SmSE. PZQ exposure did not significantly alter protein expression in SmBH worms. In contrast, SmSE males showed 74 differentially expressed proteins post-treatment, with 58 upregulated, including proteins with antioxidant and antiapoptotic functions commonly associated with drug resistance. SmSE females showed upregulation of three proteins after treatment, mostly related to cytoskeletal and muscular structure, suggesting less PZQ-induced damage. These results suggest that SmSE exhibits adaptive proteomic responses to PZQ-induced oxidative stress, which may contribute to its increased survival after treatment. Our findings provide molecular insight into strain-specific responses to PZQ and highlight potential mechanisms underlying reduced drug susceptibility in S. mansoni.
{"title":"Proteomic analysis reveals differential responses to praziquantel in two Schistosoma mansoni strains with distinct phenotypes","authors":"Marilia Bergamini Valentini, Tiago Manuel Fernandes Mendes, Fernanda Janku Cabral, Silmara Marques Allegretti","doi":"10.1016/j.molbiopara.2025.111709","DOIUrl":"10.1016/j.molbiopara.2025.111709","url":null,"abstract":"<div><div>Different <em>Schistosoma mansoni</em> strains may exhibit distinct phenotypes, which can influence parasite distribution, treatment outcomes, and control strategies. In this study, we conducted a label-free quantitative proteomic analysis to compare two strains of <em>S</em>. <em>mansoni</em>, Belo Horizonte (SmBH) and Sergipe (SmSE), which differ in phenotypic traits and susceptibility to praziquantel (PZQ). BALB/c mice were infected and treated with a sub-curative dose of PZQ (50 mg/kg) 45 days post-infection. Male and female worms were recovered 15 days after treatment, and pooled samples were processed for trypsin digestion and mass spectrometry. Over 1000 proteins were identified. No significant differences were observed in protein expression between untreated females of the two strains. In untreated males, 16 proteins showed differential expression: 11 upregulated in SmBH, mostly related to metabolic and energy production pathways, and 5 upregulated in SmSE. PZQ exposure did not significantly alter protein expression in SmBH worms. In contrast, SmSE males showed 74 differentially expressed proteins post-treatment, with 58 upregulated, including proteins with antioxidant and antiapoptotic functions commonly associated with drug resistance. SmSE females showed upregulation of three proteins after treatment, mostly related to cytoskeletal and muscular structure, suggesting less PZQ-induced damage. These results suggest that SmSE exhibits adaptive proteomic responses to PZQ-induced oxidative stress, which may contribute to its increased survival after treatment. Our findings provide molecular insight into strain-specific responses to PZQ and highlight potential mechanisms underlying reduced drug susceptibility in <em>S</em>. <em>mansoni</em>.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111709"},"PeriodicalIF":1.5,"publicationDate":"2025-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145391441","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 : 2025-10-24DOI: 10.1016/j.molbiopara.2025.111706
Sundas Afresham , Muhammad Kasib Khan , Muhammad Adnan Sabir Mughal , Muhammad Shahid Mehmood , Sultan Ali , Maryam Bashir , Zaheer Abbas , Abdullah Azeem , Waqar Ahmed , Muhammad Imran , Rao Zahid Abbas , Zia-ud-Din Sindhu , Muhammad Sohail Sajid
Parasitic infections present a significant health risk to the public, affecting millions of people, particularly in underdeveloped and developing countries. In developing countries, these infections are also responsible for causing significant economic challenges due to elevated healthcare expenditure. Accurate diagnosis and effective treatment methods are essentially required to combat this global issue. For decades, traditional diagnostic methods such as microscopy, serological testing, histopathology, and culturing have been used for the diagnosis of these parasitic infections. While these methods can be effective and helpful in many ways, they often consume a lot of time, require an elevated level of expertise, and have limited applications particularly in endemic regions having issues like poor infrastructure and limited access to healthcare facilities. This review aims to highlight the urgent need for a revolution to replace these conventional techniques with more affordable, quick, and field-adjustable tools such as rapid diagnostic tests (RDTs) and molecular methods and provides a comprehensive picture of advanced diagnostic tools used in the identification of parasites. With the advancements in science and technology, molecular methods such as Polymerase chain reaction, Next generation sequencing, and isothermal loop-mediated amplification have remarkably enhanced the sensitivity and accuracy of parasite detection and identification. The range of these diagnostic methods has further extended by advanced serological methods, imaging techniques, and immunological methods. Moreover, the innovations in nanotechnology, CRISPR-Cas methods, and multi-omics techniques for identification of parasite DNA, antigens, metabolites, and host responses are invaluable for diagnostic accuracy, comprehensive understanding of parasite biology, and for the discovery of new therapeutic targets and diagnostic biomarkers. However, further research and developments are required for an effective and long-lasting impact of these advancements.
{"title":"Recent advancements in the diagnosis of parasitic diseases","authors":"Sundas Afresham , Muhammad Kasib Khan , Muhammad Adnan Sabir Mughal , Muhammad Shahid Mehmood , Sultan Ali , Maryam Bashir , Zaheer Abbas , Abdullah Azeem , Waqar Ahmed , Muhammad Imran , Rao Zahid Abbas , Zia-ud-Din Sindhu , Muhammad Sohail Sajid","doi":"10.1016/j.molbiopara.2025.111706","DOIUrl":"10.1016/j.molbiopara.2025.111706","url":null,"abstract":"<div><div>Parasitic infections present a significant health risk to the public, affecting millions of people, particularly in underdeveloped and developing countries. In developing countries, these infections are also responsible for causing significant economic challenges due to elevated healthcare expenditure. Accurate diagnosis and effective treatment methods are essentially required to combat this global issue. For decades, traditional diagnostic methods such as microscopy, serological testing, histopathology, and culturing have been used for the diagnosis of these parasitic infections. While these methods can be effective and helpful in many ways, they often consume a lot of time, require an elevated level of expertise, and have limited applications particularly in endemic regions having issues like poor infrastructure and limited access to healthcare facilities. This review aims to highlight the urgent need for a revolution to replace these conventional techniques with more affordable, quick, and field-adjustable tools such as rapid diagnostic tests (RDTs) and molecular methods and provides a comprehensive picture of advanced diagnostic tools used in the identification of parasites. With the advancements in science and technology, molecular methods such as Polymerase chain reaction, Next generation sequencing, and isothermal loop-mediated amplification have remarkably enhanced the sensitivity and accuracy of parasite detection and identification. The range of these diagnostic methods has further extended by advanced serological methods, imaging techniques, and immunological methods. Moreover, the innovations in nanotechnology, CRISPR-Cas methods, and multi-omics techniques for identification of parasite DNA, antigens, metabolites, and host responses are invaluable for diagnostic accuracy, comprehensive understanding of parasite biology, and for the discovery of new therapeutic targets and diagnostic biomarkers. However, further research and developments are required for an effective and long-lasting impact of these advancements.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111706"},"PeriodicalIF":1.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145362934","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 : 2025-10-24DOI: 10.1016/j.molbiopara.2025.111707
Maria Paluch, Maja Cudzik, Aleksandra Kędra, Martyna Olszyna, Agata Dziura, Paulina Jaskulska, Grzegorz Król, Wioleta Kondziołka
Cancer deaths are increasing year by year worldwide. Many factors contribute to the development of cancer, including genetic and epigenetic factors, as well as environmental factors such as diet, physical activity, stimulants (tobacco, alcohol), exposure to excessive UV radiation, stress, and infections. In recent years, many studies have shown a strong correlation between parasitic infections and the oncogenic process leading to the development of human cancers. Studies indicate an association between progressive inflammation, risk of infection, or bacterial/viral co-infection during parasitosis and oncogenesis. This article discusses six species of flukes listed by the International Agency for Research on Cancer (Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Opisthorchis viverrini, Clonorchis sinensis, and Opisthorchis felineus) for their carcinogenic potential, biology, and epidemiology. Particular attention was paid to the molecular mechanisms that are altered during fluke invasion, which ultimately lead to the development of neoplastic lesions in humans and animals.
{"title":"Can flukes cause cancer? Insight into molecular links between parasites and carcinogenesis","authors":"Maria Paluch, Maja Cudzik, Aleksandra Kędra, Martyna Olszyna, Agata Dziura, Paulina Jaskulska, Grzegorz Król, Wioleta Kondziołka","doi":"10.1016/j.molbiopara.2025.111707","DOIUrl":"10.1016/j.molbiopara.2025.111707","url":null,"abstract":"<div><div>Cancer deaths are increasing year by year worldwide. Many factors contribute to the development of cancer, including genetic and epigenetic factors, as well as environmental factors such as diet, physical activity, stimulants (tobacco, alcohol), exposure to excessive UV radiation, stress, and infections. In recent years, many studies have shown a strong correlation between parasitic infections and the oncogenic process leading to the development of human cancers. Studies indicate an association between progressive inflammation, risk of infection, or bacterial/viral co-infection during parasitosis and oncogenesis. This article discusses six species of flukes listed by the International Agency for Research on Cancer (<em>Schistosoma haematobium, Schistosoma japonicum, Schistosoma mansoni, Opisthorchis viverrini</em>, <em>Clonorchis sinensis</em>, and <em>Opisthorchis felineus</em>) for their carcinogenic potential, biology, and epidemiology. Particular attention was paid to the molecular mechanisms that are altered during fluke invasion, which ultimately lead to the development of neoplastic lesions in humans and animals.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111707"},"PeriodicalIF":1.5,"publicationDate":"2025-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145370347","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 : 2025-10-16DOI: 10.1016/j.molbiopara.2025.111705
Yasser Alraey
Background and Aim
Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the Toxoplasma gondii parasite. Given the serious side effects and recurrence of resistance, there is an unmet need to develop effective novel drugs with low toxicity against T. gondii. This study aims to identify novel anti-parasitic compounds targeting human Tankyrase-1 involved in T. gondii infection using bioinformatics and in vitro approaches.
Methods
For lead identification, high-throughput virtual screening (HTVS) against the ChemBridge library was followed by Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques. Human TNKS1 (PARP5A) colorimetric assay was performed. The RH-2F strain of T. gondii tachyzoites that expressed beta-galactosidase was maintained in the human foreskin fibroblasts (HFFs) to determine the parasite growth-inhibitory efficacy of the lead candidate. MTT assay was used to detect the inhibition rate on host cell viability.
Results
HTVS identified ZT-5483 with favorable binding affinities of 8.8 kcal/mol towards TNKS1. Molecular dynamic simulations demonstrated stable binding interactions for ZT-5483 and TNKS1 with Root Mean Square Deviation values around 0.04 nm. The ΔG binding calculation was −43.09 kcal/mol, favoring sturdy binding. ADME analysis supported favorable small-molecule characteristics. ZT-5483 dose responsively inhibited TNKS1 activity with an IC50 value of 140.8 nM. ZT-5483 suppressed the parasite growth with an IC50 value of 297.8 nM. The compound's cytotoxicity to HFF host cells (TD50 value) was determined to be 3354 nM. The in vitro toxicity index (TI) of ZT-5483 was 11.26 based on the IC50 and TD50 values.
Conclusion
Together, these findings suggest that ZT-5483 could be a potential novel candidate against T. gondii. However, further preclinical and pharmacological evaluations are warranted.
{"title":"Targeted inhibition of human Tankyrase-1 (TNKS1) by ZT-5483 exhibited anti-parasitic activity in Toxoplasma gondii: An in silico–based, high–throughput virtual screen and in vitro approach","authors":"Yasser Alraey","doi":"10.1016/j.molbiopara.2025.111705","DOIUrl":"10.1016/j.molbiopara.2025.111705","url":null,"abstract":"<div><h3>Background and Aim</h3><div>Toxoplasmosis is considered one of the leading causes of mortality resulting from foodborne illness. This disease is caused by infection with the <em>Toxoplasma gondii</em> parasite. Given the serious side effects and recurrence of resistance, there is an unmet need to develop effective novel drugs with low toxicity against <em>T. gondii.</em> This study aims to identify novel anti-parasitic compounds targeting human Tankyrase-1 involved in <em>T. gondii</em> infection using bioinformatics and <em>in vitro</em> approaches.</div></div><div><h3>Methods</h3><div>For lead identification, high-throughput virtual screening (HTVS) against the ChemBridge library was followed by Protein-Ligand Interaction Profiler, GROMACS, and GMX_MMPBSA techniques. Human TNKS1 (PARP5A) colorimetric assay was performed. The RH-2F strain of <em>T. gondii</em> tachyzoites that expressed beta-galactosidase was maintained in the human foreskin fibroblasts (HFFs) to determine the parasite growth-inhibitory efficacy of the lead candidate. MTT assay was used to detect the inhibition rate on host cell viability.</div></div><div><h3>Results</h3><div>HTVS identified ZT-5483 with favorable binding affinities of 8.8 kcal/mol towards TNKS1. Molecular dynamic simulations demonstrated stable binding interactions for ZT-5483 and TNKS1 with Root Mean Square Deviation values around 0.04 nm. The ΔG binding calculation was −43.09 kcal/mol, favoring sturdy binding. ADME analysis supported favorable small-molecule characteristics. ZT-5483 dose responsively inhibited TNKS1 activity with an IC<sub>50</sub> value of 140.8 nM. ZT-5483 suppressed the parasite growth with an IC<sub>50</sub> value of 297.8 nM. The compound's cytotoxicity to HFF host cells (TD<sub>50</sub> value) was determined to be 3354 nM. The <em>in vitro</em> toxicity index (TI) of ZT-5483 was 11.26 based on the IC<sub>50</sub> and TD<sub>50</sub> values.</div></div><div><h3>Conclusion</h3><div>Together, these findings suggest that ZT-5483 could be a potential novel candidate against <em>T. gondii</em>. However, further preclinical and pharmacological evaluations are warranted.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111705"},"PeriodicalIF":1.5,"publicationDate":"2025-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145318501","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 : 2025-10-10DOI: 10.1016/j.molbiopara.2025.111703
Francois Korbmacher , Manuel Rauch , Sanketha Kenthirapalan , Taco W.A. Kooij , Alexander G. Maier , Kai Matuschewski
Plasmodium parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we profiled the spatio-temporal expression of CRT during life cycle progression employing CRT-mCherry Plasmodium berghei parasites. We show that CRT is expressed during asexual blood stage growth and localizes to the hemozoin-containing digestive vacuole. The compartmentalized CRT-mCherry signal is also abundant in gametocytes and ookinetes, indicating that CRT continues to exert important functions in this digestive organelle up until mosquito midgut colonization. Expression is switched off during sporogony and early liver infection but CRT-mCherry is present again in mature liver stages, likely in preparation for blood infection. Together, visualization of the P. berghei digestive vacuole by endogenous tagging of PbCRT revealed expression of this transport protein and the presence of this cellular compartment beyond asexual propagation inside erythrocytes.
{"title":"Stage-dependent expression and vacuolar localization of Plasmodium berghei chloroquine resistance transporter (CRT)","authors":"Francois Korbmacher , Manuel Rauch , Sanketha Kenthirapalan , Taco W.A. Kooij , Alexander G. Maier , Kai Matuschewski","doi":"10.1016/j.molbiopara.2025.111703","DOIUrl":"10.1016/j.molbiopara.2025.111703","url":null,"abstract":"<div><div><em>Plasmodium</em> parasites encode a chloroquine resistance transporter (CRT), which is an integral membrane protein of the digestive vacuole and transports the antimalarial compound chloroquine out of this organelle. Here, we profiled the spatio-temporal expression of CRT during life cycle progression employing CRT-mCherry <em>Plasmodium berghei</em> parasites. We show that CRT is expressed during asexual blood stage growth and localizes to the hemozoin-containing digestive vacuole. The compartmentalized CRT-mCherry signal is also abundant in gametocytes and ookinetes, indicating that CRT continues to exert important functions in this digestive organelle up until mosquito midgut colonization. Expression is switched off during sporogony and early liver infection but CRT-mCherry is present again in mature liver stages, likely in preparation for blood infection. Together, visualization of the <em>P. berghei</em> digestive vacuole by endogenous tagging of <em>Pb</em>CRT revealed expression of this transport protein and the presence of this cellular compartment beyond asexual propagation inside erythrocytes.</div></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"264 ","pages":"Article 111703"},"PeriodicalIF":1.5,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145280680","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}
扫码关注我们
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号