Molecular and biochemical parasitology最新文献

{"title":"Structural characterization of glutamyl-tRNA synthetase (GluRS) from Plasmodium falciparum","authors":"Vivek Kumar Sharma,&nbsp;Jyoti Chhibber-Goel,&nbsp;Manickam Yogavel,&nbsp;Amit Sharma","doi":"10.1016/j.molbiopara.2022.111530","DOIUrl":"10.1016/j.molbiopara.2022.111530","url":null,"abstract":"<div><p><span><span>Aminoacyl-tRNA synthetases (aaRSs) are essential enzymes in </span>protein translation<span> machinery that provide the charged tRNAs needed for protein synthesis. Over the past decades, aaRSs have been studied as anti-parasitic, anti-bacterial, and anti-fungal drug targets. This study focused on the cytoplasmic glutamyl-tRNA synthetase (GluRS) from </span></span><span><em>Plasmodium falciparum</em></span><span>, which belongs to class Ib in aaRSs. GluRS unlike most other aaRSs requires tRNA to activate its cognate amino acid substrate </span><span>L</span>-Glutamate (<span>L</span>-Glu), and fails to form an intermediate adenylate complex in the absence of tRNA. The crystal structures of the Apo, ATP, and ADP-bound forms of <em>Plasmodium falciparum</em> glutamyl-tRNA synthetase (<em>Pf</em>GluRS) were solved at 2.1 Å, 2.2 Å, and 2.8 Å respectively. The structural comparison of the Apo- and ATP-bound holo-forms of <em>Pf</em><span>GluRS showed considerable conformational changes in the loop regions around the ATP-binding pocket of the enzyme. Biophysical characterization of the </span><em>Pf</em><span>GluRS showed binding of the enzyme substrates </span><span>L</span>-Gluand ATP.. The sequence and structural conservation were evident across GluRS compared to other species. The structural dissection of the <em>Pf</em><span>GluRS gives insight into the critical residues involved in the binding of ATP substrate, which can be harvested to develop new antimalarial drugs.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111530"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10735606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency in TLR4 impairs regulatory B cells production induced by Schistosome soluble egg antigen","authors":"Fang Tian ,&nbsp;Kangwen Xian ,&nbsp;Bin Yang ,&nbsp;Qiufang Duan ,&nbsp;Li Qian ,&nbsp;Chanhong Shi","doi":"10.1016/j.molbiopara.2022.111532","DOIUrl":"10.1016/j.molbiopara.2022.111532","url":null,"abstract":"<div><p><span>Regulatory B cells<span> (Bregs) producing IL-10 have negative regulatory function. Several studies have shown the important roles for Toll-like receptor 2 (TLR2), TLR4<span>, and TLR9 ligation in the development of Bregs. We have reported that </span></span></span><span><em>Schistosome</em></span><span> soluble egg antigen (SEA) induced the production of Bregs. However, it remains unclear whether such activation is via the TLR pathway. The present study showed that IL-10 and TLR4 mRNA expression in spleen B cells of significantly increased in C57BL/10 J mice spleen B cells following SEA stimulation. The level of secreted IL-10 and IL-10</span>⁺ B cell proportion decreased in spleen B cells derived from TLR4-deficient C57BL/10ScNJ (TLR4^-/^-<span>) mice following SEA or LPS stimulation compared with C57BL/10 J mice. The CD1d</span>^hiCD5⁺ B cells proportion decreased in spleen B cells of TLR4^-/^-<span> mice following SEA stimulation compared with control mice. NF-κB, ERK, p38MAPK<span><span> and JNK </span>signal transduction inhibitors significantly suppressed IL-10 secretion in CD1d</span></span>^hiCD5⁺<span> B cells induced by SEA or LPS. The phosphorylation levels of IκBα, p65, ERK, JNK and p38 were increased in CD1d</span>^hiCD5⁺<span> B cell of C57BL/10 J mice treated with LPS or SEA. In conclusion, this study suggests that TLR4 plays a critical role in Bregs activation induced by SEA. And the TLR4-triggered NF-κB and MAPK pathways activation in CD1d</span>^hiCD5⁺ B cells stimulated with SEA. The findings elucidated the mechanism of SEA induction of CD1d^hiCD5⁺<span> B cells and helped us to understand the immune regulation during </span><span><em>Schistosoma japonicum</em></span> infection.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111532"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10736101","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The microbiota, the malarial parasite, and the mosquito [MMM] – A three-sided relationship","authors":"Sathishkumar Vinayagam ,&nbsp;Devianjana Rajendran ,&nbsp;Kathirvel Sekar ,&nbsp;Kaviyarasi Renu ,&nbsp;Kamaraj Sattu","doi":"10.1016/j.molbiopara.2023.111543","DOIUrl":"10.1016/j.molbiopara.2023.111543","url":null,"abstract":"<div><p><span>The mosquito gut microbiota is vital to the proper functioning of the host organism. Mosquitoes may benefit from this microbiota in their guts because it promotes factors including blood digestion, fecundity, metamorphosis, and living habitat and inhibits malarial parasites (</span><em>Plasmodium</em><span>) growth or transmission. In this overview, we analyzed how mosquitoes acquire their gut microbiota, characterized those bacteria, and discussed the functions they provide. We also investigated the effects of microbiota on malaria vectors, with a focus on the mosquito species </span><span><em>Anopheles</em></span>, as well as the relationship between microbiota and <em>Plasmodium</em>, the aspects in which microbiota influences <em>Plasmodium</em><span> via immune response, metabolism, and redox mechanisms, and the strategies in which gut bacteria affect the life cycle of malaria vectors and provide the ability to resist insecticides. This article explores the difficulties in studying triadic interactions, such as the interplay between Mosquitoes, Malarial parasite, and the Microbiota that dwell in the mosquitoes' guts, and need additional research for a better understanding of these multiple connections to implement an exact vector control strategies using Gut microbiota in malaria control.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111543"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In silico analysis of two Haemonchus spp. serine protease peptides (S28) and their immunomodulatory activity in vitro","authors":"René Camas-Pereyra ,&nbsp;Génesis A. Bautista-García ,&nbsp;Guillermina Avila ,&nbsp;Yazmin Alcala-Canto ,&nbsp;Jocelyn Maza-Lopez ,&nbsp;David E. Reyes-Guerrero ,&nbsp;Rosa Isabel Higuera-Piedrahita ,&nbsp;María Eugenia López-Arellano","doi":"10.1016/j.molbiopara.2023.111545","DOIUrl":"10.1016/j.molbiopara.2023.111545","url":null,"abstract":"<div><p>The aim of this study was to evaluate the <em>in vitro</em><span><span> immune modulation of two de novo peptides with hypothetical identity to the </span>serine protease family (S28) from </span><span><em>Haemonchus</em></span> spp. Expression of mRNAs encoding these peptides was confirmed by RT<img>qPCR in L₃ and adult stage parasites. Antibodies from serum samples collected from an <em>H. contortus</em><span>-infected lamb at 60 days post infection detected both peptides, as assessed by indirect ELISA<span>. Lamb peripheral blood mononuclear cells<span> (PBMCs) were exposed to each peptide, as well as to the peptide mixture, and cell proliferation assays were performed at 24, 48 and 72 h. The relative expression of the </span></span></span><em>IL4</em>, <em>IL5</em>, <em>IL6</em>, <em>IL13</em>, <em>CXCL8</em> and <em>FCεR1A</em> genes was quantified by RT<img>qPCR from lamb PBMCs exposed to the peptide mixture at 24 and 48 h. With respect to immune gene expression, 15- and 3-fold upregulation at 24 h was observed with <em>IL5</em> and <em>CXCL8</em>, respectively, and 2-fold upregulation of <em>CXCL8</em> at 48 h. In contrast, downregulation of <em>IL5</em><span> was stimulated at 48 h. These data suggest that these peptides (pep-hsp and pep-pcx), which show high identity with intestinal and excretion/secretion serine proteases, can trigger immunogenic activity, and suggest that they may be useful as potential parasite vaccines.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111545"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9281199","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modular nanotheranostic agents for protistan parasitic diseases: Magic bullets with tracers","authors":"Sutherland Kester Maciver ,&nbsp;Sumayah Abdelnasir ,&nbsp;Ayaz Anwar ,&nbsp;Ruqaiyyah Siddiqui ,&nbsp;Naveed Ahmed Khan","doi":"10.1016/j.molbiopara.2022.111541","DOIUrl":"10.1016/j.molbiopara.2022.111541","url":null,"abstract":"<div><p>Protistan parasitic infections contribute significantly to morbidity and mortality, causing more than 2 billion human infections annually. However, current treatments are often limited; due to ineffective drugs and drug resistance, thus better options are urgently required. In the present context, theranostics agents are those that offer simultaneous detection, diagnosis and even treatment of protistan parasitic diseases. “Nanotheranostics” is the term used to describe such agents, that are around 100 nm or less in size. Anti-parasitic activity of nanoparticles (NPs) has been reported, and many have useful intrinsic imaging properties, but it is perhaps their multifunctional nature that offers the greatest potential. NPs may be used as adapters onto which various subunits with different functions may be attached. These subunits may facilitate targeting parasites, coupled with toxins to eradicate parasites, and probe subunits for detection of particles and/or parasites. The modular nature of nano-platforms promises a “mix and match” approach for the construction of tailored agents by using combinations of these subunits against different protistan parasites. Even though many of the subunits have shown promise alone, these have not yet been put together convincingly enough to form working theranostics against protistan parasites. Although the clinical application of nanotheranostics to protistan parasitic infections in humans requires more research, we conclude that they offer not just a realisation of Paul Ehrlich’s long imagined “magic bullet” concept, but potentially are magic bullets combined with tracer bullets.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111541"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heat shock protein 60 in parasitic helminths: A role in immune responses and therapeutic applications","authors":"Xuedong He ,&nbsp;Yue Sun ,&nbsp;Fang Yang ,&nbsp;Guanghui Zheng ,&nbsp;Rui Li ,&nbsp;Mengqi Liu ,&nbsp;Wanjing Li ,&nbsp;Dong-Hui Zhou ,&nbsp;Yadong Zheng","doi":"10.1016/j.molbiopara.2023.111544","DOIUrl":"10.1016/j.molbiopara.2023.111544","url":null,"abstract":"<div><p><span><span>Heat shock protein 60 (HSP60) is an unique member of the heat shock protein family, being involved in parasite infections. To cope with harsh environments where parasites live, HSP60s are indispensable and involved in a variety of </span>biological processes<span>. HSP60s have relative low similarity among parasites, but their ATPase /Mg</span></span>²⁺<span> active sites are highly conserved. The interactions of HSP60s with signaling pathway<span><span> regulators in immune cells suggest a crucial role in immune responses, rendering them a potential therapeutic target. This paper reviews the current understandings of HSP60s in parasitic </span>helminths in aspects of molecular characteristics, immunoregulatory responses and HSP60-based therapeutics.</span></span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111544"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9296296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characteristics of γδTCR on myeloid cells from C57BL/6 mice with Plasmodium yoelii nigeriensis infection","authors":"Dianhui Chen ,&nbsp;Feng Mo ,&nbsp;Meiling Liu ,&nbsp;Yongjing Ma ,&nbsp;Lin Liu ,&nbsp;Junmin Xing ,&nbsp;Feihu Shi ,&nbsp;Anqi Xie ,&nbsp;Hongyan Xie ,&nbsp;Xingfei Pan ,&nbsp;Xinhua Wang ,&nbsp;Jun Huang","doi":"10.1016/j.molbiopara.2022.111540","DOIUrl":"10.1016/j.molbiopara.2022.111540","url":null,"abstract":"<div><p><strong>Recently</strong>, there is a paucity of studies focus on the characteristics of myeloid cells which expressed γδTCR. The aim of this study was to observe the properties of γδTCR-expressing myeloid cells in the spleen of C57BL/6 mice infected by <em>P. yoelii nigeriensis</em> NSM<em>.</em><span> Haematoxylin-eosin (HE) staining was used to observe pathological changes in the spleens from infected mice. The differentially expressed genes (DEGs) between the infection and control groups were analyzed by RNA sequencing (RNA -seq). Flow cytometry (FCM) was used to evaluate the frequency of γδTCR</span>⁺ cells and the characteristics of γδTCR⁺ cells in <em>P. yoelii nigeriensis</em> NSM-infected mice. Obvious infiltration of inflammatory were observed in the spleens from infected C57BL/6 mouse. The proportions of γδTCR⁺ cells and CD11b⁺ γδTCR⁺ cells from infected group were higher than that from normal group. CD11b⁺ γδTCR⁺ cells expressed high levels of activated-mediated genes and inflammatory-mediated genes. The heterogeneous pathway activities among CD11b⁺ γδTCR⁺<span><span> cells from normal and infected group were characterized. The oxidative phosphorylation, respiratory </span>electron transport chain<span><span> and leukocyte activation involved in immune response pathways were up-regulated, while the alpha-beta </span>T cell<span> activation and myeloid leukocyte migration pathways were down-regulated in infected mice. Importantly, </span></span></span><em>Ly6c2</em> was higher expressed in CD11b⁺ γδTCR⁺ cells than <em>Ly6g</em>. Consistent with it, flow cytometry results revealed that a subset of Ly6C⁺ cells was higher than Ly6G⁺ cells in the spleen. Taken together, our data suggest the existence of a population of γδTCR-expressing myeloid cells and they might be multifunctional cells, which play a role in couse of <em>Plasmodium</em> infection.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111540"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10726093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phylogeny and population structure of Echinococcus granulosus (sensu stricto) based on full-length cytb-nad2-atp6 mitochondrial genes – First report from Sialkot District of Pakistan","authors":"Mughees Aizaz Alvi ,&nbsp;Rana Muhammad Athar Ali ,&nbsp;Li Li ,&nbsp;Muhammad Saqib ,&nbsp;Warda Qamar ,&nbsp;Ali Hassan ,&nbsp;Muzafar Ghafoor ,&nbsp;Siddiq Ur Rahman ,&nbsp;Muhammad Umar Zafar Khan ,&nbsp;Bao-Quan Fu ,&nbsp;Youyu Liu ,&nbsp;Hong Yin ,&nbsp;Hong-Bin Yan ,&nbsp;Wan-Zhong Jia","doi":"10.1016/j.molbiopara.2022.111542","DOIUrl":"10.1016/j.molbiopara.2022.111542","url":null,"abstract":"<div><p><span><span>Cystic echinococcosis is a </span>zoonotic disease of livestock having serious economic setbacks. The etiological agents of the disease belong to </span><span><em>Echinococcus</em><em> granulosus</em></span> sensu lato. Despite of worldwide distribution of the disease, the molecular studies mainly employ amplification of <em>cox</em>1, <em>nad</em>1 and <em>nad</em><span>5 genes. To further strengthen the knowledge about significance of other molecular markers<span> and to investigate the genetic diversity and population structure of </span></span><em>Echinococcus</em> species in Pakistan, the current study was designed in which full length mitochondrial <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2 genes were amplified. Based on BLAST searches of the generated <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2 gene sequences from a total of 18 hydatid cysts collected from cattle, 12 isolates were identified as <em>E</em>. <em>granulousus</em> G3 and 6 as <em>E</em>. <em>granulosus</em><span> (G1). The phylogeny inferred by the Bayesian method using nucleotide sequences of </span><em>cyt</em>b-<em>atp</em>6-<em>nad</em>2 further confirmed their identity. The diversity indices indicated a high haplotype and a low nucleotide diversity. The negative values of Tajima’s D and Fu’s Fs test demonstrated deviation from neutrality suggesting a recent population expansion. To the best of our knowledge, the present study described the genetic variation of <em>E</em>. <em>granulosus</em> population for the first time in Pakistan using full-length <em>cyt</em>b, <em>atp</em>6 and <em>nad</em><span>2 mitochondrial genes. The findings on the genetic variation of </span><em>E</em>. <em>granulosus</em> in Pakistan will constitute useful baseline information for future studies on the prevalence and population structure of <em>E</em>. <em>granulosus</em> based on full-length <em>cyt</em>b, <em>atp</em>6 and <em>nad</em>2.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"253 ","pages":"Article 111542"},"PeriodicalIF":1.5,"publicationDate":"2023-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10726588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biophysical description of Bromosulfophthalein interaction with the 28-kDa glutathione transferase from Schistosoma japonicum","authors":"Kagiso Pooe,&nbsp;Monare Thulo,&nbsp;Hattie Makumbe,&nbsp;Blessing Akumadu,&nbsp;Oluwatobin Otun,&nbsp;Chinyere Aloke,&nbsp;Ikechukwu Achilonu","doi":"10.1016/j.molbiopara.2022.111524","DOIUrl":"10.1016/j.molbiopara.2022.111524","url":null,"abstract":"<div><p><span><span><span>Glutathione<span><span><span> transferases (GSTs) are major detoxification </span>enzymes vital for the survival and reproduction of </span>schistosomes<span> during infection in humans. Schistosoma encode two GST isoenzymes, the 26- and 28-kDa </span></span></span>isoforms<span>, that show different substrate specificities<span> and cellular localisations. Bromosulfophthalein (BSP) has been identified and characterised as a potent 26-kDa </span></span></span>Schistosoma japonicum<span> GST (Sj26GST) inhibitor with an anthelmintic<span><span> potential. This study describes the structure, function, and ligandin properties of the 28-kDa Schistosoma japonicum GST (Sj28GST) towards BSP. Enzyme kinetics show that BSP is a potent </span>enzyme inhibitor, with a specific activity decrease</span></span></span><del>s</del> from 60.4 µmol/min/mg to 0.0742 µmol/min/mg and an IC₅₀<span> in the micromolar range of 0.74 µM. Far-UV circular dichroism<span> confirmed that purified Sj28GST follows a typical GST fold, which is predominantly alpha-helical. Fluorescence spectroscopy<span> suggests that BSP binding occurs at a site distinct from the glutathione-binding site (G-site); however, the binding does not alter the local G-site environment. Isothermal titration calorimetry studies show that the binding of BSP to Sj28GST is exergonic (∆</span></span></span><em>G</em><span>°= −33 kJ/mol) and enthalpically-driven, with a stoichiometry of one BSP per dimer. The stability of Sj28GST (∆G</span>_(H2O) = 4.7 kcal/mol) is notably lower than Sj26GST, owing to differences in the enzyme’s dimeric interfaces. We conclude that Sj28GST shares similar biophysical characteristics with Sj26GST based on its kinetic properties and susceptibility to low concentrations of BSP. The study supports the potential benefits of re-purposing BSP as a potential drug or prodrug to mitigate the scourge of schistosomiasis.</p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111524"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10451752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Praziquantel: An update on the mechanism of its action against schistosomiasis and new therapeutic perspectives","authors":"Ranielly Araujo Nogueira ,&nbsp;Maria Gabriela Sampaio Lira ,&nbsp;Irlla Correia Lima Licá ,&nbsp;Gleycka Cristine Carvalho Gomes Frazão ,&nbsp;Vitor Augusto Ferreira dos Santos ,&nbsp;Antonio Camilo Correia Mendes Filho ,&nbsp;João Gustavo Mendes Rodrigues ,&nbsp;Guilherme Silva Miranda ,&nbsp;Rafael Cardoso Carvalho ,&nbsp;Flávia Raquel Fernandes Nascimento","doi":"10.1016/j.molbiopara.2022.111531","DOIUrl":"10.1016/j.molbiopara.2022.111531","url":null,"abstract":"<div><p><span>Praziquantel<span> (PZQ) is the drug of choice for the treatment of all forms of schistosomiasis, although its mechanisms of action are not completely understood. PZQ acts largely on adult worms. This narrative literature review describes what is known about the mechanisms of action of PZQ against schistosomes from </span></span><em>in vitro</em> and <em>in vivo</em><span><span> studies and highlights the molecular targets in parasites and immune responses induced in definitive hosts by this drug. Moreover, new therapeutic uses of PZQ are discussed. Studies have demonstrated that in addition to impacting voltage-operated Ca2 + channels, PZQ may interact with other schistosome molecules, such as myosin regulatory light chain, glutathione S-transferase, and transient receptor potential<span><span> channels. Following PZQ administration, increased T regulatory type 1 (Tr1) cell differentiation and decreased inflammation were observed, indicating that PZQ promotes immunoregulatory pathways. Although PZQ is widely used in mass drug administration schemes, the existence of resistant parasites has not been proven; however, it is a concern that should be constantly investigated in human populations. In addition, we discuss studies that evaluate health applications of PZQ (other than </span>helminth infection), such as its effect in cancer therapy and its adjuvant action in vaccines against </span></span>viruses.</span></p></div>","PeriodicalId":18721,"journal":{"name":"Molecular and biochemical parasitology","volume":"252 ","pages":"Article 111531"},"PeriodicalIF":1.5,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10452049","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}