Biomechanics of parasite migration within hosts

Trends in Parasitology, Год журнала: 2024, Номер 40(2), С. 164 - 175

Опубликована: Янв. 2, 2024

Язык: Английский

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Systemic Immune Modulation by Gastrointestinal Nematodes

Annual Review of Immunology, Год журнала: 2024, Номер 42(1), С. 259 - 288

Опубликована: Янв. 26, 2024

Gastrointestinal nematode (GIN) infection has applied significant evolutionary pressure to the mammalian immune system and remains a global economic human health burden. Upon infection, type 2 sentinels activate common antihelminth response that mobilizes remodels intestinal tissue for effector function; however, there is growing appreciation of impact GIN also on distal state. Indeed, this effect observed even in tissues through which GINs never transit. This review highlights how modulates systemic immunity (

Язык: Английский

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Schistosomiasis

Advances in experimental medicine and biology, Год журнала: 2024, Номер unknown, С. 75 - 105

Опубликована: Янв. 1, 2024

Язык: Английский

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RNAi screening of uncharacterized genes identifies promising druggable targets in Schistosoma japonicum

PLoS Pathogens, Год журнала: 2025, Номер 21(3), С. e1013014 - e1013014

Опубликована: Март 28, 2025

Schistosomiasis affects more than 250 million people worldwide and is one of the neglected tropical diseases. Currently, treatment schistosomiasis relies on a single drug-praziquantel-which has led to increasing pressure from drug resistance. Therefore, there an urgent need find new treatments. The development genome sequencing provided valuable information for understanding biology schistosomes. In Schistosoma japonicum , approximately 11% protein-coding sequences are uncharacterized genes (UGs) annotated as “hypothetical protein” or “protein unknown function.” These poorly understood have been unjustifiably neglected, although some may be essential survival parasites serve potential targets. this study, we systematically mined highly expressed UGs in both genders parasite throughout key developmental stages their mammalian host, using our previously published S. RNA-seq data. By employing vitro RNA interference (RNAi), screened 126 that lack homologs Homo sapiens identified 8 vitality. We further investigated two UGs, Sjc_0002003 Sjc_0009272 which resulted most severe phenotypes. Fluorescence situ hybridization demonstrated were body without sex bias. Silencing either reduced cell proliferation body. Furthermore, vivo RNAi indicated required growth host. For characterize underlying molecular cause observed phenotype. Through analysis functional studies, revealed silencing reduces expression series intestinal genes, including Sjc_0007312 (hypothetical protein), Sjc_0008276 (vha-17), Sjc_0002942 (PLA2G15), Sjc_0003646 (SJCHGC09134 leading gut dilation. Our work highlights importance schistosomes promising targets schistosomiasis.

Язык: Английский

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Wnt/β-catenin signalling underpins juvenile Fasciola hepatica growth and development

PLoS Pathogens, Год журнала: 2025, Номер 21(2), С. e1012562 - e1012562

Опубликована: Фев. 7, 2025

Infection by the liver fluke, Fasciola hepatica, places a substantial burden on global agri-food industry and poses significant threat to human health in endemic regions. Widespread resistance limited arsenal of chemotherapeutics, including frontline flukicide triclabendazole (TCBZ), renders F. hepatica control unsustainable accentuates need for novel therapeutic target discovery. A key facet biology is population specialised stem cells which drive growth development - their dysregulation hypothesised represent an appealing avenue control. The exploitation this system as impeded lack understanding molecular mechanisms underpinning development. Wnt signalling pathways govern myriad cell processes during embryogenesis tumorigenesis adult tissues animals. Here, we identify five putative ligands Frizzled receptors fluke transcriptomic datasets find that Wnt/β-catenin most active juveniles, pathogenic life stage. FISH-mediated transcript localisation revealed partitioning ligands, with each displaying distinct expression pattern, consistent regulating different cell/tissue types. silencing individual or gene yielded reductions juvenile worm and, select cases, blunted proliferation neoblast-like cells. Notably, FhCTNNB1, effector signal cascade led aberrant neuromuscular ultimately proved lethal first report RNAi-induced phenotype hepatica. absence any discernible phenotypes following inhibitory destruction complex components low activity rapidly developing worms, corroborates profiles underscores importance driver early-stage fluke. pharmacological inhibition using commercially available inhibitors phenocopied RNAi results provides impetus drug repurposing. Taken together, these data functionally chemically validate targeting strategy undermine pathogenicity

Язык: Английский

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Neuroschistosomiasis presenting as recurrent seizures: A case report

Surgical Neurology International, Год журнала: 2025, Номер 16, С. 51 - 51

Опубликована: Фев. 14, 2025

Cerebral pseudotumoral schistosomiasis is an uncommon and underreported condition, posing significant diagnostic challenges due to its ability mimic other neurological conditions, especially in patients presenting with persistent seizures imaging findings indicative of infectious etiology. We report the case a 16-year-old male who presented headaches recurrent despite adherence antiseizure medications. Neuroimaging suggested process but were inconclusive differentiating between tuberculoma cerebral schistosomiasis. Given differing therapeutic approaches required for these definitive diagnosis was pursued through brain tissue biopsy, which confirmed This guided appropriate treatment, leading clinical improvement. highlights critical role biopsy establishing when results are suggests importance exploring use adjunct methods like magnetic resonance spectroscopy, hence decreasing or potentially eliminating need open biopsy.

Язык: Английский

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Prostaglandin regulation of type 2 inflammation: From basic biology to therapeutic interventions

European Journal of Immunology, Год журнала: 2021, Номер 51(10), С. 2399 - 2416

Опубликована: Авг. 16, 2021

Type 2 immunity is critical for the protective and repair responses that mediate resistance to parasitic helminth infection. This immune response also drives aberrant inflammation during atopic diseases. Prostaglandins are a class of lipid mediators released type integral in controlling initiation, activation, maintenance, effector functions, resolution inflammation. In this review, we explore roles different prostaglandin family members receptors they bind allergen- helminth-induced mechanism through which prostaglandins promote or suppress Furthermore, discuss potential role produced by parasites regulation host-pathogen interactions, how may regulate inverse relationship between infection allergy. Finally, opportunities capitalize on our understanding pathways develop new therapeutic options humans experiencing inflammatory disorders have significant prostaglandin-driven component including allergic rhinitis asthma.

Язык: Английский

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SchistoCyte Atlas: A Single-Cell Transcriptome Resource for Adult Schistosomes

Trends in Parasitology, Год журнала: 2021, Номер 37(7), С. 585 - 587

Опубликована: Май 9, 2021

Язык: Английский

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Using ChEMBL to Complement Schistosome Drug Discovery

Pharmaceutics, Год журнала: 2023, Номер 15(5), С. 1359 - 1359

Опубликована: Апрель 28, 2023

Schistosomiasis is one of the most important neglected tropical diseases. Until an effective vaccine registered for use, cornerstone schistosomiasis control remains chemotherapy with praziquantel. The sustainability this strategy at substantial risk due to possibility praziquantel insensitive/resistant schistosomes developing. Considerable time and effort could be saved in schistosome drug discovery pipeline if available functional genomics, bioinformatics, cheminformatics phenotypic resources are systematically leveraged. Our approach, described here, outlines how schistosome-specific resources/methodologies, coupled open-access database ChEMBL, can cooperatively used accelerate early-stage, efforts. process identified seven compounds (fimepinostat, trichostatin A, NVP-BEP800, luminespib, epoxomicin, CGP60474 staurosporine) ex vivo anti-schistosomula potencies sub-micromolar range. Three those (epoxomicin, also demonstrated potent fast-acting effects on adult completely inhibited egg production. ChEMBL toxicity data were leveraged provide further support progressing (as well as luminespib TAE684) a novel anti-schistosomal compound. As very few currently advanced stages pipeline, our approaches highlight by which new chemical matter quickly progressed through preclinical development.

Язык: Английский

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An improved medium for in vitro studies of female reproduction and oviposition in Schistosoma japonicum

Parasites & Vectors, Год журнала: 2024, Номер 17(1)

Опубликована: Март 7, 2024

Abstract Background Schistosomiasis is a disease primarily caused by eggs laid pathogens called schistosomes. Among the schistosome species infecting humans, Schistosoma japonicum possesses largest fecundity; each adult female produces an average of 3500 per day. The lack proper culture conditions supporting continuous oviposition in vitro has precluded detailed investigation mechanisms regulating sexual maturation and egg production . Methods We optimized replacing reagents that are part classical ABC169 medium. Fast Blue BB staining 4′,6-diamidino-2-phenylindole (DAPI) labeling were applied to observe development status females. In RNA interference (RNAi) technology was used validate capability modified detection male β-alanyl-tryptamine (BATT) conducted using liquid chromatography–mass spectrometry (LC–MS). Results Both m-AB169 (1640) AB169 media capable facilitating paired virgin S. , as well sustaining mature reproductive organs for at least 22 days vitro. M-AB169 provided more stable condition maturity evidenced consistent initiation compared with (1640). Through comparative analysis mansoni diverse media, we demonstrated these closely related display distinct demands their production, suggesting potential influence nutritional factors on observed variations host ranges among different species. Importantly, successfully identified presence pheromone previously highlighting its conserved role development. employment double-stranded (dsRNA) treatment silence two genes involved either ( gli1 glioma-associated oncogene homolog 1 ) or vf1 vitellogenic factor side male-induced confirmed combination RNAi capacity facilitate studies ’s processes. Conclusions developed novel medium, (1640), not only maintains up but also supports subsequent egg-laying females after pairing worms. This study provides valuable platform functional underlying fascinating biology which may accelerate new strategies targeting production. Graphical

Язык: Английский

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