Anti-Toxoplasma gondii effect of tylosin in vitro and in vivo DOI Creative Commons

Ruxia Han,

Pi-Cheng Jiang,

Bing Han

и другие.

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

Опубликована: Фев. 10, 2024

Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective sometimes cause serious side effects. There urgent need the development more drugs relatively low toxicity. Methods The effect tylosin on viability host cells was measured using CCK8 assays. To assess inhibition T. proliferation, a real-time PCR targeting B1 gene developed detection quantification. Total RNA extracted from parasites treated then subjected to transcriptome analysis by sequencing (RNA-seq). Finally, murine infection models were evaluate protective efficacy against virulent RH strain or avirulent ME49 strain. Results We found that displayed toxicity, its 50% inhibitory concentration 175.3 μM. Tylsoin also inhibited intracellular tachyzoite 9.759 Transcriptome showed remarkably perturbed expression , genes involved in “ribosome biogenesis (GO:0042254)” (GO:0005840)” significantly dys-regulated. In model, alone (100 mg/kg, i.p.) combination sulfadiazine sodium (200 i.g.) prolonged survival time raised rate animals infected Meanwhile, decreased parasite burdens multiple organs spleen index mice acute toxoplasmosis. Conclusions Our findings suggest exhibited potency both vitro vivo, which offers promise human Graphical

Язык: Английский

The molecular architecture of the nuclear basket DOI Creative Commons
Digvijay Singh, Neelesh Soni, Joshua Hutchings

и другие.

Cell, Год журнала: 2024, Номер 187(19), С. 5267 - 5281.e13

Опубликована: Авг. 9, 2024

The nuclear pore complex (NPC) is the sole mediator of nucleocytoplasmic transport. Despite great advances in understanding its conserved core architecture, peripheral regions can exhibit considerable variation within and between species. One such structure cage-like basket. crucial roles mRNA surveillance chromatin organization, an architectural has remained elusive. Using in-cell cryo-electron tomography subtomogram analysis, we explored NPC's structural variations basket across fungi (yeast; S. cerevisiae), mammals (mouse; M. musculus), protozoa (T. gondii). integrative modeling, computed a model yeast that revealed how hub nucleoporins (Nups) ring binds to basket-forming Mlp/Tpr proteins: coiled-coil domains form struts basket, while their unstructured termini constitute distal densities, which potentially serve as docking site for preprocessing before

Язык: Английский

Процитировано

27

Comprehensive Overview of Toxoplasma gondii-Induced and Associated Diseases DOI Creative Commons
Darine Daher,

Ahmad Shaghlil,

Eyad Sobh

и другие.

Pathogens, Год журнала: 2021, Номер 10(11), С. 1351 - 1351

Опубликована: Окт. 20, 2021

Toxoplasma gondii (T. gondii) is a prevalent protozoan parasite of medical and veterinary significance. It the etiologic agent toxoplasmosis, neglected disease in which incidence symptoms differ between patients regions. In immunocompetent patients, toxoplasmosis manifests as acute chronic forms. Acute presents mild or asymptomatic that evolves, under host immune response, into persistent healthy individuals. Chronic establishes latent tissue cysts brain skeletal muscles. immunocompromised may reactivate, leading to potentially life-threatening condition. Recently, association various diseases has been shown. These span primary neuropathies, behavioral psychiatric disorders, different types cancer. Currently, direct pre-clinical clinical molecular connotation most its associated remains poorly understood. this review, we provide comprehensive overview on Toxoplasma-induced with focus available knowledge players dictating these associations. We will also abridge existing therapeutic options highlight current gaps explore implications advance treatment modalities.

Язык: Английский

Процитировано

75

Schizophrenia: The new etiological synthesis DOI Creative Commons
Markus J. Rantala, Severi Luoto, Javier I. Borráz-León

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2022, Номер 142, С. 104894 - 104894

Опубликована: Сен. 28, 2022

Schizophrenia has been an evolutionary paradox: it high heritability, but is associated with decreased reproductive success. The causal genetic variants underlying schizophrenia are thought to be under weak negative selection. To unravel this paradox, many explanations have suggested for schizophrenia. We critically discuss the constellation of hypotheses schizophrenia, highlighting lack empirical support most existing hypotheses—with exception relatively well supported mismatch hypothesis. It posits that evolutionarily novel features contemporary environments, such as chronic stress, low-grade systemic inflammation, and gut dysbiosis, increase susceptibility Environmental factors microbial infections (e.g., Toxoplasma gondii) can better predict onset than polygenic risk scores. However, researchers not able explain why only a small minority infected people develop new etiological synthesis indicates interaction between host genotype, microbe infection, stress causes neuroinflammation dysbiosis mediating pathway. Instead just alleviating symptoms drugs, parasite x genotype model emphasizes treatment should focus on detecting treating possible infection(s), neuroinflammation, stress.

Язык: Английский

Процитировано

50

A heterotrimeric complex of Toxoplasma proteins promotes parasite survival in interferon gamma-stimulated human cells DOI Creative Commons
Eloise J. Lockyer, Francesca Torelli, Simon Butterworth

и другие.

PLoS Biology, Год журнала: 2023, Номер 21(7), С. e3002202 - e3002202

Опубликована: Июль 17, 2023

Toxoplasma gondii secretes protein effectors to subvert the human immune system sufficiently establish a chronic infection. Relative murine infections, little is known about which parasite disarm responses. Here, we used targeted CRISPR screening identify secreted required for survival in IFNγ-activated cells. Independent screens were carried out using 2 strains that differ virulence mice, leading identification of We GRA57 and other proteins, GRA70 GRA71, together form complex enhances ability parasites persist foreskin fibroblasts (HFFs). Components machinery export proteins into host cell also found be important resistance IFNγ cells, but these components function independently identified complex. Host-mediated ubiquitination vacuole has previously been associated with increased clearance from find vacuoles GRA57, GRA70, GRA71 knockout are surprisingly less ubiquitinated by cell. hypothesise this likely secondary consequence deletion complex, unlinked mediated effectors.

Язык: Английский

Процитировано

34

Global seroprevalence of Toxoplasma gondii infection among patients with mental and neurological disorders: A systematic review and meta‐analysis DOI Creative Commons
Habtye Bisetegn, Habtu Debash, Hussen Ebrahim

и другие.

Health Science Reports, Год журнала: 2023, Номер 6(6)

Опубликована: Июнь 1, 2023

Toxoplasmosis is the most widespread zoonotic disease that affects one-third of world's population, and imposes a major public health problem worldwide. This study aimed to assess prevalence toxoplasmosis among patients with neuropsychiatric patients.

Язык: Английский

Процитировано

27

Function and regulation of cGAS-STING signaling in infectious diseases DOI Creative Commons
Yang Du, Zhiqiang Hu,

Yien Luo

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Фев. 6, 2023

The efficacious detection of pathogens and prompt induction innate immune signaling serve as a crucial component defense against infectious pathogens. Over the past decade, DNA-sensing receptor cyclic GMP-AMP synthase (cGAS) its downstream adaptor stimulator interferon genes (STING) have emerged key mediators type I (IFN) nuclear factor-κB (NF-κB) responses in health infection diseases. Moreover, both cGAS-STING pathway developed delicate strategies to resist each other for their survival. mechanistic functional comprehension interplay between is opening way development application pharmacological agonists antagonists treatment Here, we briefly review current knowledge DNA sensing through pathway, emphatically highlight potent undertaking host pathogenic organisms.

Язык: Английский

Процитировано

26

Biogenesis of extracellular vesicles in protozoan parasites: The ESCRT complex in the trafficking fast lane? DOI Creative Commons
Abel Cruz Camacho, Daniel Alfandari, Ewa Kozela

и другие.

PLoS Pathogens, Год журнала: 2023, Номер 19(2), С. e1011140 - e1011140

Опубликована: Фев. 23, 2023

Extracellular vesicles (EVs) provide a central mechanism of cell–cell communication. While EVs are found in most organisms, their pathogenesis-promoting roles parasites particular interest given the potential for medical insight and consequential therapeutic intervention. Yet, key feature human parasitic protozoa remains elusive: mechanisms biogenesis. Here, we survey current knowledge on biogenesis pathways secreted by four main clades protozoa: apicomplexans, trypanosomatids, flagellates, amoebae. In particular, shine light findings pertaining to Endosomal Sorting Complex Required Transport (ESCRT) machinery, as mammals it plays important EV This review highlights diversity protozoa, well related involvement ESCRT system these unique organisms.

Язык: Английский

Процитировано

24

Immune responses to Toxoplasma gondii DOI Creative Commons
Imtiaz A. Khan, Magali Moretto

Current Opinion in Immunology, Год журнала: 2022, Номер 77, С. 102226 - 102226

Опубликована: Июль 1, 2022

Язык: Английский

Процитировано

38

Toxoplasmosis vaccines: what we have and where to go? DOI Creative Commons
Yizhuo Zhang, Dan Li, Shaohong Lu

и другие.

npj Vaccines, Год журнала: 2022, Номер 7(1)

Опубликована: Окт. 31, 2022

Abstract Despite recent major advances in developing effective vaccines against toxoplasmosis, finding new protective vaccination strategies remains a challenging and elusive goal as it is critical to prevent the disease. Over past few years, various experimental approaches have shown that an vaccine T. gondii achievable. However, more unknown due its complicated life cycle, difficulties clinical translation, lack of standardized platform. This minireview summarizes development main obstacles safe, durable vaccine. The successes failures testing candidates for are also discussed, which may facilitate future vaccines.

Язык: Английский

Процитировано

38

Toxoplasma gondii in Foods: Prevalence, Control, and Safety DOI Creative Commons
Pablo Jesús Marín‐García, Núria Planas, Lola Llobat

и другие.

Foods, Год журнала: 2022, Номер 11(16), С. 2542 - 2542

Опубликована: Авг. 22, 2022

Toxoplasma gondii is an obligate intracellular parasite that causes toxoplasmosis, with approximately one third of the population around world seropositive. The consumption contaminated food main source infection. These include meat products T. tissue cysts, and dairy tachyzoites. Recently, contamination has been detected in fresh oocysts marine products. Despite great health problems are caused by gondii, currently there no standardized methods for its detection industry. In this review, we analyze current methods, prevalence different products, control measures. bioassays, cell culture, molecular microscopic techniques, serological but some these do not have applicability As a result, emerging techniques being developed aimed at multiple parasites simultaneously would make their application more efficient Since high many (meat milk, vegetables), it necessary to standardize as well implement

Язык: Английский

Процитировано

35