neurotropic
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The incidences of multiple sclerosis have risen worldwide, yet neither the trigger nor efficient treatment is known. Some research is dedicated to looking for treatment by parasites, mainly by helminths. However, little is known about the effect of helminths that infect the nervous system. Therefore, we chose the neurotropic avian schistosome Trichobilharzia regenti, which strongly promotes M2 polarization and tissue repair in the central nervous system, and we tested its effect on the course of experimental autoimmune encephalomyelitis (EAE) in mice. Surprisingly, the symptoms of EAE tended to worsen after the infection with T. regenti. The infection did not stimulate tissue repair, as indicated by the similar level of demyelination. Eosinophils heavily infiltrated the infected tissue, and the microglia number increased as well. Furthermore, splenocytes from T. regenti-infected EAE mice produced more interferon (IFN)-γ than splenocytes from EAE mice after stimulation with myelin oligodendrocyte glycoprotein. Our research indicates that the combination of increased eosinophil numbers and production of IFN-γ tends to worsen the EAE symptoms. Moreover, the data highlight the importance of considering the direct effect of the parasite on the tissue, as the migrating parasite may further tissue damage and make tissue repair even more difficult.
- Klíčová slova
- EAE, IFN-γ, Trichobilharzia regenti, demyelination, eosinophilia, experimental autoimmune encephalomyelitis, neurotropic parasite, neurotropic schistosome,
- MeSH
- encefalomyelitida autoimunitní experimentální * imunologie patologie MeSH
- eozinofily imunologie MeSH
- interferon gama * metabolismus MeSH
- myši inbrední C57BL * MeSH
- myši MeSH
- roztroušená skleróza imunologie patologie MeSH
- Schistosomatidae fyziologie MeSH
- slezina patologie parazitologie imunologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interferon gama * MeSH
The importance of neurotropic vitamins in the prevention and adjuvant therapy of peripheral neuropathy - A pharmacist's comprehensive view Peripheral neuropathy is one of the most common neurological diseases of the peripheral nervous system. According to current statistics, it affects 2.4% of the Czech population, and its prevalence continues to increase with age. The possibilities of its treatment are to a large extent limited, and its effectiveness and the patient's tolerance of pharmacotherapy are individual. Neurotropic vitamins, which support the function of neurons and contribute to their protection and regeneration, represent a promising possibility for prevention and use in adjuvant therapy for patients suffering from this disease. Despite the fact that the diagnosis and treatment of peripheral neuropathy belong to the doctor, the role of the pharmacist can be crucial not only in the area of ensuring effective and safe pharmacotherapy and adherence to it, but also in pre-screening of at-risk persons visiting pharmacies. The primary aim of the article is therefore to familiarize readers with the significance of neurotropic vitamins in the prevention and adjunct therapy of peripheral neuropathy, as well as the role of the pharmacist in the care of patients suffering from this condition.
- Klíčová slova
- Peripheral neuropathy, Pharmaceutical Care, neurotropic vitamins,
- MeSH
- farmaceuti * MeSH
- lidé MeSH
- nemoci periferního nervového systému * prevence a kontrola farmakoterapie MeSH
- role odborníka MeSH
- vitaminy * terapeutické užití MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- vitaminy * MeSH
The European subtype of tick-borne encephalitis virus (TBEV-Eur; species Orthoflavivirus encephalitidis, family Flaviviridae) was the only tick-borne flavivirus present in central Europe known to cause neurologic disease in humans and several animal species. Here, we report a tick-borne flavivirus isolated from Alpine chamois (Rupicapra rupicapra rupicapra) with encephalitis and attached ticks, present over a wide area in the Alps. Cases were detected in 2017 in Salzburg, Austria, and 2023 in Lombardy and Piedmont, Italy. The virus strains exhibit 94.8-97.3% nucleotide identities to each other and are more closely related to Louping ill viruses (LIV; Orthoflavivirus loupingi; 90-92% identities) than to TBEV-Eur (less than 88%). The chamois-derived virus strains, tentatively termed "Alpine chamois encephalitis virus", form a well-supported independent genetic clade with Spanish goat encephalitis virus, clearly separated from other LIV. This supports its designation as a new virus subtype with the proposed shared taxonomic name "Spanish goat and Alpine chamois encephalitis virus subtype" within the species Orthoflavivirus loupingi. The zoonotic potential of this newly identified virus subtype as well as its host range in other animal species including farm animals needs to be further investigated.
- Klíčová slova
- Alpine chamois, Flaviviridae, Ixodes ricinus, Rupicapra rupicapra, Spanish goat encephalitis virus, encephalitis, flavivirus, louping ill virus, neurotropic, tick-borne encephalitis virus,
- MeSH
- fylogeneze MeSH
- genom virový MeSH
- klíšťata virologie MeSH
- klíšťová encefalitida * veterinární virologie epidemiologie MeSH
- Rupicapra * virologie MeSH
- viry klíšťové encefalitidy * genetika izolace a purifikace klasifikace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Itálie epidemiologie MeSH
- Rakousko epidemiologie MeSH
Neurotropic pathogens, notably, herpesviruses, have been associated with significant neuropsychiatric effects. As a group, these pathogens can exploit molecular mimicry mechanisms to manipulate the host central nervous system to their advantage. Here, we present a systematic computational approach that may ultimately be used to unravel protein-protein interactions and molecular mimicry processes that have not yet been solved experimentally. Toward this end, we validate this approach by replicating a set of pre-existing experimental findings that document the structural and functional similarities shared by the human cytomegalovirus-encoded UL144 glycoprotein and human tumor necrosis factor receptor superfamily member 14 (TNFRSF14). We began with a thorough exploration of the Homo sapiens protein database using the Basic Local Alignment Search Tool (BLASTx) to identify proteins sharing sequence homology with UL144. Subsequently, we used AlphaFold2 to predict the independent three-dimensional structures of UL144 and TNFRSF14. This was followed by a comprehensive structural comparison facilitated by Distance-Matrix Alignment and Foldseek. Finally, we used AlphaFold-multimer and PPIscreenML to elucidate potential protein complexes and confirm the predicted binding activities of both UL144 and TNFRSF14. We then used our in silico approach to replicate the experimental finding that revealed TNFRSF14 binding to both B- and T-lymphocyte attenuator (BTLA) and glycoprotein domain and UL144 binding to BTLA alone. This computational framework offers promise in identifying structural similarities and interactions between pathogen-encoded proteins and their host counterparts. This information will provide valuable insights into the cognitive mechanisms underlying the neuropsychiatric effects of viral infections.
- Klíčová slova
- Bioinformatics, Cognition, Mitochondria, Psychiatry, Virus,
- MeSH
- kognice fyziologie MeSH
- lidé MeSH
- molekulární mimikry * MeSH
- molekulární modely MeSH
- sekvence aminokyselin MeSH
- vazba proteinů MeSH
- virové proteiny metabolismus chemie MeSH
- výpočetní biologie metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- virové proteiny MeSH
Trichobilharzia species are parasitic flatworms (called schistosomes or flukes) that cause important diseases in birds and humans, but very little is known about their molecular biology. Here, using a transcriptomics-bioinformatics-based approach, we explored molecular aspects pertaining to the nutritional requirements of Trichobilharzia szidati ('visceral fluke') and T. regenti ('neurotropic fluke') in their avian host. We studied the larvae of each species before they enter (cercariae) and as they migrate (schistosomules) through distinct tissues in their avian (duck) host. Cercariae of both species were enriched for pathways or molecules associated predominantly with carbohydrate metabolism, oxidative phosphorylation and translation of proteins linked to ribosome biogenesis, exosome production and/or lipid biogenesis. Schistosomules of both species were enriched for pathways or molecules associated with processes including signal transduction, cell turnover and motility, DNA replication and repair, molecular transport and/or catabolism. Comparative informatic analyses identified molecular repertoires (within, e.g., peptidases and secretory proteins) in schistosomules that can broadly degrade macromolecules in both T. szidati and T. regenti, and others that are tailored to each species to selectively acquire nutrients from particular tissues through which it migrates. Thus, this study provides molecular evidence for distinct modes of nutrient acquisition between the visceral and neurotropic flukes of birds.
- MeSH
- cerkárie klasifikace genetika patogenita MeSH
- DNA helmintů klasifikace genetika MeSH
- fylogeneze * MeSH
- kachny genetika parazitologie MeSH
- lidé MeSH
- nemoci ptáků genetika parazitologie MeSH
- ptáci genetika parazitologie MeSH
- Schistosomatidae genetika patogenita MeSH
- schistosomóza genetika parazitologie MeSH
- Trematoda klasifikace genetika patogenita MeSH
- výpočetní biologie MeSH
- živiny MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- DNA helmintů MeSH
The bird nasal schistosome Trichobilharzia regenti is a new agent of cercarial dermatitis. Cercariae are able to penetrate the skin of birds and mammals including man. The parasite then attacks the central nervous system. The present study has shown that schistosomula avoid penetration of blood capillaries and enter the peripheral nerves of the legs of mice and ducks as early as 1 day post-infection (p.i.) and 1.5 days p.i., respectively. These peripheral nerves are used as a route to the spinal cord. In the specific host (duck) schistosomula were found in the spinal cord from 2 days p.i. until 15 days p.i. and in the brain from 12 days p.i. until 18 days p.i. In non-specific hosts (mice; inbred strains BALB/c, hr/hr, SCID) living schistosomula were found in the spinal cord from 2 days p.i. until 21 or 24 days p.i. (depending on the mouse strain) and in the brain of two (BALB/c, SCID) of three inbred strains from 3 days p.i. until 24 days p.i. No correlation was found between the infection dose and clinical status of the experimental hosts. A high affinity of schistosomula for the peripheral nerves was also proved in vitro, suggesting a new type of migratory behaviour in schistosomatids.
- MeSH
- druhová specificita MeSH
- helmintózy centrálního nervového systému parazitologie veterinární MeSH
- infekce červy třídy Trematoda parazitologie veterinární MeSH
- interakce hostitele a parazita MeSH
- kachny parazitologie MeSH
- mícha parazitologie MeSH
- mozek parazitologie MeSH
- myši inbrední BALB C MeSH
- myši SCID MeSH
- myši MeSH
- nemoci ptáků parazitologie MeSH
- periferní nervy parazitologie MeSH
- progrese nemoci MeSH
- Schistosomatidae patogenita MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- elektronová mikroskopie MeSH
- králíci MeSH
- krysa rodu Rattus MeSH
- mozková kůra účinky léků ultrastruktura MeSH
- parasympatomimetika farmakologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- parasympatomimetika MeSH
- Klíčová slova
- VIRUS DISEASES/immunology *,
- MeSH
- lidé MeSH
- neutralizující protilátky * MeSH
- oxidace-redukce * MeSH
- RNA-viry * MeSH
- virové nemoci imunologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Albánie MeSH
- Názvy látek
- neutralizující protilátky * MeSH
- MeSH
- centrální nervový systém účinky léků MeSH
- cyklofosfamid farmakologie MeSH
- imunosupresiva farmakologie MeSH
- myši MeSH
- neuroglie účinky léků MeSH
- neurony účinky léků MeSH
- virové nemoci MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- cyklofosfamid MeSH
- imunosupresiva MeSH
- Klíčová slova
- PSYCHOPHARMACOLOGY *, REFLEX, CONDITIONED/pharmacology *,
- MeSH
- fyziologické jevy * MeSH
- klasické podmiňování farmakologie MeSH
- nervový systém - fyziologické jevy * MeSH
- psychofarmakologie * MeSH
- reflex * MeSH
- Publikační typ
- časopisecké články MeSH