- Klíčová slova
- McKenzie mechanická diagnostika,
- MeSH
- krční obratle * patofyziologie MeSH
- lidé MeSH
- muskuloskeletální bolest diagnóza klasifikace rehabilitace MeSH
- muskuloskeletální systém patofyziologie MeSH
- terapie cvičením * metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
- MeSH
- Hepacivirus fyziologie genetika patogenita MeSH
- herpesvirus B fyziologie genetika patogenita MeSH
- infekce viry z rodu Deltaretrovirus genetika MeSH
- lidské papilomaviry fyziologie genetika patogenita MeSH
- nádorové buněčné linie klasifikace virologie MeSH
- onkogenní viry * růst a vývoj MeSH
- transformace genetická MeSH
- virová transformace buněk MeSH
- virus hepatitidy B fyziologie genetika patogenita MeSH
The tick-borne encephalitis virus (TBEV) causes a most important viral life-threatening illness transmitted by ticks. The interactions between the virus and ticks are largely unexplored, indicating a lack of experimental tools and systematic studies. One such tool is recombinant reporter TBEV, offering antibody-free visualization to facilitate studies of transmission and interactions between a tick vector and a virus. In this paper, we utilized a recently developed recombinant TBEV expressing the reporter gene mCherry to study its fitness in various tick-derived in vitro cell cultures and live unfed nymphal Ixodes ricinus ticks. The reporter virus was successfully replicated in tick cell lines and live ticks as confirmed by the plaque assay and the mCherry-specific polymerase chain reaction (PCR). Although a strong mCherry signal determined by fluorescence microscopy was detected in several tick cell lines, the fluorescence of the reporter was not observed in the live ticks, corroborated also by immunoblotting. Our data indicate that the mCherry reporter TBEV might be an excellent tool for studying TBEV-tick interactions using a tick in vitro model. However, physiological attributes of a live tick, likely contributing to the inactivity of the reporter, warrant further development of reporter-tagged viruses to study TBEV in ticks in vivo.
Východiská: Imunoterapia predstavuje efektívny spôsob liečby mnohých ochorení spojených s poruchami imunitného systému prostredníctvom modulácie imunitnej odpovede organizmu. Zahŕňa viacero možností manipulácie imunitného systému, ktoré buď imunitnú odpoveď potláčajú, alebo ju naopak stimulujú. V súčasnosti má nesmierny význam nielen v kontexte liečby autoimunitných ochorení a imunodeficiencií, ale je taktiež perspektívnou metódou liečby nádorových ochorení. Snaha vedcov využiť vlastnú protinádorovú odpoveď organizmu viedla k objaveniu alternatívnych spôsobov liečby nádorov. Cieľ: Cieľom predloženého príspevku je poskytnúť literárny prehľad zameraný na súčasné možnosti imunoterapie nádorových ochorení. Okrem klasických postupov, akými sú chemoterapia a rádioterapia, sa čoraz viac indikujú liečebné postupy spočívajúce v adoptívnej bunkovej terapii a inhibícii kontrolných bodov imunitnej reakcie. Najnovšou podobou adoptívnej bunkovej terapie je využitie T-lymfocytov exprimujúcich chimerické antigénne receptory. Tento typ liečby je indikovaný pri hematologických nádorových ochoreniach. V posledných rokoch sa do popredia dostáva nový prístup nádorovej terapie využívajúci blokáciu tzv. inhibítorov kontrolných bodov prostredníctvom monoklonálnych protilátok. V súčasnosti sa protinádorová terapia zameriava na blokáciu inhibičných molekúl – cytotoxic T-lymfocyte antigen 4 (CTLA-4) a programovej bunkovej smrti 1 (PD-1). Podaním monoklonálnych protilátok špecifických proti receptorom CTLA-4 dochádza k blokácii väzby medzi CTLA-4 receptormi a B7 ligandmi, čím sa zabráni inhibícii aktivovaných cytotoxických T-lymfocytov. K ďalšiemu typu kontrolných bodov imunitnej reakcie patria molekuly PD-1 exprimované na povrchu T-lymfocytov, B-lymfocytov, ale aj na povrchu myeloidných buniek. Blokácia receptorov PD-1 a ligandov PD-L1 zabraňuje inhibícii T-lymfocytov nádorovými bunkami, čo vedie k zvyšovaniu schopnosti imunitného systému rozpoznať nádorové bunky a následne ich deštruovať. Alternatívnou formou liečby nádorov je aj podávanie nádorových vakcín a nádorovo špecifických monoklonálnych protilátok (mAbs). Využitie mAbs k likvidácii nádorov vyžaduje expresiu tumor špecifických antigénov na povrchu nádorových buniek. Prostredníctvom týchto receptorov mAb nasmeruje cytotoxické bunky, toxíny, liečivá alebo rádioizotopy k nádorovým bunkám, a tým ich deštruuje. Taktiež sú mAbs schopné blokovať angiogenézu, ktorá je kľúčová pri množení nádorových buniek.
Background: Immunotherapy is an effective way to treat many diseases associated with disorders of the immune system by modulating immune response. It involves several ways of manipulating the immune system, which either suppress the immune response or, on the contrary, stimulates it. Immunotherapy is currently of immense importance not only in the context of the treatment of autoimmune diseases and immunodeficiencies, but it is also a promising method for treating cancer. Efforts to use the body‘s own anti-tumor response have led to the discovery of alternative treatments for cancer. Purpose: The aim of this paper is to provide a literature review focused on the current possibilities of cancer immunotherapy. In addition to classical procedures such as chemotherapy and radiotherapy, treatments consisting of adoptive cell therapy and blockade of immune checkpoints are being increasingly indicated. The latest form of adoptive cell therapy is the use of T-lymphocytes expressing chimeric antigen receptors. This type of treatment is indicated for hematological cancers. In recent years, a new approach to the treatment of cancer has emerged using blockade of immune checkpoints by monoclonal antibodies. At present, antitumor therapy focuses on blocking of inhibitory molecules – cytotoxic T-lymfocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1). Administration of anti-CTLA-4 receptor specific monoclonal antibodies blocks binding between CTLA-4 receptors and B7 ligands, thereby preventing inhibition of activated cytotoxic T cells. Another type of checkpoints of the immune response include PD-1 molecules expressed on the surface of T-lymphocytes, B-lymphocytes, but also on the surface of myeloid cells. Blockade of PD-1 receptors and PD-L1 ligands prevents the inhibition of T-lymphocytes by tumor cells, leading to an increase in the immune system‘s ability to recognize tumor cells and subsequently destroy them. Blockade of PD-1 receptors and PD-L1 ligands prevents the inhibition of T-lymphocytes by tumor cells, leading to an increased immune response to the recognition of tumor cells and their subsequent destruction. An alternative form of tumor treatment is the administration of tumor vaccines and tumor-specific monoclonal antibodies (mAbs). The use of mAbs to kill tumors requires the expression of tumor-specific antigens on the surface of tumor cells. Through these receptors, mAb targets cytotoxic cells, toxins, drugs, or radioisotopes to tumor cells and thereby destroys them. Also, mAbs are able to block angiogenesis, which is crucial in tumor cell proliferation.
- MeSH
- buněčná a tkáňová terapie MeSH
- imunoterapie metody MeSH
- lidé MeSH
- monoklonální protilátky terapeutické užití MeSH
- nádory * farmakoterapie imunologie MeSH
- protinádorové vakcíny MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Sucking lice (Anoplura) are known to have established symbiotic associations multiple times with different groups of bacteria as diverse as Enterobacteriales, Legionellales, and Neisseriales. This diversity, together with absence of a common coevolving symbiont (such as Buchnera, in aphids), indicates that sucking lice underwent a series of symbiont acquisitions, losses, and replacements. To better understand evolution and significance of louse symbionts, genomic and phylogenetic data are needed from a broader taxonomic diversity of lice and their symbiotic bacteria. In this study, we extend the known spectrum of the louse symbionts with a new lineage associated with Neohaematopinus pacificus, a louse species that commonly parasitizes North American chipmunks. The recent coevolutionary analysis showed that rather than a single species, these lice form a cluster of unique phylogenetic lineages specific to separate chipmunk species (or group of closely related species). Using metagenomic assemblies, we show that the lice harbor a bacterium which mirrors their phylogeny and displays traits typical for obligate mutualists. Phylogenetic analyses place this bacterium within Enterobacteriaceae on a long branch related to another louse symbiont, "Candidatus Puchtella pedicinophila." We propose for this symbiotic lineage the name "Candidatus Lightella neohaematopini." Based on the reconstruction of metabolic pathways, we suggest that like other louse symbionts, L. neohaematopini provides its host with at least some B vitamins. In addition, several samples harbored another symbiotic bacterium phylogenetically affiliated with the Neisseriales-related symbionts described previously from the lice Polyplax serrata and Hoplopleura acanthopus. Characterizing these bacteria further extend the known diversity of the symbiotic associations in lice and show unique complexity and dynamics of the system.
- Publikační typ
- časopisecké články MeSH
Obligate symbiotic bacteria associated with the insects feeding exclusively on vertebrate blood are supposed to complement B vitamins presumably lacking in their diet. Recent genomic analyses revealed considerable differences in biosynthetic capacities across different symbionts, suggesting that levels of B vitamins may vary across different vertebrate hosts. However, a rigorous determination of B vitamins content in blood of various vertebrates has not yet been approached. A reliable analytical method focused on B vitamin complex in blood can provide valuable informative background and understanding of general principles of insect symbiosis. In this work, a chromatographic separation of eight B vitamins (thiamine, riboflavin, niacin, pantothenic acid, pyridoxine, biotin, folic acid, and cyanocobalamine), four B vitamin derivatives (niacinamide, pyridoxal-5-phosphate, 4-pyridoxic acid, and tetrahydrofolic acid), and 3 stable isotope labelled internal standards was developed. Detection was carried out using dual-pressure linear ion trap mass spectrometer in FullScan MS/MS and SIM mode. Except for vitamin B9 (tetrahydrofolic acid), the instrument quantitation limits of all analytes were ranging from 0.42 to 5.0 μg/L, correlation coefficients from 0.9997 to 1.0000, and QC coefficients from 0.53 to 3.2%. Optimization of whole blood sample preparation step was focused especially on evaluation of two types of protein-precipitation agents: trichloroacetic acid and zinc sulphate in methanol. The best results were obtained for zinc sulphate in methanol, but only nine analytes were successfully validated. Accuracy of the procedure using this protein-precipitating agent was ranging from 89 to 120%, precision from 0.5 to 13%, and process efficiency from 65 to 108%. The content of B vitamins in whole blood samples from human and various vertebrates is presented as an application example of this newly developed method.
- MeSH
- chromatografie kapalinová metody MeSH
- kyselina listová analýza MeSH
- lidé MeSH
- methanol MeSH
- riboflavin analýza MeSH
- síran zinečnatý MeSH
- tandemová hmotnostní spektrometrie metody MeSH
- thiamin analýza MeSH
- vitamin B komplex * MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: Kissing bugs (Triatominae) are blood-feeding insects best known as the vectors of Trypanosoma cruzi, the causative agent of Chagas' disease. Considering the high epidemiological relevance of these vectors, their biology and bacterial symbiosis remains surprisingly understudied. While previous investigations revealed generally low individual complexity but high among-individual variability of the triatomine microbiomes, any consistent microbiome determinants have not yet been identified across multiple Triatominae species. METHODS: To obtain a more comprehensive view of triatomine microbiomes, we investigated the host-microbiome relationship of five Triatoma species sampled from white-throated woodrat (Neotoma albigula) nests in multiple locations across the USA. We applied optimised 16S rRNA gene metabarcoding with a novel 18S rRNA gene blocking primer to a set of 170 T. cruzi-negative individuals across all six instars. RESULTS: Triatomine gut microbiome composition is strongly influenced by three principal factors: ontogeny, species identity, and the environment. The microbiomes are characterised by significant loss in bacterial diversity throughout ontogenetic development. First instars possess the highest bacterial diversity while adult microbiomes are routinely dominated by a single taxon. Primarily, the bacterial genus Dietzia dominates late-stage nymphs and adults of T. rubida, T. protracta, and T. lecticularia but is not present in the phylogenetically more distant T. gerstaeckeri and T. sanguisuga. Species-specific microbiome composition, particularly pronounced in early instars, is further modulated by locality-specific effects. In addition, pathogenic bacteria of the genus Bartonella, acquired from the vertebrate hosts, are an abundant component of Triatoma microbiomes. CONCLUSION: Our study is the first to demonstrate deterministic patterns in microbiome composition among all life stages and multiple Triatoma species. We hypothesise that triatomine microbiome assemblages are produced by species- and life stage-dependent uptake of environmental bacteria and multiple indirect transmission strategies that promote bacterial transfer between individuals. Altogether, our study highlights the complexity of Triatominae symbiosis with bacteria and warrant further investigation to understand microbiome function in these important vectors. Video abstract.
- MeSH
- Chagasova nemoc parazitologie MeSH
- divoká zvířata klasifikace mikrobiologie MeSH
- mikrobiota genetika fyziologie MeSH
- RNA ribozomální 16S genetika MeSH
- Triatominae klasifikace mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- audiovizuální média MeSH
- časopisecké články MeSH
- práce podpořená grantem MeSH
