Aberrant glycosylation of glycoproteins has been linked with various pathologies. Therefore, understanding the relationship between aberrant glycosylation patterns and the onset and progression of the disease is an important research goal that may provide insights into cancer diagnosis and new therapy development. In this study, we use a surface plasmon resonance imaging biosensor and a lectin array to investigate aberrant glycosylation patterns associated with oncohematological disease-myelodysplastic syndromes (MDS). In particular, we detected the interaction between the lectins and glycoproteins present in the blood plasma of patients (three MDS subgroups with different risks of progression to acute myeloid leukemia (AML) and AML patients) and healthy controls. The interaction with lectins from Aleuria aurantia (AAL) and Erythrina cristagalli was more pronounced for plasma samples of the MDS and AML patients, and there was a significant difference between the sensor response to the interaction of AAL with blood plasma from low and medium-risk MDS patients and healthy controls. Our data also suggest that progression from MDS to AML is accompanied by sialylation of glycoproteins and increased levels of truncated O-glycans and that the number of lectins that allow discriminating different stages of disease increases as the disease progresses.

• MeSH
• akutní myeloidní leukemie * MeSH
• biosenzitivní techniky * MeSH
• glykoproteiny metabolismus   MeSH
• glykosylace MeSH
• krevní plazma metabolismus   MeSH
• lektiny MeSH
• lidé MeSH
• myelodysplastické syndromy * terapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Galectin-3 plays a crucial role in cancerogenesis; its targeting is a prospective pathway in cancer diagnostics and therapy. Multivalent presentation of glycans was shown to strongly increase the affinity of glycoconjugates to galectin-3. Further strengthening of interaction with galectin-3 may be accomplished using artificial glycomimetics with apt aryl substitutions. We established a new, as yet undescribed chemoenzymatic method to produce selective C-3-substituted N,N'-diacetyllactosamine glycomimetics and coupled them to human serum albumin. From a library of enzymes, only β-N-acetylhexosaminidase from Talaromyces flavus was able to efficiently synthesize the C-3-propargylated disaccharide. Various aryl residues were attached to the functionalized N,N'-diacetyllactosamine via click chemistry to assess the impact of the aromatic substitution. In ELISA-type assays with galectin-3, free glycomimetics exhibited up to 43-fold stronger inhibitory potency to Gal-3 than the lactose standard. Coupling to human serum albumin afforded multivalent neo-glycoproteins with up to 4209-fold increased inhibitory potency per glycan compared to the monovalent lactose standard. Surface plasmon resonance brought further information on the kinetics of galectin-3 inhibition. The potential of prepared neo-glycoproteins to target galectin-3 was demonstrated on colorectal adenocarcinoma DLD-1 cells. We investigated the uptake of neo-glycoproteins into cells and observed limited non-specific transport into the cytoplasm. Therefore, neo-glycoproteins primarily act as efficient scavengers of exogenous galectin-3 of cancer cells, inhibiting its interaction with the cell surface, and protecting T-lymphocytes against galectin-3-induced apoptosis. The present neo-glycoproteins combine the advantage of a straightforward synthesis, selectivity, non-toxicity, and high efficiency for targeting exogenous galectin-3, with possible application in the immunomodulatory treatment of galectin-3-overexpressing cancers.

• MeSH
• biomimetické materiály chemická syntéza   chemie   farmakologie   MeSH
• galektiny antagonisté a inhibitory   genetika   metabolismus   MeSH
• glykoproteiny chemie   metabolismus   MeSH
• kinetika MeSH
• krevní proteiny antagonisté a inhibitory   genetika   metabolismus   MeSH
• lidé MeSH
• molekulární struktura MeSH
• vztah mezi dávkou a účinkem léčiva MeSH
• vztahy mezi strukturou a aktivitou MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Galectin-3 (gal-3) is lectin which is presumed to interact with extracellular matrix proteins and cell surface glycoproteins in normal and pathophysiological conditions. The expression of gal-3 at the fetal-maternal interface partially overlaps that of gal-1, suggesting that an interplay between them might be important for hypertensive disorders in pregnancy like preeclampsia. The aim of our study was to test the hypothesis whether galectin-3 could be used as a predictive marker for early-onset preeclampsia development. 32 patients with early-onset preeclampsia were examined, mean age 28.8 ± 5.5; and 22 age matched normal pregnancies mean age 28.5 ± 6.0. The enzyme-linked immunosorbent assay (ELISA) was used for measuring serum galectin-3 levels. There were no significant differences between serum levels of galectin-3 in sera of preeclampsia patients compared to normal pregnant women - 14.1 ± 4.77 vs. 15.7 ± 5.95 ng/ml (p>0.05). Serum galectin-3 levels correlated with maternal age (r=0.33; p=0.03) and BMI (body mass index) (r=0.52; p=0.01). Our data suggest that determination of serum galectin-3 levels may not be a useful method for prediction of early-onset preeclampsia. Studies should be aimed to other categories of biomarkers.

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• ELISA MeSH
• galektin 3 * krev   MeSH
• index tělesné hmotnosti MeSH
• lidé MeSH
• mladý dospělý MeSH
• preeklampsie * krev   diagnóza   MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Extensive exploitation of titanium dioxide nanoparticles (TiO2NPs) augments rapid release into the marine environment. When in contact with the body fluids of marine invertebrates, TiO2NPs undergo a transformation and adhere various organic molecules that shape a complex protein corona prior to contacting cells and tissues. To elucidate the potential extracellular signals that may be involved in the particle recognition by immune cells of the sea urchin Paracentrotus lividus, we investigated the behavior of TiO2NPs in contact with extracellular proteins in vitro. Our findings indicate that TiO2NPs are able to interact with sea urchin proteins in both cell-free and cell-conditioned media. The two-dimensional proteome analysis of the protein corona bound to TiO2NP revealed that negatively charged proteins bound preferentially to the particles. The main constituents shaping the sea urchin cell-conditioned TiO2NP protein corona were proteins involved in cellular adhesion (Pl-toposome, Pl-galectin-8, Pl-nectin) and cytoskeletal organization (actin and tubulin). Immune cells (phagocytes) aggregated TiO2NPs on the outer cell surface and within well-organized vesicles without eliciting harmful effects on the biological activities of the cells. Cells showed an active metabolism, no oxidative stress or caspase activation. These results provide a new level of understanding of the extracellular proteins involved in the immune-TiO2NP recognition and interaction in vitro, confirming that primary immune cell cultures from P. lividus can be an optional model for swift and efficient immune-toxicological investigations.

• MeSH
• buněčná adheze imunologie   MeSH
• fagocyty imunologie   MeSH
• galektiny imunologie   MeSH
• glykoproteiny imunologie   MeSH
• ježovky imunologie   MeSH
• nanočástice aplikace a dávkování   MeSH
• nektiny imunologie   MeSH
• Paracentrotus imunologie   MeSH
• proteinová korona imunologie   MeSH
• proteom imunologie   MeSH
• titan imunologie   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• alergologie a imunologie MeSH
• imunitní systém MeSH
• Publikační typ
• učebnice MeSH

• Konspekt
• Patologie. Klinická medicína
• Učební osnovy. Vyučovací předměty. Učebnice
• NLK Obory
• alergologie a imunologie

The etiology and pathogenesis of celiac disease remains obscure but remains the focus of intense research investigation. It is generally believed to be an immune-mediated small intestinal mucosal disorder that can cause diarrhea, impaired nutrient assimilation and weight loss. A key component in this process occurs at the intestinal epithelial cell surface that is closely associated with the luminal intestinal microbiome. Here, epithelial membrane glycoproteins and glycolipids are present along with adsorbed molecules that permit interaction with the intestinal microbiome. In recent years, use of specific sugar residue seeking proteins, lectins, that can be found in the diet have been employed topographically to map the small intestinal cell surface and goblet cell secretory mucins to further elucidate the structure and function of this tissue. Evidence has accumulated to indicate that this microenvironment may be critically important in further understanding the etiology and pathogenesis of celiac disease and other sprue-like intestinal disorders.

• MeSH
• celiakie * etiologie   patofyziologie   MeSH
• glykoproteiny MeSH
• lecitiny MeSH
• lidé MeSH
• střevní mikroflóra MeSH
• Check Tag
• lidé MeSH

Lectins, a distinct group of glycan-binding proteins, play a prominent role in the immune system ranging from pathogen recognition and tuning of inflammation to cell adhesion or cellular signalling. The possibilities of their detailed study expanded along with the rapid development of biomaterials in the last decade. The immense knowledge of all aspects of glycan-lectin interactions both in vitro and in vivo may be efficiently used in bioimaging, targeted drug delivery, diagnostic and analytic biological methods. Practically applicable examples comprise photoluminescence and optical biosensors, ingenious three-dimensional carbohydrate microarrays for high-throughput screening, matrices for magnetic resonance imaging, targeted hyperthermal treatment of cancer tissues, selective inhibitors of bacterial toxins and pathogen-recognising lectin receptors, and many others. This review aims to present an up-to-date systematic overview of glycan-decorated biomaterials promising for interactions with lectins, especially those applicable in biology, biotechnology or medicine. The lectins of interest include galectin-1, -3 and -7 participating in tumour progression, bacterial lectins from Pseudomonas aeruginosa (PA-IL), E. coli (Fim-H) and Clostridium botulinum (HA33) or DC-SIGN, receptors of macrophages and dendritic cells. The spectrum of lectin-binding biomaterials covered herein ranges from glycosylated organic structures, calixarene and fullerene cores over glycopeptides and glycoproteins, functionalised carbohydrate scaffolds of cyclodextrin or chitin to self-assembling glycopolymer clusters, gels, micelles and liposomes. Glyconanoparticles, glycan arrays, and other biomaterials with a solid core are described in detail, including inorganic matrices like hydroxyapatite or stainless steel for bioimplants.

• MeSH
• Bacteria chemie   MeSH
• biokompatibilní materiály chemie   normy   MeSH
• cukry chemie   MeSH
• galektiny chemie   metabolismus   MeSH
• lektiny typu C chemie   metabolismus   MeSH
• lektiny chemie   metabolismus   MeSH
• molekuly buněčné adheze metabolismus   MeSH
• receptory buněčného povrchu metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Lectin biochips and biosensors are used to detect and study the protein glycosylation. Glycosylation changes are accompanied by changes in physiological state, which may be associated with certain types of diseases such as cancer, rheumatoid arthritis, multiple sclerosis, etc. In recent years, this issue has been attracting more and more scientists and enormous advances have been achieved in this field. This work is focused on the use of surface plasmon resonance (SPR) in combination with lectin biosensors and biochips enabling tracking glycosylation and its changes. SPR is commonly used to detect proteins and to study the protein-protein and protein-drug interactions. Lectin SPR biochips additionally allow us to detect the glycan (glycoprotein)-lectin (protein) interactions. The great advantage of SPR, as compared to most other methods used for this purpose, is the possibility of real-time and label-free measurements. On the other hand, the measurement of large number of samples is time consuming. This is possible to overcome by using the SPR imaging (SPRi) techniques allowing simultaneous measurement of several samples. Practical applications of the lectin SPR biosensors and biochips are not only in biology and biomedicine research and diagnosis of diseases and detection of pathogenic microorganisms, but also in environmental monitoring, food control and even in the military for the detection of substances based on glycoprotein toxins.

• MeSH
• biosenzitivní techniky * metody   MeSH
• glykosylace MeSH
• lektiny MeSH
• povrchová plasmonová rezonance * metody   MeSH
• Publikační typ
• práce podpořená grantem MeSH

BACKGROUND: Infection caused by parasites from L. donovani complex can manifest as a serious visceral disease or a self-healing milder cutaneous form. The different tropism and pathology in humans is caused by the interaction between parasites, host and vector determinants but the mechanisms are not well understood. In Cukurova region in Turkey we previously identified a major focus of cutaneous leishmaniasis caused by L. donovani/infantum hybrids (CUK strain) and isolated this parasite from the locally abundant sand fly, Phlebotomus tobbi. Here, we present the first experimental study with P. tobbi. We tested the susceptibility of this species to various Leishmania under laboratory conditions, characterized glycoproteins in the P. tobbi midgut putatively involved in parasite-vector interaction and compared the development of the CUK strain in the sand fly with one other dermotropic and three viscerotropic strains belonging to the L. donovani complex. METHODS: Females of laboratory reared P. tobbi, P. perniciosus and Lutzomyia longipalpis were infected using membrane feeding on rabbit blood containing promastigotes of various Leishmania species with different tropisms. The individual guts were checked microscopically for presence and localization of Leishmania parasites; the number of parasites was assessed more precisely by qPCR. In addition, glycosylation of midgut proteins of P. tobbi was studied by lectin blotting of midgut lysate with lectins specific for terminal sugars of N-type and O-type glycans. RESULTS: High infection rates, heavy parasite loads and late-stage infection with colonization of the stomodeal valve were observed in P. tobbi infected by Leishmania major or L. infantum CUK hybrid. In parallel, lectin blotting revealed the presence of O-glycosylated proteins in the P. tobbi midgut. In P. perniciosus and L. longipalpis all five Leishmania strains tested developed well. In both vectors, significantly higher parasite numbers were detected by qPCR for dermotropic L. donovani from Cyprus, however, in all other parameters studied, including localization of infection and colonization of stomodeal valve, dermotropic and viscerotropic strains were not significantly different. CONCLUSIONS: We showed high susceptibility of P. tobbi to various Leishmania spp. This, together with the presence of O-glycosylated midgut proteins in their midguts demonstrate that P. tobbi is a permissive vector. Two dermotropic and three viscerotropic strains from the L. donovani complex developed late-stage infections in natural L. infantum vectors, P. perniciosus and L. longipalpis and none of the parameters studied seem to be linked with different tropism of parasites in the vertebrate host.

• MeSH
• gastrointestinální trakt parazitologie   MeSH
• hmyz - vektory parazitologie   MeSH
• králíci MeSH
• Leishmania infantum genetika   růst a vývoj   izolace a purifikace   MeSH
• Leishmania major genetika   růst a vývoj   izolace a purifikace   MeSH
• leishmanióza kožní epidemiologie   parazitologie   MeSH
• lidé MeSH
• Phlebotomus parazitologie   MeSH
• Psychodidae parazitologie   MeSH
• tropismus MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• lidé MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH
• Geografické názvy
• Turecko MeSH

BACKGROUND: The most demanding challenge in research on molecular aspects within the flow of biological information is posed by the complex carbohydrates (glycan part of cellular glycoconjugates). How the 'message' encoded in carbohydrate 'letters' is 'read' and 'translated' can only be unraveled by interdisciplinary efforts. SCOPE OF REVIEW: This review provides a didactic step-by-step survey of the concept of the sugar code and the way strategic combination of experimental approaches characterizes structure-function relationships, with resources for teaching. MAJOR CONCLUSIONS: The unsurpassed coding capacity of glycans is an ideal platform for generating a broad range of molecular 'messages'. Structural and functional analyses of complex carbohydrates have been made possible by advances in chemical synthesis, rendering production of oligosaccharides, glycoclusters and neoglycoconjugates possible. This availability facilitates to test the glycans as ligands for natural sugar receptors (lectins). Their interaction is a means to turn sugar-encoded information into cellular effects. Glycan/lectin structures and their spatial modes of presentation underlie the exquisite specificity of the endogenous lectins in counterreceptor selection, that is, to home in on certain cellular glycoproteins or glycolipids. GENERAL SIGNIFICANCE: Understanding how sugar-encoded 'messages' are 'read' and 'translated' by lectins provides insights into fundamental mechanisms of life, with potential for medical applications.

• MeSH
• glykoproteiny chemie   MeSH
• konformace proteinů MeSH
• konformace sacharidů MeSH
• molekulární modely MeSH
• molekulární sekvence - údaje MeSH
• oligosacharidy chemie   MeSH
• polysacharidy chemie   MeSH
• sacharidové sekvence MeSH
• sacharidy chemie   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH