In Vitro Assessment of Immunobiological Effectivity of Synthetic Non-Ionic Glycolipids.

Immunobiological activity of selected decyl and (thio)dodecyl hexopyranosides based on d-glucose, d-galactose, N-acetyl d-glucosamine and d-mannose and their effect on leukemia cell lines L1210 and HL-60 and Candida's biofilm were studied. Alkyl d-glucosides and d-galactosides showed mainly similar antiproliferative properties on leukemia cell lines, while N-acetyl d-glucosaminides revealed diverse properties with lower efficacy. Also, the cytokine response of RAW 264.

Glycolipids mimicking biosurfactants of the synthetic origin as new immunomodulating and anticandidal derivatives.

The immunobiological effectivity of glycolipids mimicking biosurfactants of the synthetic origin was followed up using macrophages cell line RAW264.7. These derivatives with different number of mannose units connected glycosidically or through triazole linker, and all having octyl aglycone, were evaluated with respect to their structure - immunomodulation activity relationship.

Amphoteric Mannan as an Immune Response Modifier. New Model Immunobiologically Active Mannan-Based Formula.

Background: Currently, the incidence and prevalence of serious fungal infections is increasing, especially in immunosuppressed individuals. The co-administration of antibiotic and immunosuppressive therapies has driven the emergence of new multidrug-resistant fungal pathogens. Their significant increase and their ability to form biofilms is associated with rising morbidity and mortality.

Effectivity of polyphenolic polysaccharide-proteins isolated from medicinal plants as potential cellular immune response modulators.

Traditional medicinal herbs as and are recommended as a complementary supplementation for the treatment of diseases associated with immunological inflammation (e.g. common cold, coughs, bronchitis, upper respiratory infections, immunodeficiencies).

Cell-Mediated Immunoreactivity of Poly(2-isopropenyl-2-oxazoline) as Promising Formulation for Immunomodulation.

Poly(2-isopropenyl-2-oxazoline) (PIPOx) represents a functional polymer with high potential for drug delivery, tissue engineering, and immunomodulation. The immunomodulatory efficiency of the PIPOx formulation has been studied in vitro following splenic cells and RAW 264.7 macrophages exposition.

Synthesis of Biotin-Tagged Chitosan Oligosaccharides and Assessment of Their Immunomodulatory Activity.

Chitin, a polymer of β-(1→4)-linked -acetyl-d-glucosamine, is one of the main polysaccharide components of the fungal cell wall. Its N-deacetylated form, chitosan, is enzymatically produced in the cell wall by chitin deacetylases. It exerts immunomodulative, anti-inflammatory, anti-cancer, anti-bacterial, and anti-fungal activities with various medical applications.

In vitro evaluation of immunobiological activity of simple mannolipids.

Immunomodulation, cytotoxicity and anti-cancer activity of selected amphiphilic non-ionic (thio)alkyl α-D-mannosides (with aglycone of C6-C12) were investigated in vitro in human cervix epitheloid carcinoma cell line HeLa, murine melanoma cancer cells B16, murine lymphocytic leukemia cell line L1210, murine fibroblast cell line NIH 3 T3 and murine macrophage cell line RAW 264.7. Toxicological studies revealed structure-dependent immunobiological effectivity based on a tight interaction with relevant cells.

Importance of Antigenic Factors: Structure-Driven Immunomodulation Properties of Synthetically Prepared Mannooligosaccharides in RAW264.7 Macrophages.

The incidence and prevalence of serious fungal infections is rising, especially in immunosuppressed individuals. Moreover, co-administration of antibiotics and immunosuppressants has driven the emergence of new multidrug-resistant pathogens. The significant increase of multidrug-resistant pathogens, together with their ability to form biofilms, is associated with morbidity and mortality.

Bioimmunological activities of Candida glabrata cellular mannan.

Candida glabrata is a second most common human opportunistic pathogen which causes superficial but also life-threatening systemic candidosis. According to the localisation of mannans and mannoproteins in the outermost layer of the cell wall, mannan detection could be one of the first steps in the cell recognition of Candida cells by the host innate immune system. Mannans from the cell wall provide important immunomodulatory activities, comprising stimulation of cytokine production, induction of dendritic cells (DCs) maturation and T-cell immunity.

N-Oxy lipid-based click chemistry for orthogonal coupling of mannan onto nanoliposomes prepared by microfluidic mixing: Synthesis of lipids, characterisation of mannan-coated nanoliposomes and in vitro stimulation of dendritic cells.

New synthetic aminooxy lipid was designed and synthesized as a building block for the formulation of functionalised nanoliposomes (presenting onto the outer surface of aminooxy groups) by microfluidic mixing. Orthogonal binding of cellular mannan (Candida glabrata (CCY 26-20-1) onto the outer surface of functionalised nanoliposomes was modified by orthogonal binding of reducing termini of mannans to oxime lipids via a click chemistry reaction based on aminooxy coupling (oxime ligation). The aminooxy lipid was proved as a suitable active component for preparation of functionalised nanoliposomes by the microfluidic mixing method performed with the instrument NanoAssemblr™.

Extracellular biopolymers produced by Dictyosphaerium family - Chemical and immunomodulative properties.

Many microalgal species produce a wide range of highly-value products which are interesting for biotechnological applications. Cultivation of microalgal species Dictyosphaerium pulchellum and Dictyosphaerium tetrachotomum, strains Růžicka and Fott resulted yields of 0.2, 0.

Immunobiological Activity of Synthetically Prepared Immunodominant Galactomannosides Structurally Mimicking Galactomannan.

The study is oriented at the evaluation of the immunobiological activity and efficacy of synthetically prepared isomeric pentasaccharides representing fragments of cell-wall galactomannan and containing β-(1→5)-linked tetragalactofuranoside chain attached to O-6 () or O-3 () of a spacer-armed mannopyranoside residue. These compounds were studied as biotinylated conjugates which both demonstrated immunomodulatory activities on the RAW 264.7 cell line murine macrophages as innate immunity cell model.

Immunobiological efficacy and immunotoxicity of novel synthetically prepared fluoroquinolone ethyl 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate.

The present study examined the cytotoxicity, anti-cancer reactivity, and immunomodulatory properties of new synthetically prepared fluoroquinolone derivative 6-fluoro-8-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate (6FN) in vitro. The cytotoxicity/toxicity studies (concentrations in the range 1-100μM) are focused on the cervical cancer cells HeLa, murine melanoma cancer cells B16, non-cancer fibroblast NIH-3T3 cells and reconstructed human epidermis tissues EpiDerm™. The significant growth inhibition of cancer cells HeLa and B16 was detected.

Assessment of Immunomodulatory Activities and in vitro Toxicity of New Quinolone 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate.

Unlabelled: Our previous studies on leukemia cells L1210 and cervical cancer HeLa cells revealed cytotoxic effects of the 7-ethyl 9-ethyl-6-oxo-6,9-dihydro[1,2,5]selenadiazolo[3,4-h]quinoline-7-carboxylate (E2h), a new synthetically prepared quinolone derivative, toward selected cancer cell lines. The aim of the present study was to examine the cytotoxicity of E2h toward next cell lines and tissues; that is, human cancer HL-60 and A549 cells, human non-cancer fibroblast BHNF-1 cells, and reconstructed human epidermis tissues. Further we investigated the immunomodulatory activity of E2h on murine macrophage RAW 264.

The evaluation of β-(1 → 3)-nonaglucoside as an anti-Candida albicans immune response inducer.

Synthetically prepared bovine serum albumin (BSA) conjugate of linear β-(1 → 3)-nonaglucoside ligand (G9) has been applied as a biological response immunomodulator in vivo and ex vivo. Active immunization of Balb/c mice revealed effective induction of specific humoral responses in comparison with Candida β-D-glucan and Candida whole cells. Induced post-vaccination serum exhibited a growth-inhibition effect on the multi-azole-resistant clinical strain Candida albicans CCY 29-3-164 in experimental mucocutaneous infection ex vivo.

Ex Vivo and In Vitro Studies on the Cytotoxicity and Immunomodulative Properties of Poly(2-isopropenyl-2-oxazoline) as a New Type of Biomedical Polymer.

Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes.

One-pot preparation of labelled mannan-peptide conjugate, model for immune cell processing.

An efficient method for preparation of fluorescently labelled mannan-peptide glycoconjugates has been developed. After selective Dess-Martin periodinane oxidation of mannan, it was conjugated to the fluorescent label alone and a peptide with the label via reductive amination. Prepared glycoconjugates were characterised by HPSEC, FTIR-ATR and UV-VIS spectroscopy.

Humoral immune responses to Candida albicans complement receptor 3-related protein in the atopic subjects with vulvovaginal candidiasis. Novel sensitive marker for Candida infection.

In vitro evaluation of specific anti-Candida albicans sera antibodies based on synthetically prepared complement receptor 3-related protein (CR3-RP) mimicking the structure of native complement receptor 3 in a cohort of 72 patients with atopy and recurrent Candida vulvovaginitis (RVC) revealed effective humoral response against Candida CR3-RP. The most significant have been IgM and IgA isotype antibodies (33 and 47% positive cases, respectively). The quantitative evaluation of anti-CR3RP isotype antibodies was confronted with results of commercial ELISA anti-C.

Increased antifungal antibodies in bronchoalveolar lavage fluid and serum in pulmonary sarcoidosis.

The recent studies suggest a role of fungi in development of sarcoidosis. Moreover, the immune response in sarcoidosis and fungal infection shows a striking similarity. We formulated a hypothesis of the possible increase in antifungal antibodies in bronchoalveolar lavage fluid (BALF) and serum in pulmonary sarcoidosis.

Immunological basis of anti-Candida vaccines focused on synthetically prepared cell wall mannan-derived manno-oligomers.

The increasing incidence of diseases caused by Candida species and complications in individuals with impaired immunity require new strategies for candidiasis treatment and prevention. The available therapies are often of limited effectiveness in immunocompromised patients, resulting in treatment failures, chronic infections and high mortality rates. Research directed at identifying the composition of an effective vaccine is required.

Immune cell response to Candida cell wall mannan derived branched α-oligomannoside conjugates in mice.

Background: Constructs composed of cell wall mannan-derived moieties conjugated to immunogenic proteins could be promising agents for induction of protective anti-Candida immune responses.

Methods: This report is focused on the cellular immune response differences induced by BSA-based conjugates bearing synthetic α-1,6-branched oligomannosides. For monitoring of the immune responses following active immunization we evaluated changes in the frequencies of T and B lymphocytes and their activation status in the blood and spleen.

Synthetically prepared glycooligosaccharides mimicking Candida albicans cell wall glycan antigens--novel tools to study host-pathogen interactions.

The immunobiological efficacy of synthetically prepared mannooligosaccharides and a glucooligosaccharide mimicking the structure of Candida albicans cell wall glycans was assessed in vivo and in vitro to exploit immune responses. The exposure of mice splenocytes to BSA-based conjugates of synthetic oligomannosides and oligoglucoside revealed intense influence on T-cell subset polarization. The conjugates biased the immune responses towards Th1 and Th17 with respect to the prevalence of interferon-gamma (IFN-γ) and interleukin (IL)-17 (IL-17) over IL-4 and IL-10 levels.

Effect of branched α-oligomannoside structures on induction of anti-Candida humoral immune response.

Several studies have established the potential efficacy of humoral immunity, primarily mannan-specific antibodies, in host protection against major fungal pathogen Candida albicans. In this study, we analysed humoral immune response induced by immunization with BSA-based conjugates bearing synthetic α-1,6-branched oligomannosides (pentamannosides (M5) or hexamannosides (M6)) mimicking antigenic sequences of Candida cell wall mannan. We analysed the ability of antibodies prepared by immunization to recognize relevant antigenic determinants in mannan polysaccharide structure and in C.

Humoral and cell-mediated immunity following vaccination with synthetic Candida cell wall mannan derived heptamannoside-protein conjugate: immunomodulatory properties of heptamannoside-BSA conjugate.

Chemically defined glycoprotein conjugate composed of synthetically prepared mannan-derived heptamannoside with terminal β-1,2-linked mannose residue attached to the α-1,3-linked mannose residues and BSA as carrier protein (M7-BSA conjugate) was analysed for the capacity to induce protective humoral immunity and appropriate alteration cellular immunity. To identify protective antigenic structure of Candida cell wall mannan M7-BSA conjugate was used for BALB/c mice immunization. The obtained results were compared with placebo group and with heat-inactivated C.