Effect of Polysaccharides Isolated from Saussurea salicifolia (L.) DC on Th2-Dependent Immune Response.

The effect of polysaccharides isolated from the aboveground parts of Saussurea salicifolia (L.) DC on Th2 type immune response reactions was studied. Administration of water-soluble polysaccharides presented by arabino-galacturonans (weight average molecular weight 158.49 kDa) to mice against the background of experimental Th2 immunity reduced the severity of anaphylactic and local immediate type hypersensitivity reactions. It also suppressed the production of ovalbumin-specific IgE and IgG1 and increased the stability of mast cell membranes. The studied polysaccharide complex increased IFNγ secretion and inhibited IL-4 synthesis. These findings suggest that these polysaccharides may be considered as potential anti-allergic agents that suppress the development of allergy in its early stages.

Effect of Modified Forms of Sodium Humate PowHumus on the Balance of Arginine in Peritoneal Macrophages of Intact Mice.

Substances of silver nanoparticles dialyzed through a 13 kDa membrane, synthesized in a medium of humic ligands modified with hydroquinone and 2-hydroxynaphthoquinone from PowHumus brown coal, specifically enhance the M2 properties of peritoneal macrophages due to inhibition of NO synthase and significant activation of arginase, thus enhancing anti-inflammatory properties of cells. In small, but effective concentrations, they do not have cytotoxic properties and do not contain pyrogenic impurities. The studied humates are able to influence the mechanisms of immune response formation and are an effective means for correcting inflammation and regeneration.

The Role of Intracellular Signaling Molecules in Macrophage Activation by Peat Humic Acids.

Humic acids isolated by sodium pyrophosphate extraction from various types of peat activate macrophages in the classical proinflammatory pathway and stimulate nitric oxide production by these cells. This effect is mediated by activation of intracellular signaling pathways involving MAPK p38, PI3K, MEK 1/2 kinase, cAMP, and NF-κB via TLR-2 and TLR-4 receptors.

Pharmacokinetic Parameters of Oral Pegylated IFN-λ1.

We studied the pharmacokinetics of a pegylated IFN-λ1 (PEG IFN-λ1) after its oral administration to rats in different therapeutic doses. The hypothesis on linear pharmacokinetics of PEG IFN-λ1 within the dose range of 2.6-7.8 µg/kg was confirmed, high for protein molecules bioavailability from 17.5 to 21%, the absence of intravascular deposition, and effective elimination with feces and urine (85 and 15% of the administered dose, respectively) were demonstrated. At the same time, the mean retention time for PEG IFN-λ1 in the circulation is 6.46-6.65 h and half-life is 3 h. These findings give ground for continuing experimental studies of PEG IFN-λ1 pharmacokinetics, in particular, tissue distribution of the drug.

Anti-Allergic Properties of Humic Acids Isolated from Pine-Sphagnum-Cotton Sedge Peat.

The course administration of humic acids isolated by the sodium pyrophosphate method from pine-sphagnum-cotton sedge peat reduced the general anaphylaxis reaction in mice and guinea pigs immunized with ovalbumin and decreased serum content of IgG1 and IgE in mice. The serum from mice treated with humic acids and sensitized with ovalbumin did not increase the rate of degranulation of mast cells isolated from intact Wistar rats in the presence of ovalbumin in comparison with the serum of control animals.

Influence of Humic Acids Isolated from Raised Bog Sphagnum Peat on Development of Th1/Th2 Immune Response.

The course administration of humic acids isolated with sodium pyrophosphate from raised bog sphagnum peat reduces the parameters of a Th1-type immune response in C57BL/6 mice, the severity of an anaphylactic shock in outbred CD1 mice, and degranulation of mast cells after their immunization with ovalbumin. The addition of humic acids increases the stimulated production of IL-4, IL-10 and reduces the production of IL-2, IFNγ by peripheral blood mononuclear cells of healthy donors.

The Influence of Water-Soluble Polysaccharides of Crataegus sanguinea Pall. on Nitric Oxide Production by Macrophages.

The in vitro addition of water-soluble polysaccharides isolated from the leaves of Crataegus sanguinea Pall. to culture of mouse peritoneal macrophages induced classical activation of antigen-presenting cells by increasing NO synthase activity and reducing arginase expression.

Promising New Salt of Oseltamivir.

A synthetic method for the promising new drug oseltamivir ethoxysuccinate is described in detail. Various conditions for obtaining the target substance are considered. Its complete physicochemical characteristics are given. The obtained agent is shown to be effective against influenza virus A (H1N1)pdm09.

The Role of Intracellular Signaling Molecules in the Production of Granulocytic CSF Mononuclear Phagocytes in Stress and Cytostatic Influence.

Under conditions of steady-state hemopoiesis, nuclear factor NF-κB, in contrast to MAP kinase p38, plays an important role in the maintenance of the initial level of secretory activity of monocytes. The increase in the production of G-CSF under stress conditions (10-h immobilization) is mainly regulated by the alternative p38MARK signaling pathway via activation of p38 synthesis. It was shown that under conditions of cytostatic-induced myelosuppression, the production of protein kinase p38 in cells decreases, and it, like NF-κB, is not the main one in the production of hemopoietin by mononuclear phagocytes.

Immunomodulating Properties of Humic Acids Extracted from Oligotrophic Sphagnum magellanicum Peat.

Humic acids extracted with sodium pyrophosphate from Oligotrophic Sphagnum magellanicum peat reduce mitogen-stimulated production of anti-inflammatory cytokine IL-10 by mouse peritoneal macrophages and do not affect the secretion of IL-4 by lymphocytes. The studied humic acid sample stimulates the production of proinflammatory cytokines IL-12, TNFα, IL-1ß, and IFNγ by immunocompetent mouse cells and human mononuclear cells. Course administration of humic acids to mice enhances the humoral immunity, increasing the number of antibody-forming cells in the spleen and the titer of antibodies in the blood serum after immunization with sheep red blood cells.

Study of Immunotropic Properties of Water-Soluble Polysaccharides Isolated from Conium maculatum Grass.

Addition of water-soluble polysaccharides isolated from Conium maculatum L. to the mouse peritoneal macrophage culture induces classical activation of antigen-presenting cells due to an increase in NO synthase activity and a decrease in arginase expression.

Involvement of Signaling Cascades in Granulocytopoiesis Regulation under Conditions of Cytostatic Treatment.

Suppression of the production of granulocytic CSF under the effect of 5-fluorouracyl is related to disorders in the NF-κB-, cAMP-dependent signaling pathways and MAPK cascade. These secondary messengers are involved in the regulation of functional activity of nonadherent myelokaryocytes starting from day 10 of the experiment (initial period of the hemopoietic granulocytic stem regeneration after antimetabolite challenge). Granulocytic CSF does not play essential role in the formation of colony-stimulating activity of cells of the adherent and nonadherent fractions of the bone marrow. Only cAMP-dependent pathway is involved in the regulation of the realization of the granulocytic precursor growth potential in response to the challenge.

Effects of Humic Acids, Isolated from High-Moor Pine-Peat Moss-Cotton Grass Peat on the Production of Cytokines by Mouse and Human Immunocompetent Cells and on Humoral Immune Response.

A course of treatment with humic acids extracted with sodium pyrophosphate from high-moor pine-peat moss-cotton grass peat improves humoral immune response of C57BL/6 mice, stimulates the production of TNFα, IL-1ß, and IL-12 by the animal peritoneal macrophages and the production of IFNγ and TNFα by donor peripheral blood mononuclears, causing no changes in the production of IL-10 in vitro.

Role of Signaling Molecules in the Regulation of Granulocytopoiesis during Stress-Inducing Stimulation.

The role of signaling molecules in synthesis of humoral regulators of granulocytopoiesis by the hematopoietic microenvironmental cells during stress was analyzed using specific inhibitors. The major role in stimulation of the synthesis of granulocytic CSF during stressful stimulation is played by PI3K/Akt signaling cascade. Nuclear transcription factor NF-κB plays an auxiliary role in the regulation of functional activity of the bone marrow mononuclears. However, this factor affects the synthesis of granulocytic CSF by CD4+ cells of the bone marrow in response to stressful stimulation. Different degree and specific character of involvement of the signaling proteins in the regulation of the production of humoral factors determining colony-stimulating activity are explained by changes in functional state of monocyte-derived macrophages in different periods of stress response.

Role of NF-κB, PI3K, MAPK/ERK 1/2, and p38 in Erythropoietin Production by Bone Marrow Nuclears under Conditions of Immobilization Stress.

The involvement of the studied signal cascades in the regulation of erythropoietin production by bone marrow nuclears under conditions of immobilization stress depends on the type of the hemopoiesis-inducing microenvironment cells and the period of blood system reaction to stress exposure. Secretory activity of monocytes is regulated mainly by PI3K improving cell resistance to disturbances. The functional role of signal cascades involved in the production of erythropoietin by T cells is determined by the stage of the common adaptation syndrome.

Role of PI3K, MAPK/ERK 1/2, and p38 in Production of Erythropoietic Activity by Bone Marrow Cells after Blood Loss.

The leading role in the regulation of erythropoietic activity of adherent bone marrow cells under conditions of post-hemorrhagic anemia is played by classical MAP kinase pathway (ERK pathway). Erythropoietin is not the decisive factor in the formation of erythropoietic activity of adherent cells. PI3K, MAPK/ERK 1/2, and p38-signaling proteins are not the main regulators of local production of erythropoietin after 30% loss of circulating blood volume.

Effects of Humic Acids Isolated from Peat of Various Origin on in Vitro Production of Nitric Oxide: a Screening Study.

A screening study of biological activity of native humic acids isolated from peat was performed; several physical and chemical parameters of their structures were studied by UV- and infrared spectroscopy. Spectroscopy yielded similar shape of light absorption curves of humic acids of different origin, which can reflect similarity of general structural principles of these substances. Alkaline humic acids have more developed system of polyconjugation, while molecular structures of pyrophosphate humic acids were characterized by higher aromaticity and condensation indexes. Biological activity of the studied humic acids was assessed by NO-stimulating capacity during their culturing with murine peritoneal macrophages in a wide concentration range. It was shown that due to dose-dependent enhancement of NO production humic acids can change the functional state of macrophages towards development of pro-inflammatory properties. These changes were associated with high activity of humic acids isolated by pyrophosphate extraction, which allows considering effects of isolation method on biological activity.

Immunotropic Properties of Immobilized Interferon-α2b.

Course treatment with IFN-α2b immobilized on polyethylene glycol stimulates phagocytic activity of peritoneal macrophages and neutrophils, enhances humoral immune response in CBA/CaLac mice, stimulates IL-4 synthesis, and suppresses IFN-γ production by mitogenstimulated splenocytes from experimental animals.

Effects of Water-Soluble Polysaccharides with Different Chemical Structure, Isolated from Acorus calamus L. and Trifolium pratense L., on Nitric Oxide Production: A Screening Study.

Screening study of the effects of sweet flag (Acorus calamus L.) rhizome and clover (Trifolium pratense L.) aerial part on the production of NO by mouse macrophages was carried out. The polysaccharides were separated by ion exchange chromatography into fractions differing by monomeric composition and ramification type and were used in concentrations of 20, 40, and 100 µg/ml. Four fractions of Acorus calamus L. (PSF-101, PSF-102, PSF-103, and PSF-105), used in different concentrations, moderately stimulated nitrite production by macrophages. Three of five Trifolium pratense L. polysaccharides (PS62-3, PS62-4, and PS62-5) exhibited a significant specific effect on NO production. Rhamnogalactouronans from clover PS63-3 in all concentrations and from PS62-5 in a concentration of 100 µg/ml exhibited the highest activity, comparable to the NO-stimulatory activity of the reference LPS, while polysaccharide PS62-3 in a concentration of 40 µg/ml exhibited even higher activity.

Role of PI3K, ERK, and p38 Signaling Pathways in the Production of Humoral Erythropoiesis Regulators under Normal Conditions.

PI3- and MAP-kinase signaling pathways duplicate and interchange each other in production of agents that determine total erythropoietic activity under conditions of balanced erythropoiesis. The alternative p38-dependent MAP-kinase pathway is the major regulator of erythropoietic activity of adherent bone marrow cells. Blockade of PI3K and p38 signaling pathways stimulated production of erythropoietin by cells that do not produce it constitutively.