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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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature.)

An investigation was carried out on humic substances (HSs) isolated from the coal of the Kansk-Achinsk basin (Krasnoyarsk Territory, Russia). The coal HSs demonstrate the main parameters of molecular structure inherent to this class of natural compounds. An assessment was performed for the chemical, microbiological, and pharmacological safety parameters, as well as the biological efficacy. The HS sample meets the safety requirements in microbiological purity, toxic metals content (lead, cadmium, mercury, arsenic), and radionuclides. The presence of 11 essential elements was determined. The absence of general, systemic toxicity, cytotoxicity, and allergenic properties was demonstrated. The coal HS sample was classified as a Class V hazard (low danger substances). High antioxidant and antiradical activities and immunotropic and cytoprotective properties were identified. The ability of the HS to inhibit hydroxyl radicals and superoxide anion radicals was revealed. Pronounced actoprotective and nootropic activities were also demonstrated in vivo. Intragastric administration of the HS sample resulted in the improvement of physical parameters in mice as assessed by the "swim exhaustion" test. Furthermore, intragastric administration in mice with cholinergic dysfunction led to a higher ability of animals with scopolamine-induced amnesia to form conditioned reflexes. These findings suggest that the studied HS sample is a safe and effective natural substance, making it suitable for use as a dietary bioactive supplement.

The genus Saussurea has been used in the preparation of therapies for a number of medical problems, yet not much is known about the therapeutic high-molecular-weight compounds present in extracts from these plants. Since polysaccharides are important in immune modulation, we investigated the chemical composition and immunomodulatory activity of Saussurea salicifolia L. and Saussurea frolovii Ledeb polysaccharides. Water-soluble polysaccharides from the aerial parts of these plants were extracted using water at pHs of 2 and 6 and subsequently precipitated in ethanol to obtain fractions SSP2 and SSP6 from S. salicifolia and fractions SSF2 and SSF6 from S. frolovii . The molecular weights of fractions SSP2, SSP6, SFP2, and SFP6 were estimated to be 143.7, 113.2, 75.3, and 64.3 kDa, respectively. The polysaccharides from S. frolovii contained xylose (67.1-71.7%) and glucose (28.3-32.9%), whereas the polysaccharides from S. frolovii contained xylose (63.1-76.7%), glucose (11.8-19.2%), galactose (4.7-8.3%), and rhamnose (6.8-9.4%). Fractions SSP2, SSP6, and SFP2 stimulated nitric oxide (NO) production by murine macrophages, and NO production induced by SSP2, SSP6, and SFP2 was not inhibited by polymyxin B treatment of the fractions, whereaspolymyxin B treatment diminished the effects of SFP6, suggesting that SFP6 could contain lipopolysaccharide (LPS). The LPS-free fractions SSP2, SSP6, and SFP2 had potent immunomodulatory activity, induced NO production, and activated transcription factors NF-κB/AP-1 in human monocytic THP-1 cells and cytokine production by human MonoMac-6 monocytic cells, including interleukin (IL)-1α, IL-1β, IL-6, granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-γ, monocyte chemotactic protein 1 (MCP-1), and tumor necrosis factor (TNF). These data suggest that at least part of the beneficial therapeutic effects reported for water extracts of the Saussurea species are due to the modulation of leukocyte functions by polysaccharides.

The activation of c -Jun N-terminal kinase (JNK) plays an important role in stroke outcomes. Tryptanthrin-6-oxime (TRYP-Ox) is reported to have high affinity for JNK and anti-inflammatory activity and may be of interest as a promising neuroprotective agent. The aim of this study was to investigate the neuroprotective effects of TRYP-Ox in a rat model of transient focal cerebral ischemia (FCI), which involved intraluminal occlusion of the left middle cerebral artery (MCA) for 1 h. Animals in the experimental group were administered intraperitoneal injections of TRYP-Ox 30 min before reperfusion and 23 and 47 h after FCI. Neurological status was assessed 4, 24, and 48 h following FCI onset. Treatment with 5 and 10 mg/kg of TRYP-Ox decreased mean scores of neurological deficits by 35-49 and 46-67% at 24 and 48 h, respectively. At these doses, TRYP-Ox decreased the infarction size by 28-31% at 48 h after FCI. TRYP-Ox (10 mg/kg) reduced the content of interleukin (IL) 1β and tumor necrosis factor (TNF) in the ischemic core area of the MCA region by 33% and 38%, respectively, and attenuated cerebral edema by 11% in the left hemisphere, which was affected by infarction, and by 6% in the right, contralateral hemisphere 24 h after FCI. TRYP-Ox reduced c -Jun phosphorylation in the MCA pool at 1 h after reperfusion. TRYP-Ox was predicted to have high blood-brain barrier permeability using various calculated descriptors and binary classification trees. Indeed, reactive oxidant production was significantly lower in the brain homogenates from rats treated with TRYP-Ox versus that in control animals. Our data suggest that the neuroprotective activity of TRYP-Ox may be due to the ability of this compound to inhibit JNK and exhibit anti-inflammatory and antioxidant activity. Thus, TRYP-Ox may be considered a promising neuroprotective agent that potentially could be used for the development of new treatment strategies in cerebral ischemia.

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

The emission centers and excited state characteristics of silica glasses implanted with Gd ions were studied by time-resolved pulsed cathodoluminescence. It was found that in the process of ion implantation, two types of new emission centers associated with Gd ions as well as Si quantum dots are formed in glassy silica. The distributions of excited states over the lifetime were found for both new centers and Si quantum dots. The nature of dispersion of the emission decay time was discussed in terms of structural disorder in the matrix. Thermal annealing and an increase in the ion fluence lead to the stimulation of the formation of Gd-related new centers and Si quantum dots. The micromechanisms for the formation of new Gd-related centers and two types of Si quantum dots were proposed on the basis of two scenarios for the introduction of Gd ions into the SiO 2 network: insertion of Gd into interstitial voids near oxygen-deficient centers and Gd  →  Si substitution with subsequent expulsion of Si atoms to the interstitial voids. New emission oxygen-deficient centers and quantum dots created by ion-beam technology in silica glasses are of interest for the development of new functional materials for photonics, and micro- and opto-electronics.

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., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

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-1β, 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.

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.

Purpose: This article focuses on new method to estimate biological activity of peat humic acids (HAs) using artificial neural network (ANN) to process spectroscopic measurements in infrared and visible ranges. Conventional approaches generally rely on biological models and direct detection of chemical substances related to bioactivity. These methods proved to be accurate and reliable, but at the expense of speed and simplicity., Materials and Methods: Recently, a conception of quantitative structure-activity relationship (QSAR) has been introduced and successfully implemented to predict effects of HAs on toxicity of polycyclic aromatic hydrocarbons. Our research stems from this conception, but employs multilayer perceptron (MLP) model to improve overall performance. The developed MLP model allowed us to estimate biological activity of the complete vertical peat cores collected from oligotrophic peat bog, located in southern taiga zone of West Siberia (north-eastern spurs of the Great Vasyugan Mire, 56°58' N 82о36' E). In total, 42 samples taken from the cores were collected. The protocol included spectroscopy (in infrared and visible ranges) and biological model with peritoneal activated macrophages as a reference method to directly measure biological activity of HAs., Results: and discussion. Numerical experiments confirmed consistency of the measured and estimated bioactivity, coefficient of determination R2 = 0.97. These experiments also showed that the MLP model significantly outperforms conventional linear multiple regression models, mainly due to essential nonlinearity of structure-activity relationships., Conclusions: Our research demonstrates that biological activity of HAs extracted from peat samples can be estimated using an artificial neural network model trained on infrared and visible spectra., (Copyright © 2020. Published by Elsevier Inc.)

A novel specific inhibitor of c-Jun N-terminal kinase, 11 H -indeno[1,2- b ]quinoxalin-11-one oxime sodium salt (IQ-1S), has a high affinity to JNK3 compared to JNK1/JNK2. The aim of this work was to study the mechanisms of neuroprotective activity of IQ-1S in the models of reversible focal cerebral ischemia (FCI) in Wistar rats. The animals were administered with an intraperitoneal injection of IQ-1S (5 and 25 mg/kg) or citicoline (500 mg/kg). Administration of IQ-1S exerted a pronounced dose-dependent neuroprotective effect, not inferior to the effects of citicoline. Administration of IQ-1S at doses of 5 and 25 mg/kg reduced the infarct size by 20% and 50%, respectively, 48 h after FCI, whereas administration of citicoline reduced the infarct size by 34%. The administration of IQ-1S was associated with a faster amelioration of neurological status. Control rats showed a 2.0-fold increase in phospho-c-Jun levels in the hippocampus compared to the corresponding values in sham-operated rats 4 h after FCI. Administration of IQ-1S at a dose of 25 mg/kg reduced JNK-dependent phosphorylation of c-Jun by 20%. Our findings suggest that IQ-1S inhibits JNK enzymatic activity in the hippocampus and protects against stroke injury when administered in the therapeutic and prophylactic regimen in the rat model of FCI.

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-1β, 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.

We studied activation of macrophages with humic acids extracted from peat of large deposits in the Tomsk region by two extraction methods: by hydroxide or sodium pyrophosphate. Humic acid of lowland peat types containing large amounts of aromatic carbon, phenolic and alcohol groups, carbohydrate residues and ethers, irrespectively of the extraction methods contained LPS admixture that probably determines their activating properties. Humic acid of upland peat types characterized by high content of carbonyl, carboxyl, and ester groups enhance NO production and reduce arginase expression, but these effects were minimized when sodium hydroxide was used as an extraction solvent. Pyrophosphate samples of the upland peat types were characterized by aromaticity and diversity of functional groups and have a significant advantage because of they induce specific endotoxin-independent stimulating action on antigen presenting cells.

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.

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.

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.

Specific JNK and p53 inhibitors stimulated the formation of fibroblast colonies (CFU-F) and clusters (ClFU-F) and increased proliferative activity of mesenchymal progenitor cells. No effects of inhibitors of JNK and p53 on differentiation of progenitor elements were revealed.

We studied the role of signaling pathways in the regulation of erythropoiesis against the background of myelosuppression caused by administration of 5-fluorouracil. The important role of cyclic AMP in the maturation of erythroid progenitors after cytostatic treatment was demonstrated. The secretory activity of myelokaryocytes during the period of erythroid hemopoiesis recovery is mainly regulated via the p38 MAPK signaling pathway; non-erythropoietin factors are involved in the formation of erythropoietic activity of adherent cells of the microenvironment.