RESUMEN
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.
Asunto(s)
Arginasa , Arginina , Sustancias Húmicas , Macrófagos Peritoneales , Plata , Animales , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Ratones , Arginina/farmacología , Arginina/química , Arginasa/metabolismo , Plata/química , Plata/farmacología , Nanopartículas del Metal/química , Hidroquinonas/farmacología , Hidroquinonas/química , Masculino , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Naftoquinonas/farmacología , Naftoquinonas/químicaRESUMEN
In male Syrian hamsters fed a synthetic high-fat diet enriched with cholesterol (0.3%), administration of a polysaccharide from birch leaves L-rhamnopyranosyl-6-O-methyl-D-galacturonan (3 g/100 g of diet) resulted in a decrease in total cholesterol levels, mainly due to the LDL fraction, triglycerides, and bile acids in blood serum; the content of triglycerides and cholesterol in the liver also decreased, while excretion of bile acids with feces increased. Thus, the lipid-lowering effect of L-rhamnopyranosyl-6-O-methyl-D-galacturonan is related to its ability to bind bile acids in the intestine and interrupt their enterohepatic circulation.
Asunto(s)
Betula , Colesterol , Cricetinae , Masculino , Animales , Mesocricetus , Ácidos y Sales Biliares/metabolismo , Triglicéridos , Pectinas , Hígado/metabolismo , Dieta Alta en Grasa , HecesRESUMEN
The effect of humic acids and substances with similar action - derivatives of succinic acid (ethylmethylhydroxypyridine succinate) and combined agent consisting of succinic acid, nicotinamide, riboflavin, and riboxin on the performance and stress resistance of experimental rats was studied. Performance was assessed in the test of exhaustive forced swimming with a load, stress resistance was evaluated by the serum level of corticosterone and open field behavior, and the state of anaerobic metabolism was estimated by the serum level of lactate after swimming test. Humic acids from peat showed anti-stress activity comparable to that of the officinal preparation and preventive effect on fatigue during physical exercise. They can be recommended as a component for the development of drugs that increase human performance and stress resistance.
Asunto(s)
Sustancias Húmicas , Suelo , Ratas , Humanos , Animales , Sustancias Húmicas/análisis , Ácido Succínico , Fatiga , NataciónRESUMEN
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.
Asunto(s)
Sustancias Húmicas , Suelo , Activación de Macrófagos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Transducción de Señal , FN-kappa B/metabolismo , Óxido Nítrico/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Lipopolisacáridos/farmacologíaRESUMEN
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.
Asunto(s)
Antialérgicos , Sphagnopsida , Animales , Antialérgicos/farmacología , Degranulación de la Célula , Cobayas , Sustancias Húmicas , Inmunoglobulina E , Mastocitos , Ratones , Ovalbúmina , Ratas , Ratas Wistar , SueloRESUMEN
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.
Asunto(s)
Sustancias Húmicas , Sphagnopsida , Ratones , Animales , Sustancias Húmicas/análisis , Suelo , Leucocitos Mononucleares/química , Humedales , Ratones Endogámicos C57BL , Inmunidad , Células Th2 , Citocinas , Células TH1RESUMEN
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.
Asunto(s)
Crataegus/química , Macrófagos Peritoneales/efectos de los fármacos , Óxido Nítrico/metabolismo , Polisacáridos/farmacología , Animales , Arginasa/efectos de los fármacos , Arginasa/metabolismo , Células Cultivadas , Femenino , Macrófagos Peritoneales/enzimología , Macrófagos Peritoneales/metabolismo , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Extractos Vegetales/farmacología , Hojas de la Planta/química , Polisacáridos/aislamiento & purificación , Solubilidad , Agua/químicaRESUMEN
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.
Asunto(s)
Sustancias Húmicas , Suelo , Animales , Interleucina-12/metabolismo , Interleucina-1beta/metabolismo , Macrófagos Peritoneales/metabolismo , Ratones Endogámicos C57BL , Sphagnopsida/química , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
We studied an original radiolabeled complex of antimicrobial peptides UBI29-41 and UBI18-35, ubiquicidin derivatives, for distinguishing between bacterial and aseptic inflammation. For radiolabeling of the peptides with technetium-99m, a bifunctional chelating agent succinimide-1-yl 6-(bis(pyridin-2-ylmethyl)amino)hexanoate was used. The obtained complexes 99mТÑ-DPAH-UBI29-41 and 99mТÑ-DPAH-UBI18-35 had radiolabeling yield >80% and radiochemical purity >96%. Accumulation of the complexes in the focus of bacterial inflammation in bone structures and the absence of this complex in the site of aseptic inflammation was confirmed in a rat model of traumatic osteomyelitis by single-photon emission computed tomography.
Asunto(s)
Osteomielitis/tratamiento farmacológico , Proteínas Citotóxicas Formadoras de Poros/química , Proteínas Ribosómicas/química , Tecnecio/química , Animales , Diagnóstico Diferencial , Femenino , Ratas , Ratas Wistar , Tomografía Computarizada de Emisión de Fotón ÚnicoRESUMEN
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.
Asunto(s)
Citocinas/metabolismo , Sustancias Húmicas , Inmunidad Humoral/efectos de los fármacos , Animales , Células Cultivadas , Humanos , Sustancias Húmicas/análisis , Inmunidad Humoral/fisiología , Inmunocompetencia/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Leucocitos Mononucleares/metabolismo , Macrófagos Peritoneales/efectos de los fármacos , Macrófagos Peritoneales/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Pinus/química , Poaceae/química , Sphagnopsida/químicaRESUMEN
One of prospective methods for immunotherapy of tumors is modulation via immunological checkpoints, specifically, via the PD-1(CD279)/PD-L1(CD274) system. Interactions between tumor cell receptor (CD279) and the ligand on lymphocytes (CD274) leads to lymphocyte inactivation, which allows tumor escape from the immune control. Experiments on C57BL/6 mice with Lewis lung carcinoma demonstrate the possibility of reducing the expression of CD279 and CD274 on the peripheral blood and tumor tissue lymphocytes under the effects of Tussilago farfara L. polysaccharides. This phenomenon can underlie the antitumor and antimetastatic effects of these substances.
Asunto(s)
Antígeno B7-H1/metabolismo , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Carcinoma Pulmonar de Lewis/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/metabolismo , Polisacáridos/uso terapéutico , Receptor de Muerte Celular Programada 1/metabolismo , Tussilago/química , Animales , Femenino , Citometría de Flujo , Inmunoterapia , Ratones , Ratones Endogámicos C57BLRESUMEN
Myelotoxicity is a serious side effect of anticancer drugs. The search for drugs that can reduce the hematological complications of chemotherapy through modulation of hematopoietic stem cells is an urgent task of oncopharmacology. In the present study we showed that administration of Tussilago farfara L. polysaccharides to C57BL/6 mice treated with cyclophosphamide can increase the number of hematopoietic stem cells (CD117+34+) in the bone marrow.
Asunto(s)
Antineoplásicos Alquilantes/toxicidad , Células de la Médula Ósea/efectos de los fármacos , Médula Ósea/efectos de los fármacos , Ciclofosfamida/antagonistas & inhibidores , Células Madre Hematopoyéticas/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antígenos CD34/genética , Antígenos CD34/inmunología , Biomarcadores/metabolismo , Médula Ósea/inmunología , Células de la Médula Ósea/citología , Células de la Médula Ósea/inmunología , Recuento de Células , Ciclofosfamida/toxicidad , Femenino , Expresión Génica , Células Madre Hematopoyéticas/citología , Células Madre Hematopoyéticas/inmunología , Inmunofenotipificación , Inyecciones Intraperitoneales , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/química , Polisacáridos/aislamiento & purificación , Proteínas Proto-Oncogénicas c-kit/genética , Proteínas Proto-Oncogénicas c-kit/inmunologíaRESUMEN
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.
Asunto(s)
Conium/metabolismo , Polisacáridos/química , Solubilidad , Agua/química , Alcaloides/metabolismo , Animales , Células Presentadoras de Antígenos , Arginasa/metabolismo , Femenino , Sistema Inmunológico , Linfocitos/metabolismo , Ratones , Ratones Endogámicos C57BL , Óxido Nítrico/química , PoaceaeRESUMEN
The study substantiated the possibility of using peat humic acids for improving endurance during extreme physical exertion. The mature outbred Wistar rats weighing 200-250 g (n=40) were subjected to forced swim test until complete exhaustion. The humic acids (1%) were administered intragastrically (0.5 ml/100 g body weight) 30 min prior to the test. Chronic administration of peat humic acids for 5 days increased physical capacity and endurance of rats in exhaustive forced swim test without the changes in serum lactate and corticosterone.
Asunto(s)
Factores Biológicos/farmacología , Sustancias Húmicas/análisis , Condicionamiento Físico Animal/fisiología , Resistencia Física/efectos de los fármacos , Esfuerzo Físico/efectos de los fármacos , Suelo/química , Animales , Corticosterona/sangre , Absorción Gástrica/fisiología , Ácido Láctico/sangre , Masculino , Resistencia Física/fisiología , Ratas , Ratas Wistar , Natación/fisiologíaRESUMEN
Prions are proteins that can exist under the same conditions in two or more conformations, at least one of them is infectious. Usually, acquisition of infectious prion conformation is associated with the formation of amyloids - protein aggregates with a characteristic spatial structure. About 10 prions have been identified in the yeast Saccharomyces cerevisiae. The Gln3 protein, which is one of the key regulators of nitrogen metabolism in S. cerevisiae, contains an amyloidogenic region manifesting prion-like properties. The prion properties of the full-length Gln3 have not been studied. We have found that the amyloidogenic region of Gln3 acts as a template and initiates aggregation of the full-length Gln3 in the presence of the [PIN+] prion when Gln3 is overexpressed. Full-length Gln3 in its aggregated form manifests prion-like properties, including infectivity and dependence on the anti-prion agents; however, unlike other known yeast prions, prion-like state of Gln3 is observed only upon the protein overproduction. Here, we suggest the term "conditional prions" for proteins, whose prion state is maintained exclusively under non-physiological conditions.
Asunto(s)
Priones/metabolismo , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Factores de Transcripción/metabolismo , Farmacorresistencia Fúngica/efectos de los fármacos , Metalotioneína/genética , Microscopía Confocal , Agregado de Proteínas/fisiología , Proteínas de Saccharomyces cerevisiae/genética , Sirolimus/farmacología , Factores de Transcripción/genéticaRESUMEN
The cardioprotective and inotropic effects of standardized active natural substance based on high-molecular-weight compounds of humic origin were studied on the model of global ischemia (40 min) and reperfusion of isolated perfused rat heart. Preventive administration of the test substance (0.1 mg/ml) before ischemia/reperfusion modeling reduced reperfusion contracture and necrotic death of cardiomyocytes and promoted recovery of myocardial contractility. Blockade of NO synthase with L-NAME (100 µM) abolished the above effects of the test substance. It was hypothesized that NO synthase plays an important role in the development of the cardioprotective and inotropic effects of the test natural substance.
Asunto(s)
Isquemia/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Miocardio/metabolismo , Óxido Nítrico Sintasa/metabolismo , Animales , Corazón , Sustancias Húmicas , Isquemia/genética , Masculino , Daño por Reperfusión Miocárdica/genética , NG-Nitroarginina Metil Éster/metabolismo , Óxido Nítrico Sintasa/genética , Ratas , Ratas WistarRESUMEN
A possibility for correction of damaging effects of polychemotherapy on the intestinal epithelium with Tussilago farfara L. polysaccharides was studied on C57Bl/6 mice with Lewis lung carcinoma. The polysaccharides had protective and/or stimulating effects on the intestinal epithelium during polychemotherapy and promoted reparative regeneration in the intestine.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Mucosa Intestinal/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma Pulmonar de Lewis/patología , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Eosina Amarillenta-(YS) , Etopósido/administración & dosificación , Etopósido/efectos adversos , Femenino , Hematoxilina , Histocitoquímica , Mucosa Intestinal/patología , Irinotecán/administración & dosificación , Irinotecán/efectos adversos , Ratones , Ratones Endogámicos C57BL , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Extractos Vegetales/química , Polisacáridos/aislamiento & purificaciónRESUMEN
Prion and some other incurable human neurodegenerative diseases are associated with misfolding of specific proteins, followed by the formation of amyloids. Despite the widespread usage of the transmission electron and of the atomic force microscopy for studing such amyloids, many related methodological issues still have not been studied until now. Here, we consider one of the first amyloids found in Saccharomyces cerevisiae yeast, i.e. Sup35NMp, to study the adsorption of monomeric protein and its fibrils on the surface of mica, silica, gold and on formvar film. Comparison of linear characteristics of these units calculated by processing of images obtained by the atomic force, transmission and scanning electron microscopy was carried out. The minimal number of measurements of fibril diameters to obtain the values in a given confidence interval were determined. We investigated the film formed by monomeric protein on mica surface, which veiled some morphology features of fibrils. Besides, we revealed that parts of the Sup35NMp excluded from the fibril core can form a wide "coat". The length of the protein forming the core of the fibrils was estimated.
Asunto(s)
Amiloide/química , Factores de Terminación de Péptidos/química , Priones/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/química , Adsorción , Silicatos de Aluminio/química , Amiloide/ultraestructura , Oro/química , Microscopía de Fuerza Atómica/métodos , Microscopía Electrónica de Rastreo/métodos , Microscopía Electrónica de Transmisión/métodos , Factores de Terminación de Péptidos/ultraestructura , Priones/ultraestructura , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/ultraestructura , Proteínas de Saccharomyces cerevisiae/ultraestructura , Dióxido de Silicio/química , Propiedades de SuperficieRESUMEN
Using DNA comet assay we found that polysaccharides from Tussilago farfara L. reduced the intensity of polychemotherapy-induced apoptosis and DNA damage in bone marrow cells and small intestinal epithelium of C57Bl/6 mice, which attested to genoprotective properties of these polysaccharides.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/antagonistas & inhibidores , Células de la Médula Ósea/efectos de los fármacos , ADN/química , Mucosa Intestinal/efectos de los fármacos , Polisacáridos/farmacología , Tussilago/química , Animales , Antineoplásicos Fitogénicos/aislamiento & purificación , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidad , Apoptosis/efectos de los fármacos , Células de la Médula Ósea/citología , Células de la Médula Ósea/metabolismo , Cisplatino/antagonistas & inhibidores , Cisplatino/toxicidad , Ensayo Cometa , ADN/metabolismo , Duodeno/citología , Duodeno/efectos de los fármacos , Duodeno/metabolismo , Femenino , Inyecciones Intraperitoneales , Mucosa Intestinal/citología , Mucosa Intestinal/metabolismo , Irinotecán/antagonistas & inhibidores , Irinotecán/toxicidad , Ratones , Ratones Endogámicos C57BL , Paclitaxel/antagonistas & inhibidores , Paclitaxel/toxicidad , Extractos Vegetales/química , Polisacáridos/aislamiento & purificaciónRESUMEN
The experiments on C57Bl/6 mice with Lewis lung carcinoma showed that addition of Tussilago farfara L. polysaccharides to conventional cisplatin/paclitaxel polychemotherapy moderated neutropenia caused by antitumor therapy and increased its efficiency. The stimulating effect of polysaccharides on the granulopoietic lineage cells is comparable with that of recombinant CSF Neupogen.