[Microbiota markers level in the blood and cerebrospinal fluid of patients with different types of multiple sclerosis and radiologically isolated syndrome]. / Issledovanie soderzhaniya markerov mikrobioty v tsel'noi krovi i tserebrospinal'noi zhidkosti patsientov s razlichnymi tipami techeniya rasseyannogo skleroza i lits s radiologicheski izolirovannym sindromom.

OBJECTIVE: To assess the level of microbiota markers in the blood and cerebrospinal fluid (CSF) of patients with different types of multiple sclerosis (MS), people with radiologically isolated syndrome (RIS) and control subjects. MATERIAL AND METHODS: We used gas chromatography-mass spectrometry (GC-MS) to evaluate the levels of microbiota markers in 69 patients with different types of MS (27 patients in the acute stage, 35 patients with MS in remission, 7 patients with primary-progressive MS), 10 people with RIS, and 47 control subjects (different diseases of the nervous system of a non-autoimmune or inflammatory nature). RESULTS: We showed a statistically significant increase in the content of various microbiota markers in the CSF of patients with MS compared with the control group. We found no change in the content of these markers in blood of patients with MS. This suggests a change of markers of microbial load at the level of the central nervous system, but not at the level of the whole organism. The greatest number of statistically significant differences with the control group was found in the content of markers in CSF of patients with MS in remission. In the acute stage, on the contrary, we found no statistically significant differences compared to the control group. In particular, in CSF of patients with MS in remission, a statistically significant increase in the content of bacterial plasmalogen (4.5 times), and increase in the level of microbial markers specific to Peptostreptococcus anaerobius, Pseudomonas aeruginosa, Eubacterium, Bifidobacterium, Butirivibrio, Moraxella, Acinetobacter, Propionibacterium acnes, as well as an increase of markers of the Epstein-Barr virus were found. In addition, there was an increase of campesterol, the likely source of which is campesterol-producing microfungi. In the CSF of subjects with RIS there were a statistically significant increase in the level of markers of the Epstein-Barr virus, Propionibacterium acnes, as well as Pseudomonas, Moraxella, and Acinetobacter. CONCLUSION: An association of MS with polymicrobial infection is possible. It is also likely that there is a certain pattern of increase of microbiota markers in the CSF of patients with MS, but not in blood.

Evaluation of the structure of the human microbiome in multiple sclerosis by the concentrations of microbial markers in the blood.

The relationship between multiple sclerosis and the state of the human microbiome was studied, namely, the change in the representation of microbiota phylotypes, the proportion of coccal flora, the proportion of anaerobic, gram-negative, proteolytically active microflora, as well as the concentration of markers of bacterial plasmalogen and endotoxin in the blood. Microbiome studies were carried out by gas chromatography - mass spectrometry of microbial markers in the blood. A statistically significant increase in blood concentrations of the total level of microbial markers of bacterial plasmalogen and endotoxin was determined in multiple sclerosis, which may be associated with an increase in the permeability of the intestinal wall. In multiple sclerosis, the proportion of coccal, gram-negative, anaerobic microflora with a proteolytic type of metabolic activity increases. The correlations of the representation of microbiota phylotypes change due to the switching of the direct relationship Proteobacteria-Bacteroides to Proteobacteria-Firmicutes. In multiple sclerosis, Actinobacteria and Proteobacteria increase and Firmicutes decrease. Conclusion. The multiple sclerosis disease may be associated with pathological changes in the structure of the microbiome and the growth of endotoxemia, which may be one of the factors in the pathogenesis of the disease. New laboratory markers for diagnosing and predicting the course of MS have been proposed.

[Prospects for the use of polyphenols in multiple sclerosis]. / Perspektivy primeneniya polifenolov pri rasseyannom skleroze.

Multiple sclerosis (MS) is a chronic demyelinating autoimmune disease. Therapy for MS does not always slow down the progression of the disease. In many cases, pathogenetic therapy of MS leads to serious side-effects, in particular, to immunosuppression, limiting using of various disease modifying therapy (DMT) in MS. In this regard, it is important to study the potential use of drugs that have immunomodulatory and neuroprotective effects, as well as a favorable safety profile. Polyphenols (compounds containing phenolic and hydroxyl groups, often of natural origin) have the ability to modulate immunoregulatory targets, reducing the production of various pro-inflammatory cytokines that play an important role in the pathogenesis of MS. The combined use of DMT and substances with a favorable safety profile, anti-inflammatory activity, and the ability to penetrate the blood-brain barrier, such as polyphenols, may be one of the promising strategies in the treatment of MS to improve the quality of life of patients. In this review, we consider the mechanisms of action of polyphenols in MS, their application in experimental models of MS, and the results of clinical studies of polyphenols in MS.

[The role of macrophages in the development of neuroinflammation in multiple sclerosis]. / Rol' makrofagov v razvitii neirovospaleniya pri rasseyannom skleroze.

Multiple sclerosis (MS) is a chronic demyelinating and neurodegenerative disease of the central nervous system with an autoimmune mechanism of development. It is known that along with T- and B-lymphocytes, cells of the innate immune system also play a significant role in the pathogenesis of MS. Macrophages are central to the functioning of the innate immune response and, depending on the phenotype, have pro-and anti-inflammatory properties. In the central nervous system, resident macrophages form microglia capable of presenting antigens and producing cytokines and, depending on phenotype, may participate in the development of autoimmune inflammation or maintaining immunological tolerance. The brief report presents data on the participation of macrophages in the pathogenesis of experimental autoimmune encephalomyelitis and MS. In addition, current methods of modulation of macrophage functions for the treatment of MS are discussed.

[The influence of fluoxetine on interleukin-6 and interleukin-1ß production by dendritic cells in multiple sclerosis in vitro]. / Vliyanie fluoksetina na produktsiyu dendritnymi kletkami interleikina-6 i interleikina-1ß pri rasseyannom skleroze in vitro.

THE AIM OF THE STUDY: Was to evaluate the effect of selective serotonin reuptake inhibitor fluoxetine on the production of cytokines interleukin-6 (IL-6) and interleukin-1ß (IL-1ß) by dendritic cells in multiple sclerosis (MS). MATERIAL AND METHODS: 5 patients with relapsing-remitting MS and five healthy subjects were examined. Levels of IL-6 and IL-1ß were measured by ELISA in culture supernatants obtained from lipopolysaccharide stimulated dendritic cells. To assess the effect of fluoxetine on cytokine production, dendritic cells were stimulated in the presence of fluoxetine and antagonists of 5-HT1A-, 5-HT2A-, 5-HT2B-receptors or agonist of 5-HT2B-receptors. RESULTS: Cytokine production by dendritic cells was comparable in both groups. Fluoxetine suppressed IL-6 and IL-1ß production in both groups. Blockade of 5-HT2B-receptors with specific antagonist RS 127445 reduced the inhibitory effect of fluoxetine on IL-1ß production in both groups and IL-6 production in healthy subjects. In contrast, activation of 5-HT2B-receptors by specific agonist BW 723C86 increased the inhibitory effect of fluoxetine on IL-6 production by dendritic cells in both groups, but did not affect on IL-1ß production. CONCLUSION: These data suggest an anti-inflammatory effect of fluoxetine in MS by modulating pro-inflammatory cytokines production by dendritic cells. This effect could be mediate by activation of 5-HT2B-receptors.

[Serotonergic system as a therapeutic target in multiple sclerosis]. / Serotoninergicheskaia sistema kak terapevticheskaia mishen' pri rasseiannom skleroze.

The article presents the current literature on the role of serotonin in immunomodulation in multiple sclerosis, in particular, on the effect of serotonin on Th17-immune response and function of dendritic cells. The role of serotonin in the regulation of the gut-brain axis and the prospects for serotoninergic drugs as pathogenetic therapy in multiple sclerosis are discussed.

[Norepinephrine and intestinal microbiome in the early stages of demyelination: clinical-immunological parallels]. / Noradrenalin i mikrobiom kishechnika na rannikh stadiiakh demieliniziruiushchego protsessa: kliniko-immunologicheskie paralleli.

Biogenic amines are key mediators of neuroimmune interaction and may influence on multiple sclerosis (MS) pathogenesis and MS course. At the same time, the role of biogenic amines in immunoregulation of early stages of demyelination, in particular clinically isolated syndrome (CIS) and radiologically isolated syndrome (RIS) is still unclear. This literature review addresses a role of norepinephrine in the regulation of neuroimmune interactions in the early stages of the demyelination. Neuropsychological disorders, immunological characteristics, gut-brain axis as well as the role of norepinephrine in these interactions in patients with CIS, RIS and early MS are discussed.

[Estimating ability of dihydroquercetin to inhibit oxidation of fibrinogen by ozone].

The ability of dihydroquercetin to inhibit the oxidation of fibrinogen has been evaluated. It is established that dihydroquercetin inhibits oxidation of fibrinogen by ozone, thus preventing oxidative modification of fibrinogen and preserving its functional activity.

[Antihypertensive and neuroprotective activity of quercetin and its derivatives].

Data available in the literature on the pharmacological activity of quercetin and its derivatives, which possess various biological properties including antihypertensive and neurotropic activity, are reviewed. The mechanisms of these effects and results of clinical trials are considered and prospects for the clinical use of quercetin and its derivatives are discussed.

[Antiproliferative and antioxidant activity of new dihydroquercetin derivatives].

Effect of nine new derivatives of dihydroquercetin (taxifolin) on the viability of cultivated normal and tumor cells, their antioxidant activity, and interconnection of the antioxidant activity with the chemical structure have been studied. Among these dihydroquercetin derivatives, the maximum antiproliferative activity on the model of rat fibroblast culture exhibited KN-2, KN-4, KN-7, and KN-8 compounds, while KN-7 and KN-8 compounds also showed maximum activity on the model of MCF-7 tumor cell culture (human breast cancer). The maximum general antioxidant activity was observed for the native dihydroquercetin and KN-8 compound. There is a strong correlation (with a correlation coefficient of 0.93) between the antiproliferative effects of dihydroquercetin derivatives on murine skin fibroblasts and MCF-7 cells (human breast cancer).