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Many factors underlie the development of inflammatory bowel disease (IBD) in humans. In particular, imbalance of microbiota and thinning of the mucosal layer in the large intestine play a huge role. Pathogenic microorganisms also exacerbate the course of diseases. In this research the role of mucin 2 deficiency in the formation of intestinal microflora in the experimental model using the Muc2 gene knockout mice in the presence of Helicobacter spp. was investigated. Also, restorative and anti-inflammatory effect of the dietary L-fucose in the Muc2

Fucose, the terminal glycan of the intestinal glycoprotein Mucin2, was shown to have an anti-inflammatory effect in mouse colitis models and modulate immune response due to macrophage polarization changes. In this study we evaluated the effect of 0.05% L-fucose supplementation of drinking water on immune parameters in the intestine of homozygous mutant Muc2−/−, compared to Muc2+/+ mice. To get into innate and adaptive immunity mechanisms of gut inflammation, we tested PrkdcSCIDMuc2−/− strain, Muc2 knockout on SCID background, that is characterized by lack of lymphocytes, in comparison with PrkdcSCID mice. We evaluated intestinal cytokine profiling, macrophage and eosinophil infiltration, and expression of Nos2 and Arg1 markers of macrophage activation in all strains. Markers of Th1, Treg and Th17 cells (Tbx21, Foxp3, and Rorc expression) were evaluated in Muc2−/− and Muc2+/+ mice. Both Muc2−/− and PrkdcSCIDMuc2−/− mice demonstrated increased numbers of macrophages, eosinophils, elevated levels of TNFa, GM-CSF, and IL-10 cytokines. In Muc2−/− mice we observed a wide range of pro-inflammatory cytokines elevated, such as IFN-gamma, IL-1b, IL-12p70, IL-6, M-CSF, G-CSF, IL-17, MCP-1, RANTES, MIP1b, MIP2. Muc2−/− mice demonstrated increase of Nos2, Tbx21 and Foxp3 genes mRNA, while in PrkdcSCIDMuc2−/− mice Arg1 expression was increased. We found that in Muc2−/− mice L-fucose reduced macrophage infiltration and IL-1a, TNFa, IFNgamma, IL-6, MCP-1, RANTES, MIP1b levels, decreased Nos2 expression, and induced the expression of Treg marker Foxp3 gene. On the contrary, in PrkdcSCIDMuc2−/− mice L-fucose had no effect on macrophage and eosinophil numbers, but increased TNFa, GM-CSF, IL-12p70, IL-6, IL-15, IL-10, MCP1, G-CSF, IL-3 levels and Nos2 gene expression, and decreased Arg1 gene expression. We demonstrated that anti-inflammatory effect of L-fucose observed in Muc2−/− mice is not reproduced in PrkdcSCIDMuc2−/−, which lack lymphocytes. We conclude that activation of Treg cells is a key event that leads to resolution of inflammation upon L-fucose supplementation in Muc2−/− mice.

Актуальность исследования обусловлена тем, что систематическое проведение энергетических обследований электрических сетей с целью выявления потерь электроэнергии составляет основу энергосбережения и энергоэффективности. Обработка результатов энергетических обследований представляет собой работу с большим объемом неструктурированных данных, которые плохо поддаются полному учету. Цель исследования: рассмотрение возможности решения проблемы обработки результатов энергетических обследований на основе агрегирования предпочтений, что обеспечит возможность эффективного сжатия данных без потери информации и наглядную визуализацию результатов энергоаудита. В качестве объектов исследования рассмотрены магистральные электрические сети, входящие в Единую национальную электрическую сеть России. Магистральные электрические сети, в свою очередь, состоят из предприятий магистральных электрических сетей, каждое из которых объединяет большое количество подстанций. Данные ежегодных энергетических обследований магистральных электрических сетей России содержатся в базе ПАО «ФСК ЕЭС». Методы. Предложен основанный на агрегировании предпочтений метод, позволяющий представить большой объем данных инструментальных обследований потери энергии подстанциями сетей распределения электрической энергии в форме компактной интегральной оценки в порядковой шкале, удобной для принятия решений и визуализации. Обсуждается применение предложенного метода для анализа реальных данных энергетического обследования магистральных электрических сетей России. Результаты. Метод позволяет выявить источники экономически нерациональных затрат энергетических ресурсов и неоправданных потерь энергии, обеспечить сжатие больших объемов данных энергообследований без потери существенной информации. Предложенный метод может стать удобным перспективным инструментом для организаций, занимающихся энергоконсалтингом.

The mucus layer in the intestine plays a critical role in regulation of host–microbe interactions and maintaining homeostasis. Disruptions of the mucus layer due to genetic, environmental, or immune factors may lead to inflammatory bowel diseases (IBD). IBD frequently are accompanied with infections, and therefore are treated with antibiotics. Hence, it is important to evaluate risks of antibiotic treatment in individuals with vulnerable gut barrier and chronic inflammation. Mice with a knockout of the Muc2 gene, encoding the main glycoprotein component of the mucus, demonstrate a close contact of the microbes with the gut epithelium which leads to chronic inflammation resembling IBD. Here we demonstrate that the Muc2−/− mice harboring a gut protozoan infection Tritrichomonas sp. are susceptible to an antibiotic-induced depletion of the bacterial microbiota. Suppression of the protozoan infection with efficient metronidazole dosage or L-fucose administration resulted in amelioration of an illness observed in antibiotic-treated Muc2−/− mice. Fucose is a monosaccharide presented abundantly in gut glycoproteins, including Mucin2, and is known to be involved in host–microbe interactions, in particular in microbe adhesion. We suppose that further investigation of the role of fucose in protozoan adhesion to host cells may be of great value.

The disruption of the protective intestinal barrier—the ‘leaky gut’—is a common complication of the inflammatory bowel disease. There is limited data on the mechanisms of the intestinal barrier disruption upon low-grade inflammation characteristic of patients with inflammatory bowel disease in clinical remission. Thus, animal models that recapitulate the complexity of chronic intestinal inflammation in vivo are of particular interest. In this study, we used Mucin-2 (Muc2) knockout mice predisposed to colitis to study intestinal barrier upon chronic inflammation. We used 4-kDa FITC-Dextran assay and transmission electron microscopy to demonstrate the increased intestinal permeability and morphological defects in intercellular junctions in Muc2 knockout mice. Confocal microscopy revealed the disruption of the apical F-actin cytoskeleton and delocalization of tight junction protein Claudin-3 from the membrane. We further demonstrate mitochondrial damage, impaired oxygen consumption and the reduction of the intestinal ATP content in Muc2 knockout mice. Finally, we show that chemically induced mitochondrial uncoupling in the wild type mice mimics the intestinal barrier disruption in vivo and causes partial loss of F-actin and membrane localization of Claudin-3. We propose that mitochondrial damage and metabolic shifts during chronic inflammation contribute to the leaky gut syndrome in Muc2 knockout animal model of colitis.

The dry eye syndrome ranges among widespread and persisting ophthalmic diseases. It is also called a disease of civilization. Among the causes particularly often leading to the dry eye syndrome adenoviral infection has to be listed. Over the last years, in Saint Petersburg, an increasing incidence rate of the epidemic adenoviral keratoconjunctivitis is noted, which is proceeding in severe membranous and infiltrative forms, involving the cornea. Occurring therewith secondary dry eye syndrome demands using effective medications. In the article, the experience in Cationorm (Santen, Japan) clinical use for secondary dry eye syndrome treatment is disclosed.

Growing evidence suggests that intestinal mucosa homeostasis impacts immunity, metabolism, the Central Nervous System (CNS), and behavior. Here, we investigated the effect of the monosaccharide fucose on inflammation, metabolism, intestinal microbiota, and social behavior in the Dextran Sulfate Sodium (DSS)-induced chronic colitis mouse model. Our data show that chronic colitis is accompanied by the decrease of the serum tryptophan level and the depletion of the intestinal microbiota, specifically tryptophan-producing E. coli and Bifidobacterium. These changes are associated with defects in the male mouse social behavior such as a lack of preference towards female bedding in an odor preference test. The addition of fucose to the test animals&rsquo, diet altered the bacterial community, increased the abundance of tryptophan-producing E. coli, normalized blood tryptophan levels, and ameliorated social behavior deficits. At the same time, we observed no ameliorating effect of fucose on colon morphology and colitis. Our results suggest a possible mechanism by which intestinal inflammation affects social behavior in male mice. We propose fucose as a promising prebiotic, since it creates a favorable environment for the beneficial bacteria that promote normalization of serum tryptophan level and amelioration of the behavioral abnormalities in the odor preference test.

The intellectual and political elite discourse, which plays an important role in adopting new ideas in the society, often use the terms expressing abstract concepts. “Internationalism” in the Soviet Russia was one of these terms.The goal of this paper is to analyze the origins of the international discourse in the Bolshevik milieu at the beginning of the 20th century. This research is based on discourse analysis drawing on the methodology of social constructivism, which considers discourse as a constitutive of the social reality and a social phenomenon.The author concludes that the word “internationalism” had appeared in RSDLP(b) intellectual party elite discourse before Bolsheviks coming to power and laid the foundations for the Soviet Union ideology and policies towards nationalities inside the country, as well as foreign policy. Double orientation of “internationalism” motto (which literally means “between nations”) was linked to Bolsheviks’ recognition of double meaning of the term of “nation” – national minority on the one hand, national state on the other.