Toll-like receptors in the pathophysiology of obesity

Obesity is a complex and relevant global medical and social problem. The adipose tissue is not only a place of deposition of energy substrates but also a source of secretion of pro-inflammatory and anti-inflammatory mediators involved in the development of the chronic latent systemic inflammatory process in the organism with obesity. The metabolic signal in obesity contributes to the polarization of macrophages in the M1 direction and triggers the Th1 immune response, causing the development of adipose tissue inflammation. A chronic inflammatory condition plays a key role in the pathophysiology of obesity-induced insulin resistance. Toll-like receptors (TLRs) may be a possible pathophysiological link in the development of insulin resistance in inflammation. At the same time, inflammation-induced lipolysis is necessary for the release of energy resources during the development of the infectious process. Thus, low-grade inflammation is important to protect against adipocyte dysfunction. These results suggest that pro-inflammatory signaling is not exclusively pathogenic in obesity. In this regard, the study of inflammatory signaling pathways involved in the modulation of chronic inflammation of adipose tissue is particularly relevant. This review summarizes current views on the structure, function of TLRs and their involvement in the pathogenesis of chronic inflammation in obesity. The possibility of using TLRs as a therapeutic target in this pathology is discussed. Obviously, further study of inflammatory signaling pathways involving TLRs initiating the development of chronic inflammation of adipose tissue will allow the development of new and effective therapeutic strategies for obesity and its metabolic complications

The Mechanisms of the Regulation of Immune Response in Patients with Comorbidity of Chronic Obstructive Pulmonary Disease and Asthma

Background. Comorbidity of chronic obstructive pulmonary disease (COPD) and asthma (asthma COPD overlap syndrome, ACOS) is a significant problem in pulmonary practice, whose pathogenetic issues are not clarified yet. Objective. To study the features of the regulation of immune response in patients with comorbid COPD and asthma. Methods. We assessed the levels of CD3+, CD4+, CD8+, CD4+/CD8+, CD19+, CD25+, HLA-DR, total IgE, TNF-α, IL-4, IFN-γ, TXB2, and LTB4 in patients with comorbid COPD and asthma. Results. The study involved 44 people with COPD, 39 people with asthma, and 12 people with comorbid COPD and asthma. The specific features in comorbid COPD and asthma were lymphocytosis, increased absolute count of T-helper cells, increased cytotoxic T-lymphocytes in relative and absolute count, increased relative and absolute numbers of B-lymphocytes, and high levels of total IgE. The elevated levels of TNF-α and IL-4 and inhibition of IFN-γ production were detected. The content of LTB4 was maximal; TXB2 levels were higher than in control group but lower than in COPD and asthma. Conclusion. In comorbid COPD and asthma inflammation increased even during stable period. High levels of eicosanoids, low production of Th1-type cytokines, and active synthesis of opposition IL-4, along with increased IgE, indicate the activation of Th2-type immune response

The principal properties of molibdenum-phosphate heteropolianions and their application as catalysts

Polyoxometallates (POMs) are increasingly used as electrocatalysts for the determination of several types of species. Dawson and Keggin-type heteropoly anions are preferentially used in industry as catalysts. Properties of Dawson-type molybdophosphate heteropoly anions are discussed in the present review. Electrochemical behavior of Keggin- and Dawsontype molybdophosphate heteropoly anions has been reviewed. The oxidation-reduction potentials of electron reductions of the [P2Mo18O62] 6– anion in solutions with various pH and in different media are cited. Special focus is made on methods of designing of electrodes modified by POMs. The most common deposition techniques of POMs include chemisorption, electrodeposition, encapsulation in polymers or sol–gels, and formation of hybrid POM–organic species. Advantages and disadvantages of various techniques are discussed. Modified electrodes are characterized by electrochemical stability, shifting of characteristic peaks and sensitivity to pH change. Проаналізовано результати досліджень електрохімічних властивостей і стабільності молібдофосфорних гетерополікомплексiв структури Кеггіна і Доусона. Визначено характерні потенціали електронних переходів 18-МФА та їх залежність від рН у водних розчинах. Розглянуто основні методи формування електродів, модифікованих ГПК, та порівнюються їх каталітичні властивості iз вихідними речовинами. Проанализированы результаты исследований электрохимических свойств и стабильности молибдофосфорных гетерополикомплексов структуры Кеггина и Доусона. Определены характерные потенциалы электронных переходов 18-МФА и их зависимость от рН в водных растворах. Рассмотрены основные методы формирования электродов, модифицированных ГПК, и сравниваются их каталитические свойства с исходными вещеставами

Effect of Prolonged High-Fat Diet on Thiol-Disulfide Homeostasis in Rats

The aim of this study was to determine the effect of a prolonged high-fat (HF) on thiol-disulfide homeostasis via the activity of the glutathione redox-system (GRS) in rat blood and liver. Methods: The experiment was conducted on male Wistar rats. They were divided into groups and fed on the HF diet for 30, 90 and 180 days, respectively. The HF diet consisted of beef fat and cholesterol (19 % and 2 % of the total diet, respectively). The state of the GRS was assessed in the erythrocytes and liver tissue by the glutathione, glutathione reductase (GR) and glutathione peroxidase (GP) activity. The levels of the initial and final products of lipid peroxidation – lipid hydroperoxides (LOOHs), diene conjugates (DC) and malondialdehydes (MDA) in the blood and liver were investigated. Results: Within 30 days, the HF diet inhibits the glutathione enzyme activity in the blood (GR: P<0.01; GP: P<0.001) and liver (GR, P<0.01). Within 90 days the HF diet kick-starts the beginning of the GRS compensatory response and restores the thiol-disulfide homeostasis. At 180 days, the HF diet shows failure of the compensatory processes in the glutathione system caused by the redox-imbalance in the thiol-disulfide exchange, which reveals lowered levels of glutathione, GR and GP activity (P<0.001 for all) in the blood and liver. Conclusion: Our results suggest that the thiol-disulfide status of the cells depends upon the nature of the nutrition, a long-term breach of which triggers a compensatory response and a failure of the compensatory processes in the GRS

Microflora of the polar bear (Ursus maritimus) from natural population of the Russian Arctic

The paper presents the results of studying the microflora of the polar bear (Ursus maritimus) organism. Samples from 22 individuals were collected during three comprehensive scientific expeditions arranged in 2014 and 2015 at the request of PJSC Rosneft Oil Company. Based on the results of laboratory processing of the samples obtained, for the first time in the Russian history of studying the species, the species and quantitative composition of microorganisms in the oral cavity and conjunctiva of the polar bear’s eye was assessed. From the mucous membrane materials of the studied polar bear individuals, 91 isolates of microorganisms were obtained and identified up to 23 genera and species. These microorganisms were represented by both bacteria and microscopic fungi. Pathogenicity factors of the isolated microflora were determined: hemolytic properties, presence of plasma coagulase and lecithinase enzymes, virulence. The antibiotic resistance of the isolated microflora was assessed. The data obtained in the course of microbiological studies will not only help to determine the health status of the studied animals but can also be used in the future as one of the components of a comprehensive monitoring of the state of Arctic marine ecosystems

Regulatory signal mechanisms of systemic inflammation in respiratory pathology

The paper presents data from literature and own studies of regulatory mechanisms of systemic inflammatory response in chronic obstructive pulmonary disease (COPD) and asthma. At the heart of the formation of a systemic inflammatory reaction is a complex of disturbances in the regulation of intra- and intercellular signaling. Etiopathogenesis of COPD and asthma differs, but immune disorders and regulatory mechanisms of systemic inflammation in the diseases have common characteristics. There are multi-type Th immune responses in both COPD and asthma, the nature of which depends on severity or control of the disease. Mixed phenotypes Th1/Th17 and Th2/Th17 appear and are followed by the formation of Th17 type of immune response associated with a worsening of the disease. General mechanisms of maintenance of systemic inflammation in the diseases have been found. These include hyperproduction of cytotoxic eicosanoids, decreased expression of CB2 receptors, the formation of mitochondrial dysfunction due to violations of the fatty acid composition of the organelle, increased synthesis of nitric oxide. The authors presented a new view on the role of immune, lipoxygenase, nitroxidergic, endocannabinoid signaling systems in the formation of systemic inflammation in chronic respiratory diseases

Lipid-Induced Mechanisms of Metabolic Syndrome

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS

1-<i>O</i>-alkyl-glycerols from Squid <i>Berryteuthis magister</i> Reduce Inflammation and Modify Fatty Acid and Plasmalogen Metabolism in Asthma Associated with Obesity

Asthma associated with obesity is considered the most severe phenotype and can be challenging to manage with standard medications. Marine-derived 1-O-alkyl-glycerols (AGs), as precursors for plasmalogen synthesis, have high biological activity, making them a promising substance for pharmacology. This study aimed to investigate the effect of AGs from squid Berryteuthis magister on lung function, fatty acid and plasmalogen levels, and cytokine and adipokine production in obese patients with asthma. The investigational trial included 19 patients with mild asthma associated with obesity who received 0.4 g of AGs daily for three months in addition to their standard treatment. The effects of AGs were evaluated at one and three months of treatment. The results of the study demonstrated that intake of AGs increased the FEV1 and FEV1/VC ratios, and significantly decreased the ACQ score in 17 of the 19 patients after three months of treatment. The intake of AGs increased concentration of plasmalogen and n–3 PUFA in plasma, and modified leptin/adiponectin production by adipose tissue. The supplementation of AGs decreased the plasma levels of inflammatory cytokines (TNF-α, IL-4, and IL-17a), and oxylipins (TXB2 and LTB4), suggesting an anti-inflammatory property of AGs. In conclusion, 1-O-alkyl-glycerols could be a promising dietary supplement for improving pulmonary function and reducing inflammation in obese asthma patients, and a natural source for plasmalogen synthesis. The study highlighted that the beneficial effects of AG consumption can be observed after one month of treatment, with gradual improvement after three months of supplementation

Role of Toll-Like Receptor 2 in Regulation of T-Helper Immune Response in Chronic Obstructive Pulmonary Disease

Objective. According to modern views, the differences in the clinical course of chronic obstructive pulmonary disease (COPD) are associated with certain types of T-helper (Th) immune response. Recent data have shown that toll-like receptor 2 (TLR2) is involved in the development of Th immune response. However, TLR2-mediated regulation of Th subpopulation balance in COPD needs to be elucidated. The aim of our work is to determine the mechanisms of TLR2-mediated regulation of Th immune response in COPD of varying severity. Methods. The study included 323 smokers/ex-smokers with stable COPD (GOLD I, GOLD II, and GOLD III) and 97 healthy nonsmokers (control group). Serum levels of Th1 (TNF-α and IFN-γ), Th2 (IL-4), Th17 (IL-6 and IL-17A), Treg (IL-10) cytokines, and the percentage of peripheral blood Th cells expressing TLR2 (CD4+CD282+) were assessed by flow cytometry. Serum concentrations of IL-21 (Th17) and TGF-β1 (Treg) were measured using the ELISA method. The predominant Th cytokine profile in serum was determined by calculating the ratios between levels of Th1 and Th17 cytokines. Spearman’s correlation test was performed. Results. Patients with COPD GOLD II and III with Th1 and Th17 cytokine profiles exhibited an increase in the percentage of CD4+CD282+ cells compared to the control group. In COPD GOLD I–III, positive correlations between CD4+CD282+ cell frequency and Th17 cytokine levels (IL-6, IL-17A, and IL-21) were found. In COPD GOLD I, IL-10 concentration was negatively correlated with the percentages of studied cells; in COPD GOLD II, a positive correlation between these parameters was noted. Conclusions. Enhanced TLR2 expression on CD4+ cells shifts cytokine profile toward Th17 phenotype that plays a crucial role in COPD progression. The level of TLR2 expression on peripheral blood CD4+ cells may be considered as a biomarker for diagnosing and predicting the progression of COPD