Ceramides: focus on obesity

It is generally known that obesity increases the risk of developing cardiovascular disease. A pathological increase in the mass of adipose tissue leads to a violation of the control of lipid accumulation at the molecular level, abnormal lipid metabolism with the formation of metabolites, which are critical for the development of these pathologies against the background of obesity. Ceramides are one of these metabolites. Ceramides perform many physiological functions, but under pathological conditions they induce insulin resistance, uncouple cellular respiration and phosphorylation, activate cell apoptosis, and play an important role in the induction of adipose tissue dysfunction. Altering ceramide biosynthesis through dysregulation of key enzymes leads to the formation and accumulation of ceramides, which block insulin signaling and induce adipose tissue inflammation.This review highlights the metabolism of ceramides, the reasons for their ectopic deposition in tissues in obesity, as well as potential intracellular signaling pathways that modulate ceramide activity

Electrochemical study of semiconductor properties for bismuth silicate-based photocatalysts obtained via hydro-/solvothermal approach

Three bismuth silicate-based photocatalysts (composites of Bi2SiO5 and Bi12SiO20) prepared via the hydro-/solvothermal approach were studied using electrochemical methods. The characteristic parameters of semiconductors, such as flat band potential, donor density, and mobility of their charge carriers, were obtained and compared with the materials’ photocatalytic activity. An attempt was made to study the effect of solution components on the semiconductor/liquid interface (SLI). In particular, the Mott–Schottky characterization was made in a common model electrolyte (Na2SO4) and with the addition of glycerol as a model organic compound for photocatalysis. Thus, a medium close to those in photocatalytic experiments was simulated, at least within the limits allowed by electrochemical measurements. Zeta-potential measurements and electrochemical impedance spectroscopy were used to reveal the processes taking place at the SLI. It was found that the medium in which measurements were carried out dramatically impacted the results. The flat band potential values (Efb) obtained via the Mott–Schottky technique were shown to differ significantly depending on the solution used in the experiment, which is explained by different processes taking place at the SLI. A strong influence of specific adsorption of commonly used sulfate ions and neutral molecules on the measured values of Efb was shown

The role of newly diagnosed diabetes mellitus for poor in-hospital prognosis of coronary artery bypass grafting

Background: The management of coronary artery disease in patients with type 2 diabetes (T2DM) who need myocardial revascularization is a great challenge. Aims: To study the role of newly diagnosed T2DM in the development of in-hospital adverse outcomes after coronary artery surgery (CABG). Methods: 708 consecutive patients underwent CABG were included. All patients without history of T2DM and with border fasting hyperglycemia underwent an oral glucose tolerance test. Results: The screening allowed to diagnose T2DM in 8.9% and prediabetes in 10.4% of the study population. The the number of patients with T2DM increased from 15.2% to 24.1%, and with prediabetes from 3.0% to 13.4%. The total number of patients with carbohydrate metabolism disorders increased from 18.2% to 37.5%. The trend towards higher rate of in-hospital complications after CABG was defined among patients with newly diagnosed and previously diagnosed T2DM. The regression analysis demonstrated the presence of the relationships between the previously diagnosed T2DM and the total number of significant complications (odds ratio (OR) 1.350, 95% confidence interval (CI): 1.0571.723, p=0.020) and prolonged in-hospital stay (OR 1.609, 95%CI 1.2022.155, p=0.001). The significance of these relationships increased with the addition of newly diagnosed T2DM to the regression model (for in-hospital complications: OR 1.731, 95% CI 1.1312.626, p=0.012; for prolonged in-hospital stay: OR 2.229, 95%CI 1.4123.519, p0.001). Moreover, additional associations between T2DM and the risk of developing multiple organ dysfunction (OR 2.911, 95% CI 1.0727.901, p=0.039), urgent lower extremity surgery (OR 1.638, 95%CI 1.00915.213, p=0.020) and the need for extracorporeal correction of hemostasis (OR 3.472, 95%CI 1.04211.556, p=0.044) have been defined. Importantly, the presence of these associations would not have been identified without including newly diagnosed DM in the regression model. Conclusion: The newly diagnosed T2DM affects the prognosis of CABG as well as the previously diagnosed T2DM. The obtained results suggest the importance of active preoperative T2DM screening

Adipokine-cytokine profile of adipocytes of epicardial adipose tissue in ischemic heart disease complicated by visceral obesity

Introduction. To date, cardiovascular diseases (CVD) remain the main cause of disability and mortality in population. The majority of ectopic fat deposits demonstrated a reliable association with cardiometabolic risks and clinical manifestations of most CVD. The elucidation of the metabolic features of adipocytes of epicardial adipose tissue localized in the immediate vicinity of the lesion in ischemic heart disease (IHD) can have both theoretical and practical significance for pathophysiology and cardiology. Aim. To study the adipokine-cytokine profile of epicardial adipocytes (EA) and subcutaneous adipose tissue (SCAT), blood serum in relation to the area of visceral adipose tissue (AVAT), biochemical and rhelinic characteristics of IHD patients. Methods. 84 patients (70 men and 14 women) with IHD were examined. In the presence of visceral obesity (VO), patients were divided into two groups. In patients with VO, adipocyte EA and SCAT were sampled, followed by cultivation and evaluation of adipokine and proinflammatory activity. The parameters of carbohydrate and lipid metabolism, adipokine and proinflammatory status in blood serum were determined. Results. It has been established that the adipokine-cytokine profile of the adipocytes EA and SCAT differ. Adipocytes of EA in IHD on the background of VO are characterized by an increase in IL-1, TNF-α, leptin-adiponectin ratio and a decrease in the protective factors: adiponectin and anti-inflammatory cytokine IL-10. While adipocytes of SCAT were characterized by a decrease in the concentration of the soluble receptor to leptin and a more pronounced leptin resistance, and the increase in inflammatory cytokines was compensated by an increase in the concentration of IL-10, the presence of VO was associated with multivessel coronary disease, multifocal atherosclerosis, insulin resistance, atherogenic dyslipidemia, adipokine imbalance, and markers of inflammation. Thus, the value of the area of VO determined higher values of leptin concentration, TNF-α in adipocytes and serum, lipid and carbohydrate metabolism and a lower soluble receptor for leptin content. The conclusion. Thus, in IHD with VO the state of adipocytes, EA is characterized as "metabolic inflammation" and may indicate the direct involvement of adipocytes in the pathogenesis of IHD due to the formation of adipokine imbalance and the activation of proinflammatory reactions

Expression of adipocytokines in heart fat depots depending on the degree of coronary artery atherosclerosis in patients with coronary artery disease.

In coronary artery disease (CAD) the adipocytokine content in the heart fat depot is altered, but it has not been established whether these changes are associated with the degree of atherosclerotic damage to the coronary artery (CA). Were examined 84 patients with CAD, and according to the degree of atherosclerotic state based on the SYNTAX Score scale, were divided: 39 moderate (≤22 points), 20 severe (23-31 points) and 25 extremely severe (≥32 points). Biopsies of subcutaneous (SAT), epicardial (EAT) and perivascular adipose tissue (PVAT) were obtained during elective coronary artery bypass grafting (CABG). The expression of adipocytokine was determined using real-time PCR. The concentration of the studied adipocytokines in adipocyte culture medium was measured by ELISA. Statistical analysis was performed using logistic regression analysis. In the adipocytes of the cardiac depot of patients with CAD, an increase in the expression and secretion of leptin and IL-6 and a decrease in adiponectin, with a maximum manifestation in severe and extremely severe CA lesions, was observed. EAT adipocytes were characterized by minimal expression of the adiponectin gene maximal gene expression leptin and IL-6 compared to SAT and PVAT adipocytes

Relationship between Epicardial and Coronary Adipose Tissue and the Expression of Adiponectin, Leptin, and Interleukin 6 in Patients with Coronary Artery Disease

Adipose tissue (AT) is an endocrine and paracrine organ that synthesizes biologically active adipocytokines, which affect inflammation, fibrosis, and atherogenesis. Epicardial and perivascular fat depots are of great interest to researchers, owing to their potential effects on the myocardium and blood vessels. The aim of the study was to assess the expression and secretion of adipocytokine genes in the AT of patients with coronary artery disease (CAD) and patients with aortic or mitral valve replacement. This study included 84 patients with CAD and 50 patients with aortic or mitral valve replacement. Adipocytes were isolated from subcutaneous, epicardial (EAT), and perivascular AT (PVAT), and were cultured for 24 h. EAT exhibited the lowest level of adiponectin gene expression and secretion, regardless of nosology, and high expression levels of the leptin gene and interleukin-6 (IL-6). However, EAT adipocytes in patients with CAD were characterized by more pronounced changes in comparison with the group with heart defects. High leptin and IL-6 levels resulted in increased pro-inflammatory activity, as observed in both EAT and PVAT adipocytes, especially in individuals with CAD. Therefore, our results revealed the pathogenetic significance of alterations in the adipokine and cytokine status of adipocytes of EAT and PVAT in patients with CAD

Pericentromeric Non-Coding DNA Transcription Is Associated with Niche Impairment in Patients with Ineffective or Partially Effective Multiple Myeloma Treatment

Mesenchymal stromal cells (MSC) ‘educated’ by tumor cells are an essential component of the multiple myeloma (MM) tumor microenvironment (TME) involved in tumor progression. Transcription of tandemly repeated (TR) non-coding DNA is often activated in many tumors and is required for tumor progression and cancer cells genome reorganization. The aim of the work was to study functional properties including the TR DNA transcription profile of MSC from the hematopoietic niche of treated MM patients. Healthy donors (HD) and patients after bortezomib-based treatment (with partial or complete response, PoCR, and non-responders, NR) were enrolled in the study. Their trephine biopsies were examined histologically to evaluate the hematopoietic niche. MSC cultures obtained from the biopsies were used for evaluation of the proliferation rate, osteogenic differentiation, presence of tumor MSC markers, resistance to bortezomib, and pericentromeric TR DNA transcription level. The MSC ‘education’ by multiple myeloma cells was mimicked in co-culture experiments with or without bortezomib. The TR DNA transcription profile was accessed. The histological examination revealed the persistence of the tumor microenvironment (especially of the vasculature) in treated patients. In co-culture experiments, MSC of bortezomib-treated patients were more resistant to bortezomib and protected cancer MM cells of the RPMI8226 cell line more effectively than HD-MSC did. The MSC obtained from PoCR and NR samples differed in their functional properties (proliferation capacity, osteogenic potential, and cancer-associated fibroblasts markers). Transcriptome analysis revealed activation of the TR transcription in cells of non-hematopoietic origin from NR patients’ bone marrow. The pericentromeric TR DNA of HS2/HS3 families was among the most upregulated in stromal MSC but not in cancer cells. The highest level of transcription was observed in NR-MSC. Transcription of HS2/HS3 was not detected in healthy donors MSC unless they were co-cultured with MM cancer cells and acquired cancer-associated phenotype. Treatment with TNFα downregulated HS2/HS3 transcription in MSC and upregulated in MM cells. Our results suggest that the hematopoietic niche retains the cancer-associated phenotype after treatment. Pericentromeric non-coding DNA transcription is associated with the MSC cancer-associated phenotype in patients with ineffective or partially effective multiple myeloma treatment