The interactions between inflammation and insulin resistance: molecular mechanisms in insulin-producing and insulin-dependent tissues

In the modern world the prevalence of obesity and type 2 diabetes mellitus (T2DM) significantly increases. In this light the risks of obesity-associated complications also grow up. The crucial linkage between obesity and its metabolic and cardiovascular complications is inflammatory process. The mechanism of this linkage is similar in pancreas and insulin-dependent tissues both on cells, cell-to-cell communication and signaling pathway levels: the catalysts are different lipids (cholesterol, free fatty acids, triglycerides), which are able to activate Toll-like receptors of innate immunity and inflammation. Nextly, IKK- and JNK-dependent cascades activate the secretion of inflammatory cytokines TNFa, IL-1b, IL-6 and others, which act by paracrine and autocrine manner and support inflammation both in local and systemic levels. Thus, insulin-producing and insulin-dependent tissues, which are involved in T2DM pathogenesis, through the inflammatory process integrate in pathogenic and self-maintaining cycle, which leads to the suppression of insulin secretion, pancreatic β-cell failure and the development of insulin-dependent tissues insulin resistance

The interactions between inflammation and insulin resistance: prospects of immunoregulation as a potential approach for the type 2 diabetes mellitus treatment

In the modern world the prevalence of obesity and type 2 diabetes mellitus (T2DM) significantly increases. In this light the risks of obesity-associated complications also grow up. The crucial linkage between obesity and its complications is inflammation, which is a convenient target for potential anti-diabetic therapy. There are some anti-inflammatory therapy strategies: action on secreted cytokines, circulating lipids or intracellular signaling cascades. Canakinumab (antibody to IL-1b receptor) and colchicine (IL-6 secretion blocker) have the most balanced anti-diabetic and cardioprotective action among cytokine anti-inflammatory therapy. Lipid-lowering therapy is very diverse, but bempedoic acid nowadays has the best combination of anti-inflammatory and cardioprotective effects. Salicylate is an inhibitor of IKK-dependent inflammatory signaling cascade and significantly lowers glycated hemoglobin and C-reactive protein levels among obese patients. The future of anti-inflammatory T2DM therapy can be related with anti-inflammatory cytokines (IL-4, IL-37), chimeric engineered cytokines (IC7Fc), novel inhibitors of inflammatory and cytokines signaling cascades (imatinib, CC90001) and cell-based therapy (mesenchymal stem cells). In summary, despite on the limitations of current clinical trials, anti-inflammatory drugs have a potential to become a part of modern combined T2DM therapy with anti-diabetic and cardioprotective properties. Novel findings in potential anti-inflammatory T2DM therapy have great perspectives in protection against T2DM and related complication prevention

Molecular dynamics simulations of oxide memory resistors (memristors)

Reversible bipolar nano-switches that can be set and read electronically in a solid-state two-terminal device are very promising for applications. We have performed molecular-dynamics simulations that mimic systems with oxygen vacancies interacting via realistic potentials and driven by an external bias voltage. The competing short- and long-range interactions among charged mobile vacancies lead to density fluctuations and short-range ordering, while illustrating some aspects of observed experimental behavior, such as memristor polarity inversion.Comment: 15 pages, 5 figure

SPECIAL ASPECTS OF INITIAL OPTICAL SCHEME SELECTION FOR DESIGN OF NON-IMAGING OPTICAL SYSTEMS

Subject of Research. The research results, structural composition analysis and the parametric synthesis of the projected imaging and non-imaging optical systems were presented. We made an attempt to use the gained experience about imaging systems while designing non-imaging systems, by adapting the composition theory for the calculations of non-imaging systems. Several patterns were revealed, which provide a deeper understanding of the design process of non-imaging optical systems; measures of its optimization were proposed. Method. We investigated the applicability of the theory of composition and synthesis of non-imaging optical systems. The main provisions of the theory of composition are based on the division of all available optical elements in four types depending on their functionality, which corresponds to a modular design. Similar items were identified in non-imaging optical systems and adaptation of composition theory to their design became possible. Main Results. General design patterns of imaging and non-imaging optical systems were studied. Classification of systems, components, as well as technical and generic characteristics of imaging and non-imaging optical systems was determined. Search mechanism of the initial optical system by means of structural and parametric synthesis of non-imaging optical system was formalized. The basic elements were determined included in non-imaging systems and their classification by functionality was done. They were subdivided into basic, corrective, wide angle and high aperture ones. The rules for formation of these elements and their composition were determined: surface reflecting, refracting, spherical and nonspherical elements with total internal reflection. The foundations of composition theory for non-imaging optical systems were laid. The approbation of this method was carried out on the example of the illumination system calculation for surgical room. A 3D model of an illumination optical system for surgical room was obtained, consisting of three identical domes. The illuminator designed with the use of the proposed methodology showed high energy efficiency (92.3%). Practical Relevance. The results can find application in optical design of non-imaging systems having various functionality, for example, illuminators, concentrators, etc. and can provide import substitution of similar foreign devices. The results can be useful by engineers specializing in the design and/or operation of non-imaging optical systems