Currently, significant attention is attracted to the problem of the development of the specific architecture and composition of the surface layer in order to control the biocompatibility of implants made of titanium and its alloys. The titanium surface properties can be tuned both by creating an inorganic sublayer with the desired morphology and by organic top coating contributing to bioactivity. In this work, we developed a composite biologically active coatings based on hybrid molecules obtained by chemical cross-linking of amino acid bisphosphonates with a linear tripeptide RGD, in combination with inorganic porous sublayer created on titanium by plasma electrolytic oxidation (PEO). After the addition of organic molecules, the PEO coated surface gets nobler, but corrosion currents increase. In vitro studies on proliferation and viability of fibroblasts, mesenchymal stem cells and osteoblast-like cells showed the significant dependence of the molecule bioactivity on the structure of bisphosphonate anchor and the linker. Several RGD-modified bisphosphonates of β-alanine, γ-aminobutyric and ε-aminocaproic acids with BMPS or SMCC linkers can be recommended as promising candidates for further in vivo research.

To assess the role that polymorphisms of cytokine genes play in genetic predisposition to chronic obstructive pulmonary disease (COPD), the allele and genotype distributions of IL1B, IL1RN, TNFA, LTA, IL6, IL8, and IL10 were studied in COPD patients (N = 319) and healthy individuals (N = 403), residents of Ufa, Bashkortostan. Genotype IL1RN*2/IL1RN*2 of IL1RN was identified as a risk factor for COPD, its frequency being 9.80% in the COPD patients and 4.67% in the healthy subjects (x ² = 5.45, df = 1, P = 0.02, OR = 2.21). Genotype GG of the LTA polymorphism A252G was significantly more common in the COPD patients than in the controls (7.84% vs. 3.72%; x ² = 5.00, df = 1, P = 0.026). In patients with COPD stage IV, the frequency of this genotype was twice as high as in those with COPD stages II and III (11.18% vs. 4.79%; x ² = 3.08, df = 1, P = 0.08). Genotype GG of the TNFA polymorphism G(−308)A in combination with genotype AA of the LTA polymorphism A252G was significantly less frequent in the COPD patients than in the healthy subjects (38.55% vs. 46.93%; x ² = 8.82, df = 1, P = 0.0039). Genotype GG of the IL6 polymorphism G(−174)C was more frequent in the patients with COPD stage IV (43.75% vs. 31.54% in the patients with COPD stages II and III, x ² = 4.15, P = 0.042). No significant differences were found between the groups of COPD patients and healthy subjects concerning the genotype frequencies of the polymorphisms T(−511)C and T3953C of IL1B, G(−308)A of TNFA, G(−174)C of IL6, A(−251)C of IL8, and C(−627)A of IL10.

Epicardial adipose tissue (EAT) has unique properties due to its special anatomical structure, thermoregulation, and metabolic activity. Dysregulated EAT provokes the synthesis of pro-inflammatory cytokines, disorders in the metabolism of fats and glucose, as well as contributes to fatty degeneration of the myocardium and heart failure development. EAT may serve as a risk factor and biomarker for cardiovascular diseases, and is also a potential therapeutic target. The purpose of this review was to highlight current research data on EAT, secreted adipokines, their effect on target tissue metabolism, and to systematize the relationship between EAT and cardiovascular diseases. In particular, its function, role in heart failure, atrial fibrillation, as well as the prognostic value of various microRNAs determined in EAT are highlighted.

Titanium is considered to be the most essential metal in the field of implantology. The main factors determining metal biocompatibility, among others, include the morphology and chemical composition of the titanium surface. Therefore, the aim of this work was to develop approaches to control the biological activity of the titanium surface by creating coatings that combine both an inorganic phase with a given morphology and organic molecules containing an integrin-selective peptide that regulate cell adhesion and proliferation. As such, we synthesized new c(RGDfC) derivatives of amino acid bisphosphonates (four examples) with different bisphosphonate anchors and maleimide linkers. These molecules were deposited on a highly developed porous surface obtained via the plasma electrolytic oxidation (PEO) of coarse-grained and nanostructured titanium. In vitro studies demonstrated the increase in the viability degree of mesenchymal stem cells and fibroblasts on the surface of coarse-grained or nanostructured titanium modified with PEO and a c(RGDfC) derivative of ε-aminocaproic acid bisphophonate with an SMCC linker. As a result, the use of conjugates of amino acid bisphosphonates with a cyclic RGD peptide for the modification of PEO-coated titanium opens the ways for the effective control of the biological activity of the metal implant surface.

СВОБОДНОРАДИКАЛЬНОЕ ОКИСЛЕНИЕ И КАНЦЕРОГЕНЕЗ: ДИСКУССИОННЫЕ ВОПРОСЫ