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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.

Objective ― The aim of the work was to study the contribution of the immune response mediator genes polymorphism (TNFA rs1800629, LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601, PADI4 rs2240336) to the formation of the predisposition to juvenile idiopathic arthritis (JIA) and its clinical variants. Material and Methods ― The JIA group included 330 patients and the control group – 342 volunteers without autoimmune diseases from the Republic of Bashkortostan, Russia. Genotyping was conducted by the real-time polymerase chain reaction. Results ― Taking into account the differences by sex, it was established, that the alleles/genotypes of the TNFA rs1800629, LTA rs909253, IL2-IL21 rs6822844, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype are associated with the development of JIA as a whole (p<0.05); alleles/genotypes of the LTA rs909253, IL1B rs16944, IL2-IL21 rs6822844, IL2RA rs2104286, IL6 rs1800795, IL10 rs1800872, MIF rs755622, CTLA4 rs3087243, NFKB1 rs28362491, PTPN22 rs2476601 polymorphic loci and the TNFA rs1800629*G – LTA rs909253*G haplotype – with some of JIA clinical variants (p<0.05). Conclusion ― In this work, the relationship of the alleles, genotypes and haplotypes of a number of the immune response mediator genes polymorphic loci with the risk of the development of JIA and its clinical variants was established. Specific associations were observed for girls and boys, which indicates the existence of sexual dimorphism in the JIA pathogenesis.

Objective-The aim of the study was to investigate the relationship of the alleles and genotypes of the immune response mediator genes polymorphic loci (rs1800629, rs909253, rs16944, rs6822844, rs2104286, rs1800795, rs1800872, rs3087243, rs755622 rs28362491, rs2240336, rs2476601) with the etanercept efficacy in juvenile idiopathic arthritis (JIA) patients. Material and Methods-The study included 39 JIA patients from Bashkortostan, Russia. Achieving the American College of Rheumatology Pediatric 70 (ACR Pedi 70) response was regarded as the presence of the response to etanercept (otherwise-as the absence), while achieving clinical remission on medication-as the sufficient response (otherwise-as the insufficient). Genotyping was performed using real-time polymerase chain reaction method. Results-The predictors of an increased risk of the non-response to etanercept were the IL1B rs16944*TT (p cor =0.023), NFKB1 rs28362491*II (p cor =0.042) genotypes, and of the increased risk of the insufficient response to etanercept-the IL2RA rs2104286*AA (p cor =0.010), NFKB1 rs28362491*II (p cor =0.026) genotypes. The markers of the decreased risk of the non-response to etanercept were the IL1B rs16944*C (p cor =0.046), NFKB1 rs28362491*D (p cor =0.029) alleles, and of the decreased risk of the insufficient response to etanercept-the IL2RA rs2104286*AG genotype (p cor =0.049), IL2RA rs2104286*G allele (p cor =0.005). Conclusion-In this study the association of the alleles and genotypes of the IL1B rs16944, IL2RA rs2104286, NFKB1 rs28362491 polymorphic loci with the etanercept efficacy in JIA patients was established.

We investigated the association of matrix metalloproteinases, the disintegrin and metalloprotease 33 and the tissue and serum inhibitors of proteinase gene polymorphisms with severe chronic respiratory diseases in Tatar children. We analyzed the case-control data sample from a total of 592 Tatar individuals, consisting of 119 children with chronic bronchitis, 138 with recurrent pneumonia and 335 control children residing in Ufa (Russia). The percentage of heterozygous genotype for the MMP9 (2660A>G) was higher among healthy children (52.54% vs 36.13% in chronic bronchitis patients, P(adj)=0.0033, P(cor)=0.033, odds ratio (OR)=0.51; and 36.96% in recurrent pneumonia group, P(adj)=0.0034, P(cor)=0.034, OR=0.53). The MMP12 (-82A>G) locus was associated with chronic bronchitis in the additive model (P(adj)=0.0091, P(cor)=0.09, OR=0.45, β=-0.798). The relationship between the 6A6A genotype of MMP3 (-1171 5A>6A) (P(adj)=0.0013, P(cor)=0.013, OR=3.91) and the 6A-A haplotype of MMP3 (-1171 5A>6A) and MMP12 (-82A>G) and recurrent pneumonia were unraveled (Padj=0.001, P(cor)=0.01, OR=2.07). This haplotype was also associated with a higher risk of chronic bronchitis (P(adj)=0.0012, P(cor)=0.012, OR=2.15). The TIMP3 (-1296T>C) was associated with recurrent pneumonia in the dominant model (P(adj)=0.0031, P(cor)=0.031, OR=1.91). The MMP9, MMP3 and TIMP3 (tissue inhibitors of matrix metalloproteinases) polymorphisms and MMP3 and MMP12 haplotypes may play a substantial role in susceptibility to severe airway and lung injury in children with chronic bronchitis and recurrent pneumonia.

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.