Institute of Medical Biotechnology

Berdsk, Russia

Institute of Medical Biotechnology

Berdsk, Russia
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Vielreicher M.,Institute of Medical Biotechnology | Gellner M.,Institute of Medical Biotechnology | Friedrich O.,Institute of Medical Biotechnology
Journal of Tissue Engineering and Regenerative Medicine | Year: 2015

Collagen I is the major fibrous extracellular component of bone responsible for its ultimate tensile strength. In tissue engineering, one of the most important challenges for tissue formation is to get cells interconnected via a strong and functional extracellular matrix (ECM), mimicking as closely as possible the natural ECM geometry. Still missing in tissue engineering are: (a) a versatile, high-resolution and non-invasive approach to evaluate and quantify different aspects of ECM development within engineered biomimetic scaffolds online; and (b) deeper insights into the mechanism whereby cellular matrix production is enhanced in 3D cell-scaffold composites, putatively via enhanced focal adhesion linkage, over the 2D setting. In this study, we developed sensitive morphometric detection methods for collagen I-producing and bone-forming mesenchymal stem cells (MSCs), based on multiphoton second harmonic generation (SHG) microscopy, and used those techniques to compare collagen I production capabilities in 2D- and 3D-arranged cells. We found that stimulating cells with 1% serum in the presence of ascorbic acid is superior to other medium conditions tested, including classical osteogenic medium. In contrast to conventional 2D culture, having MSCs packed closely in a 3D environment presumably stimulates cells to produce strong and complex collagen I networks with defined network structures (visible in SHG images) and improves collagen production. © 2015 John Wiley & Sons, Ltd.


Sun J.,Institute of Medical Biotechnology | Liu C.,Soochow University of China | Gao L.,Red Cross | Guo Y.,Institute of Medical Biotechnology | And 5 more authors.
Clinical Immunology | Year: 2015

CD276 (B7-H3) is a costimulatory molecule that plays a potent role in T cell responses, however, the role of B7-H3 in autoimmune diseases has not been elucidated. We analyzed B7-H3 expression in rheumatoid arthritis (RA) for the first time and found B7-H3 was significantly up-regulated on monocytes in RA patients, while the levels of soluble B7-H3 in serum were lower than in controls (. P<. 0.0001). These differences correlated with clinical and laboratory disease parameters and informatory factor TNF-α. Through in vitro experiments, we demonstrated that B7-H3 promoted TNF-α secretion. In addition, a new polymorphism variant, B7-H3-T-A-C-T, was identified and shown to be associated with the incidence of RA and the decreased release of sB7-H3. These results suggest that B7-H3 may be a promising biomarker associated with the pathogenesis of RA. Notably, the new B7-H3-T-A-C-T polymorphism variant is associated with RA risk and might be associated with the release of soluble B7-H3. © 2015 Elsevier Inc.


Kahumoku E.P.,Auburn University | Vazsonyi A.T.,Auburn University | Pagava K.,Tbilisi State Medical University | Phagava H.,Institute of Medical Biotechnology | And 2 more authors.
Journal of Adolescent Health | Year: 2011

Purpose The current study tested both descriptive and explanatory similarities and differences in a latent objectified body consciousness (OBC) construct and its relationship to three mental health indicators among Georgian and Swiss adolescents. Few studies have been conducted on adolescents; similarly, most work has been completed on U.S. college-age women. Methods School-based questionnaire data were collected from a total of 18,239 adolescents in Georgia (n = 9,499) and Switzerland (n = 8,740), following the same protocol. Participants rated three measures of OBC (body shame, body surveillance, and appearance control beliefs) and three mental health indicators (depressive symptoms, somatic complaints, and suicidal ideation). Final study samples included 2,657 (mean age = 16.4 years) and 3,803 female youth (mean age = 17.8 years), respectively. Data analyses included mean level comparisons, confirmatory factor analysis, path analysis, and multigroup invariance tests. Results Findings provide support for a latent OBC construct across cultures, with partial evidence of cultural differences (one of two manifest indicators). By contrast, multigroup invariance tests provide consistent evidence of no differences in the relationships between the OBC latent construct and three mental health indicators between Georgian and Swiss samples. Conclusion Despite mean level differences, findings support a latent OBC construct in both cultures, perhaps slightly more so among Swiss youth. The links between OBC and mental health indicators were also invariant across the two cultures, providing greater support for a global or universal (vs. "cultured") framework of adolescent development related to the constructs and relationships studied. © 2011 Society for Adolescent Health and Medicine.


Sun J.,Institute of Medical Biotechnology | Mao Y.,Soochow University of China | Zhang Y.-Q.,Institute of Medical Biotechnology | Guo Y.-D.,Institute of Medical Biotechnology | And 3 more authors.
Oncology Letters | Year: 2013

B7-H3, a member of the B7 family of molecules, is expressed in certain types of human cancer and is important in tumor development and progression. Although several studies have reported that the expression of B7-H3 is correlated with poor outcomes in patients with cancer, its exact role in cancer remains unknown. In the present study, the expression levels of B7-H3 in the pathological specimens of 105 patients treated for non-small cell lung cancer (NSCLC) were examined by immunohistochemistry. A high expression level of B7-H3 was observed in 46.9% of the 105 NSCLC tissue specimens. These patients demonstrated a more advanced tumor grade and a shorter survival time. In addition, we also examined the levels of tumor-associated macrophages (TAMs) in NSCLC tissues and observed that the levels were positively correlated with the expression of B7-H3, and that higher levels of macrophages were associated with lower levels of infiltrating T cells and a shorter survival time. These results demonstrated that TAMs are important in the evasion of tumor immune surveillance in NSCLC. Furthermore, through knockdown of B7-H3 by RNA interference, we observed that soluble B7-H3 was capable of inducing macrophages to express higher levels of macrophage mannose receptor (MMR) and lower levels of human leukocyte antigen (HLA)-DR, as well as higher levels of interleukin-10 (IL-10) and lower levels of IL-1β in vitro. These observations are characteristic of an anti-inflammatory/reparatory (alternative/ M2) phenotype. Therefore, our data suggests that B7-H3 proteins are involved in the progression of NSCLC by inducing the development of monocytes into anti-inflammatory cells.


Pantsulaia I.,Institute of Medical Biotechnology | Pantsulaia I.,Tbilisi State Medical University | Kalichman L.,Ben - Gurion University of the Negev | Kobyliansky E.,Tel Aviv University
Osteoarthritis and Cartilage | Year: 2010

Objective: The aim of the study was to evaluate the association between prevalence and severity of radiographic hand osteoarthritis (OA) and serum levels of systemic inflammatory markers in a community-based population sample. Design: A cross-sectional observational study was conducted on a population comprised 1452 Chuvashians (763 males, aged 49.23±17.43; and 689 females, aged 50.37±17.47 years). OA was evaluated in 14 joints of each hand using Kellgren and Lawrence (K-L), joint space narrowing (JSN) and osteophyte (OS) scores. Serum levels of systemic inflammatory and osteoclastogenic cytokines were measured by an enzyme-linked immunosorbent assay (ELISA). Statistical analyses included descriptive statistics, correlation analysis and multiple linear regressions. Results: Monocyte chemotactic protein-1 (MCP-1) and osteoprotegerin (OPG) levels were associated with OA traits, but the statistically significant correlations were weak and/or moderate. In particular, the MCP-1 inflammation marker showed a statistically significant association with JSN (β= 0.077, P= 0.022) and OS (β= 0.067, P= 0.024) scores, but not with the number of affected joints (K-L≥2). OPG was significantly correlated with the scores as to the number of affected joints (β= 0.063, P= 0.035) and OS (β= 0.077, P= 0.028). No significant associations were found between levels of other inflammatory [interleukin (IL)-6, tumor necrosis factor (TNF)-α, IL-17] and osteoclastogenic [receptor activator for nuclear factor κ B ligand (RANKL), macrophage colony-stimulating factor (M-CSF)] cytokines and OA characteristics. Conclusions: This study strengthens the premise that OPG might be a valid biomarker of hand OA. Confirmation of these results in larger cohorts of patients will reinforce our theory that the RANKL/OPG pathway is a suitable target for developing novel agents against OA. © 2010.


Kalichman L.,Ben - Gurion University of the Negev | Pantsulaia I.,Institute of Medical Biotechnology | Pantsulaia I.,Tbilisi State Medical University | Kobyliansky E.,Research Unit
Clinical and Experimental Rheumatology | Year: 2011

Background. A recent study showed that the level of soluble Vascular Cell Adhesion Molecule 1 (VCAM-1) emerged as a strong and independent predictor of the risk of hip and knee joint replacement due to severe osteoarthritis (OA). Therefore, we hypothesized that soluble VCAM-1 level can be associated with prevalence and severity of radiographic hand OA. Objective. To evaluate the association between soluble VCAM-1, and radiographic hand OA in a large community-based sample. Methods. The study population comprised Chuvashians (473 males age 45.90±17.16; and 451 females, age 46.18±16.70 years). OA was evaluated for 14 joints of each hand using Kellgren and Lawrence (K-L). OA was characterised by the number of affected joints and by the presence of at least one affected joint. The VCAM-1 level was determined by a sandwich enzyme immunoassay technique using ELISA-OSTEO kit. Statistical analyses included multiple linear and logistic regressions. Results. The linear regression model showed a significant association of a number of affected joints with VCAM-1 level (p=0.004) after adjustment for age, sex, BMI. In the logistic regression model the level of association between the presence of at least one affected joint and soluble VCAM-1 level was p=0.070 (OR(95%CI): 1.003 (1.000, 1.007)). Conclusions. In this cross-sectional population-based study, we found that the serum level of soluble VCAM-1 level is positively associated with the number of affected joints of hand OA. © Copyright Clinical and Experimental Rheumatology 2011.


Lebedev L.R.,Institute of Medical Biotechnology | Danilenko E.D.,Institute of Medical Biotechnology | Telegina Y.V.,Institute of Medical Biotechnology | Zaitsev B.N.,Institute of Medical Biotechnology
Biochemistry (Moscow) Supplement Series B: Biomedical Chemistry | Year: 2016

An osteotropic agent based on the human recombinant tumor necrosis factor alpha (TNF-alpha) has been designed for treatment of bone metastases. It represents a molecular construct containing yeast double- stranded ribonucleic acid (dsRNA) covered by the conjugate of polyanion dextran with TNF-alpha and bisphosphonate alendronic acid. This construct is characterized by the combination of substances possessing antitumor activity (TNF-alpha, dsRNA) and a vector molecule (bisphosphonate) providing tropism to hydroxyapatite, the main mineral component of the bone tissue matrix. The conjugation conditions were optimized and the conjugates of TNF-alpha and alendronic acid with dextran were synthesized. The molecular constructs were obtained by self-assembly, and the resultant complexes were separated by gel filtration on Sepharose CL-6B. The electrophoretic analysis has shown decreased mobility of dsRNA in the complex with the conjugate as compared to mobility of the original dsRNA. This confirms formation of the designed structures. Transmission electron microscopy confirmed the presence of particles with sizes of 30–40 nm in the drug preparation. Evaluation by the sorption/desorption method showed a higher affinity of TNF-alpha conjugates to hydroxyapatite as compared to original TNF-alpha molecules (from 1.0–1.8 mol/L vs. 0.3 mol/L of potassium phosphate buffer for desorption, respectively). © 2016, Pleiades Publishing, Ltd.


Danilenko E.D.,Institute of Medical Biotechnology | Belkina A.O.,Institute of Medical Biotechnology
Russian Journal of Biopharmaceuticals | Year: 2014

In the review experimental data on various strategies for design and study of bisphosphonate-conjugated drugs of different nature to treat bone diseases such as osteoporosis, osteoarthritis, bone metastases and a number of other pathologies of the skeletal system are considered. © 2014 Folium Ltd. All rights reserved.


PubMed | Institute of Medical Biotechnology
Type: Journal Article | Journal: Biomeditsinskaia khimiia | Year: 2015

A novel drug for treatment of bone metastases based on human recombinant tumor necrosis factor (TNF-alpha) has been designed. The drug is a molecular structure containing yeast double-stranded ribonucleic acid (dsRNA) covered by the conjugate of polyanion dextran with TNF-alpha and bisphosphonate, alendronic acid. The structure is characterized by the combination of substances possessing antitumor activity (TNF-alpha, dsRNA) and a vector molecule (bisphosphonate) providing tropism to hydroxyapatite, the main mineral component of the bone tissue matrix. The conjugation conditions were optimized and the conjugates of TNF-alpha and alendronic acid with dextran were synthesized. Molecular structures were obtained by self-assembly, and the resulting complexes were separated by gel filtration on Sepharose CL-6B. The electrophoretic analysis method revealed decreased mobility of dsRNA in the complex with the conjugate as compared to the mobility of the original dsRNA. This confirms formation of the designed structures. Transmission electron microscopy confirmed the presence of particles with sizes of 30-40 nm in the drug. Evaluation by the sorption/desorption method showed a higher affinity of TNF-alpha conjugates to hydroxyapatite as compared to the original TNF-alpha molecules (from 1.0 to 1.8 mol/L vs. 0.3 mol/L of potassium phosphate buffer for desorption, respectively).


PubMed | Institute of Medical Biotechnology
Type: Journal Article | Journal: Bulletin of experimental biology and medicine | Year: 2011

Antitumor activity of TNF- incorporated in nanoparticles (VLP-TNF-) and dynamics of its accumulation and elimination from the blood and tumor tissue were studied in ICR mice. The VLP-TNF- preparation exhibited higher antitumor activity compared to free TNF-, presumably due to longer circulation of the cytokine in the blood and its more intensive accumulation by tumor tissue.

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