Biomimetic sol-gel mineralization of polysaccharides by silicon and titanium polyolates

In this work, we have demonstrated that in addition to silicon tetraglycerolate, a new water-soluble biocompatible polyolate precursors – silicon tetrapolyethylene glycolate Si[O(CH2CH2O)nH]4 [5, 6] and titanium tetrapolyethylene glycolate Ti[O(CH2CH2O)nH]4 [5] – can be successfully utilized in biomimetical mineralization of polysaccharides of various nature. By the example of chitosan (cationic), xanthan gum (anionic), and hydroxyethyl cellulose (uncharged) polysaccharides, an accelerating effect has been demonstrated on the gelation process and a stabilizing effect has been revealed on the hydrogels formed as transparent monoliths showing resistance to syneresis. Thus formed silicon- and titanium-containing 3D-network of gels is found to be polymeric and appears to have ordered amorphous morphostructure, which can be explained as caused by the influence from the polysaccharides serving as templates. The presence of polyolate bridges between silicon or titanium atoms in the polymeric network is characteristic of polyolate precursors only and is determined mainly by the nature of the precursor and by the contents of polyol and water in the system. The formation of polyolate bridges is facilitated by the low reactivity of the precursor, by low water content, and also by polyol excess in the system. The sol-gel process utilized to obtain the silicon- and titanium-polysaccharide-containing hydrogels proceeds under the mild conditions at room temperature, with no catalyst or any organic solved to be used, and thus can be regarded as belonging to the green chemistry methods that show promise for biomedical materials applications.This work was carried out in the framework of the Russian State Assignment (theme № АААА-А19-119011790134-1)

Analysis of the features of educational motivation of undergraduate students of the faculty of dentistry of USMU

The aim of the study - analysis of the features of educational motivation of junior students in teaching therapeutic dentistry.Цель исследования – анализ особенностей учебной мотивации студентов младших курсов при обучении терапевтической стоматологии

Clinical-laboratory analysis of effectiveness of application of anti-inflammatory toothpastes in gingivitis patients

Successful conservative periodontal therapy of patients with periodontal inflammation assumes constant supporting treatment which involves patient’s ability to maintain satisfactory oral hygiene and personal commitment to use recommended therapeutic and prophylactic tooth pastes. The article presents clinical laboratory analysis of effects of modern tooth pastes (TP) on tooth tissue, periodontium and oral mucosa. Clinical effectiveness of Parodontax Ultra Clean and Рarodontax Complete Protection is assessed for patients with gingivitis. Examination is carried out in 60 patients, three groups are formed. The joint research conducted by the Department of Preventive Dentistry and Propedeutics of Dental Disease, the Department of General Chemistry of Ural State Medical University and Department of Control Systems Modeling of Ural State Federal University made it possible to asses and calculate the efficiency of TP based on dynamic indices, parameters of oral condition and mixed saliva of participants along with patients’ survey results before and after the treatment course of TP, thus, proving benefits of each TP.Результативная консервативная пародонтальная терапия у пациентов с воспалительными заболеваниями пародонта предполагает проведение постоянной поддерживающей терапии, заключающейся в умении пациента сохранять удовлетворительное гигиеническое состояние полости рта и личную приверженность в использовании рекомендованных зубных паст с лечебно-профилактическим эффектом. В статье представлен клинико-лабораторный анализ воздействия современных зубных паст (ЗП) на ткани зуба, пародонта и слизистую оболочку полости рта. Выполнена оценка клинической эффективности применения ЗП «Parodontax Ультра Очищение» и «Рarodontax Комплексная Защита» у больных с гингивитом. В исследовании приняли участие 60 пациентов, сформировано три группы. Совместная исследовательская работа кафедры терапевтической стоматологии и пропедевтики стоматологических заболеваний, кафедры общей химии УГМУ и кафедры моделирования управляемых систем УрФУ позволила оценить и рассчитать эффективность применения ЗП на основании динамически изменяющихся индексных оценок, показателей состояния полости рта и смешанной слюны участников, а также результатов анкетирования пациентов до и после курсового применения ЗП, обосновывая таким образом преимущества использования каждой из ни

Tumor Suppressor RASSF1A Promoter: p53 Binding and Methylation

Oncogenes and tumor suppressors work in concert to regulate cell growth or death, which is a pair of antagonist factors for regulation of tumorigenesis. Here we show promoter characteristic of tumor suppressor RASSF1A, which revealed a p53 binding site in the distal and a GC-rich region in the proximal promoter region of RASSF1A, in despite of TATA box-less. The GC-rich region, which is ∼300 bp upstream from the RASSF1A ATG, showed the strongest promoter activity in an assay of RASSF1A-driving GFP expression. Methylation analysis of the CpG island showed that 78.57% of the GC sties were methylated in testis tumor samples compared with methylation-less in normal testis. Hypermethylation of the GC-rich region is associated with RASSF1A silencing in human testis tumors. In addition, electrophoretic mobility shift assay indicated that p53 protein bound to the RASSF1A promoter. Further chromatin immunoprecipitation confirmed p53 binding to the RASSF1A. Moreover, p53 binding to the promoter down-regulated RASSF1A expression. These results suggest that p53 protein specifically binds to the RASSF1A promoter and inhibits its expression. Our results provide new insight into the mechanism of action of tumor suppressors and may be a starting point for development of new approaches to cancer treatment

P53 in human melanoma fails to regulate target genes associated with apoptosis and the cell cycle and may contribute to proliferation

<p>Abstract</p> <p>Background</p> <p>Metastatic melanoma represents a major clinical problem. Its incidence continues to rise in western countries and there are currently no curative treatments. While mutation of the <it>P53 </it>tumour suppressor gene is a common feature of many types of cancer, mutational inactivation of <it>P53 </it>in melanoma is uncommon; however, its function often appears abnormal.</p> <p>Methods</p> <p>In this study whole genome bead arrays were used to examine the transcript expression of P53 target genes in extracts from 82 melanoma metastases and 6 melanoma cell lines, to provide a global assessment of aberrant P53 function. The expression of these genes was also examined in extracts derived from diploid human melanocytes and fibroblasts.</p> <p>Results</p> <p>The results indicated that P53 target transcripts involved in apoptosis were under-expressed in melanoma metastases and melanoma cell lines, while those involved in the cell cycle were over-expressed in melanoma cell lines. There was little difference in the transcript expression of P53 target genes between cell lines with null/mutant <it>P53 </it>compared to those with wild-type <it>P53</it>, suggesting that altered expression in melanoma was not related to <it>P53 </it>status. Similarly, down-regulation of P53 by short-hairpin RNA (shRNA) had limited effect on P53 target gene expression in melanoma cells, whereas there were a large number of P53 target genes whose mRNA expression was significantly altered by P53 inhibition in melanocytes. Analysis of whole genome gene expression profiles indicated that the ability of P53 to regulate genes involved in the cell cycle was significantly reduced in melanoma cells. Moreover, inhibition of P53 in melanocytes induced changes in gene expression profiles that were characteristic of melanoma cells and resulted in increased proliferation. Conversely, knockdown of P53 in melanoma cells resulted in decreased proliferation.</p> <p>Conclusions</p> <p>These results indicate that P53 target genes involved in apoptosis and cell cycle regulation are aberrantly expressed in melanoma and that this aberrant functional activity of P53 may contribute to the proliferation of melanoma.</p

JC Virus Small t Antigen Binds Phosphatase PP2A and Rb Family Proteins and Is Required for Efficient Viral DNA Replication Activity

BACKGROUND: The human polyomavirus, JC virus (JCV) produces five tumor proteins encoded by transcripts alternatively spliced from one precursor messenger RNA. Significant attention has been given to replication and transforming activities of JCV's large tumor antigen (TAg) and three T' proteins, but little is known about small tumor antigen (tAg) functions. Amino-terminal sequences of tAg overlap with those of the other tumor proteins, but the carboxy half of tAg is unique. These latter sequences are the least conserved among the early coding regions of primate polyomaviruses. METHODOLOGY AND FINDINGS: We investigated the ability of wild type and mutant forms of JCV tAg to interact with cellular proteins involved in regulating cell proliferation and survival. The JCV P99A tAg is mutated at a conserved proline, which in the SV40 tAg is required for efficient interaction with protein phosphatase 2A (PP2A), and the C157A mutant tAg is altered at one of two newly recognized LxCxE motifs. Relative to wild type and C157A tAgs, P99A tAg interacts inefficiently with PP2A in vivo. Unlike SV40 tAg, JCV tAg binds to the Rb family of tumor suppressor proteins. Viral DNAs expressing mutant t proteins replicated less efficiently than did the intact JCV genome. A JCV construct incapable of expressing tAg was replication-incompetent, a defect not complemented in trans using a tAg-expressing vector. CONCLUSIONS: JCV tAg possesses unique properties among the polyomavirus small t proteins. It contributes significantly to viral DNA replication in vivo; a tAg null mutant failed to display detectable DNA replication activity, and a tAg substitution mutant, reduced in PP2A binding, was replication-defective. Our observation that JCV tAg binds Rb proteins, indicates all five JCV tumor proteins have the potential to influence cell cycle progression in infected and transformed cells. It remains unclear how these proteins coordinate their unique and overlapping functions