Vitamin D binding protein polymorphysm in patients with acute coronary syndrome in kaliningrad region

BACKGROUND: Vitamin D binding protein is a main vitamin D carrier in serum. It also has an impact on macrophagial function. Role of vitamin D and macrophages in the pathogenesis of atherosclerosis is scientifically proven but there is lack of data on vitamin D binding protein in this regard. AIMS: To evaluate the vitamin D binding protein polymorphism in patients with acute coronary syndrome without diabetes mellitus, autoimmune diseases and malignant tumors. Determine correlation, if there is, between vitamin D binding protein allele and features of acute coronary syndrome among this patient group. MATERIALS AND METHODS: It is a cross-sectional observational study. Study subjects are patients with acute coronary syndrome. Exclusion criteria are the presence of diabetes mellitus, autoimmune diseases and malignant tumors. In all participants were evaluated: predisposing factors for heart diseases, CBC, biochemical blood test, troponin, coronarography, echocardiography. The study lasted for 5 months from November 2017 until March 2018. Primary end point – assessment of vitamin D binding protein polymorphysm in this group of patients with acute coronary syndrome by means of vitamin D binding protein gene sequencing. 50 patients were enrolled into this study who were urgently admitted to hospital and diagnosed with acute coronary syndrome. Among them – 36 males and 14 females. Mean age was 60 (55;66) years. All participants were sequenced for single nucleotide polymorphysm in VDBP p.T436K (rs4588) and P.432E (rs7041). RESULTS: Gene polymorphysms of interest were found in 43 patients among 50 enrolled. Haplotype Gc1s/2 (rs7041G-rs4588A) was found in 7 (14%) patients, Gc2 (rs7041T-rs4588A) — in 9 (18%) patients, Gc1s (rs7041G-rs4588C) – in 20 (40%) patients, Gc1f (rs7041T-rs4588C) in 14 (28%). Coronarography showed that coronary artery occlusions obstructing more than 50% of vessel lumen was found in 16 patients; obstruction greater than 90% was seen in 8 patients; total occlusion – in 4 patients. CONCLUSIONS: In patient group with acute coronary syndrome prevalence of vitamin D binding protein gene polymorphysm was high – in 86% of participants. The features of Gc2 haplotype were higher frequency of recurrent myocardial infarction and total coronary artery occlusion, as well as tendency to decreased serum vitamin D3 (25(OH)D) levels

The role of Leu260Phe polymorphism of the receptor gene to GLP-1 incretin in the pathogenesis of diabetes type 2 diabetes with obesity

BACKGROUND: Glucagon-like peptide-1 (GLP-1) stimulates the proliferation of β-cells, enhances their resistance to apoptosis and increases glucose-dependent insulin secretion. AIMS: Study of the relationship of Leu260Phe polymorphism (rs1042044) of the GLP-1R gene with postprandial hormone production (C-peptide, insulin, ghrelin, GLP-1) in obese patients with type 2 diabetes. MATERIALS AND METHODS: A total of 174 patients, 82 patients with obesity with type 2 diabetes (BMI=40.4±14.3 kg/m2)and 92 conditionally healthy donors (BMI=22.6±2.7 kg/m2) were studied. The material for the study was venous blood taken on an empty stomach and 60 minutes after the test breakfast. Genotyping was performed by PCR using the sets for determining polymorphism (rs1042044) of the GLP-1R gene (Sintol) and the amplificator (CFX96 BioRad, USA). Plasma hormone levels were evaluated by flow fluorimetry (Bio-PlexProteinAssaySystem, Bio-Rad, USA) using commercial test systems (Bio-PlexProHumanDiabetes 10-Plex Assay, Bio-Rad, USA). Statistical analysis and graphs were obtained at R Statistical Software. RESULTS: A violation of postprandial production of GLP-1 and ghrelin after a test breakfast in obese patients with type 2 diabetes was found. A postprandial increase in C-peptide levels of 3.25[1.83;4.16] ng/ml and insulin 3048 [1978;4972] ng/ml in carriers of the CC genotype compared with carriers of the CA genotype in the group of patients with obesity with type 2 diabetes type In carriers of the CA genotype, there was a decrease in the C-peptide level of 2.21 [1.8;2.49] ng/ml and insulin 1462 [1146; 2304] ng/ml with a constant concentration of GLP-1. The postprandial level of ghrelin in carriers of the CA genotype of the Leu260Phe polymorphism increased to 118[96.1;157] ng/ml compared to carriers of the AA 98 genotype [86; 109] ng/ml. CONCLUSION: The presence of the CC genotype of the Leu260Phe polymorphism of the GLP-1 receptor gene is associated with an increase in postprandial plasma levels of C-peptide and insulin in obese patients with type 2 diabetes, and the CA genotype with a decrease in these indicators and an increase in ghrelin content

Pathogenetic significance of single nucleotide polymorphisms in the gastric inhibitory polypeptide receptor gene for the development of carbohydrate metabolism disorders in obesity

Aim. To investigate the association of the GIPR gene polymorphisms rs2302382 and rs8111428 with increased risk of type 2 diabetes mellitus and abdominal obesity. Materials and methods. The study involved 163 patients with abdominal obesity (BMI, 39.5 ± 8.3 kg/m2; age, 44.7 ± 8.9 years; men, 61; women, 102), 72 with type 2 diabetes mellitus (BMI, 43.70 ± 9.32 kg/m2; age, 46.5 ± 10.1 years; men, 29; women, 43) and 91 patients without carbohydrate metabolism disorders (BMI, 36.13 ± 6.72 kg/m2; age, 43.93 ± 8.35 years; men, 32; women 59). The control group comprised 109 relatively healthy volunteers (BMI, 22.6 ± 2.7 kg/m2; age, 39.5 ± 7.6 years; men, 66; women, 43). Genotypes were analysed by real-time PCR and serum insulin and C-peptide levels were evaluated by ELISA. Results. The AA genotype in the rs2302382 polymorphism of GIPR was associated with an increased risk for type 2 diabetes mellitus in abdominal obesity and the CA genotype was associated with a reduced risk. In individuals with abdominal obesity and type 2 diabetes mellitus carrying the CA genotype in rs2302382 polymorphism of GIPR, serum insulin and C-peptide levels were elevated to 56.27 mU/L (55.49–58.41 mU/L) and 2.04 ng/ml (1.37–2.85 ng/ml), respectively (p 0.05). In obese patients with the same genotype and without type 2 diabetes, serum insulin levels and C-peptide levels were 22.73 mU/L (19.07–25.76 mU/L) and 0.73 ng/ml (0.53–1.03 ng/ml), respectively (p 0.05). The GIPR rs8111428 polymorphism was not associated with increased risk of type 2 diabetes mellitus in obesity for any of the groups examined. Conclusion. Serum insulin and C-peptide levels were increased in patients with abdominal obesity who were carriers of the CA genotype in the rs2302382 polymorphism of GIPR, which is associated with a decreased risk of type 2 diabetes mellitus in obesity compared with the CC genotype

The study of galectin-3, Ki-67, ubiquitin, HMGA-2 by polymerase chain reaction in real time (RT-PCR) in the puncture specimens of nodular goiter

Actuality. The differential diagnosis of follicular adenoma, follicular variant of papillary thyroid cancer and follicular thyroid cancer (TC) is one of the main topics of research. For this purpose several molecular markers were approbated, however their diagnostic effectiveness differs. Aim. Quantification of candidate mRNA markers for differentiated thyroid cancer (galectin-3, Ki-67, ubiquitin, HMGA2) using polymerase chain reaction in real time (RT-PCR) of thyroid nodules pre-operative material. To evaluate the efficiency of this method for thyroid malignancy diagnostics. Materials and methods. The study included 55 patients with a clinical diagnosis of nodular / multinodular goiter. A quantitative analysis of mRNA of galectin-3, Ki-67, ubiquitin, HMGA2 was performed on material puncture by reverse transcription and RT-PCR. The Second Derivative Maximum Method was used to analyze the results. Results. The study included 46 women (83.6%) and 8 men (14.5%). The average age of the patients was 52.1 (from 23 to 82) years old. According to the results of histological examination, there were 35 (63.6%) benign tumors, 20 (36.4%) – cancer tumors (papillary carcinoma). There were no cases of follicular cancer in the histological findings. We found significant differences in the expression of mRNA of the ubiquitin gene between malignant and benign thyroid nodules. Conclusion. The method of ubiquitin gene 8.24 mRNA estimation has a sensitivity of 68.4% and a specificity of 68.6% in the well-differentiated cancer diagnostics. The estimation of mRNA of gene Ki-67, galectin-3, HMGA by RT-PCR did not show itself as a reliable method for the differential diagnosis of thyroid nodules in the preoperative stage

Synthesis and photophysical properties of copolyfluorenes for light-emitting applications: Spectroscopic experimental study and theoretical DFT consideration

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Comparative Analysis of Biological Properties of Large-Scale Expanded Adult Neural Crest-Derived Stem Cells Isolated from Human Hair Follicle and Skin Dermis

Introduction. The adult neural crest-derived stem cells (NCSCs) have significant perspectives for use in regenerative medicine. The most attractive sources for adult NCSC isolation are the hair follicles (HF) and skin dermis (SD) because of easy access and minimally invasive biopsy. The aim of this study was to compare the biological properties of HF- and SD-derived NCSCs after their large-scale expansion. Methods. The conventional explant method was used to obtain HF NCSCs. For the isolation of SD NCSCs, a new combined technique consisting of preplating and subsequent culturing in 3D blood plasma-derived fibrin hydrogel was applied. The studied cells were characterized by flow cytometry, ICC, qPCR, Bio-Plex multiplex assay, and directed multilineage differentiation assays. Results. We have obtained both adult SD and HF NCSCs from each skin sample (n=5). Adult SD and HF NCSCs were positive for key neural crest markers: SOX10, P75 (CD271), NESTIN, SOX2, and CD349. SD NCSCs showed a higher growth rate during the large-scale expansion compared to HF NCSCs (p<0.01). Final population of SD NCSCs also contained more clonogenic cells (p<0.01) and SOX10+, CD271+, CD105+, CD140a+, CD146+, CD349+ cells (p<0.01). Both HF and SD NCSCs had similar gene expression profiling and produced growth factors, but some quantitative differences were detected. Adult HF and SD NCSCs were able to undergo directed differentiation into neurons, Schwann cells, adipocytes, and osteoblasts. Conclusion. The HF and SD are suitable sources for large-scale manufacturing of adult NCSCs with similar biological properties. We demonstrated that the NCSC population from SD was homogenous and displayed significantly higher growth rate than HF NCSCs. Moreover, SD NCSC isolation is cheaper, easier, and minimally time-consuming method

Calcium Phosphate Coating Prepared by Microarc Oxidation Affects hTERT Expression, Molecular Presentation, and Cytokine Secretion in Tumor-Derived Jurkat T Cells

Calcium phosphate (CaP) materials are among the best bone graft substitutes, but their use in the repair of damaged bone in tumor patients is still unclear. The human Jurkat T lymphoblast leukemia-derived cell line (Jurkat T cells) was exposed in vitro to a titanium (Ti) substrate (10 &times; 10 &times; 1 mm3) with a bilateral rough (average roughness index (Ra) = 2&ndash;5 &mu;m) CaP coating applied via the microarc oxidation (MAO) technique, and the morphofunctional response of the cells was studied. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and energy dispersive X-ray spectroscope (EDX) analyses showed voltage-dependent (150&ndash;300 V) growth of structural (Ra index, mass, and thickness) and morphological surface and volume elements, a low Ca/PaT ratio (0.3&ndash;0.6), and the appearance of crystalline phases of CaHPO4 (monetite) and &beta;-Ca2P2O7 (calcium pyrophosphate). Cell and molecular reactions in 2-day and 14-day cultures differed strongly and correlated with the Ra values. There was significant upregulation of hTERT expression (1.7-fold), IL-17 secretion, the presentation of the activation antigens CD25 (by 2.7%) and CD95 (by 5.15%) on CD4+ cells, and 1.5&ndash;2-fold increased cell apoptosis and necrosis after two days of culture. Hyperactivation-dependent death of CD4+ cells triggered by the surface roughness of the CaP coating was proposed. Conversely, a 3.2-fold downregulation in hTERT expression increased the percentages of CD4+ cells and their CD95+ subset (by 15.5% and 22.9%, respectively) and inhibited the secretion of 17 of 27 test cytokines/chemokines without a reduction in Jurkat T cell survival after 14 days of coculture. Thereafter, cell hypoergy and the selection of an hTERT-independent viable CD4+ subset of tumor cells were proposed. The possible role of negative zeta potentials and Ca2+ as effectors of CaP roughness was discussed. The continuous (2&ndash;14 days) 1.5&ndash;6-fold reductions in the secretion of vascular endothelial growth factor (VEGF) by tumor cells correlated with the Ra values of microarc CaP-coated Ti substrates seems to limit surgical stress-induced metastasis of lymphoid malignancies

Zn- or Cu-containing CaP-Based Coatings Formed by Micro-Arc Oxidation on Titanium and Ti-40Nb Alloy: Part II—Wettability and Biological Performance

This work describes the wettability and biological performance of Zn- and Cu-containing CaP-based coatings prepared by micro-arc oxidation on pure titanium (Ti) and novel Ti-40Nb alloy. Good hydrophilic properties of all the coatings were demonstrated by the low contact angles with liquids, not exceeding 45&deg;. An increase in the applied voltage led to an increase of the coating roughness and porosity, thereby reducing the contact angles to 6&deg; with water and to 17&deg; with glycerol. The free surface energy of 75 &plusmn; 3 mJ/m2 for all the coatings were determined. Polar component was calculated as the main component of surface energy, caused by the presence of strong polar PO43&minus; and OH&minus; bonds. In vitro studies showed that low Cu and Zn amounts (~0.4 at.%) in the coatings promoted high motility of human adipose-derived multipotent mesenchymal stromal cells (hAMMSC) on the implant/cell interface and subsequent cell ability to differentiate into osteoblasts. In vivo study demonstrated 100% ectopic bone formation only on the surface of the CaP coating on Ti. The Zn- and Cu-containing CaP coatings on both substrates and the CaP coating on the Ti-40Nb alloy slightly decreased the incidence of ectopic osteogenesis down to 67%. The MAO coatings showed antibacterial efficacy against Staphylococcus aureus and can be arranged as follows: Zn-CaP/Ti &gt; Cu-CaP/TiNb, Zn-CaP/TiNb &gt; Cu-CaP/Ti

Synthesis, Photo- and Electroluminescence of New Polyfluorene Copolymers Containing Dicyanostilbene and 9,10-Dicyanophenanthrene in the Main Chain

Using palladium-catalyzed Suzuki polycondensation, we synthesized new light-emitting fluorene copolymers containing the dicyano derivatives of stilbene and phenanthrene and characterized them by gel permeation chromatography, UV-vis absorption spectroscopy, spectrofluorimetry, and cyclic voltammetry. The photoluminescence spectra of the synthesized polymers show significant energy transfer from the fluorene segments to the dicyanostilbene and 9,10-dicyanophenanthrene units, which is in agreement with the data of theoretical calculations. OLEDs based on these polymers were fabricated with an ITO/PEDOT-PSS (35 nm)/p-TPD (30 nm)/PVK (5 nm)/light emitting layer (70–75 nm)/PF-PO (20 nm)/LiF (1 nm)/Al (80 nm) configuration. Examination of their electroluminescence revealed that copolymers of fluorene with dicyanostilbene show yellow-green luminescence, while polymers with 9,10-dicyanophenanthrene have a greenish-blue emission. The 9,10-dicyanophenanthrene units have a more rigid structure compared to dicyanostilbene and, in OLEDs based on them, an increase in maximum brightness is observed with an increase in the content of the additive to the polymer chain. In particular, the device using fluorene copolymer with 9,10-dicyanophenanthrene (2.5 mol%) exhibited a maximum brightness of 9230 cd/m2 and a maximum current efficiency of 3.33 cd/A