Transferability of the PRS estimates for height and BMI obtained from the European ethnic groups to the Western Russian populations.

Genetic data plays an increasingly important role in modern medicine. Decrease in the cost of sequencing with subsequent increase in imputation accuracy, and the accumulation of large amounts of high-quality genetic data enable the creation of polygenic risk scores (PRSs) to perform genotype-phenotype associations. The accuracy of phenotype prediction primarily depends on the overall trait heritability, Genome-wide association studies cohort size, and the similarity of genetic background between the base and the target cohort. Here we utilized 8,664 high coverage genomic samples collected across Russia by "Evogen", a Russian biomedical company, to evaluate the predictive power of PRSs based on summary statistics established on cohorts of European ancestry for basic phenotypic traits, namely height and BMI. We have demonstrated that the PRSs calculated for selected traits in three distinct Russian populations, recapitulate the predictive power from the original studies. This is evidence that GWAS summary statistics calculated on cohorts of European ancestry are transferable onto at least some ethnic groups in Russia.

Poly(3-hydroxybutyrate)/poly(ethylene glycol) scaffolds with different microstructure: the effect on growth of mesenchymal stem cells.

Development of biocompatible 3D scaffolds is one of the most important challenges in tissue engineering. In this study, we developed polymer scaffolds of different design and microstructure to study cell growth in them. To obtain scaffolds of various microstructure, e.g., size of pores, we used double- and one-stage leaching methods using porogens with selected size of crystals. A composite of poly(3-hydroxybutyrate) (PHB) with poly(ethylene glycol) (PEG) (PHB/PEG) was used as polymer biomaterial for scaffolds. The morphology of scaffolds was analyzed by scanning electron microscopy; the Young modulus of scaffolds was measured by rheometry. The ability to support growth of mesenchymal stem cells (MSCs) in scaffolds was studied using the XTT assay; the phenotype of MSC was preliminarily confirmed by flow cytometry and the activity of alkaline phosphatase and expression level of CD45 marker was studied to test possible MSC osteogenic differentiation. The obtained scaffolds had different microstructure: the scaffolds with uniform pore size of about 125 µm (normal pores) and 45 µm (small pores) and scaffolds with broadly distributed pores size from about 50-100 µm. It was shown that PHB/PEG scaffolds with uniform pores of normal size did not support MSCs growth probably due to their marked spontaneous osteogenic differentiation in these scaffolds, whereas PHB/PEG scaffolds with diverse pore size promoted stem cells growth that was not accompanied by pronounced differentiation. In scaffolds with small pores (about 45 µm), the growth of MSC was the lowest and cell growth suppression was only partially related to stem cells differentiation. Thus, apparently, the broadly distributed pore size of PHB/PEG scaffolds promoted MSC growth in them, whereas uniform size of scaffold pores stimulated MSC osteogenic differentiation.

Biosynthesis of poly(3-hydroxybutyrate) copolymers by Azotobacter chroococcum 7B: A precursor feeding strategy.

A precursor feeding strategy for effective biopolymer producer strain Azotobacter chroococcum 7B was used to synthesize various poly(3-hydroxybutyrate) (PHB) copolymers. We performed experiments on biosynthesis of PHB copolymers by A. chroococcum 7B using various precursors: sucrose as the primary carbon source, various carboxylic acids and ethylene glycol (EG) derivatives [diethylene glycol (DEG), triethylene glycol (TEG), poly(ethylene glycol) (PEG) 300, PEG 400, PEG 1000] as additional carbon sources. We analyzed strain growth parameters including biomass and polymer yields as well as molecular weight and monomer composition of produced copolymers. We demonstrated that A. chroococcum 7B was able to synthesize copolymers using carboxylic acids with the length less than linear 6C, including poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) (PHB-4MHV) using Y-shaped 6C 3-methylvaleric acid as precursor as well as EG-containing copolymers: PHB-DEG, PHB-TEG, PHB-PEG, and PHB-HV-PEG copolymers using short-chain PEGs (with n ≤ 9) as precursors. It was shown that use of the additional carbon sources caused inhibition of cell growth, decrease in polymer yields, fall in polymer molecular weight, decrease in 3-hydroxyvalerate content in produced PHB-HV-PEG copolymer, and change in bacterial cells morphology that were depended on the nature of the precursors (carboxylic acids or EG derivatives) and the timing of its addition to the growth medium.

Biosynthesis of poly(3-hydroxybutyrateco-3-hydroxy-4-methylvalerate) by Strain Azotobacter chroococcum 7B.

Production of novel polyhydroxyalkanoates (PHAs), biodegradable polymers for biomedical applications, and biomaterials based on them is a promising trend in modern bioengineering. We studied the ability of an effective strain-producer Azotobacter chroococcum 7B to synthesize not only poly(3-hydroxybutyrate) homopolymer (PHB) and its main copolymer poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV), but also a novel copolymer, poly(3-hydroxybutyrate-co-3-hydroxy-4-methylvalerate) (PHB4MV). For the biosynthesis of PHB copolymers, we used carboxylic acids as additional carbon sources and monomer precursors in the chain of synthesized copolymers. The main parameters of these polymers' biosynthesis were determined: strain-producer biomass yield, polymer yield, molecular weight and monomer composition of the synthesized polymers, as well as the morphology of A. chroococcum 7B bacterial cells. The physico-chemical properties of the polymers were studied using nuclear magnetic resonance spectroscopy (NMR), differential scanning calorimetry (DSC), contact angle test, and other methods. In vitro biocompatibility of the obtained polymers was investigated using stromal cells isolated from the bone marrow of rats with the XTT cell viability test. The synthesis of the novel copolymer PHB4MV and its chemical composition were demonstrated by NMR spectroscopy: the addition of 4-methylvaleric acid to the culture medium resulted in incorporation of 3-hydroxy-4-methylvalerate (3H4MV) monomers into the PHB polymer chain (0.6 mol%). Despite the low molar content of 3H4MV in the obtained copolymer, its physico-chemical properties were significantly different from those of the PHB homopolymer: it has lower crystallinity and a higher contact angle, i.e. the physico-chemical properties of the PHB4MV copolymer containing only 0.6 mol% of 3H4MV corresponded to a PHBV copolymer with a molar content ranging from 2.5% to 7.8%. In vitro biocompatibility of the obtained PHB4MV copolymer, measured in the XTT test, was not statistically different from the cell growth of PHB and PHBV polymers, which make its use possible in biomedical research and development.

[Abnormal expression of genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer].

Retinoids are signaling molecules that control a wide variety of cellular processes and possess antitumor activity. This work presents a comprehensive description of changes in the expression of 23 genes that regulate retinoid metabolism and signaling in non-small-cell lung cancer tumors compared to adjacent normal tissues obtained using RT-PCR. Even at early stages of malignant transformation, a significant decrease in ADH1B, ADH3, RDHL, and RALDH1 mRNA levels was observed in 82, 79, 73, and 64% of tumor specimens, respectively, and a considerable increase in AKR1B10 mRNA content was observed in 80% of tumors. Dramatic changes in the levels of these mRNAs can impair the synthesis of all-trans retinoic acid, a key natural regulatory retinoid. Apart from that, it was found that mRNA levels of nuclear retinoid receptor genes RXRγ, RARα, RXRα, and gene RDH11 were significantly decreased in 80, 67, 57, and 66% of tumor specimens, respectively. Thus, neoplastic transformation of lung tissue cells is accompanied with deregulated expression of key genes of retinoid metabolism and function.

[MALDI-TOF mass spectrometric identification of novel intercellular space peptides].

We performed the matrix-assisted laser desorption/ionisation, time-of-flight mass spectrometry (MALDI-TOF) analysis of the peptides entering into the composition of not yet explored bioregulators derived from the extracellular matrix of the tissues of the various organs of the mammals, and also plants and fungi. The study included 15 different mammalian tissues, 13 species of plants, and 2 species of fungi. Exploring the bioregulators derived from eye tissues, we demonstrated that their composition includes peptide components with the same values of the molecular weight. The composition of the bioregulators derived from the tissues of various organs of mammals or different species of plants and fungi includes the peptides with different values of molecular weight. Obtained data indicate the growing evidence of the assumptions about the major function of the bioregulators of this group--their involvement in the regulation of tissue-organ homeostasis in the biological systems.

Structural-functional characteristics of a new bioregulator isolated from bovine pigmented epithelium tissue.

A new bioregulator operating in ultralow doses corresponding to 10(-17) mg/ml has been isolated from tissue of pigmented epithelium of bovine eyes. It has been established that the functional basis of this bioregulator is a complex of a low molecular weight regulatory peptide (4372 Da) and a modulator consisting of a mixture of proteins with molecular weights of 14.980-66.283 kDa. It has been shown that the regulatory peptide is responsible for membranotropic activity of the bioregulator, and the modulator proteins are responsible for biological action in ultralow doses. The data demonstrate an interrelation between nanocondition of the bioregulator and its ability to show activity in ultralow doses.

[Electric impulse therapy of hypertensive patients].

Patients with mild arterial hypertension and hypersympathicotonia treated with electroimpulse therapy improved their clinicofunctional state, blood pressure (especially systolic pressure), its variability, sympathic activity, central regulation of cardiac rhythm, capillary reserves.

[Clinical polymorphism of autoimmune polyglandular syndrome of type 1. Role of molecular genetic diagnosis].

Autoimmune polyglandular syndrome type 1 (APS-1) is a rare monogenous disease with autosomal-recessive inheritance. The gene responsible for the development of this disease is designated as the gene AIRE and encodes for the protein autoimmune regulator whose function is unknown. The disease more frequently manifests itself in childhood. Its typical manifestations are chronic cutaneous and mucous candidiasis, hypoparathyroidism, and chronic adrenal insufficiency. The presence of 2 of these signs gives ground to establish its clinical diagnosis. However, the clinical manifestations of this disease are highly polymorphic. Thirty-nine patients with the established diagnosis of APS-1 were followed up. There was a high frequency of R2S7X mutation in the gene AIRE. Its clinical picture is untypical in 26% of cases despite the presence of the identical R257X mutation. The molecular genetic diagnosis permits diagnosis of untypical cases of APS-1.

[Clinical variants of McCune-Albright-Braitsev syndrome in girls]. / Klinicheskie varianty sindroma Mak-K'iuna-Olbraita-Braitseva u devochek.

The authors analyze published data on clinical variants and hormonal parameters in patients with this syndrome and present their own observations of children with this condition. Besides early sexual maturation, they describe the clinical picture of Cushing's syndrome, thyroid nodular hyperplasia. The said disorders do not depend on the tropic effect of the hypothalamohypophyseal system. A hypothesis is put forward about primary activation of adenylate cyclase system in the origin of the disease.

[The enzyme activity and cationic proteins in the blood cells in the modelling of tourniquet shock in rats]. / Aktivnost' fermentov i kationnye belki v kletkakh krovi pri modelirovanii turniketnogo shoka u krys.

The activity of red cell enzymes and the cationic protein content in the granulocytes were studied in different periods of tourniquet shock. The activity of lactic dehydrogenase and glucose-6-phosphate dehydrogenase reduced 3-6 hours after removal of the tourniquet; the activity of glutathione reductase did not change. The value of the lysosomal-cationic test diminished 6 hours after application of the tourniquet and increased 2 hours after its removal. The results of the study allow the lysosomal-cationic test to be recommended for determining the unspecific resistance in shock.

[Insulinomas in children (characteristics of clinical picture and surgical treatment)]. / Insulinomy u detei (osobennosti kliniki i khirurgicheskogo lecheniia).

The paper treats of the main characteristics of the clinical picture and diagnosis of insulinoma in children as compared to adults. Seven children were operated on for insulinomas at the Surgery Department of the All-Union Research Endocrinology Center of the USSR AMS. The clinical course of insulinomas in children was characterized by a short-term disease history, the lack of overweight, and the convulsive syndrome as the leading symptom of hypoglycemia. As to the diagnostic tests, the fasting test appeared not desirable in the majority of children because of the low blood content of glucose in the morning hours and development of a marked hypoglycemic attack. Examination of immunoreactive insulin was not so indicative as in adults. During convulsions, electroencephalography in children was not feasible. Visceral arteriography turned out a reliable method of topical diagnosis of insulinoma in children. Tumor was most frequently located in the tail of the pancreas. The postoperative period in children ran a more favourable course than in adults. No clinical signs of pancreatitis were recorded. According to follow-up studies, the patients did not show any clinical or biochemical signs of hypoglycemia. Histological examination demonstrated that children had mainly neoplasms from beta-cells of islets of Langerhans. It is suggested that children have very low power to adjust themselves to acute and chronic hypoglycemia as compared to adults.

[Current aspects of the diagnosis and treatment in congenital dysfunction of the adrenal cortex in children]. / Sovremennye aspekty diagnostiki i lecheniia vrozhdennoi disfunktsii kory nadpochechnikov u detei.

The paper treats of current diagnostic criteria for congenital dysfunction of the adrenal cortex in children. They include investigation of HLA-antigens, identification of heterozygote and homozygote carriership, prenatal diagnosis of the disease, and the screening tests. The leading position in the disease diagnosis is assigned to its clinical manifestations, measurement of 17-hydroxyprogesterone and testosterone in blood serum together with excretion of 17-ketosteroids with urine. Emphasis is laid on the importance of early disease diagnosis and establishment of sex appurtenance, which is promoted by studies of sex chromatin, karyotype and ultrasonic scanning of the internal genitalia. The treatment policy for patients with congenital dysfunction of the adrenal cortex has been elaborated as have been its aspects: hormonal, surgical and psychotherapeutic. The treatment protocols using current hormonal drugs with changes in conventional time of their intake are described in detail. The long-term results of hormonal therapy are provided on the basis of large clinical material (over 500 patients with congenital dysfunction of the adrenal cortex were examined).

[Corticosteroid and ACTH levels in relation to the age and sex of children with congenital adrenocortical dysfunction]. / Zavisimost' sederzhaniia kortikosteroidov i AKTG ot vozrasta i pola u detei s vrozhdennoi disfunktsiei kory nadpochechnikov.

The authors studied adrenal and corticotropic functions of the pituitary in 98 children with congenital adrenal dysfunction and in 41 normal children. The children's age ranged from 2 to 16 years. The bone age of the sick children ranged within 6 to 16 years. The content of hydrocortisone and ACTH in the sick children was shown to be within the age norm. This attests to the preservation in these children of the functional potentialities of the adrenals and pituitary. It was emphasized that high content of 11-deoxycortisol in untreated patients decreased in the course of treatment. Therefore, the level of 11-deoxycortisol may serve as criterion of the adequacy of the hormonal therapy received by the patients.