[Cell technologies as a basis for the development of regenerative principles for the treatment of lacrimal gland diseases]. / Kletochnye tekhnologii kak osnova razrabotki regeneratornykh printsipov lecheniya zabolevanii sleznoi zhelezy.

The lacrimal gland (LG) is a tubuloacinar exocrine gland composed of acinar, ductal, and myoepithelial cells. Three-dimensional distribution of acinar lobules, ducts, and myoepithelial cells is necessary for the effective functioning of the organ. LG is the main organ of immune surveillance of the ocular surface system. The embryogenesis of the gland is regulated by the interaction of genetic mechanisms, internal epigenetic (enzyme systems, hormones) and exogenous factors. There is no doubt that there is a clear genetic program for the implementation of the complex process of embryonic development. The mechanisms regulating LG organogenesis initiate the work of a huge number of structural oncogenes, transcription and growth factors, etc. Studying the expression and selective activity of regulatory genes during organ development, their participation in the differentiation of different cell types is a current trend at the nexus of clinical genetics, molecular biology, embryology and immunocytochemistry. Due to its relatively simple structure and accessibility, human LG is a suitable object for potential application in regenerative medicine. Development of a universal protocol for obtaining functional differentiated secretory epithelium of LG capable of expressing tissue-specific markers is an urgent task. Determining the nature and origin of stem cells and progenitor cells will allow the isolation and multiplication of these cells in culture. After obtaining a functionally active culture of LG cells, it is possible to create a model of autoimmune diseases.

[The role of miRNA in the pathogenesis of diseases associated with functional dysregulation of the lacrimal gland]. / Rol' mikroRNK v patogeneze zabolevanii, svyazannykh s narusheniem funktsii sleznoi zhelezy.

At this time, the mechanism causing lacrimal gland dysfunction is not understood completely. In diseases associated with lacrimal gland involvement (Sjogren's syndrome, sarcoidosis, IgG4-associated disease, etc.) patients have been observed to experience elevated cellular apoptosis, active production of autoantibodies to glandular tissue, increased level of pro-inflammatory cytokines, functional disruption of signaling molecules leading to changes in tear production. Difficulties in differential diagnosis of lacrimal gland dysfunction in above-listed diseases are associated, on the one hand, with similarity of the clinical picture of ophthalmological manifestations, and on the other hand - with complicated morphological interpretation of changes in the glandular tissues. In this view, miRNA is a promising diagnostic and prognostic marker that would help with differential diagnosis as well as with choosing the treatment tactics. Methods of molecular profiling and identification of "molecular phenotypes" of lacrimal gland and ocular surface damage will allow the use of miRNA as biomarkers and prognostic factors for personalized treatment.

[Evolution of dry eye disease diagnostics]. / Evolyutsiya metodov diagnostiki sindroma sukhogo glaza.

This article reviews modern functional and instrumental examination methods included in the diagnostic algorithm for dry eye disease. The described methods can serve as an objective criterion for the effectiveness of the therapy.

[Predictive significance of genetic analysis of the development of dry eye disease of different origin]. / Prediktivnaya znachimost' geneticheskogo analiza razvitiya sindroma «sukhogo glaza¼ razlichnogo geneza.

One of the etiological causes of dry eye disease (DED) is systemic autoimmune diseases (AID): primary Sjögren's syndrome (PSS), rheumatoid arthritis (RA); their manifestation may begin with ophthalmic symptoms. The relationship of PSS and RA with genetic factors is proven. The contribution of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22 in the development of these diseases is established, as well as their connection with the development of DED. A panel of genetic markers for evaluating the risk of developing DED in PSS and RA is developed, and its sensitivity and specificity is determined. PURPOSE: The aim of the study was to determine the prognostic significance of a panel of polymorphic gene markers in the development of dry eye syndrome in patients with primary Sjögren's syndrome and rheumatoid arthritis over a five-year follow-up period. MATERIAL AND METHODS: Patients with a verified diagnosis of PSS and RA without signs of DED were examined (n=35 and n=42, respectively). The control group included 82 volunteers without AID and DED. The observation period was 5 years. Every year all study subjects underwent an ophthalmological clinical and functional examination. RESULTS: Dry eye disease had developed in groups of patients with AID with predisposing genotypes of polymorphic markers of the genes THBS1, MUC1, TRIM21, STAT4, PTPN22. The peak of DED development in these patients was in the third year of the follow-up. As a result of ROC analysis, it was found that the sensitivity and specificity of determining the predisposing genotypes of polymorphic markers of the THBS1, MUC1, TRIM21, STAT4, PTPN22 genes was 68 and 87%, respectively (p<0.0001). CONCLUSION: Genetic research methods are essential for minimally invasive early diagnosis of dry eye disease, and can subsequently become the basis for a personalized approach to its treatment.

[Association of polymorphic markers rs7947461 of the TRIM21 gene and rs33996649 of the PTPN22 gene with the risk of developing exogenous dry eye syndrome]. / Assotsiatsiya polimorfnykh markerov rs7947461 gena TRIM21 i rs33996649 gena PTPN22 s riskom razvitiya sindroma sukhogo glaza ekzogennoi etiologii.

In this age of technological advancement, an increasing number of people is being exposed to external risk factors of damaging their ocular surface (wearing contact lenses, electromagnetic radiation from computers, mobile devices, etc.). However, the presence of external factors does not lead to a 100% risk of developing the dry eye disease (DED). The trigger mechanism in the development of autoimmune lesions of the ocular environment in some systemic diseases is known to be associated with molecular genetic factors. The search for molecular genetic disorders is based on the analysis of polymorphic markers of a number of genes responsible for the state of the eye surface. PURPOSE: To study the relationship of polymorphic markers rs7947461 of the TRIM21 gene and rs33996649 of the PTPN22 gene with the risk of developing dry eye syndrome of exogenous etiology. MATERIAL AND METHODS: The study included 57 people with exogenous risk factors for DED development. The control group included volunteers without a history of ophthalmic pathologies (n=75). Genotyping was done by real-time polymerase chain reaction followed by melting curve analysis. Statistical processing of data was done using the Statistica 6.1 RUS software for statistical analysis. RESULTS: In the course of the study, 31 patients of the main group were diagnosed with DED and separated into the 1st subgroup; DED diagnosis was not confirmed in 26 patients, who were put into the 2nd subgroup. The 1st subgroup showed a significant increase in the frequency of predisposing genotypes of the TRIM21 and PTPN22 genes. The relative risk of developing DED turned out to be 2.5 and 4.86 times higher, respectively. In the 2nd subgroup, no statistically significant data was found on the presence of predisposing genotypes of polymorphic markers of the TRIM21 and PTPN22 genes (p=0.3). CONCLUSION: The revealed association of polymorphic markers rs7947461 of the TRIM21 gene and rs33996649 of the PTPN22 gene with the risk of developing DED of exogenous etiology puts these loci as possible markers for diagnosing this pathology.

The Role of Polymorphic Markers rs1478604, rs2292305, and rs2228262 in THBS1 Gene in the Development of Autoimmune Dry Eye Syndrome.

An association of polymorphic marker rs2228262 in the THBS1 gene with the risk of developing dry eye in Sjögren syndrome was revealed. Confocal microscopy data suggest that this polymorphic marker is responsible for the high probability of corneal nerve fiber lesion in Sjögren syndrome even in the absence of clinical and functional signs of dry eye syndrome. A significant correlation was established between polymorphic markers rs1478604, rs2228262 in THBS1 gene and the coefficients of anisotropy and orientation symmetry of corneal nerve fibers. These results allow considering these polymorphic markers as a genetic factor of predisposition to dry eye syndrome in patients with Sjögren syndrome.

[Polymorphic markers of certain genes in the development of dry keratoconjunctivitis in patients with rheumatoid arthritis and Sjogren's syndrome]. / Polimorfnye markery nekotorykh genov v razvitii sukhogo keratokon''iunktivita u patsientov s revmatoidnym artritom i sindromom Shegrena.

The article reviews literature on relationships between polymorphic variants of the genes THBS1, GTF2I, MUC1, TRIM21, STAT4, PTPN22 with clinical features of dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome. The development and implementation of a method for analyzing polymorphic gene variants used to diagnose dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's syndrome will allow assessment of the possibility of developing dry keratoconjunctivitis and/or its progression in patients with autoimmune diseases or in people at risk. Determination of clinical and morphological regularities of dry keratoconjunctivitis in accordance with the revealed molecular and genetic changes will contribute to better understanding of the etiology and pathogenesis of ophthalmological manifestations of autoimmune diseases, and will also help improve the diagnostics and prognosis of dry keratoconjunctivitis.

[Association of polymorphisms of the TRIM21 gene with the severity of dry keratoconjunctivitis in rheumatoid arthritis and Sjogren's disease]. / Vzaimosviaz' polimorfizmov gena TRIM21 s tiazhest'iu sukhogo keratokon''iunktivita pri revmatoidnom artrite i bolezni Shegrena.

Ophthalmologic manifestation of Sjogren's disease (SD) and rheumatoid arthritis (RA) is dry keratoconjunctivitis (dry eye disease; DED). PURPOSE: To study the relationship of polymorphic markers rs7947461 (C/T), rs915956 (C/T), rs4144331 (C/A) of the TRIM21 gene with the severity of DED in patients with RA and SD. MATERIAL AND METHODS: The study included 70 patients with RA (n=27) and SD (n=43). The control group consisted of volunteers without a history of RA or SD (n=35). Alleles of the polymorphic marker C660T rs7947461 of the TRIM21 gene were identified using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method; alleles of the polymorphic marker rs915956 (C/T) and rs4144331 (C/A) of the TRIM21 gene were identified by analyzing DNA melting curves. RESULTS: An association was found between the predisposing genotype (TT) of rs7947461 polymorphic marker and the risk of developing severe DED. The AA genotype of rs4144331 polymorphic marker was found only in severe DED (c2=7.74; OR=17.46, CI95%=1.96-318.38, p=0.02). CONCLUSION: An association was established between rs7947461 (rs660) and rs4144331 and the risk of developing severe DED.

[Molecular genetic examination for dry eye syndrome prognosis]. / Molekuliarno-geneticheskie issledovaniia v prognoze techeniia sukhogo keratokon''iunktivita.

The article reviews the results of Russian and foreign studies concerning the search of susceptibility genes for widespread multifactorial diseases: Sjogren's syndrome and rheumatoid arthritis. Studying regularity patterns of genome changes in autoimmune processes with ophthalmic manifestations and their correlation with the severity of dry keratoconjunctivitis will contribute to a better understanding of the etiology and pathogenesis of eye manifestations of the diseases, and will also allow the development of new effective methods of diagnosis and targeted therapy.

3'-Fluoro-2',3'-dideoxyribonucleoside 5'-triphosphates: terminators of DNA synthesis.

It is shown that dNTP(3'F) are terminators of DNA synthesis and may serve as very effective tools for DNA sequencing with E.coli DNA polymerase I and AMV reverse transcriptase. The dNTP(3'F) are found to be chain terminator substrates for calf thymus terminal deoxyribonucleotidyl transferase but not for calf thymus DNA polymerase alpha. The optimal dNTP(3'F) concentration for DNA sequencing by DNA polymerase I is found to be an order of magnitude lower than that of ddNTPs. dNTP(3'F) produce a more clear sequence pattern than do ddNTPs.

[Antiviral activity of 2'-deoxy-2'-fluoroguanosine against influenza and herpes simplex viruses in cultured cells]. / Protivovirusnaia aktivnost' 2'-dezoksi-2'-ftorguanozina v otnoshenii virusov grippa i prostogo gerpesa v kul'turakh kletok.

High antiviral activity of 2'-deoxy-2'fluoroguanosine (2'-D-2'-FG) was observed in chicken embryo cells infected with FPV/Rostock/34 (H7N1) influenza virus and herpes simplex virus (HSV) type I (strain 1C). 50% inhibitory concentration (IC50) of 2'-D-2'-FG was 1.44 microM for FPV and 0.093 microM for HSV. IC50 of remantadine hydrochloride, ribavirin (FPV), and acycloguanosine (HSV) were < 0.46, 14.4, and 0.08 microM, respectively. Anti-HSV activity was confirmed in Vero cells: IC50 < 0.34 microM for 2'-D-2'-FG and IC50 < 0.044 microM for acycloguanosine.

[Regulation of amylolytic complex enzyme biosynthesis in Endomycopsis fibuligera strain 20-9]. / Reguliatsiia biosinteza fermentov amiloliticheskogo kompleksa Endomycopsis fibuligera shtamm 20-9

The effect of glucose and cyclic 3',5'-adenosine monophosphate (cAMP) on the synthesis of glucoamylase and alpha-amylase by the yeast Endomycopsis fibuligera str. 20-9 was investigated. The glucoamylase synthesis was inhibited by every concentration (0.05--3.0%) of glucose. The synthesis of alpha-amylase was significantly reduced by high concentrations (2.0-3.0%) of carbohydrate only. An addition of cAMP (1 X 10(-5) M) reversed compeltely the inhibitory effect of 0.5-2.0% glucose on the alpha-amylase synthesis and partially restored the glucoamylase synthesis. It is concluded that catabolite repression may be involved in the regulation of alpha-amylase and glucoamylase synthesis by Endomycopsis fibuligera str. 20-9 and that this type of regulation shows varying effectiveness in the enzyme synthesis.

[Changes in productivity of plant cells as result of cultivation under the space flight conditions]. / Izmenenie produktivnosti kletok rastenii pri kul'tivirovanii v kosmicheskikh usloviiakh.

Effects of space flight on growth and biosynthetic features of plant cells were studied in two strains of ginseng (Panax ginseng) differing in growth and particularly biosynthetic activities, a strain of Lithospermum Erythrorhizon and a strain of Macrotomia Euchroma which produce biologically active naphroquin-derived pigments. --and also differ in growth and biosynthetic properties. Following exposure aboard MIR and a Space shuttle, cells of the callosal cultures were subjected to callosal or suspension passaging. Biomass yield and biologically active substances--ginseng saponins ginsenoids and shikonin were determined in the cells cultures. There was no evidence for the biomass yield to be significantly altered by space flight; however, the content of biologically active substances was materially changed with the strain.

[Effect of nitrosoguanidine and ultraviolet light on Endomycopsis fibuligera-- producer of glucoamylase]. / Vliianie nitrozoguanidine i ul'trafioleta na Endomycopsis fibuligera--produtsent gliukoamilazy.

The effect of nitrosoguanidine (NG) and ultra-violet light (UV) on the survival and the activity of glucoamylase (GIA) was studied with Endomycopsis fibuligera. Variants which strongly differed from the control cultures in their activity of Gia were sported only by the action of NG, particularly at a concentration of 500 mcg/ml, during 90 min. In this case, about 5 per cent of variants with the activity of GIA being 160-200 per cent of the control value appeared in the population.

Chemical and enzymatic synthesis and antiviral properties of 2'-deoxy-2'-fluoroguanosine.

Chemical and enzymatic methods were employed for the synthesis of the title compound, 2'F-Guo 7. High antiviral activity of 2'F-Guo was established in chick embryo cells infected with influenza virus FPV/Rostock/34 (H7N1) and herpes simplex virus (HSV) type I (1C strain).