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Introduction@#When human body encounters external pathogens primary/innate immunity cells are activated by recognizing them and secondary/adaptive immunity is activated consecutively. In our previous study, we revealed that there is a synergistic action between TLR9 and IFN-γ signaling in the endothelial cells. @*Purpose@#To determine the role of negative and positive regulator proteins on the IFN-γ/TLR9 signaling pathway. @*Methods@#In this study, murine endothelial cell (END-D) culture was used. END-D cells pre-treated with TLR9 ligand CpG DNA and then stimulated with IFN-γ. The negative (SHP-2, SOCS1, PIAS1) and positive (p38) regulator protein expression was detected by Western blotting. @*Results and Conclusion@#Treatment by TLR9 ligand CpG DNA and IFN-γ increased positive regulator p38 phosphorylation in 0.5 hour. CpG DNA inhibited IFN-γ negative regulator PIAS1 protein expression in 6 hour and SOCS1 and SHP-2 expression could not affect in 4 hour.
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Introduction@#Toll like receptors (TLRs) are a class of proteins that key role in the innate immune system. The SOCS1 and SHP2 proteins are negative-feed loop inhibitors of signaling of JAK/STAT and TLRs pathways.@*Purpose@#To determine negative regulator protein activation which is activated through TLR7 ligand/IFN-γ signal transduction in endothelial cells. @*Methods@#We used mouse aortic linear endothelial cell (END-D); protein expressio was detected by western blotting @*Results@#We analyzed a time dependent stimulation effects of negative regulator proteins stimulated by TLR7 ligand/IFN-γ in endothelial cell cultures. Imiquimod of 10 μg/ml treatment of 1 hr was followed by 100 ng/ml IFN-γ stimulation for 1-8hr to analysis of negative regulator SOCS1 and SHP2 protein expression. </br> In untreated cells, there was low activations of negative regulator SOCS1 and SHP2 proteins. IFN-γ stimulation alone had increased SOCS1 and SHP2 protein expressions, also imiquimod treatment highly <i>elevated</i> SOCS1 and SHP2 expressions. However imiquimod and IFN-γ doubled treatment have decreased activation of negative regulator SOCS1 and SHP2 proteins. These findings suggest SOCS1 and SHP2 proteins are inhibitors in the TLR7 ligand/IFN-γ signaling. @*Conclusion@#Negative regulators, SOCS1 and SHP2 strongly suppressed activations of TLR7 ligand/IFN-γ signaling
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Introduction@#The aim of this research project is to elucidate the crosstalk of innate and adaptive immune reactions against the DNA containing bacteria.@*@#This study held in the Core laboratory, Science Technology Center, Mongolian National University of Medical Sciences (MNUMS). Murine aortal endothelial cells, END-D cultured and the cell viability checked by MTT assay. In addition, the NO production, protein and gene expression studied by Griess Reagent assay, R.T-PCR and immunoblotting, respectively. @*Results@#0.1µM, 1µM and 10µM of TLR9 ligand exhibited no cytotoxic action against the cells by MTT assay. IFN-ү alone induced NO production in END-D cells. In the other hand, TLR9 ligand at 0.1µM, 1µM and 10µM up-regulated IFN-ү induced NO production in dose dependent manner. RTPCR results exhibit that TLR9 ligand up regulates iNOS mRNA. Immunoblotting analysis showed the enhanced iNOS protein expression and phosphorylation of STAT1 in cells pre-treated with TLR9 ligand.@*Discussion@#We have demonstrated CpG DNA, TLR9 ligand, up-regulates IFN-ү induced NO via enhanced IFN-ү signaling. The result of Western Blotting and RT-PCR support the up-regulation of NO. CpG DNA can be used as agent against virus and bacteria. Further research need to be conducted. @*Conclusion@#TLR9 ligand, CpG DNA up-regulates IFN-ү induced NO production in time and dose dependent manner. TLR9 ligand augments the expression of iNOS mRNA and STAT1 phosphorylation in response to IFN-ү.
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@#BACKGROUND. Sensorineural hearing impairment (SNHI) is the most common inherited sensory defect, affecting about 3 per 1000 children. More than 50% of these patients have a genetic cause (i.e. hereditary hearing impairment; HHI). Mutations in certain genes were noted to be extraordinarily popular in the deaf patients across different populations, making molecular screening feasible for these common deafness genes. One of the most important characteristics that we have learned concerning hereditary hearing loss is that common deafness genes and their mutations are usually different according to the ethnic background. As demonstrated in our previous studies performed in Taiwanese patients, the mutation spectrums of common deafness genes, such as the GJB2 gene and the SLC26A4 gene, are different from those in the Caucasian or even other Asian populations. These findings further underscore the indispensability of the collection of local data in terms of genetic counseling. In the collaborative project, we have successfully established a cohort of >100 hearing-impaired families, and clarified the genetic epidemiology of deafness in the Mongolian population. We identified several special deafness mutations such as GJB2 c.23+1G>A, c.559_604dup, and SLC26A4 c.919-2A>G, and our results revealed that Mongolian patients demonstrate a unique genetic profile in deafness as compared to other East Asian populations (paper in preparation). Meanwhile, by organizing a seminar at National Taiwan University Hospital in March 2017, we have transferred crucial concepts and techniques regarding how to perform genetic testing for deafness to the Mongolian colleagues. In the future, we plan to strengthen the mutual collaboration by expanding the clinical cohort and upgrading the genetic examination platform using the NGS techniques.
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@#BACKGROUND: Toll like receptors (TLRs) are a class of proteins that key role in the innate immune system. TLR7 is expressed on monocytes, macrophages and dendritic cells, T cell, B cell and eosinophiles. TLR7, originally identified as recognizing imidaquinoline, loxibrine, broprimine and ssRNA, ssRNA viruses such as vesicular stomatitis virus, influenza A virus and human immunodefiency virus. It is known that virus ssRNA affects signaling molecule of IFN-y. Objective: To determine gene and protein activation of IFN-y signal transduction by TLR7 ligand in the endothelial cells. MATERIAL: In study we used mouse aortic linear endothelial cell which is cultured (END-D) in 5% heat- inactivated fetal calf serum (FCS), medium (DMEM) containing antibiotic mix(penicillin G, streptomycin, amphotericin B) at 37°C (5% CO2). Endothelial cells treated with synthetic IFN-γ and imiquimodligands, then the NO (nitric oxide) concentration in the supernatant is determined by Griess reagent. Endothelial cells are cultured in 6 well cell culture plate and in each well 2*104cells are expected to be grown for 24 hours of culture. Then, the cells are treated with synthetic IFN-γ and имиквимод ligand for 6 hours and the NO signaling gene activation iNOS mRNA expression which is induced by IFN-γ is determined by RT-qPCR. Endothelial cells are cultured in 12 well cell culture plate and in each well 2*104 cells are expected to be grown for 18 hours of culture. Then, the cells are treated with synthetic IFN-γ and imiquimodligands for 24 hours and the NO signaling protein iNOS expression which is induced by IFN-γ is determined by western blotting. The experiment was conducted as representation mean of at least three test results. The difference between statistical probabilities is determined by the “Students” t test. The p<0.01 value is assumed to be statistically different. RESULTS: TLR7 ligand imiquimodaugmented interferon gamma induced nitric oxide production TLR7 ligand imiquimodincreased interferon gamma induced iNOS mRNA gene expression. TLR7 ilgand imiquimodup-regulated interferon gamma induced iNOS protein expression. CONCLUSIONS: TLR7 ligand imiquimod augments IFN-γ signaling in the endothelial cells. This synergistic effect has revealed in the levels of gene and protein expression.
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INTRODUCTION:According to the report from 2010, Mongolian water consumption was 550 million cubic meter andapproximately 9.1% of the total Mongolian population obtain their water from inadequate hygiene waterresources - springs and rivers. Due to non-hygiene water usage has caused water-born communicableand non communicable diseases among the population. In the last years there has been issue of pollutionof one of the Mongolia’s more representative river Selenge and its following rivers -Kharaa, Orkhon andit is necessary to evaluate water pollution of these rivers.GOAL:To determine water chemical and biological pollution of Kharaa and Orkhon river and to evaluate waterqualityMaterials and MethodsWe collected water, sediments and macro invertebrates sample from three points of river -upstream,midstream, downstream and for Kharaa river the samples were collected from Tunkhel, Mandal andBayangol soum, fo Orkhon river the sequence was Orkhontuul, Orkhon, Khushaat soum. Samples werecollected June, August, October of 2011, 2013.In water sample, we determined physic-chemical 15 parameters including temperature, pH, total dissolvedsolids, conductivity, smell, color, hardness, sulfate, chloride, nitrate, nitrite, ammonia, dissolved oxygen,biological oxygen demand and mercury using their standard methods. Macro invertebrate samples werecollected to evaluate water quality and we determined mercury in sediments and macroinvertebratesamples to evaluate mercury contamination.RESULT:Physic-chemical results of the water showed that water of Kharaa, Orkhon rivers were classified lowmineralized, soft water and nutrient pollution indicators for ‘slightly polluted’category. For dissolved andbiochemical oxygen, they were belong to the category of ‘pure water’.There were no correlation between 2012 and 2013 results and mercury in water, sediments and macroinvertebrates were qualified standard value.CONCLUSION:According to research results water quality of Kharaa, Orkhon river was good and have less pollution andit is possible to use in household consumption after proper cleaning and disinfection.
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Risk of nephrotith disease increases relating with using high hardened water, not suitable diet, being sensitive for some kind of food products. Then for Mongolia, particularly Bulgan province which is located in basin of the Selenge river is consisted in regions which have high hardened water. Sickness rate of renal diseases especially nephtolith disease is high in population of Selenge soum of Bulgan province. It was main reason of choose this subject and investigate non organic substances in urine of population and determine risks of nephtolith disease for them. To determine оne of the factors affecting the formation of the disease is to study the composition of drinking water and investigate non organic substances in urine. We used cross-sectional methodology for our study. Our study was conducted from June, 2013 to November, 2014. Household water used portable water dissemination and homes with private wells and water samples from the river.Drinking water analyzed of the chemistry parameters (13 substances) in the chemistry and toxicology laboratories in Orkhon aimag. There was 300 urine analyze was done and 62 of them was confirmed nephtolith disease with it. We investigated non-organic substances in their urine. Interviews people in the study, the average age was 43.26±14.7. 64.2% of participants was answered that they use ground water (private groundwater wells), 25.4% use external water (the well water), 8.1% use river water, 2.3 use pure water when asked about their water supply. Composition of samples from drinking water standard was near to the standard assessments by comparing the maximum amount of. We were considered the most important water pH, solids, iron, chlorine analysis compares removable wells and private wells. Hardness for 53.3% of the well of 2.5-3.5 mg/l with hard water, private wells, 60.0% of 4.6-5.5 mg/l solids by of water. Wells chlorides portable 66.7% 14.4-25.3 mg/l, and private wells 13.3% of 4.3-14.3 mg /l. 20.7 percent of survey identified as the kidney and urinary tract diseases. Urat salt (32.1%), compound of urat and sodium (32.1%), oxalate (14.5%), sodium (13.4%), compound of oxalate and sodium (6.4%), phosphate (1.5%) was determined in urine analyze. It was close to the water content of the standard performance. The well water solids of 2.5-3.5 mg/l and private groundwater wells solids of 4.6-5.5 mg/l. And the well chlorides 14.4-25.3 mg/l and private groundwater wells chlorides 4.3-14.3 mg/l.Urat and compound of urat and sodium are dominated in composition of stone during nephrolith disease (p=0.043).
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IntroductionRheumatoid Arthritis (RA) is chronic systemic inflammatory autoimmune disorder that still remains a disease of unknown etiology and complex disease without a single treatment that is dominated by serious and debilitating sequalae resulting from synovial membrane, cartilage and progressive joint destruction involvement. There is a one major obstacle in elucidating the early events in the pathogenesis of RA has been the lack of definition of the initial features of the disease. To overcome these difficulties, various animal models have been developed. But Collagen Induced Arthritis (CIA) mouse model is known to be the most valuable animal model to explore the pathogenic process, molecular and cellular mechanisms of joint destruction, to discover the immune system respond and activation and to develop new effective treatment methods and useful drugs [1].Materials and Methods:Within this study we have used 40 male mice at age 6-8 weeksfor 0-60 days and divided into following 4 groups which are:I group–CIA induced mouse group treated with Derveger Jirgeruu (Saposhnicovia divaricata) (n=12) II group–CIA induced mouse group treated with Natriisalicylas (10%) (n=12) III group–Healthy control mouse group (n=8) IV group–CIA inducedcontrol mouse group (n=8). To induce CIA model, we have used standard method of Murali /2005/’s design. Standard drug Natriisalicylas (10mg/ 20gr), one of the often used drug anti-inflammatory and Mongolian herbal plant Derveger jirgeruu (Saposhnicovia divaricate) (0.26mg/20gr) were daily administered by orally, starting on day 21 until day 60.To evaluate and compare 2 drug’s anti-inflammatory effect, we have done clinical score evaluation (Kim W.U, 2002), laboratory testing and histological examination of the joints using standard methods.ResultTo summarize the research result, both medications have proven to be as a medication which has anti-inflammatory effect that decreased the signs and symptoms of RA by it is histological and laboratory analysis.Conclusions:1. CIA model was effectively induced, which have proven by clinical signs, laboratory result and histological examination.2. Within this study it has proven that traditional herbal medicine Derveger Jirgeruu (Saposhnicovia divaricate) (0.26mg/20g) have anti-inflammatory effect on CIA induced mouse model of Rheumatoid Arthritis, which have had similar effect asstandard non-steroid medicine Natriisalicylas (10mg/20g).