Genetic Mechanisms in Aspirin-Exacerbated Respiratory Disease

Aspirin-exacerbated respiratory disease (AERD) refers to the development of bronchoconstriction in asthmatics following the exposure to aspirin or other nonsteroidal anti-inflammatory drugs. The key pathogenic mechanisms associated with AERD are the overproduction of cysteinyl leukotrienes (CysLTs) and increased CysLTR1 expression in the airway mucosa and decreased lipoxin and PGE2 synthesis. Genetic studies have suggested a role for variability of genes in disease susceptibility and the response to medication. Potential genetic biomarkers contributing to the AERD phenotype include HLA-DPB1, LTC4S, ALOX5, CYSLT, PGE2, TBXA2R, TBX21, MS4A2, IL10, ACE, IL13, KIF3A, SLC22A2, CEP68, PTGER, and CRTH2 and a four-locus SNP set composed of B2ADR, CCR3, CysLTR1, and FCER1B. Future areas of investigation need to focus on comprehensive approaches to identifying biomarkers for early diagnosis

Prediction Forecast for Culex tritaeniorhynchus Populations in Korea

AbstractObjectivesJapanese encephalitis is considered as a secondary legal infectious disease in Korea and is transmitted by mosquitoes in the summer season. The purpose of this study was to predict the ratio of Culex tritaeniorhynchus to all the species of mosquitoes present in the study regions.MethodsFrom 1999 to 2012, black light traps were installed in 10 regions in Korea (Busan, Gyeonggi, Gangwon, Chungbuk, Chungnam, Jeonbuk, Jeonnam, Gyeongbuk, Gyeongnam, and Jeju) to capture mosquitoes for identification and classification under a dissecting microscope. The number of mosquitoes captured/week was used to calculate its daily occurrence (mosquitoes/trap/night). To predict the characteristics of the mosquito population, an autoregressive model of order p (AR(p)) was used to execute the out-of-sample prediction and the in-sample estimation after presumption.ResultsCompared with the out-of-sample method, the sample-weighted regression method's case was relatively superior for prediction, and this method predicted a decrease in the frequency of Cx. tritaeniorhynchus for 2013. However, the actual frequency of this species showed an increase in frequency. By contrast, the frequency rate of all the mosquitoes including Cx. tritaeniorhynchus gradually decreased.ConclusionThe number of patients with Japanese encephalitis has been strongly associated with the occurrence and density of vector mosquitoes, and the importance of this infectious disease has been highlighted since 2010. The 2013 prediction indicated an increase after an initial decrease, although the ratio of the two mosquito species decreased. The increase in vector density may be due to changes in temperature and the environment. Thus, continuous prevalence prediction is warranted

Efficacy and safety of daclatasvir and asunaprevir for hepatitis C virus genotype 1b infection

Background/Aims: The treatment strategy for hepatitis C virus (HCV) has been changing rapidly since the introduction of direct-acting antivirals such as daclatasvir (DCV) and asunaprevir (ASV). We evaluated the efficacy and safety of DCV and ASV for HCV in real-life practice. Methods: Patients were treated with 60 mg of DCV once daily plus 200 mg of ASV twice daily for 24 weeks, and followed for 12 weeks. The primary endpoint was a sustained virological response at 12 weeks after treatment (SVR12) and safety. Results: This retrospective study included eight patients with chronic HCV genotype 1b infection. All of the enrolled patients were diagnosed with liver cirrhosis, and their mean age was 65.75 years. One patient was a nonresponder and two patients relapsed with previous pegylated interferon (PegIFN) and ribavirin (RBV) treatment. None of the patient showed NS5A mutation. An SVR12 was achieved in 88% of cases by the DCV and ASV combination therapy. The serum transaminase level and the aspartate-aminotransferase-to-platelet ratio were improved after the treatment. DCV and ASV were well tolerated in most of the patients, with treatment discontinuation due to adverse events (elevated liver enzyme and decompensation) occurring in two patients. Conclusion: In this study, combination of DCV and ASV treatment achieved a high sustained virological response with few adverse events even in those with cirrhosis, advanced age, and nonresponse/relapse to previous interferon-based therapy. Close monitoring of safety issues may be necessary when treating chronic HCV patients receiving DCV and ASV, especially in older patient and those with cirrhosis

STAT1 and Nmi are downstream targets of Ets-1 transcription factor in MCF-7 human breast cancer cell

AbstractEts-1 is a cellular homologue of the product of the viral ets oncogene of the E26 virus, and it functions as a tissue-specific transcription factor. It plays an important role in cell proliferation, differentiation, lymphoid cell development, transformation, angiogenesis, and apoptosis. Ets-1 controls the expression of critical genes involved in these processes by binding to ets binding sites present in the transcriptional regulatory regions. Here, we transiently overexpressed Ets-1 in MCF-7 and comprehensively searched for potential downstream targets of Ets-1 by cDNA microarray analysis. The expressions of several interferon-related genes including STAT1 and Nmi were augmented by the overexpression of Ets-1. RT-PCR and Western blotting confirmed the increase in the levels of STAT1 and Nmi mRNA and protein. In contrast, Ets-1 siRNA decreased the expression of STAT1 and Nmi proteins. As in our transient transfection experiments, stable overexpression of Ets-1, also increased the protein expression of STAT1 and Nmi in MCF-7 cells. Taken together, our results indicate that STAT1 and Nmi are downstream targets of Ets-1 in MCF-7 human breast cancer cells

Assessment of organic acid and sugar composition in apricot, plumcot, plum, and peach during fruit development

Variation in content of organic acids and soluble sugars, and in physical characteristics was evaluated in apricot (P. armeniaca L. cv. Harcot), plumcot (plum-apricot hybrid, P. salicina ⅹ P. armeniaca L. cv. Harmony), plum (P. salicina Lindl. cv. Formosa), and peach (P. persica L. Batsch cv. Jinmi). The content of organic acids and sugars, as well as parameters of fruit quality (weight, dimensions, firmness, total soluble solids, and total acidity) in Prunus fruits during fruit development were determined. Organic acids, including oxalic acid, quinic acid, malic acid, shikimic acid, citric acid, and quinic acid, sugars, including sucrose, fructose, glucose, and sugar alcohol (sorbitol), were identified and quantified using HPLC. Organic acid mostly increased during the early stages of fruit growth (30 - 60 days after full bloom) and decreased until fruits were fully ripened. In general, plum was the highest in most organic acids compared with the other fruits, while apricot contained the lowest acid content except for citric acid. Sucrose, fructose, and glucose content increased with fruit development, unlike content of sorbitol. Plumcot contained the highest fructose, and peach showed the maximum content of sucrose at full maturation stages. Total soluble solids averaged 17.5, 14.8, 11.9, and 10.6 ºBrix in apricot, plumcot, plum, and peach, respectively, whereas total acidity was 0.9, 1.4, 0.5, and 0.3% in four Prunus cultivars at ripened stages. Shikimic acid was significantly correlated with oxalic acid in apricot, plumcot, and plum, but not in peach. Fructose and glucose were highly correlated in plumcot, plum, and peach.

Polymorphisms of Aspirin-Metabolizing Enzymes CYP2C9, NAT2 and UGT1A6 in Aspirin-Intolerant Urticaria

Acetyl salicylic acid (ASA) is metabolized by UDP-glucuronosyltransferase 1A6 (UGT1A6), cytochrome P4502C9 (CYP2C9), and N-acetyl transferase 2 (NAT2). Variations in the activities of these enzymes may modulate adverse ASA-related symptoms such as urticaria. We examined whether polymorphisms in the UGT1A6, CYP2C9, and NAT2 genes are related to ASA-intolerant urticaria (AIU). The genotypes of 148 subjects with AIU (AIU group) and 260 normal healthy control subjects (NC group) were analyzed with respect to the following single nucleotide polymorphisms: CYP2C9 -1188T>C and CYP2C9*3A1075C; UGT1A6 T181A A>G and UGT1A6 R184S A>C; and NAT2 9796A>T, NAT2 197G>A, NAT2 286G>A, NAT2 9601A>G, and NAT2 9306A>G. There were significant differences in the allele frequencies for the CYP2C9 polymorphisms between the two groups. The frequency of the minor allele CYP2C9 -1188T>C was significantly higher in the AIU group than in the NC group (P=0.005). The frequency of the variant genotype CC was higher in the AIU group compared with the controls in both the co-dominant (P=0.007) and recessive models (P=0.012). The frequency of haplotype 2 [CA] was also significantly higher in the AIU group in both the co-dominant (P=0.006) and dominant models (P=0.012). There was no significant difference in genotype frequencies for any of the UGT1A6 or NAT2 polymorphisms between the two groups. Clinical parameters did not differ according to genotype. These results suggest that the C allele of CYP2C9 -1188T>C may be associated with AIU

Ubiquitous-Severance Hospital Project: Implementation and Results

OBJECTIVES: The purpose of this study was to review an implementation of u-Severance information system with focus on electronic hospital records (EHR) and to suggest future improvements. METHODS: Clinical Data Repository (CDR) of u-Severance involved implementing electronic medical records (EMR) as the basis of EHR and the management of individual health records. EHR were implemented with service enhancements extending to the clinical decision support system (CDSS) and expanding the knowledge base for research with a repository for clinical data and medical care information. RESULTS: The EMR system of Yonsei University Health Systems (YUHS) consists of HP integrity superdome servers using MS SQL as a database management system and MS Windows as its operating system. CONCLUSIONS: YUHS is a high-performing medical institution with regards to efficient management and customer satisfaction; however, after 5 years of implementation of u-Severance system, several limitations with regards to expandability and security have been identifiedope

Ring finger protein 126 (RNF126) suppresses ionizing radiation-induced p53-binding protein 1 (53BP1) focus formation

Cells have evolved sophisticated mechanisms to maintain genomic integrity in response to DNA damage. Ionizing radiation (IR)-induced DNA damage results in the formation of IR-induced foci (iRIF) in the nucleus. The iRIF formation is part of the DNA damage response (DDR), which is an essential signaling cascade that must be strictly regulated because either the loss of or an augmented DDR leads to loss of genome integrity. Accordingly, negative regulation of the DDR is as critical as its activation. In this study, we have identified ring finger protein 126 (RNF126) as a negative regulator of the DDR from a screen of iRIF containing 53BP1. RNF126 overexpression abolishes not only the formation of 53BP1 iRIF but also of RNF168, FK2, RAP80, and BRCA1. However, the iRIF formation of H2AX, MDC1, and RNF8 is maintained, indicating that RNF126 acts between RNF8 and RNF168 during the DDR. In addition, RNF126 overexpression consistently results in the loss of RNF168-mediated H2A monoubiquitination at lysine 13/15 and inhibition of the non-homologous end joining capability. Taken together, our findings reveal that RNF126 is a novel factor involved in the negative regulation of DDR, which is important for sustaining genomic integrity

Profiling age-related epigenetic markers of stomach adenocarcinoma in young and old subjects

The purpose of our study is to identify epigenetic markers that are differently expressed in the stomach adenocarcinoma (STAD) condition. Based on data from The Cancer Genome Atlas (TCGA), we were able to detect an age-related difference in methylation patterns and changes in gene and miRNA expression levels in young (n = 14) and old (n = 70) STAD subjects. Our analysis identified 323 upregulated and 653 downregulated genes in old STAD subjects. We also found 76 miRNAs with age-related expression patterns and 113 differentially methylated genes (DMGs), respectively. Our further analysis revealed that significant upregulated genes (n = 35) were assigned to the cell cycle, while the muscle system process (n = 27) and cell adhesion-related genes (n = 57) were downregulated. In addition, by comparing gene and miRNA expression with methylation change, we identified that three upregulated genes (ELF3, IL1??, and MMP13) known to be involved in inflammatory responses and cell growth were significantly hypomethylated in the promoter region. We further detected target candidates for age-related, downregulated miRNAs (hsa-mir-124-3, hsa-mir-204, and hsa-mir-125b-2) in old STAD subjects. This is the first report of the results from a study exploring age-related epigenetic biomarkers of STAD using high-throughput data and provides evidence for a complex clinicopathological condition expressed by the age-related STAD progression. © the authors, publisher and licensee Libertas Academica Limitedopen