• Title/Summary/Keyword: risk expression

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A Study on the Correlation between SLC25A26 Polymorphism and Gastritis and Gastric Ulcers in Koreans (한국인의 SLC25A26 유전자 다형성과 위염, 위궤양과의 상관성에 관한 연구)

  • Soyeun PARK;Dahyun HWANG
    • Korean Journal of Clinical Laboratory Science
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    • v.55 no.4
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    • pp.291-297
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    • 2023
  • Gastritis is an inflammation of the gastric mucosa and gastric ulcers are a break in the mucosa of the stomach lining. Past research on gastritis and gastric ulcers has been mainly conducted from the perspective that environmental factors are the primary cause of these gastric diseases. However, recently the importance of genetic factors has been emphasized due to current developments in genetic research. The SLC25A26 gene is believed to be associated with the accumulation of reactive oxygen species. Oxidative stress promotes an inflammatory response, which increases the production of free radicals and causes cellular damage, and these lead to the development of gastric diseases. In this study, the correlation between SLC25A26 and gastric diseases was analyzed. Polymorphisms in SLC25A26 were analyzed in 1,369 domestic gastric disease patients and 7,471 healthy controls. As a result, 11 single nucleotide polymorphisms (SNPs) (in the genotype) and 13 SNPs (in the imputation) showed statistical significance (P<0.05), and high relative risk of gastric diseases. Among them, the rs13874 allele of SLC25A26 showed a highly significant association with gastric diseases. In the genotype-based mRNA expression analysis, the minor allele (C) group showed increased mRNA expression and this could increase oxidative stress. In conclusion, SLC25A26 polymorphisms are associated with gastric diseases. These results may provide a basis for new guidelines for gastric disease management in the Korean population.

The Combination of Gefitinib and Acetaminophen Exacerbates Hepatotoxicity via ROS-Mediated Apoptosis

  • Jiangxin Xu;Xiangliang Huang;Yourong Zhou;Zhifei Xu;Xinjun Cai;Bo Yang;Qiaojun He;Peihua Luo;Hao Yan;Jie Jin
    • Biomolecules & Therapeutics
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    • v.32 no.5
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    • pp.647-657
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    • 2024
  • Gefitinib is the well-tolerated first-line treatment of non-small cell lung cancer. As it needs analgesics during oncology treatment, particularly in the context of the coronavirus disease, where patients are more susceptible to contract high fever and sore throat. This has increased the likelihood of taking both gefitinib and antipyretic analgesic acetaminophen (APAP). Given that gefitinib and APAP overdose can predispose patients to liver injury or even acute liver failure, there is a risk of severe hepatotoxicity when these two drugs are used concomitantly. However, little is known regarding their safety at therapeutic doses. This study simulated the administration of gefitinib and APAP at clinically relevant doses in an animal model and confirmed that gefitinib in combination with APAP exhibited additional hepatotoxicity. We found that gefitinib plus APAP significantly exacerbated cell death, whereas each drug by itself had little or minor effect on hepatocyte survival. Mechanistically, combination of gefitinib and APAP induces hepatocyte death via the apoptotic pathway obviously. Reactive oxygen species (ROS) generation and DNA damage accumulation are involved in hepatocyte apoptosis. Gefitinib plus APAP also promotes the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated the antioxidant factor, Nuclear factor erythroid 2-related factor 2 (Nrf2), by inhibiting p62 expression. Taken together, this study revealed the potential ROS-mediated apoptosis-dependent hepatotoxicity effect of the combination of gefitinib and APAP, in which the p62/Keap1/Nrf2 signaling pathway participates and plays an important regulatory role.

Responses of Misgurnus anguillicaudatus and Cyprinus carpio Fed on Disease Resistant(OsCK1) Rice Variety (병저항성 GM(OsCK1)벼가 미꾸리(Misgurnus anguillicaudatus)및 잉어(Cyprinus carpio)에 미치는 영향)

  • Oh, Sung-Dug;Lee, Kijong;Park, Soo-Yun;Lee, Dae-Yong;Sohn, Soo-In;Kim, Min-Young;Ryu, Tae-Hun
    • Korean Journal of Environmental Agriculture
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    • v.32 no.3
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    • pp.231-239
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    • 2013
  • BACKGROUND: The disease resistant (OsCK1) rice was generated by inserting choline kinase (CK1) and phosphinothricin acetyltransferase (PAT) genes isolated from Oriza sativa and Streptomyces hygroscopicus into the genome of rice (Nakdongbyeo). With the potential problems of safety, the non-target organism evaluation is required as an essential element for the environmental risk assessment of genetically modified (GM) crops. In present study, we studied the effects on survival of Misgurnus anguillicaudatus and Cyprinus carpio, commonly used as a model organism in ecotoxicological studies. METHODS AND RESULTS: The M. anguillicaudatus and C. carpio were fed on disease resistant (OsCK1) rice and non-genetically modified (non-GM) rice (Nakdongbyeo) to 0, 10, 100, 1,000 and 5,000 mg/L, as treatment concentration respectively. The OsCK1 rice used for the test was confirmed to have the OsCK1/PAT gene expression by the PCR and ELISA analysis. Feeding test showed that no significant differences in cumulative immobility and abnormal response of M. anguillicaudatus and C. carpio fed on between OsCK1 rice and non-GM rice. The 96hr-$LC_{50}$ values showed no difference between OsCK1 rice (>5,000 mg/L) and non-GM rice (>5,000 mg/L). CONCLUSION(S): The results of this study suggested that there was no significant difference in toxicity for M. anguillicaudatus and C. carpio between OsCK1 rice and non-GM counterparts.

No Association of Hypoxia Inducible Factor-1α Gene Polymorphisms with Breast Cancer in North-West Indians

  • Sharma, Sarika;Kapahi, Ruhi;Sambyal, Vasudha;Guleria, Kamlesh;Manjari, Mridu;Sudan, Meena;Uppal, Manjit Singh;Singh, Neeti Rajan
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9973-9978
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    • 2014
  • Background: Hypoxia inducible factor-1 alpha (HIF-$1{\alpha}$) is the key regulator of cellular responses to hypoxia and plays a central role in tumour growth. Presence of Single nucleotide polymorphisms (SNPs) in the critical regulatory domains of HIF-$1{\alpha}$ may result in the overexpression of the protein and subsequent changes in the expression of the downstream target genes. The aim of study was to investigate the association of three SNPs (g.C111A, g.C1772T and g.G1790A) of HIF-$1{\alpha}$ with the risk of breast cancer in North Indian sporadic breast cancer patients. Materials and Methods: A total of 400 subjects, including 200 healthy controls and 200 patients with breast cancer were recruited in this study. Genotypes were determined using polymerase chain reaction - restriction fragment length polymorphism (PCR-RFLP) method. Results: The CC and CA genotype frequency of HIF-$1{\alpha}$ g.C111A polymorphism was 100 vs 99% and 0 vs 1% in breast cancer patients and healthy controls respectively. The frequencies of CC, CT and TT genotype of g.C1772T polymorphism were 76 vs 74.5%, 19 vs 21% and 5 vs 4.5% in breast cancer patients and control individuals respectively. There was no significant difference in genotype and allele frequencies of HIF-$1{\alpha}$ g.C1772T polymorphism between cases and control individuals (p>0.05). For g.G1790A genotypes, all patients and controls had only GG genotype. Conclusions: The three HIF-$1{\alpha}$ polymorphisms (g.C111A, g.C1772T and g.G1790A) are not associated with breast cancer risk in North-West Indian patients.

Association of Histopathological Markers with Clinico-Pathological Factors in Mexican Women with Breast Cancer

  • Bandala, Cindy;De la Garza-Montano, Paloma;Cortes-Algara, Alfredo;Cruz-Lopez, Jaime;Dominguez-Rubio, Rene;Gonzalez-Lopez, Nelly Judith;Cardenas-Rodriguez, Noemi;Alfaro-Rodriguez, A;Salcedo, M;Floriano-Sanchez, E;Lara-Padilla, Eleazar
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.18
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    • pp.8397-8403
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    • 2016
  • Background: Breast cancer (BCa) is the most common malignancy in Mexican women. A set of histopathological markers has been established to guide BCa diagnosis, prognosis and treatment. Nevertheless, in only a few Mexican health services, such as that of the Secretariat of National Defense (SEDENA for its acronym in Spanish), are these markers commonly employed for assessing BCa. The aim of this study was to explore the association of Ki67, TP53, HER2/neu, estrogenic receptors (ERs) and progesterone receptors (PRs) with BCa risk factors. Materials and Methods: Clinical histories provided background patient information. Immunohistochemical (IHC) analysis was conducted on 48 tissue samples from women diagnosed with BCa and treated with radical mastectomy. The Chi square test or Fisher exact test together with the Pearson and Spearman correlation were applied. Results: On average, patients were $58{\pm}10.4$ years old. It was most common to find invasive ductal carcinoma (95.8%), histological grade 3 (45.8%), with a poor Nottingham Prognostic Index (NPI; 80.4%). ERs and PRs were associated with smoking and alcohol consumption, metastasis at diagnosis and Ki67 expression (p<0.05). PR+ was also related to urea and ER+ (p<0.05). Ki67 was associated with TP53 and elevated triglycerides (p<0.05), and HER2/neu with ER+, the number of pregnancies and tumor size (p<0.05). TP53 was also associated with a poor NPI (p<0.05) and CD34 with smoking (p<0.05). The triple negative status (ER-/PR-/HER2/neu-) was related to smoking, alcohol consumption, exposure to biomass, number of pregnancies, metastasis and a poor NPI (p<0.05). Moreover, the luminal B subty was associated with histological type (p=0.007), tumor size (p=0.03) and high cholesterol (p=0.02). Conclusions: Ki67, TP53, HER2/neu, ER and PR proved to be related to several clinical and pathological factors. Hence, it is crucial to determine this IHC profile in women at risk for BCa. Certain associations require further study to understand physiological/biochemical/molecular processes.

Genome-wide hepatic DNA methylation changes in high-fat diet-induced obese mice

  • Yoon, AhRam;Tammen, Stephanie A.;Park, Soyoung;Han, Sung Nim;Choi, Sang-Woon
    • Nutrition Research and Practice
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    • v.11 no.2
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    • pp.105-113
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    • 2017
  • BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet). Food intake, body weight, and liver weight were measured. Hepatic triacylglycerol and cholesterol levels were determined using enzymatic colorimetric methods. Changes in genome-wide DNA methylation were determined by a DNA methylation microarray method combined with methylated DNA immunoprecipitation. The level of transcription of individual genes was measured by real-time PCR. RESULTS: The DNA methylation statuses of genes in biological networks related to lipid metabolism and hepatic steatosis were influenced by HFD-induced obesity. In HFD group, a proinflammatory Casp1 (Caspase 1) gene had hypomethylated CpG sites at the 1.5-kb upstream region of its transcription start site (TSS), and its mRNA level was higher compared with that in CD group. Additionally, an energy metabolism-associated gene Ndufb9 (NADH dehydrogenase 1 beta subcomplex 9) in HFD group had hypermethylated CpG sites at the 2.6-kb downstream region of its TSS, and its mRNA level was lower compared with that in CRCD group. CONCLUSIONS: HFD alters DNA methylation profiles in genes associated with liver lipid metabolism and hepatic steatosis. The methylation statuses of Casp1 and Ndufb9 were particularly influenced by the HFD. The expression of these genes in HFD differed significantly compared with CD and CRCD, respectively, suggesting that the expressions of Casp1 and Ndufb9 in liver were regulated by their methylation statuses.

Evaluation of Distribution and Inflammatory Effects of Airborne Fungus in Korea (국내 실외공기의 곰팡이 분포 및 노출에 따른 염증영향평가)

  • Yoon, Wonsuck;Lim, Jaehoon;Kim, Dasarang;Kim, Seunghyun;Lee, Hyo-sun;Kim, Chae-Bong;Kang, Ju-Wan;Lee, Keun-Hwa;Oh, Inbo;Kim, Yangho;Seo, Jung-Wook;Hong, Young-Seoub;Yoo, Young
    • Journal of Environmental Health Sciences
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    • v.45 no.6
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    • pp.638-645
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    • 2019
  • Objectives: For the risk management of airborne fungal diseases, our aim was to evaluate airborne fungi and study the toxicity associated with fungal allergic diseases using fungal species native to Korea. Methods: Fungi were isolated from outdoor air samples collected from Seoul, Incheon, Cheonan, Gwangju, Ulsan, Busan, and Jeju and tested for their cytotoxicity potential and their ability to induce proliferation and secretion of macrophage-derived chemokine (MDC) in human mast cells (HMC-1). Results: More than 18 species of fungi were collected from outdoor air in Korea over one year, and the strains were identified and systematically analyzed. The results showed that the Cladosporium (59%) and Alternaria (22%) strains are the most common in outdoor air. Three of the collected strains (Fusarium, Trichoderma, and Penicillium) showed mild toxicity in cells involved in allergic inflammation, and twelve induced cell proliferation in HMC-1 cells. More importantly, many strains (Edgeworthia, Trametes, Emmia, Irpex, Talaromyces, Penicillium, Periconia, Epicocum, Bipolaris) induced the MDC protein in activated HMC-1 cells. Conclusion: Nineteen percent of the tested strains caused cytotoxicity in mast cell lines, whereas, most of the non-toxic strains contributed to cell activity. Among the tested strains, more than 80% increased the expression of MDC protein, which contributes to the severity of atopic dermatitis, asthma, and rhinitis. It is, in fact, one of the markers for these conditions. Therefore, airborne fungus could be considered as an important marker for environmental risk management for allergic diseases in Korea.

Shoulder Surfing Attack Modeling and Security Analysis on Commercial Keypad Schemes (어깨너머공격 모델링 및 보안 키패드 취약점 분석)

  • Kim, Sung-Hwan;Park, Min-Su;Kim, Seung-Joo
    • Journal of the Korea Institute of Information Security & Cryptology
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    • v.24 no.6
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    • pp.1159-1174
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    • 2014
  • As the use of smartphones and tablet PCs has exploded in recent years, there are many occasions where such devices are used for treating sensitive data such as financial transactions. Naturally, many types of attacks have evolved that target these devices. An attacker can capture a password by direct observation without using any skills in cracking. This is referred to as shoulder surfing and is one of the most effective methods. There has been only a crude definition of shoulder surfing. For example, the Common Evaluation Methodology(CEM) attack potential of Common Criteria (CC), an international standard, does not quantitatively express the strength of an authentication method against shoulder surfing. In this paper, we introduce a shoulder surfing risk calculation method supplements CC. Risk is calculated first by checking vulnerability conditions one by one and the method of the CC attack potential is applied for quantitative expression. We present a case study for security-enhanced QWERTY keyboard and numeric keypad input methods, and the commercially used mobile banking applications are analyzed for shoulder surfing risks.

Chronic Alcohol Consumption Results in Greater Damage to the Pancreas Than to the Liver in the Rats

  • Lee, Seong-Su;Hong, Oak-Kee;Ju, Anes;Kim, Myung-Jun;Kim, Bong-Jo;Kim, Sung-Rae;Kim, Won-Ho;Cho, Nam-Han;Kang, Moo-Il;Kang, Sung-Koo;Kim, Dai-Jin;Yoo, Soon-Jib
    • The Korean Journal of Physiology and Pharmacology
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    • v.19 no.4
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    • pp.309-318
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    • 2015
  • Alcohol consumption increases the risk of type 2 diabetes. However, its effects on prediabetes or early diabetes have not been studied. We investigated endoplasmic reticulum (ER) stress in the pancreas and liver resulting from chronic alcohol consumption in the prediabetes and early stages of diabetes. We separated Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a type-2 diabetic animal model, into two groups based on diabetic stage: prediabetes and early diabetes were defined as occurrence between the ages of 11 to 16 weeks and 17 to 22 weeks, respectively. The experimental group received an ethanol-containing liquid diet for 6 weeks. An intraperitoneal glucose tolerance test was conducted after 16 and 22 weeks for the prediabetic and early diabetes groups, respectively. There were no significant differences in body weight between the control and ethanol groups. Fasting and 120-min glucose levels were lower and higher, respectively, in the ethanol group than in the control group. In prediabetes rats, alcohol induced significant expression of ER stress markers in the pancreas; however, alcohol did not affect the liver. In early diabetes rats, alcohol significantly increased most ER stress-marker levels in both the pancreas and liver. These results indicate that chronic alcohol consumption increased the risk of diabetes in prediabetic and early diabetic OLETF rats; the pancreas was more susceptible to damage than was the liver in the early diabetic stages, and the adaptive and proapoptotic pathway of ER stress may play key roles in the development and progression of diabetes affected by chronic alcohol ingestion.

Mechanical model for analyzing the water-resisting key stratum to evaluate water inrush from goaf in roof

  • Ma, Kai;Yang, Tianhong;Zhao, Yong;Hou, Xiangang;Liu, Yilong;Hou, Junxu;Zheng, Wenxian;Ye, Qiang
    • Geomechanics and Engineering
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    • v.28 no.3
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    • pp.299-311
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    • 2022
  • Water-resisting key stratum (WKS) between coal seams is an important barrier that prevents water inrush from goaf in roof under multi-seam mining. The occurrence of water inrush can be evaluated effectively by analyzing the fracture of WKS in multi-seam mining. A "long beam" water inrush mechanical model was established using the multi-seam mining of No. 2+3 and No. 8 coal seams in Xiqu Mine as the research basis. The model comprehensively considers the pressure from goaf, the gravity of overburden rock, the gravity of accumulated water, and the constraint conditions. The stress distribution expression of the WKS was obtained under different mining distances in No. 8 coal seam. The criterion of breakage at any point of the WKS was obtained by introducing linear Mohr strength theory. By using the mechanical model, the fracture of the WKS in Xiqu Mine was examined and its breaking position was calculated. And the risk of water inrush was also evaluated. Moreover, breaking process of the WKS was reproduced with Flac3D numerical software, and was analyzed with on-site microseismic monitoring data. The results showed that when the coal face of No. 8 coal seam in Xiqu Mine advances to about 80 m ~ 100 m, the WKS is stretched and broken at the position of 60 m ~ 70 m away from the open-off cut, increasing the risk of water inrush from goaf in roof. This finding matched the result of microseismic analysis, confirming the reliability of the water inrush mechanical model. This study therefore provides a theoretical basis for the prevention of water inrush from goaf in roof in Xiqu Mine. It also provides a method for evaluating and monitoring water inrush from goaf in roof.