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Vici Syndrome with Novel Compound Heterozygous Mutations in EPG5 (EPG5 유전자 변이가 확인된 Vici 증후군 1례)

  • Shin, Jehee;Lee, Hyunjoo;Lee, Young-Mock
    • Journal of The Korean Society of Inherited Metabolic disease
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    • v.20 no.2
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    • pp.50-54
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    • 2020
  • Vici syndrome is a rare, autosomal recessive multisystem disorder characterized by agenesis of the corpus callosum, cataracts, cardiomyopathy, hypopigmentation, immunodeficiency, and delayed development. We report the case of a 3-year-old boy diagnosed with Vici syndrome. He initially presented with hypotonia and sucking problem. Whole-exome sequencing identified novel compound heterozygous mutations, namely c.2254C>T (p.Gln752Ter) and c.5511-5518+2 del TATGCAAAGT in the EPG5 gene. The diagnostic challenges can be attributed to the diverse clinical manifestations. Thus, whole-exome sequencing is a useful diagnostic tool for the genetically and clinically heterogeneous Vici syndrome. This is the first Korean report of a patient with Vici syndrome.

An Analysis of the Water Quality Improvement Measures and Evaluation of Wonju Stream (원주천 수질개선 방안 및 개선효과 평가)

  • Kum, Donghyuk;Shin, Minhwan;Yu, Nayeong;Lee, Seolo;Kim, Dongjin;Sung, Younsoo;Lee, Sang Soo
    • Journal of The Korean Society of Agricultural Engineers
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    • v.63 no.1
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    • pp.61-73
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    • 2021
  • Recently, the deterioration of water quality in Wonju stream has been reported due to the increase in diverse pollution sources along with community development and urbanization. Various types of attempts with a huge budget were made for better water quality so far, but its effectiveness is still doubted. In order to establish site-oriented measures for water quality improvement, the topographic and hydrologic factors were evaluated based on site inspection and survey. As the major streams merged into the Wonju stream, the Hwa and Heungyang streams were found to have higher pollution loads and contributions compared to other streams due to the scattered livestock farms and industries, and vulnerable land use. Notably, the discharge water from the Wonju Public Sewage Treatment Plant had the highest level of pollution load, impacting on the water quality of Wonju Stream. According to the SWAT model as water quality measures, the improvement effect of water quality in this treatment plant can be reached to the reductions in BOD 11.06%, T-N 23.56%, T-P 10.60% when the proper managements applied, whereas the improvement of water quality would be 3.89%, 1.23%, and 3.32% for BOD, T-N, T-P, respectively, for the industries. The reduction of the livestock industry was generally very high as a pollution source, but it was not much higher at the end of Wonju Stream than other measures. These results recommended that the water q uality improvement measures should be designated for each upper-middle-lower section in Wonju stream.

Expression of miR-29a in whole Blood of Patients with Colorectal Neoplasm

  • Hwang, Dasom;Kim, Dahye;Chang, Yunhee;Hirgo, Workneh Korma;Lee, Hyeyoung
    • Biomedical Science Letters
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    • v.27 no.4
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    • pp.216-222
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    • 2021
  • Colorectal cancer (CRC) is major cancer with high incidence and mortality worldwide. It is known that most CRCs arise from precursor adenomatous polyps (APs). Recently, microRNA (miRNA) has been proposed as a biomarker for various cancers including CRC. In this study, the expression patterns of miR-29a in the whole blood (WB) of CRC, AP, and control groups were analyzed by reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) to evaluate the expression level of miR-29a in patients with colorectal neoplasm (CRN) including CRC and AP. As a result, the relative expression of miR-29a was significantly decreased in the patients with CRN compared to the control group (P<0.001). The results were in agreement with previous in vitro cell studies and studies that used tissue and feces samples, suggesting that miR-29a in WB may be useful in demonstrating the status of colorectal tissue. Additionally, we divided the control group into healthy control (HC) without any colorectal symptoms and non-tumor control (NTC) with colorectal symptoms but without any CRN. And then the relative expression of miR-29a was also significantly decreased in the NTC group compared to the HC group (P<0.001). Therefore, our study revealed that miR-29a can differentiate patients with CRN from HC group, but they are also involved in the early stage of inflammatory response and cannot be specific biomarkers for CRN.

Inhibitory effect of Cinnamomi Cortex extract on motility of prostate cancer cells through reducing YAP activity (육계의 전립선암세포에서 YAP 활성 억제를 통한 전이 저해 효능 연구)

  • Jung, Hyo Won;Kim, Ok-Hyeon;Wang, Tsu Yu;Kim, Seong Eun;Park, Yong-Ki;Lee, Hyun Jung
    • The Korea Journal of Herbology
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    • v.34 no.3
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    • pp.55-61
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    • 2019
  • Objectives : Recently, natural bioactive components catch a major attention for their potent anticarcinogenic activity. In this study, the inhibitory effect of Cinnamomi Cortex (CC) was examined in PC3 prostate cancer cells. Methods : The toxicity of CC extract was evaluated with cell viability and cell morphology. The activity of Yes associated protein (YAP) was tested with qRT-PCR for the target gene expression such as CTGF and AMOTL2. Western blotting was performed for the evaluation of phospho-YAP level. For cell motility analysis, cellular motility was imaged by live imaging system for 6 hr. Successive images were used for the generation of movie file. Using this movie file, cellular migration was manually tracked and analyzed using time-lapse microscope and Fiji software. Results : Cytotoxicity of CC extract was not detected at $500{\mu}g/m{\ell}$ or below concentration. Although $500{\mu}g/m{\ell}$ of CC extract reduced CTGF and AMOTL2 gene expression as YAP target genes, it was not statistically significant (CTGF expression P=0.0605, AMOTL2 expression P=0.4478). However, phosphorylated YAP was highly enhanced by CC extract treatment, when normalized with total YAP protein expression, suggesting YAP activation was inhibited. Finally prostate cancer cell motility was markedly reduced by $500{\mu}g/m{\ell}$ of CC extract. Conclusions : CC extract suppresses cancer cell motility and migration ability through inhibiting YAP activation without prostate cancer cell death, suggesting that this herb might be effective therapeutic drug for prostate cancer metastasis.

Benzyl Isothiocyanate-Induced Cytotoxicity via the Inhibition of Autophagy and Lysosomal Function in AGS Cells

  • Po, Wah Wah;Choi, Won Seok;Khing, Tin Myo;Lee, Ji-Yun;Lee, Jong Hyuk;Bang, Joon Seok;Min, Young Sil;Jeong, Ji Hoon;Sohn, Uy Dong
    • Biomolecules & Therapeutics
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    • v.30 no.4
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    • pp.348-359
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    • 2022
  • Gastric adenocarcinoma is among the top causes of cancer-related death and is one of the most commonly diagnosed carcinomas worldwide. Benzyl isothiocyanate (BITC) has been reported to inhibit the gastric cancer metastasis. In our previous study, BITC induced apoptosis in AGS cells. The purpose of the present study was to investigate the effect of BITC on autophagy mechanism in AGS cells. First, the AGS cells were treated with 5, 10, or 15 μM BITC for 24 h, followed by an analysis of the autophagy mechanism. The expression level of autophagy proteins involved in different steps of autophagy, such as LC3B, p62/SQSTM1, Atg5-Atg12, Beclin1, p-mTOR/mTOR ratio, and class III PI3K was measured in the BITC-treated cells. Lysosomal function was investigated using cathepsin activity and Bafilomycin A1, an autophagy degradation stage inhibitor. Methods including qPCR, western blotting, and immunocytochemistry were employed to detect the protein expression levels. Acridine orange staining and omnicathepsin assay were conducted to analyze the lysosomal function. siRNA transfection was performed to knock down the LC3B gene. BITC reduced the level of autophagy protein such as Beclin 1, class III PI3K, and Atg5-Atg12. BITC also induced lysosomal dysfunction which was shown as reducing cathepsin activity, protein level of cathepsin, and enlargement of acidic vesicle. Overall, the results showed that the BITC-induced AGS cell death mechanism also comprises the inhibition of the cytoprotective autophagy at both initiation and degradation steps.

Prediction of Covid-19 confirmed number of cases using ARIMA model (ARIMA모형을 이용한 코로나19 확진자수 예측)

  • Kim, Jae-Ho;Kim, Jang-Young
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.25 no.12
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    • pp.1756-1761
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    • 2021
  • Although the COVID-19 outbreak that occurred in Wuhan, Hubei around December 2019, seemed to be gradually decreasing, it was gradually increasing as of November 2020 and June 2021, and estimated confirmed cases were 192 million worldwide and approximately 184 thousand in South Korea. The Central Disaster and Safety Countermeasures Headquarters have been taking strong countermeasures by implementing level 4 social distancing. However, as the highly infectious COVID-19 variants, such as Delta mutation, have been on the rise, the number of daily confirmed cases in Korea has increased to 1,800. Therefore, the number of cumulative confirmed COVID-19 cases is predicted using ARIMA algorithms to emphasize the severity of COVID-19. In the process, differences are used to remove trends and seasonality, and p, d, and q values are determined and forecasted in ARIMA using MA, AR, autocorrelation functions, and partial autocorrelation functions. Finally, forecast and actual values are compared to evaluate how well it was forecasted.

Ginsenoside Re inhibits myocardial fibrosis by regulating miR-489/myd88/NF-κB pathway

  • Jinghui Sun;Ru Wang;Tiantian Chao;Jun Peng;Chenglong Wang;Keji Chen
    • Journal of Ginseng Research
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    • v.47 no.2
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    • pp.218-227
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    • 2023
  • Background: Myocardial fibrosis (MF) is an advanced pathological manifestation of many cardiovascular diseases, which can induce heart failure and malignant arrhythmias. However, the current treatment of MF lacks specific drugs. Ginsenoside Re has anti-MF effect in rat, but its mechanism is still not clear. Therefore, we investigated the anti-MF effect of ginsenoside Re by constructing mouse acute myocardial infarction (AMI) model and AngII induced cardiac fibroblasts (CFs) model. Methods: The anti-MF effect of miR-489 was investigated by transfection of miR-489 mimic and inhibitor in CFs. Effect of ginsenoside Re on MF and its related mechanisms were investigated by ultrasonographic, ELISA, histopathologic staining, transwell test, immunofluorescence, Western blot and qPCR in the mouse model of AMI and the AngII-induced CFs model. Results: MiR-489 decreased the expression of α-SMA, collagenI, collagen III and myd88, and inhibited the phosphorylation of NF-κB p65 in normal CFs and CFs treated with AngII. Ginsenoside Re could improve cardiac function, inhibit collagen deposition and CFs migration, promote the transcription of miR-489, and reduce the expression of myd88 and the phosphorylation of NF-κB p65. Conclusion: MiR-489 can effectively inhibit the pathological process of MF, and the mechanism is at least partly related to the regulation of myd88/NF-κB pathway. Ginsenoside Re can ameliorate AMI and AngII induced MF, and the mechanism is at least partially related to the regulation of miR-489/myd88/NF-κB signaling pathway. Therefore, miR-489 may be a potential target of anti-MF and ginsenoside Re may be an effective drug for the treatment of MF.

V608 CASSIOPEIAE: A W UMA-TYPE ECLIPSING BINARY WITH TWO POSSIBLE CIRCUMBINARY COMPANIONS

  • Park, Jang-Ho;Lee, Jae Woo
    • Journal of The Korean Astronomical Society
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    • v.55 no.1
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    • pp.1-9
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    • 2022
  • We present the photometric properties of V608 Cas from detailed studies of light curves and eclipse timings. The light curve synthesis indicates that the eclipsing pair is an overcontact binary with parameters of ∆T = 155 K, q = 0.328, and f = 26%. We detected the third light ℓ3, which corresponds to about 8% and 5% of the total systemic light in V and R bands, respectively. Including our 6 timing measurements, a total of 38 times of minimum light were used for a period study. It was found that the orbital period of V608 Cas has varied in some combination of an upward parabola and two periodic variations. The continuous period increase with a rate of +3.99 × 10-7 d yr-1 can be interpreted as a mass transfer from the secondary component to the primary star at a rate of 1.51 × 10-7 M yr-1. The periods and semi-amplitudes of the two periodic variations are about P3 = 16.0 yr and P4 = 26.3 yr, and K3 = 0.0341 d and K4 = 0.0305 d, respectively. The most likely explanation of both cycles is a pair of light-traveling time effects operated by the possible presence of third and fourth components with estimated masses of M3 = 2.20 M and M4 = 1.27 M in eccentric orbits of e3 = 0.66 and e4 = 0.52. Because the contribution of ℓ3 is very low compared to the estimated masses of two circumbinary objects, they can be inferred as very faint compact objects.

Production of Mono-Hydroxylated Derivatives of Terpinen-4-ol by Bacterial CYP102A1 Enzymes

  • Jeong-Hoon Kim;Chan Mi Park;Hae Chan Jeong;Gyeong Han Jeong;Gun Su Cha;Sungbeom Lee;Chul-Ho Yun
    • Journal of Microbiology and Biotechnology
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    • v.34 no.3
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    • pp.725-734
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    • 2024
  • CYP102A1 from Bacillus megaterium is an important enzyme in biotechnology, because engineered CYP102A1 enzymes can react with diverse substrates and produce human cytochrome P450-like metabolites. Therefore, CYP102A1 can be applied to drug metabolite production. Terpinen-4-ol is a cyclic monoterpene and the primary component of essential tea tree oil. Terpinen-4-ol was known for therapeutic effects, including antibacterial, antifungal, antiviral, and anti-inflammatory. Because terpenes are natural compounds, examining novel terpenes and investigating the therapeutic effects of terpenes represent responses to social demands for eco-friendly compounds. In this study, we investigated the catalytic activity of engineered CYP102A1 on terpinen-4-ol. Among CYP102A1 mutants tested here, the R47L/F81I/F87V/E143G/L188Q/N213S/E267V mutant showed the highest activity to terpinen-4-ol. Two major metabolites of terpinen-4-ol were generated by engineered CYP102A1. Characterization of major metabolites was confirmed by liquid chromatography-mass spectrometry (LC-MS), gas chromatography-MS, and nuclear magnetic resonance spectroscopy (NMR). Based on the LC-MS results, the difference in mass-to-charge ratio of an ion (m/z) between terpinen-4-ol and its major metabolites was 16. One major metabolite was defined as 1,4-dihydroxyp-menth-2-ene by NMR. Given these results, we speculate that another major metabolite is also a mono-hydroxylated product. Taken together, we suggest that CYP102A1 can be applied to make novel terpene derivatives.

Prevalence and predictors of multidrug-resistant bacteremia in liver cirrhosis

  • Aryoung Kim;Byeong Geun Song;Wonseok Kang;Dong Hyun Sinn;Geum-Youn Gwak;Yong-Han Paik;Moon Seok Choi;Joon Hyeok Lee;Myung Ji Goh
    • The Korean journal of internal medicine
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    • v.39 no.3
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    • pp.448-457
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    • 2024
  • Background/Aims: Improved knowledge of local epidemiology and predicting risk factors of multidrug-resistant (MDR) bacteria are required to optimize the management of infections. This study examined local epidemiology and antibiotic resistance patterns of liver cirrhosis (LC) patients and evaluated the predictors of MDR bacteremia in Korea. Methods: This was a retrospective study including 140 LC patients diagnosed with bacteremia between January 2017 and December 2022. Local epidemiology and antibiotic resistance patterns and the determinants of MDR bacteremia were analyzed using logistic regression analysis. Results: The most frequently isolated bacteria, from the bloodstream, were Escherichia coli (n = 45, 31.7%) and Klebsiella spp. (n = 35, 24.6%). Thirty-four isolates (23.9%) were MDR, and extended-spectrum beta-lactamase E. coli (52.9%) and methicillin-resistant Staphylococcus aureus (17.6%) were the most commonly isolated MDR bacteria. When Enterococcus spp. were cultured, the majority were MDR (MDR 83.3% vs. 16.7%, p = 0.003), particularly vancomycin-susceptible Enterococcus faecium. Antibiotics administration within 30 days and/or nosocomial infection was a significant predictor of MDR bacteremia (OR: 3.40, 95% CI: 1.24-9.27, p = 0.02). MDR bacteremia was not predicted by sepsis predictors, such as positive systemic inflammatory response syndrome (SIRS) or quick Sequential Organ Failure Assessment (qSOFA). Conclusions: More than 70% of strains that can be treated with a third-generation cephalosporin have been cultured. In cirrhotic patients, antibiotic administration within 30 days and/or nosocomial infection are predictors of MDR bacteremia; therefore, empirical administration of broad-spectrum antibiotics should be considered when these risk factors are present.