• Molecules and Cells
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• v.45 no.12
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• pp.886-895
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• 2022

Malignant rhabdoid tumor (MRT) is a highly aggressive pediatric malignancy with no effective therapy. Therefore, it is necessary to identify a target for the development of novel molecule-targeting therapeutic agents. In this study, we report the importance of the runt-related transcription factor 1 (RUNX1) and RUNX1-Baculoviral IAP (inhibitor of apoptosis) Repeat-Containing 5 (BIRC5/survivin) axis in the proliferation of MRT cells, as it can be used as an ideal target for anti-tumor strategies. The mechanism of this reaction can be explained by the interaction of RUNX1 with the RUNX1-binding DNA sequence located in the survivin promoter and its positive regulation. Specific knockdown of RUNX1 led to decreased expression of survivin, which subsequently suppressed the proliferation of MRT cells in vitro and in vivo. We also found that our novel RUNX inhibitor, Chb-M, which switches off RUNX1 using alkylating agent-conjugated pyrrole-imidazole polyamides designed to specifically bind to consensus RUNX-binding sequences (5'-TGTGGT-3'), inhibited survivin expression in vivo. Taken together, we identified a novel interaction between RUNX1 and survivin in MRT. Therefore the negative regulation of RUNX1 activity may be a novel strategy for MRT treatment.

• Pediatric Infection and Vaccine
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• v.30 no.2
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• pp.55-61
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• 2023

Purpose: Urinary tract infections (UTIs) pose a significant disease burden in children. This study aims to determine whether a short-course regimen is non-inferior to a standard-course regimen in children with UTIs without complication and presence of bacteremia, and to define, in the optimal way possible, the term "short-course" in this context. Methods: We conducted a rapid systematic review of research up to April 2021 in PubMed, Embase, and Cochrane databases. We included studies that compared clinical outcomes in pediatric UTIs treated with short-course(≤4 days) or standard (≥5-7 days) courses. Results: Our analysis suggests that short-course regimes have equivalent efficacy to standard-course regimens, with similar clinical cure rates and recurrence rates. All 10 studies comparing the clinical cure rates of short- and standard-course regimens reported comparable outcomes. The study evaluating renal scarring indicated no inferiority of short-course regimens compared to standard-course ones. Regarding UTI relapse, 8 out of 10 studies reported no significant difference in outcomes between short- and standard-course regimens. Conclusions: Our results purpose that short-course UTI regimens of 6 days or less are just as effective as standard-term regimens of 7 days or more in terms of infection cure and prevention of recurrence. Considering the equivalent rates of clinical cure and relapse between short- and standard-course regimens, it could be inferred that short-course regimens might be a more optimal strategy for managing pediatric UTIs without increasing the risk of complications.

• Journal of Ginseng Research
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• v.47 no.3
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• pp.376-384
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• 2023

Background: Hepatic lipid disorder impaired mitochondrial homeostasis and intracellular redox balance, triggering development of non-alcohol fatty liver disease (NAFLD), while effective therapeutic approach remains inadequate. Ginsenosides Rc has been reported to maintain glucose balance in adipose tissue, while its role in regulating lipid metabolism remain vacant. Thus, we investigated the function and mechanism of ginsenosides Rc in defending high fat diet (HFD)-induced NAFLD. Methods: Mice primary hepatocytes (MPHs) challenged with oleic acid & palmitic acid were used to test the effects of ginsenosides Rc on intracellular lipid metabolism. RNAseq and molecular docking study were performed to explore potential targets of ginsenosides Rc in defending lipid deposition. Wild type and liver specific sirtuin 6 (SIRT6, 50721) deficient mice on HFD for 12 weeks were subjected to different dose of ginsenosides Rc to determine the function and detailed mechanism in vivo. Results: We identified ginsenosides Rc as a novel SIRT6 activator via increasing its expression and deacetylase activity. Ginsenosides Rc defends OA&PA-induced lipid deposition in MPHs and protects mice against HFD-induced metabolic disorder in dosage dependent manner. Ginsenosides Rc (20mg/kg) injection improved glucose intolerance, insulin resistance, oxidative stress and inflammation response in HFD mice. Ginsenosides Rc treatment accelerates peroxisome proliferator activated receptor alpha (PPAR-α, 19013)-mediated fatty acid oxidation in vivo and in vitro. Hepatic specific SIRT6 deletion abolished ginsenoside Rc-derived protective effects against HFD-induced NAFLD. Conclusion: Ginsenosides Rc protects mice against HFD-induced hepatosteatosis by improving PPAR-α-mediated fatty acid oxidation and antioxidant capacity in a SIRT6 dependent manner, and providing a promising strategy for NAFLD.

• Korean Journal of Clinical Laboratory Science
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• v.54 no.1
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• pp.38-48
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• 2022

Carcinoembryonic antigen (CEA) is an oncofetal antigen primarily detected in the peripheral blood of cancer patients, particularly in those with colorectal cancer. CEA is considered a valuable target for antigen-specific immunotherapy. In this study, we induced the anti-tumor immunity for CEA through the administration of a dendritic cell (DC) vaccine. However, there was a limitation in inducing tumor regression in the DC vaccinated mice. To enhance the efficacy of anti-tumor immunity in MC38/CEA2 tumor-bearing mice, we evaluated the effects of DC vaccine in combination with cyclophosphamide (CYP). Administration of CYP 100 mg/kg in mice resulted in significant inhibition of tumor growth in the 2-day tumor model, whereas a lower inhibition of tumor growth was seen in the 10-day tumor model. Therefore, the 10-day tumor model was selected for testing chemo-immunotherapy. The combined CYP and DC vaccine not only increased tumor antigen-specific immune responses but also induced synergistic anti-tumor immunity. Furthermore, the adverse effects of CYP such as weight loss and immunosuppression by regulatory T cells and myeloid-derived suppressor cells showed a significant reduction in the combined chemo-immunotherapy treatment compared with CYP alone. Our data suggest that chemoimmunotherapy with the DC vaccine may offer a new therapeutic strategy to induce a potent anti-tumor effect and reduce the adverse effects of chemotherapy.

• Journal of Life Science
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• v.32 no.3
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• pp.210-221
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• 2022

This study investigated the mechanisms underlying the anti-cancer effects of non-steroidal anti-inflammatory drugs (NSAIDs) in human cancer cells in combination with either N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor, or MHY2245, a new synthetic sirtuin 1 inhibitor. The results showed both DAPT and MHY2245 as novel chemosensitizers of human colon cancer KM12 and human hepatocellular carcinoma SNU475 cells to NSAIDs involving celecoxib and 2, 5-dimethyl celecoxib. The NSAID-induced cytotoxicity of these cells was significantly increased by DAPT and MHY2245 in a cyclooxygenase-2 independent manner. In addition, DAPT and MHY2245 reduced levels of p62, Notch1 intracellular domain, and multiple cancer stemness (CS)-related markers including Notch1, CD44, CD133, octamer-binding transcription factor 4, mutated p53 and c-Myc. However, the level of activating transcription factor 4 (ATF4) was enhanced, probably indicating the down-regulation of multiple CS-related markers by DAPT or MHY2245-mediated autophagy induction. Moreover, the NSAID-mediated reduction of p62/nuclear factor erythroid-derived 2-like 2 and CS-related marker proteins and the up-regulation of C/EBP homologous protein (CHOP)/ATF4 were accelerated by DAPT and MHY2245. As such, the combination of NSAID and either DAPT or MHY2245 resulted in higher cytotoxicity than NSAID alone by accelerating the down-regulation of multiple CS-related markers and PARP activation, indicating that both inhibitors promote NSAID-mediated autophagic cell death, possibly through the CHOP/ATF4 pathway. In conclusion, either combination strategy may be useful for the effective treatment of human cancer cells expressing CS-related markers.

• Korean Journal of Healthcare-Associated Infection Control and Prevention
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• v.21 no.2
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• pp.50-56
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• 2016

Background: Alternatives to carbapenem are increasingly needed to decrease the usage of carbapenem. We evaluated the possibility of using non-carbapenem antibiotics against urinary tract infections (UTI) caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). Methods: This retrospective study was performed at 2 university hospitals between October 2010 and December 2012. All diagnosed adult cases of ESBL-PE UTI were identified from the microbiological database. The subjects were divided into 3 groups based on the empirical antibiotic classes and susceptibility: carbapenem (C) group, susceptible non-carbapenem (SNC) group, and non-susceptible non-carbapenem (NSNC) group. Results: A total of 84 patients were eligible for analysis. For empirical therapy, 41, 23, and 20 patients were included in the NSNC, SNC, and C empirical groups, respectively. During the empirical therapy, 7 patients (17.1%) in the NSNC group, 18 patients (78.3%) in the SNC group, and 19 patients (78.3%) in the C group experienced clinical improvement. No significant difference was observed between the SNC and C empirical groups (P=0.192). Severe sepsis or shock was the predictor of empirical SNC treatment failure (P=0.048). There was a tendency to use carbapenem as a definite therapy in cases of NSNC. In contrast, empirical SNC was maintained as a definite therapy. Conclusion: SNC could be considered as an alternative to carbapenems for treating ESBL-PE UTI. This strategy might decrease the usage of carbapenem without clinical deterioration. However, it should be noted that SNC therapy may fail in the case of severe sepsis or shock.

• Tuberculosis and Respiratory Diseases
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• v.86 no.2
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• pp.82-93
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• 2023

Tuberculosis (TB) is a significant public health concern. Globally, TB is among the top 10 and the leading cause of death due to a single infectious agent. Providing standard anti-TB therapy for at least 6 months is recommended as one of the crucial strategies to control the TB epidemic. However, the long duration of TB treatment raised the issue of non-adherence. Non-adherence to TB therapy could negatively affect clinical and public health outcomes. Thus, directly observed therapy (DOT) has been introduced as a standard strategy to improve anti-TB medication adherence. Nonetheless, the DOT approach has been criticized due to inconvenience, stigma, reduced economic productivity, and reduced quality of life, which ultimately could complicate adherence issues. Apart from that, its effectiveness in improving anti-TB adherence is debatable. Therefore, digital technology could be an essential tool to enhance the implementation of DOT. Incorporating the health belief model (HBM) into digital technology can further increase its effectiveness in changing behavior and improving medication adherence. This article aimed to review the latest evidence regarding TB medication non-adherence, its associated factors, DOT's efficacy and its alternatives, and the use of digital technology and HBM in improving medication adherence. This paper used the narrative review methodology to analyze related articles to address the study objectives. Conventional DOT has several disadvantages in TB management. Integrating HBM in digital technology development is potentially effective in improving medication adherence. Digital technology provides an opportunity to improve medication adherence to overcome various issues related to DOT implementation.

• Korean Journal of School Psychology
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• v.16 no.3
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• pp.283-313
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• 2019

The purpose of this study was to develop and examine the effectiveness of 'Coping Resources Improvement Program' designed for emerging adults experiencing psychosocial difficulties during college to work transition. Based on transition model of Scholossberg(1995), the program was developed to intervene in 4S (Situation, Self, Support, Strategy) required in the transition. Participants included 31 job applicants who are senior or above and were assigned to the experimental group (N=10), comparison group (N=10), and control group (N=11). Data to verify effectiveness were collected pre-, mid-, and post treatment. Results indicated that the level of coping resources and psychosocial difficulties in the transition changed significantly after the program and those changes were still maintained after a month in the experimental group. However, there were no statistically significant changes on job-search burnout and career-adaptability in all groups. The implication and limitation of the study and the suggestions for the future studies were discussed.

• Journal of Food Hygiene and Safety
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• v.38 no.6
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• pp.508-516
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• 2023

The consumption of enoki mushrooms has been associated with cases of listeriosis produced by Listeria monocytogenes, highlighting the significance of sanitizing food-contact surface, such as the velcro used in welding processing of enoki mushrooms, to ensure microbial safety. We investigated the inhibitory activity of nine chemical disinfectants at regular concentrations against L. monocytogenes isolated from a mushroom farm environment. The bacterial suspension was prepared in phosphate buffered saline and mushroom extract broth and inoculated onto the velcro surface. After inoculation, most disinfectants reduced the initial 8 log CFU/coupon concentration by less than 2 log CFU/coupon during a 5-min treatment. Slightly acidic hypochlorous water showed a reduction of approximately 4 log CFU/coupon when tested for more than 30 min at the maximum allowable concentration of 200 mg/L. Sodium hypochlorite solution showed a reduction of approximately 5 log CFU/coupon when used at 100 mg/L for 60 min. Peracetic acid, at the maximum allowable concentration of 300 mg/L, showed the most effective reduction of 5 log CFU/coupon or more when the surface was treated with 37.5 mg/L for 30 min. These results indicate that peracetic acid can be used as the disinfectant strategy to control cross-contamination of L. monocytogenes on the velcro surface of plastic wrappers used in the welding processing of enoki mushrooms.

• The Transactions of the Korea Information Processing Society
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• v.13 no.6
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• pp.260-268
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• 2024

Cervical cancer is the fourth most common cancer in women worldwide, and more than 604,000 new cases were reported in 2020 alone, resulting in approximately 341,831 deaths. The Cox regression model is a major model widely adopted in cancer research, but considering the existence of nonlinear associations, it faces limitations due to linear assumptions. To address this problem, this paper proposes ResSurvNet, a new model that improves the accuracy of cervical cancer mortality prediction using ResNet's residual learning framework. This model showed accuracy that outperforms the DNN, CPH, CoxLasso, Cox Gradient Boost, and RSF models compared in this study. As this model showed accuracy that outperformed the DNN, CPH, CoxLasso, Cox Gradient Boost, and RSF models compared in this study, this excellent predictive performance demonstrates great value in early diagnosis and treatment strategy establishment in the management of cervical cancer patients and represents significant progress in the field of survival analysis.