• Title/Summary/Keyword: treatment strategy

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Enhancing the Anti-cancer Activity of Non-steroidal Anti-inflammatory Drug and Down-regulation of Cancer Stemness-related Markers in Human Cancer Cells by DAPT and MHY2245 (DAPT 및 MHY2245의 비스테로이드소염제(NSAID)의 항암 활성 증강 및 종양줄기세포관련 표지자 발현 감소 활성에 대한 분자적 기전)

  • Moon, Hyun-Jung;Kang, Chi-Dug;Kim, Sun-Hee
    • 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.

Use of Non-carbapenem Antibiotics in Patients with Urinary Tract Infection Caused by Extended-spectrum Beta-lactamase-producing Enterobacteriaceae (Extended-spectrum β-lactamase 를 생산하는 Enterobacteriaceae 요로감염에서 카바페넴 이외의 항생제 사용 가능성에 대한 고찰)

  • Seo, Yu Bin;Kim, Young Keun;Lee, Jacob;Song, Wonkeun
    • 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.

Improving Tuberculosis Medication Adherence: The Potential of Integrating Digital Technology and Health Belief Model

  • Mohd Fazeli Sazali;Syed Sharizman Syed Abdul Rahim;Ahmad Hazim Mohammad;Fairrul Kadir;Alvin Oliver Payus;Richard Avoi;Mohammad Saffree Jeffree;Azizan Omar;Mohd Yusof Ibrahim;Azman Atil;Nooralisa Mohd Tuah;Rahmat Dapari;Meryl Grace Lansing;Ahmad Asyraf Abdul Rahim;Zahir Izuan Azhar
    • 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.

The Development and Effects of a Group Counseling Program for Adaptive College to Work Transition through Enhancing Coping Resources (대학-직장 이행을 위한 대처자원 향상 집단상담 프로그램 개발 및 효과성 검증)

  • Kim, Ji Geun;Lee, JinKoo;Ki-Hak, Lee
    • 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.

Efficacy of Commercial Sanitizers for the Inactivation of Listeria monocytogenes on the Processing Equipment for Enoki Mushrooms (팽이버섯 재배 현장에서 Listeria monocytogenes의 성장을 억제하기 위한 살균 처리 기술 개발)

  • Kyung Min Park;Su-Bin Lee;Do-Young Jung;Song-Yi Choi;Injun Hwang;Se-Ri Kim
    • 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.

Antiproliferative Activity of Piceamycin by Regulating Alpha-Actinin-4 in Gemcitabine-Resistant Pancreatic Cancer Cells

  • Jee-Hyung Lee;Jin Ho Choi;Kyung-Min Lee;Min Woo Lee;Ja-Lok Ku;Dong-Chan Oh;Yern-Hyerk Shin;Dae Hyun Kim;In Rae Cho;Woo Hyun Paik;Ji Kon Ryu;Yong-Tae Kim;Sang Hyub Lee;Sang Kook Lee
    • Biomolecules & Therapeutics
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    • v.32 no.1
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    • pp.123-135
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    • 2024
  • Although gemcitabine-based regimens are widely used as an effective treatment for pancreatic cancer, acquired resistance to gemcitabine has become an increasingly common problem. Therefore, a novel therapeutic strategy to treat gemcitabine-resistant pancreatic cancer is urgently required. Piceamycin has been reported to exhibit antiproliferative activity against various cancer cells; however, its underlying molecular mechanism for anticancer activity in pancreatic cancer cells remains unexplored. Therefore, the present study evaluated the antiproliferation activity of piceamycin in a gemcitabine-resistant pancreatic cancer cell line and patient-derived pancreatic cancer organoids. Piceamycin effectively inhibited the proliferation and suppressed the expression of alpha-actinin-4, a gene that plays a pivotal role in tumorigenesis and metastasis of various cancers, in gemcitabine-resistant cells. Long-term exposure to piceamycin induced cell cycle arrest at the G0/G1 phase and caused apoptosis. Piceamycin also inhibited the invasion and migration of gemcitabine-resistant cells by modulating focal adhesion and epithelial-mesenchymal transition biomarkers. Moreover, the combination of piceamycin and gemcitabine exhibited a synergistic antiproliferative activity in gemcitabine-resistant cells. Piceamycin also effectively inhibited patient-derived pancreatic cancer organoid growth and induced apoptosis in the organoids. Taken together, these findings demonstrate that piceamycin may be an effective agent for overcoming gemcitabine resistance in pancreatic cancer.

Combined Effect of Afidopyropen, Chlorfenapyr and Cyantraniliprole to Insecticide-resistant Cotton Aphid, Aphis gossypii (Hemiptera: Aphididae) (살충제 저항성 목화진딧물에 대한 afidopyropen과 chlorfenapyr, cyantraniliprole의 혼합효과 평가)

  • Dong-Hyun Kang;Yuno Lee;Ha Hyeon Moon;Se Eun Kim;Hyun-Na Koo;Hyun Kyung Kim;Gil-Hah Kim
    • Korean journal of applied entomology
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    • v.63 no.1
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    • pp.53-61
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    • 2024
  • The susceptibility of Aphis gossypii populations collected from three fields (WJ, CC, and GS) was evaluated to three insecticides (afidopyropen, chlorfenapyr and cyantraniliprole) and three binary mixtures. Three field populations showed resistance ratios of over 100 to all insecticides. The Combination Index (CI), %M(synergism), Co-Toxicity Coefficient (CTC), Wadley Ratio (WR), Synergism Ratio (SR) and Abbott Ratio (AR) were used to evaluate combined effect of the insecticides. Afidopyropen + chlorfenapyr (CI ≤ 0.16; %M(synergism) ≥ 94; CTC ≥ 764.5; WR ≥ 6.4; SR ≥ 6.9 and AR ≥ 1.1) showed a synergism in all filed populations. WJ and CC populations showed a synergism in all binary mixtures of insecticides, but GS population showed an antagonism for chlorfenapyr + cyantraniliprole (CI, 1.63; %M(synergism), 30; CTC, 64.0; WR, 0.6 and AR, 0.54) and afidopyropen + cyantraniliprole (CI, 6.7; %M(synergism), 1; CTC, 19.8; WR, 0.2 and AR ≤ 0.55). All mixtures (afidopyropen + chlorfenapyr, chlorfenapyr + cyantraniliprole and afidopyropen + cyantraniliprole) showed a control value of over 99% after 21 days of treatment in the field. This study highlights that binary mixtures of three insecticides serve as an effective control strategy for A. gossypii.

High-fat diet alters the thermogenic gene expression to β-agonists or 18-carbon fatty acids in adipocytes derived from the white and brown adipose tissue of mice

  • Seonjeong Park;Seung A Ock;Yun Jeong Park;Yoo-Hyun Lee;Chan Yoon Park;Sunhye Shin
    • Journal of Nutrition and Health
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    • v.57 no.2
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    • pp.171-184
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    • 2024
  • Purpose: Although activating thermogenic adipocytes is a promising strategy to reduce the risk of obesity and related metabolic disorders, emerging evidence suggests that it is difficult to induce adipocyte thermogenesis in obesity. Therefore, this study aimed to investigate the regulation of adipocyte thermogenesis in diet-induced obesity. Methods: Adipose progenitor cells were isolated from the white and brown adipose tissues of control diet (CD) or high-fat diet (HFD) fed mice, and fully differentiated white and brown adipocytes were treated with β-agonists or 18-carbon fatty acids for β-adrenergic activation or peroxisome proliferator-activated receptor (PPAR) activation. Results: Compared to the CD-fed mice, the expression of uncoupling protein 1 (Ucp1) was lower in the white adipose tissue of the HFD-fed mice; however, this was not observed in the brown adipose tissue. The expression of peroxisome proliferator-activated receptor gamma (Pparg) was lower in the brown adipose progenitor cells isolated from HFD-fed mice than in those isolated from the CD-fed mice. Norepinephrine (NE) treatment exerted lesser effect on peroxisome proliferator-activated receptor-γ coactivator (Pgc1a) upregulation in white adipocytes derived from HFD-fed mice than those derived from CD-fed mice. Regardless which 18-carbon fatty acids were treated, the expression levels of thermogenic genes including Ucp1, Pgc1a, and positive regulatory domain zinc finger region protein 16 (Prdm16) were higher in the white adipocytes derived from HFD-fed mice. Oleic acid (OLA) and γ-linolenic acid (GLA) upregulated Pgc1a expression in white adipocytes derived from HFD-fed mice. Brown adipocytes derived from HFD-fed mice had higher expression levels of Pgc1a and Prdm16 compared to their counterparts. Conclusion: These results indicate that diet-induced obesity may downregulate brown adipogenesis and NE-induced thermogenesis in white adipocytes. Also, HFD feeding may induce thermogenic gene expression in white and brown primary adipocytes, and OLA and GLA could augment the expression levels.

Cox Model Improvement Using Residual Blocks in Neural Networks: A Study on the Predictive Model of Cervical Cancer Mortality (신경망 내 잔여 블록을 활용한 콕스 모델 개선: 자궁경부암 사망률 예측모형 연구)

  • Nang Kyeong Lee;Joo Young Kim;Ji Soo Tak;Hyeong Rok Lee;Hyun Ji Jeon;Jee Myung Yang;Seung Won Lee
    • 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.

Ecological Niche of Quercus acutissima and Quercus variabilis (상수리나무와 굴참나무의 생태적 지위에 관한 연구)

  • Kim, Hae-Ran;Jeong, Heon-Mo;Kim, Hyea-Ju;You, Young-Han
    • Korean Journal of Environmental Biology
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    • v.26 no.4
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    • pp.385-391
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    • 2008
  • In Korea, Quercus acutissima distributed in good condition with high nutrients and moisture content, but Quercus variabilis in dry soil or rock habitate. In order to understand this ecological distribution of Q. acutissima and Q. variabilis, we cultivated the seedlings of two oak species treated with light, soil moisture and nutrient gradients each four level, from May to October in glass house. Then we measured the ecological niche breadth and niche overlap of the two species, and analyzed the relationship of competition using cluster analysis and PCA ordination. Ecological niche breadths of Q. acutissima under moisture and nutrient treatments were slightly wider than those under light one. Among 14 characters measured, 6 characters related with length items were wider in all the environmental treatments, but 8 characters connected with weight terms narrower in light treatment. Ecological niche breadths of Q. variabilis under moisture and nutrient treatment were wider than those of light one. Ecological niche of Q. acutissima was wider than those of Q. variabilis in all the environmental treatments. Ecological overlap between two species was higher with a range of 0.87$\sim$0.92, especially higher in soil moisture factor. These results means that Q. acutissima is more competitive than Q. variabilis, especially in soil moisture condition. Two species were ordinated with distinct group based on 9 characters. From these results, it can be explained that what Q. variabilis distributed in bad soil condition is due to the escape strategy, because of its low competitive ability to Q. acutissima in natural communities.