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Ginsenoside F1 attenuates pirarubicin-induced cardiotoxicity by modulating Nrf2 and AKT/Bcl-2 signaling pathways

  • Yang Zhang;Jiulong Ma;Shan Liu;Chen Chen;Qi Li;Meng Qin;Liqun Ren
    • Journal of Ginseng Research
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    • v.47 no.1
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    • pp.106-116
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    • 2023
  • Background: Pirarubicin (THP) is an anthracycline antibiotic used to treat various malignancies in humans. The clinical usefulness of THP is unfortunately limited by its dose-related cardiotoxicity. Ginsenoside F1 (GF1) is a metabolite formed when the ginsenosides Re and Rg1 are hydrolyzed. However, the protective effects and underlying mechanisms of GF1 on THP-induced cardiotoxicity remain unclear. Methods: We investigated the anti-apoptotic and anti-oxidative stress effects of GF1 on an in vitro model, using H9c2 cells stimulated by THP, plus trigonelline or AKT inhibitor imidazoquinoxaline (IMQ), as well as an in vivo model using THP-induced cardiotoxicity in rats. Using an enzyme-linked immunosorbent test, the levels of malondialdehyde (MDA), brain natriuretic peptide (BNP), creatine kinase (CK-MB), cardiac troponin (c-TnT), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and glutathione (GSH) were determined. Nuclear factor (erythroid-derived2)-like 2 (Nrf2) and the expression of Nrf2 target genes, including heme oxygenase-1 (HO-1), glutathione-S-transferase (Gst), glutamate-cysteine ligase modifier subunit (GCLM), and expression levels of AKT/Bcl-2 signaling pathway proteins were detected using Western blot analysis. Results: THP-induced myocardial histopathological damage, electrocardiogram (ECG) abnormalities, and cardiac dysfunction were reduced in vivo by GF1. GF1 also decreased MDA, BNP, CK-MB, c-TnT, and LDH levels in the serum, while raising SOD and GSH levels. GF1 boosted Nrf2 nuclear translocation and Nrf2 target gene expression, including HO-1, Gst, and GCLM. Furthermore, GF1 regulated apoptosis by activating AKT/Bcl-2 signaling pathways. Employing Nrf2 inhibitor trigonelline and AKT inhibitor IMQ revealed that GF1 lacked antioxidant and anti-apoptotic effects. Conclusion: In conclusion, GF1 was found to alleviate THP-induced cardiotoxicity via modulating Nrf2 and AKT/Bcl-2 signaling pathways, ultimately alleviating myocardial oxidative stress and apoptosis.

The Role of Workers' Awareness of Disaster Safety Management and Disaster Management Capabilities of Companies and Governments for Infectious Disease Disaster Management: Focused on Workers in the Automobile Manufacturing Industry (감염병 재난관리에서 근로자의 재난안전관리 인식이 지방정부와 기업의 재난관리 역량 및 성과에 미치는 영향에 대한 연구: 자동차 제조업 종사자를 중심으로)

  • Han Hwangbo;Chang Yull Lee;Ha Kyoung Kim;Byoung Gwon Kim
    • Journal of the Society of Disaster Information
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    • v.19 no.3
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    • pp.451-470
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    • 2023
  • Purpose: Since COVID-19 was first discovered in China in December 2019, it has rapidly spread around the world, causing serious economic and social problems not only in individuals' lives, but also in businesses and countries. Individuals, businesses, and governments have all made various efforts to prevent the spread of COVID-19. Although the roles of individuals, companies, and the government are important to respond to and manage infectious diseases, previous studies have only partially studied the roles. Therefore, in this study, the roles of individuals, companies, and the government to achieve results in responding to infectious diseases disaster management A comprehensive study was conducted on this issue, and it was attempted to understand the impact of workers' perceptions of infectious disease disaster management and government and corporate capabil]ities on disaster response performance. Method: The survey was conducted for workers in the automobile manufacturing industry in Ulsan, Gyeongju, and Yangsan, and frequency analysis, factor analysis, correlation analysis, and regression analysis were performed. Result: It was found that worker perception had a positive effect on both government and corporate capabilities as well as disaster management performance. In addition, government capacity and corporate capacity had a positive effect on disaster management performance. Conclusion: The results of this study are meaningful in that they reveal that not only workers' perceptions but also the capabilities of the government and companies are important to achieve disaster response performance. In addition, workers should make good use of opportunities for education and participation provided by the government and corporations, and make the most social efforts that workers can make.

The Effect of Smart Safety and Health Activities on Workers' Intended Behavior (스마트 안전보건활동이 근로자의 의도된 행동에 미치는 영향)

  • Choonhwan Cho
    • Journal of the Society of Disaster Information
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    • v.19 no.3
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    • pp.519-531
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    • 2023
  • With the aim of preventing safety accidents at construction sites, the company aims to create safe behaviors intended through variables called smart safety and health activities to help reduce industrial accidents. Purpose: It analyzes how smart safety and health activities affect accidents caused by unsafe behavior and changes in worker behavior, which is the root cause, and verifies the hypothesis that it helps prevent safety accidents and protect workers' lives. Method: Smart safety and health activities were selected as independent variables (X), and intended safety and anxiety, which are workers' behavioral intentions, were set as dependent variables (Y), attitude and subjective norms, and planned behavioral control as parameters (M). Exploratory factor analysis, discriminant validity analysis, and intensive validity analysis of safety and health activities were used to analyze the scale's reliability and validity. To verify the hypothesis of behavior change, the study was verified through Bayesian model analysis and MC simulation's probability density distribution. Result: It was found that workers who experienced smart safety and health activities at construction sites had the highest analysis of reducing unstable behavior and performing intended safety behavior. The research hypothesis that this will affect changes in worker behavior has been proven, the correlation between variables has been verified in the structural equation and path analysis of the research analysis, and it has been confirmed that smart safety and health activities can control and reduce worker instability. Conclusion: Smart safety and health activities are a very important item to prevent accidents and change workers' behavior at construction sites.

A Study on the Outport for the conquest of Usanguk through the Location Analysis of Natural Environment in the Port of the East Coast (동해안 항포구의 자연환경 입지분석을 통한 우산국 정벌의 출항지 검토)

  • JANG, Dong-Ho;KIM, Jang-soo
    • Journal of The Geomorphological Association of Korea
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    • v.17 no.3
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    • pp.59-75
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    • 2010
  • In this study, location evaluation of the natural environment of ports in the Joseon Dynasty was carried out to investigate the outport of east coast for the conquest of Usanguk. As a result of study, there were 55 ports and naval stations in the Joseon Dynasty, including the Yeongokpo, Aninpo, Samcheokpo, Susanpo, and Wolsongpo. As a result of the restoration work in the sea level that was done in the sixth century, the sea level at that time was about 1m higher than that at present. In terms of the location type, three types were identified via natural-environment analysis. Location type I consists of a total of 21 ports suitable for defense due to the sand spit in all the sides and because it is located in the bay of small and medium rivers. Location type II is composed of 22 ports close to the open seas, and location type III consists of a total of 12 ports centering on the bay. A total of nine ports satisfied the location factor in the shortest distance analysis(targeting location type I), 15 ports in the slope analysis, 13 ports in the hinterland analysis, 13 ports in the visibility analysis, and 11 ports in the ocean current analysis. It was found in the final evaluation that the I level regions consist of two ports(Obunjin and Mangyangjin). Obunjin has a location characteristic that is advantageous for defense and that makes it suitable to serve as an anchorage harbor for a large-scale fleet as its water level is deep and as it has a wide embayment. In conclusion, Obunjin is considered the outport that has the highest possibility of serving as Isabu's departure port for the conquest of Usanguk.

Clinical Outcomes and Contributors in Contemporary Kidney Transplantation: Single Center Experience (근래의 신장이식 임상성적과 관련인자들: 단일기관 연구)

  • Ahn, Jae-Sung;Park, Kyung Sun;Park, Jongha;Chung, Hyun Chul;Park, Hojong;Park, Sang Jun;Cho, Hong Rae;Lee, Jong Soo
    • Korean Journal of Transplantation
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    • v.31 no.4
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    • pp.182-192
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    • 2017
  • Background: In recent years, introduction of novel immunosuppressive agents and its proper implementation for clinical practice have contributed to improving clinical outcomes of kidney transplantation (KT). Here, we report clinical outcomes of KTs and related risk factors. Methods: From July 1998 to June 2016, 354 KTs (182 from living and 172 from deceased donors) have been performed at Ulsan University Hospital. We retrospectively reviewed the clinical characteristics and outcomes of KT recipients, then estimated graft and patient survival rate were estimated and analyzed risk factors using Cox-regression. Results: The median follow-up period was 53 months (range; 3 to 220 months). The mean ages of recipients and donors were 45.0 years (SD, 12.5) and 44.7 years (SD, 13.6) years, respectively. During follow-up, 18 grafts were lost and 5- and 10-year death-censored graft survival was 96.7% and 91.5%, respectively. Biopsy-proven acute rejection (BPAR) occurred in 71 patients (55 cases of acute cellular rejection and 16 of antibody-mediated rejection). Cox-regression analysis showed that BPAR was a risk factor related to graft loss (hazard ratio [HR], 14.38; 95% confidence interval [CI], 3.79 to 54.53; P<0.001). In addition, 15 patients died, and the 5- and 10-year patient survival was 97.2% and 91.9%, respectively. Age ≥60 years (HR, 6.03; 95% CI, 1.12 to 32.61; P=0.037) and diabetes (HR, 6.18; 95% CI, 1.35 to 28.22; P=0.019) were significantly related to patient survival. Conclusions: We experienced excellent clinical outcomes of KT in terms of graft failure and patient survival despite the relatively high proportion of deceased donors. Long-term and short-term clinical outcomes have improved in the last two decades.

Neuroprotective effects of antioxidant constituents isolated from Opuntia ficus-indica var. saboten Makino

  • K.J. Jung;Lee, E.H.;Kim, H.J.;Lee, J.Y.;Y.S. Song;Lee, Y.H.;J. Cho;Park, M.;Park, H.
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 2003.11a
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    • pp.63-63
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    • 2003
  • Opuntia ficus-indicavar. saboten Makino (Cactaceae) is a tropical or subtropical plant that has been widely used as folk medicine for the treatment of diabetes, asthma, burn, edema and gastritis. The purposes of the present study were to identify antioxidant constituents from fruits and stems of the plant cultivated in Cheju island, Korea, and examine their in vitro neuroprotective activities. Using a chromatographic fractionation method, ten chemical constituents were isolated from ethyl acetate extracts. By means of chemical and spectroscopic methods, those were identified as eight flavonoids such as kaempherol (a), quercetin (b), kaempferol 3-methyl ether (c), quercetin 3-methyl ether (d), narcissin (e), dihydrokaernpferol (f), dihydroquercetin (g) and erioclictyol (h), and two terpenoids such as 3-oxo-${\alpha}$-ionol-${\beta}$-d-glucopyranoside (i) and roseoside (j). Among the isolated compounds, comrounds c~e and h~j were those reported for the first titre from the plant. Compounds b, d and g showed DPPH free radical scavenging activities with IC$\sub$50/ values of 28, 19 and 31, ${\mu}$M respectively. Compounds d and g also inhibited iron-dependent lipid peroxidation with IC$\sub$50/ values of 2.4 and 3.5 ${\mu}$M. In a primary rat cortical neuronal cell culture system, compounds b, d and g inhibited xanthine/xanthine oxidase-induced (IC$\sub$50/ values of 18.2, 2.1 and 54.6 ${\mu}$M) and H$_2$O$_2$-induced (IC$\sub$50/ values of 13.6, 1.9 and 25.7 ${\mu}$M) cytotoxicities. In addition, compounds d and g inhibited NMDA-induced excitotoxicity by 21 and 33%, and only compound d inhibited growth factor withdrawal-induced apoptosis by 31% at a tested concentration of 3 ${\mu}$M. The results suggest that the antioxidant constituents with in vitroneuroprotective activities may serve as lead chemicals for the development of neuroprotective agent.

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The responsibility of C-terminal domain in the thermolabile haemolysin activity of Vibrio parahaemolyticus and inhibition treatments by Phellinus sp. extracts

  • Tran Thi Huyen;Ha Phuong Trang;Nguyen Thi-Ngan;Bui Dinh-Thanh;Le Pham Tan Quoc;Trinh Ngoc Nam
    • Fisheries and Aquatic Sciences
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    • v.26 no.3
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    • pp.204-215
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    • 2023
  • The thermolabile haemolysin (tlh) of Vibrio parahaemolyticus (Vptlh) from V. parahaemolyticus is a multiple-function enzyme, initially describes as a haemolytic factor activated by lecithin and phospholipase A2 enzymatic activity (Shinoda, 1991; Vazquez-Morado, 2021; Yanagase et al., 1970). Until now, the tlh structure has hypothesized including N-terminal and C-terminal domain, but what domain of the Vptlh structure does the haemolytic activity has not been refined yet. In this study, a 450-bp VpTLH nucleotide sequence of the entire Vptlh gene encoded the C-terminal domain cloned firstly to examine its responsibility in the activity of the Vptlh. The C-terminal domain fused with a 6-His-tag named the His-tag-VpC-terminal domain was expressed successfully in soluble form in the BL21 (DE3) PlysS cell. Remarkably, both expression and purification results confirmed a high agreement in the molecular weight of the His-tag-VpC-terminal domain was 47 kDa. This work showed the His-tag-VpC-terminal domain lysed the erythrocyte membranes in the blood agar and the phosphate buffered saline (0.9%) media without adding the lecithin substrate of the phospholipase enzyme. Haemolysis occurred at all tested diluted concentrations of His-tag-VpC-terminal domain (p < 0.05), providing evidence for the independent haemolytic activity of the His-tag-VpC-terminal domain. The content of 100 ㎍ of the His-tag-VpC-terminal domain brought the highest haemolytic activity of 80% compared to that in the three remaining contents. Significantly, the His-tag-VpC-terminal domain demonstrated not to involve the phospholipase activity in Luria-Bertani agar supplemented with 1% (vol/vol) egg yolk emulsion. All results proved the vital responsibility of the His-tag-VpC-terminal domain in causing the haemolytic activity without the required activation by the phospholipase enzyme. Raw extracts of Phellinus igniarus and Phellinus pipi at 10-1 mg/mL inhibited the haemolytic activity of the His-tag-VpC-terminal domain from 67.7% to 87.42%, respectively. Hence applying the His-tag-VpC-terminal domain as a simple biological material to evaluate quickly potential derivatives against the Vptlh in vivo conditions will accessible and more advantageous than using the whole of the Vptlh.

A Study on the Physical Characteristics of Grout Material for Backfilling Ground Heat Exchanger (지중 열교환기용 뒤채움재의 물리적 특성 연구)

  • Choi, Hang-Seok;Lee, Chul-Ho;Choi, Hyo-Pum;Woo, Sang-Baik
    • Journal of the Korean Geotechnical Society
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    • v.24 no.1
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    • pp.37-49
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    • 2008
  • A geothermal heat pump system is a preferable alternative energy system in Korea because it uses the heat energy of the earth, which is environmentally friendly and inexhaustible. In order to characterize the thermal conductivity and viscosity of grout materials used for backfilling ground heat exchangers, nine bentonite grouts, one marine clay from Boryung, and cement grouts adapted in the United State have been considered in this study. The bentonite grouts indicate that the thermal conductivity and viscosity increase with the content of bentonite or filler (silica sand). In addition, material segregation can be observed when the viscosity of grout is relatively low. The marine clay turns out to be unsuitable for backfilling the ground heat exchanger due to its insufficient swelling potential. The saturated cement grouts appear to possess much higher thermal conductivity than the saturated bentonite grouts, and the reduction of thermal conductivity in the cement grouts after drying specimens is less than that in the case of the bentonite grouts. Maintaining the moisture content of grouts is a crucial factor in enhancing the efficiency of ground heat exchangers.

Morbidity and Mortality Trends in Preterm Infants of <32 Weeks Gestational Age with Severe Intraventricular Hemorrhage : A 14-Year Single-Center Retrospective Study

  • Eui Kyung Choi;Hyo-jeong Kim;Bo-Kyung Je;Byung Min Choi;Sang-Dae Kim
    • Journal of Korean Neurosurgical Society
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    • v.66 no.3
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    • pp.316-323
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    • 2023
  • Objective : Owing to advances in critical care treatment, the overall survival rate of preterm infants born at a gestational age (GA) <32 weeks has consistently improved. However, the incidence of severe intraventricular hemorrhage (IVH) has persisted, and there are few reports on in-hospital morbidity and mortality. Therefore, the aim of the present study was to investigate trends surrounding in-hospital morbidity and mortality of preterm infants with severe IVH over a 14-year period. Methods : This single-center retrospective study included 620 infants born at a GA <32 weeks, admitted between January 2007 and December 2020. After applying exclusion criteria, 596 patients were included in this study. Infants were grouped based on the most severe IVH grade documented on brain ultrasonography during their admission, with grades 3 and 4 defined as severe. We compared in-hospital mortality and clinical outcomes of preterm infants with severe IVH for two time periods : 2007-2013 (phase I) and 2014-2020 (phase II). Baseline characteristics of infants who died and survived during hospitalization were analyzed. Results : A total of 54 infants (9.0%) were diagnosed with severe IVH over a 14-year period; overall in-hospital mortality rate was 29.6%. Late in-hospital mortality rate (>7 days after birth) for infants with severe IVH significantly improved over time, decreasing from 39.1% in phase I to 14.3% in phase II (p=0.043). A history of hypotension treated with vasoactive medication within 1 week after birth (adjusted odds ratio, 7.39; p=0.025) was found to be an independent risk factor for mortality. When comparing major morbidities of surviving infants, those in phase II were significantly more likely to have undergone surgery for necrotizing enterocolitis (NEC) (29.2% vs. 0.0%; p=0.027). Additionally, rates of late-onset sepsis (45.8% vs. 14.3%; p=0.049) and central nervous system infection (25.0% vs. 0.0%; p=0.049) were significantly higher in phase II survivors than in phase I survivors. Conclusion : In-hospital mortality in preterm infants with severe IVH decreased over the last decade, whereas major neonatal morbidities increased, particularly surgical NEC and sepsis. This study suggests the importance of multidisciplinary specialized medical and surgical neonatal intensive care in preterm infants with severe IVH.

The Prediction of Survival of Breast Cancer Patients Based on Machine Learning Using Health Insurance Claim Data (건강보험 청구 데이터를 활용한 머신러닝 기반유방암 환자의 생존 여부 예측)

  • Doeggyu Lee;Kyungkeun Byun;Hyungdong Lee;Sunhee Shin
    • Journal of Korea Society of Industrial Information Systems
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    • v.28 no.2
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    • pp.1-9
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    • 2023
  • Research using AI and big data is also being actively conducted in the health and medical fields such as disease diagnosis and treatment. Most of the existing research data used cohort data from research institutes or some patient data. In this paper, the difference in the prediction rate of survival and the factors affecting survival between breast cancer patients in their 40~50s and other age groups was revealed using health insurance review claim data held by the HIRA. As a result, the accuracy of predicting patients' survival was 0.93 on average in their 40~50s, higher than 0.86 in their 60~80s. In terms of that factor, the number of treatments was high for those in their 40~50s, and age was high for those in their 60~80s. Performance comparison with previous studies, the average precision was 0.90, which was higher than 0.81 of the existing paper. As a result of performance comparison by applied algorithm, the overall average precision of Decision Tree, Random Forest, and Gradient Boosting was 0.90, and the recall was 1.0, and the precision of multi-layer perceptrons was 0.89, and the recall was 1.0. I hope that more research will be conducted using machine learning automation(Auto ML) tools for non-professionals to enhance the use of the value for health insurance review claim data held by the HIRA.