• BMB Reports
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• v.55 no.12
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• pp.609-614
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• 2022

Mutation of the gene for adenomatous polyposis coli (APC), as seen in Apc^Min/+ mice, leads to intestinal adenomas and carcinomas via stabilization of β-catenin. Transmembrane 4 L six family member 5 (TM4SF5) is involved in the development of non-alcoholic fatty liver disease, fibrosis, and cancer. However, the functional linkage between TM4SF5 and APC or β-catenin has not been investigated for pathological outcomes. After interbreeding Apc^Min/+ with TM4SF5-overexpressing transgenic (Tg^TM4SF5) mice, we explored pathological outcomes in the intestines and livers of the offspring. The intestines of 26-week-old dual-transgenic mice (Apc^Min/+:Tg^TM4SF5) had intramucosal adenocarcinomas beyond the single-crypt adenomas in Apc^Min/+ mice. Additional TM4SF5 overexpression increased the stabilization of β-catenin via reduced glycogen synthase kinase 3β (GSK3β) phosphorylation on Ser9. Additionally, the livers of the dualtransgenic mice showed distinct sinusoidal dilatation and features of hepatic portal hypertension associated with fibrosis, more than did the relatively normal livers in Apc^Min/+ mice. Interestingly, TM4SF5 overexpression in the liver was positively linked to increased GSK3β phosphorylation (opposite to that seen in the colon), β-catenin level, and extracellular matrix (ECM) protein expression, indicating fibrotic phenotypes. Consistent with these results, 78-week-old Tg^TM4SF5 mice similarly had sinusoidal dilatation, immune cell infiltration, and fibrosis. Altogether, systemic overexpression of TM4SF5 aggravates pathological abnormalities in both the colon and the liver.

• The Korea Journal of Herbology
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• v.38 no.2
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• pp.17-26
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• 2023

Objectives : A persistent inflammatory response can cause diseases such as fibrosis, cancer, and allergies. This study aimed to investigate the anti-inflammatory activity of Curcumae longae Rhizoma and Cinnamomi Ramulus Mixture (CCM) in lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Methods : The total polyphenol and flavonoid contents of CCM were confirmed through an in vitro experiment. Also, radical scavenging activities of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and Hydroxyl were confirmed. Moreover, ferric reducing antioxidant power (FRAP) activity were confirmed. After, CCM (50, 100, and 200 ㎍/mL) were applied to 0.1 ㎍/mL LPS-stimulated RAW264.7 cells. The levels of nitric oxide (NO) and pro-inflammatory cytokines in the supernatant fraction were determined. Also, the expressions of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) pathways were detected using Western blot. Results : As a result of in vitro experiments, there was an excellent antioxidant activity in CCM-treated cells. In addition, in RAW264.7 cells stimulated with LPS, the increased NO level was inhibited in a concentration-dependent manner by the treatment of CCM. In addition, inflammatory cytokines production were significantly inhibited in a concentration-dependent manner in CCM-treated group. CCM treatment significantly decreased the protein expressions of MAPKs. Moreover, the expressions of NF-κBp65 and cyclooxygenase-2 (COX-2) were significantly decreased when 200 mg/kg of CCM was applied, and phospho-inhibitor of nuclear factor kappa B-α (p-IκBα) and inducible nitric oxide synthase (iNOS) were significantly decreased at all concentrations treated with CCM. Conclusion : Our findings show that CCM exhibited excellent antioxidant activity and exhibited superior anti-inflammatory effect through the MAPKs and NF-κB pathways in LPS-stimulated RAW 264.7 macrophages.

• Journal of Environmental Health Sciences
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• v.49 no.2
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• pp.108-117
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• 2023

Background: When particles are absorbed into the human body, they penetrate deep into the lungs and interact with the tissues of the body. Heavy metals in PM_2.5 can cause various diseases. The main source of PM_2.5 emissions in South Korea's atmosphere has been surveyed to be places of business. Objectives: The concentration of heavy metals in PM_2.5 near the Ulsan Industrial Complex was measured and a health risk assessment was performed for residents near the industrial complex for exposure to heavy metals in PM_2.5. Methods: Concentrations of heavy metals in PM_2.5 were measured at four measurement sites (Ulsan, Mipo, Onsan, Maegok) near the industrial complexes. Heavy metals were analyzed according to the Air Pollution Monitoring Network Installation and Operation Guidelines presented by the National Institute of Environmental Research. Among them, only five substances (Mn, Ni, As, Cd, Cr⁶⁺) were targeted. The risk assessment was conducted on inhalation exposure for five age groups, and the excess cancer risk and hazard quotient were calculated. Results: In the risk assessment of exposure to heavy metals in PM_2.5, As, Cd, and Cr⁶⁺ exceeded the risk tolerance standard of 10^-6 for carcinogenic hazards. The highest hazard levels were observed in Onsan and Mipo industrial complexes. In the case of non-carcinogenic hazards, Mn was identified as exceeding the hazard tolerance of 1, and it showed the highest hazard in the Ulsan Industrial Complex. Conclusions: This study presented a detailed health risk from exposure to heavy metals in PM_2.5 by industrial complexes located in Ulsan among five age groups. It is expected to be utilized as the basis for preparing damage control and industrial emission reduction measures against PM_2.5 exposure at the Ulsan Industrial Complex.

• Journal of Radiopharmaceuticals and Molecular Probes
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• v.7 no.2
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• pp.105-111
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• 2021

⁸⁹Zr is a positron-emitting radioisotope, which has known as well-suited radioisotope for use in a monoclonal antibody-based imaging agent for immuno-PET. The purpose of this study was to quantitatively evaluate the diagnostic ability of general trastuzumab and thio-trastuzumab as HER2 positive receptors based on Df hexadentate iron chelator. Desferrioxamine-p-SCN (Df-Bz-NCS) and desferroixamine-maleimide (Df-Mal) were purchased from Macrocyclics (Dallas, TX, USA). The trastuzumab was purchased from Roche (Schweiz), and thio-trastuzumab was obtained from professor Hyo-Jeong Hong group (Kangwon National University). The radioisotope ⁸⁹Zr was produced by domestic purification system and KIRAMS using medical cyclotron (50 MeV, Scantronix). The conjugates of Df-trastuzumab and Df-thio-trastuzumab were prepared with Df-Bz-NCS and Df-Mal under basic aqueous solution (pH 8-9) at room temperature, respectively. The conjugates purified by PD-10 column were mixed with dried ⁸⁹Zr chloride. ⁸⁹Zr-labeled conjugates were purified and concentrated by Amicon ultra centrifugal filter. The preparation step and time of ⁸⁹Zr-labeled conjugates was shorted as 4 steps within 2 hours. ⁸⁹Zr-labeled conjugates showed the highly radiochemical purity of over 98%, and were very stable until 7 days by the analysis of radio-ITLC method. Each radio-labeled conjugates were also exhibited the highly stability in both PBS buffer and mouse serum. Immuno-PET imaging of ⁸⁹Zr-labeled conjugates in mice bearing gastric cancer xenograft tumors with HER2 expression showed high tumor uptake in the NCI-N87 HER2-expressing. However, ⁸⁹Zr-Df-Mal-thio-trastuzumab showed a relatively lower tumor-to-background ratio than ⁸⁹Zr-Df-Bz-trastuzumab, as well as whole-body distribution. In the results, ⁸⁹Zr-Df-Bz-trastuzumab was evaluated to have a relatively higher HER2 diagnostic ability than ⁸⁹Zr-Df-Mal-thio-trastuzumab.

• Journal of Environmental Health Sciences
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• v.49 no.4
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• pp.218-227
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• 2023

Background: Since 2019, the Ministry of Environment has implemented a seasonal fine dust management system from December to March, targeting high PM_2.5 levels with the aim of reducing PM_2.5 concentrations and protecting public health. The focus of improving the seasonal management system lies in the atmospheric PM_2.5 levels. Considering the primary goal of protecting public health, it is necessary to analyze the policy effects from an exposure perspective rather than a concentration-based approach. Objectives: This study aims to quantitatively assess the improvement of indoor PM_2.5 levels and the health impacts of the seasonal management system by comparing the periods before and during its implementation in residential environments. Methods: PM_2.5 concentrations within residential environments in a metropolitan area were measured using an optical particle counter (IAQ-C7, K-weather, Ltd, Korea) at one-minute intervals during the pre-implementation period (November 21~25, 2022) and during the implementation period (December 19~23, 2022). Based on the measured PM_2.5 concentrations, a quantitative evaluation of cancer and mortality risks was conducted according to age and gender. Results: The results of comparing indoor and outdoor PM_2.5 concentrations before and during the implementation of the seasonal management system showed a decrease of approximately 56.6% and 47.9%, respectively. Health risk assessments revealed that both the safety-limit-based and safety-target-based Hazard Quotients (HQ) exceeded the threshold of 0.1 for children under 19 years of age, both before and after the implementation. The mortality risk decreased by approximately 47.9% after the implementation, with children aged 0-9 showing the highest mortality risk at 0.9%. Conclusions: The findings of this study confirmed the positive health impacts of the seasonal management system across all age groups, particularly children under 19 who are more vulnerable to fine dust exposure.

• Nuclear Engineering and Technology
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• v.55 no.8
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• pp.2935-2940
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• 2023

A polystyrene phantom was developed following the guidance of the International Atomic Energy Association (IAEA) for gamma knife (GK) quality assurance. Its performance was assessed by measuring the absorbed dose rate to water and dose distributions. The phantom was made of polystyrene, which has an electron density (1.0156) similar to that of water. The phantom included one outer phantom and four inner phantoms. Two inner phantoms held PTW T31010 and Exradin A16 ion chambers. One inner phantom held a film in the XY plane of the Leksell coordinate system, and another inner phantom held a film in the YZ or ZX planes. The absorbed dose rate to water and beam profiles of the machine-specific reference (msr) field, namely, the 16 mm collimator field of a GK Perfexion^TM or Icon^TM, were measured at seven GK sites. The measured results were compared to those of an IAEA-recommended solid water (SW) phantom. The radius of the polystyrene phantom was determined to be 7.88 cm by converting the electron density of the plastic, considering a water depth of 8 g/cm². The absorbed dose rates to water measured in both phantoms differed from the treatment planning program by less than 1.1%. Before msr correction, the PTW T31010 dose rates (PTW Freiberg GmbH, New York, NY, USA) in the polystyrene phantom were 0.70 (0.29)% higher on average than those in the SW phantom. The Exradin A16 (Standard Imaging, Middleton, WI, USA) dose rates were 0.76 (0.32)% higher in the polystyrene phantom. After msr correction factors were applied, there were no statistically significant differences in the A16 dose rates measured in the two phantoms; however, the T31010 dose rates were 0.72 (0.29)% higher in the polystyrene phantom. When the full widths at half maximum and penumbras of the msr field were compared, no significant differences between the two phantoms were observed, except for the penumbra in the Y-axis. However, the difference in the penumbra was smaller than variations among different sites. A polystyrene phantom developed for gamma knife dosimetry showed dosimetric performance comparable to that of a commercial SW phantom. In addition to its cost effectiveness, the polystyrene phantom removes air space around the detector. Additional simulations of the msr correction factors of the polystyrene phantom should be performed.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.5
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• pp.457-470
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• 2023

The aim of this study was to investigate the role of kinesin superfamily member 15 (KIF15) in nasopharyngeal carcinogenesis (NPC) and explore its underlying mechanisms. We employed various assays, including the CCK-8 assay, flow cytometry, the Transwell and scratch assay, Western blotting, and nude mice transplantation tumor, to investigate the impact of KIF15 on NPC. Our findings demonstrate that KIF15 plays a critical role in the proliferation, apoptosis, migration, and invasion of NPC cells. Furthermore, we discovered that silencing KIF15 inhibits cell proliferation, migration, and invasion while promoting apoptosis, and that KIF15's effect on NPC cell growth is mediated through the PI3K/AKT and P53 signaling pathways. Additionally, we showed that KIF15 promotes nasopharyngeal cancer cell growth in vivo. Our study sheds light on the significance of KIF15 in NPC by revealing that KIF15 knockdown inhibits NPC cell growth through the regulation of AKT-related signaling pathways. These findings suggest that KIF15 represents a promising therapeutic target for the prevention and treatment of NPC.

• The Korea Journal of Herbology
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• v.24 no.3
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• pp.161-167
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• 2009

Objectives : Maekmoondong-tang (MMDT), a Korean herbal medicine, has been used to treat severe dry cough in patients with bronchitis and pharyngitis. MMDT has been reported to have anti-inflammatory, anti-allergic, immunomodulatory, secretory-modulating, and metabolic regulatory actions. However, there are no evidence in regard to the effects of MMDT on carcinogenesis and metastasis. Here, we investigated the effects of 70% ethanol extract of MMDT on cell viability, apoptosis, and motility in human hepatocarcinoma HepG2 cells. Methods : Cell viability was measured using the CCK-8 assay, and the apoptosis induction was evaluated by caspase-3 activity. To detect apoptotic features, the cells treated with MMDT were stained with 4'-6-diamidino-2-phenylindole (DAPI). Cell motility was examined by Boyden chamber assay and Real-time Cell Index of Migration assay. Gelatin zymography also performed to measure matrix metalloproteinase (MMP)-2/9 activity. Results : We found that MMDT significantly inhibited cell proliferation and increased caspase-3 activity in a dose-dependent manner in HepG2 cells. Apoptotic features such as chromatin condensation and apoptotic bodies were observed in MMDT-treated cells by DAPI staining. MMDT also suppressed PMA-induced cell motility and activities of MMP-2/9. Conclusions : Our results exhibited that MMDT possess the anti-carcinogenetic and anti-metastatic activities via caspase-3 activation and down-regulation of cell motility and invasion in HepG2 cells. Therefore, these findings suggest that MMDT could be potentially applied to the prevention and treatment of cancer.

• Journal of Korean Clinical Nursing Research
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• v.29 no.1
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• pp.24-41
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• 2023

Purpose: This study aimed to update the previously published nursing practice guideline for prevention of venous thromboembolism (VTE). Methods: The guideline was updated according to the manuals developed by National Institute for Health and Care Excellence (NICE) and Scottish Intercollegiate Guidelines Network (SIGN), and a Handbook for Clinical Practice Guideline Developer Version 10. Results: The updated nursing practice guideline for prevention of VTE was consisted of 16 domains, 46 subdomains, and 216 recommendations. The recommendations in each domain were: 4 general issues, 8 assessment of risk and bleeding factors, 5 interventions for prevention of VTE, 18 mechanical interventions, 36 pharmacological interventions, 36 VTE prevention starategies for medical patients, 25 for cancer patients, 13 for pregnancy, 8 for surgical patients, 7 for thoractic and cardiac surgery, 16 for orthopedic surgery, 10 for cranial and spinal surgery, 5 for vascular surgery, 13 for other surgery, 3 educations and information, and 2 documentation and report. For these recommendations, the level of evidence was 32.1% for level I, 51.8% for level II, and 16.1% for level III according to the infectious diseases society of America (IDSA) rating system. A total of 112 new recommendations were developed and 49 previous recommendations were deleted. Conclusion: The updated nursing practice guideline for prevention of VTE is expected to serve as an evidence-based practice guideline for prevention of VTE in South Korea. It is recommended that this guideline will disseminate to clinical nursing settings nationwide to improve the effectiveness of prevention of VTE practice.

• Journal of Life Science
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• v.33 no.4
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• pp.371-381
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• 2023

Endocrine disrupting chemicals (EDCs), used in a variety of products in modern society, are hormone-like substances that cause various diseases. Humans are exposed to EDCs through their inclusion in pesticides, plastics, cosmetics, detergents, and drugs. Bisphenol A (BPA), one of the representative endocrine disruptors, is an estrogen-like substance that has been widely used commercially in plastic and epoxy resins. BPA is a chemical that can disrupt the endocrine system, leading to reduced reproductive function, obesity, cancer, and neurodevelopmental disorders. Since the adverse health effects of BPA began to be reported the use of BPA has been regulated worldwide. Various alternatives to BPA have been widely used worldwide; representatively, bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used in commercial contexts. BPS and BPF may cause endocrine-disrupting effects like those of BPA due to their similar chemical structures. Recent studies have reported that BPS and BPF disrupt the neurodevelopmental process and cause neurodevelopmental disorders. Therefore, future studies will be required for safety verification of BPA alternatives and the development of new alternatives to BPA for brain health. In this review, we reviewed the effects of BPA and the alternatives, BPS and BPF, on the nervous system.