• Molecules and Cells
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• v.46 no.3
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• pp.165-175
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• 2023

The transcription factor Nrf2 was originally identified as a master regulator of redox homeostasis, as it governs the expression of a battery of genes involved in mitigating oxidative and electrophilic stress. However, the central role of Nrf2 in dictating multiple facets of the cellular stress response has defined the Nrf2 pathway as a general mediator of cell survival. Recent studies have indicated that Nrf2 regulates the expression of genes controlling ferroptosis, an iron-and lipid peroxidation-dependent form of cell death. While Nrf2 was initially thought to have anti-ferroptotic function primarily through regulation of the antioxidant response, accumulating evidence has indicated that Nrf2 also exerts anti-ferroptotic effects via regulation of key aspects of iron and lipid metabolism. In this review, we will explore the emerging role of Nrf2 in mediating iron homeostasis and lipid peroxidation, where several Nrf2 target genes have been identified that encode critical proteins involved in these pathways. A better understanding of the mechanistic relationship between Nrf2 and ferroptosis, including how genetic and/or pharmacological manipulation of Nrf2 affect the ferroptotic response, should facilitate the development of new therapies that can be used to treat ferroptosis-associated diseases.

• Journal of Microbiology and Biotechnology
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• v.34 no.2
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• pp.240-248
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• 2024

In cancer treatment, multi-target approach has paid attention to a reasonable strategy for the potential agents. We investigated whether (E)-2-methoxy-4-(3-(4-methoxyphenyl) prop-1-en-1-yl) phenol (MMPP) could exert an anticancer effect by dual-regulating VEGFR2 and PPARγ. MMPP showed modulating effects in TNBC type (MDA-MB-231 and MDA-MB-468) and luminal A type (MCF7) breast cancer cell lines. MMPP enhanced PPARγ transcriptional activity and inhibited VEGFR2 phosphorylation. MMPP-induced signaling by VEGFR2 and PPARγ ultimately triggered the downregulation of AKT activity. MMPP exhibited anticancer effects, as evidenced by growth inhibition, inducement of apoptosis, and suppression of migration and invasion. At the molecular level, MMPP activated pro-apoptotic proteins (caspase3, caspase8, caspase9, and bax), while inhibiting the anti-apoptotic proteins (bcl2). Additionally, MMPP inhibited the mRNA expressions of EMT-promoting transcription factors. Therefore, our findings showed molecular mechanisms of MMPP by regulating VEGFR2 and PPARγ, and suggested that MMPP has potential to treat breast cancer.

• IMMUNE NETWORK
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• v.21 no.2
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• pp.16.1-16.8
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• 2021

Patients with severe coronavirus disease 2019 (COVID-19) demonstrate dysregulated immune responses including exacerbated neutrophil functions. Massive neutrophil infiltrations accompanying neutrophil extracellular trap (NET) formations are also observed in patients with severe COVID-19. However, the mechanism underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced NET formation has not yet been elucidated. Here we show that 2 viral proteins encoded by SARS-CoV-2, the nucleocapsid protein and the whole spike protein, induce NET formation from neutrophils. NET formation was ROSindependent and was completely inhibited by the spleen tyrosine kinase inhibition. The inhibition of p38 MAPK, protein kinase C, and JNK signaling pathways also inhibited viral protein-induced NET formation. Our findings demonstrate one method by which SARSCoV-2 evades innate immunity and provide a potential target for therapeutics to treat patients with severe COVID-19.

• Progress in Medical Physics
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• v.29 no.1
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• pp.1-7
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• 2018

The $TomoTherapy^{(R)}$ beam-delivery method creates helical beam-junctioning patterns in the dose distribution within the target. In addition, the dose discrepancy results in the particular region where the resonance by pattern of dose delivery occurs owing to the change in the position and shape of internal organs with a patient's respiration during long treatment times. In this study, we evaluated the dose pattern of the longitudinal profile with the change in respiration. The superior-inferior motion signal of the programmable respiratory motion phantom was obtained using AbChes as a four-dimensional computed tomography (4DCT) original moving signal. We delineated virtual targets in the phantom and planned to deliver the prescription dose of 300 cGy using field widths of 1.0 cm, 2.5 cm, and 5.0 cm. An original moving signal was fitted to reflecting the beam delivery time of the $TomoTherapy^{(R)}$. The EBT3 film was inserted into the phantom movement cassette, and static, without the movement and with the original movement, was measured with signal changes of 2.0 s, 4.0 s, and 5.0 s periods, and 2.0 mm and 4.0 mm amplitudes. It was found that a dose fluctuation within ${\pm}4.0%$ occurred in all longitudinal profiles. Compared with the original movement, the region of the gamma index above 1 partially appeared within the target and the border of the target when the period and amplitude were changed. Gamma passing rates were 95.00% or more. However, cases for a 5.0 s period and 4.0 mm amplitude at a field width of 2.5 cm and for 2.0 s and 5.0 s periods at a field width of 5.0 cm have gamma passing rates of 92.73%, 90.31%, 90.31%, and 93.60%. $TomoTherapy^{(R)}$ shows a small difference in dose distribution according to the changes of period and amplitude of respiration. Therefore, to treat a variable respiratory motion region, a margin reflecting the degree of change of respiration signal is required.

• Journal of Korean society of Dental Hygiene
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• v.9 no.4
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• pp.670-684
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• 2009

Objectives : This research analyzed the general characteristics that closely affect the children's dental health and the mothers' dental health knowledge and dental health behavior to identify the correlation of the latter with the status of children's dental health in order to provide the basic data for the development of dental health business that would target children. Methods : Research subjects were selected arbitrarily from three nursery schools located in Busan metropolitan city, targeting 186 children between the ages of four to six and their mothers. The children were subjected to dental Inspection, and the status of their dental caries was studied whereas the mothers were subjected to the surveys on the general characteristics, dental health knowledge and dental health behavior. Results : 1. Level of mothers' dental health knowledge is higher when the mothers' educational level is higher(p=0.02) and when the household's monthly income is higher(p=0.009). 2. When the level of mothers' dental health knowledge is higher, children tended to brush their toothbrushing using proper method(p=0.025). Moreover, when the level of mothers' dental health knowledge is higher, they tended to take their children to dental clinic mostly for preventive measures than for treating cavity(p=0.023). 3. When the level of mothers' dental health knowledge is higher, children's dmft index was significantly low(p=0.02). When the mothers use fluoride-containing toothpaste, children's children' dmft index was even lower(p=0.02). 4. As the children tended to brush their teeth more often, dmft index was lower(p=0.003). When the reason that the children visited dental clinic was more to prevent, than to treat cavity, dmft index was even lower(p=0.000) Conclusions : When the above mentioned results are summarized, it is possible to know that the mothers' dental health knowledge and dental health behavior significantly affect children's dental health. Accordingly, it is necessary to develop maternal and child dental health program that factors in both the mothers and children in order to prevent children's dental caries and to increase their dental health, and continued care is required to discover and treat dental caries early on.

• Journal of the Society of Disaster Information
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• v.1 no.1
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• pp.3-26
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• 2005

In recent years, there is growing concern about the potential use of biological agents in war or acts of terrorism accompanied an increased realization that rapid preparedness and response are needed to prevent or treat the human damage that can be caused by these agents. The threat is indeed serious, and the potential for devastating numbers of casualties is high. The use of agents as weapons, even on a small scale, has the potential for huge social and economic disruption and massive diversion of regional and national resources to combat the threat, to treat primary disease, and to clean up environmental contamination. Biological weapons are one of weapons of mass destruction (or mass casualty weapons, to be precise. since they do not damage non-living entities) that are based on bacteria, viruses, rickettsia, fungi or toxins produced by these organisms. Biological weapons are known to be easy and cheap to produce and can be used to selectively target humans, animals, or plants. Theses agents can cause large numbers of casualties with minimal logistical requirements (in wide area). The spread of disease cannot be controlled until there is awareness of the signs of infection followed by identification of agents; and if the organism is easily spread from person to person, as in the case of smallpox, the number of casualties could run into the tens of thousands. Biological weapons could be used covertly, there can be a lot of different deployment scenarios. A lot of different agents could be used in biological weapons. And, there are a lot of different techniques to manufacture biological weapons. Terrorist acts that make use of Biological Agents differ in a number of ways from those involving chemicals. The distinction between terrorist and military use of Biological Weapon is increasingly problematic. The stealthy qualities of biological weapons further complicate the distinction between terrorism and war. In reality, all biological attacks are likely to require an integrated response involving both military and civilian communities. The basic considerations when public health agencies establish national defence plan against bioterrorism must be 1) arraying various laws and regulations to meet the realistic needs, 2)education for public health personnels and support of concerned academic society, 3)information collection and cooperative project with other countries, 4)Detection and surveillance(Early detection is essential for ensuring a prompt response to biological or chemical attack, including the provision of prophylactic medicines, chemical antidotes, or vaccines) and 5) Response(A comprehensive public health response to a biological or chemical terrorist event involves epidemiologic investigation, medical treatment and prophylaxis for affacted persons, and the initiation of disease prevention or environmental decontamination measures). The purpose of this paper is providing basic material of preparedness and response for biological terrorism in modern society.

• Korean Journal of Clinical Pharmacy
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• v.26 no.4
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• pp.306-311
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• 2016

Objective: This study was performed to compare the changes in the blood concentrations of tacrolimus when either itraconazole or voriconazole is together with tacrolimus to prevent or treat invasive aspergillus pneumonia (IAP) in patients with lung transplants. Therefore we can compare the degree of drug-drug interactions between tacrolimus and itraconazole against tacrolimus and voriconazole. Methods: Patients who were admitted and had lung transplants in a territory referral hospital from September 2012 to May 2015 were analyzed retrospectively. The effects of itraconazole and voriconazole on the plasma concentrations of tacrolimus were analyzed. Results: Mean tacrolimus concentrations was $10.49{\pm}2.35ng/mL$ vs. $10.95{\pm}2.98ng/mL$ (p=0.722), and mean concentration of tacrolimus over the dose of tacrolimus per day was $8.510{\pm}5.890(ng/mL)/(mg/d)$ vs. $15.45{\pm}28.47(ng/mL)/(mg/d)$ (p=0.947) in itraconazole vs. voriconazole group each. The ratio of the number of the results out of target tacrolimus concentrations to the total number of tacrolimus concentration results was $18.0{\pm}13.3%$ vs. $24.4{\pm}18.5%$ (p=0.185). Conclusion: There were no significant differences between itraconzaole and voriconazole to have influences on mean concentrations of tacrolimus over tacrolimus dose per weight per day. However voriconazole tended to raise tacrolimus plasma concentrations more than itraconazole. Safer and more effective drug management to prevent and treat fungal infections should be done by therapeutic drug monitoring not only of tacrolimus but of itraconazole and voriconazole in lung transplant patients.

• Journal of Life Science
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• v.21 no.3
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• pp.349-357
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• 2011

Inhibitors of EGFR (epidermal growth factor receptor) kinase activity may prove useful to therapeutically intervene in cancer and to treat other proliferative diseases. In this study, we investigated the inhibitive effects of two compounds named 63013 and 63033 possess a [1,4]-dioxino quinazoline structure that links the alkoxy side chains together and their structural characteristics are considered to allow better solubility than the dialkoxyquinazoline derivatives. The EGFR kinase activities of A431 human epidermoid carcinoma cells, stimulated by EGF were inhibited by treatment with 63013 and 63033 in a dose-dependent manner respectively. Consistent with the compound-mediated EGFR kinase suppression, the major EGF-related downstream target molecules, such as MEK1/2, MAPK p44/42, AKT and STAT3, were also suppressed by both compounds. Interestingly, both compounds led to cell growth inhibition at a lower concentration than that of Gefitinib (Iressa$^{(R)}$). Collectively, our study showed that both compounds may have good therapeutic potential as an EGFR kinase specific inhibitor to treat EGFR-related diseases.

• The Korean Journal of Nuclear Medicine
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• v.34 no.2
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• pp.129-134
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• 2000

Purpose: It is difficult to determine the activity of tuberculosis radiologically. Therefore there have been efforts to assess the activity using radiopharmaceuticals such as $^{67}Ga,\;^{99m}Tc-tetrofosmin,\;and\;^{99m}Tc-MIBI$. But there may be some discrepancy in defining the term 'activity' between clinicians and nuclear physicians. While negative conversion of sputum acid fast bacilli (AFB) is defined as 'disappearance of activity' by clinicians, a loss of uptake in previously positive lesion is accepted as 'disappearance of activity' by nuclear physicians. We designed a prospective study to see if the negative conversion of sputum AFB could directly match the disappearance of radioactivity of the lesion. Materials and Methods: Fifteen patients with bacteriologically confirmed active localized pulmonary tuberculosis were scanned 10 and 60 min after intravenous injection of 550 MBq $^{99m}Tc$-MIBI. In 6 patients, who showed negative conversion of sputum AFB after 3-7 months of chemotherapy, $^{99m}Tc$-MIBI scan was repeated. For the purpose of comparison, target/nontarget ratios of the lesions were determined. Results: 12/15 (80%) patients with active pulmonary tuberculosis showed increased uptake of $^{99m}Tc$-MIBI in tuberculous lesion. After negative conversion of sputum AFB, 5/6 (83%) patients still showed increased uptake, although the intensity of uptake decreased. Conclusion: Uptake of radioactivity decreased but did not disappear after negative conversion of sputum AFB. $^{99m}Tc$-MIBI scan may be useful to address the degree of inflammation of pulmonary tuberculous lesion, but the uptake did not directly match the activity defined by positivity of sputum AFB. We nuclear physicians might have used the term 'activity' somewhat differently from clinicians who treat patients with tuberculosis.

• The Journal of Korean Society for Radiation Therapy
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• v.30 no.1_2
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• pp.153-160
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• 2018

Purpose : We retrospectively analyzed doses of each radiation therapy technique used in the treatment for left breast cancer patients after partial mastectomy through dose results for normalorgans and tumor volume to use this as a clinical reference for radiation therapy of domestic left breast cancer patients. Materials and Methods : 40 patients who underwent partial mastectomy on left breast cancer were classified in 3 treatment methods. The treatment plan was evaluated by HI(homogeneity index), $D_{95%}$, and CI(conformity index), and the $V_{hot}$ for gross tumor volume and clinical target volume of each treatment method. In Cyberknife treatment, tumor volume was the same as high dose volume in the other techniques, so no consideration was given to clinical target volume. Treatment plan evaluation for normal organs were evaluated by mean dose on ipsilateral lung, heart, left anterior descending artery, opposite breast and lung, and non-target tissue. Result : Treatment with volumetric arc radiotherapy(VMAT) showed $95.84{\pm}0.75%$ of $D_{95%}$ on the clinical target volume, significantly higher than that of 3D-CRT. The $D_{95%}$ value of the total tumor volume was slightly higher than the other treatments. In Cyberknife treatment, the dose to the normal organs was significantly lower than other treatments. Overall, the maximum dose and mean dose to the heart were $26.2{\pm}6.12Gy$ and $1.88{\pm}0.2Gy$ in VMAT treatment and $20.25{\pm}9.35Gy$ and $1.04{\pm}0.19Gy$ in 3D-CRT therapy, respectively. Conclusion : In comparison on 3D-CRT and VMAT, most of the dosimetric parameters for the evaluation of the treatment plan showed similar values, so that there is no significant difference in treatment plan evaluation. It is possible to select the treatment method according to the patient's anatomical structure or possibility of breath control. Cyberknife treatment is very useful treatment for normal organs because of its accurate dose exposure to the tumor volume However, it has restrictions to treat the local area, to have relatively long treatment time and to involve invasive procedure.