• Animal cells and systems
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• v.16 no.3
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• pp.173-182
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• 2012

The p53 protein plays a pivotal role in tumor suppression. The cellular level of p53 is normally kept low by proteasome-mediated degradation, allowing cell cycle progression and cell proliferation. Under stress conditions, such as DNA damage, p53 is stabilized and activated through various post-translational modifications of itself as well as of its regulatory proteins for induction of the downstream genes responsible for cell cycle arrest, DNA repair, and apoptosis. Therefore, the level of p53 should be tightly regulated for normal cell growth and for prevention of the accumulation of mutations in DNA under stress conditions, which otherwise would lead to tumorigenesis. Since the discovery of Mdm2, a critical ubiquitin E3 ligase that destabilizes p53 in mammalian cells, nearly 20 different E3 ligases have been identified and shown to function in the control of stability, nuclear export, translocation to chromatin or nuclear foci, and oligomerization of p53. So far, a large number of excellent reviews have been published on the control of p53 function in various aspects. Therefore, this review will focus only on mammalian ubiquitin E3 ligases that mediate proteasome-dependent degradation of p53.

• Journal of Animal Reproduction and Biotechnology
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• v.36 no.4
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• pp.285-291
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• 2021

Mesenchymal stem cells (MSCs) have been recognized as a therapeutic tool for various diseases due to its unique ability for tissue regeneration and immune regulation. However, poor survival during in vitro expansion and after being administrated in vivo limits its clinical uses. Accordingly, protocols for enhancing cell survivability is critical for establishing an efficient cell therapy is needed. CDDO-Me is a synthetic C-28 methyl ester of 2-cyano-3,12-dioxoolean-1,9-dien-28-oic acid, which is known to stimulate nuclear factor erythroid 2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway. Herein, report that CDDO-Me promoted the proliferation of MSCs and increased colony forming units (CFU) numbers. No alteration in differentiation into tri-lineage mesodermal cells was found after CDDO-Me treatment. We observed that CDDO-Me treatment reduced the cell death induced by oxidative stress, demonstrated by the augment in the expression of Nrf2-downstream genes. Lastly, CDDO-Me led to the nuclear translocation of NRF2. Our data indicate that CDDO-Me can enhance the functionality of MSCs by stimulating cell survival and increasing viability under oxidative stress.

• Genomics & Informatics
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• v.20 no.1
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• pp.7.1-7.13
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• 2022

2-Methoxy-1,4-naphthoquinone (MNQ) has been shown to cause cytotoxic towards various cancer cell lines. This study is designed to investigate the regulatory effect of MNQ on the key cancer genes in mitogen-activated protein kinase, phosphoinositide 3-kinase, and nuclear factor κB signaling pathways. The expression levels of the genes were compared at different time point using polymerase chain reaction arrays and Ingenuity Pathway Analysis was performed to identify gene networks that are most significant to key cancer genes. A total of 43 differentially expressed genes were identified with 21 up-regulated and 22 down-regulated genes. Up-regulated genes were involved in apoptosis, cell cycle and act as tumor suppressor while down-regulated genes were involved in anti-apoptosis, angiogenesis, cell cycle and act as transcription factor as well as proto-oncogenes. MNQ exhibited multiple regulatory effects on the cancer key genes that targeting at cell proliferation, cell differentiation, cell transformation, apoptosis, reduce inflammatory responses, inhibits angiogenesis and metastasis.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.6
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• pp.513-520
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• 2023

Cornuside is a secoiridoid glucoside compound extracted from the fruits of Cornus officinalis. Cornuside has immunomodulatory and anti-inflammatory properties; however, its potential therapeutic effects on diabetic nephropathy (DN) have not been completely explored. In this study, we established an in vitro model of DN through treating mesangial cells (MMCs) with glucose. MMCs were then treated with different concentrations of cornuside (0, 5, 10, and 30 μM). Cell viability was determined using cell counting kit-8 and 5-ethynyl-2'-deoxyuridine assays. Levels of proinflammatory cytokines, including interleukin (IL)-6, tumor necrosis factor-α, and IL-1β were examined using enzyme-linked immunosorbent assay. Reverse transcription quantitative real-time polymerase chain reaction and Western blotting were performed to detect the expression of AKT and nuclear factor-kappa B (NF-κB)-associated genes. We found that cornuside treatment significantly reduced glucose-induced increase in MMC viability and expression of pro-inflammatory cytokines. Moreover, cornuside inhibited glucose-induced phosphorylation of AKT and NF-κB inhibitor alpha, decreased the expression of proliferating cell nuclear antigen and cyclin D1, and increased the expression of p21. Our study indicates that the anti-inflammatory properties of cornuside in DN are due to AKT and NF-κB inactivation in MMCs.

• Strategy21
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• s.31
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• pp.5-26
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• 2013

The South Korean society has experienced many changes since the sinking of ROKS Cheonan. The government reviewed its defense posture and adopted the 5·24 Measure in its relations with North Korea. As a result, the people of South Korea became more conscious of security situations on the Korean peninsula while North Korea's economy suffered badly. Meanwhile, the South Korean government has taken a flexible stance toward North Korea in terms of exchange and cooperation since September 2011. The flexible stance was to manage inter-Korea relations in a stable manner and relieve the hardships of the North Korean people while preserving the spirits and purposes of the 5·24 Measure. The UN Security Council adopted twenty-six resolutions and statements on North Korea since June 25, 1950. They include thirteen U.N. Security Council resolutions including those concerning nuclear weapons or missile programs, nine Presidential statements, and four press statements. Resolution 82, the first U.N. resolution on North Korea, came when the Korean War broke out. Resolution 825, the first one related to nuclear or missile programs, was adopted in response to North Korea's withdrawal from the NPT. Apart from these U.N. resolutions, the United States has imposed separate sanctions against North Korea. North Korea's nuclear weapons program can be considered in comparison with that of Iran in terms of the consequences they create for the regional security. The Security Council has adopted six resolutions on Iran so far. One should note that the resolutions on Iran have had much stronger sanctions compared to those imposed on North Korea. That is, while the North Korea case may be viewed as a more serious threat to international security from the perspective of nuclear weapons development or proliferation, tougher sanctions have been placed on Iran. There are two approaches that South Korea should take in addressing the related issues. First, we should aim to reduce the gap between sanctions imposed on Iran and North Korea. It is difficult to understand that a country with more serious problems is rewarded with lighter sanctions. We should take measures through the Security Council Sanctions Committee to make individuals and groups in North Korea that play a central role in developing nuclear weapons and missiles subject to additional sanctions. Second, we have to change. Other countries in the international community have become tired of North Korea's nuclear issue and now they look to South Korea for initiative. We should correctly understand this current situation and play a leading role within our capacity. Knowingly and unknowingly, the notion that the North Korean nuclear issue may be left to South Korea has been spread around the international community. Although the situation is grave, we should try to open a new horizon in ushering in the unification era by taking the initiative with confidence that there is a looming hope ahead of us. For these tasks, we should stop thinking in the old way that has been ossified for the last two decades. We should not be pushed around by neighboring great powers in dealing with North Korea related issues anymore; we should take the initiative with resolution that we will play our role at the center of four great powers and with confidence that we can do it. Based on the confidence that the Republic of Korea has become a country with enough capacity to take the initiative, we should establish a 'National Grand Strategy' representing South Korea's strategic vision that the unification is the ultimate solution to the problems related to North Korea's nuclear weapons program.

• The Journal of Korean Medicine
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• v.27 no.3 s.67
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• pp.51-62
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• 2006

Objective: Although chronic non-bacterial prostatitis is a common disease, it is very difficult to treat effectively. Lygodium japonicum has traditionally been used in treatment of urinary tract inflammation and voiding disturbance. In this study, we investigated the therapeutic effects and action mechanism of Lygodium japonicum in the rat model of non-bacterial prostatitis induced by castration and testosterone treatment. Methods: Five-month-old rats were treated with $17\beta-estradiol$ after castration for induction of experimental non-bacterial prostatitis, which is similar to human chronic prostatitis in histopathological profiles. Lygodium japonicum and testosterone were administered as an experimental specimen and a positive control, respectively. The prostates were evaluated by histopathological parameters including the epithelial score and epithelio-stromal ratio for glandular damage, proliferating cell nuclear antigen (PCNA) labeling index for cyto-proliferation and a TUNEL (deoxyuridine triphosphate biotin nick end-labeling) assay for cell apoptosis. Results: While prostates of control rats revealed severe acinar gland atrophy and stromal proliferation, the rats treated with Lygodium japonicum showed a lesser range of tissue damage. Epithelial score was improved in Lygodium japonicum than that of the control (P<0.05). The epithelio-stromal ratio was lower in Lygodium japonicum when compared to that of the control (P<0.05). Although there was no difference in PCNA and TUNEL positive cells of the glandular epithelia, we found an decreased number of PCNA positive cell and concurrent increase of TUNEL positive cells in the stroma of Lygodium japonicum treated rats (P<0.01). Conclusions: These findings suggest that Lygodium japonicum may protect the glandular epithelial cells and also inhibit stromal proliferation in association with suppression of cyto-proliferation and stimulation of apoptosis. We concluded that Lygodium japonicum may be a useful remedy agent for treating the chronic non-bacterial prostatitis.

• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.211-219
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• 2021

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

• Applied Microscopy
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• v.40 no.2
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• pp.73-80
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• 2010

Liver regeneration is a result of highly coordinated proliferation of hepatocytes and nonparenchymal liver cells. Partial hepatectomy (PH) is the most often used stimulus to study liver regeneration because, compared with other methods that use hepatic toxins, it is not associated with the tissue injury and inflammation, and the initiation of the regenerative stimulus is precisely defined. Granulocyte macrophage-colony stimulating factor (GM-CSF), which is a cytokine able to regulate the proliferation and differentiation of epithelial cells, was first identified as the most potent mitogen for bone marrow. Particularly, rrhGM-CSF, which is highly glycosylated and sustained longer than any other types of GM-CSF in the blood circulation, was specifically produced from rice cell culture. In this experiment, effects of rrhGM-CSF administration were evaluated in the regenerating liver after 78% PH of rats. Morphological changes induced by PH were characterized by destroyed hepatocyte plate around the central vein and enlarged nuclear cytoplasmic ratio and increased hepatocytes with two nuclei. And then, proliferation of liver cells (parenchymal and nonparenchymal) and rearrangement of plates and lobules seemed to be carried out during liver regeneration. These alterations in the experimental group preceded those of the control. Since proliferating cell nuclear antigen (PCNA) is known to be a nuclear protein maximally elevated in the S phase of proliferating cells, the protein was used as a marker of liver regeneration after PH in rats. PCNA levels by western blot analysis and immunohistology were compared between the two groups. PCNA protein expression of two groups at 12 hr and 24 hr after injury showed similar pattern. The protein expression showed the peak at 3 days in both groups, however, the protein level of the experimental group was higher than that of the control. On immunohistochemical observations, the reaction product of PCNA was localized at the nuclei of proliferating cells and the positive reaction in experimental group at 3 days was clearly stronger than that in control group. The results by Western blotting and immunohistology for PCNA showed similar pattern in terms of the protein levels. In conclusion, rrhGM-CSF administration during liver regeneration after 78% PH accelerated breakdown and restoration of the hepatic plate and expression of PCNA. These results suggest that rrhGM-CSF might play an important role during liver regeneration in rats.

• Strategy21
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• s.31
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• pp.57-84
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• 2013

North Korea's continuous threats and provocative behaviors have aggravated tension on the Korean peninsula particularly with the recent nuclear weapons test. South Korea's best way to cope with this situation is to maintain the balance among three policy directions: dialogue, sanctions, and deterrence. Among the three, I argue that deterrence should be prioritized. There are different sources of deterrence such as military power, economic power, and diplomatic clouts. States can build deterrence capability independently. Alternatively, they may do so through relations with other states including alliances, bilateral relations, or multilateral relations in the international community. What South Korea needs most urgently is to maintain deterrence against North Korea's local provocations through the enhancement of independent military capability particularly by addressing the asymmetric vulnerability between militaries of the South and the North. Most of all, the South Korean government should recognize the seriousness of the negative consequences that North Korea's 'Nuclear shadow strategy' would bring about for the inter-Korea relations and security situations in Northeast Asia. Based on this understanding, it should develop an 'assertive deterrence strategy' that emphasizes 'multi-purpose, multi-stage, and tailored deterrence whose main idea lies in punitive retaliation.' This deterrence strategy requires a flexible targeting policy and a variety of retaliatory measures capable of taking out all targets in North Korea. At the same time, the force structures of the army, the air force, and the navy should be improved in a way that maximizes their deterrence capability. For example, the army should work on expanding the guided missile command and the special forces command and reforming the reserve forces. The navy and the air force should increase striking capabilities including air-to-ground, ship-to-ground, and submarine-to-ground strikes to a great extent. The marine corps can enhance its deterrence capability by changing the force structure from the stationary defense-oriented one that would have to suffer some degree of troop attrition at the early stage of hostilities to the one that focuses on 'counteroffensive landing operations.' The government should continue efforts for defense reform in order to obtain these capabilities while building the 'Korean-style triad system' that consists of advanced air, ground, and surface/ subsurface weapon systems. Besides these measures, South Korea should start to acquire a minimum level of nuclear potential within the legal boundary that the international law defines. For this, South Korea should withdraw from the Nuclear Non-proliferation Treaty. Moreover, it should obtain the right to process and enrich uranium through changing the U.S.-South Korea nuclear cooperation treaty. Whether or not we should be armed with nuclear weapons should not be understood in terms of "all or nothing." We should consider an 'in-between' option as the Japanese case proves. With regard to the wartime OPCON transition, we need to re-consider the timing of the transition as an effort to demonstrate the costliness of North Korea's provocative behaviors. If impossible, South Korea should take measures to make the Strategic Alliance 2015 serve as a persisting deterrence system against North Korea. As the last point, all the following governments of South Korea should keep in mind that continuing reconciliatory efforts should always be pursued along with other security policies toward North Korea.

• The Korean Journal of Nuclear Medicine Technology
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• v.14 no.2
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• pp.186-189
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• 2010

Purpose: As many patients often showed the value of menopause although they were women of childbearing age, this study looked into their previous history. According to the findings, they were patients with a mastectomy due to breast cancer and were taking breast cancer treatment Tamoxifen (the women hormone inhibitor) after chemotherapy. This study is conducted to examine changes in FSH and E2 concentration of patients breast cancer patients of childbearing age according to Tamoxifen used to prevent recurrence of breast cancer and proliferation of mammary parenchyma. Materials and Methods: This study aims to investigate similarity in patients treated with surgery who were in their childbearing age and in values of FSH and E2 by dividing test results of FSH and E2 requested at the department of nuclear medicine among patients who visited this hospital from Jan. 2009 to Mar. 2010 into women of childbearing age (n=50), menopausal women (n=50), and patients with breast cancer surgery who take Tamoxifen (n=50) and then comparing the test results. Results: The FSH and E2 test results of 50 patients were compared and analyzed as average${\pm}$standard deviation, and the results showed that the figure of women of childbearingage (n=50) was FSH : $7.14{\pm}6.19$, E2 : $138.76{\pm}85.40$, that of menopausal women (n=50) was FSH : $52.12{\pm}24.43$, E2 : $15.06{\pm}4.43$, and that of patients with breast cancer surgery who were in their childbearing age (n=50) was FSH : $44.21{\pm}21.07$, E2 : $13.53{\pm}4.26$. When these different results of FSH and E2 were compared, the value of patients with breast cancer surgery who were in their childbearing age with Tamoxifen was somewhat similar to that of menopausal women. Conclusion: The test results of FSH and E2 have reportedly found the test values of patients with breast cancer surgery could be similar to that of menopausal women eventhough they were in their childbearing age due to the women hormone inhibitor Tamoxifen. Therefore, if a tester conducts this experiment after understanding the clinical meaning, the reliability of the tester reporting test results would be increased.