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Generation of $CD2^+CD8^+$ NK Cells from c-$Kit^+$ Bone Marrow Cells in Porcine

  • Lim, Kyu-Hee;Han, Ji-Hui;Roh, Yoon-Seok;Kim, Bum-Seok;Kwon, Jung-Kee;You, Myoung-Jo;Han, Ho-Jae;Ejaz, Sohail;Kang, Chang-Won;Kim, Jong-Hoon
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.3
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    • pp.167-174
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    • 2012
  • Natural killer (NK) cells provide one of the initial barriers of cellular host defense against pathogens, in particular intracellular pathogens. Because bone marrow-derived hematopoietic stem cells (HSCs), lymphoid protenitors, can give rise to NK cells, NK ontogeny has been considered to be exclusively lymphoid. Here, we show that porcine c-$kit^+$ bone marrow cells (c-$kit^+$ BM cells) develop into NK cells in vitro in the presence of various cytokines [interleukin (IL)-2, IL-7, IL-15, IL-21, stem cell factor (SCF), and fms-like tyrosine kinase-3 ligand (FLT3L)]. Adding hydrocortisone (HDC) and stromal cells greatly increases the frequency of c-$kit^+$ BM cells that give rise to $CD2^+CD8^+$ NK cells. Also, intracellular levels of perforin, granzyme B, and NKG2D were determined by RT-PCR and western blotting analysis. It was found that of perforin, granzyme B, and NKG2D levels significantly were increased in cytokine-stimulated c-$kit^+$ BM cells than those of controls. And, we compared the ability of the cytotoxicity of $CD2^+CD8^+$ NK cells differentiated by cytokines from c-$kit^+$ BM cells against K562 target cells for 28 days. Cytokines-induced NK cells as effector cells were incubated with K562 cells as target in a ratio of 100 : 1 for 4 h once a week. In results, $CD2^+CD8^+$ NK cells induced by cytokines and stromal cells showed a significantly increased cytotoxicity 21 days later. Whereas, our results indicated that c-$kit^+$ BM cells not pretreated with cytokines have lower levels of cytotoxicity. Taken together, this study suggests that cytokines-induced NK cells from porcine c-$kit^+$ BM cells may be used as adoptive transfer therapy if the known obstacles to xenografting (e.g. immune and non-immune problems) were overcome in the future.

The Use Criteria and Appropriateness of Korean Classification of Diseases(KCD) Focused on Emmeniopathy (월경병을 중심으로 본 한국표준질병사인분류(KCD)의 사용 기준과 적합성)

  • Kang, You-Jeong;Lee, In-Seon;Cho, Hye-Sook;Lee, Seung-Hwan;Bae, Geung-Mee
    • The Journal of Korean Obstetrics and Gynecology
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    • v.24 no.4
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    • pp.126-149
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    • 2011
  • Purpose: KCDO-3(Korean Classification of Diseases(Oriental Medicine)-third edition) being used in January, 2010 accepted the KCD(Korean Classification of Diseases) and added disease pattern and syndrome of oriental medicine. But, the diagnoses of oriental medicine are too uncertain to express in A00-Z99(KCD). In this case, you should choose in U codes under the KCD use guidelines, but U codes are not capable of representing the symptoms too. So, we suggest the use criteria and consider the weakness of the U codes with medical records of patients who visited with amenorrhea or oligomenorrhea. Methods: We referred medical records of patients who visited oriental obstetrics and gynecology from January 1st to December 31st, 2010. From among them, we set up 122 patients who related with emmeniopathy as target group and searched codes distribution based on medical records. And we described that the process of choosing appropriate codes based on the medical records of 49 amenorrhea or oligomenorrhea patients. Results and Conclusions: The emmeniopathy is divided into menstrual disorder, amenorrhea and systemic disorders at the period of menstruation. And emmeniopathy is expressed in some codes such as N91, N92, N93, N94, U321, U77. When a patient visit hospital, a doctor should choose causal codes when there is confirmed diagnosis. Otherwise, a doctor chooses symptom codes. And if there are more than two diagnosis consistent with definition of chief condition, a doctor should code the first listed diagnosis as a chief condition. Because KCD-5 is classified according to western medical diagnosis, it is difficult to choose in KCD-5 when we diagnosed with disease pattern and syndrome of oriental medicine. But U codes are also deficient to express various condition of emmeniopathy. So we should add 'deficiency and detriment of the thoroughfare and conception vessels', 'prolonged menstruation' and various systemic disorders at the period of menstruation.

VENGEANCE, VIOLENCE, VAMPIRES: Dark Humour in the Films of Park Chan-wook

  • Hughes, Jessica
    • Cross-Cultural Studies
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    • v.28
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    • pp.17-36
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    • 2012
  • This essay places the South Korean film Thirst (2009) within Park Chan-wook's oeuvre as a filmmaker notorious for graphic depictions of violence and revenge. Park's use of dark humour in his films, which is emphasized in Thirst perhaps more than ever, allows for a more self-aware depiction of violence, where both the viewer and the protagonist are awakened to the futility of revenge. This ultimately paints his characters as fascinatingly crazy - simultaneously heroes, villains, and victims. Film theorist Wes D. Gehring's three themes of dark humour ('man as beast,' 'the absurdity of the world,' and 'the omnipresence of death') become most obvious in Park's most recent film, which pays closer attention to character development through narrative detail. Rather than portraying the characters as sentimental, dark humour depicts their misfortunes in an alternative way, allowing for consideration of such taboo subjects as religion, adultery, and death/suicide. These issues are further tackled through Thirst's portrayal of its vampire protagonist, which ultimately de-mystifies the traditional vampire figure. While this character has more often been associated with romance, exoticism and the mystical powers of the supernatural, Thirst takes relatively little from the demons of Nosferatu (Murnau, 1922) and various other Dracula adaptations, nor the romantic figures of Interview with the Vampire (Jordan, 1994), and Twilight (Hardwicke, 2008). Instead, it is part of a much smaller group of contemporary vampire films, which are rather informed by a postmodern reconfiguration of the monster. Thus, this paper examines Thirst as an important contribution to the global and hybrid nature of those films in which postmodern vampires are sympathetic and de-mystified, exhibiting symptoms stemming from a natural illness or misfortune. Park's undertaking of a vampire film allows for a complex balance between narrative and visuals through his focus on the Western implications of this myth within Korean cinema. This combination of international references and traditional Korean culture marks it as highly conscious of New Korean Cinema's focus on globalization. With Thirst, Park successfully unites familiar images of the vampire hunting and feeding, with more stylistically distinct, grotesque images of violence and revenge. In this sense, dark humour highlights the less charming aspects of the vampire struggling to survive, most effective in scenes depicting the protagonist feeding from his friend's IV in the hospital, and sitting in the sunlight, slowly turning to ash, in the final minutes of the film. The international appeal of Park's style, combining conventions of the horror/thriller genre with his own mixture of dark humour and non-linear narrative, is epitomized in Thirst, which underscores South Korea's growing global interest with its overt international framework. Furthermore, he portrayal of the vampire as a sympathetic figure allows for a shift away from the conventional focus on myth and the exotic, toward a renewed construction of the vampire in terms of its contribution to generic hybridization and cultural adaptation.

A Role for Ginseng in the Control of Postprandial Glycemia and Type 2 Diabetes

  • Vuksan Vladimir;Sievenpiper John L;Xu Zheng;Zdravkovic Uljana Beljan;Jenkins Alexandra L;Arnason John T;Bateman Ryon M.;Leiter Lawrence A;Josse Robert G;Francis Thomas;Stavro Mark P
    • Proceedings of the Ginseng society Conference
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    • 2002.10a
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    • pp.1-19
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    • 2002
  • The use of herbals has increased considerably while their efficacy and safety remain untested. This unsupported surge in demand has prompted a call for their clinical evaluation. One area in which evaluations are emerging is ginseng and diabetes. Growing evidence is accumulating from in vitro and animal models indicating that various ginseng species, American (Panax quinquefolius L), Asian (Panax ginseng C.A. Meyer), Korean Red, San-chi (Panax notoginseng [Burk.] P.R. Chen), and the non-panax species Siberian (Eleutherococcus senticossus) ginsing, and their fractions, saponins (ginsenosides) and peptidoglycans (panaxans for panax species and eleutehrans for Siberian ginseng), might affect carbohydrate metabolism and related signaling molecules. Recent human studies from our laboratory have also shown a blood glucose lowering effect of American ginseng (AG) and some other ginseng spices postprandially after acute administration and chronically after administration for 8-weeks in people with type 2 diabetes. Although generally encouraging, these data only indicate a need for more evaluations of ginsengs safety and efficacy. Because of poor industry standardization, it is not known whether all ginsengs will affect blood glucose. In this regards some ginseng batches have demonstrated null effects while others have even raised postprandial glycemia. Clinical research should therefore focus on components involved in its glucose lowering effects.

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Clinical Data Analysis of 106 Breast Cancer Patients Who Received Oriental Medical Treatment (한방의료기관에 내원한 106명 유방암 환자 기초자료 분석)

  • Choi, Jin-Young;Lee, Ji-Young;Kim, Eun-Sook;Lee, Sang-Hun;Jung, Hyun-Sik;Lee, Jin-Moo;Lee, Kyung-Sub
    • The Journal of Korean Obstetrics and Gynecology
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    • v.21 no.4
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    • pp.228-236
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    • 2008
  • Purpose: The purposes of this study is to provide basic informations on oriental medical research and treatment through analysis of breast cancer patients, who visited M $\mu$ integrative cancer center, O O university East-West neo medical center. Methods: Electronic medical records of 106 breast cancer patients who visited oriental medical center from June 2, 2006 to February 28, 2008 were selected to collect clinical data of those patients. Clinical data were analyzed for types of clinical characteristics, and received therapies. For analysis of survival and recurrence, Kaplan-Meier method was used. All the data were processed and analyzed using SPSS version 13.0. Results: Average age of breast cancer patients, who visited oriental medical center was 48.72 ($\pm$10.13). The stage distribution record indicated stage I (5.8%), stage II (7.0%), stage III (5.8%), and stage IV (81.4%). Original purposes of patients were analyzed to be supplementary treatment for western therapy (68.9%), treatment for recurrence prevention (18.9%), and oriental medical treatment (12.2%) in order. While receiving oriental medical treatment, 60.4% of patients received conventional medical treatment simultaneously. Conclusion: Majority of patients who visited oriental medical hospital were stage IV at terminal stage and mainly visited for the purpose of supportive care. Further clinical study of breast cancer patients is needed to validate the effectiveness of oriental medical treatment based on this study.

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Clinical study of Chronic Urticaria (만성두드러기에 대한 임상적 고찰)

  • Kim, Hye-Jeong
    • The Journal of Korean Medicine Ophthalmology and Otolaryngology and Dermatology
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    • v.15 no.2
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    • pp.252-260
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    • 2002
  • Introduction Urticaria is widely spread disease. About 15-20 $\%$ of population has experienced at least once in a life time. The etiology of urticaria is uncertain till now, and the affcting factors are various chemical material, physical factors, alcohol, fever, exercise, and hormone, etc. The symptoms of urticaria are small or large wheal-erythema reaction and itching or tingling sense. Cause there is no probe to detect the urticaria clearly, the treatment of urticaria is symptomatic. And mostly urticaria can be chronic and very hard to treat it fundamentally. Nowadays, many trials to treat the urticaria in oriental medical way show good curability. In this paper I'd like to report the treatment rate and degree of urticaria patients mostly using anti-histamine medication. Subjects From the outpatients who visited Korean Hospital of Kyunghee Kangnam during 2000-4 and 2002-1, the 36 chronic urticaria patients, at least more than 4 weeks from onset and 2weeks of treatment period, were chosen. Methods I evaluated the results of treatment with the following scale. Very Good: The all symptoms are clearly disappeared or one third of symptoms remain and sometimes eruption is appeared. Good: Half of the symptoms are improved but most of symptoms remain. No Change: No change appears before and after treatment. Worse: The degree and duration of eruption get worse than pre-treatment state. Results For Acupuncture treatment, I chose the several Acu points like Hapgok(합곡), Taichung(대충), Gokji(곡지), Yanggok(양곡), Yanggea(양계), and lmeup(족임읍), and usually lasted it 15 minutes. With the acupuncture treatment and herb medicine, 2-3 times a week, the patients whose treatment period was 2 to 4 weeks were 17(47.2$\%$), 4 to 8 weeks were 11(30.5$\%$), 8 to 12 weeks were 3(8.3$\%$), 12 to 16 weeks were 3(8.3$\%$), longer than 16 weeks were 2(5.5$\%$) Collecting the statistics of the frequency of prescripted herb medicine, Hyangsosan(향소산) was prescripted 21 times(58.3$\%$), Hyangsapyungwisan(향사평위산) was 15 times(41.6$\%$), Hwapisan(화피산) was 9 times(25$\%$), Yangwitang(양위탕) was 6 times(16.6$\%$), Bojungikkitang(보중익기탕가미) was 4 times(11.1$\%$), Yongdamsagantang (용담사간탕가미) was 4 times(11.1$\%$). The result of the treatments, evaluating with mentioned rate scale, was 11 cases(30.5$\%$) were Very Good degree, 19 cases(52.7$\%$) were Good , 6 cases(16.6$\%$) were No Change. No cases were Worse degree. Conclusion According to this research, we could say that chronic urticaria can be treated with Oriental medical methods. But more precise probes in both Oriental and Western medicine to diagnose the chronic urticaria should be established and we need to make standards for testing and diagnosing the chronic urticaria.

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Herbal Medicine for Functional Dyspepsia with Psychological Symptoms: A Systematic Review and Meta-Analysis (기능성소화불량 환자에서 나타나는 정신적 증상의 한약 치료 : 체계적 문헌고찰과 메타분석)

  • Cho, Yun-jae;Lee, Hanul;Jeong, Hae In;Lee, Hyun-Jin;Keum, Chang-Yul;Han, Aram;Ha, Na-Yeon;Kim, Jinsung
    • The Journal of Internal Korean Medicine
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    • v.42 no.4
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    • pp.488-509
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    • 2021
  • Purpose: Functional dyspepsia (FD) is a chronic syndrome accompanied by repetitive digestive symptoms that appear in the upper gastrointestinal tract and are not caused by specific diseases. Psychological symptoms like anxiety, depression, insomnia, and somatization are frequently observed in FD. The purpose of this study was to review the effect of herbal medicine on the psychological symptoms that accompany FD. Methods: Database search (PubMed, EMBASE, KISS, Kmbase, KoreanMed, NDSL, OASIS, CNKI) was performed on February 24, 2021; a total of 1825 studies were searched. After the screening, 22 studies were included. Results: The studies were assessed by Cochrane RoB 2 and sorted into a table according to psychological symptoms. Meta-analysis was performed to estimate the effect of herbal medicine. Twenty of the twenty-two studies reported that herbal medicine was significantly more effective than the control group. Only three of the studies did not have a high risk of bias. Conclusion: Herbal medicine was significantly effective with or without Western medicine and had fewer adverse effects. Severe adverse effect was not reported. Psychological symptoms in FD affect onset and duration of FD, and some FD patients want to be treated for their anxiety before other symptoms. Reliable information about treatment for the psychological symptoms of FD is lacking. We reviewed the effect of herbal medicine treatment in this study, the results of which could be selected for primary or secondary treatment for FD.

Serum Uric Acid to Creatinine Ratio as a Predictor of Metabolic Syndrome in Healthy Adults Men (건강한 성인 남성의 대사증후군 위험 예측인자로서 혈청 요산/크레아티닌 비율)

  • Kim, Myong Soo;Shin, Kyung A
    • Korean Journal of Clinical Laboratory Science
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    • v.51 no.1
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    • pp.42-49
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    • 2019
  • This study compared the utility of the serum uric acid/creatinine ratio with that of uric acid as a risk predictor of metabolic syndrome. From November 2016 to October 2018, 14,190 adult men under the age of 20 years, who underwent a comprehensive health checkup at a general hospital in their metropolitan area, were included. Metabolic syndrome was assessed according to the American Heart Association/National Heart Lung and Blood Institute (AHA/NHLBI) criteria. Abdominal obesity was based on the WHO criteria in the Western Pacific region. The serum uric acid/creatinine ratio was found to be higher in the fourth quartile than in the first quartile, with a high incidence of metabolic syndrome and metabolic syndrome components. On the other hand, ROC analysis revealed the serum uric acid/creatinine ratio to be a similar indicator of the metabolic syndrome risk to serum uric acid (AUC, 0.554 vs 0.566). The serum uric acid/creatinine ratio showed lower sensitivity and higher specificity than uric acid. In conclusion, the utility of the serum uric acid/creatinine ratio as an independent indicator to predict the risk of metabolic syndrome is limited, and should be used only as an auxiliary marker.

Combination Therapy with a PI3K/mTOR Dual Inhibitor and Chloroquine Enhances Synergistic Apoptotic Cell Death in Epstein-Barr Virus-Infected Gastric Cancer Cells

  • Kim, Mi-Young;Kruger, Annie J.;Jeong, Ju-Yeon;Kim, Jaehee;Shin, Phil kyung;Kim, Sun Young;Cho, Joo Young;Hahm, Ki Baik;Hong, Sung Pyo
    • Molecules and Cells
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    • v.42 no.6
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    • pp.448-459
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    • 2019
  • The phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway is a promising target for gastric cancer (GC) treatment; however the efficacy of PI3K/mTOR dual inhibitors in GC has not yet been maximized. Additionally, the effect of autophagy regulation by PI3K/mTOR dual inhibitors has not been clearly elucidated in GC treatment. We aimed to show that our newly developed PI3K/mTOR dual inhibitor, CMG002, when combined with an autophagy inhibitor, chloroquine (CQ), potently induces effective cancer cell death in Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) cells, where both the PI3K/AKT/mTOR and autophagy pathways play important roles in disease pathogenesis. EBV- and mock-infected AGS and NUGC3 GC cell lines were treated with CMG002 +/- CQ. PI3K/AKT/mTOR signaling pathway mediators, cellular apoptosis and autophagy markers were confirmed by Western blot assay. Cell viability was assessed using the Cell Counting Kit-8 (CCK-8) assay. CMG002 effectively blocked the PI3K/AKT/mTOR pathway by markedly decreasing phosphorylation of AKT and its downstream mediator S6. CMG002 induced G0/G1 cell cycle arrest and enhanced apoptotic cell death in AGS and NUGC3 cells, particularly EBV-infected cells compared with mock-infected cells, as confirmed by flow cytometric analyses and TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assays. The combination of CMG002 plus CQ synergistically increased apoptotic cell death in EBV-infected GC cell lines when compared with CMG002 alone (P < 0.05). Our results suggest that the new PI3K/mTOR dual inhibitor, CMG002, when used in combination with the autophagy inhibitor, CQ, provides enhanced therapeutic efficacy against EBVaGC.

20(S)-protopanaxadiol and oleanolic acid ameliorate cognitive deficits in APP/PS1 transgenic mice by enhancing hippocampal neurogenesis

  • Lin, Kaili;Sze, Stephen Cho-Wing;Liu, Bin;Zhang, Zhang;Zhang, Zhu;Zhu, Peili;Wang, Ying;Deng, Qiudi;Yung, Ken Kin-Lam;Zhang, Shiqing
    • Journal of Ginseng Research
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    • v.45 no.2
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    • pp.325-333
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    • 2021
  • Background: Alzheimer's disease (AD) is one of the most prevalent neurodegenerative disorders. Enhancing hippocampal neurogenesis by promoting proliferation and differentiation of neural stem cells (NSCs) is a promising therapeutic strategy for AD. 20(S)-protopanaxadiol (PPD) and oleanolic acid (OA) are small, bioactive compounds found in ginseng that can promote NSC proliferation and neural differentiation in vitro. However, it is currently unknown whether PPD or OA can attenuate cognitive deficits by enhancing hippocampal neurogenesis in vivo in a transgenic APP/PS1 AD mouse model. Here, we administered PPD or OA to APP/PS1 mice and monitored the effects on cognition and hippocampal neurogenesis. Methods: We used the Morris water maze, Y maze, and open field tests to compare the cognitive capacities of treated and untreated APP/PS1 mice. We investigated hippocampal neurogenesis using Nissl staining and BrdU/NeuN double labeling. NSC proliferation was quantified by Sox2 labeling of the hippocampal dentate gyrus. We used western blotting to determine the effects of PPD and OA on Wnt/GSK3β/β-catenin pathway activation in the hippocampus. Results: Both PPD and OA significantly ameliorated the cognitive impairments observed in untreated APP/PS1 mice. Furthermore, PPD and OA significantly promoted hippocampal neurogenesis and NSC proliferation. At the mechanistic level, PPD and OA treatments resulted in Wnt/GSK-3β/β-catenin pathway activation in the hippocampus. Conclusion: PPD and OA ameliorate cognitive deficits in APP/PS1 mice by enhancing hippocampal neurogenesis, achieved by stimulating the Wnt/GSK-3β/β-catenin pathway. As such, PPD and OA are promising novel therapeutic agents for the treatment of AD and other neurodegenerative diseases.