• Title/Summary/Keyword: mechanism of disease

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Effects of Gastrodia Rhizoma Extracts on Global Coronary Circulation in Rats (천마 Extracts가 백서의 국소적 관상순환기능에 미치는 영향)

  • Kim, Eun-Ji;Ji, Geun-Eog;Kang, Young-Hee
    • Korean Journal of Food Science and Technology
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    • v.26 no.3
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    • pp.213-220
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    • 1994
  • Gastrodia (G) Rhizoma has been used clinically as an oriental herbal medicine with sedative, anticonvulsive, and depressor effects. The present study tested effects of G. Rhizoma extracts on the coronary circulation and myocardial oxygen consumption in perfused rat hearts. Sprague Dawley rats (SD) and spontaneously hypertensive rats (SHR) were employed as experimental animals and nonworking Langendorff heart perfusion technique introduced for heart experiments. G. Rhizoma extracts were prepared from grinding G. Rhizoma into powder, extracting in water and 50% ethanol for 4 or 16 hr and diluting with Krebs-Henseleit bicarbonate perfusion buffer to be 70%. Hearts were perfused with bicarbonate buffer oxygenated with 95% $O_{2}:$ 5% $CO_{2}$ at constant coronary perfusion pressure of $90cmH_{2}O$. The diluted extracts were infused into coronary arteries in a concentration of $1{\sim}5\;{\mu}M$ for $7{\sim}8 min. While in SD water- or ethanol-extracts of G. Rhizoma extracted for 16 hr increased coronary perfusate flow (CPF) and decreased coronary vascular resistance (CVR), ethanol-extracts in SHR produced coronary vasoconstriction associated with enhanced CVR. G. Rhizoma extracts-induced increase in CPF reduced myocardial oxygen extraction, and thus myocardial oxygen consumption ($MVO_{2}$) remained at that observed prior to infusion of extracts. In SD and SHR 16 hr-water-extracts markedly altered coronary venous effluent pH and $Pco_{2}$ and evoked metabolic acidosis, which could be a coronary vasodilator mechanism decreasing CVR. In this study, the extracts decreasing CVR in SD and SHR did not augment the lactate production. Therefore, although the effects of the extracts on cardiac function and coronary circulation depended on solvents and duration for extraction, the 16hr-water-extracts, at least, exhibited coronary vasodilation in SD and SHR. Conversely, ethanol-extracts constricted coronary arteries in SHR. G. Rhizoma extracts-induced vasodilation might be due to the metabolic acidosis rather than due to the increased lactate production. The results indicate that G. Rhizoma extracts obtained from proper extracting procedures can be used as a safe and clinically applicable herbal medicine in the cardiovascular diseases such as coronary artery disease and hypertension for vasodilatory and antihypertensive actions.

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Improving effect of psoriasis dermatitis by yakuchinone A in the TNF-α stimulated HaCaT cells (TNF-α 자극에 활성화된 HaCaT 세포주에서 Yakuchinone-A에 의한 건선 피부염 개선 효과)

  • Kim, Min Young;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.63 no.1
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    • pp.95-101
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    • 2020
  • Psoriasis is an autoimmune skin disease that is accompanied by hyper proliferation of the epidermis, erythema of various sizes, and ulceration. However, the mechanism of the development of psoriasis dermatitis is unclear. Recently, it is known that the inflammatory cytokines and Th17 cells as well as chemokine (CC motif) ligand 20 (CCL20) are involved in the process of keratinocytes hyper-differentiation, which is common in psoriasis dermatitis. Therefore, we studied the effects of yakuchinone-A, an active ingredient of Alpinia oxyphylla Miquel known for its anti-inflammatory activity, to improve psoriasis dermatitis. First, cytotoxicity of yakuchinone-A was observed in cell counting kit-8 assay and not observed in 10 ㎍/mL concentration on the human keratinocyte HaCaT cells. Yakuchinone-A in the presence of tumor necrosis factor-alpha (TNF-α) on HaCaT cells inhibited mRNA expression of IL-6, IL-8, and TNF-α by up to 61.4±7.5, 23.6±1.5, 46.0±4.8%. CCL20, a chemokine that attracts immune cells such Th17 cells to the inflammation location, was also significantly suppressed by yakuchinone-A. In addition, IκB and STAT3 phosphorylation involved in the CCL20 expression was inhibited by yakuchinone-A in a concentration-dependent manner up to the level of 79.1±5.0, 80.8±2.3%. Furthermore, yakuchinone-A downregulated CCL20 mRNA expression level on IL-17A-activated HaCaT cells as a concentration-dependent manner. Based on these results, yakuchinone-A is expected to be developed as a new material for improving psoriasis dermatitis in the future.

Biochemical Characteristics for the Cofactor Free Mutant of Yeast Homocysteine Catalyzing Enzyme, Cystathionine ${\beta}$-Synthase (조효소를 함유하지 않는 효모의 Homocysteine 분해효소, Cystathionine ${\beta}$-Synthase의 생화학적 특성)

  • Jhee, Kwang-Hwan;Cho, Hyun-Nam;Yang, Seun-Ah;Lee, In-Seun
    • Microbiology and Biotechnology Letters
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    • v.35 no.3
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    • pp.196-202
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    • 2007
  • Mutations in the cystathionine ${\beta}$-synthase (CBS) gene cause homocystinuria, the most frequent inherited disorder in sulfur metabolism. CBS is the unique enzyme using both heme and pyridoxal 5-phosphate (PLP) for activity. Among the reported 140 mutations, one of the most common disease-causing alterations in human CBS is G307S mutation. To investigate the pathogenic mechanism of G307S by spectroscopic methods, we engineered the full length and the truncated G247S mutation of yeast CBS that is corresponding mutation to human G307S. Yeast CBS does not contain heme and thus gives a merit to study the spectroscopic properties. The UV-visible spectra of the purified full length and the truncated G247S yeast CBSs showed the total absence of PLP in the protein. The absence of PLP in G247S mutation was also confirmed by the PLP-cyanide adduct formation experiment, which was conducted by the incubation of the purified enzyme with KCN. The adducts were detected using a circular dichroism (CD) and a spectrofluorimeter. Radio isotope activity assay of full length and truncated G247S proteins also gave no activity. Our yeast G247S mutation data suggested that G307S might make the distortion of the active site so that cofactor PLP and substrate can not fit inside the active site. Our yeast CBS study addressed the reason why the G307S mutation in human CBS makes the enzyme inactive that consequently leads to severe clinical phenotype.

Signal Transduction of MUC5AC Expression in Airway Mucus Hypersecretory Disease (기도의 점액 과분비 질환에서 MUC5AC의 발현의 신호 전달 경로에 관한 연구)

  • Shim, Jae Jeong
    • Tuberculosis and Respiratory Diseases
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    • v.55 no.1
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    • pp.21-30
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    • 2003
  • Background : Mucin synthesis in airways has been reported to be regulated by the epidermal growth factor receptor (EGFR) system. Epidermal growth factor receptor transactivation was identified as a critical element in G-protein-coupled receptors (GPCRs)-induced mitogenic signaling. EGF receptor transactivation by G-protein-coupled receptors requires metalloproteinase cleavage of proHB-EGF. This study was hypothesized that lipopolysaccharide (LPS)-induced mucin production associates with epidermal growth factor receptor transactivation, and MUC5AC production associates with epidermal growth factor receptor transactivation by G-protein-coupled receptors that regulates by metalloproteinase. Method : MUC5AC mucin production was examined in NCI-H292 cells and MUC5AC protein synthesis was assessed using ELISA. For the evaluation of mechanism of LPS-induced MUC5AC production, $TNF{\alpha}$ was measured using ELISA with or without pretreatment of heterotrimeric G-protein inhibitor, mastoparan. MUC5AC protein was measure with pretreatment of polyclonal $TNF{\alpha}$ antibody or mastoparan on LPS-induced MUC5AC production. For the evaluation of relation of G-protein and MUC5AC production, G-protein stimulant, mastopara-7, or matrix metalloproteinase, ADAM10, was added to NCI-H292 cells. MUC5AC protein was measure with pretreatment of polyclonal EGF antibody on mastoparan-7-induced MUC5AC production. Results : LPS alone did not increase significantly MUC5AC production. LPS with $TNF{\alpha}$ induced dose-dependently MUC5AC production in NCI-H292 cells. LPS increased dose-dependently $TNF{\alpha}$ secretion, which was inhibited by mastoparan. LPS with $TNF{\alpha}$-induced MUC5AC production was inhibited by neutralizing polyclonal $TNF{\alpha}$ antibody, mastoparan or AG 1472. Mastoparan-7 or ADAM10 increased dose-dependently MUC5AC production, which was inhibited by polyclonal neutralizing EGF antibody. Conclusion : In LPS-induced MUC5AC synthesis, LPS causes $TNF{\alpha}$ secretion, which induces EGFR expression. EGFR tyrosine kinase phosphorylation result in MUC5AC production. EGF-R transactivation by G-protein-coupled receptors requires matrix metalloproteinase cleavage of proHB-EGF.

Fermented Jeju Soybean Extract Promotes Hair Growth in Human Hair Follicle Organ Culture and Clinical Trial (모낭기관배양과 임상에서 제주푸른콩발효추출물의 육모 효능에 미치는 영향)

  • Lee, Yonghee;Shin, Seung Hyun;Kim, Sehyun;Jeong, Gyusang;Hong, Min Jung;Park, Hyeokgon;Kim, Seung Hun;Kim, Eun Joo;Kang, Young-Gyu;Park, Byung Cheol;Park, Won Seok;Kim, Su Na;Kim, Hyoung-June
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.47 no.3
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    • pp.255-263
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    • 2021
  • Soybean extract is known to play an important role in preventing and treating diseases associated with aging, cancer, obesity, and cardiovascular disease. A recent has revealed that soybean extract has a potent effect on hair growth in in vitro, in vivo, and clinical studies. Recently, it has been reported that their fermented extracts exhibit numerous and high efficacy, as compared to general extracts. However, the underlying mechanisms that induce hair growth after using fermented soybean extract are not well understood. The present study aimed to determine the effects of fermented Jeju soybean (FJS) extract on hair growth, with a focus on the underlying mechanisms similar to those of minoxidil. We conducted in vitro and ex vivo investigations and clinical studies. FJS extract enhanced dermal papilla cell proliferation, VEGF levels, and potassium channel opening. Moreover, it promoted human hair follicle elongation. These effects were comprehensively demonstrated in the clinical results, in which FJS extract-containing shampoo improved hair density after 24 weeks of utilization. Collectively, the results of this study demonstrate that FJS extract promotes hair growth and inhibits hair loss through a mechanism similar to that of minoxidil in hair follicles.

Brazilin downregulates CCL20 expression via regulation of STAT3 phosphorylation in TNF-α/IL-17A/IFN-γ-induced HaCaT cells (TNF-α/IL-17A/IFN-γ 유도된 HaCaT 세포에서 브라질린의 STAT3 인산화 억제를 통한 CCL20 저해 효과)

  • Kim, Mi Ran;Hwang, Hyung Seo
    • Journal of Applied Biological Chemistry
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    • v.64 no.2
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    • pp.185-192
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    • 2021
  • Psoriasis is a chronic intractable skin disease caused by various inflammatory cytokines such as IL-6, CXCL8, TNF-α, and IFN-γ, as well as IL-17A secreted from Th17 cells and is characterized by hyperkeratosis and chronic inflammation of the epidermis. Brazilin, an active ingredient of Caesalpinia sappan L., is known to exert antioxidant and anti-inflammatory activity, and function in skin barrier improvement. In particular, it was shown as a potential material for treating psoriasis in a tumor necrosis factor (TNF)-α-stimulated HaCaT keratinocyte model. However, the direct regulation of the C-C motif chemokine ligand (CCL) 20, a psoriasis-inducing factor, by brazilin has not been reported. Therefore, in this study, we investigated the suppression of CCL20 and the regulatory mechanism by brazilin using a psoriasis-like model. First, brazilin downregulated CCL20 and CXCL8 in IL-17A-stimulated HaCaT cells in a concentration-dependent manner by inhibiting signal transducer and transcription (STAT)3 phosphorylation. In addition, brazilin significantly inhibited the expression of psoriasis-related genes CXCL8, CCL20, IL-1, IL-6, and TNF-α in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. Moreover, brazilin also had a positive effect on improving the skin barrier in TNF-α/IL-17A/IFN-γ-stimulated HaCaT cells. The above results indicated that brazilin ultimately downregulated CCL20 expression by inhibiting STAT3 phosphorylation, and also suppressed the expression of psoriasis-induced cytokines. If the efficacy of brazilin in improving psoriasis is verified through animal models and clinical trials in the future, it may represent a potentially therapeutic substance for psoriasis patients.

Fatty acid analysis and regulatory effects of citron (Citrus junos Sieb. ex TANAKA) seed oil on nitric oxide production, lipid accumulation, and leptin secretion (유자씨유의 지방산분석 및 Nitric Oxide 생성, 지방축적능, 렙틴분비 조절효과)

  • Kim, Tae Woo;Kim, Kyoung Kon;Kang, Yun Hwan;Kim, Dae Jung;Choe, Myeon
    • Journal of Nutrition and Health
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    • v.47 no.4
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    • pp.221-228
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    • 2014
  • Purpose: Citron seed oil (CSO) has been reported to have high antioxidant activity. However, the composition and other biologically activities of CSO have not been reported. In this study, we confirmed the fatty acid composition of CSO, which may be beneficial to vascular disease and obesity. Methods: We investigated the oil composition of CSO using gas chromatography coupled with mass spectrometry (GC-MS) analysis, and cytotoxicity was confirmed by Cell Counting Kit-8 (CCK-8) assay. Nitric oxide (NO) production in human umbilical vein endothelial cells (HUVECs) was measured using Griess reagent, and lipid accumulation and leptin secretion in 3T3-L1 cells were measured by Oil-Red O staining and commercial ELISA kit, respectively. Results: GC-MS analysis indicated that CSO contains several components, including linoleic acid, oleic acid, palmitic acid, stearic acid, linolenic acid, palmitoleic acid, and arachidic acid. In physiological activity analysis, CSO did not induce cytotoxic effects in HUVECs and 3T3-L1 cells. Further, CSO significantly induced nitric oxide and leptin secretion as well as inhibited lipid accumulation. Conclusion: CSO increased NO release, inhibited lipid accumulation, and induced leptin secretion, suggesting it may be useful for the management of vessels and weight gain. Although further studies are required to investigate the safety and mechanism of action of CSO, our results show that the composition and physiological activity of CSO are sufficient for its use as functional edible oil.

『황제내경소문(黃帝內經素問)·칠편대론(七篇大論)』 왕빙 주본(注本)을 통(通)한 운기학설(運氣學說) 관(關)한 연구(硏究)

  • Kim, Gi-Uk;Park, Hyeon-Guk
    • The Journal of Dong Guk Oriental Medicine
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    • v.4
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    • pp.109-140
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    • 1995
  • As we considered in the main subjects, investigations on the theory of 'Doctrine on five elements' motion and six kinds of natural factors(運氣學說)' through 'Wang Bing's Commentary(王氷 注本)' of 'The seven great chapters in The Yellow Emperor's Internal Classic Su Wen' ("黃帝內經素問 七篇大論") are as follows. (1) In The seven great chapters("七篇大論")' Wang Bing supplement theory and in the academic aspects as a interpreter, judging from 'forget(亡)' character. expressed in the 'The missing chapters("素問遺篇")', 'Bonbyung-ron("本病論")' and 'Jabeob-ron(刺法論)', 'The seven great chapters("七篇大論")' must be supplementary work by Wang Bing. Besides, he quoted such forty books as medical books, taoist books, confucianist books, miscellaneous books, etc in the commentary and the contents quoted in the 'Su Wen(素問)' and 'Ling Shu("靈樞")' scripture nearly occupy in the book. As a method of interpreting scripiure as scripture, he edited the order of 'Internal Classic("內經")' ascended from the ancient time and when he compensated for commentary, with exhaustive scholarly mind and by observing the natural phenomena practically and writing the pathology and the methods of treatment. We knew that the book is combined with the study of 'Doctrine on five elements motion and six kinds of natural factors(運氣學說)' (2) When we compare, analyze the similar phrase of 'The seven great chapters in The Yellow Emperor's Internal Classic Su Wen'("黃帝內經素問ㆍ七篇大論") through 'Wang Bing's Commentary(王氷 注本)', he tells abouts organized 'five elements(五行)' and 'heaven's regularly movement(天道運行)' rather than 'Emyangengsangdae-ron("陰陽應象大論")' in 'The seven great chapters("七篇大論")'. Also the 'Ohanunhangdae-ron("五運行大論")' because the repeated sentences with 'Emyangengsangdae-ron("陰陽應象大論")' is long they are omitted. And in the 'Youkmijidae-ron("六微旨大論")', 'Cheonjin ideology(天眞四象)' based on the 'Sanggocheonjin- ron("上古天眞論")', 'Sagijosindae-ron("四氣調神大論")' is written and in the 'Gigoupyondae-ron("氣交變大論")', the syndrome and symptom are explained in detail rather than 'Janggibeobsi-ron("藏氣法時論")', 'Okgijinjang-ron ("玉機眞藏論")' and in the 'Osangieongdae-ron("五常政大論")', the concept of 'five element(五行)' of the 'Gemgwejineon-ron("金櫃眞言論")' is expanded to 'the five elements' motion concept(五運槪念)' and in the 'Youkwonjeonggidae-ron("六元正紀大論")', explanations of 'The five elements' motion and six kinds of natural factors(運氣)' function are mentioned mainly and instead systematic pathology is not revealed rather than 'Emyangengsangdae-ron("陰陽應象大論")'. And in the 'Jijinyodae-ron("至眞要大論")', explanations of the change of atmosphere which correspond to treatment principle by 'The three Yin and Yang(三陰三陽)' as a progressed concepts are revealed. Therefore there are much similarity between the phrase of 'Emyangengsangdae-ron("陰陽應象大論")' and 'chapters of addition(補缺之篇)'. Generally, the doctrine which 'The seven great chapters("七篇大論")' are added by Wang Bing(王氷) is supported because there are more profound concepts rather than the other chapter in 'The seven great chapters("七篇大論")'. (3) When we study Wang Bing's(王氷) 'Pattern on five elements motion and six kinds of natural factors(運氣格局)' in 'The seven great chapter("七篇大論")', in the 'Cheonwongi-dae-ron("天元紀大論")', With 'Cheonjin ideology(天眞思想)' and the concepts of 'Owang(旺)'${\cdot}$'Sang(相)'${\cdot}$'Sa(死)'${\cdot}$'Su(囚)'${\cdot}$'Hu(休)' and 'Cheonbu(天符)'${\cdot}$'Sehwoi(歲會)' are measured time-spacially to the concept of 'Three Sum(三合)' the concept of 'Taeulcheonbu(太乙天符)' is explained. In the 'Ounhangdae-ron("五運行大論")', 'The calender Signs five Sum(天干五合)' is compared to the concepts of 'couples(夫婦)', 'weak-strong(柔强)' and in the 'Youkmijidae-ron("六微旨大論")', 'the relationship of obedience and disobedience(順逆關係)' which conform to the 'energy status(氣位)' change and 'monarch-minister(君相)' position is mentioned. In the 'Gikyobyeondae-ron("氣交變大論")', the concept of 'Sang-duk(相得)', 'Pyungsang(平常)' is emphasized but concrete measurement is mentioned. In the 'Osangieongdae-ron("五常政大論")', the detailed explanation with twenty three 'systemic of the five elements' motion(五運體系)' form and 'rountine-contrary treatment(正治. 反治)' with 'chill-fever-warm-cold(寒${\cdot}$${\cdot}$${\cdot}$凉)' are mentioned according to the 'analyse and differentiate pathological conditions in accordance with the eight principal syndromes(八綱辨證)'. In the 'Youkwonjeonggidae-ron("六元正紀大論")', Wang Bing of doesn't mention the concepts of 'Jungwun(中運)' that is seen in the original classic. In the new corrective edition, as the concepts of 'Jungwun, Dongcheonbu, Dongsehae and Taeulcheonbu(中運, 同天符, 同歲會, 太乙天符)' is appeared, Wang Bing seems to only use the concepts of 'Daewun, Juwun, and Gaekwun(大運, 主運, 客運)'. In the 'Jijinyodaeron("至眞要大論")', Wang Bing added detailed commentary to pathology and treatment doctrine by explaining the numerous appearances of 'Sebo, sufficiency, deficiency(歲步, 有餘, 不足)' and in the relation of 'victory-defeat(勝復)', he argued clearly that it is not mechanical estimation. (4) When we observe the Wang Bing's originality on the study of 'the theory of Doctrine on five elements' motion and six kinds of natural factors(運氣學說)', he emphasized 'The idea of Jeongindogi and Health preserving(全眞導氣${\cdot}$養生思想)' by adding 'Wang Bing's Commentary(王氷 注本)' of 'The seven great chapters("七篇大論")' and explained clearly 'The theory of Doctrine on five elements' motion and six kinds of natural factors(運氣學說)' and simpled and expanded the meaning of 'man, as a microcosm, is connected with the macrocosm(天人相應)' and with 'Atmosphere theory(大氣論)' also explained the meaning of 'rising and falling mechanism(升降氣機)'. In the sentence of 'By examining the pathology, take care of your health(審察病機 無失氣宜)'. he explained the meaning of pathology of 'heart-kidney-water-fire(心腎水火)' and suggested the doctrine and management of prescription. In the estimation and treatment, by suggesting 'asthenia and sthenia(虛實)' two method's estimation, 'contrary treatment(反治)' and treatment principals of 'falling heart fire tonifyng kidney water(降心火益腎水)', 'two class of chill and fever(寒熱二綱)' were demonstrated. There are 'inside and outside in the illness and so inner and outer in the treatment(病有中外 治有表囊)'. This sentence suggests concertedly. 'two class of superfies and interior(表囊二綱)' conforming to the position of disease. Therefore Wang Bing as an excellent theorist and introduced 'Cheoniin ideology(天眞思想)' as a clinician and realized the medical science. With these accomplishes mainly written in 'The theory of Doctrine on five elements' motion and six kinds of natural factors(運氣學說)' of 'The seven great chapters("七篇大論")', he interpreted the ancient medical scriptures and expanded the meaning of scriptures and conclusively contributed to the development of the study 'Korean Oriental Medicine(韓醫學)'.

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