• The Korean Journal of Pharmacology
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• v.26 no.2
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• pp.193-207
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• 1990

Transforming growth factor ${\beta}(TGF-{\beta})$ is a multifunctional polypeptide with diverse effects on the proliferation, differentiation and other functions in many cell types. $TGF-{\beta}$ is highly abundant in bone matrix and induces divergent responses in many aspects of bone cell metabolism . Several lines of investigation indicate that matrix-associated $TGF-{\beta}$ is the products of bone cells themselves. However, exact bone cell type reponsible for the production of $TGF-{\beta}$ is still in controversy, The present study was undertaken to determine the cellular origin of matrix-associated $TGF-{\beta}$ and to assess how different bone cells respond to $TGF-{\beta}$. As a prerequisite for this, 5 bone cell populations of distinct phenotype were isolated from fetal calvaria with sequential enzyme digestion protocol and biochemical characterization. Calvarial cell populations released in early stage showed fibroblastic features whereas populations relesed later was enriched with osteoblast-like cell as judged by their acid and alkaline phosphatase activities, cAMP responsiveness to parathyroid hormone, calcitonin and prostaglandin $E_2$ and collagen synthesis rate. By polyacylamide gel and immunoblot analysis of bone and calvarial cell extracts, presence of $TGF-{\beta}$ in bone tissues and production of $TGF-{\beta}$ by bone cells were confirmed again. Subsequent analysis of calvarial cell extracts prepared as individual population revealed that all calvarial cell populations synthesize $TGF-{\beta}$. Exogenously added $TGF-{\beta}$ induced biphasic response upon bone cell proliferation under serum-free condition. In osteoblastic cell populations, it was stimulatory whereas inhibitory in fibroblastic cell populations. In contrast, collagen and noncollagen protein synthesis of all calvarial cell populations were stimulated by $TGF-{\beta}$. Enhancement of protein synthesis was found to be more general rather than specific for collagen synthesis. In addition, effects of $TGF-{\beta}$ on protein synthesis were independent to its effects on cell proliferation. In summary, production of $TGF-{\beta}$ by bone cells and differential actions on various cell populations observed in this study suggest that $TGF-{\beta}$ may play an important role in the regulation of bone metabolism by modulating the specific cellular functions in autocrine and paracrine fashion.

• Journal of Applied Biological Chemistry
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• v.53 no.2
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• pp.65-70
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• 2010

Medium-chain fatty acids (MCFA) are composed of 8-12 carbon atoms, and are found in coconut, cuphea, and palm kernel oil. MCFA were introduced into clinical nutrition in the 1950s for dietary treatment of malabsorption syndromes because of their rapid absorption and solubility. Recently, MCFA have been applied to Gastrointestinal Permeation Enhancement Technology (GIPET), which is one of the most important parts in drug delivery system in therapeutics. Therefore, to accumulate the MCFA in seed oil of rapeseed, much effort has been conducted by classical or molecular breeding. Laurate can be successfully accumulated up to 60 mol% in the seed oil of rapeseed by the expression of bay thioesterase (Uc FatB1) alone or crossed with a line over-expressing the coconut lysophosphatidic acid acyltransferase (LPAAT) under the control of a napin seed-storage protein promoter. Also, caprylate and caprate were obtained 7 mol% and 29 mol%, respectively, from plants over-expressing of the medium-chain specific thioesterase (Ch FatB2) alone or together with the chain-length-specific condensing enzyme (Ch KASIV). Despite the success of some research in utilizing parallel classical and molecular breeding to produce MCFA, commercially available seed oils have for the most part, not been realized. Recent research in the field of developing MCFA-enriched transgenic plants has established that there is no single rate-limiting step in the production of the target fatty acids. The purpose of this article is to review some of the recent progress in understanding the mechanism and regulation of MCFA production in seed oil of rapeseed.

• Pediatric Infection and Vaccine
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• v.21 no.1
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• pp.9-21
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• 2014

Purpose: To determine the clinical significance of voriconazole therapeutic drug monitoring (TDM) in the pediatric population. Methods: Twenty-eight patients with invasive fungal infections administered with voriconazole from July 2010 to June 2012 were investigated retrospectively. Fourteen received TDM, and 143 trough concentrations were analyzed. All 28 patients were assessed for adverse events and treatment response six weeks into treatment, and at the end. Results: Out of 143 samples, 53.1% were within therapeutic range (1.0-5.5 mg/L). Patients administered with the same loading (6 mg/kg/dose) and maintenance (4 mg/kg/dose) dosages prior to initial TDM showed highly variable drug levels. Adverse events occurred in 9 of 14 patients (64.3%) in both the TDM and non-TDM group. In the TDM group, voriconazole-related encephalopathy (n=2, 14.3%) and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) elevation (n=8, 57.1 %) occurred with serum levels in the toxic range (>5.5 mg/L), whereas blurred-vision (n=2, 14.3%) occurred within the therapeutic range (1.18 mg/L and 3.9 mg/L). The frequency of voriconazole discontinuation due to adverse events was lower in the TDM group (0.0% vs. 18.2%, P =0.481). Overall, 57.2% of the patients in the TDM group versus 14.3% in the non-TDM group showed clinical response after 6 weeks (P =0.055), whereas 21.4% in the TDM group versus 14.3% in the non-TDM group showed response at final outcome (P =0.664). In the TDM group, >67.0% of the serum levels were within therapeutic range for the first 6 weeks; however 45.5% were within therapeutic range for the entire duration. Conclusion: Routine TDM is recommended for optimizing the therapeutic effects of voriconazole.

• Clinical and Experimental Reproductive Medicine
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• v.35 no.4
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• pp.247-265
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• 2008

Objectives: Many types of liver diseases can damage regenerative potential of mature hepatocytes, hepatic progenitor cells or oval cells. In such cases, a stem cell-based therapy can be an alternative therapeutic option. We examined whether human amnion-derived mesenchymal stem cells (HAM) and human umbilical cord-derived stem cells (HUC) could differentiate into hepatocyte-like cells as therapeutic cells for the liver diseases. Methods: HAM and HUC were isolated from the amnion and umbilical cord of the volunteers after a caesarean section with informed consent. In order to differentiate these cells into hepatocyte-like cells, cells were cultivated in hepatogenic medium using culture plates coated with fibronectin. Effects of hepatocyte growth factor, L-ascorbic acid 2-phosphate, insulin premixture fibroblast growth gactor 4, dimethylsulfoxide, oncostatin M and/or dexamethasone were examined on the hepatic differentiation. After differentiation, the cells were analyzed by RT-PCR, immunocytochemistry, immunoblotting, albumin ELISA, urea assay and periodic acid-schiffs staining. Results: Initial fibroblast-like appearance of HAM and HUC changed to a round shape during culture in the hepatogenic medium. However, in all hepatogenic conditions examined, HUC secreted more amounts of albumin or urea into medium than HAM. Expression of some of hepatocyte-specific genes increased and expression of new genes were observed in HUC following cultivation in hepatogenic medium. Results of immunocytochemistry and immunoblotting analyses demonstrated that HUC secreted albumin into the culture medium. PAS staining further demonstrated that HUC could store glycogen inside of the cells. Conclusions: Both HUC and HAM could differentiate into albumin-secreting, hepatocyte-like cells. Under the same hepatogenic conditions examined, HUC more efficiently differentiated into hepatocyte-like cells compared with the HAM. The results suggest that HUC and HAM could be used as sources of stem cells for the cell-based therapeutics such as in liver diseases.

• Biomolecules & Therapeutics
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• v.22 no.4
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• pp.363-369
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• 2014

Synthetic cannabinoids (CBs) such as the JWH series have caused social problems concerning their abuse liability. Because the JWH series produces euphoric and hallucinogenic effects, they have been distributed illegally under street names such as "Spice" and "Smoke". Many countries including Korea have started to schedule some of the JWH series compounds as controlled substances, but there are a number of JWH series chemicals that remain uncontrolled by law. In this study, three synthetic CBs with different binding affinities to the $CB_1$ receptor (JWH-073, 081, and 210) and ${\Delta}^9$-tetrahydrocannabinol (${\Delta}^9$-THC) were evaluated for their potential for psychological dependence. The conditioned place preference test (unbiased method) and self-administration test (fixed ratio of 1) using rodents were conducted. $K_i$ values of the three synthetic cannabinoids were calculated as supplementary data using a receptor binding assay and overexpressed $CB_1$ protein membranes to compare dependence potential with $CB_1$ receptor binding affinity. All mice administered JWH-073, 081, or 210 showed significantly increased time spent at unpreferred space in a dose-dependence manner in the conditioned place preference test. In contrast, all tested substances except ${\Delta}^9$-THC showed aversion phenomenon at high doses in the conditioned place preference test. The order of affinity to the $CB_1$ receptor in the receptor binding assay was JWH-210 > JWH-081 >> JWH-073, which was in agreement with the results from the conditioned place preference test. However, no change in self-administration was observed. These findings suggest the possibility to predict dependence potential of synthetic CBs through a receptor binding assay at the screening level.

• Journal of the Korean Applied Science and Technology
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• v.37 no.1
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• pp.102-113
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• 2020

In this study, anti-arthritic effect of the mixed extract of radiation mutant Perilla frutescens var. crispa and Atractylodes macrophala koidz was investigated. Cell viability was determined by MTT assay in RAW 264.7 cells. The anti-inflammatory effect of mixed extracts was determined through measurement of the levels of reactive oxygen species (ROS) and nitric oxide (NO), release of inflammatory cytokines and expression of NF-κB, COX-2 and iNOS in LPS-induced RAW 264.7 cells after treatment of mixed extracts (5, 10, 25 ㎍/㎖). We showed that the mixed extracts was not toxic in the dose of 5, 10, 25 ug/ml, and significantly inhibited production of nitric oxide and ROS, cytokines including IL-1β, IL-6, TNF-α, and inflammatory proteins including NF-κB, COX-2 and iNOS in LPS-induced RAW 264.7 cells. Moreover, the mixed extract inhibited the type II collagen induced arthritis in DBA mice in the dose of 66.5 and 133mg/kg/day. Therefore, we suggest that mixed extract of radiation mutant Perilla frutescens var. crispa and Atractylodes macrophala koidz can be developed as a raw material for health functional food and therapeutics to treat the inflammatory arthritis.

• Journal of the Korean Applied Science and Technology
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• v.37 no.1
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• pp.124-132
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• 2020

The purpose of this study was to investigate the biological activities such as cytotoxicity and anti-inflammation using Manjakani (Quercus infectoria Olivier) extract. Manjakani was extracted from hot DW and 80% ethanol. Cell viability was assessed using MTT assay on RAW 264.7 cells. Also, anti-inflammatory activities were measured through changes in the levels of nitric oxide (NO), prostaglandin E₂ (PGE₂), leukotrien B4 (LTB₄), pro-inflammatory cytokines (IL-1β, IL-6 and tumor necrosis factor (TNF)-α) and transcription factor on LPS-induced RAW264.7 cells. The results confirmed that significant cytotoxicity does not appear in the concentration range of 1, 5, and 10 ㎍/㎖ of both extracts of this study. The production of NO was slowed by approximately MDE 37.2% and MEE 43.7% at 10 ㎍/㎖ concentration. Also, level of PGE₂ and LTB₄ was decreased MDE 30.9%/MEE 43.7% and MDE 37.1%/MEE 43.7%. In the case of inflammatory cytokine was reduced to MDE 38.8%/MEE 50.8% for IL-1β, MDE 35.0%/MEE 44.2% for IL-6 and MDE 31.9%/MEE 36.6% for TNF-α at 10 ㎍/㎖ concentration. The mRNA expression of NF-κB, iNOS and COX-2 significantly decreased by MDE 44.0%/MEE 16.0%, MDE 44.0%/MEE 55.0% and MDE 45.0%/MEE 40.0%, respectively, following the 10 ㎍/mL sample treatment when compared to the control. Both extracts were effective in anti-inflammatory activity. In addition, both extracts showed efficient changes of production of NO, PGE₂, LTB₄, pro-inflammatory cytokines and transcription factor. But MEE was found to have a higher inhibitory effect than MDE. In other words, Manjakani was showed significant biological activities showing anti-inflammation without cytotoxicity. These results will be provided as fundamental data for further development of the new health food and therapeutics related to the results above.

• Journal of Society of Preventive Korean Medicine
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• v.1 no.1
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• pp.85-104
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• 1997

As the concern about health is increased, the importance of preventive medicine that prevent disease in advance to overcome boundary of disease remedy gets emphasized in the whole world. The fundamental thoughts of oriental medicine are the harmony between the human body and nature, the unified idea regarding mind in the same light with body, and the symmetry of the cosmo dual forces. And oriental medicine is a kind of study that has developed on the ground of prevention thought. from old days, it has been developed the preventive medicine at is called 'Yangseng(養生; recuperation)' etc. with the clinical medicine. The preventive medicine of oriental medicine was taking a serious of the first preventive medicine of an incurable disease thought and the prevention thought that belongs to the second and third preventive medicine is described through the whole oriental medicine. Also the clinical and preventive medicine to apply to the clinics have an in- separable relation. Therefore I inspected the part of the preventive medicine described in some oriental medicine books and studied the characteristics of preventive medicine of oriental medicine as follows; First, the preventive medicine of oriental medicine has the characteristics that is emphasized generally in the first preventive medicine and wholly it is composed in the system of the first, second and third preventive medicine. It has the presentative theory such as 'Jungkijonae sabulkaghan(正氣存內 邪不可干; If good energy is in body, a disease. dosen't occur)', 'Husajukpung Phijeyushi(虛邪賊風 避之有時; When e infectious disease like plague break out, they must avoid the place occurring the disease)', 'Chuninsangeung(天人相應; The harmony of nature and human)' etc.. This is intimately related to the incurable disease thought of the inside diameter and oriental medicine has pursued that. Second, due to the most prerequisite theory of disease production, the balanced condition of environment, the cause of a disease and host is called the health. As oriental medicine has the system of aetiology like that, we can see the host and environments are importance most of all. Namely we can think of the relation of host >> environment > the cause a disease Up to date Jungkijonae Sabulkaghan(正氣存內 邪不可干) that the most oriental medicine doctors have had a knowledge is not whole theory but a pan of oriental medicine science and it is included in oriental medicine theory to avoid infectious disease such as Husajukpung Phijeyushi(虛邪賊風 避之有時). Third, according to the natural result of the first and second contents, we can know that its characteristics stress the remedy without drugs. Because Jungkijonae Sabulkaghan(正氣存內 邪不可干), Husasukpung Phijeyushi(虛邪賊風 避之有時), and Chuninsangeung(天人相應) mean that they prevent disease in condition of freedom from ailment, We can prevent the disease production through the positive preventive methods such as exercise, spirit, food and innate prevention etc.. fourth, the preventive medicine of oriental medicine has developed with therapeutics and it contains all oriental medical methods such as host, environment, exercise, acupuncture and moxibustion, innate or postnatal methods. Also it is the general preventive medicine that has fundamental philosophy of oriental medicine; for examples, the unified idea, the harmony of nature and human, and the unity of mind and body. fifth, to develope the above scientific merit and special features, the preventive medicine of Oriental medicine must be objectified and reemergent stud? gets more and more essential from now on. Especially we need to have the scientific concern of Oriental medicine about the cause of a disease, environmental hygiene, industrial sanitation, and personal hygiene etc..

• Biomolecules & Therapeutics
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• v.20 no.1
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• pp.43-49
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• 2012

Stimulation of mast cells through the high affinity IgE receptor (Fc${\varepsilon}$RI) induces degranulation, lipid mediator release, and cytokine secretion leading to allergic reactions. Although various signaling pathways have been characterized to be involved in the Fc${\varepsilon}$RI-mediated responses, little is known about the precious mechanism for the expression of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) in mast cells. Here, we report that rapamycin, a specific inhibitor of mammalian target of rapamycin (mTOR), reduces the expression of TNF-${\alpha}$ in rat basophilic leukemia (RBL-2H3) cells. IgE or specific antigen stimulation of RBL-2H3 cells increases the expression of TNF-${\alpha}$ and activates various signaling molecules including S6K1, Akt and p38 MAPK. Rapamycin specifically inhibits antigeninduced TNF-${\alpha}$ mRNA level, while other kinase inhibitors have no effect on TNF-${\alpha}$ mRNA level. These data indicate that mTOR signaling pathway is the main regulation mechanism for antigen-induced TNF-${\alpha}$ expression. TNF-${\alpha}$ mRNA stability analysis using reporter construct containing TNF-${\alpha}$ adenylate/uridylate-rich elements (AREs) shows that rapamycin destabilizes TNF-${\alpha}$ mRNA via regulating the AU-rich element of TNF-${\alpha}$ mRNA. The antigen-induced activation of S6K1 is inhibited by specific kinase inhibitors including mTOR, PI3K, PKC and $Ca^{2+}$chelator inhibitor, while TNF-${\alpha}$ mRNA level is reduced only by rapamycin treatment. These data suggest that the effects of rapamycin on the expression of TNF-${\alpha}$ mRNA are not mediated by S6K1 but regulated by mTOR. Taken together, our results reveal that mTOR signaling pathway is a novel regulation mechanism for antigen-induced TNF-${\alpha}$ expression in RBL-2H3 cells.

• Journal of Haehwa Medicine
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• v.10 no.1
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• pp.453-469
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• 2001

This study attempted to analyze the contents of the research papers concerning the diagnosis and treatment of Alzheimer-type dementia presented in the magazine of Chinese Medicine published in China over the period between 1998 and 2000. As a result, the following conclusion was drawn: 1. The Chinese medical category of Alzheimer-type dementia includes amnesia, dementia, stupidity, depression symptom complex, insanity and the like and uses the as the criterion for diagnosis and treatment effect evaluation. 2. The clinical symptoms of Alzheimer-type dementia include lowered intelligence, deterioration of memory, understanding and judgemental power, retardation of the reaction, emotional changes, character changes, behavioral changes and the like and are divided into mild, medium and serious according to the degree of symptom. 3. From the perspective of Bon-Heo-Pyo-Shil(state of deficient vital essence and excessive pestilential vapor), the pattern of Byun-Sung(identification) is divided into deficiency symptom complex, excessive symptom complex and indiscernible fullness and emptiness. The deficiency symptom complex includes deficiency of the liver and kidney, deficiency of essence of the kidney, deficiency of the reservoir of marrow and the like. The excessive symptom complex includes internally blocked stagnant blood, blocking of the passageway due to turbid phlegm, blood stasis due to stagnation of chi, and the like. The indiscernible fullness and emptiness symptom complex includes the deficiency of essence of kidney, blocking of the passageway due to stagnant phlegm, blood stasis due to the deficiency of kidney, blood stasis due to the deficiency of heart and the like. 4. The therapeutics and' prescription of Alzheimer-type dementia include the following: Bo-Shin-Ik-Su-Tang for tonifying the kidney, replenishing the marrow and plugging the essence; Ki-Guk-Ji-Hwang-Hwan-Ga-mi for reinforcing the vital essence of the liver and kidney; Kwi-Bi-Tang-Hap-Yang-Shim-Tang for invigorating the functioning of the spleen and nourishing the heart; Hyel-Bu-Chuk-Eo-Tang-Ga-Mi for activating the blood and resolving the stagnancy of the blood; Bo-Yang-Hwan-Oh-Tang for replenishing chi, activating the blood and resolving the stagnancy of the blood; Beoh-Kwang-Mong-Sung-Tang for invigorating the functioning of the spleen, replenishing the kidney, resolving the phlegm and enlivening the brain; n-Dam-Tang-Ga-Mi for invigorating the functioning of the spleen, replenishing chi, and removing the phlegm and unclogging the passageway); Se-Shim-Tang-Ga-Mi for removing the stagnancy of the liver and resolving the phlegm; and the like. 5. The research papers on, the medication cases of Alzheimer-type dementia understand the pathology of Alzheimer-type dementia from a consistent perspective. They view the pathology of Alzheimer-type dementia as the disease of Bon-Heo-Pyo-Shil(state of deficient vital essence and excessive pestilential vapor) with the combination of the deficiency of essence of the kidney, the deficiency of the brain marrow, blood stasis and blocked phlegm and the like and recommend the prescription of using Bo and Sa simultaneously for treating Alzheimer-type dementia. 6. The research papers on the medication cases of Alzheimer-type dementia reported that the use of creative prescriptions such as Si-Sam-Hang-Ji-Tang, Ji-Yung-Tang, Ka-Mi-Yunh-Ji-Hwan, Ja-Sin-Hwal-Hyel-Tang, Kal-Chang-Ik-Ji-Tang, Ho-Su-Bok-Ji-Tang, Kun-Noe-Ok-Ji-Hap-Je and the like led to the average high efficacy of 85.5%.