• Title/Summary/Keyword: human diseases

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Mutant p53-Notch1 Signaling Axis Is Involved in Curcumin-Induced Apoptosis of Breast Cancer Cells

  • Bae, Yun-Hee;Ryu, Jong Hyo;Park, Hyun-Joo;Kim, Kwang Rok;Wee, Hee-Jun;Lee, Ok-Hee;Jang, Hye-Ock;Bae, Moon-Kyoung;Kim, Kyu-Won;Bae, Soo-Kyung
    • The Korean Journal of Physiology and Pharmacology
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    • v.17 no.4
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    • pp.291-297
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    • 2013
  • Notch1 has been reported to be highly expressed in triple-negative and other subtypes of breast cancer. Mutant p53 (R280K) is overexpressed in MDA-MB-231 triple-negative human breast cancer cells. The present study aimed to determine whether the mutant p53 can be a potent transcriptional activator of the Notch1 in MDA-MB-231 cells, and explore the role of this mutant p53-Notch1 axis in curcumin-induced apoptosis. We found that curcumin treatment resulted in an induction of apoptosis in MDA-MB-231 cells, together with downregulation of Notch1 and its downstream target, Hes1. This reduction in Notch1 expression was determined to be due to the decreased activity of endogenous mutant p53. We confirmed the suppressive effect of curcumin on Notch1 transcription by performing a Notch1 promoter-driven reporter assay and identified a putative p53-binding site in the Notch1 promoter by EMSA and chromatin immunoprecipitation analysis. Overexpression of mutant p53 increased Notch1 promoter activity, whereas knockdown of mutant p53 by small interfering RNA suppressed Notch1 expression, leading to the induction of cellular apoptosis. Moreover, curcumin-induced apoptosis was further enhanced by the knockdown of Notch1 or mutant p53, but it was decreased by the overexpression of active Notch1. Taken together, our results demonstrate, for the first time, that Notch1 is a transcriptional target of mutant p53 in breast cancer cells and suggest that the targeting of mutant p53 and/or Notch1 may be combined with a chemotherapeutic strategy to improve the response of breast cancer cells to curcumin.

Effect of Ethanol Extract of Yukmijiwhang-Whan on Trabecular Bone Area in OVX Rats (육미지황환(六味地黃丸) 에탄올 추출물이 난소제거 흰쥐의 경골 소주골에 미치는 영향)

  • Kim, Chung-Sook;Ha, Hye-Kyung;Lee, Je-Hyun;Song, Kye-Yong;Kim, Hye-Jin;Shin, Sun-Mi
    • Korean Journal of Oriental Medicine
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    • v.6 no.1
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    • pp.123-132
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    • 2000
  • Bone is continuously remodeled during adult life with the resorption of old bone by osteoclasts and its subsequent replacement by osteoblast. Bone homeostasis is maintained by a balance between activities of osteoblasts and osteoclasts, but an imbalance between resorption and formation results in bone diseases including osteoporosis. Osteoblasts line up on the bone surface, especially regions of new bone formation, lay down bone matrix (osteoid) in orderly lamellae and induce its mineralization. Thus, the increased activity of osteoblasts is helpful to treat and prevent osteoporosis. In this study, we examined whether 80% EtOH extract of yukmijiwhang-whan is capable of affecting osteoblast proliferation using human osteoblast-like cell line, MG-63 and Saos-2. In an in vivo experiment, extract of yukmijiwhang-whan was administered for 9 weeks to ovariectomized (OVX) rats. At necropsy, uterus weights were measured, and trabecular bone areas (TBAS) of tibia and the sixth lumbar vertebra were measured by bone histomorphology. The maximum cell proliferation of MG-63 caused by extract of yukmijiwhang-whan at $5\;{\times}\;10^{-6}\;mg/ml$ was approximately 115% compared with control. In Saos-2, cell proliferation was approximately 145% of control at $5\;{\times}\;10^{-4}\;mg/ml$ and maximum alkaline phosphatase (ALP) activity was approximately 143% of control at $5\;{\times}\;10^{-5}\;mg/ml$. In animal study, however, the tibia and lumbar TBAS of the yukmijiwhang-whan group did not increased than the OVX control group. In conclusion, the 80% EtOH extract of yukmijiwhang-whan increased proliferation of osteoblasts but did not prevent bone loss in OVX rats.

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A Study on the Antimicrobial Effect of Glyceryl Caprylate in Cosmetics (Glyceryl Caprylate의 화장품에서의 항균력에 관한 연구)

  • Ahn, Gi-Woong;Choi, Min-Hee;Woo, Yun-Taek;Jo, Byoung-Kee
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.33 no.1 s.60
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    • pp.47-52
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    • 2007
  • The antimicrobial properties of medium-chain ($C_{8-12}$) free fatty acids and their 1-monoglyceride derivatives against a wide range of microorganisms we well known. However, previous studies have been mainly focused on the antimicrobial activity against pathogenic bacteria and viruses causing diseases in human or domestic animals' infection. But, there have been few reports describing comprehensive surveys of antimicrobial effects against microorganisms in cosmetics. For a start of this study, we evaluated and compared the preservative activities of $C_8$ (glyceryl caprylate) and $C_{12}$(glyceryl laurate) 1-monoglyceride in cosmetic formulations. From the result, we found that both of them have very excellent preservative activity against bacteria, but less against fungi. And $C_8$ 1-monoglyceride was a little bit more effective than $C_{12}$ 1-monoglyceride. According to the test results to evaluate each antimicrobial activity of glyceryl caprylate towards 5 kinds of microorganisms used in preservation efficacy test in cosmetics, gram-positive bacteria S. aureus and yeast C. albicans were sensitive and mold A. niger was most tolerant to glyceryl caprylate. Therefore, we tried to improve the antimicrobial activity of glyceryl caprylate agianst mold such as A. niger so that we could make it used as a preservative for cosmetic products. As a result, we confirmed that the antimicrobial activity of glyceryl caprylate is much improved under acidic conditions in formulation. In addition, we found optimal combinations of glyceryl caprylate with other antimicrobial agents. Among tested 7 antimicrobial agent, methyparaben showed the highest preservative activity in combination with gglyceryl caprylate.

Immuno-enhancing Effect of Protaetia brevitarsis seulensis (white grub) Extracts on RAW 264.7 Cell Line. (굼벵이 추출물의 RAW 264.7 세포에 대한 면역증강 효과)

  • Park, Bog-Im;Seo, Jae-Bin;Jin, Yu-Mi;Kim, Seong-Seon;Sim, Hyeon-Jae;Lee, Hoon-Yeon;Kim, Seong-Oh;kim, Dong-Keun;Jo, Mi-Na;Cho, Yong-Jin;Kim, Chong-Tai;Kim, Tae-Eun;Jeon, Yong-Deok;Jin, Jong-Sik
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2018.10a
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    • pp.102-102
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    • 2018
  • Protaetia Brevitarsis Seulensis(white grub) has been traditionally used as medicinal stuff to treat blood stasis, occlusion of menstruation, tetanus and liver cancer in Asian countries (Korea, Japan, China, Taiwan, India and Myanmar). Especially, Donguibogam, which is traditional korean medicinal book, described the white grub as traditional medicine to treat hepatic diseases and vascular disorders. The white grub has been considered as highly nutritional food. The major constituents of white grub are rich in protein, healthy fats, iron, calcium. Recent studies announced that white grub has hepatoprotective effect and anti-microbacterial effect. However, the immuno-enhancing effect of white grub extracts in RAW 264.7 macrophage cells has not been studied yet. In this study, the various concentrations of white grub extract were examined to find immuno-enhancing effects on RAW 264.7 cells. Cytotoxicity was determined by MTT assay and immuno-enhancing effect of white grub extract was investigated by measuring nitric oxide (NO) production compared with only lipopolysaccharide (LPS) treatment. White grub extracts (0.001 - 10 mg/ml) did not show cytotoxicity. Additionally, white grub extracts (0.001 - 1mg/ml) had Immuno-enhancing effect on RAW 264.7 cells compared with only LPS treated group. These results might be provided proof to develop beneficial immuno-enhancing material for human health.

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Effect of Acupuncture and Radix Astragali aqua-acupuncture at Synsu(BL23) on transcriptional expression of mouse cytokine IL-6 (신수혈의 침자극과 황기약침이 실험용 생쥐의 면역활성물질인 cytokine의 IL-6 발현에 미치는 영향)

  • Kim Jong-Soo;Sin Sang-Sup;Kim Cheul-Ho;Park Sun-Dong;Park Won-Hwan
    • Journal of Acupuncture Research
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    • v.15 no.2
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    • pp.147-155
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    • 1998
  • Acupuncture and Radix Astragali aqua-acupuncture stimuli have long been used to cure human diseases. However, it still remains to be unkown on its action mechanism, physiolosical and biochemical aspects. Thus, many attempts were made to show the scientific background covering the above mentioned mechanisms. Most recent studies show that these tests improve blood circulatory system and increase leucocyte counts. In this study, we have applied the acupuncture stimuli to mouse Sinsu(BL-23), which is a stimulative point of oriental medicine, to see if cytokine such as IL-6 can be detected. Mice were treated with lipopolysaccharide(LPS) for inflammation induction, and then reverse transcriptase-polymerase chain reaction (RT-PCR) using each primer set was performed to trace the amounts of mRNA. The results are summarized as follows ; 1. IL-6 was not temporarily expressed in normal mice 15 min after the acupuncture was pulled out. But, it started to show a feeble expression at 30 min after the removal of acupuncture and it started to reduce at 1h. after the acupuncture was pulled out 2. IL-6 was specifically expressed in LPS-treated mouse 30 min after the acupuncture was pulled out. The transcriptional expressions of LPS-treated mice were more effective than those of normal mice at 30 min after the removal of acupuncture 3. IL-6 was not temporarily expressed in normal mice 15 min after Radix Astragali aqua-acupuncture. But it expressed most highly at 30 min, and the transcriptional expressions of IL-6 was continued to 3 h. 4. IL-6 was not expressed in all the time after Radix Astragali aqua-acupuncture in LPS-treated mice. Therefore, a follow-up of cytokine IL-6 can be used not only a basis of the effect of acupuncture and Radix Astragali aqua-acupuncture but a diagnosis giude through the immunological action of thats. And, it is suggested that cytokine's expression by Acupuncture and Radix Astragali aqua-acupuncture stimulation should be continuously elucidated.

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Hepatoprotective effect of Paeoniae radix via Nrf2 activation (Nrf2 활성화(活性化)를 통한 작약(芍藥)의 간보호효과(肝保護效果))

  • Lee, Soo Hwan;Jung, Ji Yun;Park, Sang Mi;Jegal, Kyung Hwan;Byun, Sung Hui;Cho, Il Je;Kim, Sang Chan;Kim, Kwang Joong;Kim, Young Woo
    • The Korea Journal of Herbology
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    • v.31 no.1
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    • pp.33-40
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    • 2016
  • Objectives : Liver is one of the largest organs in the human, and has a function of detoxification and energy sensing to prevent severe disease. Paeoniae radix has been used to treat a variety of liver diseases such as hepatitis and chronic hepatic failure. Although P. radix has been used as an medicinal herb for a long time, the effects of P. radix on severe oxidative stress and its action mechanism on the liver was not clearly verified.Methods : This study investigated the protective effects of P. radix extract (PRE), and the underlying mechanism of its action in the liver. tert-butyl hydroperoxide (t-BHP) and carbon tetrachlroride (CCl4) were used to induce oxidative stress in the HepG2 hepatocyte cell line and Sprague-Dawley rats, respectively.Results : t-BHP significantly induced cell death and ROS production in HepG2 cell, as indicated by MTT and FACS analysis. However, pretreatment of PRE inhibited a decrease in cell viability and H2O2 production in the HepG2 cells. PRE also blocked the ability of t-BHP to damage in mitochondrial membrane transition. More importantly, PRE induced Nrf2 activation and antioxidant Phase II enzyme, which may have a role in the effects of PRE. In mice, PRE inhibited the liver damage induced by CCl4.Conclusions : PRE inhibited oxidative stress and hepatic damages as mediated with Nrf2 activation. This study unveil, in part, the effect and mechanism of old medicinal herb, P. radix.

A Scanning Electron Microscopic Study on the Effect of Nd:YAG Laser Irradiation on the Cervical Cementum (Nd:YAG 레이저조사가 치경부 백악질에 미치는 영향에 관한 주사전자현미경적 연구)

  • Choi, Bok;Lee, Jeong-Yeon;Shin, Keum-back
    • Journal of Oral Medicine and Pain
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    • v.25 no.4
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    • pp.415-425
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    • 2000
  • In order to obtain the basic data concerning the optimal lasing conditions in using Nd:YAG laser as an adjunctive modality of periodontal therapy of root planing without irreversible structural deterioration of cervical cementum, the author selected 36 human teeth having no cervical abrasion and caries (; 12 anteriors, 12 premolars. 12 molars) extracted due to periodontal diseases, and divided them into 4 groups as Group I, II, III and IV (; each group of 3 anteriors, 3 premolars, 3 molars), and prepared a cementum specimen with thickness of $1.0mm{\pm}0.2mm$ sectioned longitudinally at the middle of mesio-distal thickness (; Group I) or horizontally at 1mm-2mm below the cemento-enamel junction (; Group II, III, IV) from each tooth of each group by low speed diamond wheel saw, and treated them with 0.5 M ethylene diamine tetraacetic acid (; EDTA, pH=7.4) for 2 minutes for elimination of remnants during tooth-sectioning. And the author applied the laser energy from a fiberoptic delivered, free running, pulsed Nd:YAG laser (; wavelength 1064nm. pulse duration $120{\mu}sec$, fiber diameter $320{{\mu}m}$) to cementum surfaces in triplicates of one experiment under the following lasing conditions: 1. stationary mode of fiber in contact to cementum surfaces without air-spray (; Group I )/with air-spray (; Group II), 2. unidirectional moving mode of fiber in contact to cementum surfaces under speed of 3mm-4mm/sec without air-spray (; Group III)/with air-spray (; Group IV), 3. energy per pulse (mJ/pulse) [; energy density ($J/cm^{2}$)] in order of 1.0W/10Hz (100J/pulse); $124J/cm^{2}$, 0.5W/10Hz (50mJ/pulse); $62J/cm^{2}$, 0.4W/10Hz (40mJ/pulse); $50J/cm^{2}$, 0.3W/10Hz (30mJ/pulse); $37J/cm^{2}$, 4. exposure time of 1 second. And the author applied the platinum coating on surfaces of cementum specimens, and evaluated the characteristics of ultrastructural change on surfaces of cementum using the scanning electron microscopy. In general the ultrastructural loss of cervical cementum irradiated under the same lasing condition of laser energy density occurred least in specimens of Group IV. And especially, the ultrastructural loss of cervical cementum irradiated under the laser energy density of $37J/cm^{2}$ almost did not occur in specimens of Group IV. Therefore, it is considered that the pulsed Nd:YAG laser should be applied with the lasing conditions of unidirectional moving mode of fiber in contact to cementum surfaces under speed of 3mm-4mm/sec with air-spray and of laser energy density within $37J/cm^{2}$ as an adjunctive modality of periodontal therapy of root planing without irreversible structural deterioration of cervical cementum.

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Ulcerative Colitis is Associated with Novel Polymorphisms in the Promoter Region of MIP-3${\alpha}$/CCL20 Gene

  • Choi, Suck-Chei;Lee, Eun-Kyung;Lee, Sung-Ga;Chae, Soo-Cheon;Lee, Myeung-Su;Seo, Geom-Seog;Kim, Sang-Wook;Yeom, Joo-Jin;Jun, Chang-Duk
    • IMMUNE NETWORK
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    • v.5 no.4
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    • pp.205-214
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    • 2005
  • Background: We examined global gene expression profiles of peripheral blood mononuclear cells (PBMCs) in patients with ulcerative colitis (DC), and tested whether the identified genes with the altered expression might be associated with susceptibility to UC. Methods: PBMCs from 8 UC and 8 normal healthy (NH) volunteers were collected, and total RNAs were subjected to the human 8.0K cDNA chip for the micro array analysis. Real time-PCR (RT-PCR) was performed to verify the results of micro array. One hundred forty UC patients and 300 NH controls were recruited for single nucleotide polymorphism (SNP) analysis. Results: Twenty-five immune function-related genes with over 2-fold expression were identified. Of these genes, two chemokines, namely, CXCL1 and CCL20, were selected because of their potential importance in the evocation of host innate and adaptive immunity. Four SNPs were identified in the promoter and coding regions of CXCL1, while there was no significant difference between all patients with UC and controls in their polymorphisms, except minor association at g.57A>G (rs2071425, p=0.02). On the other hand, among three novel and one known SNPs identified in the promoter region of CCL20, g. -1,706 G>A (p=0.000000055), g. -1,458 G>A (p=0.0048), and g. -962C>A (p=0.0006) were found to be significantly associated with the susceptibility of Uc. Conclusion: Altered gene expression in mononuclear cells may contribute to IBD pathogenesis. Although the findings need to be confirmed in other populations with larger numbers of patients, the current results demonstrated that polymorphisms in the promoter region of CCL20 are positively associated with the development of Uc.

Anti-obesity Effects of Ginsenoside Rd via AMPK and PPAR Gamma (진세노사이드 Rd의 AMPK 및 PPAR 감마의 신호전달경로를 통한 항비만효과)

  • Kim, Myung-Sunny;Lee, Myoung-Soo;Kim, Soon-Hee;Kim, Sung-Hee;Kim, Hyun-Jin;Sung, Mi-Jeong;Kim, Hye-Young;Kwon, Dae-Young;Hwang, Jin-Taek
    • KSBB Journal
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    • v.22 no.5
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    • pp.341-344
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    • 2007
  • Obesity is a major obstacle for human health, which induces various diseases such as cardiac injury and type 2 diabetes. Ginsenosides, active components of ginseng extract, exert various physiological effects. However, There are still no evidence for their anti obesity effects. In this study, we investigated the effects of ginsenoside Rd on adipocyte differentiation in 3T3-L1 cells. Our data show that ginsenoside Rd (80 uM) was effective in adipocyte differentiation inhibition. These inhibitory effects of ginsenosides on adipocyte differentiation were accompanied by PPAR gamma inhibition in rosiglitazone-treated cells. We also tested whether AMP-activated protein kinase (AMPK) activation was involved in the effects of these ginsenosides. AMPK is a master target for obesity, ginsenoside Rd significantly activated AMPK. Taken together, these results suggest that the anti obesity effects of ginsenoside Rd involve the AMPK signaling pathway and PPAR-gamma inhibition.

Effect of Osmotic Pressure on hCTLA-lg Production in Transgenic Rice Cell Suspension Cultures (형질전환된 벼세포 배양에 있어서 삼투압 조절에 따른 hCTLA4-lg 생산성 변화)

  • Choi Sung-Hun;Lee Song-Jae;Hong Seok-Mi;Cho Ji-Suk;Kim Dong-Il
    • KSBB Journal
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    • v.20 no.4
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    • pp.278-284
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    • 2005
  • An immunosuppressive agent, human cytotoxic T lymphocyte antigen 4 (hCTLA4), is used for the prevention of graft rejection and treatment of autoimmune diseases. hCTLA4-Ig, a CTLA4-immunoglobulin fusion protein, was produced and secreted from transgenic rice cell suspension cultures using rice a-amylase (RAmy3D) expression system. In this system, hCTLA4-Ig expression was regulated metabolically by sugar starvation. For the purpose of improving hCTLA4-Ig production, the effects of osmotic pressure was investigated in suspension cultures of transgenic rice cells. The highest production level was achieved at 40 mM sorbitol $(140\;mOsm{\cdot}kg^{-1}\;H_2O)$. Using the medium with 8 mM glucose, the level of hCTLA4-Ig in the medium reached 45.3 mg/L. By adjusting the osmotic pressure of induction medium, it was found that the hCTLA4-Ig production could be increased up to 2.1-fold compared with that in batch culture.