• Title/Summary/Keyword: Biological mechanism

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Experimental Studies on Antitumor Activity of Herb Drugs (I)-Effectiveness on Rat Natural Killer Cell Activity- (수종(數種)의 생약(生藥)에 대(對)한 항암효과(抗癌效果)의 실험적(實驗的) 연구(硏究)(I) -백서(白鼠)의 자연살해세포활성(自然殺害細胞活性)에 미치는 영향(影響)-)

  • Kang, Yun-Ho;Kim, Byung-Woon;Ha, Youn-Mun;Park, Jai-Kyung;Nam, Sang-Yun;Choi, Kyu-Chul;Choi, Yong-Mook
    • Korean Journal of Pharmacognosy
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    • v.18 no.2
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    • pp.118-126
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    • 1987
  • Natural Killer cells are considerd to play an important role in antitumor immune surveilance mechanism. In this study, 21 putative anticancer drugs selected from reference were assessed by evaluating the effect on rat Natural Killer cell activity (NKCA). All 21 herb drugs were extracted in boiling water, lyophilized, autoclaved, and then used for experiment. Culture supernatant of concanavalin-A (Con-A)-stimulated rat spleen cells as a source of lymphokine was also used as a control of comparison. Rat spleen cells were used as effector and NKCA was measured in 4hr $^{51}Cr-release$ assay against Yac-1 mouse lymphoma cell line. In order to determine the optimal conditions for NKCA augmentation, effector cells were treated with 3 different concentrations of each drug for 24, or 48 hrs before testing of NKCA, In optimal conditions determined from previous results, the effect of herb drugs on NKCA were assessed in 3 to 5experiments. NKCA was significantly enhanced by treatment with 4 herb drugs(Ponciri Fructus, Houttuyniae Herba, Aurantii Pericarpium, Nepetae Herba). Culture supernatant of Con-A-stimulated spleen cells also augmented the rat NKCA more significantly. The results show that 4 of the herb medicines supposed to display anticancer effect may have activity as a biological response modifier through augmentation of NKCA.

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Physiological Function of Isoflavones and Their Genetic and Environmental Variations in Soybean (콩 Isoflavone의 생리활성 기능과 함량 변이)

  • Kim Yong-Ho;Kim Seok-Dong;Hong Eun-Hi;Ahn Wan-Sik
    • KOREAN JOURNAL OF CROP SCIENCE
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    • v.41 no.spc1
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    • pp.25-45
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    • 1996
  • Soyfoods have potential roles in the prevention and treatment of chronic diseases, most notably cancer, osteoporosis, and heart disease. There is evidence that carcinogenesis are supressed by isolated soybean derived products in vivo such as a protease inhibitor, phytic acid, saponins and isoflavones. It is believed that supplementation of human diets with soybean products markedly reduces human cancer mortality rates. Especially, recent papers recognize the potential benefit of soybean isoflavone components for reducing the risk of various cancers. Isoflavones exhibit a multitude of medicinal effects that influence cell growth and regulation, which may have potential value in the prevention and treatment of cancer. In addition to potential biological effects, soybean isoflavones have the important physiological functions such as the induction of Bradyrizobium japonicum nod genes and the responses of soybean tissues to infection by Phytophthora megasperma as well as biochemical activities such as antifungal and antibacterial actions. Genistin, daidzin, glycitin and their aglycone (genistein, daidzein, glycitein) are the principal isoflavones found in soybean. Malonyl and acetyl forms have also been detected but they are thermally unstable and are usually transformed during the processing in glucoside form. Most soy products, with the exception of soy sauce, alcohol-extracted soy protein concentrate, and soy protein isolate, have total isoflavone concentrations similar to those in the whole soybean. Soybean-containing diets inhibit mammary tumorigenesis in animal models of breast cancer, therefore, it is possible that dietary isoflavones are an important factor accounting for the lower incidence and mortality from breast cancer. Of the total soybean seed isoflavones, $80\~90\%$ were located in cotyledons, with the remainder in the hypocotyls. The hypocotyls had a higher concentrations of isoflavones on a weight basis compared with cotyledons. Isoflavone contents were influenced by genetics, crop years, and growth locations. The effect of crop year had a greater impact on the isoflavone contents than that of location. The climate condition might be the attribution factor to variation in isoflavone contents. Also, while the isoflavone content of cotyledons exhibited large variations in response to high temperature during seed development, hypocotyls showed high concentration in isoflavone content. So, it is concluded that one of the factors affecting isoflavone content in soybean seeds is temperature during seed development. High temperature, especially in maturity stage, causes lower isoflavone content in soybean seed. It is also suggested that there may exist a different mechanism to maintain isoflavone contents between cotyledon and seed hypocotyls. In a conclusion, soy foods may be able to have a significant beneficial impact on public health.

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Potential Involvement of p62, a Phosphotyrosine-independent Ligand of SH2 Domain of $p56^{lck}$, on UV-induced Apoptosis in Jurkat T-cell Line ($p56^{lck}$ SH2 domain 결합 단백질 p62가 Jurkat T-세포주의 세포예정사에 미치는 영향)

  • 정인실
    • Development and Reproduction
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    • v.2 no.2
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    • pp.165-171
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    • 1998
  • p62 is a novel cytoplsmic protein that binds to SH2 domain of p56$^{lck}$, lymphocyte-specific protein tyrosine kinase, and the expression of p62 was observed in most tissues. In addition p62 interacts with various proteins including ubiquitin and atypical PKC isoform, indicating its diverse biological role in different tissues. However, little is known about functional connection between p62 and its binding proteins. In the present study, a novel cellular protein, p62 has been shown to bind to 14-3-3 $\tau$ isoform that is specific for T cells. Moreover, overexpression of p62 in T cells caused to delay onset of UV-induced apoptosis characterized by DNA fragmentation and breakdown of poly (ADP-ribose) polymerase (PARP). Lately, 14-3-3 proteins have been shown to mediate survival signal via interacting proapoptotic Bad protein in the Iymphocyte. These results suggested the presence of p62-mediated regulatory mechanism during apoptosis in T cells, in which activation-induced apoptotic signal could be interfered by p62 and 14-3-3 protein.n.

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Acupuncture Analgesia : A Sensory Stimulus Induced Analgesia Observed by functional Magnetic Resonance Imaging (침의 진통효과: 체성감각신경자극으로 유도된 진통작용에 대한 기능성자기공명영상장치를 이용한 연구)

  • Cho, Zang-hee;Hwang, Seon-chool;Son, Young-don;Kang, Chang-ki;Wong, Edward K.;Bai, Sun-joon;Lee, Un-jung;Sung, Kang-kyung;Park, Tae-seok;Kim, Young-bo;Min, Hoon-ki;Oleson, Terry
    • Journal of Acupuncture Research
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    • v.21 no.2
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    • pp.57-71
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    • 2004
  • Objective : Physiological evidence regarding acupuncture's effect in human patients is not yet well established, despite considerable evidence for its therapeutic efficacy. Besides target or disease specificity of acupuncture, acupuncture analgesia (AA) appears to be another large subclass that poses many questions, such as whether there is point specificity with respect to which acupoint is most effective for a particular condition. Methods : We observed brain activation with functional magnetic resonance imaging (fMRI) using a set of stimuli that consist of pain, pain following Meridian acupuncture, and pain following Sham acupuncture. Results : Among the new observations, the most interesting fact is that data sets of both Meridian acupuncture and Sham acupuncture show decreased activation of the same brain areas related to the pain processing signals. Present functional MRI study demonstrate two important biological observations that could elucidate AA mechanism in human participants: the effects of acupuncture occur through mediation of the higher brain areas. Sham acupuncture stimulation appears to be almost as effective as traditional Meridian acupoint stimulation, suggesting that acupuncture is not entirely point specific. Decreased activation in the limbic paleo cortical areas appears to be the probable neurological manifestation of AA and strongly implies that acupuncture stimulation inhibits the transmission of ascending pain signals to the higher cortical areas by the previously known descending pain inhibitory circuit. Conclusion : We, therefore, a hypothesized that this pain inhibitory circuit is initiated and mediated via the broad sense Hypothalamus Pituitary Adrenal (BS HPA) axis in conjunction to the "sensory stimulation."

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Changes of SDS-PAGE Pattern and Allergenicity of BSA and BGG in Beef Extract Treated with Heat and High Pressure (물리적 처리에 따른 우육추출물중의 BSA와 BGG단백질의 SDS-PAGE패턴 및 항원성의 변화)

  • Han, Gi-Dong;Fan, Jiang Ping;Suzuki, Atsushi
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.35 no.5
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    • pp.594-599
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    • 2006
  • In our previous report, we indicated that not only BSA but also BGG played an important role in the allergenicity of beef. In this study, the effect of heat or high-pressure treatments to beef extract on the SDS-PAGE patterns was examined. The antigenicity of each treated samples was also investigated by Western blots assay with the sera of BGG-positive beef allergic patients. The BGG band and its antigenicity slightly disappeared but not generally in $100^{\circ}C$ group, indicating $100^{\circ}C$ treatment is not sufficient to totally eliminate the antigenicity of beef allergens. Compared with BGG band, BSA band significantly disappeared in SDS-PAGE with $100^{\circ}C$ treatment, indicating BSA is more heat- sensitive than BGG. When the beef extract was heated at $120^{\circ}C$, not only BSA but also BGG bands was largely disappeared in both SDS-PAGE and Western blots. High pressure (HP) treatment even at 600 MPa did not affect SDS-PAGE and Western blots pattern of BSA. On the contrary, BGG treated with HP showed visible changes in SDS-PAGE. 600 MPa treatment significantly reduced the antigencity. Interestingly, these behaviors of BGG were not found in the same experiments with pure BGG treated with HP. From these results, it was speculated that some kinds of proteolytic enzymes in beef extracts were involved in the BGG molecular degradation by HP treatment. The aging experiments of beef extracts treated with HP supported this hypothesis. Further studies are needed to clarify the function and working mechanism of enzymes associated with BGG degradation in beef extracts by HP treatment.

BIOLOGICAL RESPONSES OF OSTEOBLAST-LIKE CELLS TO DIFFERENT TITANIUM SURFACE BY ANODIZING MODIFICATION

  • Kim Myung-Joo;Kim Chang-Whe;Lim Young-Jun;Park Hyun-Joo
    • The Journal of Korean Academy of Prosthodontics
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    • v.43 no.6
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    • pp.751-763
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    • 2005
  • Statement of problem. To improve a direct implant fixation to the bone, various strategies have been developed focusing on the surface of materials. The surface quality of the implant depends on the chemical, physical, mechanical and topographical properties of the surface. The different properties will interact with each other and a change in thickness of the oxide layer may also result in a change in surface energy, the surface topography and surface, chemical composition. However, there is limited the comprehensive study with regard to changed surface and biologic behavior of osteoblast by anodization. Purpose of study. The aim of this study was to analyze the characteristics of an oxide layer formed and to evaluate the cellular biologic behaviors on titanium by anodic oxidation (anodization) by cellular proliferation, differentiation, ECM formation and gene expression. And the phospholipase activity was measured on the anodized surface as preliminary study to understand how surface properties of Ti implant are transduced into downstream cellular events. Methods and Materials. The surface of a commercially pure titanium(Grade 2) was modified by anodic oxidation. The group 1 samples had a machined surface and other three experimental specimens were anodized under a constant voltage of 270 V(Group 2), 350 V(Group 3), and 450 V(Group 4). The specimen characteristics were inspected using the following five categories; the surface morphology, the surface roughness, the thickness of oxide layer, the crystallinity, and the chemical composition of the oxide layer. Cell numbers were taken as a marker for cell proliferation. While the expression of alkaline phosphatase and Runx2 (Cbfa1) was used as early differentiation marker for osteoblast. The type I collagen production was determined, which constitutes the main structural protein of the extracellular matrix. Phospholipase $A_2$ and D activity were detected. Results. (1) The anodized titanium had a porous oxide layer, and there was increase in both the size and number of pores with increasing anodizing voltage. (2) With increasing voltage, the surface roughness and thickness of the oxide film increased significantly (p<0.01), the $TiO_2$phase changed from anatase to rutile. During the anodic oxidization, Ca and P ions were more incorporated into the oxide layer. (3) The in vitro cell responses of the specimen were also dependant on the oxidation conditions. With increasing voltage, the ALP activity, type I collagen production, and Cbfa 1 gene expression increased significantly (p<0.01), while the cell proliferation decreased. (4) In preliminary study on the relation of surface property and phospholipase, PLD activity was increased but $PLA_2$ activity did not changed according to applied voltage. Conclusion. The anodized titanium shows improved surface characteristics than the machined titanium. The surface properties acquired by anodization appear to give rise more mature osteoblast characteristics and might result in increased bone growth, and contribute to the achievement of a tight fixation. The precise mechanism of surface property signaling is not known, may be related to phospholipase D.

Effects of Chlorophyll a on UVB-induced Cellular Responses and Type I pN Collagen Synthesis in vitro (클로로필 a가 UVB 유도성 산화적 스트레스와 matrix metalloproteinases (MMPs) 활성화 및 콜라겐 합성에 미치는 영향)

  • Jeon, Hee-Young;Kim, Jeong-Kee;Seo, Dae-Bang;Lee, Sang-Jun
    • Korean Journal of Food Science and Technology
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    • v.41 no.6
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    • pp.700-705
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    • 2009
  • Several studies have demonstrated that chlorophyll has many beneficial properties, including anti-inflammatory, anti-tumor, and antioxidant properties. Chlorophyll has been also shown to have an excellent chemopreventive potential against skin tumor. Its preventive mechanism against skin tumor, however, has not been examined in detail. Furthermore, the effects of chlorophyll on UVB-induced cellular responses have not been investigated. Solar UV radiation, in particular its UVB component, is the primary cause of many adverse biological effects, which is responsible for the photoaging and skin cancer. We investigated the preventive effects of chlorophyll a on UVB-mediated responses in human immortalized HaCaT kerationocytes and normal human fibroblast. We found that treatment of chlorophyll a markedly inhibited UVB-induced generation of reactive oxygen species and lipid peroxidation. Chlorophyll a also prevented UVB-induced MMP-1 expression and MMP-2 activation and increased Type I pN collagen synthesis. These results suggest that chlorophyll a is a potent candidate for the prevention and treatment of UVB-induced skin cancer and photoaging.

A Study on the changes of electric change induced by Tanchim (彈鍼) manipulation during acupuncture therapy (자침시(刺鍼時) 탄침(彈鍼)의 수기자극(手技刺戟)이 전위변화(電位變化)에 미치는 영향(影響))

  • Kim, Yong-Deug;Kim, Young-Tae;Park, Sung-Sub;Park, Gwi-Jong;Sohn, In-Cheul;Kim, Kyung-Sik
    • Korean Journal of Acupuncture
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    • v.21 no.4
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    • pp.1-19
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    • 2004
  • Objectives : To understanding biological mechanism of acupuncture therapy, we have proposed a hypothesis. First of all, there exists electric property in meridian and meridian point. Second of all, energy flowing in meridian is related with electric property. Third of all, there is electronic interaction between the operator who performs acupuncture therapy and the receiver who is given acupuncture therapy. Forth of all, acupuncture effects may depend on the electric capacity which is transferred between the operator and the receiver via acupuncture needle. Methods : Under the hypothesis, we studied the effects of electric change in $ST_{37}(+)\;and\;ST_{39}(-)$ generated by Tanchim (彈鍼) manipulation which was stimulated at $ST_{36}$ point. And compared with data on the changes of electric change from the hand of the operator during acupuncture stimulation. Electric charge induced via acupuncture needle from the operator may be important factor that causes the changes of electric change in meridian and acupoint in the receiver. Therefore we investigated the changes of electric charge induced by the operator using Maclab 400 by the following methods. The one was in stable electric circle condition and the other was in unstable electric circle condition. Results : In this experiments, the changes of electric change from the stimulation type of Tanchim manipulation performed in our lab condition in acupuncture therapy was induced at least three factor, one was the difference of bio-potentials between the operator and the receiver of acupuncture therapy, another was the depth of acupuncture insertion from the skin of the receiver, the other was an electromyogram of the receiver. Conclusion : The data imply that the first factor should make a capacitance current when the operator touched the acupuncture needle which was inserted in the receiver. Therefore, the results suggest that capacitance currents stimulus in electronic view may be important factor in acupuncture therapy between the operator and the receiver of acupuncture therapy.

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Screening of the Biologoical Activity from Water Extracts of the Medicinal Plants and the Protective Effect of R. palmatum on MTPT-induced Neurotoxicity (한약재 물 추출물의 생리활성 검색 및 MPTP-유도 신경독성에 대한 대황의 보호효과)

  • Kim Tae Eun;Yoon Yeo Min;Park Yong In;Kim Youn Seok;Jeon Byung Hun;Kim Myung Dong
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.18 no.6
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    • pp.1666-1685
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    • 2004
  • This present study was designed to screen medicinal plants for the treatment of brain diseases such as Parkinson's disease or aging. We tested the effects of the water extracts from 38 species medicinal plants on antioxidant capacity, monoamine oxidase B (MAO-B) inhibitory activity, acetylcholinesterase (AChE) inhibition and antiperoxidation activity in vitro. The water extracts from 38 species were tested on their antioxidant activity using radical scavenging effects against ABTS+. The water extract of C. sappan was showed the highest antioxidant capacity, the antioxidant activity at 1 Jig of herbal extract being 0.38mM TE. Lipid peroxidation in brain homogenates induced by NADPH and ADP-Fe/sup 2+/ was strong inhibited by C. sappan and R. palmatum extracts. Among the 38 medicinal plants investigated, R. palmatum showed significant biological activity (antioxidant capacity, MAO-B inhibiory activity, and AChE inhibitory activity). The protective efficacy of R. palmatum water extract on 1-methyl-4­phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism and its possible mechanism were studied in C57BL/6 mice. Treatment of R. palmatum water extract protected biomacromolecules such as lipids from oxidative damage induced by MPTP. The content of MDA in brain tissue was decreased significantly by R. palmatum extract. These results suggest that R. palmatum water extract plays on effective role in attenuating MPTP-induced neurotoxicity in mice. This protective effect of R. palmatum might be estimated the result from the inhibitory activity on monoamine oxidase B and the enhancement of antioxidant activity.

A New Histone Deacetylase Inhibitor, MHY4381, Induces Apoptosis via Generation of Reactive Oxygen Species in Human Prostate Cancer Cells

  • Richa, Sachan;Dey, Prasanta;Park, Chaeun;Yang, Jungho;Son, Ji Yeon;Park, Jae Hyeon;Lee, Su Hyun;Ahn, Mee-Young;Kim, In Su;Moon, Hyung Ryong;Kim, Hyung Sik
    • Biomolecules & Therapeutics
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    • v.28 no.2
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    • pp.184-194
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    • 2020
  • Histone deacetylase (HDAC) inhibitors represent a novel class of anticancer agents, which can be used to inhibit cell proliferation and induce apoptosis in several types of cancer cells. In this study, we investigated the anticancer activity of MHY4381, a newly synthesized HDAC inhibitor, against human prostate cancer cell lines and compared its efficacy with that of suberoylanilide hydroxamic acid (SAHA), a well-known HDAC inhibitor. We assessed cell viability, apoptosis, cell cycle regulation, and other biological effects in the prostate cancer cells. We also evaluated a possible mechanism of MHY4381 on the apoptotic cell death pathway. The IC50 value of MHY4381 was lower in DU145 cells (IC50=0.31 µM) than in LNCaP (IC50=0.85 µM) and PC-3 cells (IC50=5.23 µM). In addition, the IC50 values of MHY4381 measured in this assay were significantly lower than those of SAHA against prostate cancer cell lines. MHY4381 increased the levels of acetylated histones H3 and H4 and reduced the expression of HDAC proteins in the prostate cancer cell lines. MHY4381 increased G2/M phase arrest in DU145 cells, and G1 arrest in LNCaP cells. It also activated reactive oxygen species (ROS) generation, which induced apoptosis in the DU145 and LNCaP cells by increasing the ratio of Bax/Bcl-2 and releasing cytochrome c into the cytoplasm. Our results indicated that MHY4381 preferentially results in antitumor effects in DU145 and LNCaP cells via mitochondria-mediated apoptosis and ROS-facilitated cell death pathway, and therefore can be used as a promising prostate cancer therapeutic.