• Title/Summary/Keyword: degeneration

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Study of hepatoprotective effect of Haegan-jeon through activation of nuclear factor erythroid 2-related factor 2 and optimization of herbal composition based on molecular mechanism (Nuclear factor erythroid 2-related factor 2 활성화를 통한 해간전(解肝煎)의 간세포 보호 효능 및 분자기전을 활용한 해간전(解肝煎) 구성 약물의 최적화 연구)

  • Kim, Jae Kwang;Jung, Ji Yun;Park, Sang Mi;Park, Chung A;Ku, Sae Kwang;Byun, Sung Hui;Cho, Il Je;Kim, Sang Chan
    • Herbal Formula Science
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    • v.26 no.3
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    • pp.207-221
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    • 2018
  • Objectives : Present study investigated hepatoprotective effect of Haegan-jeon extract (HE) and tried to elucidate molecular mechanism involved. According to molecular mechanism, present study optimized herbal composition of HE (op-HE) and compared in vitro and in vivo hepatoprotective effects of op-HE to HE. Methods : For in vitro experiments, HepG2 cells were exposed to arachidonic acid (AA, $10{\mu}M$) and iron ($5{\mu}M$) for inducing oxidative stress. Cell viability, GSH contents, $H_2O_2$ production, mitochondrial membrane potential, immunoblot and reporter gene assay were performed to investigate cytoprotective effects and responsible molecular mechanisms. For in vivo experiments, hepatoprotective effect of HE and op-HE were assessed on $CCl_4-induced$ liver injury mice model. Results : HE pretreatment prevented AA+iron-mediated hepatocytes apoptosis. In addition, AA+iron-induced mitochondrial dysfunction, $H_2O_2$ production, glutathione depletion were reduced by HE pretreatment. In addition, nuclear factor erythroid 2-related factor 2 (Nrf2) phosphorylation, antioxidant response element (ARE)-driven reporter gene activity, and antioxidant genes expression were increased by HE. Based on reporter gene and MTT assays, we found that op-HE consisting three medicinal herbs also significantly increased transactivation of Nrf2 and reduced the AA+iron-mediated cytotoxicity. Moreover, in $CCl_4-induced$ liver injury mice model, HE-op had an ability to ameliorate $CCl_4-mediated$ increases in serum alanine transferase and aspartate aminotransferase activity, hepatic degeneration, inflammatory cell infiltration, and collagen deposition. Hepatoprotective effects of op-HE were comparable to those of HE. Conclusions : Present study suggests that op-HE as well as HE exhibit hepatoprotective effect against oxidative stress-mediated liver injury via Nrf2 activation.

Regulatory mechanism of Angelica Gigas extract powder on matrix metalloproteinases in vitro and in vivo model (참당귀 추출분말이 in vitro and in vivo model에서 MMPs 조절 기전)

  • Kwon, Jin-Hwan;Han, Min-Seok;Lee, Yong-Moon
    • Analytical Science and Technology
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    • v.28 no.6
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    • pp.361-369
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    • 2015
  • The precise mechanism underlying the therapeutic efficacy of an extraction powder of Angelica gigas (AGE) for the treatment of degenerative osteoarthritis was investigated in primary cultured rabbit chondrocytes and in a monosodium-iodoacetate (MIA)-induced osteoarthritis rat model. The treatment with AGE (50 μg/mL) effectively inhibited NF-B activation. The anti-inflammatory mechanism was clarified by gelatin zymography and western blotting measurements of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) activities. The AGE (50 μg/mL) treatment significantly reduced MMP-9 activity. The constituents of AGE— decursinol, decursin, and decursinol angelate—were determined by LC-MS/MS after a 24 hr treatment of rabbit chondrocytes. The contents of the major products, decursin and decursinol angelate, were 3.62±0.47 and 2.14 ±0.36 μg/mg protein, respectively in AGE-treated (50 μg/mL) rabbit chondrocytes. An in vivo animal study on rats fed a diet containing 25, 50, and 100 mg/kg AGE for 3 weeks revealed a significant inhibition of the MMPs in the MIA-induced rat articular cartilage. The genetic expression of arthritic factors in the articular cartilage was examined by RT-PCR of collagen Type I, collagen Type II, aggrecan, and MMP (MMP3, MMP-9, MMP13). Specifically, AGE up-regulated the expression of collagen Type I, collagen Type II, and aggrecan and inhibited MMP levels at all tested concentrations. Collectively, AGE showed a strong specific site of action on MMP regulation and protected against the degeneration of articular cartilage via cellular regulation of MMP expression both in vitro and in vivo.

A Study of Low-Voltage Low-Power Bipolar Linear Transconductor and Its Application to OTA (저전압 저전력 바이폴라 선형 트랜스컨덕터와 이를 이용한 OTA에 관한 연구)

  • Shin, Hee-Jong;Chung, Won-Sup
    • Journal of the Institute of Electronics Engineers of Korea SC
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    • v.37 no.1
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    • pp.40-48
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    • 2000
  • 1A novel bipolar linear transconductor and its application to operational transconductance amplifier(OTA) for low-voltage low-power signal processing is proposed. The transconductor consists of a npn differential-pair with emitter degeneration resistor and a pnp differential-pair connected to the npn differential-pair in cascade. The bias current of the pnp differential-pair is used with the output current of the npn differential-pair for wide linearity and temperature stability. The OTA consists of the linear transconductor and a translinear current cell followed by three current mirrors. The proposed transconductor has superior linearity and low-voltage low-power characteristics when compared with the conventional transconductor. The experimental results show that the transconductor with transconductance of 50 ${\mu}S$ has a linearity error of less than ${\pm}$0.06% over an input voltage range from -2V to +2V at supply voltage ${\pm}$3V. Power dissipation of the transconductor was 2.44 mW. A prototype OTA with a transconductance of 25 ${\mu}S$ has been built with bipolar transistor array. The linearity of the OTA was same as the proposed transconductor. The OTA circuit also exhibits a transconductance that is linearly dependent on a bias current varying over four decades with a sensitivity of 0.5 S/A.

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Human Embryonic Stem Cells Co-Transfected with Tyrosine Hydroxylase and GTP Cyclohydrolase I Relieve Symptomatic Motor Behavior in a Rat Model of Parkinson′s Disease

  • Kil, Kwang-Soo;Lee, Chang-Hyun;Shin, Hyun-Ah;Cho, Hwang-Yoon;Yoon, Ji-Yeon;Lee, Gun-Soup;Lee, Young-Jae;Kim, Eun-Young;Park, Se-Pill
    • Proceedings of the Korean Society of Developmental Biology Conference
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    • 2003.10a
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    • pp.101-101
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    • 2003
  • Main strategy for a treatment of Parkinson's disease (PD), due to a progressive degeneration of dopaminergic neurons, is a pharmaceutical supplement of dopamine derivatives or ceil replacement therapy. Both of these protocols have pros and cons; former exhibiting a dramatic relief but causing a severe side effects on long-term prescription and latter also having a proven effectiveness but having availability and ethical problems Embryonic stem (ES) cells have several characteristics suitable for this purpose. To investigate a possibility of using ES cells as a carrier of therapeutic gene(s), human ES (hES, MB03) cells were transfected with cDNAs coding for tyrosine hydroxylase (TH) in pcDNA3.1 (+) and the transfectants were selected using neomycin (250 $\mu /ml$). Expression of TH being confirmed, two of the positive clone (MBTH2 & 8) were second transfected with GTP cyclohydrolase 1 (GTPCH 1) in pcDNA3.1 (+)-hyg followed by selection with hygromycin-B (150 $\mu /ml$) and RT-PCR confirmation. By immune-cytochemistry, these genetically modified but undifferentiated dual drug-resistant cells were found to express few of the neuronal markers, such as NF200, $\beta$-tubulin, and MAP2 as well as astroglial marker GFAP. This results suggest that over-production of BH4 by ectopically expressed GTPCH I may be involved in the induction of those markers. Transplantation of the cells into striatum of 6-OHDA- denervated PD animal model relieved symptomatic rotational behaviors of the animals. Immunohistochemical analyses showed the presence of human cells within the striatum of the recipients. These results suggest a possibility of using hES cells as a carrier of therapeutic gene(s).

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Biodegradable Inorganic-Organic Composite Artificial Bone Substitute -in vitro biocompatibility evaluation by cell culture- (유기질과 무기질 복합체를 이용한 체내흡수형 인공골재료에 관한 연구 -세포배양에 의한 생체적합성 평가-)

  • Ahn, Sue-Jin;Kim, Yo-Sook;Lee, Choon-Ki;Suh, Hwal
    • Journal of Biomedical Engineering Research
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    • v.16 no.3
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    • pp.331-336
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    • 1995
  • A composite material was produced as an artificial bone substitute which is gradually degrAded and replaced by the regenerated natural bones after implantation. To detect the effect of the material on the cell's activity, the composite specimens were placed in MEMs and incubated at $37^{\circ}C$ for one week. Human uterus cervical cancer origin HeLa 3 cells and mouse subcutaneous origin L929 cells were cul- tured in the specimen dissolved MEMs for 5 days to investigate cytotoxicity via cell growth rates. ${Na_2}^{51}CrO_4$ solution was added to the media, to label the HeLa 53 cells, and the released amount of $^{51}Cr$ was measured by a $\gamma$-counter. On the cell growth investigation, no significant cytotoxic phenomena were revealed in both HeLa S3 and L929 cell cultures. On the released 51CR from the incubated HeLa 53 cells, no significant cell degeneration was observed from the composite embedded MEMs.

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EVALUATION OF ECTOPIC BONE FORMATION EFFECT BY DECALCIFIED DEGREE OF ALLOGRAFTS (동종이식골의 탈회정도가 이소성 골형성유도에 미치는 영향)

  • Yun, Hong-Sik;Chin, Byung-Rho;Shin, Hong-In
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.20 no.2
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    • pp.139-147
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    • 1998
  • This study has been performed to evaluate the relationship between the remained mineral components in a decalcified bone matrix and an ectopic bone formation efficiency. The freezed rat diaphyseal cortical bones measuring 0.5cm in length were demineralized in heated 0.6N HCl at $60^{\circ}C$ for 5, 10, 15, 20, 25, 30, 35, 40 minutes, respectively, using a controlled heat ultrasonic cleaner. Each 1cc of decalcifying solution taken during decalcification procedure was used to calculate calcium content using calcium dignostics kit under 600nm of spectrophotomer. After decalcification, each specimen was also weighed. Then each prepared specimen was implanted into the dorsal pouch of 24 Sprague-Dawley rats divided into 8 groups by time course. The implants were harvested at 1, 2, and 3 weeks and prepared for routine H-E stain specimens to evaluate osteogenic activity. The results are as follows: 1. There was statistical significant difference in change of calcium concentration up to demineralization of 30 minutes and each allogenic bones decalcifed up to 20 minutes revealed 99.65% of decalcification in average. 2. There was statistical significant difference in change of weight in demineralized allogenic bone up to 20 minutes treatment but, no significant change was noted after that time. 3. The histologic analysis revealed active ectopic bone formation in the implanted allografts demineralized for 20, 25, 30 minutes, respectively. However, the other groups of allografts showed relatively poor osteoinductive activity. These findings suggest that complete decalcification with a minimized degeneration of collagen matrix is necessary to induce maximal osteogenesis by decalcified bone allograft.

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A STUDY ON THE EFFECT OF INTERMAXILLARY FIXATION ON THE CHONDROCYTES OF RABBIT MANDIBULAR CONDYLE;A light and electron microscopic study (악간고정(顎間固定)이 가토(家兎)의 하악두(下顎頭) 연골세포(軟骨細胞)에 미치는 영향(影響)에 관(關)한 연구(硏究);광학현미경적(光學顯微鏡的) 및 전자현미경적(電子顯微鏡的) 연구(硏究))

  • Ryu, Dong-Mok;Kim, Yeo-Gab;Lee, Sang-Chul
    • Maxillofacial Plastic and Reconstructive Surgery
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    • v.11 no.1
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    • pp.130-152
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    • 1989
  • The purpose of this study was to observe the effect of intermaxillary fixation on the chondrocytes of the mandibular condyle under the light and the electron microscope. For this study, twenty rabbits were placed in maxillomandibular fixation, and two were used as a control group. The experimental group was subdivided into 3, 7, 14, 21 and 28 day group. After the experimental period of 3, 7, 14, 21 and 28 days, the animals were sacrificed with a vascular perfusion of 2.5% glutaraldehyde. The condylar processes were exenterated, and decalcified in 0.1M EDTA with 2.5% glutaraldehyde solution for two weeks. The specimens were rinsed with phosphate buffer solution and the post-fixation was carried out with 2% osmium tetroxide at $4^{\circ}C$ for two hours. Thereafter the specimens were dehydrated in alcohol series, cleared with propylene oxide and embedded in Epon 812 resin. Thin sections and ultra-thin sections were made, and the cellular structures of the condylar cartilages were observed with light and electron microscope. The results were as follows: 1. In the intermaxillary fixation group, the cartilaginous tissues of mandibular condyles showed a marked decrease in the thickness compared to the control group. 2. A remarkable change was noticed in the proliferating and the hypertrophic zone of the condylar cartilages in the experimental group. 3. An atrophic change of the condylar cartilage was appeared in the 3 day experimental group and degenerative change was observed in the 7 day experimental group, and recovery was seen in thereafter 14 day experimental group. 4. Calcification, degeneration and resorption of condylar cartilage were recognizable, and the cellular zone of the condylar cartilage was appeared indistinctly in 3 day and 7 day experimental group. The chondroblasts, however, were differentiated into chondrocytes and resumed mitosis, and then the cellular zones of the condylar cartilage were reorganized from the 14 day experimental group under the findings of light microscope. 5. Under the findings of electron microscope, atrophic changes and decrease in number of intracellular organelles, degenerative changes of cytoplasm, and pyknosis of nuclei were observed in early stage, however, a gradual regeneration and reorganization of the intracellular organelles were observed from 14 day experimental group.

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Histologic changes of pulpal tissue after laser-aided ceramic bracket debonding (레이저를 이용한 도재 브라켓 제거 술식 후 치수의 조직학적 변화)

  • Kim, Yu-Jeong;Lim, Sung-Hoon;Yoon, Young-Joo;Park, Joo-Cheol;Kim, Kwang-Won
    • The korean journal of orthodontics
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    • v.34 no.4 s.105
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    • pp.343-349
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    • 2004
  • Laser-aided debonding has advantages in that the heat produced is localized and controlled, the debonding tool is not heated, and it can be used for the removal of various types of ceramic brackets, regardless of their design. However, the range of safe power usage for laser-aided debonding has not vet been confirmed. The Purpose of this study was to evaluate the histologic changes of pulpal tissue in a rabbit's incisor after Nd-YAG laser-aided ceramic bracket debonding at different levels of power. The result were as follows: 1. At 3-5W Nd-YAG laser power level and 3 seconds of exposure time, the ceramic bracket debonding procedure was not easy. At 5W of power a tie-wing fracture occurred on one bracket during debonding using Weingart plier. The histologic section of pulp represented no adverse changes. 2. At 7-13 W power level and less than 5 seconds of exposure time, the debracketing procedure was done easily and bracket facture did not occur. The histologic section of pulp represented mild and reversible changes. All the results were reversible and no pulpal degeneration or necrosis occurred. Considering the results, it appears that the laser-aided debonding technique is a safe method that does not result in irreversible pulpal changes, softens bracket bonding resin within a saie range of power and exposure time, and is useful for ceramic bracket recycling by lowering the tie- wing fracture rate.

Morphometric and Ultrastructural Change of Myelin-Associated Glycoprotein (MAG)-Immunoreactive Oligodendrocytes by Aging (노화에 의한 Myelin-Associated Glycoprotein (MAG) 면역반응 희소돌기아교세포의 형태계측학적 및 미세구조적 변화)

  • Cho, Ik-Hyun;Park, Chang-Hyun;Lee, Jong-Hwan;Bae, Chun-Sik;Ye, Sang-Kyu;Lee, Beob-Yi;Park, Seung-Hwa;Koh, Ki-Seok;Kim, Jin-Suk;Chang, Byung-Joon
    • Applied Microscopy
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    • v.36 no.2
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    • pp.119-130
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    • 2006
  • To investigate the role of myelin-associated glycoprotein (MAG) in the normal aging process, aging-related morphometric and ultrastructural analyses of the MAG-positive (MAG-(+)) oligodendrocytes were carried out in the cerebral cortex of the Sprague-Dawley rats. In the aged rats, the density of MAG-(+) oligodendrocytes was significantly decreased in the cortical layer (IV-VI) compared with that of the adult rats. However, the percentage of medium and dark types of oligodendrocytes was significantly increased by aging. In the aged rats, the mean nuclear area of the MAG-(-) oligodendrocytes was interestingly reduced compared with that of MAG-(+) oligodendrocytes. In addition, MAG immunoreactive products were markedly decreased in the medium-dark type of oligodendroglial cytoplasm and processes, and were scarcely localized in the dark type of oligodendrocytes of the aged rats. These results suggest that degeneration of oligodendrocytes-myelin system by aging is associated with down regulation of MAG, and that may contribute to further understanding of the biology of MAG in the oligodendrocytes-myelin system.

Expression of Myelin-Associated Glycoprotein (MAG) in the Aged Rat Cerebrum (노화된 흰쥐대뇌 에서 Myelin-Associated Glycoprotein (MAG)의 발현)

  • Cho, Ik-Hyun;Park, Chang-Hyun;Lee, Jong-Hwan;Bae, Chun-Sik;Ye, Sang-Kyu;Lee, Beob-Yi;Park, Seung-Hwa;Koh, Ki-Seok;Kim, Jin-Suk;Chang, Byung-Joon
    • Applied Microscopy
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    • v.36 no.2
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    • pp.101-108
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    • 2006
  • Myelin-associated glycoprotein (MAG) has been known to have a crucial role to the formation of myelin sheath during initial stage of myelination. In the present study, we investigated the aging-related expressional changes of MAG in the rat cerebrum. MAG expression was markedly decreased in cerebral cortex by aging. In the adult rat cerebrum, MAG-positive rolls were process-bearing cells with large nucleus, and extensively distributed. However, in the aged rat brain, MAG-positive cells showed small and round morphology with little cytoplasm and few processes. MAG was co-expressed with galatocerebroside, but not with Iba-1, or GFAP. These results suggest that the expressional change of MAG-positive cells is associated with degeneration of oligodendrocyte-myelin system by aging, and that MAG is likely to be a reliable marker for the mature oligodendrocytes in the aged rat brain.