• Restorative Dentistry and Endodontics
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• 제34권6호
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• pp.537-550
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• 2009

본 연구에서는 Porphyromonas endodontalis와 죽상경화증 및 심혈관질환과의 관계를 알아보기 위해, P. endodontalis가 사람의 관상동맥 내피세포에 침투했을 때 나타나는 유전자 발현의 변화를 microarray와 real-time PCR로 측정하였고, 발현이 증가된 유전자 중에서 죽상경화증과 연관된 유전자들이 관련 KEGG pathway 상에서 유의성 있는 영향을 미치는지를 분석하여 다음과 같은 결과를 얻었다. 1. Porphyromonas endodontalis는 사람의 관상동맥 내피세포에 침투하였다. 2. Microarray 분석결과, 대조군보다 발현이 2배 이상 증가된 유전자는 625개였고, 1/2이하로 감소된 유전자는 154개였다. 3. 발현이 2배 이상 증가된 유전자 중에는 염증성 cytokine 및 chemokine, 세포자멸사, 혈액응고와 면역반응 관련 유전자들이 포함되었다. 4. Microarray 분석결과를 확인하기 위해 발현이 2배 이상 증가된 유전자 중에서 10개의 유전자를 선택하여 real-time PCR을 시행하였고, 그 결과 microarray에서와 마찬가지로 발현 정도가 대조군보다 모두 높게 나타났다. 따라서 P. endodontalis가 사람의 관상동맥 내피세포에 만성적으로 작용했을 때, 심혈관질환에서 중요한 부분을 차지하는 죽상경화증을 유발하는 위험 요소 중의 하나로 작용할 수 있을 것으로 판단된다. 이와 관련된 자세한 기전을 이해하기 위해서는 앞으로 더 많은 연구가 필요할 것으로 보인다.

• 대한수의학회지
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• 제51권2호
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• pp.139-149
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• 2011

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory disease in the murine central nervous system (CNS) and has long been used as an animal model for human multiple sclerosis. Development of EAE requires coordinated expression of a number of genes that are involved in the activation and effector functions of inflammatory cells. Galectin-3 (Gal-3) is a member of the betagalactoside- binding lectin family and plays an important role in inflammatory responses through its functions on cell activation, cell migration or inhibition of apoptosis. We investigated the functional role of Gal-3 in EAE mice following immunization with myelin oligodendrocyte glycoprotein $(MOG)_{35-55}$ peptide. During the peak stage of EAE, the localization of Gal-3 in inflammatory cells markedly increased in subarachnoid membranes and perivascular regions of CNS. In contrast, Gal-3 was weakly detected in cerebrum and spinal of the recovery stage of EAE. Consistent with this finding, western blot analysis revealed that Gal-3 expression was significantly increased at the peak stage while it was slightly decreased at the recovery stage in the CNS. In addition, the population of $CD11b^{+}$ macrophage expressing Gal- 3 in spleen of EAE mice was markedly increased compared with control mice. In fact, most of activated macrophages isolated from spleen of EAE mice expressed Gal-3. Taken together, our results demonstrate that the over-expression of Gal-3 in activated macrophages may play a key role in promoting inflammatory cells in the CNS during EAE.

• 한국약용작물학회지
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• 제25권5호
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• pp.322-327
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• 2017

Background: Cynaroside is a flavone, a flavonoid-like compound, known by different names (luteoloside and cinaroside). It is commonly found in Lonicera japonica Thunb., Chrysanthemum moriflium, and Angelica keiskei. The process of cell death has been classified as necrosis and apoptosis. Necrosis refers to unregulated cell death induced by a chemotherapeutic agent. Doxorubicin is an anthracycline anti-cancer drug used to treat acute leukemia, cancer, and lymphoma. However, it induces nephrotoxicity including tubular damage. Therefore, we investigated the protective effect of cynaroside against doxorubicin-induced necrosis in HK-2 cells. Methods and Results: To confirm the beneficial effect of cynaroside on doxorubicin-induced necrosis, HK-2 cells, a human proximal tubule epithelial cell line were treated with $10{\mu}M$ doxorubicin and $80{\mu}M$ cynaroside. Doxorubicin treatment resulted in increased DNA fragmentation, caspase-3 activity and mitochondria hyperactivation during cell necrosis. However, pretreatment with $80{\mu}M$ cynaroside attenuated DNA fragmentation, caspase-3 activity and mitochondria hyperactivation induced by $10{\mu}M$ doxorubicin in HK-2 cells. Conclusions: These results indicated that pretreatment with cynaroside ameliorated doxorubicin-induced necrosis in HK-2 cells. Therefore, cynaroside be used as a therapeutic agent for improving doxorubicin-induced nephrotoxicity. However, further studies are required to evaluated the toxicity of cynaroside treatment in animals and to determine its protective effect against doxorubicin-induced nephrotoxicity in an animal model.

• 한국안광학회지
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• 제13권4호
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• pp.161-169
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• 2008

목적: 알칼리 화상 후 초기 임상적 손상반응의 진행과 치료를 위한 각막 재생의 이해를 높이기 위하여, 화학적 손상 후 동반하는 다양한 인자에 대한 면역조직화학적 변화를 조사하였다. 방법: 알칼리 화상을 입은 각막의 자가치유과정을 면역형광염색법과 H-E 염색, 그리고 TUNEL assay를 통해 면역조직화학적 측면에서 관찰하였다. 결과: 화상 후 각막의 치유는 진행되었지만 각막기질(stroma)과 내피세포의 세포사는 지속적으로 관찰되었다. 각막가장자리의 혈관신생과 손상된 각막의 ${\alpha}$-SMA의 발현은 알칼리 화상 3일 후부터 나타났으며, 각막기질에서의 콜라젠 III(collagen III)의 형성과 콘드로이친황산(chondroitin sulfate)의 발현은 ${\alpha}$-smooth muscle actin(${\alpha}$-SMA)와 transforming growth factor-${\beta}$(TGF-${\beta}$)의 발현증가와 일치하는 결과를 얻었다. 결론: 각막혼탁을 막기 위해서는 알칼리 화상 후 3일 이내에 혈관신생, 콜라젠 및 콘드로이친황산의 형성을 억제하는데 주력하는 치료가 효과적일 것이라 사료된다. 이 연구는 알칼리 화상을 입은 각막의 치유과정에 있어서의 면역조직화학적 지식을 제공함으로써, 각막의 재생을 촉진하는 치료제의 개발과 이용에 초석이 되리라 사료된다.

• 대한한방내과학회지
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• 제22권2호
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• pp.145-160
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• 2001

Objectives : The purpose of this investigation is to evaluate the effect of Geupoongjibo-dan Extracts on Reversible Forebrain Ischemia in Mongolian Gerbils. Methods : The change rate of water content in cerebral tissues, the numercal change of the CA1 pyramidal neuron in the hippocampus, the change of delayed neuronal death(necrosis apoptosis) through light microscopy, the reactivity change of glycoprotein in neuronal membrane and the ultrastructural change of pyramidal neuron through electron microscopy caused by dalayed neuronal death were investigated. Results : 1. The change rate of water content in the normal group showed 78.90% on the third day, and 79.12% on the seventh day after an attack of ischemia. The rate in the control group showed 82.25% and 85.13%, respectively. The rate in the sample group showed a significant decrease: 81.72% and 83.66%. 2. Light microscopy revealed that the cells, continuous and systematic forms in the pyramidal cells of hippocampus, changed into discontinuous and unsystematic forms in the normal group when compared with the control group. The cells were less damaged in the sample group. 3. The mean of the numerical change of the CA1 pyramidal neurons in the hippocampus was 104 in the normal group. The mean of the control group was decreased to 27. The mean of the sample group was 44. 4. TUNEL staining examination reveals that the whole part of the hippocampus of the normal group had negative reactivity. As far as CA1 pyramidal neurons in the hippocampus, the control group had positive reactivity. The sample group was more positive than the control group. 5. Electron microscopy reveals that the ischemic injury of the control group had both necrotic and apoptotic morphology. The sample group was less necrotic, and more apoptotic morphology than the control group. 6. Lectin histochemisrical examination reveals that the normal group had positive reactivity to PNA and SBA in interneuron, and weak positive reactivity to WGA Con A LCA in intercelluar space. The reactivity to PNA and WGA decreased in the control group. The reactivity to PNA and WGA tended to increase in the sample group. Conclusions : The data shows that the effect of Geupoongjibo-dan Extracts on Reversible Forebrain Ischemia in MG is a significant result.

• 동의신경정신과학회지
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• 제22권4호
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• pp.201-218
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• 2011

Objectives : The aim of this study was to investigate the effects of Guibi-Tang(GBT) on focal brain ischemic injury induced by intraluminal filament insertion in rats. Methods : The ischemia was induced by intraluminal filament insertion into middle cerebral artery. Sprague-Dawley rats were divided into five groups, normal group(n=8); control group was ischemia induced and no treatment(n=8); GBT 1X group was ischemia induced and administrated 42.2 mg/ml/kg of Guibi-Tang orally(n=8); GBT 3X group was ischemia induced and administrated 126.6 mg/ml/kg of Guibi-Tang orally(n=8); GBT 6X group was ischemia induced and administrated 253.2 mg/ml/kg of Guibi-Tang orally(n=8) for 21 days. mGluR5, Bax, Bcl-2 and cytochrome C were investigated to observe the effects of Guibi-Tang on apoptosis. The effects of Guibi-Tang on neuroprotective/apoptotic agents in cresyl violet, choline acetyltranferase(ChAT) with ischemic injury were investigated. Results : The intensity of mGluR5 mRNA in the hippocampal CA1 was increased in normal and GBT(Guibi-Tang) 1X groups compared with the control group. The intensity of Bax mRNA in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. However it was increased unexpectedly in GBT 3X group. The intensity of Bcl-2 mRNA in the hippocampal CA1 was increased in normal and GBT 1X groups compared with the control group. The intensity of Bax/Bcl-2 ratio in the hippocampal CA1 was decreased in normal and GBT 1X groups compared with the control group. The intensity of cytochrome C protein in the hippocampal CA1 was decreased in normal, GBT 1X and GBT 6X groups compared with the control group. The density of neurons stained by cresyl violet and ChAT was increased in normal and GBT 1X groups compared with the control group. Conclusions : These results suggest that Guibi-Tang may have protective effect on vascular dementia.

• 동의생리병리학회지
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• 제19권2호
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• pp.416-425
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• 2005

This study demonstrated neuroprotective and anti-oxidative effects of Puerariae Radix for cerebral ischemia. Neuroprotective effects were studied by using oxygen/glucous deprivation of the organotypic hippocampal slice cultures to complement limitations of in vivo and in vitro models for cerebral ischemia study. Anti-oxidative effects were studied on BV-2 microglia cells damaged by $H_2O_2$ and nitric oxide. The results obtained are as follows; The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in CA1 region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of neuronal cell death area and cell death area percentages in DG region of ischemic damaged hippocampus cultures during whole 48 hours of the experiment. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of TUNEL-positive cells in both CA1 region and DG region of ischemic damaged hippocampus cultures. The group treated with $50\;{\mu}g/m{\ell}$ of Puerariae Radix demonstrated significant decrease of TUNEL-positive cells in CA1 region. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant decreases of LDH concentrations in culture media of ischemic damaged hippocampus cultures. The groups treated with 0.5 and $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increases of cell viabilities of BV-2 microglia cells damaged by $H_2O_2$. The group treated with $5{\mu}g/m{\ell}$ of Puerariae Radix revealed significant increase of cell viability of BV-2 microglia cells damaged by nitric oxide. These results suggested that Puerariae Radix of cerebral ischemic revealed neuroprotective effects through the control effect of apoptosis and oxidative damages.

• Toxicological Research
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• 제27권4호
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• pp.253-259
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• 2011

Transforming growth factor ${\beta}$ (TGF-${\beta}$) is involved in cellular processes including growth, differentiation, apoptosis, migration, and homeostasis. Generally, TGF-${\beta}$ is the inhibitor of cell cycle progression and plays a role in enhancing the antagonistic effects of many growth factors. Unlike the antiproliferative effect of TGF-${\beta}$, E2, an endogeneous estrogen, is stimulating cell proliferation in the estrogen-dependent organs, which are mediated via the estrogen receptors, $ER{\alpha}$ and $ER{\beta}$, and may be considered as a critical risk factor in tumorigenesis of hormone-responsive cancers. Previous researches reported the cross-talk between estrogen/$ER{\alpha}$ and TGF-${\beta}$ pathway. Especially, based on the E2-mediated inhibition of TGF-${\beta}$ signaling, we examined the inhibition effect of 4-tert-octylphenol (OP) and 4-nonylphenol (NP), which are well known xenoestrogens in endocrine disrupting chemicals (EDCs), on TGF-${\beta}$ signaling via semi-quantitative reverse-transcription PCR. The treatment of E2, OP, or NP resulted in the downregulation of TGF-${\beta}$ receptor2 (TGF-${\beta}$ R2) in TGF-${\beta}$ signaling pathway. However, the expression level of TGF-${\beta}1$ and TGF-${\beta}$ receptor1 (TGF-${\beta}$ R1) genes was not altered. On the other hand, E2, OP, or NP upregulated the expression of a cell-cycle regulating gene, c-myc, which is a oncogene and a downstream target gene of TGF-${\beta}$ signaling pathway. As a result of downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc, E2, OP, or NP increased cell proliferation of BG-1 ovarian cancer cells. Taken together, these results suggest that E2 and these two EDCs may mediate cancer cell proliferation by inhibiting TGF-${\beta}$ signaling via the downregulation of TGF-${\beta}$ R2 and the upregulation of c-myc oncogene. In addition, it can be inferred that these EDCs have the possibility of tumorigenesis in estrogen-responsive organs by certainly representing estrogenic effect in inhibiting TGF-${\beta}$ signaling.

• Biomolecules & Therapeutics
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• 제23권4호
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• pp.367-373
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• 2015

Cordyceps species including Cordyceps bassiana are a notable anti-cancer dietary supplement. Previously, we identified several compounds with anti-cancer activity from the butanol fraction (Cb-BF) of Cordyceps bassiana. To expand the structural value of Cb-BF-derived anti-cancer drugs, we employed various chemical moieties to produce a novel Cb-BF-derived chemical derivative, KTH-13-amine-monophenyl [4-isopropyl-2-(1-phenylethyl) aniline (KTH-13-AMP)], which we tested for anti-cancer activity. KTH-13-AMP suppressed the proliferation of MDA-MB-231, HeLa, and C6 glioma cells. KTH-13-AMP also dose-dependently induced morphological changes in C6 glioma cells and time-dependently increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, the levels of the active full-length forms of caspase-3 and caspase-9 were increased. In contrast, the levels of total forms of caspases-3, caspase-8, caspase-9, and Bcl-2 were decreased in KTH-13-AMP treated-cells. We also confirmed that the phosphorylation of STAT3, Src, and PI3K/p85, which is linked to cell survival, was diminished by treatment with KTH-13-AMP. Therefore, these results strongly suggest that this compound can be used to guide the development of an anti-cancer drug or serve as a lead compound in forming another strong anti-proliferative agent.

• 생명과학회지
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• 제26권2호
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• pp.265-274
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• 2016

Toxin-antitoxin (TA) system은 박테리아와 고세균에서 진화적으로 보존되어 흔히 발견되는 유전적 모듈이다. 기본적으로 이 시스템은 세포 내 toxin과 그들의 억제자로 작용하는 antitoxin으로 구성되어있으며, 현재 총 다섯가지 유형으로 구분된다. 공통적으로 toxin은 스트레스 조건에서 활성화됨으로써 세포 내 다양한 과정을 억제하는 활성을 가지는데 이는 결과적으로 세포 사멸 혹은 가역적인 생장 저해를 일으킨다. Toxin의 이러한 효과들은 유전자 발현의 조절, 성장 조절, programmed cell arrest, programmed cell death, persister cell의 형성, 박테리오파지 방어기작, 가동성 유전인자의 안정화, 플라스미드 유지 기작 등 다양한 생리학적 역할을 나타낸다. 그러므로 TA system은 일반적인 스트레스 반응모듈로서 여겨진다. 하지만 이를 역이용한다면 TA system으로부터 toxin을 활성화 시키는 인자를 개발하여 새로운 항균 물질로 이용할 수 있다. 그뿐만 아니라 TA system은 toxin의 세포 사멸 효과를 이용하여 원하는 타겟 유전자가 존재하는 세포만 선택적으로 살아남도록 하는 효율적인 클로닝 전략에 이용될 수 있다. 또한, toxin의 서열 특이적 리보핵산 가수분해효소 활성을 이용하여 타겟 단백질 이외의 단백질 합성을 막아 효과적인 단일 단백질 대량 생산을 위해서도 이용할 수 있다. 더 나아가 일부 TA system의 toxin은 진핵 세포에서도 세포 독성을 나타내기 때문에 암세포, 바이러스 감염 세포에서 toxin의 발현을 유도하여 세포사멸을 일으킴으로써 인간의 질병 치료로 이어질 수 있다.