• The Korean Journal of Physiology and Pharmacology
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• 제25권4호
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• pp.307-319
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• 2021

Dysregulation of the Wnt pathway causes various diseases including cancer, Parkinson's disease, Alzheimer's disease, schizophrenia, osteoporosis, obesity and chronic kidney diseases. The modulation of dysregulated Wnt pathway is absolutely necessary. In the present study, we evaluated the anti-inflammatory effect and the mechanism of action of Wnt-C59, a Wnt signaling inhibitor, in lipopolysaccharide (LPS)-stimulated epithelial cells and macrophage cells. Wnt-C59 showed a dose-dependent anti-inflammatory effect by suppressing the expression of proinflammatory cytokines including IL6, CCL2, IL1A, IL1B, and TNF in LPS-stimulated cells. The dysregulation of the Wnt/β-catenin pathway in LPS stimulated cells was suppressed by WntC59 treatment. The level of β-catenin, the executor protein of Wnt/β-catenin pathway, was elevated by LPS and suppressed by Wnt-C59. Overexpression of β-catenin rescued the suppressive effect of Wnt-C59 on proinflammatory cytokine expression and nuclear factor-kappa B (NF-κB) activity. We found that the interaction between β-catenin and NF-κB, measured by co-immunoprecipitation assay, was elevated by LPS and suppressed by Wnt-C59 treatment. Both NF-κB activity for its target DNA binding and the reporter activity of NF-κB-responsive promoter showed identical patterns with the interaction between β-catenin and NF-κB. Altogether, our findings suggest that the anti-inflammatory effect of Wnt-C59 is mediated by the reduction of the cellular level of β-catenin and the interaction between β-catenin and NF-κB, which results in the suppressions of the NF-κB activity and proinflammatory cytokine expression.

• Biomolecules & Therapeutics
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• 제31권6호
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

• 생명과학회지
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• 제29권8호
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• pp.904-915
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• 2019

전립선암은 전이성 종양 중의 하나로 치료를 위해 호르몬 요법이나 외과 적 거세 방법이 주로 수행되지만 많은 부작용을 나타내었다. 최근 많은 연구자들이 이러한 상황을 해결하기 위해 종양 미세 환경을 연구하고 있으며 그 중 면역 세포, 특히 대식세포는 종양 미세 환경의 중요한 구성요소이다. 정상적인 조건에서 대식세포는 여러 암세포에 대해 약한 종양 살균 활성을 갖으나 $interferon-{\gamma}$ 또는 lipopolysaccharide에 의해 활성화되면, 염증성 사이토카인 및 케모카인을 분비함으로써 암세포를 직접 또는 간접적으로 사멸 시키게 된다. 본 연구에서는, 마우스 대식세포인 RAW 264.7 세포에 Phellinus linteus 추출물을 처리하여 산화질소의 방출과 pro-inflammatory cytokine들을 real-time PCR과 ELISA 방법으로 분석하였다. RAW 264.7의 조정 배지는 48시간 동안 전립선 암세포처리하여 상피간엽세포전이 관련 유전자의 발현을 측정 하였다. 그 때에 mesenchymal 관련 유전자들인 N-cadherin, snail, twist, slug 및 cadherin 11이 감소했을 뿐만 아니라 epithelial 관련 유전자인 E-cadherin은 증가하였다. 또한 암 전이 및 신생 혈관 형성에 관여하는 vimentin, ccl2 및 vegfa가 감소되었는데, 이는 EMT가 암세포의 이동과 침범에 밀접한 관련이 있기 때문이다. 따라서 Phellinus linteu에 의해 자극된 RAW 264.7 세포의 조정 배지는 인간 전립선 암세포주인 PC-3 세포의 이동과 전이를 억제하고 EMT 경로를 조절한다는 것을 나타낸다.

• Applied Microscopy
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• 제25권4호
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• pp.124-131
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• 1995

이상과 같은 실험결과를 다음과 같은 요약할 수 있다. 1) $Hg_{1-x}\;Tl_{x}\;Ba_{2}(Ca_{0.86}\;Sr_{0.14})_{2}\;Cu_{3}\;O_{8+\delta}$의 구조는 Hg-1223과 같은 구조를 이루며 Hg 위치에 T1이 치환되어 있음을 알 수 있다. 2) 격자상수는 탈륨이 증가할수록 감소하는 경향을 나타냈으나 x=0.25 시료에서는 현저히 감소됨을 보였다. 3) x=0.25 시료에서는 적층 결함 1234구조가 1223구조와 intergrowth함을 보였고 불순물 상이 다소 나타났다. 4) 탈륨이 증가할 수록 보다 치밀하고 결함이 없는 안정된 조직을 보였다. 5) 모든 시료가 관찰 도중 전자빔에 대하여 손상되었으나 탈륨의 양이 증가할 수록 손상에 대한 저항이 커져 보다 안정된 상을 보였다.

• 한국약용작물학회지
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• 제8권2호
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• pp.157-164
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• 2000

활성산소에 기인하는 다양한 성인병을 예방 치료할 수 있는 안전하고 우수한 항산화 물질을 천연물로 부터 개발하기 연구의 일환으로 오배자의 주성분에 대한 항산화효과 및 간보호효과를 연구하여 다음과 같은 결과를 얻었다. 1. Ferric-Thiocyanate 법에 의하여 과산화반응 억제에 따른 항산화 활성을 측정한 결과 모두 tocopherol보다 강한 과산화반응 억제 활성을 보였으며 gallic acid methyl ester, protocatechuic acid와 syringic acid는 tocopherol 보다는 강한 활성을 보였으며 BHA와는 유사 또는 그 이상의 활성을 보였다. 특히 1, 2, 3, 4, $6-penta-O-galloyl-{\beta}-D- glucose$는 tocopherol과 BHA보다 매우 강한 과산 화반응억제 활성을 보였다. 2. TBA 법에 의한 과산화지질의 생성의 지표인 MDA 억제효과에 의한 항산화효과를 측정한 결과 gallic acid 는 $1.6{\times}10^{-4}$의 농도에서 BHA 보다 높은 억제율을, protocatechuic acid는 $1.6{\times}10^{-6}$의 농도에서 BHA 보다 높은 억제율을 보였다. gallic acid methyl ester와 1, 2, 3, 4, $6-penta-O-galloyl-{\beta}-D-glucose$는 농도가 증가함에 따라 우수한 MDA의 억제활성을 나타내었다. 3. Glycyrrhizin을 비교군으로 하여 간 보호 실험을 한 결과 1, 2, 3, 4, $6-penta-O-galloyl-{\beta}-D-glucose$의 0.5mg/ml첨가군에서는 GOT의 강한 감소 효과를 보였으며 GPT 실험에서는 각 시료 0.5mg/ml 첨가군에서 감소하는 경향을 나타내었다.

• 분석과학
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• 제13권6호
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• pp.751-758
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• 2000

사용후핵연료에 미량 함유되어 있는 요오드를 정량하기 위하여 분리 및 회수를 위한 최적조건을 실험하였다. 사용후핵연료의 용해를 위하여 모의 사용후핵연료를 이용하였으며 용해과정에서 요오드가 휘발되지 않는 혼합산(질산:염산)의 최적 혼합비는 80:20 mol%이었으며 비휘발성 요오드의 생성을 촉진시키기 위하여 오존을 사용하였을 때 요오드의 회수율이 6회 평균 측정값이 9.6% 증가를 나타내었다. 사염화탄소에 의한 요오드 추출과정에서 ${IO_3}^-$를 $I_2$으로 환원시키기 위하여 $NH_2OH{\cdot}HCl$을 사용하였으며 요오드 환원에 적합한 용해용액의 산도는 2.5 M 그리고 $NH_2OH{\cdot}HCl$의 양은 $1.5{\times}10^{-3}mole$ 이상이었다. 분리된 요오드는 이온 크로마토그래피로 정량하였으며 이때 회수율은 $82.8{\pm}4.1%$로서 $^{131}I$를 추적자로 사용하여 보정하였다.

• 한국임상수의학회지
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• 제19권2호
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• pp.125-131
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• 2002

The present experiment was performed in order to know the therapeutic effect of laserpuncture and aquapuncture with methionine on recovery in artificially induced hepatic damaged rats by carbon tetrachloride. The animals were divided into control, laserpuncture and aquapuncture groups. The changes of serum enzyme activities(ALT and AST), serum total protein contents, protein fractions(ALB and GLB) and A/G ratio were examined before and after application of laserpuncture and aquapuncture. In change of serum ALT activity, recovery with treatment in laser and aquapuncture groups was more rapid than that of control. The significant decreased value was shown on 3rd(P < 0.05) and 7th day(P < 0.01) after treatment in laserpuncture group and on 7th day(P < 0.05) after treatment in aquapuncture group. In addition, significance was detected on 2nd day(P < 0.05) between laserpuncture and aquapuncture groups. In change of serum AST activity, recovery with treatment in laserpuncture and aquapuncture groups was more rapid than that of control. The significant lower values on 7th day(P<0.01) in aquapuncture groups. In addition, significant low value was detected on 7th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture group. The change of serum TP contents showed similar pattern in control, laser and aquapuncture groups. The significances were detected on 7th day(P < 0.05) in both experimental groups. In addition, significant high value was detected on 2nd day(P < 0.05) in laserpuncture group comparing with that of aquapuncture group. The change of serum ALB content with treatment in laser and aquapuncture groups was more rapid than that of control. The significant high value was shown on 2nd(P < 0.01), 5th(P < 0.05) and on 7th day(P < 0.01) in laserpuncture group. In addition, significant high value was detected on 3rd day(P<0.01) only in aquapuncture group comparing with laserpuncture group. The change of serum GLB content showed similar pattern among groups. The significant low values were detected on 2nd day(P < 0.05) in aquapuncture group. In addition significant high value was detected on 5th day(P < 0.01) only in laserpuncture group comparing with that of aquapuncture group. In change of A/G ratio laser and aquapuncture groups showed higher values than that of control. The significant high values were detected on 1st day(P < 0.Of) and 2nd day(P < 0.05) in laserpuncture group, and on 1st day(P < 0.05) and 2nd day(P < 0.01) in aquapuncture group. In addition, significant high value was detected on 5th day(P < 0.05) in aquapuncture group comparing with that of laserpuncture. Considering above findings collectively, it was considered that both laserpuncture and aquapuncture were effective; aquapuncture was more effective than laserpuncture for recovery of hepatic damage.

• 한국균학회지
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• 제27권1호통권88호
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• pp.82-86
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• 1999

영지버섯(Ganoderma lucidum WK-003) 균사체의 액체 배양에 의하여 세포외 생물고분자 물질의 산업적 생산을 위한 최적 조건을 검토하였다. 세포외 고분자물질 생산을 위한 산업용배지의 최적 농도는 molasses 5%와 CSL 2.5%에서 균사체 생장(12.4 g/l)과 균체외 다당체 생산(3.6g/l)이 최대를 나타났으며, 5 l 발효조 배양시에는 균사체 생장이 합성배지(8.1g/l)일때가 산업용배지(7.3 g/l)보다 높게 나타났으나, 균체외 다당체 생산은 합성배지(7.2 g/l)보다 산업용 배지(11.2 g/l)일 때가 더 높게 나타났다. 간 보호 효과는 합성배지와 최적화된 산업용 배지에서 생산된 균체외 다당체를 $CCl_4$ 독성이 유발된 rat에 경구 투여하였을 때 주요 지표를 나타내는 GPT활성은 산업용배지에서 생산된 균체외 다당체 인 경우 704IU/L에서 356IU/L로 낮추었으며, 합성배지에서 생산된 균체외 다당체는 704IU/L에서 349IU/L로 낮춘 결과를 보였다. 따라서 합성배지와 산업용 배지에서 생산된 균체외 다당체의 간 보호 작용은 거의 차이가 없는 것으로 나타났다.

• IMMUNE NETWORK
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• 제22권3호
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• pp.22.1-22.25
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• 2022

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndromecoronavirus-2 (SARS-CoV-2), has spread over the world causing a pandemic which is still ongoing since its emergence in late 2019. A great amount of effort has been devoted to understanding the pathogenesis of COVID-19 with the hope of developing better therapeutic strategies. Transcriptome analysis using technologies such as RNA sequencing became a commonly used approach in study of host immune responses to SARS-CoV-2. Although substantial amount of information can be gathered from transcriptome analysis, different analysis tools used in these studies may lead to conclusions that differ dramatically from each other. Here, we re-analyzed four RNA-sequencing datasets of COVID-19 samples including human bronchoalveolar lavage fluid, nasopharyngeal swabs, lung biopsy and hACE2 transgenic mice using the same standardized method. The results showed that common features of COVID-19 include upregulation of chemokines including CCL2, CXCL1, and CXCL10, inflammatory cytokine IL-1β and alarmin S100A8/S100A9, which are associated with dysregulated innate immunity marked by abundant neutrophil and mast cell accumulation. Downregulation of chemokine receptor genes that are associated with impaired adaptive immunity such as lymphopenia is another common feather of COVID-19 observed. In addition, a few interferon-stimulated genes but no type I IFN genes were identified to be enriched in COVID-19 samples compared to their respective control in these datasets. These features are in line with results from single-cell RNA sequencing studies in the field. Therefore, our re-analysis of the RNA-seq datasets revealed common features of dysregulated immune responses to SARS-CoV-2 and shed light to the pathogenesis of COVID-19.

• 대한한의학방제학회지
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• 제15권1호
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• pp.163-173
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• 2007

Jeungaektang (JAT) is the herbal formula, has the effect of moistening the dryness by activating lung Qi and by nourishing Yin, has being used for dryness syndromes. Generally the herbal formulae for moistening dryness are used for exogenous or endogenous dryness syndromes. JAT has been clinically used for the treatment of endogenous dryness syndromes. It is composed of Scrophulariae Radix. Rehmanniae Radix and Liriopis Tuber. Recent studies showed that JAT has a protective effect against $CCl_{4}-induced$ hepatotoxicity and anti-inflammatory effects against ear swelling of mouse induced by Crotonis Fructus. However, the effect of JAT on the immunological activity was rarely studied. Therefore, this study evaluated the effects of JAT the regulatory mechanism of nitric oxide (NO) and cytokines in the lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. After the treatment of JAT water extract, cell viability was measured by MTT assay, NO production was monitored by measuring the nitrite content in culture medium. Cyclooxygenase-2 (COX -2) and inducible nitric oxide synthase (iNOS) were determined by immunoblot analysis, and levels of cytokine were analyzed by sandwich immunoassays. Results provided evidence that JAT inhibited the production of nitrite and nitrate ($0.1{\sim}1.0$ mg/ml), iNOS ($0.1{\sim}1.0$ mg/ml), $interleukin-1{\beta}$ ( $0.1{\sim}1.0$ mg/ml) and tumor necrosis $factor-{\alpha}$ ($0.1{\sim}1.0$ mg/ml) in RAW 264.7 cells activated with LPS. Furthermore, JAT inhibited the expression of COX-2 expression and production of prostagladin E2 ($0.1{\sim}1.0$ mg/ml). These findings suggest that JAT can produce anti-inflammatory effect, which may play a role in adjunctive therapy in Gram-negative bacterial infections.