• 대한한의학방제학회지
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• 제14권1호
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• pp.105-119
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• 2006

Objectives & Methods : This present study was performed to investigate the effect of Hwadamtongrak-Tang extract (HTT) on the regulation of cerebral hemodynamics in terms of regional cerebral blood flow (rCBF) and mean arterial blood pressure (MABP)] in normal and cerebral ischemic rats. Also the effects of HTT on changes in local blood flow, inhibition of LD H activity in neuronal cells, and levels of cytokine production in the serum were determined in the ischemic rat model. The major findings are summarized below. Results : 1. HTT significantly increased rCBF in a dose-dependent manner, but MABP was not changed by HTT treatment. These results suggest that HTT may increase rCBF by dilating cerebral arterial diameter. 2. HTT-induced increase in rCBF was blocked by pretreatment with cyclooxygenase inhibitor indomethacin (IDN, 1 mg/kg, i.p.) and MABP was significantly increased by ID N. 3. Pretreatment of methylene blue $(MTB,\;10\;{\mu}g/kg,\;i.p.)$, an inhibitor of guanylate cyclase, significantly decreased both rCBP and MABP in HTT-treated rats. 4. HTT treatment significantly increased rCBP to a stable level during the period of cerebral reperfusion. 5. HTT significantly inhibited LD H activity in neuronal cells, suggesting a neuroprotection by HTT. 6. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after middle cerebral arterial occlusion in HTT-treated rats. IL-10 levels in the serum were significantly increased by HTT treatment whereas transforming growth factor $(TGF)-{\beta}$ levels were similar between HTT-treated and control groups. 7. Serum interleukin $(IL)-1{\beta}$ and tumor necrosis factor $(TNF)-{\alpha}$ levels were significantly decreased in the femoral artery 1 hr after reperfusion in HTT-treated rats. Serum IL-10 levels were significantly decreased in HTT-treated rats compared with the control group, and no significant changes in $(TGF)-{\beta}$ in the serum were observed by HTT treatment. Conclusions: The present data suggest that HTT may have an anti-ischemic effect via the improvement of cerebral hemodynamics and thus protect the brain from ischemic damage.

• 대한한방내과학회지
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• 제28권2호
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• pp.304-320
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• 2007

목적 : 황기추출물이 생쥐의 5-FU로 유발된 골수억제와 삶의 질 저하의 개선에 미치는 효과를 연구하고자 한다. 방법 : 골수억제에 미치는 영향이 평가를 위해 Complete Blood Count, Histological Analysis of BM, Cell Colony Forming Assay for Hematopoietic Progenitor를 시행하고, 삶의 질에 미치는 영향을 평가하기 위해 Swimming Test, Survival Rate, Nitric Oxide (NO) Assay, $^{51}Cr$ Release Assay in NK Cell, mRNA Expressions of $IL-1{\beta}$, IL-2, IL-4, IL-6, IL-10, $TNF-{\alpha}$, $IFN-{\gamma}$, $TGF-{\beta}$ and GM-CSF in Spleen Cells를 시행하였다. 결과 : 황기추출물을 골수억제를 호전시켜 말초혈액수치를 회복시키고, 골수파괴를 보호하는 효과를 보이며, 대조군에 비해 혈구생성을 촉진시키며, 대조군에 비해 생존율과 수영시간을 증가시키며, 대식세포와 자연살상세포의 활동성을 증가시키며, 종양면역과 관련된 싸이토카인(IL-2, IL-6, $IFN-{\gamma}$)의 발현을 증가시켰다. 결론 : 5-FU로 유발된 골수억제와 삶의 질 저하의 개선에 미치는 황기추출물의 유용성이 기대되며 향후 이에 대한 지속적인 연구가 필요할 것으로 사료된다.

• 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.

• 생명과학회지
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• 제29권4호
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• pp.499-508
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• 2019

암줄기세포는 전이와 재발의 주요한 요인이 되는 자가재생능력, 분화할 수 있는 능력, 치료에 대한 저항성 및 암 형성 능력의 특성을 가진다. WNT/${\beta}$-catenin, Hedgehog, Notch, BMI1, BMP 및 TGF-${\beta}$와 같은 암줄기세포의 특성을 획득 및 유지할 수 있는 신호기전의 연구 결과가 존재하지만, 현재까지 선택적으로 암줄기세포를 표적할 수 있는 치료 전략은 미미하다. 최근, 면역관문억제제인 CTLA-4, PD-1/PD-L1 단일클론항체는 흑색종, 폐암, 췌장암 및 혈액암에 괄목할만한 임상 시험 결과를 나타냈으며, 긴 항암지속효과와 적은 부작용은 기존 항암제보다 개선 된 모습을 보였다. 또한 두경부편평상피암, 흑색종, 유방암 줄기세포를 선택적으로 제거 하였다. 위의 결과를 종합하면, 면역관문억제제는 이전 항암제에 비해 효과적인 항암전략이며, 동시에 암줄기세포를 선택적으로 제거할 수 있는 가능성을 시사한다. 따라서 본 리뷰에서는 암줄기세포와 면역관문억제제의 이해를 통해, 면역관문억제제의 암줄기세포 표적 가능성에 대해 고찰하고자 한다.

• 한방안이비인후피부과학회지
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• 제32권3호
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• pp.58-76
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• 2019

Objectives : This study was designed to examine the effects of Daecheonglyong-tang(DCL) on atopic dermatitis induced by DNCB in mice Methods : The Nc/Nga mice were divided into 5 groups, and four groups excluding the normal group were applied by 2,4-dinitrochlorobenzene(DNCB), to cause AD and were orally administered with distilled water(negative control), dexamethasone(positive control), and DCL 200 or 400mg/kg once a day for 4 weeks respectively. The visual changes on skin, changes in skin tissue thickness and eosinophil infiltration were observed. IgE, Histamine, Cytokines, immune cells and the amount of gene expression of filaggrin, VEGF, $TGF-{\beta}1$, EGF were measured. Results : Dermatitis score showed a gross improvement on all DCL groups, similar to or better than positive control. All DCL groups showed no significant change in the basophils, while neutrophils and eosinophils decreased. In only DCL 400 mg/kg groups, white blood cells and mononuclear cells were decreased and lymphocytes were increased. In particular, neutrophils had similar or better effects than the positive control. In all DCL groups, IgE, Histamine, $IL-1{\beta}$, IL-4, IL-5, IL-6 and $TNF-{\alpha}$ were decreased and IL-2 was increased. In only DCL 400 mg/kg groups, IL-10 decreased and $IFN-{\gamma}$ increased. In particular, $IL-1{\beta}$ and $IFN-{\gamma}$ showed a similar rate of increase and decrease comparing positive control in DCL 400 mg/kg. $TGF-{\beta}$1 was increased in all DCL groups, filaggrin and VEGF were increased in only DCL 400 mg/kg groups. EGF did not make any changes. Epidermis, dermis thickness and eosinophil infiltration were also decreased in all DCL groups. Conclusions : By increasing Th1 cytokine and decreasing Th2 cytokine, DCL extracts appear to be effective in controlling immune response imbalances, anti-inflammatory and skin regeneration and are likely to be available as a treatment for AD.

• Journal of Ginseng Research
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• 제45권3호
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• pp.408-419
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• 2021

Background: The decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. Methods: Sprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. Results: After SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. Conclusion: These results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

• 대한한방부인과학회지
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• 제20권4호
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• pp.56-73
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• 2007

Purpose: 이 실험은 골다공증의 치료약물로 자하거의 골질재흡수 억제효과를 검토하기 위하여 설계되었다. Methods: 자하거의 골질재흡수 효과를 확인하기 위하여 생쥐의 두개골 골모세포를 이용하여 Cyclooxygenase-1(COX-1), COX-2, $TGF-{\beta}$, $L-1{\beta}$, $TNF-{\alpha}$, IL-6, prostaglandin E2등의 활성화 정도를 측정하였으며, 골조직의 미세구조적 변화를 확인하였다. Results: 자하거는 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6 또는 그 세가지의 조합에 의하여 유발된 PGE2의 생성 뿐만 아니라 COX-2 mRNA 수치도 감소시켰으나 COX-1 mRNA 수치에는 영향을 주지 않았다. 이로써 자하거는 시험관내에서 그리고 생체내에서 펩티드의 인산화를 억제함으로써 골의 재흡수를 저해하였다. 그리고 자하거는 생쥐에서 $IL-1{\beta}$에 의해 유발된 고칼슘혈증을 감소시켰고, 골의 재흡수를 저해하는 경로를 통하여 골에 대한 보호효과를 보여줌으로써 조기에 난소 절제한 쥐에서 골질감소와 미세구조적 변화를 부분적으로 방지하였다. 이러한 결과는 PGE2 생성에 대한 $IL-1{\beta}$, $TNF-{\alpha}$, IL-6사이의 상승효과는 COX-2의 유전자 발현이 증가한 결과이며 이러한 tyrosine kinase가 생쥐의 두개골 골모세포에서 COX-2의 신호전달에 관계한다는 것을 보여준다. Conclusion: 자하거가 생쥐의 두개골 골모세포에서 여러 신호전달물질의 활성화를 통하여 골질재흡수를 저해하는 특성을 확인함으로써 앞으로 골다공증의 예방과 치료에 대한 추가적인 임상연구가 필요할 것으로 사료된다.

• 치위생과학회지
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• 제13권2호
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• pp.158-164
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• 2013

임플란트 식립 시 가장 빈번하게 맞게 되는 문제점으로 임플란트 식립 부위에서의 불충분한 골량과 해부학적 구조에 의한 접근성의 문제를 들 수 있다. 일반적으로 성장 인자들은 치유 과정이나 조직 형성에 있어서 가장 기본적인 필수 요소로 인정되고 있다. 이러한 이유로 골 이식 재료의 효과를 증진시키기 위한 성장 인자들이 최근에 주목을 받고 있다. 혈소판 내 granules에는 높은 농도의 다양한 성장 인자들이 포함되어 있다. 특히, platelet-rich fibrin (PRF)는 2세대 혈소판 농축 인자로 항응고제가 들어있지 않은 상태로 얻을 수가 있고, 혈소판과 많은 성장 인자들이 풍부한 섬유소 막을 포함하고 있다. 이번 연구의 목적은 in vitro 상에서 골아 세포에 대한 PRF의 영향을 알아보고자 하였다. 특히 치유와 재생에 연관된 주요 기능으로써 증식과 분화에 대한 영향을 조사하고자 하였다. 이를 위해서, PRF 내에서 방출되는 성장 인자(platelet-derived growth factor subunit B와 transforming growth factor-${\beta}1$)의 농도, 세포의 생존능력, alkaline phosphatase (ALP) activity, type 1 collagen 합성, 골아 세포의 분화 지표로써 ALP와 Runx2의 발현 정도와 골 기질 단백질로써 type 1 collagen의 발현 정도에 대해서 조사하였다. 이 실험을 통하여 PRF는 치유 시 필요한 타당한 기간 동안에 충분히 자가 성장 인자의 방출을 유지하고 있음을 알 수 있었고, 골아 세포의 증식과 분화에 대해서 긍정적인 효과가 있음을 보여 주였다. 제한적인 실험이지만, 골재생을 위한 PRF의 사용은 골 치유와 골 개조에 있어서 증진 효과를 가져다줄 수 있는 촉망되는 방법 중 하나가 될 수 있을 것이다.

• Asian-Australasian Journal of Animal Sciences
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• 제31권5호
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• pp.650-657
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• 2018

Objective: The study investigated the biological functions and mechanisms for controlling cashmere growth of Liaoning cashmere goat by ovarian carcinoma immunoreactive antigen-like protein 2 (OCIAD2) and decorin (DCN) genes. Methods: cDNA library of Liaoning cashmere goat was constructed in early stages. OCIAD2 and DCN genes related to cashmere growth were identified by homology analysis comparison. The expression location of OCIAD2 and DCN genes in primary and secondary hair follicles (SF) was performed using in situ hybridization. The expression of OCIAD2 and DCN genes in primary and SF was performed using real-time polymerase chain reaction (PCR). Results: In situ hybridization revealed that OCIAD2 and DCN were expressed in the inner root sheath of Liaoning cashmere goat hair follicles. Real-time quantitative PCR showed that these genes were highly expressed in SF during anagen, while these genes were highly expressed in primary hair follicle in catagen phase. Melatonin (MT) inhibited the expression of OCIAD2 and promoted the expression of DCN. Insulin-like growth factors-1 (IGF-1) inhibited the expression of OCIAD2 and DCN, while fibroblast growth factors 5 (FGF5) promoted the expression of these genes. MT and IGF-1 promoted OCIAD2 synergistically, while MT and FGF5 inhibited the genes simultaneously. MT+IGF-1/MT+FGF5 inhibited DCN gene. RNAi technology showed that OCIAD2 expression was promoted, while that of DCN was inhibited. Conclusion: Activation of bone morphogenetic protein (BMP) signaling pathway up-regulated OCIAD2 expression and stimulated SF to control cell proliferation. DCN gene affected hair follicle morphogenesis and periodic changes by promoting transforming growth $factor-{\beta}$ ($TGF-{\beta}$) and BMP signaling pathways. OCIAD2 and DCN genes have opposite effects on $TGF-{\beta}$ signaling pathway and inhibit each other to affect the hair growth.

• 대한임상검사과학회지
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• 제43권4호
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• pp.194-204
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• 2011

This study was carried out to compare the histopathological differences of liver lesions in carbon tetrachloride ($CCI_4$), dimethylnitrosamine (DMN), thioacetamide (TAA) and bile duct ligation (BDL)-induced rats. $CCl_4$, DMN and TAA were administered intraperitoneally and conducted bile duct ligation for 4 weeks to induce hepatic fibrosis. Indices of liver cell injury (steatosis, hydropic degeneration, bile duct hyperplasia, hemorrhage & hemosiderin deposition), the extent of liver fibrosis (fibrotic area) and the rate of regeneration (number of PCNA-positive cells) were investigated in each group. Liver tissues were stained with hematoxylin-eosin (HE), sirius red, prussian blue and immunostained with ${\alpha}$-smooth muscle actin (${\alpha}$-SMA), transforming growth factor-${\beta}1$ (TGF-${\beta}1$), proliferative cell nuclear antigen (PCNA), and quantified using a computerized image analysis system. Liver cell steatosis was significantly increased in $CCl_4$ and TAA groups, and hydropic degeneration and bile duct hyperplasia were significantly increased in TAA and BDL groups when compared with that in normal control, respectively. Fibrosis area was significantly increased in all four groups, especially in $CCl_4$ group. Correlation between ${\alpha}$-SMA and TGF-${\beta}1$ expressions in four groups was good. Hemorrhage area in liver parenchyma was significantly increased in DMN group only when compared with that in normal control, while hemosiderin deposition area was significantly increased in TAA and BDL groups as well as DMN group. The Number of PCNA-positive cells was significantly increased in all four groups, especially in TAA group. These results indicate that the duration and methods of hepatotoxic drug treatment are very important factors to make plans for animal experimentation on the induction of hepatic fibrogenesis in rats.