• Journal of Physiology & Pathology in Korean Medicine
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• v.28 no.2
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• pp.154-161
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• 2014

The purpose of this study is to evaluate the antioxidant activity and hair growth effects of a natural herbal ethanol extract, Samhwang-Sasimtang(SS). In case of antioxidant ability of SS, the content of phenolic compounds was 28.44mg/g. The extract showed strong electron donating ability and free radical scavenging activity in a concentration-dependent manner. SOD-like activity also rose through increasing the concentrations of SS. In order to estimate the hair growth effects, the extract was applied to the back of seven-week-old C57BL/6 male mice ($150{\mu}{\ell}$ a day, five days a week, for four weeks) in four groups (C, control, saline; PC, positive control, 3% minoxidil; E1, experimental 1, 1% SS; E2, experimental 2, 2% SS). Ten mice were assigned to each group and five mice in each group were sacrificed at weeks 2 and 4, respectively. There was no a significant difference in body weight change among experimental groups. In macroscopic observation of hair growth at week 4, the scores of hair growth on the backs of mice were 80, 60, 40 and 20% in the PC, E2, E1 and C groups. In terms of histological observation, the ratio and thickness of hair follicles, the enzyme activities of ALP and ${\gamma}$-GT, immunohistological examination of IGF-1 and VEGF which are the hair growth factors, in each group were significantly high in this order: PC, E2, E1 and C group, at week 4. Meanwhile, hair growth inhibition factors, TGF-${\beta}1$ and Caspase-3, were reduced in PC, E1 and E2 groups compared with C group. These results indicate that SS extract may be effective in promoting hair growth, and suggest that it can be used practically as a superior natural agent for hair growth promotion.

• Proceedings of the Korea Contents Association Conference
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• 2011.05a
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• pp.201-202
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• 2011

본 연구에는 7.0T 동물용 자기공명영상장치를 이용하여 인간의 췌장암 세포인 CFPAC-1를 이종 이식한 쥐에서 자기공명영상을 획득하여 최적화된 검사 Protocol을 정립하며, 동물 실험에서 밝혀진 종양특성과 확산강조영상과의 비교 분석을 해보고 현성확산계수 영상이 췌장암 이종이식 모형의 종양 세포 내부 구조에 관하여 어떠한 정보를 제공 할 수 있는지 알아보고자 한다. 13마리의 쥐의 26개의 종양을 전형적으로 주입 후에 2~4주 뒤에 직경이 5~10mm가 되었을 때 imaged 하였으며, pathologic specimenm을 위해 sacrificed 하였다. isofluoran gas anesthesia를 이용하여 동물 마취 하였다. 사용된 장비로는 small-animal MR images (7.0-T)를 (Bruker BioSpin GmbH, Rheinstetten, Germany)이용하여 Fast T2-weighted 와 single-shot EPI DW image를 얻었다. 종양은 H&E 염색과 CD31와 VEGF에 대한 면역조직학 염색을 하여 종양의 cellularity와 microvessel density(MVD), 종양 내 괴사 정도를 평가하였다. CFPAC-1의 현성확산계수값은 $0.7327{\pm}0.1075{\pm}10^{-3}mm2/s$이였으며, 현성확산계수는 종양내 괴사 정도와 연관성을 보였다(R = 0.7417, p = 0.0001) 이처럼 현성확산계수는 종양 내 괴사 정도 등의 현미경적구조변화를 반영하는 대리인자로 사용될 수 있음을 확인하였다.

• BMB Reports
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• v.48 no.9
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• pp.525-530
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• 2015

Activation of the Wnt/β-catenin pathway plays a pathogenic role in age-related macular degeneration (AMD) and is thus a potential target for the development of therapeutics for this disease. Here, we demonstrated that Wnt5a antagonized β-catenin response transcription (CRT) induced with Wnt3a by promoting β-catenin phosphorylation at Ser33/Ser37/Thr41 and its subsequent degradation in human retinal pigment epithelial (RPE) cells. Wnt5a decreased the levels of vascular endothelial growth factor (VEGF), tumor necrosis factor-α(TNF-α), and nuclear factor-κB (NF-κB), which was up-regulated by Wnt3a. Furthermore, Wnt5a increased E-cadherin expression and decreased cell migration by down-regulating Snail expression, thereby abrogating the Wnt3a-induced epithelial-mesenchymal transition (EMT) in human RPE cells. Our findings suggest that Wnt5a suppresses the pathogenic effects of canonical Wnt signaling in human RPE cells by promoting β-catenin phosphorylation and degradation. Therefore, Wnt5a has significant therapeutic potential for the treatment of AMD. [BMB Reports 2015; 48(9): 525-530]

• The Korea Journal of Herbology
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• v.25 no.2
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• pp.71-79
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• 2010

Objectives : In this study, the neuroprotective effects of modified Boyanghwano-Tang (mBHT) and the major medicinal plants, Astragali Radix(AR) and Salviae Miltiorrhizae Radix(SMR) were investigated in transient middle cerebral artery occlusion (tMCAO)-induced ischemic stroke of rats. Methods : mBHT(400 mg/kg) and AR(154 mg/kg) or SMR(62 mg/kg) water extract orally injected in rats after 90 min occlusion of MCA and then allow reperfusion to 24 h. Brain infarction was measured by TTC staining and the expressions of NOS isoforms and apoptotic molecules were determined in ischemic brain by Western blot. Results : The results showed that mBHT has stronger neuropreotective property through inhibitions of the PARP cleaved and caspase-3 activation in ischemic rats, and could reduced infarction volumes comparison of those of AR or SMR, respectively. While, AR extract has an angiogenic property through increasing the expressions of eNOS and VEGF, and SMR extract has a strong anti-inflammatory effects through inhibition of iNOS expression in ischemic brains. Conclusions : These results suggest that mBHT has multifactorial therapeutic advantages through anti-apoptosis, anti-inflammation and angiogenesis for ischemic stroke based on a synergistic combination of ingradients rather than monotherapy.

• IMMUNE NETWORK
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• v.20 no.1
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• pp.11.1-11.14
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• 2020

Most patients with hepatocellular carcinoma (HCC) are diagnosed at an advanced stage of disease. Until recently, systemic treatment options that showed survival benefits in HCC have been limited to tyrosine kinase inhibitors, antibodies targeting oncogenic signaling pathways or VEGF receptors. The HCC tumor microenvironment is characterized by a dysfunction of the immune system through multiple mechanisms, including accumulation of various immunosuppressive factors, recruitment of regulatory T cells and myeloid-derived suppressor cells, and induction of T cell exhaustion accompanied with the interaction between immune checkpoint ligands and receptors. Immune checkpoint inhibitors (ICIs) have been interfered this interaction and have altered therapeutic landscape of multiple cancer types including HCC. In this review, we discuss the use of anti-PD-1, anti-PD-L1, and anti-CTLA-4 antibodies in the treatment of advanced HCC. However, ICIs as a single agent do not benefit a significant portion of patients. Therefore, various clinical trials are exploring possible synergistic effects of combinations of different ICIs (anti-PD-1/PD-L1 and anti-CTLA-4 antibodies) or ICIs and target agents. Combinations of ICIs with locoregional therapies may also improve therapeutic responses.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.31 no.5
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• pp.440-453
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• 2005

Objectives : To develop a bioactive membrane for guided bone regeneration (GBR), the biocompatibility and bone regenerating capacity of the cellulose membrane obtained from the Ascidians squirt skin were evaluated. Materials and methods : After processing the pure cellulose membrane from the squirt skin, the morphological study, amino acid analysis and the immunoreactivity of the cellulose membrane were tested. Total eighteen male Spraque-Dawley rats (12 weeks, weighing 250 to 300g) were divided into two control (n=8) and another two experimental groups (n=10). In the first experimental group (n=5), the cellulose membrane was applicated to the 8.0 mm sized calvarial bone defect and the same sized defect was left without cellulose membrane in the first control group (n=4). In the another experimental group (n=5), the cellulose membrane was applicated to the same sized calvarial bone defect after femoral bone graft and the same sized defect with bone graft was left without cellulose membrane in the another control group (n=4). Each group was sacrificed after 6 weeks, the histological study with H&E and Masson trichrome stain was done, and immunohistochemical stainings of angiogenin and VEGF were also carried out. Results : The squirt skin cellulose showed the bio-inductive effect on the bone and mesenchymal tissues in the periosteum of rat calvarial bone. This phenomenon was found only in the inner surface of the cellulose membrane after 6 weeks contrast to the outer surface. Bone defect covered with the bioactive cellulose membrane showed significantly greater bone formation compared with control groups. Mesenchymal cells beneath the inner surface of the bioactive cellulose membrane were positive to the angiogenin and VEGF antibodies. Conclusion : We suppose that there still remains extremely little amount of peptide fragment derived from the basement membrane matrix proteins of squirt skin, which is a kind of anchoring protein composed of glycocalyx. This composition could prevent the adverse immunological hypersensitivity and also induce bioactive properties of cellulose membrane. These properties induced the effective angiogenesis with rapid osteogenesis beneath the inner surface of cellulose membrane, and so the possibilities of clinical application in dental field as a GBR material will be able to be suggested.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.539-544
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• 2005

Purpose : The aim of this study was to investigate the pathophysiologic role of serum E-selectin, vascular endothelial growth factor(VEGF)-induced cell adhesion mollecule in Kawasaki disease(KD) and to look for the evidence of direct relationship between the plasma levels of soluble E-selectin and the incidence of coronary artery lesion(CAL). Methods : Changes in plasma levels of sE-selectin(n=98) over time were measured by enzyme-linked immunosorbent assay(ELISA) in 23 patients with acute KD and 25 age-matched febrile children. Results : Compared with control values, the peak levels of plasma sE-selectin were significantly elevated($mean{\pm}S.E$. : $22.89{\pm}12.53ng/mL$ vs $10.65{\pm}3.42ng/mL$, P=0.01) in KD. 5 patients with CAL, plasma sE-selectin levels before treatment were higher than in 18 patients without CAL($mean{\pm}S.E$. : $39.43{\pm}15.08ng/mL$ and $19.00{\pm}8.32ng/mL$, respectively; P=0.01). Plasma sE-selectin declined rapidly in the majority of KD patients regardless of the presence of CAL. Plasma sE-selectin levels after treatment and convalesent period were similar in KD patients with and without CAL. The plasma levels sE-selectin were correlated with those of white blood cell count(r=0.299, P<0.05), CRP(r=0.430, P<0.05), serum albumin(r=-0.483, P<0.05), serum protein(r=-0.502, P<0.05) and hemoglobin(r=-0.372, P<0.05) not with those of ESR, platelet, or duration of fever. There were significant differences in the initial level of serum sE-selectin between KD with and without CAL($mean{\pm}S.E$. : $39.44{\pm}15.08ng/mL$ vs. $19.00{\pm}17.18ng/mL$) in multivariated linear tests. Conclusion : Plasma sE-selectin levels were significantly higher in KD than in other febrile illness. Higher plamsa levels of sE-selectin may have potential as a predictor of CAL in patients with KD.

• Toxicological Research
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• v.29 no.3
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• pp.195-201
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• 2013

The anti-inflammatory effects of glycosaminoglycan (GAG) derived from Isaria sinclairii (IS) and of IS extracts were investigated in a complete Freund's adjuvant (CFA)-treated chronic arthritis rat model. Groups of rats were treated orally with 30 mg/kg one of the following: [1] saline control, extracts of [2] water-IS, [3] methanol-IS, [4] butanol-IS, [5] ethyl acetate-IS, or [6] Indomethacin(R) as the positive control for a period of two weeks. The anti-paw edema effects of the individual extracts were in the following order: water-IS ex. > methanol ex. > butanol ex. > ethyl acetate ex. The water/methanol extract from I. sinclairii remarkably inhibited UV-mediated upregulation of NF-${\kappa}B$ activity in transfected HaCaT cells. GAG as a water-soluble alcohol precipitated fraction also produced a noticeable anti-edema effect. This GAG also inhibited the pro-inflammatory cytokine levels of prostaglandin $E_2$-stimulated lipopolysaccharide in LAW 264.7 cells, cytokine TNF-${\alpha}$ production in splenocytes, and atherogenesis cytokine levels of vascular endothelial growth factor (VEGF) production in HUVEC cells in a dose-dependent manner. In the histological analysis, the LV dorsal root ganglion, including the articular cartilage, and linked to the paw-treated IS GAG, was repaired against CFA-induced cartilage destruction. Combined treatment with Indomethacin(R) (5 mg/kg) and IS GAG (10 mg/kg) also more effectively inhibited CFA-induced paw edema at 3 hr, 24 hr, and 48 hr to levels comparable to the anti-inflammatory drug, indomethacin. Thus, the IS GAG described here holds great promise as an anti-inflammatory drug in the future.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.8
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• pp.3977-3982
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• 2012

Inhibitors of histone deacetylase activity are emerging as a potentially important new class of anticancer agents. In this study, we assessed the anticancer effects of valproic acid (VPA) on ovarian cancer in vitro and in vivo. Cultured SKOV3 cells were treated by VPA with different concentrations and time, then the effects on cell growth, cell cycle, apoptosis, and related events were investigated. A human ovarian cancer model transplanted subcutaneously in nude mice was established, and the efficacy of VPA used alone and in combination with diammine dichloroplatinum (DDP) to inhibit the growth of tumors was also assessed. Proliferation of SKOV3 cells was inhibited by VPA in a dose and time dependent fashion. The cell cycle distribution changed one treatment with VPA, with decrease in the number of S-phase cells and increase in G1-phase. VPA could significantly inhibit the growth of the epithelial ovarian cancer SKOV3 cells in vivo without toxic side effects. Treatment with VPA combined with DDP demonstrated enhanced anticancer effects. The result of flow cytometry (FCM) indicated that after VPA in vitro and in vivo, the expression of E-cadherin was increased whereas vascular endothelial growth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) were decreased. This study suggests that VPA could be a novel attractive agent for treatment of ovarian cancer.

• The Journal of Pediatrics of Korean Medicine
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• v.28 no.2
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• pp.72-87
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• 2014

Objectives This study was carried out to investigate the effect of Ganoderma lucidum extract (GLE) and microneedle therapy system (MTS) on hair growth in an alopecia model of C57BL/6N mice. Methods Five-week old mice were depilated and separated in 4 groups ; CON (50% EtOH), MXD (5% Minoxidil), MTS and GLE + MTS. The treatments were applied twice a week for 3 weeks. The hair growth was determined photographically, the hair density, thickness and length were identified by Folliscope and the weights of body and organs were measured. In dorsal skin tissue, the expression of hair growth-related gene and protein was analyzed by RT - PCR or Western blot. In addition, the hair follicles in the dermis were observed by H&E staining. Results The promotion of hair growth was observed in GLE + MTS and MTS compared to CON. The hair density, thickness and length were also improved in GLE + MTS and MTS compared to CON. The mRNA expression of TGF-${\alpha}$, TGF-${\beta}1$, IGF-1, PRL and PL and the protein expression of VEGF and IGF-1 were increased in GLE + MTS and MTS compared to CON. The hair follicles and hair root growth were improved in GLE + MTS and MTS compared to CON. In the above results, GLE + MTS were more effective than MTS. Conclusions These results suggest that GLE and MTS has a hair growth activity and can be useful for the treatment of alopecia.