• The Journal of Pediatrics of Korean Medicine
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• v.34 no.3
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• pp.67-75
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• 2020

Objectives This study is conducted to evaluate Th2 skewed condition control through skin fat barrier formation from the treatment using Coptidis Rhizoma and Glycyrrhiza uralensis extract. Methods The 6-week-old NC/Nga mice were divided into 4 groups: Control group (Ctrl), lipid barrier eliminate treatment group (LBET), Coptidis Rhizoma and Glycyrrhiza uralensis feeding treatment after lipid barrier elimination group (CGFT), dexamethasone feeding treatment after lipid barrier elimination group (DxFT). After 3 days, differences in skin condition, improvement of skin fat barrier, and control of Th2 skewed condition of each group were observed. Results Pathologic skin damage and tissue changes were less in the CGFT group than in the LBET and DxFT groups, and Transepidermal water loss (TEWL) and pH were also significantly decreased (p < 0.05). The filaggrin intensity and positive response also increased significantly in the CGFT group (p < 0.05). Kallikrein-related peptidase (KLK) 7, Protease activated receptor (PAR)-2, Thymic stromal lymphopoietin (TSLP), Interleukin (IL)-4, and the products of the Th2 differentiation process also showed a significant decrease compared to the LBET and DxFT groups (all p < 0.05). Conclusions The Coptidis Rhizoma and Glycyrrhiza uralensis extract causes skin barrier recovery and function recovery through the formation of skin fat barrier. This leads to the conclusion that Coptidis Rhizoma and Glycyrrhiza uralensis extract can control Th2 differentiation through the formation of skin fat barrier.

• The Journal of Pediatrics of Korean Medicine
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• v.34 no.4
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• pp.22-30
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• 2020

Objectives This study was conducted to confirm the inhibitory effect of β-glucan on epithelial inflammation induced by atopic dermatitis through Endocannabinoid system (ECS) activity. Methods Six-week-old NC/Nga mice were divided into a control group (Ctrl), atopic dermatitis elicitation group (ADE), and a β-glucan-treated group (β-glucan treatment after atopy dermatitis elicitation, β-GT). After 3 weeks, CB1, CB2, and GPR55 were observed to confirm the regulation of ECS activity, and filaggrin in the stratum corneum and Kallikrein-related peptidase (KLK) 7 in the stratum corneum and protease activated receptor (PAR)-2 were observed to confirm the inhibition of the inflammation, Phosphorylated extracellular signal-related kinase (p-ERK), Phosphorylated mammalian target of rapamycin (p-mTOR), and E-Cadherin were observed to confirm microenvironmental regulation. Results β-GT was significantly increased in CB1, CB2, and GPR55 positive reactions compared to that of the ADE. In positive reaction of the filaggrin in the stratum corneum, β-GT was significantly increased than that of the ADE. For KLK7 positive and PAR2 positive, β-GT was significantly reduced compared to the ADE. The p-ERK-positive and p-mTOR-positive reactions were significantly reduced in β-GT than in ADE. E-cadherin positive reaction was significantly increased in β-GT than in ADE (All p < 0.01). Conclusions It was confirmed that β-glucan has the effect of inhibiting the epithelium induced by atopic dermatitis through the ECS activity.

• The Korean Journal of Physiology and Pharmacology
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• v.19 no.6
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• pp.549-555
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• 2015

We attempted to investigate molecular mechanisms underlying phenotypic change of vascular smooth muscle cells (VSMCs) by determining signaling molecules involved in chemokine production. Treatment of human aortic smooth muscle cells (HAoSMCs) with thrombin resulted not only in elevated transcription of the (C-C motif) ligand 11 (CCL11) gene but also in enhanced secretion of CCL11 protein. Co-treatment of HAoSMCs with GF109230X, an inhibitor of protein kinase C, or GW5074, an inhibitor of Raf-1 kinase, caused inhibition of ERK1/2 phosphorylation and significantly attenuated expression of CCL11 at transcriptional and protein levels induced by thrombin. Both Akt phosphorylation and CCL11 expression induced by thrombin were attenuated in the presence of pertussis toxin (PTX), an inhibitor of Gi protein-coupled receptor, or LY294002, a PI3K inhibitor. In addition, thrombin-induced production of CCL11 was significantly attenuated by pharmacological inhibition of Akt or MEK which phosphorylates ERK1/2. These results indicate that thrombin is likely to promote expression of CCL11 via PKC/Raf-1/ERK1/2 and PTX-sensitive protease-activated receptors /PI3K/Akt pathways in HAoSMCs. We propose that multiple signaling pathways are involved in change of VSMCs to a secretory phenotype.

• Journal of Ginseng Research
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• v.32 no.2
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• pp.107-113
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• 2008

In this study, we have investigated the effect of panaxatriol (PT) on phosphoinositides (PIS) breakdown and $Ca^{2+}$-elevation in thrombin-induced platelet aggregation. Thrombin (5U/ml), a potent platelet agonist which activates phospholipase $C_{\beta}$ via protease activated receptor (PAR), hydrolyzed PIS in platelet membrane. The phosphatidylinositol 4, 5-bisphosphate $(PIP_2)$ was hydrolyzed after 10 sec of the thrombin-stimulation, and both the phosphatidylinositol 4-monophosphate (PIP) and phosphatidylinositol (PI) were brokendown after 30 sec of the thrombin-stimulation. However, PT inhibited the thrombin-stimulated hydrolysis of $PIP_2$, PIP, and PI. On the other hand, thrombin increased the level of phosphatidic acid (PA) which is phosphorylated from diacylglycerol (DG) generated by PIS-hydrolysis. However, Pr inhibited the thrombin-increased PA level non-significantly. Thrombin increased cytosolic free $Ca^{2+}([Ca^{2+}])_i$) up to 72% as compared with control $(30.8{\pm}0.9 nM)$ in intact platelet. However, PT (100 ${\mu}g/ml$) inhibited the thrombin-elevated $[Ca^{2+}]_i$ to 100%. These results suggest that PT may have a beneficial effect on platelet aggregation-mediated thrombotic disease by inhibiting thrombin-induced platelet aggregation via suppression of the $[Ca^{2+}]_i$ level and PIS breakdown.

• Journal of Life Science
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• v.20 no.9
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• pp.1324-1331
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• 2010

Mifepristone (MIF) and Tamoxifen (TAM) have been used in the treatment of prostate cancer and breast cancer for more than a decade. MIF can induce apoptosis in both AR-positive and negative prostate cancer cells. Because of its pleiotropic ligand-receptor properties, TAM exerts cytotoxic activity in estrogen (ER)-positive and various ER.negative cancer cells. However, the molecular mechanisms of these two substances are not yet clear. In the present work, we report that the cytotoxic effects of MIF and TAM are due to the modulation of intracellular $Ca^{2+}$ level in DU-145, androgen-insensitive cells. When the cells were treated with micromolar concentrations of either MIF or TAM, the growth and viability were significantly decreased in a dose- and time-dependent manner. The apoptosis induced by MIF or TAM was further proved and analyzed by confocal laser scanning microscopy (CLSM) and fluorescence-activated cell sorting (FACS). In the cells cultivated in a normal 1.5 mM $Ca^{2+}$ medium, both MIF and TAM also induced an increase of the intracellular $Ca^{2+}$ level in a dose-dependent fashion. Since a change in calcium level could not be found in cells of the $Ca^{2+}$-free medium, the increase of intracellular $Ca^{2+}$ level might be due to an increase in extracellular calcium uptake. Our results show that the apoptotic effect was more prominent in TAM treatment compared to MIF treatment in DU-145 cells. The above findings might be due to the difference in the uppermost pathways of apoptosis induced by either MIF or TAM. When we checked the level of procaspase-8 activation, TAM showed minor level of activation, as opposed to MIF, which exerted strong activation. In both treatments, the levels of anti-apoptotic protein Bcl-2 decreased, and pro-apoptotic protein Bax level increased more than 2-fold. The activation of caspase-3, a key protease enzyme in the downstream pathway of apoptosis, was much higher in the cells treated with TAM, compared to the MIF treatment. The overall apoptotic activity shown in the present work was closely related to intracellular $Ca^{2+}$ concentration levels. Therefore, the cytotoxic activity induced by MIF and TAM might have been due to intracellular calcium modulation.

• Journal of Life Science
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• v.25 no.1
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• pp.101-112
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• 2015

A type of cell junction that is formed between different parts within the same cell is called autotypic cell junction. Autotypic junction proteins form tight junctions found between membrane lamellae of a cell, especially in myelinating glial cells. Some of them have postsynaptic density-95/disks large/zonula occludens-1 (PDZ) domains, which interact with the carboxyl (C)-terminal PDZ-binding motif of other proteins. PDZ domains are protein-protein interaction modules that play a role in protein complex assembly. The PDZ domain, which is widespread in bacteria, plants, yeast, metazoans, and Drosophila, allows the assembly of large multi-protein complexes. The multi-protein complexes act in intracellular signal transduction, protein targeting, and membrane polarization. The identified PDZ domain-containing proteins located at autotypic junctions include zonula occludens-1 (ZO-1), ZO-2, pals-1-associated tight junction protein (PATJ), multi-PDZ domain proteins (MUPPs), membrane-associated guanylate kinase inverted 2 (MAGI2), and protease-activated receptor (PAR)-3. PAR-3 interacts with atypical protein kinase C and PAR-6, forming a ternary complex, which plays an important role in the regulation of cell polarity. MAGI2 interacts with ${\alpha}$-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptor at excitatory synapses. PATJ is detected in paranodal loops associated with claudin-1. On the other hand, MUPP1 is found in mesaxons and Schmidt-Lanterman incisures with claudin-5. ZO-1, ZO-2, and PAR-3 are found at all three sites. Different distributions of PDZ domain-containing proteins affect the development of autotypic junctions. In this review, we will describe PDZ domain-containing proteins at autotypic tight junctions in myelinating Schwann cells and their roles.

• Journal of Life Science
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• v.32 no.12
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• pp.979-988
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• 2022

Halophytes have been reported to possess a variety of physiological activities, such as anti-cancer, anti-oxidant, anti-diabetes, anti-inflammatory, and anti-obesity. Studies on the roots of the halophyte Rosa rugosa, in particular, have shown a variety of physiological activities and are known to be effective for nursing diabetic complications in traditional Korean medicine. In this study, the effect of R. rugosa on adipogenesis was investigated in 3T3-L1 pre-adipocytes treated with crude extract and solvent fractions (H₂O, n-BuOH, 85% aq. MeOH, and n-Hex) obtained from R. rugosa roots. Treatment with extract and the solvent fractions inhibited the formation of intracellular lipid droplets in differentiated 3T3-L1 adipocytes compared to the untreated group. In particular, n-BuOH and 85% aq. MeOH fractions effectively decreased the expression of adipogenic transcription factors: peroxisome proliferator activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1c (SREBP1c) in both mRNA and protein levels. In conclusion, these results suggest that R. rugosa contains anti-adipogenic molecules that can be utilized as a nutraceutical against obesity. Further refining of n-BuOH and 85% aq. MeOH fractions and analysis of their action mechanisms could yield potential therapeutic agents with anti-adipogenic effects.