• BMB Reports
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• v.56 no.9
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• pp.482-487
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• 2023

Hematopoiesis is regulated by crosstalk between long-term repopulating hematopoietic stem cells (LT-HSCs) and supporting niche cells in the bone marrow (BM). Here, we describe the role of KAI1, which is mainly expressed on LT-HSCs and rarely on other hematopoietic stem-progenitor cells (HSPCs), in niche-mediated LT-HSC maintenance. KAI1 activates TGF-β1/Smad3 signal in LT-HSCs, leading to the induction of CDK inhibitors and inhibition of the cell cycle. The KAI1-binding partner DARC is expressed on macrophages and stabilizes KAI1 on LT-HSCs, promoting their quiescence. Conversely, when DARC+ BM macrophages were absent, the level of surface KAI1 on LT-HSCs decreases, leading to cell-cycle entry, proliferation, and differentiation. Thus, KAI1 acts as a functional surface marker of LT-HSCs that regulates dormancy through interaction with DARC-expressing macrophages in the BM stem cell niche. Recently, we showed very special and rare macrophages expressing α-SMA+ COX2+ & DARC+ induce not only dormancy of LT-HSC through interaction of KAI1-DARC but also protect HSCs by down-regulating ROS through COX2 signaling. In the near future, the strategy to combine KAI1-positive LT-HSCs and α-SMA/Cox2/DARC triple-positive macrophages will improve the efficacy of stem cell transplantation after the ablative chemo-therapy for hematological disorders including leukemia.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.185.2-185.2
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• 2003

The typical approach of virtual screening is to prepare a 3D database and dock each member to the receptor, and carry out a post-analysis to make a final selection of compounds to be tested. The biological test of these compounds leads to 'hit'. The size of the 3D database is rate-determining factor because the docking process is still time-consuming method. The number of compounds for biological testing is cost-determining factor because the materials used in the test are cost-consuming. The use of the representative subsets derived from the entire database help reduce runtime of docking procedure. (omitted)

• Korean Journal of Plant Resources
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• v.30 no.2
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• pp.144-151
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• 2017

This study examined the anti-inflammatory and whitening effects of Amaranth (Amaranthus spp L.) seed extract. Amaranthus spp L. seeds were extracted using 70% ethanol and then fractionated sequentially with n-hexane, dichloromethan, ethyl acetate and butanol. For the study of anti-inflammatory activity in RAW 264.7 cells, EtOAc fraction of Amaranthus spp L. seeds significantly inhibited nitrogen oxide production as well as the protein level of iNOS. Furthermore, EtOAc fraction of Amaranthus spp L. seeds inhibited expression of $TNF-{\alpha}$, PGE2 and the protein level of COX-2 in a dose-dependent manner. Inaddition, the tyrosinase inhibitory activities of the Amaranthus spp L. seed 70% ethanol extract and subfractions were also measured to see if these extracts can be used as an ingredient for whitening cosmetics. Tyrosinase is an oxidase that is a rate-limiting enzyme for controlling the production of melanin. Therefore, tyrosinase inhibitors have become increasingly important in cosmetics and medical products with regards to hyperpigmentation. EtOAc fraction of Amaranthus spp L. seeds showed mushroom tyrosinase inhibitory activity in a dose-dependent manner. This activity was more potent than that of a positive control cynandione A. These results suggest that Amaranthus spp L. seeds may be a valuable natural ingredient for the food and cosmetics industries.

• Natural Product Sciences
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• v.18 no.3
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• pp.183-189
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• 2012

It is well known that inflammation is associated with neurodegenerative disorders, including Alzheimer' disease, Parkinson's disease and ischemia. Nitric oxide (NO), a pro-inflammatory mediator, is produced by inducible NO synthase (iNOS) in microglia as well as macrophages and appears to account for neurodegeneration. In this study, we aimed to isolate NO inhibitors from Pyrus pyrifolia by activity guided purification. As a result, we identified daucosterol and ${\beta}$-sitosterol, which have not been isolated from this plant before. This article also describes NO inhibitory activities of the methanol extract of Pyrus pyrifolia fruit and the isolated compounds from this, which are lupeol, betulin, betulinic acid, ${\beta}$-sitosterol and daucosterol, in LPS-activated RAW 264.7 and BV2 cell lines. Western blot analysis was performed to clarify the underlying mechanism of NO inhibition in the two cell lines.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.5
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• pp.401-408
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• 2009

$K^+$-$Cl^-$-cotransport (KCC) has been reported to have various cellular functions, including proliferation and apoptosis of human cancer cells. However, the signal transduction pathways that control the activity of KCC are currently not well understood. In this study we investigated the possible role of phospholipase $A_2$ ($PLA_2$)-arachidonic acid (AA) signal in the regulatory mechanism of KCC activity. Exogenous application of AA significantly induced $K^+$ efflux in a dose-dependent manner, which was completely blocked by R-(+)-[2-n-butyl-6,7 -dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1Hinden-5-yl]oxy]acetic acid (DIOA), a specific KCC inhibitor. N-Ethylmaleimide (NEM), a KCC activatorinduced $K^+$ efflux was significantly suppressed by bromoenol lactone (BEL), an inhibitor of the calciumindependent $PLA_2$ ($iPLA_2$), whereas it was not significantly altered by arachidonyl trifluoromethylketone ($AACOCF_3$) and p-bromophenacyl bromide (BPB), inhibitors of the calcium-dependent cytosolic $PLA_2$ ($cPLA_2$) and the secretory $PLA_2$ ($sPLA_2$), respectively. NEM increased AA liberation in a doseand time-dependent manner, which was markedly prevented only by BEL. In addition, the NEM-induced ROS generation was significantly reduced by DPI and BEL, whereas $AACOCF_3$ and BPB did not have an influence. The NEM-induced KCC activation and ROS production was not significantly affected by treatment with indomethacin (Indo) and nordihydroguaiaretic acid (NDGA), selective inhibitors of cyclooxygenase (COX) and lipoxygenase (LOX), respectively. Treatment with 5,8,11,14-eicosatetraynoic acid (ETYA), a non-metabolizable analogue of AA, markedly produced ROS and activated the KCC. Collectively, these results suggest that $iPLA_2$-AA signal may be essentially involved in the mechanism of ROS-mediated KCC activation in HepG2 cells.

• Journal of Embryo Transfer
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• v.31 no.1
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• pp.53-59
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• 2016

This study was to investigate effect of progesterone ($P_4$) on prostaglandin (PG) synthases and plasminogen activators (PAs) system in bovine endometrium during estrous cycle. Endometrium tissues were collected from bovine uterus on follicular and luteal phase and were incubated with culture medium containing 0 (Control), 0.2, 2, 20 and 200 ng/ml $P_4$ for 24 h. The $PGF_{2{\alpha}}$ synthase (PGFS), $PGE_2$ synthase (PGES), cyclooxygenase-2 (COX-2), urokinase PA (uPA), and PA inhibitors 1 (PAI-1) mRNA in bovine endometrium were analyzed using reverse transcription PCR and PA activity was measured using spectrophotometry. In results, COX-2 was higher at 2 ng/ml $P_4$ group than control group in luteal phase (p<0.05), but, it did not change in follicular phase. Contrastively, PGES was significantly increased in 2 ng/ml $P_4$ group compared to control group in follicular phase, but there were no significant differ among the treatments in luteal phase. uPA was no significant difference between $P_4$ treatment groups and control group in both of different phase. PAI-1 was decreased in 20 ng/ml $P_4$ group compared to control group in follicular phase (p<0.05). PA activity was decreased in 2 ng/ml $P_4$ group compared to other groups in follicular and luteal phase (p<0.05). In conclusion, we suggest that $P_4$ may influence to translation and post-translation process of PG production and PA activation in bovine endometrium.

• The Academic Congress of Korean Shoulder and Elbow Society
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• 2005.03a
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• pp.42-44
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• 2005

• Proceedings of the PSK Conference
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• 2005.04a
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• pp.67-68
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• 2005

• Journal of Dental Anesthesia and Pain Medicine
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• v.22 no.4
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• pp.277-287
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• 2022

Background: Inflammatory dental diseases that occur during pregnancy can cause preterm labor and/or intrauterine growth restriction. Therefore, proactive treatment of dental diseases is necessary during pregnancy. Dexmedetomidine (DEX) is a widely used sedative in the dental field, but research on the effect of DEX on pregnancy is currently insufficient. In this study, we investigated the effects of co-treatment with DEX and lipopolysaccharide (LPS) on inflammatory responses in human amnion-derived WISH cells. Methods: Human amnion-derived WISH cells were treated with 0.001, 0.01, 0.1, and 1 ㎍/mL DEX with 1 ㎍/mL LPS for 24 h. Cytotoxicity of WISH cells was evaluated by 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide (MTT) assay. The protein expression of cyclooxygenase-2 (COX-2), prostaglandin E₂ (PGE₂), p38, and nuclear factor kappa B (NF-𝜅B) was examined by western blot analysis. The mRNA expression of pro-inflammatory cytokines such as interleukin (IL)-1𝛽 and tumor necrosis factor (TNF)-𝛼 was analyzed by real-time quantitative polymerase chain reaction. Results: Co-treatment with DEX and LPS showed no cytotoxicity in the WISH cells. The mRNA expression of IL-1𝛽 and TNF-𝛼 decreased after co-treatment with DEX and LPS. DEX and LPS co-treatment decreased the protein expression of COX-2, PGE₂, phospho-p38, and phospho-NF-𝛋B in WISH cells. Conclusion: Co-treatment with DEX and LPS suppressed the expression of COX-2 and PGE₂, as well as pro-inflammatory cytokines such as IL-1𝛽 and TNF-𝛼 in WISH cells. In addition, the anti-inflammatory effect of DEX and LPS co-treatment was mediated by the inhibition of p38/NF-𝜅B activation.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2003.11a
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• pp.102-102
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• 2003

The inhibitors of prostaglandin biosynthesis and nitric oxide production by corresponding inducible isozyme have been considered as potential anti-inflammatory and cancer chemopreventive agents. In our continuous search for cancer chemopreventive agents from natural products, we have evaluated the inhibitory potential of PGE$_2$and NO production in lipopolysaccharide (LPS)-induced mouse macrophage RAW264.7 cells. As a result, pinosylvin (3,5-dihydroxy-trans-stilbene), a stilbenoid, mainly found from the heartwood and leaves of the Pinus sylvestris, showed potential inhibitory activity of LPS-induced PGE$_2$and NO production in a dose-dependent manner. Pinosylvin also suppressed the LPS-induced iNOS protein expression. Further study revealed that pinosylvin exhibited antioxidant activity by the DPPH free radical scavenging potential and inhibitory effect of xanthine oxidase activity. In addition, pinosylvin inhibited COX -2 overexpressed human colon cancer cell (HT-29) growth in a time- and dose-dependent manner. These findings suggest that pinosylvin might be a promising candidate for developing cancer chemopreventive agent.