• Molecules and Cells
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• v.38 no.11
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• pp.966-974
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• 2015

Despite the presence of toll like receptor (TLR) expression in conventional $TCR{\alpha}{\beta}$ T cells, the direct role of TLR signaling via myeloid differentiation factor 88 (MyD88) within T lymphocytes on graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect after allogeneic stem cell transplantation (allo-SCT) remains unknown. In the allo-SCT model of C57BL/6 ($H-2^b$) ${\rightarrow}$ B6D2F1 ($H-2^{b/d}$), recipients received transplants of wild type (WT) T-cell-depleted (TCD) bone marrow (BM) and splenic T cells from either WT or MyD88 deficient (MyD88KO) donors. Host-type ($H-2^d$) P815 mastocytoma or L1210 leukemia cells were injected either subcutaneously or intravenously to generate a GVHD/GVL model. Allogeneic recipients of MyD88KO T cells demonstrated a greater tumor growth without attenuation of GVHD severity. Moreover, GVHD-induced GVL effect, caused by increasing the conditioning intensity was also not observed in the recipients of MyD88KO T cells. In vitro, the absence of MyD88 in T cells resulted in defective cytolytic activity to tumor targets with reduced ability to produce IFN-${\gamma}$ or granzyme B, which are known to critical for the GVL effect. However, donor T cell expansion with effector and memory T-cell differentiation were more enhanced in GVHD hosts of MyD88KO T cells. Recipients of MyD88KO T cells experienced greater expansion of Foxp3- and IL4-expressing T cells with reduced INF-${\gamma}$ producing T cells in the spleen and tumor-draining lymph nodes early after transplantation. Taken together, these results highlight a differential role for MyD88 deficiency on donor T-cells, with decreased GVL effect without attenuation of the GVHD severity after experimental allo-SCT.

• Journal of Life Science
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• v.24 no.2
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• pp.167-172
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• 2014

Optimal conditions for extraction of bakkenolide B from Petasites japonicus leaves were determined by using response surface methodology. A second-order Box-Behnken design representing three extraction temperatures (80, 100, $120^{\circ}C$), three extraction times (30, 45, 60 min), and three solvent pH's (5, 7, 9) was executed. The efficiency of the extraction conditions was defined using the ${\beta}$-hexosamidase assay by comparing both the bakkenolide B content and its anti-allergic activity expressed as extract inhibition on degranulation. The response surface plot described for the bakkenolide B content showed that the maximum content was predicted as 121.6 ${\mu}g/g$ with extraction conditions of $127.1^{\circ}C$, 46.6 min, and pH 7.7. Extraction temperature and time were important factors in determining bakkenolide B content. Using regression analysis, correlation between the inhibition effect of mast cell degranulation and bakkenolide B content was found to be low.

• Microbiology and Biotechnology Letters
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• v.45 no.2
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• pp.110-117
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• 2017

The anti-inflammatory effect of Sargassum patens C. Agardh ethanol extract (SPEE) was examined based on the lipopolysaccharide (LPS)-induced inflammatory response in this study. SPEE treatment was not cytotoxic to macrophages compared to the control. The production of NO was suppressed by SPEE by approximately 28% at $100{\mu}g/ml$, and levels of interleukin-6, tumor necrosis $factor-{\alpha}$, and $interleukin-1{\beta}$ decreased in a dose-dependent manner. In addition, the expression of inducible nitric oxide synthase, cyclooxygenase-2, and nuclear $factor-{\kappa}B$ was suppressed by SPEE treatment. In vivo, croton oil-induced mouse ear edema was attenuated by SPEE and the infiltration of mast cells into the tissue decreased. Based on these results, SPEE inhibits the release of LPS-induced pro-inflammatory cytokines and mediators, suggesting that SPEE is a potential agent for anti-inflammatory therapies.

• Proceedings of the KWS Conference
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• 2010.05a
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• pp.79-79
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• 2010

저온용 무연 솔더의 대표 조성으로 고려되고 있는 Sn-58Bi(융점: $138^{\circ}C$) 공정(eutectic) 조성은 우수한 강도에도 불구하고 연성(ductility) 측면에서의 문제점이 지속적으로 보고되고 있다. 따라서 이 합금계의 연성을 최대로 개선시킬 수 있으면서도 실제 상용화가 가능한 합금 조성의 개발 연구가 요청된다. 본 연구에서는 Sn-Bi 2원계 조성에서 최대의 연성을 나타내는 것으로 보고된 Sn-40Bi 조성에 미량의 합금원소를 첨가함으로써 최대의 연성을 확보하는 한편, 그 연성 특성이 변형속도에 어느 정도 민감한지를 인장 실험을 통해 결정하고자 하였다. 합금원소로는 0.1~0.5 wt%의 Ag, Mn, In, Cu를 선택하였으며, 인장 시편을 제조하여 $10^{-2}$, $10^{-3}$, $10^{-4}\;s^{-1}$의 3종류로 변형속도를 변형시켜가며 응력-변형 곡선(stress-strain curve)을 측정하였고, 조성별, 변형속도별로 최대인장강도(ultimate tensile stress, UTS) 및 연신율 결과들을 정리하였다. 합금원소를 첨가한 조성의 경우는 모든 시험 조건에서 Sn-40Bi보다 우수한 연신률을 나타내는 것으로 측정되었으나, $10^{-2}\;s^{-1}$의 빠른 변형속도에서는 그 향상 정도가 상대적으로 감소하는 경향이 관찰되었다. 특히 Sn-40Bi-0.5Ag 조성의 경우 느린 변형속도에서 특히 눈에 띄는 연신률 값을 나타내며, 모든 변형속도 조건에서 가장 우수한 연성을 나타내었다. 한편 Sn-40Bi-0.1Cu 조성의 경우 변형속도에 따른 연신률의 변화 정도, 즉, 변형속도에 따른 연신률의 민감도가 매우 커 $10^{-4}\;s^{-1}$ 속도에서는 Sn-40Bi-0.5Ag에 버금가는 연신률 값이 측정되었으나, $10^{-2}\;s^{-1}$ 속도에서는 가장 나쁜 연신률 특성을 보여주었다. Sn-40Bi-0.2Mn 조성은 최고의 연신률 향상 특성을 나타내지는 않았으나, In을 첨가한 경우보다는 대체적으로 우수한 연성을 나타내었다. 이상의 각 합금별 연성 특성은 인장시험 전의 미세조직 관찰 결과와 인장시험 후 파면부의 조직변화 관찰 결과로부터 해석되었다. 그 결과 석출상의 형성 여부, 인장 시험 중 재결정 조직의 형성 여부, 라멜라(lamellar) 조직의 분율과 라멜라 간격(lamellar spacing)의 정도 또는 $\beta$-Sn과 라멜라 조직 사이의 결정립계와 라멜라 조직 내 결정립계에서의 슬라이딩 모드(sliding mode) 변형 정도, 석출상의 크기와 분포 정도 등이 연신률 및 변형속도 민감도와 같은 연성 특성에 가장 큰 영향을 미치는 인자인 것으로 분석되었다.

• Archives of Pharmacal Research
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• v.27 no.6
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• pp.676-681
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• 2004

Acetyl-L-camitine (ALC), a naturally occurring endogenous compound, has been shown to improve the cognitive performance of patients with senile dementia Alzheimer＇s type, and to be involved in cholinergic neurotransmission. Because ALC is an endogenous compound, valida-tion of the analytical methods of ALC in the biological fluids is very important and difficult. This study was presented validation and correction for plasma ALC concentrations and pharmacok-inetics after oral administration of ALC to human volunteers. ALC concentrations in human plasma were corrected by subtracting the concentration of blank plasma from each sample. Precision and accuracy (bias %) for uncorrected ALC concentrations were below 2.6 and 6.5% for intra-days, and 4.0 and 9.4% for inter-days, respectively. Precision and accuracy (bias %)for corrected ALC concentrations were below 10.9 and 6.0% for intra-days, and 10.5 and 16.9% for inter-days, respectively. Quantitation limit was $0.1{\;}\mu\textrm{g}／mL$. After oral administration of a 500 mg ALC tablet to 8 healthy volunteers, the principle pharmacokinetic parameters were 4.2 h of the half-life$ (t_{1/2},{\beta})$, the area under the curve $(AUC_{0{\rightarrow}8){\;}of{\;}9.88{\;}\mu\textrm{g}{\cdot}h/mL$, and 3.1 h of the time ($T_{max}$) to reach $C_{max}$. This study first describes the pharmacokinetic study after oral admin-istration of a single dose of ALC in human volunteers.

• Mass Spectrometry Letters
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• v.9 no.1
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• pp.24-29
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• 2018

DC23, a triazolothione resorcinol analogue, is known to inhibit heat shock protein 90 and pyruvate dehydrogenase kinase which are up-regulated in cancer and diabetes, respectively. This study was performed to elucidate the metabolism of DC23 in human liver microsomes (HLMs). HLMs incubated with DC23 in the presence of uridine 5'-diphosphoglucuronic acid (UDPGA) and/or ${\beta}$-nicotinamide adenine dinucleotide phosphate (NADPH) resulted in the formation of four metabolites, M1-M4. M1 was identified as DC23-N-Oxide, on the basis of LC-MS/MS analysis. DC23 was further metabolized to its glucuronide conjugates (M2, M3, and M4). In vitro metabolic stability studies conducted with DC23 in HLMs revealed significant glucuronide conjugation with a $t_{1/2}$ value of 1.3 min. The inhibitory potency of DC23 on five human cytochrome P450s was also investigated in HLMs. In these experiments, DC23 inhibited CYP2C9-mediated tolbutamide hydroxylase activity with an $IC_{50}$ value of $8.7{\mu}M$, which could have implications for drug interactions.

• Tissue Engineering and Regenerative Medicine
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• v.15 no.6
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• pp.781-791
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• 2018

BACKGROUND: Glucosamine hydrochloride (GlcN HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. METHOD: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) $TGF-{\beta}$ ($5ng\;mL^{-1}$) and IGF-I ($10ng\;mL^{-1}$), GlcN HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. RESULTS: The two glucosamines showed opposite effects in monolayer culture: GlcN HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. CONCLUSION: GlcN HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.

• Journal of Microbiology and Biotechnology
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• v.31 no.1
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• pp.115-122
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• 2021

Phenol-soluble modulins (PSMs) are responsible for regulating biofilm formation, persister cell formation, pmtR expression, host cell lysis, and anti-bacterial effects. To determine the effect of psm deletion on methicillin-resistant Staphylococcus aureus, we investigated psm deletion mutants including Δpsmα, Δpsmβ, and Δpsmαβ. These mutants exhibited increased β-lactam antibiotic resistance to ampicillin and oxacillin that was shown to be caused by increased N-acetylmannosamine kinase (nanK) mRNA expression, which regulates persister cell formation, leading to changes in the pattern of phospholipid fatty acids resulting in increased anteiso-C15:0, and increased membrane hydrophobicity with the deletion of PSMs. When synthetic PSMs were applied to Δpsmα and Δpsmβ mutants, treatment of Δpsmα with PSMα1-4 and Δpsmβ with PSMβ1-2 restored the sensitivity to oxacillin and slightly reduced the biofilm formation. Addition of a single fragment showed that α1, α2, α3, and β2 had an inhibiting effect on biofilms in Δpsmα; however, β1 showed an enhancing effect on biofilms in Δpsmβ. This study demonstrates a possible reason for the increased antibiotic resistance in psm mutants and the effect of PSMs on biofilm formation.

• Biomolecules & Therapeutics
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• v.31 no.3
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• pp.285-297
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• 2023

Alzheimer's disease (AD) is a neurodegenerative disease with progressive memory loss and the cognitive decline. AD is mainly caused by abnormal accumulation of misfolded amyloid β (Aβ), which leads to neurodegeneration via a number of possible mechanisms such as down-regulation of brain-derived neurotrophic factor-tropomyosin-related kinase B (BDNF-TRKB) signaling pathway. 7,8-Dihydroxyflavone (7,8-DHF), a TRKB agonist, has demonstrated potential to enhance BDNF-TRKB pathway in various neurodegenerative diseases. To expand the capacity of flavones as TRKB agonists, two natural flavones quercetin and apigenin, were evaluated. With tryptophan fluorescence quenching assay, we illustrated the direct interaction between quercetin/apigenin and TRKB extracellular domain. Employing Aβ folding reporter SH-SY5Y cells, we showed that quercetin and apigenin reduced Aβ-aggregation, oxidative stress, caspase-1 and acetylcholinesterase activities, as well as improved the neurite outgrowth. Treatments with quercetin and apigenin increased TRKB Tyr516 and Tyr817 and downstream cAMP-response-element binding protein (CREB) Ser133 to activate transcription of BDNF and BCL2 apoptosis regulator (BCL2), as well as reduced the expression of pro-apoptotic BCL2 associated X protein (BAX). Knockdown of TRKB counteracted the improvement of neurite outgrowth by quercetin and apigenin. Our results demonstrate that quercetin and apigenin are to work likely as a direct agonist on TRKB for their neuroprotective action, strengthening the therapeutic potential of quercetin and apigenin in treating AD.

• Journal of Life Science
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• v.29 no.12
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• pp.1371-1377
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• 2019

Oxidative stress induced by the over-production of reactive oxygen species (ROS) in the brain is the most common cause of neurodegenerative diseases such as Alzheimer's. In the present study, we investigated the protective effects of flavonoids and their glycosides, namely kaempferol, kaempferol-3-O-glucoside, quercetin, and quercetin-3-β-D-glucoside, against H₂O₂-induced oxidative stress in the C6 glial cells. The H₂O₂-treated glial cells exhibited decreased cell viability and increased ROS production when compared with normal cells. However, cells treated with each of the four flavonoids/glycosides demonstrated significantly increased viability and suppressed ROS production when compared with the H₂O₂-treated control group. These results indicate that flavonoids/glycosides attenuate oxidative stress induced by H₂O₂ in C6 glial cells. To confirm the protective molecular mechanisms, we measured pro-inflammatory factors such as inducible nitric oxide synthase, cyclooxygenase-2, and interleukin-1β. H₂O₂ treatment was seen to elevate these factors and decrease IκB-α in the C6 glial cells, while the flavonoids/glycosides induced a down-regulation of the pro-inflammatory factors and increased IκB-α, indicating a neuroprotective effects through attenuation of the inflammation. In particular, quercetin and its glycoside showed a higher neuroprotective effect than the kaempferol treatments. These results suggest that these flavonoids and their glycosides could be promising therapeutic agents for neurodegenerative diseases via the attenuation of oxidative stress.