• Biomolecules & Therapeutics
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• v.29 no.2
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• pp.211-219
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• 2021

Alopecia is a distressing condition caused by the dysregulation of anagen, catagen, and telogen in the hair cycle. Dermal papilla cells (DPCs) regulate the hair cycle and play important roles in hair growth and regeneration. Myristoleic acid (MA) increases Wnt reporter activity in DPCs. However, the action mechanisms of MA on the stimulation of anagen signaling in DPCs is not known. In this study, we evaluated the effects of MA on anagen-activating signaling pathways in DPCs. MA significantly increased DPC proliferation and stimulated the G2/M phase, accompanied by increasing cyclin A, Cdc2, and cyclin B1. To elucidate the mechanism by which MA promotes DPC proliferation, we evaluated the effect of MA on autophagy and intracellular pathways. MA induced autophagosome formation by decreasing the levels of the phospho-mammalian target of rapamycin (phospho-mTOR) and increasing autophagy-related 7 (Atg7) and microtubule-associated protein 1A/1B-light chain 3II (LC3II). MA also increased the phosphorylation levels of Wnt/β-catenin proteins, such as GSK3β (Ser9) and β-catenin (Ser552 and Ser675). Treatment with XAV939, an inhibitor of the Wnt/β-catenin pathway, attenuated the MA-induced increase in β-catenin nuclear translocation. Moreover, XAV939 reduced MA-induced effects on cell cycle progression, autophagy, and DPC proliferation. On the other hand, MA increased the levels of phospho (Thr202/Tyr204)-extracellular signal regulated kinases (ERK). MA-induced ERK phosphorylation led to changes in the expression levels of Cdc2, Atg7 and LC3II, as well as DPC proliferation. Our results suggest that MA promotes anagen signaling via autophagy and cell cycle progression by activating the Wnt/β-catenin and ERK pathways in DPCs.

• The Korea Journal of Herbology
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• v.33 no.1
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• pp.17-26
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• 2018

Objective : In this study, we investigated the effect of SAL5(mixing extracts of Schisandra chinensis Baillon, Artemisia capillaris Thunb., and Aloe vera Linne) on chronic ethanol-induced fatty liver model. Methods : Sprague-Dawley male rats were fed Liber-DeCarli (normal), ethanol liquid diet (control), SAL5 (200 mg/kg). We administrated the SAL5 on chronic ethanol-induced fatty liver model for 5 weeks. We measured alkaline phosphtase (ALP), alanine transminase (ALT), aspartate transminase (AST) and ${\gamma}-glutamyl$ transpeptase (${\gamma}-GTP$) in serum and triglyceride (TG), superoxide dismutase (SOD), catalase, glutathione (GSH) and malondialdehyde (MDA) level in liver. Liver histopathology was examined by Hematoxylin-eosin and Oil red O staining of the fixed liver tissues. Real-time PCR was performed to measure the mRNA expression of inflammatory cytokines and MMP-2, MMP-9. Results : SAL5 administration resulted in significantly decreased liver marker enzymes activities of alanine transminase (ALT), ${\gamma}-glutamyl$ transpeptase (${\gamma}-GTP$) in serum and triglyceride (TG) activities in liver. The control group decreased the activities of superoxide dismutase (SOD), catalase (CAT) with the reduced level of glutathione (GSH) in liver. On the other hand, SAL5 group increased the activities of SOD, CAT and the level of GSH. SAL5 delayed the development of an alcoholic fatty liver by reversing fat accumulation in the liver, as evidenced in histological observations. The gene expression of mRNA were significantly decreased at the $IL-1{\beta}$, $TNF-{\alpha}$, NOS-II and MMP-2 by SAL5. Conclusions : These results indicate that SAL5 might have protective effect chronic ethanol-induced fatty liver models.

• Journal of Periodontal and Implant Science
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• v.34 no.4
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• pp.781-790
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• 2004

골아세포의 생물학적 기능을 증진시키기 위해 키토산의 표면개질에 대하여 연구하였다. 생체적합성 천연고분자인 키토산은 1차 아미노기를 소유하고 있으므로 적정한 공유결합제를 사용하여 세포성장인자와 같은 생리활성을 지닌 단백질을 키토산의 표면에 고정시킬 수 있다. 본 연구에서는 키토산을 필름형태로 제조하여 세포성장인자 중 형질전환성장인자를 고정하고 골아세포의 부착, 성장 및 분화를 증가시키고자 하였다. 형태전환성장인자의 고정화 효율은 단순한 흡착방법에 비해 높았으며, 표면에 형성된 공유결합은 매우 안정하였다. 골아세포를 배양하여 초기세포부착능에 대한 영향을 연구한 결과, 배양 후 4시간, 1일째, 형질전환성장인자를 고정한 키토산 표면에서 고정하지 않은 키토산의 표면에 비해 더 많은 수의 골아세포가 부착되었고, 더 많이 신장된 부착형태를 보였다. 세포활성정도와 배양 후 4주일째의 칼슘축적량을 측정한 결과, 형질전환성장인자를 고정한 키토산 표면에서 고정하지 않은 키토산의 표면에 비해 더 높았다. 위의 결과는 키토산 표면에 형태전환성장인자의 고정이 성공적으로 이루어졌으며, 또한 실제로 활성이 있는 것이 증명되었다. 위의 연구 결과에서 형질전환성장인자로 고정된 키토산은 골아세포의 초기 부착 및 분화를 촉진시켰음을 알 수 있었던 바 성장인자의 표면고정은 임플란트 및 조직공학용 지지체에도 적용하여 생체적합성과 세포기능을 증진시키는데 이용할 수 있음을 알 수 있었다.

• The Korean Journal of Nuclear Medicine Technology
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• v.16 no.2
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• pp.149-155
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• 2012

Purpose : Serum insulin levels are useful indicator which of reflecting the function of insulin secretion in pancreatic ${\beta}$ cell and diagnosis of diabetes, differentiating the cause of impaired glucose tolerance. Insulin measurement kits have shown some differences in many ways such as test methods as well as quality control. The purpose of this study was to evaluate the diagnostic performance of seven manufacturing companies commercial kits. Materials and Methods : The values of insulin measured by three manufacturing companies (Biosource, Siemens, TFB) with 59 samples in August 2009 were compared with those measured by four manufacturing companies (Immunotech, Izotope, BNIBT, Cisbio) with 68 samples in December 2011. We evaluated precision, recovery rate, dilution test and correlation of serum insulin measurement using seven manufacturing company kits. Statistical program SPSS 12.0 was used for the verification of results. Results : The coefficients variation of the precision on all seven different kits were showed within 5.0%. Recovery rate of Biosource, Siemens, TFB kits on three different levels showed 94.2~103.7%, 99.0~104.6%, 99.7~107.6% respectively. Immunotech, Izotope, BNIBT, Cisbio were 93.5~99.1%, 91.4~99.1%, 99.2~131.0%, 84.8~102.3% respectively. There was strong correlation between the measurement of insulin by Biosource kit and that by two commercial kits, Siemens (R2=0.96), TFB (R2=0.99). There was good correlation between the measurement of insulin by TFB kit and that by three commercial kits, Immunotech (R2=0.97), Izotope (R2=0.96), Cisbio (R2=0.97). In the dilution test performed with more than 200 ${\mu}IU/ml$ high concentration samples, samples with diabetes correctly was measured in all seven manufacturing kits. However, as measured with insulinoma samples TFB, Siemens, Izotope, Cisbio kits were correctly measured, but Biosource and Immunotech kits were measured 47.4 ${\mu}IU/ml$, 72.3 ${\mu}IU/ml$, respectively. Conclusion : Serum Insulin radioimmunoassay kits were showed excellent precision, correlation and good recovery rate. However, some kits were not measured correctly in the high concentration insulin values. when selecting a kit should be considered many factors that cost effectiveness, compatible for automation equipment, high performance kit, the environment for each laboratory such as reaction time and reporting time.

• Proceedings of the Plant Resources Society of Korea Conference
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• 2018.04a
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• pp.13-13
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• 2018

The anti-inflammatory (INF) compounds (1-15) were isolated from Agrimonia pilosa Ledeb. (APL) by activity-guided isolation technique. The isolated compounds (1-15) were identified as quercetin-7-O-rhanmoside (1), apigenin-7-O-glycoside (2), kaempferol-7-O-glycoside (3), apigenin-7-O-[6"-(butyl)-glycoside] (4), querceitn (5), kaempferol (6), apigenin (7), apigenin-7-O-[6"-(pentyl)-glycoside] (8), agrimonolide (9), agrimonolide-6-O-glucoside (10), desmethylagrimonolide (11), desmethylagrimonolide-6-O-glucoside (12), luteolin (13), vitexin (14) and isovitexin (15). Flavonoids, compound 2, 3, 11, and 14-15 have been found in APL for the first time. Furthermore, two novel flavone derivatives, compound 4 and 8, have been isolated inceptively in plant. In the no cytotoxicity concentration ranges of $0-20{\mu}M$, nitric oxide (NO) production level of 1-15 was estimated in LPS-treated Raw 264.7 macrophage cells. The flavone aglycones, 7 (apigenin, $IC_{50}=3.69{\pm}0.34{\mu}M$), 13 (luteolin, $IC_{50}=4.62{\pm}0.43{\mu}M$), 6 (kaempferol, $IC_{50}=14.43{\pm}0.23{\mu}M$) and 5 (quercetin, $IC_{50}=19.50{\pm}1.71{\mu}M$), exhibited excellent NO inhibitory (NOI) activity in dose-dependent manner. In the structure activity relationship (SAR) study of apigenin-derivatives (APD), apigenin; Api, apigenin-7-O-glucoside; Api-G, apignenin-7-O-[6"-(butyl)-glycoside]; Api-BG and apignenin-7-O-[6"-(pentyl)-glycoside]; Api-P, from APL on INF activity was investigated. The INF mediators level such as NO, INF-cytokines, NF-KB proteins, iNOS and COX-2 were sharply increased in Raw 264.7 cells by LPS. When pretreatment with APD in INF induced macrophages, NOI activity of Api was most effective than other APD with $IC_{50}$ values of $3.69{\pm}0.77{\mu}M$. And the NOI activity was declined in the following order: Api-BG ($IC_{50}=8.91{\pm}1.18{\mu}M$), Api-PG ($IC_{50}=13.52{\pm}0.85{\mu}M$) and API-G ($IC_{50}=17.30{\pm}0.66{\mu}M$). The NOI activity of two novel compounds, Api-PG and Api-BG were lower than their aglycone; Api, but more effective than Api-G (NOI: Api-PG and Api-BG). And their suppression ability on INF cytokines such as $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA showed the similar tendency. Therefore, the anti-INF mechanism study of Api-PG and Api-BG on nuclear factor-kappa B ($NF-{\kappa}B$) pathway, representative INF mechanism, was investigated and Api was used as positive control. Api-BF was more effectively prevent the than phosphorylation of $pI{\kappa}B$ kinase (p-IKK) and p65 than Api-PG in Raw 264.7 cells. In contrast, Api-PG and Api-BG were not reduced the phosphorylation of inhibitor of kappa B alpha ($I{\kappa}B{\alpha}$). Moreover, pretreatment with Api-PG and Api-BG, dose-dependently inhibited LPS-induced expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) mRNAs and proteins in macrophage cells, and their expression were correlated with their NOI activity. Therefore, APL can be utilized to health promote agent associated with their AIN metabolites.

• Journal of Life Science
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• v.21 no.8
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• pp.1134-1141
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• 2011

Transmembrane protein 21 (TMP21) is a member of the p24 cargo protein family and has been shown to modulate ${\alpha}$-secretase-mediated A${\beta}$ production which was specifically observed in the brains of subjects with Alzheimer's disease (AD). In order to investigate whether TMP21 could affect nerve growth factor (NGF) receptor signaling pathway, the alteration of NGF receptors and their downstream proteins were detected in TMP21 over-expressed cells. CMV/hTMP21 vector used in this study was successfully expressed into TMP21 proteins in B35 cells after lipofectamin transfection. Expressed TMP21 proteins induced the down-regulation of ${\gamma}$-secretase complex components including Presenlin-1 (PS-1), PS-2, Nicastrin (NST), Pen-2 and APH-1. Also, the expression level of NGF receptor $p75^{NTR}$ and RhoA were significantly higher in CMV/hTMP21 transfectants than vehicle transfectants, while their levels returned to vehicle levels after NGF treatment. However, the phosphorylation of NGF receptor TrkA was dramtically decreased in NGF No-treated CMV/hTMP21 transfectants compared with vehicle transfectants, and increased in NGF treated CMV/hTMP21 transfectants. In TrkA downstream signaling pathway, the phosphorylation level of ERK was also decreased in CMV/hTMP21 transfectants, while the phosphorylation of Akt was increased in the same transfectants. Furthermore, NGF treatment induced the increase of phosphorylation level of Akt and ERK in CMV/hTMP21 transfectants. Therefore, these results suggested that over-expression of TMP21may simultaneously induce the up-regulation of $p75^{NTR}$/RhoA expression and the down-regulation of TrkA/ERK phosphorylation through the inhibition of ${\gamma}$-secretase activity.

• Journal of Life Science
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• v.29 no.5
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• pp.596-606
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• 2019

The study investigated the physiochemical properties and the antioxidant and anti-inflammatory activities of the sea tangle (Saccharina japonica) in a water extract before (STWE) and after (STFL) fermentation with Lactobacillus brevis. The pH values of STWE and STFL were 6.18 and 4.16, and the sugar contents were $8.50^{\circ}Brix$ and $7.40^{\circ}Brix$, respectively. The main free amino acids of STWE and STFL were glutamic acid, aspartic acid, and alanine, and the ${\gamma}$-amino butyric acid (GABA) content was increased by fermentation. The total polyphenol contents of STWE and STFL were 498.29 and 615.77 mg gallic acid equivalent (GAE)/ml, respectively. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activities of STWE and STFL were markedly increased in a dose-dependent manner, and revealed about 89.89% and 96.94% activities, respectively, at 10% concentration (p<0.05). The superoxide dismutase (SOD) activities of STWE and STFL were also markedly increased in a dose-dependent manner, and the activity of STFL was significantly increased when compared with STWE (p<0.05). The anti-inflammatory activity was examined in lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. STWE and STFL decreased the production of reactive oxygen species (ROS), which had levels of about 189.90% and 174.69% at 1% concentration, respectively (p<0.05). The contents of pro-inflammatory cytokines, such as tumor necrosis factor-alpha ($TNF-{\alpha}$) and interleukin-6 (IL-6), were decreased more by addition of STFL than by addition of STWE. The STWE and STFL showed high antioxidant and anti-inflammatory activity, and these activities were increased by fermentation. Therefore, sea tangle extracts can be used as functional food materials.

• IMMUNE NETWORK
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• v.1 no.3
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• pp.230-235
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• 2001

Background: Finding of the regulation of various gene expression by cytokine including $IFN-{\gamma}$ in hematopoietic stem cell will light up the understanding of pathogenesis of aplastic anemia in various aspects. To study on aplastic anemia, however, we have to circumvent the difficulty of directly obtaining bone marrow stem cells from the patient. Therefore, we tried to find out a cell can replace the bone marrow stem cells for study on cell signaling pathway and regulation of gene expression by $IFN-{\gamma}$. Materials and Methods: HL-60 cells, of 20 ng/mL of $IFN-{\gamma}$. Total RNA was isolated from the cells and RT-PCR of the indoleamine 2,3-dioxygenase (IDO), $IFN-{\gamma}$, TNF-${\alpha}$, $MIP-1{\alpha}$, and $TGF-{\beta}2$ was carried out for the estimation of the gene expression. Results: $IFN-{\gamma}$ induced IDO gene expression of mononuclear cells from umbilical cord blood showed similar pattern as compared to that of bone marrow. Whether $INF-{\gamma}$ was treated or not, $TNF-{\alpha}$ was expressed in both mononuclear cells from umbilical cord blood and bone marrow. However, HL-60 cells showed different expression patterns. HL-60 cells would express neither IDO nor $TNF-{\alpha}$ even under the culture with 20ng/mL of $IFN-{\gamma}$. Conclusion: Our results showed bone marrow can be replaced with mononuclear cells from umbilical cord blood in the study on the relation between aplastic anemia and $IFN-{\gamma}$ including $IFN-{\gamma}$ cell signaling pathway.

• Parasites, Hosts and Diseases
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• v.55 no.2
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• pp.207-212
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• 2017

Infections of Toxoplasma gondii and Babesia microti are reported in many wild animals worldwide, but information on their incidence and molecular detection in Korean wild fields is limited. In this study, the prevalence of T. gondii and B. microti infection in blood samples of 5 animal species (37 Chinese water deer, 23 raccoon dogs, 6 roe deer, 1 wild boar, and 3 Eurasian badgers) was examined during 2008-2009 in Gangwon-do (Province), the Republic of Korea (=Korea) by using serological and molecular tests. The overall seropositivity of T. gondii was 8.6% (6/70); 10.8% in Chinese water deer, 4.3% in raccoon dogs, and 16.7% in roe deer. PCR revealed only 1 case of T. gondii infection in Chinese water deer, and phylogenic analysis showed that the positive isolate was practically identical to the highly pathogenetic strain type I. In B. microti PCR, the positive rate was 5.7% (4/70), including 2 Chinese water deer and 2 Eurasian badgers. Phylogenetic analysis results of 18S rRNA and the ${\beta}$-tubulin gene showed that all positive isolates were US-type B. microti. To our knowledge, this is the first report of B. microti detected in Chinese water deer and Eurasian badger from Korea. These results indicate a potentially high prevalence of T. gondii and B. microti in wild animals of Gangwon-do, Korea. Furthermore, Chinese water deer might act as a reservoir for parasite infections of domestic animals.

• Clinical and Experimental Pediatrics
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• v.55 no.11
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• pp.438-444
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• 2012

Mucolipidosis II (ML II) or inclusion cell disease (I-cell disease) is a rarely occurring autosomal recessive lysosomal enzyme-targeting disease. This disease is usually found to occur in individuals aged between 6 and 12 months, with a clinical phenotype resembling that of Hurler syndrome and radiological findings resembling those of dysostosis multiplex. However, we encountered a rare case of an infant with ML II who presented with prenatal skeletal dysplasia and typical clinical features of severe secondary hyperparathyroidism at birth. A female infant was born at $37^{+1}$ weeks of gestation with a birth weight of 1,690 g (<3rd percentile). Prenatal ultrasonographic findings revealed intrauterine growth retardation and skeletal dysplasia. At birth, the patient had characteristic features of ML II, and skeletal radiographs revealed dysostosis multiplex, similar to rickets. In addition, the patient had high levels of alkaline phosphatase and parathyroid hormone, consistent with severe secondary neonatal hyperparathyroidism. The activities of ${\beta}$-D-hexosaminidase and ${\alpha}$-N-acetylglucosaminidase were moderately decreased in the leukocytes but were 5- to 10-fold higher in the plasma. Examination of a placental biopsy specimen showed foamy vacuolar changes in trophoblasts and syncytiotrophoblasts. The diagnosis of ML II was confirmed via GNPTAB genetic testing, which revealed compound heterozygosity of c.3091C>T (p.Arg1031X) and c.3456_3459dupCAAC (p.Ile1154GlnfsX3), the latter being a novel mutation. The infant was treated with vitamin D supplements but expired because of asphyxia at the age of 2 months.