• Annals of dermatology
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• v.30 no.6
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• pp.653-661
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• 2018

Background: Citron is well known for an abundance of antioxidative and anti-inflammatory ingredients such as vitamin C, polyphenol compounds, flavonoids, and limonoids. Objective: In this study, we aimed to evaluate the effects of citron essential oils on rosacea mediators in activated keratinocytes in vitro. Methods: Normal human epidermal keratinocytes (NHEKs) were stimulated with $1{\alpha}$, 25-dihydroxyvitamin $D_3$ ($VD_3$) and interleukin 33 (IL-33) with LL-37 to induce rosacea mediators such as kallikrein 5 (KLK5), cathelicidin, vascular endothelial growth factor (VEGF), and transient receptor potential vanilloid 1 (TRPV1). These mediators were analyzed by performing reverse-transcription polymerase chain reaction (PCR), quantitative real-time PCR, immunocytofluorescence and enzyme-linked immunosorbent assay after NHEKs were treated with citron seed and unripe citron essential oils. Results: The messenger RNA (mRNA) and protein levels of KLK5 and LL-37 induced by $VD_3$ were suppressed by citron seed and unripe citron essential oils. Furthermore, the mRNA and protein levels of VEGF and TRPV1 induced by IL-33 with LL-37 were also suppressed by citron essential oils. Conclusion: These results show that citron essential oils have suppressive effects on rosacea mediators in activated epidermal keratinocytes, which indicates that the citron essential oils may be valuable adjuvant therapeutic agents for rosacea.

• Archives of Pharmacal Research
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• v.28 no.12
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• pp.1337-1340
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• 2005

A lignan derivative, (-)-(7R, 8S)-dihydrodehydrodiconiferyl alcohol (DHDA), was isolated from Kalopanax septemlobus L. and was observed to have neuritogenic activity. DHDA at 50 $\mu$M caused a marked induction of neurite outgrowth and an enhancement of nerve growth factor (NGF)-mediated neurite outgrowth from PC12 cells. However, it did not exhibit any neurotrophic action. At 50 $\mu$M, DHDA enhanced NGF-induced neurite-bearing activity. This activity was partially blocked by the mitogen-activated protein kinase (MAPK) inhibitor PD98059 and by GF109203X, a protein kinase C (PKC) inhibitor. These results suggest that DHDA can induce neurite outgrowth and enhance NGF-induced neurite outgrowth from PC12 cells by amplifying up-stream steps such as MAPK and PKC.

• Parasites, Hosts and Diseases
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• v.57 no.4
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• pp.445-450
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• 2019

Human infections due to the monkey malaria parasite Plasmodium knowlesi is increasingly being reported from most Southeast Asian countries specifically Malaysia. The parasite causes severe and fatal malaria thus there is a need for urgent measures for its control. In this study, the level of polymorphisms, haplotypes and natural selection of full-length pkmsp8 in 37 clinical samples from Malaysian Borneo along with 6 lab-adapted strains were investigated. Low levels of polymorphism were observed across the full-length gene, the double epidermal growth factor (EGF) domains were mostly conserved, and non-synonymous substitutions were absent. Evidence of strong negative selection pressure in the non-EGF regions were found indicating functional constrains acting at different domains. Phylogenetic haplotype network analysis identified shared haplotypes and indicated geographical clustering of samples originating from Peninsular Malaysia and Malaysian Borneo. This is the first study to genetically characterize the full-length msp8 gene from clinical isolates of P. knowlesi from Malaysia; however, further functional characterization would be useful for future rational vaccine design.

• BMB Reports
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• v.54 no.8
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• pp.425-430
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• 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces coronavirus disease 2019 (COVID-19) and may increase the risk of adverse outcomes in lung cancer patients. In this study, we investigated the expression and function of mucin 1 (MUC1) after SARS-CoV-2 infection in the lung epithelial cancer cell line Calu-3. MUC1 is a major constituent of the mucus layer in the respiratory tract and contributes to pathogen defense. SARS-CoV-2 infection induced MUC1 C-terminal subunit (MUC1-C) expression in a STAT3 activation-dependent manner. Inhibition of MUC1-C signaling increased apoptosis-related protein levels and reduced proliferation-related protein levels; however, SARS-CoV-2 replication was not affected. Together, these results suggest that increased MUC1-C expression in response to SARS-CoV-2 infection may trigger the growth of lung cancer cells, and COVID-19 may be a risk factor for lung cancer patients.

• BMB Reports
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• v.57 no.3
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• pp.143-148
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• 2024

Pulmonary fibrosis is a serious lung disease that occurs predominantly in men. Genistein is an important natural soybean-derived phytoestrogen that affects various biological functions, such as cell migration and fibrosis. However, the antifibrotic effects of genistein on pulmonary fibrosis are largely unknown. The antifibrotic effects of genistein were evaluated using in vitro and in vivo models of lung fibrosis. Proteomic data were analyzed using nano-LC-ESI-MS/MS. Genistein significantly reduced transforming growth factor (TGF)-β1-induced expression of collagen type I and α-smooth muscle actin (SMA) in MRC-5 cells and primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Genistein also reduced TGF-β1-induced expression of p-Smad2/3 and p-p38 MAPK in fibroblast models. Comprehensive protein analysis confirmed that genistein exerted an anti-fibrotic effect by regulating various molecular mechanisms, such as unfolded protein response, epithelial mesenchymal transition (EMT), mammalian target of rapamycin complex 1 (mTORC1) signaling, cell death, and several metabolic pathways. Genistein was also found to decrease hydroxyproline levels in the lungs of BLM-treated mice. Genistein exerted an anti-fibrotic effect by preventing fibroblast activation, suggesting that genistein could be developed as a pharmacological agent for the prevention and treatment of pulmonary fibrosis.

• Journal of Periodontal and Implant Science
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• v.37 no.3
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• pp.497-509
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• 2007

Bone morphogenetic proteins(BMPs) are regarded as members of the transforming growth $factor-{\beta}$ superfamily with characteristic features in their amino acid sequences. A number of studies have demonstrated the biologic activities of BMPs, which include the induction of cartilage and bone formation. Recently there was a attempt to overcome a limitation of mass production, and economical efficieny of rh-BMPs. The method producing PTD by using bacteria have advantages of acquiry a mass of proteins. Hences, a new treatment which deliver protein employed by protein transduction domain(PTD) has been tried. The purpose of this study was to evaluate the bone regenerative effect of TATBMP-2 and TAT-HA2-BMP-2 employed by PTD from HlV-1 TAT protein for protein translocation in the rat calvarial model. An 8mm calvarial, critical size osteotomy defect was created in each of 32 male Spraque-Dawley rats(weight $250{\sim}300g$). The animals were divided into 4 groups of 32 animals each (4 animals/group/healing interval). The defect was treated with TATBMP-2/ACS(Absorbable collagen sponge) (TATBMP-2 0.1mg/ml), TAT-HA2-BMP-2/ACS(TAT-HA2-BMP-2 0.1mg/ml), ACS alone or left untreated for surgical control(negative control). The rats were sacrificed at 2 or 8 weeks postsurgery, and the results were evaluated histologically. The results were as follows: New bone formation were not significantly greater in the TATBMP-2/ACS group relative to negative, and positive control groups. New bone was evident at the defect sites in TAT-HA2-BMP-2/ACS group relative to negative, positive control and TATBMP-2 groups. There were a little bone regeneration in TATBMP-2 groups. While, enhanced local bone formation were observed in TAT-HA2-BMP-2 group. But, The results was not the same in all rat defects. Therefore, further investigations are required to develop a method. which disperse homogenously, and adhere to target cells.

• Asian-Australasian Journal of Animal Sciences
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• v.15 no.12
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• pp.1760-1764
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• 2002

In order to elucidate the physiological function of circulating IGF-I on muscle protein synthesis in the chicken under malnutritional conditions, we administrated recombinant chicken IGF-I using a osmotic mini pump to fasted young chickens and measured the rate of muscle protein synthesis and plasma metabolite. The pumps delivered IGF-I at the rate of $22{\mu}g/d\{300{\mu}g{\cdot}(kg\;body\;weight{\cdot}d)^{-1}\}$. Fractional rate of protein synthesis in the muscle was measured using a large dose injection of L-[$2,6-^3H$]phenylalanine. Constant infusion of chicken IGF-I did not affect plasma glucose level. Significant interaction between dietary treatment and IGF-I infusion was observed in plasma NEFA and total cholesterol concentrations. When chicks were fasted, IGF-I infusion decreased plasma NEFA and total cholesterol concentrations. On the other hand, IGF-I administration did not affect plasma levels of both metabolites. Fasting reduced plasma triglyceride concentration significantly. IGF-I infusion also decreased the level of plasma triglyceride. Plasma IGF-I concentration of young chickens was halved by fasting for 1 d. IGF-I infusion using an osmotic minipump for 1 d increased plasma IGF-I concentration in fasted chicks to the level of fed chicks. Fasting decreased body weight and the loss of body weight was significantly ameliorated by IGF-I infusion. There was a significant interaction between dietary treatment and IGF-I infusion in the fractional rate of breast muscle protein synthesis. There was no effect of IGF-I infusion on muscle protein synthesis in fed chicks. Muscle protein synthesis reduced by fasting was ameliorated by IGF-I infusion, but did not reach to the level of fed control. Muscle weight of fasted chicks infused with IGF-I was similar to fasted birds without IGF-I infusion, which suggests that muscle protein degradation would be increased by IGF-I infusion as well as protein synthesis in fasted chicks.

• Journal of Life Science
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• v.19 no.12
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• pp.1731-1736
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• 2009

Recent studies determined that a chronic western-style diet increased the endogenous small heterodimer partner (SHP) protein levels in mice. In experiments with cell cultures, chenodeoxy cholic acid (CDCA) treatment increased endogenous SHP protein levels and reduced the degradation rate of exogenously expressed flag-SHP levels in the human hepatoma cell line, HepG2 cells. In addition, bile acid-induced intestinal fibroblast growth factor-19 (FGF-19) increased the half-life of the exogenously expressed SHP when HepG2 cells were transfected with ad-flag-SHP. However, both the expression level and the degradation rate of the endogenous SHP in response to cholic acid and FGF-19 have not been well understood, either in mice or in cultured HepG2 cells. This study examined the effects of cholic acid treatment on the endogenous SHP protein levels in mice and the effects of FGF-19 on the degradation rate of the endogenous SHP protein in HepG2 cells. Mice fed 0.5% cholic acid in normal chow showed an increase in endogenous SHP protein levels during both 12 hr and 24 hr treatment periods as compared to control mice fed only normal chow. In cultured HepG2 cells, treatment with CDCA did not noticeably change the rate of degradation in the endogenous SHP protein from cells not treated with CDCA. Although consistent with the previous studies on the exogenous ad-flag-SHP protein, treatment with FGF-19 significantly decreased the degradation rate of the endogenous SHP protein when HepG2 cells were treated with cyclohexamide. These results suggest that both bile acids and FGF-19 increase the endogenous SHP protein levels in mouse liver and HepG2 cells.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.1
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• pp.54-63
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• 2010

Baicalin, a flavonoid, was shown to have diverse effects such as anti-inflammatory, anti-cancer, anti-viral, anti-bacterial and others. Recently, we found that the baicalin inhibits adipogenesis through the modulations of anti-adipogenic and pro-adipogenic factors of the adipogenesis pathway. In the present study, we further characterized the molecular mechanism of the anti-adipogenic effect of baicalin using microarray technology. Microarray analyses were conducted to analyze the gene expression profiles during the differentiation time course (0 day, 2 day, 4 day and 7 day) in 3T3-L1 cells with or without baicalin treatment. We identified a total of 3972 genes of which expressions were changed more than 2 fold. These 3972 genes were further analyzed using hierarchical clustering analysis, resulting in 20 clusters. Four clusters among 20 showed clearly up-regulated expression patterns (cluster 8 and cluster 10) or clearly down-regulated expression patterns (cluster 12 and cluster 14) by baicalin treatment for over-all differentiation period. The cluster 8 and cluster 10 included many genes which enhance cell proliferation or inhibit adipogenesis. On the other hand, the cluster 12 and cluster 14 included many genes which are related with proliferation inhibition, cell cycle arrest, cell growth suppression or adipogenesis induction. In conclusion, these data provide detailed information on the molecular mechanism of baicalin-induced inhibition of adipogenesis.

• Clinical and Experimental Reproductive Medicine
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• v.37 no.2
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• pp.125-134
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• 2010

Objective: The aim of this study was to measure the concentrations of cytokines contained in the hydrosalpingeal fluid and to evaluate the effect on the mouse embryo development with the different cytokine concentration. Methods: The hydrosalpingeal fluids (HSF) were collected during the surgery for hydrosalpinx which was confirmed by hysterosalphingogram. The cytokines in HSF including interleukin (IL)-$1{\alpha}$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, Interferon-$\gamma$ (IFN-$\gamma$), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), monocyte chemotactic protein-1 (MCP-1) were measured by ELISA method. HSF were added up to culture media with 5%, 10%, and 30% concentrations. The blastulation rates were compared. Results: IL-$\alpha$, IL-$1{\beta}$, IL-2, IL-4, IL-6, IL-8, IL-10, TNF-$\alpha$, IFN-$\bamma$, VEGF, EGF, and MCP-1 were detected, but the concentrations were different from each sample. IL-6 and IL-10 were increased in HSF-1 group, and IFN-$\gamma$, MCP-1, VEGF were increased in HSF-2 compared with normal serum range. The Th1/Th2 ratio of HSF-2 (IFN-$\gamma$:IL10) was highly elevated to 61.64, compared with that of HSF-1 (3.69). The blastulation rate was significantly decreased in HSF-2 group (27.7%) compared those of the HSF-1 group (74%) and control group (76.7%). It showed the trend that the blastulation rate was decreased depending on the concentration HSF of culture media in HSF-2 group, but it was not statistically significant. Conclusion: The composition and concentration of cytokines in each HSF were different, and increased proinflammatory cytokines in HSF might be associated with poor embryonic development. Further study will be needed about the effect of each cytokines in HSF.