• Toxicological Research
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• v.35 no.4
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• pp.361-369
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• 2019

1,2-Dichloropropane (1,2-DCP) has been used as an industrial solvent and a chemical intermediate, as well as in soil fumigants. Human exposure may occur during its production and industrial use. The target organs of 1,2-DCP are the eyes, respiratory system, liver, kidneys, central nervous system, and skin. Repeated or prolonged contact may cause skin sensitization. In this study, 1,2-DCP was dissolved in corn oil at 0, 2.73, 5.75, and 8.75 mL/kg. The skin of mice treated with 1,2-DCP was investigated using western blotting, hematoxylin and eosin staining, and immunohistochemistry. 1,2-DCP was applied to the dorsal skin and both ears of C57BL/6J mice. The thickness of ears and the epidermis increased significantly following treatment, and the appearance of blood vessels was observed in the dorsal skin. Additionally, the expression of vascular endothelial growth factor, which is tightly associated with neovascularization, increased significantly. The levels of protein kinase-B (PKB), phosphorylated PKB, mammalian target of rapamycin (mTOR), and phosphorylated mTOR, all of which are key components of the phosphoinositide 3-kinase/PKB/mTOR signaling pathway, were also enhanced. Taken together, 1,2-DCP induced angiogenesis in dermatitis through the PI3K/PKB/mTOR pathway in the skin.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.5
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• pp.341-347
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• 2020

Objectives: Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck cancer. MicroRNAs, as new biomarkers, are recommended for diagnosis and treatment of different types of cancers. Bevacizumab, sold under the trade name Avastin, is a humanized whole monoclonal antibody that targets and blocks VEGF-A (vascular endothelial growth factor A; angiogenesis) and oncogenic signaling pathways. Materials and Methods: This study comprised 50 cases suffering from OSCC and 50 healthy participants. Peripheral blood samples were collected in glass test tubes, and RNA extraction was started immediately. Expression levels of miR-155, miR-191, and miR-494 biomarkers in the peripheral blood of OSCC-affected individuals and healthy volunteers in vivo were evaluated using real-time PCR. The influence of Avastin on the expression levels of the aforementioned biomarkers in vitro and in the HN5 cell line was also investigated. Results: Expression levels of miR-155, miR-191, and miR-494 in the peripheral blood of individuals affected by OSCC were higher than in those who were healthy. Moreover, Avastin at a concentration of 400 μM caused a decrease in the expression levels of the three biomarkers and a 1.5-fold, 3.5-fold, and 4-fold increase in apoptosis in the test samples compared to the controls in the HN5 cell line after 24, 48, and 72 hours, respectively. Conclusion: The findings of this study demonstrate that overexpression of miR-155, miR-191, and miR-494 is associated with OSCC, and Avastin is able to regulate and downregulate the expression of those biomarkers and increase apoptosis in cancerous cells in the HN5 cell line.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.6
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• pp.671-680
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• 2017

This study was conducted to examine the effects and potential mechanisms of action of black soybean extracts and fermented black soybean extracts by Lactobacillus rhamnosus GG (LGG) and Bifidobacterium animals subsp. lactis BB-12 (BB-12) on proliferation of human follicle dermal papilla cells (HFDPC). We examined changes in pH, total polyphenol, sugar, and reducing sugar contents according to fermentation period of black soybean extracts. Assay using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide was performed to determine cell toxicity levels of the four black soybean extracts [black soybean water extract (BWE), black soybean ethanol extract (BEE), fermented BWE (F-BEW), and fermented BEE (F-BEE)]. Changes in mRNA expression levels of hair growth promoting factors and hair growth inhibiting factors by the four black soybean extracts were measured by real-time PCR. In addition, phosphorylation levels of mitogen-activated protein kinase family proteins were measured by western blot analysis. As a result, fermentation of black soybeans significantly reduced pH, total polyphenols, and sugar/reducing sugar contents. All four black soybean extracts showed no cellular toxicity in HFDPC. In fact, BEE significantly enhanced cell viability of HFDPC at $100{\mu}g/mL$ compared to control. BWE, BEE, and BWE-F significantly increased mRNA expression of vascular endothelial growth factor, and all four extracts increased mRNA expression of fibroblast growth factor. However, mRNA expression levels of apoptosis-related genes were not affected by black soybean extracts in HFDPC. Furthermore, BWE, BEE, and BWE-F significantly increased phosphorylation levels of extracellular signal-regulated kinase compared to control. Taken together, we demonstrated that black soybean extracts enhanced proliferation of human follicle dermal papilla cells partially via activation of hair growth promoting factors, although no particular significant effects on proliferation were observed by fermentation of black soybeans.

• Korean Journal of Clinical Laboratory Science
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• v.51 no.3
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• pp.360-369
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• 2019

Cadherins are essential transmembrane proteins that promote cell-cell adhesion and maintain the corpus luteum structure in the ovary. This study examined the influence of prostaglandin F2 alpha ($PGF2{\alpha}$) on E-cadherin, N-cadherin, and adhesion in luteal theca cells (LTCs). The luteal cells were isolated from the mid-phase corpus luteum, and the LTCs were cultured separately from the luteal heterogeneous cells according to the morphology of the mesenchymal cells and to determine if steroidogenic and endothelial cells of LTCs, 3beta-hydroxysteroid dehydrogenase ($3{\beta}$-HSD), and vascular endothelial growth factor receptor 2 (VEGFR2) mRNA were used. The LTCs were then incubated in the culture medium supplemented with 0.01, 0.1, and 1.0 mM $PGF2{\alpha}$ for 24 h, and the E-cadherin and N-cadherin proteins in the LTCs were detected by confocal laser scanning microscopy. The results revealed $3{\beta}$-HSD mRNA expression in the LTC but no VEGF2R mRNA expression. The E-cadherin and N-cadherin proteins of the LTCs were damaged in the 0.01, 0.1, and 1.0 mM $PGF2{\alpha}$ treatment groups, and the expression of the N-cadherin protein was reduced significantly in 0.01 mM $PGF2{\alpha}$ compared to the 0 mM $PGF2{\alpha}$ treatment groups (P<0.05). In addition, the number of attached LTCs were significantly lower in the 0.01 mM $PGF2{\alpha}$ treatment group than in the 0 mM $PGF2{\alpha}$ treatment group (P<0.05). In conclusion, $PGF2{\alpha}$ affected the disruption of cadherin proteins and cell adhesion in LTCs. These results may help better understand the cadherin and adhesion mechanism during corpus luteum regression in the ovary.

• Journal of Life Science
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• v.28 no.8
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• pp.945-954
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• 2018

Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.39
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• pp.7.1-7.9
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• 2017

Background: This study was to investigate the effect of biomechanical stimulation on osteoblast differentiation of human periosteal-derived stem cell using the newly developed bioreactor. Methods: Human periosteal-derived stem cells were harvested from the mandible during the extraction of an impacted third molar. Using the new bioreactor, 4% cyclic equibiaxial tension force (0.5 Hz) was applied for 2 and 8 h on the stem cells and cultured for 3, 7, and 14 days on the osteogenic medium. Biochemical changes of the osteoblasts after the biomechanical stimulation were investigated. No treatment group was referred to as control group. Results: Alkaline phosphatase (ALP) activity and ALP messenger RNA (mRNA) expression level were higher in the strain group than those in the control group. The osteocalcin and osteonectin mRNA expressions were higher in the strain group compared to those in the control group on days 7 and 14. The vascular endothelial growth factor (VEGF) mRNA expression was higher in the strain group in comparison to that in the control group. Concentration of alizarin red S corresponding to calcium content was higher in the strain group than in the control group. Conclusions: The study suggests that cyclic tension force could influence the osteoblast differentiation of periosteal-derived stem cells under optimal stimulation condition and the force could be applicable for tissue engineering.

• Clinical and Experimental Pediatrics
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• v.48 no.5
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• pp.539-544
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• 2005

Purpose : The aim of this study was to investigate the pathophysiologic role of serum E-selectin, vascular endothelial growth factor(VEGF)-induced cell adhesion mollecule in Kawasaki disease(KD) and to look for the evidence of direct relationship between the plasma levels of soluble E-selectin and the incidence of coronary artery lesion(CAL). Methods : Changes in plasma levels of sE-selectin(n=98) over time were measured by enzyme-linked immunosorbent assay(ELISA) in 23 patients with acute KD and 25 age-matched febrile children. Results : Compared with control values, the peak levels of plasma sE-selectin were significantly elevated($mean{\pm}S.E$. : $22.89{\pm}12.53ng/mL$ vs $10.65{\pm}3.42ng/mL$, P=0.01) in KD. 5 patients with CAL, plasma sE-selectin levels before treatment were higher than in 18 patients without CAL($mean{\pm}S.E$. : $39.43{\pm}15.08ng/mL$ and $19.00{\pm}8.32ng/mL$, respectively; P=0.01). Plasma sE-selectin declined rapidly in the majority of KD patients regardless of the presence of CAL. Plasma sE-selectin levels after treatment and convalesent period were similar in KD patients with and without CAL. The plasma levels sE-selectin were correlated with those of white blood cell count(r=0.299, P<0.05), CRP(r=0.430, P<0.05), serum albumin(r=-0.483, P<0.05), serum protein(r=-0.502, P<0.05) and hemoglobin(r=-0.372, P<0.05) not with those of ESR, platelet, or duration of fever. There were significant differences in the initial level of serum sE-selectin between KD with and without CAL($mean{\pm}S.E$. : $39.44{\pm}15.08ng/mL$ vs. $19.00{\pm}17.18ng/mL$) in multivariated linear tests. Conclusion : Plasma sE-selectin levels were significantly higher in KD than in other febrile illness. Higher plamsa levels of sE-selectin may have potential as a predictor of CAL in patients with KD.