• Journal of Life Science
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• v.24 no.5
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• pp.498-504
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• 2014

Mammalian hyaluronidases (HAase, EC 3.2.1.35) are a family of enzymes that hydrolyse N-acetyl-D-glucosamine (1-4) glycosidic bonds in hyaluronic acid, which is found in skin, cartilage, and the vitreous body. Although HAase is generally present in an inactive form within subcellular lysosomes, it is released in an active form in some types of inflammation and tissue injuries, thereby contributing to the inflammatory response. The HAase inhibitory activity of 500 methanolic extracts of 500 species from medicinal plants was screened using a Morgan microplate assay. The viscosity of the hyaluronic acid was measured with an Ubbelohde viscometer. Three MeOH extracts inhibited more than 50% of HAase activity at a concentration of 2 mg/ml. HAase inhibitory rates (%) of three species of medicinal plant extracts, Styrax japonica, Deutzia coreana, and Osmanthus insularis were 57.28%, 53.50%, and 53.19%, respectively. The rate of HAase inhibition of the extracts was dose dependent. In the HAase inhibitory assay using the Ubbelohde viscometer, the results were in good agreement with the results from the Morgan assay. The results suggest that HAase inhibitory compounds extracted from the stem of S. japonica, D. coreana, and O. insularis might be multifunctional and prevent the degradation of hyaluronic acid and the induction of allergic reactions and inflammation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.47.1-47.10
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• 2019

Background: Hyaluronic acid (HA) has been applied as a primary biomaterial for temporary soft tissue augmentation and as a carrier for cells and the delivery of growth factors to promote tissue regeneration. Although HA derivatives are the most versatile soft tissue fillers on the market, they are resorbed early, within 3 to 12 months. To overcome their short duration, they can be combined with cells or growth factors. The purpose of this study was to investigate the stimulating effects of human fibroblasts and basic fibroblast growth factors (bFGF) on collagen synthesis during soft tissue augmentation by HA hydrogels and to compare these with the effects of a commercial HA derivative (Restylane^®). Methods: The hydrogel group included four conditions. The first condition consisted of hydrogel (H) alone as a negative control, and the other three conditions were bFGF-containing hydrogel (HB), human fibroblast-containing hydrogel (HF), and human fibroblast/bFGF-containing hydrogel (HBF). In the Restylane^® group (HGF), the hydrogel was replaced with Restylane^® (R, RB, RF, RBF). The gels were implanted subdermally into the back of each nude mouse at four separate sites. Twelve nude mice were used for the hydrogel (n = 6) and Restylane^® groups (n = 6). The specimens were harvested 8 weeks after implantation and assessed histomorphometrically, and collagen synthesis was evaluated by RT-PCR. Results: The hydrogel group showed good biocompatibility with the surrounding tissues and stimulated the formation of a fibrous matrix. HBF and HF showed significantly higher soft tissue synthesis compared to H (p < 0.05), and human collagen type I was well expressed in HB, HF, and HBF; HBF showed the strongest expression. The Restylane^® filler was surrounded by a fibrous capsule without any soft tissue infiltration from the neighboring tissue, and collagen synthesis within the Restylane^® filler could not be observed, even though no inflammatory reactions were observed. Conclusion: This study revealed that HA-based hydrogel alone or hydrogel combined with fibroblasts and/or bFGF can be effectively used for soft tissue augmentation.

• Journal of the Korean Society of Radiology
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• v.12 no.1
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• pp.9-16
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• 2018

Hangover after drinking is different from person to person symptoms and degree, but usually thirst, fatigue, headache, general boredom, gastrointestinal disorder, vomiting, diarrhea, deficiency of vitamin appears. This hanging phenomenon is caused by the action of precursors such as ethyl acetate and acetaldehyde, which are the by products of fermentation contained in alcohol and alcohol accumulated in hepatocytes and body. In order to solve the hangover phenomenon, the same Origin as polysaccharide Polydeoxyribonucleotide, which is a nucleic acid-sugar-phosphate complex, which is a semen or testicular extract in salmon extract, and a water soluble salmon extract powder having the same structure and lower price than Polydeoxyribonucleotide And D-Glucuronic acid and N-Acetyl glucosamine. It has excellent biocompatibility, viscoelasticity and moisturizing power. It has effect on reduction of body water loss and skin moisture content in hangover phenomenon. It is antioxidant and skin moisturizing effect Hyaluronic acid was irradiated with gamma rays, and the composition was prepared by using the salmon extract powder and the main raw material. The ethanol degradation, the acetaldehyde reduction amount, the blood acetaldehyde concentration and the acetic acid concentration were measured to evaluate the alcoholysis effect, Skin moisture evaporation rate To examine the evaluation unit water content of the skin was improved determine whether the antioxidant and provide skin moisturizing effect. The addition of ethanol extracts of salmon extracts showed a decrease of 5 to 7 times compared with no addition, and a decrease of 3 to 5 times of acetaldehyde. In addition, the change of acetaldehyde concentration and acetic acid concentration in blood showed a rapid decrease compared to the no - added control group. In addition, when the raw material of hyaluronic acid was used, skin moisture content was high and skin moisture evaporation amount was decreased. Therefore, hyaluronic acid, which is a polysaccharide polymer, has excellent viscoelasticity and moisturizing ability, It is considered to provide antioxidant and skin moisturizing effect. Therefore, it can be said that the composition containing salmon extract powder and hyaluronic acid as a main ingredient is effective for the hangover phenomenon which occurs after drinking.

• Biomolecules & Therapeutics
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• v.30 no.4
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• pp.368-379
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• 2022

Hyaluronic acid (HA), a ligand of CD44, accumulates in some types of tumors and is responsible for tumor progression. The nuclear factor erythroid 2-like 2 (NRF2) regulates cytoprotective genes and drug transporters, which promotes therapy resistance in tumors. Previously, we showed that high levels of CD44 are associated with NRF2 activation in cancer stem like-cells. Herein, we demonstrate that HA production was increased in doxorubicin-resistant breast cancer MCF7 cells (MCF7-DR) via the upregulation of HA synthase-2 (HAS2). HA incubation increased NRF2, aldo-keto reductase 1C1 (AKR1C1), and multidrug resistance gene 1 (MDR1) levels. Silencing of HAS2 or CD44 suppressed NRF2 signaling in MCF7-DR, which was accompanied by increased doxorubicin sensitivity. The treatment with a HAS2 inhibitor, 4-methylumbelliferone (4-MU), decreased NRF2, AKR1C1, and MDR1 levels in MCF7-DR. Subsequently, 4-MU treatment inhibited sphere formation and doxorubicin resistance in MCF7-DR. The Cancer Genome Atlas (TCGA) data analysis across 32 types of tumors indicates the amplification of HAS2 gene is a common genetic alteration and is negatively correlated with the overall survival rate. In addition, high HAS2 mRNA levels are associated with increased NRF2 signaling and poor clinical outcome in breast cancer patients. Collectively, these indicate that HAS2 elevation contributes to chemoresistance and sphere formation capacity of drug-resistant MCF7 cells by activating CD44/NRF2 signaling, suggesting a potential benefit of HAS2 inhibition.

• Journal of the Korean institute of surface engineering
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• v.56 no.4
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• pp.273-282
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• 2023

In this study, the surface of Polyetheretherketone (PEEK) disks was modified to have a hydrophilic surface by applying a coating of Polyethylene glycol (PEG), Hyaluronic acid(HA), and Poly-Dopamine(PDA). The investigation aimed to examine whether the coated surfaces showed enhanced bioactivity for orthopedic applications compared to the pure PEEK. The microstructure, surface characteristics, and wettability of PEEK coated with PEG, HA, and PDA were analyzed using scanning electron microscopy(SEM), FT-IR spectrophotometer, Roughness Measurement System, Micro-Vickers, and Contact angle measurement. The mechanical properties were analyzed using a tensile testing machine, while the MTT assay for cell activity was analyzed using a microplate reader to measure optical density. According to the SEM and FT-IR results, the composition and crystal structure of PEG, HA and PDA coated surface were verified. Also, roughness, hardness, and contact angle were all improved in the coating group compared to the pure PEEK. We checked the HepG2 cell proliferation by using MTT assay on 7th days. In MTT assay results, HepG2 cell proliferation was increased with time, at 7 days, cell viability on discs coated with PDA was significantly higher than pure PEEK, PEG, HA coated group. PDA coated PEEK exhibited the highest surface roughness, hardness, contact angle, and cell activity. The mechanical properties were not affected by the presence of the coating.

• Polymer(Korea)
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• v.34 no.3
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• pp.282-288
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• 2010

The porcine small intestinal submucosa (SIS) has been widely used as a biomaterial without immuno rejection responses and hyalunonic acid (HA) can be used as biocompatible materials to regenerate tissue. We developed the SIS sponge and HA loaded SIS sponges (SIS/HA) for the possibility of the application of the tissue engineering using annulus fibrosus (AF). SEM observation shows that SIS and SIS/HA sponges have interconnected and open pores. We demonstrated the presence of HA in SIS/HA sponge from C-O functional group observed by the FTIR analysis. In conclusion, we suggest that SIS/HA sponge may be useful to tissue engineering using AF cell. This may be due to the enhanced biocompatibility and higher water retention capacity of HA.

• Biomaterials and Biomechanics in Bioengineering
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• v.2 no.1
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• pp.23-32
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• 2015

Facile immobilization of growth factors in hyaluronic acid (HA) hydrogels using dual enzymes is reported in the paper. The hydrogels were formed by using horseradish peroxidase (HRP) and hydrogen peroxide ($H_2O_2$) and transforming growth factor-${\beta}3$ (TGF-${\beta}3$) was covalently conjugated on the hydrogels in situ using tyrosinase (Ty) without any modifications. For the preparation of hydrogels, HA was grafted with poly(ethylene glycol) (PEG), which was modified with a tyrosine. The gelation times of the HA hydrogels were ranging from 415 to 17 s and the storage moduli was dependent on the concentration of $H_2O_2$ and Ty (470-1600 Pa). A native TGF-${\beta}3$ (200 ng/mL) was readily encapsulated in the HA hydrogels and 17% of the TGF-${\beta}3$ was released over 1 month at the Ty concentration of 0.5 KU/mL, while the release was faster when 0.3 KU/mL of Ty was used for the encapsulation (27%). It can be suggested that the growth factors resident in the hydrogels for a long period of time may lead cells proliferating and differentiating, whereas the growth factors that are initially released from the hydrogels can induce the ingrowth of cells into the matrices. Therefore, the dual enzymatic methods as facile gel forming and loading of various native growth factors or therapeutic proteins could be highly promising for tissue regenerative medicines.

• Proceedings of the Polymer Society of Korea Conference
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• 2006.10a
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• pp.251-251
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• 2006

A real time bio-imaging of HA degradation was successfully carried out using HA-quantum dot conjugates. HA-ADH with ADH content of ca. 70 mol% was synthesized and conjugated with quantum dots containing carboxyl terminal ligands which were activated by the addition of HOBt and EDC in DMSO. When the concentration of HA-ADH solution was higher than 4 wt%, HA-ADH hydrogels incorporating quantum dots could be synthesized in 30 minutes. These novel HA-quantum dot conjugates and the precursor solution of HA hydrogels incorporating quantum dots were injected to the nude mouse and investigated to elucidate the biological roles of HA in the body for various future tissue engineering applications.

• Microbiology and Biotechnology Letters
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• v.48 no.3
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• pp.344-357
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• 2020

Strain improvement and bioprocess development were undertaken to enhance hyaluronic acid(HA) production by Streptococcus zooepidemicus cells. Using a high-yielding mutant strain, statistical medium optimization was carried out in shake flask cultures, resulting in 52% increase in HA production (5.38 g/l) at the optimal medium composition relative to the parallel control cultures. For sufficient supply of dissolved oxygen (DO), which turned out to be crucial for enhanced production of HA, agitation system and speed were intensively investigated in 5 L bioreactor cultures. Increase in oxygen mass transfer coefficient (k_La) through increment of agitation speed (rpm) and 35% expansion of diameter of the newly-designed impellers showed significantly positive effects on HA production. By installing an expanded Rushton-turbine impeller for efficient break-down of sparged air, and an extended marine impeller above the Rushton-turbine impeller for efficient mixing of the air-born viscous fermentation broth, maximum amount of HA (9.79 g/l) was obtained at 450 rpm, 1.8 times higher level than that of the corresponding flask culture. Subsequently, the possibility of bioprocess scale-up to a 50 L bioreactor was investigated. Despite almost identical maximum HA production (9.11 vs 9.25 g/l), the average HA volumetric productivity (r_p) of the 50 L culture turned out only 74% compared to the corresponding 5 L culture during the exponential phase, possibly caused by shear damages imposed on the producing cells at the high stirring in the 50 L culture. The scale-up process could be successfully achieved if a scale-up criterion of constant oxygen mass transfer coefficient (k_La) is applied to the 50 L pilot-scale bioreactor system.

• Journal of Chitin and Chitosan
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• v.23 no.4
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• pp.262-266
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• 2018

Even though the saps have been consumed as beverage in Korea, however a little research has been conducted on the chemical composition. We determined free sugars, mineral in the sap from Juglans mandshurica Maxim. collected from BongHwa region. The contents of glucose, sucrose, and fructose in the sap from J. mandshurica were 0.15, 2.73, and 0.09%, respectively. The prominent minerals in the sap from J. mandshurica were calcium and potassium. The contents of Ca, K, Mg, Fe, and Mn of sap from J. mandshurica were 0.61, 0.57, 0.12, 0.002, and 0.014 ppm, respectively. The sap from J. mandshurica show inhibitory effect on elastase. And real-time RT-PCR showed that sap from J. mandshurica increased mRNA level of AQP3 and HAS2 gene and increased hyaluronic acid production in HaCaT cells. These results indicated that the sap from J. mandshurica can potentially be used for developing cosmetic ingredient for skin moisturizing and anti-aging.