• Journal of Biomedical Engineering Research
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• v.34 no.3
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• pp.117-122
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• 2013

Hyaluronic acid(HA) microbeads were synthesized by dropping the sodium hyaluronate(Streptococcus) solutions in NaOH into a solution mixture of divinyl sulfone(DVS) in 2-methyl-1-propanol, followed by stirring, cleaning and drying process at room temperature. The initial experimental conditions are crosslinking time(CLTi) of 5 h, crosslinking temperature(CLTe) of room temperature, injection air pressure(IAPr) of 5 psi, and DVS concentration( DVSc) of 0.2 vol%, respectively. Then, parametric studies were performed by varying the parameters to investigate the morphology, the porosity, the swelling ratio and the size of the beads. The microbead size pattern was not regular to function of the degree of crosslink. It was observed that the swelling ratio, the degree of crosslink, and the pore size can be controlled by adjusting the CLTi, CLTe and DVSc. Among the parameters investigated, the smallest bead size can be achieved by varying the CLTi parameter. The lowest swelling ratio, as an indication of the highest degree of crosslink, can be obtained by varying CLTe.

• KSBB Journal
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• v.21 no.4
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• pp.255-259
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• 2006

The biodegradable hyaluronic acid(HA) membranes cross-linked with lactide using the crosslinking agent, 1-ethyl-3(3-dimethyl aminopropyl) carbodiimide(EDC) were prepared as a potential biocompatible material for tissue engineering. HA membranes having different mechanical properties were synthesised by varying degree of the mole ratio of lactide to HA, EDC concentration, and crosslinking temperature. HA membranes were degradable in water solution and the degradation became slower with the increasing mole ratio of lactide to HA. HA membranes were sterilized using ethylene oxide gas and extracted with cell culture medium for 24 h at $37^{\circ}C$ and 200 rpm. Cytotoxicity of the extract was tested using NIH/3T3 mouse embryo fibroblast as a model cell. Growth inhibition was not observed in the extracts of HA membranes with the mole ratios of lactide to HA, 5 or 10, and 10% EDC concentration, however 11% of growth inhibition was observed in the extract with the mole ratio of 13. Growth inhibition was not observed in the extracts of HA membranes prepared with 5% EDC or 10% EDC and the mole ratio of lactide to HA, 10, however 12% of growth inhibition was observed in the extract with 20% EDC. Cytotoxicity was not observed in the extracts of HA membranes prepared at varying crosslinking temperatures, $15^{\circ}C,\;25^{\circ}C,\;and\;28^{\circ}C$ with the mole ratio of lactide to HA, 10 and 10% EDC.

• Korean Journal of Veterinary Research
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• v.57 no.4
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• pp.215-222
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• 2017

Temporal and subcellular distributions of hyaluronic acid (HA) as a degradable nanoparticle (NP) in animals were investigated to determine if HA-NP could be utilized as an appropriate drug delivery system. After mice were intravenously injected with 5 mg/kg of Cy5.5-labeled HA-NP sized 350-400 nm or larger HA-polymers, the fluorescence intensity was measured in all homogenized organs from 0.5 h to 28 days. HA-NP was greatly detected in spleen, liver and kidney until day 28, while it was maintained at low levels in other organs. HA-polymer was observed at low levels in all organs. HA-NP quantities in spleen and liver were reduced until day 3, but increased sharply between days 3 and 7, then decreased again, while their HA-polymers were maintained at low levels until day 28. In kidneys, both HA-NP and HA-polymer showed high levels after 0.5 h of administration, but steadily decreased until day 28. According to ultrastructural analyses, HA-NP was engulfed in Kupffer cells of liver and macrophages of spleen and kidney at day 1 and was accumulated in the cytoplasm of kidney tubular cells at day 7. Overall, these findings suggest that HA-NP could be considered a desirable drug carrier in the liver, kidney, or spleen.

• Korean Journal of Food Science and Technology
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• v.54 no.1
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• pp.8-16
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• 2022

Rice (brown rice: milled rice=50:50) was cooked using different concentrations of hyaluronic acid (HA) solution (0.1, 0.3, 0.5, and 0.7%, respectively) as the cooking water, and the properties of the cooked rice were compared. As the HA content increased, the moisture content of the cooked rice significantly increased, and the textural properties, including hardness, cohesiveness, and adhesiveness, except springiness, significantly decreased. For color, as the HA amount increased, the L^* value decreased, whereas the b^* values increased. The free radical scavenging effect and total polyphenol content also increased significantly as the amount of HA increased. In the sensory test, the hardness of the samples containing HA was higher than that of the control; however, there was no significant difference in the overall acceptability. Based on the above results, much softer cooked brown rice could be produced using HA solution (up to 0.7%) as the cooking water, and additional beneficial characteristics, such as antioxidant effect, can be obtained.

• Polymer(Korea)
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• v.31 no.6
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• pp.505-511
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• 2007

Poly(lactide-co-glycolide)(PLGA) and hyaluronic acid (HA) has been widely used as biocompatible scaffold materials to regenerate tissue. In this present study, we fabricated microporous PLGA and HA loaded PLGA scaffolds by a emusion freeze-drying method. In order to confirm that the release profile of cytokine or water-soluble drugs, we manufactured the granulocyte macrophage colony stimulating factor(GM-CSF) loaded PLGA and HA-PLGA scaffold. All scaffolds were characterized using scanning electron microscope(SEM), mercury porosimeter and wettability measurement. Cell proliferation and viability were assessed by a 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium-bromide (MTT) test. The porosity of HA-PLGA scaffold was greater than 95% with the total pore area of $261\;m^2/g$. The HA-FLGA scaffold exhibited well interconnected pores to allow greater cell adhesion and prolixferation. It was proven by higher cell viability in the HA-PLGA scaffold than PLGA alone. This may be due to the enhanced natural properties and higher water retention capacity of HA.

• Biomolecules & Therapeutics
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• v.31 no.6
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• pp.629-639
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• 2023

Cardiovascular diseases (CVDs) are the most common cardiovascular system disorders. Cellular senescence is a key mechanism associated with dysfunction of aged vascular endothelium. Hyaluronic acid and proteoglycan link protein 1 (HAPLN1) has been known to non-covalently link hyaluronic acid (HA) and proteoglycans (PGs), and forms and stabilizes HAPLN1-containing aggregates as a major component of extracellular matrix. Our previous study showed that serum levels of HAPLN1 decrease with aging. Here, we found that the HAPLN1 gene expression was reduced in senescent human umbilical vein endothelial cells (HUVECs). Moreover, a recombinant human HAPLN1 (rhHAPLN1) decreased the activity of senescence-associated β-gal and inhibited the production of senescence-associated secretory phenotypes, including IL-1β, CCL2, and IL-6. rhHAPLN1 also downregulated IL-17A levels, which is known to play a key role in vascular endothelial senescence. In addition, rhHAPLN1 protected senescent HUVECs from oxidative stress by reducing cellular reactive oxygen species levels, thus promoting the function and survival of HUVECs and leading to cellular proliferation, migration, and angiogenesis. We also found that rhHAPLN1 not only increases the sirtuin 1 (SIRT1) levels, but also reduces the cellular senescence markers levels, such as p53, p21, and p16. Taken together, our data indicate that rhHAPLN1 delays or inhibits the endothelial senescence induced by various aging factors, such as replicative, IL-17A, and oxidative stress-induced senescence, thus suggesting that rhHAPLN1 may be a promising therapeutic for CVD and atherosclerosis.

• Korean Journal of Veterinary Research
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• v.57 no.2
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• pp.105-111
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• 2017

Hyaluronic acid (HA) has been investigated for biomedical and pharmaceutical applications. This study was conducted to determine the distributions of HA nanoparticles (NPs; size 350-400 nm) and larger HA polymers in mice at intervals after application. $^{177}Lutetium$ (Lu)-labeled HA-NPs or HA polymers were intravenously injected (5 mg/kg) into male ICR mice, and radioactivity levels in blood and target organs were measured from 0.25 h to 28 days post-injection. In blood, the radioactivities of HA-NPs and HA polymer peaked at 0.5 h after injection but were remarkably decreased at 2 h; subsequently, they maintained a constant level until 6 days post-injection. HA-NPs and HA polymers were observed in the liver, spleen, lung, kidney, and heart (in ascending order) but were seldom observed in other organs. After 3 days, both the HA-NP and HA polymer levels showed similar steady decreases in lung, kidney, and heart. However, in liver and spleen, the HA-NP levels tended to decrease gradually after 1 day and both were very low after 14 days, whereas the HA polymer level accumulated for 28 days. The results indicate that HA-NPs, with their faster clearance pattern, may act as a better drug delivery system than HA polymers, especially in the liver and spleen.

• Microbiology and Biotechnology Letters
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• v.48 no.4
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• pp.525-532
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• 2020

A continuous fermentation process was carried out to enhance hyaluronic acid (HA) production using Streptococcus zooepidemicus cells. During the 1st stage continuous operation from 8 h with a dilution rate of 0.029/h (D1), HA was produced in the range of 7.5-10 g/l. During the 2nd stage from 44 h with a dilution rate of 0.036/h (D2), HA production (8.28 g/l) was initially reduced to a small extent due to increase of dilution rate from D1 to D2, and then a new pseudo-steady state was formed within a few hours with a concurrent small variations of HA production. The HA amount produced during the latter part of the 2nd stage was stably maintained in the range of 8.28-9.48 g/l, about 4.7% less amount compared to the 1st stage. Due to 24% increase of dilution rate from D1 to D2, however, maximum volumetric productivity (DP) amounting to 0.341 g/l/h was obtained at 96 h during the 2nd stage. This maximum productivity obtained from the continuous culture turned out only a small increase (3%) as compared to the corresponding batch fermentation. However, it should be noted that, in the case of batch process, one run typically consists of serial stages of growth culture plus one final production culture. This implies that, if the continuous fermentation that practically needs no dead time necessary for the multi-stage growth cultures is run for longer period, the total amount of the accumulated HA would be far greater than the amount obtained from the corresponding batch culture performed for the identical period.

• Journal of the Society of Cosmetic Scientists of Korea
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• v.44 no.4
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• pp.447-453
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• 2018

Acetyl hexapeptide 8 (AH8) is a synthetic peptide for anti-wrinkle cosmetics ingredient. It was developed as a mimetic of botox, patternd after N -terminal end of the protein synatosomal-associated protein 25 (SNAP25), a substrate of botulinum toxin. While AH8 has good efficacy and safety profiles, the permeation through the skin is poor. Therefore, we tried to enhance the transdermal delivery of AH8 by using of hyaluonic acid (HA), a linear polysaccharide of N-acetyl glucosamine and glucuronic acid. To investigate the effect of HA on AH8 penetration, we analyzed paraffin sections of $Micropig^{(R)}$ skin. Fluorescence labeled AH8 was applied to micropig skin with or without HA. The absorption of AH8 was limited to the stratum corneum (SC) without HA. On the other hand, AH8 penetrated to the dermis with HA. Especially, low molecular weight HA (5 kDa) was most efficient compared to 500 kDa HA and 2000 kDa HA. Experiments using fourier-transform infrared (FTIR) spectroscopy revealed that lower molecular weight HA had a tendency to increase the fluidity of the SC lipids more, which means enhancing the skin penetration. Therefore, HA could be expected to enhance the anti-wrinkle effect of AH8.

• Journal of Microbiology and Biotechnology
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• v.33 no.2
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• pp.235-241
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• 2023

Hyaluronidase (HAase) can enhance drug diffusion and dissipate edema by degrading hyaluronic acid (HA) in the extracellular matrix into unsaturated HA oligosaccharides in mammalian tissues. Microorganisms are recognized as valuable sources of HAase. In this study, a new hyaluronate lyase (HAaseD) from Bacillus sp. CQMU-D was expressed in Escherichia coli BL21, purified, and characterized. The results showed that HAaseD belonged to the polysaccharide lyase (PL) 8 family and had a molecular weight of 123 kDa. HAaseD could degrade chondroitin sulfate (CS) -A, CS-B, CS-C, and HA, with the highest activity toward HA. The optimum temperature and pH value of HAaseD were 40℃ and 7.0, respectively. In addition, HAaseD retained stability in an alkaline environment and displayed higher activity with appropriate concentrations of metal ions. Moreover, HAaseD was an endolytic hyaluronate lyase that could degrade HA to produce unsaturated HA oligosaccharides. Together, our findings indicate that HAaseD from Bacillus sp. CQMU-D is a new hyaluronate lyase and with excellent potential for application in industrial production.