• BMB Reports
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• v.54 no.6
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• pp.329-334
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• 2021

Collagen type I is the most abundant form of collagen in human tissues, and is composed of two identical α-1 type I chains and an α-2 type I chain organized in a triple helical structure. A previous study has shown that human collagen α-2 type I (hCOL1A2) promotes collagen synthesis, wound healing, and elastin production in normal human dermal fibroblasts (HDFs). However, the biological effects of human collagen α-1 type I (hCOL1A1) on various skin properties have not been investigated. Here, we isolate and identify the hCOL1A1-collagen effective domain (CED) which promotes collagen type I synthesis. Recombinant hCOL1A1-CED effectively induces cell proliferation and collagen biosynthesis in HDFs, as well as increased cell migration and elastin production. Based on these results, hCOL1A1-CED may be explored further for its potential use as a preventative agent against skin aging.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.6
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• pp.421-429
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• 2003

Purpose : Neoadjuvant chemotherapy is commonly used to treat cancer patients as adjunct treatment, but if the microvascular tissue transfer is performed simulataneously with cancer resection surgery, the induction chemotherapy might affect the survival rate of vascularized free flap. Our study will focus on the effect of induction chemotherapy on the free flaps which were made on white rat abdomen after injection of 5-FU. Materials and Methods: The experimental rat groups were divided into three groups (total 24 rats) as a normal control group, 24 hrs group after 5-FU injection, 3 days group after 5-FU injection. Inferior abdominal island flaps of 8 Sprague Dawley rats on each group were made and immediately were induced into an ischemic state by clamping the supplying inferior epigastric artery and vein with microvascular clamp for a hour to induce a similiar free flap circumstance, then the inferior abdominal skin flaps were reperfused by releasing the clamps. The flaps on abdomen were repositioned and sutured. The experimental data for flap survival rate was collected by digital photo taking, analysed by computer image program to compare with the flap luminosity. The rats were sacrificed at 3 days, 5 days, 7 days after flap preparation and specimens of the flap were taken and stained with H-E staining. The microscopic finding was made under magnification of 200 and 400. Results: 1. Gross findings on each groups showed the healing condition was good as following sequences; normal, 24 hrs group after chemotherapy, 3 days group after chemotherpy. 2. The values of flap luminosity for evaluation of flap survival rate also showed the same sequences as gross findings of healing state. 3. The microscopic findings of epidermis necrosis, inflammation state, dermis fibrosis, vessel change, fatty tissue layer thinning were compared with each group. The 3 days group after chemotherapy showed remarkably poor healing condition compared to other groups. Conclusion: Chemotherapy agents affected the healing process of free flap, but healing condition was recovered spontaneously as post-injection periods passed out. In opposite to our expectation, 3 days group showed the bad flap condition in comparing with 24 hours group which was considered as immatured body circulation state of chemotherapy agent. It showed that 3 weeks in human being after chemotherapy was not proper as timing of microvascular tissue transfer if 3 days group in rat was considered as same healing period of 3 weeks in human being. More delayed healing timing than 3 weeks might be required in clinical application of free tissue transfer.

• Korean Journal of Clinical Laboratory Science
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• v.50 no.3
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• pp.337-344
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• 2018

Hepatocellular carcinoma (HCC), a major type of hepatoma, is associated with high recurrence and mortality because of its uncontrolled metastatic feature. Silymarin is a polyphenolic flavonoid from Silybum marianun (milk thistle) and exhibits anti-carcinogenic activity through modulation of the epithelial-mesenchymal transition (EMT) in several cancer cells. In this study, the inhibitory mechanism of silymarin against migration and invasion was investigated in the Huh7 HCC cell line. Wound healing and in vitro invasion assays were conducted to examine the effects of silymarin on migration and invasion. Western blot analysis was also applied to evaluate the inhibitory effects of silymarin on the EMT-related genes and their upstream signaling molecules. Silymarin inhibited the migratory and invasive activities of Huh7 cells. In addition, silymarin attenuated the protein expression levels of vimentin and matrix metalloproteinase (MMP)-9 as well as their transcription factors, Snail, and nuclear factor $(NF)-{\kappa}B$, while the expression of E-cadherin was increased by the silymarin treatment. Among the upstream signaling molecules, the phosphorylation of Akt was inhibited by the silymarin treatment, which was confirmed by the selective inhibitor, LY294002. Consequently, silymarin inhibited the invasive and migratory activities in Huh7 cells through the modulation of EMT-related gene expression by the PI3K/Akt signaling pathway, which may have potential as a chemopreventive agent against HCC metastasis.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.3
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• pp.309-316
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• 2017

Transient receptor potential vanilloid 3 (TRPV3) is a non-selective cation channel with modest permeability to calcium ions. It is involved in intracellular calcium signaling and is therefore important in processes such as thermal sensation, skin barrier formation, and wound healing. TRPV3 was initially proposed as a warm temperature sensor. It is activated by synthetic small-molecule chemicals and plant-derived natural compounds such as camphor and eugenol. Schisandra chinensis (Turcz.) Baill (SC) has diverse pharmacological properties including antiallergic, anti-inflammatory, and wound healing activities. It is extensively used as an oriental herbal medicine for the treatment of various diseases. In this study, we investigated whether SC fruit extracts and seed oil, as well as four compounds isolated from the fruit can activate the TRPV3 channel. By performing whole-cell patch clamp recording in HEK293T cells overexpressing TRPV3, we found that the methanolic extract of SC fruit has an agonistic effect on the TRPV3 channel. Furthermore, electrophysiological analysis revealed that ${\gamma}$-schisandrin, one of the isolated compounds, activated TRPV3 at a concentration of $30{\mu}M$. In addition, ${\gamma}$-schisandrin (${\sim}100{\mu}M$) increased cytoplasmic $Ca^{2+}$ concentrations by approximately 20% in response to TRPV3 activation. This is the first report to indicate that SC extract and ${\gamma}$-schisandrin can modulate the TRPV3 channel. This report also suggests a mechanism by which ${\gamma}$-schisandrin acts as a therapeutic agent against TRPV3-related diseases.

• Journal of Periodontal and Implant Science
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• v.30 no.2
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• pp.257-277
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• 2000

New techniques for regenerating the destructed periodontal tissue have been studied for many years. Current acceptable methods of promoting periodontal regeneration are basis of removal of diseased soft tissue, root treatment, guided tissue regeneration, graft materials, and biological mediators. Platelet Rich Plasma has been reported as a biological mediator which regulates activities of wound healing progress including cell proliferation, migration, and metabolism. The purpose of this study is to evaluate the effects of using the Platelet Rich Plasma as a regeneration promoting agent for furcation involvement defect. Five adult beagle dogs were used in this experiment. The dogs were anesthetized with Ketamin HCl(0.1 ml/kg, IV)and Xylazine hydrochloride($Rompun^{(R)}$, Bayer, 0.1 ml/kg, IM) and conventional periodontal prophylaxis were performed with ultrasonic scaler and hand instruments. With intrasulcular and crestal incision, mucoperiosteal flap was elevated. Following decortication with 1/2 high speed round bur, degree II furcation defect was made on mandibular third(P3), forth(P4) and fifth(P5) premolar, and stopping was inserted. After 4 weeks, stopping was removed, and bone graft was performed. Ca-P was grafted in P3(experimental group I), Combination of Ca-P and plasma rich platelet were grafted in P4(experimental group II), and P5 was remained at control group.Systemic antibiotics(gentamicin sulfate)and anlgesics(phenyl butazone) were administrated intramuscular for 2 weeks after surgery. Irrigation with 0.1% Chlorhexidine Gluconate around operate sites was performed during the whole experimental period except one day immediate after surgery. Soft diets were fed through the whole experiment period. After 4, 8 weeks, the animals were sacrificed by perfusion technique. Tissue block was excised including the tooth and prepared for light microscope with Gomori's trichrome staining. At 4 weeks after surgery, there were rapid osteogenesis phenomenon on the defected area of the Platelet Rich Plasma plus Ca-P BBP group and early trabeculation pattern was made with new osteoid tissue produced by activated osteoblast. Bone formation was almost completed to the fornix of furcation by 8 weeks after surgery. In conclusion, Platelet Rich Plasma can promote rapid osteogenesis during healing of periodontalregeneration.

• Journal of Periodontal and Implant Science
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• v.38 no.sup2
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• pp.325-334
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• 2008

Purpose: The carrier used as delivery agent for bone morphogenetic proteins(BMPs) should also act as a scaffold for new bone formation. Moreover, bone formation should be predictable in terms of the volume and shape. This study examined the osteogenic effect of macroporous biphasic calcium phosphate (MBCP) block combined with ePTFE membrane as a carrier for recombinant human bone morphogenetic proteins (rhBMP-2). In addition, the additive effect of ePTFE membrane on bone formation was evaluated. Materials and Methods: Eight-millimeter critical sized calvarial defects were created surgically in 28 male Sprague-Dawley rats. The animals were divided into 2 groups containing 14 animals each. The defects were treated with either rhBMP-2/MBCP block (rhBMP-2/MBCP group) or rhBMP-2/MBCP block/ePTFE membrane (rhBMP-2/MBCP/ePTFE group). A disc-shaped MBCP block (3 mm height and 8 mm diameter) was used as the carrier for the rhBMP-2 and ePTFE membrane was used to cover the rhBMP-2/MBCP block. The histologic and histometric parameters were used to evaluate the defects after 2- or 8-week healing period (7 animals/group/healing interval). Results: The level of bone formation in the defects of both groups was significantly higher at 8 weeks than that at 2 weeks (P < 0.05). The ePTFE membrane has no additional effect compared with the rhBMP-2/MBCP block only. However, at 8 weeks, rhBMP-2/MBCP/ePTFE group showed more even bone formation on the top of the MBCP block than the rhBMP-2/MBCP group. Conclusion: These results suggest that the ePTFE membrane has no additive effect on bone formation when a MBCP block is used as a carrier for rhBMP-2.

• Journal of Periodontal and Implant Science
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• v.26 no.2
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• pp.396-413
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• 1996

Current acceptable methods for promoting periodontal regeneration are based on removal of diseased soft tissue. root treatment, guided tissue regeneration, introduction of new graft materials and biological mediators. Insulin-like growth factor-I(IGF-I) and Platelet-derived growth factor-BB(PDGF-BB), the members of the polypeptuyde growth factor family have been reported as the biological mediators which regulate a variety cellular matrix biologic activities of wound healing process including the cell proliferation, migration and extracellular matrix synthesis.The purposes of this study is to evaluate the combination effects of IGF-I and PDGF-BB on the cellular activity of the periodontal ligament cells to act as a regeneration promoting agent of periodontal tissue. Human periodontal ligament cells were prepared from the first premolar tooth extracted for the orthodontic treatment and were cultured in DMEM containing 10% FBS at the $37^{\circ}C$, 5% CO2 incubator. Author measured the DNA synthetic activity, and total protein, collagen and noncollagenous protein synthetic activities according to the concentration of 10,100ng/ml IGF-I and1,10 ng/ml PDGF-BB in combination. The results were as follows: Significantly increased in the 1 ng/ml PDGF-BB alone compared to the 10 ng/ml PDGF-BB alone(P<0.01) and in the 1 ng/ml PDGF-BB and 10, 100ng/ml IGF-I in combination compared to the 1 ng/ml PDGF-BB alone(P<0.05, P<0.0l). The synthetic activity of the total protein and collagen is significantly increased like to the synthetic activity of the DNA(P<0.05). The synthetic activity of the noncollagenous protein is increased according to the concentration of IGF_I, but not statistically statistically significant(P>0.05). The percent of the collagen is significantly in the 1ng/ml PDGF-BB and 10ng/ml IGF-I in combination compared to the 1ng/ml PDGF-BB alone(P<0.05) and in the 10ng/ml IGF-I in combination compared to the 10ng/ml PDGF-BB alone(P<0.05). The synthetic activity of the DNA is In conclusions, the percent study shows that PDGF-BB and IGF-I in combination have a potentiality to enhance the DNA synthesis and the total protein and collagen synthesis of The periodontal ligament cells, especially it is more significant in the low concentration of PDGF-BB compared to the high one. Thus, the PDGF-BB and IGF-I in combination may have important roles in promotion of periodontal litgment healing, and consequently, may useful for clinical application in periodontal regenerative procedures.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.5
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• pp.394-404
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• 2007

Oral squamous cell carcinoma is the most prevalent oral cancer, which is characterized by its high metastasis and recurrent rates and poor prognosis. Taxol is an anticancer agent which is microbial products extracted from jew tree. It combines with the tubulin and induces apoptosis by inhibiting mitosis of cell with microtubule stabilization. Recently, it was reported to be effective in various solid tumors, but only very slight effect has been seen in oral squamous cell carcinomas due to its cell-specific potencies. Cyclosporin A is used as immune suppressant and is being applied in anticancer therapy as its mechanism of induction of change of apoptotic process in various cells have been known. In this study, oral squamous cell carcinoma HN22 cell line was used for in vitro experiment and as for the experimental group taxol and cyclosporin A were applied alone and to observe the synergistic effect of apoptosis, Taxol and cyclosporin A were coadministered with different concentration of taxol for comparison. The results were obtained as follow: 1. There was no difference in Bcl-2, Bax, caspase 3, 8, 9 mRNA expression when cyclosprin A or taxol was applied alone to HN 22 cell line. 2. Caspase 3, 9 mRNA expression was prominently increased when cyclosprin A and taxol were applied together to cancer cell. 3. No significant difference was observed when cyclosporin A and taxol($1{\mu}g/ml$ and $3{\mu}g/ml$) were applied together to cancer cell line. 4. No significant difference was seen in Bcl-2, Bax, and caspase 8 mRNA expression in all the groups of in vitro experiments. 5. When cyclosporin A was applied alone in vivo study on the nude mice, histopathologi cal findings was similar to those of the control group. Oral squamous cell carcinoma induced by inoculation of HN 22 cell line was not reduced after treatment of cyclosporin A. 6. When taxol was applied alone, the islands of squamous cell carcinoma still remained, which meant insignificant healing effect. There was a lesser volume increase compared with the cyclosporin A alone. 7. When taxol and cyclosporin A were applied together, the connective tissue and calcification were seen in the histopathologic findings. Oral squamous cell carcinoma was decreased and cancer cell was disappeared. In observing the tumor mass change with time, there was a gradual decreased size and healing features. As the results of the in vitro experiment, it could conclud that only when the two agents are applied together, mitochondria-mediated apoptosis occurred by considerable increase of caspase 3, 9 mRNA expression, irrespectable of the concentration of taxol. In vivo experiment, there was a discrete synergistic effect when the two agents were applied together. But single use of cyclosporin A was not effective in this study. Based on the results of this experiment, if further clinical studies are done, taxol and cyclosporin A could be effectively used in treatment of oral squamous cell carcinomas.

• Journal of Life Science
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• v.32 no.10
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• pp.749-761
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• 2022

This study evaluated the antioxidizing and antiproliferative effects of Angelica japonica extract and its solvent-partitioned fractions. A dried sample of the halophyte A. japonica was extracted twice using methylene chloride (CH₂Cl₂) and extracted twice again using methanol (MeOH). The combined crude extracts were then fractionated by solvent polarity into distilled water (water), n-butanol (n-BuOH), 85% aqueous methanol (85% aq.MeOH), and n-hexane fractions. The antioxidant activities of the crude extracts and their solvent-partitioned fractions were assessed according to their DPPH radical and peroxynitrite scavenging abilities, formation of intracellular reactive oxygen species (ROS), DNA oxidation, NO production, and ferric reducing antioxidant power (FRAP). The crude extract showed significant antioxidant activity in the overall antioxidizing bioassay systems. Among solvent-partitioned fractions, good antioxidant activities were observed in n-BuOH and 85% aq.MeOH fractions and significantly correlated with the polyphenol and flavonoid contents of the samples. Furthermore, all samples tested, including the crude extract, not only showed cytotoxic effects against human cancer cells (AGS, HT-29, MCF-7, and HT-1080) but also prevented cell migration in a dose-dependent manner in the wound healing assay using HT 1080. Among the solvent-partitioned fractions, the 85% aq.MeOH fraction most effectively inhibited the invasion of HT-1080 cells. Therefore, these results suggest that A. japonica may be a potential antioxidizing and antiproliferative agent.

• Journal of Veterinary Science
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• v.24 no.3
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• pp.44.1-44.17
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• 2023

Background: Antibiotic resistance is a significant public health concern around the globe. Antimicrobial peptides exhibit broad-spectrum and efficient antibacterial activity with an added advantage of low drug resistance. The higher water content and 3D network structure of the hydrogels are beneficial for maintaining antimicrobial peptide activity and help to prevent degradation. The antimicrobial peptide released from hydrogels also hasten the local wound healing by promoting epithelial tissue regeneration and granulation tissue formation. Objective: This study aimed at developing sodium alginate based hydrogel loaded with a novel antimicrobial peptide Chol-37(F34-R) and to investigate the characteristics in vitro and in vivo as an alternative antibacterial wound dressing to treat infectious wounds. Methods: Hydrogels were developed and optimized by varying the concentrations of crosslinkers and subjected to various characterization tests like cross-sectional morphology, swelling index, percent water contents, water retention ratio, drug release and antibacterial activity in vitro, and Pseudomonas aeruginosa infected wound mice model in vivo. Results: The results indicated that the hydrogel C proved superior in terms of cross-sectional morphology having uniformly sized interconnected pores, a good swelling index, with the capacity to retain a higher quantity of water. Furthermore, the optimized hydrogel has been found to exert a significant antimicrobial activity against bacteria and was also found to prevent bacterial infiltration into the wound site due to forming an impermeable barrier between the wound bed and external environment. The optimized hydrogel was found to significantly hasten skin regeneration in animal models when compared to other treatments in addition to strong inhibitory effect on the release of pro-inflammatory cytokines (interleukin-1β and tumor necrosis factor-α). Conclusions: Our results suggest that sodium alginate -based hydrogels loaded with Chol-37(F34-R) hold the potential to be used as an alternative to conventional antibiotics in treating infectious skin wounds.