• Biomolecules & Therapeutics
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• v.23 no.5
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• pp.434-441
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• 2015

Histone deacetylase (HDAC) inhibitors are considered novel agents for cancer chemotherapy. We previously investigated MHY219, a new HDAC inhibitor, and its potent anticancer activity in human prostate cancer cells. In the present study, we evaluated MHY219 molecular mechanisms involved in the regulation of prostate cancer cell migration. Similar to suberanilohydroxamic acid (SAHA), MHY219 inhibited HDAC1 enzyme activity in a dose-dependent manner. MHY219 cytotoxicity was higher in LNCaP ($IC_{50}=0.67{\mu}M$) than in DU145 cells ($IC_{50}=1.10{\mu}M$) and PC3 cells ($IC_{50}=5.60{\mu}M$) after 48 h of treatment. MHY219 significantly inhibited the HDAC1 protein levels in LNCaP and DU145 cells at high concentrations. However, inhibitory effects of MHY219 on HDAC proteins levels varied based on the cell type. MHY219 significantly inhibited LNCaP and DU145 cells migration by down-regulation of matrix metalloprotease-1 (MMP-1) and MMP-2 and induction of tissue inhibitor of metalloproteinases-1 (TIMP-1). These results suggest that MHY219 may potentially be used as an anticancer agent to block cancer cell migration through the repression of MMP-1 and MMP-2, which is related to the reduction of HDAC1.

• The Korean Journal of Physiology and Pharmacology
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• v.16 no.6
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• pp.387-392
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• 2012

In this study, we examined the antinociceptive effect of Cyperi rhizoma (CR) and Corydalis tuber (CT) extracts using a chronic constriction injury-induced neuropathic pain rat model. After the ligation of sciatic nerve, neuropathic pain behavior such as mechanical allodynia and thermal hyperalgesia were rapidly induced and maintained for 1 month. Repeated treatment of CR or CT (per oral, 10 or 30 mg/kg, twice a day) was performed either in induction (day 0~5) or maintenance (day 14~19) period of neuropathic pain state. Treatment of CR or CT at doses of 30 mg/kg in the induction and maintenance periods significantly decreased the nerve injury-induced mechanical allodynia. In addition, CR and CT at doses of 10 or 30 mg/kg alleviated thermal heat hyperalgesia when they were treated in the maintenance period. Finally, CR or CT (30 mg/kg) treated during the induction period remarkably reduced the nerve injury-induced phosphorylation of NMDA receptor NR1 subunit (pNR1) in the spinal dorsal horn. Results of this study suggest that extracts from CR and CT may be useful to alleviate neuropathic pain.

• Restorative Dentistry and Endodontics
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• v.46 no.4
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• pp.48.1-48.10
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• 2021

Objectives: This study aimed to evaluate the effects on bone repair of different concentrations of mineral trioxide aggregate (MTA) added to AH Plus. Materials and Methods: Bone tissue reactions were evaluated in 30 rats (Rattus norvegicus) after 7 and 30 days. In the AH + MTA10, AH + MTA20, and AH + MTA30 groups, defects in the tibiae were filled with AH Plus with MTA in proportions of 10%, 20% and 30%, respectively; in the MTA-FILL group, MTA Fillapex was used; and in the control group, no sealer was used. The samples were histologically analyzed to assess bone union and maturation. The Kruskal-Wallis and Mann-Whitney tests were performed for multiple pairwise comparisons (p ≤ 0.05). Results: At the 7-day time point, AH + MTA10 was superior to MTA-FILL with respect to bone union, and AH + MTA20 was superior to MTA-FILL with respect to bone maturity (p < 0.05). At the 30-day time point, both the AH + MTA10 and AH + MTA20 experimental sealers were superior not only to MTA-FILL, but also to AH + MTA30 with respect to both parameters (p < 0.05). The results of the AH + MTA10 and AH + MTA20 groups were superior to those of the control group for both parameters and experimental time points (p < 0.05). Conclusions: The results suggest the potential benefit of using a combination of these materials in situations requiring bone repair.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.6
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• pp.531-548
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• 2006

The purpose of this study was to investigate the biomechanical, histologic findings of distracted regenerate and TMJ response in modified distraction osteogenesis (DO) technique combined with compression force as biomechanical stimulation method which has been suggested in 2002, and developed thereafter by authors. This study was performed with two experiments. First experiment was designed to explore the optimal ratio of compression force versus distraction force for the new DO technique. Second experiment was planned to evaluate the reaction of TMJ tissue, especially condyle, disc after application of the DO technique with compression force. Total 52 New Zealand adult male-rabbits with 3.0kg body weight were used for the study. For the first study, 30 adult male-rabbits underwent osteotomy at one side of mandibular body and a external distraction device was applied on each rabbit with same manner. In the control group of 10 rabbits, final 8 mm of distraction with 1 mm rate per day was done with conventional DO technique after 5 latency days. For the experimental group of 20 rabbits, a compression force with 1 mm rate per day was added to the distracted mandible on 3-latency day after over-distraction (over-lengthening). As the amount of the rate of compression versus distraction, experimental subgroup I (10 rabbits) was set up as 2 mm compression versus 10 mm distraction (1/5) and experimental subgroup II (10 rabbits) was set up as 3 mm compression versus 11 mm distraction (about 1/3). All 30 rabbits were set up to obtain final 8 mm distraction and sacrificed on postoperative 55 day to analysis on biomechanical, and histologic findings of the bone regenerates. For second study, 22 adult male-rabbits were used to evaluate TMJ response after the DO method application with compression force. In the control group, 10 rabbits was used to be performed with conventional DO method, on the other hand, in a experimental group of 10 rabbits, 10 mm distraction with 2 mm compression (1/5 ratio) was done. The remaining 2 rabbits served as the normal control group. Histomorphologic examinations on both condyle, histological studies on condyle, disc were done at 1, 2, 3, 4, 7 weeks after distraction force application. The results were as follows: 1. On the bone density findings, the experimental group II (force ratio - 1/3) showed higher bone density than the other experimental group (force ratio - 1/5) and control group (control group - $0,2906\;g/cm^2$, experimental group I - $0.2961\;g/cm^2$, experimental group II - $0.3328\;g/cm^2$). 2. In the histologic findings, more rapid bone maturation like as wide lamellar bone site, more trabeculae formation was observed in two experimental groups compared to the conventional DO control group. 3. In morphologic findings of condyle, there were no differences of size and architecture in the condyle in the control and experimental groups. 4. In histologic findings of condyles, there were thicker fiberous and proliferative layers in experimental group than those of control group until 2 weeks after distraction with compression force. But, no differences were seen between two groups on 3, 4, 7 weeks after compression. 5. In histologic findings of disc, more collagen contents in extracellular matrix, more regular fiber bundles, and less elastin fibers were seen in experimental group than control group until 2 weeks after distraction with compression. But, no differences were seen between two groups on 3, 4, 7 weeks after distraction with compression. From this study, we could identify that the new distraction osteogenesis technique with compression stimulation might improve the quality of bone regeneration. The no remarkable differences on TMJ response between control and experimental groups were seen and TMJ tissues were recovered similarly to normal TMJ condition after 3 weeks.

• Journal of Periodontal and Implant Science
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• v.28 no.4
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• pp.545-559
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• 1998

Magnoliae cortex has been used as a drug for treatment of fractures in Chinese medicine and safflower(Carthamus tinctorius $Linn{\acute{e}}$) has been traditionally used for treatment of blood stasis. The purpose of present study was to examine the biologic effects of magnoliae cortex extract and safflower extract mixture(MSM) on human periodontal ligament cells and fetal rat calvarial osteoblasts and on healing of rat calvarial defects. The ethanolic extracts of magnoliae cortex(MCE), safflower seed(SSE), Zea May L(ZML) were prepared as positive control group. MSM mixed to the ratios of 1 : 1, 1 : 2, 1 : 5 and 1 : 10 were used as test group. The effects of each agents on the growth and survival, ALPase activity, cell proliferation and tissue regenerative effect of each extracts was evaluated by histomorphometric measuring of newly formed bone on the 8 mm defect in rat calvaria after oral administration of 2 ratio groups(1 : 5 and 1 : 10) at 3 different doses (0.1, 0.25 and 0.5g/kg per day). MSM stimulated the growth and survival rate of osteoblasts and PDL cells more than any other agents. The growth and survival rate were increased as the proportion of safflower seed extract was increased. MCE, SSE, ZML stimulated the ALPase activity of osteoblast and PDL cell in comparison to the negative control group. But all groups of MSM regardless of ratio of safflower seed extract stimulated the ALPase activity than any other agent. The ALPase activity was also increased as the proportion of safflower seed extract was increased. Although MCE, SSE, ZML stimulated the proliferation of osteoblasts. 1 : 5 and 1 : 10 ratio MSM showed significant increase in stimulation of proliferation of osteoblasts. No agent significantly increased proliferation of PDL cells. Significant new bone formation were seen where 1 : 5 ratio, 0.5g/kg group and 1 : 10 ratio, 0.25, 0.5g/kg groups were used. These results show that magnoliae cortex extract and safflower seed extract mixture can potentially increase bone regeneration ability.

• Advances in pediatric surgery
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• v.3 no.2
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• pp.98-107
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• 1997

To determine whether bile juice exclusion can prevent the mucosal damage, and Insulin-like growth factor-I can promote mucosal regeneration in ischemia-reperfusion injury of the bowel, 39 weanling rats with 10 cm of Thiry-Vella loop were studied. Animal groups were; Control, BL(common bile duct ligation), IGF{insulin-like growth factor-I(IGF-I) infusion} and IGF-BL(combined treatment). IGF-I(1.5 mg/kg/day) was continuously delivered through a subcutaneously implanted miniosmotic pump. After 15 minutes of superior mesenteric artery clamping, a tissue specimen(P) was taken after 30 minutes of reperfusion. Intestinal continuity was restored to allow oral feeding. A specimen of main tract(M) and another of the Thiry-Vella loop(T) were collected for histomorphometry after 48 hours of reperfusion and free feeding. Villus size ratio(VSR), crypt depth(CD), crypt-depth/villus-height ratio(CVR) and injury score(IS) were measured in 15 consecutive villi. The postoperative mortalities of bile duct ligation groups(BL and IGF-BL) were higher than those of other groups. In control group, VSR of M was lower(P<0.05) than P or T, but not in the other groups. VSR of M in control was lower than those in other groups. CD of T in control, IGF and IGF-BL group were higher than those of M. CD of M and T showed gradual increments from control, IGF and IGF-BL group, respectively. CVR of M and T in IGF group were higher than those in control. CVR in IGF-BL group, T was higher than M, and M was higher than P. About IS, M of BL($20.1{\pm}2.5$) and IGF-BL($20.9{\pm}3.3$) groups were significantly lower than that of control($32.4{\pm}2.5$). These results suggest that the exclusion of bile juice reduces the severity of the reperfusion injury of the mucosa, by inability to activate pancreatic enzymes and IGF-I stimulates mucosal regeneration in injured bowel, and the effect is potentiated by bile juice exclusion.

• Journal of Periodontal and Implant Science
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• v.38 no.2
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• pp.125-134
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• 2008

Purpose: Bone morphogenetic protein (BMP) is a potent differentiating agent for cells of the osteoblastic lineage. It has been used in the oral cavity under a variety of indications and with different carriers. However, the optimal carrier for each indication is not known. This study evaluated the bone regenerative effect of rhBMP-2 delivered with different carrier systems. Materials and Methods: 8 mm critical-sized rat calvarial defects were used in 60 male Sprague-Dawley rats. The animals were divided into 6 groups containing 10 animals each. Two groups were controls that had no treatment and absorbable collagen membrane only. 4 groups were experimentals that contained rhBMP-2 only and applied with absorbable collagen sponge($Collatape^{(R)}$), $MBCP^{(R)}$, Bio-$Oss^{(R)}$ each. The histological and histometric parameters were used to evaluate the defects after 2- or 8-week healing period. The shape and total augmented area were stable in all groups over the healing time. Results: New bone formation was significantly greater in the rhBMP-2 with carrier group than control group. rhBMP-2/ACS was the highest in bone density but gained less new bone area than rhBMP-2/$MBCP^{(R)}$ and rhBMP-2/Bio-$Oss^{(R)}$. The bone density after 8 weeks was greater than that after 2 weeks in all groups. However, rhBMP-2 alone failed to show the statistically significant difference in new bone area and bone density compared to control group. Also $MBCP^{(R)}$ and Bio-$Oss^{(R)}$ particles remained after 8 weeks healing period. Conclusion: These results suggest that rhBMP-2 with carrier system is an excellent inductive agent for bone formation and we can use it as the predictable bone tissue engieering technique. Future study will likely focus on the kinetics of BMP release and development of carriers that is ideal for it.

• Journal of Periodontal and Implant Science
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• v.37 no.2
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• pp.181-192
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• 2007

Periodontal surgery as part of the treatment of periodontal disease is mainly performed 1) to gain access to diseased areas for adequate cleaning; 2) to achieve pocket reduction or elimination; and 3) to restore the periodontal tissues lost through the disease; i.e., a new attachment formation of periodontal regeneration. To accomplish the latter, often referred to as the ultimate goal of periodontal therapy, a number of surgical procedures have been advocated throughout the years. Clinical studies have demonstrated that considerable gain of clinical attachment and bone can be achieved following guided tissue regeneration (GTR) therapy of intrabony defects. The aim of this study was to analyse the radiographic bone changes 2-year after GTR using a bone graft material and nonresorbable membrane. Patients attending the department of periodontics of Kyungpook National University Hospital were studied. Patients had clinical and radiographic evidence of intrabony defect(s), 33 sites of 30 patients aged 32 to 56 (mean age 45.6) were treated by GTR with a bone graft material and nonresorbable membrane. Baseline and 2-year follow-up radiographs were collected and evaluated for this study. Radiographic assessment includes a bone fill, bone crest change, defect resolution, and % of defect resolution. Pre- and post-treatment differences between variables (maxilla and mandible, defect depth, defect angle, bone graft materials) using the paired t-test were examined. We observed $2.86{\pm}1,87mm$ of bone fill, $065{\pm}0.79mm$ of crestal resorption, $3.49{\pm}2.11mm$ of defect resolution, and $44.42{\pm}19.51%$ of percentage of defect resolution. Mandible, deeper initial defect depth, narrower initial defect angle showed greater bone fill, defect resolution, and % of defect resolution. But no difference was observed between xenograft and allograft. Outcome of GTR as a therapy of intrabony defect was better than other therapy, but herein, good oral hygiene maintenance as a anti-infective treatment and periodic recall check of patients are essential.

• Nutrition Research and Practice
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• v.10 no.1
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• pp.11-18
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• 2016

BACKGROUND/OBJECTIVES: Type 2 diabetes (T2D) is more frequently diagnosed and is characterized by hyperglycemia and insulin resistance. $\small{D}$-xylose, a sucrase inhibitor, may be useful as a functional sugar complement to inhibit increases in blood glucose levels. The objective of this study was to investigate the anti-diabetic effects of $\small{D}$-xylose both in vitro and stretpozotocin (STZ)-nicotinamide (NA)-induced models in vivo. MATERIALS/METHODS: Wistar rats were divided into the following groups: (i) normal control; (ii) diabetic control; (iii) diabetic rats supplemented with a diet where 5% of the total sucrose content in the diet was replaced with $\small{D}$-xylose; and (iv) diabetic rats supplemented with a diet where 10% of the total sucrose content in the diet was replaced with $\small{D}$-xylose. These groups were maintained for two weeks. The effects of $\small{D}$-xylose on blood glucose levels were examined using oral glucose tolerance test, insulin secretion assays, histology of liver and pancreas tissues, and analysis of phosphoenolpyruvate carboxylase (PEPCK) expression in liver tissues of a STZ-NA-induced experimental rat model. Levels of glucose uptake and insulin secretion by differentiated C2C12 muscle cells and INS-1 pancreatic ${\beta}$-cells were analyzed. RESULTS: In vivo, $\small{D}$-xylose supplementation significantly reduced fasting serum glucose levels (P < 0.05), it slightly reduced the area under the glucose curve, and increased insulin levels compared to the diabetic controls. $\small{D}$-xylose supplementation enhanced the regeneration of pancreas tissue and improved the arrangement of hepatocytes compared to the diabetic controls. Lower levels of PEPCK were detected in the liver tissues of $\small{D}$-xylose-supplemented rats (P < 0.05). In vitro, both 2-NBDG uptake by C2C12 cells and insulin secretion by INS-1 cells were increased with $\small{D}$-xylose supplementation in a dose-dependent manner compared to treatment with glucose alone. CONCLUSIONS: In this study, $\small{D}$-xylose exerted anti-diabetic effects in vivo by regulating blood glucose levels via regeneration of damaged pancreas and liver tissues and regulation of PEPCK, a key rate-limiting enzyme in the process of gluconeogenesis. In vitro, $\small{D}$-xylose induced the uptake of glucose by muscle cells and the secretion of insulin cells by ${\beta}$-cells. These mechanistic insights will facilitate the development of highly effective strategy for T2D.

• Implantology
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• v.22 no.4
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• pp.242-254
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• 2018

The aim of the current study was to evaluate the results of horizontal guided bone regeneration (GBR) with xenograf t (deproteinized bovine bone mineral, DBBM), allograf t (irradiated allogenic cancellous bone and marrow), titanium membrane, resorbable collagen membrane, and advanced platelet-rich fibrin (A-PRF) in the anterior maxilla. The titanium membrane was used in this study has a three-dimensional (3D) shape that can cover ridge defects. Case 1. A 32-year-old female patient presented with discomfort due to mobility and pus discharge on tooth #11. Three months after extracting tooth #11, diagnostic software (R2 GATE diagnostic software, Megagen, Daegu, Korea) was used to establish the treatment plan for implant placement. At the first stage of implant surgery, GBR for horizontal augmentation was performed with DBBM ($Bio-Oss^{(R)}$, Geistlich, Wolhusen, Switzerland), irradiated allogenic cancellous bone and marrow (ICB $cancellous^{(R)}$, Rocky Mountain Tissue Bank, Denver, USA), 3D-titanium membrane ($i-Gen^{(R)}$, Megagen, Daegu, Korea), resorbable collagen membrane (Collagen $membrane^{(R)}$, Genoss, Suwon, Korea), and A-PRF because there was approximately 4 mm labial dehiscence after implant placement. Five months after placing the implant, the second stage of implant surgery was performed, and healing abutment was connected after removal of the 3D-titanium membrane. Five months after the second stage of implant surgery was done, the final prosthesis was then delivered. Case 2. A 35-year-old female patient presented with discomfort due to pain and mobility of implant #21. Removal of implant #21 fixture was planned simultaneously with placement of the new implant fixture. At the first stage of implant surgery, GBR for horizontal augmentation was performed with DBBM ($Bio-Oss^{(R)}$), irradiated allogenic cancellous bone and marrow (ICB $cancellous^{(R)}$), 3D-titanium membrane ($i-Gen^{(R)}$), resorbable collagen membrane (Ossix $plus^{(R)}$, Datum, Telrad, Israel), and A-PRF because there was approximately 7 mm labial dehiscence after implant placement. At the second stage of implant surgery six months after implant placement, healing abutment was connected after removing the 3D-titanium membrane. Nine months after the second stage of implant surgery was done, the final prosthesis was then delivered. In these two clinical cases, wound healing of the operation sites was uneventful. All implants were clinically stable without inflammation or additional bone loss, and there was no discomfort to the patient. With the non-resorbable titanium membrane, the ability of bone formation in the space was stably maintained in three dimensions, and A-PRF might influence soft tissue healing. This limited study suggests that aesthetic results can be achieved with GBR using 3D-titanium membrane and A-PRF in the anterior maxilla. However, long-term follow-up evaluation should be performed.