• Molecules and Cells
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• v.43 no.7
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• pp.662-670
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• 2020

We have investigated the involvement of the pre-mRNA processing factor 4B (PRP4) kinase domain in mediating drug resistance. HCT116 cells were treated with curcumin, and apoptosis was assessed based on flow cytometry and the generation of reactive oxygen species (ROS). Cells were then transfected with PRP4 or pre-mRNA-processing-splicing factor 8 (PRP8), and drug resistance was analyzed both in vitro and in vivo. Furthermore, we deleted the kinase domain in PRP4 using Gateway™ technology. Curcumin induced cell death through the production of ROS and decreased the activation of survival signals, but PRP4 overexpression reversed the curcumin-induced oxidative stress and apoptosis. PRP8 failed to reverse the curcumin-induced apoptosis in the HCT116 colon cancer cell line. In xenograft mouse model experiments, curcumin effectively reduced tumour size whereas PRP4 conferred resistance to curcumin, which was evident from increasing tumour size, while PRP8 failed to regulate the curcumin action. PRP4 overexpression altered the morphology, rearranged the actin cytoskeleton, triggered epithelial-mesenchymal transition (EMT), and decreased the invasiveness of HCT116 cells. The loss of E-cadherin, a hallmark of EMT, was observed in HCT116 cells overexpressing PRP4. Moreover, we observed that the EMT-inducing potential of PRP4 was aborted after the deletion of its kinase domain. Collectively, our investigations suggest that the PRP4 kinase domain is responsible for promoting drug resistance to curcumin by inducing EMT. Further evaluation of PRP4-induced inhibition of cell death and PRP4 kinase domain interactions with various other proteins might lead to the development of novel approaches for overcoming drug resistance in patients with colon cancer.

• Pediatric Infection and Vaccine
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• v.10 no.1
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• pp.71-80
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• 2003

Purpose : Four kinds of Haemophilus influenzae type b protein conjugate vaccines, PRPD, PRP-T, PRP-OMP and PRP-CRM197, have been developed, and PRP-T vaccines are currently produced by two manufacturer, $ActHib^{(R)}$ by Aventis and $Hiberix^{TM}$ by GlaxoSmith-Kline Biologicals. The purpose of this study is to evaluate the immunogenicity and safety of $Hiberix^{TM}$ in Korean infants. Methods : Seventy-three healthy infants(43 male infants) were recruited for this study after parental informed consent was obtained. Each infant was vaccinated at 2, 4 and 6 months of age with the study vaccine. At each visit, infants were also immunized with DTaP, trivalent oral polio vaccine and hepatitis B vaccine when indicated. The serum anti-PRP antibody was measured at prevaccination, 2 month later after the 2nd dose, and 1 month later after the 3rd dose by the ELISA method. The local and systemic adverse reactions of vaccination were monitored for 3 consecutive days after each immunization. Immunogenicity of vaccine was evaluated in infants who received all the scheduled immunization and the adverse reactions were evaluated for infants who received at least one dose of the study vaccine. Results : Among seventy three infants, enrolled in this study; sixty three(37 male infants) completed all the scheduled immunizations. The geometric mean titer(GMT) of anti-PRP antibodies at prevaccination was 0.17 ${\mu}g/mL$(95% confidence interval[CI]; 0.13~0.22). The GMT of anti-PRP antibodies increased to 4.14 ${\mu}g/mL$(95% CI; 2.65~6.48) at 2 month later after the 2nd dose of PRP-T and 14.65 ${\mu}g/mL$(95% CI; 10.83~19.81) at 1 month later after the 3rd dose. Anti-PRP antibody ${\geq}0.15$ ${\mu}g/mL$, was observed in 98.4%(95% CI; 91.8~100) after 2 doses and 100%(95% CI; 100~100) after 3 doses. Anti-PRP antibody ${\geq}1.0$ ${\mu}g/mL$, was obtained in 77.8%(95% CI; 67.5~88.0) after 2 doses, and 98.4%(95% CI; 95.3~100) after 3 doses. Most of the adverse reaction after vaccination were mild. Irritability, the most common systemic reaction, was observed in 45.5%, followed by drowsiness(30.5%), poor feeding(26.7%) and fever(5.6%). Among the local reactions tenderness was observed in 7.9%, redness(${\geq}5$ mm) in 2.8% and swelling(${\geq}5$ mm) in 1.8%. Conclusion : The PRP-T vaccine used in this study was highly immunogenic and safe in Korean young infants. The finding that high GMT and high frequency of infants with a protective titer achieved after 2 doses is consistent with the previous studies which were done with a PRP-T vaccine of other manufacturer. This study suggests that the immunization schedule of PRP-T vaccine for Korean infants may need re-evaluation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.29 no.2
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• pp.113-122
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• 2007

Purpose: Platelet-rich plasma (PRP) is known to accelerate and/or enhance hard and soft tissue healing and regeneration. As such, PRP has been used in various clinical fields of surgery. Recently there have been several attempts to use PRP in the field of tissue engineering. However, some controversies still exist on exact mechanism and benefits of PRP. Therefore various animal experiments are necessary to reveal the effect of the PRP. However, even if animal experiment is performed, the efficacy of the experiment could not be validated due to absence of an animal PRP model. The purpose of this study is to establish rat PRP model by comparing several PRP fabricating methods, and to assay growth factor concentration in the PRP. Materials and methods: Rat blood samples were collected from nine SD rat (body weight: 600-800g). PRP was prepared using three different PRP fabricating methods according to previously reported literatures. (Method 1: 800 rpm, 15 minute, single centrifuge; Method 2: 1000 rpm, 10 minute, double centrifuge; Method 3: 3000 rpm, 4min and 2500 rpm, 8 min, double centrifuge). Platelet counts were evaluated in an automated machine before and after PRP fabrications. In terms of growth factor assay, prepared PRP were activated with 100 unit thrombin and 10% calcium chloride. Growth factor (PDGF-BB, VEGF) concentrations on incubation time were determined by sandwich-ELISA technique. Results: An average of 3ml (via infraorbital venous plexus) to 15ml (via celiac axis) the rat blood could be collected. By using Method 3 (3000 rpm, 4 min and 2500 rpm, 8 min, double centrifugation), around 1.5ml of PRP could be prepared. This method allowed us to concentrate platelet 3.77-fold on average. PDGF-BB concentration (mean, 1942.10 pg/ml after 1 hour incubation) and VEGF concentration (mean, 952.71 pg/ml after 1 hour incubation) in activated PRP were higher than those in untreated blood. Also PDGF-BB showed constant concentration during 4-hour incubation, while VEGF concentration was decreased after 1 hour. Conclusion: Total 11,000 g minute separation and condensation double centrifuge method can produce efficient platelet-rich plasma. Platelet-rich plasma activated with thrombin has showed higher concentrations of growth factors such as PDGF-BB and VEGF, compared to the control group. Platelet-rich plasma model in a rat model was confirmed in this study.

• Journal of Veterinary Clinics
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• v.36 no.4
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• pp.200-206
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• 2019

This study was performed to assess the anti-inflammatory and cartilage regenerative effects of platelet-rich plasma (PRP) on canine chondrocytes. Proliferation and migration assays under both normal and lipopolysaccharide (LPS)-induced inflammatory conditions were performed with various concentrations of PRP (1% to 10%). The expression levels of genes related to osteoarthritis were evaluated in the following groups: PRP group, LPS group and LPS + PRP group. mRNA expression levels were detected using real-time polymerase chain reaction (RT-PCR). Proliferation assays showed significantly enhanced proliferation in all PRP-treated groups compared with the no serum group. Compared with 10% fetal bovine serum (FBS), PRP concentrations above 3% in the normal condition and 1% to 7% PRP in the LPS-induced inflammatory condition were found to significantly promote chondrocyte proliferation. In the normal condition, all PRP-treated groups showed significantly increased cell migration compared with the no serum group. Chondrocyte migration was decreased with LPS-induced inflammation, but PRP treatment resulted in significantly enhanced migration compared with the other groups in this condition. According to RT-PCR, the LPS + PRP group showed significantly higher levels of COL1A1, IL-6, aggrecan and lower levels of $TNF-{\alpha}$, MMP-1, MMP-3 mRNA expression compared to the LPS group. The results of this study suggest that PRP application can enhance the proliferation and migration of canine chondrocytes and improve canine articular cartilage regeneration.

• The Journal of Korean Academy of Prosthodontics
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• v.39 no.6
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• pp.659-681
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• 2001

Platelet-rich plasma(PRP) has been known to increase the rate and degree of bone formation by virtue of growth factors in concentrated platelets. Although its great healing effect on bone defect or pre-implantation site preparation in conjunction with bone substitute has been reported, the effect associated with implant is unknown. The purpose of this study was to investigate the effect of PRP on rapid osseointegration of endosseous dental implants in the rabbit tibiae. Twenty two adult female New Zealand white rabbits, weighing approximately 2.7-3.3kg, were used for this study. Twelve of the 22 animals were used for histomorphometric analysis and ten of the 22 were for removal torque test. Each animal received two implants in each tibia (two treated with PRP and two as control) and was given fluorochrome intramuscularly. For histomorphometric analysis, rabbits were divided into four groups according to the healing period. At 1 week, 2 weeks, 4 weeks and 8 weeks postoperatively, each three animals were sacrificed serially and the amount and rate of bone formation around dental implant were examined on the undecalcified sections under fluorescent microscope, polarized microscope and light microscope connected to a personal computer equipped with image analysis system. For removal torque test, rabbits were divided into two groups and removal torque tests were performed at 4 weeks, 10 weeks after implant placement. In total, 88 screw shaped, commercially pure titanium implants (Neoplant, Neobiotech, Seoul, Korea) were used in this study. Labeling pattern reflected differences of two groups in bone formation rate at each period. Histomorphometrically, PRP group showed significantly higher bone volume within threads compared to control group at 2 weeks ($70.30{\pm}4.96%$ vs. $50.68{\pm}6.33%$; P < .01) and 4 weeks ($82.59{\pm}5.94%$ vs. $72.94{\pm}4.57%$; P < .05 ). PRP group at 1, 2 and 4 weeks revealed similar degree of bone volume formation comparable to control group at 2, 4 and 8 weeks, respectively. On the other hand, while PRP group showed higher bone-implant contact ($47.37{\pm}8.09%$) than control group ($33.16{\pm}13.47%$) at 2 weeks, there were no significant differences between PRP group and control group for any experimental period. Removal torque values also showed no significant differences between PRP group and control group at any experimental period (P > .05). These findings imply that PRP could induce rapid, more bone formation around implant during early healing period and get faster secondary stability for reducing healing period, though it has not induced bone maturation enough to resist functional loading.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.417-433
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• 2006

Purpose : Platelet rich plasma (PRP) is an autologous material with many growth factors, such as BMPs, PDGF, $TGF-{\beta}_1$, $TGF-{\beta}_2$, VEGF, and IGF, facilitating bone healing process. The prominent osteoconductive activity and the biodegradable nature of beta-tricalciumphosphate (${\beta}-TCP$) for bone grafts in animal experiments have been reported. The purpose of this study was to evaluate the effect of PRP on the osteogenesis of ${\beta}-TCP$. Materials & Methods : Two artificial calvarial bone defects were made in 32 rabbits which were divided into 2 groups. In one group of 16 rabbits, autogenous bone / ${\beta}-TCP$ was grafted on each side of cranial bone defect. In the other group of 16 rabbits, mixture of ${\beta}-TCP$ and PRP / PRP alone was grafted on each side of the cranial bone defect. The animals were sacrificed at 2, 4, 8, and 12 weeks after surgery. The specimens were harvested and examined histologically and immunohistochemically by the expression of BMP2/4/7, PDGF, VEGF and $TGF-{\beta}_1$. Results : The mean volume of new bone formation was significantly higher at 4, 8, 12 weeks in autogenous graft than that in ${\beta}-TCP$. The BMP2/4 expression was significantly higher at 4 weeks in autogenous bone graft and at 4 weeks in mixture of ${\beta}-TCP$ and PRP and at 12 weeks in ${\beta}-TCP$. The expression of BMP7, PDGF, VEGF and $TGF-{\beta}_1$ showed no significant difference in autogenous, ${\beta}-TCP$, mixture of ${\beta}-TCP$ and PRP, and PRP alone during grafted bone regeneration. Conclusion : The results showed that PRP had no additional value in promoting healing process of ${\beta}-TCP$ grafts.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.29 no.4
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• pp.219-225
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• 2003

Purpose: Platelet Rich Plasma(PRP) application is increasing with sinus inlay bone graft, but there is few research with radiographic ananlysis on effect of PRP in maxillary sinus. The author investigated the amount of bony changes of maxillary sinus for dental implantation among the patients with maxillary inlay graft. Materials and Methods: With 10 patients who were treated with sinus inlay autologous bone grafting combined with PRP technique, and with 5 patients who were treated with sinus inlay grafting only without PRP, the panoramic radiographys which were taken at preoperation, immediate postoperation, 3months postoperation, and 4 months postoperation(a month after dental implantation)periods were analysed. The films had been scanned, and then proceeded throughout image analysis system. The bone density of maxillary grafted sites was compared with adjacent tooth enamel density and remeasured according to density luminosity of each film. The density changes on PRP group and bone graft only group were analysed with non-parameteric statistics method. Results: In PRP combined patients group, bone density on postoperation periods was increased totally. The remarkable enhanced change of bone density was observed on 3 months postoperation period, thereafter the increasing rate was slightly reduced. In only bone graft patients group, bone density on postoperation periods was also increased compared with preoperation period, but the bone density of 4 months postoperation period was decreased compared with 3 months postoperation period. The amount of bone density on PRP group was significantly changed according to periods in contrast to bone graft only group. Conclusion: The bone density on PRP group was remarkably increased at 3 months postoperation compared to bone graft only group and it was seemed to be associated with more new bone formation, less grafted bone resorption at bone grafted sites with PRP.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.3
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• pp.221-226
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• 2007

Purpose The purpose of this study is to evaluation of effect on bone formation of PRP and fibrin sealant with deproteinized bovine bone(Bio-Oss) grafts on rabbit cranial defect. Material and Methods Twelve rabbits were used as experimental animal Two equal 9mm diameter cranial bone defects were created in each rabbit and immediately grafted with Bio-Oss only, Bio-Oss and PRP, and Bio-Oss and Fibrin sealant. Rabbits were sacrificed at 4 and 8 week. The defects were evaluated by histomorphometric analysis. Results Kruskal-Wallis tests were performed comparing new bone formation via histomorphometric analysis. No statistically significant difference of new bone formation was found between Bio-Oss only, Bio-Oss and PRP, and Bio-Oss and fibrin sealant at 4 and 8 weeks (P>0.05). Conclusion This study fails to find a stimulatory effect of PRP and Fibrin sealant on New bone formation of Bio-Oss grafts by histomorphometric analyses.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.27 no.6
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• pp.498-510
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• 2001

Distraction osteogenesis refers to the biological process responsible for new bone formation between bone segments by gradual distraction after osteotomy. For the past several years, various inconveniences including a protracted consolidation period that requires patients to wear a distractor frame longer, as well as higher medical costs, have not been remedied by improvements in osteotomy, distraction rate and monitoring system. Furthermore, side effects such as pin tract infections and soft tissue swelling may arise due to the long treatment period. These drawbacks form the rationale of this study which purports to seek a method by which the consolidation period can be reduced. This paper examines how platelet-rich plasma(PRP), known to facilitate osteogenesis, influences bone formation when applied in distracted area. Ten mongrel dogs, which were made to wear external distractor frames after osteotomy in both sides of the mandible, were used as subjects. After a 7day period of latency, distraction was carried out at a rate of 1mm/day for 14 consecutive days. After the onset of distraction, 2ml of PRP and a mixture of calcium gluconate and thrombine were injected into the center of the distracted callus on the left side of the mandible. The left was injected with PRP while the right side was set as the control site without PRP treatment. Execution at the onset of distraction and in 2 weeks, 4 weeks and 8 weeks after the consolidation period, clinical and radiographic tests, bone mineral density examination, histological examination and histomorphometric analysis were conducted to compare both sides. The results are summarized as follows: 1. Based on the clinical examination at two weeks, more remarkable cortical bone formation was found on the buccal and lingual side of the distracted area in the PRP treatment site than in the control site. No visual difference was found between the PRP treatment site and the control site at four eight weeks. 2. Based on the radiological examination, a distinct increase in the radiopaque appearance of the PRP treatment site was revealed at two weeks, but this increase appeared to slow down at four and eight weeks. 3. Examination of bone mineral density revealed a significant difference at two weeks with the PRP treatment site yielding density two times higher than the control site. This difference lessened after four weeks, and disappeared at eight weeks. 4. The histomorphometric examination revealed that about 20% more bony trabeculae area(20%, higher) was formed in the PRP treatment site than in the control site. In conclusion, it can be said that PRPs effect on stimulating bone formation in the PRP treatment site manifest as early as two weeks. Trabeculae formation likewise increased throughout the whole period. If this result can be applied to humans, the consolidation period can be reduced by injecting PRP into the distracted area.

• Clinics in Shoulder and Elbow
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• v.24 no.4
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• pp.215-223
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• 2021

Background: The objective of this study was to compare the efficacy of platelet-rich plasma (PRP) injection with an institution-based physical therapy (PT) program for adhesive capsulitis (AC) of the shoulder in patients with diabetes mellitus (DM). Methods: A total of seventy diabetic patients with AC of the shoulder for <6 months were assigned to two groups: PRP group and PT group. In the PRP group, 35 patients were administered a single shot of PRP (4 mL) into the glenohumeral joint. In the PT group, 35 patients were given institution-based PT that included 10 30-minute sessions of planned PT over a 2-week period. After the interventions, all patients were prospectively followed for 12 weeks. Intensity of shoulder pain, function, and range of motion were assessed at baseline and then at 3, 6, and 12 weeks. Results: Thirty-three patients in the PRP group and 32 in the PT group completed the 12-week study. At 12 weeks, patients who received PRP injections showed greater improvement in shoulder pain (p<0.001) than those recruited to the PT group. In the range of motion and shoulder function activities, patients in the PRP group showed significant improvement compared with the institution-based PT group (p<0.001). No significant complications were reported from any groups. Conclusions: In a diabetic population, PRP injections significantly improved shoulder pain and function compared with an institution-based PT program for shoulder AC. Additionally, it is a safe and well-tolerated method for AC management for diabetic patients.