• Journal of Veterinary Science
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• v.24 no.5
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• pp.69.1-69.11
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• 2023

Background: Kalkitoxin (KT) is an active lipopeptide isolated from the cyanobacterium Lyngbya majuscula found in the bed of the coral reef. Although KT suppresses cell division and inflammation, KT's mechanism of action in vascular smooth muscle cells (VSMCs) is unidentified. Therefore, our main aim was to investigate the impact of KT on vascular calcification for the treatment of cardiovascular disease. Objectives: Using diverse calcification media, we studied the effect of KT on VSMC calcification and the underlying mechanism of this effect. Methods: VSMC was isolated from the 6 weeks ICR mice. Then VSMCs were treated with different concentrations of KT to check the cell viability. Alizarin red and von Kossa staining were carried out to examine the calcium deposition on VSMC. Thoracic aorta of 6 weeks mice were taken and treated with different concentrations of KT, and H and E staining was performed. Real-time polymerase chain reaction and western blot were performed to examine KT's effect on VSMC mineralization. Calcium deposition on VSMC was examined with a calcium deposition quantification kit. Results: Calcium deposition, Alizarin red, and von Kossa staining revealed that KT reduced inorganic phosphate-induced calcification phenotypes. KT also reduced Ca⁺⁺-induced calcification by inhibiting genes that regulate osteoblast differentiation, such as runtrelated transcription factor 2 (RUNX-2), SMAD family member 4, osterix, collagen 1α, and osteopontin. Also, KT repressed Ca²⁺-induced bone morphogenetic protein 2, RUNX-2, collagen 1α, osteoprotegerin, and smooth muscle actin protein expression. Likewise, Alizarin red and von Kossa staining showed that KT markedly decreased the calcification of ex vivo ring formation in the mouse thoracic aorta. Conclusions: This experiment demonstrated that KT decreases vascular calcification and may be developed as a new therapeutic treatment for vascular calcification and arteriosclerosis.

• Molecules and Cells
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• v.46 no.10
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• pp.611-626
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• 2023

Acute myeloid leukemia (AML) is a heterogeneous disease caused by distinctive mutations in individual patients; therefore, each patient may display different cell-type compositions. Although most patients with AML achieve complete remission (CR) through intensive chemotherapy, the likelihood of relapse remains high. Several studies have attempted to characterize the genetic and cellular heterogeneity of AML; however, our understanding of the cellular heterogeneity of AML remains limited. In this study, we performed single-cell RNA sequencing (scRNAseq) of bone marrow-derived mononuclear cells obtained from same patients at different AML stages (diagnosis, CR, and relapse). We found that hematopoietic stem cells (HSCs) at diagnosis were abnormal compared to normal HSCs. By improving the detection of the DNMT3A R882 mutation with targeted scRNAseq, we identified that DNMT3A-mutant cells that mainly remained were granulocyte-monocyte progenitors (GMPs) or lymphoid-primed multipotential progenitors (LMPPs) from CR to relapse and that DNMT3A-mutant cells have gene signatures related to AML and leukemic cells. Copy number variation analysis at the single-cell level indicated that the cell type that possesses DNMT3A mutations is an important factor in AML relapse and that GMP and LMPP cells can affect relapse in patients with AML. This study advances our understanding of the role of DNMT3A in AML relapse and our approach can be applied to predict treatment outcomes.

• Journal of Genetic Medicine
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• v.20 no.2
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• pp.60-69
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• 2023

Purpose: Despite enzyme replacement therapy (ERT) and/or allogeneic hematopoietic stem cell transplantation, individuals with mucopolysaccharidosis (MPS) I or II often experience significant growth deficiencies. This study aimed to assess the safety and efficacy of recombinant human growth hormone (hGH) treatment in children diagnosed with MPS I or II. Materials and Methods: A total of nine pediatric patients-four with MPS I and five with MPS II-underwent treatment with ERT and hGH at Samsung Medical Center. Results: The mean hGH dose administered was 0.26±0.03 mg/kg/week. In the MPS I group, three patients showed an increase in height Z-score from -4.09±0.83 to -3.68±0.43 after 1 year of hGH treatment, and to -3.10±0.72 by the end of the hGH regimen. In the MPS II group, while the height Z-score of four patients decreased according to standard growth charts, it improved from 1.61±1.79 to 2.71±1.68 based on the disease-specific growth chart through hGH treatment. Two patients discontinued hGH treatment due to lack of efficacy after 22 and 6 months each of treatment, respectively. No new-onset neurological symptoms or necessity for prosthetic or orthopedic surgery were reported during hGH treatment. Conclusion: This study provides insights into the impact of hGH on MPS patients, demonstrating its potential to reverse growth deceleration in some cases. Further research is needed to explore the long-term effects of hGH on changes in body composition, muscle strength, and bone health in this population.

• IMMUNE NETWORK
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• v.22 no.2
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• pp.14.1-14.17
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• 2022

Osteoarthritis (OA) is a common degenerative joint disease characterized by breakdown of joint cartilage. Mitochondrial dysfunction of the chondrocyte is a risk factor for OA progression. We examined the therapeutic potential of mitochondrial transplantation for OA. Mitochondria were injected into the knee joint of monosodium iodoacetate-induced OA rats. Chondrocytes from OA rats or patients with OA were cultured to examine mitochondrial function in cellular pathophysiology. Pain, cartilage destruction, and bone loss were improved in mitochondrial transplanted-OA rats. The transcript levels of IL-1β, TNF-α, matrix metallopeptidase 13, and MCP-1 in cartilage were markedly decreased by mitochondrial transplantation. Mitochondrial function, as indicated by membrane potential and oxygen consumption rate, in chondrocytes from OA rats was improved by mitochondrial transplantation. Likewise, the mitochondrial function of chondrocytes from OA patients was improved by coculture with mitochondria. Furthermore, inflammatory cell death was significantly decreased by coculture with mitochondria. Mitochondrial transplantation ameliorated OA progression, which is caused by mitochondrial dysfunction. These results suggest the therapeutic potential of mitochondrial transplantation for OA.

• Journal of Periodontal and Implant Science
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• v.53 no.5
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• pp.376-387
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• 2023

Purpose: Peri-implantitis (PI) is an inflammatory condition associated with the destruction of bone tissue around a dental implant, and diode lasers can be used to treat this disease. In this study, we aimed to evaluate the effectiveness of a 940-nm diode laser for the nonsurgical treatment of PI. Methods: Twenty patients (8 women and 12 men) were enrolled in a split-mouth randomized controlled study. In the control group (CG), mechanical debridement with titanium curettes accompanied by airflow was performed around the implants. The test group (TG) was treated similarly, but with the use of a diode laser. Clinical measurements (plaque index, gingival index [GI], probing pocket depth [PPD], bleeding on probing [BOP], clinical attachment level, and interleukin-1β [IL-1β] in the peri-implant crevicular fluid) were evaluated and recorded at baseline and 3 months. IL-1β levels were determined using the enzyme-linked immunosorbent assay method. Results: The symptoms were alleviated in both groups at 3 months as assessed through clinical measurements. GI, BOP, and PPD were significantly lower in the TG than in the CG (P<0.05). The IL-1β level increased post-treatment in both groups, but this increase was only statistically significant (P<0.05) in the CG. Conclusions: The diode laser enabled improvements in clinical parameters in the periimplant tissue. However, it did not reduce IL-1β levels after treatment. Further studies about the use of diode lasers in the treatment of PI will be necessary to evaluate the effects of diode lasers in PI treatment.

• The Journal of the Korean bone and joint tumor society
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• v.12 no.1
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• pp.1-8
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• 2006

Purpose: To analyze the clinical outcome of stage IIB osteosarcomas arisen in the long bones. Materials and Methods: Since February 1993, 58 Enneking stage IIB osteosarcomas arisen in long bones were managed and followed at least one year at our four university hospitals. There were 48 wide resections, 2 marginal resections and 8 amputations. The mean follow up period was 4.1years (up to 12.2years). Local recurrence, distant metastasis, complication, survival rate, and oncologic and functional results were evaluated. Results: At the last follow up, 35 patients were CDF, 9 were NED, 5 were AWD, 7 were DOD and the remained 2 died with unrelated disease. Eight local recurrences (13.8%) and 18 distant metastases (31.0%) were occurred. Nine infections were developed after 48 reconstructions (18.8%). Overall functional outcome was 24.3 (81.%). The 5 year overall survival rate was 84.6% and the continuous disease-free survival rate was 68.7% at 5 years and 42.3% at 10 years. Conclusion: Forty-six of 58 stage IIB osteosarcomas arisen in long bones (79.3%) showed CDF or NED at an average 4.1 year follow up. Overall 5-year survival rate was 84.6% and overall functional outcome score was 24.3, which were comparable to those of other studies.

• Radiation Oncology Journal
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• v.13 no.2
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• pp.191-198
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• 1995

Purpose: This analysis was to compare the result of radiation alone and chemoradiation in cervical cancer in terms of response, survival, failure, and complication. Materials and Methods: A retrospective analysis of 135 cervical cancer patients treated with definitive radiotherapy from November 1985 to December 1991 was performed. Fifty-six patients were treated with radiation alone and 79 patients were treated with cisplatin-based chemotherapy plus radiation. Follow-up period ranged from 5 to 105 months with a median 47 months. According to the FIGO classification, the patients were subdivided into 18 $(13.3\%)$ stage IB, 7 $(5.2\%)$ stage IIA, 97 $(71.9\%)$ stage IIB, and 9 $(6.7\%)$ stage IIIB. Results: A complete response was noted in 51 patients $(91.1\%)$ of the radiation alone group, and 68 patients $(86.1\%)$ of the chemoradiation group. There was no statistical difference in complete response rate between the two groups. Overall survival rate at 5 years was $73.3\%$. According to stage, overall survival rates at 5 years were $88.9\%$ in stage IB, $85.7\%$ in stage IIA, $73.8\%$ in stage IIB, and $37.5\%$ in stage IIIB, respectively. According to treatment modality, overall survival rates at 5 years were $81.9\%$ in the radiation alone group, $67.0\%$ in the chemoradiation group (p=0.22). Disease-free survival rate at 5 years were $70.4\%$ in the radiation alone group. $68.5\%$ in the chemoradiation group (p=0.85) Locoregional control rates at 5 years were $76.1\%$ in the radiation alone group, $73.8\%$ In the chemoradiation group (p=0.70). Distant disease-free survival rates at 5 years were $83.9\%$ in the radiation alone group, $90.3\%$ in the chemoradiation group (p=0.59). Treatment-related bone marrow suppressions were noted in 3 $(5.4\%)$ patients of the radiation alone group, 14 patients $(17.7\%)$ of the chemoradiation group (p(0.05). Grade 2 vesical complications were noted in 14 patients of the radiation alone group. and 10 Patients of the chemoradiation group. Grade 2 rectal complications were noted in 2 patients of the radiation alone group, and 3 Patients of the chemoradiation group. One case of rectal perforation was noted in the chemoradiation group, and grade 2 small bowel obstructions were noted in 2 patients of the radiation alone group. There were no statistical differences in the incidence of vesicar, rectal, and small bowel complicaions between the two groups. Conclusion: No statistical difference was found between the radiation alone group and the chemoradiation group in terms of response, survival, and failure. but the incidence of bone marrow suppression was higher in the chemoradiation group.

• The Journal of the Korean bone and joint tumor society
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• v.11 no.1
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• pp.46-53
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• 2005

Purpose: Bisphosphonates (BPs) are the analogues of endogenous pyrophosphates: they have been used in the treatment of skeletal diseases such as Paget's disease, osteoporosis, and tumorinducing ostelysis, and are used in treatment of osteolytic metastasis of breast cancer recently. They are also used as one of the therapeutic agents for metastasis of prostatic cancer of which metastasis makes the mixed nature of osteolysis and ostegenesis. Although the action mechanism of BPs are well known for diseases with excessive osteoclastic bone resorption, the direct effect of BPs has not been known yet. This study was intended to see the tumor suppression capability of Zoledronic acid(ZOL) using nude mouse with osteosarcoma. Materials and Methods: MG-63 and HOS osteosarcoma cell lines were used and the transforemed MG-63-GFP and HOS-GFP cells, which were made for detection under fluorescent light, were subcutaneously injected to make osteosarcoma. The five 6-week male mice were used for the experiment at each group. After the injection, mice were cultivated until tumor pieces grow up to $3{\times}3{\times}3$ $mm^3$ and ZOL of 120 ug/kg was subcutaneously injected twice a week. Sizes of tumor were measured twice a week and photographed under fluorescent light. Results: In in vivo test with HOS osteosarcoma cell lines, mean size of tumors was 2,520 $mm^3$ in control group and was 131 $mm^3$ in ZOL group, which showed 94% of reduction comparing with the control ; with MG-63 osteosarcoma cell lines, mean size of tumors was 2,866 $mm^3$ in control group and was 209 $mm^3$ in test group with 72% of reduction (p<0.05). Conclusion: In in vivo tests with nude mice, we suggest that ZOL has direct effect on osteosarcoma cells and it would be used as one of the therapeutic agents for osteosarcoma, especially to ZOL-sensitive osteosarcoma cells.

• Journal of Acupuncture Research
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• v.17 no.1
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• pp.27-41
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• 2000

The meridian system is the most essential and basic connecting structure that maintains the vital activities of viscera and bowels by connecting them with each part of body's surface. Doctors can understand the healthy condition, and the region and deficiency-excessiveness of disease by observing the condition of Qi flowing. Deficiency and excessiveness could be differentiated by various symptoms expressed in meridian system. Especially there could be several clues like pain, heat-cold, protuberance-depression, change of color and shine in the line of channel leads to the judgment of deficiency-excessiveness The diagnosis of deficiency and excessiveness can be generalized by quantification of elastic status in skin surface along the meridian system. By comparing data from measurement of elastic condition with those from traditional deficiency and excessiveness, it could be utilized for the development of oriental medicine. All biological activities in the human body are based on meridian system according to the oriental medicine. Also the meridian system is viewed as basic and essential structure connecting internal viscera and each part of body. The areas of expressed channel phenomena are muscle to bone, muscle to muscle and bone to bone. These areas are called depression where meridian system is present and any changing state on those points can be measured. It could be difficult in diagnosing the reaction of meridian system because doctor can depend on his own judgment. Therefore, it is necessary to quantify and indexate channel reactions. To quantify the channel reactions, specially manufactured instrument was used to quantify the protuberance and depression to differentiate the deficiency and excessiveness. The results follow as below; 1. The elastic index measurement by the equipment proved a pattern of agreement showing the values that ranged within standard deviation 0.05kgf/cm throughout the experiment except few cases' measurement in CV-17. 2. To evaluate the state of deficiency & excessiveness of elastic index measurements in frontal point, elastic index measurements in the front paint were compared to the elastic index measured surrounding the point within 2.5 cm. Such result of indexing procedure was closely matched to the concept of palpitation. 3. If the elastic index values in the surrounding front point closely located to the elastic index values in the front point, the judgement on the state of deficiency and excessiveness was delayed. Otherwise, it was judged as deficiency or excessiveness. 4. Out of total 12 cases of comparing the elastic index values to the elastic index values in the surrounding front point, Three to nine front points were judged as either in the state of deficiency or excessiveness. 5. Among the nine front points judged as either in the state of deficiency or excessiveness, Four cases were matched to the electric index measured by EAV that evaluating the internal organs by five different phases. If more clinical cases are accumulated, it is expected to systematically theorize and improve the concept of deficiency and excessiveness in the internal organs using the front point.

• Journal of Life Science
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• v.20 no.4
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• pp.607-613
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• 2010

Osteoporosis is a disease involving a decrease in bone mineral density and an increased risk of fractures. The MC3T3-E1 pre-osteoblastic cell line is a well-accepted model of osteogenesis in vitro. Pine needles have long been used as a traditional health-promoting medicinal food in Korea. In this study, MTT assay, the alkaline phosphatase (ALP) activity and collagen synthesis of osteoblast cells were investigated to determine the effects of pine needle extracts on cell proliferation and differentiation. Pine needle extracts were prepared using hexane, ethanol and water. The effects of the pine needle extracts were examined by comparing the results with those of commercial agents, such as proanthocyanidin. The MC3T3-E1 cells exposed to proanthocyanidin showed increased proliferation in a concentration-dependent manner. The cells exposed to the hexane extract showed a similar increase in proliferation to that observed with proanthocyanidin. The hexane extract showed the highest ALP activity. Moreover, a supplement of pine needle extracts induced collagen synthesis in MC3T3-E1 cells. The pine needle extract produced the highest level of collagen synthesis at concentrations of $10{\sim}50\;{\mu}g/ml$. These results indicate that pine needle extracts have an anabolic effect on bone by promoting osteoblastic differentiation, and may be used in the treatment of common metabolic bone diseases.