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Hypoxia Mediates Runt-Related Transcription Factor 2 Expression via Induction of Vascular Endothelial Growth Factor in Periodontal Ligament Stem Cells

  • Xu, Qian;Liu, Zhihua;Guo, Ling;Liu, Rui;Li, Rulei;Chu, Xiang;Yang, Jiajia;Luo, Jia;Chen, Faming;Deng, Manjing
    • Molecules and Cells
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    • v.42 no.11
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    • pp.763-772
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    • 2019
  • Periodontitis is characterized by the loss of periodontal tissues, especially alveolar bone. Common therapies cannot satisfactorily recover lost alveolar bone. Periodontal ligament stem cells (PDLSCs) possess the capacity of self-renewal and multilineage differentiation and are likely to recover lost alveolar bone. In addition, periodontitis is accompanied by hypoxia, and hypoxia-inducible $factor-1{\alpha}$ ($HIF-1{\alpha}$) is a master transcription factor in the response to hypoxia. Thus, we aimed to ascertain how hypoxia affects runt-related transcription factor 2 (RUNX2), a key osteogenic marker, in the osteogenesis of PDLSCs. In this study, we found that hypoxia enhanced the protein expression of $HIF-1{\alpha}$, vascular endothelial growth factor (VEGF), and RUNX2 ex vivo and in situ. VEGF is a target gene of $HIF-1{\alpha}$, and the increased expression of VEGF and RUNX2 proteins was enhanced by cobalt chloride ($CoCl_2$, $100{\mu}mol/L$), an agonist of $HIF-1{\alpha}$, and suppressed by 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole (YC-1, $10{\mu}mol/L$), an antagonist of $HIF-1{\alpha}$. In addition, VEGF could regulate the expression of RUNX2, as RUNX2 expression was enhanced by human VEGF ($hVEGF_{165}$) and suppressed by VEGF siRNA. In addition, knocking down VEGF could decrease the expression of osteogenesis-related genes, i.e., RUNX2, alkaline phosphatase (ALP), and type I collagen (COL1), and hypoxia could enhance the expression of ALP, COL1, and osteocalcin (OCN) in the early stage of osteogenesis of PDLSCs. Taken together, our results showed that hypoxia could mediate the expression of RUNX2 in PDLSCs via $HIF-1{\alpha}$-induced VEGF and play a positive role in the early stage of osteogenesis of PDLSCs.

Formulation of a rational dosage regimen of ceftiofur hydrochloride oily suspension by pharmacokinetic-pharmacodynamic (PK-PD) model for treatment of swine Streptococcus suis infection

  • Luo, Wanhe;Wang, Dehai;Qin, Hua;Chen, Dongmei;Pan, Yuanhu;Qu, Wei;Huang, Lingli;Xie, Shuyu
    • Journal of Veterinary Science
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    • v.22 no.6
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    • pp.41.1-41.14
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    • 2021
  • Background: Our previously prepared ceftiofur (CEF) hydrochloride oily suspension shows potential wide applications for controlling swine Streptococcus suis infections, while the irrational dose has not been formulated. Objectives: The rational dose regimens of CEF oily suspension against S. suis were systematically studied using a pharmacokinetic-pharmacodynamic model method. Methods: The healthy and infected pigs were intramuscularly administered CEF hydrochloride oily suspension at a single dose of 5 mg/kg, and then the plasma and pulmonary epithelial lining fluid (PELF) were collected at different times. The minimum inhibitory concentration (MIC), minimal bactericidal concentration, mutant prevention concentration (MPC), post-antibiotic effect (PAE), and time-killing curves were determined. Subsequently, the area under the curve by the MIC (AUC0-24h/MIC) values of desfuroylceftiofur (DFC) in the PELF was obtained by integrating in vivo pharmacokinetic data of the infected pigs and ex vivo pharmacodynamic data using the sigmoid Emax (Hill) equation. The dose was calculated based on the AUC0-24h/MIC values for bacteriostatic action, bactericidal action, and bacterial elimination. Results: The peak concentration, the area under the concentration-time curve, and the time to peak for PELF's DFC were 24.76 ± 0.92 ㎍/mL, 811.99 ± 54.70 ㎍·h/mL, and 8.00 h in healthy pigs, and 33.04 ± 0.99 ㎍/mL, 735.85 ± 26.20 ㎍·h/mL, and 8.00 h in infected pigs, respectively. The MIC of PELF's DFC against S. suis strain was 0.25 ㎍/mL. There was strong concentration-dependent activity as determined by MPC, PAE, and the time-killing curves. The AUC0-24h/MIC values of PELF's DFC for bacteriostatic activity, bactericidal activity, and virtual eradication of bacteria were 6.54 h, 9.69 h, and 11.49 h, respectively. Thus, a dosage regimen of 1.94 mg/kg every 72 h could be sufficient to reach bactericidal activity. Conclusions: A rational dosage regimen was recommended, and it could assist in increasing the treatment effectiveness of CEF hydrochloride oily suspension against S. Suis infections.

Effects of Intake Gas Mixture Cooling on Enhancement of The Maximum Brake Power in a 2.4 L Hydrogen Spark-ignition Engine (수소 내연기관의 흡기 냉각 방법에 따른 최고 출력 향상에 관한 연구)

  • Kim, Yongrae;Park, Cheolwoong;Oh, Sechul;Choi, Young;Lee, Jeongwoo
    • Journal of the Korean Institute of Gas
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    • v.25 no.5
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    • pp.11-18
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    • 2021
  • Since hydrogen has the lower minimum ignition energy than that of gasoline, hydrogen could be also appropriate for the IC engine systems. However, due to the low ignition energy, there might be a 'back-fire' and 'pre-ignition' problems with hydrogen SI(Spark-ignition) combustion. In this research, cooling effects of intake gas mixture on the improvement of the maximum power output were evaluated in a 2.4 L SI engine. There were two ways to cool intake gas mixtures. The first one was cooling intake fresh air by adjusting inter-cooler system after turbocharger. The other one was cooling hydrogen fuel before supplying by using heat ex-changer. Cooling hydrogen was performed under natural aspired condition. The result showed that cooling fresh air from 40 ℃ to 20~30 ℃ improved the maximum brake power up to 6.5~8.6 % and cooling hydrogen fuel as -6 ℃ enhanced the maximum brake power likewise.

Assessing an Economic Feasibility of Coastal Marine Ranching Project in Uluengdo (울릉도 연안바다목장사업의 경제적 타당성분석)

  • Pyo, Heedong
    • Journal of Korea Port Economic Association
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    • v.37 no.1
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    • pp.1-18
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    • 2021
  • A coastal marine ranching project in Uleungdo had been conducted for 5 years from 2013 to 2017 with investment costs of 5 billion won, for the special purpose of the deployment of artificial reefs, the release of young fishes. The paper focuses on an ex-post analysis of the economic feasibility for the project after completing the project, which is apart from a preliminary viability. For economic analysis, the economic benefits are derived from direct benefits including increasing effects of fisheries income and saving effects of harvesting costs, and indirect benefits including increasing effects of recreational fishing and preservation effects of coastal marine ecosystems while economic costs include releasing and purchasing costs of artificial reef and juvenile fish, R&D costs, maintenance costs and harvesting costs. The result shows that the project should not be accepted according to NPV=-0.125 billion won, IRR=4.5% and B/C ratio=0.98 under Scenario 1 which considers direct benefits and indirect benefits excluding the preservation values, while the project should be accepted under Scenario 2 indicating NPV=30.9 billion won, IRR=11.3% and B/C ratio=1.49 which considers the direct benefits as well as the indirect ones including the preservation values, based on 4.5% of the social rate of discount.

The Effects of Medium and Small-sized Venture Firms' Liability of Foreignness on Business Performance - Comparison of Taiwanese and Korean Firms - (대만과 한국 중소벤처기업의 외국비용이 경영성과에 미치는 영향)

  • Cho, Dae-Woo
    • International Area Studies Review
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    • v.12 no.3
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    • pp.293-319
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    • 2008
  • Medium and small-sized venture firms as well as multinational companies pay liabilities of foreignness. We defined these costs as three different factors which are liability of handicaps(deficit of time, money, experience and, increase of financial risk), overseas market entry costs(information gathering costs, network building costs, marketing costs, channelling costs, monitoring costs), internationalization preparing costs(forecasting and market research of local markets, ex-ante cooperation with local firms), and then empirically tested how each of these factors affects on their business performances. The more important both Taiwanese and Korean firms consider liability of handicaps, the more bigger they pay overseas market entry costs(H1). On the contrary, the more important they consider overseas entry costs, the more they focus on internationalization preparation(H4) and get the better business performances(H5). The more important Korean firms consider liability of handicaps, the bigger they focus on internationalization preparation, on the contrary, the less Taiwanese firms do this(H2). Taiwanese firms as well as Korean firms rejected Hypothesis 3 and 6 which mean both liability of handicaps and internationalization preparation are no relation with their own business performances.

An Empirical Study on the Determinants of Foreign Market Entrance of Japanese Enterprises -focusing on the Viewpoint Macro Economy- (일본기업의 해외시장 진출의 결정요인에 관한 경험적 연구 -거시경제 관점을 중심으로-)

  • Kim, il sik
    • International Area Studies Review
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    • v.13 no.3
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    • pp.385-412
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    • 2009
  • This study first analyzes economical environment change (factor) of investment nation Japan and Japanese enterprise at the analysis of Japanese enterprise's over-seas expansion factor and influence. As a result of an analysis of the factor about Japanese enterprise's overseas expansion from 1990 to 1996 and from 1998 to 2006, commonly applied factors were Yen exchange rate, interest rates, wage, enterprise profit, facility investment, and consumption expenditure. Especially, as a result of regression analysis, a sudden change of "low interest rate" was main factor at Japanese enterprise's overseas expansion from 1990 to 1996, and Japan's "Yen ex-change rate" was drawn as an important factor from 1998 to 2006. That is, from 1990 to 1996, a shock by a sudden rise in Yen value could be viewed gradually accumulated and absorbed inside Japanese economy from 1998 to 2006. Whereas it could be said that Japanese enterprise's overseas expansion was accelerated under Japanese government's overseas supporting policy and "low interest rate" together with the factor in the rise of Yen value from 1998 to 2006.

Effects of Curcumae Longae Rhizoma Pharmacopuncture on Monosodium Iodoacetate-induced Osteoarthritis Rats (강황(薑黃) 약침이 Monosodium Iodoacetate 유도 골관절염 흰쥐에 미치는 영향)

  • Lee, Jong-Hoon;Woo, Chang-Hoon
    • Journal of Korean Medicine Rehabilitation
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    • v.29 no.2
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    • pp.115-133
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    • 2019
  • Objectives The purpose of this study was to evaluate the effects of Curcumae Longae Rhizoma pharmacopuncture on the monosodium iodoacetate (MIA)-induced osteoarthritis rats. Methods Osteoarthritis was induced by injection of MIA ($50{\mu}L$ with 80 mg/mL) into knee joint cavity of rats. Rats were divided into 6 groups. Normal group was injected by normal saline into knee joint cavity only. Control group was induced for osteoarthritis by MIA and orally administered with distilled water. Normal Saline group was induced for osteoarthritis by MIA and injected with normal saline $100{\mu}L$. Positive comparison group was injected with MIA and orally administered with indomethacin 5 mg/kg. Curcumae Longae Rhizoma pharmacopuncture low concentration (CL) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture low concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture high concentration (CH) group was induced for osteoarthritis by MIA and injected with Curcumae Longae Rhizoma pharmacopuncture high concentration $100{\mu}L$. Curcumae Longae Rhizoma pharmacopuncture was injected at ST35 and EX-LE4 each group (CL, CH). After that, hind paw weight distribution was measured and oxidative stress biomarker in serum, liver function biomarker in serum, western blot analysis were measured. Histological analysis of knee joint tissue was performed by hematoxylin and eosin staining, Safranin-O staining and Masson's trichrome staining. Results Hind paw weight distribution was significantly improved in both group. alanine aminotransferanse and aspartate aminotransferase were decreased significantly in CH group compare with Indomethacin threated group. Antioxidant enzyme glutathione peroxidase, Catalase and heme oxygenase-1 were increased in CH group compare with control group. Inflammatory cytokine cyclooxygenase-2, inducible nitric oxide synthase and interleukin-1 beta were decreased significantly in CH group. Histological analysis result shows that protective effects of joint and cartilage were observed in both CH and CL groups in a concentration-dependent. Conclusions The result suggest that Curcumae Longae Rhizoma pharmacopuncture has anti-oxidation effect, anti-inflammatory effect and also can prevent progression of osteoarthritis and protect joint cartilage.

Systematic Review of Korean Medicine for the Treatment of Sixth Cranial Nerve Palsy (외전신경마비의 한의학 치료에 대한 체계적 문헌 고찰)

  • Won, Seo-young;Kim, Min-ji;Cha, Ji-yun;Jung, Eun-sun;Cho, Hyun-kyoung;Yoo, Ho-ryong;Seol, In-chan;Kim, Yoon-sik
    • The Journal of Internal Korean Medicine
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    • v.40 no.3
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    • pp.409-424
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    • 2019
  • Objectives: This research aimed to confirm the efficacy of oriental medicine in sixth cranial nerve palsy and to evaluate the quality of the studies. Methods: Using the medical subject heading (MeSH) keywords "abducens nerve palsy", "abducens nerve paralysis", "sixth nerve palsy", "herbal medicine", "Chinese medicine", "oriental medicine" and "acupuncture", we collected the research papers through an electronic database search in Oriental Medicine Advanced Searching Integrated System (OASIS), National Discovery for Science Leaders (NDSL), PubMed, Cochran Library, and China National Knowledge Infrastructure (CNKI). Results: A total of 136 papers were searched from the databases. Among these, 15 case reports and 8 randomized controlled trials (RCTs) met our criteria. 17 articles were found on the use of acupuncture as the main intervention, 11 on the use of herbal medicine as the main intervention, and 9 on the use of electroacupuncture as the main intervention. The frequently used acupoints were LI4, EX-HN5, GB1, BL2, TE23, LR3, BL1, ST2, GB20, and ST36. All 23 studies confirmed the efficacy of Korean medicine. According to the assessment using the risk of bias, the overall quality of the RCTs was low. Conclusions: Twenty-three papers suggested that Korean medicine treatment for abducens nerve palsy was effective in many cases. Analyzing the potential bias was difficult.

Evaluation of the Femoral Stem Implant in Canine Total Hip Arthroplasty: A Cadaver Study

  • Cho, Hyoung Sun;Kwon, Yonghwan;Kim, Young-Ung;Kang, Jin-Su;Lee, Kichang;Kim, Namsoo;Kim, Min Su
    • Journal of Veterinary Clinics
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    • v.36 no.1
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    • pp.53-61
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    • 2019
  • Total hip arthroplasty (THA) is a successful surgical treatment for both patients with chronical lameness and dogs who are nonresponsive to medical treatments, providing excellent joint function for returning dogs to the normal gait in 80% to 98% of hip dysplasia (HD) patients. The THA surgical implant system manufactured by BioMedtrix and Kyon are today widely accepted. When comparing the BioMedtrix biological fixation (BFX) system to the BioMedtrix cemented fixation (CFX) system, the many advantages of BFX, which include longer potential implant life, decreased risk of postoperative or later infection, and better implant stability, become evident. However, BFX implies a greater risk of femoral fracture during reaming and requires a more precise surgical technique to achieve good implant fit, given the press-fit nature of cementless THA. The purposes of this study are to both describe the mistakes and complications during stem implantation for beginner surgeons with both the BFX and the CFX systems and to document the initial result of 12 implantations in canine cadavers. Given the detailed evaluations of 3 specialists, who are Diplomate American College of Veterinary Surgeons (DACVS), only 3 of 11 stems were appropriately sized. Specifically, 6 stems were anteverted rather than being retroverted; further, although 7 stems were coaxial with the femoral long axis in the frontal plane, the other stems were in the varus at the frontal plane, with the proximal medial stem adjacent to the medial femoral cortex. Moderate angulation from the cranial to the caudal directions was found in 4 cases in the sagittal plane. Additionally, 1 case of femoral fissure and 1 case of perforated femoral cortex were reported. It is not easy for surgeons performing cementless THA for the first time to achieve a good result, even though they completed an educational course about it and given that catastrophic complications often occurred during early surgical clinical cases. Therefore, ex-vivo studies are sincerely required to get an expertise by rehearsing the preparation of the femoral envelop in isolated bones. Further studies should be conducted to achieve both highly accurate implant size and correct orientation during the preoperative planning. Additionally, surgeons' learning curve should be examined in future investigations.

Immunomodulatory and anti-metastatic activities of a crude polysaccharide isolated from Korean apple vinegar (한국산 사과식초에서 분리한 다당의 면역 및 항전이 활성)

  • Kim, Han Wool;Shin, Kwang-Soon
    • Korean Journal of Food Science and Technology
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    • v.51 no.2
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    • pp.152-159
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    • 2019
  • To characterize new physiologically active components in Korean apple vinegar, a crude polysaccharide (KAV-0) was prepared by precipitation with 80% (v/v) ethanol. KAV-0 mainly comprises 38.2% mannose, 19.1% galactose and 14.3% glucose. In an in vitro cytotoxicity analysis, KAV-0 promoted the proliferation of peritoneal macrophages and RAW 264.7 cells in a dose-dependent manner, and showed no cytotoxicity in B16-BL6 melanoma cells. Murine peritoneal macrophages and RAW 264.7 cells stimulated by KAV-0 produced various cytokines such as interleukin (IL)-6, IL-12, and tumor necrosis factor $(TNF)-{\alpha}$, and nitric oxide (NO). Intravenous (i.v.) administration of KAV-0 significantly augmented NK cell cytotoxicity against Yac-1 tumor cells. In experimental lung metastasis caused by B16-BL6 melanomas, prophylactic i.v. administration of KAV-0 at a dosage of $1,000{\mu}g/mouse$ inhibited lung metastasis by 53.0%. These results suggest that the crude polysaccharide (KAV-0) isolated from Korean apple vinegar has a considerably high anti-metastatic activity and immunomodulatory activities beneficial to human health.