• Journal of Yeungnam Medical Science
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• v.30 no.2
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• pp.90-94
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• 2013

Background: This study was conducted to examine if basal luteinizing hormone (LH) levels could be useful for screening central precocious puberty (CPP) in girls. Methods: A total of 90 girls under the age of 8 years were included in this study. They underwent the gonadotropin-releasing hormone (GnRH) stimulation test at Good Gang-An Hospital from March 2008 to December 2012 for evaluation of premature sexual development. Patients were classified into two groups: the pubertal response group of patients who had 5 IU/L peak LH levels in the GnRH stimulation test, and the prepubertal response group of patients who had LH levels <5 IU/L. Chronological and bone ages, height, weight, body mass index, gonadotropin response to GnRH stimulation, and basal levels of LH, follicle-stimulating hormone, and estradiol were studied in both groups. The relationship between basal LH and peak-stimulated LH was evaluated using Spearman's correlation. To determine the optimal cut-off values of basal LH levels for differentiating between two groups, the receiver operating characteristic (ROC) curves were analyzed. Results: When the correlation between basal LH levels and peak LH after GnRH stimulation was analyzed in all subjects (N=90), basal LH levels had a statistically significant positive correlation with peak stimulated LH levels (rs=0.493, p<0.001). The cut-off level of optimal basal LH was 0.1 IU/L, according to the ROC curves. Its sensitivity was 73.3%, and its specificity was 77.8%. Conclusion: The study results showed that serum basal LH levels are useful for screening CPP in girls.

• IMMUNE NETWORK
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• v.6 no.4
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• pp.169-178
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• 2006

Background: Adipose tissues were initially introduced as energy storages, but recently they have become famous as an endocrine organ which produces and secretes various kinds of molecules to make physiologic and metabolic changes in human body. It has been studied that these molecules are secreted in abundance as the adipose tissue becomes bigger along with obesity. Furthermore, it has been found that they are mediating systemic inflammation and generation of metabolic diseases such as type 2 diabetes and atherosclerosis. On the basis of these, we studied previous papers which have been researched about the interaction between preadipocytes and macrophages, adipose tissues and lymph nodes, and adipose tissue secreting molecules. Results: Firstly, preadipocytes and macrophages are expressing similar transcriptomes and proteins, and preadipocytes can be converted to mature macrophages which have phagocytic activity. Moreover, the monocytes, which initially located in the bone marrow, are filtrated to the adipose tissue by monocyte chemotatic protein-1 and are matured to macrophages by colony stimulating factor-1. Secondly, adipose tissues and their associated lymph nodes are interacting each other in terms of energy efficiency. Lymph nodes promote lipolysis in adipose tissues, and polyunsaturated fatty acids in adipocytes become energy sources for dendritic cells. Lastly, adipose tissues produce and secrete proinflammatory molecules such as leptin, adiponectin, TNF-${\alpha}$, IL-6, and acute phase proteins, which induce the inflammation and potentially generate metabolic diseases. Conclusion: According to these, we can link adipose tissues to inflammation, but we need to affirm the actual levels and roles of adipose tissue-derived proinflammatory molecules in human body.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.33 no.6
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• pp.617-624
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• 2007

Insulin-like growth factor(IGF) is the most abundant growth factor in bone matrix. Recent studies have shown that it can sensitize apoptotic cell death of osteoblasts. Thus, this study investigated whether IGF-II aggravates irradiation-induced cell death of osteoblasts. Cultured MC3T3 osteoblasts were irradiated and IGF-II was added at the concentration of 50 ng/ml immediately after the irradiation. Cell viability was measured by MTT assay. Changes in cell death and cell cycle were analyzed by flow cytometry. The expression of proapoptotic gene bax and antiapoptotic gene bcl-2 was quantified by real time RT-PCR and Western blot. A dose of 30 Gy caused G2/M arrest and increased cell death through both necrosis and apoptosis, while irradiation from 4 to 10 Gy little affected cell cycle and death. IGF-II treatment reduced cell viability without stimulating cell proliferation and changing cell cycle. Combined treatment of IGF-II with irradiation decreased cell viability and proliferation and increased cell death along with G2/M arrest. These effects were not different from those of irradiation only. At transcriptional and protein levels, IGF-II treatment did not affect bax and bcl-2 expression, whereas irradiation increased the expression ofbax without changes in bcl-2. IGF-II in combination with irradiation showed similar findings. These results suggest that IGF-II could modulate apoptotic cell death through mechanisms other than an imbalance between bax and bcl-2 gene expression, although its effect was overridden by irradiation.

• BMB Reports
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• v.44 no.5
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• pp.335-340
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• 2011

In this study, we attempted to isolate novel mast cell-stimulating molecules from Staphylococcus aureus. Water-soluble extract of S. aureus cell lysate strongly induced human interleukin-8 in human mast cell line-1 and mouse interleukin-6 in mouse bone marrow-derived mast cells. The active molecule was purified to homogeneity through a $C_{18}$ reverse phase HPLC column. By determination of its structure by MALDITOF and $^1H$- and $^{13}C$-NMR, adenosine was revealed to be responsible for the observed cytokine induction activities. Further studies using 8-sulfophenyl theophylline, a selective adenosine receptor blocker, verified that purified adenosine can induce interleukin-8 production via adenosine receptors on mast cells. Moreover, adenosine was purified from S. aureus-engulfed RAW264.7 cells, a murine macrophage cell line, used to induce phagocytosis of S. aureus. These results show a novel view of the source of exogenous adenosine in vivo and provide a mechanistic link between inflammatory disease and bacterial infection.

• Molecules and Cells
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• v.40 no.10
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• pp.706-713
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• 2017

Osteoclasts are bone-resorbing cells that are derived from hematopoietic precursor cells and require macrophage-colony stimulating factor and receptor activator of nuclear factor-${\kappa}B$ ligand (RANKL) for their survival, proliferation, differentiation, and activation. The binding of RANKL to its receptor RANK triggers osteoclast precursors to differentiate into osteoclasts. This process depends on RANKL-RANK signaling, which is temporally regulated by various adaptor proteins and kinases. Here we summarize the current understanding of the mechanisms that regulate RANK signaling during osteoclastogenesis. In the early stage, RANK signaling is mediated by recruiting adaptor molecules such as tumor necrosis factor receptorassociated factor 6 (TRAF6), which leads to the activation of mitogen-activated protein kinases (MAPKs), and the transcription factors nuclear factor-${\kappa}B$ (NF-${\kappa}B$) and activator protein-1 (AP-1). Activated NF-${\kappa}B$ induces the nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), which is the key osteoclastogenesis regulator. In the intermediate stage of signaling, the co-stimulatory signal induces $Ca^{2+}$ oscillation via activated phospholipase $C{\gamma}2$ ($PLC{\gamma}2$) together with c-Fos/AP-1, wherein $Ca^{2+}$ signaling facilitates the robust production of NFATc1. In the late stage of osteoclastogenesis, NFATc1 translocates into the nucleus where it induces numerous osteoclast-specific target genes that are responsible for cell fusion and function.

• Journal of Microbiology and Biotechnology
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• v.30 no.9
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• pp.1395-1403
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• 2020

There is an increasing interest in using inactivated probiotics to modulate the host immune system and protect against pathogens. As the immunomodulatory function of heat-killed Lactobacillus brevis KCTC 12777BP (LBB) and its mechanism is unclear, we investigated the effect of LBB on immune response based on the hypothesis that LBB might exert stimulatory effects on immunity. In the current study, we demonstrate that administration of LBB can exert immune-stimulatory effects and promote clearance of foreign matters through enhancing phagocytosis. Treatment with LBB induced the production of TNF-α, IL-6, and nitric oxide in macrophages. Importantly, LBB directly increased the phagocytic activity of macrophages against bacterial particles. LBB was able to promote the production of TNF-α in bone marrow-derived macrophages and splenocytes and also increase the proliferation rate of splenocytes, suggesting that the immune-stimulating activity of LBB can be observed in primary immune cells. Investigation into the molecular mechanism responsible revealed that LBB upregulates TAK1 activity and its downstream ERK, p38, and JNK signaling pathways. To further confirm the immunomodulatory capability of LBB in vivo, we orally administered LBB to mice and assessed the effect on primary splenocytes. Splenocytes isolated from LBB-treated mice exhibited higher TNF-α expression and proliferative capacity. These results show that heat-killed L. brevis, a wildly consumed probiotic, may provide protection against pathogens through enhancing host immunity.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.1
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• pp.75-83
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• 2019

Objectives Previous animal studies have shown that mixtures of Cynanchum wilfordii and Phlomis umbrosa extract (IPLUS-CWPU) increases femur length and insulin like growth factor-1 (IGF-1) secretion. IPLUS-CWPU may thus be a promising ingredient in functional foods aimed at growing child's height. The purpose of the study is to investigate the effect of IPLUS-CWPU on height growth in children with short stature. Methods For this purpose, we recruited 90 children aged 4 to 12 years who had heights ranging from the 5th to 25th percentiles of Korean children's growth curve and randomized to either the IPLUS-CWPU or the placebo group. Results The IPLUS-CWPU group showed a significant increase in the change of the height growth compared to the placebo group after 20 weeks of administration (p=0.02). The height growth velosity also showed a statistically significant difference in the test group compared to the placebo group at 10 weeks (p=0.04). The IGF-1 levels showed a tendency to increase in the IPLUS-CWPU group (p=0.08). Moreover, the IPLUS-CWPU significantly increased IGF-1/IGFBP-3 ratio (p=0.02). However, there were no significant differences in blood biochemical parameters including growth hormone, bone age, thyroid stimulating hormone, and osteocalcin levels. Conclusions In conclusion, the data of this trial indicate that IPLUS-CWPU is effective and safe, generally well-tolerated without severe adverse events, in the treatment of children with short stature over a 20 weeks period.

• Journal of Animal Science and Technology
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• v.61 no.2
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• pp.61-68
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• 2019

The hG-CSF (human Granulocyte Colony-Stimulating Factor) is a growth and stimulation factor capable of inducing the proliferation of bone marrow cells, several types of leukocytes, among other hematopoietic tissue cells. hG-CSF is used in used to treat anomalies that reder a small number of circulating white blood cells, which may compromise the immune defenses of the affected person. For these reasons, the production of hG-CSF in a bioreactor system using the mammary gland of genetic modified animals is a possibility of adding value to the bovine genetic material and reducing the costs of hG-CSF production in pharmaceutical industry. In this study, we aimed the production of transgenic hG-CSF bovine through the lipofection of bovine primary fibroblasts with an hG-CSF expression cassette and cloning these fibroblasts by the somatic cell nuclear transfer (SCNT) technique. The bovine fibroblasts transfected with the hG-CSF cassette presented a stable insertion of this construct into their genome and were efficiently synchronized to G0/G1 cell cycle stage. The transgenic fibroblasts were cloned by SCNT and produced 103 transferred embryos and 2 pregnancies, one of which reached 7 months of gestation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.36 no.5
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• pp.386-391
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• 2010

Introduction: Bone resorption is a unique function of osteoclasts. Osteoclasts are a specialized macrophage polykaryon whose differentiation is regulated principally by macrophage colony-stimulating factors, receptor activator of nuclear factor ${\kappa}B$ ligand (RANK) ligand, osteoprotegerin (OPG), and interleukins (IL). Reflecting the integrin-mediated signals, osteoclasts develop a specialized cytoskeleton that allows it to establish an isolated micro-environment between itself and the bone, wherein matrix degradation occurs by a process involving proton transport. The levels of IL-1, IL-6, OPG, and prostaglandin $E_2$ ($PGE_2$) expression were evaluated to study the correlations between dental implant teeth and the adjacent teeth. Materials and Methods: The exudate of the gingival crevice acquired from dental implants, adjacent teeth, opposite teeth and contralateral teeth of 24 patients. Results: 1. The levels of IL-1, IL-6, OPG and $PGE_2$ expression in dental implant teeth were higher than those of the contralateral teeth. 2. IL-1 revealed a higher expression level in the adjacent teeth than in dental implant teeth. 3. The dental implant teeth and adjacent teeth did not show a remarkable difference in the level of IL-1 expression. 4. All the other cytokines were strongly expressed in the dental implant compared to the adjacent teeth. Conclusion: These results suggest that there might be close correlation between dental implant teeth and adjacent teeth in terms of the expressions of cytokines that affect the development and regulation of osteoclasts.

• Journal of Life Science
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• v.26 no.3
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• pp.331-337
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• 2016

Although fibroblast growth factor 23 (FGF23) is exclusively produced in osteoblasts and osteocytes, its main target is the kidney, where it decreases phosphate reabsorption by suppressing Na-phosphate cotransporters. Independently of its action on phosphate homeostasis, FGF23 also inhibits bone formation in vivo. In a calvarial osteoblastic cell model, FGF23 was shown to negatively affect extracellular matrix mineralization. This study investigated whether FGF23 had similar effects on osteoblast maturation, including differentiation and mineralization of bone marrow-derived mesenchymal stem cells (MSCs). D1 MSCs were cultured in an osteogenic medium containing β-glycerophosphate, ascorbic acid, and dexamethazone. Osteoblastic differentiation was evaluated by alkaline phosphatase (Alp) staining, and matrix mineralization was evaluated by alizarin red staining and calcium deposition. The expression of differentiation-stimulating genes Runx2, Alp, and osteocalcin and mineralization-inhibiting genes Enpp1 and Ank was analyzed using semiquantitative RT-PCR. Supraphysiological doses of FGF23 did not stimulate proliferation or osteoblastic differentiation of MSCs. Matrix mineralization 1, 2, and 3 weeks after the FGF23 treatment did not vary between control and FGF23 groups, although time-dependent enhancement of mineralization was obvious. Calcium deposition was also unchanged after the FGF23 treatment. mRNA expression levels of differentiation- and mineralization-related genes were also similar between the groups. Despite these negative findings, FGF23 signaling through FGF receptors seemed to function normally, with phosphorylation of the Erk protein more evident in the FGF23 group than in controls. These findings suggest that unlike calvarial osteoblasts, FGF23 is not likely to affect osteoblastic differentiation and mineralization of MSCs.