• Archives of Pharmacal Research
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• v.22 no.2
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• pp.108-112
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• 1999

Recombinant murine stem cell factor (rmSCF) or recombinant murine nerve growth factor (rmNGF) induced the morphological change of large numbers of rat peritoneal mast cells (RPMC). We investigated the role of phosphatidylinositol $3^{l}-kinase$ (PI3-kinase) in receptors-mediated morphological change in RPMC. Exposure of RPMC to PI3-kinase inhibitor, wortmannin, before the addition of rmSCF and rmNGF antagonized those factors-induced morphological change. These results suggest that the PI3-kinase is involved in the signal transduction pathway responsible for morphological change following stimulation of rmSCF and rmNGF and that wortmannin blocks these responses.

• Korean Journal of Biological Psychiatry
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• v.18 no.2
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• pp.90-94
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• 2011

Objectives It is well-known that tobacco smoking is related to various disease entities including chronic obstructive pulmonary disease, inflammation, cardiovascular disease, and neoplasms. The prohibition of smoking is important for the protection of these health problems. Regarding leptin, ghrelin, glucagon-like peptide 1 (GLP-1), and nerve growth factor (NGF) levels, correlations with the smoking are suggested but the reports on the effects after smoking cessation are not sufficient. Method The changes of plasma levels of leptin, ghrelin, GLP-1, and NGF levels were analyzed after quitting smoking in Korean adults. Eleven participants succeeding in quitting smoking among 37 male smokers were included in the final analysis. The plasma levels of NGF, leptin, ghrelin, and GLP-1 were measured before and after 8-weeks period of smoking cessation. Results The plasma level of leptin increased after 4 weeks of smoking cessation. In addition, the plasma level of NGF increased after 8 weeks of smoking cessation (p < 0.05). Conclusion Our results suggested that smoking cessation induces increases in leptin and the NGF level after smoking cessation. Many toxic materials including nicotine in the cigarette may be related to these changes of plasma level of leptin and NGF, playing a key role in neurogenesis and synaptic plasticity.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.441-449
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• 2018

Objective : Notch receptors are heterodimeric transmembrane proteins that regulate cell fate, such as differentiation, proliferation, and apoptosis. Dysregulated Notch pathway signaling has been observed in glioblastomas, as well as in other human malignancies. Nerve growth factor (NGF) is essential for cell growth and differentiation in the nervous system. Recent reports suggest that NGF stimulates glioblastoma proliferation. However, the relationship between NGF and Notch1 in glioblastomas remains unknown. Therefore, we investigated expression of Notch1 in a glioblastoma cell line (U87-MG), and examined the relationship between NGF and Notch1 signaling. Methods : We evaluated expression of Notch1 in human glioblastomas and normal brain tissues by immunohistochemical staining. The effect of NGF on glioblastoma cell line (U87-MG) was evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. To evaluate the relationship between NGF and Notch1 signaling, Notch1 and Hes1 expression were evaluated by reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis, respectively. To confirm the effects of NGF on Notch1 signaling, Notch1 and Hes1 small interfering RNAs (siRNAs) were used. Results : In immunohistochemistry, Notch1 expression was higher in glioblastoma than in normal brain tissue. MTT assay showed that NGF stimulates U87-MG cells in a dose-dependent manner. RT-PCR and Western blot analysis demonstrated that Notch1 and Hes1 expression were increased by NGF in a dose-dependent manner. After transfection with Notch1 and Hes1 siRNAs, there was no significant difference between controls and 100 nM $NGF-{\beta}$, which means that U87-MG cell proliferation was suppressed by Notch1 and Hes1 siRNAs. Conclusion : These results indicate that NGF stimulates glioblastoma cell proliferation via Notch1 signaling through Hes 1.

• Macromolecular Research
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• v.11 no.5
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• pp.334-340
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• 2003

In order to fabricate new sustained delivery device of nerve growth factor (NGF), we developed NGF-loaded biodegradable poly(L-lactide-co-glycolide) (PLGA, the mole ratio of lactide to glycolide 75:25, molecular weight: 83,000 and 43,000 g/mole, respectively) film by novel and simple sandwich solvent casting method for the possibility of the application of neural tissue engineering. PLGA was copolymerized by direct condensation reaction and the molecular weight was controlled by reaction time. Released behavior of NGF from NGF-loaded films was characterized by enzyme linked immunosorbent assay (ELISA) and degradation characteristics were observed by scanning electron microscopy (SEM) and gel permeation chromatography (GPC). The bioactivity of released NGF was identified using a rat pheochromocytoma (PC-12) cell based bioassay. The release of NGF from the NGF-loaded PLGA films was prolonged over 35 days with zero-order rate of 0.5-0.8 ng NGF/day without initial burst and could be controlled by the variations of molecular weight and NGF loading amount. After 7 days NGF released in phosphate buffered saline and PC-12 cell cultured on the NGF-loaded PLGA film for 3 days. The released NGF stimulated neurite sprouting in cultured PC-12 cells, that is to say, the remained NGF in the NGF/PLGA film at 37 $^{\circ}C$ for 7 days was still bioactive. This study suggested that NGF-loaded PLGA sandwich film is released the desired period in delivery system and useful neuronal growth culture as nerve contact guidance tube for the application of neural tissue engineering.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.28 no.5
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• pp.375-395
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• 2006

Purpose: Lingual nerve (LN) damage may be caused by either tumor resection or injury such as wisdom tooth extraction, Although autologous nerve graft is sometimes used to repair the damaged nerve, it has the disadvantage of necessity of another operation for nerve harvesting. Moreover, the results of nerve grafting is not satisfactory. The nerve growth factor (NGF) is well-known to play a critical role in peripheral nerve regeneration and its local delivery to the injured nerve has been continuously tried to enhance nerve regeneration. However, its application has limitations like repeated administration due to short half life of 30 minutes and an in vivo delivery model must allow for direct and local delivery. The aim of this study was to construct a well-functioning $rhNGF-{\beta}$ adenovirus for the ultimate development of improved method to promote peripheral nerve regeneration with enhanced and extended secretion of hNGF from the injured nerve by injecting $rhNGF-{\beta}$ gene directly into crush-injured LN in rat model. Materials and Methods: $hNGF-{\beta}$ gene was prepared from fetal brain cDNA library and cloned into E1/E3 deleted adenoviral vector which contains green fluorescence protein (GFP) gene as a reporter. After large scale production and purification of $rhNGF-{\beta}$ adenovirus, transfection efficiency and its expression at various cells (primary cultured Schwann cells, HEK293 cells, Schwann cell lines, NIH3T3 and CRH cells) were evaluated by fluorescent microscopy, RT-PCR, ELISA, immunocytochemistry. Furthermore, the function of rhNGF-beta, which was secreted from various cells infected with $rhNGF-{\beta}$ adenovirus, was evaluated using neuritogenesis of PC-12 cells. For in vivo evaluation of efficacy of $rhNGF-{\beta}$ adenovirus, the LNs of 8-week old rats were exposed and crush-injured with a small hemostat for 10 seconds. After the injury, $rhNGF-{\beta}$ adenovirus($2{\mu}l,\;1.5{\times}10^{11}pfu$) or saline was administered into the crushed site in the experimental (n=24) and the control group (n=24), respectively. Sham operation of another group of rats (n=9) was performed without administration of either saline or adenovirus. The taste recovery and the change of fungiform papilla were studied at 1, 2, 3 and 4 weeks. Each of the 6 animals was tested with different solutions (0.1M NaCl, 0.1M sucrose, 0.01M QHCl, or 0.01M HCl) by two-bottle test paradigm and the number of papilla was counted using SEM picture of tongue dorsum. LN was explored at the same interval as taste study and evaluated electro-physiologically (peak voltage and nerve conduction velocity) and histomorphometrically (axon count, myelin thickness). Results: The recombinant adenovirus vector carrying $rhNGF-{\beta}$ was constructed and confirmed by restriction endonuclease analysis and DNA sequence analysis. GFP expression was observed in 90% of $rhNGF-{\beta}$ adenovirus infected cells compared with uninfected cells. Total mRNA isolated from $rhNGF-{\beta}$ adenovirus infected cells showed strong RT-PCR band, however uninfected or LacZ recombinant adenovirus infected cells did not. NGF quantification by ELISA showed a maximal release of $18865.4{\pm}310.9pg/ml$ NGF at the 4th day and stably continued till 14 days by $rhNGF-{\beta}$ adenovirus infected Schwann cells. PC-12 cells exposed to media with $rhNGF-{\beta}$ adenovirus infected Schwann cell revealed at the same level of neurite-extension as the commercial NGF did. $rhNGF-{\beta}$ adenovirus injected experimental groups in comparison to the control group exhibited different taste preference ratio. Salty, sweet and sour taste preference ratio were significantly different after 2 weeks from the beginning of the experiment, which were similar to the sham group, but not to the control group.

• Journal of Life Science
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• v.22 no.5
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• pp.569-574
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• 2012

This study was conducted to investigate the effect of exercise on oxidative stress, nerve growth, and hepatocyte growth factors in obese children. After 12 weeks of aerobic exercise training, the aforementioned parameters before and after the training were compared. As a result, the nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) were shown to be lower in the OT than in the NT before and after the training, respectively ($p$ <0.05). The NGF was shown to have increased in both groups after the training ($p$ <0.05). The hepatocyte growth factor (HGF) was shown to be higher in the OT than in the NT before the training ($p$ <0.05), with no difference found afterwards. The malondialdehyde (MDA), ox-LDL, and 8-OHdG (Oxo-2'-deoxyguanosine) were shown to be higher in the OT than in the NT ($p$ <0.05). For ox-LDL, a difference was found between before and after the training ($p$ <0.05). The results of this study showed that obesity induced oxidative stress and caused the abnormalities of nerve and HGF secretion in obese children, and that the 12 weeks of aerobic exercise increased NGF levels, thereby promoting the development of neurogenesis in children.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.27 no.5
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• pp.415-423
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• 2005

Distraction osteogenesis (DO) is frequently used technique in reconstruction of bony defects resulted from tumor resection, congenital deformity, and trauma in the maxillofacial region. Although the histologic and ultrastructural changes associated with distraction osteogenesis have been extensively described, the exact changing of the surrounding tissues, such as nerve tissues, were still unclear. This study observed the histological changes and the expression of nerve growth factor (NGF) in the inferior alveolar nerve (IAN) after distraction osteogenesis. Unilateral mandibular distraction (0.5 mm twice per day for 10 days) was performed in eight mongrel dogs. Two animals were sacrificed at 7, 14, 28 and 56 days after completion of distraction, respectively. The distracted IAN and contralateral control nerve were harvested and processed for histological and innunohistochemical examinations. The signs of acute nerve injuries, such as demyelination and partial discontinuation of nerver fiber, were observed in the distracted IAN on 7 and 14 days after distraction. The initial remyelination and regeneration of distracted IAN were showed at 14 days after completion of distraction. At 56 days later, the histologic features of distracted IAN was similar to those of the normal control IAN. The expression of NGF was significantly increased in most distracted nerve tissues on 7, 14 and 28 days after distraction. On 56 days after distraction, the expression of NGF returned to the normal level. This study suggested that the acute IAN injury caused by mandibular distraction were mostly recovered during consolidation period. The NGF was seemed to be induced from Schwann cell and damaged nerve tissues, and it may have important roles in the initial healing of damaged nerves.

• The Korean Journal of Physiology and Pharmacology
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• v.6 no.5
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• pp.275-279
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• 2002

Nerve growth factor (NGF) is an important autocrine growth factor and also a survival factor for keratinocytes. NGF may act in the hyperproliferative condition, psoriasis. Clinically, the combination of psoralen and UVA (PUVA) has been used in the treatment of a wide variety of cutaneous disorders, such as psoriasis and vitiligo. However, the precise therapeutic mechanism of PUVA on the dermatologic diseases remains unclear. The purpose of this study was to examine whether the expression of NGF in cultured keratinocytes is influenced by PUVA. Thus, normal human keratinocytes were isolated from neonatal foreskin, and the third to fifth-passaged cells were used in this study. The cells were exposed to various doses of UVA (30, 60, 120 $mJ/cm^2)$ after adding 8-methoxypsoralen (8-MOP) to examine the expression of NGF mRNA. The RNA and protein of the cells were extracted at various time points (1, 8, 24 hours) after UVA irradiation to examine the expression of NGF mRNA and production of NGF protein. In keratinocytes, there were no differences in the expression of NGF mRNA between the different doses of UVA irradiation, however, the expression of NGF mRNA in UVA and PUVA groups tended to increase as the time increased. The expression of NGF mRNA was the highest in PUVA group, followed by UVA group and the lowest in 8-MOP group. The expressions of NGF protein at 1 and 8 hours after UVA irradiation were lower in the PUVA group than in the other groups. This study showed that the expression level of NGF protein in keratinocytes was relatively lower in the PUVA groups than in the other groups, suggesting that the therapeutic mechanism of PUVA in psoriasis is related to the decrease of NGF protein.

• Korean Journal of Biological Psychiatry
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• v.14 no.3
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• pp.161-166
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• 2007

Objectives:Recent studies have raised the possibility that nerve growth factor(NGF) is abnormally regulated in the central nervous system(CNS) of animal models with alcohol dependence. The possible alteration of NGF by prolonged alcohol intake may play an important role in alcohol-induced neurotoxicity. Carbohydrate-deficient transferrin(CDT) is regarded as a reliable biological marker of alcohol dependence. The goal of this study was to estimate the changes of %CDT and serum NGF level according to the duration of alcohol abstinence, and to identify whether %CDT level is associated with the serum NGF level in the patients with alcohol dependence. Methods:The subjects were 24 patients with alcohol dependence. We used the Axis-Shield ASA to measure the %CDT level and the enzyme-linked immunosorbent assay(ELISA) to measure the serum NGF level. %CDT and NGF levels were measured immediately after the admission and at 2 weeks after the admission. Results:Decreased %CDT were observed during the period of 2 weeks after the admission. NGF level was not significantly different after 2 weeks. The NGF levels were not correlated with %CDT. The possibility of %CDT as a predictor of alcohol-induced neurotoxicity was not confirmed. Conclusion:Serum NGF levels is not a reliable indicator of abstinence state in the patients with alcohol dependence. Further studies are needed to evaluate the relation between two indicators in regard to hematological and neurological changes in alcohol dependence.

• Journal of Life Science
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• v.13 no.6
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• pp.950-957
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• 2003

The purpose of this study is to classify the contrast group and experiment group of a male white rat, and to identify a result of NFG's change that press the sciatic nerves injured peripheral ones for curing 1day, 3days, 5days and 7days. In contrast group, the nerve cells of immune-reaction were increased on 1 day and they were decreased for 3 days, 5 days, 7 days as a normal one. In experiment group, they were increased on 1 day but, decreased for 3 days, 5 days, 7 days more than contrast group. In conclusion, it is certain that the Needle TENS can make a NFG decrease and effect on the therapy.