• 혜화의학회지
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• 제15권2호
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• pp.181-186
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• 2006

Peripheral axons in vertebrate animals can regenerate after nerve injury and accomplish its functional recovery. Numerous studies have revealed that diverse molecular factors are induced during axonal regeneration and their potential roles in axonal regeneration have been studied. Examples is N-CAM, L1, P0, nerve growth factors, GAP-43 and so forth. However, most of the studies on axonal regeneration have been primarily focused on axon fiber regrowth and elucidating molecular factors, and relatively less is known about functional recovery. Also, specific drugs or drug components used in the oriental medicine in relation to nerve fiber regeneration have not been known. And thus, in the present, a study on the effect of Yukmijihwang-tang components and Yukmijihwang-tang extracts to regeneration of peripheral axon fiber is underway by immunofluorescence staining. Therefore, this prior application of Yukmijihwang-tang with documents consideration is reported with a plea for further investigation.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제31권3호
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• pp.239-247
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• 2005

This study demonstrated that xenogenic human marrow mesenchymal stem cells (hMSCs) could elicit the regeneration of the sensory nerve after axotomy in the adult rats infraorbital nerves without immunosuppression. For this, we evaluated the behavioral testing for functional recovery of the nerve and histological findings at weeks 3 and 5 compared to controls. Xenogenic hMSCs did not evoke any significant inflammatory or immunologic reaction after systemic and local administrations. HMSCs-treated rats exhibited significant improvement on sensory recovery tested with von Frey monofilaments. At 5 postoperative weeks, in the hMSCs treated nerve, expression of myelin basic protein (MBP), neurofilament (NF) at the site of axotomy was higher than control. And mRNA expression of neurotropin receptor Trk precursor (TrkPre), nerve growth factor receptor (NGFR) and neuropeptide (NPY) in trigeminal ganglion were also higher. The number of myelinated nerve at distal stump and cells in trigeminal ganglion were higher in hMSC treated rats. So it was supposed that transplanted MSCs contributed to reducing post-traumatic degeneration and production of neurotrophic factors. Immunofluorescence labeling showed small portion of hMSCs (<10%) expressed a phenotypic marker of Schwann cell (S-100). Xenogenic or allogenic mesenchymal stem cells might have immune privileged characteristics and useful tool for cell based nerve repair.

• BMB Reports
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• 제50권2호
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• pp.60-70
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• 2017

Glaucoma is characterized by a slow and progressive degeneration of the optic nerve, including retinal ganglion cell (RGC) axons in the optic nerve head (ONH), leading to visual impairment. Despite its high prevalence, the biological basis of glaucoma pathogenesis still is not yet fully understood, and the factors contributing to its progression are currently not well characterized. Intraocular pressure (IOP) is the only modifiable risk factor, and reduction of IOP is the standard treatment for glaucoma. However, lowering IOP itself is not always effective for preserving visual function in patients with primary open-angle glaucoma. The second messenger cyclic adenosine 3',5'-monophosphate (cAMP) regulates numerous biological processes in the central nervous system including the retina and the optic nerve. Although recent studies revealed that cAMP generated by adenylyl cyclases (ACs) is important in regulating aqueous humor dynamics in ocular tissues, such as the ciliary body and trabecular meshwork, as well as cell death and growth in the retina and optic nerve, the functional role and significance of cAMP in glaucoma remain to be elucidated. In this review, we will discuss the functional role of cAMP in aqueous humor dynamics and IOP regulation, and review the current medications, which are related to the cAMP signaling pathway, for glaucoma treatment. Also, we will further focus on cAMP signaling in RGC growth and regeneration by soluble AC as well as ONH astrocytes by transmembrane ACs to understand its potential role in the pathogenesis of glaucoma neurodegeneration.

• Journal of Microbiology and Biotechnology
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• 제9권3호
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• pp.323-327
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• 1999

It was shown that brain-derived neurotrophic factors (BDNFs) secreted from human neuroblastoma cells can significantly improve the growth of the neurites of PC12 nerve cells. The addition of purified BDNFs elongated the neurites of PC 12 nerve cells two to three times more than the case where the addition was not made. The perfusion rate strongly affected the change of the size of human neuroblastoma cells because the cell size decreased as the perfusion rate increased. This could also influence the productivity of BDNF from the cells. It is also important to note that the BDNF production was decreased when the cell size was reduced. BDNF production rate also decreased at a fast perfusion rate in a smaller cell size. At the relatively fast perfusion rate of 18 ml/h, the ratio of apoptotic to necrotic cells dramatically decreased, which possibly caused the decrease of BDNF production. It has been proven that the secretion of BDNF from human neuroblastoma cells was a partially growth-related process by yielding 6.2$\times l0^{-8}/g$ of BDNF/cell/h of growth related parameter and $0.48{\times}l0^{-9}/g$ of BDNF/cell/h of nongrowth-related parameter in a growth kinetic model. In addition, it was also found that the perfusion rate played a very important role in controlling the cell death mechanism.

• The Korean Journal of Pain
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• 제36권1호
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• pp.60-71
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• 2023

Background: The purpose of this research was to assess the role of heparanase (HPSE)/syndecan1 (SDC1)/nerve growth factor (NGF) on cancer pain from melanoma. Methods: The influence of HPSE on the biological function of melanoma cells and cancer pain in a mouse model was evaluated. Immunohistochemical staining was used to analyze HPSE and SDC1. HPSE, NGF, and SDC1 were detected using western blot. Inflammatory factors were detected using ELISA assay. Results: HPSE promoted melanoma cell viability, proliferation, migration, invasion, and tumor growth, as well as cancer pain, while SST0001 treatment reversed the promoting effect of HPSE. HPSE up-regulated NGF, and NGF feedback promoted HPSE. High expression of NGF reversed the inhibitory effect of HPSE down-regulation on melanoma cell phenotype deterioration, including cell viability, proliferation, migration, and invasion. SST0001 down-regulated SDC1 expression. SDC1 reversed the inhibitory effect of SST0001 on cancer pain. Conclusions: The results showed that HPSE promoted melanoma development and cancer pain by interacting with NGF/SDC1. It provides new insights to better understand the role of HPSE in melanoma and also provides a new direction for cancer pain treatment.

• 한국진공학회:학술대회논문집
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• 한국진공학회 2009년도 제38회 동계학술대회 초록집
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• pp.44-45
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• 2010

We are currently conducting studies on culturing and biocompatibility assessment of various cells such as neural stem cells and induced pluripotent stem cells(IPS cells) on carbon nanotube (CNT), on nerve regeneration electrodes, and on silicon wafers with a focus on developing nerve integrated CNT based bio devices for interfacing with living organisms, in order to develop brain-machine interfaces (BMI). In addition, we are carried out the chemical modification of carbon nanotube (mainly SWCNTs)-based bio-nanosensors by the plasma ion irradiation (plasma activation) method, and provide a characteristic evaluation of a bio-nanosensor using bovine serum albumin (BSA)/anti-BSA binding and oligonucleotide hybridization. On the other hand, the researches in the case of "novel plasma" have been widely conducted in the fields of chemistry, solid physics, and nanomaterial science. From the above-mentioned background, we are conducting basic experiments on direct irradiation of body tissues and cells using a micro-spot atmospheric pressure plasma source. The device is a coaxial structure having a tungsten wire installed inside a glass capillary, and a grounded ring electrode wrapped on the outside. The conditions of plasma generation are as follows: applied voltage: 5-9 kV, frequency: 1-3 kHz, helium (He) gas flow: 1-1.5 L/min, and plasma irradiation time: 1-300 sec. The experiment was conducted by preparing a culture medium containing mouse fibroblasts (NIH3T3) on a culture dish. A culture dish irradiated with plasma was introduced into a $CO_2$-incubator. The small animals used in the experiment involving plasma irradiation into living tissue were rat, rabbit, and pick and are deeply anesthetized with the gas anesthesia. According to the dependency of cell numbers against the plasma irradiation time, when only He gas was flowed, the growth of cells was inhibited as the floatation of cells caused by gas agitation inside the culture was promoted. On the other hand, there was no floatation of cells and healthy growth was observed when plasma was irradiated. Furthermore, in an experiment testing the effects of plasma irradiation on rats that were artificially given burn wounds, no evidence of electric shock injuries was found in the irradiated areas. In fact, the observed evidence of healing and improvements of the burn wounds suggested the presence of healing effects due to the growth factors in the tissues. Therefore, it appears that the interaction due to ion/radicalcollisions causes a substantial effect on the proliferation of growth factors such as epidermal growth factor (EGF), nerve growth factor (NGF), and transforming growth factor (TGF) that are present in the cells.

• 대한한방내과학회지
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• 제33권2호
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• pp.126-144
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• 2012

Background : Peripheral nerves more rapidly recover than central nerves. However, it has been known that the degree of reaction of axons of peripheral nerves is affected by distinctive characteristics of axons and environmental factors near the axons. Taxol is a widely used medicine as for ovarian, breast, lung and gastric cancer. However it causes patients difficulties under treatment due to its toxic and side effects, which include persistent pain. Objectives : This study reviewed how SJT extract in vitro and in vivo affects nerve tissues of a sciatic nerve damaged by Taxol. It also studied how SJT extract in vivo affects axons of the sciatic nerve after the sciatic nerve was damaged by pressing. Methods : After vehicle, Taxol, and Taxol plus SJT were treated respectively for tissue of the sciatic nerve in vitro and then tissues were observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and anti-cdc2. SJT was also oral medicated by injecting Taxol into the sciatic nerve of in vivo rats. Tissues of the sciatic nerve and axons of DRG sensory nerves were then observed using Neurofilament 200, Hoechst, ${\beta}$-tubulin, $S100{\beta}$, caspase-3 and p-Erk1/2. After inflicting pressing damage to the sciatic nerve of in vivo rats, tissues of the sciatic nerve and DRG sensory nerve were observed using Neurofilament 200, Hoechst, $S100{\beta}$, caspase-3, anti-cdc2, phospho-vimentin, ${\beta}1$-integrin, Dil reverse tracking and p-Erk1/2. Results : The group of in vitro Taxol plus SJT treatment had meaningful effects after sciatic nerve tissue was damaged by Taxol. The group of in vivo SJT treatment had effects of regenerating Schwann cells and axons which were damaged by Taxol treatment. The group of in vivo SJT had effects of regenerating axons in damaged areas after the sciatic nerve was damaged by pressing, and also had variations of distribution in Schwann cells at DRG sensory nerves and axons. Conclusions : This study confirmed that SJT treatment is effective for growth of axons in the sciatic nerve tissues and improvement of Schwann cells after axons of the sciatic nerve tissues was damaged. After tissues of sciatic nerve was damaged by pressing in vivo, SJT treatment had effects on promoting regeneration of axon in the damaged area and reactional capabilities in axons of DRG sensory nerves.

• Molecules and Cells
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• 제37권8호
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• pp.613-619
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• 2014

The optic nerve often suffers regenerative failure after injury, leading to serious visual impairment such as glaucoma. The main inhibitory factors, including Nogo-A, oligodendrocyte myelin glycoprotein, and myelin-associated glycoprotein, exert their inhibitory effects on axonal growth through the same receptor, the Nogo-66 receptor (NgR). Oncomodulin (OM), a calcium-binding protein with a molecular weight of an ~12 kDa, which is secreted from activated macrophages, has been demonstrated to have high and specific affinity for retinal ganglion cells (RGC) and promote greater axonal regeneration than other known polypeptide growth factors. Protamine has been reported to effectively deliver small interference RNA (siRNA) into cells. Accordingly, a fusion protein of OM and truncated protamine (tp) may be used as a vehicle for the delivery of NgR siRNA into RGC for gene therapy. To test this hypothesis, we constructed OM and tp fusion protein (OM/tp) expression vectors. Using the indirect immunofluorescence labeling method, OM/tp fusion proteins were found to have a high affinity for RGC. The gel shift assay showed that the OM/tp fusion proteins retained the capacity to bind to DNA. Using OM/tp fusion proteins as a delivery tool, the siRNA of NgR was effectively transfected into cells and significantly down-regulated NgR expression levels. More importantly, OM/tp-NgR siRNA dramatically promoted axonal growth of RGC compared with the application of OM/tp recombinant protein or NgR siRNA alone in vitro. In addition, OM/tp-NgR siRNA highly elevated intracellular cyclic adenosine monophosphate (cAMP) levels and inhibited activation of the Ras homolog gene family, member A (RhoA). Taken together, our data demonstrated that the recombinant OM/tp fusion proteins retained the functions of both OM and tp, and that OM/tp-NgR siRNA might potentially be used for the treatment of optic nerve injury.

• Journal of Korean Neurosurgical Society
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• 제44권6호
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• pp.375-381
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• 2008

Objective : The effects on neural proliferation and differentiation of neural stem cells (NSC) of basic fibroblast growth factor-2 (bFGF). insulin growth factor-I (IGF-I). brain-derived neurotrophic factor (BDNF). and nerve growth factor (NGF) were assessed. Also, following combinations of various factors were investigated : bFGF+IGF-I, bFGF+BDNF, bFGF+NGF, IGF-I+BDNF, IGF-I+NGF, and BDNF+NGF. Methods : Isolated NSC of Fisher 344 rats were cultured with individual growth factors, combinations of factors, and no growth factor (control) for 14 days. A proportion of neurons was analyzed using $\beta$-tubulin III and NeuN as neural markers. Results : Neural differentiations in the presence of individual growth factors for $\beta$-tubulin III-positive cells were : BDNF, 35.3%; IGF-I, 30.9%; bFGF, 18.1%; and NGF, 15.1%, and for NeuN-positive cells was : BDNF, 34.3%; bFGF, 32.2%; IGF-I, 26.6%; and NGF, 24.9%. However, neural differentiations in the absence of growth factor was only 2.6% for $\beta$-tubulin III and 3.1% for NeuN. For $\beta$-tubulin III-positive cells, neural differentiations were evident for the growth factor combinations as follows : bFGF+IGF-I, 73.1 %; bFGF+NGF, 65.4%; bFGF+BDNF, 58.7%; BDNF+IGF-I, 52.2%; NGF+IGF-I, 40.6%; and BDNF+NGF, 40.0%. For NeuN-positive cells : bFGF+IGF-I, 81.9%; bFGF+NGF, 63.5%; bFGF+BDNF, 62.8%; NGF+IGF-I, 62.3%; BDNF+NGF, 56.3%; and BDNF+IGF-I, 46.0%. Significant differences in neural differentiation were evident for single growth factor and combination of growth factors respectively (p<0.05). Conclusion : Combinations of growth factors have an additive effect on neural differentiation. The most prominent neural differentiation results from growth factor combinations involving bFGF and IGF-I. These findings suggest that the combination of a mitogenic action of bFGF and post-mitotic differentiation action of IGF-I synergistically affects neural proliferation and NSC differentiation.

• 대한후두음성언어의학회지
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• 제12권2호
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• pp.126-132
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• 2001

Background and Objectives : Signal traduction through phospholipase C(PLC) participate in the regulation of cell growth and differentiation. Growth factors bind to their receptors and thereby induce tyrosine phophorylation of the phospholipase C-${\gamma}$1(PLC-${\gamma}$1). PLC-${\gamma}$1 is a substrate for several receptor tyrosine kinases and its catalytic activity is increased by tyrosine phosphorylation. Tyrosine kinase phosphorylation of PLC-${\gamma}$1 stimulates PLC activation and cell proliferation. However the signal transduction pathway and the significance of PLC in injured recurrent laryngeal nerve regeneration is unknown. Therefore after we obtained fuctionally recovered rats using PEMF in this study, we attempt to provide some evidence that PLC plays a role in nerve regeneration itself and regeneration related to PEMF through the analysis of the difference between fucntional recovery group and non-recovery group in the recurrent laryngeal nerve. Materials and Method : Using 32 healthy male Sprague-Dawley rats, transections and primary anastomosis were performed on their left recurrent laryngeal nerves. Rats were then randomly assigned to 2 groups. The experimental group(n=16) received PEMS by placing them in custom cages equipped with Helm-holz coils(3hr/day, 5days/wk, for 12wk). The control group(n=16) were handled the same way as the experimental group, except that they did not receive PEMS. Laryngo-videoendoscopy was performed before and after surgery and followed up weekly. Laryngeal EMG was obtained in both PCA and TA muscles. Immunohistochemisty staining and Western blotting analysis using monoclonal antibody was performed to detect PLC-${\gamma}$1 in recurrent laryngeal nerve and nodose ganglion. Results : 10 rats(71%) in experimental group and 4 rats(38%) in the control group showed recovery of vocal fold motion. Functionally-recoverd rats show PLC-${\gamma}$1 positive cells in neuron and ganglion cells after 12 weeks from nerve injury. Conclusion : This study shows that PLC1-${\gamma}$ involved in singnal trasduction pathway in functinal recovery of injured recurrent laryngeal nerve and PEMF enhance the functional recovery by effect on this molecule.