• 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 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.

• 생명과학회지
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• 제22권11호
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• pp.1444-1450
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• 2012

본 연구의 목적은 1회성 축구활동이 남자 청소년의 혈청 뉴로트로핀 수준과 신경인지 기능에 미치는 영향을 규명하는데 있다. 연구의 대상은 건강한 남자 청소년 15명으로 하였으며, 연구 대상은 축구활동 처치(SOC) 조건과 자율학습 처치(CON) 조건의 2가지 처치 조건에 참여하였다. 채혈은 처치 전(Pre), 처치 후(Post), 처치 후 2시간(Post-2 h) 시점에서 총 3회 실시하였으며, 채취된 혈액을 이용하여 혈청 serum brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), insulin-like growth factor-1 (IGF-1)을 분석하였다. 신경인지 기능의 평가는 Stroop 색체-단어 검사를 이용하였으며, 채혈 시점과 동일한 시점에서 측정하였다. 연구 결과, 혈청 BDNF, NGF, IGF-1 수준은 축구활동 후 유의하게 증가하였으며(p<0.05), Post 시점에서 SOC 조건이 CON 조건과 비교하여 유의하게 높게 나타났다(p<0.05). Stroop 색체-단어 검사는 색체-단어 검사 점수에서 축구활동 후 유의한 증가를 나타내었으며(p<0.05), Post 시점과 Post-2 h 시점에서 SOC 조건이 CON 조건과 비교하여 유의하게 높게 나타났다(p<0.05). 이상의 결과를 종합하면, 1회성 축구활동이 뉴로트로핀을 증가시켜 신경인지 기능에 긍정적 영향을 나타낸 것으로 판단된다.

• 대한기계학회:학술대회논문집
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• 대한기계학회 2008년도 추계학술대회A
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• pp.1585-1587
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• 2008

Fibroblast is constantly subjected to mechanical loads in connective tissues where mechanical signals are converted to intercellular biochemical events. The aim of this study is to understand the effects of tensile stress on the neurotrophin (NT) and transforming growth factor (TGF) expression of fibroblast in vitro. Nerve growth factor (NGF) stimulates fibroblast migration, and TGF is related to tissue repair. In this study, at the uniaxial stretch of 10% strain and frequency of 0.5 Hz, different resting times of 0, 20, and 60 min are placed in between 10 min stimulations periods. Results show increase in NGF mRNA levels and a substantial decrease in NT3 mRNA after 1 hr of stimulation, indicating that the tensile stress may regulate NGF and NT3, key factors for the neurocosmetic applications. The mRNA level for TGF-${\alpha}$ and TGF-${\beta}2$ had increased up to two-folds after 1 hr of stimulation, showing that the tensile stress may control TGF, an important part of wound healing.

• Radiation Oncology Journal
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• 제32권3호
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• pp.208-212
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• 2014

Marfan syndrome is one of the collagen vascular diseases that theoretically predisposes patients to excessive radiation-induced fibrosis yet there is minimal published literature regarding this clinical scenario. We present a patient with a history of Marfan syndrome requiring radiation for a diagnosis of a right brachial plexus malignant nerve sheath tumor. It has been suggested that plasma transforming growth factor beta 1 (TGF-${\beta}1$) can be monitored as a predictor of subsequent fibrosis in this population of high risk patients. We therefore monitored the patient's TGF-${\beta}1$ level during and after treatment. Despite maintaining stable levels of plasma TGF-${\beta}1$, our patient still developed extensive fibrosis resulting in impaired range of motion. Our case reports presents a review of the literature of patients with Marfan syndrome requiring radiation therapy and the limitations of serum markers on predicting long-term toxicity.

• 한국공작기계학회:학술대회논문집
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• 한국공작기계학회 2005년도 춘계학술대회 논문집
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• pp.3-8
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• 2005

We introduced mechanical stimuli and micropatterned substrate with micro fibers to investigate the effects of those on neurite outgrowth along with nerve growth factor (NGF) in vitro. Microfiber substrates were fabricated using an electrospinning process. And PC-12 cells cultured on substrates were simulated with nerver growth factor and laminar flow shear stress in a fluid flow system The results suggest that microfiber substrates and fluid-induced shear stress are promising for simulating neuronal regeneration in a desired direction.

• Molecules and Cells
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• 제40권4호
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• pp.254-261
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• 2017

Glioblastomas (GBM) are very difficult to treat and their aggressiveness is one of the main reasons for this as well as for the frequent recurrences. MicroRNAs post-transcriptionally regulate their target genes through interaction between their seed sequence and 3'UTR of the target mRNAs. We previously reported that miR-296-3p is regulated by neurofibromatosis 2 (NF2) and enhances the invasiveness of GBM cells via SOCS2/STAT3. In this study, we investigated whether miR-296-5p, which originates from the same precursor miRNA as miR-296-3p, can increase the invasiveness of GBM cells. It was observed that miR-296-5p potentiated the invasion of various GBM cells including LN229, T98G, and U87MG. Through bioinformatics approaches, two genes were identified as miR-296-5p targets: caspase-8 (CASP8) and nerve growth factor receptor (NGFR). From results obtained from Ago2 immunoprecipitation and luciferase assays, we found that miR-296-5p downregulates CASP8 and NGFR through direct interaction between seed sequence of the miRNA and 3'UTR of the target mRNA. Knockdown of CASP8 or NGFR also increased the invasive ability of GBM cells, indicating that CASP8 and NGFR are involved in potentiation of invasiveness by miR-296-5p. Consistent with our findings, CASP8 was downregulated in brain metastatic lung cancer cells, which have a high level of miR-296-5p, compared to parental cells, suggesting that miR-296-5p may be generally associated with the acquisition of invasiveness. Collectively, our results implicate miR-296-5p as a potential cause of invasiveness in cancer and suggest it as a promising therapeutic target for GBM.

• 생명과학회지
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• 제22권9호
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• pp.1180-1186
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• 2012

본 연구는 사회적 고립 스트레스로 인한 해마에서의 nerve growth factor (NGF), Synapsin I 및 choline acetyltranferase (ChAT) 감소에 있어서 사전운동경험(exercise preconditioning: EPC)이 미치는 영향을 규명하고자 실시되었다. 목적을 위해 Sprague-Dawley (SD) 쥐(수컷, 22주령, $500.1{\pm}48.41$ g)를 이용해 크게 통제집단(Con)과 운동(Ex)집단으로 구분하여 운동(트레드밀, 5일/주, 최대 18-20 m/min; 50분까지 점진적 증가, 경사 없음, 8주)을 적용하였으며, 이후 각각 사회적 고립(Isolation, 8주)을 적용하여 분석하였다(Group/Con: GC, Group/Ex: GE, Isolation/Con: IC, Isolation/Ex: IE, 각 집단별 n=8). 실험결과, IC집단에서 GC집단에 비해 해마에서 NGF, Synapsin I 및 ChAT가 유의하게 감소한 것으로 나타났다. 반면 IE집단에서 IC집단에 비해 NGF, Synapsin I 및 ChAT의 감소가 유의하게 개선된 것으로 나타났다. 이상의 결과 사회적 고립에 의한 해마에서의 NGF, Synapsin I 및 ChAT 단백질 감소는 EPC에 의해 개선되며, 이를 통해 해마의 기능 저하를 일부 완충 시킬 수 있을 것으로 판단된다.

• Journal of Ginseng Research
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• 제43권2호
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• pp.272-281
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• 2019

Background: Diabetic sensorineural damage is a complication of the sensory neural system, resulting from long-term hyperglycemia. Red ginseng (RG) has shown efficacy for treatment of various diseases, including diabetes mellitus; however, there is little research about its benefit for treating sensorineural damage. Therefore, we aim to evaluate RG efficacy in alloxan-induced diabetic neuromast (AIDN) zebrafish. Methods: In this study, we developed and validated an AIDN zebrafish model. To assess RG effectiveness, we observed morphological changes in live neuromast zebrafish. Also, zebrafish has been observed to have an ultrastructure of hair-cell cilia under scanning electron microscopy. Thus, we recorded these physiological traits to assess hair cell function. Finally, we confirmed that RG promoted neuromast recovery via nerve growth factor signaling pathway markers. Results: First, we established an AIDN zebrafish model. Using this model, we showed via live neuromast imaging that RG fostered recovery of sensorineural damage. Damaged hair cell cilia were recovered in AIDN zebrafish. Furthermore, RG rescued damaged hair cell function through cell membrane ion balance. Conclusion: Our data suggest that RG potentially facilitates recovery in AIDN zebrafish, and its mechanism seems to be promotion of the nerve growth factor pathway through increased expression of topomyosin receptor kinase A, transient receptor potential channel vanilloid subfamily type 1, and mitogen-activated protein kinase phosphorylation.