• Journal of Gastric Cancer
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• v.3 no.4
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• pp.201-205
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• 2003

Purpose: Telomerase activity is generally absent in primary cell cultures and normal tissues. Telomerase is known to be induced upon immortalization or malignant transformation of human cells. Telomerase activity can be increased in immature lymphocytes and activated lymphocytes, but it is not detected in the peripheral blood of normal persons. The authors analyzed peripheral blood telomerase from patients of gastric cancer to evaluate the possibility of using it for diagnosis and as a prognostic factor. Materials and Methods: We obtained blood samples from 11 inflammatory patients and 64 gastric cancer patients. The telomerase activity was measured using the [PCR-ELISA] method. The results were correlated with the T, N, M stage, cell differentiation, vascular, neural, and lymphatic invasion, tumor size, and tumor location. Results: In the 11 inflammatory patients, telomerase activity was not detected while in the gastric cancer patients, a positive rate of $28.1\%$ was noted. The peripheral telomerase activity was not related with tumor size, tumor site, lymphatic and vascular invasion, stage, or histologic differentiation. Conclusion: The peripheral blood telomerase activity for patients of gastric cancer can be utilized as a marker for the diagnosis of not only advanced gastric cancer, but also relatively early stage gastric cancer, but not as a prognostic factor.

• Molecules and Cells
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• v.43 no.6
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• pp.581-589
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• 2020

Neurons have multiple dendrites and single axon. This neuronal polarity is gradually established during early processes of neuronal differentiation: generation of multiple neurites (stages 1-2); differentiation (stage 3) and maturation (stages 4-5) of an axon and dendrites. In this study, we demonstrated that the neuron-specific n-glycosylated protein NELL2 is important for neuronal polarization and axon growth using cultured rat embryonic hippocampal neurons. Endogenous NELL2 expression was gradually increased in parallel with the progression of developmental stages of hippocampal neurons, and overexpression of NELL2 stimulated neuronal polarization and axon growth. In line with these results, knockdown of NELL2 expression resulted in deterioration of neuronal development, including inhibition of neuronal development progression, decreased axon growth and increased axon branching. Inhibitor against extracellular signal-regulated kinase (ERK) dramatically inhibited NELL2-induced progression of neuronal development and axon growth. These results suggest that NELL2 is an important regulator for the morphological development for neuronal polarization and axon growth.

• Journal of Animal Reproduction and Biotechnology
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• v.35 no.1
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• pp.42-49
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• 2020

As a preclinical study, many researchers have been attempted to convert the porcine PSCs into several differentiated cells with transplantation of the differentiated cells into the pigs. Here, we attempted to derive neuronal progenitor cells from pig embryonic germ cells (EGCs). As a result, neuronal progenitor cells could be derived directly from pig embryonic germ cells through the serum-free floating culture of EB-like aggregates (SFEB) method. Treating retinoic acid was more efficient for inducing neuronal lineages from EGCs rather than inhibiting SMAD signaling. The differentiated cells expressed neuronal markers such as PAX6, NESTIN, and SOX1 as determined by qRT-PCR and immunostaining. These data indicated that pig EGCs could provide valid models for human therapy. Finally, it is suggested that developing transgenic pig for disease models as well as differentiation methods will provide basic preclinical data for human regenerative medicine and lead to the success of stem cell therapy.

• Journal of Korean Neurosurgical Society
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• v.61 no.2
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• pp.258-266
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• 2018

Objective : The diagnosis of insufficiency fractures of the sacrum in an elder population increases annually. Fractures show very different morphology. We aimed to classify sacral insufficiency fractures according to the position of cortical break and possible need for intervention. Methods : Between January 1, 2008 and December 31, 2014, all patients with a proven fracture of the sacrum following a low-energy or an even unnoticed trauma were prospectively registered : 117 females and 13 males. All patients had a computer tomography of the pelvic ring, two patients had a magnetic resonance imaging additionally : localization and involvement of the fracture lines into the sacroiliac joint, neural foramina or the spinal canal were identified. Results : Patients were aged between 46 and 98 years (mean, 79.8 years). Seventy-seven patients had an unilateral fracture of the sacral ala, 41 bilateral ala fractures and 12 patients showed a fracture of the sacral corpus : a total of 171 fractures were analyzed. The first group A included fractures of the sacral ala which were assessed to have no or less mechanical importance (n=53) : fractures with no cortical disruption ("bone bruise") (A1; n=2), cortical deformation of the anterior cortical bone (A2; n=4), and fracture of the anterolateral rim of ala (A3; n=47). Complete fractures of the sacral ala (B; n=106) : parallel to the sacroiliac joint (B1; n=63), into the sacroiliac joint (B2; n=19), and involvement of the sacral foramina respectively the spinal canal (B3; n=24). Central fractures involving the sacral corpus (C; n=12) : fracture limited to the corpus or finishing into one ala (C1; n=3), unidirectional including the neural foramina or the spinal canal or both (C2; n=2), and horizontal fractures of the corpus with bilateral sagittal completion (C3; n=8). Sixty-eight fractures proceeded into the sacroiliac joint, 34 fractures showed an injury of foramina or canal. Conclusion : The new classification allowes the differentiation of fractures of less mechanical importance and a risk assessment for possible polymethyl methacrylate leaks during sacroplasty in the direction of the neurological structures. In addition, identification of instable fractures in need for laminectomy and surgical stabilization is possible.

• Molecules and Cells
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• v.40 no.4
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• pp.271-279
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• 2017

Ran-binding protein family member, RanBP9 has been reported in various basic cellular mechanisms and neuropathological conditions including schizophrenia. Previous studies have reported that RanBP9 is highly expressed in the mammalian brain and retina; however, the role of RanBP9 in retinal development is largely unknown. Here, we present the novel and regulatory roles of RanBP9 in retinal development of a vertebrate animal model, zebrafish. Zebrafish embryos exhibited abundant expression of ranbp9 in developing brain tissues as well as in the developing retina. Yeast two-hybrid screening demonstrated the interaction of RanBP9 with Mind bomb, a component of Notch signaling involved in both neurogenesis and neural disease autism. The interaction is further substantiated by co-localization studies in cultured cells. Knockdown of ranbp9 resulted in retinal dysplasia with defective proliferation of retinal cells, downregulation of neuronal differentiation marker huC, elevation of neural proliferation marker her4, and alteration of cell cycle marker p57kip2. Expression of the $M{\ddot{u}}ller$ glial cell marker glutamine synthase was also affected in knockdown morphants. Our results suggest that Mind bomb-binding partner RanBP9 plays a role during retinal cell development of zebrafish embryogenesis.

• Animal cells and systems
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• v.12 no.1
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• pp.23-33
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• 2008

The Zic family is a group of genes encoding zinc finger proteins that are highly expressed in the mammalian cerebellum. Zic genes are the vertebrate homologue of Drosophila pair-rule gene, odd-paired(opa), which plays important roles in the parasegmental subdivision as well as in the visceral mesoderm development of Drosophila embryos. Recent studies on human, mouse, frog, fish and ascidian Zic homologues support that Zic genes are involved in a variety of developmental processes, including neurogenesis, myogenesis, skeletal patterning, and left-right axis establishment. In an effort to explore possible functions of Zic proteins during vertebrate embryogenesis, we initially examined more detailed expression pattern of zebrafish homologue of zic3(zic3z). zic3z transcripts are detected in the neuroectoderm, neural plate, dorsal neural tube, and brain regions including eye field during early embryonic development. Marker DNA studies found that zic3z transcription is modulated by BMP, Wnt, and Nodal signals particularly in the dorsal and vegetal neuroectoderm at gastrula. Interfering with zic3z translation with zic3z-specific morpholino causes abnormal brain formation and expansion of the optic stalk cells. Retinal ganglion cells(RGCs) undergo abnormal neuronal differentiation. These findings suggest that zic3z defines the dorsal and vegetal neuroectoderm to specify brain formation and retinal neurogenesis during early embryonic development.

• Journal of the Korean Institute of Intelligent Systems
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• v.14 no.4
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• pp.402-410
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• 2004

In this paper, an optimal design method of clonal selection based Fuzzy-Neural Networks (FNN) model for complex and nonlinear systems is presented. The FNNs use the simplified inference as fuzzy inference method and Error Back Propagation Algorithm as learning rule. Also Advanced Clonal Selection (ACS) is proposed to find the parameters such as parameters of membership functions, learning rates and momentum coefficients. The proposed method is based on an Immune Algorithm (IA) using biological Immune System and The performance is improved by control of differentiation rate. Through that procedure, the antibodies are producted variously and the parameter of FNN are optimized by selecting method of antibody with the best affinity against antigens such as object function and limitation condition. To evaluate the performance of the proposed method, we use the time series data for gas furnace and traffic route choice process.

• Journal of Web Engineering
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• v.14 no.15
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• pp.3125-3135
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• 2022

Alzheimer's disease (AD) is an irreversible neurodegenerative disease characterized by memory and cognitive impairments. Neurogenesis, which is related to memory and cognitive function, is reduced in the brains of patients with AD. Therefore, enhancing neurogenesis is a potential therapeutic strategy for neurodegenerative diseases, including AD. Hesperidin (HSP), a bioflavonoid found primarily in citrus plants, has anti-inflammatory, antioxidant, and neuroprotective effects. The objective of this study was to determine the effects of HSP on neurogenesis in neural stem cells (NSCs) isolated from the brain of mouse embryos and five familial AD (5xFAD) mice. In NSCs, HSP significantly increased the proliferation of NSCs by activating adenosine monophosphate (AMP)-activated protein kinase (AMPK)/cAMP-response element-binding protein (CREB) signaling, but did not affect NSC differentiation into neurons and astrocytes. HSP administration restored neurogenesis in the hippocampus of 5xFAD mice via AMPK/brain-derived neurotrophic factor/tropomyosin receptor kinase B/CREB signaling, thereby decreasing amyloid-beta accumulation and ameliorating memory dysfunction. Collectively, these preclinical findings suggest that HSP is a promising candidate for the prevention and treatment of AD.

• Clinical and Experimental Pediatrics
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• v.49 no.10
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• pp.1100-1105
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• 2006

Purpose : Because NELL2 expression is strictly restricted only in neurons in developing and post-differentiated neural tissues, it is thought to be involved in the neuronal differentiation during development and in the maintenance of neuronal physiology in the post-differentiated neurons. In this study, we examined whether NELL2 is involved in the regulation of cell cycle and apoptosis in the hippocampal neuroprogenitor HiB5 cells. Methods : Effects of NELL2 on the cultured HiB5 cell numbers, DNA fragmentation, and proteins involved in the regulation of the cell cycle were measured. Results : NELL2 induced a decrease in cell numbers and an increase in G1 phase arrest. Moreover, transfection of NELL2 resulted in an increase of DNA fragmentation that shows an evidence of apoptosis. Contents of proteins involved in the regulation of cell cycle were also changed by transfection of NELL2 expression vectors. Conclusion : This study suggests that NELL2 plays an important role in the regulation of cell cycle and apoptosis of neurons.

• Journal of Life Science
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• v.27 no.3
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• pp.370-381
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• 2017

Protein dephosphorylation is important for cellular regulation, which is catalyzed by protein phosphatases. Among protein phosphatases, carboxy-terminal domain (CTD) phosphatases are recently emerging and new functional roles of them have been revealed. There are 7 CTD phosphatases in human genome, which are composed of CTD phosphatase 1 (CTDP1), CTD small phosphatase 1 (CTDSP1), CTD small phosphatase 2 (CTDSP2), CTD small phosphatase-like (CTDSPL), CTD small phosphatase-like 2 (CTDSPL2), CTD nuclear envelope phosphatase (CTDNEP1), and ubiquitin-like domain containing CTD phosphatase 1 (UBLCP1). CTDP1 dephosphorylates the second phosphor-serine of CTD of RNA polymerase II (RNAPII), while CTDSP1, STDSP2, and CTDSPL dephosphorylate the fifth phosphor-serine of CTD of RNAPII. In addition, CTDSP1 dephosphorylates new substrates such as mothers against decapentaplegic homologs (SMADs), cell division cycle-associated protein 3 (CDCA3), Twist1, tumor-suppressor protein promyelocytic leukemia (PML), and c-Myc. CTDP1 is related to RNA polymerase II complex recycling, mitosis regulation and cancer cell growth. CTDSP1, CTDSP2 and CTDSPL are related to transcription factor recruitment, tumor suppressor function and stem cell differentiation. CTDNEP1 dephosphorylates LIPIN1 and is related to neural tube formation and nuclear envelope formation. CTDSPL2 is related to hematopoietic stem cell differentiation. UBLCP1 dephosphorylates 26S proteasome and is related to nuclear proteasome regulation. In conclusion, noble roles of CTD phosphatases are emerging through recent researches and this review is intended to summarize emerging roles of CTD phosphatases.