• Tunnel and Underground Space
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• v.30 no.1
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• pp.63-75
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• 2020

When tunnel is excavated via drilling and blasting, the excessive overbreak is the primary cause of personal or equipment safety hazards and increasing the cost of the tunnel operation owing to additional ground supports such as shotcrete. The practical management of overbreak is extremely difficult due to the complex causative mechanism of it. The study examines the relationship between rock mass characteristics (unsupported face condition, uniaxial compressive strength, face weathering and alteration, discontinuities- frequency, condition and angle between discontinuities and tunnel contour) and the depth of overbreak through using feed-forward artificial neuron networks. Then, Overbreak Resistance Factor (ORF) has been developed based on the weights of rock mass parameters to the overbreak phenomenon. Also, a new concept of tunnel overbreak management system using ORF has been suggested.

• Journal of Yeungnam Medical Science
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• v.39 no.3
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• pp.181-189
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• 2022

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative condition characterized by loss of motor neurons, resulting in motor weakness of the limbs and/or bulbar muscles. Pain is a prevalent but neglected symptom of ALS, and it has a significant negative impact on the quality of life of patients and their caregivers. This review outlines the epidemiology, clinical characteristics, underlying mechanisms, and management strategies of pain in ALS to improve clinical practice and patient outcomes related to pain. Pain is a prevalent symptom among patients with ALS, with a variable reported prevalence. It may occur at any stage of the disease and can involve any part of the body without a specific pattern. Primary pain includes neuropathic pain and pain from spasticity or cramps, while secondary pain is mainly nociceptive, occurring with the progression of muscle weakness and atrophy, prolonged immobility causing degenerative changes in joints and connective tissue, and long-term home mechanical ventilation. Prior to treatment, the exact patterns and causes of pain must first be identified, and the treatment should be tailored to each patient. Treatment options can be classified into pharmacological treatments, including nonsteroidal anti-inflammatory drugs, antiepileptic drugs, drugs for cramps or spasticity, and opioid; and nonpharmacological treatments, including positioning, splints, joint injections, and physical therapy. The development of standardized and specific assessment tools for pain-specific to ALS is required, as are further studies on treatments to reduce pain, diminish suffering, and improve the quality of life of patients with ALS.

• Journal of Ginseng Research
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• v.45 no.3
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• pp.401-407
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• 2021

Background: Gintonin is an exogenous ginseng-derived G-protein-coupled lysophosphatidic acid (LPA) receptor ligand. LPA induces in vitro morphological changes and migration through neuronal LPA1 receptor. Recently, we reported that systemic administration of gintonin increases blood-brain barrier (BBB) permeability via the paracellular pathway and its binding to brain neurons. However, little is known about the influences of gintonin on in vivo neuron morphology and migration in the brain. Materials and methods: We examined the effects of gintonin on in vitro migration and morphology using primary hippocampal neural precursor cells (hNPC) and in vivo effects of gintonin on adult brain neurons using real time microscopic analysis and immunohistochemical analysis to observe the morphological and locational changes induced by gintonin treatment. Results: We found that treating hNPCs with gintonin induced morphological changes with a cell rounding following cell aggregation and return to individual neurons with time relapses. However, the in vitro effects of gintonin on hNPCs were blocked by the LPA1/3 receptor antagonist, Ki16425, and Rho kinase inhibitor, Y27632. We also examined the in vivo effects of gintonin on the morphological changes and migration of neurons in adult mouse brains using anti-NeuN and -neurofilament H antibodies. We found that acute intravenous administration of gintonin induced morphological and migrational changes in brain neurons. Gintonin induced some migrations of neurons with shortened neurofilament H in the cortex. The in vivo effects of gintonin were also blocked by Ki16425. Conclusion: The present report raises the possibility that gintonin could enter the brain and exert its influences on the migration and morphology of adult mouse brain neurons and possibly explains the therapeutic effects of neurological diseases behind the gintonin administration.

• Biomolecules & Therapeutics
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• v.21 no.3
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• pp.222-228
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• 2013

Although the role of ${\alpha}$-synuclein aggregation on Parkinson's disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of ${\alpha}$-synuclein are unclear yet. We recently reported that ${\alpha}$-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing ${\alpha}$-synuclein in neuron, on ${\alpha}$-synuclein expression in rat primary astrocytes. VPA concentration-dependently increased the protein expression level of ${\alpha}$-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted ${\alpha}$-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in ${\alpha}$-synuclein. Whether the increased ${\alpha}$-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.73-80
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• 1994

From December 1989 to February 1993, 108 patients with Non-Small Cell Lung Cancers(NSCLC) were studied retrospectively to evaluate radiotherapeutic significance of serum levels of NSE. We considered elevated serum neuron specific enolase(S-NSE) level as one of the neuroendocrine features in NSCLC. Histopathologic evaluation revealed 86 squamous cell carcinomas, 11 adenocarcinomas.3 large cell carcinomas, 3 mucoepidermoid carcinomas, and 5 unknown pathology. Eight Patients had stage 1,40 stage IlIA, and 60 stage lIIB.S-NSE level greater than 15 ng/ml was considered as elevated, and below this considered as normal. All patients recieved radiotherapy as primary treatment modality. The responders to radiotherapy had significantly higher mean S-NSE level than non-responders (28.5 ng/ml vs 20 ng/ml, p=0.01). Overall 2-year survival rate(YSR) was 23.6$ \% $. According to radiotherapy response, 2 YSR for Patients with CR, PR, and NR were 39.2$ \% $, 28.6$ \% $, and 6.2$ \% $ respectively(p=0.001). 2 YSR for patients with elevated and normal S-NSE were 14.6$ \% $ and 31.7$ \% $(p=0.02). The patients with NR showed no difference in survival according to S-NSE level. When we considered all patients, S-NSE level showed no significant impact on response. But for squamous cell carcinomas alone, patients with elevated S-NSE had more responders(80$ \% $ vs 61$ \% $, p=0.05). There was no correlation between tumor characteristics and S-NSE level. But the patients with elevated S-NSE had more patients with higher nodal stage, Based on our and other datas, NSCLC with neuroendocrine features have different response to treatment and clinical behavior compared to other NSCLC. Thus, this subgroup may need different treatment modality, and S-NSE level may have prognostic significance.

• Natural Product Sciences
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• v.10 no.6
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• pp.289-295
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• 2004

Myristica fragrans seed from Myristica fragrans Houtt (Myristicaceae) has various pharmacological activities peripherally and centrally. The present study aims to investigate the effect of the methanol extract of Myristica fragrans seed (MF) on N-methyl-D-aspartate (NMDA)-induced neurotoxicity in primary cultured rat cerebellar granule neuron. MF, over a concentration range of 0.05 to $5\;{\mu}g/ml$, inhibited NMDA (1 mM)- induced neuronal cell death, which was measured by trypan blue exclusion test and 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl-tetrazolium bromide (MTT) assay. MF $(0.5\;{\mu}g/ml)$ inhibited glutamate release into medium induced by NMDA (1 mM), which was measured by HPLC. Pretreatrnent of MF $(0.5\;{\mu}g/ml)$ inhibited NMDA (1 mM)-induced elevation of cytosolic calcium concentration $([Ca^{2+}]_c)$, which was measured by a fluorescent dye, Fura 2-AM, and generation of reactive oxygen species (ROS). These results suggest that MF prevents NMDA-induced neuronal cell damage in vitro.

• Journal of Acupuncture Research
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• v.20 no.4
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• pp.145-156
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• 2003

Objective : This study is to investigate the effect of electro-acupuncture ST36 on altered transmission of afferent somatosensory information caused by amyloid-${\beta}$(A-${\beta}$) that caused Alzheimer's disease. Methods : The effects of topical application of A-${\beta}$, A-${\beta}$ with ST36, aggregated A-${\beta}$(aA-${\beta}$), aA-${\beta}$ with ST36 and ST36 on the afferent sensory transmission to the neurons in the primary somatosensory(SI) cortex was observed in anesthetized rats. Quantitative determination of the effects of A-${\beta}$, A-${\beta}$ with ST36, aA-${\beta}$, aA-${\beta}$ with ST36 and ST36 was made by generating poststimulus time histogram of evoked response of individual cortical neuron by electrical stimulation of the receptive located in peripheral area(forepaw) Results : The results obtained in present study were summerized as follow : 1. Application of physiological concentrative 0.5 nM A-${\beta}$ caused afferent sensory transmission of SI cortex facilitated. 0.5 nM A-${\beta}$ with ST36 exerted much stronger effects than 0.5 nM A-${\beta}$ alone. 2. Application of $10{\mu}M$ A-${\beta}$ caused afferent sensory transmission of SI cortex unchangeable. But $10{\mu}M$ A-${\beta}$ with ST36 is facilitated at 30 min of post-drug period 3. Application of $10{\mu}M$ aA-${\beta}$ caused afferent sensory transmission of SI cortex diminished. $10{\mu}M$ aA-${\beta}$ with ST36 is diminished after 15min of post-drug period but is facilitated after 75min.

• Parasites, Hosts and Diseases
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• v.55 no.3
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• pp.267-285
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• 2017

Angiostrongylus cantonensis invades the central nervous system (CNS) of humans to induce eosinophilic meningitis and meningoencephalitis and leads to persistent headache, cognitive dysfunction, and ataxic gait. Infected mice (nonpermissive host), admittedly, suffer more serious pathological injuries than rats (permissive host). However, the pathological basis of these manifestations is incompletely elucidated. In this study, the behavioral test, histological and immunohistochemical techniques, and analysis of apoptotic gene expression, especially caspase-3, were conducted. The movement and motor coordination were investigated at week 2 post infection (PI) and week 3 PI in mice and rats, respectively. The cognitive impairs could be found in mice at week 2 PI but not in rats. The plaque-like lesion, perivascular cuffing of inflammatory cells, and dilated vessels within the cerebral cortex and hippocampus were more serious in mice than in rats at week 3 PI. Transcriptomic analysis showed activated extrinsic apoptotic pathway through increased expression of TNFR1 and caspase-8 in mice CNS. Immunohistochemical and double-labeling for NeuN and caspase-3 indicated the dramatically increased expression of caspase-3 in neuron of the cerebral cortex and hippocampus in mice but not in rats. Furthermore, western-blotting results showed high expression of cleaved caspase-3 proteins in mice but relatively low expression in rats. Thus, extrinsic apoptotic pathway participated in neuronal apoptosis might be the pathological basis of distinct behavioral dysfunctions in rodents with A. cantonensis infection. It provides the evidences of a primary molecular mechanism for the behavioral dysfunction and paves the ways to clinical diagnosis and therapy for A. cantonensis infection.

• Biomolecules & Therapeutics
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• v.18 no.1
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• pp.48-55
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• 2010

Neural progenitor cells (NPCs) differentiate into astrocytes, neurons and oligodendrocytes, which is controlled by various factors in brain. Recent evidences suggest that small molecules modulating the proliferation and differentiation of NPCs may have therapeutic value as well as the potential use as chemical probes. Phylligenin is a lignan with anti-inflammatory activity that is isolated from the fruits of Forsythia koreana. We investigated effects of phylligenin on proliferation and differentiation of NPCs. Treatment of phylligenin decreased the number of proliferating NPCs in culture without effects on the differentiation and survival of neural cells such as neurons and astrocytes. To examine the mechanism of the decreased NPCs number, we performed cell cycle analysis. Proliferation of NPCs was decreased via G1-S transition block by phylligenin treatment, and it was mediated by the increase of p21 level. However, phylligenin did not induce apoptosis of NPCs as determined by TUNEL assay and PARP cleavage. We also found that viability of glioma cell lines such as C6 and U87MG glioma cells, but not that of primary neuron and astrocyte, was inhibited by phylligenin. These results suggest that phylligenin selectively inhibits proliferation of rapidly growing cells such as neural stem cells and glioma cells. Given that the possible role of brain tumor stem cells in the pathology of brain cancers, the inhibitory effects of phylligenin might be useful in the development of new therapeutic agents against brain cancers.

• Biomolecules & Therapeutics
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• v.25 no.6
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• pp.593-598
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• 2017

The $Na^+/H^+$ exchanger-1 (NHE-1) is a ubiquitously expressed pH-regulatory membrane protein that functions in the brain, heart, and other organs. It is increased by intracellular acidosis through the interaction of intracellular $H^+$ with an allosteric modifier site in the transport domain. In the previous study, we reported that glutamate-induced NHE-1 phosphorylation mediated by activation of protein kinase C-${\beta}$ (PKC-${\beta}$) in cultured neuron cells via extracellular signal-regulated kinases (ERK)/p90 ribosomal s6 kinases (p90RSK) pathway results in NHE-1 activation. However, whether glutamate stimulates NHE-1 activity solely by the allosteric mechanism remains elusive. Cultured primary cortical neuronal cells were subjected to intracellular acidosis by exposure to $100{\mu}M$ glutamate or 20 mM $NH_4Cl$. After the desired duration of intracellular acidosis, the phosphorylation and activation of PKC-${\beta}$, ERK1/2 and p90RSK were determined by Western blotting. We investigated whether the duration of intracellular acidosis is controlled by glutamate exposure time. The NHE-1 activation increased while intracellular acidosis sustained for >3 min. To determine if sustained intracellular acidosis induced NHE-1 phosphorylation, we examined phosphorylation of NHE-1 induced by intracellular acidosis by transient exposure to $NH_4Cl$. Sustained intracellular acidosis led to activation and phosphorylation of NHE-1. In addition, sustained intracellular acidosis also activated the PKC-${\beta}$, ERK1/2, and p90RSK in neuronal cells. We conclude that glutamate stimulates NHE-1 activity through sustained intracellular acidosis, which mediates NHE-1 phosphorylation regulated by PKC-${\beta}$/ERK1/2/p90RSK pathway in neuronal cells.