• Journal of Life Science
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• v.31 no.5
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• pp.527-535
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• 2021

Lysosomes are organelles surrounded by membranes that contain acid hydrolases; they degrade proteins, macromolecules, and lipids. According to nutrient conditions, lysosomes act as signaling hubs that regulate intracellular signaling pathways and are involved in the homeostasis of cells. Therefore, the lysosomal dysfunction occurs in various diseases, such as lysosomal storage disease, neurodegenerative diseases, and cancers. Multiple forms of stress can increase lysosomal membrane permeabilization (LMP), resulting in the induction of lysosome-mediated cell death through the release of lysosomal enzymes, including cathepsin, into the cytosol. Here we review the molecular mechanisms of LMP-mediated cell death and the enhancement of sensitivity to anticancer drugs. Induction of partial LMP increases apoptosis by releasing some cathepsins, whereas massive LMP and rupture induce non-apoptotic cell death through release of many cathepsins and generation of ROS and iron. Cancer cells have many drug-accumulating lysosomes that are more resistant to lysosome-sequestered drugs, suggesting a model of drug-induced lysosome-mediated chemoresistance. Lysosomal sequestration of hydrophobic weak base anticancer drugs can have a significant impact on their subcellular distribution. Lysosome membrane damage by LMP can overcome resistance to anticancer drugs by freeing captured hydrophobic weak base drugs from lysosomes. Therefore, LMP inducers or lysosomotropic agents can regulate lysosomal integrity and are novel strategies for cancer therapy.

• Journal of Life Science
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• v.26 no.2
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• pp.212-219
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• 2016

Glioblastoma multiforme is the most common and most aggressive type of primary brain tumor in humans. Despite intensive treatment, including surgery, radiation, and chemotherapy, most patients die of the disease. Although the anti-cancer activity of resveratrol has been demonstrated in various cancer cell types, its underlying mechanism in glioma cells is not fully elucidated. The present study was undertaken to investigate the effect of resveratrol on cell viability and to determine the molecular mechanism in A172 human glioma cells. Resveratrol caused the generation of reactive oxygen species (ROS), and resveratrol-induced cell death was prevented by antioxidants (N-acetylcysteine and catalase), suggesting that an oxidative mechanism is responsible for resveratrol-induced cell death. Resveratrol-induced phosphorylation of extracellular signal-regulated kinase (ERK), p38 kinase, and c-Jun N-terminal kinase (JNK), and resveratrol-induced cell death were prevented by inhibitors of these kinases. Resveratrol-induced activation of caspase-3 and cell death were prevented by the caspase inhibitors. ERK activation and caspase-3 activation induced by resveratrol was blocked by N-acetylcysteine. Taken together, these results suggest that resveratrol causes a caspase-dependent cell death via activation of ERK, p38, and JNK, mediated by ROS generation, in human glioma cells.

• Journal of Veterinary Clinics
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• v.26 no.3
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• pp.212-219
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• 2009

Anticholinergics, which are commonly given as a pre-anesthetic medication to prevent adverse effects in canine anesthesia, can cause cardiac adverse effects. To determine the effects of atropine and glycopyrrolate on the balance of sympathetic nervous tone and parasympathetic nervous tone of the heart during ketamine anesthesia in beagle dogs, heart rate variability(HRV), duration of anesthesia and behavioral changes were evaluated. There were no significant temporal domain differences between atropine and glycopyrrolate. Concerning the frequency domain component, atropine and glycopyrrolate effects were significantly lower(P<0.05) than the control saline-treated group. However, the root mean square of the interval differences between consecutive R peaks(RMSSD) and the standard deviation of Poincare plot perpendicular to the line-of-identity(SD1) in atropine were significantly decreased(P<0.05) from the baseline value, and the low frequency/high frequency ratio(LF:HF ratio) in glycopyrrolate was significantly increased from baseline value(P<0.05). The change of SD1 agreed with that of the high frequency(HF) in the frequency domain component and also with those of respiratory rate and $SpO_2-R$. Our results prove that glycopyrrolate is more suitable as a pre-anesthetic anticholinergic in ketamine anesthesia of dogs with respect to safety and duration of action.

• Journal of the Korea Institute of Information and Communication Engineering
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• v.8 no.8
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• pp.1732-1739
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• 2004

In this paper, we proposed a visualization system with ANN algorithm that traits the motion of particles that move colliding in the water, where we got a great deal of variable information and predicts the distribution of particles according to the flowing of water and the pattern of their precipitation. We adopted ART2 to detect sensitively the collision between particles in this visualzation. Various particles and their mutual collision influencing the force such as buoyancy force, gravitational force, and the pattern of precipitation are considered in this system. Flowing particles whose motion is changed with the environment can be visualized in the system presented here as they are in real water.

• Korean Journal of Psychosomatic Medicine
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• v.7 no.2
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• pp.263-273
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• 1999

Headache is a symptom with varied etiologies and extraordinarily frequent. Headaches can be a symptom of another diseases, such as meningitis, subarachnoid hemorrhage or brain tumor, may represent the disease entity itself as the case in migraine. The international Headache Society criteria were the first to distinguish between primary and secondary headache disorders. When evaluating a patient who presents with headache, the physician abviously needs to identify or exclude the myriad conditions that can cause secondary headache and initial diagnostic workup should be considered. If patient meets the criteria for a primary headache disorder, treatment commonly initiated without additional neurodiagnostic tests. The headache type, its associated feature, and the duration and the intensity of the pain attack all can influence the choice of acute therapy in migraine. Pharmacologically, such as NSAIDs, combination analgesics, vasoactive antimigraineous drugs, neuroleptics, antidepressants, or corticosteroids. Other approches to managing headache include a headache diary to identify triggers, biofeedback, relaxation technique and behavioral modification. Daily preventive medication should be considered by his attack frequency and intensity, and maintained for 4 to 6 months. Tension-type headaches are distinguished between episodic and chronic tension-type headache, but physician must make sure that patient is not drug-overuse or independent during symptomatic abortive therapy or preventive medication. The most difficult headache patients to treat are those with chronic daily headache. They often have physical dependency, low frustration tolerance, sleep problems, and depression. So discontinuation of overused medication is crucial. New developments in migraine therapy are broadening the scope of abortive and prophylactic treatment choices available to the physician. The enhanced ease of the use of sumatriptan and DHE will likely increase patient compliance and satisfaction.

• Journal of the korean academy of Pediatric Dentistry
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• v.26 no.2
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• pp.350-364
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• 1999

The distribution of mast cells and nerves were investigated in the submandibular and sublingual glands of postnatal rats, using morphometric, histochemical and immunohistochemical techniques. Mast cells were observed in the submandibular and sublingual glands of postnatal development. Number of mast cells gradually increased in both glands following development. At birth, mast cells were relatively fewer in submandibular gland than those in sublingual gland, and they were mainly distributed in parenchymal tissues. At $2{\sim}4$ weeks, most of the mast cells were observed in the connective tissues, surrounding neurovascular elements, but some mast cells were closely related with the acini of submandibular gland. PGP 9.5 immunoreactive nerve fibers were found in the submandibular and sublingual glands of all developmental age. The nerve fibers were showed in varicose shape, and mainly located in adjacent area of ducts and vascular components of both glands. The number of nerve fibers were increased rapidly until 8 weeks, but they were not increased any more until 24 weeks. Therefore, it is suggested that mast cells and nerve fibers related with each other, and that their interactions may play roles not only in maturation of secretory units but also growth and differentiation of the tubular structures of the rat submandibular and sublingual glands during postnatal development.

• Proceedings of the Korea Technical Association of the Pulp and Paper Industry Conference
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• 2001.11a
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• pp.59-59
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• 2001

전보에서 발표한 바와 같이, 대상 라이너지 제조공장의 습부 운전조건이 지극히 악화되어 있으며 초지 시스템이 지종교체 등의 충격에 전혀 완충작용을 못하는 이유로 는 용수를 포함한 지료의 전하특성을 조절해주지 못하기 때문인 것으로 판단되었다. 특 히 양이온성 고분자로서 유일하게 사용하고 있는 보류향상제가 적절히 작용하지 못하 기 때문에 보류도가 저하되고, 제품내에 보류되지 못한 다량의 미세분이 백수 중에 존 재함으로서 결과적으로 지료의 전기적 특성을 더욱 악화시키는 악순환이 되풀이 되는 것으로 판단되었다. 이와 같이 강하게 음으로 하전된 지료의 전기적 특성을 조절하기 위해서는 양이온성 고분자의 사용량을 증가시키거나 고분자의 전하밀도 또는 분자량을 변화시켜 보는 것이 일반적인 습부첨가제 사용방법이라고 할 수 있다. 따라서 대상 습부공정의 조업조건을 호전시키기 위해서는 적절한 보류향상시스 템의 적용이 가장 시급한 현안이라고 판단되어 선규 보류제의 현장적용시험을 수행한 결과, 백수의 COD와 미세분이 격감하고 탈수성이 향상되어 습부공정의 운전조건이 호 전됨을 관측할 수 있었다. 그러나 2달 이상에 걸친 보류제 현장적용시험 기간 중에 생 산된 라이너지의 제반 물성들은 별다른 변화를 관측할 수 없었다. 이는 적용된 보류제 의 상당 부분이 계내의 미세분과 작용하여 소모되기 때문으로 판단되었다. 본 연구에서는 보류제의 투입 이전에 보류제와는 상대적으로 저분자량과 고 전 하밀도를 가진 고분자 전해질 4종을 사용하여 라이너지 지료의 전하를 중화시키고자 하였으며, 이러한 공정으로 생산된 라이너지의 물성변화를 관측하였다. 물성으로는 파 열강도, 압축강도, 습윤인장강도 및 염료 고착능력 등을 살펴보았다.시아노에틸화한 PYA가 안정된 분자구조를 유지하고 있음을 확인할 수 있었다. 시아노에틸화한 PYA용액의 점탄성 평가를 위하여 storage modulus와 loss modulus 를 분석하였다. 일반적 유변특성 평가 결과 PYA용액은 shear-thinning, pseudoplastic 한 특성을 나타내어 표면사이즈 공정에서의 적용 가능성을 확인할 수 있었다. 사용하는 통계기법 중의 하나인 주성분회귀분석을 실시하였다. 주성분 분석은 여러 개의 반응변수에 대하여 얻어진 다변량 자료의 다차원적인 변 수들을 축소, 요약하는 차원의 단순화와 더불어 서로 상관되어있는 반응변수들 상호간 의 복잡한 구조를 분석하는 기법이다. 본 발표에서는 공정 자료를 활용하여 인공신경망 과 주성분분석을 통해 공정 트러블의 발생에 영향 하는 인자들을 보다 현실적으로 추 정하고, 그 대책을 모색함으로써 이를 최소화할 수 있는 방안을 소개하고자 한다.금 빛 용사 둥과 같은 표면처리를 할 경우임의 소재 표면에 도금 및 용 사에 용이한 재료를 오버레이용접시킨 후 표면처리를 함으로써 보다 고품질의 표면층을 얻기위한 시도가 이루어지고 있다. 따라서 국내, 외의 오버레이 용접기술의 적용현황 및 대표적인 적용사례, 오버레이 용접기술 및 용접재료의 개발현황 둥을 중심으로 살펴봄으로서 아직 국내에서는 널리 알려지지 않은 본 기 술의 활용을 넓이고자 한다. within minimum time from beginning of the shutdown.및 12.36%, $101{\sim}200$일의 경우 12.78% 및 12.44%, 201일 이상의 경우 13.17% 및 11.30%로 201일 이상의 유기의 경우에만 대조구와 삭

• Journal of Ginseng Research
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• v.24 no.1
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• pp.18-22
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• 2000

In previous reports we have shown that ginsenosides inhibit high threshold voltage-dependent $Ca^{2+}$ channels in neuronal cells. However, these studies did not show whether ginsenosides-induced inhibition of $Ca^{2+}$ currents discriminates among the various $Ca^{2+}$ channel subtypes, although it is known that there are at least five different $Ca^{2+}$ channel subtypes in neuronal cells. In this study we investigated the effect of ginsenosides on high threshold voltage-dependent $Ca^{2+}$ channel subtypes using their selective $Ca^{2+}$ channel blockers nimodipine (L-type), $\omega$-conotoxin GVIA (N-type), or $\omega$-agatoxin IVA (P-type) in bovine chromaffin cells. We could observe that ginsenosides inhibited high threshold voltage-dependent $Ca^{2+}$ currents in a dose-dependent manner. The $IC_{50}$/ was about 120 $\mu$g/ml. Nimodipine had no effect on ginsenosides response. However, the effect of ginsenosides on $Ca^{2+}$ currents was reduced by $\omega$-conotoxin GVIA, $\omega$-agatoxin IVA, and mixture of nimodipine, $\omega$-contoxin GVIA, and $\omega$-agatoxin IVA. These data suggest that ginsenosides are negatively coupled to three types of calcium channels in bovine chromaffin cell, including an $\omega$-conotoxin GVIA-sensitive (N-type) channel, an $\omega$-agatoxin IVA-sensitive (P-type) channel and nimodipine/$\omega$-conotoxin GVIA/$\omega$-agatoxin IVA-resistant (presumptive Q-type) channel.Q-type) channel.

• Journal of Yeungnam Medical Science
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• v.13 no.2
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• pp.159-172
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• 1996

대기오염물질이면서 동시에 생체내 화학반응의 산물이기도 한 nitric oxide(NO)는 그 생체내 분포가 광범위하고 생리적 역할이 다양하여, 최근의 생명과학 분야에서 가장 크게 주목받는 몇가지 연구대상 중 하나이다. 세포에서의 NO 산생은 nitric oxide synthase (NOS)에 의해 촉매되는데, 이들은 brain form (bNOS, neuronal; nNOS, NOS I), inducible form (iNOS), 및 endothelial form(eNOS)로 구분되는데, 이중 bNOS(nNOS)와 eNOS는 inducible form에 대비되는 constitutive form(cNOS)에 해당하므로 각각 ncNOS 와 ecNOS로도 불리운다. NOS는 아미노산인 L-arginine을 산소와 결합시켜 L-citrulline으로 변환시키면서 NO를 유리하고, 이 NO는 세포내의 guanylate cyclase를 활성화하여 cyclic GMP를 생산하거나, superoxide(O2-) 및 수소이온과 차례로 결합하여 반응성이 매우 높은 수산화기(-OH)를 발생시켜 세포독작용을 유발하기도 한다. 정상상태에서 뇌혈관내피세포의 ecNOS로 부터 유리된 NO는 혈관을 확장시켜 신경세포에 대한 산소공급을 원활히 유지해 주지만, 순환장애를 일으켰을 때는 뇌조직내의 iNOS로부터 대량의 NO가 유출되어 신경세포의 손상을 가져온다. 호흡기에서는 NO가 기도평활근을 이완시키고 폐혈류를 개선하므로, 미숙아나 성인의 호흡장애시에 소량의 NO를 흡입시키면 oxygenation을 호전시킬 수 있다. 그러나 대기오염이나 흡연 등으로 대량의 NO를 흡입할 경우 치명적인 폐부종이나 methemoglobin혈종을 일으킬 수 있다. 순환계에서는 cNOS가 혈관을 확장시켜 조직의 혈류를 유지하는데 일익을 담당한다. 세균내 독소(lipopolysaccharide; LPS)나 각종 명역조절물질들이 혈관내피세포와 혈관평활근세포로 부터 과다한 NO를 유리시키면 혈압이 급격히 떨어져 순환허탈상태에 빠지게 된다. 심장에서는 관상혈관 내피세포의 eNOS가 심근의 혈류를 유지해 주지만 허혈이나 세균내독소 또는 면역조절물질 등에 의하여 심근세포나 침윤된 대식세포의 iNOS로 부터 과량의 NO가 유리되면 심근세포의 손상이 초래된다. 신장에서는 내피세포의 cNOS에 의하여 사구체여과가 조절되고 있는데, 세균내독소나 면역 조절물질 등에 의하여 사구체관막세포(mesangial cell)등의 iNOS로 부터 과량의 NO가 유리되면 신조직과 사구체의 손상을 초래한다. 위와 같이 대부분의 장기에서 ecNOS는 조직의 혈류를 유지하는 역할을 하며, iNOS는 애초 세균 등 침입자에 대한 세포독작용이 그 존재 목적이라고 풀이할 수 있겠으나 일종의 부작용으로 자체조직의 손상을 초래하게 되는 것으로 본다. 따라서 NO와 관련된 각종 병변의 치료를 위해서는 NOS의 비선택성 억제제인 arginine 유도체 보다는 iNOS에 대한 선택적 억제제인 S-methylisothiourea(SMT), aminoethylisothiourea(AETU), aminoguanidine (AMG), agmatine, L-canavanine, transforming growth factor b1(TGF-b1) 등의 사용을 검토해 보는 것이 타당할 것으로 사료된다.

• Journal of Life Science
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• v.26 no.5
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• pp.509-518
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• 2016

Asparagus cochinchinensis is a medical plant that has long been used to treat fever, cough, kidney disease, breast cancer, inflammatory disease and brain disease in northeast Asian countries. Although several studies have been conducted on the anti-neuroinflammatory effects of A. cochinchinensis, the correlation between these effects and nerve growth factor (NGF) has not yet been examined. In this study, we investigated the effects of an aqueous extract of A. cochinchinensis (AEAC) on the secretion and action mechanism of NGF in neuronal cells. The concentration of the NGF protein in the supernatant collected from cultured cells increased significantly in B35 cells treated with AEAC in comparison with the vehicle-treated group without any specific cytotoxicity. Furthermore, the mRNA expression of NGF showed a very similar pattern to its protein concentration. To examine the bioactivity of NGF secreted from B35 cells, undifferentiated PC12 cells were cultured in an AEAC-conditioned medium and neuritic outgrowth was observed. The dendrite length of PC12 cells in the AEAC-treated group was significantly higher than that in the vehicle-treated group. Moreover, the level of the downstream effectors p-TrkA and p-ERK of the high-affinity NGF receptor was significantly higher in the AEAC-treated group, while the expression of the downstream effectors of the low-affinity NGF receptor was significantly lower in the same group. These results suggest that AEAC may contribute to the regulation of NGF expression and secretion in neuronal cells; it is therefore an excellent candidate for further investigation as a therapeutic drug for neurodegenerative diseases.