• 대한본초학회지
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• 제30권1호
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• pp.77-84
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• 2015

Objectives : Brain inflammation early activates the microglia and activated microglia secrete a variety of pro-inflammatory cytokines. Kaempferol, which is a flavonoid in Cuscutae Semen, shows a wide range of physiological activities, including neurons protection and anti-inflammatory actions through inhibition of pro-inflammatory mediators. The present study examined the modulatory effect of kaempferol on cytokines [tumor necrosis factor- alpha ($TNF-{\alpha}$), interleukin-1beta ($IL-1{\beta}$) and interleukin-6 (IL-6)] and cyclooxygenase-2 (COX-2) mRNA expression and microglia activation in the brain tissue of the mouse. Methods : Kaempferol was administered orally three doses of 10, 20 and 30 mg/kg respectively, once 1 hour before the lippolysaccharide(LPS) (3 mg/kg, i.p.) injection. Brain tissue was removed at 4 hours after LPS injection. Cytokines and COX-2 mRNA expression in the brain tissue was measured by the quantitative real-time polymerase chain reaction (PCR) method. Iba1 expression was calculated by western blotting method. Microglia was observed with immunohistochemistry. Immunohistochemistry stained microglia was analyzed by using ImageJ software. Results : Kaempferol 20 and 30 mg/kg was significantly attenuated the expression of $TNF-{\alpha}$, $IL-1{\beta}$ and IL-6 mRNA. Kaempfrol 10, 20 and 30 mg/kg significantly attenuated COX-2 mRNA expression in the brain tissue. Kaempferol 30 mg/kg significantly suppressed the increase of Iba1 protein expression by LPS. Kaempferol 30 mg/kg significantly decreased the number of microglia in the cerebral cortex and the number and cell size of microglia in the hypothalamic region and the area percentage of ionized calcium binding adaptor molecule 1(Iba1)-expressed microglia in the hippocampus. Conclusions : This results indicate that kaempferol plays an anti-inflammatory role in the brain.

• Anatomy and Cell Biology
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• 제50권3호
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• pp.207-213
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• 2017

Glycogen synthase kinase $(GSK)-3{\beta}$ and related enzymes are associated with various forms of neuroinflammation, including spinal cord injury (SCI). Our aim was to evaluate whether lithium, a non-selective inhibitor of $GSK-3{\beta}$, ameliorated SCI progression, and also to analyze whether lithium affected the expression levels of two representative $GSK-3{\beta}$-associated molecules, nuclear factor erythroid 2-related factor-2 (Nrf-2) and heme oxygenase-1 (HO-1) (a target gene of Nrf-2). Intraperitoneal lithium chloride (80 mg/kg/day for 3 days) significantly improved locomotor function at 8 days post-injury (DPI); this was maintained until 14 DPI (P<0.05). Western blotting showed significantly increased phosphorylation of $GSK-3{\beta}$ (Ser9), Nrf-2, and the Nrf-2 target HO-1 in the spinal cords of lithium-treated animals. Fewer neuropathological changes (e.g., hemorrhage, inflammatory cell infiltration, and tissue loss) were observed in the spinal cords of the lithium-treated group compared with the vehicle-treated group. Microglial activation (evaluated by measuring the immunoreactivity of ionized calcium-binding protein-1) was also significantly reduced in the lithium-treated group. These findings suggest that $GSK-3{\beta}$ becomes activated after SCI, and that a non-specific enzyme inhibitor, lithium, ameliorates rat SCI by increasing phosphorylation of $GSK-3{\beta}$ and the associated molecules Nrf-2 and HO-1.

• Biomolecules & Therapeutics
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• 제29권5호
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• pp.483-491
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• 2021

Parkinson's disease (PD) is a neurodegenerative disorder that involves the loss of dopaminergic neurons in the substantia nigra (SN). Matrix metalloproteinases-8 (MMP-8), neutrophil collagenase, is a functional player in the progressive pathology of various inflammatory disorders. In this study, we administered an MMP-8 inhibitor (MMP-8i) in Leucine-rich repeat kinase 2 (LRRK2) G2019S transgenic mice, to determine the effects of MMP-8i on PD pathology. We observed a significant increase of ionized calcium-binding adapter molecule 1 (Iba1)-positive activated microglia in the striatum of LRRK2 G2019S mice compared to normal control mice, indicating enhanced neuro-inflammatory responses. The increased number of Iba1-positive activated microglia in LRRK2 G2019S PD mice was down-regulated by systemic administration of MMP-8i. Interestingly, this LRRK2 G2019S PD mice showed significantly reduced size of cell body area of tyrosine hydroxylase (TH) positive neurons in SN region and MMP-8i significantly recovered cellular atrophy shown in PD model indicating distinct neuro-protective effects of MMP-8i. Furthermore, MMP-8i administration markedly improved behavioral abnormalities of motor balancing coordination in rota-rod test in LRRK2 G2019S mice. These data suggest that MMP-8i attenuates the pathological symptoms of PD through anti-inflammatory processes.

• 대한본초학회지
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• 제28권6호
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• pp.145-153
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• 2013

Objectives : Neuroinflammation is characterized by microglial activation and the expression of major inflammatory mediators. The present study investigated the inhibitory effect of ginsenoside Rg1 ($GRg_1$), a principle active ingredient in Panax ginseng, on pro-inflammatory cytokines and microglial activation induced by systemic lipopolysaccharide (LPS) treatment in the mouse brain tissue. Methods : Varying doses of $GRg_1$ was orally administered (10, 20, and 30 mg/kg) 1 h before the LPS injection (3 mg/kg, intraperitoneally). The mRNA expression of pro-inflammatory cytokines in the brain tissue was measured using the quantitative real-time PCR method at 4 h after the LPS injection, Microglial activation was evaluated using western blotting and immunohistochemistry against ionized calcium binding adaptor molecule 1 (Iba1) in the brain tissue. Cyclooxigenase-2 (COX-2) expressions also observed using western blotting and immunohistochemistry at 4 h after the LPS injection, In addition, double-immunofluorescent labeling of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) and COX-2 with microglia and neurons was processed in the brain tissue. Results : $GRg_1$ (30 mg/kg) significantly attenuated the upregulation of TNF-${\alpha}$, interleukin (IL)-$1{\beta}$ and IL-6 mRNA in the brain tissue at 4 h after LPS injection. Morphological activation and Iba1 protein expression of microglia induced by systemic LPS injection were reduced by the $GRg_1$ (30 mg/kg) treatment. Upregulation of COX-2 protein expression in the brain tissue was also attenuated by the $GRg_1$ (30 mg/kg) treatment. Conclusion : The results suggest that $GRg_1$ is effective in the early stage of neuroinflammation which causes neurodegenerative diseases.

• Journal of Veterinary Science
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• 제25권3호
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• pp.35.1-35.13
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• 2024

Importance: Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis characterized by inflammation within the central nervous system. However, inflammation in non-neuronal tissues, including the lungs, has not been fully evaluated. Objective: This study evaluated the inflammatory response in lungs of EAE mice by immunohistochemistry and histochemistry. Methods: Eight adult C57BL/6 mice were injected with myelin oligodendrocyte glycoprotein_35-55 to induce the EAE. Lungs and spinal cords were sampled from the experimental mice at the time of sacrifice and used for the western blotting, histochemistry, and immunohistochemistry. Results: Histopathological examination revealed inflammatory lesions in the lungs of EAE mice, characterized by infiltration of myeloperoxidase (MPO)- and galectin-3-positive cells, as determined by immunohistochemistry. Increased numbers of collagen fibers in the lungs of EAE mice were confirmed by histopathological analysis. Western blotting revealed significantly elevated level of osteopontin (OPN), cluster of differentiation 44 (CD44), MPO and galectin-3 in the lungs of EAE mice compared with normal controls (p < 0.05). Immunohistochemical analysis revealed both OPN and CD44 in ionized calcium-binding adapter molecule 1-positive macrophages within the lungs of EAE mice. Conclusions and Relevance: Taken together, these findings suggest that the increased OPN level in lungs of EAE mice led to inflammation; concurrent increases in proinflammatory factors (OPN and galectin-3) caused pulmonary impairment.

• 한국임상약학회지
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• 제29권3호
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• pp.166-172
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• 2019

Background: Hypercalcemia is an important metabolic emergency condition in cancer patients. Bisphosphonate is the treatment of choice for hypercalcemia, whereas calcitonin and hydration with furosemide are recommended for acute supportive therapy. However, data regarding real-world treatment patterns and outcomes of pharmacological treatments are limited. Therefore, we aimed to investigate the treatment patterns and clinical outcomes of hypercalcemia treatment in solid tumor patients. Methods: Electronic medical records of 123 adults with solid cancers and albumin-corrected calcium levels >10.5 mg/dL or ionized calcium levels >1.35 mmol/L were reviewed. We retrospectively analyzed the pharmacological treatment and recovery rate according to the severity of hypercalcemia. Results: A total of 177 cases were identified, of which 49 were not treated and 30 were treated with hydration only. In moderate-to-severe cases, 86.5% received pharmacological treatment. Thirty-four cases (19.2%) were treated with bisphosphonate alone and 58 cases (32.8%) were treated with bisphosphonate and calcitonin. In mild hypercalcemia cases, the recovery rate was higher for those receiving hydration only or pharmacological treatment (79.7%) than for those receiving no treatment (61.4%, p = 0.041). Most moderate-to-severe cases were treated with medication and of those treated, 56.3% recovered. The recovery rate was lower in those treated with bisphosphonate alone (38.2%) than in those who underwent calcitonin combination treatment (73.7%, p = 0.001). Conclusions: Bisphosphonate combined with calcitonin was found to be more effective than bisphosphonate alone for the treatment of moderate-to-severe hypercalcemia. Considering the current shortage of calcitonin, further efforts are required to ensure its stable supply.

• Journal of Chest Surgery
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• 제31권10호
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• pp.945-951
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• 1998

개심술시 총순환정지는 매우 유용한 방법이나 뇌손상등 부작용으로 그 사용이 제한되고 있다. 이러한 뇌손상의 분석에 유용한 지표로서 뇌 허혈성 손상의 특이한 효소인 크레아티닌 카이네이즈 BB(CK-BB)의 유용성을 재고하고 뇌손상에 영향을 미치는 인자들의 분석을 시도하였다. 총순환정지를 이용하여 개심술을 시행한 18명의 환자를 대상으로 하였다. 이들은 다시 비청색증형 심기 형군과 청색증형 심기형군으로 나누어 각각 6명과 12명으로 하였다. 각 환자에서 총순환정지전 및 후 15, 30, 60, 120, 240, 480, 720분에 동맥혈을 채취하여 CK-BB분획을 측정하였고 이와 동시에 혈색소농도, 이 온화 칼슘농도, 혈당량 등을 측정하였다. 총순환정지시간과 CK-BB와 통계적으로 유의한 관계를 보이는 채혈시간은 찾을 수 없었다. 또 총순환 정지전의 문제로 인한 영향을 줄이기 위하여 각각의 측정치에서 총순환정지전의 측정치를 뺀 값을 구하 여 각기 CKBBD15, CKBBD30....등으로 표시하고 상관관계를 구하였으나 역시 유의한 상관관계를 보이 지 않았다. CKBB30과 CKBBD30값은 비청색증형 군과 청색증형 군 사이에 유의한 차이를 보이지 않았 다. CK-BB농도와 혈색소 농도는 유의한 상관관계를 보였다. 단일 채혈에 의한 CK-BB농도의 지표는 순환정지시간과 유의한 관계가 없음이 확인되었다. 또한 청색 증형 심질환군이 총순환정지에 의한 뇌손상에 비청색증형 심질환군에 비해 더 취약하지는 않은 것으로 생각된다.

• Journal of Preventive Medicine and Public Health
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• 제24권4호
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• pp.516-530
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• 1991

일상생활을 통한 연섭취로 인한 고혈압 발생 가능성 및 이때 연이 혈압에 영향을 미칠 수 있는 기전을 밝히기 위한 연구의 일환으로 환자 대조군 연구를 실시하였다. 대상자로서 울산 및 그 인근지역의 직업적 연폭로 과거력이 없는 남자 근로자 중 고혈압 환자 72명, 대조군 69명을 선택하였다. 혈중 연과 혈장레닌활성도(Plasma renin activity, PRA)를 측정하였으며 동시에 흡연유무, 음주유무, 고혈압 가족력 유무를 확인하고 body mass index(BMI), 혈청 소디움, 포타시움, 이온화 칼슘, 크레아티닌 및 총 콜레스테롤을 측정하였다. 고혈압군의 혈중 연농도는 $19.8{\pm}5.5{\mu}g/dl$로서 대조군의 $12.5{\pm}4.7{\mu}g/dl$에 비해 유의하게 높았고(p<0.01) 또한 혈중 연의 고혈압발생에 대한 교차비(odds ratio)가 1.38로서 역시 유의하였다(p<0.01). PRA나 In(PRA)가 고혈압군과 대조군 사이에 유의한 차이가 없었으나 고혈압군에서 혈중 연농도가 증가함에 따라 PRA도 어느정도 증가하는 양상을 보였고(p<0.1), In(PHA)를 종속변수로 하는 중회귀분석을 실시하였을 때 혈중 연농도(회귀계수 ; 0.037)가 10% 수준에서 유의하였다. 본 연구를 통해 볼 때, 지금까지 알려진 정상치 범위 이내의 혈중 연과 고혈압 발생간의 인과 관계에 대해 계속 연구해 볼 필요성을 느끼며 이때 PRA의 변화가 작용 기전의 일부에 관여할 가능성이 있을 것으로 추측된다.

• 한국임상수의학회지
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• 제32권6호
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• pp.544-547
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• 2015

11살 수컷 페키니즈가 10일간의 발작을 주증으로 내원하였다. 내원 15일전 파행으로 지역병원에서 소염제를 처방 받았었고 10일 전 간헐적 전신발작을 시작으로 내원 2일 전에는 실조와 정신둔감이 함께 발생하였다. 혈액검사와 영상학적 검사상 특이소견은 관찰되지 않았으나, 신경계 검사상 위협반사와 동공 빛 반사가 떨어짐을 확인할 수 있었다. 내원 9시간 후 호흡곤란이 발생하였고 그 후 12시간 후 보호자의 요청으로 안락사를 실시하였다. 부검상 가로 단면에서 확장된 종양으로 인해 현저한 중심선 이동을 관찰할 수 있었다. 조직학적 분석을 통해 신경아교세포의 거짓 울타리화된 괴사와 미세혈관의 증식을 확인할 수 있었다. 면역염색 결과 종양 부위에서 GFAP, PCNA, Iba-a 에 염색된 세포가 관찰되었다. 이와 같은 결과를 바탕으로 아교모세포종으로 진단되었다. 원발성 두강내 종양은 수의학에서 흔하지 않다. 이번 증례는 페키니즈견에서 아교모세포종의 임상적, 조직학적 발견에 대한 보고이다.

• 대한구강악안면병리학회지
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• 제42권5호
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• pp.111-118
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• 2018

Nicotine of tobacco component has a controversial impact in the clinical outcome of dental implants. Although numerous nicotine effects on bone healing around implants have been presented, it is rarely reported in vitro study about normal human osteoblast(NHost) from oral and maxillofacial area at the surface of implants. The purpose of the present study was to evaluate the effect of nicotine on the proliferation and differentiation response of NHost to plasmatic and salivary levels of nicotine reported in smokers at the surface of screw-type plasma-sprayed titanium implants. NHosts were seeded on the surface of titanium implants and cultured for 21 days in ${\alpha}-MEM$ supplemented with 10% FBS, 50mg/ml ascorbic acid, 5mM ${\beta}$-glycerophosphate and 100nM dexamethasone. Seeded implants were exposed to various nicotine concentration(0.05-0.5mg/ml) from 1 to 21 days, and characterized for cell morphology, proliferation, differentiation, alkaline phosphatase(ALP) activity and ionized calcium concentration(Cai) of medium. Continuous exposure to higher nicotine concentration(above 0.3mg/ml) induced a dose- and time-dependent vacuolation of the cytoplasm, and a tendency to detach from the implant surface. 0.05mg/ml(lower nicotine concentration) did not cause significant effects in the cell proliferation and ALP activity. 0.1-0.2mg/ml caused evident dose-dependent effects in increased cell proliferation, ALP activity and earlier onset of matrix mineralization at levels up to 0.2mg/ml, while a dose-dependent inhibitory effect at 0.3-0.5mg/ml. Cai concentration of control group was decreased at 14 days. Increased Cai concentration at 0.1-0.2mg/ml, decreased Cai concentration at 0.3mg/ml and no change at 0.5mg/ml during the culture period were seen. It suggested that nicotine concentration could paly an role in modulating NHost activity as a contributing factor associated with proliferation and differentiation of NHost at the surface of implants.