• Toxicological Research
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• 제28권3호
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• pp.179-185
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• 2012

Paecilomyces sinclairiis (PS) is known as a functional food or human health supplement. However concerns have been raised about its kidney toxicity. This study was performed to investigate the kidney toxicity of PS by 13 week-oral administration to rats. Blood urea nitrogen (BUN), serum creatinine, and kidney damage biomarkers including beta-2-microglobulin (${\beta}2m$), glutathione S-transferase alpha (GST-${\alpha}$), kidney injury molecule 1 (KIM-1), tissue inhibitor of matrix metalloproteinase 1 (TIMP-1), vascular endothelial growth factor (VEGF), calbindin, clusterin, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL) and osteopontin were measured during or after the treatment of PS. BUN, creatinine and kidney damage biomarkers in serum were not changed by PS. However, kidney cell karyomegaly and tubular hypertrophy were observed dose-dependently with higher severity in males. KIM-1, TIMP-1 and osteopontin in kidney and urine were increased dose dependently in male or at the highest dose in female rats. Increased urinary osteopontin by PS was not recovered at 2 weeks of post-exposure in both genders. Cystatin C in kidney was decreased at all treatment groups but inversely increased in urine. The changes in kidney damage biomarkers were more remarkable in male than female rats. These data indicate that the PS may provoke renal cell damage and glomerular filtration dysfunction in rats with histopathological lesions and change of kidney damage biomarkers in kidney or urine. Kidney and urinary KIM-1 and cystatin C were the most marked indicators, while kidney weight, BUN and creatinine and kidney damage biomarkers in serum were not influenced.

• Applied Microscopy
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• 제23권1호
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• pp.35-55
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• 1993

cis-Dichlorodiammineplatinum (II) (cis-Platin), a metallic compound, has widely been used as an effective anticancer chemotherapeutic agent. The precise mechanism of action of this agent is still unknown, but it is postulated that cis-Platin may act on the cancer cell like bifunctional alkylating agents. Although this agent is very beneficial to the patients with cervical cancer, germinoma of testis, neuroblastoma and others, it may also damage to the normal cell so that many side effects; severe hemorrhagic enterocolitis, bone marrow depression, renal damage and liver damage will develope. This experiment has been undertaken to pursue the cytotoxic effects of the cis-Platin on the ultrastructures of the interalveolar septum in the mouse lung. A total of 55 healthy male mice of ICR strain were used as experimental animals and divided into 5 mice of normal control group and 50 mice of cis-Platin treated group. The mice of cis-Platin treated group were sacrificed by carotid exsanguination at 6, 12, 24 hours, 3 days and 7 days after intraperitoneal injection of 6.0 mg of cis-Platin ($Abiplatin^R$ Abic Co. Ltd.) per kg of mouse body weight. The specimen obtained from the lower lobe of left lung were sliced into $1mm^3$ and prefixed with 2% glutaraldehyde -2.5% paraformaldehyde solution prepared with Millonig's phosphatae buffer solution (pH 7.4) at $4^{\circ}C$ for 3-4 hours. After postfixation with 1% osmium tetroxide solution all specimens were embedded in Epon 812. Ultrathin sections about $600-800{\AA}$ in thickness were stained with uranyl acetate and lead citrate and observed with Hitachi-600 electron microscope. The results obtained were as follows: 1. Local swellings with increase of electron density and number of pinocytic vesicles in the cytoplasms of the type I pneumocyte and endothelial cell of the blood air barrier in interalveolar septum of cis-platin treated mice were observed. 2. Cisternae of rough endoplasmic reticulum were dilated and sacculated in association with detachment of membrane bound ribosomes of the type II pneumocyte in interalveolar septum of cis-Platin treated mice. 3. Swollon mitochondria with uneven electron density of their matrix were observed in the type II pneumocyte of interalveolar septum in the cis-Platin treated mice. 4. The lamellae of lammelar bodies in type II pneumocyte of interalveolar septum in cis-Platin treated mice were devoided or transformed into homogeneous electron dense material. It is consequently suggested that cis-Platin would induce the cellular edema of type I pneumocyte and endothelial cell, and degenerative changes of cytoplasmic organelles of the type II pneumocyte in the interalveolar septum of the mouse lung.

• The Korean Journal of Physiology and Pharmacology
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• 제24권6호
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• pp.473-479
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• 2020

Endothelial cell injury is a major contributor to cardiovascular diseases. The 2,3,5,4'-Tetrahydroxystilbene-2-O-β-D-Glucoside (TSG) contributes to alleviate human umbilical vein endothelial cells (HUVECs) injury through mechanisms still know a little. This study aims to clarify the TSG effects on gene expression (mRNA and microRNA) related to oxidative stress and endoplasmic reticulum stress induced by H₂O₂ in HUVECs. We found that TSG significantly reduced the death rate of cells and increased intracellular superoxide dismutase activity. At qRT-PCR, experimental data showed that TSG significantly counteracted the expressions of miR-9-5p, miR-16, miR-21, miR-29b, miR-145-5p, and miR-204-5p. Besides, TSG prevented the expression of ATF6 and CHOP increasing. In contrast, TSG promoted the expression of E2F1. In conclusion, our results point to the obvious protective effect of TSG on HUVECs injury induced by H₂O₂, and the mechanism may through miR16/ATF6/ E2F1 signaling pathway.

• 한국산학기술학회논문지
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• 제18권10호
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• pp.178-184
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• 2017

본 연구는 2007년 1월부터 2015년 12월까지 본원에서 쯔쯔가무시병으로 진단을 받고 치료 중인 상태에서 뇌경색이 발생하거나, 뇌경색이 생겨 입원 치료를 받던 중 쯔쯔가무시병이 발견된 16명의 환자를 대상으로 하였다. 급성기 뇌경색의 진단은 뇌자기공명영상 및 뇌자기공명혈관영상으로 하였으며 쯔쯔가무시병의 진단은 PCR (Polymerase chain reaction)로 하였다. 일반적인 뇌경색과 쯔쯔가무시병을 동반한 뇌경색의 차이점을 구별하기 위해 내원시 혈압과 체온을 측정하여 보았다. 일반적으로 급성기 뇌경색에서는 혈압이 올라가는데 흥미롭게도 본 연구에서는 수축기 혈압이 130mmHg 미만인 환자가 12명으로 급성기 뇌경색에서 흔히 보이는 혈압 양상과는 다른 모습을 보였다. 쯔쯔가무시병을 동반한 뇌경색의 특징을 알아보기 위해 발병 위치 및 단일 혹은 다발성 뇌경색 여부를 확인하여 보았는데, 앞순환 동맥 영역의 뇌경색 발생 환자가 13명이었으며 뒤순환 동맥 영역의 뇌경색 발생 환자는 3명이었다. 응고장애를 진단하기 위해 트롬보플라스틴시간(Prothrombin Time, PT), 활성화부분트롬보플라스틴시간(activated partial thromboplastin time, aPTT), D-dimer, 섬유소원(fibrinogen), 섬유소분해산물(fibrin degradation product, FDP)를 기록하였다. 뇌경색시 일반적으로 수치가 증가하는 것으로 알려진 D-dimer의 경우 13명의 환자에서 큰 폭의 증가 소견을 보였다. 섬유소분해산물(FDP)는 15명의 환자에서 큰 폭의 증가 소견을 보였다. 쯔쯔가무시병의 병태생리학적 기전은 혈관염으로 알려져 있는데 이로 인한 대뇌혈관의 내피세포 손상 및 증식이 있을 수 있고 그 과정에서 응고장애가 동반되어 뇌경색이 발생할 수 있다. 또는 내피세포 손상 및 증식이 없더라도 혈관염으로 인한 혈관연축이 발생하여 혈관수축이 오며 뇌경색이 발생 할 수도 있다.

• Childhood Kidney Diseases
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• 제2권2호
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• pp.138-144
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• 1998

목 적 : 면역억제제로 사용되는 cyclosporine과 항암제로 사용되는 mitomycin의 신장에 미치는 직접적인 독성여부를 확인하고 이들 약제의 사용으로 초래되는 신장병변의 발생기전을 알아보고자 본 연구를 시행하였다. 대상 및 방법 : 실험동물은 체중 250-300gm의 Sprague-Dawley계 흰쥐를 암수 구별없이 사용하였으며 약물 투여는 Hoyer등이 기술한 방법을 다소 변형한 일측성 신관류 방법을 사용하여 좌측 신장을 대동맥과 대정맥의 혈류로부터 차단하고 좌측 신동맥을 통하여 좌측신을 관류시켰다. Cyclosporine은 4 mL에 2.5 mg, mitomycin은 4 mL에 1.6mg의 농도로 하였고 대조군은 생리적 식염수를 .사용하였으며 혈관 clamping으로부터 감자제거까지 소요된 총 ischemic time은 15분을 초과하지 않았다. 약제 투여후 48시간에 실험 동물을 도살하고 좌측 신장을 적출하여 광학 및 전자 현미경 검사를 시행하였다. 결 과 : Cyclosporine투여군에서는 사구체 내피세포 및 상피세포의 심한 종창이 있었으며 간질내 모세혈관의 내피세포도 심한 종창을 보였다. Mitomycin투여군에서는 사구체 내피세포 및 상피세포의 심한 종창을 보였으며 일부의 모세 혈관에는 혈소판의 응집, 종창 및 탈과립 현상과 섬유소 물질도 포함된 혈전성 미세혈관 병변의 소견을 보였다. 결 론 : Cyclosporine과 mitomycin은 신장 내피세포에 직접적인 손상을 초래하며 그러므로 이들 약제 사용으로 인한 혈전성 미세혈관 병변 (용혈성 요독증)의 발생 기전에는 이들 약제의 신장 내피세포에의 직접적인 손상이 중요한 시발점이 되는 것으로 생각된다.($41.4\%$)이 신초음파에서 이상소견을 보였다. 방광요관역류가 있었던 32명(53역류신장)은 역류정도에따라 Grade $I:25.0\%,\;II:44.5\%,\;III:64.3\%,;IV:92.9\%,\;V:100\%$에서 초기 DMSA 신주사상 이상소견을 보였다. 53역류신장중 전체적으로 DMSA신주사에서 36신장($68.0\%$), 신초음파에서 26신장($49.1\%$)이 이상소견을 보여 유의한 차이를 보였으며(P<0.05). 특히 Grade IV 역류신장에서 유의한 차이가 있었다(P<0.05). 결 론 : DMSA신주사를 이용한 급성신우신염의 진단은 신초음파검사 보다 유용하며, 초기 DMSA신주사 소견상 이상소견을 보인 경우 약 8-12주 후 추적검사를 시행하여 변화를 관찰하고 섭취결손 부분이 남아있는 경우에는 향후 새로운 병소의 출현 혹은 정상화 여부를 보기 위한 추적검사가 필요하리라 사료된다. 방광요관역류 환아에서 DMSA신주사소견은 방광요관역류의 정도가 심할수록 이상소견을 보일 확률이 높으며 신초음파 검사보다 민감도가 높은 것을 알 수 있었다.이는 혈압을 조절시키지 못하였고 저단백식이 항고혈압제투여군은 저단백식이 단독투여군보다 혈압조절 및 단백뇨의 감소 소견은 유의한 차이를 보였으나, mesangial matrix expansion score,대상성 사구체비대는 통계적으로 유의한 차이를 보이지 않았다. 그러므로 만성신부전의 진행을 지연시키는데 있어서 저단백식이와 함께 항고혈압제를 추가하였을 때 항고혈압제에 의한 추가적인 지연 효과는 관찰되지 않았다.학생이 남학생보다 높고, 물리치료과를 타의로

• 통합자연과학논문집
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• 제6권3호
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• pp.125-137
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• 2013

Promising evidence suggests that amyloid beta peptide ($A{\beta}$), a key mediator in age-dependent neuronal and cerebrovascular degeneration, activates death signalling processes leading to neuronal as well as non-neuronal cell death in the central nervous system. A major cellular event in $A{\beta}$-induced apoptosis of non-neuronal cells, including cerebral endothelial cells, astrocytes and oligodendrocytes, is mitochondrial dysfunction. The apoptosis signalling cascade upstream of mitochondria entails $A{\beta}$ activation of neutral sphingomyelinase, resulting in the release of ceramide from membrane sphingomyelin. Ceramide then activates protein phosphatase 2A (PP2A), a member in the ceramide-activated protein phosphatase (CAPP) family. PP2A dephosphorylation of Akt and FKHRL1 plays a pivotal role in $A{\beta}$-induced Bad translocation to mitochondria and transactivation of Bim. Bad and Bim are pro-apoptotic proteins that cause mitochondrial dysfunction characterized by excessive ROS formation, mitochondrial DNA (mtDNA) damage, and release of mitochondrial apoptotic proteins including cytochrome c, apoptosis inducing factor (AIF), endonuclease G and Smac. The cellular events activated by $A{\beta}$ to induce death of non-neuronal cells are complex. Understanding these apoptosis signalling processes will aid in the development of more effective strategies to slow down age-dependent cerebrovascular degeneration caused by progressive cerebrovascular $A{\beta}$ deposition.

• Journal of Yeungnam Medical Science
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• 제40권4호
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• pp.328-334
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• 2023

An aging population and changes in dietary habits have increased the incidence of diabetes, resulting in complications such as diabetic foot ulcers (DFUs). DFUs can lead to serious disabilities, substantial reductions in patient quality of life, and high financial costs for society. By understanding the etiology and pathophysiology of DFUs, their occurrence can be prevented and managed more effectively. The pathophysiology of DFUs involves metabolic dysfunction, diabetic immunopathy, diabetic neuropathy, and angiopathy. The processes by which hyperglycemia causes peripheral nerve damage are related to adenosine triphosphate deficiency, the polyol pathway, oxidative stress, protein kinase C activity, and proinflammatory processes. In the context of hyperglycemia, the suppression of endothelial nitric oxide production leads to microcirculation atherosclerosis, heightened inflammation, and abnormal intimal growth. Diabetic neuropathy involves sensory, motor, and autonomic neuropathies. The interaction between these neuropathies forms a callus that leads to subcutaneous hemorrhage and skin ulcers. Hyperglycemia causes peripheral vascular changes that result in endothelial cell dysfunction and decreased vasodilator secretion, leading to ischemia. The interplay among these four preceding pathophysiological factors fosters the development and progression of infections in individuals with diabetes. Charcot neuroarthropathy is a chronic and progressive degenerative arthropathy characterized by heightened blood flow, increased calcium dissolution, and repeated minor trauma to insensate joints. Directly and comprehensively addressing the pathogenesis of DFUs could pave the way for the development of innovative treatment approaches with the potential to avoid the most serious complications, including major amputations.

• Journal of Ginseng Research
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• 제46권5호
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• pp.700-709
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• 2022

Background: Ginsenoside Rd is a natural compound with promising neuroprotective effects. However, the underlying mechanisms are still not well-understood. In this study, we explored whether ginsenoside Rd exerts protective effects on cerebral endothelial cells after oxygen-glucose deprivation/reoxygenation (OGD/R) treatment and its potential docking proteins related to the underlying regulations. Method: Commercially available primary human brain microvessel endothelial cells (HBMECs) were used for in vitro OGD/R studies. Cell viability, pyroptosis-associated protein expression and tight junction protein degradation were evaluated. Molecular docking proteins were predicted. Subsequent surface plasmon resonance (SPR) technology was utilized for validation. Flow cytometry was performed to quantify caspase-1 positive and PI positive (caspase-1+/PI+) pyroptotic cells. Results: Ginsenoside Rd treatment attenuated OGD/R-induced damage of blood-brain barrier (BBB) integrity in vitro. It suppressed NLRP3 inflammasome activation (increased expression of NLRP3, cleaved caspase-1, IL-1β and GSDMD-N terminal (NT)) and subsequent cellular pyroptosis (caspase-1+/PI + cells). Ginsenoside Rd interacted with SLC5A1 with a high affinity and reduced OGD/R-induced sodium influx and potassium efflux in HBMECs. Inhibiting SLC5A1 using phlorizin suppressed OGD/R-activated NLRP3 inflammasome and pyroptosis in HBMECs. Conclusion: Ginsenoside Rd protects HBMECs from OGD/R-induced injury partially via binding to SLC5A1, reducing OGD/R-induced sodium influx and potassium efflux, thereby alleviating NLRP3 inflammasome activation and pyroptosis.

• 대한한방내과학회지
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• 제34권1호
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• pp.100-111
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• 2013

Objectives : This study investigated the impact of Caesalpinia sappan L. on oxidative damage and inflammatory relevant factor in RAW 264.7 cells and human umbilical vein endothelial cells (HUVEC). Methods : We determined whether fractionated EtOH extracts of Caesalpinia sappan L. (CSL) inhibit free radical generation such as 2,2-diphenyl-1-picrylhydrazyl (DPPH), reactive oxygen species (ROS) and nitric oxide (NO) and pro-inflammatory cytokines in lipopolysaccharide (LPS)-treated RAW 264.7 cells and HUVEC. Result : 1. DPPH removal capacity was increased by CSL. 2. LPS-induced ROS, and NO inhibitory capacity were increased by CSL. 3. LPS-induced cell death of Raw 264.7 cells was decreased by CSL. 4. The amount of cytokine generation in Raw 264.7 cell was decreased significantly by CSL. 5. The amount of cytokine generation in HUVEC was decreased significantly by CSL. Conclusions : These results suggest that CSL supplement may attenuate oxidative stress by elevated antioxidative processes, and suppress inflammatory mediator activation.

• Biomolecules & Therapeutics
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• 제16권1호
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• pp.14-20
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• 2008

In the present study, we examined how the transport of choline is regulated at the blood-brain barrier (BBB) under the central nervous system (CNS) cellular damages by oxidative stress using a conditionally immortalized rat brain capillary endothelial cells (TR-BBB), in vitro the BBB model. It was also tested whether the choline uptake is influenced by membrane potential, extracellular pH, protonophore (FCCP) and amiloride in TR-BBB cells. In result, $[^3H]choline$ uptake was inhibited by FCCP and dependent on extracellular pH. The treatment of TR-BBB cells with 20 ng/mL tumor necrosis $factor-{\alpha}$ $(TNF-{\alpha})$, 10 ng/mL lipopolysaccharide (LPS), 100 ${\mu}M$ diethyl maleate (DEM) and 100 ${\mu}M$ glutamate resulted in 3.0-fold, 2.6-fold, 1.8-fold and 2.0-fold increases of $[^3H]choline$ uptake at the respective peak time, respectively. In contrast, hydrogen peroxide and raffinose did not show any significant effects on choline uptake. In addition, choline efflux was significantly inhibited by $TNF-{\alpha}$, LPS and DEM producing cell damage states. In conclusion, the influx and efflux transport system for choline existed in TR-BBB cell line and this process was affected by several oxidative stress inducing agents.