神经退化性老化疾病研究团队
神经退化性老化疾病研究团队
神经退化性老化疾病研究团队
主持人: 陳景宗教授
研究專長: 巴金森氏症、疼痛、憂鬱症、藥物成癮研究
研究团队成员:
陈景宗老师、王鸿利老师、萧颖聪老师、黄英儒医师、黄荣棋老师、黄国正老师
研究计画:
说明
老化是神经退化性疾病（Neurodegenerative diseases）的重要危险因子，神经退化性疾病佔老年人口的比例已经逐年增加，相对的医疗资源用在预防与治疗与老年相关的神经疾病，也以同步的速度递增；其中老年失智症（又称為阿兹海默症；Alzheimer’s disease「AD」）和帕金森氏症（Parki苍蝉辞苍’蝉&苍产蝉辫;disease「PD」）无论是欧美或是我国，均是最常见的神经退化性疾病；随着老年人口的快速增加，可以预期AD、PD或其他神经退化性疾病将是未来影响全球医疗、经济、家庭与社会的重要议题。欲思对神经退化性疾病的防制有所突破，必须从多方面的医疗与研究着手，才能收到预期的成效。有鑑於世界各国的医疗团队不乏有卓越的阿兹海默氏症和帕金森氏症研究中心，本研究團隊建立的主要目的乃利用长庚大学醫、工與管理學院對神經老化疾病既有的研發基礎與長庚醫療體系龐大的資料庫做人力與資源的配合與整合，期能開發早期預警的生物指標（biomarker）、生物标记(biosignature)与开创神经退化性疾病特有的动物与细胞模式，提供基础研究从事病变机转或连结临床疾病判断和当做药物测试平台；此外将藉由医工与管理专才对健康老年人和神经退化病患的生理参数作数据整合与分析，提供临床医护未来对老年生活品质提升的重要依据。本研究团队成立的初期是以神经退化性疾病的各研究平台建立為主要目标，目前业已开发出各种研究退化性疾病的细胞与动物模式，并积极与国际一流医学研究团队建立团队合作关係，使本中心的神经科学群达到国际顶尖的水準，以培训本中心基础研究人才，达到卓越与国际化的目标。未来本中心的发展将参考国外研究退化性疾病的最新趋势，扩充本研究团队的动能与开发新的研究议题，以符合科研精进的精神与目的。
背景
神经退化性疾病是一个缓慢的病变过程，涉及遗传与非遗传的环境因素，经由共通性的病理变化造就最终的疾病表徵（disease phenotypes），瞭解疾病的起始原因和过程除可掌握病情的发展外，尚可发展出早期预警指标，以帮助病患改善生活品质，并节省社会医疗成本。在眾多的神经退化性疾病中，阿兹海默症和帕金森氏症的罹病人口最多，带给家庭与社会上的压力也最大，而背后的原因复杂，包括体内氧化压力的上升、代谢症候群、免疫力下降导致的慢性感染和发炎因子在脑部的堆积等等因素。其中帕金森氏症患者脑部或因基因的突变或因外在环境因子的诱发，导致a-synuclein蛋白的堆积，形成Lewy body的病理结构，致使纹状体内多巴胺神经末稍退化影响运动功能；而阿兹海默症患者在大脑皮质和海马迴因為b-amyloid蛋白的不正常聚合而形成plague的病理结构，或是因為Tau蛋白质过度磷酸化而导致微管(microtubule)的崩散，这些病理变化最终造成患者的失智症与认知功能受损。有鑑於此，国内最庞大的医疗体系-長庚醫院業已成立相關的研究中心，針對失智症、帕金森氏症和運動功能障礙從事病理分析、臨床診斷與基礎研究。本校老化中心內的「神經退化性疾病研究團隊」在過去頂尖大學研究计画的經費支助下成立，當時即與長庚醫院既有的醫療研究團隊以及「神經科學中心」充分合作，利用長庚醫療體系的病患基因檢體分析與分子影像檢析，與本校各個核心实验室(蛋白质体中心、生医影像中心、基因体中心、代谢体中心、生物资讯实验室)的尖端研發平台，並配合「動物行為核心实验室」的設立，得以縱深性的從生物指標的確認到動物模式的建立與臨床病例做關聯，達到相輔相成的成效，與基礎與臨床結合的目標。此外，本中心以早期預警的生物標記為主要研究目標，所獲得的資料將可與老化中心內其他研究團隊配合與合作，以建構起多方位的老年醫療研究中心，提升國民健康指數。
目的
神经退化性疾病是一个缓慢的病变过程，涉及遗传与非遗传的诱发因子，经由共通性的病理变化造就最终的疾病表徵（disease phenotypes），瞭解疾病的起始原因除可掌握病情的發展外，並可發展出早期預警指標，幫助病患改善生活品質減緩疾病的發展過程，以節省整體社會醫療成本。在眾多的神經退化性疾病中，阿茲海默症和帕金森氏症的罹病人口最多，帶給家庭與社會上的壓力也最大；有鑑於此，本研究團隊成立的主要目的在於開發神經退化性疾病的各細胞與動物模式，以提供退化性疾病病變過程的機制研究、測試環境因子導致神經退化的原因與治療性藥物測試的平台，我們的利基在於長庚醫療體系已有神經科學中心、失智症中心與帕金森氏症研究中心，針對退化性疾病與運動功能障礙從事病理分析與臨床診斷，尤其利用遺傳分析與分子影像造影技術已成功的確認若干家族性病例的基因病變位點。本中心的成立除可利用本校既有的各核心实验室的研發平台，配合臨床病例以開發出特有的退化性疾病動物與細胞模式，達到基礎與臨床結合的目標，以期最終能增進全民健康福祉。
方法
（一）开发退化性疾病的生物指标或标记（biomarker/biosignature identification）：利用帕金森氏症和失智症病患的基因、血液或其他生物檢體，配合长庚大学既有的分析平台:例如基因体学、次世代基因定序（NGS）、蛋白質體學、代謝質體學、分子及生醫影像和生物資訊等尖端的分析平台，綜合性與複合式的搜寻病變基因位點、早期預警生物指標或病變的生物標記以及腦病變過程的分子影像profile，提供临床病变过程的追踪与确认。此外，我们也藉由团队中具光电专长的周晟教授利用高灵敏的SPR表面电浆技术侦测帕金森氏症血液中a-synuclein以及失智症患者血液中b-amyloid不正常蛋白质聚合体的形成，当作早期预警或疾病进展的生物指标。
（二）神经退化性疾病的细胞与动物模式研究（disease models）：神经退化性疾病的成因包含诸多环境因子与基因的交互作用，藉由生物指标的开发、我国特有病变家族的基因型确定以及环境毒素（environmental toxin）的确认等先决条件，可供长庚实验动物中心製作特定的失智症或帕金森氏症动物模式；并利用业已於HARC设立的动物行為及活性实验室的测试平台做功能性评估；此外，藉由本团队吴琼媛老师先进的piggyBac iPS (induced pluripotent stem cell)技术，可以开发出疾病特有的细胞模式，供研究者了解病变的细胞生理过程和做药物筛选平台；或是利用神经肿瘤细胞株予以发炎因子的刺激当作模拟神经细胞病变退化的细胞模式。这些动物和细胞模式的成功建立，对未来相关神经退化性疾病的诸多研究课题，进行系统性的机制探讨。
（叁）老年医疗的整合性生物资讯：神经退化性疾病发作前的各项生理参数往往可提供极有价值的医疗资讯，配合生物指标的侦测，作為疾病发作前的临床预警。利用长庚医、工、管经营「养生文化村」既有的研发经验导入失智症与退化性疾病的研究群，将可提供老化研究重要的资讯平台。充分运用Dr. E观念做非侵入性检测、无线追踪日常生活作息、人际活动、饮食与生理参数，提供未来老化研究与退化性疾病发展的重要参考数据。
（四）推動国际合作機制：本研發團隊建立的另一目標就是藉由提升研發深度以達國際頂尖研究的水準，已利推動国际合作。團隊內的神經內科陸清松醫師長期與荷蘭鹿特丹（Rotterdam, Netherlands）Erasmus医学中心有研究合作，将分析有关帕金森氏症家族性病变的特定致病基因，此外生医影像团队也参与多项的国际厂商合作，在这样的基础上我们未来将持续推动进行以深化合作基础，对本团队的研究国际化将具有正面的意义。
主要成果
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Lin YT, Kao SC, Day YJ, Chang CC, Chen JC (2016). Altered nociception and morphine tolerance in neuropeptide FF receptor type 2 over-expressing mice. European journal of pain 20(6): 895-906.
Lin YT, Liu TY, Yang CY, Yu YL, Chen TC, Day YJ, Chang CC, Huang GJ, Chen JC (2016). Chronic activation of NPFFR2 stimulates the stress-related depressive behaviors through HPA axis modulation. Psychoneuroendocrinology DOI: 10.1016/j.psyneuen.2016.05.014
Wu KY, Liu CY, Chen CS, Chen CH, Hsiao IT, Hsieh CJ, et al (2016). Beta-amyloid deposition and cognitive function in patients with major depressive disorder with different subtypes of mild cognitive impairment: (18)F-florbetapir (AV-45/Amyvid) PET study. Eur J Nucl Med Mol Imaging 43(6): 1067-1076.
Yang CM, Lin CC, Hsieh HL (2016). High-Glucose-Derived Oxidative Stress-Dependent Heme Oxygenase-1 Expression from Astrocytes Contributes to the Neuronal Apoptosis. Mol Neurobiol.
Chang CC, Hsiao IT, Huang SH, Lui CC, Yen TC, Chang WN, et al (2015). (1)(8)F-FP-(+)-DTBZ positron emission tomography detection of monoaminergic deficient network in patients with carbon monoxide related parkinsonism. Eur J Neurol 22(5): 845-852, e859-860.
Chang YF, Tsao KC, Liu YC, Chen YC, Yu PC, Huang YC, et al (2015). Diagnosis of human metapneumovirus in patients hospitalized with acute lower respiratory tract infection using a metal-enhanced fluorescence technique. J Virol Methods 213: 151-156.
Chen HT, Chen JC (2015). Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity. Learn Mem 22(3): 149-158.
Cheng ML, Wang CH, Shiao MS, Liu MH, Huang YY, Huang CY, et al (2015). Metabolic disturbances identified in plasma are associated with outcomes in patients with heart failure: diagnostic and prognostic value of metabolomics. J Am Coll Cardiol 65(15): 1509-1520.
Chiu CC, Yeh TH, Lai SC, Wu-Chou YH, Chen CH, Mochly-Rosen D, et al (2015). Neuroprotective effects of aldehyde dehydrogenase 2 activation in rotenone-induced cellular and animal models of parkinsonism. Experimental Neurology 263: 244-253.
Chou AH, Chen YL, Chiu CC, Yuan SJ, Weng YH, Yeh TH, et al (2015). T1-11 and JMF1907 ameliorate polyglutamine-expanded ataxin-3-induced neurodegeneration, transcriptional dysregulation and ataxic symptom in the SCA3 transgenic mouse. Neuropharmacology 99: 308-317.
Lan MY, Yeh TH, Chang YY, Kuo HC, Sun HS, Lai SC, et al (2015). Clinical and genetic analysis of Taiwanese patients with hereditary spastic paraplegia type 5. Eur J Neurol 22(1): 211-214.
Lin CC, Hsieh HL, Liu SW, Tseng HC, Hsiao LD, Yang CM (2015). BK Induces cPLA2 Expression via an Autocrine Loop Involving COX-2-Derived PGE2 in Rat Brain Astrocytes. Mol Neurobiol 51(3): 1103-1115.
Shih RH, Wang CY, Yang CM (2015). NF-kappaB Signaling Pathways in Neurological Inflammation: A Mini Review. Front Mol Neurosci 8: 77.
Tang HY, Ho HY, Wu PR, Chen SH, Kuypers FA, Cheng ML, et al (2015). Inability to maintain GSH pool in G6PD-deficient red cells causes futile AMPK activation and irreversible metabolic disturbance. Antioxid Redox Signal 22(9): 744-759.
Wang CH, Cheng ML, Liu MH, Shiao MS, Hsu KH, Huang YY, et al (2015). Increased p-cresyl sulfate level is independently associated with poor outcomes in patients with heart failure. Heart Vessels.
Yang CC, Lin CC, Chien PT, Hsiao LD, Yang CM (2015). Thrombin/Matrix Metalloproteinase-9-Dependent SK-N-SH Cell Migration is Mediated Through a PLC/PKC/MAPKs/NF-kappaB Cascade. Mol Neurobiol.
Yang CM, Hsieh HL, Yu PH, Lin CC, Liu SW (2015). IL-1beta Induces MMP-9-Dependent Brain Astrocytic Migration via Transactivation of PDGF Receptor/NADPH Oxidase 2-Derived Reactive Oxygen Species Signals. Mol Neurobiol 52(1): 303-317.
Yang HC, Cheng ML, Hua YS, Wu YH, Lin HR, Liu HY, et al (2015). Glucose 6-phosphate dehydrogenase knockdown enhances IL-8 expression in HepG2 cells via oxidative stress and NF-kappaB signaling pathway. J Inflamm (Lond) 12: 34.
Yang ST, Hsiao IT, Hsieh CJ, Chiang YH, Yen TC, Chiu WT, et al (2015). Accumulation of amyloid in cognitive impairment after mild traumatic brain injury. J Neurol Sci 349(1-2): 99-104.
Chang YF, Chao CH, Lin LY, Tsai CH, Chou C, Lee YJ (2014). Determination of urine cofilin-1 level in acute kidney injury using a high-throughput localized surface plasmon-coupled fluorescence biosensor. J Biomed Opt 19(1): 011004.
Chou AH, Chen YL, Hu SH, Chang YM, Wang HL (2014). Polyglutamine-expanded ataxin-3 impairs long-term depression in Purkinje neurons of SCA3 transgenic mouse by inhibiting HAT and impairing histone acetylation. Brain research 1583: 220-229.
Chou JS, Chen CY, Chen YL, Weng YH, Yeh TH, Lu CS, et al (2014). (G2019S) LRRK2 causes early-phase dysfunction of SNpc dopaminergic neurons and impairment of corticostriatal long-term depression in the PD transgenic mouse. Neurobiol Dis 68: 190-199.
Hsiao IT, Weng YH, Hsieh CJ, Lin WY, Wey SP, Kung MP, et al (2014). Correlation of Parkinson disease severity and 18F-DTBZ positron emission tomography. JAMA Neurol 71(6): 758-766.
Hsiao IT, Weng YH, Lin WY, Hsieh CJ, Wey SP, Yen TC, et al (2014). Comparison of 99mTc-TRODAT-1 SPECT and 18 F-AV-133 PET imaging in healthy controls and Parkinson's disease patients. Nucl Med Biol 41(4): 322-329.
Hsieh HL, Chi PL, Lin CC, Yang CC, Yang CM (2014). Up-regulation of ROS-dependent matrix metalloproteinase-9 from high-glucose-challenged astrocytes contributes to the neuronal apoptosis. Mol Neurobiol 50(2): 520-533.
Huang CY, Chen YL, Li AH, Lu JC, Wang HL (2014). Minocycline, a microglial inhibitor, blocks spinal CCL2-induced heat hyperalgesia and augmentation of glutamatergic transmission in substantia gelatinosa neurons. J Neuroinflammation 11: 7.
Lan MY, Chang YY, Yeh TH, Lai SC, Liou CW, Kuo HC, et al (2014). High frequency of SPG4 in Taiwanese families with autosomal dominant hereditary spastic paraplegia. BMC Neurol 14: 216.
Lin CC, Hsieh HL, Chi PL, Yang CC, Hsiao LD, Yang CM (2014). Upregulation of COX-2/PGE2 by ET-1 mediated through Ca2+-dependent signals in mouse brain microvascular endothelial cells. Mol Neurobiol 49(3): 1256-1269.
Lin CC, Lee IT, Chi PL, Hsieh HL, Cheng SE, Hsiao LD, et al (2014). C-Src/Jak2/PDGFR/PKCdelta-dependent MMP-9 induction is required for thrombin-stimulated rat brain astrocytes migration. Mol Neurobiol 49(2): 658-672.
Su LC, Tian YC, Chang YF, Chou C, Lai CS (2014). Rapid detection of urinary polyomavirus BK by heterodyne-based surface plasmon resonance biosensor. J Biomed Opt 19(1): 011013.
Hsieh HL, Lin CC, Hsiao LD, Yang CM (2013). High glucose induces reactive oxygen species-dependent matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Mol Neurobiol 48(3): 601-614.
Lao CL, Lu CS, Chen JC (2013). Dopamine D3 receptor activation promotes neural stem/progenitor cell proliferation through AKT and ERK1/2 pathways and expands type-B and -C cells in adult subventricular zone. Glia 61(4): 475-489.
Lin CC, Hsieh HL, Shih RH, Chi PL, Cheng SE, Yang CM (2013). Up-regulation of COX-2/PGE2 by endothelin-1 via MAPK-dependent NF-kappaB pathway in mouse brain microvascular endothelial cells. Cell Commun Signal 11(1): 8.
Lin CC, Lee IT, Wu WB, Liu CJ, Hsieh HL, Hsiao LD, et al (2013). Thrombin mediates migration of rat brain astrocytes via PLC, Ca(2)(+), CaMKII, PKCalpha, and AP-1-dependent matrix metalloproteinase-9 expression. Mol Neurobiol 48(3): 616-630.
Meir YJ, Lin A, Huang MF, Lin JR, Weirauch MT, Chou HC, et al (2013). A versatile, highly efficient, and potentially safer piggyBac transposon system for mammalian genome manipulations. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 27(11): 4429-4443.
Tseng HC, Lee IT, Lin CC, Chi PL, Cheng SE, Shih RH, et al (2013). IL-1beta promotes corneal epithelial cell migration by increasing MMP-9 expression through NF-kappaB- and AP-1-dependent pathways. PLoS One 8(3): e57955.
Wei KC, Chu PC, Wang HY, Huang CY, Chen PY, Tsai HC, et al (2013). Focused ultrasound-induced blood-brain barrier opening to enhance temozolomide delivery for glioblastoma treatment: a preclinical study. PLoS One 8(3): e58995.
Wei KC, Tsai HC, Lu YJ, Yang HW, Hua MY, Wu MF, et al (2013). Neuronavigation-guided focused ultrasound-induced blood-brain barrier opening: a preliminary study in swine. AJNR Am J Neuroradiol 34(1): 115-120.
Wu TC, Chen HT, Chang HY, Yang CY, Hsiao MC, Cheng ML, et al (2013). Mineralocorticoid receptor antagonist spironolactone prevents chronic corticosterone induced depression-like behavior. Psychoneuroendocrinology 38(6): 871-883.
Yang CM, Hsieh HL, Lin CC, Shih RH, Chi PL, Cheng SE, et al (2013). Multiple factors from bradykinin-challenged astrocytes contribute to the neuronal apoptosis: involvement of astroglial ROS, MMP-9, and HO-1/CO system. Mol Neurobiol 47(3): 1020-1033.
Yeh TH, Lai SC, Weng YH, Kuo HC, Wu-Chou YH, Huang CL, et al (2013). Screening for C9orf72 repeat expansions in parkinsonian syndromes. Neurobiol Aging 34(4): 1311 e1313-131
Chao CH, Chang YF, Chen HC, Lin LY, Yu PC, Chang YS, et al (2012). Detection of urine cofilin-1 from patients hospitalized in the intensive care unit using the metal-enhanced fluorescence technique. Sensor Actuat B-Chem 173: 184-190.
Chao KT, Tsao HH, Weng YH, Hsiao IT, Hsieh CJ, Wey SP, et al (2012). Quantitative analysis of binding sites for 9-fluoropropyl-(+)-dihydrotetrabenazine ([(1)(8)F]AV-133) in a MPTP-lesioned PD mouse model. Synapse 66(9): 823-831.
Chen CY, Weng YH, Chien KY, Lin KJ, Yeh TH, Cheng YP, et al (2012). (G2019S) LRRK2 activates MKK4-JNK pathway and causes degeneration of SN dopaminergic neurons in a transgenic mouse model of PD. Cell death and differentiation 19(10): 1623-1633.
Chen HT, Ruan NY, Chen JC, Lin TY (2012). Dopamine D2 receptor-mediated Akt/PKB signalling: initiation by the D2S receptor and role in quinpirole-induced behavioural activation. ASN Neuro 4(6): 371-382.
Chi PL, Chen YW, Hsiao LD, Chen YL, Yang CM (2012). Heme oxygenase 1 attenuates interleukin-1beta-induced cytosolic phospholipase A2 expression via a decrease in NADPH oxidase/reactive oxygen species/activator protein 1 activation in rheumatoid arthritis synovial fibroblasts. Arthritis and rheumatism 64(7): 2114-2125.
Hsiao IT, Huang CC, Hsieh CJ, Hsu WC, Wey SP, Yen TC, et al (2012). Correlation of early-phase 18F-florbetapir (AV-45/Amyvid) PET images to FDG images: preliminary studies. Eur J Nucl Med Mol Imaging 39(4): 613-620.
Hsieh HL, Lin CC, Chan HJ, Yang CM (2012a). c-Src-dependent EGF receptor transactivation contributes to ET-1-induced COX-2 expression in brain microvascular endothelial cells. J Neuroinflammation 9: 152.
Hsieh HL, Lin CC, Shih RH, Hsiao LD, Yang CM (2012). NADPH oxidase-mediated redox signal contributes to lipoteichoic acid-induced MMP-9 upregulation in brain astrocytes. J Neuroinflammation 9: 110.
Huang KL, Lin KJ, Ho MY, Chang YJ, Chang CH, Wey SP, et al (2012). Amyloid deposition after cerebral hypoperfusion: evidenced on [(18)F]AV-45 positron emission tomography. J Neurol Sci 319(1-2): 124-129.
Kung MP, Weng CC, Lin KJ, Hsiao IT, Yen TC, Wey SP (2012). Amyloid plaque imaging from IMPY/SPECT to AV-45/PET. Chang Gung Med J 35(3): 211-218.
Lin CC, Hsieh HL, Shih RH, Chi PL, Cheng SE, Chen JC, et al (2012). NADPH oxidase 2-derived reactive oxygen species signal contributes to bradykinin-induced matrix metalloproteinase-9 expression and cell migration in brain astrocytes. Cell Commun Signal 10(1): 35.
Liu HL, Yang HW, Hua MY, Wei KC (2012). Enhanced therapeutic agent delivery through magnetic resonance imaging-monitored focused ultrasound blood-brain barrier disruption for brain tumor treatment: an overview of the current preclinical status. Neurosurg Focus 32(1): E4.
Lu CS, Lai SC, Wu RM, Weng YH, Huang CL, Chen RS, et al (2012). PLA2G6 mutations in PARK14-linked young-onset parkinsonism and sporadic Parkinson's disease. Am J Med Genet B Neuropsychiatr Genet 159B(2): 183-191.
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Yang HW, Hua MY, Liu HL, Tsai RY, Chuang CK, Chu PC, et al (2012). Cooperative dual-activity targeted nanomedicine for specific and effective prostate cancer therapy. ACS Nano 6(2): 1795-1805.
Yang HW, Hua MY, Liu HL, Tsai RY, Pang ST, Hsu PH, et al (2012). An epirubicin-conjugated nanocarrier with MRI function to overcome lethal multidrug-resistant bladder cancer. Biomaterials 33(15): 3919-3930.
Chou AH, Chen SY, Yeh TH, Weng YH, Wang HL (2011). HDAC inhibitor sodium butyrate reverses transcriptional downregulation and ameliorates ataxic symptoms in a transgenic mouse model of SCA3. Neurobiol Dis 41(2): 481-488.
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Hua MY, Yang HW, Liu HL, Tsai RY, Pang ST, Chuang KL, et al (2011). Superhigh-magnetization nanocarrier as a doxorubicin delivery platform for magnetic targeting therapy. Biomaterials 32(34): 8999-9010.
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Lin YT, Ro LS, Wang HL, Chen JC (2011). Up-regulation of dorsal root ganglia BDNF and trkB receptor in inflammatory pain: an in vivo and in vitro study. J Neuroinflammation 8: 126.
Liu HL, Chen PY, Yang HW, Wu JS, Tseng IC, Ma YJ, et al (2011). In vivo MR quantification of superparamagnetic iron oxide nanoparticle leakage during low-frequency-ultrasound-induced blood-brain barrier opening in swine. J Magn Reson Imaging 34(6): 1313-1324.
Shih RH, Cheng SE, Hsiao LD, Kou YR, Yang CM (2011). Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells. J Neuroinflammation 8: 104.
Tung WH, Hsieh HL, Lee IT, Yang CM (2011). Enterovirus 71 induces integrin beta1/EGFR-Rac1-dependent oxidative stress in SK-N-SH cells: role of HO-1/CO in viral replication. Journal of cellular physiology 226(12): 3316-3329.
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Yang HW, Hua MY, Liu HL, Huang CY, Tsai RY, Lu YJ, et al (2011). Self-protecting core-shell magnetic nanoparticles for targeted, traceable, long half-life delivery of BCNU to gliomas. Biomaterials 32(27): 6523-6532.