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NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases 被引量:1
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作者 Napissara Boonpraman Sun Shin Yi 《Neural Regeneration Research》 SCIE CAS CSCD 2024年第9期1961-1966,共6页
Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NAD... Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions. 展开更多
关键词 Alzheimer’s disease ASTROCYTES mitochondrial dysfunction MYELOPERoxidase NADPH oxidase 4 NADPH oxidase 4 inhibitors neurodegenerative diseases OSTEOPONTIN Parkinson’s disease reactive oxygen species
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Knockdown of NADPH oxidase 4 reduces mitochondrial oxidative stress and neuronal pyroptosis following intracerebral hemorrhage 被引量:4
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作者 Bo-Yun Ding Chang-Nan Xie +5 位作者 Jia-Yu Xie Zhuo-Wei Gao Xiao-Wei Fei En-Hui Hong Wen-Jin Chen Yi-Zhao Chen 《Neural Regeneration Research》 SCIE CAS CSCD 2023年第8期1734-1742,共9页
Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious... Intracerebral hemorrhage is often accompanied by oxidative stress induced by reactive oxygen species,which causes abnormal mitochondrial function and secondary reactive oxygen species generation.This creates a vicious cycle leading to reactive oxygen species accumulation,resulting in progression of the pathological process.Therefore,breaking the cycle to inhibit reactive oxygen species accumulation is critical for reducing neuronal death after intracerebral hemorrhage.Our previous study found that increased expression of nicotinamide adenine dinucleotide phosphate oxidase 4(NADPH oxidase 4,NOX4)led to neuronal apoptosis and damage to the blood-brain barrier after intracerebral hemorrhage.The purpose of this study was to investigate the role of NOX4 in the circle involving the neuronal tolerance to oxidative stress,mitochondrial reactive oxygen species and modes of neuronal death other than apoptosis after intracerebral hemorrhage.We found that NOX4 knockdown by adeno-associated virus(AAV-NOX4)in rats enhanced neuronal tolerance to oxidative stress,enabling them to better resist the oxidative stress caused by intracerebral hemorrhage.Knockdown of NOX4 also reduced the production of reactive oxygen species in the mitochondria,relieved mitochondrial damage,prevented secondary reactive oxygen species accumulation,reduced neuronal pyroptosis and contributed to relieving secondary brain injury after intracerebral hemorrhage in rats.Finally,we used a mitochondria-targeted superoxide dismutase mimetic to explore the relationship between reactive oxygen species and NOX4.The mitochondria-targeted superoxide dismutase mimetic inhibited the expression of NOX4 and neuronal pyroptosis,which is similar to the effect of AAV-NOX4.This indicates that NOX4 is likely to be an important target for inhibiting mitochondrial reactive oxygen species production,and NOX4 inhibitors can be used to alleviate oxidative stress response induced by intracerebral hemorrhage. 展开更多
关键词 caspase 1 caspase4/11 gasdermin D intracerebral hemorrhage mitochondria reactive oxygen species inhibitor NADPH oxidase 4 neuronal pyroptosis neuronal tolerance reactive oxygen species secondary brain injury
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Effects of Terpinen-4-ol on Four Metabolic Enzymes and Polyphenol Oxidase (PPO) in Mythimna separta Walker 被引量:4
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作者 MA Zhi-qing HAN Xiu-ling FENG Jun-tao LI Guang-ze ZHANG Xing 《Agricultural Sciences in China》 CAS CSCD 2008年第6期726-730,共5页
To study insecticidal mechanism of terpinen-4-ol, a main insecticidal composition in the essential oil of Sabina vulgaris, the 5th instar larvae of Mythimna separta, were investigated with terpinen-4-ol by topical app... To study insecticidal mechanism of terpinen-4-ol, a main insecticidal composition in the essential oil of Sabina vulgaris, the 5th instar larvae of Mythimna separta, were investigated with terpinen-4-ol by topical application. The activities of phosphatase, glutathione S-transferase (GSTs), cytochrome P450 (P450), and polyphenol oxidase (PPO) of tested insects were determined in all poisoning stages, including exciting stage, convulsing stage, paralysis stage, and recover stage. The result showed that the activities of both acid phosphatase (ACP) and alkaline phosphatase (AKP) in treated insects were induced by terpinen-4-ol, but ACP was inhibited in paralysis stage. The activities of GSTs were inhibited in exciting stage, convulsing stage, and paralysis stage, but gradually recovered in recover stage. O-demethylase activity of cytochrome P450 was inhibited by terpinen-4-ol, and the inhibition rate in all poisoning stages were 26.27, 46.03, 80.24, and 90.22%, respectively. PPO activities were strongly inhibited by terpinen-4-ol both in vitro and in vivo. In conclusion, the activities of P450, GSTs, and PPO could have relation with toxicity of terpinen-4-ol against larvae of the Mythimna separta, but recover stage of the poisoning insects might be related to GSTs induced. As a new insecticide or synergist, terpinen- 4-ol has a potential value in field of insecticide resistance management. 展开更多
关键词 TERPINEN-4-OL Mythimna separate polyphenol oxidase (PPO) metabolic enzymes insecticidal mechanism
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NADPH氧化酶4在心血管损伤中的作用机制
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作者 石丹丹 宁梓淇 +1 位作者 刘美霞 刘剑刚 《心血管病学进展》 CAS 2024年第2期136-140,共5页
心血管结构和功能损伤是许多心血管疾病的重要病理基础,许多研究表明氧化应激在缺血性心脏病、动脉粥样硬化、高血压等诸多病理性心血管损伤中发挥重要作用。NADPH氧化酶(Nox)是调控氧化还原信号的关键酶,而血管内的活性氧主要来源于Nox... 心血管结构和功能损伤是许多心血管疾病的重要病理基础,许多研究表明氧化应激在缺血性心脏病、动脉粥样硬化、高血压等诸多病理性心血管损伤中发挥重要作用。NADPH氧化酶(Nox)是调控氧化还原信号的关键酶,而血管内的活性氧主要来源于Nox4。随着研究的不断深入,发现Nox4在不同阶段或不同刺激下会发挥不同甚至截然相反的作用,如双向调节动脉粥样硬化的进展、双向作用影响血压等。现总结Nox4在不同心血管损伤中的不同影响及作用机制,为后续的研究提供一定的理论基础。 展开更多
关键词 NADPH氧化酶4 活性氧 心血管损伤
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NOX4 exacerbates Parkinson's disease pathology by promoting neuronal ferroptosis and neuroinflammation
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作者 Zhihao Lin Changzhou Ying +6 位作者 Xiaoli Si Naijia Xue Yi Liu Ran Zheng Ying Chen Jiali Pu Baorong Zhang 《Neural Regeneration Research》 SCIE CAS 2025年第7期2038-2052,共15页
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati... Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease. 展开更多
关键词 dopaminergic neuron ferroptosis NADPH oxidase 4(NOX4) NEUROINFLAMMATION Parkinson's disease
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血清NOX4联合Nrf2水平检测对稳定期COPD患者急性加重的预测价值 被引量:1
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作者 金小乐 钱晶 +2 位作者 韩英 邵宪萍 张丹 《浙江医学》 CAS 2024年第2期167-171,共5页
目的探讨血清NADPH氧化酶4(NOX4)联合核因子E2相关因子2(Nrf2)水平检测对稳定期慢性阻塞性肺疾病(COPD)患者急性加重的预测价值。方法选取2019年8月至2021年12月在河北北方学院附属第一医院住院治疗并在出院后随访1年内有急性加重发作... 目的探讨血清NADPH氧化酶4(NOX4)联合核因子E2相关因子2(Nrf2)水平检测对稳定期慢性阻塞性肺疾病(COPD)患者急性加重的预测价值。方法选取2019年8月至2021年12月在河北北方学院附属第一医院住院治疗并在出院后随访1年内有急性加重发作情况的138例稳定期COPD患者作为研究对象,根据出院后1年内急性加重发作次数分为急性加重发作次数≥2次的频发组52例和发作次数≤1次的非频发组86例。比较两组患者临床资料及血清NOX4、Nrf2水平,采用多因素logistic回归分析稳定期COPD患者1年内急性加重频繁发作的影响因素;采用ROC曲线评估NOX4、Nrf2预测稳定期COPD患者1年内急性加重频繁发作的效能。结果频发组患者合并糖尿病比例、血清NOX4水平均高于非频发组,ALB、Nrf2水平均低于非频发组,差异均有统计学意义(均P<0.05)。多因素logistic回归分析显示,合并糖尿病、NOX4水平升高是稳定期COPD患者1年内急性加重频繁发作的危险因素,Nrf2水平升高是稳定期COPD患者1年内急性加重频繁发作的保护因素(均P<0.05);ROC曲线分析显示,血清NOX4及Nrf2水平对稳定期COPD患者1年内急性加重频繁发作具有预测价值,两者联合预测的灵敏度和特异度分别为0.814和0.885。结论血清NOX4和Nrf2有望成为评价COPD患者1年内急性加重频繁发作风险的潜在标志物。 展开更多
关键词 慢性阻塞性肺疾病 急性加重 频繁发作 预测 NADPH氧化酶4 核因子相关因子2
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NOX4 promotes tumor progression through the MAPK-MEK1/2-ERK1/2 axis in colorectal cancer
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作者 Yu-Jie Xu Ya-Chang Huo +4 位作者 Qi-Tai Zhao Jin-Yan Liu Yi-Jun Tian Lei-Lei Yang Yi Zhang 《World Journal of Gastrointestinal Oncology》 SCIE 2024年第4期1421-1436,共16页
BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.A... BACKGROUND Metabolic reprogramming plays a key role in cancer progression and clinical outcomes;however,the patterns and primary regulators of metabolic reprogramming in colorectal cancer(CRC)are not well understood.AIM To explore the role of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4)in promoting progression of CRC.METHODS We evaluated the expression and function of dysregulated and survival-related metabolic genes using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes.Consensus clustering was used to cluster CRC based on dysregulated metabolic genes.A prediction model was constructed based on survival-related metabolic genes.Sphere formation,migration,invasion,proliferation,apoptosis and clone formation was used to evaluate the biological function of NOX4 in CRC.mRNA sequencing was utilized to explore the alterations of gene expression NOX4 over-expression tumor cells.In vivo subcutaneous and lung metastasis mouse tumor model was used to explore the effect of NOX4 on tumor growth.RESULTS We comprehensively analyzed 3341 metabolic genes in CRC and identified three clusters based on dysregulated metabolic genes.Among these genes,NOX4 was highly expressed in tumor tissues and correlated with worse survival.In vitro,NOX4 overexpression induced clone formation,migration,invasion,and stemness in CRC cells.Furthermore,RNA-sequencing analysis revealed that NOX4 overexpression activated the mitogen-activated protein kinase-MEK1/2-ERK1/2 signaling pathway.Trametinib,a MEK1/2 inhibitor,abolished the NOX4-mediated tumor progression.In vivo,NOX4 overexpression promoted subcutaneous tumor growth and lung metastasis,whereas trametinib treatment can reversed the metastasis.CONCLUSION Our study comprehensively analyzed metabolic gene expression and highlighted the importance of NOX4 in promoting CRC metastasis,suggesting that trametinib could be a potential therapeutic drugs of CRC clinical therapy targeting NOX4. 展开更多
关键词 Colorectal cancer Metabolic reprogramming METASTASIS Nicotinamide adenine dinucleotide phosphate oxidase 4 Mitogen-activated protein kinase signaling
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MRI联合血清赖氨酸氧化酶样蛋白4、信号转导和转录激活因子3检测用于原发性肝癌诊断的价值
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作者 赖全友 高远 +1 位作者 王尚毓 彭伟 《陕西医学杂志》 CAS 2024年第10期1398-1401,1406,共5页
目的:探讨磁共振成像(MRI)联合血清赖氨酸氧化酶样蛋白4(LOXL4)、信号转导和转录激活因子3(STAT3)检测用于原发性肝癌诊断的价值。方法:选取肝占位性病变患者214例,比较分析原发性肝癌和肝脏良性病变患者血清LOXL4、STAT3水平差异,以及... 目的:探讨磁共振成像(MRI)联合血清赖氨酸氧化酶样蛋白4(LOXL4)、信号转导和转录激活因子3(STAT3)检测用于原发性肝癌诊断的价值。方法:选取肝占位性病变患者214例,比较分析原发性肝癌和肝脏良性病变患者血清LOXL4、STAT3水平差异,以及原发性肝癌不同患者间差异,同时分析MRI联合血清LOXL4、STAT3水平诊断原发性肝癌的价值。结果:确诊为原发性肝癌患者92例,肝脏良性病变122例。原发性肝癌患者血清LOXL4、STAT3明显高于肝脏良性病变患者(均P<0.05)。TNM分期Ⅲ-Ⅳ患者血清LOXL4、STAT3明显高于肝脏良性病变患者(均P<0.05)。低分化患者血清LOXL4、STAT3明显高于中高分化患者(均P<0.05)。血清LOXL4、STAT3水平诊断原发性肝癌的ROC曲线下面积分别为0.890和0.896(均P<0.05)。MRI联合血清LOXL4、STAT3水平诊断原发性肝癌的灵敏性和阴性预测值分别为95.65%和96.00%,高于MRI检查(均P<0.05)。结论:原发性肝癌患者血清LOXL4、STAT3水平升高,与TNM分期及分化程度有关;MRI联合血清LOXL4、STAT3检测诊断原发性肝癌有较好的应用价值。 展开更多
关键词 磁共振成像 赖氨酸氧化酶样蛋白4 信号转导和转录激活因子3 原发性肝癌 预测模型 诊断价值
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SREBP2、LOXL2和PEBP4在原发性肝癌中的表达及与患者临床病理特征的相关性
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作者 高文广 李龙辉 王建华 《国际消化病杂志》 CAS 2024年第4期251-257,共7页
目的 探讨胆固醇调节元件结合蛋白2(SREBP2)、赖氨酰氧化酶样蛋白2(LOXL2)和磷脂酰乙醇胺结合蛋白4(PEBP4)在原发性肝癌(以下简称肝癌)中的表达及与患者临床病理特征的相关性。方法 选择2016年1月至2019年12月在廊坊市第四人民医院接受... 目的 探讨胆固醇调节元件结合蛋白2(SREBP2)、赖氨酰氧化酶样蛋白2(LOXL2)和磷脂酰乙醇胺结合蛋白4(PEBP4)在原发性肝癌(以下简称肝癌)中的表达及与患者临床病理特征的相关性。方法 选择2016年1月至2019年12月在廊坊市第四人民医院接受手术治疗的72例原发性肝癌患者作为研究对象,收集其临床资料。采用实时荧光定量PCR法检测组织中SREBP2、LOXL2和PEBP4的mRNA表达水平,分析肝癌组织中SREBP2、LOXL2和PEBP4的mRNA表达与患者临床病理特征及血管生成拟态(VM)的相关性,并分析肝癌组织中不同SREBP2、LOXL2和PEBP4 mRNA表达的患者的生存情况。结果 肝癌组织中SREBP2、LOXL2和PEBP4的mRNA表达水平均较癌旁组织显著升高(P均<0.05)。肝癌组织中SREBP2、LOXL2和PEBP4的m RNA表达与患者的TNM分期、病理分级、脉管侵犯均有相关性(P均<0.05)。72例患者的肝癌组织中有27例(37.50%)VM形成,VM染色阳性的肝癌组织中SREBP2、LOXL2和PEBP4的mRNA表达水平均显著高于VM染色阴性的肝癌组织(P均<0.05)。多因素logistic回归分析结果显示肝癌组织中SREBP2、LOXL2和PEBP4的mRNA高表达均为VM的危险因素(P均<0.05)。Kaplan-Meier生存分析结果显示,肝癌组织中SREBP2、LOXL2和PEBP4 mRNA高表达者的3年总生存率均较低表达者显著降低(P均<0.05)。结论 肝癌组织中SREBP2、LOXL2和PEBP4的m RNA均呈高表达,且与患者的部分临床病理特征、肝癌细胞VM形成均相关,并可影响预后。 展开更多
关键词 胆固醇调节元件结合蛋白2 赖氨酰氧化酶样蛋白2 磷脂酰乙醇胺结合蛋白4 原发性肝癌 临床病理特征 血管生成拟态
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Construction of Cox7a2 fluorescent vector and its effect on cytochrome C oxidase activity in mouse Sertoli cell line TM4
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作者 刘保兴 《外科研究与新技术》 2011年第4期260-260,共1页
Objective To construct Cox7a2 fluorescent vector and study its effect on cytochrome C oxidase ( COX) activity in mouse Sertoli cell line TM4. Methods The coding region of CoxTa2 was amplified from mouse Sertoli cell l... Objective To construct Cox7a2 fluorescent vector and study its effect on cytochrome C oxidase ( COX) activity in mouse Sertoli cell line TM4. Methods The coding region of CoxTa2 was amplified from mouse Sertoli cell line TM4 by RT-PCR. PCR product was 展开更多
关键词 line cell Construction of Cox7a2 fluorescent vector and its effect on cytochrome C oxidase activity in mouse Sertoli cell line TM4 TM
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The Amperometric Glucose Enzyme Electrode by Immobilized Glucose Oxidase in Glucose Oxidase/N-ethyl-Poly (4-vinyl)pyridine Multilayer
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作者 Ma, YZ 《Chinese Chemical Letters》 SCIE CAS CSCD 1998年第11期0-0,0,共3页
Multilayers of glucose oxidase(GOD)/N-ethyl-poly (4-vinyl) pyridine (EPVP) have been assembled on thiol self-assembled monolayers on gold electrode.This electrode can be used as an amperometric enzyme elcctrode for gl... Multilayers of glucose oxidase(GOD)/N-ethyl-poly (4-vinyl) pyridine (EPVP) have been assembled on thiol self-assembled monolayers on gold electrode.This electrode can be used as an amperometric enzyme elcctrode for glucose. Fe (CN)63-/4- incorporated in EPVP layer acts as the electron mediator, the linear range was 0.1 to 6 mmol/L when the number of GOD layers was 5. 展开更多
关键词 Enzyme electrode glucose oxidase N-ethyl-poly (4-vinyl) pyridine. multilayer.
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原发性肝癌患者介入治疗后血清LOXL4水平与复发的相关性分析 被引量:5
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作者 高越 万里新 +2 位作者 曾庆 池盟盟 邓俊魁 《中西医结合肝病杂志》 CAS 2023年第8期698-701,共4页
目的:检测原发性肝癌(PHC)患者介入治疗后血清赖氨酰氧化酶样蛋白4(LOXL4)水平,并分析其与复发的关系。方法:选取2018年1月至2022年1月就诊并确诊为PHC的97例患者为研究组,根据介入治疗6个月后是否复发分为复发组(n=40)和未复发组(n=57)... 目的:检测原发性肝癌(PHC)患者介入治疗后血清赖氨酰氧化酶样蛋白4(LOXL4)水平,并分析其与复发的关系。方法:选取2018年1月至2022年1月就诊并确诊为PHC的97例患者为研究组,根据介入治疗6个月后是否复发分为复发组(n=40)和未复发组(n=57),选取进行健康体检的志愿者90例为对照组。收集所有对象的一般资料,采用实时荧光定量PCR法检测血清中LOXL4表达水平,Spearman法分析LOXL4表达水平与PHC患者介入治疗后复发的相关性,用受试者工作特征(ROC)曲线评价血清LOXL4水平对PHC患者介入治疗后复发的预测价值,采用多因素Logistic回归分析PHC患者介入治疗后复发的影响因素。结果:与未复发组比较,复发组患者血清中LOXL4水平明显升高(P<0.05),分化程度低、淋巴结转移占比均较高(P<0.05)。Spearman相关性分析结果显示,血清中LOXL4水平与PHC患者介入治疗后复发呈正相关(r=0.680,P<0.05);ROC曲线结果显示,血清LOXL4水平预测PHC患者介入治疗后复发的曲线下面积(AUC)为0.918(95%CI=0.773~0.922),对应的敏感度为85.00%,特异度为92.98%;多因素Logistic回归分析显示,LOXL4、淋巴结转移、分化程度是PHC患者介入治疗后复发的影响因素(P<0.05)。结论:LOXL4在复发的PHC患者血清中表达上调,可有效帮助预测患者的复发情况。 展开更多
关键词 原发性肝癌 赖氨酰氧化酶样蛋白4 复发 相关性
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NOX4介导的氧化应激参与垂体腺瘤出血性卒中的发生 被引量:2
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作者 杨为祝 刘忠 +3 位作者 张峰林 黄延林 孙瑾 田新华 《基础医学与临床》 2023年第7期1040-1044,共5页
目的探讨还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)在垂体腺瘤出血性卒中(PA)中的作用。方法取厦门大学附属中山医院神经外科垂体腺瘤手术剩余标本,根据术后病理分为出血卒中(PA)组和非卒中(non-PA)组,每组18例。苏木精-伊红... 目的探讨还原型烟酰胺腺嘌呤二核苷酸磷酸(NADPH)氧化酶4(NOX4)在垂体腺瘤出血性卒中(PA)中的作用。方法取厦门大学附属中山医院神经外科垂体腺瘤手术剩余标本,根据术后病理分为出血卒中(PA)组和非卒中(non-PA)组,每组18例。苏木精-伊红(HE)染色明确是否出血;免疫组织化学染色检测NOX4阳性细胞百分数;Western blot检测NOX4蛋白表达量;DCFH-DA探针检测活性氧(ROS)平均荧光强度;TUNEL法检测细胞凋亡率。结果出血卒中组组织间大量红细胞渗出,非卒中组未见红细胞。出血卒中组表达的NOX4阳性细胞百分数为21.53%±4.25%,显著高于非卒中组的4.29%±1.71%(P<0.001)。出血卒中组NOX4蛋白表达水平显著高于非卒中组(P<0.001)。出血卒中组ROS平均荧光强度显著高于非卒中组(P<0.001)。出血卒中组细胞凋亡率为38.64%±12.46%,显著高于非卒中组的6.19%±2.40%(P<0.001)。结论NOX4参与垂体腺瘤出血性卒中的发生。NOX4介导的氧化应激调控细胞凋亡可能是垂体腺瘤出血性卒中的潜在机制。 展开更多
关键词 NADPH氧化酶4(NOX4) 垂体腺瘤 出血性卒中 氧化应激 凋亡
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老年全身麻醉手术患者肺部感染病原菌和NADPH oxidase与TLR4及PA水平
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作者 王岑岑 祁琦 应江明 《中华医院感染学杂志》 CAS CSCD 北大核心 2024年第12期1821-1825,共5页
目的探讨老年全身麻醉手术患者肺部感染血清还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NADPH oxi-dase)、Toll样受体4(TLR4)、前白蛋白(PA)水平.方法选取2018年12月-2023年4月临安区第一人民医院收治的79例合并肺部感染的老年全身麻醉手术... 目的探讨老年全身麻醉手术患者肺部感染血清还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶(NADPH oxi-dase)、Toll样受体4(TLR4)、前白蛋白(PA)水平.方法选取2018年12月-2023年4月临安区第一人民医院收治的79例合并肺部感染的老年全身麻醉手术患者作为病例组,89例未合并肺部感染的老年全身麻醉手术患者作为对照组;统计老年全身麻醉手术患者肺部感染的病原菌特征;检测血清NADPH oxidase相关亚基P22、P67、TLR4、PA水平;比较两组及不同肺部感染程度的老年全身麻醉手术患者血清P22、P67、TLR4、PA水平.结果79例合并肺部感染的老年全身麻醉手术患者共培养分离病原菌86株,革兰阳性菌33株占38.37%,革兰阴性菌53株占61.63%;血清P22、P67、TLR4水平病例组比对照组高(P<0.05),且中度组和重度组比轻度组高(P<0.05),重度组比中度组高(P<0.05);血清PA水平病例组比对照组低(P<0.05),且中度组和重度组比轻度组低(P<0.05),重度组比中度组低(P<0.05);Spearman相关性分析结果发现血清P22、P67、TLR4水平与老年全身麻醉手术患者肺部感染程度呈正相关(r=0.760,0.712,0.755,P均<0.05),血清PA水平与老年全身麻醉手术患者肺部感染程度呈负相关(r=-0.773,P<0.05).结论老年全身麻醉手术患者肺部感染以革兰阴性菌感染居多,且肺部感染发生后血清NADPH oxidase相关亚基P22、P67、TLR4水平呈高表达,PA水平呈低表达;NADPH oxidase相关亚基P22、P67、TLR4、PA水平与患者肺部感染程度密切相关. 展开更多
关键词 全身麻醉手术 肺部感染 术后感染 还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶 TOLL样受体4 前白蛋白 病原菌 老年人
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紫草酸甲酯抑制海马Nox4介导的铁死亡改善小鼠术后学习记忆障碍 被引量:1
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作者 刘铁龙 亓文强 +3 位作者 江洪洋 王瑞雪 代志刚 殷姜文 《安徽医科大学学报》 CAS 北大核心 2023年第7期1071-1076,共6页
目的探讨紫草酸甲酯(PAME)对小鼠术后学习记忆障碍的影响及机制。方法将C57BL/6J雄性小鼠随机分为Sham组、手术组、手术+PAME组(PAME组)、手术+NADPH氧化酶4(Nox4)腺相关病毒过表达组(Nox4过表达组)、手术+Nox4腺相关病毒空载组(AAV空载... 目的探讨紫草酸甲酯(PAME)对小鼠术后学习记忆障碍的影响及机制。方法将C57BL/6J雄性小鼠随机分为Sham组、手术组、手术+PAME组(PAME组)、手术+NADPH氧化酶4(Nox4)腺相关病毒过表达组(Nox4过表达组)、手术+Nox4腺相关病毒空载组(AAV空载组)、手术+PAME+Nox4过表达组(PN组)。手术模型采用剖腹探查术,PAME(20 mg/kg)给药时间为术后连续灌胃7 d,Nox4腺相关病毒在手术前28 d注射到海马脑区。Morris水迷宫实验和条件性恐惧实验检测小鼠学习记忆能力;免疫荧光观察Nox4表达变化;Western blot法检测Nox4、长链脂酰辅酶A合成酶4(ACSL4)和谷胱甘肽过氧化物酶4(GPX4)表达;分光光度法检测活性氧(ROS)和铁含量。结果与Sham组相比,手术组、Nox4过表达组、AAV空载组小鼠学习记忆能力下降,Nox4、ACSL4表达升高,GPX4表达降低,ROS、铁含量增加,PAME治疗后小鼠术后学习记忆能力改善,海马神经元Nox4和铁死亡减轻。结论PAME治疗后可提高术后小鼠学习记忆能力,与其抑制海马Nox4介导的铁死亡有关。 展开更多
关键词 紫草酸甲酯 学习记忆 NADPH氧化酶4 铁死亡 海马
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基于Nox4/PKC_(α)/Gal-3通路探讨柴胡皂苷D对心肌梗死大鼠心肌纤维化的影响 被引量:1
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作者 李耀征 白保强 +1 位作者 孙亚勤 王贺 《中西医结合心脑血管病杂志》 2023年第20期3724-3729,共6页
目的:基于NADPH氧化酶4(Nox4)/蛋白激酶C_(α)(PKC_(α))/半乳糖凝集素3(Gal-3)通路探讨柴胡皂苷D对心肌梗死大鼠心肌纤维化的影响。方法:将SD大鼠随机分为假手术组、模型组、柴胡皂苷D组(50 mg/kg)、Apocynin组(10 mg/kg)、柴胡皂苷D+A... 目的:基于NADPH氧化酶4(Nox4)/蛋白激酶C_(α)(PKC_(α))/半乳糖凝集素3(Gal-3)通路探讨柴胡皂苷D对心肌梗死大鼠心肌纤维化的影响。方法:将SD大鼠随机分为假手术组、模型组、柴胡皂苷D组(50 mg/kg)、Apocynin组(10 mg/kg)、柴胡皂苷D+Apocynin组(柴胡皂苷D 50 mg/kg+Apocynin 10 mg/kg),每组12只。除假手术组外,其余各组制备心肌梗死模型。经药物处理后,采用超声测量各组大鼠心室功能指标左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)、左室射血分数(LVEF)、左室短轴缩短率(LVFS);苏木精-伊红(HE)染色检测各组大鼠心肌组织形态;Masson染色检测各组大鼠心肌组织纤维化改变,并计算心肌组织胶原容积积分(CVF);酶联免疫吸附法(ELISA)检测各组大鼠血清白细胞介素(IL)-1β、IL-6、转化生长因子(TGF)-β_(1)水平;蛋白免疫印迹法(Western Blot)检测各组大鼠心肌组织Nox4/PKC_(α)/Gal-3通路相关蛋白表达含量。结果:相较于假手术组,模型组大鼠心肌组织有严重的病理损伤,胶原增生明显,心肌CVF、LVEDD、LVESD及血清IL-1β、IL-6、TGF-β_(1)水平升高,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达升高(P<0.05),LVEF及LVFS降低(P<0.05)。相较于模型组,各药物组大鼠心肌组织病理损伤减轻,胶原增生减少,CVF、LVEDD、LVESD及血清IL-1β、IL-6、TGF-β_(1)水平降低,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达降低(P<0.05),LVEF及LVFS升高(P<0.05)。相较于柴胡皂苷D组、Apocynin组,柴胡皂苷D+Apocynin组大鼠心肌组织病理损伤进一步减轻,且胶原增生进一步减少,CVF、LVEDD、LVESDE及血清IL-1β、IL-6、TGF-β_(1)水平降低,心肌组织Nox4、PKC_(α)及Gal-3蛋白表达降低(P<0.05),LVEF及LVFS升高(P<0.05)。结论:柴胡皂苷D可抑制Nox4/PKC_(α)/Gal-3通路激活,减轻心肌梗死大鼠心肌组织炎症损伤,缓解心肌纤维化,改善心功能。 展开更多
关键词 心肌梗死 心肌纤维化 NADPH氧化酶4/蛋白激酶C_(α)/半乳糖凝集素3通路 柴胡皂苷D 大鼠 实验研究
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人参皂苷Rg1通过抑制NOX4/MAPK通路减轻棕榈酸钠诱导HMCs细胞的纤维化 被引量:2
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作者 周慧敏 张洁 +5 位作者 黄蕾 孙冉 姬朋敏 孔亮亮 李维祖 李卫平 《中国药理学通报》 CAS CSCD 北大核心 2023年第5期917-925,共9页
目的探讨人参皂苷Rg1对棕榈酸钠(sodium palmitate,PA)诱导的人肾小球系膜细胞(human mesangial cells,HMCs)纤维化的抑制作用及机制。方法(1)用不同浓度的PA将HMCs处理24 h,通过油红O染色观察脂质变化,H2DCFDA法检测ROS生成情况;(2)将H... 目的探讨人参皂苷Rg1对棕榈酸钠(sodium palmitate,PA)诱导的人肾小球系膜细胞(human mesangial cells,HMCs)纤维化的抑制作用及机制。方法(1)用不同浓度的PA将HMCs处理24 h,通过油红O染色观察脂质变化,H2DCFDA法检测ROS生成情况;(2)将HMCs细胞分为对照组、PA(160μmol·L^(-1))组、HG(25 mmol·L^(-1))组、PA+HG组,用活细胞成像观察细胞24 h内形态变化;(3)将HMCs细胞分为对照组、PA(160μmol·L^(-1))组、PA+Rg1(5μmol·L^(-1))组、PA+Rg1(10μmol·L^(-1))组、PA+Apocynin(50μmol·L^(-1))组,免疫荧光法检测Col4的表达,Real-time PCR检测Col4、TGF-β和FN的mRNA表达;Western blot测定TGF-β、FN以及NOX4、MAPK通路相关蛋白表达。结果PA各浓度处理HMCs可剂量依赖性增加细胞内脂质沉积和ROS生成;PA组和PA+HG组均能导致HMCs细胞形态异常变化;Apocynin和Rg1(5、10μmol·L^(-1))可抑制PA引起的HMCs内脂质积累、ROS的增多,以及Col4、TGF-β和FN mRNA的过表达,并明显下调PA诱导的HMCs中TGF-β、FN、NOX4和MAPK相关蛋白的增多。结论人参皂苷Rg1能明显抑制PA诱导的HMCs细胞的纤维化,其机制可能与减少脂质沉积、抑制NOX4/MAPK通路等有关。 展开更多
关键词 人参皂苷RG1 人肾小球系膜细胞 棕榈酸钠 NADPH氧化酶4 MAPK 纤维化
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Regulation of cytochrome c oxidase contributes to health and optimal life
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作者 Bernhard Kadenbach 《World Journal of Biological Chemistry》 CAS 2020年第2期52-61,共10页
The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulate... The generation of cellular energy in the form of ATP occurs mainly in mitochondria by oxidative phosphorylation.Cytochrome c oxidase(CytOx),the oxygen accepting and rate-limiting step of the respiratory chain,regulates the supply of variable ATP demands in cells by“allosteric ATP-inhibition of CytOx.”This mechanism is based on inhibition of oxygen uptake of CytOx at high ATP/ADP ratios and low ferrocytochrome c concentrations in the mitochondrial matrix via cooperative interaction of the two substrate binding sites in dimeric CytOx.The mechanism keeps mitochondrial membrane potentialΔΨm and reactive oxygen species(ROS)formation at low healthy values.Stress signals increase cytosolic calcium leading to Ca^2+-dependent dephosphorylation of CytOx subunit I at the cytosolic side accompanied by switching off the allosteric ATPinhibition and monomerization of CytOx.This is followed by increase ofΔΨm and formation of ROS.A hypothesis is presented suggesting a dynamic change of binding of NDUFA4,originally identified as a subunit of complex I,between monomeric CytOx(active state with highΔΨm,high ROS and low efficiency)and complex I(resting state with lowΔΨm,low ROS and high efficiency). 展开更多
关键词 Cytochrome c oxidase Regulation of respiration Allosteric ATP-inhibition NDUFA4 Reversible phosphorylation Efficiency of ATP synthesis Dimerization of cytochrome c oxidase
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BnGLO4 gene cloning and bioinformatics analysis in Brassica napus L
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作者 Xi Li Xiaodan Wang +5 位作者 Shijun Li Zechuan Peng Dongfang Zhao Bingqian Zhou Chunyun Guan Mei Guan 《Oil Crop Science》 CSCD 2023年第3期133-142,共10页
High oleic acid rapeseed oil offers superior nutritional and health benefits,but its mass production is limited due to poor resistance and slightly lower yield.Photosynthesis serves as the foundation of biological sur... High oleic acid rapeseed oil offers superior nutritional and health benefits,but its mass production is limited due to poor resistance and slightly lower yield.Photosynthesis serves as the foundation of biological survival and closely correlates with crop resistance to stresses,yield,and quality.To identify photosynthesis-related genes,transcriptome sequencing was conducted on high oleic acid rapeseed Gaoyousuan No.1 and low oleic acid rapeseed Xiangyou 15 resulting in the identification of a total of 9396 differentially expressed genes(4669 upregulated and 4727 down-regulated).From these genes nine candidate genes were screened using GO and KEGG analysis with BnGLO4 being selected for cloning purposes.The BnGLO4 gene fragment has a length of 1161 bp with an ORF sequence of 1092 bp encoding a theoretical isoelectric point of pI 7.60;it encodes an unstable lipid-soluble protein localized in peroxisomes without transmembrane structural domains or signal peptides.Its amino acid sequence homology was highest with that of BnaA01G0355200ZS,BnaA01G0355600ZS,BnaA05G0410400ZS,BnaC01G0441800ZS,and Brassica rapa(XP_009117145.1),Brassica napus(CDY39100.1),Brassica cretica(KAF3533604.1)and Brassica oleracea var.oleracea(XP_013610644.1)belonging to the same cruciferous family.The BnGLO4 gene may be associated with responses to abiotic stresses such as salt,drought,and temperature extremes along with photosynthesis and growth in rapeseed plants.The expression levels of the GLO4 gene(BnaA01G0355200 ZS)were highest in filaments while being higher at each stage in seeds and siliques with the highest expression level at day 14 in seeds.Expression was significantly upregulated after 3 h of salt stress treatment,reaching a maximum at 12 h before slightly decreasing at 24 h.The findings of this study lay a foundation for further investigation on photosynthesis and stress response in high oleic rapeseed. 展开更多
关键词 High oleic acid TRANSCRIPTOME Glycolate oxidase GLO4
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2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸合成路线的改进
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作者 谢珺 崔杏 +1 位作者 王建塔 汤磊 《化学与生物工程》 CAS 2023年第7期30-33,共4页
在课题组前期2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸合成路线的基础上进行改进,以5-氟水杨醛为起始原料,经环合、还原、亲电取代、硫代、环合、水解反应得到目标化合物,化合物结构经^(1)HNMR、^(13)CNMR和HRMS确证。与... 在课题组前期2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸合成路线的基础上进行改进,以5-氟水杨醛为起始原料,经环合、还原、亲电取代、硫代、环合、水解反应得到目标化合物,化合物结构经^(1)HNMR、^(13)CNMR和HRMS确证。与原合成路线相比,该路线减少了合成步骤,目标化合物总收率由0.3%提高到5.0%。 展开更多
关键词 黄嘌呤氧化酶 2-[(2-乙基-5-氟苯并呋喃-3-基)甲基]-4-甲基-5-噻唑甲酸 合成 改进
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