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Role of microRNA in regulation of myeloma-related angiogenesis and survival
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作者 Michal A Rahat Meir Preis 《世界血液学杂志》 2016年第2期51-60,共10页
Multiple myeloma(MM)is a malignant disease caused by clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage.Despite the uniform clinical signs,the disease is very diverse... Multiple myeloma(MM)is a malignant disease caused by clonal proliferation of plasma cells that result in monoclonal gammopathy and severe end organ damage.Despite the uniform clinical signs,the disease is very diverse in terms of the nature and sequence of the underlying molecular events.Multiple cellular processes are involved in helping the malignant cells to remain viable and maintain proliferative properties in the hypoxic microenvironment of the bone marrow.Specifically,the process of angiogenesis,triggered by the interactions between the malignant MM cells and the stroma cells around them,was found to be critical for MM progression.In this review we highlight the current understanding about the epigenetic regulation of the proliferation and apoptosis of MM cells and its dependency on angiogenesis in the bone marrow that is carried out by different microRNAs. 展开更多
关键词 Multiple MYELOMA MICRORNA ANGIOGENESIS Proliferation Apoptosis HYPOXIA Vascular ENDOTHELIAL growth FACTOR Hypoxia-induce FACTOR Macrophages ENDOTHELIAL cells
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Effect of lentiviral vector-mediated overexpression of hypoxia-inducible factor 1 alpha delivered by pluronic F-127 hydrogel on brachial plexus avulsion in rats 预览
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作者 Tao Wang Li-Ni Zeng +6 位作者 Zhe Zhu Yu-Hui Wang Lu Ding Wei-Bin Luo Xiao-Min Zhang Zhi-Wei He Hong-Fu Wu 《中国神经再生研究:英文版》 SCIE CAS CSCD 2019年第6期1069-1078,共10页
Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles.However,no satisfactory treatment is currently available.Hypoxia-inducible factor 1αis a critical ... Brachial plexus avulsion often results in massive motor neuron death and severe functional deficits of target muscles.However,no satisfactory treatment is currently available.Hypoxia-inducible factor 1αis a critical molecule targeting several genes associated with ischemia-hypoxia damage and angiogenesis.In this study,a rat model of brachial plexus avulsion-reimplantation was established,in which C5–7 ventral nerve roots were avulsed and only the C6 root reimplanted.Different implants were immediately injected using a microsyringe into the avulsion-reimplantation site of the C6 root post-brachial plexus avulsion.Rats were randomly divided into five groups:phosphate-buffered saline,negative control of lentivirus,hypoxia-inducible factor 1α(hypoxia-inducible factor 1αoverexpression lentivirus),gel(pluronic F-127 hydrogel),and gel+hypoxia-inducible factor 1α(pluronic F-127 hydrogel+hypoxia-inducible factor 1αoverexpression lentivirus).The Terzis grooming test was performed to assess recovery of motor function.Scores were higher in the hypoxia-inducible factor 1αand gel+hypoxia-inducible factor 1αgroups(in particular the gel+hypoxia-inducible factor 1αgroup)compared with the phosphate-buffered saline group.Electrophysiology,fluorogold retrograde tracing,and immunofluorescent staining were further performed to investigate neural pathway reconstruction and changes of neurons,motor endplates,and angiogenesis.Compared with the phosphate-buffered saline group,action potential latency of musculocutaneous nerves was markedly shortened in the hypoxia-inducible factor 1αand gel+hypoxia-inducible factor 1αgroups.Meanwhile,the number of fluorogold-positive cells and ChAT-positive neurons,neovascular area(labeled by CD31 around av ulsed sites in ipsilateral spinal cord segments),and the number of motor endplates in biceps brachii(identified byα-bungarotoxin)were all visibly increased,as well as the morphology of motor endplate in biceps brachil was clear in the hypoxia-inducible factor 1αand gel+hypoxia-inducible f 展开更多
关键词 NERVE REGENERATION peripheral NERVE injury brachial plexus AVULSION HYPOXIA ischemia hypoxia-inducible factor 1αoverexpression PLURONIC F-127 motor neurons axonal REGENERATION angiogenesis neural REGENERATION
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Evaluation of a locked nucleic acid form of antisense oligo targeting HIF-1α in advanced hepatocellular carcinoma
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作者 Jennifer Wu Merly Contratto +5 位作者 Krishna P Shanbhogue Gulam A Manji Bert H O’Neil Anne Noonan Robert Tudor Ray Lee 《世界临床肿瘤学杂志(英文版)》 2019年第3期149-160,共12页
BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO70... BACKGROUND Hypoxia-inducible factor 1α(HIF-1α) is a gene that regulates tumor survival,neovascularization and invasion. Overexpression of HIF-1α correlates with poor prognosis in hepatocellular carcinoma(HCC). RO7070179 is a HIF-1α inhibitor that decreases HIF-1α mRNA and its downstream targets, it could be a potential treatment in HCC.AIM To evaluate safety and preliminary activity of RO7070179 in patients with previously treated HCC, with focus on a patient with prolonged response to RO7070179.METHODS In the preclinical study of RO7070179 in a HCC xenograft model, the mice wereseparated into 4 groups with each group received doses of 0, 3, 10 and 30 mg/kg for total 10 doses. HCC patients who failed at least one line of systemic treatment,received RO7070179 as a weekly infusion, each cycle is 6 wk. We evaluated the safety and HIF-1α mRNA levels of RO7070179.RESULTS Preclinical evaluation of RO7070179 in orthotopic HCC xenograft model showed no significant differences in HCC tumor weight between the 3 and 10 mg/kg groups. However, dose of 10 mg/kg of RO7070179, has shown 76% reduction of the amount of HIF-1α mRNA in HCC tissue. In the phase 1 b study of RO7070179 in previously treated HCC patients, 8 out of 9 were evaluable: 1 achieved PR and1 SD. The patient with PR responded after 2 cycles treatments, which has been maintained for 12 cycles. This patient also showed reduction in perfusion of dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI) after 1 cycle of treatment. After 1 cycle of treatment, both patients with PR and SD showed decrease in HIF-1α mRNA at the root of biopsies(each biopsy was divided into 2 specimens, the tip and the root).CONCLUSION RO7070179 can reduce HIF-1α mRNA level in HCC patients with SD or PR. It is well tolerated at 10 mg/kg, with transaminitis as the dose of increased toxicity.This study indicates that RO7070179 might benefit HCC patients, and an early signal for clinical benefit can potentially be predicted through changes in either m RNA level or DCE-MRI withi 展开更多
关键词 HEPATOCELLULAR carcinoma Hypoxia-inducible factor RO7070179 Superresponder Dynamic contrast-enhanced-magnetic resonance imaging
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低氧诱导胶质瘤细胞上皮间质转化及差异表达的长非编码RNA的筛选 预览
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作者 唐尚鸿 宋磊 +2 位作者 谢舒乐 李群星 林钊宇 《广东医学》 CAS 2019年第4期477-482,共6页
目的探索低氧诱导条件下神经胶质瘤细胞发生上皮间质转化相关的长非编码RNA与其侵袭转移的关系。方法通过芯片检测低氧诱导前后胶质瘤细胞的长非编码RNA的表达差异。通过qRT-PCR验证芯片结果的准确性以及上皮间质转化相关基因的表达变... 目的探索低氧诱导条件下神经胶质瘤细胞发生上皮间质转化相关的长非编码RNA与其侵袭转移的关系。方法通过芯片检测低氧诱导前后胶质瘤细胞的长非编码RNA的表达差异。通过qRT-PCR验证芯片结果的准确性以及上皮间质转化相关基因的表达变化。通过转染敲低长非编码RNA的表达水平。通过蛋白免疫印迹检测蛋白水平的表达变化。通过侵袭迁移实验检测侵袭迁移能力的变化。结果低氧诱导神经胶质瘤细胞可发生上皮间质转化,芯片检测发现多个差异表达的长非编码RNA,长非编码RNA HOTTIP在低氧诱导后表达升高最为明显(P<0.01),降低其表达水平后可逆转其上皮间质转化的过程,并显著降低侵袭迁移能力(P<0.01)。结论长非编码RNA HOTTIP的表达升高可能与低氧诱导所发生的上皮间质转化以及增强的侵袭迁移能力密切相关。 展开更多
关键词 低氧诱导 上皮间质转化 长非编码RNA 侵袭迁移
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Lysyl oxidase and hypoxia-inducible factor 1α: biomarkers of gastric cancer
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作者 Ya-Lin Han Li Chen +3 位作者 Rui Qin Guan-Qing Wang Xiao-Hua Lin Guang-Hai Dai 《世界胃肠病学杂志:英文版》 SCIE CAS 2019年第15期1828-1839,共12页
BACKGROUND Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM To inve... BACKGROUND Gastric cancer (GC) is one of the main causes of cancer mortality worldwide. Recent studies on tumor microenvironments have shown that tumor metabolism exerts a vital role in cancer progression. AIM To investigate whether lysyl oxidase (LOX) and hypoxia-inducible factor 1α(HIF1α) are prognostic and predictive biomarkers in GC. METHODS A total of 80 tissue and blood samples were collected from 140 patients admitted to our hospital between August 2008 and March 2012. Immunohistochemical staining was performed to measure the expression of LOX and HIF1α in tumor and adjacent tissues collected from patients with GC. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis was used to detect the mRNA expression levels of LOX and HIF1α in patients with GC. In addition, single-factor analysis was applied to analyze the relationship between LOX, HIF1α and prognosis of GC. RESULTS Immunohistochemical staining suggested that the expression levels of LOX and HIF1α increased in tumor tissues from patients with GC. QRT-PCR analysis indicated that mRNA expression of LOX and HIF1α was also upregulated in tumor tissues, which was in accordance with the above results. We also detected expression of these two genes in blood samples. The expression level of LOX and HIF1α was higher in patients with GC than in healthy controls. Additional analysis showed that the expression level of LOX and HIF1α was related to the clinicopathological characteristics of GC. Expression of LOX and HIF1α increased with the number of lymph node metastases, deeper infiltration depth and later tumor–node–metastasis stages. Single-factor analysis showed that high expression of LOX and HIF1α led to poor prognosis of patients with GC. CONCLUSION LOX and HIF1α can be used as prognostic and predictive biomarkers for GC. 展开更多
关键词 Lysyl OXIDASE Hypoxia-inducible factor Gastric cancer BIOMARKER PROGNOSIS
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Role of ROS/Kv/HIF Axis in the Development of Hypoxia-Induced Pulmonary Hypertension 预览
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作者 Wen Wu Yan Li Dunquan Xu 《中国医学科学杂志:英文版》 CAS CSCD 2017年第4期253-259,共7页
Hypoxic pulmonary hypertension (HPH) is a common complication in patients with chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, or dwellers in high altitude. The exact mechanisms underlying th... Hypoxic pulmonary hypertension (HPH) is a common complication in patients with chronic obstructive pulmonary disease (COPD), sleep-disordered breathing, or dwellers in high altitude. The exact mechanisms underlying the development of HPH still remain unclear. Reactive oxygen species (ROS),hypoxia inducible factors (HIF), and potassium channels (KV) are believed as the main factors during the development of HPH. We propose that the “ROS/Kv/HIF axis” may play an important initiating role in the development of HPH. Being formed under a hypoxic condition, ROS affects the expression and function of HIFs or KV, and consequently triggers multiple downstream signaling pathways and genes expression that participate in promoting pulmonary vasoconstriction and arterial remodeling. Thus, further study determining the initiating role of “ROS/Kv/HIF axis” in the development of HPH could provide theoretic evidences to better understand the underlying mechanisms of HPH, and help identify new potential targets in the treatment of HPH. 展开更多
关键词 hypoxia-induced pulmonary hypertension reactive oxygen species HYPOXIA INDUCIBLE factors potassium channels VASOCONSTRICTION ARTERIAL REMODELING
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急性脑出血患者血清HIF-1α与VEGF、Hsp70动态表达情况研究 预览 被引量:1
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作者 岑丽霞 靳敏 袁汝康 《临床与病理杂志》 2016年第8期1177-1181,共5页
目的:研究分析急性脑出血患者血清低氧诱导因子(hypoxia-inducible factor-1α,HIF-1α)与血管生长因子(vascular endothelial growth factor,VEGF)、热休克蛋白70(heat shock protein 70,Hsp70)动态表达情况。方法:将2014年... 目的:研究分析急性脑出血患者血清低氧诱导因子(hypoxia-inducible factor-1α,HIF-1α)与血管生长因子(vascular endothelial growth factor,VEGF)、热休克蛋白70(heat shock protein 70,Hsp70)动态表达情况。方法:将2014年3月至2015年4月我院急诊收治的35例急性脑出血患者,根据其出血量分为小量组、中量组、大量组,测定比较各分组人员发病后12 h、1 d、3 d、5 d、7 d的静脉血HIF-1α与VEGF、Hsp70差异,同时研究分析这3者与出血量之间的相关关系。结果:大量组患者不同时间点HIF-1α与VEGF、Hsp70指标均明显高于同时间点其他两组患者,P〈0.05;单因素方差分析HIF-1α与VEGF、Hsp70与患者出血量间关系,均成正相关(r=0.563,P〈0.05;r=0.771,P〈0.05;r=0.602,P〈0.05)。结论:HIF-1α、VEGF、Hsp70在急性脑出血患者中表达较高,在脑出血12 h后升高,并随着脑出血的发展呈现动态表达,且与出血量成正相关关系。 展开更多
关键词 急性脑出血 低氧诱导因子-1α 血管生长因子 热休克蛋白70 hypoxia-inducible factor-1α (HIF-1α) vascular endothelial growth factor (VEGF) heat shock protein 70 (Hsp70)
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缺氧诱导因子HIF-1a和Endoglin在子痫前期患者胎盘中的表达及其与母体血清sEng的相关性研究 被引量:1
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作者 何美荣 舒竞铖 +1 位作者 黄星 尹时华 《中国伤残医学》 2015年第3期23-25,共3页
目的:检测HIF-1a、Endoglin和sEng在子痫前期患者胎盘及血清中的表达,并探讨他们在子痫前期发病机制中的作用。方法:选择子痫前期病人35例,随机选取同期正常孕妇40例作为对照组。采用免疫组织化学和酶联免疫吸附试验(ELISA)分别... 目的:检测HIF-1a、Endoglin和sEng在子痫前期患者胎盘及血清中的表达,并探讨他们在子痫前期发病机制中的作用。方法:选择子痫前期病人35例,随机选取同期正常孕妇40例作为对照组。采用免疫组织化学和酶联免疫吸附试验(ELISA)分别检测各组胎盘组织中HIF-1 a、Endoglin的表达及母体血清中sEng的水平。结果:轻度子痫前期组血清sEng明显高于正常对照组(P<0.05),重度子痫前期组明显高于轻度子痫前期组(P<0.05)。轻度子痫前期组HIF-1 a和Endoglin的表达均显著高于正常对照组,重度子痫前期组均显著高于轻度子痫前期组(P<0.05)。子痫前期组胎盘组织中HIF-1a与Endoglin及sEng的表达均呈正相关(r分别为0.859,0.895)。结论:子痫前期患者胎盘HIF-1α、Endoglin和血清sEng的表达均升高,3者可能共同参与了子痫前期发病的病理生理过程。 展开更多
关键词 子痫前期 缺氧诱导因子 内皮因子 可溶性内皮因子 胎盘
缺氧诱导因子-1α及促红细胞生成素在大鼠角膜新生血管中的表达 预览 被引量:3
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作者 王济民 石蕊 +2 位作者 魏会玲 马勇 高丹 《国际眼科杂志》 CAS 2014年第12期2139-2142,共4页
目的:探讨缺氧诱导因子-1α( hypoxia-inducible factor-1α,HIF-1α)及促红细胞生成素( erythropoietin,EPO)在碱烧伤大鼠角膜组织中的表达,评估其在角膜新生血管( corneal neovascularization,CNV)发生发展中的作用。 方法:... 目的:探讨缺氧诱导因子-1α( hypoxia-inducible factor-1α,HIF-1α)及促红细胞生成素( erythropoietin,EPO)在碱烧伤大鼠角膜组织中的表达,评估其在角膜新生血管( corneal neovascularization,CNV)发生发展中的作用。 方法:健康3月龄SD大鼠,随机分为实验组和对照组,碱烧伤法建立CNV模型,分别于造模成功后1,3,5,7,14 d测量CNV的长度并计算面积,同时取角膜组织以免疫组织化学检测HIF-1α及EPO的表达部位,并以RT-PCR法检测其mRNA的表达情况,实验数据采用SPSS 20.0处理。 结果:碱烧伤后1,3,5,7,14d,CNV的面积随时间逐渐增加,7 d生长最为旺盛,14 d后生长减慢。免疫组织化学提示:正常角膜各层未见HIF-1α的表达,可见微量EPO,碱烧伤后1 d时HIF-1α及EPO免疫活性增强,主要表达于角膜上皮及内皮层。 RT-PCR 结果显示 HIF-1α及EPO mRNA的表达在正常大鼠角膜组织中表达极少,在角膜碱烧伤后3 d表达增强,7 d达到高峰,14 d后明显下降;不同时间点组间比较存在统计学差异(P〈0.05)。 结论:HIF-1α和EPO与CNV的形成密切相关。 展开更多
关键词 角膜新生血管 碱烧伤 缺氧诱导因子-1Α 促红细胞生成素 hypoxia-inducible factor-1α
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An inhibitor of HIF-αsubunit expression suppresses hypoxiainduced dedifferentiation of human NSCLC into cancer stem cell-like cells
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作者 Miho Akimoto Hideko Nagasawa +3 位作者 Hitoshi Hori Yoshihiro Uto Yoshio Honma Keizo Takenaga 《世界医学遗传学杂志》 2013年第4期41-54,共14页
ferentiation of non-small cell lung cancer(NSCLC)cells and whether a hypoxia-inducible factor(HIF)inhibitor is able to suppress the process.METHODS:Human lung adenocarcinoma A549 cells and squamous carcinoma QG56 cell... ferentiation of non-small cell lung cancer(NSCLC)cells and whether a hypoxia-inducible factor(HIF)inhibitor is able to suppress the process.METHODS:Human lung adenocarcinoma A549 cells and squamous carcinoma QG56 cells were cultured under normoxic(21%O2)or hypoxic(4%or 1%O2)conditions.The expression of the following genes were examined by reverse transcription-polymerase chain reaction,Western blotting and/or immunofluorescence:HIF-1αand HIF-2αsubunits;differentiation marker genes,namely surfactant protein C(SP-C)(typeⅡalveolar cell marker),CC10(typeⅠalveolar cell marker)and aquaporin 5(AQP5)(Clara cell marker);and stem cell-associated genes,namely CD133,OCT4,and Musashi-1(MSI1).The tumor sphere-forming ability of the cells was evaluated by culturing them in serum-free growth factor-rich medium containing epidermal growth factor(EGF)and fibroblast growth factor(FGF).CD133 expression in hypoxic regions in A549 tumors was examined by double-immunostaining of tissue cryosections with an anti-2-nitroimidazole EF5 antibody and an anti-CD133 antibody.The metastatic ability of A549 cells was examined macroscopically and histologically after injecting them into the tail vein of immunocompromised mice.RESULTS:A549 cells primarily expressed SP-C,and QG56 cells expressed CC10 and AQP5.Exposure of A549 cells to hypoxia resulted in a marked downregulation of SP-C and upregulation of CD133,OCT4,and MSI1 in a time-dependent manner.Moreover,hypoxia mimetics,namely desferrioxamine and cobalt chloride,elicited similar effects.Ectopic expression of the constitutively active HIF-1αsubunit also caused the downregulation of SP-C and upregulation of CD133 and MSI1 but not OCT4,which is a direct target of HIF-2.Hypoxia enhanced the sphere-forming activity of A549 cells in serum-free medium containing EGF and FGF.Similarly,hypoxia downregulated the expression of CC10 and AQP5 genes and upregulated CD133,OCT4,and MSI1 genes in QG56 cells.TX-402(3-amino-2-quinoxalinecarbonitrile 1,4-dioxide),which is a small molecule inhibitor of th 展开更多
关键词 Non-small cell lung CANCER Tumor microenvironment HYPOXIA Hypoxia-inducible FACTOR Differentiation CANCER stem CELLS Hypoxia-inducible FACTOR INHIBITOR
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天麻对大鼠大脑皮质神经元细胞缺氧后超微结构及Bax和Bcl-2表达的影响 被引量:4
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作者 陶陶 周建 +3 位作者 徐坚 刘智 罗开俭 叶兰 《中华中医药杂志》 CAS CSCD 北大核心 2013年第4期946-951,共6页
目的:探讨天麻对大脑皮质神经元细胞缺氧后超微结构及Bax和Bcl-2表达的影响。方法:制备体外培养大鼠大脑皮层神经元原代培养及缺氧的模型,模型成功后随机分为正常对照组、缺氧组、天麻组(低、中、高剂量组)、尼莫地平组;采用倒置显... 目的:探讨天麻对大脑皮质神经元细胞缺氧后超微结构及Bax和Bcl-2表达的影响。方法:制备体外培养大鼠大脑皮层神经元原代培养及缺氧的模型,模型成功后随机分为正常对照组、缺氧组、天麻组(低、中、高剂量组)、尼莫地平组;采用倒置显微镜、超微病理学、免疫组化的方法,观察天麻对大脑皮质神经元细胞缺氧后超微结构及Bax和Bcl-2表达的影响。结果:①超微结构的观察:天麻可明显改善缺氧对神经细胞的损伤。②免疫组化观察:在缺氧处理前用天麻预处理可提高Bcl-2的表达,抑制Bax的表达,与缺氧组相比有显著性差异(P〈0.05)。结论:天麻可明显改善缺氧后神经细胞损伤的超微结构;提高Bcl-2的表达,抑制Bax的表达,减少缺氧引起的神经细胞凋亡的发生,对神经细胞起到保护作用。 展开更多
关键词 细胞培养 神经元细胞 缺氧 天麻 超微结构 BAX Bcl-2
IL-17在低氧诱导肺动脉高压过程中的作用 预览 被引量:3
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作者 王宏飞 张安臣 +3 位作者 李飞飞 刘波 李冬寒 杜心灵 《华中科技大学学报:医学版》 CAS CSCD 北大核心 2013年第3期273-277,共5页
目的观察不同时程低氧诱导的肺动脉高压小鼠肺组织中IL-17mRNA及其蛋白表达水平的变化,探讨IL-17在低氧诱导肺动脉高压中的作用。方法建立小鼠低氧诱导肺动脉高压模型,监测小鼠血流动力学改变、右心室肥厚指数(RV/LV+S),RT-PCR技术... 目的观察不同时程低氧诱导的肺动脉高压小鼠肺组织中IL-17mRNA及其蛋白表达水平的变化,探讨IL-17在低氧诱导肺动脉高压中的作用。方法建立小鼠低氧诱导肺动脉高压模型,监测小鼠血流动力学改变、右心室肥厚指数(RV/LV+S),RT-PCR技术检测对照组及低氧3周、6周组肺组织IL-17mRNA表达水平变化,Western blot技术检测相应蛋白表达水平变化及免疫组化方法对IL-17进行定位。结果与对照组相比,低氧诱导下小鼠右心室收缩压力及右心室肥厚指数均明显升高,且差异有统计学意义(均P〈0.01),证实肺动脉高压模型成功建立。随着低氧时间的延长,IL-17mRNA及其蛋白表达水平也逐渐增加,差异均有统计学意义(P〈0.05或P〈0.01)。IL-17主要定位于内皮细胞,肺泡上皮细胞也有表达。结论 IL-17可能在低氧诱导肺动脉高压发生、发展过程中扮演了重要角色。 展开更多
关键词 肺动脉高压 白细胞介素-17 低氧诱导 内皮细胞
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Hypoxia and cytokines regulate carbonic anhydrase 9 expression in hepatocellular carcinoma cells in vitro
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作者 Feray Kockar Hatice Yildrim +7 位作者 Rahsan Ilikci Sagkan Carsten Hagemenn Yasemin Soysal Jelena Anacker Ahmed Ayad Hamza Dirk Vordermark Michael Flentje Harun M Said 《世界临床肿瘤学杂志》 2012年第6期82-91,共10页
AIM:To study the expression of carbonic anhydrase(CA)9 in human hepatocellular carcinoma(HCC)cells.METHODS:We studied CA9 protein,CA9 mRNA and hypoxia-inducible factor-1 alpha(HIF-1α)protein levels in Hep3B cells exp... AIM:To study the expression of carbonic anhydrase(CA)9 in human hepatocellular carcinoma(HCC)cells.METHODS:We studied CA9 protein,CA9 mRNA and hypoxia-inducible factor-1 alpha(HIF-1α)protein levels in Hep3B cells exposed in different parallel approaches.In one of these approaches,HCC cells were exposed to extreme in vitro hypoxia(24 h 0.1%O2)without or with interleukin(IL)-1,IL-6,tumor necrosis factoralpha(TNF-α)and transforming growth factor-beta(TGF-β)stimulation for the same hypoxic exposure time or exposed to normoxic oxygenation conditions without or with cytokine stimulation.RESULTS:The tumour cell line analysed showed a strong hypoxic CA9 mRNA expression pattern in response to prolonged severe hypoxia with cell-line specific patterns and a marked induction of CA9 protein in response to severe hypoxia.These results were paralleled by the results for HIF-1αprotein under identical oxygenation conditions with a similar expression tendency to that displayed during the CA9 protein expression experimental series.Continuous stimulation with the cytokines,IL-1,IL-6,TNF-αand TGF-β,under normoxic conditions significantly increased the carbonic anhydrase 9 expression level at both the protein and mRNA level,almost doubling the CA9 mRNA and CA9 and HIF-1αprotein expression levels found under hypoxia.The findings from these experiments indicated that hypoxia is a positive regulator of CA9 expression in HCC,and the four signal transduction pathways,IL-1,IL-6,TNF-αand TGF-β,positively influence CA9 expression under both normoxic and hypoxic conditions.CONCLUSION:These findings may potentially be considered in the design of anti-cancer therapeutic approaches involving hypoxia-induced or cytokine stimulatory effects on expression.In addition,they provide evidence of the stimulatory role of the examined cytokine families resulting in an increase in CA9 expression under different oxygenation conditions in human cancer,especially HCC,and on the role of the CA9 gene as a positive disease regulator in human cancer. 展开更多
关键词 Angiogenesis Carbonic ANHYDRASE 9 HYPOXIA Hypoxia-inducible factor-1 alpha Oxygen Radiotherapy TRANSFORMING growth FACTOR-BETA TUMOUR microenviroment
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VHb在产L-苯丙氨酸工程菌中的表达及其抗贫氧效率 预览 被引量:2
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作者 黄钦耿 吴伟斌 +2 位作者 翁雪清 施巧琴 吴松刚 《氨基酸和生物资源》 CAS 2012年第2期9-12,共4页
人工设计合成密码子优化的VHb基因及其天然的低氧启动子序列,并进行融合T7终止子克隆至L—Phe的高表达质粒中,构建高产L—phe的抗贫氧高密度发酵基因工程菌。高密度发酵过程中的低氧情况可诱导VHb基因的表达,含VHb的工程菌较对照工... 人工设计合成密码子优化的VHb基因及其天然的低氧启动子序列,并进行融合T7终止子克隆至L—Phe的高表达质粒中,构建高产L—phe的抗贫氧高密度发酵基因工程菌。高密度发酵过程中的低氧情况可诱导VHb基因的表达,含VHb的工程菌较对照工程菌发酵结果显示:菌株的稳定期延长约4h,提高菌株的产酸周期,L—phe产量提高约14%。 展开更多
关键词 L-苯丙氨酸 透明颤菌血红蛋白 低氧诱导 发酵
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PMA及乏氧诱导VEGF上调的细胞模型构建及用于RNAi研究
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作者 杨艳 吕国军 +5 位作者 郭昕 张德蒙 于炜婷 张英 刘袖洞 马小军 《现代生物医学进展》 CAS 2012年第2期 265-269,共5页
目的:探讨佛波酯(PMA)与乏氧诱导对小鼠黑色素瘤细胞B16-F10中血管内皮细胞生长因子(VEGF)表达量的影响,构建适合RNA干扰(RNAi)的体外细胞模型。方法:通过酶联免疫吸附试验(ELISA法)在蛋白质水平上检测细胞分泌的VEGF量,并用... 目的:探讨佛波酯(PMA)与乏氧诱导对小鼠黑色素瘤细胞B16-F10中血管内皮细胞生长因子(VEGF)表达量的影响,构建适合RNA干扰(RNAi)的体外细胞模型。方法:通过酶联免疫吸附试验(ELISA法)在蛋白质水平上检测细胞分泌的VEGF量,并用激光共聚焦显微镜观察小干扰RNA(siRNA)转染的细胞胞吞及细胞形态。结果:1 M PMA处理细胞2 h能明显上调B16-F10细胞中VEGF蛋白的合成及分泌,与常规培养相比,细胞可增加50%的VEGF水平。再经乏氧诱导48 h,稳定释放到培养液里的VEGF浓度大幅提高200%,范围在55-65 pg/mL/h。结论:经PMA和乏氧诱导后,B16-F10细胞稳定的VEGF分泌量与一定时间内分泌的稳定性均表明其适合作为RNAi的体外细胞模型。初步的RNAi结果表明,TKO/siRNA纳米粒与壳聚糖/siRNA纳米粒对于VEGF的沉默效率达40%。 展开更多
关键词 小鼠黑色素瘤细胞 血管内皮细胞生长因子 PMA诱导 乏氧诱导 RNAi模型
脑神康胶囊对高糖环境下氧化损伤大鼠海马神经元HIF-1α表达的影响 被引量:2
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作者 林炜炜 刘德山 +1 位作者 李伟 常萍 《山东大学学报:医学版》 CAS 北大核心 2010年第1期63-66,69共5页
目的研究高糖环境下体外培养大鼠海马神经元氧化损伤时乏氧诱导因子-lα(HIF-lα)表达的变化以及脑神康胶囊对神经元的保护作用。方法原代培养大鼠海马神经元,将细胞随机分成8组:对照组、高糖组、黄嘌呤/黄嘌呤氧化酶组(X/XO组)、... 目的研究高糖环境下体外培养大鼠海马神经元氧化损伤时乏氧诱导因子-lα(HIF-lα)表达的变化以及脑神康胶囊对神经元的保护作用。方法原代培养大鼠海马神经元,将细胞随机分成8组:对照组、高糖组、黄嘌呤/黄嘌呤氧化酶组(X/XO组)、川芎嗪组、生理盐水组、脑神康低(5mL/kg)、中(10mL/kg)、高浓度组(20mL/kg),对照组用低糖型DMEM培养基培养,其余7组用葡萄糖浓度为25mmol/L的DMEM培养基培养。除对照组及高糖组正常培养,其余各组均用黄嘌呤/黄嘌呤氧化酶处理建立氧化损伤模型,其中中药各浓度组及川芎嗪组分别于加入黄嘌呤/黄嘌呤氧化酶之前换以不同浓度含药血清和川芎嗪的DMEM培养液,采用Real-Time PCR法检测各组海马神经元HIF-1αmRNA的表达。结果与对照组相比,高糖组及X/XO组HIF-lα mRNA表达均明显上升(P均〈0.01);与高糖组相比,X/XO组HIF-1α mRNA的表达量升高(P〈0.05);与X/XO组比较,川芎嗪组及中药各浓度组HIF-1αmR-NA的表达量均降低,其中中浓度组最低,具有明显的统计学意义(P均〈0.01),川芎嗪组与低浓度组接近,无统计学差异(P〉0.05)。结论脑神康胶囊对高糖环境下培养的大鼠海马神经元氧化损伤有明显的保护作用,其作用机制可能与其抑制HIF-1α的表达、改善组织缺氧密切相关。 展开更多
关键词 海马神经元 脑神康胶囊 高糖 黄嘌呤/黄嘌呤氧化酶 乏氧诱导因子-lα 大鼠 Wistar
高原适应遗传学缺氧诱导因子通路相关基因及其药理学研究进展
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作者 贺启莲 格日力 +1 位作者 李占强 芦殿香 《药学学报》 CAS CSCD 北大核心 2019年第4期611-619,共9页
人类对高原缺氧环境的适应表现、机制及相关药理学研究一直是科研探索的热点。一个世纪以来,主要集中于青藏高原、南美洲安第斯高原和埃塞俄比亚高原的高原世居人群对于慢性缺氧所具有的独特生理适应已经得到了科学验证,而近10年来的基... 人类对高原缺氧环境的适应表现、机制及相关药理学研究一直是科研探索的热点。一个世纪以来,主要集中于青藏高原、南美洲安第斯高原和埃塞俄比亚高原的高原世居人群对于慢性缺氧所具有的独特生理适应已经得到了科学验证,而近10年来的基因研究也证实高原适应具有遗传学基础,尤其与缺氧诱导因子(hypoxia inducible factor,HIF)通路及缺氧反应基因(hypoxia response elements,HREs)具有密切关系。但有趣的是,对高原缺氧的适应表现和遗传机制在上述三大高原世居人群中却并不完全相同,其中西藏人具有更好的高原适应表现,并且HIF通路是其最关键的适应机制。同时,由于HIF通路涉及广泛,可调节数以百计的下游基因表达,并与癌症、炎症、缺血、急性脏器损伤和感染等多种疾病密切相关,因此HIF通路的激活剂和抑制剂研究也取得了很大进展。本文就三大高原世居人群对高原环境的不同适应反应、HIF及HREs在不同种族高原适应中的遗传学作用机制、HIF通路的药理学研究进展进行了综述,以期为高原低氧遗传性适应及HIF相关性疾病的进一步研究提供参考。 展开更多
关键词 缺氧 高原 适应 缺氧诱导因子 脯氨酸羟化酶
胰岛素样生细长胞因凋子亡-1的对抑氯制化作钴用诱导的PC12 预览
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作者 马珂 徐会友 +5 位作者 赵飞 张健 江继鹏 代晨 王仁杰 陈旭义 《天津医药》 CAS 北大核心 2019年第4期371-376,共6页
目的探讨胰岛素样生长因子-1(IGF-1)对氯化钴(CoCl2)诱导的肾上腺嗜铬细胞瘤PC12细胞凋亡的作用及机制。方法取对数生长期的PC12细胞,分别以10、20、40、80 mol/L的CoCl2溶液和100、200、400 g/L的IGF-1溶液处理细胞,CCK-8法检测细胞活... 目的探讨胰岛素样生长因子-1(IGF-1)对氯化钴(CoCl2)诱导的肾上腺嗜铬细胞瘤PC12细胞凋亡的作用及机制。方法取对数生长期的PC12细胞,分别以10、20、40、80 mol/L的CoCl2溶液和100、200、400 g/L的IGF-1溶液处理细胞,CCK-8法检测细胞活力,得出CoCl2和IGF-1最佳干预浓度。根据选定的实验条件,应用CoCl2处理PC12细胞建立HIE细胞模型,实验分为对照组、CoCl2处理组、IGF-1+CoCl2处理组。分组处理24h后采用CCK-8法检测细胞存活率;TUNEL染色检测细胞凋亡情况;Westernblot检测各组细胞Bax、Bcl-2及Caspase-3的蛋白的表达水平。最后在上述实验的基础上,设CoCl2处理组、CoCl2+IGF-1处理组、HIF-1α抑制剂2-甲氧雌二醇(2-MeOE2)+CoCl2组和CoCl2+2-MeOE2+IGF-1组,Westernblot观察IGF-1、2-MeOE2及两者共用对PC12细胞HIF-1α及Bax的表达水平的影响。结果CCK-8检测结果显示,40 mol/LCoCl2和200 g/LIGF-1为最佳干预浓度。利用以上浓度分组干预细胞24h后,与CoCl2组相比,IGF-1+CoCl2处理组细胞存活率明显提升,TUNEL阳性细胞数和细胞比例降低,同时抗凋亡蛋白Bcl-2表达上调,促凋亡蛋白Bax、Caspase-3,HIF-1α表达下调,差异均有统计学意义(均P<0.05)。应用2-MeOE2对细胞进行预处理后,CoCl2+2-MeOE2组与2-MeOE2+IFG-1组HIF-1α和Bax蛋白表达差异无统计学意义,但均较CoCl2+IGF-1组明显下调(P<0.01)。结论IGF-1可抑制CoCl2诱导的PC12细胞凋亡,其保护作用可能与HIF-1α表达下调有关。 展开更多
关键词 胰岛素样生长因子Ⅰ 缺氧缺血 细胞凋亡 缺氧诱导因子1 Α亚基 PC12细胞 氯化钴
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华法林的耐缺氧保护机制与抗凝及HIF-1有关 预览
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作者 徐锦芝 汪玉玲 +2 位作者 董克江 杨如江 陈容前 《齐齐哈尔医学院学报》 2019年第2期136-138,共3页
目的探讨华法林的耐缺氧保护作用及机制。方法耐缺氧动物实验以考察华法林的耐缺氧保护作用;监测血浆INR值以评价华法林的抗凝效果;Elisa法检测血清肌钙蛋白T(Tn T)及缺氧诱导因子-1(HIF-1)水平以探讨华法林的耐缺氧保护机制。结果与缺... 目的探讨华法林的耐缺氧保护作用及机制。方法耐缺氧动物实验以考察华法林的耐缺氧保护作用;监测血浆INR值以评价华法林的抗凝效果;Elisa法检测血清肌钙蛋白T(Tn T)及缺氧诱导因子-1(HIF-1)水平以探讨华法林的耐缺氧保护机制。结果与缺氧暴露对照组相比,华法林干预能有效提高缺氧小鼠存活时间(P<0.01)、血浆INR值(P<0.05)及血清HIF-1水平(P<0.01),但对血清Tn T水平无显著影响。结论华法林的耐缺氧保护功能与其抗凝及上调HIF-1有关。 展开更多
关键词 华法林 缺氧耐受 抗凝 HIF-1
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新生未成熟大鼠缺氧缺血性脑损伤时微小RNA-200b对缺氧诱导因子1α的调控作用
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作者 高笑妮 杨丽君 +1 位作者 张囡 崔红 《中华新生儿科杂志(中英文)》 CAS 2019年第1期58-62,共5页
目的 探讨新生未成熟大鼠缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)时微小RNA 200b(micro RNA-200b,miR-200b)对缺氧诱导因子1α(hypoxia-inducible factors-1α,HIF-1α)的调控作用,为早产儿HIBD的治疗提供思路。 方法 选... 目的 探讨新生未成熟大鼠缺氧缺血性脑损伤(hypoxic ischemic brain damage,HIBD)时微小RNA 200b(micro RNA-200b,miR-200b)对缺氧诱导因子1α(hypoxia-inducible factors-1α,HIF-1α)的调控作用,为早产儿HIBD的治疗提供思路。 方法 选取3日龄新生Sprague-Dawley(SD)大鼠240只,随机分为单纯缺氧缺血组(HI组)、造模后双侧侧脑室注射miR-200b激动剂组、注射miR-200b拮抗剂组、注射miR-200b激动剂阴性对照剂组、注射miR-200b拮抗剂阴性对照剂组和正常对照组,每组40只。除正常对照组不予特殊处理外,其他各组均建立未成熟新生大鼠HIBD模型。应用实时定量聚合酶链反应检测各组大鼠侧脑室注射后12 h、1 d、3 d和7 d脑组织中HIF-1α的相对表达量,比较HIF-1α表达的变化。 结果 (1)与正常对照组比较,单纯HI组侧脑室注射生理盐水后12 h HIF-1α表达量开始升高,1 d达高峰,差异有统计学意义(P<0.05),随后逐渐下降,7 d与正常对照组接近,差异无统计学意义(P>0.05)。(2)单纯HI组与HI miR-200b激动剂阴性对照组及HI miR-200b拮抗剂阴性对照组HIF-1α表达量比较,差异无统计学意义(P>0.05),miR-200b纳米载体对HIF-1α表达无明显影响。(3)HI miR-200b拮抗剂组HIF-1α持续处于高表达状态,12 h明显高于单纯HI组,差异有统计学意义(P<0.05);注射后1、3、7 d HI miR-200b拮抗剂组与单纯HI组比较,差异无统计学意义(P>0.05)。HI miR-200b激动剂组HIF-1α表达持续低于单纯HI组,1 d时差异有统计学意义(P<0.05)。 结论 miR-200b过度表达抑制了HIF-1α表达,miR-200b低表达可上调HIF-1α表达水平,但作用时间有限。因此miR-200b有可能通过调控HIF-1α的表达参与新生大鼠HIBD后减轻脑损伤的调节。 展开更多
关键词 缺氧缺血 脑损伤 微小RNA-200b 缺氧诱导因子1 Α亚基 大鼠
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